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Biomedical subjects

R K Mirakhur

Publications and source records attributed to R K Mirakhur.

At least 19 recordsLinked to original sources
PubMed1992

Estimation of the potency of ORG 9426 using two different modes of nerve stimulation.

The potency of ORG 9426, a new nondepolarising muscle relaxant, has been estimated using two different modes of nerve stimulation in patients anaesthetised with thiopentone, nitrous oxide-oxygen and intravenous fentanyl. The force of contraction of adductor pollicis was measured following a single twitch (ST) at 0.1 Hz or a train-of-four (TOF) mode of stimulation at 2 Hz every ten seconds. Dose-response curves were constructed using a single-dose method. The ED50, ED90 and ED95 were 147,272 and 305 micrograms.kg-1 respectively using the ST mode and 125,230 and 257 micrograms.kg-1 using the TOF mode of stimulation. The ED50S were not significantly different but the differences between ED90S and ED95S were significant (P less than 0.05) indicating greater sensitivity of the neuromuscular junction using TOF stimulation. The results of this study suggest that the information obtained by single-twitch stimulation is not the same as that obtained from the first response of the TOF stimulation, suggesting apparently increased sensitivity (and apparently greater potency) with the TOF mode of stimulation. Org 9426 appears to be a drug with relatively low potency.

Adolescent↗
PubMed1992

Effect of doxapram on the rate of recovery from atracurium and vecuronium neuromuscular block.

We have studied the effect of doxapram on the rates of spontaneous and neostigmine-induced recovery from neuromuscular block with atracurium and vecuronium, by measurement of the time to recovery of T1 (first twitch in the train-of-four) from 25 to 75% of control (recovery index, RI). After each neuromuscular blocking drug, RI was measured without administering either doxapram or neostigmine (control group), or after administration of doxapram 1 mg kg-1, neostigmine 50 micrograms kg-1 or a combination of doxapram and neostigmine, in groups of 10 patients. RI was significantly longer after vecuronium in the presence of doxapram compared with control (20.1 min vs 14.6 min). There was no significant difference in the RI after atracurium in the presence of doxapram compared with control (12.5 min vs 11.8 min) or when neostigmine was administered with or without doxapram (2.4 min vs 2.4 min, respectively after vecuronium; 3.3 min vs 2.9 min, respectively, after atracurium).

Adolescent↗
PubMed1992

Comparison of intubating conditions after administration of Org 9246 (rocuronium) and suxamethonium.

We have assessed intubating conditions after administration of Org 9426 (rocuronium) 600 micrograms kg-1 at 60 or 90 s in groups of 20 patients anaesthetized with thiopentone, nitrous oxide in oxygen and small doses of fentanyl, and compared the data with those obtained after suxamethonium 1 mg kg-1 in similar groups of patients. The influence of prior suxamethonium administration on the potency of Org 9426 was studied also by constructing a dose-response curve. Intubating conditions after Org 9426 were found to be clinically acceptable (good or excellent) in 95% of patients at 60 s and in all patients at 90 s and in all patients at both times after suxamethonium. The average time for the onset of block following Org 9426 at this dose was 89 s (which is shorter than with any of the currently available non-depolarizing neuromuscular blocking drugs); the duration of clinical relaxation (25% recovery of twitch height) 30 min. Prior administration of suxamethonium did not appear to influence the potency of Org 9426.

Adolescent↗
PubMed1992

Dose-response relationships for neostigmine antagonism of vecuronium-induced neuromuscular block in adults and the elderly.

We have studied the dose-response relationship for neostigmine in 36 adult (ages 18-50 yr) and 36 elderly (ages > 70 yr) subjects during antagonism of neuromuscular block induced by vecuronium. All patients received vecuronium 0.08 mg kg-1 and neuromuscular block was monitored mechanomyo-graphically using the train-of-four (TOF) mode of stimulation. Six patients of each age group were allocated randomly to receive neostigmine 5, 15, 25, 35 or 45 micrograms kg-1 or saline at 10% recovery of T1 (first response in the TOF). TOF ratios were recorded continuously over the next 10 min and the values at 1-min intervals from 5 min onwards were used to construct the dose-response relationships. There was a significant difference (P < 0.05) in the time to spontaneous recovery of T1 to 10% between the adults (24 (SD 5.5) min) and the elderly (33 (7.8) min). Dose-response curves for neostigmine were parallel in the two age groups, but those for the elderly were significantly to the right of the curves for the adults. This suggests an apparently lesser relative potency of neostigmine, or the requirement of a larger dose, in the elderly for attaining antagonism of a moderately intense vecuronium block at the same time as in adults.

Adolescent↗
PubMed1992

Muscle pains and biochemical changes following suxamethonium administration after six pretreatment regimens.

The incidence of muscle pains and changes in serum concentrations of potassium, calcium and creatine kinase following suxamethonium were investigated after no pretreatment or pretreatment with intravenous tubocurarine 0.05 mg.kg-1, intravenous chlorpromazine 0.1 mg.kg-1, alphatocopherol (vitamin E) 600 mg in three divided doses orally, aspirin 600 mg orally or intravenous calcium chloride 5 mg.kg-1 in groups of 20 patients each. The incidence of myalgia was reduced significantly by tubocurarine, chlorpromazine and alphatocopherol. However, the increase in creatine kinase was attenuated only in the groups of patients who received tubocurarine and chlorpromazine. The changes in serum potassium and calcium concentrations were within acceptable limits. The intubating conditions were not as good in the patients who received tubocurarine as in the other groups. Effectiveness of chlorpromazine in preventing both the myalgia and the biochemical changes suggests the involvement of phospholipases in the pathogenesis of suxamethonium-induced muscle damage.

Adolescent↗
PubMed1992

Clinical evaluation of doxacurium chloride.

Doxacurium was administered to 50 adult patients for determination of potency (n = 10), onset and duration of clinical relaxation (n = 40). Cumulative dose-response showed the ED95 to be 33.24 micrograms.kg-1 (95% confidence limits 27.4-39.3). Doxacurium 33 micrograms.kg-1 was then administered to four groups of 10 patients each who had anaesthesia maintained with either fentanyl-droperidol or halothane and nerve stimulation carried out with single-twitch stimulation at 0.1 Hz or train-of-four stimulation at 2 Hz every 12 s. The onset and duration showed wide individual variation. The mean (SD) times to occurrence of maximal block were 8.5 (4.6), 6.1 (1.9), 6.7 (1.8) and 4.7 (1.3) min in the single twitch-fentanyl, train-of-four--fentanyl, single twitch-halothane and train-of-four--halothane groups respectively, although it ranged from 3.4 to 13.1 min in individual patients. The mean (SD) durations of clinical relaxation (recovery of single twitch or first response in train-of-four to 25%) were 65 (22.8), 52 (21.7), 70 (33.4) and 72 (21.0) min respectively with individual values ranging from 31 to 103 min. Although halothane administration increased the duration of clinical relaxation and train-of-four stimulation accelerated the onset of effect, the changes due to these were not significant. There were no adverse effects on heart rate or indirectly measured arterial pressure.

Adult↗
PubMed1992

Postoperative oxygenation in the elderly following general or local anaesthesia for ophthalmic surgery.

Peripheral oxygen saturation was recorded on the pre-operative night (between 2400 and 0600 h), the immediate postoperative period (first 60 min) and the first postoperative night (2400 to 0600 h) in 18 elderly patients aged 70 years or over presenting for elective ophthalmic surgery. Nine patients had surgery performed under general anaesthesia employing muscle relaxants and controlled ventilation and nine under local anaesthesia using a peribulbar block. The median (interquartile range) percentage of time during which the patients had an oxygen saturation of less than 90% was 0 (0-0.2) and 0.04 (0-0.4) on the pre-operative night, 0.7 (0-1.4) and 0.3 (0-1.2) in the immediate postoperative period, and 0.05 (0-0.16) and 0 (0-0.3) on the postoperative night in the general and local anaesthesia patients respectively. There were no significant differences between general and local anaesthesia in respect of these data and the overall incidence of significant desaturation was low. The present study could not demonstrate any adverse effect of general anaesthesia on oxygen saturation in patients undergoing minimally invasive surgery.

Aged↗
PubMed1992

Onset and duration of action of vecuronium in the elderly: comparison with adults.

The onset and duration of action of vecuronium were studied in young adult (n = 30; mean age 34 +/- 11.1 (s.d.) yr), middle-aged (n = 20; mean age 60 +/- 5.8 yr) and elderly patients (n = 30; mean age 80 +/- 4.6 yr) anaesthetised with thiopentone, nitrous oxide in oxygen and halothane. Neuromuscular block was monitored by applying the train-of-four (TOF) stimulation at 2 Hz to the ulnar nerve every 12 s. Half the patients in each group received 0.08 and the other half 0.12 mg kg-1 of the relaxant. The time to return of T1 (first response in the TOF sequence) to 25% of control was 28 +/- 5.2 (s.d.), 34 +/- 7.1 and 39 +/- 10.2 min following 0.08 mg kg-1 dose (P less than 0.05 between the elderly and young adults) and 45 +/- 9.2, 48 +/- 6.2 and 69 +/- 19.2 min following 0.12 mg kg-1 dose, respectively, in the three age groups (P less than 0.05 between the elderly and the other two groups). The recovery indices (time for 25-75% recovery of T1) after the 0.08 mg kg-1 was 9.6 +/- 3.4, 13.6 +/- 5.1 and 17.4 +/- 6.1 min, respectively (P less than 0.05 between the elderly and young adults). There was no significant difference in any of the parameters between the young adults and the middle-aged. The onset of block at each dose was not significantly different between the three age groups; however, the time to maximum effect was significantly shorter with the higher dose in the young and the middle-aged, but not in the elderly. Regression analysis of the data between age and the duration of action and recovery index suggested a significant prolongation (P less than 0.05) of these parameters in the elderly.

Adult↗
PubMed1992

Lack of interaction between propofol and vecuronium.

We estimated the potency of vecuronium and measured the onset and duration of its action during total intravenous anesthesia with propofol to examine the possibility of any interaction between these two drugs. Propofol infusion was administered according to a three-step dosage scheme, and neuromuscular block was monitored by measuring the force of contraction of the adductor pollicis muscle after single-twitch stimulation of the ulnar nerve at 0.1 Hz. A control group of patients were similarly studied during anesthesia with thiopental, nitrous oxide, oxygen, and fentanyl. The ED50 and ED95 (dose required to produce a 50% and 95% depression of twitch tension, respectively) of vecuronium in patients given total intravenous anesthesia (n = 24) were 24 (22-27, 95% confidence limits) and 41 (37-48, 95% confidence limits) micrograms/kg, respectively, and in the control group (n = 24), 20 (17-24) and 39 (34-37) micrograms/kg, respectively. The onset of action of an 80-micrograms/kg dose (2 x ED95) of vecuronium was 3.6 +/- 1.2 and 4.1 +/- 1.7 min (mean +/- SD), in the propofol (n = 10) and control (n = 10) groups, respectively. The respective times to recovery of the twitch height to 25% of control and the recovery indices (25%-75% recovery of twitch height) in the propofol versus control groups were 28.3 +/- 6.6 and 28.0 +/- 1.7 min and 13.3 +/- 6.8 and 15.4 +/- 11.9 min, respectively. There were no significant differences in any of the measured variables between the propofol and control groups, indicating the lack of any interaction between propofol and vecuronium.

Adult↗
PubMed1992

Newer neuromuscular blocking drugs. An overview of their clinical pharmacology and therapeutic use.

Four new nondepolarising muscle relaxants, pipecuronium bromide, doxacurium chloride, mivacurium chloride and Org 9426 (rocuronium) offer alternatives to the established agents atracurium besilate and vecuronium bromide. Pipecuronium and Org 9426 are steroidal compounds, the latter being a monoquaternary agent, whereas doxacurium and mivacurium are bisquaternary benzylisoquinolinium compounds. Pipecuronium and doxacurium have a relatively slow onset and a long duration of action. Pipecuronium produces maximum block in 3 to 6 min when given in a dose of 45 to 80 micrograms/kg, and a duration of clinical relaxation of between 40 and 110 min. Doxacurium is more potent, but is the least rapid and the longest acting relaxant currently available. When administered in doses of 37 to 80 micrograms/kg, it produces maximum block within 3.5 to 10 min, with a duration of clinical relaxation of 77 to 164 min. The advantage of both pipecuronium and doxacurium is their cardiovascular stability. Both agents are primarily eliminated via the kidneys and both have now been licensed for use in the US. Mivacurium is a muscle relaxant with a short duration of action. When administered in doses of 0.1 to 0.25 mg/kg it produces maximum block in 2 to 4 min, but the duration of clinical relaxation is less than 20 min. Higher doses which could induce a faster neuromuscular block are unfortunately associated with some histamine liberation. The drug is metabolised by plasma cholinesterase. Mivacurium has also been licensed for use in the US. Org 9426 is an agent with a rapid onset but an intermediate duration of action. A dose of 0.5 to 0.6 mg/kg induces maximum block in about 1.5 min and has a duration of clinical relaxation of about 30 min. The rapid onset of effect could be useful for early intubation as an alternative to suxamethonium chloride. However, much more clinical experience is needed with this agent, particularly with regard to duration of action of larger doses and occurrence of side effects. The drug is mainly eliminated via the liver.

Aging↗
PubMed1991

Continuous vecuronium infusion for prolonged muscle relaxation in children.

Facilitation of mechanical ventilation of the lungs using an infusion of vecuronium in 11 infants and children and four neonates in an intensive care unit is described. A loading dose of vecuronium of 0.1 mg.kg-1 was followed by an infusion at an initial rate of 0.1 mg.kg-1.hr-1. The infusion rate was adjusted to maintain a neuromuscular block of approximately 90% as assessed by the presence of one response to a train-of-four stimulation. The duration of the infusions varied from 9.5 to 179 hr. The mean dose of vecuronium administered was 0.14 mg.kg-1.hr-1 (+/- 0.05, SD) in the children and 0.11 mg.kg-1.hr-1 (+/- 0.05) in the neonates. Mean recovery times from the time of stopping the infusion until absence of apparent fade in response to tetanic stimulation were 51.7 (+/- 17.6) and 46.8 (+/- 16.5) min for the children and neonates respectively. No adverse cardiovascular or toxic effects were noted. This technique of vecuronium infusion to facilitate mechanical ventilation of the lungs is feasible and satisfactory in clinical use.

Female↗
PubMed1991

Effect of H2-receptor antagonist pretreatment on vecuronium- and atracurium-induced neuromuscular block.

Seventy-two patients were studied in a double-blind randomized controlled design to assess the effects of oral administration of cimetidine 400 mg, ranitidine 150 mg or placebo 90 min before anaesthesia on the neuromuscular blocking effects of atracurium 0.45 mg kg-1 or vecuronium 0.08 mg kg-1. The times to reappearance of T1 (first response in the train-of-four stimulation) and its recovery to 25% of control were 22.5 (SD) 5.2 and 30 (7.1) min, 30 (10) and 43 (15.4) min, and 25.8 (4.1) and 34 (6.2) min, respectively in the vecuronium groups pretreated with placebo, cimetidine and ranitidine, the times following cimetidine pretreatment being prolonged significantly (P less than 0.05). The respective recovery indices (times for 25-75% recovery of T1) in these three groups were 11.0 (3.5), 17.4 (6.8) and 13.0 (3.9) min. There were no significant differences in any of the variables following ranitidine pretreatment and either neuromuscular blocker or following cimetidine pretreatment and atracurium.

Administration, Oral↗
PubMed1991

Pathogenesis of suxamethonium-induced muscle damage in the biventer cervicis muscle in the chick.

Muscle damage induced by suxamethonium, and the influence of halothane on it, has been examined by measuring the efflux of creatine kinase (CK) in the biventer cervicis muscle of the chick. Whereas halothane and suxamethonium alone did not increase the enzyme efflux significantly, the combination of the two was associated with significant increase in the concentration of CK in the bathing medium by 59-157%. The increase in CK was prevented by adding chlorpromazine 100 mumol litre-1 to the medium, suggesting the involvement of phospholipases in the pathogenesis of suxamethonium-induced muscle damage.

Animals↗
PubMed1991

A comparison of different pre-oxygenation techniques in the elderly.

The efficacy of five different techniques of pre-oxygenation before a modified rapid intubation sequence was assessed, using oxygen saturation measurement, in patients aged over 65 years. Twenty patients in each group were pre-oxygenated using four deep breaths or normal tidal breathing for 1, 2, 3, or 4 minutes. The acceptable period of apnoea was defined as the time taken to desaturate to 93%. The mean times (SD) taken to reach this end-point were 3.7 (1.6), 4.1 (1.2), 5.4 (1.7), 5.4 (1.4) and 5.2 (1.7) minutes respectively. The apnoea times with 2, 3 and 4 minutes pre-oxygenation were not significantly different from each other but were significantly longer than after four deep breaths and 1 minute. It is concluded that a pre-oxygenation period of at least 2 minutes should be employed in the elderly before a rapid sequence induction.

Aged↗
PubMed1991

Comparison of the haemodynamic effects of pipecuronium and pancuronium during fentanyl anaesthesia.

Haemodynamic variables were measured following administration of pipecuronium 70 micrograms.kg-1 and pancuronium 90 micrograms.kg-1 (approximately equivalent to 1.5 x ED95) in patients anaesthetised with fentanyl 50 micrograms.kg-1 and scheduled to undergo coronary artery bypass grafting. There were significant increases in heart rate (22%), mean arterial pressure (10%), cardiac index (16%), and the rate pressure product (35%) following administration of pancuronium. The absolute values of these parameters were, however, within acceptable clinical limits. Administration of pipecuronium produced minimal and insignificant changes in these parameters. Other measured or derived indices showed only small changes with both agents and these were generally insignificant. There were no incidences of significant bradycardia following pipecuronium administration. The results from the present study suggest that pipecuronium would have advantages for use in patients with significant cardiovascular disease.

Androstane-3,17-diol↗
PubMed1991

Preanaesthetic medication: a survey of current usage.

A survey has been carried out amongst the UK based members of the Association of Anaesthetists of Great Britain and Ireland regarding their practice of premedication. Ninety-three per cent of respondents (reply rate 51.7%) used sedative-hypnotic premedication routinely in adults and 84% in children. However, anticholinergic premedication was used by only 36% in adults and 56% in children. Temazepam was the most frequently used sedative premedicant in adults and trimeprazine in children. Atropine and hyoscine were the most frequently used anticholinergic drugs. The main reasons for using sedative-hypnotic premedication were allaying anxiety and providing sedation. The main reasons for using anticholinergic drugs were drying of secretions and protection against vagal overactivity. This survey concludes that while sedative-hypnotic premedication continues to be used in the majority of patients with oral benzodiazepines the most frequently used drugs, the use of anti-cholinergic premedication continues to decline.

Ambulatory Surgical Procedures↗
PubMed1991

Neuromuscular effects of pipecuronium bromide.

The neuromuscular effects of pipecuronium bromide have been evaluated in 90 adult patients anaesthetized with thiopentone, nitrous oxide in oxygen and intravenous fentanyl with or without halothane. Eighty patients received pipecuronium 45 micrograms kg-1 and the remaining ten 70 micrograms kg-1. A separate group of 10 patients received pancuronium in a dose of 60 micrograms kg-1 (equipotent to pipecuronium 45 micrograms kg-1). Neuromuscular block was measured using a single-twitch or train-of-four mode of stimulation. The time to onset of maximum block with pipecuronium 45 micrograms kg-1 varied between 3.5 and 5.7 min depending on the mode of stimulation and the anaesthetic technique used. The time to 25% recovery of this dose varied between 41 and 54 min. The recovery index (time from 25 to 75% recovery) averaged 29 min. These values were generally similar in the group receiving pancuronium 60 micrograms kg-1. The time to onset of complete block with 70 micrograms kg-1 of pipecuronium averaged 2.5 min and the duration to 25% recovery 95 min. There were no significant changes in heart rate and arterial pressure with the use of pipecuronium. The results show pipecuronium to be a drug resembling pancuronium in its neuromuscular effects when used in equipotent doses.

Adult↗