First pass uptake of fentanyl, meperidine, and morphine in the human lung.

The first pass uptake of fentanyl, meperidine, and morphine in human lung was studied in patients using a double indicator dilution technique. A bolus containing one of the drugs and indocyanine green dye (ICG) was rapidly injected into the central venous catheter of patients prior to anesthesia for surgery. Sequential arterial blood samples were collected at 1-s intervals for 45 s after injection. The total amount of drug taken up by the lung during the first pass and the instantaneous extraction of drug at each time point during the first pass were calculated from the differences in the arterial blood concentration versus time curves of the nondiffusible indicator (ICG) and the drug. The total uptake (mean +/- SE) during the first pass through the human lung for fentanyl and meperidine was 75.2 +/- 3.2% and 64.7 +/- 7.8% of the injected dose, respectively. The pulmonary uptake of morphine was very small, with 96.5 +/- 7.1% of the injected dose recovered in arterial blood after the first pass through the lung. The arterial blood concentration of drug and dye versus time showed a slight delay of the fentanyl and meperidine peaks compared to ICG. It was also observed that greater than 90% of these drugs were extracted from the blood in the early part of the first pass, but the extraction decreased with time during the first pass through the lung. These findings indicate that some of the drug taken up by the lung can diffuse back out into the blood.2+off

Myocardial ischemia during cardiovascular surgery as detected by an ST segment trend monitoring system.

The incidence of intraoperative myocardial ischemia was determined in 312 patients undergoing cardiovascular surgery using ECG recordings obtained from a prototype system that trends ST segment changes. Prior to cardiopulmonary bypass, ischemic ECG changes were observed in 11.9% of patients, the incidence being lower during coronary artery bypass grafting (CABG) procedures (8.1%) than in patients undergoing repeated CABG (23.5%), valve replacement (25.9%), or concomitant valve replacement and CABG (35.3%). The occurrence of intraoperative myocardial ischemia was statistically greater in patients with a history of hypertension, two or more previous myocardial infarctions, or kidney disease. The incidence of ischemia was also significantly greater in patients with left ventricular end-diastolic pressures of 15 mm Hg or higher at cardiac catheterization. The incidence during induction was significantly reduced by the addition of hypnotics to narcotics, and, during maintenance, by the addition of an inhalational agent. The majority of ischemic events were temporally related to some hemodynamic disturbance, and many coincided with surgical manipulation. The incidence of intraoperative myocardial ischemia was substantially less than that reported in comparable studies. Since the incidence decreased significantly following clinical acceptance of the prototype system, the authors conclude that such capability increases sensitivity to small ST segment changes. This heightened awareness and prompt remedial action reduced the incidence of ischemia during CABG to 6% during the final 2 years of the study.

Effects of fentanyl-diazepam-nitrous oxide anaesthesia on arterial baroreflex control of heart rate in man.

The effects of fentanyl 7.5 micrograms kg-1 (group I), 10.0 micrograms kg-1 (group II) and 12.5 micrograms kg-1 (group III) with diazepam 0.25 mg kg-1 and 70% nitrous oxide on baroreflex control of heart rate in humans were investigated. Phenylephrine (the pressor test), sodium nitroprusside (the depressor test) and graded neck suction provoked baroreflex responses. In group I the pressor, depressor and neck suction baroreflex slopes decreased during anaesthesia. In groups II and III the depressor test slopes were also decreased during anaesthesia. However, the slopes derived from the pressor and neck suction tests did not decrease. These data suggest that baroreflex control of heart rate is attenuated during low doses of fentanyl (7.5 micrograms kg-1). Baroreflex mediated tachycardia is decreased by higher doses of fentanyl (10.0 and 12.5 micrograms kg-1). However, baroreflex-mediated bradycardia is maintained during the higher doses of fentanyl. We suggest this effect is the result of enhanced vagal efferent activity mediated by fentanyl.

Halothane anesthesia attenuates cardiopulmonary baroreflex control of peripheral resistance in humans.

The effects of halothane anesthesia on cardiopulmonary (low pressure) baroreflex control of peripheral resistance were studied in 10 ASA class I young men. Graded (-5, -7.5, -10, -12.5 mmHg) lower body negative pressure (LBNP) was used to produce progressive decreases in thoracic blood volume and central venous pressure. These stimuli activate reflexes from cardiopulmonary baroreceptors. Volunteers were studied while awake and during 1 MAC (0.75%) and 1.25 MAC (0.93%) halothane anesthesia. Hetastarch (6%) in 0.9% normal saline was infused into patients before baseline recordings were initiated. Blood pressure, stroke volume, cardiac output, and systemic and forearm vascular resistance decreased and forearm blood flow increased during halothane anesthesia. In awake subjects, LBNP did not alter heart rate or blood pressure, but stroke volume and cardiac output decreased. Blood pressure was maintained by cardiopulmonary baroreflex-mediated increases in peripheral resistance. In anesthetized subjects, decreases in stroke volume and cardiac output during LBNP were similar to awake responses, however, hypotension occurred because reflex resistance increases were markedly attenuated. The authors conclude that halothane anesthesia blunts cardiopulmonary baroreflex resistance responses provoked by mild decreases in thoracic blood volume in humans.

Baroreceptor reflex control of heart rate during morphine sulfate, diazepam, N2O/O2 anesthesia in humans.

The effect of morphine, diazepam, N2O/O2 anesthesia on baroreflex control of heart rate in humans was investigated in this study. Group 1 subjects (n = 11) received morphine 0.5 mg/kg, diazepam 0.25 mg/kg, and 70% N2O with O2. Group 2 subjects (n = 10) received morphine 0.75 mg/kg, diazepam 0.25 mg/kg, and 70% N2O with O2. Phenylephrine (the pressor test), sodium nitroprusside (the depressor test), and graded neck suction were employed to alter the stimulation of baroreceptor sites. The pressor, the depressor, and neck suction baroreflex slopes declined significantly in both groups from awake to anesthetized. There was no significant difference in the degree of depression between the two groups for all three tests. Neck suction derived slopes compared favorably to the pressor test slopes (r = 0.70, P less than 0.01). This study indicates that the depression of arterial baroreflex-heart rate responses under morphine, diazepam, N2O/O2 anesthesia is similar to that seen with potent inhalational anesthetics such as isoflurane. Furthermore, there was no difference between the two morphine doses that were studied.