Edward J. Norris

Perioperative Morbidity in Patients Randomized to Epidural or General Anesthesia for Lower Extremity Vascular Surgery

Background:Perioperative morbidity may be modifiable in high risk patients by the anesthesiologists choice of either regional or general anesthesia. This clinical trial compared outcomes between epidural (EA) and general (GA) anesthesia/analgesia regimens In a group of patients at high risk for cardiac and other morbidity who were undergoing similarly stressful surgical procedures. Methods:One hundred patients scheduled for elective vascular reconstruction of the lower extremities were randomized to receive either EA for surgery followed by epidural analgesia, or GA for surgery followed by intravenous patient-controlled analgesia. Hemodynamic monitoring, blood pressure, and heart rate limits were determined prior to randomization. Management of anesthesia in the immediate postoperative period was standardized. The data collected included continuous electrocardiographic monitoring from the day before surgery through the third postoperative day, serial electrocardiograms, and cardiac enzymes. Cardiac ischemia, myocardial infarction, unstable angina, and cardiac death were identified by a cardiologist blinded to the type of anesthesia received. Other major morbidity was determined at the time of hospital discharge and at 1 and 6 months after surgery. Results:Eleven patients who received GA required regrafting or an embolectomy during their hospital stay, compared with two patients who received EA. This association of GA with reoperation remained significant after adjustment for baseline differences. Cardiac outcomes were similar in the two groups with respect to perioperative death (1 EA and 1 GA), death within 6 months (4 EA and 3 GA), nonfatal myocardial infarction within 7 days (2 EA and 2 GA), unstable angina (0 EA and 2 GA), and myocardial ischemia following randomization (17 EA and 23 GA). Rates of major infections in the two groups (1 EA and 2 GA), renal failure (3 EA and 3 GA), and pulmonary complications (3 EA and 7 GA) also were similar. Conclusions:Carefully conducted epidural and general anesthesia appear to be associated with comparable rates of cardiac and most other morbidity in patients undergoing lower extremity vascular surgery. However, compared with general anesthesia, epidural anesthesia is associated with a lower incidence of reoperatlon for inadequate tissue perfusion and, therefore, may be advantageous for this surgical population.

Unintentional Hypothermia Is Associated with Postoperative Myocardial Ischemia

BackgroundHypothermia occurs commonly during surgery and can be associated with increased metabolic demands during rewarming in the postoperative period. Although cardiac complications remain the leading cause of morbidity after anesthesia and surgery, the relationship between unintentional hypothermia and myocardial ischemia during the perioperative period has not been studied. MethodsOne hundred patients undergoing lower extremity vascular reconstruction received continuous Hotter monitoring throughout the first 24 h postoperatively. Myocardial ischemia was determined by a cardiologist masked to clinical variables. The patients sublingual temperature on arrival at the intensive care unit immediately after the surgical procedure was used to divide the patients into two groups: hypothermic (temperature, < 35°C; n = 33) and normothermic (temperature, ≤ 35°C; n = 67). The relationship between unintentional hypothermia and myocardial ischemia occurring during the first postoperative day was evaluated by univariate and multivariate analyses. ResultsA greater percentage of patients had electrocardiographic changes consistent with myocardial ischemia in the hypothermic group (36%, 12 of 33) compared with those in the normothermic group (13%, 9 of 67, P = 0.008). Preoperative risk factors for perioperative cardiac morbidity were similar between the two groups, except for patient age. The mean age was 70 ± 2 yr and 62 ± 1 yr in the hypothermic and normothermic groups, respectively (P = 0.001). When subgroup and multivariate analyses were used to adjust for differences in age, temperature remained an independent predictor of ischemia (odds ratio, 1.82 per degree Celsius; 95% confidence interval, 1.09–3.02). The incidence of postoperative angina was greater in the hypothermic group (18%, 6 of 33) than in the normothermic group (1.5%, 1 of 67, P = 0.002). The incidence of PaO2 < 80 mmHg in the arterial blood was greater in the hypothermic group (52%, 17 of 33) than in the normothermic group (30%, 20 of 67, P = 0.03). ConclusionsUnintentional hypothermia is associated with myocardial ischemia, angina, and PaO2 < 80 mmHg during the early postoperative period in patients undergoing lower extremity vascular surgery.

The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis

Background:The purpose of this clinical trial was to compare the effects of different anesthetic and analgesic regimens on hemostatic function and postoperative arterial thrombotic complications. Methods:Ninety-five patients scheduled for elective lower extremity vascular reconstruction were randomized to receive either epidural anesthesia followed by epidural fentanyl (RA) or general anesthesia followed by intravenous morphine (GA). Intraoperative and postoperative care were controlled by protocol using predetermined limits for heart rate, blood pressure, and other monitoring criteria. Data collection included serial physical examinations, electrocardiograms, and cardiac isoenzymes to detect arterial thrombosis (defined as unstable angina, myocardial infarction, or vascular graft occlusion requiring reoperation). Fibrinogen, plasminogen activator inhibitor-1 (PAI-1), and D-dimer levels were measured preoperatively and at 24 and 72 h postoperatively. Results:Preoperative fibrinogen levels were similar in both groups, remained unchanged after 24 h, and increased equally (45%) in the first 72 h postoperatively. PAI-1 levels in the GA group increased from 13.6 ± 2.1 activity units (AU)/ml to 20.2 ± 2.6 AU/ml at 24 h and returned to baseline at 72 h. In contrast, PAI-1 levels in the RA group remained unchanged over time. Twenty-two of 95 patients (23%) had postoperative arterial thrombosis, 17 of whom had received GA and 5 of whom, RA. Preoperative PAI-1 levels were higher in patients who developed postoperative arterial thrombosis (20.5 ± 3.6 AU/ml vs. 11.2 ± 1.4 AU/ml). Multiple logistic regression analysis indicated that GA and preoperative PAI-1 levels were predictive of postoperative arterial thrombotic complications. Conclusions:Impaired fibrinolysis may be related causally to postoperative arterial thrombosis. Because RA combined with epidural fentanyl analgesia appears to prevent postoperative inhibition of fibrinolysis, this form of perioperative management may decrease the risk of arterial thrombotic complications in patients undergoing lower extremity revascularization.

Double-masked randomized trial comparing alternate combinations of intraoperative anesthesia and postoperative analgesia in abdominal aortic surgery

Background Improvement in patient outcome and reduced use of medical resources may result from using epidural anesthesia and analgesia as compared with general anesthesia and intravenous opioids, although the relative importance of intraoperative versus postoperative technique has not been studied. This prospective, double-masked, randomized clinical trial was designed to compare alternate combinations of intraoperative anesthesia and postoperative analgesia with respect to postoperative outcomes in patients undergoing surgery of the abdominal aorta. Methods One hundred sixty-eight patients undergoing surgery of the abdominal aorta were randomly assigned to receive either thoracic epidural anesthesia combined with a light general anesthesia or general anesthesia alone intraoperatively and either intravenous or epidural patient-controlled analgesia postoperatively (four treatment groups). Patient-controlled analgesia was continued for at least 72 h. Protocols were used to standardize perioperative medical management and to preserve masking intraoperatively and postoperatively. A uniform surveillance strategy was used for the identification of prospectively defined postoperative complications. Outcome evaluation included postoperative hospital length of stay, direct medical costs, selected postoperative morbidities, and postoperative recovery milestones. Results Length of stay and direct medical costs for patients surviving to discharge were similar among the four treatment groups. Postoperative outcomes were similar among the four treatment groups with respect to death, myocardial infarction, myocardial ischemia, reoperation, pneumonia, and renal failure. Epidural patient-controlled analgesia was associated with a significantly shorter time to extubation (P = 0.002). Times to intensive care unit discharge, ward admission, first bowel sounds, first flatus, tolerating clear liquids, tolerating regular diet, and independent ambulation were similar among the four treatment groups. Postoperative pain scores were also similar among the four treatment groups. Conclusions In patients undergoing surgery of the abdominal aorta, thoracic epidural anesthesia combined with a light general anesthesia and followed by either intravenous or epidural patient-controlled analgesia, offers no major advantage or disadvantage when compared with general anesthesia alone followed by either intravenous or epidural patient-controlled analgesia.

Epidural versus general anesthesia, ambient operating room temperature, and patient age as predictors of inadvertent hypothermia.

To elucidate the multifactorial nature of perioperative changes in body temperature, the influence of several clinical variables, including anesthetic technique, ambient operating room temperature, and age, were evaluated. Perioperative oral sublingual temperatures were measured in 97 patients undergoing lower extremity vascular surgery randomized to receive either general (GA) or epidural (EA) anesthesia. Surgery and anesthesia were performed in operating rooms (OR) with a relatively warm mean ambient temperature (24.5 +/- 0.4 degrees C) (GA, n = 30; EA, n = 33) or relatively cold mean ambient temperature (21.3 +/- 0.3 degrees C) (GA, n = 21; EA, n = 13). Patients were 35-94 yr old, with a mean age of 64.5 +/- 1.1 yr. A regression analysis was performed to determine the variables that correlated with intraoperative decrease in temperature and postoperative rewarming rate. The major correlates of greater intraoperative decrease in temperature were 1) GA (P = 0.003); 2) cold ambient OR temperature (P = 0.07); and 3) advancing patient age (P = 0.03). There was significant interaction between ambient OR temperature and type of anesthesia (P = 0.03): there was a greater intraoperative decrease in temperature with GA compared to EA in a cold OR but a similar decrease with GA and EA in a warm OR. The data also suggest an interaction between type of anesthesia and patient age (P = 0.06), showing a greater decrease in temperature with GA compared to EA in the younger patients, but a similar decrease between GA and EA in older patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Preoperative acute normovolemic hemodilution: a meta‐analysis

BACKGROUND: Acute normovolemic hemodilution (ANH) involves withdrawal of whole blood with concurrent infusion of fluids to maintain normovolemia. The aim of this study was to quantify the efficacy and safety of preoperative ANH with a systematic review and meta‐analysis.

Determinants of Catecholamine and Cortisol Responses to Lower Extremity Revascularization

BackgroundSurgical trauma elicits diffuse changes in hormonal secretion and autonomic nervous system activity. Despite studies demonstrating modulation of the stress response by different anesthetic/analgesic regimens, little is known regarding the determinants of catecholamine and cortisol responses to surgery. MethodsPlasma catecholamines and cortisol secretion data were obtained from 60 patients undergoing lower extremity revascularization. Patients were randomized to receive either general anesthesia combined with patient-controlled intravenous morphine (GA) or epidural anesthesia combined with epidural fentanyl analgesia (RA). All aspects of intra-and postoperative clinical care were defined by written protocol. Plasma catecholamines were measured before Induction, intraoperatively, and for the first 18 h postoperatively (by HPLC). Urine cortisol was measured intra-and postoperatively using RIA. Data were evaluated using univariate and multivariate analyses to evaluate demographic and perioperative variables as determinants of stress hormone secretion. ResultsPlasma catecholamines Increased during skin closure in the GA group, and remained higher relative to the RA group in the postoperative period. Multivariate analysis indicated that age and anesthetic regimen predicted increases in catecholamines during skin closure (P < 0.005), although duration of surgery, blood loss, and body temperature were not correlated. Early postoperative norepinephrine concentrations were correlated with pain score and duration of surgery (P < 0.004), but not with anesthetic management, blood loss, or body temperature. All postoperative norepinephrine levels were highly correlated (r = 0.7) with norepinephrine levels during skin closure. Cortisol excretion was higher postoperatively than intraoperatively. No patient or perioperative variable predicted cortisol excretion, and cortisol excretion was not correlated with catecholamine levels at any time. ConclusionsThese data Indicate that patient factors, such as age and Inherent sympathetic responsivity, are important determinants of the catecholamine response to surgery. Modulation of the norepinephrine response by regional anesthesia/analgesia appears to be related, in part, to superior analgesia. The lack of correlation between catecholamine and cortisol secretion indicates that the stress response may consist of discrete systems responding to different stimuli.

The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution******

OBJECTIVE Because of allogenic red blood cell (RBC) availability and infection problems, novel alternatives, including hemoglobin-based oxygen-carrying solutions (HBOC), are being explored to minimize the perioperative requirement of RBC transfusions. This study evaluated HBOC-201, a room-temperature stable, polymerized, bovine-HBOC, as a substitute for allogenic RBC transfusion in patients undergoing elective infrarenal aortic operations. METHODS In a single blind, multicenter trial, 72 patients were prospectively randomized two-to-one to HBOC (n = 48) or allogenic RBC (n = 24) at the time of the first transfusion decision, either during or after elective infrarenal aortic reconstruction. Patients randomized to the HBOC group received 60 g of HBOC for the initial transfusion and had the option to receive three more doses (30 g each) within 96 hours. In this group, any further blood requirement was met with allogenic RBCs. Patients randomized to the allogenic RBC group received only standard RBC transfusions. The efficacy analysis was a means of assessing the ability of HBOC to eliminate the requirement for any allogenic RBC transfusions from the time of randomization through 28 days. Safety was evaluated by means of standard clinical trial methods. RESULTS The two treatment groups were comparable for all baseline characteristics. Although all patients in the allogenic RBC group required at least one allogenic RBC transfusion, 13 of 48 patients (27%; 95% CI, 15% to 42%) in the HBOC group did not require any allogenic RBC transfusions. The only significant changes documented were a 15% increase in mean arterial pressure and a three-fold peak increase in serum urea nitrogen concentration after HBOC. The complications were similar in both groups, with no allergic reactions. There were two perioperative deaths (8%) in the allogenic RBC group and three perioperative deaths (6%) in the HBOC group (P = 1.0). CONCLUSION HBOC significantly eliminated the need for any allogenic RBC transfusion in 27% of patients undergoing infrarenal aortic reconstruction, but did not reduce the median allogenic RBC requirement. HBOC transfusion was well tolerated and did not influence morbidity or mortality rates.

Catecholamine and cortisol responses to lower extremity revascularization: Correlation with outcome variables

OBJECTIVE To determine whether catecholamine and cortisol secretory responses to surgery contribute to postoperative complications. DESIGN Prospective, randomized, case series. SETTING A university hospital operating suite and surgical intensive care unit. PATIENTS Sixty patients undergoing lower extremity vascular surgery. INTERVENTIONS Patients were randomized to receive either epidural anesthesia/epidural opiate analgesia (regional anesthesia) or general anesthesia/intravenous patient-controlled analgesia (general anesthesia). MEASUREMENTS AND MAIN RESULTS Anesthesia was managed according to a prospectively designed protocol. Hemodynamic parameters and plasma catecholamine concentrations were determined at specific intraoperative and postoperative time points. Intraoperative and postoperative urine samples were collected and analyzed for free cortisol concentrations. Outcomes evaluated were cardiac (nonfatal myocardial infarction and cardiac death) and surgical (graft occlusion). Mean arterial pressure during emergence from anesthesia and in the early postoperative period correlated positively with plasma norepinephrine concentration (p < .01). In addition, plasma catecholamine concentrations were higher in patients with postoperative hypertension. Plasma norepinephrine concentrations at the time of emergence from anesthesia and postoperatively were also higher in patients requiring repeat surgery for graft revision, thrombectomy, or amputation (p < .05). Multivariate analysis indicated that the norepinephrine concentration at the time of emergence, but not type of anesthesia, correlated with reoperation for graft occlusion, suggesting that the previously reported beneficial effect of regional anesthesia may be due to modulation of the stress response. Myocardial infarction or cardiac death occurred in three patients. These patients had markedly increased catecholamine concentrations. CONCLUSIONS The catecholamine response to lower extremity vascular surgery contributes to the development of postoperative hypertension and may also be important in the development of thrombotic complications.

Breath ethane: a specific indicator of free-radical-mediated lipid peroxidation following reperfusion of the ischemic liver.

A major component of the organ injury mediated by toxic oxidants, such as seen following reperfusion of the ischemic liver, is due to the peroxidation of polyunsaturated fatty acids, especially of cell membranes. We utilized the measurement of exhaled breath ethane, a metabolic product unique to oxidant-mediated lipid peroxidation, as a noninvasive indicator of this process in swine liver subjected to warm ischemia/reperfusion. Under rigorously controlled anesthesia conditions, pig livers were subjected to 2 h of warm total ischemia, followed by reperfusion in situ. Expired air was collected and its ethane content quantitated by a novel gas chromatographic technique. The time course of breath ethane generation correlated closely with the appearance of hepatocellular injury as measured by impairment of Factor VII generation and other measures of liver integrity. Moreover, the administration of the specific superoxide free radical scavenger, superoxide dismutase (SOD), significantly attenuated both the elaboration of ethane and the hepatocellular injury. These findings not only provide confirmation of the previously reported link between hepatocellular injury by free radicals generated at reperfusion, but also establish the use of expired breath ethane analysis as a sensitive, specific, and noninvasive indicator of the injury process in real time.