Drugs and sex differences: a review of drugs relating to anaesthesia.
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Biomedical subjects
Publications and source records attributed to A Holdcroft.
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Women frequently use a mixture of analgesics to gain relief from the distress of childbirth and antenatally require information on their effectiveness and side-effects. One such example would be the reported long-term neonatal behavioural changes following systemic opioids such as pethidine. The most frequently reported maternal effects of epidural or spinal analgesia are prolonged symptoms of headache, backache and neurological sequelae. Large retrospective studies of postpartum symptomatology have focused on correlations with regional nerve blockade rather than on other more commonly used analgesics. Post-dural puncture headache is a recognized long-term complication of epidural nerve blockade. However, prospective studies have not confirmed any causal relationship between epidural analgesia and backache and neurological complications are five times more common after childbirth itself than after regional nerve blockade. Postpartum symptomatology describes significant morbidity in the community but its relationship to analgesia in labour is still to be proved.
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Hypothermia during prolonged surgery may be prevented by active and passive warming methods. We have compared randomly two types of occlusive body wraps in groups of 20 patients. One wrap had additional reflective properties which, by reducing radiative in addition to convective and evaporative heat loss, was expected to improve heat conservation. Patients were studied during hepatopancreatobiliary surgery and both groups were similar in characteristics. Skin and core body temperatures increased and core temperature exceeded 37 degrees C in 40% of patients in both groups. This continuous increase in temperature was unexpected and the observed heat gain may have been stimulated endogenously by the type of surgery rather than that supplied externally. Overall, mean hourly heat gain was similar in both groups: 71 (SD 28) kJ h-1 in the reflective group and 67 (33) kJ h-1 in the other group.
Cannabinoids have analgesic and, possibly, anti-inflammatory properties but their clinical use has been restricted by legislation. This is the first United Kingdom report of the controlled use of a standardised pharmaceutical preparation of cannabinoids in capsular form. The therapy was assessed in a patient with familial Mediterranean fever, who presented with chronic relapsing pain and inflammation of gastrointestinal origin. After determining a suitable analgesic dosage, a double-blind placebo-controlled cross-over trial was conducted using 50 mg tetrahydrocannabinol daily in five doses in the active weeks and measuring effects on parameters of inflammation and pain. Although no anti-inflammatory effects of tetrahydrocannabinol were detected during the trial, a highly significant reduction (p < 0.001) in additional analgesic requirements was achieved. Future study designs can now incorporate prescribable forms of cannabinoids but the choice of previous cannabis users only as patients has clinical limitations. Cannabis naive patients would tolerate controlled investigations but may generate medicolegal problems.
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Visceromotor and cardiovascular responses to colonic distension were measured in female rats, anesthetized with halothane in oxygen, in the proestrus, estrus, metestrus and diestrus phases of the estrous cycle. Ten rats were studied in each group and responses were measured at 5-min intervals for 60 min. A mixed model analysis of variance showed that there was no real change in either the visceral or cardiovascular response with time. There was a highly significant difference in visceromotor responses between the phases of the estrous cycle (P < 0.001). During the phase of proestrus the balloon pressure at which a response was triggered was much lower, with a mean value (95% confidence interval) of 18.7 (16.1, 21.8) mmHg, than the other phases with mean values (95% confidence interval) of 31.9 (27.4, 37.2) mmHg for estrus, 28.1 (24.2, 32.8) mmHg for metestrus, and 31.1 (26.7, 36.3) mmHg for diestrus. The mean arterial blood pressure increased in all groups (range 3.2, 5.4%) as a response to the stimulus, but there was no associated heart rate variability and no significant differences in cardiovascular changes between the groups (P = 0.6). The visceromotor responses measured during the phase of proestrus occurred at a significantly lower threshold than in the other phases of estrous.
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Prospective multidisciplinary audit from both hospital and community has identified neurological complications persisting for more than 6 weeks in association with pregnancy and delivery. They occurred at a frequency of 1 in 2530 deliveries in the North West Thames Region. Extradural analgesia was considered contributory to a neurological disorder in one of 13,007 patients. The woman had prolonged paraesthesiae along a nerve root. The types of sensory, motor and sympathetic neurological problems presented ranged from transient problems to more serious disorders resulting in death in one case. Seven of 19 patients had a continuing neurological disability for more than 1 yr. Although obstetrics may be associated with lumbar and sacral neurological disorders, problems occurred with the same frequency in the upper as in the lower half of the body. Significant morbidity is not being recognized in hospitals where women are being delivered and it is within the community that these disorders are recognized. This has implications for training, audit and risk assessment.
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A 20-year-old primiparous woman, with a history of type 1 hereditary angioneurotic oedema, presented for induction of labour. She was hirsute, obese and presented technical difficulties for both general and epidural/spinal anaesthesia. Her management included prophylactic C1 esterase inhibitors and epidural analgesia for pain relief. A spontaneous vaginal delivery was achieved and no adverse complications occurred. Five days after delivery she had abdominal pain which was investigated and resolved spontaneously. The management of this condition is discussed.
The objective of the study was to investigate the sociodemographic and psychological factors which are associated with choice or refusal of regional anesthesia for lower segment Caesarean section. A semi-structured questionnaire was administered preoperatively to consecutive women presenting for elective operation at two hospital sites in the same health authority. The questionnaires were administered to 39 pregnant women by two anesthetists, one at each site. Sociodemographic and past and present obstetric and anesthetic details were obtained. The Hospital Anxiety and Depression scale and the FEAR questionnaire were used with an additional visual analog scale to assess fearfulness associated with the proposed operation. A 'panic checklist' of ten items was also constructed to identify procedures associated with feelings of panic. Ten women requested general anesthesia. These women had a similar level of anxiety to the others, but were significantly more depressed, had had more pregnancies overall and more without live babies. There were also more aspects of the procedure at which they thought they might panic. Women who have suffered the loss of a conception with its associated grief and often obstetric intervention are more reluctant to be conscious during an operative delivery for a subsequent baby. Preventive measures should be considered at the time of fetal loss to avoid this. However, preoperatively a simple visual analog scale for fearfulness would identify these women so that any unresolved fears could receive full psychological assessment.
Changes in aortic blood flow were measured in rabbits with both normal and surfactant depleted lungs in order to elucidate the effect of different modes of ventilation on the circulation while optimizing arterial oxygenation (PaO2). Conventional mechanical ventilation (CMV), reversed inspiratory to expiratory ratio of CMV (IRV), high frequency positive pressure ventilation (HFV), and high frequency oscillation (HFO) were used. Normocapnia was maintained throughout during different modes of ventilation. In normal lungs the aortic blood flow during IRV was significantly lower with similar levels of PaCO2 compared with CMV, HFV, and HFO. In lavaged lungs, without positive end-expiratory pressure (PEEP), the aortic blood flow during CMV was significantly higher than with other modes of ventilation. When 10 cm H2O of PEEP was applied, the PaO2 increased maximally to normal values at all modes of ventilation, but the aortic blood flow was significantly reduced (P < 0.05) during CMV and IRV compared to HFV and HFO. The aortic blood flows at 5 cm H2O of PEEP were very similar during CMV, HFV, and HFO but significantly reduced during IRV. This study showed that at an optimal arterial oxygenation with higher PEEP levels, maintenance of aortic blood flow was maximal during HFV and HFO.
We compared high frequency ventilation (HFV) to conventional mechanical ventilation (CMV) under normoxic and normocapnic condition in surfactant depleted rabbits with bilateral pneumothoraces. We hypothesized that lower airway pressures would be required with HFV under these conditions. We applied CMV and HFV in 8 anaesthetized rabbits with a prototype ventilator at frequencies of 30, 100, 200, and 300 cycles/min. A positive end-expiratory pressure (PEEP) just below the pressure sufficient to open the air leak from the pneumothoraces was applied at all frequencies. Airway pressures, gas exchange, heart rate, and mean arterial pressure were recorded. Peak airway pressure decreased significantly from 2.50 to 2.10 kPa when the frequency of ventilation was increased from 30 to 300 cycles/min. There were no significant changes in mean airway pressure, PaO2, arterial pH, heart rate, and mean arterial pressure when HFV was compared to CMV. In conclusion, during HFV peak airway pressures measured at the mouth were decreased. Our ability to maintain adequate gas exchange in the face of ongoing pulmonary air leaks may reflect lower alveolar pressures.
We have studied in anaesthetized dogs the effects of alfentanil, fentanyl, pethidine and lignocaine administered intrathecally on nociceptive responses evoked by low and high frequency supramaximal electrical stimulation of the tibial and radial nerves. Doses were selected to abolish both A delta and C fibre somatosympathetic reflexes to single stimuli. Pethidine and lignocaine eliminated reflex pressor and heart rate responses to repeated single stimuli and almost completely abolished responses to train stimulation. The pressor response to single stimuli was abolished by fentanyl and reduced by alfentanil, but these drugs did not reduce significantly this response to train stimulation, suggesting a stimulation rate-dependent effect. Of the opioids, only pethidine had an effect comparable to that of lignocaine. The absence of sympathetic block and antagonism by naloxone imply a lack of significant local anaesthetic effect. We suggest that the greater analgesic efficacy of pethidine is a result of endogenous synergism between a minor local anaesthetic and a major opioid effect.