Philip W. Lebowitz

Twitch, tetanus and train-of-four as indices of recovery from nondepolarizing neuromuscular blockade

This study was undertaken to compare the sensitivities of the train-of-four response (2 Hz for 2 s), the single twitch (0.15 Hz), and the tetanic response (50 Hz for 5 s) as indices of residual nondepolarizing block. Spontaneous or induced recovery of evoked thumb adduction in response to ulnar nerve stimulation was studied. One hundred and seven adult surgical patients were divided according to the relaxant used, into six groups. We found that when the single twitch recovered to control height, the train-of-four ratio was well below 1.0. This ratio was significantly lower during spontaneous recovery than following neostigmine antagonism of the block (P < 0.01). The tetanic response was fully sustained when the train-of-four ratio was above 0.7. When the ratio was less than 0.7, variable degrees of fade of tetanus were evident. Analysis of variance indicated similar train-of-four ratios among the six groups at complete recovery of the single twitch irrespective of the relaxant technique used (P < 0.1). It is concluded that a train-of-four ratio of 0.7 or higher reliably indicates the recovery of the single twitch to control height and a sustained response to tetanic stimulation at 50 Hz for 5 s. The clinical significance of this study is as follows: the train-of-four response provides the same indication of clinical recovery from nondepolarizing block as obtained from tetanic stimulation at a physiological frequency; and reliance on the recovery of the single twitch to control height as a criterion of spontaneous return to normal clinical neuromuscular function may be misleading.

Potentiation of neuromuscular blockade in man produced by combinations of pancuronium and metocurine or pancuronium and d-tubocurarine

Simultaneous administration of combinations of pancuronium, metocurine, and d-tubocurarine (dTc) were given to A.S.A. class l-ll surgical patients during N2O-narcotic-thiopental anesthesia to determine the degree of neuromuscular blockade produced. The pancuronium-metocu-rine and the pancuronium-dTc combinations were each significantly more potent (p < 0.05) than the additive effects of each of the individual drugs given alone. This greater than additive neuromuscular blocking effect was not seen with the metocurine-dTc combination. Despite the potentiation of neuromuscular blocking intensity by the pancuronium-metocurine and the pancuronium-dTc combination, the duration of blockade was not prolonged. Possibly, such potentiation of neuromuscular blockade might be attributed to simultaneous pre- and postjunctional receptor inhibition. Additional mechanisms might involve augmented conformational attachment to pre- and postjunctional cholinergic receptors or altered protein binding such that a greater than expected proportion of unbound drug reaches its neuromuscular site of activity. Regardless of mechanism, combining pancuronium with dTc or with metocurine can provide surgical relaxation or ideal conditions for endotracheal intubation with smaller amounts of each drug than would be anticipated if their effects were simply additive.

Comparative cardiovascular effects of midazolam and thiopental in healthy patients

Midazolam, a water-soluble benzodiazepine that is shorter-acting, more potent, and less irritating to veins than diazepam, has been suggested for use for induction of anesthesia. The cardiovascular effects of an induction-sized dose (0.25 mg/kg) of midazolam in A. S. A. class I or II surgical patients (N = 11) sedated with morphine and N2O-O2were compared in a double-blind fashion with a similar group of patients (N = 9) receiving thiopental (4.0 mg/kg). Consistent with earlier studies, patients given thiopental experienced downward trends from base line in mean arterial pressure, stroke volume, cardiac output, and heart rate; mean right a trial pressure increased slightly, whereas systemic vascular resistance did not change. Induction of anesthesia with midazolam was associated with more gradual and less pronounced hemodynamic alteration; the only significant changes from base line were decreases in mean arterial pressure 5 and 10 minutes after injection. When the two groups were compared, no significant differences were found. Midazolam is, then, as acceptable for induction of anesthesia as thiopental from a hemodynamic point of view in A. S. A. class I and II patients.

Scheduling a delay between different surgeons' cases in the same operating room on the same day using upper prediction bounds for case durations.

At some surgical suites, elective cases are only scheduled if they can be completed during regularly scheduled hours. At such a surgical suite, a surgeon may be scheduled to perform one or more cases in an operating room (OR), to be followed by another surgeon who will perform one or more cases. Scheduling a delay between the two surgeons’ cases will improve the likelihood that the second surgeon’s case(s) will start on time. We show that the mathematics of calculating a scheduled delay between the different surgeons’ cases in the same OR on the same day is that of calculating an upper prediction bound for the duration of the second surgeon’s case(s). We test an analytical expression for the upper prediction bound for the last one case of the day in an OR, and a Monte Carlo simulation method for the last two cases. We show that these 90% upper prediction bounds are at least as long as the actual durations for 90% ± 0.2% of single cases and 92% ± 0.6% of pairs of cases. We conclude that our methodology can be used to calculate an appropriate, and reasonably accurate, scheduled delay between two surgeons’ cases in the same OR on the same day.

Combination of pancuronium and metocurine: neuromuscular and hemodynamic advantages over pancuronium alone.

Combination of pancuronium and metocurine or pancuronium and d-tubocurarine produces potentiation of neuromuscular blocking effects such that administration of relatively small doses of these drugs can yield clinically effective neuromuscular blockade. The clinical characteristics of the block produced in A. S. A. class I-II patients during N2O-narcotic-thiopental anesthesia by the pancuronium-metocurine combination at the calculated ED95 (N = 8) and at twice the ED95 (N = 9) were compared with the block produced by pancuronium alone at its ED95 (N = 20) and at twice the ED95 (N = 6). Onset time (from drug injection to 95% twitch suppression) and the maximum twitch depression achieved were comparable between corresponding groups, but the 25% recovery time (from drug injection to 25% recovery of twitch height) was significantly shorter in the groups that received the pancuronium-metocurine combination. Furthermore, at twice the ED95, heart rate increased significantly more in the pancuronium group than in the pancuronium-metocurine combination group. Mean systemic blood pressure did not change significantly in either group. We conclude that patients given a combination of pancuronium and metocurine in large doses experience less hemodynamic change and more rapid recovery of neuromuscular function than do patients given equivalent doses of pancuronium alone.

Pharmacokinetics of d-tubocurarine in patients with thermal injury

d-Tubocurarine (dTc) requirements are increased following thermal injury. Significant increases in plasma binding only partially account for the altered requirement. To characterize the pharmacokinetic component of the increased requirement, the disposition of dTc was studied in eight patients with burns ranging from 15% to 80% of body surface area and compared with that in six nonburned surgical patients of comparable age and weight. Plasma levels of dTc were measured by radioimmunoassay at multiple times for 24 hours after a single bolus dose. Derived pharmacokinetic parameters were corrected for the predicted (not measured) fraction bound to plasma. The plasma disappearance curve of dTc was explained by linear sum of two or three exponential terms. The unbound central volume of distribution and renal excretion at 24 hours were significantly increased in burned patients (0.11 ± 0.03 L/kg vs 0.057 ± 0.015 L/kg, p < 0.05, 57% ± 7% vs 40% ± 11 %, p < 0.05, respectively). On the other hand, comparable elimination half-lives (6.5 ± 1.8 hr vs 6.2 ± 1.3 hr, p > 0.05), unbound volume of distribution (0.86 ± 0.2 L/kg vs 0.96 ± 0.5 L/kg, p > 0.05), and intrinsic clearances (1.62 ± 0.6 ml/kg/min vs 1.56 ± 0.4 ml/kg/min, p > 0.05) were present in burned patients and control patients, respectively. Thus, altered kinetics contributes little to the increased doses required. Similar clearances and elimination half-lives in both groups suggest that loss of dTc through burned tissue is minimal.

Cardiovascular effects of midazolam and thiopentone for induction of anaesthesia in Ill surgical patients

The cardiovascular effects of midazolam (0.15 mg kg-) and thiopentone (3.0 mg kg1) were compared during induction of anaesthesia in 20 American Society of Anesthesiologists class HI patients. In patients given thiopentone (N = 11), cardiac output, mean arterial pressure, heart rate, and systemic vascular resistance all decreased significantly over the course of the study period; mean right atrial pressure rose slightly, and stroke volume remained the same. Patients receiving midazolam (N = 9) experienced similar haemodynamic changes which were significant relative to baseline only for the fall in mean arterial pressure and the rise in mean right atrial pressure at ten minutes. There were no significant differences between the two groups. Midazolam thus appears to be at least as acceptable an induction agent as thiopentone in ill patients, from a haemoaynamic point of view.RésuméOn a comparé les effets cardiovasculaires obtenus pendant I’administration de I’anesthésie avec le midazolam (0.15 mg kg-1) et le thiopentone (30 mg kg1) chez 20patients appartenant ä la Classe III (American Society of Anesthesiologists). Chez les patients recevant le thiopentone (N = 11), on a observé que le débit cardiaque, la fréquence cardiaque, la résistance vasculaire générale et la tension artérielle ont baissé sensiblement durant le cours de notre recherche. La pression moyenne de I’auriculaire cardiaque droite haussa faiblement tandis que le débit systolique resta le même. Les patients auxquels on administra le midazolam (N = 9) ont éprouvé des changements hémodynamiques significatifs par rapport à la valeur de base oi l’on observa settlement une baisse de la pression artérielle moyenne et une hausse à dix minutes de la pression moyenne de l’ auriculaire cardiaque droite. Il n’y a done pas áe différences significatives entre les deux groupes. Le midazolam apparaît être un agent d’induction aussi acceptable que le thiopentone chez les malades, au point de vue hémodynamique.

Clinical characteristics of long-term succinylcholine neuromuscular blockade during balanced anesthesia

Thumb adductor twitch response to train-of-four (2 Hz for 2 seconds) stimulation of the ulnar nerve was used to assess the clinical characteristics of long-term neuromuscular blockade induced with continuous infusion of succinylcholine during balanced (N2O-O2-narcotic-thiopental) anesthesia. Twitch depression of 80 to 90% was maintained for 86 to 365 minutes by continuous infusion of succinylcholine at 86 ± 5(SEM) μg/kg/min. Of 32 patients, 24 developed phase II block, defined as a train-of-four ratio of less than 50%. There was a large degree of individual variability in sensitivity to development of phase II block. This precluded defining a narrow dose range where transition from phase I to phase II occurred. Tachyphylaxis occurred in 25% of patients and was independent of the type of block. Neither dose nor duration of infusion was predictive of spontaneous recovery rate from phase II block. Of 24 patients who developed phase II block, 50% recovered spontaneously at a rate comparable to the recovery rate from a phase I block. The other 50% manifested prolonged recovery of neuromuscular function. After observing spontaneous recovery in these patients for 31 ± 5(SEM) minutes, successful antagonism of residual phase II block with anticholinesterase agents was achieved.

Comparative renal effects of midazolam and thiopental in humans

Midazolam is a water-soluble benzodiazepine whose quick onset after intravenous injection, short duration of action, absence of venous irritation, and mild cardiovascular and respiratory effects suggest its use for induction of anesthesia. The renal effects of midazolam-N20–02 anesthesia, as determined by renal clearance of injected inulin and para-aminohippuric acid (PAH), in hydrated ASA Class III surgical patients (N = 8) were compared in a double-blind fashion with a similar group of patients (N = 9) anesthetized with thiopental-N20–02. Except for glomerular filtration rate, there were no significant changes in any of the measured variables (blood pressure, effective renal plasma flow, renal blood flow, and renal vascular resistance). The per cent reduction in glomerular filtration rate in patients given thiopental differed significantly from that in patients given midazolam. This study suggests that midazolam, as opposed to thiopental, offers minimal advantage in maintaining renal performance at least during the period of anesthetic administration

Trimethaphan versus sodium nitroprusside for the control of proximal hypertension during thoracic aortic cross-clamping: the effects on spinal cord ischemia.

Sodium nitroprusside (SNP) has been used to control the proximal hypertension associated with thoracic aortic cross-clamping (TACC) during thoracic aortic surgery. It worsens neurologic outcome, presumably by further decreasing distal arterial pressure and increasing cerebrospinal fluid (CSF) pressure, thereby worsening the spinal cord perfusion pressure (SCPP). Trimethaphan does not increase CSF pressure. Therefore, the present study investigates the effect of trimethaphan versus SNP to control proximal hypertension during TACC on neurologic outcome. Two groups, each with eight mongrel dogs, were studied. All animals underwent descending TACC for 45 min. The mean proximal aortic blood pressure was maintained at 95-100 mm Hg by the use of SNP or trimethaphan. Distal aortic pressure was allowed to vary. The dogs were neurologically evaluated 24 and 48 h later by a blinded observer. During cross-clamping, there was no difference in mean proximal aortic pressure between groups. After 10 min of cross-clamping, distal aortic pressure was higher (P < 0.01), CSF pressure was lower (P < 0.01), and SCPP was higher (P < 0.005) in the trimethaphan group as compared with the SNP group (group effect). Neurologic outcome as assessed by Tarlovs score was better at 24 and 48 h in the trimethaphan group (P < 0.05). Histopathologic injury trended with worsened neurologic outcome. We conclude that 1) trimethaphan produced higher SCPP than SNP, and 2) neurologic outcome was better in the trimethaphan group. (Anesth Analg 1996;82:68-74)