Relief of cancer pain in man: alcohol-induced neuroadenolysis vs. electrical stimulation of the pituitary gland.

To explore new methods for the control of intractable pain caused by advanced cancer, the analgesic effect of electrical stimulation of the pituitary gland was investigated in 25 patients. The results were compared with a control study and with the effects of alcohol-induced pituitary neuroadenolysis (NALP) in the same patients. The pain score (0: no pain at all, 4: extreme pain) in the control study was 3.88 +/- 0.33. After electrical stimulation of the pituitary gland it was 1.24 +/- 1.61; and after NALP it was 1.0 +/- 1.60. The pain scores after electrical stimulation and NALP were significantly lower (P less than 0.01) than those in the control study; but there was no significant difference when the two were compared with each other. The duration of pain relief following NALP (59.65 +/- 68.72 days) was significantly longer compared with that recorded following electrical stimulation (2.97 +/- 2.58 days). Autopsy examinations of 3 patients who expired from their malignancies revealed that the pain relief was unrelated to the degree of necrosis induced in the pituitary by alcohol. Naloxone administration did not inhibit the analgesic effect of either NALP or electrical stimulation. The advantages and disadvantages of electrical stimulation, the pain relief mechanism activated by this method, and potential clinical applications are also discussed.

Laryngospasm-induced pulmonary edema.

Laryngospasm developed in a 33-year-old woman following attempted endotracheal intubation. Following establishment of the airway, the patient developed pulmonary edema which was successfully treated by conventional means. The sequence of events suggests that laryngospasm precipitated the development of the pulmonary edema in this patient.

The pituitary inhibitory system: its role in pain perception.

The present study was designed to investigate the pain relief mechanism of electrical stimulation to the pituitary and the relationship between hypothalamic and pituitary analgesic mechanism through the observation of monkey behavior and characteristics of tooth pulp-evoked potentials. The results suggest that pituitary-stimulating analgesia should be differentiated from hypothalamic-stimulating effect. In view of the facts, the theory of the Pituitary Inhibitory System is proposed.

Respiratory distress and beta-endorphin-like immunoreactivity in humans.

Beta-endorphin-like immunoreactivity was determined in the plasma of twenty patients suffering from hypoxia of various etiologies and in twenty healthy adult volunteers who served as controls. Mean beta-endorphin-like immunoreactivity in the hypoxic patients was 53.2 +/- 5.5 (SEM) pg/ml, as compared to the volunteer subjects in whom the mean level was 6.2 +/- 1.9 pg/ml (P less than 0.01). Significant negative correlations were present between both arterial pH (r = -0.85; P less than 0.01) and arterial PO2 (r = -0.80; P less than 0.01) and beta-endorphin-like immunoreactivity. These findings seem to lend support to the hypothesis that hypoxia and acidosis represent stressful conditions which may stimulate the release of beta-endorphin in humans.

[Use of ketamine in cardiac surgery. A preliminary report]. / Die Anwendung von Ketamine in der Herzchirurgie. Ein vorläufiger Bericht

The phencyclidine derivative, ketamine hydrochloride, combines cardiovascular stimulating effects with antiarrhythmic properties and, therefore, the drug has been shown to be a highly suitable anesthetic for coronary artery surgery. This intravenously and intramuscularly administered "dissociative" anesthetic selectively depresses pathways and regions of the central nervous system associated with pain conduction and perception, thereby avoiding undesirable total nervous system depression. 129 patients suffering from marked coronary artery insufficiency underwent aortocoronary by-pass surgery, ketamine being the main anesthetic agent. Ketamine-induced anesthesia proved to be a simple and safe method of pain control during coronary artery reconstructive surgery and, compared with halothane anesthesia, showed a marked reduction of postoperative mortality (5%).

The significance of diffusion hypoxemia.

The phenomenon of "diffusion hypoxemia" seems to be a well-defined entity. To determine the degree of deoxygenation of the arterial blood due to diffusion hypoxemia, experiments were performed in monkeys which were anesthetized with ketamine, intubated, and allowed to breathe spontaneously. Blood PaO2 values were continuously monitored with the aid of an intra-arterially placed IBC PO2 electrode capable of instantly recording changes in oxygen tension. After stabilization of the blood PaO2 values with the animal breathing different mixtures of oxygen and nitrous oxide, the inspired mixture was abruptly changed to normal air. The blood PaO2 values did not show any significant fall in PaO2 with any mixture containing more than 21% oxygen. It is suggested that diffusion hypoxemia of any degree can be seen only if a patient is breathing a gas mixture containing no more than 21% oxygen.

Etomidate: an ultrashort-acting nonbarbiturate agent for anesthesia induction.

Clinical evaluation of etomidate, an ultrashortacting nonbarbiturate hypnotic agent, shows it to be useful for anesthetic induction in adults. It produces sleep in 1 arm-brain circulation time, metabolites apparently peaking at 7 minutes postinjection. Cardiovascular and respiratory systems appear minimally affected and there is no indication of organ toxicity or other biochemical or hematologic drug-induced disturbances. Moderate pain on injection at some sites and transient myoclonia were the principal disadvantages observed.

Effect of etomidate on the cardiovascular system.

Following intravenous injection of 0.3 mg/kg of etomidate, the only noteworthy change in measured cardiovascular parameters was a 10 percent increase in heart rate. This suggests relatively stable cardiovascular response associated with administration of this new nonbarbiturate anesthesia induction agent.

Electrophysiologic evidence for involvement of the pituitary region in opiate analgesia.

In the past, various reports have discussed the relationship between the pituitary and analgesia. The purpose of the present study was to explore the possible role of the pituitary region in the mediation of pain by opioids. Tooth pulp evoked potentials recorded from primary somatosensory cortex and from the pituitary region of rabbits were recorded before and after an injection of opiates. Tooth pulp evoked potentials recorded from the primary somatosensory cortex were markedly inhibited after admission of fentanyl, while the tooth pulp evoked potentials recorded from the pituitary region were facilitated. It is concluded that the pituitary region plays a role in the mediation of pain and that this area is involved in the mechanism of opiate analgesia.

Comparison of two benzodiazepines for anaesthesia induction: midazolam and diazepam.

Ro 21-3981 is a newly synthesized water soluble benzodiazepine derivative. Its pharmacological properties are similar to diazepam. This investigation was designed to establish the effective induction dosage of Ro 21-3981 and to compare it with diazepam for induction of anaesthesia. The ED50 for Ro 21-3981 induction is 0.15 mg/kg and ED 100 is 0.2 mg/kg. Ro 21-3981 is one and one-half times as potent as diazepam (0.3 mg/kg) and more rapid in action. There is significantly less pain on injection with Ro 21-3981 as compared to diazepam. Cardiovascular stability and apnoea were observed with both drugs. Ro 21-3981 is a promising anaesthetic induction drug that merits further human study.

Further studies of the neural mechanisms of ketamine-induced anesthesia in the rhesus monkey.

Bipolar stimulation of tooth pulp was used to elicit evoked potentials in the cortex, thalamus, and midbrain reticular formation (MBRF) of 4 monkeys. Averaged evoked potentials in MBRF and medial thalamic nuclei were either completely obliterated or markedly reduced in amplitude by anesthetic dosages of ketamine. In contrast, little effect was observed upon the primary response elicited in the ventrobasal complex of the thalamus. These results suggest that anesthetic doses of ketamine block afferent signals concerned with the affective-emotional components of pain perception, but conduction of signals related to the localization of somatic stimuli in time and space may be relatively unimpaired.

The role of profound hypothermia in infants undergoing surgical correction of complicated heart defects.

A series of 110 children, ranging in age from 2 days to 4 years and in weight from 2.4 to 12.9 kg, underwent total surgical correction of complicated heart defects with the aid of profound hypothermia and total circulatory arrest. Combined surface and core cooling, in conjunction with light general anesthesia, proved to be a safe and effective method to provide optimal working conditions for the surgeon. The technic of cooling and rewarmining, as well as hemodynamic and metabolic parameters monitored, are important, and factors such as type of heart defect, age, weight should be considered in relation to postoperative morbidity and mortality.

Butorphanol and morphine: a double-blind comparison of their parenteral analgesic activity.

The analgesic effects of butorphanol tartrate and morphine sulfate were compared in 127 patients judged to have moderate to severe pain following major operations. The study was double-blind, and the drugs were given IM at several dosage levels. Scores for pain intensity and relief, as well as pain-intensity difference, were determined at 30, 60 and 120 minutes after medication, then were analyzed by a parallel-line assay method in a modified computer program. The analysis indicated butorphanol tartrate to be 7 times as potent as morphine sulfate. Peak analgesic effects were obtained at 60 minutes with both drugs. Side effects were minimal in degree and incidence. Neither butorphanol nor morphine induced any changes in blood pressure, pulse rate, or respiratory rate. These data, along with those from studies elsewhere, suggest that butorphanol is a safe, potent, and effective analgesic agents, with probably a low potential for inducing drug dependence.

Ketamine-facilitated induced anxiety therapy and its effect upon clients' reactions to stressful situations.

Evaluated the role of physiological arousal in the Induced Anxiety therapy procedure. Assigned 21 normal Ss to either conventional Induced Anxiety Induced Anxiety supplemented by the drug ketamine during arousal, or a no-treatment condition. The ketamine group was superior to the conventional group which was superior to the no-treatment group in reducing negative affect experienced during stressful situations. Most of the reduction was in depressive affect. The superior results obtained by increasing physiological arousal could not be accounted for by increased subjective emotional arousal.