How doctors communicated with parents in a neonatal intensive care: Communication and ethical issues.

AIM: Doctors have a moral and legal obligation to keep patients and their families informed, and this is an integral part of care. We explored the communication strategies used by doctors when they spoke to parents in a French neonatal intensive care unit (NICU). METHODS: This was a single-centre qualitative pilot study carried out from October 2015 to January 2016. We asked five doctors (three female) to audiotape their discussions with the parents of newborn infants during their NICU stay. The doctors' mean age was 43 years, and they had a mean of 14 years of NICU experience. Each discussion was subjected to thematic content analysis. RESULTS: We analysed 40 discussions carried out between doctors on 26 newborn infants. Five communication strategy themes emerged: building understanding, how the communication was constructed, the role of the doctor, and of the parents, in the overall care of the newborn infant and how the information given to the parents developed over time. CONCLUSION: Analysing the content of the information discussed with parents provided us with the opportunity to understand the communication and ethical issues surrounding the delivery of information in a NICU. This could be used to improve future discussions between doctors and parents.

Comparing Three Methods for Dilution Accuracy of Intravenous Preparations.

PURPOSE: Dilutions of intravenous medications may be inaccurate. The mixing technique may be a crucial factor. DESIGN: Three factors of dilution were tested: volume for dilution (large vs small), method for mixing (shaking vs inversion), and number of maneuvers (3 times vs 10). METHODS: Dilutions of glucose in saline solution were made by nurses, after a random factorial plan. The judgment criteria were the comparison between measured (Cmes) and expected (Cexp) concentration. FINDING: Cmes (n = 40) ranged from 89.5% to 123.6% of Cexp and was more accurate when made with a large volume (98.4% of Cexp vs 106.5%) and when mixed by inversion (100.6% of Cexp vs 104.6%). CONCLUSIONS: Inversion rather than shaking and dilution in a large volume is a simple procedure for bedside medication preparation that allows better accuracy. The 3 versus 10 mixing procedures resulted in the same accuracy, which may be important for these time-consuming procedures. These results should be confirmed in clinical situations.

Neonatal ethanol exposure from sanitizers in isolettes: a bench study.

BACKGROUND: Ethanol-based hand sanitizer (EBHS) is used repeatedly in neonatology. Inadequately dried hands can increase ambient ethanol concentrations in air, especially in a small, enclosed space as isolette. We sought to better document the potential exposure to alcohol vapors on a newborn placed in an isolette, by mimicking common neonatal situations. METHODS: EBHS were rubbed on hands for 10 or 30 seconds, before inserting hands in the isolette of 1 or 2 experimenters for 6 minutes. Ethanol concentrations were measured every 30 seconds with photoionization detector. RESULTS: Twenty-six trials were made, with 286 measurements. With four hands, the concentration peak was in mean about 700 (±900) ppm and with two hands about 300 ppm. With 10-second rubbing time, the concentrations peak was in mean about 850 ppm, and with 30-second rubbing time, mean concentrations were about 100 pm. When respecting normal use (rubbing time 30 seconds), observed ethanol concentrations were low, always below 200 ppm with 2 or 4 hands. CONCLUSIONS: Concentrations of ethanol are very high when drying of EHBS is incomplete. The exposure is of short duration, but ethanol inhalation may be negatively experienced by the child during procedures, especially since they may be frequent and repeated. To minimize the child's exposure to ethanol, we suggest the hands should be completely dried before being inserted into the isolette.

Long Term Neurodevelopmental Outcomes after Sevoflurane Neonatal Exposure of Extremely Preterm Children: A Cross-Sectional Observationnal Study.

Sevoflurane, a volatile anesthetic, is used when extremely preterm neonates (EPT) undergo painful procedures. Currently, no existing studies analyze sevoflurane's long-term effects during the EPT's immediate neonatal period. Our primary objective was to compare the EPT's neurocognitive development regardless of any sevoflurane exposure prior to 45 weeks corrected gestational age (GA). We analyzed those live discharges, less than 28 weeks GA, who were either exposed, unexposed, and/or multiply exposed to sevoflurane before 45 weeks GA. All data were obtained from a cross-sectional multicenter study (GPQoL study, NCT01675726). Children, both exposed and non-exposed to sevoflurane, were sampled using a propensity-guided approach. Neurological examinations (Touwen), cognitive and executive functions (WISC IV, NEPSY, Rey figure), and assessments when the children were between 7 and 10 years old, were correlated to their neonatal sevoflurane exposure. There were 139 children in the study. The mean gestational age was 26.2 weeks (±0.8) GA and the mean birth weight was 898 g (±173). The mean age of their evaluation was 8.47 years old (±0.70). Exposure to sevoflurane to the mean corrected age 27.10 (3.37) weeks GA had a significant correlation with cerebral palsy (adjusted odds ratio (aOR): 6.70 (CI 95%: 1.84-32.11)) and other major disorders (cerebral palsy and/or severe cognitive retardation) (aOR: 2.81 [95% CI: 1.13-7.35]). Our results demonstrate the possibility of long-term effects on EPT infants who had a sevoflurane exposure before 45 weeks corrected GA. However, these results will require further confirmation by randomized controlled trials.

Efficacy and mode of action of a noise-sensor light alarm to decrease noise in the pediatric intensive care unit: a prospective, randomized study.

OBJECTIVES: To determine whether a sound-activated light-alarm device could reduce the noise in the central area of our pediatric intensive care unit and to determine whether this reduction was significant enough to decrease the noise that could be perceived by a patient located in a nearby room. The secondary objective was to determine the mode of action of the device. DESIGN: In a 16-bed pediatric and neonatal intensive care unit, a large and clearly noticeable sound-activated light device was set in the noisiest part of the central area of our unit, and noise measurements were made in the central area and in a nearby room. In a prospective, quasi-experimental design, sound levels were compared across three different situations--no device present, device present and turned on, and device present but turned off--and noise level measurements were made over a total of 18 days. PATIENTS/SUBJECTS: None. INTERVENTIONS: Setting a sound-activated light device on or off. RESULTS: When the device was present, the noise was about 2 dB lower in the central area and in a nearby room, but there was no difference in noise level with the device turned on vs. turned off. CONCLUSION: The noise decrease in the central area was of limited importance but was translated in a nearby room. The sound-activated light device did not directly decrease noise when turned on, but repetition of the visual signal throughout the day raised staff awareness of noise levels over time.

Malignant pertussis in infants: factors associated with mortality in a multicenter cohort study.

BACKGROUND: Malignant pertussis (MP) affects young infants and is characterized by respiratory distress, perpetual tachycardia and hyperleukocytosis up to 50 G/l, leading to multiple organ failure and death in 75% of cases. Leukodepletion may improve prognosis. A therapeutic strategy based on leukodepletion and extracorporeal life support (ECLS) according to different thresholds of leucocytes has been proposed by Rowlands and colleagues. We aimed at identifying factors associated with death and assess whether the respect of the Rowlands' strategy is associated with survival. METHODS: We reviewed all MP infants hospitalized in eight French pediatric intensive care units from January 2008 to November 2013. All infants younger than 3 months of age, admitted for respiratory distress with a diagnosis of pertussis and WBC count ≥ 50 G/l were recorded. Evolution of WBC was analyzed and an optimal threshold for WBC growth was obtained using the ROC-curve method. Clinical and biological characteristics of survivors and non-survivors were compared. Therapeutic management (leukodepletion and/or ECLS) was retrospectively assessed for compliance with Rowlands' algorithm (indication and timing of specific treatments). RESULTS: Twenty-three infants were included. Nine of 23 (40%) died: they presented more frequently cardiovascular failure (100% vs 36%, p = 0.003) and pulmonary hypertension (PHT; 100% vs 29%, p = 0.002) than survivors and the median [IQR] WBC growth was significantly faster among them (21.3 [9.7-28] G/l/day vs 5.9 [3.0-6.8] G/l/day, p = 0.007). WBC growth rate > 12 G/l/day and lymphocyte/neutrophil ratio < 1 were significantly associated with death (p = 0.001 and p = 0.003, respectively). Ten infants (43%) underwent leukodepletion, and seven (30%) underwent ECLS. Management following Rowlands' strategy was associated with survival (100% vs 0%; p < 0.001, relative risk of death = 0.18, 95%-CI [0.05-0.64]). CONCLUSIONS: A fast leukocyte growth and leukocytosis with neutrophil predominance during acute pertussis infection were associated with death. These findings should prompt clinicians to closely monitor white blood cells in order to early identify infants at risk of fatal outcome during the course of malignant pertussis. Such an early signal in infants at high risk of death would increase feasibility of compliant care to Rowlands' strategy, with the expectation of a better survival.

Sevoflurane for central catheter placement in neonatal intensive care: a randomized trial.

OBJECTIVE: To compare the efficacy and safety of sevoflurane deep sedation with glucose and nonnutritive sucking (GNNS) in reducing the duration of the procedure and in preventing pain-related effects during peripherally inserted central catheter (PICC) placement. BACKGROUND: PICC placement in neonatal intensive care is a delicate and stressful procedure that requires pain prevention. GNNS has been recommended in this situation but remain often inefficient. METHODS: We designed a randomized controlled study in a sixteen-bed pediatric and neonatal unit in a tertiary hospital. Fifty-nine neonates at >28 weeks of gestation with continuous positive airway pressure or invasive mechanical ventilation and requiring PICC placement were included. Patients were randomized to receive inhaled sevoflurane (IS) or glucose and non-nutritive sucking (GNNS). Procedural duration and conditions, hemodynamic and respiratory parameters, occurrence of movements and complications were compared (http://clinicaltrials.gov trial register no. NCT00420693). RESULTS: The two groups had similar demographics. There were no between-group differences in procedural duration (P = 0.84) despite greater immobility in IS group (P = 0.017). IS was also associated with fewer episodes of hypertension (P = 0.003), tachycardia (P < 0.001), and bradycardia (P = 0.02). Occurrences of hypotension were not different between the groups (P = 0.06). The GNNS group showed more desaturation during the 4 h after the procedure (P = 0.03). Complications during intensive care stay did not differ between groups. CONCLUSION: Inhaled sevoflurane does not make easier catheters placement but prevent pain-related symptoms. Because sevoflurane is responsible for hypotension, it requires careful monitoring and treatment adaptation.

Atelectasis prevention during anaesthesia using high-flow nasal cannula therapy: A paediatric randomised trial using MRI images.

BACKGROUND: Atelectasis frequently occurs early on during anaesthesia in children. We hypothesised that positive expiratory pressure (PEP) generated via high-flow nasal cannula (HFNC) could prevent atelectasis in non-intubated children under general anaesthesia. The objective was to compare the volume of atelectasis present in patients treated via HFNC to that of patients treated via a face bag-mask without PEP. The outcome used for this comparison was the ratio of the atelectasis volume to the total pulmonary volume. METHODS: A prospective single-centre, single-blind, randomised trial was conducted in a tertiary hospital from November 2018 through May 2019. The trial subjects were infants and children between six months and six years of age who required anaesthesia for an MRI. The children were randomised to receive sevoflurane for maintenance of anaesthesia either via a classic face bag-mask or by HFNC. The atelectasis volume was measured from thoracic MRI images. The judgement criterion was the ratio of the atelectasis volume to the lung volume. RESULTS: Of a trial group of 42 patients, 21 received anaesthesia via a face bag-mask and 21 via HFNC. After three patients were excluded for technical issues, the data for 39 patients were analysed. The atelectasis volume to the lung volume ratio in the HFNC group was significantly smaller than the ratio for the face bag-mask group (1.6% vs 6.8%, respectively; p=0.002). CONCLUSION: HFNC was associated with a lower atelectasis lung ratio compared to using a face bag-mask during anaesthesia for children maintained with spontaneous ventilation. Registered on Clinicaltrials.gov: NCT03592589.

Effect of head posture on pediatric oropharyngeal structures: implications for airway management in infants and children.

PURPOSE OF REVIEW: Although head and neck posture has direct effects on the upper airway in infants and children, many of these effects remain unclear or not well established. As airway patency and airway access are critical in sedated and/or unconscious children, recent developments in this area should be made known to pediatric anesthesiologists, intensive care physicians and other emergency caregivers. RECENT FINDINGS: All recent studies observed large interindividual variability in anatomical measurements, especially in trachea length. More evidence has been gained that lateral position improves upper airway patency in sedated children. Several studies brought indirect information on head posture for laryngoscopy and intubation. SUMMARY: The site of obstruction of the airway in sedated children in different postures is now more clear. Implications of head flexion and extension in intubated children have been extensively studied, and clinical consequences have been detailed. Due to large interindividual anatomic variability, depth marks set on the tubes by their manufacturers and guidelines regarding calculations of insertion depth should be made with caution in infants and neonates. Despite several studies, there is still little scientific evidence regarding proper head posture for laryngoscopy and intubation.

Effects of head posture on the oral, pharyngeal and laryngeal axis alignment in infants and young children by magnetic resonance imaging.

BACKGROUND: Objective anatomical studies supporting the different recommendations for laryngoscopy in infants and young children are scarce. The objective of this study was to measure by magnetic resonance imaging (MRI) the consequences of head extension on the oral, pharyngeal and laryngeal axes in infants and young children. METHODS: Thirty patients (age: 33 +/- 28 months; weight 14 +/- 9 kg), under general inhalated anesthesia delivered via a laryngeal mask airway, were studied in two anatomic positions: head in the resting position and in simple extension. The following measurements were made on each scan: the face and the neck axes, the pharyngeal axis, the laryngeal axis, and the line of vision of glottis. The various angles between these axes were defined: delta angle between line of vision and laryngeal axis, and beta angle between pharyngeal axis and laryngeal axis. From an anatomical point of view, laryngoscopy and passage of a naso-tracheal tube would be facilitated if these angles are narrow. RESULTS: Placing the patient from the resting position into extension led to a narrowing of the angle delta but a widening of the angle beta. CONCLUSIONS: In infants and young children, under general anesthesia and with a laryngeal mask airway in place, just a slight head extension improves alignment of the line of vision of the glottis and the laryngeal axis (narrowing of angle delta) but worsened the alignment of the pharyngeal and laryngeal axes (widening of angle beta).

Airway humidification with a heat and moisture exchanger in mechanically ventilated neonates : a preliminary evaluation.

OBJECTIVE: We set out to evaluate the efficacy of passive inspiratory gas conditioning in mechanically ventilated neonates and compared it with that of a heated humidifier (HH). DESIGN: Prospective, randomized, controlled study. SETTING: Neonatal and pediatric intensive care unit. PATIENTS: Fourteen mechanically ventilated neonates nursed in incubators. INTERVENTIONS: The HH was set to deliver a temperature of 37 degrees C and an absolute humidity of 40 mgH(2)O/l at the incubator entrance. Inspired temperature (T degrees ) and absolute humidity (AH) were measured by the psychometric method, transpulmonary pressure (Tpres) by means of a differential pressure transducer. Measurements were performed at 5, 10, and 15 min. MEASUREMENTS AND RESULTS: The values of T degrees were significantly higher using the HH (34.6+/-1.6 degrees C) than the heat and moisture exchanger (HME) (33.8+/2.3, p<0.001). The values of AH were significantly higher using the HH (36.6+/-2.5 mgH(2)O/l) than the HME (32.4+/-2.8 mgH(2)O/l, p<0.001). No significant changes were observed in transpulmonary pressure. A significant positive correlation was observed between incubator temperature and the temperature delivered by the HH (R(2)=0.61, p<0.001). CONCLUSIONS: The use of HMEs in neonates made it possible to achieve an absolute humidity of 28 mgH(2)O/l or more and a temperature of 30 degrees C or more. Higher values are obtained using a HH.

Tunneled central venous catheter for neonates: A simple technique for prolonged indwelling central catheters in intensive care.

OBJECTIVE: To describe and evaluate a new technique to insert a 24-gauge Silastic catheter in a central vein with a subcutaneous tunneled catheter in newborns after peripherally inserted central catheter (PICC) insertion failure. DESIGN: Retrospective chart review. SETTING: Pediatric and neonatal intensive care unit. PATIENTS: Twenty-nine newborns in whom a new technique was used to insert a prolonged indwelling jugular, femoral, or subclavian Silastic tunneled central catheter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This new technique was used in 29 newborns between January 1, 2004, and December 31, 2005. The mean gestational age was 34 +/- 5 wks with a mean weight of 2440 +/- 1101 g. Thirty-four insertion attempts were carried out. Access sites were internal jugular (28 of 34), femoral (three of 34) or subclavian (three of 34) vein. In five cases, catheter insertion failed. Pneumothorax occurred two times, and no other serious complication were observed. CONCLUSIONS: This technique is an interesting alternative when PICC insertion is not possible.

Upper airway modifications in head extension during development.

BACKGROUND: One of the requirements of laryngoscopy is to determine which head position will result in optimal visualization. Our hypothesis was that parameters derived from magnetic resonance imaging (MRI) can help quantify the effect of age on airway modifications due to head extension during development. METHOD: In children undergoing planned MRI, additional sequences on the upper airways were performed: one in a near-neutral position, the other with the head extended at 35°. The axis of the face, the pharynx, the larynx, the trachea, and the line of glottic visualization were determined. The following angles were calculated: the Visu-Lar angle, formed by the line of glottic visualization and the laryngeal axis, and the Phar-Lar angle, formed by the pharyngeal and laryngeal axes. RESULTS: One hundred and fifty-five patients (1 to 222 months of age [25-145] months) were included and 54% were under general anaesthesia. Age had no effect on the variation in the Visu-Lar angle, which diminished as a function of head extension, nor on the variation in the Phar-Lar angle, which was minimal in the neutral position. During extension, anatomical axes rotated similarly, and the visualization axis rotated the most, followed by the pharyngeal and laryngeal axes. These results were not correlated with general anaesthesia. CONCLUSION: Regardless of age, head extension diminished the Visu-Lar angle, and increased the Phar-Lar angle. This study supports that, as in adults, head extension is probably the key factor for good visualization conditions during laryngoscopy on children, but clinical data is needed to confirm this result.

Retrospective study of imported falciparum malaria in French paediatric intensive care units.

OBJECTIVE: The World Health Organization (WHO) severity criteria for paediatric Plasmodium falciparum (Pf) malaria are based on studies in countries of endemic malaria. The relevance of these criteria for other countries remains unclear. We assessed the relevance of these criteria in an industrialised country. DESIGN: Retrospective case-control study. SETTING: Eight French university hospitals, from 2006 to 2012. PATIENTS: Children with Pf malaria admitted to paediatric intensive care units (cases: n=55) or paediatric emergency departments (controls: n=110). MAIN OUTCOME MEASURES: Descriptive analysis of WHO severity criteria and major interventions (mechanical ventilation, blood transfusion, fluid challenge, treatment of cerebral oedema, renal replacement therapy). Thresholds were set by receiver operating characteristics curve analysis. RESULTS: Altered consciousness (71% vs 5%), shock (24% vs 1%), renal failure (20% vs 1%), anaemia <50 g/L (7% vs 2%), acidosis (38% vs 0%), bilirubin level >50 µmol/L (25% vs 8%) and parasitaemia >10% (30% vs 8%) were more frequent in cases (p<0.01). All these criteria were associated with major interventions (p<0.001). Respiratory distress (six cases), and hypoglycaemia (two cases) were infrequent. Thrombocytopenia <50 000/mm3 (46% vs 7%) and anaemia (haemoglobin concentration <70 g/L (41% vs 13%)) were more frequent in cases (p<0.0001). CONCLUSIONS: The WHO severity criteria for paediatric Pf malaria are relevant for countries without endemic malaria. The infrequent but severe complications also provide a timely reminder of the morbidity and mortality associated with this condition worldwide. In non-endemic countries haemoglobin <70 g/L and platelet count <50 000/mm3 could be used as additional criteria to identify children needing high level of care.

Night shift decreases cognitive performance of ICU physicians.

BACKGROUND: The relationship between tiredness and the risk of medical errors is now commonly accepted. The main objective of this study was to assess the impact of an intensive care unit (ICU) night shift on the cognitive performance of a group of intensivists. The influence of professional experience and the amount of sleep on cognitive performance was also investigated. METHODS: A total of 51 intensivists from three ICUs (24 seniors and 27 residents) were included. The study participants were evaluated after a night of rest and after a night shift according to a randomized order. Four cognitive skills were tested according to the Wechsler Adult Intelligence Scale and the Wisconsin Card Sorting Test. RESULTS: All cognitive abilities worsened after a night shift: working memory capacity (11.3 ± 0.3 vs. 9.4 ± 0.3; p < 0.001), speed of processing information (13.5 ± 0.4 vs. 10.9 ± 0.3; p < 0.001), perceptual reasoning (10.6 ± 0.3 vs. 9.3 ± 0.3; p < 0.002), and cognitive flexibility (41.2 ± 1.2 vs. 44.2 ± 1.3; p = 0.063). There was no significant difference in terms of level of cognitive impairment between the residents and ICU physicians. Only cognitive flexibility appeared to be restored after 2 h of sleep. The other three cognitive skills were altered, regardless of the amount of sleep during the night shift. CONCLUSIONS: The cognitive abilities of intensivists were significantly altered following a night shift in the ICU, regardless of either the amount of professional experience or the duration of sleep during the shift. The consequences for patients' safety and physicians' health should be further evaluated.

Calculated serum osmolality can lead to a systematic bias compared to direct measurement.

The reference method to measure serum osmolality (Mosm) is the delta cryoscopic method. However, the technology may not be available. Clinicians therefore must calculate osmolality (Cosm) as the sum of concentrations of selected principal solutes such as sodium, potassium, urea, and glucose. To evaluate the validity of Cosm in patients in hyperosmolar state we compared Cosm to Mosm. Twenty-two ICU patients treated by infusion of hypertonic solutes for intracranial hypertension following head injury were prospectively studied. A control group of 10 patients with hypernatremia due to medical causes was also evaluated. Na+, blood urea nitrogen (BUN), and glucose were measured to calculate serum osmolality: Cosm = (2 x Na+) + BUN + glucose (in mOsm/kg). Measurement of serum osmolality was performed using the delta-cryoscopic method. The results of the two methods were compared by correlating the difference (Mosm-Cosm) between each pair of results with the mean of the pairs of results. Cosm underestimated Mosm (3.4 mOsm/kg, P < 0.02) in the control group whereas Cosm overestimated Mosm in patients who received hypertonic fluids (2.3 mOsm/kg, P < 0.03). Calculation of osmolality introduced a systematic bias, overestimating osmolality in the lower ranges and underestimating it in the higher ranges. In the range of hyperosmolality commonly used to manage intracranial hypertension following head trauma, serum osmolality, as determined by sum of principal serum solutes, compares poorly with direct measurement using standard osmometry.

Strategies to reduce curative antibiotic therapy in intensive care units (adult and paediatric).

Emerging resistance to antibiotics shows no signs of decline. At the same time, few new antibacterials are being discovered. There is a worldwide recognition regarding the danger of this situation. The urgency of the situation and the conviction that practices should change led the Société de Réanimation de Langue Française (SRLF) and the Société Française d'Anesthésie et de Réanimation (SFAR) to set up a panel of experts from various disciplines. These experts met for the first time at the end of 2012 and have since met regularly to issue the following 67 recommendations, according to the rigorous GRADE methodology. Five fields were explored: i) the link between the resistance of bacteria and the use of antibiotics in intensive care; ii) which microbiological data and how to use them to reduce antibiotic consumption; iii) how should antibiotic therapy be chosen to limit consumption of antibiotics; iv) how can antibiotic administration be optimized; v) review and duration of antibiotic treatments. In each institution, the appropriation of these recommendations should arouse multidisciplinary discussions resulting in better knowledge of local epidemiology, rate of antibiotic use, and finally protocols for improving the stewardship of antibiotics. These efforts should contribute to limit the emergence of resistant bacteria.

Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants, a population pharmacokinetic modelling approach.

Phenobarbital is widely used for treatment of neonatal seizures. Its optimal use in neonates and young infants requires information regarding pharmacokinetics. The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated. Routine clinical pharmacokinetic data were retrospectively collected from 48 neonates and infants (weight: 0.7-10 kg; patient's postnatal age: 0-206 days; GA: 27-42 weeks) treated with phenobarbital, who were administered as intravenous or suspension by oral routes and hospitalized in a paediatric intensive care unit. Total mean dose of 4.6 mg/kg (3.1-10.6 mg/kg) per day was administered by 30-min infusion or by oral route. Pharmacokinetic analysis was performed using a nonlinear mixed-effect population model software). Data were modelled with an allometric pharmacokinetic model, using three-fourths scaling exponent for clearance (CL). The population typical mean [per cent relative standard error (%RSE)] values for CL, apparent volume of distribution (Vd ) and bioavailability (F) were 0.0054 L/H/kg (7%), 0.64 L/kg (15%) and 48.9% (22%), respectively. The interindividual variability of CL, Vd , F (%RSE) and residual variability (%RSE) was 17% (31%), 50% (27%), 39% (27%) and 7.2 mg/L (29%), respectively. The absolute bioavailability of phenobarbital in neonates and infants was estimated. The dose should be increased when switching from intravenous to oral administration.

Vancomycin: Predictive Performance of a Population Pharmacokinetic Model and Optimal Dose in Neonates and Young Infants.

INTRODUCTION: Model evaluation is an important issue in population pharmacokinetic analyses. The objectives were to evaluate the predictive performance of previously published pediatric population pharmacokinetic models for vancomycin in a new data set and to propose an optimal dose to obtain a vancomycin concentration target. METHODS: External evaluation was conducted for all the published models of vancomycin in neonates and young infants with a new data set of 70 patients. Bias and accuracy were calculated. Advanced analyses were performed to evaluate the predictive performance of the best model. This population pharmacokinetic analysis was performed to simulate doses of vancomycin according to the appropriate target concentration. RESULTS: All models gave almost the same results, except 2 that were not acceptable. Nevertheless, the model described by Oudin et al presented the best results with a bias and accuracy of 4.0% and 27.8%, respectively. Simulations showed that the maintenance dose should be adjusted more precisely to each neonate based on his or her weight and serum creatinine value. CONCLUSION: Simulations have allowed the authors to describe new dosage schedules, and a chart was created to help clinicians to adapt dosage of vancomycin. Because of pharmacokinetic variability, vancomycin still requires therapeutic drug monitoring.