We have reported the results of an international, multicenter effort to examine nutrition practices in mechanically ventilated children in the PICU. The findings of this study are notable for the high prevalence of malnutrition on admission, and a striking inability to deliver the prescribed energy and protein in critically ill children during their course in the PICU. Failure to deliver the prescribed energy goal was associated with higher likelihood of mortality in this vulnerable population. The use of a protocol for initiating and advancing nutrition delivery was associated with decreased infectious complications during the PICU course. To our knowledge, this is the first study describing the association of actual nutrition bedside practices over time in a wide distribution of PICUs, with relevant clinical outcomes such as mortality and nosocomial infections.
The prevalence of severe malnutrition on admission to the PICU was over 30%, and reflects similar numbers reported in critically ill children for the past 3 decades (10
). We recorded a widespread inadequacy of both energy (34% prescribed) and protein (35% prescribed) delivered via enteral route over the course of this vulnerable population. Fluid restriction, feeding intolerance, and interruption of EN for procedures are some of the reasons responsible for energy and protein deprivation in the acute phase of pediatric critical illness previously reported in single centers (5
). On average, nearly half the patients in most reports fail to reach nutrition goals, with 37%–70% of prescribed energy delivered prior to discharge from the PICU (5
). Patients with cardiac diagnoses and those on mechanical ventilator support have previously been identified as groups that are most at risk of suboptimal nutrition in the PICU (4
). Mechanically ventilated children with a surgical diagnosis were more likely to have suboptimal macronutrient intake in our current study. This relationship has been previously shown in adult critical care population, and is likely multifactorial (15
). Future studies must explore challenges to optimal nutrient intake in this subpopulation. The failure of nutrient delivery may result in a significant decline in weight-for-age z-score at the time of discharge from the PICU (5
). Our international cohort study confirms these findings and in addition, demonstrates an association between suboptimal macronutrient intake and outcomes such as mortality and acquired infections in the PICU population.
We divided patients into tertiles based on the percentage of energy intake (in relation to prescribed goal). Patients receiving less than a third of the prescribed energy on average during the first 10 days after admission to the PICU had significantly higher odds of mortality compared to the rest. An increase in the energy intake by one tertile (33%–66% prescribed goal) significantly decreased the odds of mortality. This relationship with survival was only observed for increased energy intake via the enteral route, and was significant even after adjusting for severity of illness scores, nutrition days, and PICU site. Energy deficit from suboptimal energy intake has been associated with poor outcomes in critically ill adults (16
). Negative energy balance is associated with complications such as adult respiratory distress syndrome, sepsis, renal failure, pressure sores, and need for surgical intervention (18
). Increasing intakes of energy by 1000 kcals/day in critically ill adults is associated with significant reduction in the odds of mortality (OR 0.76; [0.61–0.95], p
= .014), especially in those with preexisting malnutrition (19
). Based on our results, increasing the energy adequacy from 33% to 66% could result in significant improvement in mortality.
The acute stress response to critical illness is characterized by extreme protein catabolism, which in the absence of adequate protein intake results in ongoing negative nitrogen balance and loss of lean body mass. Protein underfeeding during critical illness exaggerates the cumulative protein deficit, which is most notable in the preterm infants with low reserves of lean body mass (7
). Significantly higher protein intake (up to 3g/kg/day) via an aggressive feeding strategy and protein supplements may be essential to offset the catabolic losses and achieve positive nitrogen balance in children with acute illness (20
). Although, daily protein prescribed in our cohort was on average 1.7 g/kg, actual intake delivered was much lower. Optimizing protein intake to prevent lean body mass depletion is one of the most important goals of nutrition therapy in the PICU.
Healthcare associated infections significantly impact patient outcomes, including morbidity and mortality rates, length of hospital stay, and costs of intensive care unit care. Prevention of ventilator-associated pneumonia, blood stream infections, and urinary tract infections is a national patient safety goal and an area of intense research. Optimizing energy and protein delivery significantly reduces infections in critically ill adults (24
). The use of protocols for feeding was associated with reduced prevalence of acquired infections in our study, and this effect was independent of PICU site, severity of illness scores, energy intake, and nutrition days. The use of a protocolized or standardized approach allows early initiation of nutrition and achievement of energy goals in critically ill children and adults (26
). However, existing PICU protocols are varied in their approach and include strategies that are based on insufficient evidence (30
). The common features in all protocols adopted by sites in our study included, guidelines for nutrition assessment, early initiation of EN, explicit rates for advancement of feeds, and determination of energy delivery goal. Furthermore, a majority of these protocols outlined guidelines for monitoring and managing intolerance to enteral feeding such as high gastric residual volumes, had clear indications for the use of prokinetic drugs and recommended post-pyloric feeding in eligible patients, as adjuncts to nutrition support. Increased duration of interruptions to EN was associated with decreased energy adequacy achieved via EN route in our study. EN is preferred in the PICU due to decreased risk of infectious complications and lower costs compared to PN (4
). Consequently, a variety of measures have been used to optimize EN, and PN use in the intensive care unit has been declining (13
). Less than 9% of patients received PN as the source of nutrition in our study, and a majority of the patients were fed exclusively via the enteral route. We observed a trend towards higher energy adequacy achieved via EN and the use of promitility agents. This effect was not statistically significant, especially in multiple predictor modelling. Although promotility agents have been increasingly applied in adult intensive care units, the evidence for their use in the pediatric population has been lacking (30
). The use of post-pyloric (small bowel) feeding did not influence adequacy of energy intake in our study. Small bowel feeding has been associated with delivery of a higher proportion of daily energy goal compared to the gastric fed group in the PICU, but it did not impact the prevalence of micro-aspiration or feed intolerance (36
). The benefits of post-pyloric enteral feeding in the PICU have not yet been demonstrated, although the use of post-pyloric enteral feeding may be prudent in patients who have failed gastric feeding or are at risk of aspiration.
We would like to acknowledge some of the weaknesses of our study. Due to inaccuracies associated with the use of equations to estimate energy expenditure, indirect calorimetry has been recommended as the gold standard method for assessing energy needs during critical illness (30
). However, similar to previous reports, indirect calorimetry was used in a minority of centers in our study (6
). The likelihood of both underestimation and overestimation of energy needs by standard equations cannot be ruled out (39
). Severity of illness is an important confounder that might influence the ability to achieve adequate enteral nutrient intake and consequentially the reliance on PN. We adjusted for severity of illness using admission scores; however, data were missing for this variable in 31% of patients in our study. Hence despite accounting for this variable, the impact of severity on nutrient intake cannot be eliminated. We restricted the study to centers with eight or more PICU beds, in an effort to homogenize the group in terms of size, and available resources. However, the variability in medical staff skills, availability and adherence to nutrition protocols, availability of resources, and the case mix in individual units might have influenced our results. Given the observational nature of this study, we cannot make definitive causal inferences from our findings.