Biomedical subjects
Publications and source records attributed to H H Ali.
We describe the anaesthetic management of a patient with a rare form of muscular dystrophy (Facioscapulohumeral or Landouzy-Dejerine type). Anaesthesia and controlled ventilation using alfentanil-nitrous oxide and atracurium was satisfactory. In this patient, sensitivity to atracurium was found to be similar to that of the normal population, but more rapid recovery was observed.
The dose-effect relationship of mivacurium chloride on arterial blood pressure, heart rate, and plasma histamine was determined in 97 consenting ASA physical status I-II patients receiving nitrous oxide-oxygen-opiate-barbiturate anesthesia. In the absence of surgical stimulation during steady state anesthetic conditions with controlled ventilation, average maximum change in tachograph-counted heart rate was 7% or less after 10-15-s injection of mivacurium at all doses from 0.03 to 0.30 mg/kg. Average peak change in mean arterial pressure measured via radial arterial catheter was 7% or less after all doses from 0.03 to 0.15 mg/kg. Transient (0.2-4.5 min) decreases in arterial blood pressure were noted after 10-15-s injection in some patients at 0.20, 0.25, and 0.30 mg/kg. When they occurred, these changes were usually accompanied by facial erythema lasting 2-5 min and were correlated with increases in plasma histamine level (P less than 0.001). Facial erythema, decrease in blood pressure, and elevation of histamine level were all accentuated by increasing the dose of mivacurium and by more rapid injection of the drug. For example, mean blood pressure decreased an average of 13% after injection of mivacurium 0.25 mg/kg over 10-15 s. In contrast, during administration over 30 and 60 s of this dose, arterial pressure decreased 7.6 and 1.5%, respectively (P less than 0.001, 10-15 s vs. 60-s injection). Average peak histamine level, which increased to 132% of control after administration of 0.25 mg/kg over 10-15 s, did not change after injection over 60 s.(ABSTRACT TRUNCATED AT 250 WORDS)
Clinical monitoring of neuromuscular function can be accomplished by either measuring the evoked mechanical or EMG response of a skeletal muscle via an accessible motor nerve. The pattern of motor nerve stimulation varies from supramaximal single repeated stimuli at a specified frequency to tetanic stimulation, posttetanic single stimuli at the pretetanic frequency, and train-of-four stimuli at 2 Hz. The response to relaxants is unpredictable in the population at large and more so in pathologic states. This makes monitoring of the muscle response to motor nerve stimulation extremely valuable and helpful. The train-of-four technique of measurement has proved to be valuable not only as a reliable clinical tool to measure the response to relaxants and monitoring recovery, but also as a research tool for studies of old and new neuromuscular blocking drugs. Evoked responses and clinical criteria for adequate recovery from muscle relaxants should complement each other. The more criteria fulfilled, the better and safer the conclusion that the patient has recovered from clinical neuromuscular blockade.
Mivacurium chloride (BW B1090U) is a new, short-acting non-depolarizing neuromuscular blocking agent. It is a synthetic bis-benzylisoquinolinium diester, which is hydrolysed rapidly by plasma cholinesterase. This study compares mivacurium, atracurium and vecuronium by continuous i.v. infusion. The duration of mivacurium infusion ranged from 29.5 to 286 min. The steady state infusion rates necessary to maintain 95 (SEM 4)% twitch suppression were: mivacurium 8.3 (0.7) micrograms kg-1 min-1; atracurium 7.9 (0.4) micrograms kg-1 min-1; vecuronium 1.2 (0.3) micrograms kg-1 min-1. Following infusions of mivacurium, various recovery times (for example: 25-75%, 6.9 (0.3) min; 25-95%, 11.0 (0.4) min; 5-95% 14.5 (0.4) min) did not differ significantly from those following single bolus doses. Recovery times following cessation of mivacarium infusions were approximately 50% of those for equivalent durations of infusion of atracurium (10.9 (0.3) min for 25-75% recovery and 26.6 (0.4) min for 5-95% recovery). For vecuronium, corresponding recovery times were 13.8 (0.9) and 32.0 (1.2) min, respectively. Comparative recovery times for mivacurium were 40-50% of those for vecuronium. There was a significant correlation between the infusion rate of mivacurium required to maintain 95% twitch depression and the plasma cholinesterase activity of individual subjects.
Mivacurium chloride (BW B1090U), a bis-benzylisoquinolinium diester compound, was found to undergo hydrolysis in vitro by purified human plasma cholinesterase in a pH-stat titrator at 88% of the rate of succinylcholine at pH 7.4, 37 degrees C and 5 microM substrate concentration. In 72 consenting ASA Physical Status I-II patients receiving nitrous oxide/oxygen-narcotic-thiopental anesthesia, the neuromuscular blocking effect of mivacurium was assessed following bolus doses from 0.03 to 0.30 mg/kg, as well as during and following continuous infusions from 35 to 324 min in length. The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.08 mg/kg. At 0.1 mg/kg, 96% block developed, onset to maximum block required 3.8 +/- 0.5 min, and recovery to 95% twitch height occurred 24.5 +/- 1.6 (SE) min after injection. At 0.25 mg/kg, onset was 2.3 +/- 0.3 min; 95% recovery developed within 30.4 +/- 2.2 min, an increase in duration of action of only 24% versus 150% higher dosage. Comparative recovery indices from 5 to 95% or from 25 to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.3 mg/kg (range 12.9 to 14.7 and 6.6 to 7.2 min, respectively). In 38 patients who received mivacurium by continuous infusion (duration 88.1 +/- 7.1/47.1 min, SE/SD) for maintenance of 95 +/- 4% twitch inhibition, the mean 5-95% and 25-75% recovery indices after discontinuation of infusion were 14.4 +/- 0.6 and 6.5 +/- 0.3 min (P greater than 0.5 vs. all single bolus doses). The train-of-four (T4) ratio, within 2.6 +/- 0.5 min after 95% twitch recovery following bolus doses, averaged 79.5 +/- 1.8% (n = 32). Similarly, after discontinuation of infusions, the T4 ratio reached 73.4 +/- 1.9% within 3.4 +/- 1.9 min after 95% twitch recovery (n = 33). Antagonism of residual block was seldom indicated, but, to test ease of reversal, eight patients electively received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at 67 to 93 (76.6 +/- 3.5) % block. Twitch returned to 95% of control within 4.5 to 9.5 (6.3 +/- 0.5) min after neostigmine. Mivacurium may offer increased versatility in providing clinical muscle relaxation in a variety of situations. Further studies seem appropriate.
Doxacurium chloride (BW A938U) is a bis-quaternary benzylisoquinolinium diester nondepolarizing neuromuscular blocking compound that is minimally hydrolyzed by human plasma cholinesterase. The effect of bolus doses of doxacurium ranging from 10 to 80 micrograms/kg were studied in 81 consenting ASA physical status I and II patients anesthetized with nitrous oxide-oxygen-fentanyl-thiopental. The neuromuscular and cardiovascular effects of doxacurium were compared with those of eight patients receiving 100 micrograms/kg of pancuronium receiving identical anesthesia. The calculated ED95 for evoked twitch inhibition of the adductor pollicis at 0.15 Hz was 30 micrograms/kg. At 1.3 times the ED95 dose of doxacurium, recovery times to 5% and 25% of control twitch height were 59.2 +/- 4.1 (n = 23 of 26) and 75.7 +/- 5.6 (n = 23 of 26) min respectively. For pancuronium comparable recovery times were 81.7 +/- 10.3 (n = 8 of 8) and 83.0 +/- 8.4 (n = 5 of 8) min. Residual doxacurium blockade was readily antagonized by neostigmine. No dose-related effect on heart rate or mean arterial pressure was seen with doxacurium at doses up to and including 2.7 times the ED95 (80 micrograms/kg). Doxacurium administration did not result in any elevation of plasma histamine at doses up to and including 2.7 times the ED95. In this study doxacurium appears to be a long-acting nondepolarizing relaxant with readily reversible neuromuscular blocking effects and devoid of cardiovascular effects. This profile offers clinical advantages over current long-acting agents and further clinical trials seem appropriate.
Moderate to deep (67-99% single twitch depression) pancuronium-induced neuromuscular blockade was antagonised with neostigmine (30 micrograms/kg, 60 micrograms/kg, or 80 micrograms/kg) in combination with glycopyrronium. Twenty-seven patients were reversed from 91%-99% twitch depression. Recovery of the first twitch of a train-of-four to 95% of control twitch took at least 20 minutes with neostigmine 30 micrograms/kg. The higher doses were significantly faster (60 micrograms/kg p less than 0.05, 80 micrograms/kg p less than 0.01) and took 15.8 and 14.8 minutes respectively. Reversal to a train of four ratio of 0.75 was not consistently achieved in under 30 minutes with any dose of neostigmine. Nineteen patients were antagonised from a 67%-80% depression of first twitch and in all but two recovery to 95% of control took under 10 minutes. To achieve a train of four ratio of 0.75 took less than 12.5 minutes except in three patients, two of whom, both given neostigmine 30 micrograms/kg, took longer than 20 minutes. Neostigmine 60 micrograms/kg produced as rapid a degree of antagonism as 80 micrograms/kg. Heart rates after reversal decreased gradually in all groups, although the decrease was initially greater in the low dose neostigmine (30 micrograms/kg) group. A fixed 5:1 ratio of neostigmine and glycopyrronium will usually antagonise a moderate (70%-80%) pancuronium block to a train of four of greater than 75% within 12.5 minutes if at least 60 micrograms/kg of neostigmine is administered. More than 30 minutes may be required for reversal whatever the dose of neostigmine, for antagonism from greater than 90% twitch depression.
Three cases of azathioprine-induced complex of liver diseases are described, and their light microscopy and ultrastructural findings are detailed. It was found that the drug produces a spectrum of pathological changes that include veno-occlusive disease, peliosis hepatis, perisinusoidal (Disse space) fibrosis, and nodular regenerative hyperplasia. It is suggested that the explanation for this spectrum is the variable degree of damage to the endothelial cells lining the sinusoids and the terminal hepatic venules. This spectrum is seen almost exclusively in male patients with renal transplant.
Monitoring neuromuscular transmission provides valuable information to the anesthesiologist. The acquisition of relevant data contributes to a more predictable and rational approach to the use of muscle relaxants and assures improved patient care during and in the immediate postoperative period. Clinical noninvasive criteria such as the presence or absence of diplopia and or ptosis, the ability to open the eyes widely, protrude the tongue or swallow, measurement of hand grip strength or head lift or assessment of the vital capacity are limited to awake and cooperative patients. Measurement of inspiratory force and tidal volume can be evaluated in anesthetized patients breathing spontaneously. Central depressant drugs tend to depress these respiratory parameters. Accordingly, the assumption that relaxants are responsible for respiratory depression at the end of an anesthetic can only be documented when impairment of neuromuscular transmission can be demonstrated. The most reliable method of measuring neuromuscular function is to stimulate an accessible peripheral motor nerve and measurement of the evoked response of the skeletal muscle or muscles innervated by the stimulated motor nerve. The evoked muscle response depends on the pattern of motor nerve stimulation: Single twitch stimuli at a defined frequency, tetanic stimulation, posttetanic single twitch stimulation or train-of-four stimulation. The response to these different modes of stimulation can be assessed either mechanically (evoked tension response) or electrically (evoked electromyography: EMG or integrated EMG). These response criteria can be employed either individually or combined to evaluate the response to muscle relaxants and to assess the adequacy of recovery from neuromuscular blockade.
The safety and efficacy of atracurium 0.8 mg kg-1 was determined in healthy patients with particular attention to the speed of onset of blockade, and to changes in haemodynamic variables. Atracurium 0.8 mg kg-1 had a shorter onset time than atracurium 0.5 mg kg-1, and satisfactory intubating conditions were achieved earlier. "Priming" produced no significant improvement in onset time or intubating conditions. Onset times were significantly shorter with nitrous oxide-opioid anaesthesia than following thiopentone alone. Although a 0.8-mg kg-1 bolus resulted in a significant reduction in mean arterial pressure to 75% of control and was associated with a significant increase in plasma histamine concentrations, this response could be prevented by injecting the drug over 75 s. "Priming" or a 30-s injection produced no haemodynamic protection. The protection achieved by pretreatment with anti-histamines was incomplete: mean arterial pressure decreased to 83% of control.
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We compared the pharmacokinetics and pharmacodynamics of atracurium in eight normal and eight anephric patients during isoflurane anesthesia. Plasma concentrations were measured by high performance liquid chromatography after a single injection of 0.5 mg/kg, and neuromuscular effects were evaluated by the single twitch method. With regard to pharmacokinetic or pharmacodynamic parameters, we found no statistically significant differences between normal and anephric patients. We conclude that during isoflurane anesthesia, anephric patients distribute and eliminate atracurium much as normal patients do.
This study was designed to determine the effects of a rapid bolus dose of atracurium 0.6 mg kg-1 on arterial pressure, heart rate and plasma histamine concentration (n = 9), and to compare these values with those obtained by (a) giving the same dose of atracurium slowly (over 75 s) (n = 9), or (b) pre-treating with H1- and H2- antagonists (n = 9). The rapid (5-s) bolus dose of atracurium i.v. resulted in a significant increase in plasma histamine concentration (P less than 0.05) and was associated with a decrease in mean arterial pressure and an increase in heart rate. Administering the same dose of atracurium slowly (over 75 s) prevented the increase in plasma histamine concentration, and abolished the subsequent haemodynamic response. Pretreatment with cimetidine 4 mg kg-1 i.v. and chlorpheniramine 0.1 mg kg-1 i.v. abolished the haemodynamic response despite a moderate increase in histamine concentration (0.1 greater than P greater than 0.05).
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Cumulative dose-response curves were constructed for pancuronium, metocurine, d-tubocurarine and gallamine in 56 children anaesthetized with thiopentone, N2O/O2 and narcotic. The dose response curves of the four relaxants did not deviate significantly from parallelism. The effective dose causing 95 per cent depression of the twitch at 0.1 Hz was: pancuronium 0.08 mg X kg-1, metocurine 0.34 mg X kg-1, d-tubocurarine 0.6 mg X kg-1, and gallamine 3.4 mg X kg-1. Thus, pancuronium is 40 times more potent than gallamine, while metocurine and d-tubocurarine are seven and four times more potent than gallamine. The recovery of twitch height from 5-25 per cent of control for pancuronium (15.6 +/- 1.7 min) was significantly faster (p less than 0.01) than metocurine (27.3 +/- 1.9 min), d-tubocurarine (32.2 +/- 4.8 min), or gallamine (30 +/- 3.3 min). Compared to studies in adults, the present data indicate that children have a tendency (statistically not significant) to require more relaxant and recover more quickly than adults.
A case of pneumatosis intestinalis studied by light and electron microscopy is presented. The cysts are dilated lymphatic vessels. Abundant fine fatty globules are found in the cysts and in the histiocytes and multinucleated giant cells which line the lymphatics and which are present in the interstitium. The giant cell formation and florid histiocytic reaction are most probably due to leakage of fatty material from the dilated lymphatics.
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