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Biomedical subjects

R B Morris

Publications and source records attributed to R B Morris.

16 recordsLinked to original sources
PubMed1989

Del(4)(q33----qter): another case report of a child with mild dysmorphism.

A male child is described with some growth and developmental delay and other minor dysmorphic features. Chromosome analysis showed a de novo deletion of the q33----qter terminal segment of a chromosome 4. There has been published discussion concerning the severity of phenotypic malformations in the seven cases described so far with this particular deletion. We add details of our patient to help to delineate further features of this syndrome.

Chromosome Aberrations↗
PubMed1988

Control of perioperative hypertension during coronary artery surgery. A randomised double-blind study comparing isosorbide dinitrate and nitroglycerin.

A reduction in the causes of myocardial ischaemia remains of prime importance during coronary artery surgery. Hypertension with the ensuing increase in myocardial oxygen demand is a major factor in the aetiology of perioperative myocardial ischaemia. Nitroglycerin (NTG) has long been used beneficially to reduce myocardial oxygen demand by its effects on the systemic and peripheral vascular resistances. An alternative nitrate, isosorbide dinitrate (ISDN) is now available as an intravenous preparation, and may offer technical advantages, both due to its stability in solution and also its longer in vivo half-life. We designed and carried out a multi-centre study to compare and evaluate the efficacy of ISDN and NTG in the management of perioperative hypertension in 85 patients undergoing elective coronary artery surgery. A total of 288 events in which the systolic blood pressure (SBP) exceeded a predetermined trigger value were observed. ISDN was successful in treating hypertension in 63% of the events, whereas NTG had an 83% success. The SBP was significantly lowered after treatment with either ISDN, 155 mmHg to 138 mmHg, or NTG, 160 mmHg to 130 mmHg. The mean successful dose rate for ISDN was 6.5 micrograms kg-1 min-1, whereas for NTG this was 3.8 micrograms kg-1 min-1. In the ISDN group less events took place possibly due to the longer duration of this drug. In many previous studies NTG has been found to be effective in controlling hypertension; ISDN offers and alternative approach in reducing hypertension.

Coronary Artery Bypass↗
PubMed1983

The cardiovascular effects of vecuronium (ORG NC45) and pancuronium in patients undergoing coronary artery bypass grafting.

Vecuronium is a new nondepolarizing muscle relaxant which has been shown to cause no significant cardiovascular effects. Utilizing invasive monitoring in patients undergoing coronary artery bypass grafting, the authors compared the cardiovascular effects of vecuronium (0.28 mg/kg) in seven anesthetized patients with those of pancuronium (0.1 mg/kg) in five anesthetized patients. This dose of pancuronium represents three times its ED90 (dose producing a 90% depression of evoked twitch tension), while the vecuronium dose represents twelve times its ED90. This relatively large dose of vecuronium was chosen deliberately in an attempt to manifest any possible cardiovascular effects. Following administration of vecuronium, cardiac output increased 9% and systemic vascular resistance decreased 12%, while pancuronium produced a significantly greater 17% increase in cardiac output without change in systemic vascular resistance. Heart rate and systemic mean arterial pressure did not change following vecuronium, while increasing 22% and 24%, respectively, following pancuronium. The authors conclude that large doses of vecuronium have minimal cardiovascular effects and thus offer an advantage over pancuronium in patients anesthetized for coronary artery surgery.

Adrenergic beta-Antagonists↗
PubMed1983

Comparison of thiopental and midazolam on the neuromuscular responses to succinylcholine or pancuronium in humans.

Midazolam (0.3 mg/kg) was compared to thiopental (4.0 mg/kg) for possible interactions with succinylcholine or pancuronium when used for induction of anesthesia. Neuromuscular function was monitored by recording the force of thumb adduction in response to ulnar nerve stimulation. Following induction of anesthesia with either midazolam (N = 10) or thiopental (N = 10), stable muscle-twitch tension was obtained and succinylcholine (1 mg/kg) was given intravenously. The duration of blockade, recovery time, intensity of fasciculations, or adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam or thiopental. An additional group of patients anesthetized and monitored in the same manner received pancuronium (0.025 mg/kg) in incremental doses until a 99% depression of muscle-twitch tension was obtained. Dose-response curves for pancuronium, duration of blockade, and adequacy of relaxation for tracheal intubation did not differ between patients receiving midazolam (N = 10) or thiopental (N = 10). We conclude that the neuromuscular blockade produced by succinylcholine or pancuronium was no different in patients receiving either midazolam or thiopental for induction of anesthesia.

Anesthesia, Intravenous↗
PubMed1982

Edrophonium: duration of action and atropine requirement in humans during halothane anesthesia.

Edrophonium's onset and duration of antagonism (n = 26) and atropine requirement (n = 24) were determined under conditions of d-tubocurarine (dTc) neuromuscular blockade and halothane, nitrous oxide anesthesia. Results are compared with previous work in our laboratory on neostigmine and pyridostigmine under similar conditions. dTc was administered by continuous infusion to maintain a 90% depression of muscle twitch tension. Edrophonium (0.03-1.0 mg/kg) was injected as an iv bolus in combination with atropine (0.5 mg). dTc infusion was continued until a stable 90% depression of muscle twitch tension was reestablished. Time-to-peak effect (onset of action), duration, and magnitude of antagonism were recorded. The atropine requirement was determined during spontaneous recovery from dTc (0.3 mg/kg) and stable halothane, nitrous oxide anesthesia. Edrophonium (0.5 mg/kg) was mixed with 7, 15, or 30 micrograms/kg of atropine and compared to neostigmine (0.043 mg/kg) and atropine (15 micrograms/kg). Blood pressure, heart rate, and rhythm were recorded for 60 min following edrophonium administration. The time-to-peak antagonism for edrophonium (0.8-2.0 min) was far more rapid than neostigmine (7-11 min) or pyridostigmine (12-16 min). The ED50 for edrophonium was 0.125 mg/kg, however, the dose-response curve was not parallel to those for neostigmine or pyridostigmine. In equiantagonistic doses, the duration of antagonism by edrophonium (66 min) did not differ from neostigmine (76 min), but was shorter than pyridostigmine. Edrophonium required one-half the amount of atropine as did neostigmine to prevent bradycardia. The authors concluded that edrophonium has a more rapid onset than neostigmine and an equivalent duration of antagonism, and requires less atropine to prevent bradycardia.

Anesthesia, General↗
PubMed1981

Pharmacokinetics of Org NC45 (norcuron) in patients with and without renal failure.

To determine the influence of renal failure on the pharmacokinetics and neuromuscular blockade of Org NC 45 (Norcuron), a new monoquaternary homologue of pancuronium, 13 patients under halothane and nitrous oxide anesthesia were studied. Org NC 45 was administered by 2-min infusion in doses of 0.28 mg kg-1 (normal renal function group, n = 4) and 0.14 mg kg-1 (renal failure group, n = 5). Four additional patients with normal renal function were given Org NC 45 0.14 mg kg-1 to determine the onset, duration and recovery rate of neuromuscular blockade. The serum concentration of Org NC 45 was determined by normal-phase high performance liquid chromatography (sensitivity 50 ng ml-1), and a two-compartment open pharmacokinetic model was fitted to resulting data. Estimates of distribution half-life (T 1/2 alpha), elimination half-life (T 1/2 beta), volume of distribution at steady state (Vss) and clearance of Org NC 45 did not differ significantly between patients with normal renal function and those with renal failure. The onset, duration and recovery rate times of the neuromuscular blockade by Org NC 45 0.14 mg kg-1 in patients with normal renal function and those with renal failure did not differ significantly.

Adult↗
PubMed1981

Pharmacokinetics of edrophonium in anephric and renal transplant patients.

The pharmacokinetics of edrophonium were determined in patients anaesthetized with nitrous oxide and halothane undergoing kidney transplant nephrectomy (n=6) or transplantation of a live related donor kidney (n = 6). Serum concentrations of edrophonium were assayed by high pressure liquid chromatography and pharmacokinetic variables computed using non-compartmental analysis. Patients undergoing transplant nephrectomy had a significant increase in elimination half-life and a significant decrease (67%) in serum clearance when compared with kidney transplant recipients or patients with normal renal function. Pharmacokinetic indices for edrophonium in patients receiving a kidney transplant did not differ from those in patients with normal renal function. We conclude that absence of renal function decrease excretion of edrophonium to an extent similar to that of other acetylcholinesterase inhibitors, neostigmine and pyridostigmine.

Adult↗
PubMed1981

Pharmacokinetics of edrophonium and neostigmine when antagonizing d-tubocurarine neuromuscular blockade in man.

The pharmacokinetics and effectiveness of edrophonium antagonism of d-tubocurarine neuromuscular blockade were compared with that of neostigmine in surgical patients anesthetized with halothane and nitrous oxide. After an intravenous (iv) injection of d-tubocurarine (0.3 mg/kg), the single twitch tension was allowed to return to five per cent of the control level. Edrophonium, 0.5 or 1.0 mg/kg (n = 12), or neostigmine, 0.07 mg/kg (n = 6), was then given iv in combination with atropine, 1.0 mg, as a 2-min controlled infusion. Train-of-four and single twitch tension were followed for 60 min in all patients. Twelve patients were monitored for 90 min, six patients for 120 min, four patients for 150 min, and two patients for 240 min. Blood was sampled intermittently for four hours and assayed for edrophonium or neostigmine using high-pressure liquid chromatography. Edrophonium was found to promptly antagonize the d-tubocurarine blockade. Twitch tension rapidly increased to a plateau (a rate of increase in twitch tension of less than 2 per cent of control per min) which was sustained in all cases. The mean time to plateau for edrophonium was 2.9 +/- 0.21 (+/-SE) min as compared to 6.1 +/- 0.75 min for neostigmine. Neuromuscular blockade did not reappear in any patient. The degree of antagonism of the neuromuscular blockade by neostigmine and edrophonium was not significantly different. Except for a longer distribution half-life, the pharmacokinetic variables for edrophonium did not differ significantly from those for neostigmine. The elimination half-lives of edrophonium and neostigmine were 110 +/- 34 min (mean +/- SD) and 77 +/- 47 min, respectively. The authors therefore conclude that edrophonium, 0.5-1.0 mg/kg, has pharmacokinetic variables comparable to neostigmine and produces prompt, sustained, and effective antagonism of d-tubocurarine neuromuscular blockade.

Adult↗
PubMed1981

Clinical pharmacology of ORG NC45 (NorcuronTM): a new nondepolarizing muscle relaxant.

To determine the neuromuscular effects of a new muscle relaxant, ORG NC45 (Norcuron), a monoquaternary homologue of pancuronium, 84 ASA Class I or II patients were studied under halothane and nitrous oxide anesthesia. The ED50 (dose of muscle relaxant causing a 50% depression of twitch tension) of pancuronium and ORG NC45 was 0.022 mg/kg (r = 0.90) and 0.015 mg/kg (r =0.80), respectively, for a potency ratio of 1.5 (0.022/0.015). The duration of action (time from injection to 90% recovery of control twitch tension) was 27 +/- 5 min with ORG NC45, 0.02 mg/kg, and 65 +/- 16 min with pancuronium in an equivalent dose of 0.03 mg/kg. The increase in duration of neuromuscular blockade from repetitive doses was greater with pancuronium than with ORG NC45. Reversal of an ORG NC45 neuromuscular blockade was accomplished with doses of neostigmine slightly less than those required for pancuronium. Under thiopental-nitrous oxide anesthesia, endotracheal intubation was easily performed using ORG NC45, 0.07-0.14 mg/kg. The duration of action of ORG NC45, 0.07 mg/kg, was about one-third that of pancuronium (0.1 mg/kg). It was concluded that ORG NC45 is more potent and has a shorter duration of action with both initial and repetitive doses than does pancuronium. With these characteristics and the reported lack of cardiovascular effects, the authors believe further clinical trials are warranted.

Adult↗