PubMed Health⌕ Search

Biomedical subjects

T G Short

Publications and source records attributed to T G Short.

52 records · Page 3Linked to original sources
PubMed1993

Pharmacokinetic model-controlled infusion of midazolam. A prospective evaluation during general anaesthesia.

The accuracy of a computer-controlled infusion of midazolam, based on previously published pharmacokinetic parameters, was tested prospectively in 12 adult female patients undergoing general anaesthesia. Anaesthesia consisted of an initial bolus followed by an exponentially decreasing infusion of midazolam given according to body weight, fentanyl, nitrous oxide and vecuronium. Venous blood samples were taken at 15 min-intervals throughout the procedures and for 1-2 h postoperatively. The bias of the model was -5.1% (95% CI -11.3 to 1.2%) and precision 24.8% (95% CI 20.9 to 28.6%). Least squares regression analysis decreased the bias to -2.8% but did not alter precision. Retrospective fitting of an alternative set of published parameters for midazolam resulted in significant deterioration of the model. The precision was similar to that found in past studies of intravenous anaesthetic agents. Further improvement in the accuracy of midazolam infusion awaits improved understanding of the causes of pharmacokinetic variability.

Adult↗
PubMed1993

The influence of the H1 and H2 receptor antagonists, terfenadine and ranitidine on the hypotensive and gastric pH effects of the histamine releasing drugs, morphine and tubocurarine.

Morphine and tubocurarine may release histamine by direct mast cell degranulation which may result in systemic effects such as cutaneous flushing, local wheal and flare formation and hypotension. This randomised, double-blind study examined whether preoperative combined oral terfenadine (60 mg) and ranitidine (150 mg) attenuates the reduction in blood pressure and cutaneous flushing after the administration of tubocurarine and morphine in 60 patients undergoing elective gynaecological surgery. In addition, investigation was made of whether tubocurarine and morphine cause a significant decrease in gastric pH in comparison to the nonhistamine-releasing agents fentanyl and vecuronium. Patients were randomly assigned to one of three groups receiving either pre-operative terfenadine and ranitidine and intra-operative tubocurarine and morphine (group A); pre-operative placebo and intra-operative tubocurarine and morphine (group B); pre-operative placebo and intra-operative fentanyl and vecuronium (group C). Compared to group B, group A had less hypotension and tachycardia but no significant decrease in cutaneous flushing immediately following morphine and tubocurarine (p > 0.05). There were no significant differences in haemodynamic changes between the groups A and C. In those patients not pretreated with terfenadine and ranitidine (groups B and C), gastric pH decreased between 5 and 10 min following bolus administration of morphine and tubocurarine (group B), whereas patients receiving fentanyl and vecuronium (group C) had an increase in gastric pH. This suggests that histamine release following administration of morphine and tubocurarine is sufficient to increase gastric acidity.(ABSTRACT TRUNCATED AT 250 WORDS)

Double-Blind Method↗
PubMed1992

Systemic absorption of glycine irrigation solution during endometrial ablation by transcervical endometrial resection.

OBJECTIVE: To study systemic absorption of glycine irrigation solution and its consequences during transcervical endometrial resection (TCER). DESIGN, SETTING, PATIENTS: A prospective study of 20 consecutive female patients who underwent elective TCER in a teaching hospital. METHOD: During the operation, patients were monitored with electrocardiography, automated oscillotonometry, pulse oximetry, capnography and a central venous pressure recorder. Plasma sodium and potassium levels were measured at 15-minute intervals. Blood haemoglobin concentration, serum osmolality, and plasma sodium, potassium and glycine concentrations were measured before and after surgery. RESULTS: Plasma glycine concentration increased in all patients after TCER. The highest concentration recorded was 5575 mumol/L. The increase correlated only with the maximum intraoperative decrease in plasma sodium, which was 7 mmol/L in two patients whose plasma glycine level increased by 3001 mumol/L and 5335 mumol/L. CONCLUSION: Systemic absorption of glycine irrigation solution occurred in all patients during TCER. Serial measurement of plasma sodium was necessary to detect this complication. A decrease in plasma sodium level by 7 mmol/L or more during surgery would indicate fluid absorption that could cause severe hyperglycinaemia and other potential complications.

Absorption↗
PubMed1992

Hypnotic and anaesthetic interactions between midazolam, propofol and alfentanil.

We have examined interactions between midazolam, propofol and alfentanil using two end-points of light sedation (hypnosis) and anaesthesia. Quantal dose-response curves were determined in 400 female patients for the drugs individually and in combination. At the hypnotic end-point, interactions were analysed by fitting the data to a mathematical model where the response depended on the doses of the three drugs with additional terms included to describe non-additive interactions of the various combinations of the three drugs. There were significant interactions for hypnosis; the decrease in expected ED50 for the various combinations were: midazolam-propofol = 37%, midazolam-alfentanil = 46%, propofol-alfentanil = 20%, midazolam-propofol-alfentanil = 42%. Whilst all responses to the two-drug combinations were synergistic, the three-drug combination led to a response that was less than that expected from the effects of the individual agents and their two drug interactions. For anaesthesia, dose-related effects could not be demonstrated for midazolam or alfentanil when used alone. The decrease in ED50 of propofol in the presence of the other compounds was propofol-midazolam = 52%, propofol-alfentanil = 73%, propofol-midazolam-alfentanil = 82%. When comparing the different combinations, the responses varied markedly at each end-point assessed and could not be predicted from the responses of the individual agents.

Adolescent↗
PubMed1992

A clinical evaluation of the Hemocue haemoglobinometer using capillary, venous and arterial samples.

The 'Hemocue' device for rapid estimation of haemoglobin concentration was evaluated in a clinical setting. Repeatable accuracy of capillary, venous and arterial samples was examined and then compared with standard laboratory venous haemoglobin estimates using a 'Coulter JT' analyser in 42 patients. The mean values for haemoglobin (g/l) and coefficient of variation were capillary 108.2 (8.0); venous 104.9 (2.2); arterial 105.9 (2.0); and laboratory venous 104.6 (1.3). Although the mean haemoglobin values were similar, capillary samples were significantly less repeatable than venous or arterial samples (Pitman test, P < 0.001). Comparison of variance between the laboratory sample and each sampling technique demonstrated that capillary samples were significantly more variable than venous or arterial samples. Peripheral skin temperature did not influence the accuracy of capillary samples. Hemocue estimations of venous samples were found to be as accurate as laboratory estimations. The lack of repeatable accuracy of capillary estimations was sufficiently large that their use cannot be recommended in clinical practice.

Adolescent↗
PubMed1991

Hypnotic and anaesthetic action of thiopentone and midazolam alone and in combination.

This study examined the interaction between i.v. administered midazolam and thiopentone on the loss of response to verbal command ("hypnosis") and the loss of response to transcutaneous electrical stimulation of the ulnar nerve ("anaesthesia") in patients presenting for minor elective surgery. Dose-response curves for thiopentone and midazolam individually and in combination were determined using the two end-points in 300 unpremedicated patients. For hypnosis a highly significant (P less than 0.001) supra-addictive (synergistic) interaction was found, the combination having 1.8 times the expected potency of the individual agents. Although midazolam failed to produce anaesthesia in the dose range used, the dose of thiopentone required to produce anaesthesia was reduced by 50% in the presence of midazolam. The mechanism of interaction and the potential role of benzodiazepine-barbiturate combinations are discussed and the observed synergistic anaesthesia interaction is used to explain the potentially dangerous combination of benzodiazepines with other potent CNS depressants such as barbiturates and alcohol.

Adult↗
PubMed1991

Propofol and midazolam act synergistically in combination.

We have studied interactions between i.v. propofol and midazolam for induction of anaesthesia in 200 unpremedicated female patients undergoing elective gynaecological surgery. Using end-points of "hypnosis" (loss of response to verbal command) and "anaesthesia" (loss of response to a 5-s transcutaneous tetanic stimulus), we determined dose-response curves for propofol and midazolam alone and in combination. For hypnosis, synergistic interaction was found (P less than 0.01), the combination having 1.44 times the potency of the individual agents. Although midazolam failed to produce anaesthesia in the dose range used, the dose of propofol required to produce anaesthesia was reduced by 52% in the presence of midazolam (P less than 0.01). The reduction in arterial pressure at induction was the same for the combination as for the individual agents. The cause of the synergism was not clear, but may have been interaction at CNS GABAA receptors.

Adolescent↗
PubMed1991

Acute tolerance from benzodiazepine night sedation.

The hypothesis that benzodiazepine night sedation causes acute tolerance to benzodiazepine sedation given the following morning was examined in six volunteers in a double blind, randomised, crossover study. Before each of three study days, subjects received midazolam 15 mg or flunitrazepam 2 mg or placebo as oral night sedation. They were then given intravenous midazolam 5 mg the following morning and the resulting sedative effects examined, using an observers sedation scale and a psychomotor test battery (critical flicker fusion frequency, digit-symbol substitution, reflex time, tapping test and a visual analogue sedation scale). Although a consistent pattern emerged with the greatest degree of sedation following the placebo night sedation and the least degree of sedation following the midazolam, with flunitrazepam intermediate, no statistically significant differences were present between the three treatment groups. The results indicate that single use of benzodiazepine night sedation is not an important influence on benzodiazepine requirements for intravenous sedation.

Adult↗
PubMed1990

Statistical modeling of the effects of drug combinations.

A method is described for identifying and quantitating departures from additivity (i.e., synergism and antagonism) when drugs having like effects are given in combination. It is applicable for both graded and quantal (e.g., after probit or logit transformation) responses. Log(dose)-response curves of both drugs should be linear but need not be parallel. The following model is fitted to dose-response data for both the individual drugs and combinations of drugs: Y = beta 0 + beta 1 log(A + P.B + beta 4(A.P.B)1/2) where Y is the response, A is the amount of drug A, B is the amount of drug B, and P is a relative potency of the drugs given by log(P) = beta 2 + beta 3 log(B'), in which B' is the solution to B' - B - A/P = 0. If log(dose)-response curves of the two drugs are parallel, beta 3 = 0, and P becomes a constant parameter to be estimated. A positive value of beta 4 corresponds to synergism and a negative value to antagonism. Hypothesis tests may be carried out to determine whether beta 4 is significantly different from zero.

Dose-Response Relationship, Drug↗
PubMed1989

Patient-administered anxiolysis--a pilot study.

The feasibility of self-premedication with intravenous diazepam was examined in an open study of 50 preoperative patients. Using a Bard 'Harvard PCA' patient-controlled analgesia system, patients were instructed to deliver the drug in a dose sufficient to remove their anxiety for the scheduled surgical procedure. Aliquots of diazepam 2 mg were delivered on demand up to a total dose of 20 mg over a 30 minute premedication period. The mean dose administered was 8.1 mg (range 0-16 mg) producing a highly significant reduction in both patient- and anaesthetist-assessed anxiety rating. Neither the patient's sex nor the nature of the surgical procedure influenced the dose administered. Although poor, the best predictor of self-premedicating dose was patient's own preoperative anxiety rating with the anaesthetist's assessment of patient anxiety not correlating with the dose administered. No patient was considered excessively sedated by the premedication. Patient-administered anxiolysis is suggested as a useful research tool in the examination of anxiety and of value in premedicating patients with high preoperative anxiety levels.

Adult↗
PubMed1989

Double-blind comparison of midazolam and temazepam as oral premedicants for outpatient anaesthesia.

Oral premedication with midazolam 7.5 mg was compared with temazepam 20 mg in a double-blind study of sixty patients undergoing day-stay urological surgery. One hour following ingestion similar degrees of anxiolysis and sedation were reported by patients for both compounds. However, midazolam was observed by anaesthetists to produce the greater anxiolytic effect and was given the better overall assessment. Midazolam produced significantly greater amnesia both at the time of induction and 30 minutes postoperatively. At the time of discharge four hours postoperatively no significant difference could be observed in psychomotor performance or subjective sedation although on the evening of surgery the temazepam group had a greater incidence of sleepiness and an earlier time to retiring. Although the differences were small, the residual post-discharge effects of temazepam lead us to conclude that midazolam 7.5 mg is the more suitable premedicant for outpatient use.

Adult↗
PubMed1989

Residual psychomotor effects following reversal of midazolam sedation with flumazenil.

The ability of flumazenil to reverse the effects of midazolam sedation was examined in a randomised, crossover, placebo controlled study in six male volunteers. Subjects received intravenous injections of either (a) midazolam 10 mg followed 10 minutes later by flumazenil 1.0 mg or (b) midazolam 10 mg followed after 10 minutes by flumazenil 4 mg or (c) placebo followed after 10 minutes by placebo. Post reversal drug effects were examined using a psychomotor battery (critical flicker fusion, digit symbol substitution, tapping test, ball-bearing test, number recall, reflex time) and linear analogue mood scales. It was found that a residual psychomotor deficit was present following flumazenil and that this persisted for up to 125 minutes after the 1.0 mg dose and 65 minutes following 4 mg. A small deterioration in performance was apparent after initial reversal with 1.0 mg, the peak deterioration occurring at 35 minutes.

Adult↗
PubMed1988

Total intravenous anaesthesia using propofol infusion--50 consecutive cases.

Fifty consecutive patients in the authors' practice were anaesthetised with a total intravenous technique using propofol infusion, fentanyl, vecuronium and oxygen in air. Patients were predominantly elderly and undergoing major upper gastrointestinal surgery for a mean duration of 133 minutes (range 20 minutes to 7 hours). Twenty-one patients had significant concomitant medical illness. Propofol was found to give a rapid, smooth induction with wide variation in dose requirement (0.5 to 2.9 mg/kg). There was a mean systolic blood pressure fall of 27% from preoperative values, greatest in elderly patients. Depth of anaesthesia was readily adjusted by alteration in infusion rate according to standard clinical criteria. The dose of propofol required for maintenance was highly variable (range 2-15 mg/kg/hr in the first hour). Three patients reported dreaming and two of these had shown signs of light anaesthesia. Recovery was rapid, with few side-effects, and a mean time to open eyes on command of 8.5 minutes from the end of infusion. Propofol was considered to be a satisfactory intravenous agent for the induction and maintenance of anaesthesia in the majority of patients studied. The most significant problem was hypotension following the induction dose.

Adolescent↗