Anaphylaxis following administration of papaveretum. Case report: Implication of IgE antibodies that react with morphine and codeine, and identification of an allergenic determinant.

IgE antibodies that reacted with morphine and codeine were detected in the serum of a subject who experienced a life-threatening anaphylactic reaction following the administration of Omnopon-Scopolamine (papaveretum-hyoscine). Hapten inhibition studies with morphine and a number of structurally-related analogues revealed that morphine and codeine were the most potent inhibitors of IgE binding to a morphine-solid phase. Nalorphine, meperidine, and methadone were also good inhibitors of IgE binding, but naltrexone, buprenorphine, and fentanyl proved to be poor inhibitors. From a detailed examination of structure-activity relationships, the authors conclude that the important structural features of the morphine allergenic (that is, IgE binding) determinant comprises the cyclohexenyl ring with a hydroxyl group at C-6 and, most important of all, a methyl substituent attached to the N atom. The authors' findings suggest that morphine analogues administered to such a patient may provoke clinical anaphylaxis. Hyoscine reacted weakly with IgE antibodies in the subject's serum, but this was thought to be due to weak cross-reaction between this compound and morphine.

Time course of the cerebral circulatory response to metabolic depression.

Baboons anesthetized with halothane and N2O/O2 were given an intravenous steroid anesthetic (Althesin; Glaxo Laboratories Ltd., U.K.). The drug bolus was labeled with 99mTc, and the time from central venous injection to peak radioactivity in the brain was designated drug brain arrival (DBA-peak). The electroencephalogram slowed 1.2 +/- 0.9 s after DBA-peak (P greater than 0.2), and approximately 2 s after DBA-peak, internal carotid blood flow (ICarBF) decreased and calculated internal carotid vascular resistance (ICarVR) rose. During this 2-s delay in the cerebrovascular response to the arrival of a cerebral metabolic depressant in the brain, the decrease in mean cortical Pco2 was calculated to be less than 0.26 mmHg from cortical CO2 solubility, and less than 0.32 mmHg from cortical CO2 diffusivity, which indicated that mean cortical Pco2 changes do not control cerebral blood flow (CBF). The unaltered time course of the changes in EEG, ICarBF, and ICarVR after acute cervical sympathectomy and alpha-adrenergic receptor blockade excluded the involvement of the sympathetic nervous system in the vasoconstrictor response. Intracarotid Althesin showed that the cerebral vasoconstriction was not a direct effect of the drug. The postulated link between the effects of Althesin on CBF and cerebral metabolism remains to be elucidated but is probably indirect, involving the brainstem.

Distribution of pentazocine in blood and brain of the baboon following intravenous injection.

1 In the baboon the blood levels of pentazocine between 1 and 60 min after intravenous injection of 0.5 mg/kg were measured by a gas chromatographic technique. From cerebral arteriovenous differences it was shown that the peak of the brain concentration occurred within 15 min and probably within 10 min of intravenous injection. At the time of peak concentration about 10% of the injected dose was in the brain, while the corresponding value at 60 min was 2%.2 The concentration of pentazocine in the brain was an order of magnitude greater than the concentration in cerebral venous blood both at 5 min and 60 min after injection. No major brain interregional differences were demonstrated. Cerebrospinal fluid from the cisterna magna did not yield values from which the cerebral concentration of pentazocine could be predicted.

Cerebral circulatory and metabolic effects of hypotension produced by deep halothane anaesthesia.

Hypotension to a mean blood pressure of 33 mmHg for periods of 70 to 187 minutes was induced by increasing the inspired halothane concentration in 11 baboons which were already anaesthetized with 0·5% halothane, nitrous oxide, and oxygen. During hypotension, cerebral blood flow, measured by Xenon clearance and by a carotid electromagnetic flowmeter, decreased by more than half, and sagittal sinus oxygen saturation was 46%. Cerebral oxygen uptake fell from 5·15 to 3·56 ml./100 g/min at this deeper level of halothane anaesthesia. Cerebral hyperaemia developed after hypotension in those animals which regained a mean blood pressure greater than 70 mmHg. Acidbase measurements on CSF from the cisterna magna revealed no metabolic acidosis during or after hypotension. In all four animals with intact autoregulation before hypotension, this was absent or impaired afterwards.

Measurement of extradural pressure and its relationship to other intracranial pressures. An experimental and clinical study.

Disadvantages associated with the use of ventricular catheters for the prolonged measurement of intracranial pressure have resulted in the search for an alternative technique. Measurement of pressure from the extradural space is one such possibility, but widespread acceptance of this procedure has been limited by the technical difficulties associated with this measurement and lack of information on the relationship between cerebrospinal fluid and extradural pressures. A study to investigate this relationship and to develop a simple and effective technique for measuring extradural pressure is described.