General anesthesia improves fetal cerebral oxygenation without evidence of subsequent neuronal injury.

Anesthetic exposure during pregnancy is viewed as a relatively routine medical practice. However, recent rodent studies have suggested that common anesthetic agents can damage the developing brain. Here we assessed this claim in a higher order species by exposing previously instrumented near-term pregnant sheep at gestational day 122 (+/-1) to a combination of midazolam, sodium thiopental, and isoflurane at clinically relevant doses and means of anesthetic delivery (i.e., active ventilation). Four hours of maternal general anesthesia produced an initial increase in fetal systemic oxygenation and a sustained increase in fetal cerebral oxygenation, as determined by in utero near-infrared spectroscopy. Postexposure monitoring failed to identify changes in physiologic status that could be injurious to the fetal brain. Finally, through the histologic assessment of noninstrumented sheep at the same gestational time point, we found no evidence for a direct fetal neuro-toxic effect of our triple-drug regimen. Collectively, these results appear to corroborate the presumed safety of inhalational anesthetic use during pregnancy.

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.

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.

Esmolol improves left ventricular function via enhanced beta-adrenergic receptor signaling in a canine model of coronary revascularization.

BACKGROUND: Recent American Heart Association guidelines highlight the paucity of data on effectiveness and/or mechanisms underlying use of beta-adrenergic receptor (beta AR) antagonists after acute coronary syndromes in patients subsequently undergoing revascularization. It is important to assess whether beta AR antagonists might protect the heart and improve ventricular function in this scenario. The authors therefore used esmolol (an ultra-short-acting beta AR antagonist) to determine whether beta AR antagonist treatment improves left ventricular function in a canine model of acute reversible coronary ischemia followed by coronary reperfusion during cardiopulmonary bypass (CPB). The authors also tested whether the mechanism includes preserved beta AR signaling. METHODS: Dogs were randomized to either esmolol or saline infusions administered during CPB (n = 29). Pre-CPB and end-CPB transmyocardial left ventricular biopsies were obtained; plasma catecholamine concentrations, myocardial beta AR density, and adenylyl cyclase activity were measured. In addition, left ventricular systolic shortening and postsystolic shortening were determined immediately prior to each biopsy. RESULTS: While beta AR density remained unchanged in each group, isoproterenol-stimulated adenylyl cyclase activity decreased 26 +/- 6% in the control group but increased 38 +/- 10% in the esmolol group (pre-CPB to end-CPB, mean +/- SD, P = 0.0001). Left ventricular systolic shortening improved in both groups after release of coronary (LAD) ligature; however, the esmolol group increased to 72 +/- 23% of pre-CPB values compared to 48 +/- 12% for the control group (P = 0.0008). CONCLUSIONS: These data provide prospective evidence that esmolol administration results in improved myocardial function. Furthermore, the mechanism appears to involve enhanced myocardial beta AR signaling.

Metoprolol and coronary artery bypass grafting surgery: does intraoperative metoprolol attenuate acute beta-adrenergic receptor desensitization during cardiac surgery?

UNLABELLED: Cardiac surgery results in significant impairment of beta-adrenergic receptor (beta AR) function and is a cause of depressed myocardial function after surgery. We previously demonstrated that acute administration of beta AR blocker during cardiopulmonary bypass (CPB) in an animal model of coronary artery bypass grafting (CABG) surgery attenuates beta AR desensitization, whereas chronic oral beta-blockade therapy in patients undergoing CABG surgery does not prevent it. Therefore we hypothesized that acute administration of metoprolol during CABG surgery would prevent acute myocardial beta AR desensitization. A placebo-controlled initial phase (n = 72) was performed whereby patients were randomized to either metoprolol 10 mg or placebo immediately before CPB. Then a second dose-finding study was performed where patients received 20 mg (n = 20) or 30 mg (n = 20) of metoprolol. Hemodynamic monitoring, atrial membrane adenylyl cyclase activity, atrial beta AR density, and postoperative outcomes were measured. All groups showed similar decreases in isoproterenol-stimulated adenylyl cyclase activity (13%-24%). Cardiac output remained similar in all 4 groups throughout the intraoperative and postoperative period. In addition, patients receiving metoprolol 20 or 30 mg had less supraventricular arrhythmias 24 h postoperatively compared with patients receiving metoprolol 10 mg or placebo. Therefore, unlike our previous animal model of CABG surgery, metoprolol did not attenuate myocardial beta AR desensitization. IMPLICATIONS: We investigated whether IV metoprolol given during cardiac surgery attenuates myocardial beta-adrenergic receptor (beta AR) desensitization. Although metoprolol did not reduce beta AR desensitization, the incidence of supraventricular arrhythmias was reduced by 75% in patients receiving 20 mg or 30 mg metoprolol.