Effects of regional anesthesia on perioperative outcome

ELSEVIER

Effects of Regional Anesthesia on Perioperative Outcome Peter G. Atanassoff, MD* Department

of Anesthesiology,

Yale University School of Medicine, New Haven, CT.

To provide an overview of current knowledge, this article retriews experimental and clinical data from investigations examining effects of regional anesthesia on perioperatiue morbidity in specific physiologic systems. The issues of morbidity and mortality following general and regional anesthesia are addressed, as are the development of perio@rative thromboembolism and blood loss, which are known to be increased during general anesthesia. Finally, the effects of regional anesthesia on the zlascular system, the perioperative stress response, and the pulmonary function are discussed. Keywords: Anesthesia, regional: brachial intercostal, spinal; operative outcome.

plexus; cervical plexus, epidural,

Introduction

*Assistant Professor of Anesthesiology Address correspondence to Dr. Atanassoff at the Department of Anesthesiology, T-3, Yale University School of Medicine, 333 Cedar St., P.O. Box 208051, New Haven, CT 065108051, USA. Received for publication August 15, 1995; revised manuscript accepted for publication January 9,1996.

Anesthesiologists are divided in their preference for regional versus general anesthesia. Both advocates of regional anesthesia and advocates of general anesthesia can quote personal experience and published investigations supporting their positions. A literature review dealing with this topic inevitably leads to opposite conclusions about the superiority of one or the other anesthetic technique. In 1936 Nygaard’ published an investigation comparing spinal and general anesthesia. He found fewer postoperative complications with spinal anesthesia than with an open-drop ether anesthetic. Since then, numerous additional investigators have compared outcome following regional and general anesthesia. Depending on the operative procedure, there are advantages of one anesthetic technique over the other, but many studies still show conflicting results. Scott and Kehlet* concluded that mortality and morbidity are most likely decreased by using regional anesthesia for surgical procedures below the umbilicus. An earlier publication released by Kehlet3 was more skeptical about this evidence. One approach for resolving the controversy may be to conduct large, multicenter, double-blinded, randomized, controlled trials that would simultaneously include covariates such as age, gender, ASA physical status, type of surgery, and other coexisting diseases. Such an investigation would further include various treatment groups, such as several kinds of general anesthesia, which would then be compared with different regional anesthetic techniques. The major drawback of many investigations is the small study size, having low statistical power to reveal real differences. Thus far, only once has a large multicenter study comparing types of general anesthesia been attempted,4Z5 This investigation included more than 17,000 patients, but was unable to find differences between death rates, myocardial infarction (MI), and stroke using various inhalational drugs and fentanyl anesthesia. Most likely, for lack of resources, researchers, and enthusiasm, a study of regional anesthesia versus general anesthesia of comparable size will not be attempted in the near future. In the past few decades, considerable advances have been made in the understanding of pain and the metabolic effects after surgery, coincident with a rapid expansion in anesthetic knowledge and refinement of techniques. With

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Regional anesthesia and penoperative outcome: Atanassoff

these advances, the concept of a “stress-free” perioperative period was developed. Its proponents argue that the side effects of surgery may not only be related to imperfections in perioperative technique, but may also result from inadequate pain relief and increased demands on the various organ systems caused by a marked catabolic response, which occurs after injury and trauma.6” Thus, one may reason that techniques that improve pain relief and modify this response to maintain normal organ function might lead to reduced morbidity and even mortality.’ While regional anesthesia in its present form is still not ideal, it is nevertheless the most physiologic way of providing anesthesia and analgesia. Numerous studies have shown that regional anesthesia and analgesia reduces perioperative physiologic responses to surgical stress and also provides superior pain relief. There is complete blockade of afferent input in surgical procedures below the umbilicus,’ and a great deal of the stress response can be blunted with extensive blockade (T&G, to pinprick) for upper abdominal and thoracic surgery.g The effects of regional anesthesia on perioperative outcome, particularly in ASA physical I and II patients, however, remain controversial. This article is a selective review of the effects of regional anesthesia and perioperative outcome. Most of the studies included deal with a small number of patients, and the conclusions drawn are based on available information.

Morbidity and Mortality General Anesthesia

Following

Regional

and

Mortality is a crude but nevertheless well-defined endpoint. Its incidence in modern elective surgery is very low, necessitating large numbers of patients to be studied before any benefit can be attributed to a particular regimen. Perioperative morbidity and mortality of high risk patients may be influenced by the anesthesiologist’s choice of regional or general anesthesia. Before 1987, there were 12 controlled mortality studies comparing regional anesthesia with general anesthesia in patients undergoing acute hip surgery.“-*I These high-risk patients are elderly, often malnourished, and frequently have concomitant multi-organ disease. Although only two of these studies showed a significant benefit from regional anesthesia on short-term survival,11~14 pooling of data shows that overall there was nearly a 30% reduction in early mortality in the regional anesthesia group (regional anesthesia = 6.9% mortality US.general anesthesia = 10.3% mortality). Wickstriim et aZ., in 1982 published survival rates of patients following administration of five different anesthetic methods. Patients undergoing hip surgery were given epidural, neurolept analgesia, ketamine, enflurane, or halothane anesthesia. The rate of survival was studied up to four years after surgery. Survival rates after one and six months were 93.5% and 82.8%, respectively, and after two and four years 69.8% and 50.3%, respectively. High age combined with trochanteric fracture, in contrast to neck fractures, carried the highest mortality. If the impact of age and type

of fracture were eliminated, no significant difference was seen between the anesthetic methods. The outcome after treatment for hip fractures largely depends on two major factors: the premorbid condition such as age, complicating disease, and general condition, and the treatment. Patients in the epidural and ketamine groups were older, there was a higher incidence of hypertension in the epidural and neurolept anesthesia groups, and most important in this particular surgery, patients with epidural anesthesia had a longer fracture-operation interval. These factors may have contributed to the relatively higher mortality rate in the epidural group. On the other hand, mortality was lowest in the epidural group in patients older than 80 years, particularly those with a trochanteric fracture. Sharrock and colleagues” recently carried out a loyear retrospective review of in-hospital mortality rates after elective total hip and knee arthroplasty. Patients with metastatic cancer and acute hip fractures were excluded from the study, because mortality in patients with metastatic cancer may be as high as 50%. In the 197Os, mortality rate after total hip replacement was reported to be between 1% and 2%.22,23 From 1981 to 1985, Sharrock et al. found an overall mortality rate of 0.39%, which was reduced to 0.1% during the years 1987 to 1991. Pulmonary embolism was either the presumptive or definitive cause of death in seven of the patients who died in the early 198Os, and in two patients who died during 1987 to 1991. Marked changes in anesthesia management in the latter period, including the almost universal use of epidural anesthetics, improved perioperative monitoring, and postoperative epidural analgesia with early ambulation most likely contributed to this improvement in outcome. Additionally, a number of nonanesthetic related changes, such as new medications (antibiotics, angiotensin-converting enzyme blockers, and beta-blockers), increased use of autologous blood transfusions, and reduction in the duration of surgery also may have contributed to this improved outcome. Several other investigations, one of a diverse surgical populationZ4 and three of patients undergoing either lower extremity, vascular, or carotid surgery,25-28 evaluated the effects of epidural anesthesia and cervical plexus block on postoperative morbidity in high-risk surgical patients. In the studies of Yeager et aLZ4 and Tuman et aZ.,25 when compared with a control group given a standard general anesthetic technique alone, patients who received an additional epidural anesthetic had a significant reduction in the overall postoperative complication rate (9 complications of 28 patients US. 19 of 25 patients, and 52 complications of 40 patients VS. 13 of 40, respectively). Lower mortality rates,24 cardiovascular failure and major infections,24,2’ and vascular occlusions,25 respectively, were found in those patients with an additional epidural anesthetic. Other authors found no such improvement in patients undergoing vascular surgery.2g-31 However, in one of these studies, three different postoperative analgesic regimens were administered. These regimens were left to the responsibility of the attending anesthesiologist, without being prospectively defined.*’ The authors concluded that postoperative epidural analgesia, rather than its intra-

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SpecialArticles operative use, was the factor responsible for reducing the incidence of postoperative cardiac and respiratory complications. In patients undergoing endarterectomy with either general anesthesia or cervical plexus block, one encounters a greater incidence of cardiovascular and pulmonary complications associated with general anesthesia.26,28 Studies evaluating myocardial oxygen consumption and the incidence of myocardial ischemia and MI in patients with two or more risk factors for coronary artery disease undergoing abdominal aortic surgery revealed a decreased incidence of these events in patients treated with perioperative epidural anesthesia.32,33 Postoperatively, there was a significantly lower incidence of tachycardia, ischemia, and MI in those patients given an epidural anesthetic compared with those given general anesthesia. Comparison of interscalene block with general anesthesia for ambulatory shoulder arthroscopy showed a significant decrease in postanesthesia care unit (PACU) stay and fewer unplanned admissions for therapy of severe pain, sedation, or nausea/vomiting in the regional anesthesia group.34

Thromboembolism Coagulation and fibrinolysis are profoundly altered after surgery. Postoperatively, a hypercoagulable state is observed while, after initial enhancement, fibrinolysis is subsequently decreased. In 1856, Virchow35 proposed a triad of factors leading to thrombus formation, namely, changes in the vessel wall, in the flow of blood, and in the nature of the blood itself. Regional anesthesia may have a beneficial effect on all components of Virchow’s triad, as a result of reduced platelet aggregation36 and blood viscosity,37 and greatly enhanced lower limb blood flo~.~~ In 1976, a thromboembolic frequency of 20% to 80% was reported after total hip replacement, depending on the nature of the prophylactic measures, the technique used for diagnosing thrombosis, and the general condition of the patient.3g A possible explanation was that improvements in the anesthetic techniques have increased the number of surgeries in the elderly patient. Modig et aL4’ compared the effects of continuous epidural and of general anesthesia on the incidence of thromboembolism after total hip replacement. Bilateral phlebography and chest radiography, combined with perfusion lung scanning, revealed that patients given continuous epidural anesthesia had a significantly lower incidence of deep venous thrombosis (DVT), both in the proximal (femoral and popliteal) and in the distal veins of the lower extremity. The frequency of pulmonary embolism also was significantly lower in patients receiving epidural anesthesia (10%) than in those receiving general anesthesia (33%). The beneficial effects of regional anesthesia on the incidence of DVT in hip surgery also were investigated. In patients undergoing general anesthesia, the incidence of DV’I was 54% to 76%, compared with an incidence of 29% to 46% in those patients given a spinal anesthetic.41,42 Venous occlusion plethysmography demonstrated that arte448

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rial inflow, venous emptying rate, and venous capacitance were significantly greater in patients receiving epidural anesthesia perioperatively than in patients who received general anesthesia for their operative procedure.43 These beneficial effects were attributed to the regional anesthetic-induced sympathectomy. In three of eight patients in this study, venous emptying rate and venous capacitance had decreased 3 hours postoperatively, indicating decreased blood flow with increased risk of thrombus formation. The hyperkinetic lower limb circulation following spinal and epidural anesthesia occurring at a time when the stimulus to clotting is maximal provides prophylaxis against both the formation and the propagation of thrombi. Following absorption of IocaI anesthetics into the circulation, a decrease in migration of white cells and platelets, as well as a decrease in aggregation of erythrocytes, were observed. 44 The ability of red cells to deform was shown to be increased during spinal anesthesia; all these factors aid in the increase of limb blood flow, thereby decreasing thrombus formation.4’ Centroneuraxis anesthesia, like most of the regional techniques, leads to an improvement of postoperative pain, resulting in earlier ambulation and less likelihood of thrombus formation.45 Perioperative changes in hemostasis may explain the high frequency of DVT and pulmonary embolism after surgery.46 Increased plasma concentrations of coagulation factors,47 decreased concentrations of coagulation inhibitors,48 enhanced in vitro platelet reactivity,4g and impaired in vitro fibrinolysi?’ have been reported following surgery, suggesting a hypercoagulable state. Tuman et al.*’ monitored perioperative coagulation status by thromboelastography in patients undergoing major vascular surgery. Thromboelastographic markers of fibrinogen-platelet activity declined on the first postoperative day in patients who received a combined general-epidural anesthetic, but not in patients given general anesthesia alone. Several authors compared the influence of epidural and general anesthesia on various rheologic parameters such as fibrinogen plasma levels, fibrinolysis inhibition activity, plasminogen activators, factor VIII activity, and platelet aggregation in patients following hip replacement, lower extremity vascular reconstruction surgery, and prostatectomy, respectively.36,51Z52 Primary hemostasis (in other words, platelet aggregation activity) plays an important role in the initiation of thrombus formation. Systemic absorption of local anesthetics during epidural anesthesia was shown to inhibit platelet aggregation.36 With both regional and general anesthesia, fibrinolysis inhibition activity increased after surgery,51 which is known to be a normal posttraumatic response. Over a period of one week, however, this activity was significantly lower in patients with an epidural anesthetic compared with those with general anesthesia who showed a posttraumatic increase in activity. The resting concentration of plasminogen activator, an acute phase protein initiating fibrinolysis,50 decreased significantly on the third postoperative day in the general anesthesia group, but not in patients given epiduthat ral anesthesia.51 Rosenfeld et ~1.~’ also hypothesized early postoperative increases in circulating plasminogen

Regional anesthesiaand penoperative activator inhibitor levels in general anesthesia patients may contribute to thrombus formation within the first 48 hours after surgery. The capacity for activation of factor VIII also was significantly lower in the epidural compared with the general anesthesia group.” The authors attributed the librinolytic and coagulative differences between the two types of anesthetic regimens partly to an altered neuroendocrine metabolic response to surgery associated with afferent and efferent neural blockade, to differences in blood loss and the amount of fluid and blood transfusions, and to the local anesthetic per se. A decreased requirement for fluid administration decreased the hypercoagulability induced by crystalloid administration.53 Local anesthetics decrease the adhesiveness and migration of white cells and platelets, decrease aggregation of red cells, and alter plasma proteins to decrease the incidence of thrombosis following absorption of local anesthetics into the circulation.44 Injection of 75 mg of lidocaine both and intrathecally54 decreased plasma intramuscularly30 and whole blood viscosity. This reduction in viscosity was attributed to a decrease in red cell aggregation. In conclusion, whereas general anesthesia with parenteral opioid administration has negligible effect on post25 local anesthetics influence operative hypercoagulability, the perioperative hypercoagulable state by various mechanisms such as sympathetic denervation and attenuation of excessive coagulability, and by the anticoagulant properties of the local anesthetic itself.

Intraoperative

and Postoperative

Blood Loss

With the growing concern about transmission of human immunodeficiency virus (HIV), hepatitis, and the possibility of tumor recurrence after blood transfusions, any technique that can minimize blood loss perioperatively is valuable. A notable intraoperative and postoperative finding in several studies was a significantly lower blood loss (and thus transfusion requirement) in patients given spinal anesthesia, continuous epidural anesthesia, or interscalene block when compared with a general anesthetic group following hip or knee replacement and shoulder surOperative blood loss was measured gravigery. 23.4o,42*43X55 metrically, from increase in weight of swabs and towels, and the volume of blood in the suction jars.23,42 Large variations in operative blood loss have been described, and they may be secondary to different operative techniques. Gravimetric methods for determination of blood loss have been proven as simple and reliable and are used comet al,,42 consistent with a previous study monly. Thorburn by Sculco and Ranawat,56 reduced the intraoperative blood loss in hip surgery in a spinal anesthetic group by 50% of that of a general anesthesia group, thereby reducing the number of transfusions to four of 38 patients in the spinal anesthesia group versus 33 of 47 patients in the general anesthesia group. There was no significant difference in blood loss due to wound drainage between the two groups in the postoperative period. Modig et a1.40 continued an epidural anesthetic in patients having hip surgery for 24 hours into the postoperative period, thereby de-

outcome: Atanmsoff

creasing blood loss for this time period significantly. In contrast, epidural anesthesia, used only for intraoperative purposes and discontinued at the end of surgery, was not associated with a reduction in postoperative blood 10~s.~~ An explanation for this effect of centroneuraxis anesthesia may be the hypotension following sympathectomy of the lower limb, which may result in significantly lower mean arterial pressure (MAP), pulmonary arterial pressure, right atria1 pressure, and peripheral venous pressure.57 Epidural and spinal anesthesia, owing to sympathetic denervation and subsequent vasodilatation, produce a generous flow of blood in the larger vessels of the lower limbs, while simultaneously reducing local blood flow in the smaller vessels of the surgical field.“’ Of even greater importance is the lower local venous blood pressure (BP) in the operative wound, causing decreased oozing of blood.40 Intraoperative blood loss in patients receiving regional anesthesia also has been reduced by as much as 45% during hysterectomy,58 30% d uring lower limb vascular surgery,5g 51% in lower limb amputation,31 35% during ret28% following shoulder cuff ropubic prostatectomy,60 repair under interscalene block,55 and 18% in transurethral resection of the prostate (TURP) procedures.61 Abdominal procedures with thoracic or lumbar epidural anesthesia have failed to show any significant reduction in blood loss, although the amount of transfused blood was a lesser amount62-64 than with other surgical procedures. In summary, a reduction in peripheral vascular resistance as well as an increase in venous capacity following spinal, epidural, and brachial plexus (interscalene) anesthesia may be responsible for the described decrease in blood loss as long as the administration of a local anesthetic is maintained. One may speculate that aspects of gravity, as in patients in the lateral position for hip, or the sitting position in shoulder surgery, provide additional reasons for reduced operative blood loss.

Effects of Regional

Anesthesia

in Vascular Surgery

Blood flow in a graft is one of the most important factors determining immediate graft patency in patients undergoing reconstructive arterial surgical procedures. Graft blood flow is often reduced by an increase in leg vascular resistance, which may be produced by exposure and manipulation during prolonged operations as well as by postoperative pain.38 Sympathectomy, produced by an epidural anesthetic, has been used because of its long-term effect in patients with obliterative vascular disease.38 In 13 elderly patients, Cousins and Wright38 measured the effects of epidural anesthesia on graft blood flow and on distribution of the flow between skin and the skeletal muscle. Following injection of a local anesthetic, blood flow in the arterial graft showed a significant increase of more than 50%. Because BP did not change, the authors concluded that the increase of graft blood flow was due to a reduction in vascular resistance. The increase in flow through the graft was also associated with an increase in skin temperature at the expense of muscle blood flow. A previous study65 had shown that skin blood flow may inJ. Clin. Anesth., vol. 8, September 1996

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SpecialArticles crease go-fold following maximal vasodilatation. Thus, it is not surprising that the dilatation in skin blood vessels after epidural block in Cousin and Wright’s study resulted in an increased graft flow despite a reduction in muscle flow. In the immediate postoperative period, blood flow also may be compromised by pain. Pain is known to be associated with a catecholamine response, leading to vasoconstriction and thus reduction in graft perfusion. It is during the time following surgery that vasoconstriction due to pain is most marked, and that there is a great potential for decrease in blood flo~.~s A major finding in Christopherson et al.‘s studys’ was an unexpected and significantly higher rate of graft occlusion with resultant need for reoperation in patients with general anesthesia (22%) compared with those with an additional epidural anesthetic (4%). The time necessary for regrafting, thrombectomy, or amputation also was different between the two anesthetic techniques, with reoperation becoming necessary earlier (ie, within one week postoperatively) after general than after regional anesthesia. Due to the cardiodepressant effect of both intravenous (IV) and inhalational anesthetics, general anesthesia tends to reduce cardiac output (CO) .66 This is known to generate an increase in catecholamines, with resultant vasoconstriction and impaired graft blood flow. Berlauk et aL6’ showed that, when the CO of patients undergoing lower extremity vascular surgery with general anesthesia was normalized, the patients had a lower incidence of early graft occlusion than did control subjects with a reduced CO. Unless high plasma levels following direct intravascular or high absorption are achieved, local anesthetics have no such profound cardiodepressant effect. As the level of sensory blockade normally is confined to the T,, or even lower segmental levels in lower limb vascular surgery, a serious decrease in CO secondary to a decrease in preload, particularly after preloading the patient, is not of such severity as with higher segmental levels of neural blockade. In the latter situation, however, there is a potential for changes in cardiac performance due to systemic and central nervous system hypoperfusion with onset of different symptoms including stroke. Although a reduction in the stress response is achieved with higher segmental levels of blockade, a response to decreases in CO may no longer be possible. Perioperative morbidity such as transient ischemic attacks (TIA) and stroke remain a significant problem in the treatment of cerebrovascular disease. The anesthetic technique used during carotid endarterectomy plays an important part in these perioperative complications. Electroencephalographic (EEG) monitoring or carotid artery stump pressure is often used to assess cerebral perfusion during carotid artery occlusion with the patient given general anesthesia, but each has been shown to be inaccurate.68’6g Clinically obvious or occult heart disease frequently is present in patients with atherosclerosis.6g,70 General anesthesia increases the cardiac risk in these patients, and may result in some patients being denied surgery because of severe heart disease. Use of cervical plexus block in patients undergoing carotid artery surgery was associated with a significantly shorter operative time, fewer perioper450

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ative cardiopulmonary complications, and a shorter hospitalization when compared with general anesthesia.28,71 Moreover, there was an additional reduced postoperative complication rate in the regional anesthetic group.*’ Carotid endarterectomy with cervical plexus block or cervical epidural anesthesia’* permits simple and reliable monitoring of cerebral function during the procedure by means of verbal communication with the patient and frequent evaluation of motor strength.26,‘3374 Clinical neurologic assessment of the awake patient has been shown to be more accurate in detecting significant cerebral ischemia than EEG monitoring. *’ Cervical plexus block, when compared with general anesthesia, significantly reduced the need for a carotid artery shunt to protect cerebral circulation during surgery.*’ Morbidity, such as embolic stroke, is increased with placement of such a shunt,75 surgery itself technically becomes more difficult.76 Allen et ~1.~~ concluded that cervical plexus block is safer and results in more efficient use of hospital resources than general anesthesia in the treatment of patients undergoing carotid endarterectomy.

Effect of Regional Anesthesia Neuroendocrine Response

on the

Regional anesthesia is used clinically to block afferent neural signals from the site of tissue trauma during surgical procedures. These afferent impulses provide the major stimulus for the neuroendocrine response to surgical stress in humans.” Surgical stress increases secretion of catabolic hormones such as cortisol, glucagon, and catecholamines, as well as cytokines, while at the same time inhibiting anabolic hormones such as insulin and testosterone.‘8-s3 Infusions of adrenergic and endocrine hormones, as well as cytokines, are the cause of tachycardia, fever, shock, and increased minute ventilations3 There is a relationship between the plasma concentrations of these factors and the severity of injury, as well as the outcome after injury. Thus, the theory was developed that attenuating the stress response may improve surgical outcome. Unless high doses of opioids are employed prior to surgery, general anesthesia does not suppress the stress response, but may even worsen it.s4 Epidural analgesia/anesthesia prevents an increase of cyclic aminomonophosphate (CAMP) during surgery, thereby inhibit77 ing catecholamine release.852s6 Pflug and Halter compared the effect of spinal and inhalational anesthesia on adrenergic tone and the endocrine response by measuring plasma levels of epinephrine (Epi) and norepinephrine (NE), as well as cortisol and growth hormone. Patients given a spinal anesthetic to the second thoracic (T,) level displayed a marked suppression of Epi and NE in the plasma with subsequent decrease in MAP, in contrast to those patients who received spinal anesthesia to the Ti2 level. Comparison of the groups intraoperatively showed a marked increase of plasma NE in the general anesthetic group; both NE and Epi increased during the postoperative recovery period in patients given halothanenitrous oxide (N,O) . No such increase was observed in the

Re@onal anesthesia and perioperative outcome: Atanassoff

spinal anesthesia group. Additionally, as part of a reduced stress response to surgery, patients given a spinal anesthetic displayed no increase in cortisol and growth hormone in contrast to the elevated hormonal levels observed during the recovery period in patients given inhalational anesthesia alone with haloanesthesia. ” Inhalational thane-N,O caused a significant suppression of plasma Epi:’ a finding that was also observed previously.87 This direct inhibitory effect of the inhalational anesthetic provides an explanation for the lack of operative increases in plasma Epi, but not of NE. Comparison of the effects of epidural to those of general anesthesia on the catecholamine response to infrarenal abdominal aortic aneurysm repair showed significantly higher levels of Epi and NE prior to and after aortic crossclamping in the general anesthesia group than in patients with an epidural anesthetic. ” Similar results were found in patients receiving lower extremity revascularization.” Rathat patients with severe manathan et al.‘* demonstrated preeclampsia undergoing cesarean section displayed a significantly greater stability of MAP, as well as significantly lower catecholamine, ACTH, cortisol, and beta-endorphin plasma levels during epidural anesthesia than those given a general anesthetic.“’ These differences were observed at the time of intubation, skin incision, and emergence from general anesthesia. A peripheral nerve block such as intercostal block for lumpectomy also significantly suppressed the catecholamine response postoperatively when compared with an inhalational anesthetic group.g1 The results of these studies indicate an overall reduced stress response as measured by catecholamine, cortisol, and growth hormone release following various regional block procedures when compared with a general anesthetic. Dermatome levels above T,, during spinal and epidural anesthesia totally suppress the stress response and may be associated with greater hemodynamic stability if total sympathectomy is avoided. These aspects may improve operative outcome. The breakdown of muscle protein and negative nitrogen balance are characteristic metabolic responses to surgical stress, leading to delayed healing of surgical wounds. Endocrine changes, such as the previously mentioned release of catecholamines during and after surgery, result in mobilization of substrate and ultimately in a catabolic state with negative nitrogen balance. Administering substrates,a7 insulin, and glucose’* improves nitrogen balance, but does not diminish the release of catabolic hormones induced by stress.85 By inhibiting the endocrine stress response to surgery, regional anesthesia affects the postoperative nitrogen balance. Nitrogen balance reflects the efficacy of parenteral nutrition, even if one does not know the type or source of nitrogen used. Brandt et aLs5 compared the postoperative nitrogen balance following epidural and general anesthesia. On each of the five postoperative days, the negative nitrogen balance was greater in the general than in the epidural anesthesia group. Similarly, other authorsg3,g4 showed that a cumulative 6-day nitrogen balance and urinary 3-methylhistidine excretion (a constituent of both actin and myosin, and as such, an index of skeletal muscle protein catabolism) was less in

patients receiving postoperative epidural etidocaine or bupivacaine compared with those given epidural opioid or IV opioids for analgesia. Regimens of epidural opioids that produce an equivalent level of postoperative analgesia as do local anesthetics generate a less effective block of the stress response with less impact on the catabolic state.63 Administration of IV opioids by patient-controlled analgesia postoperatively generates pain relief, but leaves the stress response with resultant catabolism unaltered.g5 Whereas local anesthetics are known to block nociceptive and non-nociceptive (sympathetic) pathways, thereby inhibiting the metabolic response profoundly, this is not the case with epidural opioids, which modulate only nociceptive pathways.g6 In abolishing the endocrine-metabolic response, epidural analgesia also inhibits the normal postoperative increase in oxygen consumption, thereby reducing the demands on the cardiovascular system.g7 Thus, the use of centroneuraxis block induced by local anesthetics results in a significantly greater reduction in the stress response to surgery, with an additional nitrogensparing effect than do epidural opioids or IV analgesics.

Postoperative

Pulmonary

Function

Many factors such as age, smoking habits, gender, personality, preoperative status, site and duration of surgery, blood loss, and sleep patterns affect postoperative lung function.g8Zgg The characteristic postoperative mechanical respiratory abnormality following upper abdominal or thoracic procedures, less so after lower abdominal surgery or laparoscopic surgical procedures, is a restrictive pattern with severely reduced inspiratory capacity and vital capacity (VC) plus smaller, but more important reductions in functional residual capacity (FRC) .loo Reductions in FRC alter the relationship between lung closing volume and end-tidal volume, thereby predisposing to atelectasis.“‘i Patients breathe rapidly with a small tidal volume and are unwilling or unable to inspire deeply. Immediately following upper abdominal surgery, VC is normally reduced to approximately 40% of preoperative values, and remains depressed for at least 10 to 14 days.“i The reduction in FRC is considered the most clinically important lung volume change leading to atelectasis and ventilationperfusion abnormalities with resultant hypoxemia, pneumonia, and postoperative pulmonary complications.“’ FRC decreases to about 70% in the first 24 hours postoperatively, stays depressed for several days, and gradually returns to normal by ‘7’and 10 days after surgery.i” The choice of either general or regional anesthesia affects the degree of pulmonary dysfunction following surgery. While general anesthesia with mechanical ventilation, muscle paralysis, inhaled anesthetics, and opioid analgesics contributes to reduction in postoperative pulmonary function, this is less so with thoracic epidural anesthesia.102*103 Comparison of forced expiratory volume in one second (FEV,) and VC in patients with postoperative epldural analgesia with those receiving subcutaneous morphine demonstrated a decrease of these ventilatory parameters in both groups, but to a significantly larger extent in J. Clin. Anesth., vol. 8, September 1996

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the patients with subcutaneous morphine.lo4 PaCO, was significantly lower in the epidural group on the third postoperative day. In the recovery room, PaO, was significantly higher in the epidural analgesia compared with the subcutaneous morphine group. Five patients in the epidural analgesia group compared with 10 patients in the subcutaneous morphine group experienced at least one episode of oxygen desaturation to less than 85% postoperatively. Catley et aLgg monitored arterial saturation and respiratory patterns after abdominal and orthopedic surgery in middle-aged and elderly adults receiving either parenteral opioids or epidural local anesthetic for postoperative pain relief. Patients given morphine intravenously had more than 450 episodes of pronounced oxygen desaturation (SaO, of less than 80%). These desaturations occurred only while the patients were asleep and all were associated with disturbances in ventilatory patterns such as obstructive apnea, paradoxic breathing, and periods of slow ventilatory rate. Oxygen saturation in patients with epidural bupivacaine for pain relief never decreased below 87%, despite the fact that both groups had comparable subjective pain relief during the study. On the other hand, in patients receiving epidural morphine, the postoperative periods of arterial desaturation were four times longer than in those given morphine intravenously or intramuscularly.‘05 In “healthy” patients, PaO, levels decreased to 60 to 75 mmHg, equivalent to SaOB of 85% to 90% during the first postoperative day following major surgery.101*106 Owing to the shape of the oxyhemoglobin dissociation curve, PaO, starts to decline rapidly once saturation has decreased below 85%. In more seriously ill patients than those studied by Catley et ah, changes in SaO, may be even more profound. From the respiratory aspect, regional anesthesia without inclusion of an opioid may be a more appropriate form of postoperative pain relief, particularly in elderly patients and those at risk than is administration of epidural or IV opioid analgesic drugs.

Conclusions This review addresses beneficial aspects of regional anesthesia on perioperative outcome. Regional anesthesia may be associated with reductions in frequency and severity of many physiologic perturbations. Spinal and epidural anesthesia proved to be advantageous for the prevention of thromboembolic disease; these two regional techniques, as well as brachial plexus block, reduced perioperative blood loss. However, in contrast to peripheral blocks such as cervical plexus block, clinically significant improvements in spinal and epidural anesthesia concerning the postoperative morbidity is currently contradictory and thus not conclusive. Depending on the level of sympathetic blockade, centroneuraxis anesthesia significantly reduces the stress response to surgery, as documented by reductions in catecholamine and other catabolic-acting hormone release. This further implies a maximally beneficial impact on perioperative metabolism with nitrogensparing effects and reduced protein breakdown, thus contributing to improved operative outcome. Finally, local 452

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anesthetics administered epidurally for postoperative pain relief proved to be superior to epidurally or intravenously administered opioids with respect to SaO, episodes. Using regional anesthesia with local anesthetics for postoperative analgesia provides a greater margin of safety in terms of respiratory side effects than does the continuous administration of opioids. Taking further into account the reduced amount of time patients with regional anesthesia spend in costly institutions such as PACU, ICU, or overall in the hospital, there is clearly an advantage of administering regional anesthesia if not as a sole, but at least as an addition to a general anesthetic for certain types of surgical procedures.

References 1. Nygaard KK: Routine spinal anesthesia in provincial hospital:

with comparative study of postoperative complications following spinal and general ether anesthesia. Acta Chir &and 1936;78: 379-446. 2. Scott NB, Kehlet H: Regional anaesthesia and surgical morbid-

ity. BrJ Surg 1988;75:299-304. 3. Kehlet H: Does regional anaesthesia reduce postoperative morbidity? Intensive Care Med 1984;10:165-7. 4. Forrest JB, Rehder K, Goldsmith CH, et al: Multicenter study of general anesthesia. I. Design and patient demography. Anesthesiology 1990;72:252-61. 5. Forrest JB, Cahalan ME;, Rehder K, et al: Multicenter study of general anesthesia. II. Results. Anesthesiology 1990;72:262-8. 6. Kehlet H: Stress free anesthesia and surgery. Acta Anaesthesiol Stand 1979;23:503-4. 7. Kehlet H: The stress response to anaesthesia and surgery: release mechanisms and modifying factors. C&n.Anaesthesiol1984; 2:315-39. 8. Kehlet H: The stress response to surgery: release mechanisms and the modifying effect of pain relief. Acta Chir Stand 1988;55O(suppl):22-8. 9. Engquist A, Brandt MR, Fernandes A, Kehlet H: The blocking effect of epidural analgesia on the adrenocortical and hyperglp cemic responses to surgery. Acta Anaesthesiol Stand 1977;21: 330-5. 10. Valentin N, Lomholt B, Jensen JS, Hejgaard N, Kreiner S: Spinal or general anaesthesia for surgery of the fractured hip? A prospective study of mortality in 578 patients. BrJAnaesth 1986;58: 284-91. 11. McKenzie PJ, Wishart HY, Smith G: Long-term outcome after repair of fractured neck of femur. Comparison of subarachnoid and general anaesthesia. BrJAmesth 1984;56:581-5. 12. Racle JP, Benkhadra A, Poy Jy, Gleizal B, Gaudray A: Comparative study of general and spinal anesthesia in elderly women in hip surgery. Ann Fr Anesth fiunim 1986;5:24-30. 13. Davis FM, Laurenson VG: Spinal anaesthesia or general anaesthesia for emergency hip surgery in elderly patients. Anaesth Intensive Care 1981;9:352-8. 14. McLaren AD: Mortality studies: a review. Reg Anesth 1982;7(S4) : 172-4. 15. Couderc E, Mauge F, Duvaldestin P, Desmonts JM: Comparative results of general and peridural anesthesia for hip surgery in the very old patient. An&h An&g Rianim 1977;34:987-97. 16. McKenzie PJ, Wishart HY, Dewar KM, Gray I, Smith G: cornparison of the effects of spinal anaesthesia and general anaesthesia on postoperative oxygenation and perioperative mortality, BrJ Anaesth 1980;52:49-54.

Regional anesthesia and @ioperative outcome: Atanassoff 17. Wickstrom I, Holmberg I, Stefansson T: Survival of female geriatric patients after hip fracture surgery. A comparison of 5 anaesthetic methods. Acta Anaesthesiol &and 1982;26:607-14. 18. White IW, Chappell WA: Anaesthesia for surgical correction of fractured femoral neck. A comparison of three techniques. Anaesthesia 1980;35:1107-10. 19. Bigler D, Adelhoj B, Petring OU, Pederson NO, Busch P, Kalhke P: Mental function and morbidity after acute hip surgery during spinal and general anaesthesia. Anaesthesia 1985;40:672-6. 20. Berggren D, Gustafson Y, Eriksson B, et al: Postoperative confusion after anesthesia in elderly patients with femoral neck fractures. Anesth Alzalg 1987;66:497-504. 21. Davis FM, Woolner DF, Frampton C, et al: Prospective, multicentre trial of mortality following general or spinal anaesthesia for hip fracture surgery in the elderly. BrJ Anaesth 1987;59: 1080-8. 22. Sharrock NE, Cazan MG, Hargett MJL, Williams-Russo P, Wilson PD Jr: Changes in mortality after total hip and knee arthroplasty over a ten-year period. Anesth An&g 1995;80:242-8. 23. Chin SP, Abou-Madi MN, Eurin B, Witvoet J, Montagne J: Blood loss in total hip replacement: extradural v. phenoperidine analgesia. BrJAnaesth 1982;54:491-5. 24. Yeager MP, Glass DD, Neff RK, BrinckJohnsen T: Epidural anesthesia and analgesia in high-risk surgical patients. Anesthesiology 1987;66:729-36. 25. Tuman KJ, McCarthy RJ, March RJ, DeLaria GA, Pate1 RV, Ivankovich AD: Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. An&h Analg 1991;73:696-704. 26. Peitzman AB, Webster MW, Loubeau JM, Grundy BL, Bahnson HT: Carotid endarterectomy under regional (conductive) anesthesia. Ann Surg 1982;196:59-64. 27. Otteman MG, Stahlgren LH: Evaluation of factors which influence mortality and morbidity following major lower extremity amputations for arteriosclerosis. Surg Gyn Obstet 1965;120:121720. 28. Allen BT, Anderson CB, Rubin BG, et al: The influence of anesthetic technique on perioperative complications after carotid endarterectomy. J Vast Surg 1994;19:834-43. 29. Baron JF, Bertrand M, Barre E, et al: Combined epidural and general anesthesia versus general anesthesia for abdominal aortic surgery. Anesthesioloa 1991;75:611-8. 30. Christopherson R, Beattie C, Frank SM, et al: Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesiology 1993; 79:422-34. 31 Mann RAM, Bisset WIK Anaesthesia for lower limb amputation. A comparison of spinal analgesia and general anaesthesia in the elderly. Anaesthesia 1983;38:1185-91. 32. Diebel LN, Lange MP, Schneider F, et al: Cardiopulmonary complications after major surgery: a role for epidural analgesia? Swgeq 1987;102:660-6. 33. de Leon-Casasola OA, Lema MJ, Karabella D, Harrison P: Post. operative myocardial ischemia: epidural versus intravenous patient-controlled analgesia. A pilot project. &g An&h 1995;2O: 105-12. 34. D’Alessio JG, Rosenblum M, Shea KP, Freitas DG: A retrospective comparison of interscalene block and general anesthesia for ambulatory surgery shoulder arthroscopy. Reg Anesth 1995; 20:62-8. 35. Virchow RLK [Collected Scientific and Medical Papers,] &ammelte Abhandlungen tw wissenschaflichen Medizin. Frankfurt/ Main: Von Meidinger Sohn und Comp, 1856. 36. Henny CP, Odoom JA, ten Cate H, et al: Effects of extradural

37.

38.

39. 40.

41.

42.

43.

44.

45. 46.

47.

48.

49.

50.

51.

52.

53.

54.

55. 56. 57.

58.

bupivacaine on the haemostatic system. Br J Anaesth 1986;58: 301-5. Orr JE; Lowe GD, Nimmo WS, Watson R, Forbes CD: A haemorheological study of lignocaine. Br J Anaesth 1986;58: 306-9. Cousins MJ, Wright CJ: Graft, muscle, skin blood flow after epidural block in vascular surgical procedures. Surg Gynecol Obstet 1971;133:59-64. Salzman EW, Harris WH: Prevention of venous thromboembolism in orthopedic patients. J Bone Joint Surg 1976;58:903-13. Modig J, Borg T, Karlstrom G, Maripuu E, Sahlstedt B: Thromboembolism after total hip replacement: role of epidural and general anesthesia. Anesth AnaZg 1983;62:174-80. Davis FM, Quince M, Laurenson VG: Deep vein thrombosis and anaesthetic technique in emergency hip surgery. BMJ1980;281: 1528-9. Thorburn J, Louden JR, Valiance R: Spinal and general anaesthesia in total hip replacement: frequency of deep vein thrombosis. Br JAnaesth 1980;52:1117-21. Modig J, Malmberg P, Karlstrom G: Effect of epidural versus general anaesthesia on calf blood flow. Acta Anaesthesiol &and 1980;24:305-9. Modig J: Influence of regional anesthesia, local anesthetics, and sympatheticomimetics on the pathophysiology of deep vein thrombosis. Actu Chir Stand 1988;55O(suppl) :119-27. Harrison PV, Allen PR: Spinal anesthesia in treating leg ulcers [Letter]. JDennatol Surg OncoZ 1986;12:753. Lindblad B, Sternby NH, Bergqvist D: Incidence of venous thromboembolism verified by necropsy over 30 years. BMJ1991; 302:709-11. Collins GJ Jr, Barber JA, Zajtchuk R, Vanek D, Malogne LA: The effects of operative stress on the coagulation profile. Am J Surg 1977;133:612-6. Andersson TR, Berner NS, Larsen ML, Odegaard OR, Abildgaard U: Plasma heparin cofactor II, protein C and antithrombin in elective surgery. Acta Chir Stand 1987;153:291-6. O’Brien JR, Tulevski VG, Etherington M, Madgwick T, Alkjaersig N, Fletcher A: Platelet function studies before and after operation and the effect of postoperative thrombosis. JLab CZin Med 1974;83:342-54. Kluft C, Verheijen JH, Jie AF, et al: The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-we plasminogen activator after trauma. &and J CZin Lab Invest 1985;45:605-10. Modig J, Borg T, Bagge L, Saldeen T: Role of extradural and of general anaesthesia in fibrinolysis and coagulation after total hip replacement. Br JAnaesth 1983;55:625-9. Rosenfeld BA, Beattie C, Christopherson R, et al: The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Perioperative Ischemia Randomized Anesthesia Trial Study Group. Anesthesioloa 1993;79:435-43. Janvrin SB, Davies G, Greenhalgh RM: Postoperative deep vein thrombosis caused by intravenous fluids during surgery. BY. J Surg 1980;67:690-3. Giasi RM D’Agostino E, Covino BG: Absorption of lidocaine following subarachnoid and epidural administration. Anesth AnaZg 1979;58:360-3. TetzlaffJE, Yoon HJ, Brems J: Interscalene brachial plexus block for shoulder surgery. fig An&h 1994;19:339-43. SCU~CO TP, Ranawat C: The use of spinal anesthesia for total hip-replacement arthroplasty. J Bone Joint Surg 1975;57:173-7. Modig J, Malmberg P: Pulmonary and circulatory reactions during total hip replacement surgery. Acta Anaesthesiol &and 1975; 19:219-37. Blunnie WP, McIlroy PD, Merrett JD, DundeeJW: CardiovascuJ. Clin. Anesth., vol. 8, September 1996

453

Special Articles lar and biochemical evidence of stress during major surgery associated with different techniques of anaesthesia. BrJ Anaesth 1983;55:611-8. 59. Cook PT, Davies MJ, Cronin KD, Moran P: A prospective randomised trial comparing spinal anaesthesia using- hyperbaric cinchocaine with general anaesthesia for lower limb vascular surgery. Anaesth Intensive Care 1986;14:373-80. 60. Hendolin H, Mattila MA, Poikolainen E: The effect of lumbar epidural analgesia on the development of deep vein thrombosis of the legs after open prostatectomy. Acta Chir Stand 1981;147: 425-9. 61. McGowan SW, Smith GF: Anaesthesia for transurethral prostatectomy. A comparison of spinal intradural analgesia with two methods of general anaesthesia. Anaesthesia 1980;35:847-53. 62. Hjortso NC, Neumann P, Frmsig F, et al: A controlled study on the effect of epidural analgesia with local anaesthetics and morphine on morbidity after abdominal surgery. Acta Anaesthesiol Scund 1985;29:790-6. 63. Modig J: The role of lumbar epidural anaesthesia as antithrombotic prophylaxis in total hip replacement. Actu Chir Stand 1985; 151:589-94. 64. Rutberg H, Hakanson E, Anderberg B, Jorfeldt L, Martensson J, Schildt B: Effects of the extradural administration of morphine, or bupivacaine, on the endocrine response to upper abdominal surgery. BrJAnaesth 1984;56:233-8. 65. Goetz RH: The rate and control of the blood flow through the skin of the lower extremities. Am Heart J 1946;31:146-82. 66. Hickey R, Eger E: Circulatory pharmacology of inhaled anesthetics. In: Miller RD (ed) Anesthesia New York: Churchill Livingstone, 1986;649-66. 67. Berlauk JF, Abrams JH, Gilmour IJ, O’Connor SR, Knighton DR, Cerra FB: Preoperative optimization of cardiovascular hemodynamics improves outcome in peripheral vascular surgery. A prospective, randomized clinical trial. Ann Surg 1991;214:289-97. 68. Evans WE, Hayes JP, Wahke EA, Vermilion BD: Optimal cerebral monitoring during carotid endarterectomy: neurologic response under local anesthesia. J Vast Surg 1985;2:775-7. 69. Hafner CD, Evans WE: Carotid endarterectomy with local anesthesia: results and advantages. / Vusc Surg 1988;7:232-9. 70. Hertzer NR, Young JR, Beven EG, et al: Coronary angiography in 506 patients with extracranial cerebrovascular disease. Arch Intern Med 1985;145:849-52. 71. Gabelman CG, Gann DS, Ashworth CJ Jr, Carney WI Jr: One hundred consecutive carotid reconstructions: local versus general anesthesia. Am J Surg 1983;145:477-82. 72. Bonnet F, Derosier JP, Pluskwa F, Abhay K, Gaillard A: Cervical epidural anaesthesia for carotid artery surgery. Can J Anaesth 1990;37:353-8. 73. ConnollyJE: Carotid endarterectomy in the awake patient. Am J Surg 1985;150:159-65. 74. Erwin D, Pick MJ, Taylor GW Anaesthesia for carotid artery surgery. Anaesthesia 1980;35:246-9. 75. Prioleau WH Jr, Alken AF, Hairston P: Carotid endarterectomy: neurologic complications as related to surgical techniques. Ann Surg 1977;185:678-83. 76. Smith LL, Jacobson JG, Hinshaw DB: Correlation of neurologic complications and pressure measurements during carotid endarterectomy. Surg Gynecol Obstet 1976;143:233-6. 77. Pflug EA, Halter JB: Effect of spinal anesthesia on adrenergic tone and the neuroendocrine responses to surgical stress in humans. Anesthesiology 1981;55:120-6. 78. Brandt M, Kehlet H, Binder C, Hagen C, McNeilly AS: Effect of epidural analgesia on the glycoregulatory endocrine response to surgery. Clin Endoc&ol1976;5:107-14. 79. Russell RC, Walker CJ, Bloom SR: Hyperglucagonaemia in the surgical patient. BMJ 1975;1:10-2. 454

J, Clin. Anesth., vol. 8, September 1996

80. Nikki P, Takki S, Tammisto T, JaattelP A: Effect of operative stress on plasma catecholamine levels. Ann Clin Res 1972;4:14& 51. 81. Brandt MR, Kehlet H, Faber 0, Binder C: C-peptide and insulin during blockade of the hyperglycaemic response to surgery by epidural analgesia. Clin Endotinol1977;6:167-70. 82. Oyama T, Maeda A, Kudo T: Effects of althesin anaesthesia and surgery on plasma concentrations of luteinizing hormone and testosterone in man. Br JAnaesth 1975;47:1093-6. 83. Douglas RG, Shaw JH: Metabolic response to sepsis and trauma. Br J&y 1989;76:115-22. 84. Giesecke K Hamberger B, Jarnberg PO, Klingstedt C, Persson B: High- and low-dose fentanyl anaesthesia: hormonal and metabolic responses during cholecystectomy. Br JAnaesth 1988; 61:575-82. 85. Brandt MR, Fernades A, Mordhorst R, Kehlet H: Epidural analgesia improves postoperative nitrogen balance. BMJ 1978;l: 1106-8. 86. Madsen SN, Brandt MR, Engquist A, Badawi I, Kehlet H: Inhibition of plasma cyclic AMP, glucose and cortisol response to surgery by epidural analgesia. Br J Surg 1977;64:669-71. 87. Halter JB, Pflug AE, Porte D Jr: Mechanism of plasma catecholamine increases during surgical stress in man. J Clin Endocrinol Metab 1977;45:936-44. 88. Gold MS, DeCrosta D, Rizzuto C, Ben-Harari RR, Ramanathan S: The effect of lumbar epidural and general anesthesia on plasma catecholamines and hemodynamics during abdominal aortic aneurysm repair. Anesth Analg 1994;78:225-30. 89. Breslow MJ, Parker SD, Frank SM, et al: Determinants of catecholamine and cortisol responses to lower extremity revascularization. The PIRAT Study Group. Anesthesiology 1993;79:1202-9. 90. Ramanathan J, Coleman P, Sibai B: Anesthetic modification of hemodynamic and neuroendocrine stress responses to cesarean delivery in women with severe preeclampsia. Anesth Analg 1991; 73:772-g. 91. Atanassoff PG, AIon E, Pasch T, Ziegler WH, Gautschi K Intercostal nerve block for minor breast surgery. Reg Anesth 1991;16: 23-7. 92. Hinton P, Allison SP, Littlejohn S, Lloyd J: Insulin and glucose to reduce catabolic response to injury in burned patients. Lancet 1971;1(703):767-9. 93. Vedrinne C, Vedrinne JM, Guiraud M, Patricot MC, Bouletreau P: Nitrogen-sparing effect of epidural administration of local anesthetics in colon surgery. Anesth Analg 1989;69:35&9. 94. Carli F, Webster J, Pearson M, et al: Protein metabolism after abdominal surgery: Effect of 24-h extradural block with local anaesthetic. Br JAnaesth 1991;67:729-34. 95. Moller IW, Dinesen K, Sondergard S, Knigge U, Kehlet H: Effect of patient-controlled analgesia on plasma catecholamine, cortisol and glucose concentrations after cholecystectomy. Br J Anaesth 1988;61:160-4. 96. Lund C, Selmar P, Hansen OB, Jensen CM, Kehlet H: Effect of extradural morphine on somatosensory evoked potentials to dermatomal stimulation, Br JAnaesth 1987;59:1408-11. 97. Renck H: The elderly patient after anaesthesia and surgery. Acta Anaesthesiol Stand 1969;34(suppl):l-136. 98. Dalrymple DG, Parbrook GD, Steel DF: Factors predisposing to postoperative pain and pulmonary complications: a study of female patients undergoing elective cholecystectomy. BYJ Anaesth 1973;45:589-98. 99. Catley DM, Thornton C, Jordan C, Lehane JR, Royston D, Jones JG: Pronounced, episodic oxygen desaturation in the postoperative period: its association with ventilator-y pattern and analgesic regimen. Anesthesiology 1985;63:20-8.

Regional

100. Meyers JR, Lembeck L, O’Kane H, Baue AE: Changes in functional residual capacity of the lung after operation. Arch Surg 1975;110:576-83. 101. Craig DB: Postoperative Analg 1981;60:46-52.

recovery of pulmonary

102. Nunn JF: Effects of anaesthesia on respiration. 65:5462.

function.

Anesth

BrJAnaesth 1990;

103. Groeben H, Schwalen A, Irsfeld S, Tarnow J, Lipfert P, Hopf HB: High thoracic epidural anesthesia does not alter airway resistance and attenuates the response to an inhalational provo-

The Ether

Dome,

Bulfinch

Building,

anesthesia and perioperatiue outcome: Atanassoff

cation test in patients with bronchial hyperreactivity. Anesthesiology 1994;81:868-74. 104. Jayr C, Thomas H, Rey A, Farhat F, Lasser P, Bourgain JL: Postoperative pulmonary complications. Epidural analgesia using bupivacaine and opioids versus parenteral opioids. Anesthesiology 1993;78:666-76. 105. Wheatley RG, Somerville ID, Sapsford DJ, Jones JG: Postoperative hypoxaemia: comparison of extradural, i.m. and patientcontrolled opioid analgesia. BTJ Anaesth 1990;64:267-75. 106. Marshall BE, Wyche MQ Jr: Hypoxemia during and after anesthesia. Anesthesiology 1972;37:178-209.

Massachusetts

General

Hospital

J. Clin. Anesth., vol. 8, September 1996

455