Effects of verapamil on indirect muscle twitch responses.

The effects on indirectly elicited muscle twitch amplitude associated with the calcium (slow) channel blocker, verapamil, with or without pancuronium were investigated using isolated bullfrog sciatic nerve-sartorius muscle preparations. Verapamil (2-8 mM) produced a dose-related depression of indirect muscle twitch height (P less than 0.05). Twitch response was depressed 11% below control by the lowest concentration employed and 86% by the highest concentration. Pancuronium (0.07 mM) depressed neuromuscular function 35% below control (P less than 0.05). The combination of 5 mM or 8 mM verapamil with 0.07 mM pancuronium caused significantly greater degrees of depression than either drug alone. Verapamil produced significant depression of twitch height in vitro in relatively high concentrations. The mechanism of action remains unknown. Verapamil possesses pharmacologic properties that may be unrelated to slow (calcium) channel inhibition. The reduction of muscle twitch height caused by verapamil alone (5 mM) could not be antagonized by neostigmine, calcium, or frequent washings.

Neuromuscular blocking action of verapamil in cats.

The effects of the calcium (slow) channel blocker verapamil, on non-cardiac excitable membranes were examined in vivo. In barbiturate anaesthetized cats, the effect of intravenously administered verapamil (0.1, 0.2, and 0.4 mg.kg-1) on isometric twitch amplitude of the flexor carpi radialis muscle, elicited by indirect and direct electrical stimulation, was determined. At all doses tested, verapamil significantly reduced muscle twitch amplitude from control values. The effect of dosage on twitch reduction was far more pronounced for indirect than direct stimulation. Full recovery to control was observed by 90 minutes only with the lowest dose (0.1 mg.kg-1 IV). Reduction of twitch amplitude (direct and indirect) lasted the duration of the experiment (180 minutes) for the two higher doses of verapamil. No significant changes in blood pressure, cardiac rate or rhythm were observed. The specific site and mechanism of verapamil's neuromuscular blocking action remains unclear. In clinical situations where potent inhalation agents, adjuncts or neuromuscular blocking agents may be used, therapeutic doses of verapamil may interact to promote muscle weakness.

Neuromuscular and electrocardiographic responses to verapamil in dogs.

Because severe muscular weakness was noted in animals receiving verapamil in doses exceeding those used in humans, we studied the effects of verapamil on neuromuscular function and its correlation with myocardial conduction. The flexor carpi radialis and its nerves were surgically exposed in mechanically ventilated dogs during pentobarbital anesthesia. Indirect and direct electrical stimulation was applied and twitch height recorded following the intravenous administration of verapamil. Twenty animals received one of four dose schedules. The results showed a significant dose-related depression of twitch height to indirect stimulation. Twitch height to direct stimulation was reduced only with the highest dose. The onset of depression of indirect stimulation was temporally associated with onset of A-V conduction delay. However, recovery following indirect stimulation lagged behind recovery of the ECG by 30 min. Recovery times of twitch height following indirect stimulation ranged from 60-208 min and also were dose-related. The qualitative similarity of pancuronium and verapamil on indirect twitch height suggests a similar site of action, i.e., the neuromuscular junction. A presynaptic or postsynaptic effect of verapamil could not be discerned in this study. Verapamil may produce an unrecognized source of weakness in the anesthetized patient either alone or through interaction with anesthetic agents or adjuncts.

Reappraisal of intravenous procaine as a short-acting anesthetic adjuvant.

Our data in 74 patients demonstrate that procaine hydrochloride is a safe anesthetic adjuvant in doses of 1 mg/kg/min even when total doses are 5 to 7 g. Blood pressure, heart rate, electrocardiographic variables, and blood gases were not adversely affected. Patients had no nausea or untoward postanesthesia symptoms. Emergence from anesthesia was rapid, within less than 15 minutes in all patients, and most were fully awake before leaving the operating room. In two patients in whom blood levels were studied the drug disappeared within 40 minutes. Procaine is inexpensive, $1.16 for 10 g, and it is not a known liver or kidney toxin. Until studies on cardiovascular dynamics and analgesic effects as in whom a low plasma cholinesterase activity is present or suspected. The clinical appraisal in 56 patients indicates its usefulness in suppressing premature venticular contractions and cough reflexes during endoscopic procedures in the respiratory tract. Procaine can be used to advantage in supplementing general anesthesia in outpatient surgery because of its brief action. For these reasons, the drug merits further study.

Intravenous procaine as a supplement to general anesthesia for carbon dioxide laser resection for carbon dioxide laser resection of laryngeal papillomas in children.

Procaine suppresses the cough reflex, decreases laryngeal irritability, and has general anesthetic properties. For these reasons, 14 pediatric patients undergoing CO2 laser resection of laryngeal papillomas were studied in which an intravenous infusion of procaine (1 mg/kg/min) was added to N2O-O2 halothane/enflurane general anesthesia immediately following endotracheal intubation. These patients were compared to nine patients receiving the same anesthesia without procaine. The mean age of both groups was 11 years. There was no difference between the groups in duration of anesthesia or surgery. Emergence, however, averaged 15 minutes in study patients compared to 36 minutes in the control group (p less than 0.01). There was no difference in anesthetic concentrations required to maintain satisfactory operative conditions in the two groups. Muscle relaxants were required intraoperatively in seven control patients but in none of the study patients. The surgeon ranked the operative conditions excellent in all study patients but poor in seven of the nine control patients. Five of the latter required postoperative treatment of laryngeal complications, including reintubation in three. Only one of the study patients had postoperative stridor. No evidence of procaine toxicity was noted in the study patients with total doses ranging from 500--3600 mg. Intravenous procaine is useful in pediatric patients having endoscopic laryngeal operations.

Pulsatile perfusion versus conventional high-flow nonpulsatile perfusion for rapid core cooling and rewarming of infants for circulatory arrest in cardiac operation.

Thirty consecutive infants undergoing hypothermia and circulatory arrest for repair of ventricular septal defect, transposition of the great vessels, or atrioventricular canal defects were alternately selected for conventional high flow nonpulsatile perfusion or pulsatile perfusion during core cooling and rewarming. All received morphine anesthesia, 30 mg/kg of Solu-Medrol, and 10 to 15 mcg/kg of phentolamine. Those receiving nonpulsatile flow were perfused at a rate of 160 to 180 cc/kg/min with a roller pump and oxygenator with arterial pressure of 50 to 55 mm Hg. In the pulsatile flow group, a roller pump and oxygenator were used, and an especially constructed Datascope PAD (pulsatile assist device) was interposed in the arterial line to provide pulsatile perfusion with 75/40 mm Hg pressure at slightly reduced flow (150 cc/kg/min). The average rectal, esophageal, and tympanic membrane temperatures were reduced to approximately 16 degrees C prior to circulatory arrest. Following repair, perfusion was resumed until these temperatures returned to 37 degrees C. Cooling and rewarming were enhanced by pulsatile perfusion, with over 30% reduction in total pump time. Additionally, the larger patients in the pulsatile group cooled almost as rapidly as the smaller. The rates of decline and subsequent rise of rectal, esophageal, and tympanic membrane temperatures were equal in the pulsatile group, but the rectal temperature lagged far behind in the nonpulsatile group. Urine production during bypass was 100% greater in the pulsatile group. The plasma free hemoglobin was similar in both groups. The average postrewarming pH was 7.31 in the nonpulsatile group and 7.42 in the pulsatile group. Infants receiving pulsatile flow awakened more quickly, were more alert, and required less postoperative mechanical ventilation. We suggest that pulsatile perfusion for core cooling and rewarming of infants is safe and is more rapid and physiological than conventional high-flow nonpulsatile perfusion.

Intravenous procaine for general anesthesia in dogs: a new look at an old technic.

New anesthetics have been introduced during the last 25 years which are not without inherent disadvantages. They are expensive, and some produce nephrotoxicity and possibly hepatotoxicity. Although the use of procaine intravenously as an anesthetic has been discarded, probably because of a convulsive effect, it is believed this disadvantage can be controlled by concomitant use of other drugs. Hence procaine, preceded by thiamylal, was administered to dogs to test its anesthetic capability, reversibility, and effects on the cardiovascular and central nervous systems. Blood levels of procaine were measured and correlated with these physiologic responses. Convulsive doses were ten times those producing anesthesia. There were no detrimental effects which would preclude a reevaluation in humans. Intravenous procaine produces definite general anesthesia, and it has the additional advantages of being rapidly hydrolyzed and providing antiarrhythmic effects. It may prove useful in modern anesthesia.

Sodium nitroprusside-induced hypotension for supine total hip replacement.

Deliberate hypotension was produced during general anesthesia by the infusion of sodium nitroprusside in 13 patients undergoing total hip replacement. Hemodynamic data from these patients were compared with those obtained from 5 patients under normotensive anesthesia for the same procedure. During the hypotensive period, which averaged 1.5 hours, the cardiac index rose 20 percent compared with controls. No acidotic tendency was seen. Blood loss in the study group averaged 475 ml, compared with 1475 ml in controls. From these data, a dose-response curve was derived which may allow the accurate prediction of the minute dosage of sodium nitroprusside required to safely induce hypotension during anesthesia.

A dosage nomogram for sodium nitroprusside-induced hypotension under anesthesia.

Sodium nitroprusside (SNP) was used to produce deliberate hypotension in 30 selected patients, 9 to 78 years of age, for total hip replacement under halothane-N2O-O2 anesthesia. Hypotension was induced in the first 13 patients by infusing a 0.01% (100 mug/ml) solution of nitroprusside (NP) in 5% dextrose. Blood pressure was diminished to a level just producing a dry surgical field. Preliminary data demonstrated that the mean arterial blood pressure (MAP) achieving this condition was 65 torr (p less than 0.01) and that the minute dosage of NP (mug/min) required to consistently reduce MAP to 65 torr could not be predicted on the basis of body weight. However, the age/weight ratio (yr/kg) of each patient, plotted against the known minute dosage of NP given during anesthesia, produced a highly significant dose-response curve (p less than 0.001, r = -0.8226). The preliminary dose-response curve was examined in a double-blind study on an additional 17 patients. The curve derived from the prospective study did not differ from that of the preliminary study. In addition, the combined data from the retrospective and prospective studies (30 patients) gave a better statistical fit than did those from the preliminary study alone (p less than 0.001, r = -0.8939). The nomogram provides an additional margin of safety in the use of this potent, fast-acting drug. SNP has been found predictable and effective in reducing surgical blood loss in selected patients undergoing total hip replacement.

Technic of deep hypothermia and circulatory arrest in the neonate and infant.

Most congenital heart anomalies now can be surgically corrected in a neonate or very young infant. Because their hearts are so small, it is advantageous to work in a bloodless and motionless operative field. Deep hypothermia with circulatory arrest provides this setting. Physiologic problems associated with hypothermia are minimized by inducing general vasodilatation with large doses of methylprednisolone. Surface cooling is done with ice blankets and small sandwich bags filled with crushed ice. The patient's temperature gradually falls to 75.2 F (24 C). After median sternotomy, core cooling can be used to bring the patient's temperature to the desired 68 F (20 C). Circulatory arrest is produced by draining blood into the reservoir and cross-clamping the great vessels and venae cavae. It can be maintained for up to 60 minutes. In infants over six months and over 6 kg (13.2 lb), moderate hypothermia 77 F (25 C) and low perfusion (1/4-1/3 of normal) with short periods (10 to 15 minutes) of circulatory arrest improve operative conditions and allow correction of the most complicated congenital heart defects.