Literature Reviews

Procedure-specific systematic review summary


Total Hip Arthroplasty

Sackett et al 2000

Evidence-Based Medicine: How to Practice and Teach EBM.

Sackett DL, Straus SE, Richardson WS, et al.

London: Churchill Livingstone; 2000.

(No abstract available)

Møiniche et al 2002

A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia.

Møiniche S, Kehlet H, Dahl JB.

Anesthesiology 2002;96(3):725–741.

Reuben et al 2000

Postoperative analgesic effects of celecoxib or rofecoxib after spinal fusion surgery.

Reuben SS, Connelly NR.

Anesth Analg 2000;91(5):1221–1225.

Nonsteroidal antiinflammatory drugs are recommended for the multimodal management of postoperative pain and may have a significant opioid-sparing effect after major surgery. The analgesic efficacy of the cyclooxygenase-2 nonsteroidal antiinflammatory drugs, celecoxib and rofecoxib, have not been evaluated after major orthopedic surgery. This study was designed to determine whether the administration of a preoperative dose of celecoxib or rofecoxib to patients who have undergone spinal stabilization would decrease patient-controlled analgesia (PCA) morphine use and/or enhance analgesia. We evaluated 60 inpatients undergoing spine stabilization by one surgeon. All patients received PCA morphine. The patients were divided into three groups. Preoperatively, they were given oral celecoxib 200 mg, rofecoxib 50 mg, or placebo. The outcome measures included pain scores and 24-h morphine use at six times during the first 24 postoperative h. The total dose of morphine and the cumulative doses for each of the six time periods were significantly more in the placebo group than in the other two groups. The morphine dose was significantly less in five of the six time intervals in the rofecoxib group compared with the celecoxib group. The pain scores were significantly less in the rofecoxib group than in the other two groups at two of the six intervals, and less than the placebo group in an additional interval. Although both rofecoxib and celecoxib produce similar analgesic effects in the first 4 h after surgery, rofecoxib demonstrated an extended analgesic effect that lasted throughout the 24-h study. We thus recommend that rofecoxib be used as a preoperative component of pain management that includes PCA morphine in patients undergoing spine stabilization surgery. Implications: The cyclooxygenase-2-specific nonsteroidal antiinflammatory drugs, celecoxib and rofecoxib, both demonstrate an opioid-sparing effect after spinal fusion surgery. Celecoxib resulted in decreased morphine use for the first 8 h after surgery, whereas rofecoxib demonstrated less morphine use throughout the 24-h study period.

Harris et al 2001

Upper gastrointestinal safety evaluation of parecoxib sodium, a new parenteral cyclooxygenase-2-specific inhibitor, compared with ketorolac, naproxen, and placebo.

Harris SI, Kuss M, Hubbard RC, Goldstein JL

Clin Ther 2001;23(9):1422–1428.

BACKGROUND: Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of ulcers and upper gastrointestinal (GI) ulcer complications, which has been attributed to the inhibition of cyclooxygenase-1. These risks are usually increased in elderly populations. Parecoxib sodium is an injectable prodrug of the cyclooxygenase-2-specific inhibitor valdecoxib that has exhibited analgesic activity in previous trials. OBJECTIVE: The purpose of this study was to compare the GI safety and tolerability profile of parecoxib sodium with that of ketorolac, naproxen, and placebo in a 7-day endoscopic trial in elderly subjects. METHODS: This was a randomized, double-blind, double-dummy, placebo-controlled, parallel-group study. After a normal baseline endoscopy, healthy elderly subjects aged 66 to 75 years were randomized to receive i.v. parecoxib sodium (10 mg BID), oral naproxen (500 mg BID), or placebo for 7 days, or placebo for 2 days followed by i.v. ketorolac (15 mg QID) for 5 days. Endoscopy was performed again after 7 days. RESULTS: Among the first 17 subjects enrolled, ulcers were observed in all treatment groups except the parecoxib sodium group (ketorolac, 4/4 subjects; naproxen, 2/4 subjects; and placebo, 2/5 subjects). Four subjects in the ketorolac group and 1 subject in the naproxen group had multiple gastric ulcers or combined gastric and duodenal ulcers. Because of the unexpectedly high incidence of gastroduodenal ulcers observed, the study was terminated early and the randomization blind broken. CONCLUSION: These findings suggest that elderly patients may be at risk for GI ulceration even after short-term use of the conventional NSAIDs ketorolac and naproxen.

Greenberg et al 2000

A new cyclooxygenase-2 inhibitor, rofecoxib (VIOXX), did not alter the antiplatelet effects of low-dose aspirin in healthy volunteers.

Greenberg HE, Gottesdiener K, Huntington M, Wong P, Larson P, Wildonger L, Gillen L, Dorval E, Waldm

J Clin Pharmacol 2000;40(12 Pt 2):1509–1515.

The present study examined whether rofecoxib (VIOXX), a new specific inhibitor of cyclooxygenase-2 (COX-2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serum-generated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double-blind, randomized, placebo-controlled, parallel study of two treatment groups (n=12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open-label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet-derived serum TXB2 (COX-1 assay) was measured in blood clotted for 1 hour at 37oC. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 µg/ml collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen-induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low-dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low-dose aspirin.

Hegi et al 2004

Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac.

Hegi TR, Bombeli T, Seifert B, Baumann PC, Haller U, Zalunardo MP, Pasch T, Spahn DR.

Br J Anaesth 2004;92(4):523–531.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors or non-steroidal anti- inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief because of potential side-effects. COX-2-selective inhibitors may have a more favourable side-effect profile. This study tested the hypothesis that the COX-2-selective inhibitor rofecoxib has less influence on platelet function than the NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and side-effects of the two drugs were compared. METHODS: In this single-centre, prospective, double-blind, active controlled study, women undergoing vaginal hysterectomy (n = 25) or breast surgery (n = 25) under general anaesthesia received preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of placebo or three doses of diclofenac 50 mg p.o. at the same time points. We assessed arachidonic acid-stimulated platelet aggregation before and 4 h after the first dose of study medication, estimated intraoperative blood loss, and haemoglobin loss until the first morning after surgery. Analgesic efficacy, use of rescue analgesics, and side-effects were also recorded. RESULTS: In the rofecoxib group, stimulated platelet aggregation was disturbed less (p = 0.02), and estimated intraoperative blood loss (p = 0.01) and the decrease in haemoglobin were lower (p = 0.01). At similar pain ratings, the use of anti-emetic drugs was less in the rofecoxib group (p = 0.03). CONCLUSION: Besides having a smaller effect on platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery provided postoperative analgesia similar to that given by three doses of diclofenac 50 mg and was associated with less use of anti-emetics and less surgical blood loss in gynaecological surgery compared with diclofenac.

Bavbek et al 2004

Safety of selective COX-2 inhibitors in aspirin/nonsteroidal anti-inflammatory drug-intolerant patients: comparison of nimesulide, meloxicam, and rofecoxib.

Bavbek S, Celik G, Ozer F, Mungan D, Misirligil Z.

J Asthma 2004;41(1):67–75.

BACKGROUND: Intolerance to acetylsalicylic acid (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) is a crucial problem in clinical practice. There is, therefore, a need for safer NSAIDs in patients with analgesic intolerance. OBJECTIVE: To assess the safety of nimesulide, meloxicam, and rofecoxib, selective COX-2 inhibitors, in a group of ASA/NSAIDs-intolerant patients. METHOD: Tolerances to nimesulide, meloxicam, and rofecoxib were assessed by single-blind placebo-controlled oral challenges. One hundred twenty-seven subjects with history of adverse reaction to ASA/NSAIDs received oral challenges with nimesulide, 61 subjects were challenged with meloxicam, 51 subjects were challenged with rofecoxib, and 37 subjects were challenged with all three drugs. Placebos were given to all patients on the first day of the study. On the second day, one-fourth and three-fourths of the therapeutic doses of the active drugs (nimesulide 100 mg, meloxicam 7.5 mg, or rofecoxib 25 mg) were given at 60-minute intervals. There was at least a 3-day interval between challenge tests. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrhea, nasal obstruction, sneezing, dyspnea, or cough associated with a decrease of at least 20% in the forced expiratory volume (FEV1) and hypotension were considered as positive reactions. RESULTS: Positive reactions to the nimesulide, meloxicam, and rofecoxib challenges were observed in 18/127 (14.3%), 5/61 (8.1%), and 1/51 (2.0%) patients, respectively. In each group of nine patients, there were two patients with asthma and four who developed skin type reactions and asthmatic reactions, respectively, to the nimesulide challenge. Among five patients who reacted to the meloxicam challenge, asthmatic type reactions were detected in two asthmatics. Only one urticarial type reaction was observed with rofecoxib challenge in one patient who presented with anaphylaxis to ASA/NSAIDs. All patients with asthma tolerated rofecoxib without any adverse effects. None of the patients reacted to the placebo. Among 37 patients challenged with all three drugs, 11 reacted to nimesulide, and one patient reacted only to meloxicam. Three patients reacted to more than one of the drugs tested, and one of them reacted to all drugs. CONCLUSION: This is the first placebo-controlled report comparing these three drugs. The results indicate that among these alternative drugs for ASA/NSAIDs-intolerant patients, rofecoxib seems to have the most favorable tolerability.

Nussmeier et al 2005

Complications of the COX-2 inhibitors parecoxib and valdecoxib after cardiac surgery.

Nussmeier NA, Whelton AA, Brown MT, Langford RM, Hoeft A, Parlow JL, Boyce SW, Verburg KM.

N Engl J Med 2005;352(11):1081–1091.

Background Valdecoxib and its intravenous prodrug parecoxib are used to treat postoperative pain but may involve risk after coronary-artery bypass grafting (CABG). We conducted a randomized trial to assess the safety of these drugs after CABG. Methods In this randomized, double-blind study involving 10 days of treatment and 30 days of follow-up, 1671 patients were randomly assigned to receive intravenous parecoxib for at least 3 days, followed by oral valdecoxib through day 10; intravenous placebo followed by oral valdecoxib; or placebo for 10 days. All patients had access to standard opioid medications. The primary end point was the frequency of predefined adverse events, including cardiovascular events, renal failure or dysfunction, gastroduodenal ulceration, and wound-healing complications. Results As compared with the group given placebo alone, both the group given parecoxib and valdecoxib and the group given placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event (7.4% in each of these two groups vs. 4.0% in the placebo group; risk ratio for each comparison, 1.9; 95% confidence interval, 1.1 to 3.2; p = 0.02 for each comparison with the placebo group). In particular, cardiovascular events (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) were more frequent among the patients given parecoxib and valdecoxib than among those given placebo (2.0% vs. 0.5%; risk ratio, 3.7; 95% confidence interval, 1.0 to 13.5; p = 0.03). Conclusions The use of parecoxib and valdecoxib after CABG was associated with an increased incidence of cardiovascular events, arousing serious concern about the use of these drugs in such circumstances.

EMEA 2004a

Committee for Medicinal Products for Human Use, European Public Assessment Report (EPAR): Bextra.


Available at

O'Connor et al 2003

Hepatocellular damage from non-steroidal anti-inflammatory drugs.

O'Connor N, Dargan PI, Jones AL.

QJM 2003;96(11):787–791.

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the management of rheumatological disorders, and as analgesics and antipyretics. Hepatotoxicity is an uncommon, but potentially lethal complication, which usually occurs within 12 weeks of starting therapy. It can occur with all NSAIDs, but appears to be more common with diclofenac and particularly sulindac. Female patients aged >50 years, with autoimmune disease, and those on other potentially hepatotoxic drugs, appear to be particularly susceptible. Liver function test abnormalities generally settle within 4-6 weeks of stopping the causative drug. However, some patients may develop acute liver failure and successful orthotopic liver transplantation may be undertaken in such patients. Recent in vitro animal studies have shown that the mechanism of diclofenac toxicity relates both to impairment of ATP synthesis by mitochondria, and to production of active metabolites, particularly n,5-dihydroxydiclofenac, which causes direct cytotoxicity. Mitochondrial permeability transition (MPT) has also been shown to be important in diclofenac-induced liver injury, resulting in generation of reactive oxygen species, mitochondrial swelling and oxidation of NADP and protein thiols. Physicians and hepatologists must be vigilant to the hepatotoxic potential of any NSAID, as increased awareness, surveillance and reporting of these events will lead to a better understanding of the risk factors and the pathophysiology of NSAID-related hepatotoxicity.

Cheng et al 2004

Cyclooxygenases, the kidney, and hypertension.

Cheng HF, Harris RC.

Hypertension 2004;43(3):525–530.

Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.

Blomme et al 2003

Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice.

Blomme EA, Chinn KS, Hardy MM, Casler JJ, Kim SH, Opsahl AC, Hall WA, Trajkovic D, Khan KN, Tripp CS

Br J Dermatol 2003;148(2):211–223.

BACKGROUND: The inducible cyclooxygenase-2 (COX-2) enzyme is upregulated in inflammatory diseases, as well as in epithelial cancers, and has an established role in angiogenesis and tissue repair. OBJECTIVE: Because of these physiological effects and the widespread use of the selective COX-2 inhibitor, celecoxib, we wanted to determine if inhibition of COX-2 would affect incisional skin wound healing. METHODS: Using a cutaneous full-thickness, sutured, incisional wound model in hairless SKH-1 mice, we evaluated the role of COX-2 in the wound healing process by comparing the effects of a nonselective COX inhibitor, diclofenac, with a selective COX-2 inhibitor, SC-791. Healing was monitored for up to 28 days postincision histologically and for recovery of wound strength. RESULTS: COX-2 expression was observed over the first week of healing, peaking at day 3 and was not affected by treatment with the selective COX-2 or nonselective COX inhibitors. Infiltrating macrophages, as well as keratinocytes and dermal fibroblasts at the wound site, expressed COX-2. Neither selective COX-2, nor nonselective COX inhibition had a significant effect on the macroscopic or microscopic morphology of the wounds, whereas dexamethasone treatment resulted in epidermal and granulation tissue atrophy. In addition, neither selective COX-2, nor nonselective COX inhibition altered keratinocyte proliferation and differentiation, dermal angiogenesis or the recovery of wound tensile strength, whereas dexamethasone reduced the tensile strength of the wounds by 30-38% throughout the healing period. CONCLUSIONS: These data indicate that selective COX-2 inhibition does not affect the healing of surgical skin wounds.

Gajraj 2003

The effect of cyclooxygenase-2 inhibitors on bone healing.

Gajraj NM.

Reg Anesth Pain Med 2003;28(5):456–465.

Fletcher et al 1995

Influence of timing on the analgesic effect of intravenous ketorolac after orthopedic surgery.

Fletcher D, Zetlaoui P, Monin S, Bombart M, Samii K.

Pain 1995;61(2):291–297.

This study evaluated the pre-emptive analgesic effect of intravenous (i.v.) ketorolac (KET) for total hip replacement (THR). Sixty patients who underwent surgery for THR under general anesthesia were randomly allocated to 3 groups. Two i.v. injections were administered: one before induction and one after surgery. The patients were studied prospectively in a double-blind manner. The control group (CONT; n = 20) received 2 ml of normal saline (NS) for both injections. The pre-operative KET group (PRE; n = 20) received 60 mg of KET and then 2 ml of NS. The postoperative KET group (POST; n = 20) received 2 ml of NS and then 60 mg of KET. General anesthesia was standardized with a intra-operative cumulated dose of fentanyl limited to 4 micrograms/kg. In the recovery room (RR), pain was controlled with an i.v. tritration of morphine; thereafter, on the surgical ward, patients used a patient-controlled analgesia (PCA) pump (Abbott). Pain was evaluated with a visual analogue scale (VAS) at rest and movement in the RR, then every hour for 6 h and every 6 h for 5 days. The side effects monitored were: sedation, respiratory depression, nausea, perioperative bleeding. The patients and surgery were similar for the 3 groups. Upon arrival in the RR, VAS scores taken at rest and at movement were lower for the PRE group than for the CONT and POST groups. Otherwise, VAS scores were similar in all 3 groups. The cumulative dose of morphine in the PRE group was lower than that for the CONT and POST groups from 0 to 6 h.

Bugter et al 2003

Prior ibuprofen exposure does not augment opioid drug potency or modify opioid requirements for pain inhibition in total hip surgery.

Bugter ML, Dirksen R, Jhamandas K, Slappendel R, Weber EW, Milne B.

Can J Anaesth 2003;50(5):445–449.

PURPOSE: In previous animal studies, a prior exposure to non-steroidal anti-inflammatory drugs (NSAID) augmented opioid drug potency. This study was designed to answer the question whether a similar effect can be attained in man. The objective was to use NSAID for preoperative pain reduction and at the same time use the NSAID exposure to reduce opioid requirements for pain inhibition in major orthopedic surgery. METHODS: In this double-blind, randomized study, 50 patients scheduled for total hip surgery were included. Patients of Group I received a placebo drug three times a day two weeks before surgery, and those allocated to Group II received ibuprofen (600 mg) three times a day. For surgical anesthesia, all patients received intrathecal bupivacaine 20 mg plus 0.1 mg morphine in a total volume of 4 ml. RESULTS: The preoperative or postoperative visual analogue scale pain scores or the amount of iv morphine showed no differences between the two groups in the first 24 hr after surgery. The median total blood loss in the ibuprofen group was 1161 ml vs 796 ml in the placebo group (p < 0.01). CONCLUSION: Pretreatment with ibuprofen before major hip surgery does not improve the pain scores or reduce morphine requirement but significantly increases blood loss. Considering the presence of relevant adverse effects, pretreatment with a non-selective NSAID is not recommended.

An et al 1991

Effects of hypotensive anesthesia, nonsteroidal antiinflammatory drugs, and polymethylmethacrylate on bleeding in total hip arthroplasty patients.

An HS, Mikhail WE, Jackson WT, Tolin B, Dodd GA.

J Arthroplasty 1991;6(3):245–250.

One hundred forty patients ranging in age from 26 to 88 years, who had primary total hip arthroplasty (performed by the same surgeon and lateral surgical approach), were analyzed for intraoperative and postoperative blood loss. The factors affecting blood loss, which include bleeding disorders, medications, duration of surgery, the mean intraoperative blood pressure, and use of cement, were all recorded. A significant reduction in the intraoperative blood loss was observed in the group of patients with hypotensive anesthesia (greater than 20 mmHg drop in the mean intraoperative blood pressure using inhalation anesthetics) compared to the group of patients who did not have hypotensive anesthesia. The patients who had been on aspirin or nonsteroidal antiinflammatory drugs prior to surgery had increased intraoperative and postoperative blood loss compared to the patients who did not take such medications. The effect of cementing with methylmethacrylate on bleeding was also observed; the patients with uncemented implants had a greater blood loss after operation than the patients who had cemented prosthetic components.

Alexander et al 2002

Comparison of the morphine-sparing effects of diclofenac sodium and ketorolac tromethamine after major orthopedic surgery.

Alexander R, El-Moalem HE, Gan TJ.

J Clin Anesth 2002;14(3):187–192.

STUDY OBJECTIVES: To compare the efficacy of diclofenac sodium with ketorolac tromethamine in reducing postoperative morphine use after major orthopedic surgery. DESIGN: Double-blind, randomized, placebo-controlled study. SETTING: Major teaching institution. PATIENTS: 102 ASA physical status II patients undergoing hip and knee replacement with general anesthesia. INTERVENTIONS: Before induction of anesthesia, patients were randomly allocated to receive intravenously either diclofenac sodium 75 mg (Group D), ketorolac tromethamine 60 mg (Group K), or placebo (Group P). Patient-controlled analgesia was supplied postoperatively using morphine. MEASUREMENTS: Visual analog scale (VAS), verbal pain score (VPS), sedation score, frequency of opioid side effects, and morphine consumption were recorded every 4 hours. MAIN RESULTS: There was a highly significant downward trend for VAS, VPS, and sedation scores over time, p = 0.001. The mean VAS and VPS scores were significantly lower in Groups D and K compared with Group P at time 0, p = 0.009 and 8 hours, p = 0.026. The mean (SD) 24-hour morphine requirements were 36.3 mg (16.9), 47.2 mg (34.9), and 51.6 mg (22.2) for Groups D, K, and P, respectively, p = 0.032. Fewer patients suffered from postoperative nausea and vomiting in the treatment groups (Groups D and K) compared with Group P (9, 8, and 19, respectively), p < 0.05. Fewer patients also suffered from pruritus in Groups D and K compared with Group P (3, 4, and 11, respectively), p < 0.01. CONCLUSIONS: Preoperative administration of intravenous diclofenac 75 mg or ketorolac 60 mg significantly reduces morphine requirements and associated side effects after major orthopedic surgery.

Bricker et al 1987

Peri-operative blood loss and non-steroidal anti-inflammatory drugs: an investigation using diclofenac in patients undergoing transurethral resection of the prostate

Bricker S, Savage M, Hanning C.

Eur J Anaesthesiol 1987;4(6):429–434.

Peri-operative blood loss was compared in a prospective, randomized double-blind study between two groups of patients undergoing transurethral prostatectomy (TURP) under spinal (subarachnoid) analgesia: the first received the non-steroidal anti-inflammatory drug diclofenac sodium, the second group received placebo. The total blood loss and the blood loss per gram of prostate resected did not differ significantly. Some 80% of patients were completely pain free at 8 and 24 h post-operation, and low pain scores recorded by the remaining 20% of patients supported the conclusion that TURP performed under spinal analgesia is not commonly associated with severe post-operative pain.

Greer et al 1999

Effect of ketorolac and low-molecular-weight heparin individually and in combination on haemostasis.

Greer I, Gibson J, Young A, Johnstone J, Walker I.

Blood Coagul Fibrinolysis 1999;10(6):367–373.

Low-molecular-weight heparins, when used in surgical patients for thromboprophylaxis, may be used concurrently with ketorolac, a non-steroidal anti-inflammatory drug that is used for analgesia. Because these two agents can influence the haemostatic system, it is important to identify any such effect. The haemostatic interaction between dalteparin and ketorolac was assessed in a double-blind, placebo-controlled, randomized, crossover study of healthy male volunteers each given all four combinations of ketorolac/placebo and dalteparin/placebo. The effect of ketorolac and dalteparin on haemostasis was assessed by measuring in-vitro platelet aggregation, anti-factor-Xa, activated partial thromboplastin times and skin bleeding time. The results were analysed for evidence of an interaction between ketorolac and dalteparin. Ketorolac inhibited platelet aggregation in whole blood and platelet-rich plasma. The administration of dalteparin led to a significant increase in levels of anti-factor-Xa and a significant prolongation in the activated partial thromboplastin time, although it remained within the range of the normal population. There was no evidence of any interaction between ketorolac and dalteparin with regard to platelet aggregation, anti-factor-Xa activity or activated partial thromboplastin time. The administration of ketorolac significantly prolonged the skin bleeding time. There was a significant interaction between ketorolac and dalteparin to prolong the bleeding time, although dalteparin alone had no effect on bleeding time. There was an interaction between ketorolac and dalteparin, which affected bleeding times. Such an interaction raises the possibility of haemorrhagic complications developing perioperatively when these agents are used concomitantly. Further studies are required to examine the clinical importance of this interaction.

Marret et al 2003

Effects of postoperative, nonsteroidal, antiinflammatory drugs on bleeding risk after tonsillectomy: meta-analysis of randomized, controlled trials.

Marret E, Flahault A, Samama CM, Bonnet F.

Anesthesiology 2003;98(6):1497–1502.

Niemi et al 1997

Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers.

Niemi T, Taxell C, Rosenberg P.

Acta Anaesthesiol Scand 1997;41(10):1353–1358.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo-oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. METHODS: Ten healthy male volunteers were given ketoprofen 1.4 mg/kg, ketorolac 0.4 mg/kg and diclofenac 1.1 mg/kg in saline i.v. on three different occasions, at more than one-week intervals, in a randomized double-blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion. RESULTS: Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 µg/ml) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (p < 0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 µg/ml) induced platelet aggregation was still seen (26.7%) (p < 0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 µM and 6 µM ) induced platelet aggregation and ketoprofen in ADP (6 µM ) induced platelet aggregation in sample 2. Bleeding time was prolonged (p < 0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs. CONCLUSION: Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.

Forrest et al 2002

Ketorolac, diclofenac, and ketoprofen are equally safe for pain relief after major surgery.

Forrest J, Camu F, Greer I, Kehlet H, Abdalla M, Bonnet F, Ebrahim S, Escolar G, Jage J, Pocock S, Velo G, Langman M, Bianchi P, Samama M, Heitlinger E.

Br J Anaesth 2002;88(2):227–233.

BACKGROUND: Ketorolac is approved for the relief of postoperative pain but concerns have been raised over a possible risk of serious adverse effects and death. Two regulatory reviews in Europe on the safety of ketorolac found the data were inconclusive and lacked comparison with other non-steroidal anti-inflammatory drugs. The aim of this study was to compare the risk of serious adverse effects with ketorolac vs diclofenac or ketoprofen in adult patients after elective major surgery. METHODS: This prospective, randomized multicentre trial evaluated the risks of death, increased surgical site bleeding, gastrointestinal bleeding, acute renal failure, and allergic reactions, with ketorolac vs diclofenac or ketoprofen administered according to their approved parenteral and oral dose and duration of treatment. Patients were followed for 30 days after surgery. RESULTS: A total of 11,245 patients completed the trial at 49 European hospitals. Of these, 5634 patients received ketorolac and 5611 patients received one of the comparators. 155 patients (1.38%) had a serious adverse outcome, with 19 deaths (0. 17%), 117 patients with surgical site bleeding (1.04%), 12 patients with allergic reactions (0.12%), 10 patients with acute renal failure (0.09%), and four patients with gastrointestinal bleeding (0.04%). There were no differences between ketorolac and ketoprofen or diclofenac. Postoperative anticoagulants increased the risk of surgical site bleeding equally with ketorolac (odds ratio=2.65, 95% CI=1.51-4.67) and the comparators (odds ratio=3.58, 95% CI=1.93-6.70). Other risk factors for serious adverse outcomes were age, ASA score, and some types of surgery (plastic/ear, nose and throat, gynaecology, and urology). CONCLUSION: We conclude that ketorolac is as safe as ketoprofen and diclofenac for the treatment of pain after major surgery.

Stevenson 2004

Aspirin and NSAID sensitivity.

Stevenson DD.

Immunol Allergy Clin North Am 2004;24(3):491–505, vii.

Aspirin and the older nonsteroidal anti-inflammatory drugs (NSAIDs) that block cyclo-oxygenase-1 (COX-1) induce asthma attacks in patients with aspirin-exacerbated respiratory disease and urticaria in patients with chronic idiopathic urticaria. Weak inhibitors of COX-1, such as acetaminophen and salsalate, crossreact also but only with high doses of the drugs. Partial inhibitors of both COX-1 and COX-2, such as nimesulide and meloxicam, also cross-react but only at high drug doses. COX-2 inhibitors do not cross-react; however, all NSAIDs, including the selective COX-2 inhibitors, can sensitize patients and induce urticaria or anaphylaxis on next exposure to the drug.

Dahl et al 2004

'Protective premedication': an option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of post-operative pain.

Dahl JB, Mathiesen O, Moiniche S.

Acta Anaesthesiol Scand 2004;48:1130–1136.

Substantial progress has been made during the last decades in our understanding of acute pain mechanisms, and this knowledge has encouraged the search for novel treatments. Of particular interest has been the observation that tissue injury initiates a number of modulations of both the peripheral and the central pain pathways, which convert the system from a 'physiological' to a 'pathological' mode of processing afferent information. Gabapentin, which binds to the alpha(2)delta subunit of the voltage-dependent calcium channel, is active in animal models of 'pathological' but not in models of 'physiological' pain. Consequently, attention has so far been focused on neuropathic pain as a target for the clinical use of gabapentin and analogues. Recently, several reports have indicated that gabapentin may have a place in the treatment of post-operative pain. This article presents a brief summary of the potential mechanisms of post-operative pain, and a systematic review of the available data of gabapentin and pregabalin for post-operative analgesia. It is concluded that the results with gabapentin and pregabalin in post-operative pain treatment published so far are promising. It is suggested that future studies should explore the effects of 'protective premedication' with combinations of various antihyperanalgesic and analgesic drugs for post-operative analgesia.

Subramaniam et al 2004

Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review.

Subramaniam K, Subramaniam B, Steinbrook RA.

Anesth Analg 2004;99(2):482–495, table of contents.

Animal studies on ketamine and opioid tolerance have shown promising results. Clinical trials have been contradictory. We performed a systematic review of randomized, double-blind clinical trials of ketamine added to opioid analgesia. Thirty-seven trials with 51 treatment arms and 2385 patients were included. Studies were divided into 5 subgroups: IV ketamine as single dose (n=11), continuous infusion (n=11), patient-controlled analgesia (PCA) (n=6), epidural ketamine with opioids (n=8), and studies in children (n=4). Outcome measures included pain scores, time to first request for analgesia, supplemental analgesics, and adverse events. Efficacy was estimated by statistical significance (p<0.05) of outcome measures as reported in studies and also by calculation of weighted mean difference for pain scores during the first 24 h after surgery. As compared to morphine alone, IV PCA with ketamine and morphine did not improve analgesia. Intravenous infusion of ketamine decreased IV and epidural opioid requirements in 6 of 11 studies. A single bolus dose of ketamine decreased opioid requirements in 7 of 11 studies. Five of 8 trials with epidural ketamine showed beneficial effects. Adverse effects were not increased with small dose ketamine. We conclude that small dose ketamine is a safe and useful adjuvant to standard practice opioid-analgesia.

O'Sullivan et al 1983

A comparison of intramuscular and sublingual buprenorphine, intramuscular morphine and placebo as premedication.

O'Sullivan G, Bullingham RE, McQuay HJ, Poppleton P, Rolfe M, Weir L, Moore RA.

Anaesthesia 1983;38(10):977–984.

Buprenorphine premedication by two routes, 0.4 mg sublingual and 0.3 mg intramuscular was compared double-blind, double-dummy with intramuscular morphine 10 mg and placebo in 74 patients undergoing elective total hip replacement. Anxiety, depressive mood, sedation, vital signs and side-effects were measured before surgery. All patients then received a standardised general anaesthetic using a muscle relaxant and ventilation. The effects of the premedication on the anaesthetic were assessed by a scoring system. Intra- and postoperative blood gases, plasma cortisol and glucose were measured and the 1 hour postoperative pain intensity, side-effects and sedation were assessed. No differences between the premedications were seen on any of the pre-, intra- or postoperative measurements, suggesting that even with adequate measurement sensitivity it is difficult to distinguish opiate from placebo premedication.

Bourke et al 2000

A Comparison of Regularly Administered Sustained Release Oral Morphine with Intramuscular Morphine for Control of Postoperative Pain

Bourke M, Hayes A, Doyle M, McCarroll M.

Anesth Analg. 2000;90(2):427–430.

We studied the efficacy and side effect profile of regularly administered, oral sustained-release morphine sulfate tablets (MST) and IM morphine in patients undergoing total hip arthroplasty under lumbar spinal anesthesia. Patients in Group I received MST 20 mg 12 hourly and a placebo IM injection 6 hourly regularly. Group II patients received an oral placebo 12 hourly and morphine sulfate 10 mg IM 6 hourly regularly. Rescue analgesia was provided with regular diclofenac suppositories and patient-controlled analgesia. Pain scores assessed by using visual analog scale and verbal pain scoring at rest and with movement were low in both groups, with no statistical difference between groups. Mean patient-controlled analgesia morphine consumption during the 48-h study was 16.7 mg in the IM group and 25.9 mg in the MST group. The difference between the groups was significant at 36 h postoperatively (0.03). Side effects of sedation and respiratory depression were not problematic in either group, with a maximal sedation score of 2 occurring once in a patient in Group II. Nausea and vomiting occurred more often in Group II, but this was not statistically significant, with a mean nausea/vomiting score for Group II of 1.7. We conclude that oral, sustained-release morphine is an attractive alternative to IM opiates in patients undergoing body surface surgery under regional anesthesia. IMPLICATIONS: Each postoperative analgesic has its own limitations for route of administration, dosage, and potential side effects. Using the oral route for drug administration seems more attractive than other methods but may not be suitable in all postoperative patients. We studied the efficacy and side effect profile of sustained-release, oral morphine compared with standard IM morphine for the treatment of pain after hip replacement surgery. We concluded that use of the oral preparation is a suitable alternative to the IM route in this population undergoing surgery under spinal anesthesia.

Reiter et al 2003

Preoperative oral administration of fast-release morphine sulfate reduces postoperative piritramide consumption.

Reiter A, Zulus E, Hartmann T, Hoerauf K.

Wien Klin Wochenschr 2003;115(12):417–420.

The aim of this prospective randomized placebo-controlled double-blind study was to investigate the effect of premedication with morphine sulfate on postoperative pain. Ninety-eight ASA I-III patients undergoing total replacement of the knee or hip joint were randomly assigned to one of two groups. Group 1 received 20 mg morphine sulfate p.o. approximately one hour before the start of surgery; group 2 received placebo. After surgery, piritramide was administered via patient-controlled analgesia over 24 hours. Piritramide consumption and pain scores (visual analog scale) were recorded. The duration of surgery (mean +/- SD) was comparable in the two groups (group 1: 145 +/- 42 min, group 2: 131 +/- 35 min). In group 1 the cumulative piritramide consumption during 24 hours postoperation was significantly less than in the placebo group (37.5 +/- 12.5 mg versus 46.8 +/- 22.1, t-test, p < 0.05), although similar pain scores were recorded (group 1: 4.8 +/- 1.8 and 3.6 +/- 1.7, group 2: 4.8 +/- 1.6 and 3.4 +/- 2.0, at 1 and 24 hours, respectively). These data show that the preoperative oral administration of morphine sulfate, regardless of its short half-life, can reduce postoperative consumption of opioids at similar pain levels.

Chin et al 1982

Blood loss in total hip replacement: extradural v. phenoperidine analgesia.

Chin SP, Abou-Madi MN, Eurin B, Witvoet J, Montagne J.

Br J Anaesth 1982;54(5):491–495.

The effects of phenoperidine and extradural analgesia on blood loss during and after total hip replacement were compared in 41 patients randomly divided into two statistically comparable groups. Mean blood loss in patients who received phenoperidine was 1065 +/- 316 ml and in patients who received extradural analgesia with 0.5% bupivacaine with adrenaline 1:200 000 it was 650 +/- 277 ml (p less than 0.001). There was no significant difference in postoperative blood loss between the two groups. The reduction in blood loss resulting from the extradural block may prove beneficial in decreasing the hazard and cost of blood transfusions and in facilitating autologous transfusion.

Souron et al 2003

Intrathecal morphine provides better postoperative analgesia than psoas compartment block after primary hip arthroplasty.

Souron V, Delaunay L, Schifrine P.

Can J Anaesth 2003;50(6):574–579.

PURPOSE: Intrathecal morphine and psoas compartment block represent two accepted techniques to provide postoperative analgesia after hip arthroplasty. We designed a prospective, randomized, single-blinded study to compare these two techniques. METHODS: Patients scheduled for primary hip arthroplasty under general anesthesia were randomized to receive either an intrathecal administration of 0.1 mg morphine (Group I, n = 27) or a psoas compartment block with ropivacaine 0.475% 25 ml (Group II, n = 26). Pain scores, morphine consumption, associated side-effects were assessed for 48 hr postoperatively. In addition, patient's acceptance and satisfaction of the postoperative analgesic technique were also recorded. RESULTS: During the first 24 hr, pain scores (3.3 +/- 9.6 mm vs 22.8 +/- 27.1 at H+6, 3.3 +/- 8.3 mm vs 25 +/- 26.7 mm at H+12, 7 +/- 14.9 mm vs 21.9 +/- 29 mm at H+18) and morphine consumption (0.56 +/- 2.12 mg vs 9.42 +/- 10.13 mg) were lower in Group I than in Group II. Urinary retention was the more frequent side-effect occurring in 37% of cases in Group I vs 11.5% in Group II (p < 0.05). No major complication occurred. Despite better analgesia provided by the use of intrathecal morphine, there was no difference in the satisfaction scores between groups. CONCLUSION: 0.1 mg intrathecal morphine administration provides better postoperative analgesia than single-shot psoas compartment block after primary hip arthroplasty.

Maurer et al 2003

Continuous spinal anesthesia/analgesia vs. single-shot spinal anesthesia with patient-controlled analgesia for elective hip arthroplasty.

Maurer K, Bonvini JM, Ekatodramis G, Serena S, Borgeat A

Acta Anaesthesiol Scand 2003;47(7):878–883.

BACKGROUND: In total hip replacement surgery several anesthesiological techniques can be used. In this study we compared continuous spinal anesthesia (CSA) and postoperative analgesia vs. single-shot spinal anesthesia (SPA) and postoperative patient-controlled intravenous analgesia with morphine (SPA). METHODS: In a prospective randomized study, 68 patients, ASA I–III, between 50 and 85 years of age were allocated to these two groups. Quality of analgesia, hemodynamic stability and technical difficulties, as well as incidence of postoperative nausea and vomiting (PONV) and post dural puncture headache (PDPH), were recorded during a 24-h period. RESULTS: Visual analog scale (VAS) scores were significantly lower in the CSA group from 3 h post operation (p < 0.05). Mean arterial pressure dropped by 21 +/- 11 mmHg in the CSA group and 29 +/- 14 in the SPA group during induction (p < 0.05). Technical difficulties and incidence of PDPH were similar in both groups. Postoperative nausea and vomiting was lower in the CSA group (p < 0.05). CONCLUSIONS: Continuous spinal anesthesia/analgesia is a very practicable method providing better postoperative analgesia and better hemodynamic stability during anesthesia induction than SPA followed by morphine PCA analgesia after total hip replacement surgery.

Mollmann et al 1999

Continuous spinal anaesthesia or continuous epidural anaesthesia for post-operative pain control after hip replacement?

Mollmann M, Cord S, Holst D, Auf der Landwehr U.

Eur J Anaesthesiol 1999;16(7):454–461.

Both continuous spinal anaesthesia and continuous epidural anaesthesia are supposed to provide adequate post-operative pain relief. The purpose of this randomized, prospective study was to compare the quality of analgesia, occurrence of side effects and patient satisfaction between spinal and epidural administration of bupivacaine during the first post-operative 72 h. One hundred and two patients scheduled for hip arthroplasty were randomly assigned to one of two groups: Group 1 received continuous spinal anaesthesia for intra-operative and post-operative management, Group 2 received continuous epidural anaesthesia. Immediately after surgery, the continuous spinal anaesthesia-group received a 1-mL bolus (bupivacaine 0.25%), followed by a continuous infusion of 10 mL over 24 h. The continuous epidural anaesthesia-group received a 10-mL bolus (bupivacaine 0.25%), followed by 2 mL h-1. The level of pain was gauged from a verbal rating score and from a visual analogue scale; the degree of motor blockade was recorded using the Bromage score. In the continuous spinal anaesthesia-group 90.2% reported complete analgesia on the verbal rating scale, but only 21.6% of the continuous epidural anaesthesia-group did. The visual analogue scale scores given by the continuous spinal anaesthesia-group were significantly lower than those of the continuous epidural anaesthesia-group. The percentage of patients with a motor block was significantly higher in the continuous spinal anaesthesia-group on the day of surgery and at the first post-operative day. During the first 24 h, nausea and vomiting occurred more often in the continuous epidural anaesthesia-group. The satisfaction was considered excellent in 92.2% of the continuous spinal anaesthesia-group and in 70.6% of the continuous epidural anaesthesia-group. It is concluded that continuous spinal anaesthesia and continuous epidural anaesthesia are effective and safe for post-operative pain relief after hip replacement. Compared with continuous epidural anaesthesia, continuous spinal anaesthesia provides faster onset of pain relief, ensures better analgesia and results in more satisfied patients.

Slappendel et al 1999

The intensity of preoperative pain is directly correlated with the amount of morphine needed for postoperative analgesia.

Slappendel R, Weber EW, Bugter ML, Dirksen R.

Anesth Analg 1999;88(1):146–148.

The aim of this study was to examine whether severity of preoperative pain intensity is related to postoperative pain and morphine consumption. Sixty consecutive patients scheduled for total hip surgery during intrathecal anesthesia were studied. Preoperative visual analog scale (VAS) scores and analgesic intake was assessed 1 day before surgery. Three groups of patients were identified: those with mild pain (n = 12, VAS score 0-4), moderate pain (n = 18, VAS score 4-7), and severe pain (n = 28, VAS score 7-10). Postoperative pain scores were recorded in the first 24 h, as was the amount of morphine delivered by the patient-controlled analgesia pump. There were no differences among the groups in VAS scores at any time. Severe preoperative pain levels correlated with significantly greater postoperative morphine intake. The mean morphine intake during the first 24 h postoperatively was 19.2 mg in the mild pain group, 21.2 mg in the moderate pain group, and 29.5 mg in the severe pain group (P < 0.05 compared with both other groups). We conclude that patients with severe preoperative pain self-medicate to achieve postoperative pain scores equivalent to those of patients with mild and moderate pain and require a greater postoperative morphine intake for adequate analgesia than patients with mild or moderate preoperative pain. IMPLICATIONS: In this study, we showed that severity of preoperative pain intensity relates to postoperative pain levels and morphine consumption. Patients scheduled for total hip surgery with severe preoperative pain require more postoperative morphine in the first 24 h.

Møiniche et al 1994

The effect of balanced analgesia on early convalescence after major orthopaedic surgery.

Møiniche S, Hjortso NC, Hansen BL, Dahl JB, Rosenberg J, Gebuhr P, Kehlet H.

Acta Anaesthesiol Scand 1994;38(4):328–335.

Forty-two patients scheduled for total knee arthroplasty (n = 20) or hip arthroplasty (n = 22) were randomly allocated to receive either continuous epidural bupivacaine/morphine for 48 h postoperatively plus oral piroxicam, or general anaesthesia followed by a conventional intramuscular opioid and acetaminophen regimen. Patients undergoing knee- or hip arthroplasty treated with epidural analgesia had significantly lower pain scores during mobilization under the 48 h epidural infusion compared with patients receiving conventional treatment, while no important differences were observed after cessation of the epidural regimen. However, the achieved pain relief had no impact on postoperative convalescence parameters, such as ambulation, patient activity including need for nursing care, fatigue or hospital stay. Late postoperative pain, fatigue and conservative attitudes and routines in the postoperative care, were the most important reasons limiting mobilization and activity. We conclude that effective early (48 h) postoperative pain relief with balanced analgesia does not per se lead to important improvements in convalescence and hospital stay.

Casati et al 2003

Intraoperative epidural anesthesia and postoperative analgesia with levobupivacaine for major orthopedic surgery: a double-blind, randomized comparison of racemic bupivacaine and ropivacaine.

Casati A, Santorsola R, Aldegheri G, Ravasi F, Fanelli G, Berti M, Fraschini G, Torri G.

J Clin Anesth 2003;15(2):126–131.

STUDY OBJECTIVE: To compare the onset time and duration of epidural anesthesia, and the quality of postoperative analgesia produced by levobupivacaine, racemic bupivacaine, and ropivacaine. DESIGN: Prospective, randomized, double-blinded study. SETTING: Inpatient anesthesia at a University Hospital. PATIENTS: 45 ASA physical status I, II, and III patients, undergoing elective total hip replacement. INTERVENTIONS: After standard intravenous midazolam premedication and infusion of 500 ml of Ringer's acetate solution, patients were randomly allocated to receive epidural block with 0.5% levobupivacaine (n=15), 0.5% bupivacaine (n=15), or 0.5% ropivacaine (n=15). Postoperatively, after pinprick sensation recovered at T(t), a patient-controlled epidural infusion was provided with 0.125% levobupivacaine, 0.125% bupivacaine, or 0.2% ropivacaine, respectively (baseline infusion rate 5 mL/hr; incremental bolus 2 ml, lockout time: 20 min). Intravenous ketoprofen was also available for rescue analgesia if required. MEASUREMENTS AND MAIN RESULTS: The onset time of sensory block was 31 +/- 16 minutes with levobupivacaine, 25 +/- 19 minutes with bupivacaine, and 30 +/- 24 minutes with ropivacaine (p=0.98), after a median (range) volume of 15 (10–18) ml in Group Levobupivacaine, 14 (10–18) ml in Group Bupivacaine, and 15 (10–18) ml in Group Ropivacaine (p=0.85). Six patients in the ropivacaine group (40%) showed an intraoperative Bromage score <2 as compared with only three patients of Group Levobupivacaine (20%) and no patient of Group Bupivacaine (p=0.02). Recovery of pinprick sensation at T(t) occurred after 214 +/- 61 minutes with levobupivacaine, 213 +/- 53 minutes with bupivacaine, and 233 +/- 34 minutes with ropivacaine (p=0.26). A similar degree of pain relief was observed in the three groups without differences in local anesthetic consumption and need for rescue analgesia. Motor blockade progressively resolved without differences among the three groups. CONCLUSIONS: Levobupivacaine 0.5% produces an epidural block of similar onset, quality, and duration as the one produced by the same volume of 0.5% bupivacaine, with a motor block deeper than that produced by 0.5% ropivacaine. When prolonging the block for the first 12 hours after surgery with a patient-controlled epidural infusion, 0.125% levobupivacaine provides adequate pain relief after major orthopedic surgery, with similar recovery of motor function as compared with 0.125% bupivacaine and 0.2% ropivacaine.

Borghi et al 2004

A prospective, randomized evaluation of the effects of epidural needle rotation on the distribution of epidural block.

Borghi B, Agnoletti V, Ricci A, van Oven H, Montone N, Casati A.

Anesth Analg 2004;98(5):1473–1478, table of contents.

We evaluated the effects of turning the tip of the Tuohy needle 45 degrees toward the operative side before threading the epidural catheter (45 degrees -rotation group, n = 24) as compared to a conventional insertion technique with the tip of the Tuohy needle oriented at 90 degrees cephalad (control group, n = 24) on the distribution of 10 mL of 0.75% ropivacaine with 10 microg sufentanil in 48 patients undergoing total hip replacement. The catheter was introduced 3 to 4 cm beyond the tip of the Tuohy needle. A blinded observer recorded sensory and motor blocks on both sides, quality of analgesia, and volumes of local anesthetic used during the first 48 h of patient-controlled epidural analgesia. Readiness to surgery required 21 +/- 6 min in the control group and 17 +/- 7 min in the 45 degree-rotation group (p > 0.50). The maximum sensory level reached on the operative side was T10 (T10-7) in the control group and T9 (T10-6) in the 45 degree-rotation group (p> 0.50); whereas the maximum sensory level reached on the nonoperative side was T10 (T12-9) in the control group and L3 (L5-T12) in the 45 degree-rotation group (p= 0.0005). Complete motor blockade of the operative limb was achieved earlier in the 45 degree-rotation than in the control group, and motor block of the nonoperative side was more intense in patients in the control group. Two-segment regression of sensory level on the surgical side was similar in the two groups, but occurred earlier on the nonoperative side in the 45 degree-rotation group (94 +/- 70 min) than in the control group (178 +/- 40 min) (p= 0.0005). Postoperative analgesia was similar in the 2 groups, but the 45 degree-rotation group consumed less local anesthetic (242 +/- 35 ml) than the control group (297 +/- 60 ml) (p = 0.0005). We conclude that the rotation of the Tuohy introducer needle 45 degrees toward the operative side before threading the epidural catheter provides a preferential distribution of sensory and motor block toward the operative side, reducing the volume of local anesthetic solution required to maintain postoperative analgesia. IMPLICATIONS: Turning the Tuohy introducer needle 45 degrees toward the operative side before threading the epidural catheter is a simple maneuver that produces a preferential distribution of epidural anesthesia and analgesia toward the operative side, minimizing the volume of local anesthetic required to provide adequate pain relief after total hip arthroplasty.

Stevens et al 2000

Lumbar plexus block reduces pain and blood loss associated with total hip arthroplasty.

Stevens RD, Van Gessel E, Flory N, Fournier R, Gamulin Z.

Anesthesiology 2000;93(1):115–121.

BACKGROUND: The usefulness of peripheral nerve blockade in the anesthetic management of hip surgery has not been clearly established. Because sensory afferents from the hip include several branches of the lumbar plexus, the authors hypothesized that a lumbar plexus block could reduce pain from a major hip procedure. METHODS: In a double-blind prospective trial, 60 patients undergoing total hip arthroplasty were randomized to receive general anesthesia with (plexus group, n=30) or without (control group, n=30) a posterior lumbar plexus block. The block was performed after induction using a nerve stimulator, and 0.4 ml/kg bupivacaine, 0.5%, with epinephrine was injected. General anesthesia was standardized, and supplemental fentanyl was administered per hemodynamic guidelines. Postoperative pain and patient-controlled intravenous morphine use were serially assessed for 48 h. RESULTS: The proportion of patients receiving supplemental fentanyl intraoperatively was more than 3 times greater in the control group (20 of 30 vs. 6 of 29, p=0.001). In the postanesthesia care unit, a greater than fourfold reduction in pain scores was observed in the plexus group (visual analogue scale [VAS] pain score at arrival 1.3 +/- 2 vs. 5.6 +/- 3, p<0.001), and "rescue" morphine boluses (administered if VAS > 3) were administered 10 times less frequently (in 2 of 28 vs. in 22 of 29 patients, p<0.0001). Pain scores and morphine consumption remained significantly lower in the plexus group until 6 h after randomization (VAS at 6 h, 1.4 +/- 1.3 vs. 2.4 +/- 1.4, p=0.007; cumulative morphine at 6 h, 5.6 +/- 4.7 vs. 12.6 +/- 7.5 mg, p<0.0001). Operative and postoperative (48 h) blood loss was modestly decreased in the treated group. Epidural-like distribution of anesthesia occurred in 3 of 28 plexus group patients, but no other side-effects were noted. CONCLUSIONS: Posterior lumbar plexus block provides effective analgesia for total hip arthroplasty, reducing intra- and postoperative opioid requirements. Moreover, blood loss during and after the procedure is diminished. Epidural anesthetic distribution should be anticipated in a minority of cases.

Fournier et al 1998

Postoperative analgesia with "3-in-1" femoral nerve block after prosthetic hip surgery.

Fournier R, Van Gessel E, Gaggero G, Boccovi S, Forster A, Gamulin Z.

Can J Anaesth 1998;45(1):34–38.

PURPOSE: To evaluate the efficacy of a single shot "3-in-1" femoral nerve block for prosthetic hip surgery in association with general anaesthesia on post-operative analgesia. METHODS: Forty patients, ASA 1 to 3, received sham block or "3-in-1" femoral nerve block, following Winnie's landmarks with a nerve stimulator, and 40 ml bupivacaine 0.5% with epinephrine were injected after induction of anaesthesia. Vecuronium, 0.1 mg/kg, was added after performing the block and anaesthesia was maintained with isoflurane, oxygen 40% and nitrous oxide 60%. Fentanyl, 1.5 µg/kg, was administered before incision to all patients. Heart rate, blood pressure, fentanyl requirements and FETiso were measured throughout surgery. During the post-operative period, 75 mg diclofenac i.m. and/or 0.1 mg/kg morphine s.c. were administered when pain score was > 3/10 and repeated when necessary. Pain scores at first analgesic intervention, at 24 hr and 48 hr as well as diclofenac and morphine requirements after surgery were recorded. RESULTS: There was no difference in anaesthetic requirements during surgery. The time from performance of sham or "3-in-1" femoral nerve block to the first analgesic intervention (261 +/- 49 min versus 492 +/- 40 min, p < 0.05) and time from extubation to the first analgesic intervention (61 +/- 44 min vs 298 +/- 39 min, p < 0.05) were prolonged in the study group. However, pain scores and the analgesic requirements in the postoperative periods (24 and 48 hr) were similar. CONCLUSION: There is a short-term benefit during the first few postoperative hours in using a single shot "3-in-1" femoral nerve block to complement general anaesthesia for elective hip surgery.

Biboulet et al 2004

Postoperative analgesia after total-hip arthroplasty: Comparison of intravenous patient-controlled analgesia with morphine and single injection of femoral nerve or psoas compartment block. A prospecti

Biboulet P, Morau D, Aubas P, Bringuier-Branchereau S, Capdevila X.

Reg Anesth Pain Med 2004;29(2):102–109.

BACKGROUND: The authors compared the analgesic effects and quality of rehabilitation of three analgesic techniques after total-hip arthroplasty in a double-blind, randomized trial. METHODS: Forty-five patients were assigned to 1 of 3 groups, patient-controlled analgesia with morphine (PCA), femoral nerve block (FNB), or psoas compartment block (PCB). At the end of the procedure performed under general anesthesia, nerve blocks using 2 mg/kg of 0.375% bupivacaine and 2 microg/kg of clonidine were performed in the FNB (n=16) and PCB (n=15) groups. In the recovery room, all 3 groups received initial intravenous morphine titration if their pain score was higher than 30 on a 100-mm visual analog scale (VAS), and then a PCA device was initiated. Morphine consumption was the primary end point to assess postoperative analgesia. RESULTS: After extubation (H0), morphine titration was higher in the PCA group (p<0.05). During the first 4 postoperative hours (H0 to H4), morphine consumption per hour and VAS pain score were lower in the PCB group (p<0.05). After H4, there was no difference in morphine consumption and VAS among groups, either at rest or during mobilization. After H4, morphine consumption remained lower than 0.5 mg/h, and VAS remained lower than 30 mm in the 3 groups. In 4 patients of the PCB group, an epidural diffusion was noted. Hip mobility and length of stay in the rehabilitation center were not different among the groups. CONCLUSIONS: PCA is an efficient and safe analgesia technique. FNB and PCB should not be used routinely after total-hip arthroplasty.

Holmstrom et al 1993

Combined spinal epidural block versus spinal and epidural block for orthopaedic surgery.

Holmstrom B, Laugaland K, Rawal N, Hallberg S.

Can J Anaesth 1993;40(7):601–606.

In a controlled study a single segment combined spinal epidural (CSE) block was compared with spinal or epidural block for major orthopaedic surgery. Seventy-five patients, age 52–86 yr, were randomly assigned to receive one of the three blocks. Bupivacaine 0.5% was used for surgical analgesia. The postoperative pain relief after 4.0 mg epidural morphine was compared with the analgesic effect of 0.2 or 0.4 mg morphine administered intrathecally. With the spinal technique good or excellent surgical analgesia and muscle relaxation were achieved rapidly (11.8 +/- 1.1 min). The time taken to provide an equally effective and reliable block with the CSE technique was no longer (14.9 +/- 2.2 min). For epidural block with the catheter technique more time was required (35.9 +/- 3.9 min) to provide acceptable surgical conditions (p < 0.05). Perioperative sedatives and concomitant analgesics were required more frequently and in larger doses by the patients undergoing surgery with epidural block (p < 0.05) than with CSE or spinal block. Our study demonstrated that the analgesia after surgery provided by 0.2 and 0.4 mg morphine administered intrathecally was comparable to that provided by 4.0 mg of epidural morphine. It is concluded that the analgesia and surgical conditions provided by the spinal and CSE blocks were similar and were superior to those provided by an epidural block.

Modig 1989

Influence of regional anesthesia, local anesthetics, and sympathicomimetics on the pathophysiology of deep vein thrombosis.

Modig J.

Acta Chir Scand Suppl 1989;550:119–124.

Studies have shown that lumbar epidural and spinal anesthesia seem to offer two distinct clinical advantages over general anesthesia, particularly in total hip replacement patients. These major regional blocks reduce the frequency of deep vein thrombosis and pulmonary embolism and reduce intraoperative and postoperative blood losses. The beneficial effects on thromboembolism are probably explained by several factors, such as hyperkinetic blood flow in the lower legs, reduced tendency to coagulation, and improved fibrinolytic function. The effects of local anesthetics on leukocytes, platelets, erythrocytes, and plasma proteins and on the interactions among various blood cells and endothelial cells are other factors in the protection against thromboembolism. Sympathicomimetic agents (i.e., epinephrine in the local anesthetic solution together with ephedrine given prophylactically to maintain a stable blood pressure) probably also play a significant role, notably on fibrinolytic function. The reduction in blood loss and thus in transfusion requirements may also be important.

Ferrante et al 1993

Regression of sensory anesthesia during continuous epidural infusions of bupivacaine and opioid for total knee replacement.

Ferrante FM, Fanciullo GJ, Grichnik KP, Vaisman J, Sacks GM, Concepcion MA.

Anesth Analg 1993;77(6):1179–1184.

The epidural administration of morphine and fentanyl delay the regression of sensory anesthesia in postoperative patients receiving epidural bupivacaine. This study was performed to determine any differential effects of two lipid-soluble opioids upon regression of sensory anesthesia during coadministration with epidural bupivacaine. Forty-eight patients scheduled for total knee replacement underwent lumbar epidural catheterization and received 1.5% etidocaine with 1:200,000 epinephrine to establish sensory anesthesia to approximately T6 bilaterally. Patients were randomized by the investigational pharmacy to receive either: (a) bupivacaine without opioid (control) (n=16), or (b) bupivacaine with 1 mg/ml of meperidine (n=16), or (c) bupivacaine with 3 µg/ml of fentanyl (n=16) in a double-blind fashion. Intraoperatively, 0.5% bupivacaine +/- opioid was administered by epidural infusion at a rate of 10 ml/h. Postoperatively, the bupivacaine concentration was decreased to 0.25% (+/- the same opioid), and the infusion rate was decreased to 4 ml/h. Pinprick sensory anesthesia and verbal numerical pain score were recorded each hour after surgery by a blinded investigator. For each patient, the study was considered terminated when the cephalad level of sensory anesthesia bilaterally decreased five dermatomal segments or the pain score reached "5" (moderate pain). Patients receiving epidural infusions of bupivacaine and meperidine had a significantly slower regression of sensory anesthesia and slower development of pain. There was no difference in the rate of regression of sensory anesthesia or the development of pain among patients receiving bupivacaine alone or bupivacaine with fentanyl.

Parker et al 2004

Anaesthesia for hip fracture surgery in adults.

Parker MJ, Handoll HH, Griffiths R.

Cochrane Database Syst Rev 2004(3):CD000521.

BACKGROUND: The majority of hip fracture patients are treated surgically, requiring anaesthesia. OBJECTIVES: To compare different types of anaesthesia for surgical repair of hip fractures (proximal femoral fractures) in adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (December 2000), MEDLINE (1996 to December Week 4 2000) and reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing different methods of anaesthesia for hip fracture surgery in skeletally mature persons. The primary focus of this review was the comparison of regional (spinal or epidural) anaesthesia versus general anaesthesia; this has been expanded to include other comparisons. The use of nerve blocks pre-operatively or in conjunction with general anaesthesia is evaluated in another review. The primary outcome was mortality. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, using a nine item scale, and extracted data. Results were pooled wherever appropriate and possible. MAIN RESULTS: Seventeen trials, involving 2305 patients, comparing regional anaesthesia with general anaesthesia were included. All trials had methodological flaws. Pooled results from eight trials showed regional anaesthesia to be associated with a decreased mortality at one month (53/781(6.8%) versus 78/826(9.4%)); this was of borderline statistical significance (relative risk (RR) 0.72, 95% confidence interval (CI) 0.51 to 1.00). The results from six trials for three month mortality were not statistically significant, although the confidence interval does not exclude the possibility of a clinically relevant reduction (86/726 (11.8%) versus 98/765 (12.8%), RR 0.92, 95% CI 0.71 to 1.21). The reduced numbers of patients at one year, coming exclusively from two studies, preclude any useful conclusions for long term mortality (80/354 (22.6%) versus 78/372 (21.0%), RR 1.07, 95% CI 0.82 to 1.41). Regional anaesthesia was associated with a tendency to a longer operation (weighted mean difference 4.8 minutes, 95% CI 1.1 to 8.6 minutes), and a reduced risk of deep venous thrombosis (39/129 (30%) versus 61/37(76%); RR 0.64, 95% CI 0.48 to 0.86), although this conclusion is insecure due to possible selection bias in the subgroups in whom this outcome was measured. No other statistically significant differences in outcome were identified. There was insufficient evidence to draw any conclusions from a further four included trials, involving a total of 179 patients, which compared other methods of anaesthesia (a 'light' general with spinal anaesthesia; intravenous ketamine; nerve blocks). REVIEWER'S CONCLUSIONS: Regional anaesthesia and general anaesthesia appear to produce comparable results for most of the outcomes studied. Regional anaesthesia may reduce short-term mortality but no conclusions can be drawn for longer term mortality.

Tan et al 2001

Intrathecal bupivacaine with morphine or neostigmine for postoperative analgesia after total knee replacement surgery.

Tan PH, Chia YY, Lo Y, Liu K, Yang LC, Lee TH.

Can J Anaesth 2001;48(6):551–556.

PURPOSE: To compare the postoperative analgesic efficacy and safety of intrathecal (IT) neostigmine and IT morphine in patients undergoing total knee replacement under spinal anesthesia. METHODS: Sixty patients scheduled for elective total knee replacement under spinal anesthesia were randomly divided into three equal groups which received IT 0.5% hyperbaric bupivacaine 15 mg with either normal saline 0.5 mL, neostigmine 50 microg, or morphine 300 microg. The maximal level of sensory block, duration of analgesia, time to use of rescue analgesics, the overall 24-hr and four-hour interval visual analogue scale (VAS) pain score, and the incidence of adverse effects were recorded for 24 hr after administration. RESULTS: There was no significant difference in maximal level of sensory block among the three groups. The morphine group had a later onset of postsurgical pain and longer time to first rescue analgesics than the neostigmine group (P <0.05). Overall 24-hr VAS pain scores were significantly higher in the saline group vs the morphine and neostigmine groups (P <0.05). Motor block lasted significantly longer in the neostigmine group than in the morphine and saline groups (P <0.05). The incidence of adverse effects was similar in the neostigmine and morphine groups except for pruritus (70%) occurring more frequently in the morphine group than in the neostigmine and saline groups (0%; P <0.05). Overall satisfaction rates were better in the neostigmine group than in the morphine and saline groups (P <0.05). CONCLUSIONS: IT neostigmine 50 microg produced postoperative analgesia lasting about seven hours with fewer side effects and better satisfaction ratings than IT morphine 300 microg.

Sinatra et al 2002

Pain management after major orthopaedic surgery: current strategies and new concepts.

Sinatra RS, Torres J, Bustos AM.

J Am Acad Orthop Surg 2002;10(2):117–129.

Several recently developed analgesic techniques effectively control pain after major orthopaedic surgery. Neuraxial analgesia provided by epidural and spinal administration of local anesthetics and opioids provides the highest level of pain control; however, such therapy is highly invasive and labor intensive. Neuraxial analgesia is contraindicated in patients receiving low-molecular-weight heparin. Continuous plexus and peripheral neural blockades offer excellent analgesia without the side effects associated with neuraxial and parenteral opioids. Intravenous patient-controlled analgesia allows patients to titrate analgesics in amounts proportional to perceived pain stimulus and provide improved analgesic uniformity. Oral sustained-release opioids offer superior pain control and greater convenience than short-duration agents provide. Opioid dose requirements may be reduced by coadministration of COX-2-type nonsteroidal analgesics.

Auroy et al 2002

Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline Service.

Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier FJ, Bouaziz H, Samii K, Mercier F.

Anesthesiology 2002;97(5):1274–1280.

BACKGROUND: Several previous surveys have estimated the rate of major complications that occur after regional anesthesia. However, because of the increase in the use of regional anesthesia in recent years and because of the introduction of new techniques, reappraisal of the incidence and the characteristics of major complications is useful. METHODS: All French anesthesiologists were invited to participate in this 10-month prospective survey based on (1) voluntary reporting of major complications related to regional anesthesia occurring during the study period using a telephone hotline service available 24 h a day and managed by three experts, and (2) voluntary reporting of the number and type of regional anesthesia procedures performed using pocket booklets. The service was free of charge for participants. RESULTS: The participants (n = 487) reported 56 major complications in 158,083 regional anesthesia procedures performed (3.5/10,000). Four deaths were reported. Cardiac arrest occurred after spinal anesthesia (n = 10; 2.7/10,000) and posterior lumbar plexus block (n = 1; 80/10,000). Systemic local anesthetic toxicity consisted of seizures only, without cardiac toxicity. Lidocaine spinal anesthesia was associated with more neurologic complications than bupivacaine spinal anesthesia (14.4/10,000 vs. 2.2/10,000). Most neurologic complications were transient. Among 12 that occurred after peripheral nerve blocks, 9 occurred in patients in whom a nerve stimulator had been used. CONCLUSION: This prospective survey based on a free hotline permanent telephone service allowed us to estimate the incidence of major complications related to regional anesthesia and to provide a detailed analysis of these complications.

Parker et al 2001a

Nerve blocks (subcostal, lateral cutaneous, femoral, triple, psoas) for hip fractures.

Parker MJ, Griffiths R, Appadu BN.

Cochrane Database Syst Rev 2001a(1):CD001159.

BACKGROUND: Various nerve blocks using local anaesthetic agents have been used in order to reduce pain after hip fracture. OBJECTIVES: To determine the effects of nerve blocks (inserted either pre-operatively, operatively or post-operatively) as part of the treatment for a hip fracture. SEARCH STRATEGY: The Cochrane Musculoskeletal Injuries Group specialised trials register, MEDLINE, and bibliographies of trial reports were searched. Date of the most recent search: October 2000. SELECTION CRITERIA: Randomised and quasi-randomised trials involving the use of nerve blocks as part of the care of a hip fracture patient. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a nine item scale, and extracted data. Wherever appropriate, results of outcome measures were pooled. MAIN RESULTS: Seven randomised or quasi-randomised trials involving 269 patients were included. Two trials related to insertion of a nerve block pre-operatively and the remaining five to peri-operative insertion. Nerve blocks resulted in a reduction of the quantity of parenteral or oral analgesia administered to control pain from the fracture/operation or during surgery and a reduction in reported pain levels. It was not possible to demonstrate if this reduction in analgesia use was associated with any other clinical benefit. REVIEWER'S CONCLUSIONS: Because of the small number of patients included in this review and the differing type of nerve blocks and timing of insertion, it is not possible to determine if nerve blocks confer any significant benefit when compared with other analgesic methods as part of the treatment of a hip fracture. Further trials with larger numbers of patients and full reporting of clinical outcomes would be justified.

Allen JG et al 1998

Postoperative analgesia following total knee arthroplasty: a study comparing spinal anesthesia and combined sciatic femoral 3-in-1 block.

Allen JG, Denny NM, Oakman N

Regional Anesthesia & Pain Medicine 1998;23(2):142–6

BACKGROUND AND OBJECTIVES: The quality of analgesia and subsequent morphine requirements following spinal anesthetic block (SAB) or combined sciatic and femoral (3-in-1) block (SFB) for total knee arthroplasty were compared. METHODS: The 39 patients studied were randomly assigned to receive either SAB (n = 19) or SFB (n = 20). All patients received a standardized general anesthetic, patient-controlled analgesia, and regular diclofenac. Visual analog pain scores and morphine requirements were recorded for 48 hours following surgery. Observations were grouped into four 12-hour periods. Pain scores (0-10 cm) were expressed as 95% confidence intervals; the criterion for analgesic success was a confidence interval in the range 0-3 cm. RESULTS: Although pain-free on awakening, the SAB patients failed to achieve analgesic success in any of the four periods, while the SFB patients did so in three of the four periods. Morphine consumption was significantly higher in the SAB group during the first two periods but similar to the SFB group thereafter. CONCLUSION: In comparison with SAB, SFB resulted in superior analgesia and reduced morphine consumption for the first 24 hours following total knee arthroplasty.

Weber et al 2001

Epinephrine does not prolong the analgesia of 20 mL ropivacaine 0.5% or 0.2% in a femoral three-in-one block.

Weber A, Fournier R, Van Gessel E, Riand N, Gamulin Z.

Anesth Analg 2001;93(5):1327–1331.

We tested the effect of epinephrine added to 20 mL ropivacaine 0.5% and 0.2% on postoperative analgesia via a femoral catheter after total knee replacement. Forty-one patients undergoing total knee replacement under combined peripheral block/general anesthesia were randomly allocated to two groups. After insertion of a femoral catheter, 21 patients in the Ropivacaine-Epinephrine (ROPI-EPI) group received 20 mL ropivacaine 0.5% plus epinephrine 1:200,000, whereas 20 patients in the Ropivacaine group (ROPI) received 20 mL plain ropivacaine 0.5%. Thereafter, a sciatic block with 30 mL bupivacaine 0.5% plus epinephrine 1:200,000 was performed in all patients, followed by general anesthesia. After surgery, patient-controlled analgesia (PCA) with ropivacaine 0.2% plus epinephrine 1:200,000 for Group ROPI-EPI and plain ropivacaine 0.2% for Group ROPI was available via the femoral catheter (200 mL ropivacaine 0.2% +/- epinephrine, bolus 20 mL, lockout 120 min). The patients were instructed to use PCA when the knee pain score was >3 cm. The interval between the initial ropivacaine injection and the first PCA injection determined the duration of 20 mL ropivacaine 0.5% +/- epinephrine, whereas the interval between the first and second PCA injection determined the duration of 20 mL ropivacaine 0.2% +/- epinephrine. The average duration of ropivacaine 0.5% was 657 +/- 345 min for the ROPI-EPI group and 718 +/- 423 min for the ROPI group (NS), whereas for ropivacaine 0.2%, the average duration was 409 +/- 245 min for the ROPI-EPI group and 419 +/- 339 min for the ROPI group (not significant). We conclude that epinephrine does not influence the duration of analgesia of the ropivacaine concentrations investigated. IMPLICATIONS: We evaluated the effect of epinephrine on the duration of analgesia of 20 mL ropivacaine 0.5% or 0.2% injected in femoral three-in-one block for pain relief after total knee replacement. Our results show that epinephrine does not alter the duration of analgesia of the two solutions investigated.

Dahl et al 1999

Intraoperative and postoperative analgesic efficacy and adverse effects of intrathecal opioids in patients undergoing cesarean section with spinal anesthesia: a qualitative and quantitative systematic

Dahl JB, Jeppesen IS, Jorgensen H, Wetterslev J, Moiniche S.

Anesthesiology 1999;91(6):1919–1927.

Gentili and Bonnet 1996

Spinal clonidine produces less urinary retention than spinal morphine.

Gentili M, Bonnet F.

Br J Anaesth 1996 Jun;76(6):872–873.

We have conducted a double-blind, randomized study in two groups of 20 patients each, undergoing hip surgery during spinal anaesthesia, to compare the incidence of urinary retention after spinal morphine or clonidine. Patients received 0.5% spinal bupivacaine 15 mg combined with either clonidine 75 micrograms or morphine 0.2 mg. After operation, patients were examined for micturition, bladder distension, or both; when they failed to void, they received naloxone 0.2 mg, and if bladder distension persisted, a catheter was inserted. At 12 h, all patients in the morphine group but only five in the clonidine group had bladder distension, and at 24 h this was present in seven and one patient in the morphine and clonidine groups, respectively (P < 0.001). Naloxone was given in 16 and one, and a catheter was placed in one and six patients in the morphine and clonidine groups, respectively (P < 0.001). We conclude that spinal clonidine impaired bladder function to a lesser extent than morphine.

Horowitz et al 1993

A Prospective Randomized Comparison of Two Surgical Approaches to Total Hip Arthroplasty.

Horowitz BR, Rockowitz NL, Goll SG, Booth RE, Balderston RA, Rothman RH, Cohn JC.

Clin Orthop 1993;291:154–163.

One hundred patients had total hip arthroplasty (THA) with either a modified Hardinge approach or transtrochanteric lateral approach. Perioperative data showed that osteotomies resulted in significantly more blood loss but required shorter operative time. Postoperative pain, using a visual analogue scale, showed no statistical difference between the two groups. Postoperative hip scores for pain, function, and range of motion (ROM), presence of limp , and abductor muscle strength scores showed no significant difference between groups at six months and one year. Roentgenographic follow-up evaluation showed a mean acetabular cup angle of 40 degrees and a neutral-to-valgus femoral stem position in all patients. Trochanteric union was present in 92%. Heterotopic ossification occurred predominantly in the Hardinge patients but was not functionally significant. Therefore, the ability to achieve adequate pain releif and funciton with THA is not affected by the type of approach.

Ravikumar et al 2001

Drainage versus non-drainage in total hip arthroplasty. A prospective randomised study.

Ravikumar KJ, Alwan T, Fordyce MJF, Tuson KWR.

Hip International 2001;11(1):49–54.

(No abstract available)

Parker et al 2001b

Arthroplasties (with and without bone cement) for proximal femoral fractures in adults.

Parker MJ, Rajan D.

Cochrane Database Syst Rev 2001b(3):CD001706.

BACKGROUND: Numerous types of arthroplasties may be used in the surgical treatment of a hip fracture (proximal femoral fracture). The main differences between the implants are the design of the stems, whether the stem is fixed in place with or without cement, whether a second articulating joint is included within the prosthesis (bipolar prosthesis) or whether the whole hip joint is replaced. OBJECTIVES: To review all randomised trials that have compared different arthroplasties for the treatment of hip fractures in adults. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register. Additional trials were identified by searching reference lists of relevant articles, conference proceedings, and contact with trialists. Date of most recent search: January 2001. SELECTION CRITERIA: All randomised and quasi-randomised trials comparing different arthroplasties (and or cement), for the treatment of hip fractures. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality, by use of a ten-item checklist and extracted data. MAIN RESULTS: Thirteen trials involving 1464 patients were included. One trial investigated two comparisons. Cemented prostheses, when compared with uncemented (four trials, 391 participants) were associated with a lower risk of failure to regain mobility (relative risk (RR) 0.60, 95% confidence interval (CI) 0.44, 0.82) and of post-operation pain at a year or later (RR 0.51, 95% CI 0.31, 0.81). For this comparison, there were no significant differences in any other outcome. Comparison of unipolar hemiarthroplasty with bipolar hemiarthroplasty (six trials, 742 participants) showed no significant differences between the two types of implant. Two trials of 269 patients compared different types of hemiarthroplasty with a total hip replacement and two trials of 151 patients compared either different types of prosthesis head or different bipolar prostheses. Because of the limited number of cases and the use of different prostheses, no definite conclusions could be made from these four studies. REVIEWER'S CONCLUSIONS: Cementing prostheses in place seems to reduce pain post-operatively and results in better mobility, but because of the under-reporting of outcomes and the small number of patients involved, no definite conclusions can be made. The role of bipolar prostheses and total hip replacement is uncertain. Further well-conducted randomised trials are required.

Brandner et al 1991

[Slit drainage versus Redon drainage in a clinical comparison--initial experiences with a new kind of wound drainage system].

Brandner P, Neis KJ, Hettenbach A, Schmidt W.

Geburtshilfe Frauenheilkd 1991;51(5):393–397.

In a prospective, randomised study we compared the clinical properties of the established Redon drain with a new type of drain called "slit drain". Both types of drains were examined regarding the amount of drained fluid, the time elapsing until removal of the drain, the frequency of occlusion of the lumen as well as the patient's pain and the required force at extraction of the drain. The statistical analysis showed both drains to have equal abilities in draining of fluid if they were used under vacuum conditions. If used as nonsuction drains, the new device was able to drain more fluid than the established type of drain (p<0.05). Statistically relevant advantages of the slit drain were seen in a lower rate of obstruction of the lumen, a higher amount of drained fluid (as non-suction device) as well as an easier and less painful extraction.

Parker et al 2003

Closed suction surgical wound drainage after orthopaedic surgery.

Parker MJ, Roberts C.

Cochrane Database Syst Rev. 2001;(4):CD001825.

Background: Closed suction drainage systems are frequently used to drain fluids, particularly blood, from surgical wounds. The aim of these systems is to reduce the occurrence of wound haematomas and infection. Objectives: To evaluate the effectiveness of closed suction drainage systems for orthopaedic surgery. Search strategy: We searched the Cochrane Musculoskeletal Injuries Group specialised register (May 2001), MEDLINE (1996-May 2001) and references from articles. Selection criteria: All randomised or quasi-randomised trials comparing the use of closed suction drainage systems with no drainage systems for all types of elective and emergency orthopaedic surgery. Data collection and analysis: Both reviewers independently assessed trial quality, using a nine item scale, and extracted data. Wherever appropriate and possible, the data are presented graphically. Main results: Twenty-one studies involving 2772 patients with 2971 wounds were included in the analysis. The types of surgery involved were hip and knee replacement, shoulder surgery, hip fracture surgery, spinal surgery, cruciate ligament reconstruction, open meniscectomy and fracture fixation surgery. Many of the studies had poor methodology and reporting of outcomes. Pooling of results indicated no difference in the incidence of wound infection, haematoma or dehiscence between those allocated to drains and the un-drained wounds. There was a tendency to an increased risk of re-operation for wound complications in the group with drains (relative risk (RR) 2.25, 95% confidence intervals (CI) 0.95 to 5.33), but due to the small numbers of cases involved definite conclusions cannot be made for this outcome. Blood transfusion was required more frequently in those who received drains (RR 1.41, 95% CI 1.10 to 1.80). The need for reinforcement of wound dressings (RR 0.22, 95% CI 0.13 to 0.40) and bruising around the operation site was more common in the group without drains. Reviewers' conclusions: There is insufficient evidence from randomised trials to support or refute the routine use of closed suction drainage in orthopaedic surgery. Further randomised trials are required before definite conclusions can be made.

Camu et al 2002

Valdecoxib, a COX-2-specific inhibitor, is an efficacious, opioid-sparing analgesic in patients undergoing hip arthroplasty.

Camu F, Beecher T, Recker DP, Verburg KM.

Am J Ther 2002;9(1):43–51.

Opioid agents are highly effective analgesics after orthopedic surgery but are associated with several adverse effects. Valdecoxib is a new, highly selective cyclooxygenase (COX)-2-specific inhibitor with a rapid onset of action and significant analgesic properties that is being developed for the management of acute pain. The objective of this study was to demonstrate the opioid-sparing efficacy of valdecoxib as part of a multimodal treatment of pain associated with hip arthroplasty. This multicenter, multiple-dose, double-blind, parallel-group study compared the opioid-sparing effects, analgesic efficacy, and safety of 20- and 40-mg doses of valdecoxib twice daily with placebo in patients receiving morphine by patient-controlled analgesia after hip arthroplasty. Study medication was first administered 1 to 3 hours preoperatively. The total amount of morphine administered, pain intensity, and patient's global evaluation of study medication were assessed over a period of 48 hours. Patients receiving 20 or 40 mg valdecoxib twice daily required on average 40% less morphine than those receiving placebo after hip arthroplasty. Pain intensity levels and patient satisfaction were significantly improved in both valdecoxib groups compared with placebo. Valdecoxib and placebo were equally well tolerated. Pre- and postoperative administration of valdecoxib reduces the amount of morphine required for postoperative pain relief and provides greater analgesic efficacy compared with morphine alone. Thus, valdecoxib has significant clinical utility for acute pain management in orthopedic surgery patients.

Hubbard et al 2003

Parecoxib sodium has opioid-sparing effects in patients undergoing total knee arthroplasty under spinal anaesthesia.

Hubbard RC, Naumann TM, Traylor L, Dhadda S.

Br J Anaesth 2003;90(2):166–172.

BACKGROUND: This multicentre, double-blind, placebo-controlled study compared the opioid-sparing effectiveness and clinical safety of parecoxib sodium over 48 h, in 195 postoperative patients after routine total knee replacement surgery. METHODS: Elective total primary knee arthroplasty was performed under spinal anaesthesia, with a single dose of spinal bupivacaine 10-20 mg, and intraoperative sedation with midazolam 0.5–1.0 mg i.v., or propofol <6 mg/kg/h. Patients were randomized to receive either parecoxib sodium 20 mg twice daily (bd) i.v. (n=65), parecoxib sodium 40 mg bd i.v. (n=67), or placebo (n=63) at the completion of surgery, and after 12, 24, and 36 h. Morphine (1–2 mg) was taken by patient-controlled analgesia or by bolus doses after 30 min. RESULTS: Patients receiving parecoxib sodium 20 mg bd and 40 mg bd consumed 15.6% and 27.8% less morphine at 24 h than patients taking placebo (both p<0.05). Both doses of parecoxib sodium administered with morphine provided significantly greater pain relief than morphine alone from 6 h (p<0.05). A global evaluation of study medication demonstrated a greater level of satisfaction among patients taking parecoxib sodium than those taking placebo. Parecoxib sodium administered in combination with morphine was well tolerated. However, a reduction in opioid-type side-effects was not demonstrated in the parecoxib sodium groups. CONCLUSION: Parecoxib sodium provides opioid-sparing analgesic effects in postoperative patients.

Rasmussen et al 2002

Intravenous parecoxib sodium for acute pain after orthopedic knee surgery.

Rasmussen GL, Steckner K, Hogue C, Torri S, Hubbard RC.

Am J Orthop 2002;31(6):336–343.

Our objective in a randomized, multicenter, double-blind, parallel- group, placebo- and active-controlled study was to evaluate and compare the analgesic effectiveness of single intravenous (IV) doses of parecoxib sodium 20 and 40 mg, morphine 4 mg, and ketorolac 30 mg in the postsurgical orthopedic pain model. After undergoing unilateral total knee replacement surgery, 208 healthy adult patients were randomized to receive placebo or a study drug within 6 hours of discontinuation of patient-controlled analgesia on postoperative day 1. Onset of analgesia was similarly rapid with IV parecoxib sodium 40 mg, morphine, and ketorolac. Level and duration of analgesia were significantly superior with parecoxib sodium than with morphine and were similar for parecoxib sodium and ketorolac. Parecoxib sodium was safe and well tolerated. In conclusion, IV parecoxib sodium 40 mg is as effective as ketorolac 30 mg and is more effective than morphine 4 mg and therefore has potential widespread utility in acute postoperative pain management.

Gajraj 2005a

The effect of cyclooxygenase-2 inhibitors on bone healing.

Gajraj NM.

Reg Anesth Pain Med 2003;28(5):456–465.

No abstract available.

Dahl et al 1995

Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty.

Dahl V, Raeder JC, Drosdal S, Wathne O, Brynildsrud J.

Acta Anaesthesiol Scand 1995;39(3):323–326.

The postoperative analgesic effect of ibuprofen was compared with a combination of ibuprofen and codeine versus placebo. The study was prospective, randomized, double blind with 123 consecutive hip arthroplasty operations. All the patients received oral diazepam as premedication and spinal anaesthesia with bupivacaine 5 mg/ml 3-4 ml. Postoperatively, when the spinal anaesthesia started to wear off, the patients were randomly assigned to one of three groups; the ibuprofen group (n=48) received 800 mg of ibuprofen orally. The ibuprofen/codeine group (IC, n=48) received 800 mg of ibuprofen combined with 60 mg of codeine. The placebo group (P, n=25), received oral placebo medication. The patients were observed for the need of additional opioid (e.g. ketobemidone), pain score (verbal and VAS), bleeding and side effects for five hours. The patients in the placebo group (P) had significantly higher pain scores (p<0.05) compared with the two other groups after 2 and 4 hours, with no significant differences after 1, 3 and 5 hours. The P group also received 45% more opioids (p<0.001) compared with the two other groups during the same period. No significant differences in bleeding or side-effects were observed between the groups. There were no significant differences between the ibuprofen group and the ibuprofen/codeine group. We conclude that a prophylactic dose of 800 mg ibuprofen orally has an opioid sparing effect with a tendency of less pain experience during the first hours after hip arthroplasty.

Iohom et al 2002

Effect of perioperative administration of dexketoprofen on opioid requirements and inflammatory response following elective hip arthroplasty.

Iohom G, Walsh M, Higgins G, Shorten G.

Br J Anaesth 2002;88(4):520–526.

BACKGROUND: In this double-blind, randomized, placebo-controlled trial, the safety and analgesic efficacy of perioperative dexketoprofen were evaluated. METHODS: Thirty ASA I or II patients undergoing elective hip arthroplasty were randomized to one of two groups. One group (D) received dexketoprofen 25 mg tds for 24 h before and 48 h after surgery; the second group (P) received placebo tablets at equivalent times. Hyperbaric 0.5% bupivacaine (17.5 mg if greater than 70 kg and 15 mg if less than 70 kg) and preservative-free morphine (0.6 mg) were administered intrathecally. Postoperatively, PCA was provided (bolus morphine sulphate 1 mg; lockout 5 min; no continuous infusion). RESULTS: The two groups were similar in terms of age, gender, weight, height, ASA class, duration of operation, and level of sensory block on arrival to the recovery room. Groups were also similar in terms of blood loss, transfusion requirements, ventilatory frequency, and haemodynamic variables. According to visual analogue pain scores patients in group D experienced less pain at 15 h (p=0.02) postoperatively. Cumulative morphine consumption was also less in group D compared with group P at 6 (0.06 (0.2) vs 0.85 (1.4) mg, p=0.04) and 48 h postoperatively (10.1 (8) vs 26.2 (20) mg, p<0.01). Plasma interleukin 6 concentrations increased postoperatively to a significantly lesser extent in group D than in group P (p=0.02). Nausea and vomiting were less (p<0.01) in group D compared with group P at 18 h postoperatively. Sedation scores were less (p=0.03) in group D. CONCLUSIONS: Perioperative administration of dexketoprofen 25 mg 8 hourly markedly improves analgesia and decreases opioid requirements (and associated adverse effects) following hip arthroplasty. It appears that this regimen decreases the postoperative pro-inflammatory response.

Kostamovaara et al 1998

Ketorolac, diclofenac and ketoprofen are equally efficacious for pain relief after total hip replacement surgery.

Kostamovaara PA, Hendolon H, Kokki H, Nuutinen LS.

Br J Anaesth 1998;81:369–372.

We have compared the efficacy of ketorolac 30 mg i.v. followed by infusion at a rate of 90 mg/15.5 h, with that of diclofenac 75 mg followed by infusion of 75 mg/15.5 h or ketoprofen 100 mg followed by infusion of 100 mg/15.5 h, on postoperative pain in 85 patients after hip replacement surgery under spinal anaesthesia in a prospective, double-blind, randomized study. Supplementary analgesia was administered during the 16-h postoperative period with bolus doses of fentanyl delivered by a patient-controlled analgesia system. Mean total consumption of PCA-administered fentanyl was 890 µg(SD 400) in the ketorolac group, 920 µg (550)  in the diclofenac group and 850 µg (350) in the ketoprofen group (ns). Median VAS scores were low over the entire study in each group and there was no significant difference between groups. No serious adverse events were recorded.

Kinsella et al 1992

Ketorolac trometamol for postoperative analgesia after orthopaedic surgery.

Kinsella J, Moffat AC, Patrick JA, Prentice JW, McArdle CS, Kenny GN.

Br J Anaesth 1992;69(1):19–22.

We have compared the postoperative morphine requirements and analgesic efficacy of four doses of i.m. ketorolac 30 mg administered 6-hourly with placebo in a double-blind study of patients undergoing major or minor orthopaedic surgery. During the 24-h postoperative study period which began at the end of surgery, patients were prescribed i.m. morphine 10 mg as required 2-hourly and assessments were made of pain at 4 and 24 h. After major surgery, the median morphine consumption over 24 h was 10 mg in patients who received ketorolac, compared with 30 mg in those who received placebo (p=0.008). Visual analogue pain scores and verbal pain assessments were better than placebo at 4 h (p=0.028 and p=0.008, respectively), but were not statistically different between the groups at 24 h. Overall assessment of pain was similar in both groups who had undergone major surgery. In the minor surgery groups, median morphine consumption was 0 mg in patients who received ketorolac, compared with 10 mg in those given placebo (ns). Visual analogue pain scores at 24 h after surgery were significantly less in patients who had received ketorolac compared with placebo (p=0.046) and the overall assessment of pain relief was better in the ketorolac group (p=0.0007). Mandatory administration of ketorolac appeared to be of benefit in both major and minor orthopaedic surgery, although the principal effects were reduction in requirement for supplementary morphine for major surgery and better overall analgesia for minor surgery.

Aubrun et al 2000

Randomised, placebo-controlled study of the postoperative analgesic effects of ketoprofen after spinal fusion surgery.

Aubrun F, Langeron O, Heitz D, Coriat P, Riou B.

Acta Anaesthesiol Scand 2000;44(8):934–939.

BACKGROUND: The additive effect of non-steroidal anti-inflammatory drugs administered with propacetamol after major orthopaedic surgery has not been studied. Thus, we performed a prospective, placebo-controlled study to assess the analgesic effects of ketoprofen in patients undergoing spinal fusion surgery and receiving propacetamol. METHODS: Fifty patients undergoing spinal fusion surgery received either 100 mg of ketoprofen every 8 h or a placebo, postoperatively. All patients received propacetamol and morphine (intravenous titration followed by patient-controlled analgesia (PCA) over 24 h). Pain was assessed using a visual analogue pain scale (VASpi). Data are mean+/-SD. RESULTS: During morphine titration, ketoprofen did not significantly reduce the dose of morphine (8+/-6 vs 11+/-4 mg, NS) whereas it significantly decreased VASpi (p<0.001). During PCA, ketoprofen significantly reduced morphine consumption (25+/-17 vs 38+/-20 mg, p=0.04) and VASpi (p=0.002). The total postoperative morphine consumption was significantly (33%) reduced with ketoprofen. CONCLUSION: Ketoprofen reduced morphine requirements and improved postoperative analgesia in patients undergoing major spinal surgery and receiving propacetamol.

DeAndrade et al 1994

The use of ketorolac in the management of postoperative pain.

DeAndrade JR, Maslanka M, Maneatis T, Bynum L, Burchmore M.

Orthopedics 1994;17(2):157–166.

Ketorolac tromethamine (Toradol) is a nonsteroidal antiinflammatory drug (NSAID) available in intramuscular (IM) and oral formulations for the management of acute pain. Intramuscular ketorolac is the only parenteral NSAID available for analgesic use in the US. The clinical profile is reviewed, and clinical studies most applicable to a postoperative patient are discussed in detail. The results of a clinical study performed at Emory University School of Medicine are presented. In this single-dose study, 176 patients received either 10 mg of oral ketorolac, 5 mg or 10 mg of IM morphine, or placebo after orthopedic surgery. The analgesic efficacy of ketorolac was comparable to both doses of morphine and significantly superior to placebo. Ketorolac, when administered intramuscularly or orally, is a safe and effective analgesic agent for the short-term management of acute postoperative pain and can be used as an alternative to opioid therapy.

Beattie et al 1997

The addition of continuous intravenous infusion of ketorolac to a patient-controlled analgetic morphine regime reduced postoperative myocardial ischemia in patients undergoing elective total hip or kn

Beattie WS, Warriner CB, Etches R, Badner NH, Parsons D, Buckley N, Chan V, Girard M.

Anesth Analg 1997;84(4):715–722.

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, p=0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, p<0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.

Fee et al 1989

Analgesia after hip replacement surgery: comparison of nalbuphine with morphine.

Fee JP, Brady MM, Furness G, Chambers M, Clarke RS.

Br J Anaesth 1989;63(6):756–758.

Two groups of 40 patients undergoing hip replacement received either nalbuphine 0.3 mg/kg or morphine 0.15 m/kg i.m. on up to three occasions: 1 h before operation, as soon as requested after operation, and 3 h subsequently if required. Pain intensity was assessed by the patient as severe, moderate or none, and pain relief by a "blind" nurse observer as slight, moderate or complete. Assessments of pain and sedation were carried out at 30-min intervals for 2 h and at 1-h intervals thereafter for up to 6 h. Six patients who received nalbuphine and eight who received morphine before operation required no postoperative analgesia. Ten patients in the nalbuphine group and two in the morphine group failed to obtain adequate pain relief (p<0.05) and were given i.v. morphine.

Frater et al 1989

Analgesia-induced respiratory depression: comparison of meptazinol and morphine in the postoperative

Frater RA, Moores MA, Parry P, Hanning CD.

Br J Anaesth 1989;63(3):260–265.

Forty-nine patients undergoing elective total hip replacement received either morphine or meptazinol for postoperative analgesia from a patient-controlled analgesia apparatus. Ventilatory rate and volume and arterial oxyhaemoglobin saturation were recorded continuously for the first 24 h following surgery. Episodic hypoxaemia was seen in both groups, associated with disturbances in ventilatory pattern. There was no significant difference in the incidence or severity of observed hypoxia between the groups, or with respect to the class of ventilatory disturbance. Mean linear analogue scores for pain and nausea were significantly (p<0.05) greater in the meptazinol group than in the morphine group 8 h after operation, but did not differ significantly at any other time. The mean number of demands for analgesic drugs was similar in the two groups. The meptazinol group had a greater requirement for anti-emetic drugs than the morphine group (p<0.05). It was concluded that meptazinol and morphine in equianalgesic doses had similar effects on ventilation in the postoperative period.

Robinson et al 1991

Morphine compared with diamorphine. A comparison of dose requirements and side-effects after hip surgery.

Robinson SL, Rowbotham DJ, Smith G.

Anaesthesia 1991;46(7):538–540.

The dose requirements and side effects of morphine were compared with those of diamorphine administered by patient-controlled analgesia in 40 patients following elective total hip replacement. Patients were allocated randomly to receive in a double-blind manner either morphine or diamorphine for postoperative pain relief. There were no significant differences between the two groups with regard to postoperative sedation, nausea, well-being, pain relief and requirements for antiemetic drugs. The dose requirement for diamorphine was approximately 50% of that for morphine.

Keita et al 2003

Comparison between patient-controlled analgesia and subcutaneous morphine in elderly patients after total hip replacement.

Keita H, Geachan N, Dahmani S, Couderc E, Armand C, Quazza M, Mantz J, Desmonts JM.

Br J Anaesth 2003;90(1):53–57.

BACKGROUND: The goal of this study was to evaluate the effectiveness on postoperative pain, and cognitive impact, of patient-controlled analgesia (PCA) compared with subcutaneous (s.c.) injections of morphine in elderly patients undergoing total hip replacement (THR). METHODS: Forty patients older than 70 yr were randomly assigned to two different postoperative analgesic techniques for 48 h: i.v. PCA morphine (dose, 1 mg; lockout interval, 8 min; PCA group) or regular s.c. morphine injections (SC group). Postoperative pain was assessed at rest and when moving, using a visual analogue scale (VAS) every 4 h. A Mini Mental Status (MMS) examination was used to assess cognitive functions before surgery, at 2 h, 24 h and 48 h after surgery, and at hospital discharge. Side-effects were also recorded systematically during the first 48 h after surgery. RESULTS: The PCA group showed significantly lower pain scores than the SC group both at rest and during mobilization. However, the clinical significance of pain scores was weak. There was no intergroup difference in postoperative MMS scores. The incidence of side-effects was similar in both groups. CONCLUSIONS: We conclude that in healthy elderly subjects undergoing THR, the flexibility of the analgesic regimen is more important than the route of administration with regard to efficacy, adverse effects and recovery of cognitive function.

McCormack et al 1993

A comparison of regularly dosed oral morphine and on-demand intramuscular morphine in the treatment of post surgical pain.

McCormack JP, Warriner CB, Levine M, Glick N.

Can J Anaesth 1993;40(9):819–824.

A randomized, placebo-controlled, double-blind clinical trial was conducted to compare the use of regularly dosed po morphine and on- demand in morphine in 47 patients undergoing total hip arthroplasty. Patients were randomized to receive either 20 mg (initial dose) of regularly dosed morphine (every four hours po) plus breakthrough pain medication on-demand consisting of both 10 mg morphine po and placebo im, or an equivalent regularly dosed oral placebo (every four hours) with breakthrough pain medication consisting of oral placebo and 5–10 mg morphine im. Subsequent to each request for breakthrough pain medication, the next regularly dosed oral solution was increased by 5 mg (or equivalent volume of placebo) to a maximum of 40 mg po Q4H. Time- averaged pain scores were lower on both postoperative day 1 and 2 in the group receiving regularly dosed morphine po (p<0.05). Fewer patients requested breakthrough pain medication on both days in the oral morphine group. The incidence of nausea and vomiting, and of decreased respiratory rates were similar in both groups. Regularly dosed oral morphine is inexpensive and should be compared to other methods of opioid delivery.

Tarradell et al 1996

Respiratory and analgesic effects of meperidine and tramadol in patients undergoing orthopedic surgery.

Tarradell R, Pol O, Farre M, Barrera E, Puig MM.

Methods Find Exp Clin Pharmacol 1996;18(3):211–218.

The respiratory and analgesic effects of i.v. meperidine, tramadol and their correlation with plasma concentrations of meperidine, tramadol and O-demethyltramadol were determined. Forty-eight patients after total hip or knee replacement were randomly distributed into 3 groups (n = 16 each). At the time of analgesia request, they received in a double-blind manner, i.v. single doses of 100 mg meperidine, 100 mg tramadol, or saline. Thirty minutes after treatment, patients who requested additional analgesia were rescued with 75 mg diclofenac and morphine as required. Patients were evaluated at the time of analgesia request and at set intervals during 4 h. Meperidine induced sedation (p<0.05), respiratory depression (tidal volume, p<0.047; respiratory rate, p < 0.004; % O2 Sat, p<0.036), and hypercapnia (PaCO2, p<0.002). Incidence of nausea and vomiting was higher with tramadol (p<0.02). For the first 30 min, meperidine produced lower pain intensity scores than tramadol or saline (p<0.05). At this time, 14/16 patients on saline, 8/16 on meperidine and 11/16 on tramadol were rescued. Onset for meperidine analgesia was 10 min and > 30 min for tramadol. Both opioids produced similar degree of analgesia in patients who were not rescued. A negative correlation (r= -0.99) between analgesia and tramadol concentrations and a poor positive correlation (r= +0.54) with O-demethyltramadol (a metabolite of tramadol) was observed. Pain intensity differences correlated negatively with meperidine plasma concentrations during the first 30 min (r= -0.97) and positively thereafter (r= +0.92). In the present study, meperidine and tramadol produced comparable analgesia, with a different time course profile, but meperidine induced sedation and respiratory depression while tramadol did not.

Galasko et al 1985

Trial of oral flupirtine maleate in the treatment of pain after orthopaedic surgery.

Galasko CS, Courtenay PM, Jane M, Stamp TC.

Curr Med Res Opin 1985;9(9):594–601.

A clinical trial was carried out in 66 patients to compare the effectiveness of oral flupirtine maleate (100 to 200 mg) and oral pentazocine (50 to 100 mg) in the treatment of pain after hip replacement surgery. The trial analgesics were used as sole analgesia from the second to the fifth post-operative day. Similar numbers of patients were withdrawn from the trial in each group (flupirtine 6, pentazocine 5) because of poor efficacy or the appearance of symptoms, the relationship to treatment of which was uncertain. Indices of the quality, speed and degree of pain relief were similar in both groups on all days of the study, no significant differences being seen. High proportions of patients in each group expressed overall satisfaction with the trial medication, somewhat more so with flupirtine (85% to 95%) than pentazocine treatment (67% to 79%). Reports of dizziness/lightheadedness were significantly more common with pentazocine (23% affected) than with flupirtine (3%). Other side-effects were reported by only small numbers of patients, but the relationship of reported symptoms to treatment was uncertain in most cases. The results suggest that flupirtine is likely to be at least as effective and acceptable as pentazocine for the treatment of pain after orthopaedic surgery and that flupirtine may offer advantages in terms of fewer central nervous system side-effects.

Smythe et al 1996

Patient-controlled analgesia versus patient-controlled analgesia plus continuous infusion after hip replacement surgery.

Smythe MA, Zak MB, O'Donnell MP, Schad RF, Dmuchowski CF.

Ann Pharmacother 1996;30(3):224–227.

OBJECTIVE: To compare the efficacy and adverse effect profile of patient-controlled analgesia (PCA) versus PCA plus continuous infusion (PCACI) after hip replacement surgery. DESIGN: Prospective, randomized, open pilot study. SETTING: Large teaching institution. PARTICIPANTS: Thirty-four patients undergoing hip replacement or revision of hip replacement surgery. INTERVENTIONS: Patients were randomized to receive PCA morphine: 1 mg with 6-minute lockout, or PCACI, using the same dose, with a 0.5-1 mg/h continuous infusion. Pain intensity, sedation, narcotic use, injection/attempt ratio (I/A), and adverse effects were assessed. RESULTS: No significant differences in pain intensity were identified. Morphine use was not different between groups: PCA 61.8 +/- 35.0 and PCACI 74.2 +/- 54.9 mg (p =0.394). A trend toward an increased 12-hour I/A ratio was evident in the PCACI group: PCA 0.73 +/- 0.18 and PCACI 0.86 +/- 0.17 (p =0.073). Patient-reported adverse effects, sedation, and inability to sleep secondary to pain occurred similarly. Eight of 18 PCACI patients required discontinuation of either the continuous infusion mode or of PCA therapy entirely secondary to adverse effects. CONCLUSIONS: When compared with PCA therapy, PCACI was not associated with improved pain control and more patients receiving PCACI required discontinuation of therapy secondary to adverse effects.

Walder et al 2001

Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. A quantitative systematic review.

Walder B, Schafer M, Henzi I, Tramer MR.

Acta Anaesthesiol Scand 2001;45(7):795–804.

BACKGROUND: The usefulness of intravenous patient-controlled analgesia (PCA) with opioids for postoperative analgesia is not well defined. METHODS: We systematically searched (MEDLINE, EMBASE, Cochrane Library, bibliographies, any language, to January 2000) for randomised trials comparing opioid-based PCA with the same opioid given intramuscularly, intravenously, or subcutaneously. Weighted mean differences (WMD) for continuous data, relative risks (RR) and numbers-needed-to-treat (NNT) for dichotomous data were calculated with 95% confidence intervals (CI) using fixed and random effects models. RESULTS: Data from 32 trials were analysed: 22 (1139 patients) were with morphine, five (682) with pethidine, three (184) with piritramide, one (47) with nalbuphine and one (20) with tramadol. In three morphine and one pethidine trial (352 patients), more patients preferred PCA (89.7% vs. 65.8%, RR 1.41 (95%CI 1.11 to 1.80), NNT 4.2). Combined dichotomous data on pain intensity and relief, and the need for rescue analgesics from eight morphine, one pethidine, one piritramide, and one nalbuphine trial (691 patients), were in favour of PCA (RR 1.22 (1.00 to 1.50), NNT 8). In two morphine trials (152), pulmonary complications were more frequently prevented with PCA (100% vs. 93.3%, RR 1.07 (1.01 to 1.14), NNT 15). There was equivalence for cumulative opioid consumption, pain scores, duration of hospital stay, and opioid-related adverse effects. CONCLUSION: These trials provide some evidence that in the postoperative pain setting, PCA with opioids, compared with conventional opioid treatment, improve analgesia and decrease the risk of pulmonary complications, and that patients prefer them.

Stubhaug et al 1995

Lack of analgesic effect of 50 and 100 mg oral tramadol after orthopaedic surgery: a randomized, double-blind, placebo and standard active drug comparison.

Stubhaug A, Grimstad J, Breivik H.

Pain 1995;62(1):111–118.

Tramadol hydrochloride is a synthetic mu-opioid agonist with additional monoaminergic activity. Tramadol's analgesic effect has been equated with that of pethidine, with a more favourable side-effect profile. Tramadol has been the most-selling prescription analgesic in Germany for several years, and it is now available in many other European countries, but still there is a lack of adequately controlled clinical studies of its analgesic properties. The purpose of this study was to compare the analgesic efficacy of 50 and 100 mg oral tramadol with our standard analgesic for postoperative pain treatment, 1000 mg paracetamol + 60 mg codeine, and placebo. A single-dose, parallel group, double-blind design was used. One hundred forty-four patients were enrolled the day after total hip replacement if they had a pain intensity of 60 mm or more on a 0–100 mm visual analogue scale. Treatments were compared on the basis of pain intensity and derived variables (pain intensity difference, and summed pain intensity differences), the need of rescue medication, and a global evaluation. Serum concentrations confirmed rapid and good absorption comparable with that reported in healthy volunteers. The active drug control, paracetamol+codeine, was significantly superior to placebo for all efficacy variable (p = 0.0002–0.004), confirming good assay sensitivity. Paracetamol+codeine was also significantly superior to both 50 mg tramadol (p = 0.002–0.03) and 100 mg tramadol (p = 0.002–0.02). There was no difference between placebo and 50 and 100 mg tramadol for any of the efficacy variables.(ABSTRACT TRUNCATED AT 250 WORDS)

Peduto et al 1998

Efficacy of propacetamol in the treatment of postoperative pain. Morphine-sparing effect in orthopedic surgery. Italian Collaborative Group on Propacetamol.

Peduto VA, Ballabio M, Stefanini S.

Acta Anaesthesiol Scand 1998;42(3):293–298.

BACKGROUND: Combined analgesic regimens have been suggested to improve the treatment of postoperative pain. The aim of our study was to evaluate the analgesic efficacy and tolerability of propacetamol, in combination with morphine. METHODS: Four i.v. infusions of propacetamol 2 g or placebo were administered, in a double-blind fashion, after orthopedic surgery (n=97). Morphine was administered by a patient-controlled analgesia (PCA) device. The total dose of morphine, pain intensity and global efficacy of treatment were evaluated. Tolerability was assessed by monitoring blood pressure, heart and respiratory rate, sedation scores, adverse events, and renal and hepatic parameters. RESULTS: The total dose of morphine was significantly decreased in the propacetamol group compared to placebo (9.4 +/- 8.5 mg vs 17.6 +/- 12 mg; p<0.001), arriving at a sparing effect of 46%. The evolution of pain intensity showed a similar pattern in the two groups. Global efficacy of treatment was rated significantly better by patients receiving the combination propacetamol + PCA morphine (87% of "good"/"excellent" ratings vs 65%; p=0.01). Tolerability was comparable in the two groups. Eight patients in the propacetamol and 4 patients in the placebo group reported adverse events, of mild/moderate intensity, most commonly nausea/vomiting. Renal and hepatic parameters were also seen to be comparable. CONCLUSION: These results confirm a significant morphine-sparing effect, significantly better scores in the final assessment by patients, and a good tolerability of propacetamol after orthopedic surgery. The drug may, therefore, represent a useful alternative to NSAIDs, as complementary drug to opioids, in the management of moderate/severe postoperative pain.

Rømsing et al 2002

Rectal and parenteral paracetamol, and paracetamol in combination with NSAIDs, for postoperative analgesia.

Rømsing J, Moiniche S, Dahl JB.

Br J Anaesth 2002;88(2):215–226.

BACKGROUND: We have reviewed the analgesic efficacies of rectal and parenteral paracetamol and tested the evidence for a possible additive analgesic effect of the combination of paracetamol with a non-steroidal anti-inflammatory drug (NSAID) in postoperative pain. METHODS: Randomized controlled trials were evaluated. Outcome measures were pain scores and demand for supplementary analgesia. RESULTS: Eight studies compared rectal paracetamol with placebo. One study of single-dose administration of rectal paracetamol 40–60 mg/kg and three studies of repeat dosing with 14–20 mg/kg showed significant analgesic efficacy, while studies of a single dose of 10–20 mg/kg were negative. Ten studies compared parenteral paracetamol with placebo and eight studies showed improved pain relief with paracetamol. Of the nine studies comparing paracetamol with a combination of paracetamol and an NSAID, six studies showed improved pain relief for the combination while only two of the six studies comparing an NSAID with a combination of an NSAID and paracetamol showed improved pain relief for the combination. CONCLUSIONS: Considering the few studies available, evidence was found of a clinically relevant analgesic effect of rectal and parenteral paracetamol. Concurrent use of paracetamol and an NSAID was superior to paracetamol alone but no evidence was found of superior analgesic effect of the combination compared with the NSAID alone.

Gustafsson et al 1986

Extradural and parenteral pethidine as analgesia after total hip replacement: effects and kinetics.

Gustafsson LL, Johannisson J, Garle M.

Eur J Clin Pharmacol 1986;29(5):529–534.

Twenty-one patients who had undergone total hip replacement were randomly assigned to one of three groups in order to compare a single dose of 1 mg/kg of pethidine im (I) and 20 mg (II) or 60 mg of extradural pethidine (III) in a double-blind design. The degree of analgesia, the adverse effects, and the kinetics were studied for 18 h. Pain was monitored using a visual analogue scale (VAS). Supplementary doses of oxycodone if required were given no earlier than 0.75 h after pethidine. Plasma concentrations of pethidine were measured with gas chromatography mass spectrometry (GCMS). Hypoalgesia to pin prick test was evaluated. Low pain scores were observed in the extradural groups between 0.25 and 1.5 h after the dose. A significant difference in pain score compared with the im group was found after the higher extradural dose only between 0.5 and 1 h (p<0.05). The area under the curve (AUC) of pain score versus time (0–18 h) was not significantly different between groups. The recorded adverse effects were minor in all three groups. The terminal half-lives and plasma clearances of pethidine, and the time to peak concentration were not different between the groups. Single patients in the extradural groups showed hypoalgesia to pin prick in parallel to the effect. The present study shows that extradural pethidine produces shortlived analgesia, in contrast to the long-lasting effect of morphine found in other studies.

Bertini et al 2001

Postoperative analgesia by combined continuous infusion and patient-controlled epidural analgesia (PCEA) following hip replacement: ropivacaine versus bupivacaine.

Bertini L, Mancini S, Di Benedetto P, Ciaschi A, Martini O, Nava S, Tagariello V.

Acta Anaesthesiol Scand 2001;45(6):782–785.

BACKGROUND: Ropivacaine is a new local anaesthetic, which compared to bupivacaine is less toxic and shows greater sensory and motor block dissociation. We hypothesised that treatment of postoperative pain with a combined regimen of continuous epidural infusion and Patient-Controlled Epidural Analgesia (PCEA) using ropivacaine could have given better results compared with those we had obtained using bupivacaine. METHODS: Patients undergoing total hip replacement were randomly assigned to two groups. They received epidural analgesia for postoperative pain treatment using ropivacaine, 2 mg/ml or bupivacaine 2 mg/ml. Both drugs were administered as a constant infusion of 6 ml/h supplemented by PCEA bolus doses of 2 ml. Patients in both groups received morphine intravenously on demand from a patient-controlled analgesia (PCA) device. An independent observer recorded pain scores, intensity of motor block and morphine consumption at regular intervals during the first 24 h after surgery. RESULTS: Fifty-one patients were evaluated. Ropivacaine and bupivacaine, in similar amounts, provided similar results assessed as adequate to very good postoperative analgesia, whereas motor block was significantly more intense in patients treated with bupivacaine. CONCLUSIONS: Despite similar analgesic effects, epidural infusion of ropivacaine combined with PCEA provides higher patient satisfaction than equal doses of bupivacaine due to lack of motor block.

Berti et al 1998

Comparison between epidural infusion of fentanyl/bupivacaine and morphine/bupivacaine after orthopaedic surgery.

Berti M, Fanelli G, Casati A, Lugani D, Aldegheri G, Torri G.

Can J Anaesth 1998;45(6):545–550.

PURPOSE: To compare epidural infusions of bupivacaine-fentanyl and bupivacaine-morphine mixtures for postoperative pain relief after total hip replacement. METHODS: In a prospective, randomized, double-blind study, 30 ASA physical status I–II patients undergoing total hip replacement were studied. Anaesthesia was provided by combined general/epidural anaesthesia without epidural opioids. Postoperative epidural analgesia was by continuous infusion of bupivacaine 0.125% (4 ml/hr) with either 0.05 mg/ml morphine (morphine, n=15) or 0.005 mg/ml fentanyl (fentanyl, n=15). Visual analogue pain scale (VAS), sedation (four-point scale), respiratory rate, pulse oximetry, rescue analgesics and supplemental oxygen were recorded by a blind observer at 1, 3, 6, 9, 12 and 24 hr after surgery. RESULTS: No differences in pain relief, sedation, or non-respiratory side effects were observed between the two groups. Rescue analgesics were required in three patients in the fentanyl group (20%) and in two receiving morphine (13.3%) (P:NS). Two patients in the fentanyl group and three in the morphine group required oxygen due to SpO2 < 90% (P:NS). Both opioid/bupivacaine mixtures decreased haemoglobin oxygen saturation compared with preoperative values. The mean +/- SD SpO2 values measured at 3, 6, 12 and 24 hr were 94.4 +/- 1, 92.6 +/- 0.9, 92 +/- 0.8, and 92.8 +/- 1 in the morphine group, 95.3 +/- 0.5, 95 +/- 0.5, 94.6 +/- 1.2, and 95.6 +/- 1 in the fentanyl group (p<0.05). CONCLUSION: Continuous epidural infusion of bupivacaine-morphine or bupivacaine-fentanyl mixtures provided similar pain relief. Patients receiving morphine showed a more marked decrease in SpO2 than those receiving fentanyl. However, the average SpO2 remained > 90% in both groups.

Kampe et al 2003

The continuous epidural infusion of ropivacaine 0.1% with 0.5 microg x mL(-1) sufentanil provides effective postoperative analgesia after total hip replacement: a pilot study.

Kampe S, Kiencke P, Delis A, Auweiler M, Konig DP, Kasper SM.

Can J Anaesth 2003;50(6):580–585.

PURPOSE: To assess the analgesic efficacy and functional outcome of postoperative epidural infusion of ropivacaine combined with sufentanil in a randomized, controlled trial. METHODS: Thirty-two ASA I–III patients undergoing elective total hip replacement (THR) were included. Lumbar epidural block using 0.75% ropivacaine was combined with either propofol sedation or general anesthesia for surgery. On arrival in the recovery room, the epidural infusion was commenced at a rate in ml calculated as follows: (height in cm - 100) x 0.1. Eleven patients received an epidural infusion of ropivacaine 0.1% with 0.5 µg/ml sufentanil (Group R+S0.5), ten patients ropivacaine 0.1% with 0.75 µg/ml sufentanil (Group R+S0.75), and 11 patients ropivacaine 0.1% with 1 µg/ml sufentanil (Group R+S1) over a postoperative study period of 44 hr. All patients had access to iv piritramide via a patient-controlled analgesia (PCA) device. Postel-Merle-d'Aubigne scoring system (PMA score) was assessed preoperatively, three weeks after surgery, and three months after surgery by an orthopedic surgeon blinded to study group. RESULTS: Motor block was negligible in all three groups. After eight hours of epidural infusion, sensory block had regressed completely in all patients. There was no significant difference with regard to visual analogue scale (VAS) scores (at rest: P = 0.55, on movement: p=0.63), consumption of rescue medication (P = 0.99), patient satisfaction (p=0.22), and the incidence of adverse events. All treatment regimens provided effective postoperative analgesia with only a minimal use of supplemental opioid PCA. There was no difference between groups regarding orthopedic PMA score (pain: p=0.24, mobility: p=0.65, and ability to walk: p= 0.44). CONCLUSION: Ropivacaine 0.1% with 0.5 µg/ml sufentanil for postoperative analgesia after THR provides efficient pain relief and, compared with 0.75 and 1 µg/ml sufentanil, reduces sufentanil consumption without compromise in patient satisfaction, VAS scores, and functional outcome.

Carabine et al 1992a

Extradural clonidine and bupivacaine for postoperative analgesia.

Carabine UA, Milligan KR, Moore J.

Br J Anaesth 1992a;68(2):132–135.

We have assessed the use of clonidine and bupivacaine for postoperative analgesia. Both drugs were administered via the extradural route, and were given both alone and in combination. The analgesia produced by clonidine was superior to that of bupivacaine; a combination of the drugs resulted in significantly better and longer duration of analgesia than each drug administered alone. Cardiovascular changes and the incidence of side effects were similar in all three groups. The sedative effects of clonidine were not marked.

Kostamovaara et al 2001

Ropivacaine 1 mg x ml(-1) does not decrease the need for epidural fentanyl after hip replacement surgery.

Kostamovaara PA, Laurila JJ, Alahuhta S, Salomaki TE.

Acta Anaesthesiol Scand 2001;45(4):489–494.

BACKGROUND: Ropivacaine is a new long-acting local anesthetic. Laboratory trials have demonstrated a synergistic analgesic effect between intrathecal opioids and local anesthetics. We tested the hypothesis that addition of ropivacaine 1 mg/ml to epidural fentanyl (10 µg/ml) postoperatively decreases the need for fentanyl, improves the quality of analgesia and decreases the side-effects of fentanyl. METHODS: Forty patients were enrolled in this double-blind, randomized study to receive either fentanyl 10 µg/ml) (group F) alone or fentanyl combined with ropivacaine 1 mg/ml (group R) for 20 h as an epidural infusion at TH12-L1 or L1-L2 for analgesia after hip replacement surgery. The patients were free to use a patient-controlled epidural analgesia device, which was programmed to infuse 3 ml of the study medication hourly and to allow a 3-ml bolus when needed (maximal hourly dose of fentanyl was 150 µg). The consumption of medication, visual pain scores at rest and on movement, hemodynamic and respiratory parameters, motor and sensory block, nausea, pruritus and sedation were recorded. RESULTS: There were no significant differences between the groups in the total mean fentanyl consumption (1.10+/-0.18 mg in group F, 1.08+/-0.31 mg in group R, 95% CI: -0.14 to 0.19, p=0.774). The pain scores were similar at rest (median scores < or = 1) and on movement (median scores < or = 3). The adverse effects were similar and of a minor nature, consisting mostly of pruritus and nausea. CONCLUSION: Addition of ropivacaine 1 mg/ml to epidural fentanyl 10 µg/ml did not significantly decrease the requirement for fentanyl administered for pain relief after hip replacement surgery.

Carabine et al 1992b

Extradural clonidine infusions for analgesia after total hip replacement.

Carabine UA, Milligan KR, Mulholland D, Moore J.

Br J Anaesth 1992b;68(4):338–343.

We have examined the effectiveness of extradural clonidine infusions for postoperative analgesia and the effect of clonidine on extradural morphine. In a double-blind, controlled study, patients, undergoing total hip replacement were allocated randomly to receive one of two doses of extradural clonidine (25 µg/h or 50 µg/h), low dose extradural morphine or a combination of morphine and clonidine. Pain scores in the morphine group were significantly greater than in the clonidine groups (p<0.01) and the combination group (p<0.05) during the first 1 h after surgery. The requirements for systemic analgesia were least in the combination and larger dose clonidine group, and the duration of effect of the initial bolus dose was significantly longer compared with the morphine and low dose clonidine groups (p<0.05). Arterial pressure was reduced in the clonidine groups, although the incidence of clinical hypotension was low. There were no significant differences between the groups in emetic symptoms or urinary retention.

Singelyn et al 1998

Effects of intravenous patient-controlled analgesia with morphine, continuous epidural analgesia, and continuous three-in-one block on postoperative pain and knee rehabilitation after unilateral total

Singelyn FJ, Deyaert M, Joris D, Pendeville E, Gouverneur JM.

Anesth Analg 1998;87(1):88–92.

In this study, we assessed the influence of three analgesic techniques on postoperative knee rehabilitation after total knee arthroplasty (TKA). Forty-five patients scheduled for elective TKA under general anesthesia were randomly divided into three groups. Postoperative analgesia was provided with i.v. patient-controlled analgesia (PCA) with morphine in Group A, continuous 3-in-1 block in Group B, and epidural analgesia in Group C. Immediately after surgery, the three groups started identical physical therapy regimens. Pain scores, supplemental analgesia, side effects, degree of maximal knee flexion, day of first walk, and duration of hospital stay were recorded. Patients in Groups B and C reported significantly lower pain scores than those in Group A. Supplemental analgesia was comparable in the three groups. Compared with Groups A and C, a significantly lower incidence of side effects was noted in Group B. Significantly better knee flexion (until 6 wk after surgery), faster ambulation, and shorter hospital stay were noted in Groups B and C. However, these benefits did not affect outcome at 3 mo. We conclude that, after TKA, continuous 3-in-1 block and epidural analgesia provide better pain relief and faster knee rehabilitation than i.v. PCA with morphine. Because it induces fewer side effects, continuous 3-in-1 block should be considered the technique of choice. Implications: In this study, we determined that, after total knee arthroplasty, loco-regional analgesic techniques (epidural analgesia or continuous 3-in-1 block) provide better pain relief and faster postoperative knee rehabilitation than i.v. patient-controlled analgesia with morphine. Because it causes fewer side effects than epidural analgesia, continuous 3-in-1 block is the technique of choice.

Ballantyne et al 1998

The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta-analyses of randomized, controlled trials.

Ballantyne JC, Carr DB, deFerranti S, Suarez T, Lau J, Chalmers TC, Angelillo IF, Mosteller

Anesth Analg 1998;86(3):598–612.

We performed meta-analyses of randomized, control trials to assess the effects of seven analgesic therapies on postoperative pulmonary function after a variety of procedures: epidural opioid, epidural local anesthetic, epidural opioid with local anesthetic, thoracic versus lumbar epidural opioid, intercostal nerve block, wound infiltration with local anesthetic, and intrapleural local anesthetic. Measures of forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), vital capacity (VC), peak expiratory flow rate (PEFR), PaO2, and incidence of atelectasis, pulmonary infection, and pulmonary complications overall were analyzed. Compared with systemic opioids, epidural opioids decreased the incidence of atelectasis (risk ratio [RR] 0.53, 95% confidence interval [CI] 0.33–0.85) and had a weak tendency to reduce the incidence of pulmonary infections (RR 0.53, 95% CI 0.18–1.53) and pulmonary complications overall (RR 0.51, 95% CI 0.20–1.33). Epidural local anesthetics increased PaO2 (difference 4.56 mm Hg, 95% CI 0.058–9.075) and decreased the incidence of pulmonary infections (RR 0.36, 95% CI 0.21–0.65) and pulmonary complications overall (RR 0.58, 95% CI 0.42–0.80) compared with systemic opioids. Intercostal nerve blockade tends to improve pulmonary outcome measures (incidence of atelectasis: RR 0.65, 95% CI 0.27–1.57, incidence of pulmonary complications overall: RR 0.47, 95% CI 0.18–1.22), but these differences did not achieve statistical significance. There were no clinically or statistically significant differences in the surrogate measures of pulmonary function (FEV1, FVC, and PEFR). These analyses support the utility of epidural analgesia for reducing postoperative pulmonary morbidity but do not support the use of surrogate measures of pulmonary outcome as predictors or determinants of pulmonary morbidity in postoperative patients. IMPLICATIONS: When individual trials are unable to produce significant results, it is often because of insufficient patient numbers. It may be impossible for a single institution to study enough patients. Meta-analysis is a useful tool for combining the data from multiple trials to increase the patient numbers. These meta-analyses confirm that postoperative epidural pain control can significantly decrease the incidence of pulmonary morbidity.

Turner et al 1996

Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery.

Turner G, Blake D, Buckland M, Chamley D, Dawson P, Goodchild C, Mezzatesta J, Scott D, Sultana A, W

Br J Anaesth 1996;76(5):606–610.

We studied 151 patients undergoing total hip or knee arthroplasty, or cruciate ligament reconstruction in a multicentre study in Australia and New Zealand. Patients were openly allocated randomly to one of five treatment groups or to a control group. General anaesthesia was induced after introduction of extradural block with 0.5% ropivacaine. After surgery, patients received an extradural infusion of 0.2% ropivacaine at 6, 8, 10, 12 or 14 ml/h or received no postoperative extradural infusion (control group). All patients had access to i.v. PCA morphine for supplementary analgesia. Morphine consumption was lower in all treatment groups compared with the control group, decreasing with increasing ropivacaine infusion rate. Median VAS scores were lower in all ropivacaine infusion groups compared with the control group for the first 10 h of the study; however by the end of the study, VAS scores were similar in all groups. The higher ropivacaine infusion rates caused a slower convergence of spread of the initial sensory block and a higher degree of motor block. The overall incidence of side effects was similar, with the exception of a higher incidence of urinary retention and hypotension in the groups receiving the higher rates of ropivacaine. The quality of treatment scores were similar for all treatment groups

Lorenzini et al 2002

Efficacy of ropivacaine compared with ropivacaine plus sufentanil for postoperative analgesia after major knee surgery.

Lorenzini C, Moreira LB, Ferreira MB.

Anaesthesia 2002;57(5):424–428.

This study compared the analgesic efficacy of an epidural infusion of ropivacaine and ropivacaine with sufentanil following major knee surgery. In a double-blind clinical trial, 115 adult patients received either epidural ropivacaine (R group, 2 mg/ml), or ropivacaine (2 mg/ml) with sufentanil (RS group, 1 µg/ml), using a patient-controlled epidural analgesia technique. Pain scores (visual analogue scale, VAS, and the simple descriptive scale, SDS), side-effects, motor block and treatment quality were recorded at 6, 12 and 24 h after the insertion of the epidural catheter. In the RS group, analgesic efficacy was significantly greater than in the R group between 12 and 24 h following insertion of the epidural catheter (VAS: 92.9% vs. 72.9%, p=0.009). There was no significant difference during the other periods. Pruritus, nausea and vomiting were significantly more frequent in the RS group. Good postoperative analgesia was obtained with an epidural infusion of ropivacaine (2 mg/ml)). When this local anaesthetic was administered with sufentanil, there was an improvement in the analgesic effect but a significant increase in the number of patients who reported adverse effects. The differences were more pronounced 12 h after the beginning of the analgesic schedule. This study failed to demonstrate any worthwhile clinical benefit from the addition of sufentanil.

Hommeril et al 1994

Ketoprofen for pain after hip and knee arthroplasty.

Hommeril JL, Bernard JM, Gouin F, Pinaud M.

Br J Anaesth 1994;72(4):383–387.

In a double-blind, randomized study, we have compared the effects of i.v. ketoprofen 200 mg followed by 12.5 mg/h over 13 h, with those of extradural morphine 4 mg in 32 patients after hip and knee arthroplasty. A visual analogue scale was used to score pain before analgesic administration (first complaint after operation), 1 h after and every 2 h subsequently. Pain reduction 1 h after the start of analgesia was mean 44% (SEM 17%) in the extradural morphine group and 54% (9%) in the ketoprofen group (ns). There were no significant differences between groups in pain scores, pain reduction and additional analgesia requirement (i.v. paracetamol). Naloxone 5 µg/kg/h was required for hypercapnia exceeding 6.0 kPa in three patients in the extradural morphine group (vs none in the ketoprofen group; ns). There were no differences between groups in side effects, except for urinary retention, which was more frequent in the extradural morphine group (p<0.05). As there were few differences between i.v. ketoprofen and extradural morphine, we conclude that ketoprofen may be an efficient alternative to extradural morphine after hip and knee arthroplasty.

Klimscha et al 1995

Hemodynamic and analgesic effects of clonidine added repetitively to continuous epidural and spinal blocks.

Klimscha W, Chiari A, Krafft P, Plattner O, Taslimi R, Mayer N, Weinstabl C, Schneider B, Zimpfer M.

Anesth Analg 1995;80(2):322–327.

Clonidine in spinal and epidural blocks prolongs anesthesia, but can cause hypotension and bradycardia. The aim of our study was to compare hemodynamic and analgesic effects of spinal versus epidural clonidine alone and after repetitive dosing. In a prospective, randomized, double-blind study, we evaluated 40 patients scheduled for lower extremity orthopedic surgery under continuous spinal or epidural anesthesia with bupivacaine 0.5% (initial dose 5 mg and 50 mg, respectively). In either spinal or epidural technique one-half of patients received clonidine (150 µg) in addition to bupivacaine. Repeat doses of the same anesthetic mixture were allowed in cases of subsequent pain. Mean arterial pressure (MAP) and heart rate were recorded for 6 h after each injection. Duration of clinically useful anesthesia was defined as the time from drug administration to first sensation of pain. Intrathecal, but not epidural, clonidine decreased MAP significantly compared with bupivacaine alone. MAP after intrathecal clonidine with bupivacaine was lower than epidural clonidine with bupivacaine 5 and 6 h after injection. Repetitive administration caused no further decrease in MAP. Onset time required to surgical anesthesia (sensory block of T11) did not differ among the four groups. Duration of spinal and epidural anesthesia was increased more than two fold by clonidine. In summary, the addition of clonidine prolongs analgesia by either route. These results may be explained by clonidine's sites of action in hemodynamic control and the density of bupivacaine-induced block.

Singelyn et al 2001

Extended femoral nerve sheath block after total hip arthroplasty: continuous versus patient-controlled techniques.

Singelyn FJ, Vanderelst PE, Gouverneur JM.

Anesth Analg 2001;92(2):455–459.

We assessed the efficacy of patient-controlled analgesia (PCA) techniques for extended femoral nerve sheath block after total hip arthroplasty. Forty-five patients were divided into three groups of 15. Over 48 h, all patients received 0.125% bupivacaine with clonidine 1 microg/mL and sufentanil 0.1 µg/ml via a femoral nerve sheath catheter as a continuous infusion at 10 ml/h in Group 1, as PCA boluses only of 10 ml/h in Group 2, or as PCA boluses of 5 ml per 30 min in Group 3. Pain scores, sensory block, supplemental analgesia, bupivacaine consumption, side effects, and satisfaction scores were recorded. Pain scores at rest and supplemental analgesia were comparable in the three groups. At 48 h, pain relief on movement was significantly better in Group 3 than in Group 1 (p=0.01). Bupivacaine consumption was significantly less in Groups 2 and 3 than in Group 1 (p<0.001). Side effects were comparable in the three groups. Satisfaction scores were significantly higher in Group 3 than in the other groups (p<0.01). We conclude that, to maintain extended femoral nerve sheath block after total hip arthroplasty, PCA techniques reduce the local anesthetic consumption without compromise in patient satisfaction or visual analog scale scores. Of the two PCA techniques tested, PCA boluses (5 ml per 30 min) of 0.125% bupivacaine with clonidine 1 microg/mL and sufentanil 0.1 µg/ml are associated with the smallest local anesthetic consumption and the most patient satisfaction.

Cox et al 2003

Toxicity of local anaesthetics.

Cox B, Durieux ME, Marcus MA.

Best Pract Res Clin Anaesthesiol 2003;17(1):111–136.

The complications of failure, neural injury and local anaesthetic toxicity are common to all regional anaesthetic techniques, and individual techniques are associated with specific complications. All potential candidates for regional anaesthesia should be thoroughly evaluated and informed of potential complications. Central neural blockades still account for more than 70% of regional anaesthesia procedures. Permanent neurological injury is 0.02-0.07%. Pain on injection and paraesthesias while performing regional anaesthesia are danger signals of potential injury and must not be ignored. The incidence of systemic toxicity to local anaesthetics has significantly decreased in the past 30 years, from 0.2 to 0.01%. Peripheral nerve blocks are associated with the highest incidence of systemic toxicity (7.5 per 10,000) and the lowest incidence of serious neural injury (1.9 per 10,000).

Fernandez-Galinski et al 1996

Spinal anesthesia with bupivacaine and fentanyl in geriatric patients.

Fernandez-Galinski D, Rue M, Moral V, Castells C, Puig MM.

Anesth Analg 1996;83:537–541.

We assessed the risks and benefits of the administration of fentanyl during spinal anesthesia in the elderly. Forty patients (70-83 yr) undergoing knee or hip replacement were studied. Preoperatively, cognitive function (minimental state examination [MMSE]), associated pathology, medications, and treatment were evaluated. Patients had spinal anesthesia with 12.5 mg bupivacaine plus saline (SS; n = 21) or 25 micrograms fentanyl (FN; n = 19). The number of ailments and drugs per patient were 2.5 and 2.3, respectively; 35%-44% of disorders were untreated, 16%-26% were symptomatic, and 33% were adequately treated. Groups were comparable regarding demographic data and characteristics of the spinal block. Group FN had more pruritus (P < 0.02) and lower SaO2 (P < 0.007), but prevalence of side effects was similar. Pain intensity (visual analog scale [VAS], facial expression test [FET] at the time of analgesia request (TAR) was lower in Group FN (P < 0.01). A poor correlation between VAS and FET (range 0.42-0.58) was obtained. MMSE at hospital discharge was no different from preoperative values. Our results show that 25 micrograms of spinal fentanyl do not modify spinal anesthesia in the elderly, but induces pruritus and O2 desaturation. The decrease in postoperative pain intensity and the preservation of cognitive function would justify the use of spinal fentanyl in the elderly.

Fournier et al 2000a

Onset and offset of intrathecal morphine versus nalbuphine for postoperative pain relief after total hip replacement.

Fournier R, Van Gessel E, Macksay M, Gamulin Z.

Acta Anaesthesiol Scand 2000a;44(8):940–945.

BACKGROUND: We designed this study to compare the postoperative analgesic effects of intrathecal morphine and nalbuphine, the endpoints being onset and offset of action. METHODS: Geriatric patients scheduled for elective total hip replacement under continuous spinal anaesthesia were randomized to two double-blinded groups in the recovery room as soon as they experienced a pain score higher than 3 cm on the visual analogue scale (VAS, 0-10 cm). Either 160 microg morphine or 400 microg nalbuphine in 4 ml normal saline were administered intrathecally. Pain scores on VAS, rescue analgesia (diclofenac and morphine, not allowed during the first 60 min), and the adverse effects (respiratory depression, postoperative nausea and vomiting, itching) were recorded for 24 h after surgery. RESULTS: The study was stopped after inclusion of 2 x 12 patients due to slow onset of analgesia in the morphine patients. In the nalbuphine group, when compared to the morphine group, the time to a pain score <3 cm (8+/-6 vs. 31+/-32 min, P<0.001), the time to the lowest pain score (18+/-11 vs. 66+/-75 min, P<0.001) and the time to the first systemic analgesic intervention for a pain score >3 cm (218+/-256 vs. 1076+/-440 min, P<0.05) were significantly shorter. The analgesic requirements during the first 24 h were significantly lower in the morphine group (P<0.001). CONCLUSION: We conclude that after total hip replacement, administration of intrathecal nalbuphine resulted in a significantly faster onset of pain relief and shorter duration of analgesia than intrathecal morphine.

Fogarty et al 1993

Comparison of the analgesic effects of intrathecal clonidine and intrathecal morphine after spinal anaesthesia in patients undergoing total hip replacement.

Fogarty DJ, Carabine UA, Milligan KR.

Br J Anaesth 1993;71(5):661–664.

We have studied the anaesthetic and analgesic properties of intrathecal clonidine and intrathecal morphine in patients undergoing total hip replacement under spinal anaesthesia. After routine spinal anaesthesia with 0.5% plain bupivacaine 2.75 ml, patients were allocated randomly to receive intrathecal clonidine, morphine or saline (control) as adjuvant to the bupivacaine. Postoperative analgesic effects were measured by consumption of morphine via patient-controlled analgesia and visual analogue pain scores. Both intrathecal clonidine and intrathecal morphine prolonged the time to first analgesia compared with saline (mean 278 (SD 93.2) min, 498 (282.4) min and 54 (61.9) min, respectively) (P < 0.001). Total morphine consumption on the first night after operation was significantly less in the intrathecal morphine group. There were no differences between the clonidine and the control group. Intrathecal clonidine prolonged the duration of spinal analgesia, but was markedly inferior to the intrathecal morphine in providing subsequent postoperative analgesia.

Rundshagen et al 1997

Continuous spinal analgesia. Comparison between patient-controlled and bolus administration of plain bupivacaine for postoperative pain relief.

Rundshagen I, Standl T, Kochs E, Muller M, Schulte am Esch J.

Reg Anesth 1997;22(2):150–156.

BACKGROUND AND OBJECTIVES: Adequate postoperative pain relief has been achieved in orthopedic patients by subarachnoid bolus administration of plain bupivacaine. This prospective randomized study compares bolus injections of bupivacaine with a patient controlled infusion via subarachnoid 28-gauge microcatheters for postoperative analgesia after elective hip replacement. METHODS: Forty-two patients (mean age, 69 +/- 11 years) were randomly allocated to one of two groups. Group. 1 patients received a constant subarachnoid infusion of 0.6 mg/h of bupivacaine by a patient-controlled device and were allowed to self-administer 0.6 mg every 30 minutes Group 2 patients received a nurse-administered bolus of 3.75 mg of plain bupivacaine on request. Pain was assessed by patients and nurses by a visual analog scale (VAS) every hour. The degree of motor block and the level of analgesia were documented every 4 hours. Hemodynamic and respiratory parameters were recorded hourly. Differences between groups were tested by analysis of variance for repeated measurement. RESULTS: Technical problems occurred in six patients were more frequent in group 1 but none in group 2. Patient-controlled analgesia resulted in lower pain scores than bolus application during 18 postoperative hours (VAS score 19 +/- 19 mm in group 1 and 39 +/- 30 mm in group 2; P < .01). Lower total doses of bupivacaine were required in group 1 (17.6 +/- 4 mg) than in group 2 (22.3 +/- 7 mg; P < .05). The groups did not differ with respect to the degree of motor block (Bromage score 3.5 +/- 0.5), the sensory level (L1-2 +/- 1), or hemodynamic or respiratory parameters. CONCLUSION: In spite of a higher incidence of technical problems, patient-controlled analgesia with a continuous background infusion via microspinal catheters provides more effective postoperative analgesia, without hemodynamic or respiratory side effects, than bolus administration

Grace et al 1995

Postoperative analgesia after co-administration of clonidine and morphine by the intrathecal route in patients undergoing hip replacement.

Grace D, Bunting H, Milligan KR, Fee JPH.

Anesth Analg 1995;80:86–91.

Postoperative analgesia after intrathecal co-administration of clonidine hydrochloride (75 micrograms) and morphine sulfate (0.5 mg) was compared with analgesia produced after either intrathecal morphine (0.5 mg) or 0.9% sodium chloride in 90 patients undergoing total hip replacement under bupivacaine spinal anesthesia. Patient-controlled morphine requirements were significantly reduced (P < 0.001) postoperation by both clonidine/morphine (median 5 mg/24 h) and morphine (median 7 mg/24 h) compared with control (saline) (median 28 mg/24 h). However, no significant additional reduction in postoperative analgesic requirements was shown with the clonidine/morphine combination compared with morphine alone. Visual analog pain scores, although good in all groups at all times, were significantly poorer in the control group at 2 h (P < 0.04) and 4 h (P < 0.001) after operation compared with both treatment groups, and significantly poorer than the clonidine/morphine group at 6 h (P < 0.002) and 24 h (P < 0.009) postoperation. Mean arterial blood pressure was significantly lower in the clonidine/morphine group than in the two other groups (P < 0.001) between 2 and 5 h after operation. The incidence of emesis was similar in the clonidine/morphine and morphine groups and was significantly more than in the control group.

Yiannakopoulos et al 2004

Innoxious removal of suction drains.

Yiannakopoulos CK, Kanellopoulos AD.

Orthopedics 2004;27(4):412–414.

Suction drains are commonly used in orthopedic elective and trauma surgery; however, drain tube removal causes pain, discomfort, and anxiety. A method of drain tube removal is described in patients who underwent total hip replacement and in adolescents who underwent lower extremity surgery. Ten milliliters of lidocaine was injected through the skin wound around the drain tube. The efficiency of this practice was evaluated using a visual analog scale score in two patient groups. Pain during tube removal and pain on post-removal were significantly decreased in the study group compared to the placebo group. Using this technique drain tube removal was painless, comfortable, and safe.

Bianconi et al 2004

The pharmacokinetics and efficacy of ropivacaine continuous wound instillation after spine fusion surgery.

Bianconi M, Ferraro L, Ricci R, Zanoli G, Antonelli T, Giulia B, Guberti A, Massari L.

Anesth Analg 2004;98(1):166–172, table of contents.

Because local anesthetic continuous wound instillation has not been evaluated after spine fusion surgery, we designed this study to determine whether this technique could enhance analgesia and improve patient outcome after posterior lumbar arthrodesis. Thirty-eight patients undergoing spine stabilization were randomly divided into two groups. The M group received a postoperative baseline IV infusion of morphine plus ketorolac for 24 h, and the R group received IV saline. In both groups, a multihole 16-gauge catheter was placed subcutaneously; in the R group, the wound was infiltrated with a solution of ropivacaine 0.5% 200 mg/40 mL, and infusion of ropivacaine 0.2% 5 mL/h was maintained for 55 h. In the M group, saline infusion was given at the same rate. Pain scores were taken at rest and on passive mobilization by nurses blinded to patient analgesic treatment. The total plasma ropivacaine concentration was evaluated. Pain scores and rescue medication requirements (diclofenac and tramadol) were significantly less in the R group than in the M group. Postoperative blood loss was less and the length of hospital stay was shorter in the R group. The ropivacaine peak total plasma concentration occurred at 24 h during infusion and was within safe limits; no toxic local anesthetic side effects were observed. These results suggest that wound infiltration and continuous instillation of ropivacaine 0.2% is effective for pain management after spine stabilization surgery. IMPLICATIONS: Postoperative pain after lumbar arthrodesis is related to soft tissue and muscle dissection and to manipulations and removal at the operation site. By blocking noxious stimuli from the surgical area, infiltration and wound perfusion with ropivacaine were more effective in controlling pain than systemic analgesia.

Bianconi et al 2003

Pharmacokinetics and efficacy of ropivacaine continuous wound instillation after joint replacement surgery.

Bianconi M, Ferraro L, Traina GC, Zanoli G, Antonelli T, Guberti A, Ricci R, Massari L.

Br J Anaesth 2003;91(6):830–835.

BACKGROUND: As continuous wound instillation with local anaesthetic has not been evaluated after hip/knee arthroplasties, our study was designed to determine whether this technique could enhance analgesia and improve patient outcome after joint replacement surgery. METHODS: Thirty-seven patients undergoing elective hip/knee arthroplasties under spinal block were randomly assigned to two analgesia groups. Group M received continuous i.v. infusion of morphine plus ketorolac for 24 h. Then, a multi-hole 16 G catheter was placed subcutaneously and infusion of saline was maintained for 55 h. Group R received i.v. saline. Thereafter the wound was infiltrated with a solution of ropivacaine 0.5% 40 ml, then a multi-hole 16 G catheter was placed subcutaneously and an infusion of ropivacaine 0.2% 5 ml h(-1) was maintained for 55 h. Visual analogue scale scores were assessed at rest and on passive mobilization by nurses blinded to analgesic treatment. Total plasma ropivacaine concentration was measured. RESULTS: Group R showed a significant reduction in postoperative pain at rest and on mobilization, while rescue medication requirements were greater in Group M. Total ropivacaine plasma concentration remained below toxic concentrations and no adverse effects occurred. Length of hospital stay was shorter in Group R. CONCLUSION: Infiltration and wound instillation with ropivacaine 0.2% is more effective in controlling postoperative pain than systemic analgesia after major joint replacement surgery.