Disposition of propofol infusions for caesarean section

The disposition of propofol was studied in women undergoing elective Caesarean section. Indices of maternal recovery and neonatal assessment were correlated with venous concentrations of propofol. After induction of anaesthesia with propofol 2.0 mg.kg-1, ten patients received propofol 6 mg.kg-1.hr-1 with nitrous oxide 50 per cent in oxygen (low group) and nine were given propofol 9 mg.kg-1.hr-1 with oxygen 100 per cent (high group). Pharmacokinetic variables were similar between the groups. The mean +/- SD Vss = 2.38 +/- 1.16 L.kg-1, Cl = 39.2 +/- 9.75 ml.min-1.kg-1 and t1/2 beta = 126 +/- 68.7 min. At the time of delivery (8-16 min), the concentration of propofol ranged from 1.91-3.82 micrograms.ml-1 in the maternal vein (MV), 1.00-2.00 micrograms.ml-1 in the umbilical vein (UV) and 0.53-1.66 micrograms.ml-1 in the umbilical artery (UA). Neonates with high UV concentrations of propofol at delivery had lower neurologic and adaptive capacity scores 15 minutes later. The concentrations of propofol were similar between groups during the infusion but they declined at a faster rate in the low group postoperatively. Maternal recovery times did not depend on the total dose of propofol but the concentration of propofol at the time of eye opening was greater in the high group than the low group (1.74 +/- 0.51 vs 1.24 +/- 0.32 micrograms.ml-1, P less than 0.01). The rapid placental transfer of propofol during Caesarean section requires propofol infusions to be given cautiously, especially when induction to delivery times are long.     

A comparison of the myocardial metabolic and haemodynamic changes produced by propofol-sufentanil and enflurane-sufentanil anaesthesia for patients having coronary artery bypass graft surgery

The purpose of this study was to compare propofol-sufentanil with enflurane-sufentanil anaesthesia for patients undergoing elective coronary artery bypass graft (CABG) surgery with respect to changes in (1) haemodynamic variables; (2) myocardial blood flow and metabolism; (3) serum cortisol, triglyceride, lipoprotein concentrations and liver function; and (4) recovery characteristics. Forty-seven patients with preserved ventricular function (ejection fraction greater than 40%, left ventricular end diastolic pressure less than or equal to 16 mmHg) were studied. Patients in Group A (n = 24) received sufentanil 0.2 microgram.kg-1 and propofol 1-2 mg.kg-1 for induction of anaesthesia which was maintained with a variable rate propofol (50-200 micrograms.kg-1.min-1) infusion and supplemental sufentanil (maximum total 5 micrograms.kg-1). Patients in Group B (n = 23) received sufentanil 5 micrograms.kg-1 for induction of anaesthesia which was maintained with enflurane and supplemental sufentanil (maximum total 7 micrograms.kg-1). Haemodynamic and myocardial metabolic profiles were determined at the awake-sedated, post-induction, post-intubation, first skin incision, post-sternotomy, and pre-cardiopulmonary bypass intervals. Induction of anaesthesia produced a larger reduction in systolic blood pressure in Group A (156 +/- 22 to 104 +/- 20 mmHg vs 152 +/- 26 to 124 +/- 24 mmHg; P less than 0.05). No statistical differences were detected at any other time or in any other variable including myocardial lactate production (n = 13 events in each group), time to tracheal extubation and time to discharge from the ICU. We concluded that, apart from hypotension on induction of anaesthesia, propofol-sufentanil anaesthesia produced anaesthetic conditions equivalent to enflurane-sufentanil anaesthesia for CABG surgery.     

Continuous infusions of atracurium and vecuronium,compared with intermittent boluses of pancuronium: dose requirements and reversal

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)     

Randomized comparison of outcome after propofol-nitrous oxide or enflurane-nitrous oxide anaesthesia in operations of long duration

A randomized, prospective, comparative study was performed to evaluate induction characteristics, haemodynamic changes and recovery in 60 ASA I-II patients undergoing mainly gynaecological laparotomies with either propofol or thiopentone-enflurane anaesthesia. The propofol group (n = 30) received 2 mg.kg-1 propofol for induction of anaesthesia followed by propofol infusion. The thiopentone-enflurane group (n = 30) received thiopentone 4 mg.kg-1 for induction followed by enflurane (0.5-2 per cent). All patients received nitrous oxide (66 per cent] in oxygen begun one minute after tracheal intubation, and fentanyl (1.5 micrograms.kg-1) four minutes prior to induction. Other drugs administered during or after anaesthesia were similar among the groups. Haemodynamic measurements were similar between propofol and enflurane groups except after tracheal intubation when the mean arterial pressure was lower in the propofol group (P less than 0.05). The propofol group had significantly less (P less than 0.01) emesis in the recovery room than the enflurane group. The propofol group experienced significantly less (P less than 0.05) dizziness, depression/sadness and hunger than the enflurane group in the postoperative period as assessed with a visual analogue questionnaire. We conclude that propofol provided better outcome than enflurane in terms of these nonvital but annoying outcome measures after relatively long intra-abdominal operations.     

Alfentanil infusion for sedation in infants and small children during cardiac catheterization

We have analyzed several sedation techniques for paediatric cardiac catheterization which offer stable conditions for a few hours investigation, and maintain spontaneous breathing. In the present study, after premedication with oral flunitrazepam 0.1 mg.kg-1, 14 children aged 1-17 mo were sedated with an individually titrated alfentanil infusion. Every patient was sedated to a level which produced no reaction to pain or any discomfort. The induction dose and the maintenance requirement of alfentanil were 24 +/- 8 micrograms.kg-1 and 32 +/- 8 micrograms.kg-1.hr-1 (mean +/- SD), respectively. These doses were less in cyanotic than in acyanotic patients: 21 +/- 6 vs 28 +/- 8 micrograms.kg-1 and 29 +/- 10 vs 34 +/- 3 micrograms.kg-1.hr-1, respectively (P less than 0.05). The mean plasma concentration of alfentanil during maintenance of sedation was 79 +/- 23 ng.ml-1. Ventilation of two children was assisted for a short time after an incremental bolus of alfentanil. It is concluded that an alfentanil infusion technique with close monitoring of breathing is a practical sedation method for paediatric cardiac catheterization.     

Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg.kg-1 to 0.25 mg.kg-1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg.kg-1 and 0.053 mg.kg-1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg.kg-1 mivacurium was 15.3 +/- 1.0 min and 21.5 +/- 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25-75 per cent) between initial bolus dose (6.1 +/- 0.5 min), repeat bolus doses (7.6 +/- 0.6 min), mivacurium infusion (6.7 +/- 0.7 min) and succinylcholine infusion (6.8 +/- 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg.kg-1. Bolus administration of 0.20 mg.kg-1 or 0.25 mg.kg-1 of mivacurium decreased MAP from 78.2 +/- 2.5 to 64.0 +/- 3.2 mmHg (range 12-59 per cent of control) (P less than 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.     

A comparison of spinal and epidural anaesthesia for hip arthroplasty

Spinal and epidural anaesthesia were compared in 65 patients undergoing hip arthroplasty, with regard to the degree of sensory and motor blockade, cardiovascular effects, operating conditions, the dose of propofol required to produce satisfactory hypnosis, and complications. Epidural anaesthesia was successful in 30 patients using an initial dose of 15 ml of 0.5% bupivacaine, and spinal anaesthesia in 32 patients, using 4 ml 0.5% isobaric bupivacaine. The two techniques were similar with regard to the level of sensory blockade (T8), degree of hypotension and perioperative haemorrhage. Differences occurred in the degree of motor blockade (mean Bromage score of 1 in the spinal group vs 3.86 in the epidural group) (P less than 0.05), time to achieve maximal cephalad spread (13 min in the spinal group vs 21 min in the epidural group) (P less than 0.05) and the dose of propofol required to produce adequate hypnosis (1.95 mg.kg-1.hr-1 in the spinal group vs 2.89 mg.kg-1.hr-1 in the epidural group) (P less than 0.05). Only seven patients required urethral catheterization in this spinal group compared with 14 in the epidural group (P less than 0.05). Spinal anaesthesia also proved advantageous by providing better operating conditions for the surgeon, with a lower incidence of patient movement.     

Thiopentone pretreatment for propofol injection pain in ambulatory patients

This study investigated propofol injection pain in patients undergoing ambulatory anaesthesia. In a randomized, double-blind trial, 90 women were allocated to receive one of three treatments prior to induction of anaesthesia with propofol. Patients in Group C received 2 ml normal saline, Group L, 2 ml, lidocaine 2% (40 mg) and Group T, 2 ml thiopentone 2.5% (50 mg). Venous discomfort was assessed with a visual analogue scale (VAS) 5–15 sec after commencing propofol administration using an infusion pump (rate 1000 μg · kg^?1 · min^?1). Loss of consciousness occurred in 60–90 sec. Visual analogue scores (mean ± SD) during induction were lower in Groups L (3.3 ± 2.5) and T (4.1 ± 2.7) than in Group C (5.6 ± 2.3); P = 0.0031. The incidence of venous discomfort was lower in Group L (76.6%; P < 0.05) than in Group C (100%) but not different from Group T (90%). The VAS scores for recall of pain in the recovery room were correlated with the VAS scores during induction (r = 0.7045; P < 0.0001). Recovery room discharge times were similar: C (75.9 ± 19.4 min); L 73.6 ± 21.6 min); T (77.1 ± 18.9 min). Assessing their overall satisfaction, 89.7% would choose propofol anaesthesia again. We conclude that lidocaine reduces the incidence and severity of propofol injection pain in ambulatory patients whereas thiopentone only reduces its severity.     

Intraocular pressure in anaesthetized dogs given flumazenil with and without prior administration of midazolam

This study examined the effect of flumazenil, a benzodiazepine antagonist, on aqueous humour pressure in dogs receiving either midazolam or no benzodiazepine. Twenty-four halothane-anaesthetized dogs were assigned to one of four groups. Group I (n = 6) received saline iv at 0, 45 and 90 min. Group 2 (n = 6) received saline at 0 min, flumazenil 0.0025 mg.kg-1 iv at 45 min and flumazenil 0.16 mg.kg-1 at 90 min. Group 3 (n = 6) received midazolam 1.6 mg.kg-1 at 0 min followed by continuous iv infusion (1.25 mg.kg-1.hr-1). Flumazenil was given at 45 and 90 min as in Group 2. In Group 4 (n = 6) aqueous humour pressure was elevated to about 35 mmHg then midazolam and flumazenil were given as in Group 3. Aqueous humour pressure was determined using a 30-gauge needle placed into the anterior chamber. Saline or flumazenil produced no change in aqueous humour pressure in Groups 1 and 2. In Groups 3 and 4, midazolam decreased aqueous humour pressure from 18 +/- 2 mmHg (mean +/- SD) to 14 +/- 3 mmHg (P less than 0.001) and from 34 +/- 5 mmHg to 31 +/- 3 mmHg (P less than 0.01) respectively. Flumazenil given during continuous infusion of midazolam produced increases of aqueous humour pressure of 2 +/- 1 (P less than 0.01) to 5 +/- 2 mmHg (P less than 0.01) that lasted less than or equal to 12 min. It is concluded that at both normal and elevated aqueous humour pressures flumazenil produces statistically significant but clinically unimportant increases of aqueous humour pressure in anaesthetized dogs receiving midazolam, but not in dogs given no benzodiazepine.     

Neostigmine and edrophonium for reversal of pipecuronium neuromuscular blockade

Neostigmine 0.06 mg.kg-1 or edrophonium 1 mg.kg-1 were administered to two groups of 15 patients each for antagonism of pipecuronium-induced neuromuscular block at 20% spontaneous recovery of the first twitch (T1) of the train-of-four (TOF) stimulation. The mean onset of action (+/-SEM) of edrophonium (18.1 +/- 2.4 sec) was significantly more rapid (P less than 0.01) than that of neostigmine (47.6 +/- 4 sec), as were the times taken to attain a TOF ratio of 0.25 and 0.5. Nevertheless, the reversal time (time taken from the end of injection of the antagonist until TOF ratio value had reached 0.75) was significantly shorter (P less than 0.01) in the neostigmine than in the edrophonium group (499.3 +/- 62 vs 767 +/- 52 sec respectively). The TOF ratio ten minutes after reversal was greater in the neostigmine group than in the edrophonium group (P less than 0.01), 0.78 +/- 0.02 vs 0.68 +/- 0.02 min respectively. At that time, 33% (5 out of 15) and 80% (12 out of 15) patients failed to be reversed adequately (TOF ratio of 0.75) after neostigmine 0.06 mg.kg-1 and edrophonium 1 mg.kg-1, respectively. Administration of one additional dose (one-third of the initial dose) of the same antagonist resulted in adequate antagonism in the remaining five patients in the neostigmine group and in nine patients in the edrophonium group. Two such doses were required in the remaining three patients in the latter group. The mean total dose of neostigmine and edrophonium employed in this study was 0.067 +/- 0.002 and 1.3 +/- 0.05 mg.kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

Propofol anaesthesia in paediatric ambulatory patients: a comparison with thiopentone and halothane

The purpose of this study was to evaluate the haemodynamic changes during induction, as well as the speed and quality of recovery when propofol (vs thiopentone and/or halothane) was used for induction and maintenance of anaesthesia in paediatric outpatients. One hundred unmedicated children, 3–12-yr-old, scheduled for ambulatory surgery were studied. The most common surgical procedures performed were eye muscle surgery (42%), plastic surgery (21%), dental restoration (15%), and urological procedures (15%). The children were randomized to an anaesthetic regimen for induction/maintenance as follows: propofol/propofol infusion; propofol/halothane; thiopentone/halothane; halothane for both induction and maintenance. Succinylcholine 1.5 mg · kg^?1 was used to facilitate tracheal intubation and N₂O/O₂ were used as the carrier gases in each case. All maintenance drugs were titrated according to the clinical response of the patient to prevent movement and/or maintain BP ± 20% of baseline. Two patients (4%) who received propofol expressed discomfort during injection. The mean propofol dose required to prevent movement was 267 ± 83 μg · kg^?1 · min^?1. The overall pattern of haemodynamic changes, as well as awakening (extubation) times were not different among the four groups. Children who received propofol recovered faster (22 vs 29–36 min) (P < 0.05), were discharged home sooner (101 vs 127–144 min) (P < 0.05), and had less postoperative vomiting (4 vs 24–48%) (P < 0.05) than all others. There were no serious complications or adverse postoperative sequelae in any of the patients in the study. It is concluded that induction and maintenance of anaesthesia with propofol is a well-tolerated anaesthetic technique in children, and is associated with faster recovery and discharged as well as less vomiting than when halothane is used.     

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.     

Treatment of intraoperative hypertension with enflurane,nicardipine, or human atrial natriuretic peptide: haemodynamic and renal effects

The purpose of this study was to assess the effects of the calcium entry blocker nicardipine and alpha human atrial natriuretic peptide (hANP) on antihypertensive and diuretic activity in hypertensive surgical patients. The site of the diuretic actions of these drugs along the nephron were also investigated by measuring the excretion rate of inorganic phosphate (PO4). Hypertension during gastrectomy was treated by increasing the concentration of enflurane, by nicardipine infusion (0.5-2.0 micrograms.kg-1 x min-1), or by hANP infusion (0.05-0.2 microgram.kg-1 x min-1) under general anaesthesia. Enflurane, nicardipine and hANP all decreased arterial pressure to the same extent. Urine flow, Na and PO4 excretion increased following the administration of nicardipine or hANP. Fractional distal reabsorption of sodium was suppressed from 89.7 +/- 2.8% to 82.1 +/- 5.0% by the hANP, but not by the nicardipine infusion. Creatinine clearance was increased by hANP infusion, but did not change in the nicardipine group. It is concluded that nicardipine and hANP can be used safely for the treatment of hypertension during surgery. Both drugs induced phosphaturic diuresis, but the site of action of the two drugs on the nephron may be different. Phosphate reabsorption is considered to occur largely in the renal proximal tubule, so that its appearance in the urine in increased quantities without the change of renal circulation in the nicardipine group suggests a proximal tubular action of this drug. However, the site of action of hANP in the kidney was not determined because GFR increased and distal sodium reabsorption was suppressed due to the drug infusion.     

A defasciculating dose of d-tubocurarine causes resistance to succinylcholine

Forty-four patients, ASA physical status I or II, undergoing thiamylal, fentanyl, N2O/O2 anaesthesia were studied to determine the dose-response to succinylcholine (Sch) without prior defasciculation (24 pt - Group 1), or three minutes following d-tubocurarine (dTC), 0.043 mg.kg-1 (20 pt - Group 2). The individual log dose-logit response curve for each patient was determined using a cumulative dose plus infusion technique and integrated EMG monitoring of the first dorsal interosseous muscle. The mean (+/- SEM) ED50, ED90 and ED95 values for Sch in Group 1 were 0.13 +/- 0.01, 0.19 +/- 0.01 and 0.22 +- 0.01 mg.kg-1, and in Group 2 were 0.16 +/- 0.01, 0.25 +/- 0.01 and 0.29 +/- 0.02 mg.kg-1, respectively. The mean ED values in Group 2 were significantly greater than the equivalent values in Group 1 (P less than 0.05). Compared with values in Group 1, ED values in Group 2 represented mean increases of 23, 32, and 32 per cent, respectively. These pharmacodynamic data indicate that the dose of Sch needs to be increased by 32 per cent following a defasciculating dose of dTC 3 mg.70 kg-1 (0.043 mg.kg-1).     

Preservation of renal blood flow during hypotension induced with fenoldopam in dogs

The introduction of drugs that could induce hypotension with different pharmacological actions would be advantageous because side effects unique to a specific drug could be minimized by selecting appropriate therapy. Specific dopamine-1, (DA1) and dopamine-2 (DA2) receptor agonists are now under clinical investigation. Fenoldopam mesylate is a specific DA1 receptor agonist that lowers blood pressure by vasodilatation. The hypothesis that fenoldopam could be used to induce hypotension and preserve blood flow to the kidney was tested. Systemic aortic blood pressure and renal blood flow were measured continuously with a carotid arterial catheter and an electromagnetic flow probe respectively, in order to compare the cardiovascular and renal vascular effects of fenoldopam and sodium nitroprusside in ten dogs under halothane general anaesthesia. Mean arterial pressure was decreased 30 +/- 8 per cent from control with infusion of fenoldopam (3.4 +/- 2.0 micrograms.kg-1.min-1) and 34 +/- 4 per cent with infusion of sodium nitroprusside (5.9 micrograms.kg-1.min-1) (NS). Renal blood flow (RBF) increased during fenoldopam-induced hypotension 11 +/- 7 per cent and decreased 21 +/- 8 per cent during sodium nitroprusside-induced hypotension (P less than 0.01). Sodium nitroprusside is a non-selective arteriolar and venous vasodilator that can produce redistribution of blood flow away from the kidney during induced hypotension. Fenoldopam is a selective dopamine-1 (DA1) receptor agonist that causes vasodilatation to the kidney and other organs with DA1 receptors and preserves blood flow to the kidney during induced hypotension.     

Comparaison de l’incidence sur le saignement de deux techniques anesthésiques midazolam-alfentanil versus propofol-alfentanil lors de la cure d’otospongiose

This study was performed to compare the incidence of bleeding associated with two anaesthetic techniques during otolaryngological microsurgery. Twenty-eight venous interpositions for otospongiosis have been carried out at random either under local anaesthesia combined with light sedation (midazolam 0.1 mg.kg-1 and alfentanil 0 micrograms.kg-1) or using general anaesthesia (propofol 2.5 mg.kg-1, then 9 mg.kg-1.hr-1 and alfentanil 30 micrograms.kg-1, then 15 micrograms.kg-1). The patients' lungs were mechanically ventilated. Every ten minutes, heart rate, arterial blood pressure and FETCO2 were observed. Bleeding was assessed on a four-point scale and evaluated according to its duration and the annoyance that it caused. General anaesthesia was clinically better tolerated. Heart rate and arterial blood pressure were lower than with general anaesthesia. The end-expiratory CO2 was 4.7 +/- 0.2 per cent. Bleeding was less frequent, lasted less time, but when it occurred the surgical disturbance was identical in the two groups. General anaesthesia produced a less bloody operating field and local anaesthesia required the cooperation of the patient.     

Pharmacokinetics and cardiovascular dynamics of pipecuronium bromide during coronary artery surgery

The haemodynamic effects of 200 micrograms.kg-1 pipecuronium and pancuronium were compared under etomidate/piritramide anaesthesia in 20 patients scheduled for elective coronary artery surgery. Following the completion of the haemodynamic measurements (ten minutes), anaesthesia was maintained by etomidate/sufentanil infusion. The mean changes in cardiac output were approximately -19 and -2 per cent and in heart rate -1 and +26 per cent for pipecuronium and pancuronium respectively. Plasma and urine concentrations of pipecuronium were also measured and the pharmacokinetic variables obtained indicated rapid initial decrease in plasma concentration (t1/2 = 7.6 minutes) followed by a longer terminal phase (t1/2 = 161 minutes). The central compartment volume was 102 +/- 24 ml.kg-1 and plasma clearance was 1.8 +/- 0.4 ml.kg-1 min-1. Approximately 56 per cent of the dose was recovered from the urine within 24 hours of administration and about 25 per cent of this was the metabolite, 3-desacetyl pipecuronium. High-dose pipecuronium administration under the anaesthetic regimen employed did not produce deleterious haemodynamic effects. The pharmacokinetic variables after bolus injection of pipecuronium did not deviate from those reported under normothermic conditions.     

A comparison of morphine-perphenazine and midazolam on preoperative sedation and arterial oxygen saturation

The effectiveness of midazolam and a mixture of morphine-perphenazine premedication to produce sedation and their effects on preoperative oxygen saturation (SaO2) were examined. Eighty-five patients whose SaO2 measured with a pulse oximeter was greater than 90% and who were not receiving narcotic sedatives or oxygen were randomized to three groups. Each patient had his SaO2 recorded before premedication with placebo (saline), midazolam 0.08 mg.kg-1 or morphine 0.15 mg.kg-1 with perphenazine 2.5-5.0 mg im. From 30-90 min later, prior to anaesthesia SaO2 was repeated, and a sedation score was obtained by a blinded observer using a seven point scale. Median sedation scores were greater for midazolam (4) than for morphine-perphenazine (2) and placebo (1) (P less than 0.0001). As well, there was a decrease in the SaO2 in the morphine-perphenazine group (1.7 +/- 2.7%, P less than 0.001) but not in the midazolam and placebo groups (0.1 +/- 2.3%, -0.8 +/- 2.1%). In conclusion midazolam produced greater sedation than morphine-perphenazine and placebo without effect on SaO2 whereas morphine-perphenazine showed a decrease in SaO2 preoperatively.     

Vecuronium is more potent in montreal than in Paris

This study was undertaken to compare the potency of vecuronium in patients anaesthetized in Montreal or Paris. Anaesthesia was induced with thiopentone and maintained with N2O, and intermittent boluses of thiopentone and fentanyl in 18 patients in Paris and 19 in Montreal. Neuromuscular blockade was measured using train-of-four stimulation of the ulnar nerve. The force of contraction of the adductor pollicis muscle was measured. Single doses of vecuronium, 20, 30, or 40 micrograms.kg-1 were given by random allocation. Dose response curves were constructed by obtaining the linear regression of the logit of the first response (T1) neuromuscular blockade versus log dose. The patients in Paris required 27% more vecuronium (95% confidence limits 5-53%; P = 0.01) for the same intensity of blockade. In Montreal, the ED50 and ED90 (+/- SEE for the mean) values were 26.0 +/- 1.4 and 44.2 +/- 2.5 micrograms.kg-1 compared with 33.0 +/- 3.3 and 71.9 +/- 7.2 micrograms.kg-1 in Paris respectively. The patients were comparable with respect to age, sex, height and weight. These results confirm, for vecuronium, the transatlantic difference in potency of neuromuscular blocking drugs which was previously observed with d-tubocurarine between London and New York.     

Hyperalgesia during sedation: effects of barbiturates and propofol in the rat

Subhypnotic doses of thiopentone are considered to possess antianalgesic or hyperalgesic properties. In this study, we have tested the hypothesis that the coincidence of sedation and hyperalgesia is a property of both barbiturate and non- barbiturate anaesthetic agents. In a randomized, prospective, blinded study, the effects of slow (20 min) iv infusions of thiopentone, pentobarbitone, methohexitone or propofol on nociceptive threshold were measured in rats by tail pressure analgesimetry and compared with saline- infused control animals. Nociceptive thresholds were correlated with measurements of plasma drug concentrations and behavioural assessments. Comparison of pre- infusion nociceptive threshold with the lowest threshold obtained during drug infusion revealed decreases in all four treatment groups. As a percentage of the pre- infusion values, the decreases were: thiopentone: 42.5% (P < 0.001), pentobarbitone : 27.8% (P = 0.014), methohexitone: 24.9% (P = 0.013), propofol: 21.6% (P = 0.006). There were no changes in nociceptive threshold in the control groups. The relationship between nociceptive threshold and plasma drug concentration was usually characterized by an initial decline followed by a rise in nociceptive threshold as the plasma concentration and degree of sedation increased. The results support the hypothesis that hyperalgesia is a property of different anaesthetic agents when administered at sub- hynotic concentrations.