Dexmedetomidine--a powerful new adjunct to anaesthesia?
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Adjuvants, Anesthesia↗
Biomedical subjects
C Prys-Roberts
Publications and source records attributed to C Prys-Roberts.
Somatic movement and oesophageal motility during isoflurane anaesthesia.
The quantal responses for somatic movement, and spontaneous and provoked lower oesophageal contractions (motility) were noted at the time of incision in 72 patients aged 40-65 yr, receiving varying concentrations of isoflurane. Probit analysis of the alveolar concentration of isoflurane required to prevent somatic movement revealed an MAC or EC50 (95% confidence limits) of 1.00 (0.82-1.17)% and EC95 of 2.16 (1.69-3.89)%. The EC50 of isoflurane to suppress spontaneous lower oesophageal contractions was 1.27 (1.12-1.43)%, and the EC95 2.13 (1.78-3.22)%. The EC50 for provoked lower oesophageal contractions was 1.31 (0.93-3.48)% and the EC95 was 6.18% (unable to compute confidence limits).
Adult↗
Propofol and alfentanil in children: infusion technique and dose requirement for total i.v. anaesthesia.
We estimated the dose of propofol (initial dose followed by a stepped infusion) when given with two different infusion rates of alfentanil for total i.v. anaesthesia in 59 children aged 3-12 yr. Patients in series 1 (four groups) received an alfentanil loading dose of 85 micrograms kg-1 and an infusion of 65 micrograms kg-1 h-1. Patients in series 2 (groups 5 and 6) received an alfentanil loading dose of 65 micrograms kg-1 and infusion of 50 micrograms kg-1 h-1. Parents gave their informed consent. Premedication comprised temazepam 0.3 mg kg-1. Glycopyrronium 5 micrograms kg-1 was administered and anaesthesia induced and maintained with alfentanil (loading dose and infusion) followed by propofol (loading dose and three-stage manual infusion scheme). Suxamethonium 1 mg kg-1 was used to facilitate tracheal intubation and the lungs were ventilated artificially to normocapnia with 30% oxygen in air. Probit analysis was used to determine the dose requirement of propofol. In series 1, the ED50 was 6.0 mg kg-1 h-1 (95% confidence limits 5.5-6.2 mg kg-1 h-1) and ED95 8.6 (6.8-7.8) mg kg-1 h-1. Corresponding values for series 2 were ED50 7.5 (8.0-9.8) mg kg-1 h-1 and ED95 10.5 (9.6-13.1) mg kg-1 h-1.
Adult↗
Oesophageal contractility during total i.v. anaesthesia with and without glycopyrronium.
Somatic movement and spontaneous and provoked oesophageal contractions were noted at time of incision in 51 patients receiving total i.v. anaesthesia with alfentanil and propofol. Probit analysis of the dose of propofol required to prevent spontaneous movement revealed an ED50 (95% confidence limits) of 2.5 (1.8-2.9) mg kg(-1) h(-1) and ED95 of 4.7 (4.0-7.5) mg kg(-1) h(-1). Corresponding venous blood concentrations gave an EC50 of 1.2 (0.4-1.6) micrograms ml(-1) and an EC95 of 4.0 (2.8-18.5) micrograms ml(-1). ED50 of propofol for preventing spontaneous oesophageal contraction was 3.0 (1.9-3.6) mg kg(-1) h(-1). ED95 was 6.9 (5.0-27.3) mg kg(-1) h(-1); EC50 for oesophageal contractions was 1.7 (0.7-2.3) micrograms ml(-1) and EC95 was 5.9 (3.7-70.6) micrograms ml(-1). Another group of 10 patients were given glycopyrronium 5 micrograms kg(-1) at induction; oesophageal contractility was significantly reduced in this group.
Adult↗
Total i.v. anaesthesia with propofol and alfentanil for coronary artery bypass grafting.
The haemodynamic effects of total i.v. anaesthesia with a combination of propofol and alfentanil infusions were studied in eight patients with good left ventricular function undergoing coronary artery bypass surgery. Haemodynamic indices were measured before anaesthesia and at specified intervals before cardiopulmonary bypass. The technique resulted in haemodynamic changes comparable to those reported with opioid-based anaesthesia for coronary artery surgery, and has potential advantages.
Alfentanil↗
Combined morphine-bupivacaine caudals for reconstructive penile surgery in children: systemic absorption of morphine and postoperative analgesia.
We wished to determine if the addition of a small dose of morphine (0.05 mg.kg-1) to a caudal solution of 0.25% bupivacaine could extend the duration of analgesia after major reconstructive penile surgery and also to measure the systemic absorption of morphine after caudal injection. Thirty children undergoing reconstructive penile surgery received a caudal injection of 0.25% bupivacaine 0.75 ml.kg-1 with or without morphine 0.05 mg.kg-1. All patients awoke pain-free, but eight of the fifteen patients receiving bupivacaine alone required supplementary injections of opioid postoperatively, whereas none of the patients receiving the bupivacaine-morphine mixture required additional opioids. The incidence of side-effects was similar for the two groups. Morphine was absorbed rapidly after caudal injection to reach a peak plasma level of 21.2 (+/- 4.8) ng.ml-1 at ten minutes and then fell to 10.1 (+/- 3.8) ng.ml-1 at one hour and 4.1 (+/- 2.6) ng.ml-1 at three hours. These levels are low compared with plasma levels associated with systemic analgesia. We conclude that the extended duration of analgesia from morphine 0.05 mg/kg given caudally is due at least in part to specific spinal analgesia.
Analgesia, Epidural↗
Plasma inorganic fluoride concentrations during and after prolonged (greater than 24 h) isoflurane sedation: effect on renal function.
We studied the effect of prolonged sedation (greater than 24 h) with isoflurane on plasma inorganic fluoride concentrations and renal function in 60 critically ill patients allocated randomly to receive either isoflurane or midazolam for sedation. In the isoflurane group, plasma fluoride increased from a mean concentration of 3.1 mumol/L to 20.0 mumol/L at the end of sedation, continued to increase to a peak of 25.3 mumol/L 16 h later, and then decreased exponentially (t1/2 = 111 h) to reach normal levels by the fifth day. In the midazolam group, the plasma fluoride increased from a mean concentration of 4.2 mumol/L to a peak of 6.8 mumol/L 12 h after starting the sedation and then decreased toward normal. Serum and urinary electrolytes, urine osmolality, and creatinine clearance during and after sedation were similar in the two groups. Isoflurane sedation was associated with an increase in plasma fluoride concentration without any clinical deterioration of renal function.
Adolescent↗
Anesthesia and chronic hypertension.
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Anesthesia↗
Plasma catecholamine concentration during sedation in ventilated patients requiring intensive therapy.
The effects of isoflurane and midazolam sedation on the catecholamine responses of ventilated patients were studied over a 24-h period. Sixty ventilated patients admitted to our intensive therapy unit were allocated randomly to receive either isoflurane or midazolam sedation. Arterial blood samples for plasma catecholamine concentrations were taken at baseline, 6 h after starting sedation and at the end of the study period. Patients sedated with isoflurane showed a progressive reduction in both adrenaline and noradrenaline concentrations during the period of sedation which reached statistical significance for adrenaline at 6 h (p less than 0.02) and at the end of the study (p less than 0.001). Patients sedated with midazolam showed no significant changes of adrenaline or noradrenaline concentrations. Overall, a more satisfactory degree of sedation was achieved with isoflurane.
Administration, Inhalation↗
Self-tuning adaptive control of induced hypotension in humans: a comparison of isoflurane and sodium nitroprusside.
Induced hypotension is commonly used during surgery to decrease arterial pressure. Sodium nitroprusside and isoflurane are well-known hypotensive agents. The use of self-tuning adaptive control of induced hypotension was assessed with the use of sodium nitroprusside and isoflurane as hypotensive agents. Nineteen surgical patients were studied during closed-loop control of hypotension induced with sodium nitroprusside. This group of patients was compared with 10 similar patients in whom infusions of sodium nitroprusside were controlled manually by an anesthesiologist. Although the results of the two studies varied, no conclusion could be drawn regarding the superiority of either manual or closed-loop control. When manual versus automatic control of isoflurane-induced hypotension was assessed in a similar fashion, the two methods of induction were found to be comparable.
Algorithms↗
Study of the possible interaction between fentanyl and propofol using a computer-controlled infusion of propofol.
A computer-controlled infusion of propofol designed to achieve a target blood concentration of propofol 3 microgram ml-1 was used to investigate the possibility of an interaction between propofol and fentanyl in 32 patients undergoing body surface surgery. In 16 patients who were not receiving a neuromuscular blocker during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood concentrations of propofol between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. In a further 16 patients who received vecuronium during maintenance anaesthesia with 67% nitrous oxide, there were no significant differences in blood propofol concentrations between eight patients who received fentanyl 5 micrograms kg-1 before induction of anaesthesia, and eight patients who did not. Fentanyl administered i.v. immediately before a computer-controlled infusion of propofol resulted in more satisfactory anaesthetic conditions than when fentanyl was not used, but did not significantly prolong the recovery time.
Adult↗
Isoflurane sedation for patients undergoing mechanical ventilation: metabolism to inorganic fluoride and renal effects.
The metabolism and renal effects of isoflurane sedation were studied for 24 h in patients undergoing mechanical ventilation. Forty-six patients admitted to our intensive therapy unit were allocated randomly to receive either 0.1-0.6% isoflurane or midazolam 0.01-0.2 mg kg-1 h-1 for sedation. In 26 patients sedated with isoflurane, plasma inorganic fluoride increased from a mean concentration of 4.03 mumol litre-1 to 13.57 mumol litre-1 12 h after stopping sedation. Plasma inorganic fluoride concentrations in 20 patients sedated with midazolam were unchanged from baseline values (mean 5.32 mumol litre-1). Serum electrolyte, urea and creatinine concentrations, and urine output rates during and after sedation in patients who received isoflurane were similar to those who received midazolam. We conclude that, following isoflurane sedation for up to 24 h, metabolism to inorganic fluoride is insufficient to cause clinical renal dysfunction.
Aged↗
Postoperative analgesia after paediatric orchidopexy: evaluation of a bupivacaine-morphine mixture.
The value of combining morphine with bupivacaine for caudal analgesia was investigated. Thirty children, undergoing orchidopexy, received a caudal block of 0.125% bupivacaine with or without morphine 0.05 mg kg-1. Analgesia, side-effects, ventilatory frequency and oxygen saturation (SaO2) were recorded after operation. None of the 15 patients receiving the bupivacaine-morphine mixture required post-operative opioids, whereas eight of 15 patients receiving bupivacaine alone needed additional opioid analgesia. The incidence of side effects after surgery was similar for the two groups and there was no detectable difference in ventilatory frequency or SaO2.
Analgesia, Epidural↗
Total i.v. anaesthesia with propofol and alfentanil: dose requirements for propofol and the effect of premedication with clonidine.
We determined in 51 healthy patients undergoing body surface surgery the dose requirements for propofol, as part of a total i.v. anaesthesia technique with an alfentanil infusion. After premedication with temazepam, patients received alfentanil 50 micrograms kg-1 followed by an infusion of 50 micrograms kg-1 h-1. Patients were anaesthetized with a loading dose of propofol followed by a three-stage infusion designed to reach one of five preselected blood concentrations of propofol. The motor response to the initial surgical incision was noted and probit analysis was used to derive the ED50 (2.94 mg kg-1 h-1; 95% confidence limits: 2.35-3.37 mg kg-1 h-1) and ED95 (4.98 mg kg-1 h-1; 95% limits: 4.13-8.8 mg kg-1 h-1) for the final propotol infusion rate under these conditions. Whole blood concentration!of propofol at the time of the incision was related linearly to the inf!sion rate and the EC50 and EC95 (probit analysis) were derived as !.44 (95% confidence limits 0.62-1.87) and 4.05 (95% confidence lim!ts 2.78-30.5) micrograms ml-1, respectively. Post-operative recovery was!rapid, uncomplicated and uneventful. In a subgroup of eight patients,!the addition of clonidine 0.6 mg to the premedication significantly decreased the requirement for propofol (P less than 0.05) during surgery, but resulted in prolonged recovery times.
Administration, Oral↗
Isoflurane compared with midazolam in the intensive care unit.
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Critical Care↗
Isoflurane compared with midazolam for sedation in the intensive care unit.
OBJECTIVE: To compare isoflurane with midazolam for sedation of ventilated patients. DESIGN: Randomised control study. Setting--Intensive care unit in university teaching hospital. PATIENTS: Sixty patients aged 18-76 who required mechanical ventilation. INTERVENTIONS: Sedation with either 0.1-0.6% isoflurane in an air-oxygen mixture (30 patients) or a continuous intravenous infusion of midazolam 0.01-0.20 mg/kg/h (30 patients). Sedation was assessed initially and hourly thereafter on a six point scale. Incremental intravenous doses of morphine 0.05 mg/kg were given for analgesia as required. The trial sedative was stopped when the patient was judged ready for weaning from ventilatory support or at 24 hours (whichever was earlier). END POINT: Achievement of a predetermined level of sedation for as much of the time as possible. MAIN RESULTS: Isoflurane produced satisfactory sedation for a greater proportion of time (86%) than midazolam (64%), and patients sedated with isoflurane recovered more rapidly from sedation. CONCLUSION: Isoflurane is a promising alternative technique for sedation of ventilated patients in the intensive care unit.
Adolescent↗
The pharmacology of propofol.
A review of the pharmacology of propofol, a new IV anesthetic agent, is presented. Solubilized in a soybean emulsion, propofol is one of a series of sterically hindered phenols that exhibit anesthetic activity. Induction of anesthesia with propofol may be associated with pain on injection, apnea, and a reduction in arterial blood pressure (BP) and cardiac output. Caution should be ascribed to its use in patients with coronary artery disease, where these effects may have the potential for producing myocardial ischemia. The hemodynamic responses to laryngoscopy and intubation are attenuated. The pharmacokinetic profile suggests suitability as an infusion for either maintenance of anesthesia or sedation. Use of propofol as an infusion during surgery may result in a further reduction in cardiac output, particularly with the concomitant administration of adjuvant increments of fentanyl. The ventilatory response to CO2 is depressed during such an infusion. The high clearance of propofol suggests that even after a prolonged infusion, recovery should be rapid. This finding has been confirmed in a series of studies establishing propofol as an ideal agent for use in a total IV anesthetic technique. Both the quality and speed of recovery, together with the absence of emetic sequelae, support the use of propofol in an outpatient setting. Propofol appears to have no long-term effect on adrenocortical function and appears safe for use in patients with acute intermittent porphyria and susceptibility to malignant hyperpyrexia.
Adult↗
Computer controlled infusion of propofol.
A computer controlled infusion pump was used to deliver propofol to two groups of eight patients undergoing body surface surgery. The patients were premedicated with morphine sulphate i.m. and anaesthesia was supplemented with 66% nitrous oxide in oxygen. Patients in group 1 breathed spontaneously, whereas patients in group 2 underwent artificial ventilation to a normal PaCO2. The computer program was designed to achieve and maintain a blood concentration of propofol 3 micrograms ml-1 as rapidly as possible, basing calculations on a three-compartment pharmacokinetic model. Mean blood propofol concentrations were found to be close to the predicted target from 10 to 120 min in group 1, but were 5-20% higher from 20 min in group 2.
Adult↗