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Biomedical subjects

G L Fraser

Publications and source records attributed to G L Fraser.

At least 37 records · Page 2Linked to original sources

Movement disorders associated with withdrawal from high-dose intravenous haloperidol therapy in delirious ICU patients.

Intravenous haloperidol is recommended as the drug of choice to treat delirium in ICU patients. Movement disorders and other adverse events commonly occur with oral haloperidol use but are rarely seen with IV haloperidol use, and withdrawal symptoms have not been reported with short-term ICU use. We describe self-limited dyskinesia during withdrawal of high-dose continuous IV haloperidol therapy in five ICU patients.

Adult↗

Changing physician behavior in ordering digoxin assays.

OBJECTIVE: To assess the ability to modify physicians' use of serum digoxin assays in a sustained fashion through (1) an educational intervention by a clinical pharmacist, and (2) changes in the computerized medical information system. DESIGN: A before/after methodology was used to compare test use by hospital staff physicians in two phases. Phase 1 was an educational intervention conducted by a clinical pharmacist with an 8-month follow-up. Phase 2 was a medical information system intervention with a 12-month follow-up. PATIENTS: Adult inpatients from July 1990 through December 1993 who received either digoxin therapy or at least one serum digoxin assay. MAIN OUTCOME MEASURE: Digoxin assays per patient day while receiving digoxin (assays/digoxin day), in-hospital mortality, and length of stay were compared before and after implementation of the interventions. RESULTS: A total of 9468 patients received a digoxin and/or serum digoxin assay. Baseline use of serum digoxin assays was 0.178 assays/digoxin day. Following phase 1, the educational intervention, use declined 20.2% to 0.142 assays/digoxin day (p < 0.03). After phase 2, the implementation of changes in the medical information system, digoxin assay use was maintained at 16.3% less than that at baseline (p < 0.03). Patient mortality was unaffected. CONCLUSIONS: A low-intensity educational intervention by a clinical pharmacist supplemented by medical information system modification resulted in an important decrease in the use of digoxin assays. The change in physician behavior was sustained for more than 18 months. The model presented is not labor intensive, does not require continuous maintenance by healthcare personnel for a sustained effect, and may be widely applicable to healthcare providers.

Aged↗

kappa-Opioid receptor recognition sites are not modulated by local anaesthetics.

Local anaesthetics and opioid drugs function synergistically to provide analgesia. In the present study, the nature of this synergy has been investigated using in vitro radioligand binding to determine whether the local anaesthetics bupivacaine and tetracaine modulate the binding of two kappa-opioid receptor ligands, [3H]U-69593 (5-alpha,7-alpha,8-beta-(-)-N-methyl-N[7-(1-pyrrolodinyl)-1-oxa spiro(4,5)dec-8-yl]-benzene acetamide) and [3H](-)-EKC (ethylketocyclazocine). [3H]U-69593 bound with a KD of 0.88 nM and a Bmax of 2.39 +/- 0.22 fmol/mg wet weight in guinea pig cerebellar membranes. The binding was inhibited by bremazocine and morphine with Hill slopes near unity and pI50 values of 9.96 and 6.84-6.86, respectively. [3H]U-69593 binding was inhibited by Gpp(NH)p (5'-guanylyl imidodiphosphate) and NaCl, consistent with an agonist action of the compound. The binding characteristics of the ligand were not changed by bupivacaine or tetracaine. [3H](-)-EKC bound with KD values of 0.55 and 0.97 nM and Bmax values of 4.22 and 0.99 fmol/mg wet weight in guinea pig cerebellar membranes and rat spinal cords, respectively. In the rat spinal cord, [3H](-)-EKC appeared to act as an agonist/antagonist, since the presence of Gpp(NH)p and NaCl only produced a small (21%) reduction in binding, but reduced the pI50 for the residual binding to inhibition by morphine from 6.33-6.39 to 5.95. As with [3H]U-69593, the binding characteristics of [3H](-)-EKC were not affected by bupivacaine or tetracaine. These studies demonstrate that effects of kappa-opioid receptor recognition site conformation are unlikely to explain the clinically observed synergy between local anaesthetics and opioids.

Anesthetics, Local↗

Mu-, delta-, kappa-opioid receptors and their subtypes. A critical review with emphasis on radioligand binding experiments.

Since the early 1970's, when specific binding sites for opiates were first described, there has been a vast literature on opiate receptors, their subtypes, and even the multiplicity of these subtypes. In the present review, the signal transduction pathways, structure, and brain and spinal cord localization of the established subtypes (mu, delta, kappa) are reviewed. In addition, evidence suggesting heterogeneity of these subtypes, in particular from radioligand binding studies, is discussed critically.

Amino Acid Sequence↗

Continuous infusion of haloperidol controls agitation in critically ill patients.

OBJECTIVE: To evaluate the safety and efficacy of continuous infusion of haloperidol in treating agitated critically ill adult patients. DESIGN: Case series of patients treated with continuous infusion of haloperidol and followed to hospital discharge, during a 6-month period. SETTING: A 34-bed multidisciplinary intensive care unit (ICU) in a 598-bed nonuniversity, tertiary care teaching hospital. PATIENTS: Consecutive sample of eight patients requiring mechanical ventilation who had severe agitation which was refractory to intermittent bolus treatment with benzodiazepines, narcotics, and haloperidol. INTERVENTIONS: Continuous infusions of haloperidol (range 3 to 25 mg/hr) were supplemented, as required, to maintain adequate sedation. MEASUREMENTS AND MAIN RESULTS: The four men and four women averaged 47 yrs of age, and the average length of hospitalization was 33 days, with 25 days spent in the ICU. On the day continuous infusion of haloperidol was initiated, the average Acute Physiology and Chronic Health Evaluation (APACHE) II and Therapeutic Intervention Scoring System (TISS) scores were 24 and 47, respectively. The Sedation-Agitation Scale score averaged +2.4 (maximum agitation score being +3) before continuous infusion of haloperidol decreasing to +1.8 after 1 day (p = .38) and to +0.8 after 2 days (p = .06) of continuous infusion of haloperidol. The average daily haloperidol dose increased from 68 mg before continuous infusion of haloperidol to 269 mg (p < .008) after 1 day. The daily total of nonhaloperidol sedatives decreased from 18.3 to 10.9 sedation-equivalent units (p = .15) and the daily number of bolus administrations of sedatives decreased from 23 to 7 (p = .01) after 1 day of continuous infusion of haloperidol. Estimated nursing time to prepare, administer, and monitor these bolus medications decreased from 320 to 96 mins per 24 hrs (p = .01). Of the five patients discharged alive (37.5% mortality rate), four were successfully weaned from assisted ventilation during continuous infusion of haloperidol. Two of these four patients were difficult to wean because of agitation and oversedation. Four possible complications were noted: minor tremors (n = 2), atrial dysrhythmias with intermittent third-degree atrioventricular block and QT interval prolongation (n = 1), and ventricular tachycardia (n = 1). CONCLUSIONS: Continuous infusion of haloperidol effectively controls severe agitation in critically ill patients, reduces requirements for bolus administration of sedatives and nursing time lost to that task, and may facilitate ventilator weaning. Parenteral administration of haloperidol was associated with few complications in > 1,340 patient-hours of continuous administration.

Adolescent↗

Isopropanol ingestion: case report with pharmacokinetic analysis.

An unusual case of acute isopropanol overdose which occurred within the confines of the emergency department is reported. Serial serum concentrations of isopropanol and its metabolite acetone were followed for 43 hours. Pharmacokinetic analysis is presented, as well as a brief literature review of diagnosis and management. CNS toxicity was related mainly to isopropanol concentrations. The calculated half-life of isopropanol was 7.3 hours. Because of the pharmacokinetic profile of isopropanol, management decisions regarding the use of hemodialysis should be made within one to two hours of patient presentation.

1-Propanol↗

Evaluation of high-dose tobramycin-carbenicillin therapy in pseudomonal infections in cystic fibrosis.

Fourteen episodes of acute pseudomonal pulmonary exacerbations of cystic fibrosis were treated with high-dose tobramycin (10.1-17.1 mg/kg/d) and carbenicillin (600 mg/kg/d). The Sawchuck-Zaske method of dosing tobramycin was used and resulted in good agreement between the desired and measured peak (8.1 +/- 0.5 vs. 8.2 +/- 1.5 micrograms/ml) and trough (0.5 +/- 0.2 vs. 1.0 +/- 0.4 micrograms/ml) concentrations. Ninety-three percent of cases improved clinically. Forced expiratory volume in one second and forced vital capacity increased significantly (39.3 +/- 24.8, p less than 0.001 and 24.1 +/- 22.8 percent, p less than 0.05, respectively) after treatment. Pseudomonas aeruginosa was eradicated from the sputa of 69 percent of the cases, with recolonization occurring within three months. Significant nephrotoxicity and ototoxicity were not seen. Liver enzymes, however, were elevated in 29 percent of those treated. Combination high-dose carbenicillin and tobramycin satisfies the treatment goals of bacteriological and clinical cure with a minimal degree of toxicity.

Adolescent↗