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Continuous epidural anesthesia and postoperative epidural narcotics in vascular surgery
Continuous Epidural Anesthesia and Postoperative Epidural Narcotics in Vascular Surgery
Robert Raggi, MD, Herbert Dardik, MD, and Alfred L. Mauro, MD, Erglewood, New Jersey
A recent survey of anesthesiologists has indicated that an overwhelming majority (92 percent) would prefer regional anesthesia for their own operation. Regional anesthesia has become the anesthetic of choice for many surgical procedures, (for example, cataract extraction, transurethral resection of the prostate, and hand surgery). There is a recent accumulation of advantageous data which merits a reexamination of the risk-benefit ratio of epidural anesthesia for vascular procedures. The advantages include metabolic stability, suppression of the surgical stress response, cerebral status monitoring, stability of high-risk patients (for example, cardiac, hypertensive, diabetic, geriatric, and chronic obstructive pulmonary disease patients), and superior postoperative pain relief. It is the goal of this study to show the advantages of epidural anesthesia combined with postoperative epidural narcotics. Material and Methods Informed consent was obtained from all patients. Ninety-six patients (American Society of Anesthesiologists classes 2, 3, and 4) were scheduled for lower extremity vascular operations. The limb salvage procedures included femoropopliteal, femorotibial, and femoroperoneal bypass grafts and femoral endarterectomy with vein patch. Associated conditions included arteriosclerotic cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, hypertension, prior myocardial infarction, prior coronary artery bypass graft, ectopic beats, smoking history, chronic renal failure, S-T depression, and prior cerebrovascular accident, All patients received preoperative preparation from their internists. Preoperative diazepam (0.1 to 0.2 mg/kg) was given orally 1 to 2 hours before operation. Monitoring was carried out utilizing electrocardiography (lead II and modified V5), direct arterial line blood pressure, blood.gases, precordial stethoscope, verbal contact, axillary temperature, urinary catheterization, intermittent pretracheal ausculatation, and Swan-Ganz catheterization when indicated (16 percent). All patients From the Departments of Surgery and Anesthesia, Englewood Hospital, Englewood, New Jersey. Requests for reprints should be addressed to Robert Raggi, MD, Pain Clinic, Englewocd Hospital, 350 Engle Street, Englewocd. New Jersey 07632. Presented at the 15th Annual Meeting of the Society for Clinical Vascular Surgery, Scottsdale, Arizona, March 25-29, 1967.
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received various amounts of intravenous sedation and 2 to 4 liters of oxygen through a nasal cannula. Eight patients received supplemental light general anesthesia (various combinations of intravenous neuroleptic anesthesia: nitrous oxide and oxygen 2:1,0.25 percent forane, and diazepam, alone or in combination) for patient anxiety, positioning, comfort, and amnesia. Activated clotting time at baseline and postheparinization were followed. Patients received intravenous volume loading to prevent hypotension due to sympathetic block. Patients were positioned, prepped with povidone-iodine (Betadine”), and draped. The most skilled anesthesiologist available administered local anesthetic skin wheal and infiltration injection at the most accessible lumbar interspace under sterile conditions. The epidural space was identified with an 18 gauge Toughy needle, using the loss of resistance technique. After negative aspiration, a 3 ml test dose of 1.5 percent xylocaine with epinephrine (concentration 1:200,000) was administered. After 3 minutes, an anesthetic dose of 10 to 12 ml of 0.5 percent or 0.75 percent bupivicaine (84 percent) and 7 percent of patients, respectively or 2 percent xylocaine (9 percent of patients) was given. A Teflon@ epidural catheter was threaded, the disposable Toughy needle removed, and the catheter secured with a sterile dressing. Further local anesthetics were administered as repeat doses through the catheter as needed. Heparin was given intraoperatively after catheter placement. Five milligrams of preservative-free morphine in 10 ml of sterile normal saline solution was given at the conclusion of the operation in 35 percent of the patients and when patients indicated they had pain (65 percent), Patients were instructed to request pain medication promptly as needed. Monitoring was carried out in the surgical intensive care unit by nurses during and 24 hours after administration of the epidural narcotics. If the catheter was not functioning or if relief was inadequate, then patients received oral or intramuscular narcotics. Results
There was a 0 incidence of epidural hematoma and myocardial infarction. In five patients, epidural anesthesia failed and required administration of general anesthesia. Six patients required ephedrine (5 to 10 mg) intravenously. No other vasopressors or afterload reducers were needed, which attest to the hemodynamic stability offered by the technique.
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Postoperatively, seven patients required diuresis for mild cardiogenic pulmonary edema. The epidural catheter was nonfunctioning during the first 24 hours in 6 patients, which left 85 patients in the study group. The onset of epidural morphine analgesia was consistent with other studies, occurring within 10 to 45 minutes [I]. The mean duration of analgesia was 15 hours as measured by requests for pain medication and nurse observation. When pain medication was requested, a subsequent epidural morphine dose provided a smooth continuum of analgesia during the first 24 postoperative hours. In those patients who received epidural narcotic immediately after operation, their first 16 hours were virtually pain free. Eighty-five percent of the patients received complete analgesia with repeat doses of epidural morphine for 48 hours. Twelve patients had nausea and required naloxone (Narcane) 7 to 10 hours after administration of epidural morphine). Three patients vomited while receiving epidural morphine. Twenty-three patients needed naloxone for pruritus. Urinary side effects in these patients with bladder catheters were not assessed. No patients had respiratory arrest although nine patients had decreases in respiration rates (7 to 10 minutes) which did not require naloxone. One patient who had a subendocardial myocardial infarction 3 days earlier required emergency operation to prevent impending gangrene. He received the combination epidural technique. The operation was successful and the myocardial infarction was limited. These results point to a possible overexaggeration of risk and failure. We have focused on the available advantages of epidural anesthesia and postoperative epidural narcotics for vascular procedures performed by a skilled surgical staff. Our findings are consistent with those of other investigators. They reveal further evidence in favor of choosing the emerging technique of epidural narcotic analgesia. Comments Historically, the progress in vascular surgery and anesthetic techniques has seen some parallel achievements. In 1884, Halstead performed the first neural blockade using cocaine [2]. While performing end-to-end anastomosis and endoaneurysmorrhaphy in 1899, Dr. Rudolph Matas pioneered spinal anesthesia. He used a hypotonic solution of 10 to 20 mg of cocaine hydrochloride in distilled water. Also, utilizing the physiologic principles forwarded by Claude Bernard (1852) [3], Rene Leriche promoted surgical sympathectomy at the Strasbourg Vascular School in the late 1920s. The first reported lumbar epidural anesthesia was performed by Fidel Page and published in the Argentine Military Journal (1921) [4]. The popularization of this new technique for surgery was
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marked by Dogliotti’s publication in Europe and in The American Journal of Surgery (1933) [5]. Since the beginning of this century, vascular surgery has been performed under spinal or general anesthesia. Until recently, the fear, risk, and taboo of epidural hematoma has deemed epidural anesthesia prohibitive. Noteworthy in the recent development of epidural anesthesia for vascular surgery are a few landmark articles. The classic article of Cousins and Wright [6], demonstrated increased blood flow through a Dacron graft after epidural sympathetic block. Redistribution of the blood flow to the skin was achieved at the expense of the muscle. In the critical postoperative phase, vasoconstriction triggered by hypothermia and surgical manipulation may be relieved by sympathetic blockade. Distribution of blood flow to the lower extremities after epidural anesthesia has been shown to be due to decreased vascular resistance. In 1980, a review of 100 cases of abdominal aortic aneurysm repair using continuous epidural anesthesia combined with light general anesthesia documented adequate operative conditions [A. No epidural hematoma or any other anesthetic complication occurred. Epidural anesthesia has been recommended for aortofemoral aortography by Miller and Fagraeus [8]. These investigators reported that it provides a motionless field for improved quality films, patient comfort, minimal cardiovascular stress, and minimum sedation. The enhanced flow to small arteries and collateral vessels yielded superior radiographic studies. With the epidural catheter in place, and supplemented by light general anesthesia, their patients underwent vascular procedures. The investigators noted rapid awakening, extubation, no epidural hematoma and, if further operation was needed, the catheter allowed reanesthetization. Patients with coronary artery disease were given epidural anesthesia in a study that yielded dramatic results [9]. Improvement in left ventricular function was demonstrated by an increased left ventricular ejection fraction and improved regional cardiac wall motion. A more favorable myocardial oxygen supply and demand ratio was implicated. The effect of thoracic epidural anesthesia was measured in experimental occlusion of the left anterior descending coronary artery [IO]. The results showed that the myocardial infarct decreased in size and regional endocardial perfusion improved at the ischemic zone when compared with what occurred in the control group. In a group of 35 patients who underwent femoropopliteal bypass, epidural anesthesia was followed by epidural morphine for postoperative pain relief [II]. Five milligrams of morphine provided significant pain relief with no elevation of arterial carbon dioxide pressure or epidural hematoma. In a study of 30 patients, intrathecal morphine infusion (100
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TABLE I
al
Benefits of the Epidural Technique In Vascular Surgery
Endocrine Inhibits surgical stress response Inhibits adrenalin and cortisol release Inhibits hyperglycemia Inhibits lymphopenia and granulocytosis Nigrogen sparing Blocks sympathetic tone Cardiovascular Less myocardial oxygen demand and afterload Decreases myocardial infarct size (experimental model) Increases endocardial perfusion at ischemic zone Less sympathetic blood pressure swings Less blood loss Less general anesthesia depressant medication needed Redistributes blood to the lower extremities Pulmonary Decreases FVC, FEV- 1, & PEFR Less shunting oxygen consumption Improves atrioventricular oxygen differentiation Less pulmonary infections Less thromboembolism Renal Increase blood flow in the renal cortex Less renovascular constriction Geriatric Less cardiorespiratory trespass Improves postoperative mental status Miscellaneous Earlier extubation, ambulation, & discharge Greater oostooerative oain control FEV-1 = forced expiratory volume in 1 second; FVC = forced vital capacity; PEFR = peak expiratory flow rate.
pg/hour) was given after coronary bypass operation. The results showed effective pain relief, no epidural hematoma, minimal postoperative sedation, and early extubation (12 to 24 hours postoperatively)
WI.
A further review of the benefits of regional anesthesia details the significant metabolic stability afforded. The most important is the blunting of the surgical stress response [13]. Epidural anesthesia prepares a deafferentated surgical site, which stops the nociceptive spinal excitability. This, in turn, inhibits the stress elevation of the key trigger, catecholamines. Without this catecholamine explosion, there is blunting of its metabolic sequelae [14]. Thus, the biologic signal of cyclic adenosine monophosphate, which promotes the cortisol and glucose elevation, is beneficially depressed. Another significant marker of blunted stress response is the lack of P-endorphin elevation (Table I). There is a much smaller increase in pituitary, renal, and adrenal hormone levels under epidural anesthesia. Near normal levels of cortisol, renin, aldosterone, and growth hormone are achieved with this technique [15]. Elevations of plasma vasopressin (adenocorticotropic hormone) levels are reduced with epidural anesthesia. General anesthesia depresses the resting metabolic rate whereas epidural anesthesia does not [16]. The effect on pancreatic 194
hormones is preservation of glucose homeostasis. Hyperglycemia is further blunted by blockage of hepatic sympathetic innervation and adrenal medullary adrenergic release. The insulin level is lowered during epidural compared with general anesthesia. Diabetic patients are easier to manage due to the inhibition of this deleterious hepatic glycogenolysis. Nitrogen sparing and improved postoperative nitrogen balance due to the inhibition of stress-released catabolic hormones are enhanced by epidural anesthesia. In addition, immunosuppression is prevented by epidural anesthesia as manifested by the absence of lymphopenia and granulocytosis [17]. Various organ systems derive specific advantages during epidural anesthesia. The cerebral status can be easily monitored without the need for an electroencephalogram. The cardiac system has improved left ventricular function, increased myocardial oxygen supply and demand ratio, less catecholamine stress, hypertensive protection after cardiac surgery, decreased mean arterial pressure afterload at 20 percent, and avoidance of the depressant general anesthetics. Studies have shown the most popular inhalation anesthetic (isoflurane) causes coronary artery steal [18]. Nitrous oxide, which is used in most general anesthesia techniques, has been shown to cause pulmonary hypertension which is quite detrimental to the compromised cardiac patient. Sympathetic-mediated reactive swings in blood pressure are avoided with the regional technique. Blood loss has been shown to be diminished with regional anesthesia during total hip replacement (35 percent), hysterectomy (44 percent), retropubic prostate&my (37 percent) and transurethral resection of the prostate (18 percent) [19]. Epidural anesthesia decreases venous capacitance and circumvents the need for positive pressure ventilation because of increased venous pressures and consequent increased blood loss. Pulmonary function after thoracotomy with light general and epidural anesthesia is enhanced due to a smaller decrease in forced vital capacity and forced expiratory volume in 1 second [20]. Additional advantages are a decreased peak expiratory flow rate and better pain relief. In morbidly obese patients undergoing gastroplasty, epidural anesthesia provides decreased intrapulmonary shunting, decreased arteriovenous oxygen differential, and decreased oxygen consumption [21,22]. Pulmonary infections and total complications are decreased by 8 percent with epidural anesthesia. Continuous technique is more protective of pulmonary function than single-dose blockade [23]. One of the most convincing arguments in favor of regional anesthesia is the lowered incidence of thromboembolism [24]. When epidural anesthesia was compared with general anesthesia by plebography (iodine-125 fibrinogen scan) there was a The American Journal ef Surgery
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strikingly lower incidence of deep venous thrombosis in the femoropopliteal(54 percent) and calf and thigh (37 percent) regions. Pulmonary embolism was reduced 23 percent after hip replacement under epidural anesthesia. There are data consistent with increased blood flow, less venous stagnation in the lower extremity, less clotting, and more efficient fibrinolysis [25]. Indeed, epidural anesthesia should be added to the thromboprophylactic armamentariurn for high-risk patients and procedures. Renal sympathetic nerves blocked with epidural anesthesia help prevent renovascular constriction and angiotension secretion [26]. This block allows greater blood flow to the renal cortex without consequent natriuresis. Indicators of proximal tubular damage (lysozyme) were never found in urine samples of the epidural group, and creatinine clearance remained lower in this group. The disadvantages of general anesthesia are worthy of mention. Regional myocardial blood flow measured by radioactive microspheres exhibit coronary vasodilatation and coronary steal in patients with coronary artery disease. It is documented that general anesthetics are negative ionotrophic drugs. Nitrous oxide promotes pulmonary hypertension and limits inspired oxygen concentration. Halothane and enflurane (Ethranea) are arrythmogenic and depressors of the hepatorenal functions. All of the general anesthetic including the induction agents (for example, sodium thiopental and methohex&al) are potent cardiorespiratory depressants. In regard to epidural hematoma, the crux of the discussion hinges on whether the epidural technique is safe enough to merit a rethinking of traditional teaching. Recently, investigators have indicated that it is. Although hematoma is not the only complication of epidural anesthesia, it is the most serious consideration for its use in vascular patients. Symptoms of incontinence, severe low back pain, fecal incontinence, and sensory and motor deficits warn of this complication and the need for urgent myelography and surgical decompression. The evaluation of the patient is improved with postoperative epidural morphine anesthesia compared with epidural somatic block. Various investigators have reported cases of this devastating complication [27]. Although it is often spontaneous, there is an increased risk in patients with blood dyscrasias, hemophilia, leukemia, thrombocytopenia, and alcoholism, and in those who undergo anticoagulation, spinal canal neoplasm antiplatelet therapy, and difficult, traumatic epidural technique [23]. There are also neurologic deficits brought about by the unrelated causes of spinal artery spasm and hypotension and intrathecal preservatives or detergents and highly acidic preparations. In the perspective of the larger series of patients, the rarity of epidural hematoma is revealed. In the summation series of Bonica et al [29] the risk was Volume 154, August 1907
less than 0.01 percent. In more recent series, there were no cases of epidural hematoma in the vascular patients with anticoagulation therapy [30-321. This may have been due to luck or a quirk of statistics, or, alternatively, to the combination of the rarity of this risk due to improved soft atraumatic catheters, increased knowledge and skill of technique, increased monitoring and suspicion of this risk, and the level of anticoagulation. Although the need for caution when considering epidural technique before anticoagulation remains, an absolute contraindication no longer exists. In fact, with the emerging technologic advances in epidural narcotics and the continued catheter and monitoring improvements, the riskbenefit ratio may be further shifted. In regard to epidural narcotics, since the classic studies of Blume (1927) and Brooks (1937), opiates have been known to have a central nervous system receptor [S]. In 1981, Kitahata demonstrated a spinal avidity of opioids by iontophoretic application. This spinal opiate receptor was described by others [33]. In 1979, Wang and Nauss [34] reported the fist clinical use of intrathecal morphine (1 mg) for chronic intractable malignant pain. Cousins and Mather [33] and Yaksh [35] have contributed extensive reviews which have aided our understanding and stimulated research. In the review of Cousins and Mather, epidural narcotics were cited for use in many areas, including open heart, thorocotomy, orthopedic, and abdominal surgery and for chronic pain (including pain of cancer), and even for acute medical conditions, such as myocardial infarction and thrombophlebitis. Inadequate, sporadic postoperative analgesia has continued to be a problem in modern medicine and a primary concern of patients. This is exemplified by the avalanche of clinical research trials of this new technique [36]. Major vascular procedures in the intrinsic high-risk geriatric and cardiac group are a glaring omission in these early studies. The present report and that of Allen and Walman [II] have shown that the use of epidural narcotics allows superior analgesia after vascular procedures with minimum risk. Epidural narcotics afford selective analgesia without sympathetic sensory or motor blockade [371. The pharmacokinetic model proposes transport of the opiod from the epidural space to the cerebrospinal fluid. This is achieved by vascular uptake through the segmental posterior radicular arteries and also by the transfer across the arachnoid granulations near the dural cuff. Once in the cerebrospinal fluid, the unionized narcotic binds to the site of action or the opiate receptor in the substantia gelatinosa of the dorsal horn. The ionized hydrophilic molecule is available for the rostral spread responsible for the side effects. The incidence of the side effects of nausea, vomiting, pruritus, urinary retention, and respiratory depression vary according to dosages and individual 195
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al
clinical study. Nausea and vomiting (17 to 50 percent of patients) occurs about 8 hours after epidural morphine and coincides with the rostra1 spread to the chemoreceptor trigger zone. Pruritus (28 to 100 percent of patients) is due to histamine release 3 hours after administration of epidural morphine and has been reported to be severe in 1 percent of patients. Urinary retention (20 percent of patients) is due to inhibition of the detrusor muscle. It is not a factor in catheterized vascular patients. Respiratory depression has a dual peak onset. The first peak is the high plasma levels about 30 minutes after injection, and the second more insidious peak is due to the cephalad spread in the cerebrospinal fluid to the fourth ventricle 6 to 22 hours after injection. This respiratory depression can manifest as an increased end-tidal carbon dioxide level, a decreased ventilatory response to carbon dioxide, or in the extreme case, as apnea. It is this last scenario that necessitates the use of special monitoring by trained nurses, the intensive care unit setting, and apnea monitors. In addition, there have been very rare isolated cases of dysphoria, sedation, and catatonia not unlike what occurs with traditional narcotic overdose. All of these side effects may be treated by small doses of naloxone while preserving the analgesia. Patients receiving long-term high-dose treatment show tolerance to these side effects. The effective dose of epidural morphine after vascular procedures is 5 mg in 10 ml of normal saline solution (available in a FDA-approved preservative-free preparation). A higher dose affords equal analgesia and a higher incidence of side effects. The complete onset of epidural morphine may take 40 minutes. The duration varies from 6 to 36 hours, with a mean of 15 hours [38]. Epidural fentanyl (Sublimazee) (0.1 mg) affords a quicker onset (4 to 10 minutes). Fewer side effects, but much shorter duration (2.5 to 4 hours) [39]. This quick onset may be beneficial in the fragile cardiac patients in severe pain. Epidural narcotics have been shown to be more effective than the technology-dependent patient-controlled analgesia [40]. The enthusiasm for this technique is easy to understand. The pain-free postoperative state can be approached if the epidural narcotic is given while the sensory block is still intact. In this way, the metabolic and other benefits of epidural anesthesia can be combined with a pain-free postoperative course in this vulnerable patient population. Summary A combination epidural technique using local anesthetics intraoperatively and morphine postoperatively is shown to offer many advantages. These benefits include inhibition of the surgical stress response, decreased cardiorespiratory depression, decreased blood loss, decreased intubation and pulmonary infection, decreased thromboembolism,
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decreased hyperglycemic and hypertensive response, nitrogen sparing, a stable resting metabolic rate, prevention of immunosuppression, simplification of cerebral status monitoring, and earlier ambulation and hospital discharge. The main disadvantage in patients undergoing vascular procedures is the risk of epidural hematoma. A review of the literature confirms the extreme rarity of this risk and, in view of the emerging benefits, argues for reconsideration of epidural technique in vascular patients. The addition of epidural morphine to this combined technique affords a postoperative pain-free continuum unmatched by any other method. This significantly decreased pain stress in cardiac patients increases safety and comfort. In conclusion, epidural anesthesia and postoperative epidural narcotics provide a safe and reliable method of management for patients undergoing vascular procedures. Acknowledgment: We thank Dr. E. Kapakjian and David Mauro for their research and Noreen Berlin for her typing assistance. References 1. Bromage P, Camporisi E. Epidural narcotics for postoperative analgesia. Anesth Analg 1980; 59: 473-80. 2. Cousins M, Bridenbraugh P, eds. Neural blockade in clinical anesthesia and management of pain. Philadelphia: JP Lippincott, 7980. 3. Bernard C. Surles Effets de la Section de la Portion Cephalique du Grand Sympathique. CR Sot Biol 1852; 4: 168. 4. Pages F. Anestesia Metamerica. Argen Milit J 1921; 11: 35165. 5. Dogliotti AM. A new method of block anesthesia: segmental peridural anesthesia. Am J Surg 1933; 20:107. 6. Cousins M, Wright C. Graft, muscle, skin blood flow after epidural block in vascular surgical procedures. Surg Gynecol Obstet 1971; 133: 59-64. 7. Lunn J, DanneMiller F. Stanley T. Cardiovascular responses to clamping of the aorta during epidural and general anesthesia. Anesth Analg 1979; 58: 5. 8. Miller P, Fagraeus L. Epidural anesthesia in aortofemoral aortography. Ann Surg 1980; 192: 227-31. 9. Baron J, Coriat P. Left ventricular ejection fraction response to lumbar epidural anesthesia in patients with coronary artery diseases. Anesthesia 1985; 63: A227. 10. Davis R, Lawrence WL. Thoracic epidural anesthesia reduces myocardial infarct size after coronary artery occlusion in dogs. Anesth Analg 1986: 71 l-7. 11. Allen P, Walman T. Epidural morphine provides postoperative pain relief in peripheral vascular and orthopedic surgical patients. Anesth Analg 1986; 65: 165-70. 12. Mathews E. Abrams L. lntrathecal morphine in open heart surgery. Lancet 1986; 2: 543. 13. Kehlet H, Brandt M. Effect of epidural analgesia on metabolic profiles during and after surgery. Br J Surg 1979; 66: 5436. 14. Hjortso N, Christensen N, Andersen T, Kehlet H. Effects of extradural anesthesia and morphine on urinary excretion of cortisol. catecholamines and nitrogen following abdominal surgery. Br J Anaesth 1985; 57: 400-6. 15. Traynor C, Patterson J. Effects of extradural analgesia and vagal blockade on the metabolic and endocrine response to
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upper abdominal surgery. Br J Anaesth 1982; 54: 319. 18. Stern P, Howe J, Perkins F. Effect of epidural anesthesia on resting metabolic rate. Anesth Analg 1988; 85: ~152. 17. Rem J, Brandt M, Kehlet H. Prevention of post-operative lymphopenia and granulocytosis by epidural analgesia. Lancet 1980; 1: 283-4. 18. Pierbe H, Gale J. Adverse effects of isoflurane on myocardial function in the presence of coronary artery stenosis. Anesthesia 1985; 63: 3A,AlO. 19. Chin S, Abou-Madi M. Blood loss in total hip replacement: extradural vs general analgesia. Br J Anaesth 1982; 54: 491-4. 20. Shulman M, Sandler N. Post-thoracotomy pain and pulmonary function following epidural and systemic morphine. Anesthesiology 1984; 61: 569-75. 21. Hedenstierna G, Lofstrom J. Effects of anesthesia on respiratory function after major lower extremity surgery. Acta Anaesthesiol Stand 1985; 29: 55-60. 22. Gelman S, Laws H. Thoracic epidural vs balanced anesthesia in morbid obesity. Anesth Analg 1980; 59: 902-8. 23. Cuschieri RJ, Morran CG, Howie JC, McArdle CS. Postoperative pain and pulmonary complications: comparison of three analgesic regimens. Br J Surg 1985; 72: 495-8. 24. Modig J, Borg T. Thromboembolism after total hip replacement: role of epidural and general anesthesia. Anesth Analg 1983; 62: 174-80. 25. Arndt J, Hock A. Peridural anesthesia and the distribution of blood in supine humans. Anesthesia 1985; 63: 616-23. 26. Gamulin Z, Forster A. Effects of renal sympathetic blockade on renal hemodynamic:; in patients undergoing major aortic abdominal surgery. Anesthesiology 1986; 65: 688-92.
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27. Gingrich T. Spinal epidural hematoma following continuous epidural anesthesia. Anesthesiology 1986; 26: 1. 28. Owens E, Gregory K. Spinal subarachnoid hematoma after lumbar puncture and heparinization. Anesth Analg 1986; 65: 1201-7. 29. Bonica J, Anderson C. Peridural block: analysis of 3,637 cases and a review. Anesthesiology 1957; 18: 732. 30. Rao T, El-Etr A. Anticoagulatlon following placement of epidural and subarachnoid catheters. Anesthesiology 1981: 55: 618-20. 31. Odoom J, Sih I. Epidural analgesia and anticoagulant therapy. Anaesthesia 1983; 38: 254-9. 32. Cunningham F, Egan J. Continuous epidural anesthesia in abdominal vascular surgery. Am J Surg 1980; 139. 33. Cousins M, Mather L. lntrathecal and epidural administration of opiods. Anesthesia 1984; 61: 276-310. 34. Wang J, Nauss L. Pain relief by intrathecally applied morphine in man. Anesthesia 1970; 50: 149-51. 35. Yaksh T. Spinal opiate analgesia: characteristics and principles of action. Pain 2: 293-346. 36. Rawal N, Sjostrand U. Epidural morphine for postoperative pain relief. Anesth Analg 1982; 61: 93-8. 37. Hjortso N, Lund C. Epidural morphine improves pain relief. Anesth Analg 1986; 65: 1033-6. 38. Matin R, Salbaing J. Epidural morphine for postoperative pain relief: a dose-response curve. Anesthesia 1982; 56: 423. 39. Lomessy A, Christophe M. Clinical advantages of fentanyl given epidurally for post-operative analgesia. Anesthesia 1984; 61: 4. 40. Harrison D. Epidural anesthesia superior for post-cesarean pain. Convention Reporter Janssen Pharm 1986; 16: 20.
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Robert Raggi, MD, Herbert Dardik, MD, and Alfred L. Mauro, MD, Erglewood, New Jersey
A recent survey of anesthesiologists has indicated that an overwhelming majority (92 percent) would prefer regional anesthesia for their own operation. Regional anesthesia has become the anesthetic of choice for many surgical procedures, (for example, cataract extraction, transurethral resection of the prostate, and hand surgery). There is a recent accumulation of advantageous data which merits a reexamination of the risk-benefit ratio of epidural anesthesia for vascular procedures. The advantages include metabolic stability, suppression of the surgical stress response, cerebral status monitoring, stability of high-risk patients (for example, cardiac, hypertensive, diabetic, geriatric, and chronic obstructive pulmonary disease patients), and superior postoperative pain relief. It is the goal of this study to show the advantages of epidural anesthesia combined with postoperative epidural narcotics. Material and Methods Informed consent was obtained from all patients. Ninety-six patients (American Society of Anesthesiologists classes 2, 3, and 4) were scheduled for lower extremity vascular operations. The limb salvage procedures included femoropopliteal, femorotibial, and femoroperoneal bypass grafts and femoral endarterectomy with vein patch. Associated conditions included arteriosclerotic cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, hypertension, prior myocardial infarction, prior coronary artery bypass graft, ectopic beats, smoking history, chronic renal failure, S-T depression, and prior cerebrovascular accident, All patients received preoperative preparation from their internists. Preoperative diazepam (0.1 to 0.2 mg/kg) was given orally 1 to 2 hours before operation. Monitoring was carried out utilizing electrocardiography (lead II and modified V5), direct arterial line blood pressure, blood.gases, precordial stethoscope, verbal contact, axillary temperature, urinary catheterization, intermittent pretracheal ausculatation, and Swan-Ganz catheterization when indicated (16 percent). All patients From the Departments of Surgery and Anesthesia, Englewood Hospital, Englewood, New Jersey. Requests for reprints should be addressed to Robert Raggi, MD, Pain Clinic, Englewocd Hospital, 350 Engle Street, Englewocd. New Jersey 07632. Presented at the 15th Annual Meeting of the Society for Clinical Vascular Surgery, Scottsdale, Arizona, March 25-29, 1967.
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received various amounts of intravenous sedation and 2 to 4 liters of oxygen through a nasal cannula. Eight patients received supplemental light general anesthesia (various combinations of intravenous neuroleptic anesthesia: nitrous oxide and oxygen 2:1,0.25 percent forane, and diazepam, alone or in combination) for patient anxiety, positioning, comfort, and amnesia. Activated clotting time at baseline and postheparinization were followed. Patients received intravenous volume loading to prevent hypotension due to sympathetic block. Patients were positioned, prepped with povidone-iodine (Betadine”), and draped. The most skilled anesthesiologist available administered local anesthetic skin wheal and infiltration injection at the most accessible lumbar interspace under sterile conditions. The epidural space was identified with an 18 gauge Toughy needle, using the loss of resistance technique. After negative aspiration, a 3 ml test dose of 1.5 percent xylocaine with epinephrine (concentration 1:200,000) was administered. After 3 minutes, an anesthetic dose of 10 to 12 ml of 0.5 percent or 0.75 percent bupivicaine (84 percent) and 7 percent of patients, respectively or 2 percent xylocaine (9 percent of patients) was given. A Teflon@ epidural catheter was threaded, the disposable Toughy needle removed, and the catheter secured with a sterile dressing. Further local anesthetics were administered as repeat doses through the catheter as needed. Heparin was given intraoperatively after catheter placement. Five milligrams of preservative-free morphine in 10 ml of sterile normal saline solution was given at the conclusion of the operation in 35 percent of the patients and when patients indicated they had pain (65 percent), Patients were instructed to request pain medication promptly as needed. Monitoring was carried out in the surgical intensive care unit by nurses during and 24 hours after administration of the epidural narcotics. If the catheter was not functioning or if relief was inadequate, then patients received oral or intramuscular narcotics. Results
There was a 0 incidence of epidural hematoma and myocardial infarction. In five patients, epidural anesthesia failed and required administration of general anesthesia. Six patients required ephedrine (5 to 10 mg) intravenously. No other vasopressors or afterload reducers were needed, which attest to the hemodynamic stability offered by the technique.
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Postoperatively, seven patients required diuresis for mild cardiogenic pulmonary edema. The epidural catheter was nonfunctioning during the first 24 hours in 6 patients, which left 85 patients in the study group. The onset of epidural morphine analgesia was consistent with other studies, occurring within 10 to 45 minutes [I]. The mean duration of analgesia was 15 hours as measured by requests for pain medication and nurse observation. When pain medication was requested, a subsequent epidural morphine dose provided a smooth continuum of analgesia during the first 24 postoperative hours. In those patients who received epidural narcotic immediately after operation, their first 16 hours were virtually pain free. Eighty-five percent of the patients received complete analgesia with repeat doses of epidural morphine for 48 hours. Twelve patients had nausea and required naloxone (Narcane) 7 to 10 hours after administration of epidural morphine). Three patients vomited while receiving epidural morphine. Twenty-three patients needed naloxone for pruritus. Urinary side effects in these patients with bladder catheters were not assessed. No patients had respiratory arrest although nine patients had decreases in respiration rates (7 to 10 minutes) which did not require naloxone. One patient who had a subendocardial myocardial infarction 3 days earlier required emergency operation to prevent impending gangrene. He received the combination epidural technique. The operation was successful and the myocardial infarction was limited. These results point to a possible overexaggeration of risk and failure. We have focused on the available advantages of epidural anesthesia and postoperative epidural narcotics for vascular procedures performed by a skilled surgical staff. Our findings are consistent with those of other investigators. They reveal further evidence in favor of choosing the emerging technique of epidural narcotic analgesia. Comments Historically, the progress in vascular surgery and anesthetic techniques has seen some parallel achievements. In 1884, Halstead performed the first neural blockade using cocaine [2]. While performing end-to-end anastomosis and endoaneurysmorrhaphy in 1899, Dr. Rudolph Matas pioneered spinal anesthesia. He used a hypotonic solution of 10 to 20 mg of cocaine hydrochloride in distilled water. Also, utilizing the physiologic principles forwarded by Claude Bernard (1852) [3], Rene Leriche promoted surgical sympathectomy at the Strasbourg Vascular School in the late 1920s. The first reported lumbar epidural anesthesia was performed by Fidel Page and published in the Argentine Military Journal (1921) [4]. The popularization of this new technique for surgery was
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marked by Dogliotti’s publication in Europe and in The American Journal of Surgery (1933) [5]. Since the beginning of this century, vascular surgery has been performed under spinal or general anesthesia. Until recently, the fear, risk, and taboo of epidural hematoma has deemed epidural anesthesia prohibitive. Noteworthy in the recent development of epidural anesthesia for vascular surgery are a few landmark articles. The classic article of Cousins and Wright [6], demonstrated increased blood flow through a Dacron graft after epidural sympathetic block. Redistribution of the blood flow to the skin was achieved at the expense of the muscle. In the critical postoperative phase, vasoconstriction triggered by hypothermia and surgical manipulation may be relieved by sympathetic blockade. Distribution of blood flow to the lower extremities after epidural anesthesia has been shown to be due to decreased vascular resistance. In 1980, a review of 100 cases of abdominal aortic aneurysm repair using continuous epidural anesthesia combined with light general anesthesia documented adequate operative conditions [A. No epidural hematoma or any other anesthetic complication occurred. Epidural anesthesia has been recommended for aortofemoral aortography by Miller and Fagraeus [8]. These investigators reported that it provides a motionless field for improved quality films, patient comfort, minimal cardiovascular stress, and minimum sedation. The enhanced flow to small arteries and collateral vessels yielded superior radiographic studies. With the epidural catheter in place, and supplemented by light general anesthesia, their patients underwent vascular procedures. The investigators noted rapid awakening, extubation, no epidural hematoma and, if further operation was needed, the catheter allowed reanesthetization. Patients with coronary artery disease were given epidural anesthesia in a study that yielded dramatic results [9]. Improvement in left ventricular function was demonstrated by an increased left ventricular ejection fraction and improved regional cardiac wall motion. A more favorable myocardial oxygen supply and demand ratio was implicated. The effect of thoracic epidural anesthesia was measured in experimental occlusion of the left anterior descending coronary artery [IO]. The results showed that the myocardial infarct decreased in size and regional endocardial perfusion improved at the ischemic zone when compared with what occurred in the control group. In a group of 35 patients who underwent femoropopliteal bypass, epidural anesthesia was followed by epidural morphine for postoperative pain relief [II]. Five milligrams of morphine provided significant pain relief with no elevation of arterial carbon dioxide pressure or epidural hematoma. In a study of 30 patients, intrathecal morphine infusion (100
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TABLE I
al
Benefits of the Epidural Technique In Vascular Surgery
Endocrine Inhibits surgical stress response Inhibits adrenalin and cortisol release Inhibits hyperglycemia Inhibits lymphopenia and granulocytosis Nigrogen sparing Blocks sympathetic tone Cardiovascular Less myocardial oxygen demand and afterload Decreases myocardial infarct size (experimental model) Increases endocardial perfusion at ischemic zone Less sympathetic blood pressure swings Less blood loss Less general anesthesia depressant medication needed Redistributes blood to the lower extremities Pulmonary Decreases FVC, FEV- 1, & PEFR Less shunting oxygen consumption Improves atrioventricular oxygen differentiation Less pulmonary infections Less thromboembolism Renal Increase blood flow in the renal cortex Less renovascular constriction Geriatric Less cardiorespiratory trespass Improves postoperative mental status Miscellaneous Earlier extubation, ambulation, & discharge Greater oostooerative oain control FEV-1 = forced expiratory volume in 1 second; FVC = forced vital capacity; PEFR = peak expiratory flow rate.
pg/hour) was given after coronary bypass operation. The results showed effective pain relief, no epidural hematoma, minimal postoperative sedation, and early extubation (12 to 24 hours postoperatively)
WI.
A further review of the benefits of regional anesthesia details the significant metabolic stability afforded. The most important is the blunting of the surgical stress response [13]. Epidural anesthesia prepares a deafferentated surgical site, which stops the nociceptive spinal excitability. This, in turn, inhibits the stress elevation of the key trigger, catecholamines. Without this catecholamine explosion, there is blunting of its metabolic sequelae [14]. Thus, the biologic signal of cyclic adenosine monophosphate, which promotes the cortisol and glucose elevation, is beneficially depressed. Another significant marker of blunted stress response is the lack of P-endorphin elevation (Table I). There is a much smaller increase in pituitary, renal, and adrenal hormone levels under epidural anesthesia. Near normal levels of cortisol, renin, aldosterone, and growth hormone are achieved with this technique [15]. Elevations of plasma vasopressin (adenocorticotropic hormone) levels are reduced with epidural anesthesia. General anesthesia depresses the resting metabolic rate whereas epidural anesthesia does not [16]. The effect on pancreatic 194
hormones is preservation of glucose homeostasis. Hyperglycemia is further blunted by blockage of hepatic sympathetic innervation and adrenal medullary adrenergic release. The insulin level is lowered during epidural compared with general anesthesia. Diabetic patients are easier to manage due to the inhibition of this deleterious hepatic glycogenolysis. Nitrogen sparing and improved postoperative nitrogen balance due to the inhibition of stress-released catabolic hormones are enhanced by epidural anesthesia. In addition, immunosuppression is prevented by epidural anesthesia as manifested by the absence of lymphopenia and granulocytosis [17]. Various organ systems derive specific advantages during epidural anesthesia. The cerebral status can be easily monitored without the need for an electroencephalogram. The cardiac system has improved left ventricular function, increased myocardial oxygen supply and demand ratio, less catecholamine stress, hypertensive protection after cardiac surgery, decreased mean arterial pressure afterload at 20 percent, and avoidance of the depressant general anesthetics. Studies have shown the most popular inhalation anesthetic (isoflurane) causes coronary artery steal [18]. Nitrous oxide, which is used in most general anesthesia techniques, has been shown to cause pulmonary hypertension which is quite detrimental to the compromised cardiac patient. Sympathetic-mediated reactive swings in blood pressure are avoided with the regional technique. Blood loss has been shown to be diminished with regional anesthesia during total hip replacement (35 percent), hysterectomy (44 percent), retropubic prostate&my (37 percent) and transurethral resection of the prostate (18 percent) [19]. Epidural anesthesia decreases venous capacitance and circumvents the need for positive pressure ventilation because of increased venous pressures and consequent increased blood loss. Pulmonary function after thoracotomy with light general and epidural anesthesia is enhanced due to a smaller decrease in forced vital capacity and forced expiratory volume in 1 second [20]. Additional advantages are a decreased peak expiratory flow rate and better pain relief. In morbidly obese patients undergoing gastroplasty, epidural anesthesia provides decreased intrapulmonary shunting, decreased arteriovenous oxygen differential, and decreased oxygen consumption [21,22]. Pulmonary infections and total complications are decreased by 8 percent with epidural anesthesia. Continuous technique is more protective of pulmonary function than single-dose blockade [23]. One of the most convincing arguments in favor of regional anesthesia is the lowered incidence of thromboembolism [24]. When epidural anesthesia was compared with general anesthesia by plebography (iodine-125 fibrinogen scan) there was a The American Journal ef Surgery
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strikingly lower incidence of deep venous thrombosis in the femoropopliteal(54 percent) and calf and thigh (37 percent) regions. Pulmonary embolism was reduced 23 percent after hip replacement under epidural anesthesia. There are data consistent with increased blood flow, less venous stagnation in the lower extremity, less clotting, and more efficient fibrinolysis [25]. Indeed, epidural anesthesia should be added to the thromboprophylactic armamentariurn for high-risk patients and procedures. Renal sympathetic nerves blocked with epidural anesthesia help prevent renovascular constriction and angiotension secretion [26]. This block allows greater blood flow to the renal cortex without consequent natriuresis. Indicators of proximal tubular damage (lysozyme) were never found in urine samples of the epidural group, and creatinine clearance remained lower in this group. The disadvantages of general anesthesia are worthy of mention. Regional myocardial blood flow measured by radioactive microspheres exhibit coronary vasodilatation and coronary steal in patients with coronary artery disease. It is documented that general anesthetics are negative ionotrophic drugs. Nitrous oxide promotes pulmonary hypertension and limits inspired oxygen concentration. Halothane and enflurane (Ethranea) are arrythmogenic and depressors of the hepatorenal functions. All of the general anesthetic including the induction agents (for example, sodium thiopental and methohex&al) are potent cardiorespiratory depressants. In regard to epidural hematoma, the crux of the discussion hinges on whether the epidural technique is safe enough to merit a rethinking of traditional teaching. Recently, investigators have indicated that it is. Although hematoma is not the only complication of epidural anesthesia, it is the most serious consideration for its use in vascular patients. Symptoms of incontinence, severe low back pain, fecal incontinence, and sensory and motor deficits warn of this complication and the need for urgent myelography and surgical decompression. The evaluation of the patient is improved with postoperative epidural morphine anesthesia compared with epidural somatic block. Various investigators have reported cases of this devastating complication [27]. Although it is often spontaneous, there is an increased risk in patients with blood dyscrasias, hemophilia, leukemia, thrombocytopenia, and alcoholism, and in those who undergo anticoagulation, spinal canal neoplasm antiplatelet therapy, and difficult, traumatic epidural technique [23]. There are also neurologic deficits brought about by the unrelated causes of spinal artery spasm and hypotension and intrathecal preservatives or detergents and highly acidic preparations. In the perspective of the larger series of patients, the rarity of epidural hematoma is revealed. In the summation series of Bonica et al [29] the risk was Volume 154, August 1907
less than 0.01 percent. In more recent series, there were no cases of epidural hematoma in the vascular patients with anticoagulation therapy [30-321. This may have been due to luck or a quirk of statistics, or, alternatively, to the combination of the rarity of this risk due to improved soft atraumatic catheters, increased knowledge and skill of technique, increased monitoring and suspicion of this risk, and the level of anticoagulation. Although the need for caution when considering epidural technique before anticoagulation remains, an absolute contraindication no longer exists. In fact, with the emerging technologic advances in epidural narcotics and the continued catheter and monitoring improvements, the riskbenefit ratio may be further shifted. In regard to epidural narcotics, since the classic studies of Blume (1927) and Brooks (1937), opiates have been known to have a central nervous system receptor [S]. In 1981, Kitahata demonstrated a spinal avidity of opioids by iontophoretic application. This spinal opiate receptor was described by others [33]. In 1979, Wang and Nauss [34] reported the fist clinical use of intrathecal morphine (1 mg) for chronic intractable malignant pain. Cousins and Mather [33] and Yaksh [35] have contributed extensive reviews which have aided our understanding and stimulated research. In the review of Cousins and Mather, epidural narcotics were cited for use in many areas, including open heart, thorocotomy, orthopedic, and abdominal surgery and for chronic pain (including pain of cancer), and even for acute medical conditions, such as myocardial infarction and thrombophlebitis. Inadequate, sporadic postoperative analgesia has continued to be a problem in modern medicine and a primary concern of patients. This is exemplified by the avalanche of clinical research trials of this new technique [36]. Major vascular procedures in the intrinsic high-risk geriatric and cardiac group are a glaring omission in these early studies. The present report and that of Allen and Walman [II] have shown that the use of epidural narcotics allows superior analgesia after vascular procedures with minimum risk. Epidural narcotics afford selective analgesia without sympathetic sensory or motor blockade [371. The pharmacokinetic model proposes transport of the opiod from the epidural space to the cerebrospinal fluid. This is achieved by vascular uptake through the segmental posterior radicular arteries and also by the transfer across the arachnoid granulations near the dural cuff. Once in the cerebrospinal fluid, the unionized narcotic binds to the site of action or the opiate receptor in the substantia gelatinosa of the dorsal horn. The ionized hydrophilic molecule is available for the rostral spread responsible for the side effects. The incidence of the side effects of nausea, vomiting, pruritus, urinary retention, and respiratory depression vary according to dosages and individual 195
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clinical study. Nausea and vomiting (17 to 50 percent of patients) occurs about 8 hours after epidural morphine and coincides with the rostra1 spread to the chemoreceptor trigger zone. Pruritus (28 to 100 percent of patients) is due to histamine release 3 hours after administration of epidural morphine and has been reported to be severe in 1 percent of patients. Urinary retention (20 percent of patients) is due to inhibition of the detrusor muscle. It is not a factor in catheterized vascular patients. Respiratory depression has a dual peak onset. The first peak is the high plasma levels about 30 minutes after injection, and the second more insidious peak is due to the cephalad spread in the cerebrospinal fluid to the fourth ventricle 6 to 22 hours after injection. This respiratory depression can manifest as an increased end-tidal carbon dioxide level, a decreased ventilatory response to carbon dioxide, or in the extreme case, as apnea. It is this last scenario that necessitates the use of special monitoring by trained nurses, the intensive care unit setting, and apnea monitors. In addition, there have been very rare isolated cases of dysphoria, sedation, and catatonia not unlike what occurs with traditional narcotic overdose. All of these side effects may be treated by small doses of naloxone while preserving the analgesia. Patients receiving long-term high-dose treatment show tolerance to these side effects. The effective dose of epidural morphine after vascular procedures is 5 mg in 10 ml of normal saline solution (available in a FDA-approved preservative-free preparation). A higher dose affords equal analgesia and a higher incidence of side effects. The complete onset of epidural morphine may take 40 minutes. The duration varies from 6 to 36 hours, with a mean of 15 hours [38]. Epidural fentanyl (Sublimazee) (0.1 mg) affords a quicker onset (4 to 10 minutes). Fewer side effects, but much shorter duration (2.5 to 4 hours) [39]. This quick onset may be beneficial in the fragile cardiac patients in severe pain. Epidural narcotics have been shown to be more effective than the technology-dependent patient-controlled analgesia [40]. The enthusiasm for this technique is easy to understand. The pain-free postoperative state can be approached if the epidural narcotic is given while the sensory block is still intact. In this way, the metabolic and other benefits of epidural anesthesia can be combined with a pain-free postoperative course in this vulnerable patient population. Summary A combination epidural technique using local anesthetics intraoperatively and morphine postoperatively is shown to offer many advantages. These benefits include inhibition of the surgical stress response, decreased cardiorespiratory depression, decreased blood loss, decreased intubation and pulmonary infection, decreased thromboembolism,
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decreased hyperglycemic and hypertensive response, nitrogen sparing, a stable resting metabolic rate, prevention of immunosuppression, simplification of cerebral status monitoring, and earlier ambulation and hospital discharge. The main disadvantage in patients undergoing vascular procedures is the risk of epidural hematoma. A review of the literature confirms the extreme rarity of this risk and, in view of the emerging benefits, argues for reconsideration of epidural technique in vascular patients. The addition of epidural morphine to this combined technique affords a postoperative pain-free continuum unmatched by any other method. This significantly decreased pain stress in cardiac patients increases safety and comfort. In conclusion, epidural anesthesia and postoperative epidural narcotics provide a safe and reliable method of management for patients undergoing vascular procedures. Acknowledgment: We thank Dr. E. Kapakjian and David Mauro for their research and Noreen Berlin for her typing assistance. References 1. Bromage P, Camporisi E. Epidural narcotics for postoperative analgesia. Anesth Analg 1980; 59: 473-80. 2. Cousins M, Bridenbraugh P, eds. Neural blockade in clinical anesthesia and management of pain. Philadelphia: JP Lippincott, 7980. 3. Bernard C. Surles Effets de la Section de la Portion Cephalique du Grand Sympathique. CR Sot Biol 1852; 4: 168. 4. Pages F. Anestesia Metamerica. Argen Milit J 1921; 11: 35165. 5. Dogliotti AM. A new method of block anesthesia: segmental peridural anesthesia. Am J Surg 1933; 20:107. 6. Cousins M, Wright C. Graft, muscle, skin blood flow after epidural block in vascular surgical procedures. Surg Gynecol Obstet 1971; 133: 59-64. 7. Lunn J, DanneMiller F. Stanley T. Cardiovascular responses to clamping of the aorta during epidural and general anesthesia. Anesth Analg 1979; 58: 5. 8. Miller P, Fagraeus L. Epidural anesthesia in aortofemoral aortography. Ann Surg 1980; 192: 227-31. 9. Baron J, Coriat P. Left ventricular ejection fraction response to lumbar epidural anesthesia in patients with coronary artery diseases. Anesthesia 1985; 63: A227. 10. Davis R, Lawrence WL. Thoracic epidural anesthesia reduces myocardial infarct size after coronary artery occlusion in dogs. Anesth Analg 1986: 71 l-7. 11. Allen P, Walman T. Epidural morphine provides postoperative pain relief in peripheral vascular and orthopedic surgical patients. Anesth Analg 1986; 65: 165-70. 12. Mathews E. Abrams L. lntrathecal morphine in open heart surgery. Lancet 1986; 2: 543. 13. Kehlet H, Brandt M. Effect of epidural analgesia on metabolic profiles during and after surgery. Br J Surg 1979; 66: 5436. 14. Hjortso N, Christensen N, Andersen T, Kehlet H. Effects of extradural anesthesia and morphine on urinary excretion of cortisol. catecholamines and nitrogen following abdominal surgery. Br J Anaesth 1985; 57: 400-6. 15. Traynor C, Patterson J. Effects of extradural analgesia and vagal blockade on the metabolic and endocrine response to
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upper abdominal surgery. Br J Anaesth 1982; 54: 319. 18. Stern P, Howe J, Perkins F. Effect of epidural anesthesia on resting metabolic rate. Anesth Analg 1988; 85: ~152. 17. Rem J, Brandt M, Kehlet H. Prevention of post-operative lymphopenia and granulocytosis by epidural analgesia. Lancet 1980; 1: 283-4. 18. Pierbe H, Gale J. Adverse effects of isoflurane on myocardial function in the presence of coronary artery stenosis. Anesthesia 1985; 63: 3A,AlO. 19. Chin S, Abou-Madi M. Blood loss in total hip replacement: extradural vs general analgesia. Br J Anaesth 1982; 54: 491-4. 20. Shulman M, Sandler N. Post-thoracotomy pain and pulmonary function following epidural and systemic morphine. Anesthesiology 1984; 61: 569-75. 21. Hedenstierna G, Lofstrom J. Effects of anesthesia on respiratory function after major lower extremity surgery. Acta Anaesthesiol Stand 1985; 29: 55-60. 22. Gelman S, Laws H. Thoracic epidural vs balanced anesthesia in morbid obesity. Anesth Analg 1980; 59: 902-8. 23. Cuschieri RJ, Morran CG, Howie JC, McArdle CS. Postoperative pain and pulmonary complications: comparison of three analgesic regimens. Br J Surg 1985; 72: 495-8. 24. Modig J, Borg T. Thromboembolism after total hip replacement: role of epidural and general anesthesia. Anesth Analg 1983; 62: 174-80. 25. Arndt J, Hock A. Peridural anesthesia and the distribution of blood in supine humans. Anesthesia 1985; 63: 616-23. 26. Gamulin Z, Forster A. Effects of renal sympathetic blockade on renal hemodynamic:; in patients undergoing major aortic abdominal surgery. Anesthesiology 1986; 65: 688-92.
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27. Gingrich T. Spinal epidural hematoma following continuous epidural anesthesia. Anesthesiology 1986; 26: 1. 28. Owens E, Gregory K. Spinal subarachnoid hematoma after lumbar puncture and heparinization. Anesth Analg 1986; 65: 1201-7. 29. Bonica J, Anderson C. Peridural block: analysis of 3,637 cases and a review. Anesthesiology 1957; 18: 732. 30. Rao T, El-Etr A. Anticoagulatlon following placement of epidural and subarachnoid catheters. Anesthesiology 1981: 55: 618-20. 31. Odoom J, Sih I. Epidural analgesia and anticoagulant therapy. Anaesthesia 1983; 38: 254-9. 32. Cunningham F, Egan J. Continuous epidural anesthesia in abdominal vascular surgery. Am J Surg 1980; 139. 33. Cousins M, Mather L. lntrathecal and epidural administration of opiods. Anesthesia 1984; 61: 276-310. 34. Wang J, Nauss L. Pain relief by intrathecally applied morphine in man. Anesthesia 1970; 50: 149-51. 35. Yaksh T. Spinal opiate analgesia: characteristics and principles of action. Pain 2: 293-346. 36. Rawal N, Sjostrand U. Epidural morphine for postoperative pain relief. Anesth Analg 1982; 61: 93-8. 37. Hjortso N, Lund C. Epidural morphine improves pain relief. Anesth Analg 1986; 65: 1033-6. 38. Matin R, Salbaing J. Epidural morphine for postoperative pain relief: a dose-response curve. Anesthesia 1982; 56: 423. 39. Lomessy A, Christophe M. Clinical advantages of fentanyl given epidurally for post-operative analgesia. Anesthesia 1984; 61: 4. 40. Harrison D. Epidural anesthesia superior for post-cesarean pain. Convention Reporter Janssen Pharm 1986; 16: 20.
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