Clinical pharmacological studies with 6-azidomorphine.

The intravenous (i.v.) administration of 4 mug/kg 6-deoxy-6-dihydroazido-isomorphine (6-AM) base to healthy, young adult male volunteers caused no circulatory and relatively little, short-lasting respiratory depression. Of the ten volunteers all felt lightheaded, two became euphoric and when they became ambulatory at the end of the experiment, three vomited and two other became nauseated. The intramuscular (i.m.) administration of the same dose of 6-AM had considerable analgesic effect against various types of experimental pain. It was more effective against ischemic pain, than against pain induced by electrical stimulation of the earlobe or the tooth pulp and it effected severe pain more than mild or moderate pain. In the six subjects investigated, 6-AM produced significant myosis. Of the 16 subjects who received 4 mug/kg 6-AM i.m. five experienced mild euphoria, two felt lightheaded, six became pale and sweaty in the course of the experiments carried out in the sitting position. When they becam ambulatory after the completion of the experiments, two subjects vomited and six others became nauseated. The findings of this study indicate that 6-AM causes less circulatory and respiratory depression than is to be expected from equianalgetic doses of morphine. Its other side effects (e.g., nausea, vomiting) are also less frequent and severe than those encountered after the administration of comparable doses of morphine to ambulating volunteers.

Alterations in cardiovascular function during neurolept anesthesia for surgery on the coronary vessels.

Induction of anesthesia for aortocoronary bypass surgery was accomplished by the administration of droperidol, morphine, oxygen and nitrous oxide-oxygen in 20 patients. They ranged from 40 to 69 years of age. Premedication consisted of diphenhydramine and morphine. Cardiovascular stability was the most important aspect of the technique. Heart rate changes were insignificant. Cardiac index increased substantially after droperiodol and remained unchanged after morphine. It stayed around control levels for the rest of the induction. A substantial decrease was observed while using mechanical ventilation. Mean arterial pressure dropped significantly after droperidol and again after morphine, then rose about 17% after oxygen to near control levels, where it stayed thereafter. Peripheral vascular resistance dropped substantially after droperidol. A significant increase occurred after oxygen, reaching almost control levels at this point. Mechanical ventilation caused a significant increase, similar to the decrease in the cardiac index. Decreased oxygen availability was compensated for by decreased oxygen consumption. Induction of neurolept anesthesia in the manner described appears to be void of the undesirable effects of either large doses of morphine, or nitrous oxide-oxygen following such morphine doses. Amnesia was complete in every patient.

Ketamine for pediatric cardiac anesthesia.

Eighty-five patients ranging from 12 h to 7 years of age were included in this study. In the first group 35 cases received ketamine, gallamine and oxygen for surgery on the great vessels. Ketamine provided satisfactory analgesia and amnesia. Heart rate did not change significantly. Gallamine gave additional safety in the prevention of bradycardia. One hundred per cent oxygen increased oxygen saturation and made more oxygen available for the tissues. The combination secured favorable conditions even in cases of sevre right to left shunt. Seven patients developed some degree of bradycardia, requiring treatment. All but one responded to epinephrime infusion. The one who did not improve died on the table. There were 6 additional deaths during the first 48 postoperative hours. Fifty infants and children received pentobarbital and morphine premedication and ketamine, pancuronium, nitrous-oxide oxygen anesthesia for open heart surgery. Cardiovascular stability with good operating conditions characterized the course of anesthesia. The increase in systolic and diastolic blood pressures and heart rate was small after induction. Further changes in these parameters during anesthesia were statistically insignificant. Perfusion pressure during cardio-pulmonary bypass was well maintained. The addition of 50 per cent nitrous oxide to inhaled oxygen significantly potentiated the duration of hypnosis and analgesia proved by ketamine. Mechanical ventilation was facilitated in both groups by the analgesia extending well into the postoperative period. There were 6 deaths in the first 48 postoperative hours in this group. The state of consciousness at the end of anesthesia and postoperative conditions of all 85 patients were comparable with that found with other agents. The techniques described provided suitable alternatives to the anesthetic management pediatric cardiac surgery.

Comparison of methotrimeprazine and meperidine as components of balanced anesthesia.

Methotrimeprazine (MTM) (0.5 mg/kg) and meperidine (1.5 mg/kg) was administered to four groups of 10 patients each. Two of these groups (I and II) received MTM or meperidine 12 minutes before, two other groups (III and IV), 3 minutes after, induction of thiopental anesthesia. N2O-O2 was administered after thiopental induction, and fractional doses of meperidine and muscle relaxants were used as required for maintenance of anesthesia. The preliminary administration of MTM or meperidine decreased the induction dose of thiopental by about 60 percent. When administered before thiopental, both had similar effects on heart rate, but whereas MTM moderately decreased, meperidine moderately increased systolic and diastolic blood pressure MTM had little or no effect on respiratory rate, which was significantly depressed by meperidine. When given after an induction dose of thiopental, the circulatory effects of MTM and meperidine were similar. Respiratory measurements were little affected by MTM but were markedly depressed by meperidine. The mug/kg/min maintenance doses of meperidine were about the same in the four groups. Postanesthetic recovery of consciousness was delayed in the two MTM groups. The incidence of postoperative nausea and vomiting was less in the MTM than in the meperidine groups. MTM appears to have several advantages over meperidine as a component of balanced anesthesia, but is not desirable if rapid postanesthetic recovery or early ambulation is important. Its use is indicated in patients in whom even transient respiratory depression is undesirable and in those in whom prolonged postoperative sedation is desired.

Common bile duct pressure changes after fentanyl, morphine, meperidine, butorphanol, and naloxone.

Five groups of 10 patients received thiamylal, enflurane, nitrous oxide-oxygen anesthesia for elective cholecystectomy. The common bile duct was intubated via the cystic duct with a 16-g plastic catheter, and the control intraductal pressure was measured. Patients then were given equi-analgesic doses of fentanyl, morphine, meperidine, butorphanol, or placebo intravenously, and the common bile duct pressure was recorded for 20 min. Fentanyl, morphine, and meperidine significantly increased pressure in the common duct (P less than 0.001). Butorphanol produced only insignificant changes. Naloxone given 20 min later significantly (P less than 0.001) decreased pressure in patients given fentanyl, morphine, and meperidine. Naloxone given without narcotics caused an increase in pressure that, although statistically significant (P less than 0.03), was clinically insignificant. In five additional patients anesthetized with thiamylal, nitrous oxide-oxygen and intermittent doses of fentanyl, common bile duct pressures were normal.

Prevention of suxamethonium-induced changes in serum potassium concentration by hexafluorenium. Is their combined use justified?

Sixty patients, none of whom was suffering from renal failure, received neurolept anaesthesia. They were divided into six groups of 10 patients each. Groups I and IV, II and V, and III and VI were given suxamethonium 0.2, 0.6 and 1.0 mg kg-1 respectively. Groups IV-VI were pretreated with hexafluorenium 0.3 mg kg-1. The serum potassium concentration decreased significantly after the induction of anaesthesia and also following the administration of hexafluorenium. Neither suxamethonium 0.2 mg nor 0.6 mg kg-1 with or without hexafluorenium restored the potassium concentration to the control value. Suxamethonium 1.0 mg kg-1 alone caused the serum potassium to increase to values greater than control; hexafluorenium attenuated this effect. The combination of hexafluorenium and suxamethonium may be of benefit in patients who are anephric or are in chronic renal failure.

Prevention of succinylcholine induced hyperkalemia by neurolept anesthesia and hexafluorenium in anephric patients.

Forty patients, half of them with normal kidney function, the other half anephric were included in the study. All received diphenhydramine, meperidine and atropine for premedication and droperidol, fentanyl, N2O and O2 for anesthesia. For endotracheal intubation and further relaxation 0.3 mg/kg hexafluorenium, followed in 5 minutes by 0.2 mg/kg succinylcholine were given intravenously. Anesthesia was maintained by 0.5 micrograms/kg increments of fentanyl, muscle relaxation by increments of 0.15 mg/kg or less hexafluorenium and 0.2 mg/kg or less succinylcholine, depending on the surgical time requirements. The drop in serum potassium concentration was sustained and similar in both groups. In the anephric group the drop after induction of neurolept anesthesia was statistically significant. The concentration remained low in both groups over the entire observation period. Unchanged serum sodium excluded hemodilution and the fact that there was no significant change in PvCO2 and pH mitigates against alkalosis as the cause for the observed drop. The anesthesia and muscle relation, as described, appears to be a suitable and hazard free alternative to other techniques.