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Biomedical subjects

G H Beemer

Publications and source records attributed to G H Beemer.

15 recordsLinked to original sources

Stability of fentanyl, bupivacaine and adrenaline solutions for extradural infusion.

Fentanyl and bupivacaine were tested for their stability when diluted with 0.9% sodium chloride to 4 micrograms ml-1 and 0.1% respectively, in 100-ml polyvinyl chloride (PVC) bags, alone and in combination, with and without adrenaline 1:200,000. Changes in drug concentration and pH were investigated for 56 days. The combination of fentanyl, bupivacaine and adrenaline was tested under varying environmental conditions of 35 degrees C, 4 degrees C, -18 degrees C, room temperature, darkness and after autoclaving. Fentanyl and bupivacaine were adsorbed onto PVC, resulting in reductions of 12.6% and 9.6% drug mass, respectively, at day 3, but remained stable thereafter. Adrenaline was progressively degraded to a maximum reduction of 37.3% at 35 degrees C by day 56. Solutions containing adrenaline became more acidic over 56 days. Fentanyl and bupivacaine were stable.

Anesthesia, Epidural

Determinants of the reversal time of competitive neuromuscular block by anticholinesterases.

We have assessed, in 200 patients, the determinants of the reversal time of competitive neuromuscular block by anticholinesterase when alcuronium and atracurium neuromuscular block were antagonized by neostigmine 0.04 and 0.08 mg kg-1 and edrophonium 0.5 and 1.0 mg kg-1. A biexponential relationship was found between the reversal time (time from injection of anticholinesterase to a train-of-four ratio of 70%) and the degree of neuromuscular block at reversal (all groups; F ratio, P less than 0.05). Reversal time was determined by two processes: direct antagonism by the anticholinesterase and spontaneous recovery of the neuromuscular blocking agent, with the latter becoming the major determinant at profound levels of neuromuscular block (0-10% of control twitch height). Neostigmine, in the doses studied, appeared to have a higher "ceiling" of neuromuscular block which it completely antagonized, although edrophonium had a more rapid onset of action. The reversal time for alcuronium became progressively longer relative to atracurium as neuromuscular block increased because of the slower spontaneous recovery rate. Avoidance of profound neuromuscular block at the completion of surgery is required to ensure reliable antagonism of the block within 5-10 min by an anticholinesterase. Neostigmine 0.08 mg kg-1 was found to be the most effective agent in antagonizing profound neuromuscular block.

Adult

Pharmacokinetics of atracurium during continuous infusion.

The pharmacokinetics of atracurium were investigated by a model-independent method during continuous infusion under propofol anaesthesia. Following an intubating dose of suxamethonium, atracurium was infused according to a predetermined profile which continually set the infusion rate to maintain stable muscle paralysis and a target steady state plasma concentration when equilibrium between the biophase and plasma had occurred. Atracurium was infused for the first 1 h to maintain a target steady state plasma concentration of 1.0 microgram ml-1. Thereafter, the target plasma concentration was adjusted to maintain 90% muscle paralysis. The maintenance infusion rate required to maintain 90% paralysis was 4.25 (SD) 1.11 micrograms kg-1 min-1, with an estimated steady state plasma concentration of atracurium required to maintain 90% paralysis (Cpss90) of 1.13 (0.24) microgram ml-1. The clearances of atracurium, estimated by the constant infusion rate required to maintain the steady state plasma concentration, at 50-60 min and during estimation of Cpss90 were 3.8 (1.0) and 3.9 (1.1) ml kg-1 min-1 (ns), respectively. The volume of distribution at steady state of atracurium after 1 h of infusion, calculated using the clearance and the area under the plasma concentration-time curve to 1 h, was 130 (50) ml kg-1. These estimates of the pharmacokinetic parameters of atracurium are markedly different from those derived from pharmacokinetic analysis of single bolus dose data. Normalization of the pharmacokinetic parameter estimates by lean body mass decreased interpatient variability and improved precision in comparison with the un-weighted data and normalization by total body weight.

Anesthesia, Intravenous

Pharmacodynamics of atracurium during propofol, thiopentone and opioid anaesthesia.

We have assessed in 20 patients the accuracy and precision of an infusion profile for atracurium, which continually set the infusion rate to maintain stable muscle paralysis and a target steady state plasma concentration, when equilibrium between the biophase and plasma had occurred. Muscle paralysis was stable after 20 min, with a mean absolute drift in muscle paralysis in the succeeding 40 min of 0.13 (SD 0.07)% T1/Tc (height of first twitch/height of control twitch) per min. The plasma samples after 30 min, which were assessed empirically as being in equilibrium with the biophase, had an overall mean bias of 8.0 (SEM 3.7)% (P less than 0.05) and an overall mean absolute prediction error of 16.4 (SEM 2.5)% from the target steady state concentration being delivered by the infusion. The profile was then used to estimate the steady state plasma concentration of atracurium required to maintain 90% paralysis (Cpss90), by manually adjusting the delivered target concentration of the infusion until muscle paralysis was stable at 88-92% inhibition of T1/Tc for 15-20 min, with three plasma samples taken over the next 10 min. Measurements were completed within 60-90 min. The mean Cpss90 of atracurium with propofol was 1.039 (SD 0.224) microgram ml-1 (n = 10), with thiopentone 1.334 (0.378) microgram ml-1 (n = 10), and with opioid anaesthesia 0.915 (0.221) microgram ml-1 (n = 10). These differences in the Cpss90 explain some of the variability in response which occurs with neuromuscular blocking drugs. The technique enables the Cpss90 of a myoneural blocker to be determined by a simple model-independent method.

Adult

Accurate monitoring of neuromuscular blockade using a peripheral nerve stimulator--a review.

For normal anaesthetic practice, monitoring of neuromuscular blockade is best performed by stimulation of the ulnar nerve at the wrist with a peripheral nerve stimulator and evaluation of the response of the thumb. Determination of the initial threshold for stimulation in the awake patient to allow estimation of the current required for supramaximal stimulation is an important set-up procedure to improve accuracy. The degree of paralysis of specific muscle groups such as the diaphragm can be inferred from their sensitivity to neuromuscular blocking agents relative to adductor pollicis. Monitoring with different stimulation patterns allows a wide spectrum of muscle paralyses to be evaluated.

Electric Stimulation

Production of laudanosine following infusion of atracurium in man and its effects on awakening.

Twenty patients were given maximal doses of atracurium or vecuronium by infusion during surgery. Anaesthesia was maintained with an infusion of thiopentone, nitrous oxide and fentanyl. In patients administered atracurium, the plasma laudanosine concentration at cessation of surgery was 0.34 (SD 0.22) micrograms ml-1; there was little tendency to cumulate during operation. A 20% higher arterial concentration of thiopentone was found at awakening in patients given atracurium, suggesting CNS stimulation by laudanosine, although the effect is too modest to be of clinical significance.

Anesthesia Recovery Period

The effect of cardiopulmonary bypass on plasma protein binding of alfentanil.

The effect of cardiopulmonary bypass (CPB) on plasma concentration and protein binding of alfentanil was studied during continuous infusions in five cardiac surgical patients. Patients were given a loading infusion of 10 micrograms.min-1.kg-1 lean body mass (LBM) over 30 s followed by a fixed rate maintenance infusion of 1 microgram.min-1.kg-1 LBM for the duration of surgery. Prior to the commencement of CPB the total plasma alfentanil concentration was 177 micrograms.l-1. This fell to 92 micrograms.l-1 2 min after commencement of CPB and rose to 155 micrograms.l-1 at the end of CPB 2.01 h later. During the same period the unbound fraction of alfentanil rose from 0.16 to 0.35 two min after the start of CPB and fell gradually to 0.22 at the end of CPB. The unbound concentration prior to CPB was 29 micrograms.l-1 and was essentially unchanged by the onset of CPB, being 35 micrograms.l-1 at two min and then 31 micrograms.l-1 at the end of CPB. There was a good correlation between alfentanil bound/unbound concentration ratio and plasma albumin concentration (r = 0.57) and plasma alpha 1-acid glycoprotein concentration (r = 0.80), indicating that the decrease in binding during CPB was due primarily to haemodilution. In assessing the effects of CPB on plasma drug concentrations, it is therefore necessary to monitor unbound as well as total concentrations because the effects on these differ greatly.

Aged

Adverse reactions to atracurium and alcuronium. A prospective surveillance study.

A multicentre prospective surveillance study was undertaken to compare the incidence and severity of adverse reactions attributed to atracurium and alcuronium. Clinical manifestations were used by the anaesthetist to diagnose an adverse reaction (a cutaneous reaction, a greater than 20% change in arterial pressure or heart rate, and bronchospasm). Of the 1956 patients receiving atracurium, 10.1% had adverse reactions compared with 17.9% of the 1425 patients receiving alcuronium (P less than 0.001). There were no longterm sequelae. The atracurium group had a markedly lower incidence of hypotension (3.4% v. 13.7%; P less than 0.0001), but a higher incidence of cutaneous reactions (4.6% v. 2.3%; P less than 0.005) which were not associated with other adverse reactions. There was a low incidence of bronchospasm in both groups (0.2% v. 0.1%).

Adult

An evaluation of eight peripheral nerve stimulators for monitoring neuromuscular blockade.

The features of eight commercially available peripheral nerve stimulators were compared with those evolved as ideal for monitoring neuromuscular blockade. The pulse waveforms were satisfactory except for that delivered by the CIG series 80 nerve/muscle stimulator. The error in timing of the stimulation patterns was up to 60% in the Professional Instruments NS-2C compared with 8% or less in the other devices. All of the stimulators had maximum current outputs suitable for monitoring with surface stimulating electrodes. The current delivered by the CIG series 80 nerve/muscle stimulator and the Stimlocator SL1.4 sagged by 21% and 25% respectively during a tetanus. The Digistim III, Bard Biomedical 750 digital and the Professional Instruments NS-2C had accurate digital readouts of delivered current.

Electric Stimulation

Continuous infusions of muscle relaxants--why and how.

The degree of neuromuscular blockade that occurs in an individual patient following the administration of competitive neuromuscular blocking agents cannot be accurately predicted because of the large individual variation in the pharmacokinetics and pharmacodynamics of these agents. Without monitoring of the neuromuscular blockade, this unpredictability predisposes to the occurrence of residual curarisation with its potentially lethal consequences. Variable rate continuous infusion of a short-acting competitive neuromuscular blocking agent with monitoring of the neuromuscular blockade is a flexible and accurate method for maintaining a precise degree of neuromuscular blockade during prolonged surgical procedures which ensues reliable reversability of the residual neuromuscular blockade. A system for the continuous infusion of atracurium with manual monitoring of the neuromuscular blockade is described, together with the results of a study demonstrating its efficacy.

Humans

Monitoring neuromuscular blockade with calf stimulators.

The efficacy of monitoring neuromuscular blockade during surgery based on visual assessment of the response to calf stimulation was determined in twenty-five patients. The calf stimulator was adjusted before the administration of any muscle relaxant to produce a brisk ankle jerk. Following an initial bolus dose of atracurium (0.5 mg/kg), further incremental doses (0.2 mg/kg) were administered when the response to calf stimulation was small and obvious. The resultant neuromuscular blockade was judged to be adequate throughout the surgical procedures, with an average of five incremental doses of atracurium being administered. In the presence of neuromuscular blockade the response to calf muscle stimulation was often greater than that produced by supramaximal stimulation of the ulnar nerve with a peripheral nerve stimulator. The response to calf muscle stimulation often persisted after that resulting from ulnar nerve stimulation was abolished. The technique has only limited accuracy in assessing neuromuscular blockade. However, it may be useful in helping to avoid the wide fluctuations in blockade which are prone to occur with the intermediate duration competitive neuromuscular blocking agents.

Adult

Postoperative neuromuscular function.

One hundred patients who received a competitive neuromuscular blocking agent during anaesthesia were randomly selected for evaluation of neuromuscular function immediately on their arrival in the recovery room. The anaesthetist was not aware that the patient would be evaluated in the recovery room. Neuromuscular function was assessed by a train-of-four (TOF) ratio, and in conscious and co-operative patients by a series of bedside tests of neuromuscular function. Twenty-one patients had a TOF ratio of less than 0.70 and seven patients a TOF ratio of less than 0.60. Bedside tests of neuromuscular function did not reliably detect this defect in neuromuscular transmission. It is concluded that a relatively large number of patients have a defect in neuromuscular transmission on their arrival in the recovery room, and suggested that this reflects the inadequacy of clinical methods used for the administration and antagonism of competitive neuromuscular blocking agents at this institution.

Adolescent