Factors affecting recovery of postoperative bowel function after pediatric laparoscopic surgery.

BACKGROUND AND AIMS: Laparoscopic pediatric surgery allows a rapid postoperative rehabilitation and hospital discharge. However, the optimal postoperative pain management preserving advantages of this surgical technique remains to be determined. This study aimed to identify factors affecting the postoperative recovery of bowel function after laparoscopic surgery in children. MATERIAL AND METHODS: A retrospective analysis of factors affecting recovery of bowel function in children and infants undergoing laparoscopic surgery between January 1, 2009 and September 30, 2009, was performed. Factors included were: Age, weight, extent of surgery (extensive, regional or local), chronic pain (sickle cell disease or chronic intestinal inflammatory disease), American Society of Anaesthesiologists status, postoperative analgesia (ketamine, morphine, nalbuphine, paracetamol, nonsteroidal anti-inflammatory drugs [NSAIDs], nefopam, regional analgesia) both in the Postanesthesia Care Unit and in the surgical ward; and surgical complications. Data analysis used classification and regression tree analysis (CART) with a 10-fold cross validation. RESULTS: One hundred and sixty six patients were included in the analysis. Recovery of bowel function depended upon: The extent of surgery, the occurrence of postoperative surgical complications, the administration of postoperative morphine in the surgical ward, the coadministration of paracetamol and NSAIDs and/or nefopam in the surgical ward and the emergency character of the surgery. The CART method generated a decision tree with eight terminal nodes. The percentage of explained variability of the model and the cross validation were 58% and 49%, respectively. CONCLUSION: Multimodal analgesia using nonopioid analgesia that allows decreasing postoperative morphine consumption should be considered for the speed of bowel function recovery after laparoscopic pediatric surgery.

Use of near-infrared spectroscopy in predicting response to intravenous fluid load in anaesthetized infants.

INTRODUCTION: The prediction of fluid responsiveness in paediatrics and infants remains problematic. We sought to test the validity of the measurement of StcO2 as a predictive parameter of fluid responsiveness in infants less than one year old during non-cardiac surgery. MATERIALS AND METHODS: This was a prospective observational study on infants aged less than 1 year without any cardiac disease during the intraoperative period of non-cardiac surgery. Cerebral oxygen saturation (StcO2) was obtained using infrared spectroscopic INVOS® monitors. Reference values were obtained 10 minutes after intubation. Fluid load indications were dependent on the anaesthesiologist caring for the patient. The objective of this study was to determine the accuracy of StcO2 values before vascular filling (StcO2B) and the difference in StcO2 values between the reference value and before vascular filling (ΔStcO2), in predicting vascular filling response defined as an increase in mean arterial pressure over 15%. Statistical analysis was carried out using ROC curve analysis with determination of grey zones. RESULTS: Twenty-nine patients were eligible for this study, 23 were included in the study (one intravenous fluid challenge per patient). There were 10 responders and 13 non-responders. The StcO2B and the ΔStcO2 were significantly different between responders and non-responders. Analysis of the ROC curve found an area under the curve of 0.75 [95% CI 0.56 to 0.95] for StcO2B and 0.83 [95% CI 0.66 to 0.99] for ΔStcO2. The grey-areas were [59-78] and [16-28] for StcO2B and ΔStcO2. CONCLUSION: NIRS appears to be an interesting additional tool for predicting an increase of blood pressure in response to intraoperative fluid challenge in infants less than one year old.

Preoperative preparation workshop reduces postoperative maladaptive behavior in children.

INTRODUCTION: Postoperative maladaptive behaviors (POMBs) are common following pediatric anesthesia, and preoperative anxiety is associated with POMBs. A family-centered preoperative preparation workshop was instituted with the aim of reducing the incidence of POMB and preoperative anxiety, and the study was constructed to evaluate its effectiveness. MATERIAL AND METHODS: A prospective cohort study was constructed, comparing patients who attended the workshop (workshop group) with patients who did not attend and who were matched for age and type of surgery (comparison group). Preoperative anxiety was measured using the mYPAS score, postoperative emergence agitation (EA) was measured using the PAED score, POMBs were assessed with the Post-Hospital Behavior Questionnaire (PHBQ) on postoperative day 7, and PACU morphine consumption and PACU length of stay were recorded. Statistical analysis was performed employing the X² test, the Fisher's exact test, and the Mann-Whitney test as appropriate. Data were expressed as median [minimum, maximum]. RESULTS: Fifty-six patients from 3 to 18 years of age were recruited. Twenty-seven patients in the workshop group were compared to 26 in the comparison group, after exclusions for missing data. Significant differences were demonstrated between groups for POMBs intensity (PHBQ score 2 [0; 9] vs 5 [0; 10], P = 0.008) and incidence (PHBQ score >6: 3.6% vs 35.7%, P = 0.003), and for mYPAS score (28 [23; 87] vs 37 [23;100], P = 0.015). No difference was found for EA, PACU morphine consumption, or PACU length of stay. CONCLUSION: The workshop appears to result in reduced preoperative anxiety and POMBs.

Intraoperative changes in blood pressure associated with cerebral desaturation in infants.

BACKGROUND: Intraoperative hypotension has been linked to poor postoperative neurological outcomes. However, the definition of hypotension remains controversial in children. We sought to determine arterial blood pressure threshold values associated with cerebral desaturation in infants. METHODS: After ethics committee approval, infants younger than 3 months were included in this prospective observational study. Cerebral saturation was assessed using near-infrared spectroscopy. The primary goal of the study was to determine percentage reductions in intraoperative systolic blood pressure (SBP) and mean blood pressure (MBP) associated with decreases in cerebral blood oxygen saturation of >20%, when compared to baseline. Analyses were performed using a bootstrap receiving operator characteristic (ROC) curves with determination of the gray zone. RESULTS: Sixty patients were recruited and 960 measurement points were recorded. Fifty-nine data points (6.1%) recorded cerebral desaturation of >20% when compared to baseline. The areas under the ROC curves were 0.79 (0.74-0.84) and 0.67 (0.6-0.75) for percentage decreases in SBP and MBP, respectively. Gray zone values with false-positive and negative rates <10% were SBP decreases of 20.5% and 37.5%, respectively, and MBP decreases of 15.5% and 44.5%, respectively. CONCLUSION: Our results indicate that falls in noninvasive systolic blood pressure of <20% from baseline are associated with a <10% chance of cerebral desaturation in neonates and infants <3 months of age undergoing noncardiac surgery. As such, maintaining systolic blood pressure above this threshold value appears a valid clinical target.

Predictive factors for homologous transfusion during paediatric scoliosis surgery.

INTRODUCTION: Blood saving strategies during paediatric spinal surgery often include recombinant erythropoietin (rEPO) and antifibrinolytic therapy (AFT). The goal of this study was to investigate additional preventive factors involved in the risk of blood transfusion. METHODS: This prospective study was designed with the aim of identifying factors associated with the perioperative (defined as the intraoperative and the first postoperative day) probability of homologous red cell transfusion during scoliosis surgery in children operated during a one year period in our institution. The predictors analysed were: age, weight less than the 3rd percentile (W<3P), indication for spinal surgery (idiopathic or neuromuscular), Cobb's angle, ASA status, preoperative haemoglobin, number of levels fused, duration of surgery, intraoperative fluid intakes, sacral fusion and thoracoplasty. Statistical analyses were performed using a multivariate logistic regression model. RESULTS: One hundred and forty-seven patients were included in the analysis. Multivariate analysis found the following variables to be independent predictors for an increased risk of homologous blood transfusion: W<3P, neuromuscular scoliosis and duration of surgery > 255 minutes. ROC analysis for the latter model found an area under the curve of 0.9 (95% confidence interval: 0.8-0.97). The accuracy of the model was 92.3% (97.4% for non-transfusion and 69.2% for transfusion). Multivariate sensitivity analysis excluding patients with no preoperative administration of EPO found similar results. CONCLUSION: The current results indicate that optimising nutritional status might prevent allogenic blood transfusion and requires further investigation.

Supraglottic airway devices vs tracheal intubation in children: a quantitative meta-analysis of respiratory complications.

BACKGROUND: Rate of perioperative respiratory complications between tracheal intubation (TI) and laryngeal mask airway remains unclear during pediatric anesthesia. OBJECTIVES: The aim of the present meta-analysis was to compare the perioperative respiratory complications between laryngeal mask airway and TI. METHODS: A meta-analysis of available controlled studies comparing laryngeal mask airway to TI was conducted. Studies including patients with airway infection were excluded. Data from each trial were combined to calculate the pooled odds ratios (OR) or mean difference (MD) and 95% confidence intervals. RESULTS: The meta-analysis was performed on 19 studies. In 12 studies, patients were given muscle relaxation, and in 16 studies, ventilation was controlled. During recovery from anesthesia, the incidence of desaturation (OR = 0.34 [0.19-0.62]), laryngospasm (OR = 0.34 [0.2-0.6]), cough (OR = 0.18 [0.11-0.27]), and breath holding (0.19 [0.05-0.68]) was lower when laryngeal mask airway was used to secure the airway. Postoperative incidences of sore throat (OR = 0.87 [0.53-1.44]), bronchospasm (OR = 0.56 [0.25-1.25]), aspiration (1.33 [0.46-3.91]) and blood staining on the device (OR = 0.62 [0.21-1.82]) did not differ between laryngeal mask airway and TI. Results were homogenous across the studies, with the exceptions of blood staining on the device. CONCLUSIONS: This meta-analysis found that the use of laryngeal mask airway in pediatric anesthesia results in a decrease in a number of common postanesthetic complications. It is therefore a valuable device for the management of the pediatric airway.

Development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients: the VPOP score.

BACKGROUND: Few data are available in the literature on risk factors for postoperative vomiting (POV) in children. OBJECTIVE: The aim of the study was to establish independent risk factors for POV and to construct a pediatric specific risk score to predict POV in children. METHODS: Characteristics of 2392 children operated under general anesthesia were recorded. The dataset was randomly split into an evaluation set (n = 1761), analyzed with a multivariate analysis including logistic regression and backward stepwise procedure, and a validation set (n = 450), used to confirm the accuracy of prediction using the area under the receiver operating characteristic curve (ROCAUC ), to optimize sensitivity and specificity. RESULTS: The overall incidence of POV was 24.1%. Five independent risk factors were identified: stratified age (>3 and <6 or >13 years: adjusted OR 2.46 [95% CI 1.75-3.45]; ≥6 and ≤13 years: aOR 3.09 [95% CI 2.23-4.29]), duration of anesthesia (aOR 1.44 [95% IC 1.06-1.96]), surgery at risk (aOR 2.13 [95% IC 1.49-3.06]), predisposition to POV (aOR 1.81 [95% CI 1.43-2.31]), and multiple opioids doses (aOR 2.76 [95% CI 2.06-3.70], P < 0.001). A simplified score was created, ranging from 0 to 6 points. Respective incidences of POV were 5%, 6%, 13%, 21%, 36%, 48%, and 52% when the risk score ranged from 0 to 6. The model yielded a ROCAUC of 0.73 [95% CI 0.67-0.78] when applied to the validation dataset. CONCLUSIONS: Independent risk factors for POV were identified and used to create a new score to predict which children are at high risk of POV.

Postoperative pain management in children and infants: an update.

Many factors contribute to suboptimal pain management in children. Current evidence suggests that severe pain in children has significant long-lasting effects, even more so than in adults. In particular, recent evidence suggests a lack of optimal postoperative pain management in children, especially following ambulatory surgery. This review provides simple guidelines for the management of postoperative pain in children. It discusses the long-term effects of severe pain and how to evaluate pain in both healthy and neurologically impaired children, including neonates. Currently available treatment options are discussed with reference to the efficacy and side effects of opioid and non-opioid and regional analgesic techniques. The impact of preoperative anxiety on postoperative pain, and the efficacy of some nonpharmacological techniques such as hypnosis or distraction, are also discussed. Finally, basic organizational strategies are described, aiming to promote safer and more efficient postoperative pain management in children.

A review of 5434 percutaneous pediatric central venous catheters inserted by anesthesiologists.

OBJECTIVE: To review the results of an anesthesiologist led pediatric percutaneous central venous access service. METHODS: Prospective data on percutaneous pediatric central venous catheter (CVC) insertions were collected over 22 years. Data included age, gender, weight, previous central CVCs, venous thromboses, investigations for great vein patency, type of CVC, external diameter, previous CVC insertions, intended use, operator identity, and the vein into which the CVC was inserted. The default technique was internal jugular vein cannulation using landmark technique (LT). Complication was defined as the following: failure to cannulate any vein, hemothorax, pneumothorax, right atrial perforation, extravenous wire positioning or CVC position and whether the patient was taken back to theater for CVC repositioning. RESULTS: Five thousand four hundred and thirty-four percutaneous CVC insertion procedures were performed on 3954 patients. One-third involved children <1 year of age (n = 1823: 34%). Five thousand one hundred and twenty-five CVCs (95.3%) were inserted into internal jugular veins. The majority were tunneled CVCs (n = 5190: 96.2%). The perioperative complication rate was 1.3%. Successful cannulation occurred in 99.5% of patients. Failure was more likely in children <3 kg, during large bore hemodialysis CVC insertions and during the first 4 years of the service - the latter suggesting a learning curve. Ninety-nine percent of CVCs were inserted using LTs. CONCLUSION: This study demonstrates a high success rate and low complication rate during pediatric percutaneous internal jugular vein CVC insertions by trained anesthesiologists using LTs. Smaller children, hemodialysis CVCs, and the team's learning curve were identified as risk factors for insertion failure.

Plethysmographic variability index (PVI) accuracy in predicting fluid responsiveness in anesthetized children.

INTRODUCTION: Plethysmographic Variability Index (PVI) has been shown to accurately predict responsiveness to fluid loads in adults. The goal of this study was to evaluate PVI accuracy when predicting fluid responsiveness during noncardiac surgery in children. MATERIAL AND METHODS: Children aged 2-10 years scheduled for noncardiac surgery under general anesthesia were included. PVI was assessed concomitantly with stroke volume index (SVI). A response to fluid load was defined by an SVI increase of more than 15%. A 10 ml·kg(-1) normal saline intravenous fluid challenge was administered before surgical incision and after anesthetic induction. After incision, fluid challenges were administered when SVI values decreased by more than 15% or where judged necessary by the anesthesiologist. Statistical analyses include receiving operator characteristics (ROC) analysis and the determination of gray zone method with an error tolerance of 10%. RESULTS: Fifty-four patients were included, 97 fluid challenges administered and 45 responses recorded. Area under the curve of ROC curves was 0.85 [0.77-0.93] and 0.8 [0.7-0.89] for baseline PVI and SVI values, respectively. Corresponding gray zone limits were [10-17%] and [22-31 ml·m(-2)], respectively. PVI values exhibited different gray zone limits for pre-incision and postincision fluid challenges, whereas SVI values were comparable. PVI value percentages in the gray zone were 34% overall and 44% for challenges performed after surgical incision. DISCUSSION: This study found both PVI and prechallenge SVI to be accurate when used to predict fluid load response during anesthetized noncardiac surgery in children. However, a third of recorded PVI values were inconclusive.

Predictive factors of PACU stay after herniorraphy in infant: a classification and regression tree analysis.

INTRODUCTION: Herniorraphy is a common surgical intervention in infants, particularly in those born prematurely. Prematurity and perioperative sedation have been shown to be risk factors for postoperative apnea. However, their influence upon PACU stay duration has not been evaluated. The goal of this study was to investigate predictive factors for PACU stay in infants undergoing herniorraphy. MATERIAL AND METHODS: This study is a retrospective analysis of perioperative data in infants <6 months of age undergoing herniorraphy during the period November 2007-November 2009. Collected data included age, gestational age at birth, post-conceptional age, weight, weight at birth, type of anesthesia (spinal vs general), perioperative administration of opioids and paracetamol, duration of surgery, duration of PACU stay, and apnea in PACU. Data analysis used classification and regression trees (CART) with a 10-fold cross-validation. RESULTS: Two hundred and ninety-six patients were included in the analysis. Five parameters were found to predict the duration of PACU stay: a post-conceptional age below 45 weeks, prematurity, general anesthesia, postoperative opioid administration, and the use of intraoperative regional analgesia. CRT method allows constructing a decision tree with eight terminal nodes. The percentage of explained variability of the model and the cross-validation were 79.7% and 76.6%, respectively. DISCUSSION: Our study allows construction of an accurate predictive tree for PACU stay during herniorraphy in infants <6 months. Parameters found to influence the duration of PACU stay were related to anesthesia techniques and perinatal outcomes.

A meta-analysis of the use of nonsteroidal antiinflammatory drugs for pediatric postoperative pain.

BACKGROUND: Opioid side effects are a great concern during the postoperative period in children. Nonsteroidal antiinflammatory drugs (NSAIDs) have been shown to effectively decrease postoperative pain, but their opioid-sparing effect is still controversial. In this present meta-analysis, we investigated the postoperative opioid-sparing effect of NSAIDs in children. METHODS: A comprehensive literature search was conducted to identify clinical trials using NSAIDs and opioids as perioperative analgesic compounds in children and infants. Outcomes measured were opioid consumption, pain intensity, postoperative nausea and vomiting (PONV), and urinary retention. All outcomes were studied during postanesthesia care unit (PACU) stay and the first 24 postoperative hours. Data from each trial were combined to calculate the pooled odds ratios (ORs) or standardized mean difference (SMD) and their 95% confidence interval. RESULTS: Twenty-seven randomized controlled studies were analyzed. Perioperative administration of NSAIDs decreased postoperative opioid requirement (both in the PACU and during the first 24 postoperative hours; SMD = -0.66 [-0.84, -0.48] and -0.83 [-1.11, -0.55], respectively), pain intensity in the PACU (SMD = -0.85 [-1.24, -0.47]), and PONV during the first 24 postoperative hours (OR = 0.75 [0.57-0.99]). NSAIDs did not decrease pain intensity during the first 24 postoperative hours (OR = 0.56 [0.26-1.2]) and PONV during PACU stay (OR = 1.02 [0.73-1.44]). Subgroup analysis according to the timing of NSAID administration (intraoperative versus postoperative), type of surgery, or coadministration of paracetamol did not show any influence of these factors on the studied outcomes except the reduction of pain intensity and the incidence of PONV during the first 24 postoperative hours, which were influenced by the coadministration of paracetamol and the type of surgery, respectively. CONCLUSION: This meta-analysis shows that perioperative NSAID administration reduces opioid consumption and PONV during the postoperative period in children.

Ketamine for perioperative pain management in children: a meta-analysis of published studies.

INTRODUCTION: Balanced analgesia, using both opioid and nonopioids agents, has become the standard care for postoperative pain management. Ketamine, a compound with analgesic and antihyperalgesic properties, has been shown to decrease postoperative pain and opioid requirements in adults. The goal of the present meta-analysis was to investigate postoperative analgesic properties of ketamine in pediatric patients. MATERIAL AND METHODS: A comprehensive literature search was conducted to identify clinical trials that used ketamine as a perioperative analgesic compound in children and infants. Outcomes measured were postoperative analgesic consumption, pain intensity and duration of sensory block (when ketamine was used by caudal route) during the postoperative care unit (PACU) stay and the early postoperative period (6-24 h after leaving the operative room). The data from each trial were combined to calculate the pooled odds ratios or standard mean differences and their 95% confidence intervals. RESULTS: Thirty-five randomized, blinded controlled studies were retrieved from the literature. Systemic ketamine was effective in decreasing PACU pain intensity and analgesic requirement but failed to influence early (6-24 h) pain intensity and analgesic requirement. Ketamine administered locally during tonsillectomy, decreased PACU and early (6-24 h) pain intensity and PACU analgesic requirements. Used as an adjuvant for caudal analgesia, ketamine increased the duration of sensory block and PACU analgesic requirement without impacting PACU pain intensity. Ketamine failed to exhibit a postoperative opioid-sparing effect. CONCLUSIONS: This meta-analysis found that administration of ketamine was associated with decreased PACU postoperative pain intensity and nonopioid analgesic requirement. However, ketamine failed to exhibit a postoperative opioid-sparing effect.

French current practice for ambulatory anesthesia in children: a survey among the French-speaking Pediatric Anesthesiologists Association (ADARPEF).

BACKGROUND: This survey aims to describe current practice in ambulatory care among pediatric anesthesiologists in France. METHODS: Members of the French-speaking Pediatric Anesthesiologists Association (ADARPEF) were sent a questionnaire examining the proportion of pediatric ambulatory anesthesia practiced by each responder, the level of adherence to pediatric ambulatory Anesthesia guidelines, and responder consensus in decision making when faced with common case scenarios in pediatric ambulatory anesthesia. For the latter, consensus was defined as a > 80% opinion. RESULTS: One hundred and forty-five pediatric anesthesiologists replied (43%). Ambulatory anesthesia appears underused in France. Recent French pediatric ambulatory anesthesia guidelines are being applied. Postoperative pain is poorly managed. The choice of scheduling children for ambulatory anesthesia appears to be more heavily influenced by practitioners' subjective evaluation than evidence from the literature. CONCLUSION: A better commitment for ambulatory care must be found among anesthesiologists. Further studies are required to improve coherence, safety, and efficiency of children selection for ambulatory anesthesia.

Ultrasound guided internal jugular vein access in children and infant: a meta-analysis of published studies.

INTRODUCTION: Central venous catheter placement is technically difficult in pediatric population especially in the younger patients. Ultrasound prelocation and/or guidance (UPG) of internal jugular vein (IJV) access has been shown to decrease failure rate and complications related to this invasive procedure. The goal of the present study was to perform a systematic review of the advantages of UPG over anatomical landmarks (AL) during IJV access in children and infants. MATERIAL AND METHODS: A comprehensive literature search was conducted to identify clinical trials that focused on the comparison of UPG to AL techniques during IJV access in children and infants. Two reviewers independently assessed each study to meet inclusion criteria and extracted data. Data from each trial were combined to calculate the pooled odds ratio (OR) or the mean differences (MD), and their 95% confidence intervals [CI 95%]. I(2) statistics were used to assess statistics heterogeneity and to guide the use of fixed or random effect for computation of overall effects. Subgroup analysis was used to clarify the effects of the techniques used (prelocation or guidance) or the experience of practitioners. RESULTS: Literature found five articles. Most of the patients were cardiac surgery patients. In comparison with AL, UPG had no effect on IJV access failure rate (OR = 0.28 [0.05, 1.47], I(2) = 75%, P = 0.003), the rate of carotid artery puncture (OR = 0.32 [0.06, 1.62], I(2) = 68%, P = 0.01), haematoma, haemothorax, or pneumothorax occurrence (OR = 0.40 [0.14, 1.13], I(2) = 17%, P = 0.30, OR = 0.72, OR = 0.81 [0.18, 3.73], I(2) = 0%, P = 0.94, respectively) and time to IJV access and haemothorax/pneumothorax occurrence. Subgroup analysis found an efficacy of ultrasound when used by novice operators or during intraoperative use. DISCUSSION: This current meta-analysis does not found the utility of ultrasound during IJV access in children and infants in increasing the success rate and in decreasing complications.

First genomic rearrangement of the RYR1 gene associated with an atypical presentation of lethal neonatal hypotonia.

Neonatal hypotonia is frequently observed with a highly variable clinical presentation. Congenital myopathies that are classically characterized by the presence of structural changes of the muscle fibres such as cores, rods and aggregates have been reported to be occasionally associated with this presentation. However, the identification of the causing defect can be a challenging task in severe neonatal forms of the disease since specific structural changes might not always be present in affected newborn's muscles. The RYR1 gene encodes the skeletal muscle isoform of a calcium channel, the ryanodine receptor, and has been involved in both dominant and recessive congenital myopathies associated with structural changes and presenting with various degree of severity. Here we report the case of a child presenting at birth with a lethal form of neonatal hypotonia associated with an atypical congenital myopathy. Molecular investigations showed that the disease was caused by two novel RYR1 mutations. One of the mutations was a large-sized genomic deletion. This is the first genomic rearrangement identified into the RYR1 gene to our knowledge. This new class of mutation of the RYR1 gene will clearly have consequences for the molecular investigation of RYR1-related diseases.

Correlations between genotype and pharmacological, histological, functional, and clinical phenotypes in malignant hyperthermia susceptibility.

Malignant hyperthermia susceptibility (MHS) is a subclinical pharmacogenetic disorder caused by an impairment of skeletal muscle calcium homeostasis in response to triggering agents. While in vitro contracture testing (IVCT) is the gold standard for defining MHS, molecular analysis is increasingly used to diagnosis MHS. Mutations associated with MHS have been reported in two genes: RYR1 and CACNA1S. Mutations in RYR1 are also responsible for central core disease (CCD), a myopathy that can be associated with a positive IVCT response. We report here the results of correlation studies performed with molecular, pharmacological, histological, and functional data obtained in 175 families (referred to as confirmed (129) or potential (46) MHS families). Extensive molecular analysis allowed us to identify a variant in 60% of the confirmed MHS families, and resulted in the characterization of 11 new variants in the RYR1 gene. Most mutations clustered to MH1 and MH2 domains of RYR1. Functional analysis allowed us to assign a causative role for seven MHS mutations that we propose to add to the panel of MHS mutations used for genetic testing. The use of genetic data to determine MHS status led to a 99.5% sensitivity for IVCT. IVCT-positive/mutation-negative diagnoses were analyzed not only in terms of specificity for IVCT, but also to assess the presence of a second MHS trait in families, and the genetic heterogeneity of the disease. Histological analyses revealed the presence of cores in more than 20% of muscle biopsies originating from 242 genotyped and tested MHS patients who did not present with clinical symptoms. This indicates that these patients must be considered as MHS patients with cores, and are clearly differentiated from CCD patients who have been tested positive for MHS.

Presence of two different genetic traits in malignant hyperthermia families: implication for genetic analysis, diagnosis, and incidence of malignant hyperthermia susceptibility.

BACKGROUND: Malignant hyperthermia susceptibility (MHS), an uncommon syndrome often inherited as an autosomal dominant trait, is characterized by a genetic and clinical heterogeneity. In this article, the authors described six pedigrees in which both parents of MHS patients were diagnosed with MHS by an diagnostic test. Haplotype and mutation analysis revealed that more than one MHS genetic trait was present in these families. METHODS: A panel of 104 MHS families were investigated with a caffeine halothane contracture test on muscle biopsy specimens. When possible, blood creatine kinase concentrations of MHS patients were measured. Haplotyping studies were conducted with chromosome 19q13.2 polymorphic markers and mutations were searched for in patients' DNA. RESULTS: In six families, the diagnostic test and genetic studies demonstrated that both, apparently unrelated, parents of MHS patients were MHS. In three families, homozygous or compound heterozygous individuals for RYR1 mutations were characterized at a molecular level. In one family, a compound heterozygous patient harboring a RYR1 mutation and a CACNA1S mutation was identified. While patients with two mutated alleles did not show differences in their muscle response to halothane or caffeine, their creatinine kinase concentrations were significantly elevated compared with the heterozygous patients. CONCLUSIONS: Based on genetic and diagnostic test data, more than one MHS allele associated with the MHS phenotype was evidenced in four families. These data should be considered in view of the use of genetics for the diagnosis of MHS and when reaching conclusions of genetic heterogeneity in MHS families. Taking into account the usual dominant mode of transmission of MHS and the size of the investigated population, the authors propose an evaluation of the incidence of the MHS in the general population based on genetic data.

Separate-lung ventilation strategy for reimplantation of esophageal bronchus.

IMPLICATIONS: We describe an original ventilation method designed to optimize lung recruitment and gas exchanges during surgery in a newborn with congenital esophageal atresia and ectopic esophageal implantation of the left mainstem bronchus. This strategy ensured constant adaptation of the mechanical ventilatory regimen to the surgical procedure-linked constraints.