Hidefumi Obara

Efficacy of Oral Clonidine Premedication in Children

BackgroundClonidine, an α2-adrenoceptor agonist, has been shown to be effective as a preanesthetic medication in adults. The current study was designed to investigate the efficacy of two doses of oral clonidine as a premedicant preceding oral atropine in children. MethodsIn a prospective, randomized, double-blind, controlled clinical trial, 105 children, aged 4–12 yr, undergoing elective ophthalmologic surgery received 0.4 mg/kg diazepam, 2 μg/kg clonidine, or 4 μg/kg clonidine orally. These agents mixed with apple juice were administered 105 min before the estimated time of induction of anesthesia, and were followed by treatment with 0.03 mg/kg oral atropine 60 min before anesthesia. A blinded observer noted the childrens level of sedation, quality of separation from parents, and degree of acceptance of mask application during inhalation of nitrous oxide used for establishment of venous access. Anesthesia was induced with 5 mg/kg thiamylal, and tracheal intubation was facilitated with 0.2 mg/kg vecuronium. Hemodynamic changes after tracheal intubation were compared among the three groups. ResultsClonidine produced significant sedation, and the effect was dose related. Clonidine, 4 μg/kg, provided better quality of separation and acceptance of mask than the two other regimens. This dose of clonidine attenuated the increases in blood pressure and heart rate after tracheal intubation. No clinically significant perioperative hypotension or bradycardia was observed. ConclusionsThese data indicate that, even in pediatric surgery, the combination of 4 μg/kg and 0.03 mg/kg oral clonidine is an effective premedication. However, the safety and optimal dose of clonidine in this setting remain to be determined.

Single catheter technique of hepatic venous isolation and extracorporeal charcoal hemoperfusion for malignant liver tumors.

BACKGROUNDnA single catheter technique of hepatic venous isolation and charcoal hemoperfusion (HVI-CHP) using a 4-lumen/2-balloon (4L-2B) catheter was developed to perform high-dose intra-arterial chemotherapy of the liver. Herein we report the technique, safety, and pharmacokinetics of this system in comparison with the original double-balloon technique.nnnPATIENTS AND METHODSnSixteen patients with malignant liver tumors were treated by hepatic arterial infusion (HAI) with adriamycin at a dose of 100 mg/m2 under HVI-CHP. Seven patients underwent HVI-CHP by the double-balloon technique (group A), in which filtered hepatic effluent and the rest of the inferior vena caval blood were separately drawn and returned to the left axillary vein. The other nine patients were treated by the single catheter technique (group B). In group B, hepatic effluent was isolated by balloon inflations and directed to filters through fenestrations of one major lumen of a 4L-2B catheter. The filtered blood was returned straight to the right atrium through the other major lumen of the catheter.nnnRESULTSnAll patients in group A had a smooth stepwise induction of HVI-CHP, whereas one of nine patients in group B developed severe hypotension requiring interruption of HVI. The hepatic venous flow rate in group B during HVI-CHP was significantly higher than that in group A (P < 0.05). Systemic adriamycin exposure, as assessed by the area under the time concentration curve in systemic serum, was significantly higher in group A compared to that in group B (P < 0.01).nnnCONCLUSIONSnThe single catheter technique is hemodynamically tolerable and feasible in the majority of patients with malignant liver tumors. In view of systemic drug exposure, the single catheter technique is superior to the original double-balloon technique.

Improvement of gas exchange following endobronchial instillation of an exogenous surfactant in an infant with respiratory failure by postoperative pulmonary haemorrhage.

We administered surfactant to a 5-month-old infant with respiratory failure due to right pulmonary haemorrhage accompanied by oedema following abdominal surgery. These pathological conditions were probably precipitated by disseminated intravascular coagulation and intra-operative excessive administration of fluids, respecitively. Endobronchial instillation of the exogenous surfactant (120 mg) after selective intubation of the right bronchus produced a dramatic improvement of gas exchange 30 min after treatment and of chest X-ray findings at 6 h post-treatment. This case on an infant indicates that administration of surfactant may be one of promising therapeutic approaches to respiratory failure due to pulmonary haemorrhage.

Effects of surfactant on lung injury induced by hyperoxia and mechanical ventilation in rabbits.

We evaluated the effects of exogenous surfactant on lung injury caused by 100% oxygen and mechanical ventilation in rabbits. Surfactant-treated rabbits (n=9) were ventilated with 100% oxygen for 36 hours and bovine surfactant was given via the trachea 12 hours after the start of mechanical ventilation. Saline-treated (n=9) rabbits were treated identically, except that they received saline without surfactant. There were no significant changes in hemodynamics, lung mechanics, or arterial oxygen tension during artificial ventilation.Albumin concentration in the bronchoalveolar lavage fluid (BALF) of saline-treated rabbits was slightly higher than those in surfactanttreated rabbits and significantly higher than in non-treated rabbits. C3a concentration in BALF was significantly higher in saline-treated rabbits than in surfactant-treated and non-treated rabbits. In addition, the wet-to-dry lung weight ratio was significantly lower in surfactanttreated rabbits than in saline-treated rabbits (5.06±0.10 vs. 5.67±0.14,P<0.05).Light microscopy revealed hyaline membrane formation in saline-, treated rabbits, but fewer changes were observed in surfactant-treated rabbits. Electron microscopy revealed extensive endothelial cell destruction in saline-treated rabbits, while such changes except endothelial cell swelling were not observed in surfactant-treated rabbits.We conclude that exogenous surfactant attenuated lung injury caused by oxygen exposure and ventilation.

Attenuation of the cardiovascular and catecholamine responses to tracheal intubation with oral guanabenz.

We conducted a randomized, placebo-controlled, and double- blind study to evaluate the efficacy of oral guanabenz, an α2−adrenergic agonist, in attenuating the cardiovascular and catecholamine responses to laryngoscopy and tracheal intubation in 30 normotensive (ASA physical status 1) patients undergoing elective surgery. They were allocated to one of three groups (n = 10 for each): placebo, 4 mg, or 6 mg of guanabenz groups. These tablets were administered 2 h before the induction of anesthesia. Anesthesia was induced with thiopental 15.0 mg/kg intravenously (IV), and tracheal intubation was facilitated by the administration of vecuronium, 0.2 mg/kg IV. During anesthesia, ventilation was assisted or controlled with 1% enflurane and 50% nitrous oxide in oxygen. Laryngoscopy lasting 30 s was attempted 2 min after the administration of thiopental and vecuronium. Patients receiving placebo showed a significant increase in mean arterial blood pressure, heart rate, and plasma catecholamine concentrations in response to tracheal intubation. These changes were significantly smaller in patients receiving either dose of guanabenz (P < 0.05). Oral administration of guanabenz before induction of anesthesia is a simple and effective method for attenuating the pressor and tachycardic responses to laryngoscopy and tracheal intubation with the drug acting at least partly via inhibition of the increases in plasma catecholamines concentrations.

A SHORT FASTING INTERVAL DOES NOT INCREASE PREOPERATIVE PLASMA ATRIAL NATRIURETIC POLYPEPTIDE CONCENTRATIONS IN CHILDREN

Sir, A long preoperative fast in children is believed to lower circulating blood volume (CBV) immediately before surgery. A shorter fast (2-3 h) before paediatric surgery has been recommended, since it does not preoperatively increase gastric fluid volume or decrease gastric pH (1, 2). Atrial natriuretic polypeptide (ANP) is a hormone from the heart, which may modulate acute changes in the volume and salt balance by enhancing diuresis and natriuresis and also lower the mean arterial pressure. Increased CBV is thought to be responsible for ANP secretion into the systemic circulation. In children, a long preoperative fast may lead to hypovolaemia at induction of anaesthesia, resulting in a lower plasma ANP concentration than after a short fast. To test this hypothesis, after institutional approval and informed consent from the parents of all patients, we measured the plasma ANP concentrations in 5 1 (n = 17 for each group) randomly selected unpremedicated children (ASA class I ) aged 1.5-13 years undergoing elective surgery. Each child ingested a large volume (approximately 10 ml/kg) of apple juice and then fasted for 2, 4, or 12 h before the estimated induction of anaesthesia. Children who had metabolic disorders and gastrointestinal or renal diseases, or who were on medication known to affect gastric fluid composition Acta Anaesthesiologica Scandinavia ISSN 0001-5172

Effect of superoxide dismutase on endothelium-dependent relaxation of aorta from endotoxin-treated rabbits

To assess the protective effect of superoxide dismutase (SOD) on the endothelium of aorta in endotoxaemia, we investigated the production of endothelium-derived relaxing factor in aorta obtained from endotoxin-treated rabbits concomitantly receiving SOD or not. Thirty-two male Japanese white rabbits were randomly divided into four groups (n = 8 for each group): one group receiving saline as a placebo, a second receiving 5 mg/kg endotoxin intravenously, a third receiving 5 mg/kg endotoxin intravenously plus SOD, and a fourth receiving SOD alone. SOD was injected intravenously at a dose of 10 000 U/kg before the endotoxin and was infused continuously at a rate of 15 000 units/kg/h throughout the experiment. The tension of the aorta was recorded in vitro 6 h after the start of in vivo treatment with endotoxin or saline. In the aorta of rabbits receiving endotoxin alone, acetylcholine-induced relaxation was reduced by 50%. The SOD fully restored the reduction of acetylcholine-induced relaxation by endotoxin. Histological studies using photomicroscopy revealed endothelial damage in the endotoxin-treated aorta, which was attenuated in the SOD-treated group. These data suggest that intravenous SOD may be an effective treatment for unstable haemodynamics in endotoxaemia.

Perioperative changes in Superoxide production in neonates and infants

We conducted a prospective study to investigate perioperative changes in the production of Superoxide anion (O2−) by neutrophils isolated from ten neonates between the ages of five and 16 days (N group) and ten infants ranging in age from one to ten months (I group). They underwent abdominal surgery under general anaesthesia with halothane and nitrous oxide in oxygen. The O2− production (speed and amount) was measured perioperatively using the cytochrome c reduction method. Both groups showed a decrease in the speed and amount of O2− production during and after surgery. The decrease in O2− production reached its lowest level three hours postoperatively or at the end of surgery in both groups. The O2− production in the I group returned to the basal value 48 hr postoperatively. In contrast, the O2− production in the N group was still lower 48 hr after surgery than before anaesthesia. Although the total amount of O2− production by neutrophils in one mL of peripheral blood remained unchanged in the I group, the total amount of O2− production in the N group decreased at the end of surgery and thereafter. These data indicate that even relatively minor abdominal surgery with halothane anaesthesia may be associated with perioperative neutrophil impairment in both neonates and infants. This impairment of neutrophil function in infants but not in neonates may be compensated by an increase in neutrophil numbers. It is possible that perioperative susceptibility of neonates to bacterial infections is attributable, at least in part, to the inhibition of O2− production in neutrophils by surgery and general anaesthesia.RésuméCette étude prospective vise l’évaluation périopératoire des changements de production de l’anion superoxyde (O2−) par les neutrophiles prélevés chez dix nouveaux-né de 5 à 16 jours (groupe N) et dix nourrissons de un à dix mois (groupe I). Tous sont soumis à une intervention abdominale sous anesthésie générale à l’halothane et au protoxyde d’azote en oxygène. La production d’O2− (vitesse et quantité) est mesurée à la période périopératoire par la méthode de la réduction du cytochrome c. Dans les deux groupes, on décèle une baisse de vitesse et de la quantité dans la production d’O2− pendant et après la chirurgie. La production d’O2− atteint dans les deux groupes son niveau le plus bas trois heures après l’intervention ou à la fin de l’intervention. Dans le groupe I, la production d’O2− revient à sa valeur initiale 48 heures après l’opération. Par contre, dans le groupe N, la production d’O2− demeure plus basse 48 heures après la chirurgie qu’avant t’anesthésie. Alors que la quantité totale d’O2− produite par les neutrophiles dans un mL de sang périphérique demeure inchangée dans le groupe I, la quantité totale d’O2− produite dans le groupe N diminue à la fin de la chirurgie et par la suite. Ces données montrent que même une chirurgie abdominale mineure avec anesthésie à l’halothane peut être associée à une atteinte pério-pératoire tant chez le nouveau-né que chez le nourrisson. Cette atteinte de la fonction des neutrophiles chez le nourisson peut être compensée par l’augmentation du nombre de neutrophiles. Il est possible, d’autre part, que la susceptibilité périopératoire des nouveaux-nés aux infections bactériennes soit attribuable, partiellement du moins, à l’inhibition de la production d’O2− dans les neutrophiles pendant la chirurgie générale et l’anesthésie.

Anesthetic management of a child with Maroteau-Lamy syndrome

Mucopolysaccharidoses (MPS) are diseases characterized by excessive storage and excretion of mucopolysaccharides. According to the sort of enzyme deficiencies, the MPS diseases are currently classified into seven types depending on mucopolysaccariduria patterns and the clinical features. Maroteaux-Lamy syndrome (MLS) is MPS type 6. The etiology of MLS is an inherited deficiency of arylsulfatase-B, which causes an increased urinary excretion of mucopolysaccarides consisting predominantly of dermatan sulfate, The clinical manifestations of MLS are a short statue, short neck, coarse facies, osseous changes, hepatosplenomegaly, umbilical and inguinal hernia, hearing loss and mental retardatton. Clinical interest in MLS has focussed on the problems caused by the accumulation of mucopolysaccharides in the cardiac t.issues and the frequent respirator infections which may increase postoperative morbidity