In vivo reversal of depolarizing neuromuscular blockade.

The antagonism of depolarizing blockers, principally succinylcholine and decamethonium, by tetraethyl- and tetrabutylammonium ions in an in vivo neuromuscular preparation in anesthetized cats is described; possible mechanisms for these effects are discussed. Tetraethyl- (50-100 mg/kg, i.v.) and tetrabutylammonium (1-5 mg/kg, i.v.) produced sharp reversals of 95-99% succinylcholine and decamethonium blocks. These reversals were effective and sustained at any point during the course of the blockades. Tetraethyl- or tetrabutylammonium, administered 2-3 min before succinylcholine or decamethonium, prevented blockade, an effect compatible with an earlier reported in vitro investigation. The studies of others disclose the interaction of depolarizing blockers with acetylcholine receptors, leading to channel opening, channel entry and binding therein of these blockers. The present studies support this in showing the prevention of succinylcholine and decamethonium block by the prior administration of tetraethylammonium, which also interacts with acetylcholine receptors. It is proposed that a possible mechanism for tetraethylammonium reversals of succinylcholine and decamethonium blocks may be attributable to the tetraethylammonium reversal of a K+ current block by quaternary ammonium ions such as succinylcholine and decamethonium. Tetraethyl- and tetrabutylammonium ions proved to be effective antagonists of succinylcholine block following inactivation of plasma cholinesterases by hexafluorenium.

Inhaled induction and emergence from desflurane anesthesia in the ambulatory surgical patient: the effect of premedication.

We studied the effect of premedication (1 microgram/kg fentanyl and 0.04 mg/kg midazolam 5 min before induction of anesthesia) on airway reactivity and hemodynamic stability during inhaled induction using desflurane in 10 ambulatory surgical patients. Eight patients who were anesthetized without premedication served as the controls. Induction and emergence were rapid and unaffected by premedication. End-tidal and inspired concentrations of desflurane at loss of consciousness were significantly reduced by premedication (10.1% end-tidal/14.1% inspired, no premedication, vs. 5.3% end-tidal/8.9% inspired, premedication). Airway irritability was markedly attenuated by premedication (100% no premedication versus 30% premedicated), as was apnea (37.5% no premedication versus 0% premedicated). We observed an increase in mean arterial blood pressure and heart rate after loss of consciousness (mean arterial pressure 103 vs 121 mm Hg, heart rate 73 vs 100 bpm) in the unpremedicated patients, whereas both groups demonstrated a decrease in mean arterial blood pressure with no change in heart rate when baseline values were compared to those at incision (103 vs 74 mm Hg, no premedication, 99 vs 81 mm Hg premedicated). Patient acceptability was satisfactory and unchanged by premedication. We recommend the use of such premedication when desflurane is used during the induction of anesthesia.

Neuromuscular pharmacology in rat neonates: development of responsiveness to prototypic blocking and reversal drugs.

The neonatal pharmacology of neuromuscular drugs was studied in vivo in newborn rats and in vitro in neonatal phrenic nerve-hemidiaphragm preparations. Drugs used to probe neuromuscular development in rat neonates were physostigmine, edrophonium, neostigmine, 4-aminopyridine, d-tubocurarine (dTc), and succinylcholine. The prejunctional actions of these drugs were monitored in relation to neonatal age by the appearance of stimulus-evoked repetitive discharge initiated by motor nerve endings and the occurrence and magnitude of the resulting enhancement of twitch tension. The occurrence and incidence of drug-induced fasciculations also served to track the development of functional motor nerve endings. Each of these prejunctional actions was inoperative until the third neonatal week, indicative of incomplete motor nerve development. In contrast, 4-aminopyridine, a nonanticholinesterase, evoked these prejunctional actions in 1-wk-old rat neonates. Neostigmine and edrophonium antagonized dTc as early as the first week; presumably, postsynaptic maturation had reached a functional level. 4-Aminopyridine also antagonized dTc at week 1. Rat neonates showed resistance to dTc blockade when tested by neonatal phrenic nerve-hemidiaphragm preparations in vitro. Relationships between age and 85%-95% transmission block declined to the adult level by week 5. This result indicates that in rat neonates, pharmacodynamic rather than pharmacokinetic mechanisms predominate in the development of responsiveness to dTc.

The interactions of ouabain with post-tetanic and facilitatory drug potentiations at cat soleus neuromuscular junctions in vivo.

Cat soleus motor nerve terminals, after high frequency conditioning, generate a post-tetanic repetition (PTR) which leads to a post-tetanic (PTP) of the muscle response. This property enables quantitative assessment of enhancement or depression of this nerve terminal excitability in vivo. The present study focuses on ionic mechanisms underlying the PTRs produced in this neuromuscular system either by high frequency stimulation or edrophonium. Ouabain was used as a specific probe for inhibition of Na(+)-K+ ATPase and its known consequences on Na+ and Ca2+ translocation. Ouabain pretreatment doubled the duration over which single stimuli, following either high frequency or edrophonium conditioning produced PTR. Ouabain in the doses used had no effect per se but as a function of dose augmented the frequency dependent responses. This pointed to Na+ loading of nerve terminals via high frequency stimulation plus ouabain inhibition of Na(+)-K+ ATPase. Ouabain potentiation of PTR responses evidently depends on exchange of intra-terminal sodium for external calcium. Thus, calcium entry blockers, Mn2+, and Co2+ suppressed or abolished the potentiations both before and after ouabain. Diphenylhydantoin, a Na+ and Ca2+ blocker, acted similarly. The effects of stimulation frequency, ouabain and the sequence of events leading to PTR in the soleus neuromuscular system appeared in general no different from those derived from the many in vitro microphysiologic studies of this phenomenon. Thus, EPPs were augmented and prolonged. It was concluded that intracellular Ca2+ is critical for regulating the stability of systems in which repetitive firing is both a normal and abnormal function.

Pulmonary function after extracorporeal shock wave lithotripsy--a comparison of general and regional anaesthesia.

The effect of general anaesthesia on postoperative pulmonary mechanics was studied by comparing pre- and postoperative spirometry in 30 patients undergoing extracorporal shock wave lithotripsy, 15 of whom received a unilateral intercostal nerve block, the remainder a general anaesthetic. Both groups of patients had significant postoperative changes in peak expiratory flow rate, expiratory reserve volume and vital capacity; forced expiratory volume at one second was not significantly changed in either group. There were no significant differences in the pre- or postoperative mechanics between the two groups. We conclude that general anaesthestics do not play a significant role in the generation of abnormalities in postoperative spirometry.

Prevention of suction-induced hypoxemia by simultaneous oxygen insufflation.

The effects of endotracheal suctioning were studied in 38 patients. A significant decline in arterial oxygen tension and saturation was noted in all patients. A new double lumen suction catheter that simultaneously insufflates oxygen while suctioning was tested in these same patients and was found to prevent hypoxemia in all patients. We recommend that the insufflation catheter be added to the protocol of hyperventilation with 100% oxygen to help prevent suction-induced hypoxemia.

Neomycin-induced neuromuscular blockade.

The unusual complication of neuromuscular blockade secondary to neomycin absorption is described. The syndrome characterized by acute muscle flaccidity, diaphragmatic breathing, and central nervous system depression presents a potentially fatal situation. Appropriate treatment of this complication includes respiratory assistance and calcium gluconate administration (IV). A review of the pediatric literature reveals 12 previous cases, of which 2 were secondary to urologic procedures.

The numenon and the phenomenon.

A bolus of 3 mg. of atropine was given intravenously (I.V.) to 123 anesthetized patients. Increases in heart rate were seen in 109 patients (88 percent), while 7 patients (5.7 percent) had decreases and 7 others (5.7 percent) had no change. A mean increase in systolic arterial blood pressure of 14 mm. Hg was noted. A certain pattern in increases in heart rate and systolic blood pressure was observed. Ninety-six percent of the patients under cyclopropane, fluorexene, ether, ketamine, or regional (spinal or epidural) anesthesia had heart-rate increases compared with only 77 to 89 percent of the patients anesthetized with halothane, enflurane, or neuroleptanalgesics. Rise in systolic blood pressure was seen in 40 to 50 percent of the former, but only in 31 to 40 percent of the latter group. The arrhythmias observed were transient A-V junctional tachycardias in three instances and bigeminal rhythm in one patient under cyclopropane anesthesia. The administration of a vagolytic dose of atropine to anesthetized patients appears not to be as arrhythmogenic as previously considered.