Mortality in ITU patients receiving neuromuscular blocking drugs.
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Critical Care↗
Biomedical subjects
J M Hunter
Publications and source records attributed to J M Hunter.
Relationship between volume of distribution of atracurium and body weight.
We have determined the central and steady state volumes of distribution of atracurium 0.25 mg kg-1 in 41 healthy adult patients. Volume of distribution, corrected for body weight (ml kg-1); correlated negatively with body weight (r = -0.612 for central volume of distribution; r = -0.737 for the steady state volume of distribution). When expressed as an absolute volume, neither central nor steady state volume of distribution correlated significantly with body weight (r = 0.120 and r = 0.131, respectively). These data cast doubt upon the necessity for the dose of atracurium to be related to body weight in the healthy adult population.
Adolescent↗
Pharmacodynamics of mivacurium chloride in patients with hepatic cirrhosis.
Ten healthy patients and 25 patients with cirrhosis of the liver (10 Child's A, 10 Child's B and 5 Child's C) received a bolus dose of mivacurium chloride 150 micrograms kg-1. The electromyographic response was monitored throughout anaesthesia until recovery of the first twitch of the train-of-four (TOF) (T1/T0) to at least 85% and the TOF ratio (T4:T1) to at least 80%. There was no significant difference between the two groups in the onset of neuromuscular block, but recovery was prolonged in the cirrhotic group compared with the healthy patients (respective mean times to recovery of T1/T0: to 5% = 20.2 vs 11.2 min (P < 0.05); to 10% = 23.8 vs 13.4 min (P < 0.005); to 25% = 28.4 vs 16.6 min (P < 0.005); to 50% = 41.1 vs 20.1 min (P < 0.005); to 75% = 43.8 vs 24.9 min (P < 0.005). Recovery of T4:T1 to 70% = 48.1 vs 27.4 min (P < 0.005)). Recovery was most prolonged in the Child's C patients. Mean plasma cholinesterase activity was less in the cirrhotic compared with the healthy group (mean 582 (SD 254) iu litre-1 vs 1125 (303) iu litre-1) (P < 0.001) and there was a significant negative correlation between plasma cholinesterase activity and all the indices of recovery (P < 0.001 for all except recovery index (P < 0.01)). We conclude that patients with hepatic cirrhosis may be sensitive to mivacurium, which could be explained, at least in part, by the lesser plasma cholinesterase activity.
Adult↗
Histamine release and neuromuscular blocking drugs.
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Adult↗
Elephantiasis: a disease of development in north east Ghana.
A reconnaissance survey for the presence of lymphatic filariasis is made in 41 chiefdoms of north east Ghana. Four disease levels are identified culminating in hyperendemic disease foci associated with two Government-introduced rice irrigation projects. Attention is also drawn to the disease effects of small village dams. Multiple concurrent infections are noted. Within the most stricken irrigation villages, aspects of concealment, stigma and marriage are considered. Failure to control lymphatic filariasis has led to hospital avoidance and neglect of the disease jointly by patients, physicians and nurses. Culpability rests with the irrigation authority and Government health services. An outline is given of possible measures for disease control. A multisectoral policy of 'prevention before development' is strongly advocated.
Agriculture↗
Use of mivacurium chloride by constant infusion in the anephric patient.
Twenty anephric and 20 healthy patients received a bolus dose of mivacurium 150 micrograms kg-1. When the first EMG response (T1) of the train-of-four had recovered to 5% of control (T0), an infusion of mivacurium 10 micrograms kg-1 min-1 was started and adjusted to keep T1 at 5%. Ten patients in each group were given neostigmine 35 micrograms kg-1 when the infusion was stopped when T1/T0 had recovered to 20%; in the others recovery was spontaneous. After the bolus dose of mivacurium, mean (SD) depression of T1 was greater in the anephric group than in the normal group (98.4 (3.5) vs 96.8 (4.4)%; P less than 0.01) and recovery of T1/T0 to 5% was slower (15.3 (6.9) vs 9.8 (3.5) min; P less than 0.01). Anephric patients required a slower infusion rate (6.3 (1.9) vs 10.4 (2.8) micrograms kg-1 min-1; P less than 0.001). Neostigmine hastened recovery of both T1/T0 and T4/T1 in both groups. Spontaneous recovery of T1/T0 (from 25% to 75%) after the infusion was also slower in anephric patients (12.2 (8.2) vs 7.7 (1.2) min; P less than 0.05). Plasma cholinesterase activity was less in the anephric group (785 (207) vs 943 (217) iu litre-1; P less than 0.05) and there was a (negative) correlation overall between cholinesterase activity and time to 5% recovery of T1/T0 after the bolus dose (r = -0.42; P less than 0.02). We conclude that patients with chronic renal failure may require a reduced dose of mivacurium.
Adult↗
A new four-parameter threshold model for the plasma atracurium concentration-response relationship.
The plasma concentration of atracurium and the electromyographic depression of the first response of the train-of-four (T1:T0) were measured during and after recovery from a 10-min infusion of atracurium 0.25 mg kg-1 in 14 patients anaesthetized with 66% nitrous oxide and 0.9% isoflurane (end-tidal) in oxygen. A standard pharmaco-dynamic model was fitted to the data; a small but consistent discrepancy was found between the time and rate of onset of depression of the ratio T1:T0 and the predictions of the standard biophase model of best fit to the data. This discrepancy is reduced by the inclusion of a threshold term (CPss theta) in the model to represent the greatest steady state plasma concentration which would just fail to evoke an effect. The values of CPss theta correlated significantly with the values of CPss50 (r = +0.627; P less than 0.02). The estimates of CPss50 and keo from the two models are very similar; the estimate of gamma, the slope of the concentration-response curve, was less in the threshold model. The relationship of the present threshold model to existing knowledge of neuromuscular physiology is discussed.
Adult↗
Dependence of the neuromuscular blocking effect of atracurium upon its disposition.
We have assessed the profiles of plasma concentration of atracurium and its neuromuscular blocking effect on the first response of the train-of-four measured by electromyography after a short infusion of atracurium 0.25 mg kg-1, in 38 patients anaesthetized by one of three techniques. Measures of the temporal profile of neuromuscular block were found to correlate with pharmacokinetic variables. When anaesthetic technique was taken into account in a multivariate model, the time to onset of 10% deprssion of T1:T0 correlated positively with the central volume of distribution (P less than 0.05). The change in T1:T0 during the 1 min after 10% depression, and the logit of maximum depression were both correlated negatively with the central volume of distribution (P less than 0.05 and P less than 0.01, respectively). Both the times to 20% and 50% recovery of T1:T0 correlated strongly negatively with clearance (P less than 0.0001 for both measures). The findings support the conclusion that the effect of atracurium is dependent upon its disposition.
Adult↗
Relationship of the train-of-four ratio to plasma atracurium concentration.
The electromyographic response to a short infusion of atracurium 0.25 mg kg-1 was recorded using the train-of-four (TOF) technique, and the plasma atracurium concentration profile measured, in 10 healthy patients. The TOF ratio (T4:T1) was depressed over a time course which did not conform to the predictions of an effect compartment model; the fit of such a model, when possible, was associated with large residual errors. In contrast, the absolute height of the fourth response of the TOF (T4:T0) may be fitted by a standard effect compartment model with smaller errors. This residual error was reduced further on fitting a threshold effect compartment model to the data set T4:T0. The parameter values of such a model were related closely to those for the first response (T1:T0). The kinetics of the effect compartments for the first and fourth response of the TOF were similar, whilst the CPss50 for the fourth response was approximately 67% that for the first response.
Adolescent↗
Effect of age, sex and anaesthetic technique on the pharmacokinetics of atracurium.
We have defined the pharmacokinetics of atracurium besylate 0.25 mg kg-1 in 41 patients anaesthetized with 0.9% isoflurane end-tidal, 0.5% halothane end-tidal or midazolam 3-10 mg as a supplement to 66% nitrous oxide in oxygen. The pharmacokinetic profile was affected by age, sex and anaesthetic technique. Advancing age was associated with a reduced clearance and a longer elimination half-time; clearance was greater and elimination half-time was shorter in males than in females. Clearance was also greater in patients anaesthetized with isoflurane than with the two other techniques. Age, sex and anaesthetic technique did not significantly affect the volume of distribution.
Adolescent↗
Biomechanics of pulley reconstruction.
The biomechanics of the reconstructed flexor retinacular pulley system are poorly defined. We used a mathematical theoretical model, confirmed by a cadaver model, and a clinical radiographic model to evaluate a variety of different joint and pulley combinations. We examined twenty-four sets of radiographs of 12 fingers in 9 patients for whom excursion was measured and predicted by the mathematical model. The 30 pulley combinations evaluated in the in vitro cadaver model showed statistical correlation with the biomechanical mathematical model. Recommendations of clinical application on the basis of this information include the following: (1) Two pulleys should be placed, one proximal and one distal to each joint. (2) These two pulleys should be balanced about the joint axis both in distance from the axis and in pulley height. (3) They should be positioned at the edge of the flare of the metaphysis. (4) The three individual joints can be balanced, one to another, by maintaining minimal bowstringing at all three joints. In this way, the relative excursion at the joint and torque at the joint will be maintained in a physiological ratio as close to normal as possible.
Biomechanical Phenomena↗
Transplacental distribution of atracurium, laudanosine and monoquaternary alcohol during elective caesarean section.
Maternal venous (MV), umbilical venous (UV) and umbilical arterial (UA) blood samples were obtained for assay of atracurium, laudanosine and monoquaternary alcohol concentrations in 22 healthy patients undergoing elective Caesarean section under general anaesthesia. At delivery (at a mean time of 8.2 min after atracurium 0.3 mg kg-1), the mean UV concentrations were 103 ng ml-1 (range 44-189 ng ml-1) for atracurium, 26 ng ml-1 (range 6-60 ng ml-1) for laudanosine and 59 ng ml-1 (range 21-148 ng ml-1) for monoquaternary alcohol. The ratios of UV:MV, UA:MV and UA:UV blood concentrations were related positively to time since injection of atracurium for all three substances (P less than 0.01 in each instance). The UV:MV ratio at delivery was greatest for laudanosine: mean 19.4% (range 1-35%), compared with 7% (range 2-21%) for atracurium and 10% (range 0-15%) for monoquaternary alcohol. These low values confirm that, although atracurium crosses the placental barrier and its metabolites may be found in the fetus, the drug is safe to use during Caesarean section.
Adolescent↗
Pharmacokinetics of atracurium.
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Atracurium↗
Resistance to non-depolarizing neuromuscular blocking agents.
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Animals↗
Clearance of atracurium and laudanosine in the urine and by continuous venovenous haemofiltration.
We have measured the steady state urinary clearances of atracurium, given by constant infusion, and laudanosine in eight patients undergoing artificial ventilation; all had normal renal function (mean creatinine clearance 81 ml min-1). Mean (SD) urinary clearance of atracurium was 0.55 (0.5) ml kg-1 min-1; that of laudanosine was 0.33 (0.2) ml kg-1 min-1. Simultaneous plasma clearances were 7.1 (1.4) ml kg-1 min-1 and 3.8 (1.5) ml kg-1 min-1, respectively. Notional haemofiltration clearances of the two substances were measured also in seven critically ill patients with renal and respiratory failure undergoing continuous venovenous haemofiltration. Mean (SD) clearances of atracurium and laudanosine in the haemofiltrate fluid were 0.11 (0.06) ml kg-1 min-1 and 0.09 (0.02) ml kg-1 min-1, respectively whilst plasma clearances were atracurium 6.7 (1.8) ml kg-1 min-1 and laudanosine 4.5 (1.8) ml kg-1 min-1. There were no significant differences between the plasma clearances of the drugs in the two groups, despite the difference in severity of sickness. Urinary clearance rates of atracurium and laudanosine were approximately 8 and 9% of that in the plasma, but the haemofiltration clearance of both substances was only 2%.
Acute Kidney Injury↗
An assessment of the Cerebrotrac 2500 for continuous monitoring of cerebral function in the intensive care unit.
Experience of the use of the Cerebrotrac 2500 EEG monitor in 17 patients subjected to artificial ventilation in an intensive care unit is reported; seven were receiving continuous sedation with morphine, midazolam and propofol singly or in combination and 10 received both sedation and the neuromuscular blocking agent, atracurium. The processed EEG patterns could not be precisely correlated with a standard clinical scoring system but were useful in determining the adequacy of sedation, particularly when a muscle relaxant was used. The monitor also shows considerable promise in the management of the paralysed patient with widespread convulsive activity in whom ischaemic brain damage may be occurring from epileptiform activity in the absence of any clinical manifestation. The ability to detect cerebral irritability or isolated epileptiform discharges using this apparatus is, however, questionable. The equipment was easy to use and robust; the running costs were 9.5p per hour.
Atracurium↗
The pharmacodynamics of alcuronium in the elderly.
Alcuronium (0.2 mg/kg) was given to 12 elderly patients, mean age 77 years (range 70-88 years) and 12 young patients, mean age 24 years (range 18-32 years) undergoing general anaesthesia. A compound muscle action potential was monitored continuously throughout anaesthesia, using an electromyograph and the train-of-four twitch technique. The rate of onset and maximum block achieved were similar in both the young and elderly patients, as were the times to 20% recovery of the first twitch compared with control (T1 : T0) and fourth twitch compared with the first, (T4 : T1). In contrast, the time to 70% recovery of T1 : T0 was significantly prolonged in the elderly (138 as compared with 89 minutes: p less than 0.01) as was the recovery index (25-75%) for T1 : T0 (95 as compared with 46 minutes: p less than 0.01) and the time to 70% recovery of T4 : T1 (181 as compared with 131 minutes: p less than 0.05). The recovery curves for T1 : T0 and T4 : T1 were also significantly different in the elderly from the young group (p less than 0.01 in both instances). These results show that the duration of action of alcuronium is significantly prolonged in the elderly.
Adolescent↗
Dacron collateral ligament reconstruction with proximal interphalangeal joint arthroplasty.
A porous Dacron (Phoenix Bioengineering, Bridgeport, PA) tendon is described for collateral ligament reconstruction and augumentation with proximal interphalangeal joint implant arthroplasty. Eight cases with a minimum follow-up of 15 months are reviewed. Diagnoses include posttraumatic arthritis and osteoarthritis, as well as rheumatoid arthritis. The porous Dacron tendon is constructed as a collagen-like weave. It has been useful in patients who have insufficient local tissue to achieve lateral proximal interphalangeal joint stability. In selected cases, it can obviate the need for a tendon graft and provide an alternative to arthrodesis.
Adult↗