John V. Booth

Subtype Specific Regulation of Human Vascular α1-Adrenergic Receptors by Vessel Bed and Age

Background—α1-adrenergic receptors (α1ARs) regulate blood pressure, regional vascular resistance, and venous capacitance; the exact subtype (α1a, α1b, α1 d) mediating these effects is unknown and varies with species studied. In order to understand mechanisms underlying cardiovascular responses to acute stress and chronic catecholamine exposure (as seen with aging), we tested two hypotheses: (1) human α1AR subtype expression differs with vascular bed, and (2) age influences human vascular α1AR subtype expression. Methods and Results—Five hundred vessels from 384 patients were examined for α1AR subtype distribution at mRNA and protein levels (RNase protection assays, ligand binding, contraction assays). Overall vessel α1AR density is 16±2.3fmol/mg total protein. α1aAR predominates in arteries at mRNA (P<0.001) and protein (P<0.05) levels; all 3 subtypes are present in veins. Furthermore, α1AR mRNA subtype expression varies with vessel bed (α1a higher in splanchnic versus central arteries, P<0.05); competiti...

Dosing study of remifentanil and propofol for tracheal intubation without the use of muscle relaxants

Sixty ASA I and II patients, premedicated with midazolam, were administered propofol 2 mg.kg−1 and remifentanil 3 μg.kg−1 (group R3), remifentanil 4 μg.kg−1 (group R4) and remifentanil 5 μg.kg−1 (group R5). Laryngoscopy and intubation were performed 1 min after the administration of the study drugs and the intubating conditions were assessed. Good to excellent conditions were observed in 12 patients in group R3 compared with 19 patients each in groups R4 and R5 (p = 0.004). Significant reductions in mean arterial pressure (MAP) and heart rate (HR) after administration of the study drug were observed in each group, p < 0.01. There was, however, no difference in mean MAP and HR between the three groups at all time points. We conclude that remifentanil 4–5 μg.kg−1 may reliably provide good to excellent conditions for tracheal intubation when administered after propofol 2 mg.kg−1.

Substance abuse among physicians: A survey of academic anesthesiology programs

UNLABELLED Efforts to reduce controlled-substance abuse by anesthesiologists have focused on education and tighter regulation of controlled substances. However, the efficacy of these approaches remains to be determined. Our hypotheses were that the reported incidence of controlled-substance abuse is unchanged from previous reports and that the control and accounting process involved in distribution of operating room drugs has tightened. We focused our survey on anesthesiology programs at American academic medical centers. Surveys were sent to the department chairs of the 133 US anesthesiology training programs accredited at the end of 1997. There was a response rate of 93%. The incidence of known drug abuse was 1.0% among faculty members and 1.6% among residents. Fentanyl was the controlled substance most often abused. The number of hours of formal education regarding drug abuse had increased in 47% of programs. Sixty-three percent of programs surveyed had tightened their methods for dispensing, disposing of, or accounting for controlled substances. The majority of programs (80%) compared the amount of controlled substances dispensed against individual provider usage, whereas only 8% used random urine testing. Sixty-one percent of departmental chairs indicated that they would approve of random urine screens of anesthesia providers. IMPLICATIONS This survey indicates that the frequency of controlled substance abuse among anesthesiologists has changed little in the past few years, despite an increase in the control and accounting procedures for controlled substances as well as increased mandatory education.

A Preliminary Investigation of Remifentanil as a Labor Analgesic

Implications In this preliminary investigation, we evaluated the safety and analgesic efficacy of IV remifentanil for labor pain. Four women were studied, and then the trial was terminated because administration of this novel synthetic opioid produced significant maternal side effects in the absence of effective pain control.

The Bispectral Index in the Diagnosis of Perioperative Stroke: A Case Report and Discussion

We discuss a case where the bispectral index (BIS; Aspect Medical, Natick, MA) was the earliest indicator of acute perioperative stroke during the removal of an Abiomed BVS 5000 ® (Penn State Cardiovascular Center, Hershey, PA) left ventricular assist device (LVAD). Up to 3% of cardiac surgical patients suffer serious, typically embolic, neurological complications, with an associated 20% mortality rate (1). The opportunity to make an earlier diagnosis may help improve outcome in this group as novel therapeutic options become available.

Comparison of remifentanil with alfentanil or suxamethonium following propofol anaesthesia for tracheal intubation.

Sixty ASA physical status I and II, premedicated patients were administered propofol 2 mg.kg−1 and remifentanil 2 μg.kg−1 (group R), alfentanil 50 μg.kg−1 (group A) or suxamethonium 1 mg.kg−1 (group S) as a rapid bolus. One minute after study drug administration, tracheal intubation was performed. Intubation conditions were then scored. Excellent or good conditions were observed in only 35% in group R compared with groups S and A (100% and 85%, respectively; p < 0.001). The haemodynamic response to tracheal intubation was blunted in groups R and A compared with group S (p < 0.001). The mean heart rate in groups R and A was significantly lower than group S (p < 0.001). We conclude that remifentanil 2 μg.kg−1 given as a rapid bolus will not produce intubating conditions as good as those obtained with alfentanil 50 μg.kg−1 or suxamethonium 1 mg.kg−1 if administered after propofol 2 mg.kg−1.

Acute depression of myocardial β-adrenergic receptor signaling during cardiopulmonary bypass. Impairment of the adenylyl cyclase moiety

BACKGROUND Previously the authors showed that myocardial beta-adrenergic (betaAR) function is reduced after cardiopulmonary bypass (CPB) in a canine model Whether CPB results in similar effects on betaAR function in adult humans is not known. Therefore the current study tested two hypotheses: (1) That myocardial betaAR signaling is reduced in adult humans after CPB, and (2) that administration of long-term preoperative betaAR antagonists prevents this process. METHODS After they gave informed consent, 52 patients undergoing aortocoronary surgery were enrolled. Atrial biopsies were obtained before CPB and immediately before discontinuation of CPB. Plasma catecholamine concentrations, myocardial betaAR density, and functional responsiveness (basal, isoproterenol, zinterol, sodium fluoride, and manganese-stimulated adenylyl cyclase activity) were assessed. RESULTS Catecholamine levels increased significantly during CPB (P < 0.005). Myocardial betaAR adenylyl cyclase coupling decreased during CPB, as evidenced by a 21% decrease in isoproterenol-stimulated adenylyl cyclase activity (750 [430] pmol cyclic adenosine monophosphate per milligram total protein 15 min before CPB compared with 540 [390] at the end of CPB, P = 0.0062, medians [interquartile range]) despite constant betaAR density. Differential activation along the betaAR signal transduction cascade localized the defect to the adenylyl cyclase moiety. Administration of long-term preoperative betaAR antagonists did not prevent acute CPB-induced myocardial betaAR dysfunction. CONCLUSIONS These data indicate that the myocardial adenylyl cyclase response to betaAR agonists decreases acutely in adults during aortocoronary surgery requiring CPB, regardless of whether long-term preoperative betaAR antagonists are administered. The mechanism underlying acute betaAR dysfunction appears to be direct impairment of the adenylyl cyclase moiety. Similar increases in manganese-stimulated activity before and at the end of CPB show preserved adenylyl cyclase catalytic activity, suggesting that other mechanisms (such as decreased protein levels or altered isoform expression or function) may be responsible for decreased adenylyl cyclase function.

Low serum magnesium level predicts major adverse cardiac events after coronary artery bypass graft surgery.

BACKGROUND Despite improved myocardial protection strategies and enhanced surgical techniques, mortality after coronary artery bypass graft surgery (CABG) remains essentially unchanged. This may be because of the increasing age of patients who undergo primary CABG. Magnesium is an important regulator of vascular tone, reperfusion injury, and thrombosis. Therefore, we decided to investigate the relationship between serum magnesium levels and major adverse cardiac events (MACE) after CABG. METHODS A total of 957 patients undergoing primary CABG were prospectively recruited into the Duke Cardiovascular database and had daily serum magnesium levels measured. Low magnesium was defined as <1.8 mmol/L(-1) at any point during the first 8 days after surgery. Adverse events were defined as Q-wave infarction or death measured 1 year after surgery. A Kaplan-Meier survival analysis was performed, followed by a Cox proportional hazards model, to account for other known predictors of adverse events. RESULTS In the low magnesium group, 12.3% of patients had adverse events, compared with 9.2% of patients in the normal magnesium group. A serum magnesium level <1.8 mmol/L(-1) decreased the event-free survival rate (2-fold increased risk of death or myocardial infarction at 1 year; hazard ratio 2.0, 95% CI 1.19-3.37). CONCLUSIONS We demonstrated a robust relationship between low serum magnesium levels after CABG and a 2-fold increased incidence of Q-wave infarction and all-cause mortality rate as long as 1 year after surgery. This relationship is independent of known preoperative and intraoperative predictors of adverse outcomes. This study provides a rationale for a randomized controlled trial of magnesium therapy during CABG.

Mitral valve surgery and acute renal injury: port access versus median sternotomy

BACKGROUND Many outcomes and complications of minimally invasive and conventional cardiac surgery await comparison. Patients undergoing mitral valve surgery commonly sustain renal injury. Using peak postoperative fractional change of serum creatinine as a marker of renal injury, we tested the hypothesis that mitral valve surgery with port access minithoracotomy (Port) and conventional surgery with a median sternotomy (MS) incision are associated with different degrees of acute renal injury. METHODS We evaluated data from all isolated mitral valve operations by a single surgeon between 1990 and 2000 (MS = 90, Port = 227). We also performed a secondary analysis of mitral valve surgeries performed by both MS and Port approaches in a concurrent period from 1996 to 2002 (MS = 93, Port = 240). Univariable and multivariable tests were used to determine the association of surgical technique with peak postoperative creatinine (CrmaxPost) and peak postoperative fractional change in creatinine (%deltaCr); p less than 0.05 was considered significant. RESULTS In our analysis that accounted for the date of surgery, we observed a highly significant independent association between surgical approach and %deltaCr, indicating a greater risk of acute renal injury in the MS group (F value 13.33; p = 0.0003). Similar findings were noted in the secondary (time-concurrent) analysis of %deltaCr (F value 12.65; p = 0.0176). CONCLUSIONS We present retrospective evidence of reduced acute renal injury associated with the port access technique in mitral valve surgery patients. Our findings suggest that a port access minithoracotomy approach to mitral valve surgery may be preferable to conventional methods for patients with high renal risk.

A review of laparoscopy for non-obstetric-related surgery during pregnancy.

PURPOSE Similar to the general population, parturients (and their fetuses) could benefit from the reduced manipulation associated with laparoscopy. The purpose of this article is to review the current state of knowledge (both clinical and experimental) with respect to the fetal effects of maternal laparoscopy for non-obstetric-related surgery during pregnancy. METHODS Human and experimental animal results are examined, and we present preliminary data from our own laboratory. CONCLUSIONS Future experiments are proposed to further develop and refine standards of care for general surgeons and obstetricians who are presented with gravid females in abdominal distress.