Postoperative decrease in plasma sodium concentration after infusion of hypotonic intravenous solutions in neonatal surgery.

BACKGROUND: Hypotonic i.v. solutions can cause hyponatraemia in the context of paediatric surgery. However, this has not been demonstrated in neonatal surgery. The goal of this study was to define the relationship between infused perioperative free water and plasma sodium in neonates. METHODS: Newborns up to 7 days old undergoing abdominal or thoracic surgery were included in this prospective, observational study. Collected data included type and duration of surgery, calculated i.v. free water intake, and pre- and postoperative plasma sodium. Statistical analyses were performed using the Pearson correlation, Mann-Whitney test, and receiver operating characteristic analysis with a 1000 time bootstrap procedure. RESULTS: Thirty-four subjects were included. Postoperative hyponatraemia occurred in four subjects (11.9%). The difference between preoperative and postoperative plasma sodium measurements (ΔNaP) correlated with calculated free water intake during surgery (r=0.37, P=0.03), but not with preoperative free water intake. Calculated operative free water intake exceeding 6.5 ml kg(-1) h(-1) was associated with ΔNaP≥4 mM with a sensitivity and specificity [median (95% confidence interval)] of 0.7 (0.9-1) and 0.5 (0.3-0.7), respectively. CONCLUSIONS: Hypotonic solutions and i.v. free water intake of more than 6.5 ml kg(-1) h(-1) are associated with reductions in postoperative plasma sodium measurements ≥4 mM. In the context of neonatal surgery, close monitoring of plasma sodium is mandatory. Routine use of hypotonic i.v. solutions during neonatal surgery should be questioned as they are likely to reduce plasma sodium.

[Opioid-sparing effect of ketamine during tonsillectomy in children]. / Effet d'épargne morphinique de la kétamine au cours de l'amygdalectomie chez l'enfant.

INTRODUCTION: In the adult population, Ketamine is currently used as an antihyperalgesic and opioid-sparing agent during the perioperative period. However, for doses of ketamine up to 0.5mg/kg, these effects have not been found in pediatric population. The aim of the present study was to evaluate the efficacy of a preoperative bolus of 1mg/kg of ketamine on postoperative pain intensity and morphine consumption in children undergoing tonsillectomy. METHODS: We have undertaken a retrospective comparison of 60 consecutive children operated for tonsillectomy in our institution before (first 30 patients) and after (last 30 patients) the introduction of a preoperative bolus of 1mg/kg of ketamine. Data collected were: age, ASA score, dose of intraoperative sufentanil, OPS score during PACU stay and the first postoperative day, morphine consumption during PACU stay and the first postoperative day, psychodysleptic manifestations, pain at first solid oral intake and postoperative respiratory complications or haemorrhage. RESULTS: No difference was found between the two groups in terms of demographic characteristics. Perioperative doses of sufentanil, postoperative opioid consumption or pain score in PACU or during 24hours were similar between the two groups. The two groups did not differ in terms of pain at first oral intake, or other adverse effects. CONCLUSION: These results suggest that 1mg/kg of ketamine administered right after anaesthesia induction in children undergoing tonsillectomy did not result in an opioid sparing effect.

[Anesthetic malignant hyperthermia: what's new in 2012?]. / Quoi de neuf en hyperthermie maligne en 2012 ?

Malignant hyperthermia (MH) is a pharmacogenetic disorder of anesthesia. Recent advances dealing with epidemiology of MH and the safe anesthetic course of MH susceptible patients are shortly presented here with a special insight into the preparation of modern anesthesia workstations, which they will share in operating room.

An individual scoring system for the prediction of postpartum anaemia.

BACKGROUND: Postpartum anaemia (PPA) is a common postpartum complication. The goal of this study was to prospectively construct a predictive score for individual risk of PPA. PATIENTS ET METHOD: We prospectively analyzed factors associated with PPA (<10gdL(-1) at 48hours postpartum). Parameters analyzed were demographic data, pregnancy characteristics, delivery and postpartum characteristics. Univariate analysis was performed using Anova or X(2); the Cox model was used for multivariate analysis. The scoring system was validated using ROC curve. RESULTS: Analysis was performed in 475 patients and validation was carried using an additional 95 patients. Multivariate analysis found four factors independently associated with PPA: anaemia during the third trimester of the pregnancy, Southeast Asian ethnic origin, episiotomy and severe postpartum haemorrhage (PPH) identified by the use of sulprostone. According to the score derived from the Cox model, patients were classified as low (22%, score=0), medium (55%, score=2 or 3) and high (86%, score>3) probability of PPA. Using the AUC of the ROC curve for both the first and the validation cohorts (performed on 95 further patients), we recorded AUCs of 72% and 70% respectively. CONCLUSIONS: This study allowed the derivation and validation of a predictive score of PPA. This score might be useful in targeting prophylactic strategies for PPA. Such strategies could include a more active treatment of iron deficiency (increasing oral iron treatment observance or intravenous iron therapy) especially in exposed population, improvement in the prevention and treatment of postpartum haemorrhage and decreasing the use of episiotomy. Future studies must focus on the external validation and generalisation of this scoring system.

Renal transplantation in children: critical analysis of age related surgical complications.

To determine age-related risk factors of urological and vascular complications. We performed a retrospective analysis of the data of 202 renal transplantations in 193 children between 1989 and 2007 at a single institution. Out of 193 grafts (combined renal and liver grafts were excluded), we observed urological complications in 42 cases (21.7%) leading to graft loss in one case and vascular complications in 27 cases (13.9%) leading to graft loss in seven. The urological complications were VUR (n=25, 12.4%), ureteral stricture (n=10, 5%), anastomotic leak (n=4, 2%), ureteral necrosis (n=2, 1%), and incrustative pyelitis (n=1, 0.5%). Vascular complications were arterial stricture (n=14, 7.2%), arterial thrombosis (n=4, 2%), venous thrombosis (n=2, 1%), and others (n=7). Donors aged less than six yr were a risk factor of vascular complications leading to graft loss (p=0.0001), whereas patients with PUV had more urological complications (p=0.001). Overall patient and graft survival is 93.1% and 84% at five yr, respectively. Surgical complications remain a major cause of graft loss (12%) and morbidity in children's kidney transplantation (38.9%). Young age of donors is the major risk factor of early graft loss as a result of vascular complication. However, donor selection based on age is limited by the shortage of organs.

Pharmacological prevention of sevoflurane- and desflurane-related emergence agitation in children: a meta-analysis of published studies.

BACKGROUND: Emergence agitation (EA) in children is increased after sevoflurane anaesthesia. The efficacy of prophylactic treatment is controversial. The aim of this study was to provide a meta-analysis of the studies of the pharmacological prevention of EA in children. METHODS: A comprehensive literature search was conducted to identify clinical trials that focused on the prevention of EA in children anaesthetized with sevoflurane, desflurane, or both. The data from each trial were combined using the Mantel-Haenszel model to calculate the pooled odds ratio (OR) and 95% confidence interval. I(2) statistics were used to assess statistics heterogeneity and the funnel plot and the Begg-Mazumdar test to assess bias. RESULTS: Thirty-seven articles were found which included a total of 1695 patients in the intervention groups and 1477 in the control ones. Midazolam and 5HT(3) inhibitors were not found to have a protective effect against EA [OR=0.88 (0.44, 1.76); OR=0.39 (0.12, 1.31), respectively], whereas propofol [OR=0.21 (0.16, 0.28)], ketamine [OR=0.28 (0.13, 0.60)], alpha(2)-adrenoceptors [OR=0.23 (0.17, 0.33)], fentanyl [OR=0.31 (0.18, 0.56)], and peroperative analgesia [OR=0.15 (0.07, 0.34)] were all found to have a preventive effect. Subgroup analysis according to the peroperative analgesia given does not affect the results. CONCLUSIONS: This meta-analysis found that propofol, ketamine, fentanyl, and preoperative analgesia had a prophylactic effect in preventing EA. The analgesic properties of these drugs do not seem to have a role in this effect.

Premedication with clonidine is superior to benzodiazepines. A meta analysis of published studies.

BACKGROUND: Premedication is considered important in pediatric anesthesia. Benzodiazepines are the most commonly used premedication agents. Clonidine, an alpha2 adrenoceptor agonist, is gaining popularity among anesthesiologists. The goal of the present study was to perform a meta-analysis of studies comparing premedication with clonidine to Benzodiazepines. METHODS: A comprehensive literature search was conducted to identify clinical trials focusing on the comparison of clonidine and Benzodiazepines for premedication in children. Six reviewers independently assessed each study to meet the inclusion criteria and extracted data. Original data from each trial were combined to calculate the pooled odds ratio (OR) or the mean differences (MD), 95% confidence intervals [95% CI] and statistical heterogeneity were accessed. RESULTS: Ten publications fulfilling the inclusion criteria were found. Premedication with clonidine, in comparison with midazolam, exhibited a superior effect on sedation at induction (OR=0.49 [0.27, 0.89]), decreased the incidence of emergence agitation (OR=0.25 [0.11, 0.58]) and produced a more effective early post-operative analgesia (OR=0.33 [0.21, 0.58]). Compared with diazepam, clonidine was superior in preventing post-operative nausea and vomiting (PONV). DISCUSSION: Premedication with clonidine is superior to midazolam in producing sedation, decreasing post-operative pain and emergence agitation. However, the superiority of clonidine for PONV prevention remains unclear while other factors such as nausea prevention might interfere with this result.

Multicentre evaluation of in vitro contracture testing with bolus administration of 4-chloro-m-cresol for diagnosis of malignant hyperthermia susceptibility.

BACKGROUND AND OBJECTIVE: The in vitro contracture test with halothane and caffeine is the gold standard for the diagnosis of susceptibility to malignant hyperthermia (MH). However, the sensitivity of the in vitro contracture test is between 97 and 99% and its specificity is 78-94% with the consequence that false-negative as well as false-positive test results are possible. 4-Chloro-m-cresol is potentially a more specific test drug for the in vitro contracture test than halothane or caffeine. This multicentre study was designed to investigate whether an in vitro contracture test with bolus administration of 4-chloro-m-cresol can improve the accuracy of the diagnosis of susceptibility to MH. METHODS: Three hundred and fifty-two patients from 11 European MH laboratories participated in the study. The patients were first classified as MH susceptible, MH normal or MH equivocal by the in vitro contracture test according to the European MH protocol. Muscle specimens surplus to diagnostic requirements were used in this study (MH susceptible = 103 viable samples; MH equivocal = 51; MH normal = 204). 4-Chloro-m-cresol was added to achieve a concentration of 75 micromol L(-1) in the tissue bath. The in vitro effects on contracture development and muscle twitch were observed for 60 min. RESULTS: After bolus administration of 4-chloro-m-cresol, 75 micromol L(-1), 99 of 103 MH-susceptible specimens developed marked muscle contractures. In contrast, only two of 204 MH-normal specimens showed an insignificant contracture development following 4-chloro-m-cresol. From these results, a sensitivity rate of 96.1% and a specificity rate of 99.0% can be calculated for the in vitro contracture test with bolus administration of 4-chloro-m-cresol 75 micromol L(-1). Forty-three patients were diagnosed as MH equivocal, but only specimens from 16 patients developed contractures in response to 4-chloro-m-cresol, indicating susceptibility to MH. CONCLUSIONS: The in vitro contracture test with halothane and caffeine is well standardized in the European and North American test protocols. However, this conventional test method is associated with the risk of false test results. Therefore, an improvement in the diagnosis of MH is needed. Regarding the results from this multicentre study, the use of 4-chloro-m-cresol could increase the reliability of in vitro contracture testing.

Recent advances in the diagnosis of malignant hyperthermia susceptibility: how confident can we be of genetic testing?

Malignant hyperthermia (MH) is a condition that manifests in susceptible individuals only on exposure to certain anaesthetic agents. Although genetically heterogeneous, mutations in the RYR1 gene (19q13.1) are associated with the majority of reported MH cases. Guidelines for the genetic diagnosis for MH susceptibility have recently been introduced by the European MH Group (EMHG). These are designed to supplement the muscle biopsy testing procedure, the in vitro contracture test (IVCT), which has been the only means of patient screening for the last 30 years and which remains the method for definitive diagnosis in suspected probands. Discordance observed in some families between IVCT phenotype and susceptibility locus genotype could limit the confidence in genetic diagnosis. We have therefore assessed the prevalence of 15 RYR1 mutations currently used in the genetic diagnosis of MH in a sample of over 500 unrelated European MH susceptible individuals and have recorded the frequency of RYR1 genotype/IVCT phenotype discordance. RYR1 mutations were detected in up to approximately 30% of families investigated. Phenotype/genotype discordance in a single individual was observed in 10 out of 196 mutation-positive families. In five families a mutation-positive/IVCT-negative individual was observed, and in the other five families a mutation-negative/IVCT-positive individual was observed. These data represent the most comprehensive assessment of RYR1 mutation prevalence and genotype/phenotype correlation analysis and highlight the possible limitations of MH screening methods. The implications for genetic diagnosis are discussed.

Familial and sporadic forms of central core disease are associated with mutations in the C-terminal domain of the skeletal muscle ryanodine receptor.

Central core disease (CCD) is an autosomal dominant congenital myopathy. Diagnosis is based on the presence of cores in skeletal muscles. CCD has been linked to the gene encoding the ryanodine receptor (RYR1) and is considered to be an allelic disease of malignant hyperthermia susceptibility. However, the report of a recessive form of transmission together with a variable clinical presentation has raised the question of the genetic heterogeneity of the disease. Analyzing a panel of 34 families exclusively recruited on the basis of both clinically and morphologically expressed CCD, 12 different mutations of the C-terminal domain of RYR1 have been identified in 16 unrelated families. Morphological analysis of the patients' muscles showed different aspects of cores, all of them associated with mutations in the C-terminal region of RYR1. Furthermore, we characterized the presence of neomutations in the RyR1 gene in four families. This indicates that neomutations into the RyR1 gene are not a rare event and must be taken into account for genetic studies of families that present with congenital myopathies type 'central core disease'. Three mutations led to the deletion in frame of amino acids. This is the first report of amino acid deletions in RYR1 associated with CCD. According to a four-transmembrane domain model, the mutations concentrated mostly in the myoplasmic and luminal loops linking, respectively, transmembrane domains T1 and T2 or T3 and T4 of RYR1.

An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor.

Central core disease (CCD) and nemaline myopathy (NM) are congenital myopathies for which differential diagnosis is often based on the presence either of cores or rods. Missense mutations in the skeletal muscle ryanodine receptor gene (RYR1) have been identified in some families with CCD. Mutations in the alpha-tropomyosin and alpha-actin genes have been associated with most dominant forms of NM. Analysis of the RYR1 cDNA in a French family identified a novel Y4796C mutation that lies in the C-terminal channel-forming domain of the RyR1 protein. This mutation was linked not only to a severe and penetrant form of CCD, but also to the presence of rods in the muscle fibres and to the malignant hyperthermia susceptibility (MHS) phenotype. The Y4796C mutation was introduced into a rabbit RYR1 cDNA and expressed in HEK-293 cells. Expression of the mutant RYR1 cDNA produced channels with increased caffeine sensitivity and a significantly reduced maximal level of Ca(2+) release. Single-cell Ca(2+) analysis showed that the resting cytoplasmic level was increased by 60% in cells expressing the mutant channel. These data support the view that the rate of Ca(2+) leakage is increased in the mutant channel. The resulting chronic elevation in myoplasmic concentration is likely to be responsible for the severe expression of the disease. Haplotyping analysis indicated that the mutation arose as a neomutation in the proband. This first report of a neomutation in the RYR1 gene has strong implications for genetic linkage studies of MHS or CCD, two diseases characterized by a genetic heterogeneity.

Protein concentration in pulmonary oedema fluid for negative pressure pulmonary oedema in children.

We report a case of acute pulmonary oedema following upper airway obstruction in a 1-year-old patient. We discuss the pathophysiology of this infrequent complication of upper airway obstruction and the interest of alveolar protein/blood protein ratio measurement to determine the mechanism of pulmonary oedema.

Thoracic pheochromocytoma revealed by ventricular tachycardia. Clinical case and review of the literature.

A case of thoracic extra-adrenal pheochromocytoma was observed in a 13-year-old girl. The initial clinical symptoms consisted of her being unwell after effort over a period of 3 years. The diagnosis was suggested after a recorded episode of paroxysmal ventricular tachycardia with concomitant hypertension, which reproduced the characteristic symptoms. Biochemical analysis confirmed hypersecretion of catecholamines and morphological examinations showed the presence of an isolated left median thoracic tumor. One year after surgical excision, the patient remained completely asymptomatic, in spite of resuming intense sporting activity. The diagnosis of ectopic pheochromocytoma should be considered as a possible etiology of cardiac rhythm disturbances or hypertension in children. Thorough biochemical and radiological examination including MIBG radioisotope scanning should be carried out systematically before surgical excision; pheochromocytomas in children are frequently extra-adrenal (30%), multifocal (50%) or associated with multiple endocrine neoplasms (NEM).

[Caffeine skinned fiber tension test: application to the diagnosis of susceptibility to malignant hyperthermia]. / Test à la caféine sur fibres pelées: application au diagnostic de la susceptibilité à l'hyperthermie maligne.

OBJECTIVE: To assess the reactivity of sarcoplasmic reticulum to caffeine, using the skinned muscle fibre tension test and to compare it with the reference in vitro contracture test in the diagnosis of malignant hyperthermia (HM) susceptibility. STUDY DESIGN: Laboratory investigation. MATERIAL: Muscle biopsies from 63 patients, including 29 classified as susceptible to MH (MHS) and 34 classified as non-susceptible (MHN) according to criteria of the European and the North American MH groups. METHOD: The reactivity to caffeine and halothane of skinned muscle fibres was compared, according to the type of fibres, with the data of the in vitro contracture test. The type of fibres (type I: oxidative, slow; type II: glycolytic, fast) were determined with strontium dose-response curves. RESULTS: The reactivity to caffeine was significantly lower in the MHS group, for both type I and type II skinned fibres. However, in comparison with the data of the in vitro contracture tests, using the ROC curve analysis, the best sensitivity-specificity compromise was 90%-71% and 74%-84% for type I and type II skinned fibres respectively. CONCLUSION: The skinned muscle fibre tension test cannot be used instead of the in vitro contracture test for the diagnostic of MHS. However, it may strengthen the data of the latter.