Phenobarbital in intensive care unit pediatric population: predictive performances of population pharmacokinetic model.

An external evaluation of phenobarbital population pharmacokinetic model described by Marsot et al. was performed in pediatric intensive care unit. Model evaluation is an important issue for dose adjustment. This external evaluation should allow confirming the proposed dosage adaptation and extending these recommendations to the entire intensive care pediatric population. External evaluation of phenobarbital published population pharmacokinetic model of Marsot et al. was realized in a new retrospective dataset of 35 patients hospitalized in a pediatric intensive care unit. The published population pharmacokinetic model was implemented in nonmem 7.3. Predictive performance was assessed by quantifying bias and inaccuracy of model prediction. Normalized prediction distribution errors (NPDE) and visual predictive check (VPC) were also evaluated. A total of 35 infants were studied with a mean age of 33.5 weeks (range: 12 days-16 years) and a mean weight of 12.6 kg (range: 2.7-70.0 kg). The model predicted the observed phenobarbital concentrations with a reasonable bias and inaccuracy. The median prediction error was 3.03% (95% CI: -8.52 to 58.12%), and the median absolute prediction error was 26.20% (95% CI: 13.07-75.59%). No trends in NPDE and VPC were observed. The model previously proposed by Marsot et al. in neonates hospitalized in intensive care unit was externally validated for IV infusion administration. The model-based dosing regimen was extended in all pediatric intensive care unit to optimize treatment. Due to inter- and intravariability in pharmacokinetic model, this dosing regimen should be combined with therapeutic drug monitoring.

Outcome Comparison in Children Undergoing Extracorporeal Life Support Initiated at a Local Hospital by a Mobile Cardiorespiratory Assistance Unit or at a Referral Center.

PURPOSE: To compare characteristics and outcome in children undergoing extracorporeal life support initiated in an extracorporeal life support center or at the patient's bedside in a local hospital, by means of a mobile cardiorespiratory assistance unit. METHODS: A retrospective study in a single PICU during 6 years. Extracorporeal life support was started either in our center (control group) or in the local hospital (mobile cardiorespiratory assistance unit group). The data collected were demographics, markers of patient's preextracorporeal life support condition, and outcome. RESULTS: One hundred twenty-six children underwent extracorporeal life support, 105 in the control group and 21 in the mobile cardiorespiratory assistance unit group. There was no difference between groups in terms of age, weight, or Pediatric Risk of Mortality II score. There was a significant difference in organ failure etiology between groups, with more respiratory cases in the mobile cardiorespiratory assistance unit group (76.2%) and more cardiac surgery cases in the control group (60%; p < 0.001). The duration of extracorporeal life support was longer in the mobile cardiorespiratory assistance unit group than in the control group (10 [1-36] vs 5 [0-33] d; p = 0.003). PICU length of stay and mortality (60% vs 47.6%; p = 0.294) were not significantly different between the two groups. To allow comparison of a more homogenous population, a subgroup analysis was performed including only respiratory failure patients from the two groups (R-control group [n = 22] and R-mobile cardiorespiratory assistance unit group [n = 16]). PICU length of stay was 17 (3-64) days in the R-control group and 23 (1-45) days in the R-mobile cardiorespiratory assistance unit group (p = 0.564), and PICU mortality rate was 54.5% in the R-control group and 43.8% in the R-mobile cardiorespiratory assistance unit group (p = 0.511). There was no difference between the R-groups for age, weight, Pediatric Risk of Mortality II score, and markers of kidney or liver dysfunction, and lactate blood levels. CONCLUSION: Extracorporeal life support can be safely initiated at children's bedside in the local hospital and then transported to the specialized referral center. Our results support the validity of an interregional organization of mobile cardiorespiratory assistance unit teams.

Post intubation tracheal stenosis in children.

Many authors have reported that tracheal stenosis is a complication that can follow tracheal intubation in both adults and children. The symptoms, when they do appear, can be confused with asthma, with subsequent treatment providing only mild and inconsistent relief. We report here the case of an 8 year old girl admitted to our hospital for whooping cough that was not responding to therapy.

[A rare cause of sudden cardiac failure: histiocytoid cardiomyopathy]. / Une cause rare de défaillance cardiaque brutale chez le nourrisson : la cardiomyopathie histiocytoïde.

Histiocytoid cardiomyopathy is a rare disease which occurs predominantly in the first two years of life, with a female preponderance. We report the cases of two girls (11 and 15-month-old) which were respectively referred to our institution for ventricular tachycardia and ventricular fibrillation without prodroma. Etiologic findings only showed mild cardiomyopathy. Autopsy and histologic examination led to the diagnosis of histiocytoid cardiomyopathy. Furthermore, in the first observation, agenesis of the corpus callosum was found.

Acute effect of a dual ETA-ETB receptor antagonist on pulmonary arterial vasculature in preterm lamb fetuses with surgically induced diaphragmatic hernia.

PURPOSE: To study the effects of tezosentan, a dual ETA and ETB receptor antagonist on the cardiopulmonary profile in a fetal lamb model of CDH in utero. METHODS: A diaphragmatic hernia was surgically created at day 75 of gestation. During 45 min of tezosentan perfusion (1 mg/kg), hemodynamic parameters (pulmonary and aortic pressures, left pulmonary and aortic flows, left auricle pressure, heart rate) were measured at day 135 of gestation. Age-matched fetal lambs served as control animals. Secondarily, parietal tension of vessels rings of pulmonary arteries was assessed in organ baths under increasing concentration of tezosentan. RESULTS: In CDH group, under perfusion of tezosentan, pulmonary artery pressure decreased from 45.8 ± 4.1 to 37.6 ± 5.9 mmHg (P < 0.05). Pulmonary artery flow and pulmonary vascular resistance remained constant. In control group, pulmonary artery flow increased from 153.9 ± 15.8 to 233.4 ± 26 ml/min (P < 0.05). Pulmonary artery pressure did not vary. Subsequently calculated pulmonary vascular resistance decreased. In organ bath, no significant relaxation was observed. CONCLUSION: In this fetal lamb model of CDH, tezosentan decreased pulmonary artery pressure but did not modify pulmonary blood flow. Endothelin may play a role in the regulation of pulmonary vascular tone in utero.

Initial predictive factors of outcome in severe non-accidental head trauma in children.

OBJECT: The aim of this study is to evaluate the outcome of young children hospitalized for non-accidental head trauma in our PICU, to evaluate PRISM II score in this sub-population of pediatric trauma and to identify factors that might influence the short-term outcome. MATERIALS AND METHODS: Files of all children less than 2 years old with the diagnosis of non-accidental head trauma over a 10-years period were systematically reviewed. We collected data on demographic information, medical history, clinical status, and management in the PICU. Three severity scores were then calculated: PRISM II, Glasgow Coma Scale (GCS), and Pediatric Trauma Score (PTS). Prognosis value of qualitative variables was tested with a univariate procedure analysis (anemia, diabetes insipidus...). Then, quantitative variables were tested with univariate procedure too (age, weight, PRISM II, GCS, Platelet count, fibrin, prothrombin time (PT)...). Potential association between variables and death was tested using univariate procedure. Variables identified by univariate analysis were then analyzed with multivariate analysis through a forward-stepping logistic regression. RESULTS: Thirty-six children were included. Mean age was 5.5 months (8 days-21.5 months). Mortality rate was 27.8%. At admission, PTS, PRISM II, GCS, PT, PTT, and diabetes insipidus were significantly altered or more frequent in non survivors. Cutoff value for PRISM II at which risk of mortality increased was 17.5 (sensitivity = 0.8; specificity = 0.88). CONCLUSION: PRISM II is a reliable and easy performing tool for assessing the prognosis of non-accidental cranial traumatism in young children. GCS and PTS, scores even simpler than PRISM II, showed good accuracy regarding survival prediction.

Phasic hemodynamics and reverse blood flows in the aortic isthmus and pulmonary arteries of preterm lambs with pulmonary vascular dysfunction.

Time-domain representations of the fetal aortopulmonary circulation were carried out in lamb fetuses to study hemodynamic consequences of congenital diaphragmatic hernia (CDH) and the effects of endothelin-receptor antagonist tezosentan (3 mg/45 min). From the isthmic aortic and left pulmonary artery (PA) flows (Q) and isthmic aortic, PA, and left auricle pressures (P) on day 135 in 10 controls and 7 CDH fetuses (28 ewes), discrete-triggered P and Q waveforms were modelized as Pt and Qt functions to obtain basic hemodynamic profiles, pulsatile waves [P, Q, and entry impedance (Ze)], and P and Q hysteresis loops. In the controls, blood propelling energy was accounted for by biventricular ejection flow waves (kinetic energy) with low Ze and by flow-driven pressure waves (potential energy) with low Ze. Weak fetal pulmonary perfusion was ensured by reflux (reverse flows) from PA branches to the ductus anteriosus and aortic isthmus as reverse flows. Endothelin-receptor antagonist blockade using tezosentan slightly increased the forward flow but largely increased diastolic backward flow with a diminished left auricle pre- and postloading. In CHD fetuses, the static component overrode phasic flows that were detrimental to reverse flows and the direction of the diastolic isthmic flow changed to forward during the diastole period. Decreased cardiac output, flattened pressure waves, and increased forward Ze promoted backward flow to the detriment of forward flow (especially during diastole). Additionally, the intrapulmonary arteriovenous shunting was ineffective. The slowing of cardiac output, the dampening of energetic pressure waves and pulsatility, and the heightening of phasic impedances contributed to the lowering of aortopulmonary blood flows. We speculate that reverse pulmonary flow is a physiological requirement to protect the fetal pulmonary circulation from the prominent right ventricular stream and to enhance blood flow to the fetal heart and brain.

Recent developments in the perioperative fluid management for the paediatric patient.

PURPOSE OF REVIEW: Maintenance fluid therapy represents the volume of fluids and amount of electrolytes and glucose needed to replace anticipated physiological losses from breath, sweat and urine and to prevent hypoglycaemia. For 50 years, this therapy was based on Holliday and Segar's formula, which proposed to match children's water and electrolyte requirements on a weight-based calculation using hypotonic solutions. Recent publications highlight the risk of hyponatraemia in the postoperative period and the facilitating role of a hypotonic infusion, leading some people to recommend replacing hypotonic with isotonic solutions. RECENT FINDINGS: The postoperative period is at risk for nonosmotic secretion of antidiuretic hormone, which reduces the ability of the kidneys to excrete free water. In the context of antidiuretic hormone release, the associated low urine output makes maintenance volume requirement decrease to 50% of the calculated hourly rate. While isotonic fluids are recommended during anaesthesia, controversies still exist on the nature of fluid for maintenance therapy in the postoperative period. The proof for a benefit of isotonic fluids in this context is weak; further investigations are needed to make a decision. Whatever the choice, an individualized maintenance infusion protocol for each patient is necessary. SUMMARY: As free water excretion is altered for all children in the postoperative period, it is necessary to reduce the volume of maintenance fluid therapy to half the previously recommended volume. The choice of an isotonic solution should be more pertinent to that of a hypotonic solution, but evidence is lacking for a definitive answer.

Repair of a type IV laryngotracheoesophageal cleft with cardiopulmonary bypass.

Laryngotracheoesophageal clefts (LTECs) are rare congenital defects of variable severity depending on the extent of malformation. Management of a complete LTEC represents a major surgical and anesthetic challenge. The main problems are achieving adequate operative exposure and maintaining ventilatory support during and after the operation. We describe correction of a type IV LTEC extending down to the carina in an infant who had respiratory distress at birth. Surgical repair was achieved in a single stage by an anterior sternotomy approach on the 11th day of life. The procedure was facilitated by cardiopulmonary bypass. After the operation, the infant was intubated, mechanically ventilated, and sedated. Nissen fundoplication and gastrostomy were carried out on the 11th postoperative day. The child was extubated on the 12th postoperative day. The rationale for this method and its advantages in comparison with other surgical approaches are discussed.

Active warming of saline or blood is ineffective when standard infusion tubing is used: an experimental study.

PURPOSE: To determine the effect of infusion rate, tubing length and fluid composition on the temperature of the infusate reaching the distal end of an infusion tubing with and without active fluid warming. METHODS: Warmed normal saline (W-NS) and packed red blood cells (W-PRBC), were infused with a fluid warmer through a modified infusion set. The fluids were delivered at eight infusion rates from 50 to 999 mL x hr(-1). The infusate temperature was monitored at 20 cm intervals on the iv tubing. The same temperature monitoring protocol was applied to PRBC without warmer (NoW-PRBC). RESULTS: In W-NS and W-PRBC groups, there was a decrease in the infusate temperature, at each flow rate, from the drip chamber to the distal end of tubing ( P <0.001). In NoW-PRBC group, there was a rapid increase in the infusate temperature from the bag to the drip chamber ( P <0.001). Thereafter, there was no change in temperature, except at the 999 mL x hr(-1) infusion rate, where a slight increase in the infusate temperature throughout the tubing was shown. In W-NS and W-PRBC groups increasing the flow rate produced a significant increase in the infusate temperature, at each measurement point ( P <0.001). In the NoW-PRBC group, increasing the flow rate did not alter the infusate temperature. The fluid composition did not influence the infusate temperature. CONCLUSION: There is an important heat exchange within the tubing, which is aggravated at low flow rates. At infusion rates appropriate for pediatric anesthesia the clinical and economic value of fluid warming without the use of heated extension tubing is questionable.