Biomedical subjects
M Keeri-Szanto
Publications and source records attributed to M Keeri-Szanto.
Drugs or drums: what relieves postoperative pain?
The cybernetic model of analgesia is a simple servo-loop: altered sensory input--complaints--medication--temporary restoration of acceptable processing of the sensory input--return of altered sensations. Under ordinary clinical circumstances the functioning of this mechanism is masked by "noise" generated by the interaction of several persons who provide the medication and time factors prolonging the interval between the onset of complaints and the action of the medication. Demand analgesia (DA) has been designed to provide prompt pain relief under the patient's direct control. The technique turned out to be useful also for the investigation of acute pain's course. The present protocol was designed to study the precision with which patients respond to minute changes in the level of a narcotic (hydromorphone) at the target site: this was achieved by varying in a double-blind fashion the amount of narcotic delivered in response to triggering the apparatus and noting how the patient adapts the dosing interval in response to the imposed changes. Thirty-four patients were studied following extensive surgery. Observation times ranged from 16 to 75 h (median 45 h) during which 89 dose changes were initiated. While the majority of subjects adapted successfully to up to 4-fold variations in drug delivery, a sizeable minority (7/34) triggered the apparatus in response to some clue other than the amount of drug received. These non-drug responders seem to correspond to the "placebo reactors" of other therapeutic settings. Our calculations allowed the estimation of how large was the contribution of drug action and non-drug action to the overall therapeutic effect. In the drug-responsive group, the mean contribution of drug action was 78%, while among the non-drug responders this amounted to only 40%. The difference between these two figures is statistically significant (P less than 0.02), at the same time it also reveals important contributions of non-drug factors in drug responders and vice versa. Whether a subject behaves as a placebo reactor or not might depend on the circumstances rather than on innate mechanisms.
Clinical studies in children.
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Asymptomatic diaphragmatic defect--a post-operative problem.
A three-hour operation on the maxilla of a woman with an unrecognized large left diaphragmatic defect using narcotic-supplemented nitrous oxide anaesthesia resulted in near-complete compression of her left lung. The condition remained asymptomatic until post-operative shivering increased the patient's metabolic requirements, leading to signs of air hunger. Aspiration of large amounts of gas from the stomach promptly relieved all symptoms in spite of significant residual X-ray findings. It is important to keep in mind that the early post-operative period is usually one of intense metabolic activity rather than of rest. Patients who are unlikely to cope with such demand should be identified pre-operatively and supported prophylactically by ventilatory assistance, ample supply of metabolic substrates and judicious sedation.
Circulatory monitoring using a carbon dioxide analyzer during planned hypotension: a clinical note.
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Supplementation of general anaesthesia with narcotic analgesics.
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The reduction of coma time in lipophilic drug overdose using castor oil.
A clinical trial of castor oil in overdoses of lipophilic drugs gave a strong clinical impression that it was effective in speeding up recovery. Therefore, animal experiments were undertaken to confirm that castor oil acts as a ligand in Ethchlorvynol poisoning and that its use reduces coma time. Serial serum levels of Ethchlorvynol were obtained from dogs given Ethchlorvynol 150 mg/kg alone, and the same dose dissolved in castor oil 15 ml/kg in a crossover fashion. The result was a reduction of peak serum levels and of the half-life of the drug when the castor oil solution was used. In order to mimic the clinical situation more closely, a further crossover study was undertaken using Ethchlorvynol 300 mg/kg alone and the same dose followed by castor oil 15 ml/kg repeated q12h. This showed no delay in reaching peak serum concentration and no reduction of peak levels. However, it did show a 31 per cent reduction in the half-life of the drug. This change is statistically significant, and supports the continued use of castor oil in lipophilic drug overdose.
Papaveretum for anaesthesia and its comparison with morphine. Anaesthetic time/dose curves VIII.
Intravenous papaveretum was used for the induction and supplementation of nitrous oxide-relaxant anaesthesia in 32 subjects undergoing major surgical operations. An anaesthetic time/dose curve was constructed from the size and timing of successive narcotic increments received by each patient and from these the loading and maintenance requirements of the group were determined. Compared with a similar series in which plain morphine was employed in the same fashion, the morphine content of papaveretum accounted for only 82 per cent of the observed anaesthetic activity. Since the remaining 18 per cent was provided by more readily inactivated alkaloids, papaveretum's therapeutic half-life was only 58 per cent (3.61 hr) of morphine (6.18 hr). All the statements outlined above proved to be statistically significant to various degrees. The advantages of a shorter acting morphine-like compound in anaesthesia are discussed.
Anaesthesia time/dose curves IX: the use of hydromorphone in surgical anaesthesia and postoperative pain relief in comparison to morphine.
Seventy unselected subjects were anaesthetized for major surgical operations with intravenous hydromorphone, nitrous oxide and muscle relaxants as required. The results were compared with earlier observations made with morphine under similar conditions on 44 other subjects from the same hospital population. Hydromorphone was found to be 8.5 times as potent as morphine in terms of the median surgical loading dose, and its median therapeutic half-life was 4.07 hours against morphine's 5.28 hours. It proved to be superior to morphine in its greater consistency of action. The mid-90 per cent variance of its loading dose was 30% less and the same variance of its therapeutic half-life was 65% less than that of morphine. All the differences were statistically significant or highly significant. Observations concerning the fraction of the surgical loading dose of hydromorphone required by the patients to prevent post-operative discomfort also revealed great consistency. This is taken to indicate that psychological factors play only a subordinate role in modulating the intensity of postoperative pain.