PHARAMACOKINETICS OF PROPOFOL IN YOUNG CHILDREN AFTER A SINGLE DOSE

The pharmacokinetics of propofol were studied following a singlebolus injection (2.5 mg kg^–1) in 10 healthy children (4–7yr). Propofol was distributed rapidly and extensively (Vss 10.9(1.2) litre kg^–1) and cleared rapidly from the body (Cl30.6 (2.9) ml min^–1 kg^–1). With the exception ofa larger central compartment volume (V 722 (113) ml kg^–1).these data are similar to those reported for young adults whoreceived an identical dose and who underwent sampling over thesame period. The larger value of V is consistent with the higherinduction dose requirement reported for children.     

Pharmacokinetics and antipyretic effects of an injectable pro-drug of paracetamol (propacetamol) in children

Propacetamol is a soluble injectable form of paracetamol, which is quickly hydrolysed after intravenous injection. We report the pharmacokinetic results of this drug in children between 10 months and 14 years of age. Three minutes after an i.v. administration of 15 mgkg^-1 the mean plasma paracetamol concentration was about 25 μgml^-1. In a course of repeated administration of propacetamol, the plasma concentration 3 min after the fourth dose remained at about the same value, showing that there was no accumulation of paracetamol. The pharmacokinetic parameters (half life, total clearance and distribution volume) were similar to those in adults. At 15 mgkg^-1 doses, the antipyretic effect is well-established.     

CLINICAL PHARMACOLOGY OF VECURONIUM IN CHILDREN: Studies During Nitrous Oxide and Halothane in Oxygen Anaesthesia

Forty-seven children (ASA I or II) were studied during nitrousoxide-oxygen, halothane anaesthesia. The dose-response curvefor vecuronium was determined after the injection of a singlebolus (40, 55 or 70 µg kg-¹) to 33 patients. The ED₅₀and ED₉₅ were 31 and 64 µg kg^–1 respectively. Fourteenchildren received a larger dose (100 µg kg^–1); goodintubating conditions were obtained in all of these within 2min. After a single bolus (100 µg kg^–1) the durationof action was 36.5 min and the recovery index was 9.3 min. Inpatients who received small maintenance doses (25 µg kg^–1)after a single bolus (100 µg kg^–1) the recoveryindex after the last maintenance dose was not increased. Therewere no significant changes in heart rate or arterial pressure.In children, has a vecuronium has a short duration of actionand lacks cumulative or cardiovascular side affects.     

VENTILATORY RESPONSES TO CARBON DIOXIDE IN CHILDREN DURING NITROUS OXIDE-HALOTHANE ANAESTHESIA

The ventilatory response to carbon dioxide was studied in 12unpremedicated children, aged 20–68 months, weighing between10 and 20 kg, under nitrous oxide-halothane anaesthesia. Tidalvolume (VT) and end-tidal carbon dioxide tension (PE'_CO2) werecontinuously measured by pneumotachograph and capnograph. Minuteventilation (), respiratory rate (f), mean in-spiratory flow (VT) and effective inspiratorycycle (T1/T^tot) were calculated during anaesthesia at threedifferent inspired halothane concentrations (0.5, 7 and 1.5%).The ventilatory response to carbon dioxide was determined byrelating the increase in ventilation during exposure to 2% carbondioxide to the change in end-tidal carbon dioxide concentration.When the inspired concentration of halothane increased, therewere significant decreases in , VT, , and a significant increase in PE'_CO2 The slope of the carbon dioxide response under lightnitrous oxide-halothane anaesthesia (0.5% halothane) was relativelyflat (18.64 ml min^–1 kg^– mm Hg^-1) when comparedwith the mean values published for anaesthetized adults, childrenor neonates. When the inspired concentration of halothane wasincreased, the slope decreased significantly (39% of initialvalue at 1 % inspired halothane, 26% at 1.5%). The additionof carbon dioxide produced significant increases in , VT and but no change in respiratory rate. No statistical differencewas observed in the slope of carbon dioxide response betweenthe initial and "control" periods which were measured at thesame inspired halothane concentration (0.5%).     

Theatre staff members and exposure to halogenated agents

Ninety-eight measurements were made to evaluate the level of pollution by halogenated anaesthetics, in 27 operating rooms of 12 hospitals in the Paris area. Air sampling was made during ordinary work sessions to evaluate the degree of personal pollution to which different members of the operating room staff were exposed. Samples were analysed by gas chromatography. The degree of personal pollution was particularly high in hospitals devoted to paediatric surgery. Anaesthetists were most at risk. Scavenging equipment and a large volume of air in the operating room helped in a reduction in the level of pollution. A high rate of air extraction and the use of a filter appeared to be necessary to reduce pollution.     

PHARMACOKINETICS OF LIGNOCAINE IN CHILDREN FOLLOWING CAUDAL ANAESTHESIA

The time course of the plasma lignocaine concentration, followingcaudal anaesthesia, was studied in 11 healthy children (3.5–9yr). Plasma lignocaine concentrations were measured for up to6 h after administration (5 mg kg^–1). Peak plasma concentrationwas 2.05+0.08 µ ml^–1 and occurred at 28.2±2.9min after administration. Pharmacokinetic parameters determinedfrom a two-compartmental model were similar to those observedafter the i.v. or extradural administration of lignocaine inadults, except for a longer half-life of elimination (155±32min). Since the total body clearance of lignocaine was similarin children (15.4±1.2 ml min^–1 kg^–1) to thatin adults, the longer half-life of elimination was attributedto a larger volume of distribution in the children (3.05 ±0.40litre kg^–1).     

Lactated Ringer with 1% dextrose: an appropriate solution for peri-operative fluid therapy in children

Peri-operative blood glucose, total protein, and electrolytes values were measured in children (3–120 months) scheduled for minor surgery and randomly assigned to three groups according to the type of fluids administered during anaesthesia: children of RL group (n= 27) received lactated Ringer, those of RLD1 group (n= 25), 1% dextrose in lactated Ringer, and those in RLD2.5 group (n= 27), 2.5% dextrose in 0.4 N saline (50% D5, 50% RL) (63 mmol·l^-1). Infusion rate was set according to children's age and weight. Fluids were infused throughout the study with volumetric infusion pumps. Blood samples were obtained at induction (T0), at the end of surgery (T1), 30 and 60 min later (T2, T3). Pre-operative blood values were within the normal ranges except for high total protein values in all groups of children and for asymptomatic hypoglycaemia (2.3 and 2.5 mmol·l^-1) in two children. Blood glucose increased significantly in the three groups post-operatively (P < 0.001), and this increase was related to the amount of glucose infused. Glucose values differed significantly between groups at T1 and T2, while blood glucose values were back to the normal ranges at T2 and T3 in the RL group. Sodium values remained unchanged post-operatively in both RL and RLD1 groups, while a significant decrease was observed in the RLD2.5 group (P < 0.001). Total protein decreased in the three groups post-operatively (P < 0.001) towards normal values. These data suggest that RLD1 is appropriate for peri-operative fluid therapy in children. Its administration at the infusion rate used in this study, resulted in moderate post-operative hyperglycaemia while avoiding the risk of peri-operative hypoglycaemia, maintaining a constant extracellular fluid composition and correcting pre-operative fluid deficit.     

Ondansetron reduces nausea and vomiting after paediatric adenotonsillectomy

The efficacy, safety and resource implications of a single intravenous dose of ondansetron (0.1 mg·kg⁻¹, maximum 4 mg) were assessed in a multinational, multicentre, randomized, double-blind, placebo-controlled trial of 427 children aged 1–12 years, undergoing tonsillectomy with/without adenoidectomy. Emesis (retching and/or vomiting) and nausea were analysed separately. Significantly more ondansetron-treated children had no episodes of emesis (127/212 (60%) vs 100/215 (47%); P =0.004) and experienced no postoperative nausea (135/211 (64%) vs 108/213 (51%); P =0.004) in the first 24 h. Ondansetron also reduced the number of emetic episodes ( P <0.001), the time to the first emetic episode ( P <0.001) and overall nausea severity ( P =0.003). Significantly fewer ondansetron-treated children were rescued or withdrawn from the study (5% vs 10%; P =0.042). Fewer ondansetron-treated patients required nursing intervention (34% vs 45%; P =0.007) and the average intervention time was significantly shorter (4.6 vs 8.1 minutes; P =0.001). Resources used to manage PONV were significantly reduced by ondansetron (43% vs 57%; P =0.014).     

Sevoflurane elimination kinetics in children

We compared the rates of elimination of sevoflurane and halothane in 29 children, aged between one and seven years, undergoing ambulatory anaesthesia. Analgesia was provided by fentanyl and muscle relaxation by atracurium. Anaesthesia was maintained by inhalation of one MAC of either sevoflurane or halothane, based on an equipotent concentration of each agent for the age of the child. Following simultaneous discontinuation of N₂O and the inhalational agent, the equation describing N₂O washout was identical in the presence of halothane and sevoflurane, showing that there was no effect of the volatile agent on the rate of N₂O elimination. The elimination of sevoflurane and N₂O give similar types of equations. Halothane elimination gives a logarithmic type of equation, showing a slower release, corresponding to residual tissue content.     

CHANGES IN VENTILATORY PATTERNS DURING HALOTHANE ANAESTHESIA IN CHILDREN

Changes in ventialtory variables (VE, VE, f, T₁/T^tot. VT/T₁.PE'_co2) were studied in 12 unpremeicated children, weighingbetween 10 and 20 kg, during halothane anaesthesia. at an inspiredconcentration of 0.5% halothane, respiratory rate increased,VT decreased, and VE did not change markedly. When the inspired.;halothane concentration increased further, there was a significantdecrease in VE, mainly as a result of a marked decrease inVT.PE'_CO2 increased significantly and inspiratory duty cycle decreasedat high inspired halothane concentrations. On return to baseline(0.5% halothane), there was a significant decrease in inspiratorytiming and a significant increase in PE'_CO2- The relations betweenthese changes and the effect of halothane on inspiratory musclesare discussed.