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Biomedical subjects

D R Cook

Publications and source records attributed to D R Cook.

At least 55 records · Page 3Linked to original sources
PubMed1992

Effects of bolus administration of ORG-9426 in children during nitrous oxide-halothane anesthesia.

ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose-response relationship of ORG-9426 in 62 children (aged 1-5 yr) during nitrous oxide-halothane anesthesia by means of log-probit transformation and least-squares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 micrograms/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. To determine the dose-response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) micrograms/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 micrograms/kg, respectively. Time from administration of 600 micrograms/kg to onset of 90% and 100% neuromuscular block was 0.8 +/- 0.1 (0.5-1.3) and 1.3 +/- 0.2 (0.7-2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 +/- 1.9 (17.2-39.0) min. The recovery index (T25-75) was 11.0 +/- 1.6 (6.0-22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) greater than or equal to 0.75 was 41.9 +/- 3.2 (26.5-57.7) min.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstanols↗
PubMed1991

Safety and efficacy of alfentanil and halothane in paediatric surgical patients.

Alfentanil, a congener of the opioid fentanyl, possesses properties that make it an attractive choice for use during short operative procedures. Since the pharmacodynamic aspects of alfentanil have not been well documented in children, this study was undertaken to evaluate the safety, efficacy, and dose requirements of alfentanil when used with nitrous oxide or halothane in paediatric patients. Eighty unpremedicated patients, ASA physical status I or II and aged 2-12 yr were studied. Patients were randomly assigned to one of four groups. After induction of anaesthesia with nitrous oxide, oxygen, and halothane, the groups were treated as follows. In Group 1 (n = 19), after halothane was discontinued, alfentanil 50 micrograms.kg-1 was infused over 30 sec. In Group 2 (n = 20), the end-tidal halothan was maintained at 0.5% and alfentanil 25 micrograms.kg-1 was infused. In Group 3 (n = 20), the end-tidal halothane concentration was maintained at 1% and alfentanil 12.5 micrograms.kg-1 was infused. In Group 4 (n = 21), the end-tidal halothane concentration was maintained at 1.5% and no alfentanil was administered. Patients in Groups 1, 2, and 3 received bolus doses of alfentanil 12.5 micrograms.kg-1 as needed to maintain haemodynamic stability. After alfentanil administration, there were transient decreases in systolic blood pressure in Groups 1 and 2, and in heart rate in Group 2. With surgical stimulation, haemodynamic stability was well maintained except in patients in Group 1, who had an increase in systolic blood pressure. Children Group 1 were alert sooner and their tracheas were extubated earlier than those in Groups 2, 3, and 4.(ABSTRACT TRUNCATED AT 250 WORDS)

Alfentanil↗
PubMed1991

Hemodynamic performance and histamine levels after desmopressin acetate administration following cardiopulmonary bypass in adult patients.

Sixteen patients undergoing cardiac surgical procedures were prospectively randomized into two groups to study the hemodynamic and histamine-releasing effects of desmopressin acetate (DDAVP) administration after cardiopulmonary bypass. Ten minutes after administration of protamine for reversal of heparin, DDAVP, 0.3 microgram/kg, was infused intravenously over 5 seconds in group 1, and the same dose of DDAVP was administered over 5 minutes as an infusion in group 2. There were no statistical differences between baseline values in groups 1 and 2. DDAVP decreased mean arterial pressure by 30% and 25% in groups 1 and 2 (69 +/- 5 mm Hg to 52 +/- 8 mm Hg, P less than 0.005, and 79 +/- 20 mm Hg to 55 +/- 8 mm Hg, P less than 0.005), respectively. The hypotension in both groups was related to decreases in systemic vascular resistance (1,616 +/- 262 dyne.s.cm-5 to 1,073 +/- 199 dyne.s.cm-5, P less than 0.005, and 1,850 +/- 541 dyne.s.cm-5 to 1,144 +/- 214 dyne.s.cm-5, P less than 0.005). Phenylephrine infusion successfully treated the DDAVP-induced hypotension in all patients. Arterial histamine levels at 3 and 5 minutes after infusion of DDAVP did not differ significantly from baseline values. It is concluded that DDAVP at 0.3 microgram/kg is a potent vasodilator when administered intravenously and that histamine is not involved in producing its hypotensive effects.

Anesthesia, Intravenous↗
PubMed1991

Double-blind comparison of oral transmucosal fentanyl citrate with oral meperidine, diazepam, and atropine as preanesthetic medication in children with congenital heart disease.

The effectiveness of oral transmucosal fentanyl citrate (OTFC) as preanesthetic medication was compared with oral meperidine, diazepam, and atropine (MDA) in 40 pediatric patients scheduled to undergo repair of congenital heart defects. In a double-blinded manner, patients received a fentanyl lollipop (20-25 micrograms/kg) and a placebo oral solution (0.4 ml/kg) (n = 20) or a placebo lollipop and an oral solution (0.4 ml/kg) of meperidine (1.5 mg/kg), diazepam (0.2 mg/kg), and atropine (0.02 mg/kg) (n = 20). The patient's vital signs, systolic and diastolic blood pressures, heart rate, respiratory rate, and oxyhemoglobin saturation (SpO2), as well as activity and apprehension scores were evaluated and recorded at baseline and at 10-min intervals. The patient's emotional status at the time of parental separation and at induction of anesthesia were also assessed. Side effects and onset of action were observed. After OTFC, onset of sedation was significantly faster than with the oral solution of meperidine, diazepam, and atropine. In both groups there was no significant change in heart rate. Although systolic blood pressure, diastolic blood pressure, and respiratory rate showed statistically significant decreases, these changes were not clinically significant. The child's emotional status at the time of separation from the parents and during induction was similar in both groups. Side effects with OTFC were more frequent: nose itching occurred in 65%, body itching in 10%, and vomiting in 30%. Two patients (10%) in the OTFC-treated group became hypoxemic (SpO2 less than 90) and required supplemental oxygen. In the group receiving oral meperidine, diazepam, and atropine, 10% had mild facial pruritus and 5% complained of a dry mouth.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1991

Effects of famotidine on gastric pH and residual volume in pediatric surgery.

Aspiration pneumonitis is a severe complication of anesthesia. The objectives of this study were to determine if preoperative famotidine, a new histamine2-receptor antagonist, given by mouth either the evening before or the morning of elective surgery, reduced gastric residual volume and increased gastric pH in pediatric patients. Either famotidine or placebo (or both) were orally administered to 58 children (aged 2-17 years). The patients were randomly assigned to four groups: Famotidine-Famotidine, Placebo-Placebo, Placebo-Famotidine, and Famotidine-Placebo; subjects in the Famotidine-Famotidine group received two doses of famotidine (0.5 mg.kg-1 per dose), those in the Placebo-Placebo group, two doses of placebo, those in the Placebo-Famotidine and Famotidine-Placebo group, one dose of each by mouth. The Famotidine-Famotidine group received one dose of famotidine at 22:00 the evening before surgery and a second dose 60-90 min before the scheduled time of surgery. The Placebo-Placebo group received two doses of placebo at the same times as the Famotidine-Famotidine group. The Placebo-Famotidine group received a dose of placebo the night before surgery and a dose of famotidine the morning of surgery; the Famotidine-Placebo group received famotidine the night before surgery and placebo the morning of surgery. The administration of famotidine on the morning of surgery significantly increased gastric pH (4.8 vs. 1.3) in comparison with placebo, as did two doses of famotidine (6.6). Famotidine failed to reduce gastric residual volume significantly in any group. The administration of famotidine significantly reduced the number of pediatric patients considered at higher risk for aspiration pneumonitis, despite not decreasing gastric residual volume.

Administration, Oral↗
PubMed1991

Oral transmission of transmissible gastroenteritis virus by muscle and lymph node from slaughtered pigs.

A study was conducted in the USA to determine whether transmissible gastroenteritis (TGE) virus could be transmitted from carcases of slaughtered pigs. Transmissible gastroenteritis virus was transmitted to 6-day-old piglets by dosing with homogenates of muscle and lymph node collected from 500 clinically normal pigs at the time of slaughter. All piglets in 2 separately housed litters showed clinical signs of TGE with 5 piglets dying within 10 d of oral dosing with homogenates. Transmissible gastroenteritis virus was isolated from 2 of these piglets and all piglets developed TGE antibody. Transmissible gastroenteritis virus was not isolated in tissue culture from muscle and lymph node homogenates, but was isolated from 4 (0.8%) of 500 tonsil samples collected from the same pigs. A survey of 250 serum samples provided an estimate of the prevalence of slaughtered pigs with TGE antibody of 34.8% in the sample population. The results indicate that carcases of some pigs from TGE endemic areas contain viable TGE virus, and that there would be a substantial risk of introducing TGE virus into Australia by the importation of uncooked pig meat from these areas.

Administration, Oral↗
PubMed1991

Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and in those with hepatic or renal failure.

We determined the pharmacokinetics and duration of action of a bolus dose of doxacurium (15 micrograms/kg) in 27 patients anesthetized with isoflurane and nitrous oxide. Nine patients had normal renal and liver functions and were undergoing a variety of surgical procedures, nine were undergoing cadaveric kidney transplantation because of end-stage renal disease, and nine were undergoing cadaveric liver transplantation because of end-stage hepatocellular disease. Plasma concentrations of doxacurium were measured for 6 h after administration using a sensitive and specific capillary gas chromatographic assay. Plasma concentration versus time data were analyzed by a noncompartmental method based on statistical moments. Neuromuscular blockade was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve. The degree of neuromuscular blockade after doxacurium administration was described as the percent of control of the first train-of-four response. The pharmacokinetic variables were (normal vs hepatic failure vs renal failure, respectively): volume of distribution at steady state (220 +/- 110 vs 290 +/- 60 vs 270 +/- 130 mL/kg [mean +/- SD]), plasma clearance (2.7 +/- 1.6 vs 2.3 +/- 0.4 vs 1.2 +/- 0.7 mL.kg-1.min-1), mean residence time (95.2 +/- 57 vs 129.4 +/- 30 vs 270 +/- 210 min), and elimination half-life (99 +/- 54 vs 115 +/- 31 vs 221 +/- 156 min). Plasma clearance and mean residence time differed significantly between patients with renal failure and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Vecuronium infusion requirements in children during halothane-narcotic-nitrous oxide, isoflurane-narcotic-nitrous oxide, and narcotic-nitrous oxide anesthesia.

We were interested in determining the infusion rate of vecuronium required to maintain approximately 95% neuromuscular blockade in children during halothane-narcotic-nitrous oxide (0.8% end-tidal concentration), isoflurane-narcotic-nitrous oxide (1.0% end-tidal concentration), or narcotic-nitrous oxide anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Effective vecuronium infusion requirements averaged 1.5 +/- 0.1 micrograms.kg-1.min-1 (mean +/- SEM) during isoflurane-narcotic-nitrous oxide anesthesia, 1.9 +/- 0.1 micrograms.kg-1.min-1 during halothane-narcotic-nitrous oxide anesthesia, and 2.4 +/- 0.3 micrograms.kg-1.min-1 during narcotic-nitrous oxide anesthesia. Infusion requirements significantly decreased after the first 30 min of infusion in the presence of both potent inhalation anesthetics, but did not change with time during narcotic-nitrous oxide anesthesia. There was no evidence of decreasing infusion requirements during prolonged vecuronium infusion (2.5 h). There was no difference in the rate of spontaneous or pharmacologically induced recovery between anesthetic groups. The mean recovery index (T25-75) after termination of the infusion was 13.7 min.

Anesthesia, General↗
PubMed1991

Alfentanil pharmacokinetics in piglets with increased intra-abdominal pressure.

Increased intra-abdominal pressure (IAP) occurs in pediatric patients with end-stage liver disease and ascites, as well as in children following surgery for diaphragmatic hernia, omphalocele, gastroschisis and orthotopic liver transplantation. Although the hemodynamic response to increased IAP is well described, little information is available regarding the effects of IAP on drug distribution and elimination. We studied the effects of increased IAP (20 mm Hg) on the pharmacokinetics of alfentanil in piglets and compared these findings with those in control animals. Increased IAP appears to have no significant effect on the volume of distribution (0.46 +/- 0.06 vs. 0.61 +/- 0.23 liter/kg), mean residence time (68.8 +/- 27.8 vs. 62.3 +/- 27.8 min) and elimination half-life (47.7 +/- 19.0 vs. 43.2 +/- 19.3 min).

Abdomen↗
PubMed1990

A brief technical communication: detection of fentanyl in urine.

A reliable and sensitive method to analyze fentanyl in urine was developed using radioimmunoassay (RIA). Fentanyl, a highly lipophilic drug (pKa 7.7), has become a common drug of abuse. We evaluated three analytical techniques to detect fentanyl in urine. This paper reports the best of the three - a modified solvent extraction combined with a fentanyl RIA.

Fentanyl↗
PubMed1990

Influence of gestational age on pharmacokinetics of alfentanil in neonates.

Alfentanil's small volume of distribution and short elimination half-life, coupled with its preservation of hemodynamic stability, make it a potentially useful drug for analgesia and anesthesia in neonates. The pharmacokinetics of alfentanil were studied in 5 infants born at 26-35 weeks' gestation and in 5 infants of greater than 36 weeks. All infants were studied in the first 3 days of life. After injection of 25 micrograms/kg alfentanil, there was no significant change in blood pressure or heart rate. No significant difference was observed in volume of distribution (0.84 +/- 0.48 l/kg vs. 0.82 +/- 0.30 l/kg), clearance (1.35 +/- 0.69 ml.kg-1.min-1 vs. 1.7 +/- 0.47 ml.kg-1.min-1), or effective half-life (455 +/- 111 min vs. 328 +/- 48 min) between the two groups. The pharmacokinetic values reported here for both preterm and full-term infants are significantly different from data reported for older children.

Alfentanil↗
PubMed1990

Neuromuscular and cardiovascular effects of high-dose vecuronium.

The effects of bolus administration of large doses of vecuronium on the onset and duration of neuromuscular blockade and histamine release were studied during fentanyl-nitrous oxide anesthesia. Forty adults were randomly assigned to receive a bolus injection of either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. The evoked electromyogram of thumb adduction to train-of-four stimulation was monitored. The time of onset and clinical duration (mean +/- SEM) after each dose were as follows: 0.1 mg/kg, 164 +/- 27 s and 42 +/- 5 min; 0.2 mg/kg, 120 +/- 17 s and 68 +/- 8 min; 0.3 mg/kg, 88 +/- 17 s and 111 +/- 19 min; 0.4 mg/kg, 78 +/- 19 s and 115 +/- 19 min. Both time of onset and duration after doses of 0.3 or 0.4 mg/kg were significantly different from values after the lower doses. No dose-related changes in blood pressure, heart rate, or histamine release were observed. The authors conclude that large bolus doses of vecuronium can be safely used to speed the onset of blockade, but with a significantly prolonged duration of action.

Adolescent↗
PubMed1990

Perioperative management of the multiorgan donor.

Organ transplantation is a multidisciplinary specialty that has seen remarkable advances in the past two decades, in the tireless pursuit of providing life-saving therapy for patients suffering from end-stage organ failure. As the scientific basis and clinical practice of organ transplantation continues to evolve, it becomes increasingly apparent that "what was inconceivable yesterday, and barely achievable today, becomes routine tomorrow" (73).

Brain Death↗
PubMed1990

Mivacurium infusion requirements in pediatric surgical patients during nitrous oxide-halothane and during nitrous oxide-narcotic anesthesia.

We were interested in determining the infusion rate of mivacurium required to maintain approximately 95% neuromuscular blockade during nitrous oxide-halothane (0.8% end-tidal) or nitrous oxide-narcotic anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity (Datex NMT) of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Mivacurium steady-state infusion requirements averaged 315 +/- 26 micrograms.m-2.min-1 during nitrous oxide-halothane anesthesia and 375 +/- 19 micrograms.m-2.min-1 (mean +/- SEM) during nitrous oxide-narcotic anesthesia. Higher levels of pseudocholinesterase activity were generally associated with a higher mivacurium infusion requirement. During both anesthetics, younger age was associated with a higher infusion requirement when the infusion requirement was calculated in terms of micrograms.kg-1.min-1. This difference was not present when the infusion rate was calculated in terms of micrograms.m-2.m-1. There was no evidence of cumulation during prolonged mivacurium infusion. There was no difference in the rates of spontaneous or reversal-mediated recovery between anesthetic groups. After the termination of the infusion, spontaneous recovery to T4/T1 greater than or equal to 0.75 occurred in 9.8 +/- 0.4 min, with a recovery index, T25-75, of 4.0 +/- 0.2 min (mean +/- SEM). In summary, pseudocholinesterase activity is the major factor influencing mivacurium infusion rate in children during nitrous oxide-narcotic or nitrous oxide-halothane (0.8% end-tidal) anesthesia.

Anesthesia, Inhalation↗
PubMed1990

Clinical pharmacology of pipecuronium in infants and children during halothane anesthesia.

We determined the cumulative dose-response relations of pipecuronium in infants and children during nitrous oxidehalothane anesthesia. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. Patients were stratified into four groups according to age: 3 mo or older but not yet 6 mo (n = 10), 6 mo or older but not yet 12 mo (n = 10), 1 yr or older but not yet 3 yr (n = 10), and 3 yr or older but not yet 6 yr (n = 9). The mean ED50 of pipecuronium in these age groups was 18, 20, 21, and 24 micrograms/kg, respectively; the mean ED95 was 33, 38, 47, and 49 micrograms/kg, respectively. The ED95 of pipecuronium was statistically significantly less for the 3-6-mo-old patients than for children between 1 and 6 yr of age. Similarly, pipecuronium dosage requirements calculated on the basis of body surface area were significantly less in infants 3-12 mo of age than in children 1-6 yr of age. Thus, compared with children, infants appear to be more sensitive to the neuromuscular blocking effects of pipecuronium. Duration (T25) of action after cumulative dosing with pipecuronium was approximately 20 min in infants and 30 min in children. Spontaneous recovery indices were not prolonged in the younger patients. The average T25-75 recovery index was 27.1 +/- 9.6 min. There were no changes in cardiac rhythm, heart rate, or blood pressure attributable to pipecuronium during this study.

Aging↗