Side-effects of postoperative epidural analgesia in children: a randomized study comparing morphine and clonidine.

BACKGROUND: Morphine is widely used in association with local anaesthetics for postoperative epidural analgesia. There are no data on the prolonged use of clonidine for postoperative analgesia in children. The primary outcome of this randomized, double-blind trial was to compare the incidence of side-effects after epidural infusion of clonidine or morphine, in association with ropivacaine in children. METHODS: After institutional approval, 26 children, aged 3-12 years, who were scheduled for abdominal surgery, had an epidural catheter placed after induction of general anaesthesia. Patients were then randomized to two different groups. After an initial bolus of 2.5 mg x kg-1 0.25% ropivacaine with either 40 micro g x kg-1 morphine (group M, n = 14) or 1 micro g x kg-1 clonidine (group C, n = 12), an epidural infusion was started at a rate of 0.4 ml x kg-1 x h-1. The patients in the M group received an infusion of 0.08% ropivacaine with 10 micro g.ml-1 morphine, those in the group C an infusion of 0.08% ropivacaine with 0.6 micro g.ml-1 clonidine. RESULTS: The two groups were similar with respect to age, sex and weight. One patient in the C group was excluded for misplacement of the epidural catheter. The incidence of vomiting and pruritus was significantly higher in the M group compared with the C group (64% and 85% versus 0%, respectively). The incidence of pain was significantly higher in the C group compared with the M group (73% versus 29%) as well as the need for rescue analgesia medications. CONCLUSIONS: Epidural clonidine is followed by a significantly lower incidence of side-effects. However, its analgesic effects, at least at the doses used in this study, are less potent than those of epidural morphine.

Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with and without biliary atresia.

BACKGROUND: Continuous epidural infusion of bupivacaine is widely practiced for postoperative pain relief in pediatric patients. However, bupivacaine may induce adverse effects in infants (convulsions or cardiac arrhythmias), likely because of decreased hepatic clearance and serum protein binding capacity. The authors wanted to examine the complex relations between age, alpha-1 acid glycoprotein (AAG) concentration, and unbound and total bupivacaine serum concentrations in infants receiving bupivacaine epidurally for 2 days. METHODS: Twenty-two infants aged 1-7 months (12 with biliary atresia and 10 with another disease) received a continuous epidural infusion of 0.375 mg x kg(-1) x h(-1) bupivacaine during 2 days (during and after surgery). Unbound and total bupivacaine concentration in serum was measured 0.5, 4, 24, and 48 h after infusion initiation. AAG concentration was measured in serum before and 2 days after surgery. In eight additional infants, the blood/plasma concentration ratio was measured in vitro at whole blood concentrations of 2 and 20 microg/ml. Bupivacaine concentration was fitted to a one-compartment model to calculate basic pharmacokinetic parameters. RESULTS: No adverse effects were observed. AAG increased markedly after surgery, and the increase was correlated to both age and preoperative AAG concentration. Two infants aged 1.8 months had unbound concentrations greater than 0.2 microg/ml. Clearance of unbound drug significantly increased with age. Because of increased drug binding, clearance of bound drug decreased both with time (from 0.5 to 48 h) and with age. Blood/plasma ratio was 0.77+/-0.08 and 0.85+/-0.24 at 2 and 20 microg/ml, respectively. CONCLUSIONS: Because of a low AAG concentration and a low intrinsic clearance, unbound bupivacaine increased to concentrations greater than 0.2 microg/ml in two infants younger than 2 months, after 2 days of infusion at a rate of 0.375 mg x kg(-1) x h(-1). The increase in AAG observed after surgery did not fully buffer this unbound fraction. Similarly, the buffer capacity of erythrocytes did not sufficiently increase at high concentration to compensate the saturation of the AAG system. Thus, we propose the use of a maximum dose of 0.25 mg x kg(-1) x h(-1) in infants younger than 4 months and a maximum of 0.3 mg x kg(-1) x h(-1) in infants older than 4 months.

Epidural analgesia in a child with sickle cell disease complicated by acute abdominal pain and priapism.

We describe a case of a 9-yr-old child with sickle cell disease complicated by abdominal vaso-occlusive crisis and priapism. Both complications were successfully treated with a combination of epidural local anesthetics and morphine.

Transient neurologic symptoms after epidural analgesia in a five-year-old child.

Transient neurologic symptoms occurred in a five-year-old child after discontinuation of epidural analgesia with bupivacaine and morphine, which had been established for two days after thoracotomy. The symptoms resolved within 12 hours with acetaminophen.

[Diagnosis of a persistent left superior vena cava in the operating room during a central venous catheterization]. / Diagnostic d'une veine cave supérieure gauche persistante au bloc opératoire lors d'un cathétérisme veineux central.

A 2-year-old boy was admitted for surgical excision of a hepatoblastome. A central venous catheter was inserted by a subclavian approach, without difficulty. The chest radiograph showed the catheter positioned along the left heart border. The diagnosis of persistent left superior vena cava was suspected after analysis of the central venous pressure curve. An postoperative chest X-ray confirmed the diagnosis. The catheter was maintained for five days without any complication.

Respiratory effects of desflurane anesthesia on spontaneous ventilation in infants and children.

UNLABELLED: Volatile anesthetics depress spontaneous ventilation in a dose-dependent manner with variations in effects among different drugs. The goal of this prospective study was to assess respiratory changes during spontaneous ventilation using desflurane/O2/N2O anesthesia in two groups of children. Both groups were undergoing minor surgery and consisted of children < 2 yr old (Group I) and children > 2 yr old (Group II). They were examined at 0.5, 1, and 1.5 minimum alveolar anesthetic concentration desflurane anesthesia. Induction of anesthesia was performed via a face mask and a mixture of O2/N2O (40:60) with halothane. At lease 20 min after stopping halothane, the respiratory variables were recorded on desflurane anesthesia. Tidal volume and minute ventilation decreased significantly (P <0.05) as desflurane increased from 0.5 to 1.5 MAC in both groups. At 1.5 MAC, the respiratory rate was greater in Group II than in Group I (P <0.05). In both groups, the increase in end-tidal CO2 was significant at 1.5 MAC versus 1 and 0.5 MAC (P <0.05). Apnea, i.e., no respiratory movement for 20 s, occurred at 1.5 MAC in one patient in each group. The respiratory duty cycle did not change in any of the groups. Both indices of paradoxical respiration--amplitude index and delay index--did not change. IMPLICATIONS: Desflurane induces respiratory depression at concentrations higher than 1 minimum alveolar anesthetic concentration mainly due to a decrease in tidal volume. Therefore, desflurane at high concentrations should be used cautiously in infants and children with spontaneous ventilation.

Determinants of life span after Kasai operation at the era of liver transplantation.

The aim of this work is to determine the influence of age, extrahepatic biliary lesions pattern (EHBP) and association to polysplenia syndrome (PS) on 10 years outcome of 164 patients with biliary atresia (BA) treated from 1984 to 1992 by initial Kasai operation (KO) and secondary liver transplantation (LT) when necessary. Actuarial crude survival without or after LT (CS), actuarial survival with native liver (NLS) and jaundice-free actuarial survival with native liver (JFS) were calculated from 1 to 10 years versus age (under/over 45 days), EHBP (favorable/ unfavorable) and PS (no/yes). Overall 10-year CS is 70%, overall 10-year NLS and JFS are 14%. In univariate analysis, age at KO under 46 days, favorable EHBP (BA with patent gallbladder, and/or cystic dilatation of extrahepatic bile duct, or BA restricted to choledocus), and absence of PS are significant determinants of a better outcome regarding CS, NLS and JFS. EHBP is more discriminant than age. Influence of PS in this series is redundant with that of EHBP since 11/11 patients with PS had unfavorable EHBP.

Clonidine in pediatric caudal anesthesia.

Extradural clonidine produces analgesia in adults. To assess its efficacy in children, we randomized 45 pediatric patients aged 1-7 yr presenting for a subumbilical surgery into three groups of 15 each. After halothane and N2O/O2 induction, and with a double-blind protocol, caudal anesthesia was performed with 1 mL/kg of 0.25% bupivacaine. Epinephrine 1/200,000 was added in one group (EG), 1 microgram/kg of clonidine in another group (CG), and no additional medication in the last group (BG). Postoperative analgesia was evaluated using the Broadman "objective pain/discomfort scale" (OPS) at 1-h intervals until the first analgesic administration. There were no differences among the groups in age, weight, duration of surgery, baseline systolic arterial pressure, and heart rate. The mean (+/- SD) duration of analgesia was longer in the CG (987 +/- 573 min) than in the EG (377 +/- 341 min) and BG (460 +/- 439 min); P < 0.01. The maximal OPS scores were lower in the CG than in the EG and BG (2.3 +/- 1.6 vs 3.4 +/- 1.4 and 3.4 +/- 1.8, respectively; P < 0.05). More patients in the CG (n = 7) than in the EG (n = 1) and BG (n = 2) required no postoperative analgesia; P < 0.05. No differences were found among the groups for the minimal respiratory rate and minimal Spo2 values in the postoperative phase, and there were no differences among the groups for heart rate and systolic arterial pressure during the 3 h after caudal anesthesia. We conclude that the duration of postoperative analgesia with caudal bupivacaine was significantly increased by the addition of 1 microgram/kg of clonidine.

[Kasabach-Merritt syndrome with pancreatic hemangioma in an infant]. / Syndrome de Kasabach-Merritt avec hémangiome pancréatique chez un nourrisson.

BACKGROUND: Kasabach-Merritt syndrome is characterized by one or more large hemangiomas associated with thrombocytopenia due to platelet trapping. The hemangiomas may be located in the abdominal viscera, in which case, treatment may be difficult. CASE REPORT: A 2 1/2 month-old boy was admitted because of the discovery of an abdominal mass. He was anemic (hemoglobin: 6.8 g%; reticulocytosis: 288,000/mm3), thrombocytopenic (50,000/mm3), hypofibrinogenemic (0.95 g/l), with fibrin split products in the blood. Ultrasonography showed that this mass was retroperitoneal and heterogeneous. X-rays delineated the mass, which distorted the duodenal loop and pressed forward against the stomach. Surgery showed that the mass included the pancreas, the root of mesenterium and the extrahepatic bile duct. This mass was biopsied. Histological examination showed infantile type hemangioendothelioma. Abdominal angiography showed that the mass was not very hypervascularized, and there were no dilated supplying blood vessels. An aortogram showed two other small vascularized areas. The patient was given methylprednisolone, but the volume of the mass remained unchanged, while hepatosplenomegaly and jaundice developed and ultrasound showed dilated extra- and intrahepatic biliary ducts. The patient was then given interferon alpha 2b for 1 month. Embolization of the small supplying arteries was performed because of a lack of improvement after 1 week of treatment. This procedure was followed by rapid disappearance of the signs of consumption coagulopathy, a progressive improvement in cholestasis, and decrease in the mass. CONCLUSION: Improvement in manifestations of this Kasabach-Merritt syndrome is difficult to assign to one of the several therapies. The rapid disappearance of consumption coagulopathy after arterial embolization suggests that this treatment was successful in our patient.

[Transplantation of reduced-size livers in children]. / Transplantation des foies réduits chez l'enfant.

Nowadays, liver reduction techniques make it possible to use livers obtained from adults or adolescents for implantation in children. These techniques have been evaluated by analysis of 100 liver transplantations performed between January 1988 and October 1991 in 85 children. Forty-six full-size grafts implanted in 38 children (group 1) were compared with 54 reduced-size grafts implanted in 47 children (group 2). The overall actuarial survival at 4 years was 86 percent. There was no statistical significant difference between the two groups as regards the rates of death (8 versus 19 percent), reoperation (54 versus 64 percent), retransplantation (15 versus 16 percent), hepatic artery thrombosis (13 versus 15 percent) and graft survival (82 versus 70 percent) respectively. Haemorrhage was significantly more frequent in group 1 than in group 2 (P = 0.04), irrespective of whether transplantation was performed urgently or electively. Using reduced-size livers considerably increases the number of liver grafts available to children. Apart from a greater risk of haemorrhage, the results obtained with reduced-size livers were identical with those obtained with full-size livers.

Pediatric liver transplantation for primary hepatocellular carcinoma associated with hepatitis virus infection.

We report two cases of early primary hepatocellular carcinoma (PHC) in children, after probable maternal transmission of hepatitis B, that were treated with orthotopic liver transplantation (OLT). Both children were 8.5 years old and had elevated levels of serum alpha-feto-protein. The diagnosis of PHC was made at 8 years and confirmed histologically. Serum hepatitis B surface antigen (HBs Ag) was detected in the mothers and suggested vertical transmission. An attempt at complete liver tumor resection failed, leading to OLT. In order to prevent recurrence of the hepatitis B virus (HBV) infection, hepatitis B immunoprophylaxis was used. Two years after OLT, one child presented with recurrent HBV infection. No tumor recurrence was observed at follow-up in either of the patients. From these two cases we conclude that (1) HBV infection may play an important causal role in PHC in children, with an even shorter incubation period than that in adults; (2) close follow-up is needed for children who are HBs Ag-positive carriers; and (3) liver transplantation should be proposed early after the diagnosis of PHC, when tumor resection is not feasible.

[Surgery of liver transplantation in children]. / Chirurgie de la transplantation hépatique chez l'enfant.

From 1988 until 1992, 94 children with end-stage liver disease were put forward for orthotopic liver transplantation (OLT) by the surgical and anesthesic teams of the Bicetre Hospital. Due to a majority of adult donors, and to the young age of the recipients (mean = 3 years 3 months), a reduced-size graft was prepared in 64 out of the 111 transplants performed (58%). A number of children (42) had to be reoperated on due to complications: hepatic artery thrombosis, one of the most severe complications following pediatric OLT, occurred in 14 cases, and was an indication for seven out of the 17 retransplantations in this series. The eight deaths which occurred in the early postoperative period were the toll of this particularly challenging surgery.

Emergency liver transplantation for fulminant liver failure in infants and children.

We report our results with orthotopic liver transplantation in children with fulminant liver failure. Thirty-five children with fulminant liver failure were evaluated for liver transplantation. The main causes of liver failure were viral hepatitis (54.2%), drug-induced liver injury (14.2%) and Wilson's disease (11.4%). Children were considered as candidates for liver transplantation only if hepatic encephalopathy was associated with a decrease in the level of factor V to below 25%. Seven children (20%) did not meet this criterion and recovered spontaneously. Six children (17.1%) had contraindications for liver transplantation and died. In three of these six children, contraindications included irreversible brain damage at the time of admission. Twenty-two children (62.8%) met the criteria for liver transplantation and were placed on the emergency transplant list. Three of them died awaiting grafts. Nineteen children underwent liver transplantation; 13 of them (68.4%) are alive without sequelae, after 6 mo to 4 yr of follow-up, at this writing. Four of the children who died after surgery had severe encephalopathy on admission that did not improve after liver transplantation. In conclusion, emergency liver transplantation appears to be an effective treatment for children with fulminant liver failure. Nevertheless, irreversible brain damage developed in 10 patients, and they died before or after surgery. We postulate that many of these deaths could have been avoided if children had been transferred to a liver transplantation facility and had undergone transplantation earlier. We emphasize that children with acute liver failure should be transferred to a center that performs liver transplantation before the development of hepatic encephalopathy.

[EMLA analgesic cream for venopuncture during anesthetic induction in children]. / Crème analgésique EMLA pour la ponction veineuse lors de l'induction anesthésique chez l'enfant.

A prospective study was designed to assess the quality of skin analgesia provided by the EMLA anaesthetic cream, an eutectic mixture of local anaesthetics (prilocaine and lidocaine). The children, aged 3 months to 15 years, and scheduled for genital and urinary surgery, were allocated to two groups, those aged less than or equal to 5 years (35 +/- 14 months, n = 17), and those aged greater than 5 years (97 +/- 26 months, n = 22). The cream (1.6 +/- 0.6 g) was applied by a nurse in the ward as a thick layer on the area of skin to be anaesthetised (on the dorsum of the hand and at the elbow), and covered by a closed adhesive dressing. This required 2.6 +/- 1.7 min, and was considered to be very easy (72%) or easy (28%). The venepuncture (22 or 20 gauge catheter) was carried out by one of the seven anaesthetists of the paediatric surgical units, 92 +/- 51 min after the cream had been applied. The children aged less than or equal to 5 years complained of pain of intensity 7.5 +/- 2.2 (CHEOPS scale, range 4 to 13) and, for those aged greater than 5 years, 24 +/- 21 on a visual analogic scale (range 0 to 100). Local adverse effects occurred in ten patients (skin paleness, erythema, or both). It was concluded that EMLA cream provides convenient analgesia for venepuncture in toddlers and children.