Reduction of gastric acid secretion. The efficacy of pre-anaesthetic oral cimetidine in children.

Cimetidine 10 mg/kg orally was given at varying times from 60 to 240 minutes pre-operatively to 100 healthy children between the ages of 6 months and 14 years. Cimetidine proved to be most effective when given between 120 and 180 minutes before the induction of anaesthesia. All patients in this group had a gastric pH of more than 2.5 and the mean volume aspirated was also significantly lower than that in the control group. The average peak blood concentration after 10 mg/kg oral cimetidine in four healthy children was 3.25 micrograms/ml (range 1.20-4.80) and occurred 75 minutes after administration (range 60-120 minutes). In these patients the mean (SD) half-life of cimetidine was 138 (18) minutes. The reduction of gastric juice volume and acidity produced by 10 mg/kg oral cimetidine given 120-180 minutes prior to induction of anaesthesia has important clinical implications.

Metabolic events in acutely damaged brain and the effect of dexamethasone in guinea pigs.

The effect on 210 guinea pigs of a special clinically used compound on substantial brain damage was evaluated. Cerebral metabolism was well preserved in small laboratory animals after blunt head injury by the administration of dexamethasone intraperitoneally. The high doses used were similar to those employed for cerebral contusion of the brain in patients. The concentrations of glucose, lactate, pyruvate and ATP were maintained better in cerebral tissue by pre- and post-traumatic use of dexamethasone than by treatment with a placebo. Analysis of the blood showed no such correlation indicating that the effect of dexamethasone was due to a local effect on the central nervous system, rather than a systemic effect. With rapid freezing, brain tissue from guinea pigs exposed to high doses of systemic dexamethasone was found to contain less lactate and pyruvate compared with untreated controls. ATP was preserved at the original non-traumatic level. This was not accompanied by an increased rate of glycolysis since the glucose level in the damaged brain was not affected by the glucocorticoid.

Therapeutic effect of dexamethasone in experimental head injuries.

Experimental head injuries, which are easily reproducible in animal studies with guinea pigs, result in a significant increase of secondary serum enzymes. Malate dehydrogenase (MDH), fructose 1,6-diphosphate-aldolase and lactate dehydrogenase (LDH), together with the isoenzymes 1 and 2, are found especially in brain in large amounts. These enzymes act as 'tracer substances' of cerebral tissue and show significantly increased serum activities in cases where acute substantial damage to the brain associated with severe alterations of the blood-brain barrier is found. In the absence of shock, hypoxia and additional bodily injuries the loss of brain tissue has to be considered the only source of enzyme outflow. The early treatment of injured animals with high doses of dexamethasone results in a protective and stabilizing effect, preventing the extrusion of enzymes from the traumatically involved brain cells. Thus by observing the characteristic serum enzyme activities of treated and untreated injured animals a therapeutic effect of dexamethasone can be demonstrated within a relatively short time.

The role of shock in the pathogenesis of fat embolism after trauma.

Experimental studies and pathological investigations indicate that intrusion of fat into the circulation is common after trauma. This may not have any effect unless frank hypovolaemia supervenes upon changes in the blood vessels, manifested by a deficient vasomotility in shock. After fat embolism disseminated intravascular coagulopathy may occur as a consequence of the haematological changes and disturbances of capillaries. The morphological appearance of massive post-traumatic fat embolism evolves from the compensatory effect of accumulated synergistic factors that primarily induced the changes. From this point of view fat embolism should be recognized in the additional important role of an epiphenomenon of post-traumatic shock.

Biochemical and biophysical changes in guinea pigs after acute head injury.

Animal experiments were set up mainly to derive additional diagnostic data from the study of biochemical changes after acute head injury. In standardized experiments guinea pigs were subjected in groups of 20 to three identical head injuries, each of either 1.0 J or 1.5 J intensity. The trauma was likely to result in a concussion or contusion syndrome similar to that found in man; 40 animals served as controls. During the 60 min after injury observation and measurement of body functions did not reveal signs of a shock-like condition or hypoxaemia in the traumatized animals compared with control animals. Superficial anaesthesia probably did not influence the findings. Temperature and respiration were altered significantly in all the animals receiving head injuries. Blood gas analysis showed a decrease of standard bicarbonate only after the 1.5 J injury but even though hypoxaemia was not present 2,3-diphosphoglycerate values and P50 increased, compared with the control animals. The fall of plasma lipid concentrations reported probably had to be seen as a sympathomimetic effect of the minor (1.0 J) trauma. Of special significance was the increased activity of malate dehydrogenase and aldolase, found only in the blood of severely traumatized animals, as this could serve as an early diagnostic aid for evaluating head injuries.