464
ANESTH ANALG 1992;75:461-71
LETTERS TO THE EDITOR
is known about the influence of general anesthesia on the cytokine network, although ongoing studies at our institution have initially shown that the induction of general anesthesia has no significant immediate influence on levels of IL-6. The effect of postoperative epidural administration of local anesthetics and/or narcotics on IL-6 levels is unknown. We support the approach taken by Tuman and colleagues of utilizing the thrombelastograph as a tool to measure fibrinogen-platelet interactions in the postoperative period, and believe that the most likely explanation for their results is an inhibition of the release of "stressrelated' hormones, and subsequent inhibition of platelet adhesion-aggregation that is normally augmented by these stress hormones. Although not examined in the study of Tuman et al., another explanation may be inhibition of the "acute phase response" in the postoperative period, which if prolonged may predispose patients to development of a hypercoagulabke state secondary to augmented fibrinogen synthesis. Further studies closely examining the influence of EAA on the inflammatory response may help further delineate the beneficial influence of postoperative epidural analgesia on morbidity/mortality in the surgical population. Charles W. Whitten, MD Paul M. Allison, MD Terry Latson, MD
w.
Departmetits of Anesthesiology and Pathology The Unirrersity of Texas Southwestern Medical Center 5323 Harry Hines Bouievard Dallas, TX 75235-8894
References 1. Steele SM, Slaughter TF, Greenberg CS, Reves JC. Epidural anesthesia and analgesia: implications for perioperative coagulability. Anesth Analg 1991;73:68%5. 2. Tuman KJ, McCarthy RJ, March RJ, DeLaria GA, Patel RV, Ivankovich AD. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 1991;73:696-704. 3. Bauer J, Herrmann F. Interleukin-6 in clinical medicine. Ann Hernatol 1991;62:20?-10.
In Response: We thank Whitten et al. for their affirmative comments about our manuscript and compliment them for the additional insight they provide into potential mechanisms by which EAA influences coagulation. We agree with Whitten et al. that if EAA is indeed associated with lesser postoperative levels of circulating fibrinogen in patients with vascular disease, this may possibly be a result of inhibition of the "acute-phase response" with attenuation of augmented fibrinogen production, but is unlikely to be a result of changes in basal fibrinogen production. Whitten et al. correctly note that the observation of decreases in coagulability as early as 24 h after surgery in patients receiving EAA is inconsistent with the pharmacokinetics of basal fibrinogen production and metabolism. The most likely explanation for the altered fibrinogen-platelet effects measured on the first postoperative day is inhibition of the release of stress-related hormones such as catecholamines with subsequent reduction in the otherwise increased platelet activity produced by such mediators, as Whitten et al. contend. We further postulate that our findings could be related to decreases in plasminogen activator inhibitor with subsequent increases in fibrin(ogen) breakdown, but addi-
tional studies will be necessary to elucidate the exact mechanisms by which EAA influences coagulation. Kenneth J. Tuman, MD Robert J. McCarthy, PharrnD Anthony D. Ivankovich, MD Department of Anesthesiology Rush-Presbyterian-St. Luke's Medical Center Chicago, IL 60612
Epidural Anesthesia and Analgesia in Vascular Surgery To the Editor: We read with interest the recent article by Tuman et al. and the accompanying editorial (1,2). There is convincing evidence that epidural anesthesia and analgesia (EAA) blunts the stress response to surgery (3); but, does this have a positive effect on outcome? Tuman et al. suggest that EAA modifies the coagulation system with salutary effects on adverse thrombotic events. In vascular surgery these adverse thrombotic events can involve either (a) the arterial graft, (b) the coronary arteries, or (c) the venous system. The resulting adverse outcomes are, respectively, (a) graft failure, (b) perioperative myocardial infarction (PMI), and (c) pulmonary embolism secondary to venous thrombosis. Interpretation of the outcome portion of the Tuman study is difficult. The study population consisted of a heterogenous set of vascular procedures. Apparently, roughly half of the procedures involved infrainguinal reconstruction and the remainder were aortofemoral bypass procedures. It is plausible that EAA-induced changes in coagulation could have a salutary effect on graft failure in infrainguinal procedures. On the other hand, graft failure in aortofemoral bypass procedures is almost entirely due to technical difficulties where anesthetic technique is unlikely to have an impact. Therefore, it would be very helpful to know if the graft failures involved infrainguinal procedures. Tuman et al. note that all the patients who had graft failure had intraoperative arteriograms at the completion of the initial operation. Are completion arteriograms standard at the study institution or did the operating surgeons obtain them in these cases because technical difficulties were already suspected? If indeed, graft failures in the control group all involved infrainguinal procedures, the relevant rate is 8/20 (40%) as half of the 40 control patients underwent infrainguinal procedures. This is much higher than the 5%-10% rate of early graft failure found in comparable series of infrainguinal procedures (4-6). Some retrospective data would be helpful here. What was the rate of early graft failure in the study institution before the initiation of the protocol? If the earlier rate of graft failure was more in line with that reported in other series (
ANESTH ANALG 1992;75:461-71
LETTERS TO THE EDITOR
is known about the influence of general anesthesia on the cytokine network, although ongoing studies at our institution have initially shown that the induction of general anesthesia has no significant immediate influence on levels of IL-6. The effect of postoperative epidural administration of local anesthetics and/or narcotics on IL-6 levels is unknown. We support the approach taken by Tuman and colleagues of utilizing the thrombelastograph as a tool to measure fibrinogen-platelet interactions in the postoperative period, and believe that the most likely explanation for their results is an inhibition of the release of "stressrelated' hormones, and subsequent inhibition of platelet adhesion-aggregation that is normally augmented by these stress hormones. Although not examined in the study of Tuman et al., another explanation may be inhibition of the "acute phase response" in the postoperative period, which if prolonged may predispose patients to development of a hypercoagulabke state secondary to augmented fibrinogen synthesis. Further studies closely examining the influence of EAA on the inflammatory response may help further delineate the beneficial influence of postoperative epidural analgesia on morbidity/mortality in the surgical population. Charles W. Whitten, MD Paul M. Allison, MD Terry Latson, MD
w.
Departmetits of Anesthesiology and Pathology The Unirrersity of Texas Southwestern Medical Center 5323 Harry Hines Bouievard Dallas, TX 75235-8894
References 1. Steele SM, Slaughter TF, Greenberg CS, Reves JC. Epidural anesthesia and analgesia: implications for perioperative coagulability. Anesth Analg 1991;73:68%5. 2. Tuman KJ, McCarthy RJ, March RJ, DeLaria GA, Patel RV, Ivankovich AD. Effects of epidural anesthesia and analgesia on coagulation and outcome after major vascular surgery. Anesth Analg 1991;73:696-704. 3. Bauer J, Herrmann F. Interleukin-6 in clinical medicine. Ann Hernatol 1991;62:20?-10.
In Response: We thank Whitten et al. for their affirmative comments about our manuscript and compliment them for the additional insight they provide into potential mechanisms by which EAA influences coagulation. We agree with Whitten et al. that if EAA is indeed associated with lesser postoperative levels of circulating fibrinogen in patients with vascular disease, this may possibly be a result of inhibition of the "acute-phase response" with attenuation of augmented fibrinogen production, but is unlikely to be a result of changes in basal fibrinogen production. Whitten et al. correctly note that the observation of decreases in coagulability as early as 24 h after surgery in patients receiving EAA is inconsistent with the pharmacokinetics of basal fibrinogen production and metabolism. The most likely explanation for the altered fibrinogen-platelet effects measured on the first postoperative day is inhibition of the release of stress-related hormones such as catecholamines with subsequent reduction in the otherwise increased platelet activity produced by such mediators, as Whitten et al. contend. We further postulate that our findings could be related to decreases in plasminogen activator inhibitor with subsequent increases in fibrin(ogen) breakdown, but addi-
tional studies will be necessary to elucidate the exact mechanisms by which EAA influences coagulation. Kenneth J. Tuman, MD Robert J. McCarthy, PharrnD Anthony D. Ivankovich, MD Department of Anesthesiology Rush-Presbyterian-St. Luke's Medical Center Chicago, IL 60612
Epidural Anesthesia and Analgesia in Vascular Surgery To the Editor: We read with interest the recent article by Tuman et al. and the accompanying editorial (1,2). There is convincing evidence that epidural anesthesia and analgesia (EAA) blunts the stress response to surgery (3); but, does this have a positive effect on outcome? Tuman et al. suggest that EAA modifies the coagulation system with salutary effects on adverse thrombotic events. In vascular surgery these adverse thrombotic events can involve either (a) the arterial graft, (b) the coronary arteries, or (c) the venous system. The resulting adverse outcomes are, respectively, (a) graft failure, (b) perioperative myocardial infarction (PMI), and (c) pulmonary embolism secondary to venous thrombosis. Interpretation of the outcome portion of the Tuman study is difficult. The study population consisted of a heterogenous set of vascular procedures. Apparently, roughly half of the procedures involved infrainguinal reconstruction and the remainder were aortofemoral bypass procedures. It is plausible that EAA-induced changes in coagulation could have a salutary effect on graft failure in infrainguinal procedures. On the other hand, graft failure in aortofemoral bypass procedures is almost entirely due to technical difficulties where anesthetic technique is unlikely to have an impact. Therefore, it would be very helpful to know if the graft failures involved infrainguinal procedures. Tuman et al. note that all the patients who had graft failure had intraoperative arteriograms at the completion of the initial operation. Are completion arteriograms standard at the study institution or did the operating surgeons obtain them in these cases because technical difficulties were already suspected? If indeed, graft failures in the control group all involved infrainguinal procedures, the relevant rate is 8/20 (40%) as half of the 40 control patients underwent infrainguinal procedures. This is much higher than the 5%-10% rate of early graft failure found in comparable series of infrainguinal procedures (4-6). Some retrospective data would be helpful here. What was the rate of early graft failure in the study institution before the initiation of the protocol? If the earlier rate of graft failure was more in line with that reported in other series (
