Gonzalo Garcia Guerra

Early versus late parenteral nutrition in critically Ill children

BACKGROUND Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear. METHODS We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided. RESULTS Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients receiving renal-replacement therapy (P=0.04) and a shorter duration of hospital stay (P=0.001). Late parenteral nutrition was also associated with lower plasma levels of γ-glutamyltransferase and alkaline phosphatase than was early parenteral nutrition (P=0.001 and P=0.04, respectively), as well as higher levels of bilirubin (P=0.004) and C-reactive protein (P=0.006). CONCLUSIONS In critically ill children, withholding parenteral nutrition for 1 week in the ICU was clinically superior to providing early parenteral nutrition. (Funded by the Flemish Agency for Innovation through Science and Technology and others; ClinicalTrials.gov number, NCT01536275.).

Neurodevelopmental outcome following exposure to sedative and analgesic drugs for complex cardiac surgery in infancy

Objectives/Aim:  To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurodevelopmental outcome.

Neurotoxicity of sedative and analgesia drugs in young infants with congenital heart disease: 4-year follow-up.

To determine whether sedation/analgesia drugs used before, during, and after infant cardiac surgery are associated with neurocognitive and functional outcomes.

Quality of life 4 years after complex heart surgery in infancy.

OBJECTIVE To determine the health-related quality of life at 4 years of age in children who had undergone cardiac surgery for congenital heart disease in early infancy. METHODS A prospective cohort study of infants undergoing cardiac surgery at 6 weeks of age or younger from July 2000 to June 2005 at the Stollery Childrens Hospital. The quality of life was assessed using the Pediatric Quality of Life Inventory, version 4.0, generic core scales, and compared with normative values for the same age. The association between the perioperative variables and health-related quality of life was explored. RESULTS A total of 242 infants underwent complex heart surgery during the study period. Of the 166 eligible survivors, 130 were included. No significant differences were present between the children with single ventricle versus biventricular repairs, except for lower physical health summary scores in the single ventricle patients (P = .007). Compared with the normative data, the children with biventricular repair had lower total Pediatric Quality of Life Inventory, version 4.0, scores (P = .001) and psychosocial health summary scores (P < .001). The children with single ventricle repair also had lower physical health summary scores (P = .003). Older age at surgery and markers of postoperative low cardiac output syndrome were associated with worse health-related quality of life, and greater socioeconomic status was associated with better quality of life. CONCLUSIONS At 4 years of age, health-related quality of life was significantly lower in children who had undergone surgery for congenital heart disease in early infancy. An association was found between age at surgery and postoperative low cardiac output and socioeconomic status and quality of life.

A Canadian survey of perceived barriers to initiation and continuation of enteral feeding in PICUs.

Objective: Clinicians believe nutrition support is important; however, delivery of enteral nutrition may be delayed or interrupted due to a lack of guidelines or perceived contraindications to administration. The aim of this national survey was to examine the knowledge and perceived barriers among clinicians which prevent enteral nutrition administration to PICU patients. Design: The survey consisted of 23 questions (19 primary and four branching). The survey was validated using a semistructured pilot test by three pediatric critical care intensivists and two pediatric critical care registered dietitians external to the study team. Setting: The survey was electronically distributed to clinicians in all PICUs across Canada. Population: One hundred sixty-two PICU clinicians, including 96 staff intensivists, eight clinical assistants, 36 fellows, and 22 registered dietitians from PICUs across Canada. Interventions: None. Measurements and Main Results: The survey was administered from January to March 2013. The response rate was 50% (55 staff intensivists, two clinical assistants, nine fellows, and 15 registered dietitians). There was high variability among clinicians regarding reasons to delay the onset of enteral nutrition or interrupt enteral nutrition administration. High variability (> 70% agreement and < 10% disagreement or vice versa) was found for some reasons to delay or interrupt enteral nutrition, including lactates (rising or > 2 or > 4 mmol/L), high gastric residual volumes, CT/MRI scans, and hypoplastic left heart syndrome. Sixty-eight percent of PICU clinicians reported no written feeding protocol to be in place. Conclusions: Overall, there is high variability among clinicians regarding acceptable procedural and clinical barriers to enteral nutrition administration; this may be improved by a standardized feeding protocol. Therefore, further research must be conducted to provide clinicians with evidence to support their practices for enteral nutrition administration.

Effect of early supplemental parenteral nutrition in the paediatric ICU: a preplanned observational study of post-randomisation treatments in the PEPaNIC trial

BACKGROUND Large randomised controlled trials have shown that early supplemental parenteral nutrition in patients admitted to adult and paediatric intensive care units (PICUs) is harmful. Overdosing of energy with too little protein was suggested as a potential reason for this. This study analysed which macronutrient was associated with harm caused by early supplemental parenteral nutrition in the Paediatric Early versus Late Parenteral Nutrition In Critical Illness (PEPaNIC) randomised trial. METHODS Patients in the initial randomised controlled trial were randomly assigned to receive suppplemental parenteral nutrition (PN) within 24 h of PICU admission (early PN) or to receive such PN after 1 week (late PN) when enteral nutrition was insufficient. In this post-randomisation, observational study, doses of glucose, lipids, and aminoacids administered during the first 7 days of PICU stay were expressed as % of reference doses from published clinical guidelines for age and weight. Independent associations between average macronutrient doses up to each of the first 7 days and likelihood of acquiring an infection in the PICU, of earlier live weaning from mechanical ventilation, and of earlier live PICU discharge were investigated using multivariable Cox proportional hazard analyses. The three macronutrients were included in the analysis simultaneously and baseline risk factors were adjusted for. FINDINGS From June 18, 2012, to July 27, 2015, 7519 children aged between newborn and 17 years were assessed for eligibility. 6079 patients were excluded, and 1440 children were randomly assigned to receive either early PN (n=723) or late PN (n=717). With increasing doses of aminoacids, the likelihood of acquiring a new infection was higher (adjusted hazard ratios [HRs] per 10% increase between 1·043-1·134 for days 1-5, p≤0·029), while the likelihood of earlier live weaning from mechanical ventilation was lower (HRs 0·950-0·975 days 3-7, p≤0·045), and the likelihood of earlier live PICU discharge was lower (HRs 0·943-0·972 days 1-7, p≤0·030). By contrast, more glucose during the first 3 days of PICU stay was independently associated with fewer infections (HRs 0·870-0·913, p≤0·036), whereas more lipids was independently associated with earlier PICU discharge (HRs 1·027-1·050, p≤0·043 days 4-7). Risk of harm with aminoacids was also shown for low doses. INTERPRETATION These associations suggest that early administration of aminoacids, but not glucose or lipids, could explain harm caused by early supplemental parenteral nutrition in critically ill children. FUNDING Flemish Agency for Innovation through Science and Technology; UZLeuven Clinical Research Fund; Research Foundation Flanders; Methusalem Programme Flemish Government; European Research Council; Fonds-NutsOhra; Erasmus-MC Research Grant; Erasmus Trustfonds.

Supporting pediatric patients with short-term continuous-flow devices

BACKGROUND Short-term continuous-flow ventricular assist devices (STCF-VADs) are increasingly being used in the pediatric population. However, little is known about the outcomes in patients supported with these devices. METHODS All pediatric patients supported with a STCF-VAD, including the Thoratec PediMag or CentriMag, or the Maquet RotaFlow, between January 2005 and May 2014, were included in this retrospective single-center study. RESULTS Twenty-seven patients (15 girls [56%]) underwent 33 STCF-VAD runs in 28 separate hospital admissions. The STCF-VAD was implanted 1 time in 23 patients (85%), 2 times in 2 patients (7%), and 3 times in 2 patients (7%). Implantation occurred most commonly in the context of congenital heart disease in 14 runs (42.2%), cardiomyopathy in 11 (33%), and after transplant in 6 (18%). The median age at implantation was 1.7 (interquartile range [IQR] 0.1, 4.1) years, and median weight was 8.9 kg (IQR 3.7, 18 kg). Patients were supported for a median duration of 12 days (IQR 6, 23 days) per run; the longest duration was 75 days. Before implantation, 15 runs (45%) were supported by extracorporeal membrane oxygenation (ECMO). After implantation, an oxygenator was required in 20 runs (61%) and continuous renal replacement therapy in 21 (64%). Overall, 7 runs (21%) resulted in weaning for recovery, 14 (42%) converted to a long-term VAD, 4 (12%) resulted in direct transplantation, 3 (9%) were converted to ECMO, and 5 (15%) runs resulted in death on the device or within 1 month after decannulation. The most common complication was bleeding requiring reoperation in 24% of runs. In addition, 18% of runs were associated with neurologic events and 15% with a culture-positive infection. Hospital discharge occurred in 19 of 28 STCF-VAD admissions (67%). In follow-up, with a median duration of 9.2 months (IQR 2.3, 38.3 months), 17 patients (63%) survived. CONCLUSIONS STCF-VADs can successfully bridge most pediatric patients to recovery, long-term device, or transplant, with an acceptable complication profile. Although these devices are designed for short-term support, longer support is possible and may serve as an alternative approach to patients not suitable for the current long-term devices.

Is propofol a friend or a foe of the pediatric intensivist? Description of propofol use in a PICU*.

Objective: The primary objective is to describe the practice patterns of nonprocedural propofol use in a single-center referral PICU. The secondary objective is to describe the rate of concordance of propofol use with the PICU local practice of a maximum mean rate of 4 mg/kg/hr and a maximum duration of 24 hours and to assess for signs and symptoms of propofol infusion syndrome. Design: Retrospective descriptive cohort study. Setting: PICU of a tertiary care teaching hospital and referral hospital for the Western Canada. Patients: Children 1 month to 17 years old who received a nonprocedural propofol infusion between January 1, 2009, and December 31, 2009. Interventions: None. Measurements and Main Results: Two hundred twenty-three infusions (representing 210 unique patients) were included in the study. The median average infusion rate (interquartile range) including boluses was 2.7 mg/kg/hr (1.9–3.6 mg/kg/hr), and the mean infusion duration (SD) was 10.3 hours (6.7 hr). Eighty-seven percent and 98% of infusions were concordant with PICU intensivists self-reported practice maximum rate and duration, respectively. No cases of propofol-related infusion syndrome or deaths associated with propofol infusions were identified. Conclusions: The use of propofol infusions was in concordance with PICU local practice, and propofol infusion syndrome did not developed in patients. In agreement with previous recommendations, propofol infusions in the PICU appear to be safe when limiting doses to 4 mg/kg/hr and for less than 24 hours; however, appropriate monitoring of adverse effects is still warranted due to absence of robust evidence.

Indications and outcomes in children receiving renal replacement therapy in pediatric intensive care.

PURPOSE We aimed to describe patient characteristics, indications for renal replacement therapy (RRT), and outcomes in children requiring RRT. We hypothesized that fluid overload, not classic blood chemistry indications, would be the most frequent reason for RRT initiation. MATERIALS AND METHODS A retrospective cohort study of all patients receiving RRT at a single-center quaternary pediatric intensive care unit between January 2004 and December 2008 was conducted. RESULTS Ninety children received RRT. The median age was 7 months (interquartile range, 1-83). Forty-six percent of patients received peritoneal dialysis, and 54% received continuous renal replacement therapy. The median (interquartile range) PRISM-III score was 14 (8-19). Fifty-seven percent had congenital heart disease, and 32% were on extracorporeal life support. The most common clinical condition associated with acute kidney injury was hemodynamic instability (57%; 95% confidence interval [CI], 46-67), followed by multiorgan dysfunction syndrome (17%; 95% CI, 10-26). The most common indication for RRT initiation was fluid overload (77%; 95% CI, 66-86). Seventy-three percent (95% CI, 62-82) of patients survived to hospital discharge. CONCLUSIONS Hemodynamic instability and multiorgan dysfunction syndrome are the most common clinical conditions associated with acute kidney injury in our population. In the population studied, the mortality was lower than previously reported in children and much lower than in the adult population.

Survival and neurocognitive outcomes in pediatric extracorporeal-cardiopulmonary resuscitation

OBJECTIVE Extracorporeal Cardiopulmonary Resuscitation (E-CPR) is the initiation of extracorporeal life support during active chest compressions. There are no studies describing detailed neurocognitive outcomes of this population. We aim to describe the survival and neurocognitive outcomes of children who received E-CPR. METHODS Prospective cohort study. Children who received E-CPR at the Stollery Childrens Hospital between 2000 and 2010 were included. Neurocognitive follow-up, including Wechsler Preschool and Primary Scales of Intelligence, was completed at the age of 4.5 years, and at a minimum of 6 months after the E-CPR admission. RESULTS Fifty-five patients received E-CPR between 2000 and 2010. Children with cardiac disease had a 49% survival to hospital discharge and 43% survival at age 5-years, with no survivors (n=4) in those with non-cardiac disease. Pediatric E-CPR survivors had a mean (SD) Full Scale Intelligence quotient (FSIQ) score of 76.5 (15.9); with 4 children (24%) having intellectual disability (defined as FSIQ over 2 standard deviations below the population mean; i.e., <70). Multiple Cox regression analysis found that mechanical ventilation prior to E-CPR, open chest CPR, longer duration of CPR, low pH and more red blood cells given on the first day of ECMO, and longer time for lactate to normalize on ECMO were associated with higher mortality at age 5-years. CONCLUSION Pediatric patients with cardiac disease who required E-CPR had 43% survival at age 5 years. Of concern, the intelligence quotient in E-CPR survivors was significantly lower than the population mean, with 24% having intellectual disability.