The role of HLA-DR-DQ haplotypes in variable antibody responses to anthrax vaccine adsorbed.

Host genetic variation, particularly within the human leukocyte antigen (HLA) loci, reportedly mediates heterogeneity in immune response to certain vaccines; however, no large study of genetic determinants of anthrax vaccine response has been described. We searched for associations between the immunoglobulin G antibody to protective antigen (AbPA) response to Anthrax Vaccine Adsorbed (AVA) in humans, and polymorphisms at HLA class I (HLA-A, -B, and -C) and class II (HLA-DRB1, -DQA1, -DQB1, -DPB1) loci. The study included 794 European-Americans and 200 African-Americans participating in a 43-month, double-blind and placebo-controlled clinical trial of AVA (clinicaltrials.gov identifier NCT00119067). Among European-Americans, genes from tightly linked HLA-DRB1, -DQA1, -DQB1 haplotypes displayed significant overall associations with longitudinal variation in AbPA levels at 4, 8, 26 and 30 weeks from baseline in response to vaccination with three or four doses of AVA (global P=6.53 × 10(-4)). In particular, carriage of the DRB1-DQA1-DQB1 haplotypes (*)1501-(*)0102-(*)0602 (P=1.17 × 10(-5)), (*)0101-(*)0101-(*)0501 (P=0.009) and (*)0102-(*)0101-(*)0501 (P=0.006) was associated with significantly lower AbPA levels. In carriers of two copies of these haplotypes, lower AbPA levels persisted following subsequent vaccinations. No significant associations were observed amongst African-Americans or for any HLA class I allele/haplotype. Further studies will be required to replicate these findings and to explore the role of host genetic variation outside of the HLA region.

Activation of the Mason-Pfizer monkey virus protease within immature capsids in vitro.

For all retroviruses, the completion of the viral budding process correlates with the activation of the viral protease by an unknown mechanism, and, as the structural (Gag) polyproteins are cleaved by the viral protease, maturation of the immature virus-like particle into an infectious virion. Unlike most retroviruses, the Mason-Pfizer monkey virus Gag polyproteins assemble into immature capsids within the cytoplasm of the cell before the viral budding event. The results reported here describe a unique experimental system in which Mason-Pfizer monkey virus immature capsids are removed from the cell, and the protease is activated in vitro by the addition of a reducing agent. The cleavage of the protease from the precursor form is a primary event, which proceeds with a half time of 14 min, and is followed by authentic processing of the Gag polyproteins. Activity of the viral protease in vitro depends on pH, with an increase in catalytic rates at acidic and neutral pH. The initiation of protease activity within immature capsids in vitro demonstrates that viral protease activity is sensitive to oxidation-reduction conditions, and that the viral protease can be activated in the absence of viral budding.

Analysis of Mason-Pfizer monkey virus Gag particles by scanning transmission electron microscopy.

Mason-Pfizer monkey virus immature capsids selected from the cytoplasm of baculovirus-infected cells were imaged by scanning transmission electron microscopy. The masses of individual selected Gag particles were measured, and the average mass corresponded to 1,900 to 2,100 Gag polyproteins per particle. A large variation in Gag particle mass was observed within each population measured.

Effectiveness of remifentanil versus traditional fentanyl-based anesthetic in high-risk outpatient surgery.

STUDY OBJECTIVE: To determine if remifentanil would offer a superior hemodynamic and recovery profile compared to the current standard of care, which implements a fentanyl-based technique. DESIGN: Randomized, single-blind study. SETTING: Outpatient center associated with tertiary care center. PATIENTS: 75 outpatients undergoing microsuspension laryngoscopy. INTERVENTIONS: Patients were randomized to either a remifentanil induction (0.5 microg/kg/min) and maintenance (0.25 microg/kg/min) versus fentanyl (maximum of 250 microg) as the only opioid. All patients received propofol as part of the induction and maintenance with or without the use of nitrous oxide. MEASUREMENTS: Assessment of hemodynamics [heart rate (HR) and blood pressure(BP)], presence of perioperative myocardial ischemia on ambulatory electrocardiographic monitoring, and time to discharge. MAIN RESULTS: Significantly fewer patients in the remifentanil group demonstrated episodes of tachycardia (HR > 100 beats per min) compared to the fentanyl group (14% vs. 40%, p<0.05), with significantly fewer episodes of tachycardia and hypertension per patient. Recovery profiles between the two groups did not show clinically significant differences. CONCLUSIONS: Remifentanil, a new short-acting opioid, offers excellent hemodynamic control for brief, intense outpatient procedures performed in high-risk patients; however, its use was not associated with any improvement in recovery profiles.

Characterisation of a Rrhodobacter sphaeroides gene that encodes a product resembling Eescherichia coli cytochrome b(561) and R. sphaeroides cytochrome b(562).

Analysis of the photoactive yellow protein (pyp) gene region of Rhodobacter sphaeroides has revealed the presence of an additional open reading frame, orfD, that had not previously been identified. Here we report the location of this new gene and the predicted amino acid sequence of the encoded protein. The translation product resembles a group of small cytochrome b-like proteins, including Escherichia coli cytochrome b(561), R. sphaeroides cytochrome b(562), and two new cytochrome b(561)-like proteins identified using the E. coli genome sequence, for which functions have not yet been established. To determine OrfD function in R. sphaeroides, an orfD mutant was constructed. The OrfD mutant exhibited growth rates and yields very similar to those of the wild-type strain when grown under a variety of growth conditions. Respiration rates, reduced-minus-oxidised spectra and levels of photosynthetic complexes were also very similar in the two strains. Although the role of OrfD was therefore not determined here, we demonstrate that the orfD gene is expressed in R. sphaeroides under aerobic, semi-aerobic and photosynthetic growth conditions.

A cell-line-specific defect in the intracellular transport and release of assembled retroviral capsids.

Retrovirus assembly involves a complex series of events in which a large number of proteins must be targeted to a point on the plasma membrane where immature viruses bud from the cell. Gag polyproteins of most retroviruses assemble an immature capsid on the cytoplasmic side of the plasma membrane during the budding process (C-type assembly), but a few assemble immature capsids deep in the cytoplasm and are then transported to the plasma membrane (B- or D-type assembly), where they are enveloped. With both assembly phenotypes, Gag polyproteins must be transported to the site of viral budding in either a relatively unassembled form (C type) or a completely assembled form (B and D types). The molecular nature of this transport process and the host cell factors that are involved have remained obscure. During the development of a recombinant baculovirus/insect cell system for the expression of both C-type and D-type Gag polyproteins, we discovered an insect cell line (High Five) with two distinct defects that resulted in the reduced release of virus-like particles. The first of these was a pronounced defect in the transport of D-type but not C-type Gag polyproteins to the plasma membrane. High Five cells expressing wild-type Mason-Pfizer monkey virus (M-PMV) Gag precursors accumulate assembled immature capsids in large cytoplasmic aggregates similar to a transport-defective mutant (MA-A18V). In contrast, a larger fraction of the Gag molecules encoded by the M-PMV C-type morphogenesis mutant (MA-R55W) and those of human immunodeficiency virus were transported to the plasma membrane for assembly and budding of virions. When pulse-labeled Gag precursors from High Five cells were fractionated on velocity gradients, they sedimented more rapidly, indicating that they are sequestered in a higher-molecular-mass complex. Compared to Sf9 insect cells, the High Five cells also demonstrate a defect in the release of C-type virus particles. These findings support the hypothesis that host cell factors are important in the process of Gag transport and in the release of enveloped viral particles.

Disseminating information using an anesthesiology consultant report: impact on patient perceptions of quality of care.

STUDY OBJECTIVE: To determine if providing an Anesthesiology Consultant Report (ACR) to patients would result in enhanced patients' perceptions of their knowledge about their care and improve their perception of the quality of their care. DESIGN: Randomized, unblinded study. SETTING: Outpatient center associated with tertiary care center. PATIENTS: 371 outpatients without adverse anesthetic events. INTERVENTIONS: Patients were randomized to receive either routine discharge instructions or routine instructions and an anesthesia discharge summary (ACR). MEASUREMENTS AND MAIN RESULTS: Short questionnaire with discharge packet regarding knowledge of anesthetic and questions regarding satisfaction and perceptions of quality of care was distributed. The patients in the group that received an ACR were more satisfied with the management of their pain and other symptoms (p < 0.05, by Wilcoxon rank sums) and were more satisfied overall with the quality of the anesthesia care (p < 0.01, by Wilcoxon rank sums). Taken another way, significantly more patients deemed the quality of their anesthetic care as excellent in the ACR group compared to control (83% vs. 67%, p < 0.01). CONCLUSIONS: Providing patients, with uneventful anesthetic courses, with information regarding their anesthetic care, in the form of the ACR, results in improved perceptions of the quality of care.

Laparoscopic cholecystectomy as a "true" outpatient procedure: initial experience in 130 consecutive patients.

Laparoscopic cholecystectomy has received nearly universal acceptance and is currently considered the "gold standard" for the treatment of cholelithiasis. Many centers have employed "short-stay" units or "23-hour admissions" for postoperative observation following laparoscopic cholecystectomy. The practice of early discharge as "true" outpatients following this procedure has not been well defined. A retrospective analysis of 130 consecutive patients undergoing laparoscopic cholecystectomy in an outpatient surgery unit was performed. A follow-up telephone survey was carried out of patients who successfully completed the procedure as outpatients. One hundred thirty patients underwent outpatient laparoscopic cholecystectomy. The patient population consisted of 78% women, with an age range of 17 to 76 years (mean age 47.1 years). Symptomatic gallstone disease was the indication for laparoscopic cholecystectomy in 92% of the patients. All patients underwent successful completion of laparoscopic cholecystectomy with no conversions to an open procedure. The mean length of operation was 75 +/- 23 minutes (range 25 to 147 minutes). The mean length of stay in the postanesthesia care unit (PACU) ranged from 95 to 460 minutes with a mean length of stay of 200 +/- 79 minutes. A total of eight patients (6.2%) were admitted to the hospital directly from the PACU in the immediate postoperative period. Six of these eight patients were discharged on the first postoperative day. Following discharge from the PACU, an additional six patients (4.6%) required hospital admission. Three of these six patients were discharged after a single day of hospitalization. Ninety-eight of 116 eligible patients were available for follow-up telephone evaluation. The outpatient experience was rated as good by 75.5% of the patients, fair by 22.5%, and poor by 2%. In retrospect, 20.4% of the patients stated that they would have preferred an inpatient to an outpatient procedure. Laparoscopic cholecystectomy can be performed as a true outpatient procedure with patients discharged to home within hours of completion of the procedure. Less than 10% of patients will fail this protocol and another 5% of the patients may require hospitalization after returning to their homes.

Is outpatient laparoscopic cholecystectomy safe and cost-effective? A model to study transition of care.

BACKGROUND: There is increasing pressure to perform traditional inpatient surgical procedures in an outpatient setting. The aim of the current trial was to determine the safety and cost savings of performing laparoscopic cholecystectomy in an outpatient setting using a "mock" outpatient setting. METHODS: Patients who were scheduled for laparoscopic cholecystectomy by four attending surgeons and for whom operating time was available in the outpatient center were studied. All patients received a standardized anesthetic, including ondansetron, and were discharged from the outpatient postanesthesia care unit if appropriate. At discharge, all patients were admitted to a clinical research center where they were observed in a "mock home" setting and monitored for complications that would have necessitated readmission. A decision analysis was created assuming all patients underwent outpatient surgery with either direct admission or discharge to home and readmission if complications developed. RESULTS: Of 99 patients who were enrolled in this study, 96 patients would have met the discharge criteria for home. No major complications were observed in these 96 patients. Eleven patients experienced postoperative nausea and vomiting, 3 of whom required an additional 24 h of hospital observation. In the decision model, the optimal strategy would be to perform the procedure on an outpatient basis and readmit patients only for complications, with an average baseline cost savings of $742/patient. CONCLUSIONS: The results show that outpatient laparoscopic cholecystectomy is safe and cost-effective in selected patients, and that the mock home setting provides a means of studying the safety of transition of care.

Safety of direct laryngoscopy as an outpatient procedure.

The safety of outpatient direct laryngoscopy has recently been challenged in the literature. We reviewed the first 589 direct laryngoscopies performed at a new outpatient surgery center. There were nine unplanned admissions to the hospital, including five airway emergencies that developed within the first 30 min after extubation. Three patients required reintubation before leaving the operating room. On postoperative telephone follow-up, 9% complained of mild to moderate sore throat. There were no major complications after discharge. We conclude that the risk of airway emergencies after direct laryngoscopy is less than 1% in carefully selected patients. The procedure can be safely performed as an outpatient procedure as long as transportation to a hospital is readily available for the few patients in whom complications arise.

Changes in cerebrospinal fluid pressure and lactate concentrations during thoracoabdominal aortic aneurysm surgery.

BACKGROUND: Although ischemic injury to the spinal cord is a well-known complication of aortic surgery, no metabolic markers have been identified as predictors of an adverse outcome. This study evaluated the effect of cerebrospinal fluid (CSF) drainage, with and without distal femoral perfusion or moderate hypothermia on blood and CSF lactate concentrations and CSF pressure during thoracoabdominal aortic aneurysm surgery. METHODS: Three nonconcurrent groups of patients were studied prospectively: patients with normal body temperature (35 degrees C) but without distal femoral bypass (n = 6), patients with normal body temperature with bypass (n = 7), and patients with hypothermia (30 degrees C) and bypass (n = 8). In all patients, CSF pressure was recorded before, during, and after aortic cross-clamping. During the surgical repair, CSF drainage was performed using a 4-Fr intrathecal silicone catheter. Blood and CSF lactate concentrations were measured throughout the operation. RESULTS: Significant increases in blood (490%) and CSF (173%) lactate concentrations were observed during and after thoracic aortic occlusion in patients with normothermia and no bypass (P < 0.02 and 0.05, respectively). Distal perfusion attenuated the increase in both blood and CSF lactate (P < 0.01), and a further reduction was achieved with hypothermia of 30 degrees C (P < 0.001). Patients who became paraplegic showed a greater increase in CSF lactate concentrations after aortic clamp release compared with those who suffered no neurological damage (275% vs. 123% of baseline; P < 0.05). Increased CSF pressure of 42-60% (P < 0.005) was noted soon after thoracic aortic occlusion, both with and without distal femoral bypass. CONCLUSIONS: Incremental reductions in CSF lactate concentrations were achieved using distal femoral bypass and hypothermia. The reduction in CSF lactate correlated with the methods used to protect the spinal cord during thoracoabdominal aortic aneurysm surgery and was associated with better outcome. Decompression by distal bypass of the hemodynamic overload caused by aortic occlusion was insufficient to eliminate the acute increase in CSF pressure. Cerebrospinal fluid lactate measurements during high aortic surgery may accurately represent the spinal cord metabolic balance.

Microleakage of amalgam restorations using dentin bonding system primers.

PURPOSE: To evaluate and compare in vitro microleakage of etched and non-etched Class I amalgam restorations lined with various dentin bonding system primers to amalgam restorations with or without a Copalite liner. MATERIALS AND METHODS: Class I amalgam preparations were made in 140 extracted molars and divided into 14 groups of 10 teeth each. Permite C dispersed phase alloy restorations were placed after the following treatments: Group 1: No liner; Group 2: Lined with two coats of Copalite; Group 3(A): Lined with Amalgambond AA and 3(B): Etched with 35% Ultra-etch and lined with Amalgambond AA; Group 4(A): Lined with Scotchbond Multi-Purpose Primer and 4(B): Etched and lined with the primer; Group 5(A): Lined with ProBond and 5(B): Etched and lined with the primer; Group 6(A): Lined with All-Bond 2 Primer A & B and 6(B): Etched and lined with the primer; Group 7(A): Lined with OptiBond and 7(B): Etched and lined with the primer; Group 8(A): Lined with Permagen Primer and 8(B): Etched and lined with the primer. All primers were applied per manufacturers' specifications. After storage in water for 24 hours, all restorations were polished and then aged in water at 37 degrees C for 90 days. The specimens were then thermocycled for 300 cycles at 5 degrees C and 55 degrees C in basic fuchsin dye with a 30-second dwell time, mounted in epoxy rings, sectioned longitudinally, mesiodistally and buccolingually into four sections, then evaluated at x100 and the extent of dye penetration at the tooth/amalgam interface scored (two scores for each section, eight for each specimen). RESULTS: The unlined and Copalite-lined groups and all non-etched groups showed considerable marginal leakage. All the etched restorations were significantly more effective in reducing microleakage than the non-etched, no liner and Copalite-lined groups. Etching prior to application of the primers is significantly more effective than nonetching, however the effectiveness of the primer alone to seal the dentin needs to be evaluated. Overall, Amalgam-bond AA had the least microleakage of all the groups.

Synthesis and assembly of retrovirus Gag precursors into immature capsids in vitro.

The assembly of retroviral particles is mediated by the product of the gag gene; no other retroviral gene products are necessary for this process. While most retroviruses assemble their capsids at the plasma membrane, viruses of the type D class preassemble immature capsids within the cytoplasm of infected cells. This has allowed us to determine whether immature capsids of the prototypical type D retrovirus, Mason-Pfizer monkey virus (M-PMV), can assemble in a cell-free protein synthesis system. We report here that assembly of M-PMV Gag precursor proteins can occur in this in vitro system. Synthesized particles sediment in isopycnic gradients to the appropriate density and in thin-section electron micrographs have a size and appearance consistent with those of immature retrovirus capsids. The in vitro system described in this report appears to faithfully mimic the process of assembly which occurs in the host cell cytoplasm, since M-PMV gag mutants defective in in vivo assembly also fail to assemble in vitro. Likewise, the Gag precursor proteins of retroviruses that undergo type C morphogenesis, Rous sarcoma virus and human immunodeficiency virus, which do not preassemble capsids in vivo, fail to assemble particles in this system. Additionally, we demonstrate, with the use of anti-Gag antibodies, that this cell-free system can be utilized for analysis in vitro of potential inhibitors of retrovirus assembly.

Catecholamine and cortisol responses to lower extremity revascularization: correlation with outcome variables. Perioperative Ischemia Randomized Anesthesia Trial Study Group.

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.

Moderate hypothermia, with partial bypass and segmental sequential repair for thoracoabdominal aortic aneurysm.

PURPOSE: Ischemic injury to the spinal cord, kidneys, and viscera occurs in a significant number of patients undergoing surgical repair of thoracoabdominal aortic aneurysms. Partial bypass has been used to perfuse the arterial system distal to the cross-clamp, but the primary determinant of ischemic morbidity remains the duration of aortic cross-clamping. Hypothermia may favorably affect outcome during these procedures, but moderate or deep hypothermia has traditionally required full cardiopulmonary bypass with cardiac arrest. METHODS: In a series of patients undergoing thoracoabdominal (n = 14) or thoracic (n = 4) aneurysm repair, we used moderate hypothermia (30 degrees C) and partial bypass (aortofemoral or atriofemoral) while maintaining an intrinsic cardiac rhythm. Body temperature was controlled with a heat exchanger in the bypass circuit, which allowed for rapid cooling and rewarming. In addition to hypothermia and bypass, a segmental sequential surgical repair was used to minimize the duration of ischemia to any given vascular bed. RESULTS: All patients survived the surgical procedure, and 16 patients survived until discharge from the hospital. None of the 18 patients had paraplegia or significant renal dysfunction. The only complication related to hypothermia was atrial fibrillation, which occurred in three patients and was amenable to therapeutic measures. CONCLUSIONS: We conclude that moderate hypothermia, partial bypass, and segmental sequential repair may reduce ischemic injury. This combination of adjuncts was not associated with significant complications in this series of patients.

Determinants of catecholamine and cortisol responses to lower extremity revascularization. The PIRAT Study Group.

BACKGROUND: Surgical 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. METHODS: Plasma 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. RESULTS: Plasma 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. CONCLUSIONS: These 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.

Perioperative morbidity in patients randomized to epidural or general anesthesia for lower extremity vascular surgery. Perioperative Ischemia Randomized Anesthesia Trial Study Group.

BACKGROUND: Perioperative morbidity may be modifiable in high risk patients by the anesthesiologist's 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 reoperation for inadequate tissue perfusion and, therefore, may be advantageous for this surgical population.

The effects of different anesthetic regimens on fibrinolysis and the development of postoperative arterial thrombosis. Perioperative Ischemia Randomized Anesthesia Trial Study Group.

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.

Spinal cord stimulation evoked potentials during thoracoabdominal aortic aneurysm surgery.

Although monitoring of somatosensory evoked potentials elicited from stimulation of lower extremity peripheral nerves has been suggested as a method for assessing neural function during thoracoabdominal aortic aneurysm surgery, this technique has been reported to yield a large number of false positives. It was believed that direct stimulation of the spinal cord would eliminate some of the problems associated with peripheral evoked potentials. The present study compared in 18 patients the use of scalp recorded evoked potential following stimulation of either the posterior tibial nerve via percutaneous needles or the spinal cord via an epidural electrode previously placed fluoroscopically. In 10 patients in whom distal bypass or shunt was not used, peripheral evoked potentials totally disappeared within 5-30 min of aortic clamping. Spinal cord stimulation evoked potentials disappeared permanently in 2 patients shortly after aortic cross-clamping; 1 died shortly after the procedure, and the other awoke densely paraplegic and died the next day. When distal perfusion was maintained by shunt or bypass, the disappearance of both peripheral and spinal evoked potentials accurately predicted the neurologic outcome of 1 paralyzed patient. Loss of spinal cord stimulation evoked potentials was found to be correlated with adverse neurologic outcome. Over the period of aortic clamping a gradual decrease in mean amplitude (50% at 45 min [P less than 0.05]) and a 20% increase in mean latency time were observed. Maintenance of adequate distal perfusion may permit the use of peripheral evoked potentials in the assessment of spinal cord ischemia during aortic cross-clamping.(ABSTRACT TRUNCATED AT 250 WORDS)