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Nutrient delivery in mechanically ventilated surgical patients in the pediatric critical care unit
Journal of Pediatric Surgery 52 (2017) 145–148
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Nutrient delivery in mechanically ventilated surgical patients in the pediatric critical care unit☆ Cristine S. Velazco a,d, David Zurakowski a,b,d, Brenna S. Fullerton a,d, Lori J. Bechard c, Tom Jaksic a,d, Nilesh M. Mehta b,c,d,⁎ a
Department of Surgery, Boston Children's Hospital Division of Critical Care Medicine; Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital Center for Nutrition, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital d Harvard Medical School, Boston, MA 02115 b c
a r t i c l e
i n f o
Article history: Received 16 October 2016 Accepted 20 October 2016 Key words: Protein Enteral nutrition Surgical PICU Interruption
a b s t r a c t Purpose: Inadequate nutrient intake is associated with poor outcomes in critically ill children. We examined macronutrient delivery in surgical patients in the pediatric intensive care unit (PICU). Methods: In a prospective international cohort study of mechanically ventilated children (1 month to 18 years), we recorded adequacy of cumulative nutrient delivery in the PICU. Surgical patients enrolled in this study were included in the current analysis. Protein intake b60% of the prescribed goal was deemed inadequate. Results: Five hundred nineteen surgical patients, 45% female, median age 2 years (IQR 0.5, 8), BMI z score −0.26, with 9-day median PICU stay and 60-day mortality 5.8% were enrolled. Three hundred forty-one (66%) patients received enteral nutrition (EN), and median time of initiation was PICU day 2. EN delivery was interrupted in 68% of these patients for a median duration of 9 hours. Median enteral protein delivery was b15% of the prescribed goal and was b 60% in two-thirds of the cohort. Patients with inadequate enteral protein delivery had longer time to EN initiation (p b 0.001) and longer duration of EN interruptions (p b 0.001) compared to those with adequate delivery. Conclusion: Enteral protein delivery in critically ill pediatric surgical patients is inadequate. Early EN initiation and minimizing interruptions may increase protein delivery and potentially improve outcomes in this population. Level of evidence: I. Type of study: Prospective study. © 2017 Elsevier Inc. All rights reserved.
Delivery of adequate nutrition is an essential component of care in the pediatric intensive care unit (PICU). Optimal nutrition is essential to offset the catabolic effects of illness. Severe malnutrition has been reported in up to 30% of patients on admission and often continues through the PICU course in the setting of widespread inadequacy of enteral energy and protein delivery [1]. Mechanically ventilated surgical patients are more likely to have suboptimal nutrient intake compared to medical patients in adult intensive care units [2]. Inadequate nutrient intake has been associated with increased mortality, increased length of stay, and nosocomial infections [1,3]. Abbreviations: ASPEN, The American Society of Parenteral and Enteral Nutrition. ☆ Author contributions:Study conception and design: Cristine S. Velazco, David Zurakowski, Lori J. Bechard, Nilesh M. Mehta.Data acquisition: Lori J. Bechard, Nilesh M. Mehta.Analysis and data interpretation: Cristine S. Velazco, David Zurakowski, Brenna S. Fullerton, Lori J. Bechard, Tom Jaksic, Nilesh M. Mehta.Drafting of the manuscript: Cristine S. Velazco, David Zurakowski, Brenna S. Fullerton, Lori J. Bechard, Tom Jaksic, Nilesh M. Mehta.Critical revision: Cristine S. Velazco, David Zurakowski, Brenna S. Fullerton, Lori J. Bechard, Tom Jaksic, Nilesh M. Mehta. ⁎ Corresponding author at: Boston Children's Hospital, MSICU Office, Bader 634, 300 Longwood Ave, Boston, MA 02115. Tel.: +1 617 355 7327. E-mail address: [email protected] (N.M. Mehta). http://dx.doi.org/10.1016/j.jpedsurg.2016.10.041 0022-3468/© 2017 Elsevier Inc. All rights reserved.
Previously, we described an association between higher adequacy of enteral nutrient (EN) intake and lower 60-day mortality [1,4]. In a more recent multicenter study, delivery of N 60% prescribed protein intake was associated with lower odds of mortality in critically ill medical and surgical children [4]. The effect of protein intake adequacy on outcomes was independent of energy intake. Achieving protein intake that is greater than 80% of prescribed daily amount was associated with improved survival and decreased time to discharge in critically ill adults [5]. Adequate protein intake might help to offset the losses incurred during the catabolic response to surgical stress in the ICU population. The American Society of Parenteral and Enteral Nutrition (ASPEN) recommendations for daily protein intake in critically ill children are higher than the values recommended in the dietary reference intake (DRI) guidelines [6]. However, suboptimal protein prescriptions and barriers at the bedside may result in inadequate delivery [7]. In our current study, we aimed to describe the adequacy of protein delivery in mechanically ventilated surgical patients in the PICU. In this subpopulation of the general PICU study cohort that was previously described, we aimed to examine prescription and barriers to adequate delivery at the bedside unique to the surgical patients.
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Table 1 Characteristics of mechanically ventilated surgical patients in the PICU (N = 519). Variable Age (years), median (IQR) Sex (F), n (%) BMI z scorea, median (IQR) Weight-for-age z score, median (IQR) Malnourishedb, n (%) PICU stay (days), median (IQR) Hospital stay (days), median (IQR) Ventilation (days), median (IQR) 60-day mortality, n (%) Any infection, n (%) Ventilator associated pneumonia Urinary tract infection Blood stream infection
2 233 −0.26 −0.81 99 9 18 5 30 52 23 22 12
(0.5, 8) (45) (−1.5, 0.9) (−2.14, +0.41) (19) (5, 18) (10, 40) (2, 11) (5.8) (10) (4) (4) (2)
BMI = body mass index, PICU = pediatric intensive care unit, IQR = interquartile range. a Four patients missing BMI data. b As defined by BMI z score b−2 on admission.
1. Methods Approval was obtained from the institutional review board of Boston Children's Hospital (IRB protocol # X10-11-0569) and each participating site. The trial was registered at clinicaltrials.gov as NCT02354521. Details of site and patient recruitment for the primary study have been previously described [4]. In brief, centers with a PICU that contained ≥ 8 beds were eligible. Consecutive children (age: one month to 18 years) that were admitted following a surgical procedure or awaiting surgical intervention surgery and requiring mechanical ventilation with anticipated PICU stay of greater than 48 hours were enrolled. Nutritional variables including prescribed energy and protein goals, daily macronutrient delivery, route of delivery, and feeding interruption (frequency and duration) were recorded. Energy and protein goals were prescribed by the local nutrition team upon admission to PICU and adjusted as deemed appropriate by the team through the PICU stay. These goals were prospectively documented by dietitians for each patient in the study, and were used to define adequacy of energy and protein delivery (percentage of the goal that was actually delivered). Additionally, the protein goals for each subject were compared with the recommended daily protein intake in 2005 Dietary Reference Intake (DRI) and 2009 ASPEN age-based guidelines [6,8]. Advancement to goal nutrition for EN and PN was left to the discretion of the local nutrition team. Cumulative percent adequacy of energy and protein delivery (delivered/prescribed × 100) was calculated more than 10 days or until PICU discharge. Based on previously reported association between protein delivery and outcomes, protein delivery in this cohort was deemed as adequate if N 60% of the prescribed goal was administered during the study period [4]. World Health Organization (WHO) growth data were used to calculate z scores for anthropometric parameters. In order to demonstrate the unique features of nutrient delivery in the surgical population, we compared this subset with the medical patients, both part of our
previously reported combined cohort [4]. We examined significant differences in clinical and nutritional variables between those with adequate vs. inadequate protein delivery, using the Mann–Whitney U test. The paired Wilcoxon signed-rank test was used to compare daily enteral protein intake, prescribed protein goal, and ASPEN. recommended values. Binary proportions and percentages were compared between groups using Fisher's exact test. Two-tailed p b 0.05 were considered statistically significant. Statistical analysis was conducted with IBM SPSS Statistics (version 23.0, IBM, Armonk, NY).
2. Results Data from 519 surgical subjects (41% of the mixed PICU cohort) who met inclusion criteria from 57 centers in fifteen countries were analyzed, with patient characteristics described in Table 1. This surgical cohort was 45% female and had a median age of 2 years (IQR: 0.5, 8). Median BMI z score on admission was − 0.26, (IQR: − 1.5, 0.9) and 19% of the cohort was classified as moderately or severely malnourished with a BMI z score of less than −2.0. In comparison, the medical group (n = 726) was 44% female (p = 0.632), median age 1.4 (IQR: 0.3, 6) (p = 0.003), and a median BMI z score on admission of − 0.065 (IQR: −1.46, 1.24) (p = 0.071). Median PICU length of stay for the surgical cohort was 9 days (IQR: 5, 18), and 60-day mortality was 5.8% (n = 30). Seventy-eight percent of patients were cared for in a closed PICU setting (n = 407), where intensivists were responsible for all medical decision making with consulting services providing input. Antacids were used in 47% of the surgical patients compared to 72% of medical patients (p b 0.001) and promotility agents were used in 66% of surgical patients compared to 89% of medical patients (p b 0.001). PICU admission was complicated by at least one infection in 10% of patients, with 4% diagnosed with urinary tract infections, 4% ventilator associated pneumonia, and 2% bloodstream infections. A total of 341 (66%) patients received EN at some point during their PICU stay, and the median time of EN initiation was day 2 (IQR: 2, 4). PN was administered in 196 patients (38% of the cohort), it was employed as a supplement to insufficient EN in 128 (65%) of this subgroup. Twenty-one percent of patients received no nutrition during their stay. Details of nutrient delivery are described in Table 2. EN delivery was interrupted in 232 (68%) patients for a median total interruption length of 9 hours (IQR: 5.5, 13). Table 2 describes the differences in these variables between the surgical and medical cohorts. Fig. 1 describes adequacy of median daily protein and energy delivered by route and by PICU day in the surgical cohort. This is in stark contrast to the medical cohort adequacy; protein and energy adequacy by EN delivery alone and EN supplemented by PN were all significantly less in the surgical cohort (p b 0.001). Median protein delivery (EN + PN) on day 7 was 60% for the medical cohort and 15% for the surgical cohort. Median protein prescription value for the surgical cohort was higher than the recommended minimum amount according to the ASPEN guidelines. However, protein delivery was significantly lower than the goal prescribed by the PICU dietitian (p b 0.001) as well as the ASPEN-
Table 2 Nutrient delivery in the PICU.⁎ Nutrition delivery
Surgical (n = 519)
Medical (n = 726)
P-value
Enteral nutrition only, n (%) Parenteral nutrition only, n (%) Patients who received any PN Parenteral nutrition as supplement, n (%) Patients who received any EN (N = 341): Time to EN initiation (days), (IQR) Patients with EN delivery interruptions, n (%) Number of interruptions per patient, median (IQR) Total duration of interruptions (hours), median (IQR)
213 (41) 68 (13) 196 (38) 128 (65) 341 (66) 2 (2, 4) 231 (68) 1 (0, 2) 9 (5.5, 13)
513 (71) 36 (5) 167 (23) 131 (78) 644 (89) 2 (1, 3) 493 (77) 1 (0, 2) 7.5 (4.7, 12)
b0.001 b0.001 b0.001 0.006 b0.001 b0.001 0.003 0.208 0.005
EN = enteral nutrition; IQR = interquartile range; PICU = pediatric intensive care unit. ⁎ Subgroup analysis of the previously described combined PICU cohort [4].
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Table 4 Bivariate analysis of protein adequacy in the critically ill surgical patients.
EN initiation, days Duration of EN interruption, hours
Inadequate EN protein intake median (IQR) (N = 346)
Adequate EN protein intake median (IQR) (N = 173)
P-value
3 10
2 5
b0.001 b0.001
(2, 4) (6, 14.4)
(1, 2) (0.8, 7)
EN = enteral nutrition.
Fig. 1. Median daily protein and energy delivery in the surgical PICU.
recommended value (p b 0.001). Table 3 describes median (g/kg per day) recommended, prescribed and delivered protein values. Median enteral protein delivery for the cohort was b15% of the prescribed goal, and two-thirds of the cohort received inadequate enteral protein intake during the first week of their PICU stay. Two-thirds of the cohort received inadequate enteral protein intake during their PICU stay. This subgroup of patients with inadequate enteral protein intake had significantly longer time to EN initiation, [3 (IQR: 2, 4) vs. 2 (IQR: 1, 2) days; (p b 0.001)] and longer total duration of EN interruptions [10, (IQR: 6, 14.4) vs. 5, (IQR: 0.8, 7) hours; p b 0.001] compared to those with adequate intake (Table 4). None of the 30 patients who died achieved adequate enteral or parenteral nutrient delivery. 3. Discussion 3.1. Summary of our results We have described the inadequacy of energy and protein delivery in a large prospective, multicenter cohort of critically ill pediatric surgical patients requiring mechanical ventilation. Despite appropriate prescription of protein goals, delays in initiating EN and prolonged total duration of EN interruptions were associated with failure to achieve adequate protein delivery in the PICU. PN was used alone or as a supplement to EN in more than a third of the patients. One in five children received no nutritional support. To our knowledge, this is the largest pediatric surgical cohort study describing nutrient prescription, barriers to and adequacy of nutrient delivery during acute critical illness. The surgical cohort was significantly undernourished compared to the medical patients.
The inadequacy of protein delivery in our current study is concerning. A dose–response relationship between increasing enteral protein intake and lower 60-day mortality was recorded in our combined cohort study [4]. This association is also supported by the adult surgical ICU literature, where inadequate protein delivery has been associated with higher mortality as well as lower rates of discharge home and worse clinical outcomes [5,9]. Protein intake is essential to balance the losses seen during the catabolic stress response to surgery. A minimum of 1.5 g/kg per day of protein has been recommended for critically ill children [6]. In our surgical cohort, greater than two-thirds of the patients received less than 60% of protein prescribed to meet their metabolic needs. This may lead to a negative protein balance in the setting of postoperative muscle breakdown, with potential for muscle wasting and poor outcomes. In a surgical population, poor nutrition impedes wound healing, and weight below the 10th percentile is a known risk factor for postoperative complications in pediatric cardiac patients [10]. 3.3. Enteral nutrition There are numerous benefits to enteral nutrition, including decreased infection rates, decreased morbidity and protection of mucosal integrity of the small intestine [11]. Initiation of EN is recommended within 24–48 hours of admission [12]. However, delivery of EN may be hindered postoperatively with ileus, delayed gastric emptying, and although controversial, high gastric residual volumes. Delivery of enteral protein reduces mortality and leads to improved outcomes. ASPEN guidelines recommend enteral nutrition as the preferred method of nutritional delivery in critically ill patients with a functioning gastrointestinal tract [6]. Early EN is feasible and leads to an improvement in the likelihood and time to adequate nutrition goals as well as lower mortality in critically ill children [13,14]. All major medical societies with nutritional guidelines recommend early initiation of EN in critically ill adults who are hemodynamically stable, and the initiation of EN within 6 hours of ICU admission is shown to be safe in both medical and surgical patients [11]. These same goals should be considered in critically ill children.
3.2. Importance of protein delivery adequacy
3.4. Barriers to EN
Average protein intake adequacy on day 7 in the PICU was significantly lower in the surgical cohort compared to the medical cohort.
Minimizing interruptions to the delivery of enteral nutrition is essential as most patients in this study experienced at least one interruption. The critical care and surgical team should strive to minimize the duration of EN delivery interruptions, and must be mindful whenever nutrition is being held. At times, this is inevitable when procedures are delayed or canceled for various reasons. Procedure delays, procedure cancelations, and technical issues with enteral feeding access, such as clogged or displaced feeding tubes, may contribute to some inevitable interruptions [15,16]. The multicenter scope of the study and remote nature of data capture at the end of each day did not allow us to document details of the reasons for EN interruptions in this study. In a previous single center study, we have described the most common reasons for EN interruptions in the PICU population that included surgical patients [16]. Interruptions because of perceived EN intolerance and preprocedural fasting were most common in this study.
Table 3 Daily recommended, prescribed and delivered protein via enteral route in the surgical PICU (N = 519). Protein (g/kg per day)
Median (IQR)
Prescribed ASPEN recommended for critical illness DRI recommended Delivered Difference between ASPEN recommended value and actual daily protein delivery
2 1.5 1.1 0.2 1.5
(1.5, 2.4) (1.5, 2.0) (0.9, 1.5) (0, 0.8) (0.9, 1.7)
ASPEN = American Society of Parenteral and Enteral Nutrition; DRI = Dietary Reference Intake 2005; PICU = pediatric intensive care unit.
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When EN interruptions are anticipated, goal daily nutrient delivery may be achieved by increasing the hourly rate of feeds to account for the interruption, and better coordination of usual scheduled breaks in the patient's enteral feeds with the scheduled procedure. In patients' with a secured airway, feeds could be continued through surgery or procedure, which is particularly true for patients fed via the postpyloric route. This issue needs further examination; and we have previously described procedural fasting as one of the leading causes of EN interruption in PICU patients [16]. Jenkins et al. have described the feasibility of perioperative feeding via a duodenal tube in pediatric and adult burn population [17]. Enteral feeds were continued throughout the surgical cases in their cohort with no increase in the rate of aspiration. On the other hand, the fasted group experienced significant caloric deficit and increased rate of wound infection. Larger, more recent studies are needed to support these findings in order to gain more widespread acceptance. If prolonged interruption is anticipated, initiation of PN may be considered in an effort to avoid macronutrient deficits. In our current study, PN was employed alone in patients that were ineligible for EN, and as a supplement to insufficient PN. The best timing for introducing supplemental PN in the PICU is not clear. A strategy of delayed PN in the first week of PICU stay, with early EN initiation, was recently reported to be superior to an early PN strategy in a randomized control trial [18]. Continuing PN through the surgical procedure is also a consideration if adequate central access is available. Algorithms for early delivery of EN have been shown to be effective in adults [19,20]. Previously, we described details of EN algorithm used in 9 PICUs [21]. Recommendations in these guidelines were highly variable and were not in agreement with national guidelines. The use of algorithms was not associated with increased energy delivery but we were not able to assess compliance of the institutions to their algorithm. A number of studies have shown a feeding algorithm may significantly reduce time to EN initiation, decrease reliance on PN as well as the time to goal rate of EN [13,22]. More studies are needed to develop and examine the role of stepwise algorithms in optimizing nutrient delivery to the surgical patients in the PICU. 4. Conclusions Preoperative malnutrition is prevalent in the critically ill pediatric surgical cohort. Energy and protein delivery is inadequate with a median delivery of less than 15% of prescribed macronutrients by pediatric intensive care unit day 7. Delayed initiation and prolonged interruptions to enteral nutrition were associated with inadequate enteral protein delivery and reliance on parenteral nutrition. There is an urgent need to prioritize adequate energy and protein delivery in surgical critically ill children. Opportunities for improving nutrient delivery may impact outcomes and therefore are important areas for future research. References [1] Mehta NM, Bechard LJ, Cahill N, et al. Nutritional practices and their relationship to clinical outcomes in critically ill children – an international multicenter cohort study*. Crit Care Med 2012;40:2204–11. http://dx.doi.org/10.1097/CCM.0b013e31824e18a8.
[2] Drover JW, Cahill NE, Kutsogiannis J, et al. Nutrition therapy for the critically ill surgical patient: we need to do better! JPEN J Parenter Enteral Nutr 2010;34:644–52. http://dx.doi.org/10.1177/0148607110372391. [3] Elke G, Wang M, Weiler N, et al. Close to recommended caloric and protein intake by enteral nutrition is associated with better clinical outcome of critically ill septic patients: secondary analysis of a large international nutrition database. Crit Care 2014; 18:R29. http://dx.doi.org/10.1186/cc13720. [4] Mehta NM, Bechard LJ, Zurakowski D, et al. Adequate enteral protein intake is inversely associated with 60-d mortality in critically ill children: a multicenter, prospective, cohort study. Am J Clin Nutr 2015;102:199–206. http://dx.doi.org/10. 3945/ajcn.114.104893. [5] Nicolo M, Heyland DK, Chittams J, et al. Clinical outcomes related to protein delivery in a critically ill population: a multicenter, multinational observation study. JPEN J Parenter Enteral Nutr 2016;40:45–51. http://dx.doi.org/10.1177/ 0148607115583675. [6] Mehta NM, Compher C. A.S.P.E.N. Clinical guidelines: nutrition support of the critically ill child. JPEN J Parenter Enteral Nutr 2009;33(3):260–76. [7] Rogers EJ, Gilbertson HR, Heine RG, et al. Barriers to adequate nutrition in critically ill children. Nutrition 2003;19:865–8. [8] National Academy of Sciences. Recommended dietary allowances10th ed. ; 1989[Washington DC]. [9] Yeh DD, Fuentes E, Quraishi SA, et al. Adequate nutrition may get you home: effect of caloric/protein deficits on the discharge destination of critically ill surgical patients. JPEN J Parenter Enteral Nutr 2016;40:37–44. http://dx.doi.org/10.1177/ 0148607115585142. [10] Leite HP, Fisberg M, Novo NF, Nogueira EB, Ueda IK. Nutritional assessment and surgical risk markers in children submitted to cardiac surgery. São Paulo Med J 1995; 113:706–14. [11] Shankar B, Daphnee DK, Ramakrishnan N, et al. Feasibility, safety, and outcome of very early enteral nutrition in critically ill patients: results of an observational study. J Crit Care 2015;30:473–5. http://dx.doi.org/10.1016/j.jcrc. 2015.02.009. [12] McClave SA, Martindale RG, Vanek VW, McCarthy M, Roberts P, Taylor B, et al. Guidelines for the provision and assessment of nutrition support therapy in the adult critically ill patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.). JPEN J Parenter Enteral Nutr 2016;33:277–316. http://dx.doi.org/10.1177/0148607109335234. [13] Hamilton S, McAleer DM, Ariagno K, et al. A stepwise enteral nutrition algorithm for critically ill children helps achieve nutrient delivery goals*. Pediatr Crit Care Med 2014;15:583–9. http://dx.doi.org/10.1097/PCC.0000000000000179. [14] Mikhailov TA, Kuhn EM, Manzi J, et al. Early enteral nutrition is associated with lower mortality in critically ill children. JPEN J Parenter Enteral Nutr 2014;38: 459–66. http://dx.doi.org/10.1177/0148607113517903. [15] Stewart ML. Interruptions in enteral nutrition delivery in critically ill patients and recommendations for clinical practice. Crit Care Nurse 2014;34:14–21. http://dx. doi.org/10.4037/ccn2014243 [quiz 22]. [16] Mehta NM, McAleer D, Hamilton S, Naples E, Leavitt K, Mitchell P, et al. Challenges to optimal enteral nutrition in a multidisciplinary pediatric intensive care unit. JPEN J Parenter Enteral Nutr 2010;34:38–45. http://dx.doi.org/10.1177/0148607109348065. [17] Jenkins ME, Gottschlich MM, Warden GD. Enteral feeding during operative procedures in thermal injuries. J Burn Care Rehabil 1994;15:199–205. [18] Fivez T, Kerklaan D, Mesotten D, et al. Early versus late parenteral nutrition in critically ill children. N Engl J Med 2016. http://dx.doi.org/10.1056/ NEJMoa1514762. [19] Compton F, Bojarski C, Siegmund B, et al. Use of a nutrition support protocol to increase enteral nutrition delivery in critically ill patients. Am J Crit Care 2014;23: 396–403. http://dx.doi.org/10.4037/ajcc2014140. [20] Taylor B, Brody R, Denmark R, et al. Improving enteral delivery through the adoption of the “Feed Early Enteral DIET adequately for Maximum Effect (FEED ME)” protocol in a surgical trauma ICU: a quality improvement review. Nutr Clin Pract 2014;29: 639–48. http://dx.doi.org/10.1177/0884533614539705. [21] Martinez EE, Bechard LJ, Mehta NM. Nutrition algorithms and bedside nutrient delivery practices in pediatric intensive care units: an international multicenter cohort study. Nutr Clin Pract 2014;29:360–7. http://dx.doi.org/10.1177/ 0884533614530762. [22] Petrillo-Albarano T, Pettignano R, Asfaw M, et al. Use of a feeding protocol to improve nutritional support through early, aggressive, enteral nutrition in the pediatric intensive care unit. Pediatr Crit Care Med 2006;7(4):340–4.
Contents lists available at ScienceDirect
Journal of Pediatric Surgery journal homepage: www.elsevier.com/locate/jpedsurg
Nutrient delivery in mechanically ventilated surgical patients in the pediatric critical care unit☆ Cristine S. Velazco a,d, David Zurakowski a,b,d, Brenna S. Fullerton a,d, Lori J. Bechard c, Tom Jaksic a,d, Nilesh M. Mehta b,c,d,⁎ a
Department of Surgery, Boston Children's Hospital Division of Critical Care Medicine; Department of Anesthesia, Perioperative and Pain Medicine, Boston Children's Hospital Center for Nutrition, Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital d Harvard Medical School, Boston, MA 02115 b c
a r t i c l e
i n f o
Article history: Received 16 October 2016 Accepted 20 October 2016 Key words: Protein Enteral nutrition Surgical PICU Interruption
a b s t r a c t Purpose: Inadequate nutrient intake is associated with poor outcomes in critically ill children. We examined macronutrient delivery in surgical patients in the pediatric intensive care unit (PICU). Methods: In a prospective international cohort study of mechanically ventilated children (1 month to 18 years), we recorded adequacy of cumulative nutrient delivery in the PICU. Surgical patients enrolled in this study were included in the current analysis. Protein intake b60% of the prescribed goal was deemed inadequate. Results: Five hundred nineteen surgical patients, 45% female, median age 2 years (IQR 0.5, 8), BMI z score −0.26, with 9-day median PICU stay and 60-day mortality 5.8% were enrolled. Three hundred forty-one (66%) patients received enteral nutrition (EN), and median time of initiation was PICU day 2. EN delivery was interrupted in 68% of these patients for a median duration of 9 hours. Median enteral protein delivery was b15% of the prescribed goal and was b 60% in two-thirds of the cohort. Patients with inadequate enteral protein delivery had longer time to EN initiation (p b 0.001) and longer duration of EN interruptions (p b 0.001) compared to those with adequate delivery. Conclusion: Enteral protein delivery in critically ill pediatric surgical patients is inadequate. Early EN initiation and minimizing interruptions may increase protein delivery and potentially improve outcomes in this population. Level of evidence: I. Type of study: Prospective study. © 2017 Elsevier Inc. All rights reserved.
Delivery of adequate nutrition is an essential component of care in the pediatric intensive care unit (PICU). Optimal nutrition is essential to offset the catabolic effects of illness. Severe malnutrition has been reported in up to 30% of patients on admission and often continues through the PICU course in the setting of widespread inadequacy of enteral energy and protein delivery [1]. Mechanically ventilated surgical patients are more likely to have suboptimal nutrient intake compared to medical patients in adult intensive care units [2]. Inadequate nutrient intake has been associated with increased mortality, increased length of stay, and nosocomial infections [1,3]. Abbreviations: ASPEN, The American Society of Parenteral and Enteral Nutrition. ☆ Author contributions:Study conception and design: Cristine S. Velazco, David Zurakowski, Lori J. Bechard, Nilesh M. Mehta.Data acquisition: Lori J. Bechard, Nilesh M. Mehta.Analysis and data interpretation: Cristine S. Velazco, David Zurakowski, Brenna S. Fullerton, Lori J. Bechard, Tom Jaksic, Nilesh M. Mehta.Drafting of the manuscript: Cristine S. Velazco, David Zurakowski, Brenna S. Fullerton, Lori J. Bechard, Tom Jaksic, Nilesh M. Mehta.Critical revision: Cristine S. Velazco, David Zurakowski, Brenna S. Fullerton, Lori J. Bechard, Tom Jaksic, Nilesh M. Mehta. ⁎ Corresponding author at: Boston Children's Hospital, MSICU Office, Bader 634, 300 Longwood Ave, Boston, MA 02115. Tel.: +1 617 355 7327. E-mail address: [email protected] (N.M. Mehta). http://dx.doi.org/10.1016/j.jpedsurg.2016.10.041 0022-3468/© 2017 Elsevier Inc. All rights reserved.
Previously, we described an association between higher adequacy of enteral nutrient (EN) intake and lower 60-day mortality [1,4]. In a more recent multicenter study, delivery of N 60% prescribed protein intake was associated with lower odds of mortality in critically ill medical and surgical children [4]. The effect of protein intake adequacy on outcomes was independent of energy intake. Achieving protein intake that is greater than 80% of prescribed daily amount was associated with improved survival and decreased time to discharge in critically ill adults [5]. Adequate protein intake might help to offset the losses incurred during the catabolic response to surgical stress in the ICU population. The American Society of Parenteral and Enteral Nutrition (ASPEN) recommendations for daily protein intake in critically ill children are higher than the values recommended in the dietary reference intake (DRI) guidelines [6]. However, suboptimal protein prescriptions and barriers at the bedside may result in inadequate delivery [7]. In our current study, we aimed to describe the adequacy of protein delivery in mechanically ventilated surgical patients in the PICU. In this subpopulation of the general PICU study cohort that was previously described, we aimed to examine prescription and barriers to adequate delivery at the bedside unique to the surgical patients.
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Table 1 Characteristics of mechanically ventilated surgical patients in the PICU (N = 519). Variable Age (years), median (IQR) Sex (F), n (%) BMI z scorea, median (IQR) Weight-for-age z score, median (IQR) Malnourishedb, n (%) PICU stay (days), median (IQR) Hospital stay (days), median (IQR) Ventilation (days), median (IQR) 60-day mortality, n (%) Any infection, n (%) Ventilator associated pneumonia Urinary tract infection Blood stream infection
2 233 −0.26 −0.81 99 9 18 5 30 52 23 22 12
(0.5, 8) (45) (−1.5, 0.9) (−2.14, +0.41) (19) (5, 18) (10, 40) (2, 11) (5.8) (10) (4) (4) (2)
BMI = body mass index, PICU = pediatric intensive care unit, IQR = interquartile range. a Four patients missing BMI data. b As defined by BMI z score b−2 on admission.
1. Methods Approval was obtained from the institutional review board of Boston Children's Hospital (IRB protocol # X10-11-0569) and each participating site. The trial was registered at clinicaltrials.gov as NCT02354521. Details of site and patient recruitment for the primary study have been previously described [4]. In brief, centers with a PICU that contained ≥ 8 beds were eligible. Consecutive children (age: one month to 18 years) that were admitted following a surgical procedure or awaiting surgical intervention surgery and requiring mechanical ventilation with anticipated PICU stay of greater than 48 hours were enrolled. Nutritional variables including prescribed energy and protein goals, daily macronutrient delivery, route of delivery, and feeding interruption (frequency and duration) were recorded. Energy and protein goals were prescribed by the local nutrition team upon admission to PICU and adjusted as deemed appropriate by the team through the PICU stay. These goals were prospectively documented by dietitians for each patient in the study, and were used to define adequacy of energy and protein delivery (percentage of the goal that was actually delivered). Additionally, the protein goals for each subject were compared with the recommended daily protein intake in 2005 Dietary Reference Intake (DRI) and 2009 ASPEN age-based guidelines [6,8]. Advancement to goal nutrition for EN and PN was left to the discretion of the local nutrition team. Cumulative percent adequacy of energy and protein delivery (delivered/prescribed × 100) was calculated more than 10 days or until PICU discharge. Based on previously reported association between protein delivery and outcomes, protein delivery in this cohort was deemed as adequate if N 60% of the prescribed goal was administered during the study period [4]. World Health Organization (WHO) growth data were used to calculate z scores for anthropometric parameters. In order to demonstrate the unique features of nutrient delivery in the surgical population, we compared this subset with the medical patients, both part of our
previously reported combined cohort [4]. We examined significant differences in clinical and nutritional variables between those with adequate vs. inadequate protein delivery, using the Mann–Whitney U test. The paired Wilcoxon signed-rank test was used to compare daily enteral protein intake, prescribed protein goal, and ASPEN. recommended values. Binary proportions and percentages were compared between groups using Fisher's exact test. Two-tailed p b 0.05 were considered statistically significant. Statistical analysis was conducted with IBM SPSS Statistics (version 23.0, IBM, Armonk, NY).
2. Results Data from 519 surgical subjects (41% of the mixed PICU cohort) who met inclusion criteria from 57 centers in fifteen countries were analyzed, with patient characteristics described in Table 1. This surgical cohort was 45% female and had a median age of 2 years (IQR: 0.5, 8). Median BMI z score on admission was − 0.26, (IQR: − 1.5, 0.9) and 19% of the cohort was classified as moderately or severely malnourished with a BMI z score of less than −2.0. In comparison, the medical group (n = 726) was 44% female (p = 0.632), median age 1.4 (IQR: 0.3, 6) (p = 0.003), and a median BMI z score on admission of − 0.065 (IQR: −1.46, 1.24) (p = 0.071). Median PICU length of stay for the surgical cohort was 9 days (IQR: 5, 18), and 60-day mortality was 5.8% (n = 30). Seventy-eight percent of patients were cared for in a closed PICU setting (n = 407), where intensivists were responsible for all medical decision making with consulting services providing input. Antacids were used in 47% of the surgical patients compared to 72% of medical patients (p b 0.001) and promotility agents were used in 66% of surgical patients compared to 89% of medical patients (p b 0.001). PICU admission was complicated by at least one infection in 10% of patients, with 4% diagnosed with urinary tract infections, 4% ventilator associated pneumonia, and 2% bloodstream infections. A total of 341 (66%) patients received EN at some point during their PICU stay, and the median time of EN initiation was day 2 (IQR: 2, 4). PN was administered in 196 patients (38% of the cohort), it was employed as a supplement to insufficient EN in 128 (65%) of this subgroup. Twenty-one percent of patients received no nutrition during their stay. Details of nutrient delivery are described in Table 2. EN delivery was interrupted in 232 (68%) patients for a median total interruption length of 9 hours (IQR: 5.5, 13). Table 2 describes the differences in these variables between the surgical and medical cohorts. Fig. 1 describes adequacy of median daily protein and energy delivered by route and by PICU day in the surgical cohort. This is in stark contrast to the medical cohort adequacy; protein and energy adequacy by EN delivery alone and EN supplemented by PN were all significantly less in the surgical cohort (p b 0.001). Median protein delivery (EN + PN) on day 7 was 60% for the medical cohort and 15% for the surgical cohort. Median protein prescription value for the surgical cohort was higher than the recommended minimum amount according to the ASPEN guidelines. However, protein delivery was significantly lower than the goal prescribed by the PICU dietitian (p b 0.001) as well as the ASPEN-
Table 2 Nutrient delivery in the PICU.⁎ Nutrition delivery
Surgical (n = 519)
Medical (n = 726)
P-value
Enteral nutrition only, n (%) Parenteral nutrition only, n (%) Patients who received any PN Parenteral nutrition as supplement, n (%) Patients who received any EN (N = 341): Time to EN initiation (days), (IQR) Patients with EN delivery interruptions, n (%) Number of interruptions per patient, median (IQR) Total duration of interruptions (hours), median (IQR)
213 (41) 68 (13) 196 (38) 128 (65) 341 (66) 2 (2, 4) 231 (68) 1 (0, 2) 9 (5.5, 13)
513 (71) 36 (5) 167 (23) 131 (78) 644 (89) 2 (1, 3) 493 (77) 1 (0, 2) 7.5 (4.7, 12)
b0.001 b0.001 b0.001 0.006 b0.001 b0.001 0.003 0.208 0.005
EN = enteral nutrition; IQR = interquartile range; PICU = pediatric intensive care unit. ⁎ Subgroup analysis of the previously described combined PICU cohort [4].
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Table 4 Bivariate analysis of protein adequacy in the critically ill surgical patients.
EN initiation, days Duration of EN interruption, hours
Inadequate EN protein intake median (IQR) (N = 346)
Adequate EN protein intake median (IQR) (N = 173)
P-value
3 10
2 5
b0.001 b0.001
(2, 4) (6, 14.4)
(1, 2) (0.8, 7)
EN = enteral nutrition.
Fig. 1. Median daily protein and energy delivery in the surgical PICU.
recommended value (p b 0.001). Table 3 describes median (g/kg per day) recommended, prescribed and delivered protein values. Median enteral protein delivery for the cohort was b15% of the prescribed goal, and two-thirds of the cohort received inadequate enteral protein intake during the first week of their PICU stay. Two-thirds of the cohort received inadequate enteral protein intake during their PICU stay. This subgroup of patients with inadequate enteral protein intake had significantly longer time to EN initiation, [3 (IQR: 2, 4) vs. 2 (IQR: 1, 2) days; (p b 0.001)] and longer total duration of EN interruptions [10, (IQR: 6, 14.4) vs. 5, (IQR: 0.8, 7) hours; p b 0.001] compared to those with adequate intake (Table 4). None of the 30 patients who died achieved adequate enteral or parenteral nutrient delivery. 3. Discussion 3.1. Summary of our results We have described the inadequacy of energy and protein delivery in a large prospective, multicenter cohort of critically ill pediatric surgical patients requiring mechanical ventilation. Despite appropriate prescription of protein goals, delays in initiating EN and prolonged total duration of EN interruptions were associated with failure to achieve adequate protein delivery in the PICU. PN was used alone or as a supplement to EN in more than a third of the patients. One in five children received no nutritional support. To our knowledge, this is the largest pediatric surgical cohort study describing nutrient prescription, barriers to and adequacy of nutrient delivery during acute critical illness. The surgical cohort was significantly undernourished compared to the medical patients.
The inadequacy of protein delivery in our current study is concerning. A dose–response relationship between increasing enteral protein intake and lower 60-day mortality was recorded in our combined cohort study [4]. This association is also supported by the adult surgical ICU literature, where inadequate protein delivery has been associated with higher mortality as well as lower rates of discharge home and worse clinical outcomes [5,9]. Protein intake is essential to balance the losses seen during the catabolic stress response to surgery. A minimum of 1.5 g/kg per day of protein has been recommended for critically ill children [6]. In our surgical cohort, greater than two-thirds of the patients received less than 60% of protein prescribed to meet their metabolic needs. This may lead to a negative protein balance in the setting of postoperative muscle breakdown, with potential for muscle wasting and poor outcomes. In a surgical population, poor nutrition impedes wound healing, and weight below the 10th percentile is a known risk factor for postoperative complications in pediatric cardiac patients [10]. 3.3. Enteral nutrition There are numerous benefits to enteral nutrition, including decreased infection rates, decreased morbidity and protection of mucosal integrity of the small intestine [11]. Initiation of EN is recommended within 24–48 hours of admission [12]. However, delivery of EN may be hindered postoperatively with ileus, delayed gastric emptying, and although controversial, high gastric residual volumes. Delivery of enteral protein reduces mortality and leads to improved outcomes. ASPEN guidelines recommend enteral nutrition as the preferred method of nutritional delivery in critically ill patients with a functioning gastrointestinal tract [6]. Early EN is feasible and leads to an improvement in the likelihood and time to adequate nutrition goals as well as lower mortality in critically ill children [13,14]. All major medical societies with nutritional guidelines recommend early initiation of EN in critically ill adults who are hemodynamically stable, and the initiation of EN within 6 hours of ICU admission is shown to be safe in both medical and surgical patients [11]. These same goals should be considered in critically ill children.
3.2. Importance of protein delivery adequacy
3.4. Barriers to EN
Average protein intake adequacy on day 7 in the PICU was significantly lower in the surgical cohort compared to the medical cohort.
Minimizing interruptions to the delivery of enteral nutrition is essential as most patients in this study experienced at least one interruption. The critical care and surgical team should strive to minimize the duration of EN delivery interruptions, and must be mindful whenever nutrition is being held. At times, this is inevitable when procedures are delayed or canceled for various reasons. Procedure delays, procedure cancelations, and technical issues with enteral feeding access, such as clogged or displaced feeding tubes, may contribute to some inevitable interruptions [15,16]. The multicenter scope of the study and remote nature of data capture at the end of each day did not allow us to document details of the reasons for EN interruptions in this study. In a previous single center study, we have described the most common reasons for EN interruptions in the PICU population that included surgical patients [16]. Interruptions because of perceived EN intolerance and preprocedural fasting were most common in this study.
Table 3 Daily recommended, prescribed and delivered protein via enteral route in the surgical PICU (N = 519). Protein (g/kg per day)
Median (IQR)
Prescribed ASPEN recommended for critical illness DRI recommended Delivered Difference between ASPEN recommended value and actual daily protein delivery
2 1.5 1.1 0.2 1.5
(1.5, 2.4) (1.5, 2.0) (0.9, 1.5) (0, 0.8) (0.9, 1.7)
ASPEN = American Society of Parenteral and Enteral Nutrition; DRI = Dietary Reference Intake 2005; PICU = pediatric intensive care unit.
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When EN interruptions are anticipated, goal daily nutrient delivery may be achieved by increasing the hourly rate of feeds to account for the interruption, and better coordination of usual scheduled breaks in the patient's enteral feeds with the scheduled procedure. In patients' with a secured airway, feeds could be continued through surgery or procedure, which is particularly true for patients fed via the postpyloric route. This issue needs further examination; and we have previously described procedural fasting as one of the leading causes of EN interruption in PICU patients [16]. Jenkins et al. have described the feasibility of perioperative feeding via a duodenal tube in pediatric and adult burn population [17]. Enteral feeds were continued throughout the surgical cases in their cohort with no increase in the rate of aspiration. On the other hand, the fasted group experienced significant caloric deficit and increased rate of wound infection. Larger, more recent studies are needed to support these findings in order to gain more widespread acceptance. If prolonged interruption is anticipated, initiation of PN may be considered in an effort to avoid macronutrient deficits. In our current study, PN was employed alone in patients that were ineligible for EN, and as a supplement to insufficient PN. The best timing for introducing supplemental PN in the PICU is not clear. A strategy of delayed PN in the first week of PICU stay, with early EN initiation, was recently reported to be superior to an early PN strategy in a randomized control trial [18]. Continuing PN through the surgical procedure is also a consideration if adequate central access is available. Algorithms for early delivery of EN have been shown to be effective in adults [19,20]. Previously, we described details of EN algorithm used in 9 PICUs [21]. Recommendations in these guidelines were highly variable and were not in agreement with national guidelines. The use of algorithms was not associated with increased energy delivery but we were not able to assess compliance of the institutions to their algorithm. A number of studies have shown a feeding algorithm may significantly reduce time to EN initiation, decrease reliance on PN as well as the time to goal rate of EN [13,22]. More studies are needed to develop and examine the role of stepwise algorithms in optimizing nutrient delivery to the surgical patients in the PICU. 4. Conclusions Preoperative malnutrition is prevalent in the critically ill pediatric surgical cohort. Energy and protein delivery is inadequate with a median delivery of less than 15% of prescribed macronutrients by pediatric intensive care unit day 7. Delayed initiation and prolonged interruptions to enteral nutrition were associated with inadequate enteral protein delivery and reliance on parenteral nutrition. There is an urgent need to prioritize adequate energy and protein delivery in surgical critically ill children. Opportunities for improving nutrient delivery may impact outcomes and therefore are important areas for future research. References [1] Mehta NM, Bechard LJ, Cahill N, et al. Nutritional practices and their relationship to clinical outcomes in critically ill children – an international multicenter cohort study*. Crit Care Med 2012;40:2204–11. http://dx.doi.org/10.1097/CCM.0b013e31824e18a8.
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