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Nalbuphine hydrochloride (Nubain; Du Pont Pharmaceuticals), a synthetic agonist-antagonist analgesic, in a dose of 20 mg was compared with pethidine 100 mg in 60 patients after elective surgery in a random double-blind study. Both drugs were given intramuscularly on the first day after surgery. The pain intensity and visual analogue scales would seem to indicate that nalbuphine has a longer duration of action than pethidine (P less than 0,05). The respiration rates in the pethidine group were significantly more depressed 30 minutes after the injection than in the nalbuphine group (P less than 0,05). Nalbuphine caused less depression of both systolic and diastolic blood pressure at both 30 and 60 minutes (P less than 0,001). The results of the study show that nalbuphine, in the dose used here, may prove to be a useful substitute for pethidine.

A hypothesis that volatile anaesthetic agents, represented by enflurane, facilitate transplacental exchange was tested by simultaneous blood sampling of both mother and fetus. A trend towards improved fetal scalp blood gas status and maternal-to-fetal acid-base matching was observed with enflurane. Our results encourage further research into the feasibility of intra-uterine fetal resuscitation by anaesthetically induced promotion of intervillous perfusion.

The effects on lower oesophageal sphincter (LOS) tone of sequential intravenous injections of metoclopramide 10 mg/atropine 0,6 mg and atropine 0,6 mg/metoclopramide 10 mg, given randomly on separate occasions to 8 healthy volunteers, were studied. The administration of metoclopramide increased mean LOS pressure by 13,6 cm H2O (P less than 0,001). Subsequent injection of atropine failed to lower LOS pressure significantly, LOS pressure being sustained at a mean of 11,2 cm H2O above basal control levels (P less than 0,01). In contrast, injection of atropine at a later date in the same subjects lowered the average LOS pressure by 10,5 cm H2O (P less than 0,001), and subsequent intravenous injections of metoclopramide restored LOS pressure to basal levels. The results of this study suggest that metoclopramide should be given prior to atropine before induction of general anaesthesia to counteract the deleterious effects of atropine on LOS tone, thereby helping to reduce the chances of regurgitation and pulmonary aspiration of acid gastric contents.

Acid aspiration in an important cause of anaesthetic mortality. 430 patients referred for gastric analysis were reviewed. According to observations made at endoscopy, patients were divided into 4 groups--no abnormality, oesophagitis/gastritis, gastric ulcers and duodenal ulcers. The volume of gastric juice varied from 0 to 400 ml, and the pH from 0-8 to 8. The percentage of patients with overnight fasting gastric volume over 25 ml and a pH of less than 2-5 was disturbingly high in all groups: controls 38-5%, oesophagitis/gastritis 51-2%, gastric ulcers 40-0%, duodenal ulcers 73-3%. This last figure is significantly greater than the group with no detectable abnormality. These results indicated that the stomach of a fasting patient often contains sufficient volume of acid gastric juice to place the subject at risk from acid aspiration during anaesthesia. Antacid therapy in all these patients seems imperative and consideration should also be given to preoperative gastric aspiration before induction of general anaesthesia.

Flunitrazepam (Rohypnol) was compared with thiopentone as an anaesthetic induction agent in children between 4 and 12 years of age who underwent elective minor surgical procedures. Successful induction of anaesthesia was achieved in both groups of patients. With flunitrazepam the induction time was longer but not statistically different from that with thiopentone. The incidence of apnoea was higher with thiopentone, but not significantly so. It is concluded that flunitrazepam could prove a reasonable alternative to thiopentone as an intravenous induction agent in children who have to undergo elective minor operations.

Endotoxins (lipopolysaccharides-LPS) and anti-endotoxin IgG antibodies were measured in racehorses before and after races of 1,000, 2,000 and 2,800 m. Results show that the mean plasma concentration of endotoxin increased significantly (p less than 0.02) while the anti-LPS IgG concentration decreased significantly (p less than 0.005) in all horses following the races. Pre-race and post-race anti-LPS IgG levels in racing-fit racehorses were significantly higher than in untrained horses (p less than 0.05). The possibility therefore exists that training-induced stress leads to leakage of LPS into the systemic circulation which results in self-immunisation against LPS. The effects of plasma LPS and anti-LPS IgG concentrations on performance of racehorses require further studies.

The time course of changes in the level of plasma lipopolysaccharides (LPS) in both the hepatic portal and the systemic arterial circulations, together with changes in cardiovascular parameters, was ascertained during a 1 hr occlusion of the superior mesenteric artery (SMA) in six primates. The LPS concentrations before occlusion of the SMA in the hepatic portal and systemic arterial circulation were 0.051 +/- 0.009 and 0.065 +/- 0.011 ng/ml, respectively (NS). At the end of the occlusion period, there was no significant increase in either the hepatic portal or systemic arterial plasma LPS concentrations. Immediately on removal of the occlusion, however, the LPS concentration in the portal plasma increased and peaked at 0.431 +/- 0.124 ng/ml (P less than 0.01) within 17.5 +/- 1.71 min, whereas in the systemic arterial circulation the LPS concentration began to rise but only after a delay of approximately 10 min to peak at 0.287 +/- 0.126 ng/ml (P less than 0.05) within 32.5 +/- 4.23 min of reperfusion. The mean arterial pressure (MAP) declined during the reperfusion period from 98.6 +/- 6.89 to 65.0 +/- 9.5 mm Hg (P less than 0.05). The heart rate showed a small but not significant increase (P greater than 0.2) after about 80 min of reperfusion. These data indicate that the gut is the source of the increased plasma LPS concentration following occlusion of the SMA.

Ischemia of the intestines damages the permeability of the intestinal wall, allowing lipopolysaccharide (LPS) (endotoxin) to leak from the gut lumen into the blood circulation, causing shock and death. We measured LPS levels associated with corticosteroid treatment vs. no treatment in cats whose superior mesenteric artery had been occluded for 60 min. In untreated cats, the preocclusion mean plasma LPS concentration remained stable at 0.069 +/- 0.015 ng/ml. Toward the end of the occlusion period, mean plasma LPS rose to 0.239 +/- 0.032 ng/ml (p less than .01). Release of the clamp and reperfusion with oxygenated blood was followed within 20 min by a large rise in plasma LPS concentration to 0.825 +/- 0.11 ng/ml (p less than .01), which had returned to preocclusion levels about 80 min later. Methylprednisolone (30 mg/kg) was infused into a second group of cats 1.5 h before SMA occlusion. In these cats there was a complete inhibition of the LPS rise both during and after occlusion. These data suggest that the reported beneficial effect of corticosteroids in the treatment of septic shock may be mediated, in part, by reducing LPS leakage from the gut.

The effects on lower oesophageal sphincter tone of intravenous ranitidine 150 mg followed by atropine 0.6 mg were studied in six healthy volunteers. Ranitidine increased the mean lower oesophageal sphincter pressure by 21.2 cm H2O (p less than 0.01). Subsequent injection of atropine lowered the lower oesophageal sphincter pressure but not significantly, mean sphincter pressure remaining 14.2 cm H2O above control. Barrier pressure to reflux (lower oesophageal sphincter pressure minus gastric pressure) increased significantly after intravenous ranitidine injection, and although it fell after intravenous atropine it was still above control levels. The results of this study suggest that ranitidine increases lower oesophageal sphincter tone. When it is given prior to atropine injection within 20 minutes before induction of anaesthesia it counteracts the deleterious effect of the latter on sphincter tone and barrier pressure to reflux.

Ketamine, a cataleptic analgesic substance which theoretically may block pain receptors in the spinal cord, providing pain relief without respiratory depression, was injected intrathecally with or without benzethonium chloride 0.1 mg/ml (a preservative) into 8 monkeys under anaesthesia. Two monkeys received saline (control group). No assessment as to relief from experimental pain was possible. All Monkeys recovered normally from anaesthesia and were found moving about in their enclosures without gross evidence of neurological impairment. No adverse reactions were noted. Ten days after the subarachnoid injection the monkeys are sacrificed. Autopsy was performed within 30 minutes. No macroscopic abnormality of the cord was noticed. Microscopic examination revealed oedema of a few nerve roots in all animals, irrespective of whether ketamine or saline was injected intrathecally. Focal degeneration with loss of myelin and axoplasm was observed within a solitary nerve root in 2 monkeys that had received ketamine, 1 with and 1 without preservative. However, in these animals lumbar puncture proved difficult and bloody taps ensued. Hence trauma could have been a contributing factor in these 2 cases. None of the other monkeys showed these changes, regardless of group.

Lipopolysaccharide (LPS) concentrations in hepatic portal and systemic arterial plasma were determined in five anesthetised monkeys heat-stressed by an environmental temperature of 41.0 +/- 0.3 degrees C and 100% relative humidity. As the rectal temperature (Tr) rose, the LPS concentrations in both the portal and systemic arterial plasma remained at the pre-heat-stress levels of 0.088 +/- 0.017 and 0.078 +/- 0.021 ng/ml (N.S.), respectively, until a Tr of 42.5-43.0 degrees C, when the LPS concentration increased slowly, first in the portal plasma and then in the systemic plasma. On the other hand, the concentration of plasma anti-LPS IgG antibodies began to decline at temperatures as low as 40 degrees C from 20.66 +/- 7.35 micrograms/ml (portal) and 22.14 +/- 7.43 micrograms/ml (arterial) to 5.51 +/- 1.28 micrograms/ml (portal) (P less than .05) and 4.6 +/- 1.69 micrograms/ml (arterial) (P less than .05) just prior to death. Above a Tr of 43 degrees C, the LPS concentration increased rapidly to a maximum of 0.244 +/- 0.05 ng/ml (portal) (P less than .01) and 0.224 +/- 0.06 ng/ml (arterial) (P less than .01). The mean arterial pressure remained more or less constant at 112 +/- 17.03 mm Hg until a Tr of 41.5 degrees C and then rapidly declined as Tr rose (P less than .01). The heart rate rose gradually from 154 +/- 14 min-1 as Tr increased and then rapidly after a Tr of 41.5 degrees C to a maximum of 307 +/- 13 min-1 at 43.0 degrees C. Thereafter it declined rapidly until death.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspiration of gastric contents, the most common anaesthetic cause of maternal mortality, is decreased by emptying of the stomach and the use of antacids and H2-receptor antagonists. One hundred and eighty-three mothers presenting for emergency Cesarean section were allocated to three groups. In group 1, the stomach was emptied before operation via an orogastric tube and thereafter 30 ml of sodium citrate 0.3 mol litre-1 was ingested 5-15 min before induction of general anaesthesia (our usual practice). Group 2 received only 30 ml of sodium citrate 0.3 mol litre-1. Group 3 received ranitidine 50 mg i.v. before operation, 5-15 min before induction of anaesthesia, in addition to sodium citrate. Our results show that preoperative gastric emptying with an orogastric tube followed by sodium citrate is preferred if anaesthesia should be induced 15-20 min later. However, the use of ranitidine and sodium citrate is preferred at subsequent times. Although our data show that preoperative gastric emptying decreased the mean intragastric volumes before Caesarean section, the number of patients at risk of acid aspiration was not reduced. In view of these findings and the unpleasantness of orogastric intubation, we suggest that routine preoperative gastric aspiration via an orogastric tube is not justified, although the manoeuvre should still be used following a recent meal.

In an open non-comparative clinical trial 64 patients older than 18 years with American Society of Anesthesiologists ratings of I and II were studied. Under standardized conditions of premedication, anaesthesia was induced by injecting midazolam (Ro 21-3981) 0,15 or 0,3 mg/kg body weight intravenously. After endotracheal intubation with suxamethonium 1 mg/kg, anaesthesia was maintained with nitrous oxide in oxygen and enflurane or halothane. There were statistically significant cardiovascular changes during and/or after intubation but there were no clinical consequences. Midazolam allows rapid induction of and recovery from anaesthesia. There was no retrograde amnesia and high proportion of the patients assessed the induction of anaesthesia as favourable. The local tolerance was very good. Midazolam seems to be a good alternative for induction of balanced anaesthesia.

Ninety patients presented for elective surgery and were randomly divided into three groups and studied on a double-blind basis to assess the efficacy of gastrozepin, a new muscarinic receptor antagonist, compared to cimetidine and placebo. Gastrozepin 10 mg, cimetidine 200 mg and a placebo were given i.v. on average 90 min prior to surgery. Gastric fluid was aspirated immediately after induction of anaesthesia and the volume and pH measured. The mean gastric fluid volume in the placebo group (19.73 ml) was significantly (P less than 0.02) greater than the mean volume of either the gastrozepin group (12.40 ml) or cimetidine group (12.72 ml). Mean gastric pH's were 4.83 (gastrozepin), 6.39 (cimetidine) and 3.21 (placebo) and each of these means differed significantly from the other two (P less than 0.001). However, the number of patients who had a gastric juice volume of more than 25 ml and a pH of less than 2.5 in each of the three groups: gastrozepin, cimetidine and placebo, were 1, 0, and 8, respectively.

The respiratory effects of intravenous indoprofen 400 mg, a highly effective non-steroidal anti-inflammatory analgesic, were compared with those of morphine 10 mg in 10 healthy volunteers. Morphine exhibited its characteristic adverse respiratory depressant properties, Indoprofen, in contrast, did not influence the subjects' breathing pattern.

Thirty mothers undergoing elective Caesarean section received thiopentone 3.5 mg kg-1 and 30 received etomidate 0.3 mg kg-1 for induction of anaesthesia. Subsequent management of anaesthesia was identical in both groups. Maternal to fetal base excess differences and the degree of biochemical correlation between mother and infant were more favourable following etomidate than following thiopentone. The clinical status of the newborn was considered superior with etomidate.

Endotoxins (lipopolysaccharides, LPS) are potent bacterial poisons always present within the intestines in considerable amounts. Several pathophysiological conditions such as hypovolaemia, hypoxia, intestinal ischaemia, burns and radiation lead to a breakdown in the barrier and depending upon the extent of the injury, endotoxins enter the systemic circulation in increasing amounts. Antibiotics do not inactivate the endotoxins which continue to exert their toxic effects leading to nausea, vomiting, diarrhoea, fever, disseminated intravascular coagulation, vascular collapse and organ failure. When nonabsorbable antibiotics are given prior to the insult, systemic endotoxaemia is prevented. Immunotherapy, using anti-lipopolysaccharide IgG, inactivates plasma endotoxins, destroys gram-negative bacteria and opsonises them and may become a major form of therapy. An outline of endotoxin and anti-lipopolysaccharide and its importance to the anaesthetist and intensive care specialist is presented.

Ten healthy adult volunteers inhaled 50% nitrous oxide in oxygen while dental treatment was simulated for a period of 30 min. During this time 15 ml of radio-opaque dye was placed at the back of the tongue. A similar control study was performed 1 week later, the subjects inhaling pure oxygen without nitrous oxide. X-ray examination revealed that two of the 10 volunteers had aspirated dye while breathing nitrous oxide and oxygen, but no aspiration was apparent in the control study.

The effect of intravenous midazolam 0.3 mg/kg on lower oesophageal sphincter (LOS) pressure was studied in 8 healthy volunteers. No effect on LOS pressure was noted. The importance of this finding in relation to the possible danger of gastro-oesophageal reflux and pulmonary aspiration of gastric acid content during induction of general anaesthesia is discussed.

The effect on lower esophageal sphincter (LES) pressure of IV atropine and neostigmine, a drug combination routinely given to antagonize nondepolarizing neuromusclar blockade at the end of a general anesthetic, was studied in 22 patients undergoing cesarean section. Atropine 1.2 mg and neostigmine 2.5 mg IV decreased LES pressure insignificantly by a mean of 0.7 kPa (p less than 0.1). In contrast, atropine 1.2 mg and neostigmine 5 mg increased LES pressure by a mean of 1.4 kPa (p less than 0.001). The latter dosage of this drug combination, therefore, appears preferable in patients presenting for emergency surgery if the integrity of the lower esophageal sphincter is to be maintained during extubation and recovery from general anesthesia.

The effects of physiotherapy and hexaprenaline sulphate administration were studied on 10 patients requiring mechanical ventilation. No significant changes in arterial oxygen tensions were noted, but alveolar pressure fell significantly after treatment, indicating improvement in pulmonary compliance.

We have attempted to update a previous review of the hazards and problems confronting the mother, fetus and anaesthetist at caesarean section. A recent survey of obstetric anaesthesia within the Republic and South West Africa indicates that a significant proportion of anaesthetic services for midwifery are provided by non-specialist practitioners in hospitals outside major population centres. We believe that both mothers and their infants will gain from the careful perusal by their doctors of this review.

The economics and advantages of non-rebreathing (semiclosed) versus rebreathing ('closed') circuit enflurane anaesthesia in spontaneously breathing patients, anaesthetized for ophthalmic procedures usually lasting less than 1 hour, were investigated. An average of 42, 5 ml liquid enflurane was used per hour of anaesthesia with the non-rebreathing apparatus, a figure close to the calcuated approximate enflurane usage for the first hour of anaesthesia (42,0 ml). Approximately half this volume was required for anaesthesia via the vaporizer out of circle (VOC) rebreathing system (19,0 ml/h; P less than 0,001). A further significant decrease resulted with the use of the vaporizer in circle (VIC) system (13,5 ml/h; P less than 0.001), but the surgical conditions provided by the latter were less satisfactory. Actual enflurane utilization with both VOC and VIC was greater than that expected for the first hour of anaesthesia (calculated approximate usage 15,0 and 11,0 ml/h respectively). Enflurane anaesthesia with the vaporizer out of circle is recommended for routine surgical procedures.

Two human squamous carcinomas of the cervix, established by serial passage in nude mice, are described. The response of the tumours to cis-diamminedichloroplatinum (CDDP) was assessed by comparing tumour weights and by histological observations. Tumours treated with CDDP 10 mg/kg/week for 2 weeks regressed significantly and microscopy revealed extensive degeneration. Treatment with CDDP 5 mg/kg/week produced tumour growth retardation and microscopy showed some degenerative changes, however, viable cells, many of which were mitotic, were evident. There was, therefore, a dose-response relationship. The sensitivity of the tumours to CDDP lends support to its use in humans with this malignancy.

Indoprofen (400 mg), a non-opioid, non-steroidal anti-inflammatory drug, was compared on a random, double-blind basis with pethidine (1,5 mg/kg) after elective caesarean section (40 patients) and after orthopaedic surgery (40 patients). The drugs were given intravenously during anaesthesia and provided adequate analgesia for a period of up to 2 hours postoperatively. No significant differences between the two drugs were noted in terms of efficacy and side-effects.

The effects of intravenous hyoscine 0-4 mg and atropine 0-6 mg on lower oesophageal sphincter tone were studied in normal human subjects. Hyoscine and atropine both decreased the lower oesophageal sphincter (L.O.S) pressure by approximately 11 cm H2O (p less than 0-01). There was also an increased incidence of reflux as seen by an indwelling pH electrode in the lower oesophagus. These findings are relevant to the preoperative preparation of patients presenting for emergency obstetrical anaesthesia; since gastro-oesophagus reflux and pulmonary aspiration of acid gastric content continues to be a significant cause of morbidity and mortality.

The concentrations of several essential trace elements in various intravenous fluids commonly used in South Africa were measured. With the exception of 4% human serum albumin and fresh freeze-dried plasma (FDP), intravenous fluids contained minimal amounts of essential trace elements. Although FDP contained significant quantities of zinc, copper, iron and chromium, the common practice of giving patients on total parenteral nutrition 1-2 units per week will not fulfil the recommended daily requirements. Additional trace element supplements should therefore be given intravenously to these patients.

A simple clinical method, allowing quantitive assessment of the effects of chest physiotherapy on patients subjected to I.P.P.V., is presented. The method involves measuring of the "alveolar" pressure using the end-expiratory retard mechanism available on the Bennet MA 1 (volume cycled) ventilator. Using this simple technique three different methods of physiotherapy were shown to significantly lower alveolar pressure, indicating an increase in pulmonary compliance. The inhalation of acetyl cysteine however, appeared to render treatment less effective in this regard.

Three metabolically stable patients, receiving total parenteral nutrition as part of their management for post-surgical intestinal fistulae, were studied over a 16-d period in order to assess the effect of two different energy sources on protein metabolism. Nutrient intake was kept constant throughout except for the energy source: for half the time the patients received glucose alone, for the other half glucose plus fat emulsion (3:1 mixture). Amino acid metabolism, as indicated by rates of leucine turnover, was measured by constant infusion of [1-14C]-leucine for 24 h at the end of each of two 8-d periods. The rates of protein synthesis in the three patients (means of two measurements) were 5.15, 2.45 and 3.8 g/kg/d. No significant difference in nitrogen balance, plasma amino acid concentrations or amino acid kinetic rates could be detected whether energy was supplied as glucose alone or glucose plus fat. The extra expense of supplying energy as fat does not seem justified when total parenteral nutrition is given to stable patients for periods of up to 8 d.