PubMed Health⌕ Search

Biomedical subjects

P M Wright

Publications and source records attributed to P M Wright.

At least 19 recordsLinked to original sources
PubMed1995

The magnitude and time course of vecuronium potentiation by desflurane versus isoflurane.

BACKGROUND: Preliminary studies suggest that desflurane and isoflurane potentiate the action of muscle relaxants equally. However, variability between subjects may confound these comparisons. A crossover study was performed in volunteers on the ability of desflurane and isoflurane to potentiate the neuromuscular effect of vecuronium, to influence its duration of action, and on the magnitude and time course of reversal of potentiation when anesthesia was withdrawn. METHODS: Adductor pollicis twitch tension was monitored in 16 volunteers given 1.25 MAC desflurane on one occasion, and 1.25 MAC isoflurane on another. In eight subjects, vecuronium bolus dose potency was determined using a two-dose dose-response technique; the vecuronium infusion dose requirement to achieve 85% twitch depression also was determined. Also in these subjects, the magnitude and time course of spontaneous neuromuscular recovery were determined when the anesthetic was withdrawn while maintaining a constant vecuronium infusion. In the other eight subjects, the time course of action of 100 micrograms/kg vecuronium was determined. RESULTS: Vecuronium's ED50 and infusion requirement to maintain 85% twitch depression were 20% less during desflurane, compared to isoflurane, anesthesia; vecuronium plasma clearance was similar during the two anesthetics. After 100 micrograms/kg vecuronium, onset was faster and recovery was longer during desflurane anesthesia. When the end-tidal anesthetic concentration was abruptly reduced from 1.25 to 0.75 MAC, twitch tension increased similarly (approximately 15% of control), and time for the twitch tension to reach 90% of the final change was similar (approximately 30 min) with both anesthetics. Decreasing anesthetic concentration from 0.75 to 0.25 MAC increased twitch tension by 46 +/- 10% and 25 +/- 7% of control (mean +/- SD, P < 0.001) with desflurane and isoflurane, respectively; 90% response times for these changes were 31 +/- 10 min and 18 +/- 7 min (P < 0.05), respectively. CONCLUSIONS: Desflurane potentiates the effect of vecuronium approximately 20% more than does an equipotent dose of isoflurane.

Adult↗
PubMed1995

Edrophonium increases mivacurium concentrations during constant mivacurium infusion, and large doses minimally antagonize paralysis.

BACKGROUND: Mivacurium, a nondepolarizing muscle relaxant, is metabolized by plasma cholinesterase. Although edrophonium does not alter plasma cholinesterase activity, we have observed that doses of edrophonium that antagonize paralysis from other nondepolarizing muscle relaxants are less effective with mivacurium. We speculated that edrophonium might after metabolism of mivacurium, thereby hindering antagonism of paralysis. Accordingly, we determined the effect of edrophonium on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion. METHODS: We infused mivacurium to maintain 90% depression of adductor pollicis twitch tension and then gave edrophonium in doses ranging from 125-2,000 micrograms/kg without altering the mivacurium infusion. Peak twitch tension after edrophonium was determined to estimate the dose of edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium; plasma cholinesterase activity and mivacurium concentrations before and after edrophonium were measured. Additional subjects were given 500 micrograms/kg edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium. RESULTS: With mivacurium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg) produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized mivacurium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereoisomers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity was unchanged. CONCLUSIONS: Edrophonium doses that antagonize d-tubocurarine and vecuronium are less effective in antagonizing the neuromuscular effects of mivacurium during constant infusion. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edrophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is impaired, and therefore we question whether edrophonium should be used to antagonize mivacurium.

Adolescent↗
PubMed1994

Onset and duration of rocuronium and succinylcholine at the adductor pollicis and laryngeal adductor muscles in anesthetized humans.

BACKGROUND: Rocuronium, a new nondepolarizing muscle relaxant, has a rapid onset of activity and may be suitable as a component of a rapid-sequence induction of anesthesia. We evaluated a range of doses on onset and duration of effect at the larynx and the adductor pollicis and compared these characteristics with those of succinylcholine. METHODS: Forty-eight patients aged 18-70 yr, of ASA physical status 1-3, were randomly allocated to receive succinylcholine (1 mg/kg) or one of three doses of rocuronium (0.4, 0.8, or 1.2 mg/kg) during surgery. Anesthesia was induced and maintained with propofol and fentanyl. The trachea was intubated without the use of muscle relaxants, and the cuff of the endotracheal tube placed between the vocal cords. Neuromuscular transmission was monitored by mechanomyography at the laryngeal adductor and adductor pollicis muscles. Muscular activity was evoked with supramaximal stimuli in a train-of-four sequence every 12 s to the anterior branch of the recurrent laryngeal nerve and the ulner nerve. RESULTS: At the laryngeal adductors, peak effect exceeded 99% in all patients given succinylcholine and in none (0%), five (42%), and ten (83%) of those given rocuronium 0.4, 0.8, and 1.2 mg/kg, respectively. At the adductor pollicis, peak effect exceeded 99% in all study patients except two who received rocuronium 0.4 mg/kg (peak effects 91% and 97%). Onset of effect with succinylcholine was significantly more rapid at the laryngeal adductors (34 +/- 12 s, mean +/- SD) than at the adductor pollicis (56 +/- 15 s); this was true also for rocuronium 0.4 mg/kg (92 +/- 29 s and 155 +/- 40 s for the laryngeal adductors and adductor pollicis, respectively). Onset times were similar at the two muscle groups with rocuronium 0.8 and 1.2 mg.kg-1: 96 +/- 29 and 74 +/- 36 s with 0.8 mg/kg and 54 +/- 30 and 65 +/- 21 s with 1.2 mg/kg at the laryngeal adductors and the adductor pollicis, respectively. CONCLUSIONS: The laryngeal adductors are more resistant to the action of rocuronium than is the adductor pollicis. Consequently, the onset of effect of rocuronium, in doses greater than 0.8 mg/kg, is similar to that of succinylcholine at the adductor pollicis but is significantly delayed compared with that of succinylcholine at the laryngeal adductors.

Adolescent↗
PubMed1994

Thoracic epidural analgesia compared with patient controlled intravenous morphine after upper abdominal surgery.

Twenty-one ASA I or II patients undergoing upper abdominal surgery were studied for 24 hours after operation. They were entered into a prospective, randomised study of patient-controlled intravenous morphine compared with continuous thoracic epidural fentanyl combined with 0.2% bupivacaine. Pain relief was superior in the bupivacaine series (P < 0.05) throughout the 24 hour study period and this was associated with significantly greater pulmonary ventilation compared with the PCA series. Forced expiratory parameters were reduced in both series after the operation but significantly less so in the epidural group. There was a reduced incidence of emetic symptoms in the epidural group (P < 0.05) but the incidence of other minor side effects did not differ significantly. Thoracic epidural fentanyl/bupivacaine results in significantly better analgesia than patient-controlled intravenous morphine.

Abdomen↗
PubMed1994

Cumulative characteristics of atracurium and vecuronium. A simultaneous clinical and pharmacokinetic study.

BACKGROUND: Cumulative effects (increased 25-75% recovery time with increasing dose) are evident with vecuronium but not with atracurium. Pharmacokinetic simulations suggest that vecuronium's cumulation occurs as recovery shifts from distribution to elimination whereas atracurium's recovery always occurs during elimination. The purpose of this study was to examine this pharmacokinetic explanation. METHODS: We assigned 12 volunteers to receive atracurium of vecuronium on three occasions during nitrous oxide-isoflurane anesthesia. Evoked adductor pollicis twitch tension was monitored. On occasion 1, the dose expected to produce 95% block (ED95) was estimated for each subject. On occasions 2 and 3, 1.2 or 3.0 multiples of ED95 were given as a bolus. Plasma was sampled for 128 min to determine muscle relaxant concentrations; pharmacodynamic modeling was used to determine effect-compartment drug concentrations (Ce). For each drug, recovery time, recovery phase half-life (rate of decrease in Ce during recovery), and Ce at 25% and 75% recovery were compared between doses. RESULTS: Atracurium's recovery time increased 2.4 +/- 2.2 min (mean +/- SD) with the larger dose, less than the increase with vecuronium (8.2 +/- 3.8 min). Atracurium's recovery phase half-life was 14.6 +/- 1.7 and 20.1 +/- 2.3 min with the small and large doses (P < 0.05); vecuronium's recovery phase half-life increased similarly from 13.5 +/- 2.3 to 18.5 +/- 5.0 min (P < 0.05). At 75% recovery, vecuronium's Ce decreased from 65 +/- 18 ng/ml with the small dose to 55 +/- 15 ng/ml with the large dose (P < 0.05). Assuming that neuromuscular junction sensitivity was constant, this difference could be explained by considering neuromuscular effects of vecuronium's metabolite, 3-desacetylvecuronium. CONCLUSIONS: Although vecuronium was cumulative (as predicted), atracurium was also slightly cumulative. Inconsistent with our hypothesis, recovery phase half-lives for both drugs increased similarly between doses; therefore, differences in cumulation were not solely explained by pharmacokinetics of the muscle relaxant. It appears that 3-desacetylvecuronium contributes to vecuronium's cumulative effect, even after usual clinical doses.

Adult↗
PubMed1994

The pharmacodynamics and pharmacokinetics of the metabolite 3-desacetylvecuronium (ORG 7268) and its parent compound, vecuronium, in human volunteers.

The pharmacology of 3-desacetylvecuronium, the principal metabolite of vecuronium, was investigated. We studied 12 healthy volunteers, each on two occasions. First they received 3-desacetylvecuronium alone and then, on a later occasion, vecuronium. Six subjects received a large dose of each drug (pharmacokinetic study), the remaining six received a small dose (pharmacodynamic study). Drug concentrations in plasma and urine were measured using capillary gas chromatography. Neuromuscular block was assessed by measuring force of contraction of the adductor pollicis. Drug plasma concentration vs. time and neuromuscular effect data were analyzed by nonlinear mixed-effects modeling. 3-Desacetylvecuronium, compared with vecuronium (median, range in parentheses), had a smaller plasma clearance, 3.51 (2.11-6.57) vs. 5.39 (5.04-7.19) ml.kg-1.min-1; a larger steady-state distribution volume, 254 (215-410) vs. 152 (111-170) ml.kg-1; a longer terminal elimination half-life 116 (44-672) vs. 34 (25-61) min and a longer mean residence time, 67 (42-145) vs. 26 (18-32) min (P < .05). Renal clearances of 3-desacetylvecuronium and vecuronium were 0.85 (0.15-1.24) and 0.58 (0.16-0.66) ml.kg-1.min-1, respectively (P < .05). Conversion to 3-desacetylvecuronium accounted for 12% of vecuronium's clearance. Concentrations of 3-desacetylvecuronium and vecuronium that produced 50% neuromuscular block were 123 (109-154) and 102 (71-123) ng.ml-1, respectively (P < .05). 3-Desacetylvecuronium is a potent neuromuscular blocking drug and may be responsible for episodes of prolonged paralysis after long-term administration of vecuronium to patients in intensive care units.

Adolescent↗
PubMed1992

Gastric emptying during lumbar extradural analgesia in labour: effect of fentanyl supplementation.

We measured gastric emptying (by paracetamol absorption) and duration of analgesia in 30 women in labour after extradural injection of 0.375% bupivacaine 10 ml either alone or combined with fentanyl 100 micrograms. Treatment was administered double blind by random allocation after the first request for analgesia. The median (range) times to maximal serum concentration of paracetamol were 60 (15-90) min and 75 (30-180) min after administration in the control and fentanyl groups, respectively (P = 0.026), and corresponding mean (95% confidence interval) maximal concentrations of paracetamol were 27.3 (18.8-35.8) micrograms ml-1 and 18.0 (15.1-20.9) micrograms ml-1 (P = 0.020). Mean duration of analgesia, from the first extradural bolus until return of pain in those given bupivacaine alone was 113 (87-139) min and 154 (131-176) min when fentanyl was added to the local anaesthetic (P = 0.016). These results confirm the prolongation of analgesia after fentanyl supplementation of lumbar extradural analgesia, but indicate that it results in delayed gastric emptying.

Acetaminophen↗
PubMed1992

Cardiovascular support during combined extradural and general anaesthesia.

We have examined the effect of prophylactic treatment with i.v. fluid 1000 ml, ephedrine 24 mg or methoxamine 4 mg on cardiovascular responses to both extradural and combined extradural and general isoflurane anaesthesia in 45 adult patients undergoing knee arthroplasty. Heart rate (HR) and systemic arterial pressure (AP) were measured using automated oscillotonometry and cardiac output was measured using continuous wave suprasternal Doppler ultrasonography. After lumbar extradural anaesthesia (LEA) there were no significant differences in arterial pressure between treatments, although cardiac index was significantly greater after fluid preloading (mean 4.3 (95% confidence interval 3.7-4.9) litre min-1 m-2) than after ephedrine (3.1 (2.6-3.6) litre min-1 m-2) or methoxamine (2.6 (2.0-3.2) litre min-1 m-2). During combined LEA and general anaesthesia, systolic AP was significantly greater after ephedrine (114 (103-125) mm Hg) than after either preloading (98 (88-107) mm Hg) or methoxamine (97 (89-105) mm Hg). The reduction in AP after induction of general anaesthesia was associated with a decrease in cardiac index after fluid preloading and a decrease in vascular resistance after methoxamine.

Adult↗
PubMed1992

Synergistic interaction between midazolam and propofol.

We gave either midazolam or propofol for induction of anaesthesia to 140 ASA I or II female patients (18-60 yr). ED50 values were obtained by probit analysis for three clinical end-points: loss of response to command; loss of eyelash reflex; failure to respond to application of an anaesthetic face mask delivering 1% isoflurane. Propofol ED50 values (95% confidence intervals) were 1.25 (0.99-1.48) mg kg-1, 1.61 (1.29-1.94) mg kg-1 and 1.51 (1.20-1.82) mg kg-1, respectively. ED50 values for midazolam were 0.26 (0.20-0.37) mg kg-1, 0.29 (0.23-0.47) mg kg-1 and 0.25 (0.20-0.32) mg kg-1, respectively. An additional 92 similar patients received one of nine dose combinations of midazolam and propofol for induction of anaesthesia, propofol being administered 2 min after midazolam. Success of induction was based on the clinical end-point of loss of response to command. Administration of 25% of the ED50 of midazolam followed by 50% of the ED50 of propofol resulted in loss of response to command in 50% of patients, while 50% of the ED50 of midazolam, followed by 25% of the ED50 of propofol had the same effect. A probit regression model specifying a synergistic interaction between midazolam and propofol fitted the data significantly better than a model specifying no interaction.

Adolescent↗
PubMed1992

The influence of naloxone infusion on the action of intrathecal diamorphine: low-dose naloxone and neuroendocrine responses.

The influence of an intravenous infusion of naloxone 1 microgram kg-1 h-1, in combination with intrathecal diamorphine, on analgesia and hormonal stress responses after laminectomy was assessed in a blinded, randomized, placebo-controlled study. Twenty-seven patients undergoing laminectomy with postoperative analgesia provided by intrathecal diamorphine were investigated. Analgesia was reduced by naloxone (P less than 0.05), and the duration of analgesia was shortened by 180 min. The postoperative concentrations of both blood glucose and serum cortisol were reduced in the naloxone group compared to the control group (P less than 0.05). These results may indicate an excitatory role for the hypothalamic mu receptor in hypothalamo-pituitary-adrenocortical axis regulation.

Adult↗
PubMed1992

Vasopressor therapy for hypotension during epidural anesthesia for cesarean section: effects on maternal and fetal flow velocity ratios.

The purpose of this study was to identify the influence of hypotension as a result of epidural anesthesia and of its treatment with either ephedrine or methoxamine on uteroplacental and umbilical flow velocity ratios and fetal acid-base status. Fifty healthy women with an uncomplicated full-term pregnancy were studied during elective cesarean section under epidural anesthesia. A method of continuously recording flow velocity waveforms was used that allowed the identification of simultaneous values of maternal and fetal Doppler indices related to events during the induction of anesthesia. In 15 patients in whom arterial blood pressure did not decrease, the uteroplacental pulsatility index (UtPI) did not change, but the umbilical pulsatility index (UmPI) decreased from a mean (95% confidence interval) of 0.98 (0.88-1.09) to 0.91 (0.82-0.99) (P less than 0.05). In 32 patients who experienced hypotension of at least 15%, the UtPI increased from 0.82 (0.76-0.89) to 1.04 (0.92-1.17) (P less than 0.01). Treatment with ephedrine had no influence on either the UtPI or UmPI, but treatment with methoxamine resulted in brief increases in the UtPI of 0.47 (0.24-0.69) during the first 5 min after its administration; the increases were brief and resolved within 2 min. The choice of vasopressor drug had no influence on the UtPI recorded just before surgery commenced (final UtPI), but those patients who experienced hypotension had significantly larger final UtPIs (1.02 (0.91-1.10)) than those who never became hypotensive (0.86 (0.72-0.99)), and this was associated with significantly increased placental hydrogen ion gradients. The choice of vasopressor drug appears to be of minor importance compared with the avoidance of hypotension.

Adult↗
PubMed1991

Preanaesthetic medication with clonidine: a dose-response study.

Eighty normotensive female patients were studied in a randomized, double-blind investigation, in which orally administered clonidine 0.1 mg, 0.2 mg and 0.3 mg were compared with a standard benzodiazepine premedicant. Clonidine 0.2 mg produced a significant reduction in anxiety (P less than 0.05) compared with all the other groups, and a better quality of induction of anaesthesia when compared with temazepam 20 mg and clonidine 0.1 mg. The decreases in arterial pressure and heart rate with clonidine 0.3 mg were significant compared with the other treatment groups. Hypotension persisted into the postoperative period after premedication with clonidine 0.3 mg, and this dose is not recommended as a routine premedicant.

Adolescent↗
PubMed1991

Acute airway obstruction, hypertension and kyphoscoliosis.

An elderly woman developed acute respiratory obstruction after choking on a bolus of food. On rigid bronchoscopy no foreign body, or anatomical obstruction was seen, but airway obstruction recurred during emergence from general anaesthesia, and was thought to be functional in nature. A recurring airway obstruction followed, relieved by induction of anaesthesia and by sedation. This was subsequently demonstrated to be caused by a tortuous aorta which impinged intermittently on the anterior tracheal wall, as a result of kyphoscoliosis of the thoracic spine. We attribute the relief of airway obstruction by general anaesthesia to a reduction in arterial blood pressure.

Aged↗
PubMed1991

Cardiovascular effects of intravenous clonidine. Partial attenuation of the pressor response to intubation by clonidine.

The effect of clonidine on the pressor and heart rate response to tracheal intubation was studied in a placebo-controlled, randomised, double-blind trial. Thirty patients were pretreated with either clonidine 1.25 micrograms/kg, or clonidine 0.625 microgram/kg or an equivalent volume of normal saline, given intravenously 15 minutes before induction of anaesthesia. The attenuation of the pressor response to intubation of both clonidine groups was statistically significant compared to the saline group. Neither dose of clonidine completely abolished the increase in either heart rate or blood pressure. There was no difference in attenuation between the clonidine treatments; this indicated that the lower dose may be the more appropriate.

Adult↗
PubMed1991

Continuous thoracic epidural fentanyl for post-thoracotomy pain relief: with or without bupivacaine?

Twenty-five ASA 1 or 2 patients undergoing thoracotomy were entered into a prospective, randomised, double-blind study comparing thoracic epidural fentanyl alone and thoracic epidural fentanyl combined with 0.2% bupivacaine. Pain relief, pulmonary function and cardiovascular stability were assessed. Pain relief was superior in the bupivacaine series (p less than 0.05) during the first day after operation and this was accompanied by better oxygenation (p less than 0.05); the difference did not persist into the second day. Forced expiratory variables were reduced in both series to 50-60% of the values before operation throughout the study (p less than 0.05) and differences did not occur between the groups. The incidence of side effects attributable to epidural fentanyl was high, but hypotension did not occur. Small doses of bupivacaine administered together with fentanyl into the thoracic epidural space improve analgesia without causing hypotension.

Adult↗
PubMed1991

The effect of intravenous clonidine on the forearm circulation.

The effect of two doses of clonidine on forearm blood flow was compared with an inert treatment using mercury strain gauge venous occlusive plethysmography. In the clonidine treated groups, forearm blood flow was unaffected in the resting state, but decreased sharply with tracheal intubation. In the saline group, blood flow increased with intubation. Forearm vascular resistance increased in the clonidine treated groups, but decreased in the saline group. These results suggest that clonidine has a peripheral action in anaesthetised normotensive individuals, and is not a purely centrally acting drug.

Adult↗
PubMed1990

Preanaesthetic medication with clonidine.

The purpose of this study was to evaluate oral clonidine in a dose of 0.3 mg as a routine premedicant. Sixty-nine normotensive female patients were studied in a randomized double-blind investigation in which clonidine was compared with an inert treatment. Clonidine produced a significant reduction in anxiety (P less than 0.05) and sedation and a reduction in the sleep dose of methohexitone (P less than 0.05). Tachycardia in response to intubation was attenuated by clonidine (P less than 0.05). However, the magnitude of the increase in arterial pressure after intubation was not affected. Intraoperative and postoperative hypotension were common after premedication with clonidine 0.3 mg and caution is urged in its use as a premedicant.

Administration, Oral↗