The effect of air fluidised bed therapy on hypermetabolism in intensive care unit patients.

Major trauma is associated with a hypermetabolic (increased resting energy expenditure) and hypercatabolic (negative nitrogen balance) response. Studies have suggested that nursing injured patients at higher temperatures reduces the metabolic response (Ryan & Clague 1990). In this study the energy expenditure and urinary nitrogen excretion of major trauma patients was examined when nursing them on an air-fluidised bed at 32 degrees C using a crossover study design. Patients were randomised into two groups. Group A patients (n = 8) remained on a standard intensive care unit bed at an environmental temperature of 22 degrees C while Group B patients (n = 6) were placed on an air-fluidised bed operating at 32 degrees C. On days 4 and 5 after injury, energy expenditure and urinary nitrogen excretion were measured. On day 6, Group A patients transferred to an air-fluidised bed and Group B patients to a standard bed. On days 7 and 8, energy expenditure and urinary nitrogen excretion were again measured. Within group comparisons of energy expenditure and urinary nitrogen excretion were made for days 3 and 4 (period 1) and days 7 and 8 (period 2). In both groups, mean energy expenditure was significantly increased in the second period irrespective of whether air-fluidised bed therapy preceded or followed a period on a standard bed. We concluded that nursing intensive care patients on an air-fluidised bed at 32 degrees C did not influence energy expenditure or urinary nitrogen.

The effects of thiopentone and propofol on delayed hypersensitivity reactions.

The effects of thiopentone and propofol on delayed hypersensitivity reactions and T lymphocyte proliferation were studied in nine healthy volunteers (five women and four men). Thiopentone 5 mg.kg-1 and propofol 2.5 mg kg-1 were given as a 10 min infusion on two separate occasions. The volunteers were exposed to a skin multitest antigen before and after administration of the two agents and their skin reactions assessed. T lymphocyte responses were studied using phytohaemagglutinin (PHA)-induced proliferation. Results showed that both drugs caused a significant depression of skin reactions in vivo but no depression in the T lymphocyte proliferation.

Effect of four i.v. induction agents on T-lymphocyte proliferations to PHA in vitro.

Anaesthetic agents are believed to have an adverse effect on human immunity. We have studied the effects of four i.v. induction agents, thiopentone, methohexitone, etomidate and propofol, on T-lymphocyte proliferations to phytohaemagglutinin in vitro. We found that at plasma concentrations similar to those obtained after induction doses, all drugs, with the exception of propofol, caused depression of T-lymphocyte function.

Neuromuscular effects and intubating conditions following mivacurium: a comparison with suxamethonium.

Mivacurium chloride has been assessed in respect of intubating conditions and neuromuscular effects. The influence of suxamethonium on the onset and duration of subsequently administered mivacurium was also studied. A dose of 0.15 mg.kg-1 of mivacurium was found to provide unacceptable intubating conditions at 2 min in 9/9 patients and further studies were conducted using 0.2 mg.kg-1. Intubating conditions with this dose were acceptable in 65% and 80% of patients at 2 min and 2.5 min respectively. In comparison, intubating conditions were acceptable in 100% of patients at 1 min following 1 mg.kg-1 of suxamethonium. The onset of block occurred in 96 s and 97 s after 0.15 mg.kg-1 and 0.2 mg.kg-1 respectively, and the durations of block in terms of recovery of the first twitch (T1) to 25% and 90% of control, and to recovery of train-of-four ratio to 0.7, were 16.1 and 17.9; 24.1 and 25.8; and 24.2 and 27.0 min respectively with the two doses. The time for the onset of complete block with suxamethonium 1.0 mg.kg-1 was 50 s and the times to 25% and 90% recovery were 9.8 min and 13.3 min. The differences between suxamethonium and both doses of mivacurium were significant (p < 0.05) but there were no significant differences between the two doses of mivacurium in any of the neuromuscular measurements. Prior administration of suxamethonium had no influence on the effects of mivacurium. Cutaneous flushing was observed in 30 out of 75 patients but this was associated with transient hypotension in only two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular effects of isoflurane and halothane in young and elderly adult patients.

We have studied the cardiovascular effects of 1 MAC end-tidal concentrations of halothane and isoflurane in young (n = 40) and elderly (n = 40) adult patients using non-invasive techniques. Cardiac output was measured by Doppler ultrasonography. Halothane reduced heart rate, systolic, mean and diastolic arterial pressures and cardiac index in both age groups (P < 0.05). Isoflurane reduced systolic, mean and diastolic arterial pressures also, but reduced cardiac index and heart rate only in the older patients (P < 0.05). Halothane depressed cardiovascular state significantly more than isoflurane in the younger adults (P < 0.05), but cardiovascular depression was similar for the two agents in the older age group. The decreases in systolic and diastolic pressures in the older patients were significantly greater with isoflurane compared with halothane (P < 0.05).

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.

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.

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.

The influence of particle size on the bioavailability of inhaled temazepam.

1. Temazepam was administered by aerosol using a standard protocol to healthy volunteers. Two studies are reported in which different dosage formulations were used: a) 30 mg of the 5 mu diameter particle (n = 6); b) 10 mg of the 2 mu diameter particle (n = 6). 2. An open crossover design was followed in each study. On one occasion in both studies subjects used a gargling procedure to remove drug which had been deposited in the mouth and oropharynx. 3. Serial venous blood samples were drawn for a period of 24 h. The mean total AUC of the 5 mu preparation was significantly reduced by gargling (3153 ng ml-1 h to 1066 ng ml-1 h) (F = 0.32). Gargling also had a significant effect on the mean AUC(0-1 h). 4. In contrast gargling had no significant effect on the mean AUC associated with the smaller diameter particle preparation (630 ng ml-1 h) vs 397 ng ml-1 h (F = 0.74). 5. These findings also indicate that temazepam deposition in the pulmonary tree is enhanced by the use of a 2 mu rather than a 5 mu diameter particle. However, the plasma drug concentrations achieved are unlikely to produce a sufficiently marked sedative effect for endoscopic investigations such as gastroscopy.

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.

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.

Arterial washin of halothane and isoflurane in young and elderly adult patients.

We have studied the effect of age on washin of isoflurane and halothane by comparing end-tidal (PE') and arterial (Pa) partial pressures of the agents in young (18-32 yr) and elderly (63-82 yr) healthy patients for 20 min after introduction of the agents, before surgery. PE' was measured by infra-red analysis and Pa by gas chromatography. Washin of isoflurane occurred at the same rate in the young and elderly, with no significant difference between young and elderly in PE' or Pa as proportions of the inspired partial pressure (PI). After 20 min of isoflurane administration, mean Pa/PI in the young was 0.57 (95% confidence limit (CL) 0.53-0.62) and 0.55 in the elderly (95% CL 0.51-0.59). Washin of halothane was slower in the elderly than in the young, with Pa/PI significantly less in the elderly from 10 min after introduction of halothane. The difference between age groups, however, was small: mean Pa/PI after 20 min of halothane administration 0.45 (95% CL 0.41-0.49) in the young and 0.38 (95% CL 0.35-0.41) in the elderly. Washin of isoflurane was significantly faster than that of halothane in both young and elderly subjects. For isoflurane, the PE'-Pa gradient was small relative to Pa and did not differ significantly between young and elderly. For halothane, PE'-Pa in the young did not differ significantly from that for isoflurane. In the elderly, PE'-Pa for halothane was significantly greater than in the young and than PE'-Pa for isoflurane.

Psychomotor and clinical assessment of flumazenil as an antagonist of midazolam.

The benzodiazepine antagonist flumazenil (0.01 mg/kg) has been compared with doxapram (1 mg/kg) and saline for the reversal of anaesthesia with intravenous midazolam, alfentanil, nitrous oxide in oxygen and isoflurane. The completeness of reversal was assessed by means of a four-choice reaction time test, 1 and 3 h following the antagonist. In addition, the level of sedation was graded using a five-point scale. Psychomotor testing showed that 60 min after administration of the antagonist, there were marked increases in reaction times (P less than 0.05) both in the control and doxapram groups, but not in those receiving flumazenil. At 180 min, however, reaction times in all groups had returned to baseline values. In contrast, there was a significant difference in the sedation scores between the saline and flumazenil groups throughout the study period (P less than 0.05). During the 4 h following midazolam, there was no evidence of re-sedation in any of the groups despite the relatively high midazolam dosage.