LETTERS TO THE EDITOR
ANESTH ANALG 1992;75461-71
Suicide Attempt After Anesthesia To the Editor:
A 58-yr-old man was admitted to a municipal hospital for an inguinal herniorraphy. He was otherwise healthy and was taking no medications. He had a negative medical and psychiatric history but was described as being excessively talkative, and the resident who took the history believed that the patient might be having paranoid delusions. Although a psychiatric consultation was requested, it was not carried out before the surgical procedure. The patient received general anesthesia (isoflurane, nitrous oxide, midazolam, fentanyl, thiopental, and atracurium) and had the hernia repaired. He had an uneventful recovery in the postanesthesia care unit, and there were no reports of unusual behavior. Several hours later, after the patient had been discharged to the ward, he was found on his bed with a deep bleeding wound across the neck. He was taken to the operating room, the neck was explored, and the hemorrhage was brought under control. He later admitted that he had tried to kill himself with a razor blade and was diagnosed as suffering from schizophrenia. Many factors surrounding anesthesia and surgery may trigger emergence delirium and postoperative psychosis. These include drugs, fever, pain, hypoxia, metabolic derangements, and psychological factors (1). This patient was already suffering from an undiagnosed psychiatric disorder that made the initial differential diagnosis somewhat difficult. The incidence of schizophrenia is much higher in the lower socioeconomic groups (2). Given the fact that municipal hospitals tend to serve this patient population, a high index of suspicion should be maintained in this setting. An elective preoperative psychiatric evaluation may be warranted in a patient suspected of suffering from a mental illness. This will not only help with the differential diagnosis of postoperative psychosis, but may also and most importantly, prevent the patient from harming himself or others. Rafael Ortega,
MD
Department of Anesthesiology Boston University Medical Center 88 East Nezuton Street Boston, MA 02118
References 1. Olympio MA. Postanesthetic delirium: historical perspectives. J Clin Anesth 1991;3:603. 2. Tucker GH. Psychiatric disorders in medical practice. In: Wyngaarden JB, Smith LH, eds. Cecil textbook of medicine. Philadelphia: WB Saunders, 19882091-103.
How Does Epidural Anesthesia and Analgesia Influence Perioperative Coagulability? To the Editor: We read with great interest the editorial by Steele and colleagues (1)accompanying the paper by Tuman et al. (2). We would like to commend Steele et al. for their review of
463
the current literature regarding the influence of epidural anesthesia and analgesia (EAA) on perioperative coagulability. Tuman et al. have put forth an outstanding effort that helps better differentiate why those of us performing general anesthetics with epidural catheters placed for postoperative pain control believe that this is superior to the more traditional approach of general anesthetics with ondemand postoperative analgesics (intermittent intramuscular, intravenous, or oral pain medications). Anesthesiologists have discovered that appropriate management of perioperative hemodynamic abnormalities can influence outcome in ”high-risk” patients, although stable perioperative hernodynamics do not necessarily ensure uneventful cardiovascular outcome. Tuman has put forth an interesting proposal of ”perioperative hypercoagulability” as another issue that must be dealt with in ”high-risk patients. How blockade of the ”perioperative stress response” may influence this propensity for hypercoagulability in the postoperative period is still not well understood. We would like to qualify and expound upon one idea put forth in the editorial by Steele et al. stating: “Fibrinogen, a glycoprotein essential to hemostasis and blood viscosity, is frequently increased in patients with vascular disease. Perhaps EAA reduces fibrinogen.” It is important to remember that the half-life of fibrinogen in humans is 3 4 days and in Tuman’s study the average utilization of epidural catheters was 2.4 -+ 0.98 days. Speculation that this intervention, administered for such a period of time, would influence fibrinogen levels significantly in the postoperative period must take the long half-life into account. It might be that augmented fibrinogen production is reduced by EAA, although this will be difficult to prove in clinical studies owing to the large variability involved in performing functional fibrinogen assays. Fibrinogen plays an essential role in hemostasis and the maintenance of blood viscosity. It mediates the formation of platelet aggregates and, in the coagulation cascade, is transformed by thrombin into fibrin monomers that polymerize to form the basis of a hemostatic plug. Ten to twenty-five percent of the total body fibrinogen is extravascular. Of the circulating fibrinogen in blood, about 3% is located in the platelet alpha granules, although it is unclear if this is the result of fibrinogen biosynthesis by megakaryocytes or due to platelet uptake from the plasma. Plasma levels of fibrinogen and a subset of other hepatic proteins increase during the “acute-phase response” to injury and infection (3). For fibrinogen, the protein level reflects a coordinated increase in the hepatic production of the mRNAs that direct the synthesis of the three pairs of nonidentical polypeptide chains that compose fibrinogen. The increase is predominantly in response to interleukin-6 (IL-6) produced by monocytes/macrophages. Interleukin-6, a key mediator in the inflammatory response, preferentially stimulates the synthesis of fibrinogen in human hepatoma cells. Whether the influence of EAA on the stress response may have some effect on the inflammatory response is unknown. The effects of stress on the inflammatory response are likely complex. Perhaps EAA decreases hypercoagulability by direct or indirect modulation of the inflammatory response (decreased production of IL-6) and subsequent inhibition of the “acute-phase response.” Little
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;75461-71
Suicide Attempt After Anesthesia To the Editor:
A 58-yr-old man was admitted to a municipal hospital for an inguinal herniorraphy. He was otherwise healthy and was taking no medications. He had a negative medical and psychiatric history but was described as being excessively talkative, and the resident who took the history believed that the patient might be having paranoid delusions. Although a psychiatric consultation was requested, it was not carried out before the surgical procedure. The patient received general anesthesia (isoflurane, nitrous oxide, midazolam, fentanyl, thiopental, and atracurium) and had the hernia repaired. He had an uneventful recovery in the postanesthesia care unit, and there were no reports of unusual behavior. Several hours later, after the patient had been discharged to the ward, he was found on his bed with a deep bleeding wound across the neck. He was taken to the operating room, the neck was explored, and the hemorrhage was brought under control. He later admitted that he had tried to kill himself with a razor blade and was diagnosed as suffering from schizophrenia. Many factors surrounding anesthesia and surgery may trigger emergence delirium and postoperative psychosis. These include drugs, fever, pain, hypoxia, metabolic derangements, and psychological factors (1). This patient was already suffering from an undiagnosed psychiatric disorder that made the initial differential diagnosis somewhat difficult. The incidence of schizophrenia is much higher in the lower socioeconomic groups (2). Given the fact that municipal hospitals tend to serve this patient population, a high index of suspicion should be maintained in this setting. An elective preoperative psychiatric evaluation may be warranted in a patient suspected of suffering from a mental illness. This will not only help with the differential diagnosis of postoperative psychosis, but may also and most importantly, prevent the patient from harming himself or others. Rafael Ortega,
MD
Department of Anesthesiology Boston University Medical Center 88 East Nezuton Street Boston, MA 02118
References 1. Olympio MA. Postanesthetic delirium: historical perspectives. J Clin Anesth 1991;3:603. 2. Tucker GH. Psychiatric disorders in medical practice. In: Wyngaarden JB, Smith LH, eds. Cecil textbook of medicine. Philadelphia: WB Saunders, 19882091-103.
How Does Epidural Anesthesia and Analgesia Influence Perioperative Coagulability? To the Editor: We read with great interest the editorial by Steele and colleagues (1)accompanying the paper by Tuman et al. (2). We would like to commend Steele et al. for their review of
463
the current literature regarding the influence of epidural anesthesia and analgesia (EAA) on perioperative coagulability. Tuman et al. have put forth an outstanding effort that helps better differentiate why those of us performing general anesthetics with epidural catheters placed for postoperative pain control believe that this is superior to the more traditional approach of general anesthetics with ondemand postoperative analgesics (intermittent intramuscular, intravenous, or oral pain medications). Anesthesiologists have discovered that appropriate management of perioperative hemodynamic abnormalities can influence outcome in ”high-risk” patients, although stable perioperative hernodynamics do not necessarily ensure uneventful cardiovascular outcome. Tuman has put forth an interesting proposal of ”perioperative hypercoagulability” as another issue that must be dealt with in ”high-risk patients. How blockade of the ”perioperative stress response” may influence this propensity for hypercoagulability in the postoperative period is still not well understood. We would like to qualify and expound upon one idea put forth in the editorial by Steele et al. stating: “Fibrinogen, a glycoprotein essential to hemostasis and blood viscosity, is frequently increased in patients with vascular disease. Perhaps EAA reduces fibrinogen.” It is important to remember that the half-life of fibrinogen in humans is 3 4 days and in Tuman’s study the average utilization of epidural catheters was 2.4 -+ 0.98 days. Speculation that this intervention, administered for such a period of time, would influence fibrinogen levels significantly in the postoperative period must take the long half-life into account. It might be that augmented fibrinogen production is reduced by EAA, although this will be difficult to prove in clinical studies owing to the large variability involved in performing functional fibrinogen assays. Fibrinogen plays an essential role in hemostasis and the maintenance of blood viscosity. It mediates the formation of platelet aggregates and, in the coagulation cascade, is transformed by thrombin into fibrin monomers that polymerize to form the basis of a hemostatic plug. Ten to twenty-five percent of the total body fibrinogen is extravascular. Of the circulating fibrinogen in blood, about 3% is located in the platelet alpha granules, although it is unclear if this is the result of fibrinogen biosynthesis by megakaryocytes or due to platelet uptake from the plasma. Plasma levels of fibrinogen and a subset of other hepatic proteins increase during the “acute-phase response” to injury and infection (3). For fibrinogen, the protein level reflects a coordinated increase in the hepatic production of the mRNAs that direct the synthesis of the three pairs of nonidentical polypeptide chains that compose fibrinogen. The increase is predominantly in response to interleukin-6 (IL-6) produced by monocytes/macrophages. Interleukin-6, a key mediator in the inflammatory response, preferentially stimulates the synthesis of fibrinogen in human hepatoma cells. Whether the influence of EAA on the stress response may have some effect on the inflammatory response is unknown. The effects of stress on the inflammatory response are likely complex. Perhaps EAA decreases hypercoagulability by direct or indirect modulation of the inflammatory response (decreased production of IL-6) and subsequent inhibition of the “acute-phase response.” Little
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 (
