BMJ 2000;321:1493 ( 16 December )

Papers

Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview of randomised trials

Anthony Rodgers, codirector aNatalie Walker, research fellow aS Schug, professor bA McKee, consultant anaesthetist cH Kehlet, professor dA van Zundert, consultant anaesthetist eD Sage, consultant anaesthetist fM Futter, consultant anaesthetist fG Saville, consultant anaesthetist gT Clark, statistician aS MacMahon, professor h

a Clinical Trials Research Unit, Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand, b Division of Anaesthesiology, University of Auckland, c Department of Anaesthetics, Green Lane Hospital, Epsom, Auckland 1003, New Zealand, d Department of Surgical Gastroenterology, Hvidovre University Hospital, DK-2650 Hvidovre, Denmark, e Department of Anesthesiology, Intensive Care and Pain Therapy, Catharina Hospital, Michelangelolaan 2, 5623 EJ Eindhoven, Netherlands, f Department of Anaesthesia, Auckland and Starship Hospitals, Private Bag 92024, Auckland, New Zealand, g Department of Anaesthesia, Royal Cornwall Hospital, Treliske, Truro TR1 3LJ, h Institute for International Health, University of Sydney, PO Box 1225, Crows Nest, Sydney, NSW 1585, Australia

Correspondence to: A Rodgers a.rodgers{at}ctru.auckland.ac.nz


    Abstract
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Abstract
Introduction
Methods
Results
Discussion
References

Objectives: To obtain reliable estimates of the effects of neuraxial blockade with epidural or spinal anaesthesia on postoperative morbidity and mortality.
Design: Systematic review of all trials with randomisation to intraoperative neuraxial blockade or not.
Studies: 141 trials including 9559 patients for which data were available before 1 January 1997. Trials were eligible irrespective of their primary aims, concomitant use of general anaesthesia, publication status, or language. Trials were identified by extensive search methods, and substantial amounts of data were obtained or confirmed by correspondence with trialists.
Main outcome measures: All cause mortality, deep vein thrombosis, pulmonary embolism, myocardial infarction, transfusion requirements, pneumonia, other infections, respiratory depression, and renal failure.
Results: Overall mortality was reduced by about a third in patients allocated to neuraxial blockade (103 deaths/4871 patients versus 144/4688 patients, odds ratio=0.70, 95% confidence interval 0.54 to 0.90, P=0.006). Neuraxial blockade reduced the odds of deep vein thrombosis by 44%, pulmonary embolism by 55%, transfusion requirements by 50%, pneumonia by 39%, and respiratory depression by 59% (all P<0.001). There were also reductions in myocardial infarction and renal failure. Although there was limited power to assess subgroup effects, the proportional reductions in mortality did not clearly differ by surgical group, type of blockade (epidural or spinal), or in those trials in which neuraxial blockade was combined with general anaesthesia compared with trials in which neuraxial blockade was used alone.
Conclusions: Neuraxial blockade reduces postoperative mortality and other serious complications. The size of some of these benefits remains uncertain, and further research is required to determine whether these effects are due solely to benefits of neuraxial blockade or partly to avoidance of general anaesthesia. Nevertheless, these findings support more widespread use of neuraxial blockade.


    Introduction
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Abstract
Introduction
Methods
Results
Discussion
References

Anaesthesia is commonly classified into two main techniques: general anaesthesia, in which gaseous or intravenous drugs achieve central neurological depression, and regional anaesthesia, in which drugs are administered directly to the spinal cord or nerves to locally block afferent and efferent nerve input.1 Regional anaesthesia for major thoracic, abdominal, or leg surgery relies on neuraxial blockade by injection of local anaesthetic drugs into either the subarachnoid space (spinal anaesthesia) or into the epidural space surrounding the spinal fluid sac (epidural anaesthesia).

The risks of fatal or life threatening events are increased several fold after major surgery, but there is debate about whether the type of anaesthesia has any substantive effect on these risks. Neuraxial blockade has several physiological effects that provide a rationale for expecting to improve outcome with this technique.2 However, the few clinical trials of epidural or spinal anaesthesia that have focused specifically on fatal or life threatening events have generally been too small to detect effects of plausible size reliably. To provide more reliable estimates of the effects of neuraxial blockade on postoperative morbidity and mortality, we conducted a systematic review of all relevant randomised trials.


    Methods
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Abstract
Introduction
Methods
Results
Discussion
References

Identification of trials and data collection
We sought to identify all trials in which patients were randomised to receive intraoperative neuraxial blockade (with epidural or spinal anaesthesia) or not. We did not exclude trials in adult populations in which the group receiving neuraxial blockade group also received general anaesthesia, the general anaesthesia group received postoperative neuraxial blockade, or there was more than one type of neuraxial blockade or general anaesthesia group (in which case similar groups were combined). Eligibility was not based on whether results were published, the language of publication, or the primary aims of the trial   ---   for example, we included a randomised trial designed to assess the effects of neuraxial blockade on cognitive function.3 Trials were ineligible if they were not randomised or were quasi-randomised (such as assignment according to date of birth) or if data were not available before 1 January 1997.

We conducted a computerised search using the electronic databases Current Contents (1995-6), Embase (Excerpta Medica, 1980-96), Medline (1966-96), and the Cochrane Library (1998). We used the key words "regional anaesthesia," "regional anesthesia," "spinal," or "epidural" and the Cochrane Collaboration search terms for randomised trials.4 Once papers were identified, authors' names and study titles were used as search terms. We scrutinised the reference lists of all identified papers and also hand searched selected conference proceedings.

We developed standard data collection sheets to record details of trial design, interventions, patient characteristics, and events. We did not use quality scores because analyses stratified by specific design characteristics are more informative.5 The definitions of events were those used in the original trials, since patients in one trial were directly compared only with those in the same trial. Two reviewers independently recorded the published findings from each study. This process was not blinded. A third reviewer compared the two sets of data collection sheets and any differences were resolved by discussion. We attempted to contact the authors of all trials to verify the data and obtain additional unpublished data. If there was more than one trial report, authors were also asked whether the patient groups overlapped. Lastly, we asked authors if they knew of any other relevant studies (published or unpublished).

Statistical analysis
Analysis was carried out on an intention to treat basis wherever possible. If no events were reported in the publication or by the authors, we assumed that none occurred. This assumption will generally provide unbiased estimates of proportional effects (the entity typically combined in meta-analysis) but will underestimate absolute effects.6 We calculated odds ratios, 95% confidence intervals, and two sided P values for each outcome of interest using Peto's modification of the Mantel-Haenszel method.7 Homogeneity was assessed by a chi 2 test. Whenever possible, we stratified analyses of cause specific outcomes by surgical group and type of anaesthetic to determine whether these factors modified the size or direction of proportional effects. However, there were often too few trials with events for such analyses to be informative, and so subgroup analyses are mostly reported for the crude outcome of total mortality.


    Results
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Abstract
Introduction
Methods
Results
Discussion
References

Study characteristics
We identified 158 potentially eligible trials. Ten studies were excluded because they were quasi-randomised,8-17 and six were excluded because not all participants were randomised and separate information on the randomised patients was not available.18-23 One trial was excluded because the groups differed with respect to heparin treatment as well as anaesthetic technique.24 The remaining 141 trials that met all the inclusion criteria included a total of 9559 patients. 3 25-192 More than one publication was available for 18 studies 46-49 59 60 62-65 72 73 84 85 87-92 94-96 99 100 106 107 124-128 134 135 145 146 156-158 161-163 173 174 187 188 but each study was counted only once. No unpublished eligible studies were identified.

The study authors for 107 (76%) eligible trials, including 8290 (87%) patients, verified the data collection sheets. In almost all cases, we obtained additional unpublished information from contacting the authors, mostly about trial design, but also about events (for example 18 deaths were not reported in original publications). Table 1 shows the patient characteristics and anaesthetic methods and tables 2 and 3 provide summary details of outcome events. We defined a neuraxial blockade group and a non-neuraxial blockade group for each trial, which necessitated collapsing similar groups in 15 trials with more than one randomised comparison. The neuraxial blockade group had no general anaesthesia in 79 (56%) trials and the same general anaesthesia as the non-neuraxial blockade group in 37 (26%) trials. In 22 (15%) trials the neuraxial blockade group received a general anaesthesia different from that in the non-neuraxial blockade group; the systemic opioid varied in seven trials, 28 34 43 84 120 186 192 the use of inhalational anaesthetic varied in two trials, 71 140 the type of inhalational anaesthetic varied in two trials, 148 165 the induction drug varied in one trial,191 and more than one aspect varied in 10 trials. 42 76 80 81 97 151 161 168 169 189 For three (2%) trials details of the general anaesthesia method were unknown.


                              
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Table 1. Characteristics of included studies


                              
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Table 2. Summary of vascular events and bleeding


                              
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Table 3. Summary of infection, other events, and mortality

Among the 56 trials for which follow up data were available, the mean duration of follow up was about 62 days. Only 13 trials provided follow up data beyond 30 days postoperatively. No events were recorded in 80 trials involving 2941 participants, which were mostly designed to assess the physiological, biochemical, and endocrine effects of neuraxial blockade. The mean follow up in the first 30 days these trials was 11 days, compared with 21 days in trials in which events were observed.

Overall mortality
A total of 247 deaths within 30 days of randomisation were recorded in 35 trials. Overall mortality was about one third less in the neuraxial blockade group (odds ratio 0.70, 95% confidence interval 0.54 to 0.90, P=0.006; fig 1) with no clear difference between different surgical groups (fig 2). A specific diagnosis was available for 162 of the deaths. Of these, 73 (45%) were due to pulmonary embolism, cardiac events, or stroke, 50 (31%) were due to infective causes, and 39 (24%) were due to other causes. The observed improvement in survival was due to trends towards reductions in deaths from pulmonary embolism, cardiac events, or stroke (0.73, 0.45 to 1.16), deaths from infection (0.68, 0.39 to 1.21), deaths from other causes (0.84, 0.44 to 1.61), and deaths from unknown causes (0.64, 0.41 to 1.01). There was about one fewer death per 100 patients in the 30 days after randomisation in the neuraxial blockade group (103/4871 (2.1%) versus 144/4688 (3.1%)). Only six intraoperative deaths were recorded, one of which was in the neuraxial blockade group (0.28, 0.06 to 1.45). Ten studies, with a total of 1371 patients, recorded 130 deaths between 30 days and six months. All but two of these studies were on orthopaedic patients. Overall, there was no clear effect of neuraxial blockade on deaths during this period (0.89, 0.61 to 1.28).



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Fig 1.   Effect of neuraxial blockade (NB) on postoperative mortality within 30 days of randomisation. Diamonds denote 95% confidence intervals for odds ratios of combined trial results. The vertical dashed line represents the overall pooled result. Size of shaded boxes is proportional to number of events. The overall event rates after adjusting for uneven randomisation193 were 113/5811 (1.9%) versus 158/5667 (2.8%). chi 2 test for heterogeneity between individual trials P=0.5



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Fig 2.   Effect of neuraxial blockade (NB) on postoperative mortality, by surgical group, type of neuraxial blockade, and use of general anaesthesia. Obstetrics and gynaecology trials are included with other surgery. One trial with unknown details of anaesthesia was grouped with lumbar epidural and neuraxial blockade plus general anaesthesia versus general anaesthesia comparisons. Diamonds denote 95% confidence intervals for odds ratios of combined trial results. The vertical dashed line represents the overall pooled result. Size of shaded boxes is proportional to number of events. chi 2 test for heterogeneity between different surgical groups, P=0.9

Mortality results by type of anaesthesia
Seven trials (with 826 participants) directly randomised patients to spinal or epidural anaesthesia. 25 32 77 104 153 181 Only 13 deaths occurred in these trials, four in the spinal group. However, an indirect comparison between trials of spinal and epidural anaesthesia showed no clear difference between their effects on total mortality (0.68, 0.49 to 0.95 for spinal anaesthesia and 0.68, 0.43 to 1.07 for epidural anaesthesia, P for homogeneity=1.0; fig 2). Mortality was reduced overall whether neuraxial blockade was continued postoperatively (0.68, 0.43 to 1.08) or not (0.70, 0.51 to 0.97). The effect on total mortality was not clearly lower in trials in which neuraxial blockade was combined with general anaesthesia (0.87, 0.53 to 1.41) than in trials in which neuraxial blockade was used alone (0.64, 0.47 to 0.87; P for homogeneity=0.3; fig 2). However, the confidence intervals were wide for the trials that used general anaesthesia. Forty four (18%) deaths occurred in the 22 trials in which the neuraxial blockade group had a different general anaesthesia to that used in the group not allocated neuraxial blockade. The overall effect in this group of trials (0.92, 0.49 to 1.71) was not clearly different (P for homogeneity=0.3) from that in other trials (0.66, 0.49 to 0.88).

Venous thromboembolism, cardiac events, and stroke
A total of 365 deep vein thromboses were reported from 18 trials. Neuraxial blockade reduced the risk of deep vein thrombosis by almost half (0.56, 0.43 to 0.72; fig 3). Since more than 80% of deep vein thromboses were recorded in orthopaedic trials, there was limited power to detect differences between surgical groups. In nine trials all patients were screened for deep vein thromboses by fibrinogen scanning, 59 87 129 venography, 74 114 132 187 or a combination of methods. 62 94 Proportional reductions in deep vein thromboses were similar in the trials with screening (0.56, 0.42 to 0.75) compared with other trials (0.54, 0.30 to 0.96). Therefore, absolute differences were much greater in the trials with screening (121/463 (26%) for neuraxial blockade versus 178/467 (38%) for no neuroaxial blockade) than in other trials (24/4408 (0.5%) versus 42/4221 (1.0%)). Outcome assessments were known to be blinded in only two trials, and deep vein thromboses were also reduced in these studies (0.46, 0.21 to 0.99). 66 98 A total of 96 pulmonary emboli were reported from 23 trials, 21 (22%) of which were fatal. Overall, there were about half as many pulmonary emboli in patients allocated to neuraxial blockade (0.45, 0.29 to 0.69; fig 3).



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Fig 3.   Effects of neuraxial blockade (NB) on postoperative complications. Diamonds denote 95% confidence intervals for odds ratios of combined trial results. The vertical dashed line represents the overall pooled result. Size of shaded boxes is proportional to number of events

A total of 104 myocardial infarctions were reported in 30 trials. Overall, there were about one third fewer myocardial infarctions in patients allocated to neuraxial blockade, but the confidence intervals were compatible with both no effect and a halving in risk (0.67, 0.45 to 1.00; fig 3). Only 42 strokes were reported from eight trials, and the confidence intervals were very wide for this outcome (0.85, 0.46 to 1.57; fig 3).

Bleeding
In total, 473 patients from 16 trials required transfusion of two or more units of blood and 100 patients from 12 trials had a postoperative bleed requiring a transfusion. The requirement for a transfusion of two or more units of blood was reduced by about half in patients allocated neuraxial blockade (0.50, 0.39 to 0.66; fig 3). A similar proportional reduction was found for postoperative bleeds requiring a transfusion (0.45, 0.29 to 0.70; fig 3). There was no clear difference in the proportional effects on either outcome across surgical groups.

Postoperative infection
In total, 62 wound infections were reported from 14 trials. There were fewer wound infections in those allocated to neuraxial blockade, although the confidence intervals were wide (0.79, 0.47 to 1.33; fig 3). Three hundred and eighty seven cases of pneumonia were recorded in 28 trials, of which 38 (10%) were fatal. The risk of developing pneumonia was less in patients randomised to neuraxial blockade (0.61, 0.48 to 0.76; fig 3). There was no clear difference in the proportional effects with the use of concomitant general anaesthesia (neuraxial blockade versus general anaesthesia: 0.63, 0.46 to 0.87; neuraxial blockade plus general anaesthesia versus general anaesthesia: 0.59, 0.42 to 0.81). However, there was some evidence (P for homogeneity=0.05) that the proportional reduction in pneumonia was greater after thoracic epidural anaesthesia (0.48, 0.35 to 0.67) than after lumbar epidural or spinal anaesthesia (0.76, 0.55 to 1.04). Twelve deaths due to an infective cause other than pneumonia were recorded in six trials, of which two occurred in patients allocated to neuraxial blockade (0.33, 0.10 to 1.07; fig 3).

Other postoperative events
A total of 64 cases of respiratory depression were reported from eight trials. The odds of respiratory depression were reduced by 59% in patients allocated to neuraxial blockade (0.41, 0.23 to 0.73; fig 3). The effect was present in trials with and without concomitant general anaesthesia (neuraxial blockade alone versus general anaesthesia 0.37, 0.11 to 1.21; neuraxial blockade plus general anaesthesia versus general anaesthesia 0.43, 0.22 to 0.81). Fifty cases of renal failure were recorded in 10 trials. Although the risk of renal failure was reduced in patients randomised to neuraxial blockade, the confidence intervals were wide and compatible with both no effect and a two thirds reduction (0.57, 0.32 to 1.00; fig 3).

Sensitivity analyses
We conducted several analyses to assess whether the effects on total mortality were dependent on trials with methodological problems or affected by the type of anaesthesia. However, all these tests lacked power to detect moderate sized differences.

An overall reduction in mortality was still evident after we excluded studies for which the total number of patients originally randomised was not available (0.68, 0.51 to 0.91) 26 180 ; original authors could not be contacted (0.69, 0.53 to 0.90) 36 38 40 82 83 86 103 115 118 131 137-144 147 150 153 155 166 171 172 179 181 185 190 ; more than 5% of all patients were lost to follow up or excluded after randomisation (0.69, 0.51 to 0.91) 3 14 32 38 57 62 71 74 75 94 108 113 114 120 129 130 140 159 164 165 171 173 181 187 ; or more than 5% of the neuraxial blockade group were excluded after randomisation (0.68, 0.51 to 0.91). 28 32 57 75 94 113 120 129 130 140 159 164 165 171 173 The reduction in mortality was also evident after exclusion of two trials that were stopped before scheduled completion (0.70, 0.53 to 0.91) and exclusion of unpublished data (0.67, 0.51 to 0.88). 28 46 94 109 130 165 Finally, there was no clear evidence of publication bias from tests for trend across groups defined by trial size.


    Discussion
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Abstract
Introduction
Methods
Results
Discussion
References

Our overview shows improved survival in patients randomised to neuraxial blockade. Additionally, we found reductions in risk of venous thromboembolism, myocardial infarction, bleeding complications, pneumonia, respiratory depression, and renal failure. There was no clear evidence that these effects, in proportional terms, differed by the type of surgical group or the type of neuraxial blockade, although there was limited power to assess subgroup effects reliably. Furthermore, there was no evidence of "catch up" mortality in the neuraxial blockade group between 30 days and 6 months.

The benefits seen for neuraxial blockade may be conferred by multifactorial mechanisms, including altered coagulation, increased blood flow, improved ability to breathe free of pain, and reduction in surgical stress responses.2 In particular, major surgery induces a "stress response" that is substantially altered by neuraxial blockade but not by general anaesthesia.2 This observation, together with the subgroup comparisons shown here, suggests that these benefits are principally due to the use of neuraxial blockade rather than avoidance of general anaesthesia. Thus the key issue seems to be whether neuraxial blockade is used or not, and the way in which this is achieved is less relevant.

Validity of findings
It is unlikely that bias could explain much of the reduction in mortality. We included all randomised trials, irrespective of their initial aims or reported findings. Most trials were not designed to assess major events, but it is unlikely that we missed many deaths or major non-fatal events because we contacted the authors of trials involving 87% of patients and few patients had no outcome data. However, incidence will have been underestimated for non-fatal events that often go undiagnosed, such as deep vein thrombosis. This finding will not bias relative risk estimates6 unless information is selectively available from trials with extreme results. For deep vein thrombosis, at least, the proportional effect of neuraxial blockade in trials designed to assess this outcome was similar to that in other trials. With regard to other potential biases, lack of blinding may have caused some selective misdiagnosis of non-fatal events, but analyses did not indicate publication bias and the overall reduction in mortality was not dependent on inclusion of trials with unconfirmed data or trials for which intention to treat analyses were not possible. Lastly, even though these data represent most of the randomised evidence potentially available, the confidence intervals were wide for many outcomes and relatively little information was available about cause of death.

If the proportional effects of neuraxial blockade are consistent in different patient populations, neuraxial blockade would be expected to result in about one fewer postoperative death and several fewer major complications for every 100 patients at similar risk to those in the studies. However, even though such benefits would be widely regarded as clinically important, the largest individual trial to date180 did not have the power to reliably detect effects of this size. Lack of statistical power may therefore be the principal reason why previous individual trials, editorials,194 and meta-analyses of trials in hip fracture patients 195 196 have concluded that neuraxial blockade had no important effect on mortality.

Implications
Our overview indicates that neuraxial blockade reduces major postoperative complications in a wide range of patients. However, uncertainty about the net benefits of neuraxial blockade is likely to remain among some clinicians and for some patient groups. For example, opinion is divided about whether neuraxial blockade is indicated or contraindicated in patients at risk of cardiac complications,197 and it is unclear whether the differences that we observed reflect the benefits of neuraxial blockade alone or are partly due to the avoidance of the adverse effects of general anaesthesia. Such uncertainties provide the rationale for large randomised trials, such as the ongoing multicentre Australian study of epidural anaesthesia and analgesia in major surgery.198 However, since serious complications associated with neuraxial blockade, such as spinal haematoma, are very rare199-201 and more common side effects, such as headache or urinary retention, are not life threatening, our data support recent trends towards increased use of neuraxial blockade. Furthermore, although we focused on intraoperative anaesthetic techniques, postoperative neuraxial blockade has been shown to have additional benefits, at least for pulmonary complications.202 Overall, therefore our data should result in more widespread use of spinal or epidural anaesthesia.


What is already known on this topic

Neuraxial blockade with epidural or spinal anaesthesia reduces the incidence of deep vein thrombosis and one month mortality in hip fracture patients

Insufficient evidence exists for other postoperative outcomes in this surgical group

What this study adds

Mortality was reduced by one third in patients allocated neuraxial blockade

Reductions in mortality did not differ by surgical group, type of blockade, or in trials in which neuraxial blockade was combined with general anaesthesia

Neuraxial blockade also reduced the risk of deep vein thrombosis, pulmonary embolism, transfusion requirements, pneumonia, respiratory depression, myocardial infarction, and renal failure



    Acknowledgments

We thank all trialists who confirmed data and provided extra information for this overview: T K Abboud, A R Aitkenhead, T Asoh, J F Baron, A Bayer, D Berggren, P Berthelsen, D Bigler, P K Bithal, W P Blunnie, R Bode, F Bonnet, N A Borovskikh, M R Brandt, S Bredbacka, M J Breslow, F P Buckley, K S Channer, S P Chin, R Christopherson, F Chung, E Couderc, R J Cuschieri, J B Dahl, F M Davies, M J Davies, M Davis, M De Kock, J Devulder, W Dick, N D Edwards, S M Frank, R L Garnett, S Gelman, S P Gerrish, M M Ghoneim, M S Gold, A Gottlieb, E Hakansson, M Hasenbos, H Hendolin, S W Henneberg, A Holdcroft, A Hole, R Hosoda, P L Houweling, A O Hughes, C Jayr, J Jenkins, N Jia, R D M Jones, L N Jorgensen, J Kanto, H Kehlet, A Lehtinen, M Licker, R A M Mann, P Maurette, S McGowan, P J McKenzie, A D McLaren, G Mellbring, N Melsen, I Milsom, J Modig, S Moiniche, I Murat, J M Murray, J A Odoom, M S J Pathy, J Pedersen, J S Poll, A V Pollock, J P Racle, S Raja, K Reinhart, H Renck, B Rosberg, B A Rosenfeld, H Rutberg, P Ryan, B Scheinin, W Seeling, N Sharrock, I Smilov, T Stathopoulou, R Stenseth, V I Strashnov, J Takala, J Takeda, M V Tseshinsky, H Tsuji, K J Tuman, N Valentin, J M Watters, L G Welborn, A Wessen, I W C White, C Wiessman, P Williams-Russo, M P Yeager, and O N Zabrodin. We thank Iain Chalmers, Rory Collins, Mike Davis, Konrad Jamrozik, John McCall, Tom Pedersen, John Rigg, and Charles Warlow for their helpful comments and Gary Whitlock, Xin-Hua Zhang, Philippa Day, and Valentine Kravtsov for help with translating papers.

Contributors: AR had the original idea for this study. All authors contributed actively to the protocol. NW and AR performed all searching for trials and AM, SS, and GS abstracted the data. NW and TC carried out all data analysis. AR, NW, AM, TC, and SS wrote the first draft of the paper and HK, AvZ, DS, MF, and SM made revisions. AR will act as guarantor for the paper.

    Footnotes

Funding: Health Research Council of New Zealand and Astra Pain, New Zealand. NW undertook this research during the tenure of a training fellowship from the Health Research Council of New Zealand. AR is a senior research fellow of the National Heart Foundation of New Zealand.

Competing interests: HK has received fees for consulting and speaking at meetings from AstraZeneca.


    References
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Abstract
Introduction
Methods
Results
Discussion
References

1. Cousins M, Bridenbaugh P, eds. Neural blockade in clinical anesthesia and management of pain. 2nd ed. Philadelphia: J B Lippincott, 1988.
2. Kehlet H. Modification of responses to surgery by neural blockade: clinical implications. In: Cousins M, Bridenbaugh P, eds. Neural blockade in clinical anesthesia and management of pain. 2nd ed. Philadelphia: J B Lippincott, 1988:145-188.
3. Jones M, Piggott S, Vaughan R, Bayer A, Newcombe R, Twining T, et al. Cognitive and functional competence after anaesthesia in patients aged over 60: controlled trial of general and regional anaesthesia for elective hip or knee replacement. BMJ 1990; 300: 1683-1687.
4. Dickersin K, Larson K. Establishing and maintaining an international register of RCTs. Oxford: Cochrane Collaboration, 1995.
5. Greenland S. Quality scores are useless and potentially misleading. Am J Epidemiol 1994; 140: 300-301[Free Full Text].
6. Rodgers A, MacMahon S. Systematic underestimation of treatment effects as a result of diagnostic test inaccuracy: implications for the interpretation and design of thromboprophylaxis trials. Thromb Haemost 1995; 73: 167-171[Medline].
7. Yusuf S, Peto R, Lewis J, Collins R, Sleight P. Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog Cardiovasc Dis 1985; 27: 335-371[Medline].
8. Bredbacka S, Blomback M, Hagnevik K, Irestedt L, Raabe N. Per-and postoperative changes in coagulation and fibrinolytic variables during abdominal hysterectomy under epidural or general anaesthesia. Acta Anaesthesiol Scand 1986; 30: 204-210[Medline].
9. Gregoretti S. Comparison of water, electrolyte and nitrogen balance in the postoperative period after epidural or general anesthesia: a randomised study of patients undergoing hysterectomy. Minerva Anestesiol 1985; 51: 87-91[Medline].
10. Jia N, Guo H, San Y, Liu L. Comparison of changes in plasma catecholamines between general anesthesia and general anesthesia plus epidural block. Acta Acad Med Sinicae 1991; 13: 112-114.
11. Konishi M, Yamada M, Yamada T, Noguchi J, Takeda J. The effects of halothane and epidural anesthesia on the gastric intramural pH and the pH of the gastric juice. Masui 1989; 38: 329-333[Medline].
12. Mitchell D, Friedman RJ, Baker JD, Cooke JE, Darcy MD, Miller MC. Prevention of thromboembolic disease following total knee arthroplasty. Epidural versus general anesthesia. Clin Orthop 1991; 269: 109-112.
13. Modig J, Malmberg P, Karlstrom G. Effect of epidural versus general anaesthesia on calf blood flow. Acta Anaesthesiol Scand 1980; 24: 305-309[Medline].
14. Modig J, Hjelmstedt A, Sahlstedt B, Maripuu E. Comparative influences of epidural and general anaesthesia on deep venous thrombosis and pulmonary embolism after total hip replacement. Acta Chir Scand 1981; 147: 125-130[Medline].
15. Modig J, Borg T, Karlstrom G, Maripuu E, Sahlstedt B. Thromboembolism after total hip replacement: role of epidural and general anesthesia. Anesth Analg 1983; 62: 174-180[Abstract/Free Full Text].
16. Perhoniemi V, Linko K. Hemodynamics of the legs and clinical symptoms following regional blocks for transurethral surgery. Eur Urol 1986; 12: 244-248[Medline].
17. Wickstrom I, Holmberg I, Stefansson T. Survival of female geriatric patients after hip fracture surgery. A comparison of 5 anesthetic methods. Acta Anaesthesiol Scand 1982; 26: 607-614[Medline].
18. Asoh T, Tsuji H. Post-operative complications of gastrectomy in patients with gastric cancer. (Unpublished.)
19. Rosberg B, Fredin H, Gustafson C. Anaesthetic techniques and surgical blood loss in total hip arthroplasty. Acta Anaesthesiol Scand 1982; 26: 189-193[Medline].
20. Shirasaka C, Tsuji H, Asoh T, Takeuchi Y. Role of splanchnic nerves in endocrine and metabolic response to abdominal surgery. Br J Surg 1986; 73: 142-145[Medline].
21. Tsuji H, Asoh Y, Takeuchi Y, Shirasaka C. Attenuation of adrenocortical response to upper abdominal surgery with epidural blockade. Br J Surg 1983; 70: 122-124[Medline].
22. Tsuji H, Shirasaka C, Asoh T, Takeuchi Y. Influences of splanchnic nerve blockade on endocrine-metabolic responses to upper abdominal surgery. Br J Surg 1983; 70: 437-439[Medline].
23. Uchida I, Asoh T, Shirasaka C, Tsuji H. Effect of epidural analgesia on postoperative insulin resistance as evaluated by insulin clamp technique. Br J Surg 1988; 75: 557-562[Medline].
24. Planes A, Vochelle N, Fagola M, Feret J, Bellaud M. Prevention of deep vein thrombosis after total hip replacement: the effect of low molecular weight heparin with spinal and general anaesthesia. J Bone Joint Surg Br 1991; 73B: 418-422.
25. Abboud TK, Nagappala S, Murakawa K, David S, Haroutunian S, Zakarian M, et al. Comparison of the effects of general and regional anesthesia for cesarean section on neonatal nuerologic and adaptive capacity scores. Anesth Analg 1985; 64: 996-1000[Abstract/Free Full Text].
26. Asbjorn J, Jakobsen B, Pilegaard H, Blom L, Ostergaard A, Brandt M. Mental function in elderly men after surgery during epidural analgesia. Acta Anaesthesiol Scand 1989; 33: 369-373[Medline].
27. Asoh T, Tsuji H, Shirasaka C, Takeuchi Y. Effect of epidural analgesia on metabolic response to major upper abdominal surgery. Acta Anaesthesiol Scand 1983; 27: 233-237[Medline].
28. Baron J, Bertrand M, Barre E, Godet G, Mundler O, Coriat P, et al. Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery. Anesthesiology 1991; 75: 611-618[CrossRef][Medline].
29. Berggren D, Gustafson Y, Eriksson B, Bucht G, Hansson LI, Reiz S, et al. Postoperative confusion after anesthesia in elderly patients with femoral neck fractures. Anesth Analg 1987; 66: 497-504[Abstract/Free Full Text].
30. Bigler D, Adelhoj B, Petring O, Pederson N, Busch P, Kalhke P. Mental function and morbidity after acute hip surgery during spinal and general anaesthesia. Anaesthesia 1985; 40: 672-676[Medline].
31. Blunnie W, McIlroy A, Merrett J, Dundee J. Cardiovascular and biochemical evidence of stress during major surgery associated with different techniques of anaesthesia. Br J Anaesth 1983; 55: 611-617[Abstract/Free Full Text].
32. Bode R, Lewis K, Zarich S, Pierce E, Roberts M, Kowalchuk G, et al. Cardiac outcome after peripheral vascular surgery: comparison of general and regional anesthesia. Anesthesiology 1996; 84: 3-13[CrossRef][Medline].
33. Bonnet F, Harari A, Thibonnier M, Viars P. Suppression of antidiuretic hormone hypersecretion during surgery by extradural anaesthesia. Br J Anaesth 1982; 54: 29-35[Abstract/Free Full Text].
34. Bonnet F, Touboul C, Picard A, Vodinh J, Becquemin J. Neuroleptanesthesia versus thoracic epidural anesthesia for abdominal aortic surgery. Ann Vasc Surg 1989; 3: 214-219[Medline].
35. Borovskikh N, Lebedev L, Strashkov V, Vinogradov A. Comparative evaluation of the effectiveness of epidural anesthesia with spontaneous respiration and general anesthesia in aorto-femoral bifurcation shunt. Vestn Khir Im I I Grek 1990; 145: 95-98[Medline].
36. Bottiglieri T, Petros A, Smith D, Ronzoni G, Carli F. The effect of extradural bupivacaine on CSF monoamine metabolites in surgical patients. Reg Anesth 1992; 17(Suppl): 95[Medline].
37. Brandt M, Fernandes A, Mordhorst R, Kehlet H. Epidural analgesia improves postoperative nitrogen balance. BMJ 1978; i: 1106-1108.
38. Bredahl C, Hindsolm KB, Frandsen PC. Changes in body heat during hip fracture surgery: a comparison of spinal analgesia and general anaesthesia. Acta Anaesthesiol Scand 1991; 35: 548-552[Medline].
39. Brichon P, Pison C, Chaffanjon P, Fayot P, Buchberger M, Neron L, et al. Comparison of epidural analgesia and cryoanalgesia in thoracic surgery. Eur J Cardiothorac Surg 1994; 8: 482-486[Abstract].
40. Bromage P, Shibata H, Willoughby R. Influence of prolonged epidural blockade on blood sugar and cortisol responses to operations upon the upper part of the abdomen and the thorax. Surg Gynecol Obstet 1971; 132: 1051-1056[Medline].
41. Brown A, Visram A, Jones R, Irwins M, Bacon-Shone J. Preoperative and postoperative oxygen saturation in the elderly following spinal or general anaesthesia   ---   an audit of current practice. Anaesth Intensive Care 1994; 22: 150-154[Medline].
42. Buckley F, Kehlet H, Brown N, Scott D. Postoperative glucose tolerance during extradural analgesia. Br J Anaesth 1982; 54: 325-331[Abstract/Free Full Text].
43. Chin S, Abou Madi M, Eurin B, Witvoet J, Montagne J. Blood loss in total hip replacement: extradural v. phenoperidine analgesia. Br J Anaesth 1982; 54: 491-495[Abstract/Free Full Text].
44. Christensen P, Brandt M, Rem J, Kehlet H. Influence of extradural morphine on the adrenocortical and hyperglycaemic response to surgery. Br J Anaesth 1982; 54: 23-26[Abstract/Free Full Text].
45. Christensen T, Waaben J, Lindeburg T, Vesterberg K, Vinnars E, Kehlet H. Effect of epidural analgesia on muscle amino acid pattern after surgery. Acta Chir Scand 1986; 152: 407-411[Medline].
46. Christopherson R, Beattie C, Frank S, Norris E, Meinert C, Gottlieb S, et al. Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Anesthesiology 1993; 79: 422-434[Medline].
47. Breslow M, Parker S, Frank S, Norris E, Yates H, Raff H, et al. Determinants of catecholamine and cortisol responses to lower extremity revascularization. Anesthesiology 1993; 79: 1202-1209[Medline].
48. Frank S, Beattie C, Christopherson R, Norris E, Rock P, Parker S, et al. Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia. Anesthesiology 1992; 77: 252-257[Medline].
49. Rosenfeld B, Beattie C, Christopherson R, Norris E, Frank S, Breslow M, et al. The effects of different anesthetic regimes on fibrinolysis and the development of postoperative arterial thrombosis. Anesthesiology 1993; 79: 435-443[Medline].
50. Chung F, Meier R, Lautenschlager E, Carmichael F, Chung A. General or spinal anesthesia: which is better in the elderly? Anesthesiology 1987; 67: 422-427[Medline].
51. Chung F, Chung A, Meier R, Lautenshlaeger E, Seyone C. Comparison of perioperative mental function after general anaesthesia and spinal anaesthesia with intravenous sedation. Can J Anaesth 1989; 36: 382-387[Abstract/Free Full Text].
52. Cook P, Davies M, Cronin K, Moran P. A prospective randomised trial comparing spinal anaesthesia using hyperbaric cinchocaine with general anaesthesia for lower limb vascular surgery. Anaesth Intensive Care 1986; 14: 373-380[Medline].
53. Couderc E, Mauge F, Duvaldestin P, Desmonts J. Resultats comparatifs de l'anesthesie generale et peridurale chez le grand vieillard dans la chirurgie de la hanche. Anesth Anal Reanim 1977; 34: 987-998.
54. Cuschieri R, Morran C, Howie J, McArdle C. Postoperative pain and pulmonary complications: comparison of three analgesic regimens. Br J Surg 1985; 72: 495-498[Medline].
55. Dahl J, Schultz P, Anker-Moller E, Christensen E, Staunstrup H, Carlsson P. Spinal anaesthesia in young patients using a 29-gauge needle: technical considerations and an evaluation of postoperative complaints compared with general anaesthesia. Br J Anaesth 1990; 64: 178-182[Abstract/Free Full Text].
56. Damask MC, Weissman C, Todd G. General versus epidural anesthesia for femoral-popliteal bypass surgery. J Clin Anesth 1990; 2: 71-75[CrossRef][Medline].
57. Darling J, Murray J, Hainsworth A, Trinick T. The effect of isoflurane or spinal anesthesia on indocyanine green disappearance rate in the elderly. Anesth Analg 1994; 78: 706-709[Abstract/Free Full Text].
58. Davies M, Silbert B, Mooney P, Dysart R, Meads A. Combined epidural and general anaesthesia versus general anaesthesia for abdominal aortic surgery: a prospective randomised trial. Anaesth Intensive Care 1993; 21: 790-794[Medline].
59. Davis F, Laurenson V. Spinal anaesthesia or general anaesthesia for emergency hip surgery in elderly patients. Anaesth Intensive Care 1981; 9: 352-358[Medline].
60. Davis F, Quince M, Laurenson V. Deep vein thrombosis and anaesthetic technique in emergency hip surgery. BMJ 1980; 281: 1528-1529.
61. Davis F, Woolner D, Frampton C, Wilkinson A, Grant A, Harrison R, et al. Prospective, multi-centre trial of mortality following general or spinal anaesthesia for hip fracture surgery in the elderly. Br J Anaesth 1987; 59: 1080-1088[Abstract/Free Full Text].
62. Davis F, Laurenson V, Gillespie W, Wells J, Foate J, Newman E. Deep vein thrombosis after total hip replacement: a comparison between spinal and epidural anaesthesia. J Bone Joint Surg Br 1989; 71B: 181-185.
63. Davis F, McDermott E, Hickton C, Wells E, Heaton D, Laurenson V, et al. Influence of spinal and general anaesthesia on haemostasis during total hip arthroplasty. Br J Anaesth 1987; 59: 561-571[Abstract/Free Full Text].
64. Davis F, Laurenson V, Lewis J, Wells J, Gillespie W. Metabolic response to total hip arthroplasty under hypobaric subarachnoid or general anaesthesia. Br J Anaesth 1987; 59: 725-729[Abstract/Free Full Text].
65. Davis F, Larenson V, Gillespie W, Foate J, Seagar A. Leg blood flow during total hip replacement under spinal or general anaesthesia. Anaesth Intensive Care 1989; 17: 136-143[Medline].
66. De Kock M, Crochet B, Morimont C, Scholtes J. Intravenous or epidural clonidine for intra- and postoperative analgesia. Anesthesiology 1993; 79: 525-531[CrossRef][Medline].
67. Dick W, Traub E, Kraus H, Tollner U, Burghard R, Muck J. General anaesthesia versus epidural anaesthesia for primary caesarean section   ---   a comparative study. Eur J Anaesthesiol 1992; 9: 15-21[Medline].
68. Dobson P, Caldicott L, Gerrish S, Cole J, Channer K. Changes in haemodynamic variables during transurethral resection of the prostate: comparison of general and spinal anaesthesia. Br J Anaesth 1994; 72: 267-271[Abstract/Free Full Text].
69. Donadoni R, Baele G, Rolly G, Devulder M. Influence of epidural anesthesia on coagulation factors in patients undergoing total hip replacement. Reg Anesth 1988; 13: 55.
70. Edwards N, Callaghan L, White T, Reilly C. Perioperative myocardial ischaemia in patients undergoing transurethral surgery: a pilot study comparing general with spinal anaesthesia. Br J Anaesth 1995; 74: 368-372[Abstract/Free Full Text].
71. Foate J, Horton H, Davis F. Lower limb blood flow during transurethral resection of the prostate under spinal or general anaesthesia. Anaesth Intensive Care 1985; 13: 383-386[Medline].
72. Frank S, Shir Y, Raja S, Fleisher L, Beattie C. Core hypothermia and skin surface temperature gradients. Anesthesiology 1994; 80: 502-507[CrossRef][Medline].
73. Fleisher L, Frank S, Shir Y, Estafanous M, Kelly S, Raja S. Cardiac sympathovagal balance and peripheral sympathetic vasoconstriction: epidural versus general anesthesia. Anesth Analg 1994; 79: 165-171[Abstract/Free Full Text].
74. Fredin H, Rosberg B. Anaesthetic techniques and thromboembolism in total hip arthroplasty. Eur J Anaesthesiol 1986; 3: 273-281[Medline].
75. Garnett R, MacIntyre A, Lindsay P, Barber G, Cole C, Hajjar G, et al. Perioperative ischaemia in aortic surgery: combined epidural/general anaesthesia and epidural analgesia vs general anaesthesia and iv analgesia. Can J Anaesth 1996; 43: 769-777[Abstract/Free Full Text].
76. Gelman S, Laws H, Potzick J, Strong S, Smith L, Erdemir H. Thoracic epidural vs balanced anesthesia in morbid obesity: an intraoperative and postoperative hemodynamic study. Anesth Analg 1980; 59: 902-908[Abstract/Free Full Text].
77. Ghoneim M, Hinrichs JV, O'Hara MW, Mehta MP, Pathak D, Kumar V, et al. Comparison of psychologic and cognitive functions after general or regional anesthesia. Anesthesiology 1988; 69: 507-515[CrossRef][Medline].
78. Godfrey P, Greenan J, Ranasinghe D, Shabestary S, Pollock A. Ventilatory capacity after three methods of anaesthesia for inguinal hernia repair: a randomized controlled trial. Br J Surg 1981; 68: 587-589[Medline].
79. Goertz A, Seeling W, Heinrich H, Lindner K, Schirmer U. Influence of high thoracic epidural anesthesia on left ventricular contractility assessed using the end-systolic pressure-length relationship. Acta Anaesthesiol Scand 1993; 37: 38-44[Medline].
80. Gold M, DeCrosta D, Rizzuto C, Ben-Harari R, Ramanathan S. The effect of lumbar epidural and general anesthesia on plasma catecholamines and hemodynamics during abdominal aortic aneurysm repair. Anesth Analg 1994; 78: 225-230[Medline].
81. Gottlieb A, McCoy C, Augereau P, Beven E. Hemodynamics of aortic clamping: a comparison between general and lumbar epidural anesthesia. Reg Anesth 1988; 13: 69.
82. Halevy S, Liu-Barnett M, Ross P, Roginsky M. Serum thyroid hormones changes in patients undergoing caesarean section under general or regional anaesthesia. Br J Anaesth 1978; 50: 1053-1057[Abstract/Free Full Text].
83. Haljamae H, Frid I, Holm J, Akerstrom G. Epidural vs general anaesthesia and leg blood flow in patients with occlusive atherosclerotic disease. Eur J Vasc Surg 1988; 2: 395-400[CrossRef][Medline].
84. Hasenbos M, van Egmond J, Gielen M, Crul J. Post-operative analgesia by epidural versus intramuscular nicomorphine after thoracotomy. Part 1. Acta Anaesthesiol Scand 1985; 29: 572-576[Medline].
85. Hasenbos M, van Egmond J, Gielen M, Crul J. Post-operative analgesia by epidural versus intramuscular nicomorphine after thoracotomy. Part 2. Acta Anaesthesiol Scand 1985; 29: 577-582[Medline].
86. Hedenstierna G, Lofstrom J. Effect of anaesthesia on respiratory function after major lower extremity surgery. Acta Anaesthesiol Scand 1985; 29: 55-60[Medline].
87. Hendolin H, Mattila M, Poikolainen E. The effect of lumbar epidural analgesia on the development of deep vein thrombosis of the legs after open prostatectomy. Acta Chir Scand 1981; 147: 425-429[Medline].
88. Hendolin H, Lansimies E. Skin and central temperatures during continuous epidural analgesia and general anaesthesia in patients subjected to open prostatectomy. Ann Clin Research 1982; 14: 181-186[Medline].
89. Hendolin H, Alhava E. Effect of epidural versus general anaesthesia on peroperative blood loss during retropubic prostatectomy. Int Urol Nephrol 1982; 14: 399-405[CrossRef][Medline].
90. Hendolin H, Lahtinen J, Lansimies E, Tuppurainen T. The effect of thoracic epidural analgesia on postoperative stress and morbidity. Ann Chir Gynaecol 1987; 76: 234-240[Medline].
91. Hendolin H, Tuppurainen T, Lahtinen J. Thoracic epidural analgesia and deep vein thrombosis in cholecystectomized patients. Acta Chir Scand 1982; 48: 405-409.
92. Hendolin H, Lahtinen J, Lansimies E, Tuppurainen T, Partanen K. The effect of thoracic epidural analgesia on respiratory function after cholecystectomy. Acta Anaesthesiol Scand 1987; 31: 645-651[Medline].
93. Henny C, Oddoom J, Ten Cate H, Ten Cate J, Oosterhoff R, Dabhoiwala N, et al. Effects of extradural bupivacaine on the haemostatic system. Br J Anaesth 1986; 58: 301-305[Abstract/Free Full Text].
94. Hjortso N, Neumann P, Frosig F, Anderson T, Lindhard A, Rogon E, et al. A controlled study on the effect of epidural analgesia with local anaesthetics and morphine on morbidity after abdominal surgery. Acta Anaesthesiol Scand 1985; 29: 790-796[Medline].
95. Hjortso N, Andersen T, Frosig F, Neumann P, Rogon E, Kehlet H. Failure of epidural analgesia to modify postoperative depression of delayed hypersensitivity. Acta Anaesthesiol Scand 1984; 28: 128-131[Medline].
96. Hjortso N, Christensen N, Andersen T, Kehlet H. Effects of the extradural administration of local anaesthetic agents and morphine on the urinary excretion of cortisol, catecholamines and nitrogen following abdomial surgery. Br J Anaesth 1985; 57: 400-406[Abstract/Free Full Text].
97. Holdcroft A, Hall G, Cooper G. Redistribution of body heat during anaesthesia. Anaesthesia 1979; 34: 758-764[Medline].
98. Hole A, Terjesen T, Breivik H. Epidural versus general anaesthesia for total hip arthroplasty in elderly patients. Acta Anaesthesiol Scand 1980; 24: 279-287[Medline].
99. Hole A, Unsgaard G. The effect of epidural and general anaesthesia on lymphocyte functions during and after major orthopaedic surgery. Acta Anaesthesiol Scand 1983; 27: 135-141[Medline].
100. Hole A, Unsgaard G, Breivik H. Monocyte functions are depressed during and after surgery under general anaesthesia but not under epidural anaesthesia. Acta Anaesthesiol Scand 1982; 26: 301-307[Medline].
101. Hole A. Per- and postoperative monocyte and lymphocyte functions: effects of sera from patients operated under general or epidural anaesthesia. Acta Anaesthesiol Scand 1984; 84: 287-291.
102. Hole A, Bakke O. T-lymphocytes and the subpopulations of T-helper and T-suppressor cells measured by monoclonal antibodies (T11,T4 and T8) in relation to surgery under epidural and general anaesthesia. Acta Anaesthesiol Scand 1984; 28: 296-300[Medline].
103. Homann B, Blumenberg D, Lerner H. The influence of anaesthesia on plasma levels of factor XIII. Anaesthesist 1984; 33: 145-148[Medline].
104. Houweling P, Ionescu T, Leguit P, Van Der Tweel I, Smalhout B. Comparison of the cardiovascular effects of intravenous, epidural and intrathecal sufentanil analgesia as a supplement to general anaesthesia for abdominal aortic aneurysm surgery. Eur J Anesthesiol 1993; 10: 403-411[Medline].
105. Jakobsen BW, Pederson J, Egeberg BB. Postoperative lymphocytopenia and leucocytosis after epidural and general anaesthesia. Acta Anaesthesiol Scand 1986; 30: 668-671[Medline].
106. Jayr C, Mollie A, Bourgain J, Truffa Bachi J, Treich G. Postoperative pulmonary complications after abdominal surgery: epidural compared with parenteral morphine analgesia. Reg Anesth 1988; 13: 6.
107. Jayr C, Mollie A, Bourgain J, Alarcon J, Masselot J, Lasser P, et al. Postoperative pulmonary complications: general anesthesia with postoperative parenteral morphine compared with epidural analgesia. Surgery 1988; 104: 57-63[Medline].
108. Jayr C, Thomas H, Rey A, Farhat F, Lasser P, Bourgain J. Postoperative pulmonary complications: epidural analgesia using bupivacaine and opioids versus parenteral opioids. Anesthesiology 1993; 78: 666-676[Medline].
109. Jenkins J, Fox J, Sharwood Smith G. Changes in body heat during transvesical prostatectomy. Anaesthesia 1983; 38: 748-753[Medline].
110. Jensen B, Berthelsen P, Brochner-Mortensen J. Glomerular filtration rate during halothane anaesthesia and epidural analgesia in combination with halothane anaesthesia. Acta Anaesthesiol Scand 1977; 21: 395-399[Medline].
111. Jensen CH, Berthelsen P, Kuhl C, Kehlet H. Effect of epidural analgesia on glucose tolerance during surgery. Acta Anaesthesiol Scand 1980; 24: 472-474[Medline].
112. Jia N, Luo L, Zhao J, Yan W, Liu B, Zhang Y, et al. Influence of epidural and general anesthesia on human plasma cAMP. Chin Med J 1985; 65: 30-33.
113. Jordanov K, Smilov I, Ninio A, Mincheva-Saeva M. A comparative study on epidural and general anaesthesia in elective caesarian section. Akush Ginekol (Sofiia) 1985; 24: 31-40.
114. Jorgensen L, Rasmussen L, Nielsen P, Leffers A, Albrecht Beste E. Antithrombotic efficacy of continuous extradural analgesia after knee replacement. Br J Anaesth 1991; 66: 8-12[Abstract/Free Full Text].
115. Kausalya R, Jacob R. Efficacy of low-dose epidural anaesthesia in surgery of the anal canal   ---   a randomised controlled trial. Anaesth Intensive Care 1994; 22: 161-164[Medline].
116. Keith I. Anaesthesia and blood loss in total hip replacement. Anaesthesia 1977; 32: 444-450[Medline].
117. Kokhnover S, Manevich L, Molchanova G. Comparative study of prolonged peridural anesthesia and combined general anesthesia in operative gynecology. Akush Ginekol (Sofiia) 1982; 6: 48-52.
118. Kossman B, Volk E, Spilker E, Maier V, Fehm H. Influence of thoracic epidural analgesia on glucose, cortisol, insulin and glucagon responses to surgery. Reg Anesth 1982; 7: 107-109.
119. Lehtinen AM, Laatikainen T, Koskimies AI, Hovorka J. Modifying effects of epidural analgesia or general anesthesia on the stress hormone response to laparoscopy for in vitro fertilization. J In Vitro Fert Embryo Transf 1987; 4: 23-29[CrossRef][Medline].
120. Licker M, Suter P, Krauer F, Rifat N. Metabolic response to lower abdominal surgery: analgesia by epidural blockade compared with intravenous opiate infusion. Eur J Anaesthesiol 1994; 11: 193-199[Medline].
121. Mann R, Bisset W. Anaesthesia for lower limb amputation: a comparison of spinal analgesia and general analgesia in the elderly. Anaesthesia 1983; 38: 1185-1191[Medline].
122. Maurette P, Castagnera L, Vivier C, Erny P. Psychological assessment in the elderly after general and spinal anaesthesia. Ann Fr Anesth Reanim 1988; 7: 305-308[CrossRef][Medline].
123. McGowan S, Smith G. Anaesthesia for transurethral prostatectomy: a comparison of spinal intradural analgesia with two methods of general anaesthesia. Anaesthesia 1980; 35: 847-853[Medline].
124. McKenzie P, Wishart H, Smith G. Long-term outcome after repair of fractured neck of femur. Comparison of subarachnoid and general anaesthesia. Br J Anaesth 1984; 56: 581-584[Abstract/Free Full Text].
125. McKenzie P, Wishart H, Dewar K, Gray I, Smith G. Comparison of the effects of spinal anaesthesia and general anaesthesia on postoperative oxygenation and perioperative mortality. Br J Anaesth 1980; 52: 49-54[Abstract/Free Full Text].
126. McKenzie P, Wishart H, Gray I, Smith G. Effects of anaesthetic technique on deep vein thrombosis: a comparison of subarachnoid and general anaesthesia. Br J Anaesth 1985; 57: 853-857[Abstract/Free Full Text].
127. McLaren A. Mortality studies. A review. Reg Anesth 1982; 7: S172-S174.
128. McLaren A, Stockwell M, Reid V. Anaesthetic techniques for surgical correction of fractured neck of femur: a comparative study of spinal and general anaesthesia in the elderly. Anaesthesia 1978; 33: 10-14[Medline].
129. Mellbring G, Dahlgren S, Reiz S, Sunnnegardh O. Thromboembolic complications after major abdominal surgery: effect of thoracic epidural analgesia. Acta Chir Scand 1983; 149: 263-268[Medline].
130. Melsen N, Thorshauge H. Patients experience of epidural anaesthesia and general anaesthesia. Ugeskr Laeger 1987; 149: 150-152[Medline].
131. Merhav H, Rothstein H, Eliraz A, Hana R, Pfeffermann R. A comparison of pulmonary function and oxygenation following local, spinal or general anaesthesia in patients undergoing inguinal hernia repair. Int Surg 1993; 78: 257-261[Medline].
132. Modig J, Malmberg P, Saldeen T. Comparative effects of epidural and general anesthesia on fibrinolysis function, lower limb rheology and thromboembolism after total hip replacement. Anesthesiology 1980; 53: S34[CrossRef].
133. Modig J, Maripuu E, Sahlstedt B. Thromboembolism following total hip replacement: a prospective investigation of 94 patients with emphasis on the efficacy of lumbar epidural anaesthesia in prophylaxis. Reg Anesth 1986; 11: 72-79.
134. Modig J, Karlstrom G. Intra- and post-operative blood loss and haemodynamics in total hip replacement when performed under lumbar epidural versus general anaesthesia. Eur J Anaesthesiol 1987; 4: 345-355[Medline].
135. Modig J. Beneficial effects on intraoperative and postoperative blood loss in total hip replacement when performed under lumbar epidural anesthesia. Acta Chir Scand Suppl 1988; 550: 95-103.
136. Moiniche S, Hjortso N, Blemmer T, Dahl J, Kehlet H. BP and heart rate during postoperative orthostatic stress and continuous epidural analgesia. Reg Anesth</