Potency and maintenance requirement of atracurium and vecuronium given alone or together

A synergism exists between some competitive muscle relaxants. However, maintenance requirement of a combination of muscle relaxants has been evaluated only in paediatric patients. We studied 45 elective adult surgical patients (ASA I-II) during propofol-alfentanyl-N₂O-O₂-anaesthesia. The first 30 patients were randomized to receive either atracurium or vecuronium to create individual dose-response curves for these muscle relaxants. ED₉₅-values for atracurium and vecuronium were 260±9 and 59±3 μg · kg^-1, respectively (mean±s.e.mean). Requirements of atracurium and vecuronium to maintain an 85–95% neuromuscular blockade were 301 and 83 μg kg^-1 h^-1, respectively. An additional 15 patients received a combination of atracurium and vecuronium (cAV) in an equipotent dose ratio. An ED₉₅ of a cAV was 94± 7 μg · kg^-1 of atracurium together with 21±2 μg · kg^-1 of vecuronium, or 72±6% of one ED₉₅ dose of a parent agent. Potentiation was significant ( P =0.0001). A maintenance requirement of a cAV was 120 μg kg^-1 h^-1 of atracurium together with 27 μg kg^-1 h^-1 of vecuronium. Thus, a significant potentiation was maintained also during the course of anaesthesia. A cAV had an effect like one intermediate-acting agent. If a cAV is used instead of using atracurium or vecuronium alone, the maximal reduction of drug consumption would be approximately 30%.     

The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

Effect of prior administration of succinylcholine on duration of action of vecuronium during enflurane anaesthesia

The effects of succinylcholine, which was given to facilitate tracheal intubation on the duration of action of subsequently administered vecuronium bromide, were evaluated in 54 adult patients who underwent abdominal surgeries under enflurane anaesthesia. The electromyographic response to train–of–four ulnar nerve stimulation was measured. Twenty–seven patients received 1 mg–kg^-1 of succinylcholine, followed by 0.15 mg kg^-1 of vecuronium when the electromyographic response recovered to 50% of control after succinylcholine–induced neuromuscular blockade. The other 27 patients served as the control group, receiving 0.15 mg kg^-1 of vecuronium without prior administration of succinylcholine. In both groups, administration of supplemental 0.04 mg kg^-1 of vecuronium was repeated whenever the electromyographic response recovered to 25% of control during surgical procedures. The duration of blockade induced by the initial 0.15 mg kg^-1 of vecuronium was 56.5 ± 12.8 (mean ± s.d.) min for the group with succinylcholine, and 58.5 ± 21.5 min for the control group. In both groups, the average duration of four consecutive supplemental doses of vecuronium was approximately 35 min. No significant differences between groups were found in the duration of neuromuscular blockade induced by initial and supplemental doses of vecuronium.     

Intestinal Vascular Responses to Dopamine During Fentanyl-Nitrous Oxide Anaesthesia, Supplemented with Dixyrazin

Intestinal haemodynamics in response to continuous i.v. administration of dopamine were investigated in cats anaesthetized with fentanyl-nitrous oxide either with or without supplement of dixyrazin. A dose-dependent vasodilatation was observed in the dopamine dose range 2.5–35 μg-kg^-1 min ^-1 and the subsequent maximal intestinal blood flow increase was 121%. No net intestinal vasoconstriction was evident even at the largest dopamine doses, although the vascular response reached a plateau at 17.5 μg-kg^-1 min^-1. Control experiments during chloralose anaesthesia gave similar results. Changes in mean arterial pressure and heart rate were small. Renal blood flow was virtually unchanged at dopamine doses below 10 μg-kg^-1 min^-1, while renal vasoconstriction was evident following dopamine doses above that level. The addition of i.v. dixyrazin (0.15-0.30 mg kg^-1) to the fentanyl-nitrous oxide anaesthesia substantially potentiated the intestinal vasodilator response to i.v. dopamine and the maximal blood flow increase was 183% at 10–15 μg kg^-1 min^-1. In vitro experiments using mesenteric resistance vessels from the rat demonstrated a dose-dependent relaxation to dopamine. At very large doses this response was counteracted, but not reversed into vasoconstriction by dopamine-induced a-adrenergic stimulation.     

Lack of effect of flumazenil on the reversal of propofol anaesthesia

Propofol, like the benzodiazepines, activates the GABA_A receptor-chloride ionophore complex; they potentiate one another. Since neither pharmacodynamic nor pharmacokinetic data concerning drug interaction between flumazenil and propofol is available, and especially considering the relationship of binding sites, flumazenil, the antagonist of benzodiazepines, was investigated to determine its effect upon recovery from propofol anaesthesia. Forty women receiving dilatation and curettage procedures were included in this double-blind test. After 50 μg fentanyl, propofol 2 mg · kg^-1 was injected for induction and followed by infusion at the rate of 15 mg · kg^-1 · hr^-1. After the operation, patients were given normal saline (Group A) or flumazenil 10 μg · kg^-1 (Group B) randomly.
Recovery time in Group A was 15.2±5.1 min and Group B 15.8±4.8 min. Propofol concentrations at the end of infusion were 4.17±1.33 μg ·ml^-1 (Group A) and 4.03±1.45 μg · ml^-1 (Group B); these then declined to 1.22±0.17 μg · ml^-1 (Group A) and 1.18±0.15 μg · ml^-1 (Group B) when patients were able to open their eyes on command. No significant differences were found between the groups based on propofol concentrations and recovery time, nor did haemodynamic changes differ between them after administration of reversal agents. It was concluded that flumazenil 10 μg · ml^-1 does not influence recovery from propofol anaesthesia.     

Propofol sedation and gastric emptying in volunteers

Background : The purpose of this study was to evaluate the effects of light propofol sedation on gastric emptying and orocecal transit time (OCT).
Methods : Ten healthy male volunteers were studied on 2 occasions separated by at least 1 week and were randomly allocated to receive either propofol sedation or i.v. saline as a control. During propofol sedation the volunteers were sedated to grade 2–3 on a 5-grade scale. This was achieved by a propofol infusion of 5 mg kg^-1 h^-1 initially, which was then titrated down to a dose of 2.4±0.7 mg kg^-1 h^-1 Paracetamol absorption was used as an indirect measure of the rate of gastric emptying and OCT was determined by use of the hydrogen breath test after ingestion of raffinose. Student's t -test for paired samples was used and the results are presented as means± SD.
Results: During propofol sedation the maximum concentration of paracetamol (C_max) was 115±26.8μl/L, time to peak concentration (T_max) 50±38.8 min, and the area under the curve during the first 60 min (AUC₆₀4793±1538 μmolXmin/L, versus C_max 99±20.8, T_max 69±41.9 and AUC₆₀ 3897±1310 during saline infusion. These differences were not statistically significant. OCT was significantly shorter during the control study, 180±32.4 min, than during propofol sedation, 217±64.9 min (P<0.05).
Conclusion : This study in volunteers has shown that gastric emptying of liquids seems uninfluenced by light propofol sedation. OCT was slightly prolonged during light propofol sedation.     

Comparison of propofol/alfentanil anaesthesia with isoflurane/N2O/fentanyl anaesthesia for renal transplantation

Total intavenous anaesthesia (TIVA) with propofol and alfentanil was compared with balanced anaesthesia (BA) in 30 uraemic patients undergoing renal transplantation. TIVA (n=15) was induced with propofol and alfentanil and maintained with propofol and alfentanil infusions, which were started immediately after induction. Thereafter the infusion rates were adjusted as needed. Ventilation was with oxygen in air. BA (n= 15) was induced with thiopentone and fentanyl and maintained with isoflurane/N20/fentanyl. Vecuronium was used for muscle relaxation in both groups. Mean infusion rates for propofol and alfentanil were 10 1.8 mg kg^-1 h^-1 and 70 9 μg kg^-1 h^-1, respectively. To control hypertension during TIVA, larger amounts of propofol and alfentanil were needed and slower recovery was observed than in previous studies in ASA 1–2 patients. Also, significantly more vecuronium was needed during TIVA than during BA ( P < 0.05). The recovery parameters were similar in both groups, except for the occurrence of nausea, which was less after TIVA. In conclusion, TIVA had no clinical advantages over BA.     

Intramuscular dexmedetomidine premedication—an alternative to midazolam-fentanyl-combination in elective hysterectomy?

Sedation, anxiolysis, intubation responses and fentanyl anaesthetic requirements were investigated in a double-blind, randomized study in twenty ASA I-II elective hysterectomy patients. Ten patients received dexmedetomidine 2.5 μg kg^-1 i.m. 60 min before induction and saline placebo i.v. 2 min prior to induction (= DP group). Ten patients received midazolam 0.08 mg kg^-1 i.m. 60 min and fentanyl 1.5 μg kg^-1 i.v. (= MF group) 2 min before induction of anaesthesia with thiopentone 4 mg kg^-1. Anaesthesia was maintained with 70% nitrous oxide in oxygen and with fentanyl 2 μg kg^-1 i.v. increments according to predetermined criteria. Both premedications induced sedation ( P < 0.01 in both groups) and anxiolysis ( P < 0.01 in DP vs <0.05 in MF group) without any differences between the groups. Haemodynamic changes following tracheal intubation did not significantly differ between the groups. Intraoperatively systolic and diastolic arterial pressure were 15% and 13% lower in DP group ( P < 0.01 and P < 0.05 for drug effect), the mean heart rate was approximately 9 beats min^-1 lower in DP group (n.s.). Fentanyl was required more often in MF group: median 3.5 (QD 1.5) vs. 2.5 (QD 0.5) times in DP group ( P < 0.05), the total amount being 57% smaller in DP group: 0.03 (QD 0.01) vs. 0.07 (QD 0.02) μg kg^-1 min^-1 ( P < 0.05). Postoperative course and analgesic requirements were similar in both groups. Dexmedetomidine premedication may offer an alternative to current anaesthesia practice in elective hysterectomy.     

A comparison of the effects of fentanyl and propofol on left ventricular contractility during myocardial stunning

Background : The intravenous anaesthetic propofol has been shown to possess free radical scavenging activity and calcium channel blocking effects in a number of in vitro models. We decided to compare the effects of propofol with those of fentanyl on myocardial contractility during and after ischaemia to determine whether propofol could protect the heart and improve recovery of ventricular contractile function in open-chested dogs.
Methods : Twenty adult beagles were acutely instrumented, under halothane anaesthesia, to measure ECG; aortic, left ventricular pressures; cardiac output; coronary flow; and segmental lengths in the regions perfused by the left anterior and left circumflex coronary arteries. After surgery and a stabilisation period halothane anaesthesia was terminated and fentanyl (100 μg. kg^-1 bolus followed by 2 μ.kg^-1·min^-1 infusion; n=10) or propofol (5 mg. kg^-1 bolus followed by 0.3 mg· kg^-1 min^-1 infusion; n=10) anaesthesia commenced. After a stabilisation period the LAD coronary artery was occluded for 10 min and then reperfused for 3 h. Measurements were taken throughout the protocol.
Results : We found no significant difference in recovery of contractile function between propofol and fentanyl as assessed by normalised preload recruitable work area (50±10 vs 47±16%), normalised systolic shortening (36±12 vs 48±14%) and peak left ventricular dP/dt (1665±276 vs 1846±151 mmHg.s^-1) at the end of reperfusion.
Conclusion : We conclude that at the concentration used in this study propofol shows no improvement in contractility during "stunning" when compared to fentanyl.     

Mivazerol prevents the tachycardia caused by emergence from halothane anesthesia partly through activation of spinalα2-adrenoceptors

Background : Mivazerol (MIV) is anα₂-adrenoceptor agonist designed to prevent adverse cardiac outcome in perioperative patients. The present study was undertaken to determine whether the hyperdynamic state observed at emergence from halothane (HAL) anesthesia in rats could be modulated by MIV and to explore the mode of action of MIV under such conditions.
Methods : Male Sprague Dawley rats were anesthetized with 1% HAL and assisted for respiration (N₂O-O₂: 70-30%). MIV 2.2–15.3μg.kg^-1.h^-1 i.v. was infused 30 min before withdrawal of anesthesia and compared for heart rate (HR) and systolic arterial blood pressure (SAP) to control animals treated with saline. In some experiments, animals were pretreated with intrathecal pertussis toxin (T2 level, 0.5μg, 7 d), or i.v. rauwolscine (0.34 mg/kg, 5 min) or were bilaterally stellectomized (30 min) prior to withdrawal of HAL.
Results : Increases in HR (65 bpm, +20%) and in SAP (25 mmHg, +26%) were observed immediately upon discontinuation of HAL and remained constant for at least 30 min. The increase in HR was abolished by removal of the stellate ganglia. MIV dose-dependently inhibited the increase in HR from 4.8μg.kg^-1.h^-1 (68% reduction, P <0.05) without affecting HR or SAP during anesthesia. Inhibition of HR increase was of 98% at 15.3μg.kg^-1.h^-1. This effect was abolished by rauwolscine, and partially (50%) inhibited by pertussis toxin pre-treatment.
Conclusion : These results demonstrate that withdrawal of HAL anesthesia in the rat produces a sustained increase in HR due to activation of the sympathetic system and that MIV inhibits this tachycardia via activation ofα₂-adrenoceptors located at least in part in the spinal cord.     

Effects of propofol on ipecacuanha-induced nausea and vomiting

Background : The purpose of this study was to evaluate if propofol has 5-HT₃ antagonistic effects. Ipecacuanha is known to release serotonin (5-HT) in the gastrointestinal tract and therefore ipecacuanha syrup was used to induce nausea and vomiting. The 5-HT₃ antagonist ondansetron was used as a control substance.
Results : During the first 150 min after ingestion of ipecacuanha there were no retchings during the ondansetron infusion ( P = 0.01 vs placebo, P =0.02 vs propofol) and significantly fewer retchings during propofol infusion compared to placebo ( P <0.02). There was no nausea during the ondansetron infusion ( P <0.01 vs placebo and propofol) but the volunteers experienced nausea both during the placebo and propofol infusion (NS).
Conclusion : This study in volunteers has shown that propofol reduces the intensity of retching after oral intake of ipecacuanha syrup. As ipecacuanha releases 5-hydroxytryptamine, it can be concluded that propofol may have a weak 5-HT₃ antagonistic effect.
Method : Ten healthy male volunteers (20–37 years) were studied on three occasions and were randomly allocated to receive a concomitant infusion of propofol (initial bolus 0.1 mg kg^-1 then 1 mg kg^-1h^-1), ondansetron (initial bolus 0.11 mg kg^-1 then 14 μg kg^-1 h^-1) and placebo on either occasion. The infusions started 30 min before oral ingestion of 30 ml of ipecacuanha and continued until 150 min after the intake. The number of retchings was recorded and the intensity of nausea was estimated by the subjects on a visual analog scale.     

Pentobarbital Plasma Concentrations and Cardiac Electrophysiology During Prolonged Pentobarbital Infusion Anaesthesia in the Dog

There is need for a prolonged stable level of anaesthesia, and we therefore investigated the cardiac electrophysiological effects of continuous pentobarbital infusion after initial pentobarbital injection to induce anaesthesia in dogs. Plasma concentrations of pentobarbital were measured by gas-liquid chromatography. Heart rate, atrial, atrioventricular (AV) nodal and His-Purkinje conduction times were measured by His bundle electrography, and atrial, AV nodal and ventricular refractoriness by programmed electrical stimulation. Over a 5-h observation period, continuous infusion of pentobarbital 3.5 mg · kg^-1 h^-1 after an initial pentobarbital injection of 25 mg · kg^-1 intravenously gave stable mean plasma concentrations of 140-135 μmol · l^-1. The cardiac electrophysiological variables studied did not change significantly during this period. We conclude that a stable experimental model for cardiac electrophysiological studies can be obtained for several hours by-continuous pentobarbital infusion.     

The effect of epidural bupivacaine on vecuronium–induced neuromuscular blockade in children

The efTect of epidural bupivacaine on potency and duration of action of vecuronium–induced neuromuscular blockade (NMB) was evaluated in 30 general surgical paediatric patients (ASA I–II) of three to ten years of age. Premedication was midazolam 0.5 μg kg^-1 orally (max 15 mg). In addition to general anaesthesia, 15 of the children received a lumbar epidural block with 0.5% bupivacaine 2.5 mg kg^-1. Anaesthesia was induced and maintained with N₂O:o₂ (2:1), propofol and alfentanil. NMB was monitored by adductor pollicis EMG with the train–of–four stimulus every 20 sec. Thirty minutes following the epidural bupivacaine injection (mean plasma concentration 0.86 μg ml^-1) or induction of anaesthesia a cumulative dose–response curve of vecuronium was established to achieve a 95% depression of the twitch response. Thereafter, NMB was allowed to recover spontaneously. ED doses of vecuronium were 19–22% greater in the control group than in the epidural group. ED^ doses were 33.8 (s.e.mean 1.3) μg kg"¹ and 28.4 (2.2) μg kg"', respectively ( P <0.05). There were no differences in recovery times from NMB between control and epidural group, the recovery index (time of twitch height to recover from 25 to 75%) being 6.4 (0.4) min and 7.0 (0.9) min, respectively. However, a negative correlation was found between bupivacaine plasma concentration and an ED₅₀ dose of vecuronium ( P =0.01). Our results indicate that vecuronium is slightly more potent in children with bupivacaine epidural block than in children without it.     

Quantifying the effect of enflurane on atracurium infusion requirements

The present study was designed to evaluate the interaction between atracurium and enflurane in 40 adult surgical patients using closed-loop feedback control of infusions of atracurium. Anaesthesia was induced with thiopentone and fentanyl and intubation was facilitated with atracurium 0.5 mg· kg^?1 lean body mass. During the first 90 min, anaesthesia was maintained with nitrous oxide in oxygen (2:1) and fentanyl. For the following 90 min the patients were randomly assigned to receive enflurane at different end-tidal concentrations: Group I, control, fentanyl-nitrous oxide anaesthesia; Group II, enflurane 0.3%-nitrous oxide; Group III, enflurane 0.6%-nitrous oxide; Group IV, enflurane 0.9%-nitrous oxide. The possible interaction of atracurium with enflurane was quantified by determining the asymptotic steady-state rate of infusion (I_ss) of atracurium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirements. Every patient served as his/her own control and the changes in the infusion rates were determined individually. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular blockade constant at the setpoint, did not differ among groups. In Group II I_ss decreased from 0.33 ± 0.12 to 0.26 ± 0.08 mg· kg^?1· hr^?1 (P < 0.01), in Group III from 0.32 ± to 0.12 to 0.24 ± 0.08 mg· kg^?1· hr^?1 (P < 0.001) and in Group IV from 0.29 ± 0.09 to 0.21 ± 0.09 mg· kg^?1 · hr^?1 (P < 0.001). In the control group atracurium requirements remained unchanged throughout the study. Enflurane reduces atracurium requirements in a dose-dependent manner. During enflurane anaesthesia the rate of atracurium infusion should be reduced but because of interindividual differences the monitoring of the neuromuscular function is important to ensure the appropriate level of neuromuscular block.     

Effect of succinylcholine on subsequently administered mivacurium in children

The interaction between mivacurium and succinylcholine when mivacurium was administered during the early recovery from succinylcholine block was studied in 30 children 2-12 years of age anaesthetized with propofolalfentanil-N₂O-O₂. Neuromuscular response was monitored by adductor pollicis EMG. Fifteen patients received 200 μg. kg^-1 of mivacurium (Group M), and another fifteen received 1500 μg. kg^-1 of succinylcholine followed by 200 μg. kg^-1 of mivacurium when the first EMG response recovered to 5% of calibration value (Group SchM). Plasma cholinesterase (pChE) activity was normal in each patient. The recovery times following mivacurium did not differ between the two groups. Times required for recovery of the first EMG response from 25 to 75% of full EMG recovery were 3.6±1.0 (mean±SD) and 4.0±0.7 min for the Groups M and SchM, respectively. The time from administration of mivacurium to the recovery of train-of-four ratio 0.70 was 13.2±3.3 min for the Group M and 13.6±3.1 min for the Group SchM (NS). Thus, in patients with normal pChE activity preceding administration of succinylcholine did not influence the recovery of neuromuscular function from subsequent mivacurium.     

Cardiovascular Effects of High-Dose Fentanyl Anaesthesia

An anaesthetic technique using high-dose fentanyl for coronary artery surgery is described. Fentanyl 160 or 70 μg kg^-1 was used as the sole anaesthetic agent, and patients were ventilated with air/O₂ (fentanyl 70 μg kg^-1) or N₂O/O₂ (fentanyl 60 μg kg^-1). Cardiovascular data from 30 patients are presented. Fentanyl caused no significant cardiovascular depression. The only statistically significant changes in cardiovascular parameters were seen in the patients who received fentanyl 60 μg kg^-1. Five minutes after skin incision there was an increase in peripheral resistance. Diastolic pressure was increased following sternotomy. Problems associated with this technique of anaesthesia are a 50% incidence of hypertension following sternotomy (requiring treatment with sodium nitroprusside) and prolonged respiratory depression. The lack of cardiovascular depression produced by fentanyl and the ability of fentanyl to reduce hormonal and metabolic responses to surgery make it a satisfactory technique for cardiac anaesthesia.     

Propofol influences the electroretinogram to a lesser degree than thiopentone

Background: The Electroretinogram (ERG) is used clinically to assess the function of retina. Anaesthetic agents are known to affect ERG, and as anaesthesia is often needed in children and uncooperative patients, knowledge about its effects is of clinical importance. Barbiturates selectively depress ERG components, and we compared thiopentone with propofol to assess if the latter preserved retinal function better.
Methods: Ten pigs, average weight 17 kg (SD ± 2 kg) were anaesthetized randomly with propofol 10 mg kg^-1 or thiopentone 30 mg kg^-1. Anaesthesia was maintained by 65% nitrous oxide in oxygen and continuous infusion of the induction agent, i.e. 10 mg kg^-1 h^-1 of propofol, or 10 mg kg^-1 h^-1 for the first hour, then 5 mg kg^-1 h^-1 of thiopentone, with doses being based on pilot studies. After an interval of one week the programme was repeated using the other agent. After 40 minutes dark-adaptation, responses to single flashes of graded intensities from a xenon flashlamp were recorded at five-minute intervals. The a- and b-wave amplitudes and implicit times (time to peak), and a-wave slopes were determined.
Results: The b-wave implicit time was significantly shorter during propofol anaesthesia than when using thiopentone. The effect was most pronounced at the lowest intensities (P < 0.01). No statistically significant differences were found in the amplitudes of the b-waves. The a-wave appeared at lower stimulus intensity (P < 0.05) and the a-wave slopes were significantly steeper (P < 0.01) during propofol anaesthesia.
Conclusion: Propofol accordingly appeared to preserve the photoreceptor response better than thiopentone, and may therefore be considered to be more suitable for ERG recordings than thiopentone.     

Isosorbide dinitrate does not interfere with heparin anticoagulation:

The possible nitrate-induced heparin resistance was studied intraoperatively in 40 patients undergoing coronary artery bypass grafting. The patients were randomized to receive a continuous infusion of placebo, nitroglycerin (0.5 μg kg^-1 min^-1) or isosorbide dinitrate (0.5 or 2.5 μg kg^-1 min^-1). After the infusion had been administered, prior to the institution of cardiopulmonary bypass, for at least 60 min, porcine intestine heparin 300 I.U. kg^-1 (as divided in two consecutive doses of 100 and 200 I.U. kg^-1, respectively) was administered to achieve systemic anticoagulation. Activated coagulation time values and plasma heparin anti-X_a activity showed no significant differences between the groups before and after the administration of heparin. It is concluded that in doses given in the present study, organic nitrates do not interfere with the anticoagulation effect of large doses of heparin required for the conduction of cardiopulmonary bypass.     

Reversal of atracurium-induced neuromuscular block in paediatric patients

We studied the efficacy of neostigmine and edrophonium to reverse an atracurium-induced 90% neuromuscular block in 80 paediatric patients anaesthetized with thiopentone, fentanyl and nitrous oxide. The patients were divided into five age groups: 0–2 months, 3–11 months, 2–5 years, 6–10 years, and 11–15 years. At the end of surgery, the neuromuscular block was randomly antagonized with either neostigmine 50 μg kg^-1 with atropine 20 μg kg^-1 or with edrophonium 1 mg kg^-1 with atropine 10 μg kg^-1. In general, the first EMG response and train-of-four (TOF) ratio recovered fastest in the youngest age groups following either reversal agent ( P <0.05). However, in each age group edrophonium had a faster onset of effect than neostigmine ( P <0.05) even though a greater TOF-ratio was finally reached with neostigmine. The effects of neostigmine were less variable and more predictable than those of edrophonium. Therefore, we recommend the use of neostigmine for routine paediatric practice.     

Recovery characteristics of propofol anaesthesia, with and without nitrous oxide: a comparison with halothane/nitrous oxide anaesthesia in children

Few studies have examined whether nitrous oxide influences the recovery characteristics of propofol anaesthesia. The present study examined the effect of nitrous oxide on the recovery characteristics of propofol anaesthesia, and compared these data with those for halothane/nitrous oxide anaesthesia. Sixty children aged 3–12 years were assigned at random to receive one of three maintenance regimens: propofol with or without nitrous oxide (70%) or halothane/nitrous oxide (70%). During propofol/N₂O anaesthesia, the infusion rate of propofol (180±39 μg·kg⁻¹·min⁻¹) required to maintain the mean arterial pressure and heart rate within 20% of the baseline values was significantly less than that during propofol/O₂ (220±37 μg·kg⁻¹·min⁻¹; P <0.005). The time from discontinuation of anaesthesia to eye-opening (11±6 min), to response to commands (12±6 min), and to return of full wakefulness (21±10 min) after propofol/N₂O were similar to those after propofol/O₂, but significantly less (by approximately 30%) than those after halothane ( P <0.05). The overall incidence of emesis after propofol/N₂O (53%) was greater than that after propofol/O₂ (17%, P <0.05) and comparable to that after halothane/N₂O (58%). These data suggest that N₂O has little effect on the rate of recovery after propofol, but significantly increases the incidence of postoperative emesis, thereby attenuating one of the main attributes of propofol anaesthesia.