Jeffrey A. Weinstein

Pharmacodynamics of vecuronium and atracurium in the obese surgical patient

The effect of obesity on the duration of action of the nondepolarizing muscle relaxants atracurium and vecuronium was studied in 28 neurosurgical patients. In obese patients given vecuronium (0.1 mg/kg), the time to go from 5 to 25% of recovery of twitch response was statistically significantly longer (14.6 7 minutes, mean SD) than it was in nonobese control patients (6.9 ± 2 minutes). Similarly, with vecuronium times for recovery from 25 to 75% were longer (33 ± 15 minutes) in obese patients than in control patients (13.2 ± 2 minutes), as was time to 75% recovery, 82 ± 30 minutes in obese patients, 50 ± 9 minutes in controls. In contrast, obese patients given atracurium (0.5 mg/kg) exhibited no difference in recovery indexes or recovery times when compared to control patients of normal weight. The prolonged duration of action of vecuronium in obese patients is most likely related to impaired hepatic clearance and/or an overdose effect with recovery occurring during the distribution phase. That the duration of action of atracurium is not prolonged in the obese is believed due to this relaxants not depending on organ function for elimination.

133Xe Blood Flow Monitoring during Arteriovenous Malformation Resection: A Case of Intraoperative Hyperperfusion with Subsequent Brain Swelling

Measurement of regional cerebral blood flow (rCBF) using the i.v. 133Xe technique was carried out during resection of a right temporooccipital arteriovenous malformation (AVM) with ipsilateral middle and posterior cerebral arterial supply. Intraoperatively, a rCBF detector was in place over the right frontotemporal area, about 5 to 6 cm from the border of the AVM. Anesthesia was 0.75% isoflurane in oxygen and nitrous oxide. After dural exposure, the rCBF was 27 ml/100 g/min at a pCO2 of 29 mm Hg and a mean arterial pressure (MAP) of 90 mm Hg. The pCO2 was then elevated to 40 mm Hg, and the rCBF was increased to 55 ml/100 g/min at a MAP of 83 mm Hg. After AVM removal, the rCBF rose to 50 ml/100 g/min at a pCO2 of 27 mm Hg and a MAP of 75 mm Hg. The pCO2 was elevated to 33 mm Hg and the rCBF increased to 86 ml/100 g/min at a MAP of 97 mm Hg. During skin closure, the rCBF was 94 ml/100 g/min at a pCO2 of 26 mm Hg and a MAP of 97 mm Hg. The patient was neurologically normal postoperatively except for a mild, new visual field defect. After 2 to 3 days, the patient gradually developed lethargy, confusion, and nausea with relatively normal blood pressure. An angiogram revealed residual enlargement of the posterior cerebral artery feeding vessel. Computed tomography showed edema extending from the area of AVM resection as far as the frontal region, producing a significant midline shift anteriorly. Intraoperative rCBF monitoring revealed significant hyperperfusion after AVM resection, which was associated with signs and symptoms of the normal perfusion pressure breakthrough syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Accelerated recovery from doxacurium-induced neuromuscular blockade in patients receiving chronic anticonvulsant therapy

STUDY OBJECTIVE To determine whether a drug interaction exists between doxacurium and anticonvulsants. DESIGN Open-label controlled study. SETTING Inpatient neuroanesthesiology service at a university medical center. PATIENTS Three groups of nine patients each, consisting of those chronically receiving carbamazepine, phenytoin, or no anticonvulsant therapy. INTERVENTION Intravenous administration of doxacurium 60 micrograms/kg during anesthesia with nitrous oxide (N2O), fentanyl, and droperidol. MEASUREMENTS AND MAIN RESULTS The adductor pollicis mechanical response to single 0.2-millisecond supramaximal pulses delivered to the ulnar nerve at 0.15 Hz was recorded. Patients receiving phenytoin or carbamazepine recovered neuromuscular function more quickly than did the control group. The times from doxacurium injection to 50% recovery of mechanomyographic response, for example, were as follows: control group, 161 +/- 55 minutes (mean +/- SD); phenytoin group, 76 +/- 31 minutes; and carbamazepine group, 66 +/- 27 minutes (p less than 0.05). The time for recovery from 75% to 25% blockade (recovery index) was decreased by 53% in the phenytoin group and by 67% in the carbamazepine group as compared with the control group (41.0 +/- 18.0 minutes and 28.6 +/- 8.6 minutes vs 86.4 +/- 45.2 minutes, respectively). CONCLUSION Chronic treatment with anticonvulsants results in more rapid recovery from neuromuscular blockade produced by doxacurium.

A Controlled Trial of Esmolol for the Induction of Deliberate Hypotension

Twenty-five patients scheduled for lumbar fusion or cerebrovascular surgery were enrolled in an open label treatment controlled study comparing blood pressure and heart rate responses during deliberate hypotension with either esmolol or nitroprusside during steady-state N2O/isoflurane anesthesia. The first 5 patients were empirically assigned to the esmolol group; the remaining 20 patients were randomized to receive either esmolol or nitroprusside. The target of 15% reduction in mean arterial pressure (MAP) from baseline determined during anesthesia was attained with esmolol 195 +/- 10 micrograms/kg/min (mean +/- SEM) for the group (n = 15) or nitroprusside 1.9 +/- 0.3 micrograms/kg/min for the nitroprusside group (n = 10). Nitroprusside use was associated with a 15.9 +/- 5.3% increase in heart rate compared to a 12.1 +/- 2.2% decrease in the esmolol group (p = 0.0001 between groups). Upon termination of the hypotensive infusions, nitroprusside patients had a MAP increase of 13.9 +/- 5.5% above baseline (p less than 0.05 compared to prehypotension) while the 7.4 +/- 3.5% increase in the esmolol group was not statistically significant. Although 30% of nitroprusside patients overshot their baseline MAP by more than 25%, no esmolol patients had this degree of rebound. One esmolol patient had a brief period of atrial premature contractions. No patient in either group suffered any adverse reaction to hypotension. It is concluded that in moderate doses esmolol is a safe and effective hypotensive agent during isoflurane anesthesia, with no reflex tachycardia and no significant potential for rebound hypertension. A MAP reduction of 30% from preanesthesia baseline was readily obtained with this combination.

Effects of Hypocarbia on the Pharmacodynamics of Sufentanil in Humans

Descriptors of power and frequency derived from power spectral analysis of the electroencephalogram (EEG) were used to determine the effects of low-dose sufentanil (0.1 μg/kg) on brain activity. The effects of hypocarbia alone and of hypocarbia with sufentanil in patients receiving a N2/O2 (70% 30%) anesthetic were also studied. Hypocarbia alone caused changes in most EEG descriptors from both the anterior (F3-C3) and posterior (P3-O1) EEG montages. All EEG descriptors in both hypocarbic and normocarbic patients significantly changed when sufentanil was administered, reflecting a shift of power into the lower frequency ranges. When the anterior EEG montages from the two groups that received sufentanil were compared, the delta power band, spectral edge 50 (median power frequency), and the relative power in the delta power band divided by the alpha plus beta power bands [D/(A + B)] in the hypocarbic group exhibited a significantly greater shift of power into the lower frequency range. It is concluded that (a) power spectral analysis is a sensitive measure of the effects of hypocarbia and small doses of sufentanil on the brain; (b) the power spectral analysis descriptors---delta power band, spectral edge 50, and [D/(A+B)]---are statistically the most sensitive to EEG changes induced by sufentanil; and (c) hypocarbia intensifies patient EEG response to sufentanil, as judged by changes in EEG descriptors.