Epidural analgesia for pain relief following hip or knee replacement

P T Choi, M Bhandari, J Scott, J Douketis, P T Choi, M Bhandari, J Scott, J Douketis

Abstract

Background: Hip and knee replacement are common operative procedures to improve mobility and quality of life. Adequate pain relief is essential in the postoperative period to enable ambulation and initiation of physiotherapy. Lumbar epidural analgesia is a common modality for pain relief following these procedures. However, there is no systematic review of the evidence comparing the efficacy of epidural analgesia with other postoperative analgesic modalities. As the use of epidural analgesia may delay the initiation of anticoagulant thromboprophylaxis due to the potential risk of epidural hematoma, a synthesis of the evidence is necessary to determine whether or not alternative analgesic modalities are worse, equivalent, or better than epidural analgesia.

Objectives: Our objective is to answer the question: "Is lumbar epidural analgesia more efficacious than systemic analgesia or long-acting spinal analgesia for postoperative pain relief in patients after elective hip or knee replacement?"

Search strategy: MEDLINE, EMBASE, CINAHL, LILACS, and the Cochrane Controlled Trials Register were searched from their inception to June 2001. Reference lists of review articles and included studies were also reviewed for additional citations.

Selection criteria: A study was included if it was a randomized or pseudo randomized controlled clinical trial of patients undergoing hip or knee replacement, in which postoperative lumbar epidural analgesia was compared to other methods for pain relief. Study selection was performed unblinded in duplicate.

Data collection and analysis: Data were collected unblinded in duplicate. Information on the patients, methods, interventions, outcomes (pain relief, postoperative function, length of stay) and adverse events were recorded. Methodological quality was assessed using a validated 5-point scale. Meta-analysis was conducted when sufficient data existed from two or more studies. Heterogeneity testing was performed using the Breslow-Day method. The fixed effects model was used unless heterogeneity was present, in which case, a random effects model was used. Continuous data were summarized as weighted mean differences (WMD) or standardized mean differences (SMD) with 95% confidence intervals (CI). Dichotomous data were summarized as odds ratios (OR) and numbers-needed-to-treat (NNT) or numbers-needed-to-harm (NNH) with their respective 95% CI. Graphical representation of continuous data used the MetaView program.

Main results: In the first four to six hours after surgery, patients receiving epidural analgesia had less pain at rest, based on visual analog scores (VAS), than patients receiving systemic analgesia (SMD -0.77; 95% CI -1.24 to -0.31). This effect was not statistically significant by 18 to 24 hours (SMD -0.29; 95% CI -0.73 to 0.16). These observations were based only on studies evaluating populations consisting of total knee replacements alone or mixed populations of total hip or total knee replacements. For pain relief with movement after surgery, patients receiving epidural analgesia reported lower pain scores than patients receiving systemic analgesia in all four studies examining these outcomes. The choice of epidural agents may also influence the extent to which epidural analgesia differs from systemic analgesia. The differences between epidural analgesia and systemic analgesia in the frequency of nausea and vomiting (OR 0.95; 95% CI 0.60 to 1.49) or depression of breathing (OR 1.07; 95% CI 0.45 to 2.54) were not statistically significant. Sedation occurred less frequently with epidural analgesia (OR 0.30; 95% CI 0.09 to 0.97) with a number-needed-to-harm of 7.7 (95% CI 3.5 to 42.0) patients for the systemic analgesia group. Retention of urine (OR 3.50, 95% CI 1.63 to 7.51; NNH 4.5, 95% CI 2.3 to 12.2), itching (OR 4.74, 95% CI 1.76 to 12.78; NNH 6.8, 95% CI 4.4 to 15.8), and low blood pressure (OR 2.78, 95% CI 1.15 to 6.72; NNH 6.7, 95% CI 3.5 to 103) were more frequent with epidural analgesia compared to systemic analgesia. There were insufficient numbers to draw conclusions on the edural analgesia compared to systemic analgesia. There were insufficient numbers to draw conclusions on the effect of epidural analgesia on serious postoperative complications, functional outcomes, or length of hospital stay.

Reviewer's conclusions: Epidural analgesia may be useful for postoperative pain relief following major lower limb joint replacements. However, the benefits may be limited to the early (four to six hours) postoperative period. An epidural infusion of local anesthetic or local anesthetic-narcotic mixture may be better than epidural narcotic alone. The magnitude of pain relief must be weighed against the frequency of adverse events. The current evidence is insufficient to draw conclusions on the frequency of rare complications from epidural analgesia, postoperative morbidity or mortality, functional outcomes, or length of hospital stay.

Conflict of interest statement

The authors of this Cochrane review have never received any honoraria or consulting fees from pharmaceutical companies that produce anticoagulants or analgesics. The authors do not have any commercial interest in anticoagulant thromboprophylaxis or postoperative analgesia and they do not hold any patents related to these fields.

Figures

1.1. Analysis
1.1. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 1 Early (4‐6 hours) postoperative pain relief at rest.
1.2. Analysis
1.2. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 2 Late (18‐24 hours) postoperative pain relief at rest.
1.3. Analysis
1.3. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 3 Early (4‐6 hours) postoperative dynamic pain relief.
1.4. Analysis
1.4. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 4 Nausea or vomiting.
1.5. Analysis
1.5. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 5 Sedation.
1.6. Analysis
1.6. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 6 Urinary retention.
1.7. Analysis
1.7. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 7 Pruritis.
1.8. Analysis
1.8. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 8 Respiratory depression.
1.9. Analysis
1.9. Analysis
Comparison 1 Epidural analgesia versus systemic analgesia, Outcome 9 Hypotension.

References

References to studies included in this review Bertini 1995 {published data only}

    1. Bertini L, Tagariello V, Molino FM, Posteraro CM, Mancini S, Rossignoli L. [Patient‐controlled postoperative analgesia in orthopedic surgery: epidural PCA versus intravenous PCA]. [Italian]. Minerva Anestesiologica 1995;61(7‐8):319‐28.
Capdevila 1999 {published data only}
    1. Capdevila X, Barthelet Y, Biboulet P, Ryckwaert Y, Rubenovitch J, d'Athis F. Effects of perioperative analgesic technique on the surgical outcome and duration of rehabilitation after major knee surgery [see comments]. Anesthesiology 1999;91(1):8‐15.
D'Ambrosio 1999 {published data only}
    1. D'Ambrosio A, Borghi B, Damato A, D'Amato G, Antonacci D, Valeri F. Reducing perioperative blood loss in patients undergoing total hip arthroplasty. International Journal of Artificial Organs 1999;22(1):47‐51.
Gustafsson 1986 {published data only}
    1. Gustafsson LL, Johannisson J, Garle M. Extradural and parenteral pethidine as analgesia after total hip replacement: Effects and kinetics. A controlled clinical study. European Journal of Clinical Pharmacology 1986;29(5):529‐34.
Hendolin 1996 {published data only}
    1. Hendolin H, Nuutinen L, Kokki H, Tuomisto L. Does morphine premedication influence the pain and consumption of postoperative analgesics after total knee arthroplasty?. Acta Anaesthesiologica Scandinavica 1996;40(1):81‐85.
Hommeril 1994 {published data only}
    1. Hommeril JL, Bernard JM, Gouin F, Pinaud M. Ketoprofen for pain after hip and knee arthroplasty. British Journal of Anaesthesia 1994;72(4):383‐87.
Jorgensen 1991 {published data only}
    1. Jorgensen LN, Rasmussen LS, Nielsen PT, Leffers A, Albrecht BE. Antithrombotic efficacy of continuous extradural analgesia after knee replacement [see comments]. British Journal of Anaesthesia 1991;66(1):8‐12.
Klasen 1999 {published data only}
    1. Klasen JA, Opitz SA, Melzer C, Thiel A, Hempelmann G. Intraarticular, epidural, and intravenous analgesia after total knee arthroplasty. Acta Anaesthesiologica Scandinavica 1999;43(10):1021‐26.
Moiniche 1994 {published data only}
    1. Moiniche S, Hjortso NC, Hansen BL, Dahl JB, Rosenberg J, Gebuhr P, et al. The effect of balanced analgesia on early convalescence after major orthopaedic surgery. Acta Anaesthesiologica Scandinavica 1994;38(4):328‐35.
Sharrock 1994 {published data only}
    1. Sharrock NE, Urquhart BL, Ganz S, Williams‐Russo PG. Epidural infusions of bupivacaine and fentanyl do not improve rehabilitation following one‐stage bilateral total knee arthroplasty. Annals of the Academy of Medicine, Singapore 1994;23(6 Suppl):3‐9.
Singelyn 1998 {published data only}
    1. Singelyn FJ, Deyaert M, Joris D, Pendeville E, Gouverneur JM. 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 knee arthroplasty. Anesthesia & Analgesia 1998;87(1):88‐92.
Weller 1991 {published data only}
    1. Weller R, Rosenblum M, Conard P, Gross JB. Comparison of epidural and patient‐controlled intravenous morphine following joint replacement surgery. Canadian Journal of Anaesthesia 1991;38(5):582‐86.
Wulf 1999 {published data only}
    1. Wulf H, Biscoping J, Beland B, Bachmann‐Mennenga B, Motsch J. Ropivacaine epidural anesthesia and analgesia versus general anesthesia and intravenous patient‐controlled analgesia with morphine in the perioperative management of hip replacement. Ropivacaine Hip Replacement Multicenter Study Group. Anesthesia & Analgesia 1999;89(1):111‐16.
References to studies excluded from this review Allen 1986 {published data only}
    1. Allen PD, Walman T, Concepcion M. Epidural morphine provides postoperative pain relief in peripheral vascular and orthopedic surgical patients: A dose‐response study. Anesthesia & Analgesia 1986;65(2):165‐70.
Allen 1998 {published data only}
    1. Allen JG, Denny NM, Oakman N. Postoperative analgesia following total knee arthroplasty: a study comparing spinal anesthesia and combined sciatic femoral 3‐in‐1 block [see comments]. Regional Anesthesia & Pain Medicine 1998;23(2):142‐6.
Banning 1986 {published data only}
    1. Banning AM, Schmidt JF, Chraemmer JB, Risbo A. Comparison of oral controlled release morphine and epidural morphine in the management of postoperative pain. Anesthesia & Analgesia 1986;65(4):385‐88.
Bennett 1994 {published data only}
    1. Bennett LP. Lumbar plexus block for the management of acute pain. Orthopaedic Nursing 1994;13(3):9‐14.
Carabine 1992 {published data only}
    1. Carabine UA, Milligan KR, Mulholland D, Moore J. Extradural clonidine infusions for analgesia after total hip replacement. British Journal of Anaesthesia 1992;68(4):338‐43.
Cooper 1993 {published data only}
    1. Cooper DW, Turner G. Patient‐controlled extradural analgesia to compare bupivacaine, fentanyl and bupivacaine with fentanyl in the treatment of postoperative pain. British Journal of Anaesthesia 1993;70(5):503‐7.
D'Ambrosio 1998 {published data only}
    1. D'Ambrosio A, Borghi B, Damato A, D'Amato G, Antonacci D, Grossi P. Interactions between epidural analgesia and antifibrinolytics. Anaesthesia 1998;53 Suppl 2:57‐58.
Dahn 1999 {published data only}
    1. Dahn J, Oster M, Moltner A, Wohrle C, Ratzer FA, Ackern K, et al. [Anesthesia in geriatric patients. The determination of physiological variables for cognitive function in geriatric patients after regional or general anesthesia]. [German]. Anaesthesist 1999;48(6):379‐86.
Dalldorf 1994 {published data only}
    1. Dalldorf PG, Perkins FM, Totterman S, Pellegrini VD, Jr. Deep venous thrombosis following total hip arthroplasty. Effects of prolonged postoperative epidural anesthesia [see comments]. Journal of Arthroplasty 1994;9(6):611‐16.
Dauphin 1997 {published data only}
    1. Dauphin A, Raymer KE, Stanton EB, Fuller HD. Comparison of general anesthesia with and without lumbar epidural for total hip arthroplasty: effects of epidural block on hip arthroplasty. Journal of Clinical Anesthesia 1997;9(3):200‐3.
Erskine 1994 {published data only}
    1. Erskine R, Janicki PK, Neil G, James MF. Spinal anaesthesia but not general anaesthesia enhances neutrophil biocidal activity in hip arthroplasty patients. Canadian Journal of Anaesthesia 1994;41(7):632‐38.
Feller 1992 {published data only}
    1. Feller JA, Parkin JD, Phillips GW, Hannon PJ, Hennessy O, Huggins RM. Prophylaxis against venous thrombosis after total hip arthroplasty. Australian & New Zealand Journal of Surgery 1992;62(8):606‐10.
Fogarty 1993 {published data only}
    1. Fogarty DJ, Carabine UA, Milligan KR. Comparison of the analgesic effects of intrathecal clonidine and intrathecal morphine after spinal anaesthesia in patients undergoing total hip replacement. British Journal of Anaesthesia 1993;71(5):661‐64.
Grace 1995 {published data only}
    1. Grace D, Fee JP. Ineffective analgesia after extradural tramadol hydrochloride in patients undergoing total knee replacement. Anaesthesia 1995;50(6):555‐58.
Kampe 1999 {published data only}
    1. Kampe S, Weigand C, Kaufmann J, Klimek M, Konig DP, Lynch J. Postoperative analgesia with no motor block by continuous epidural infusion of ropivacaine 0.1% and sufentanil after total hip replacement. Anesthesia & Analgesia 1999;89(2):395‐98.
Kohro 1998 {published data only}
    1. Kohro S, Yamakage M, Arakawa J, Kotaki M, Omote T, Namiki A. Surgical/tourniquet pain accelerates blood coagulability but not fibrinolysis. British Journal of Anaesthesia 1998;80(4):460‐63.
Kopacz 1999 {published data only}
    1. Kopacz DJ, Sharrock NE, Allen HW. A comparison of levobupivacaine 0.125%, fentanyl 4 mu g/ml, or their combination for patient‐controlled epidural analgesia after major orthopedic surgery. Anesthesia & Analgesia 1999;89(6):1497‐1503.
Lauretti 1999a {published data only}
    1. Lauretti GR, Oliveira R, Reis MP, Juliao M‐DC, Pereira NL. Study of three different doses of epidural neostigmine coadministered with lidocaine for postoperative analgesia. Anesthesiology 1999;90(6):1534‐38.
Lauretti 1999b {published data only}
    1. Lauretti GR, Oliveira R, Reis MP, Mattos AL, Pereira NL. Transdermal nitroglycerine enhances spinal sufentanil postoperative analgesia following orthopedic surgery. Anesthesiology 1999;90(3):734‐39.
Markel 1997 {published data only}
    1. Markel DC, Urquhart B, Derkowska I, Salvati EA, Sharrock NE. Effect of epidural analgesia on venous blood flow after hip arthroplasty. Clinical Orthopaedics & Related Research 1997;334:168‐74.
Mauerhan 1997 {published data only}
    1. Mauerhan DR, Campbell M, Miller JS, Mokris JG, Gregory A, Kiebzak GM. Intra‐articular morphine and/or bupivacaine in the management of pain after total knee arthroplasty. Journal of Arthroplasty 1997;12(5):546‐52.
McBeath 1995 {published data only}
    1. McBeath DM, Shah J, Sebastian L, Sledzinski K. The effect of patient controlled analgesia and continuous epidural infusion on length of hospital stay after total knee or total hip replacement. CRNA ‐ the Clinical Forum for Nurse Anesthetists 1995;6(1):31‐6.
Mitchell 1991 {published data only}
    1. Mitchell D, Friedman RJ, Baker JD, III, Cooke JE, Darcy MD, Miller MC, III. Prevention of thromboembolic disease following total knee arthroplasty. Epidural versus general anesthesia. Clinical Orthopaedics & Related Research 1991;269:109‐12.
Modig 1976 {published data only}
    1. Modig J. Respiration and circulation after total hip replacement surgery. A comparison between parenteral analgesics and continuous lumbar epidural block. Acta Anaesthesiologica Scandinavica 1976;20(3):225‐36.
Mollmann 1999 {published data only}
    1. Mollmann M, Cord S, Holst D, Auf‐der LU. Continuous spinal anaesthesia or continuous epidural anaesthesia for post‐operative pain control after hip replacement?. European Journal of Anaesthesiology 1999;16(7):454‐61.
Murphy 1984 {published data only}
    1. Murphy DF, MacGrath P, Stritch M. Postoperative analgesia in hip surgery. A controlled comparison of epidural buprenorphine with intramuscular morphine. Anaesthesia 1984;39(2):181‐3.
Nielsen 1990 {published data only}
    1. Nielsen PT, Jorgensen LN, Albrecht BE, Leffers AM, Rasmussen LS. Lower thrombosis risk with epidural blockade in knee arthroplasty. Acta Orthopaedica Scandinavica 1990;61(1):29‐31.
Nielson 1990 {published data only}
    1. Nielson WR, Gelb AW, Casey JE, Penny FJ, Merchant RN, Manninen PH. Long‐term cognitive and social sequelae of general versus regional anesthesia during arthroplasty in the elderly. Anesthesiology 1990;73(6):1103‐9.
Niemi 1994 {published data only}
    1. Niemi L, Pitkanen M, Tuominen M, Rosenberg PH. Technical problems and side effects associated with continuous intrathecal or epidural post‐operative analgesia in patients undergoing hip arthroplasty. European Journal of Anaesthesiology 1994;11(6):469‐74.
Pati 1994 {published data only}
    1. Pati AB, Perme DC, Trail M, Henry PK, Bryan WJ. Rehabilitation parameters in total knee replacement patients undergoing epidural vs. conventional analgesia. Journal of Orthopaedic & Sports Physical Therapy 1994;19(2):88‐92.
Raj 1987 {published data only}
    1. Raj PP, Knarr DC, Vigdorth E, Denson DD, Pither CE, Hartrick CT, et al. Comparison of continuous epidural infusion of a local anesthetic and administration of systemic narcotics in the management of pain after total knee replacement surgery. Anesthesia & Analgesia 1987;66(5):401‐6.
Segstro 1991 {published data only}
    1. Segstro R, Morley‐Forster PK, Lu G. Indomethacin as a postoperative analgesic for total hip arthroplasty. Canadian Journal of Anaesthesia 1991;38(5):578‐81.
Sharrock 1992 {published data only}
    1. Sharrock NE, Go G. Fibrinolytic activity following total knee arthroplasty under epidural or general anesthesia. Regional Anesthesia 1992;17(Supplement 3):94‐4.
Sharrock 1997 {published data only}
    1. Sharrock NE, Go G, Williams RP, Haas SB, Harpel PC. Comparison of extradural and general anaesthesia on the fibrinolytic response to total knee arthroplasty [see comments]. British Journal of Anaesthesia 1997;79(1):29‐34.
Silvasti 2000 {published data only}
    1. Silvasti M, Pitkanen M. Continuous epidural analgesia with bupivacaine‐fentanyl versus patient‐controlled analgesia with i.v. morphine for postoperative pain relief after knee ligament surgery. Acta Anaesthesiologica Scandinavica 2000;44(1):37‐42.
Singelyn 1999 {published data only}
    1. Singelyn FJ, Gouverneur JM. Postoperative analgesia after total hip arthroplasty: i.v. PCA with morphine, patient‐controlled epidural analgesia, or continuous "3‐in‐1" block?: a prospective evaluation by our acute pain service in more than 1300 patients. Journal of Clinical Anesthesia 1999;11(7):550‐4.
Tsueda 1998 {published data only}
    1. Tsueda K, Mosca PJ, Heine MF, Loyd GE, Durkis DA, Malkani AL, et al. Mood during epidural patient‐controlled analgesia with morphine or fentanyl. Anesthesiology 1998;88(4):885‐91.
Turner 1996 {published data only}
    1. Turner G, Blake D, Buckland M, Chamley D, Dawson P, Goodchild C, et al. Continuous extradural infusion of ropivacaine for prevention of postoperative pain after major orthopaedic surgery. British Journal of Anaesthesia 1996;76(5):606‐10.
Weir 1998 {published data only}
    1. Weir PS, Fee JPH. Double‐blind comparison of extradural block with three bupivacaine‐ketamine mixtures in knee arthroplasty. British Journal of Anaesthesia 1998;80(3):299‐301.
Wilder‐Smith 1998 {published data only}
    1. Wilder‐Smith CH, Wilder‐Smith OH, Farschtschian M, Naji P. Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing. Acta Anaesthesiologica Scandinavica 1998;42(3):299‐305.
Williams‐Russo 1992 {published data only}
    1. Williams‐Russo RP, Urquhart BL, Sharrock NE, Charlson ME. Post‐operative delirium: Predictors and prognosis in elderly orthopedic patients. Journal of the American Geriatrics Society 1992;40(8):759‐67.
Wong 1997 {published data only}
    1. Wong CS, Lu CC, Cherng CH, Ho ST. Pre‐emptive analgesia with ketamine, morphine and epidural lidocaine prior to total knee replacement. Canadian Journal of Anaesthesia 1997;44(1):31‐7.
Wright 1992 {published data only}
    1. Wright PM, Fee JP. Cardiovascular support during combined extradural and general anaesthesia. British Journal of Anaesthesia 1992;68(6):585‐9.
Zayas 1999 {published data only}
    1. Zayas VM, Liguori GA, Chisholm MF, Susman MH, Gordon MA. Dose response relationships for isobaric spinal mepivacaine using the combined spinal epidural technique. Anesthesia & Analgesia 1999;89(5):1167‐71.
References to studies awaiting assessment Lopes 1999 {published data only}
    1. Lopes MB, Sousa LR, Porsani DF, Amaral AGV, Boas‐AV J, Birchta SR. Association of intra‐articular bupivacaine and morphine for arthroscopic knee surgery postoperative analgesia. Revista Brasiliera de Anestesiologia 1999;49(3):165‐8.
Additional references Ballantyne 1998
    1. Ballantyne JC, Carr DB, deFerranti S, Suarez T, Lau J, Chalmers TC, et al. The comparative effects of postoperative analgesic therapies on pulmonary outcome: cumulative meta‐analyses of randomized, controlled trials [see comments]. Anesthesia & Analgesia 1998;86(3):598‐612.
Beattie 2001
    1. Beattie WS, Badner NH, Choi P. Epidural analgesia reduces postoperative myocardial infarction: A meta‐analysis. Anesthesia & Analgesia 2001;93(4):853‐8.
Breslow 1980
    1. Breslow NE, Day NE. Statistical Methods in Cancer Research: The Analysis of Case‐Control Studies. Vol. 1, Lyons: International Agency for Research on Cancer, 1980.
Choi 2003
    1. Choi P, Bhandari M, Scott J, Douketis JD. Epidural analgesia for pain relief following hip or knee replacement. Cochrane Database of Systematic Reviews 2003, Issue 3. [DOI: 10.1002/14651858.CD003071]
Clagett 1998
    1. Clagett GP, Anderson FA, Jr, Geerts W, Heit JA, Knudson M, Lieberman, JR, et al. Prevention of venous thromboembolism [see comments]. [Review] [424 refs]. Chest 1998;114(5 Suppl):531S‐60S.
DerSimonian 1986
    1. DerSimonian R, Laird N. Meta‐analysis in clinical trials. Controlled Clinical Trials 1986;7(3):177‐88.
Harris 1990
    1. Harris WH, Sledge CB. Total hip and total knee replacement (1). [Review] [76 refs]. New England Journal of Medicine 13‐9‐1990;323(11):725‐31.
Hull 1993
    1. Hull R, Raskob G, Pineo G, Rosenbloom D, Evans W, Mallory T, Anquist, K, Smith F, Hughes G, Green D. A comparison of subcutaneous low‐molecular‐weight heparin with warfarin sodium for prophylaxis against deep‐vein thrombosis after hip or knee implantation [see comments]. New England Journal of Medicine 4‐11‐1993;329(19):1370‐1376.
Jadad 1996
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, McQuay HJ. Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Controlled Clinical Trials 1996;17(1):1‐12.
Lawton 1995
    1. Lawton MT, Porter RW, Heiserman JE, Jacobowitz R, Sonntag VK, Dickman, CA. Surgical management of spinal epidural hematoma: relationship between surgical timing and neurological outcome [see comments]. Journal of Neurosurgery 1995;83(1):1‐7.
Leclerc 1996
    1. Leclerc JR, Geerts WH, Desjardins L, Laflamme GH, L'Esperance B, Demers C, Kassis J, Cruickshank M, Whitman L, Delorme F. Prevention of venous thromboembolism after knee arthroplasty. A randomized, double‐blind trial comparing enoxaparin with warfarin [see comments]. Annals of Internal Medicine 1‐4‐1996;124(7):619‐26.
Levine 1991
    1. Levine MN, Hirsh J, Gent M, Turpie AG, Leclerc J, Powers PJ, Jay RM, Neemeh J. Prevention of deep vein thrombosis after elective hip surgery. A randomized trial comparing low molecular weight heparin with standard unfractionated heparin [see comments]. Annals of Internal Medicine 1‐4‐1991;114(7):545‐51.
Leyvraz 1991
    1. Leyvraz PF, Bachmann F, Hoek J, Buller HR, Postel M, Samama M, et al. Prevention of deep vein thrombosis after hip replacement: randomised comparison between unfractionated heparin and low molecular weight heparin [published erratum appears in BMJ 1991 Nov 16;303(6812);1243] [see comments]. BMJ 7‐9‐1991;303(6802):543‐8.
Planes 1988
    1. Planes A, Vochelle N, Mazas F, Mansat C, Zucman J, Landais A, et al. Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thrombosis & Haemostasis 22‐12‐1988;60(3):407‐10.
Rodgers 2000
    1. Rodgers A, Walker N, Schug S, McKee A, Kehlet H, Zundert A, et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials. BMJ 2000;321:1‐12.
Schroeder 1998
    1. Schroeder DR. Statistics: detecting a rare adverse drug reaction using spontaneous reports [see comments]. Regional Anesthesia & Pain Medicine 1998;23(6 Suppl 2):183‐9.

Source: PubMed

3
Subskrybuj