ABSTRACT
Objectives:
To assess the safety of enteral nutrition (EN) in children on extracorporeal membrane oxygenation (ECMO). To describe nutritional status and the characteristics of the nutritional support in this population.
Methods:
A retrospective single-center analysis (2006–2016) including children <18 years on ECMO. Demographic data, nutritional status, characteristics of nutritional support, and development of gastrointestinal (GI) complications were recorded.
Results:
One hundred children, with a median age of 9.7 months (interquartile range [IQR] 3.9–63.1) were enrolled. Undernutrition was prevalent among children on ECMO (33.3%) mainly in patients <2 years (P = 0.042). Most patients (64%) received EN at some point during ECMO therapy. EN was administered in the first 48 hours after ECMO initiation (48HEN) to 60.3% of the children.
Mortality rate in the Pediatric Intensive Care Unit was lower in patients who received EN as the initial artificial nutrition support (ANS) (37.7 vs 51%, P = 0.005) and in children on 48HEN (34% vs 50%, P = 0.04). In the logistic regression analysis, duration of ECMO support and low cardiac output indication were the only factors associated with mortality.
Although most patients on ECMO (45%) developed digestive complications, they were mostly mild, being constipation the most prevalent. In the logistic regression analysis, EN was not associated with an increase in GI complications (P = 0.09). Only three patients developed intestinal ischemia (one without EN and two on EN).
Conclusions:
Undernutrition is prevalent among children on ECMO, mainly in infants <2 years. EN is not associated with severe gastrointestinal complications or higher mortality in these children.
Keywords: complications, enteral nutrition, extracorporeal membrane oxygenation, nutritional support, parenteral nutrition, pediatric intensive care
What Is Known
Enteral nutrition (EN) and early enteral nutrition (EEN) are safe in adult patients on extracorporeal membrane oxygenation (ECMO) support.
Undernutrition is prevalent among pediatric patients on ECMO.
What Is New
EN and 48HEN (EN administered within the first 48 hours after ECMO initiation) are safe in pediatric patients on ECMO, as gastrointestinal complications are mostly mild.
No association was found between the use of EN and mortality.
The use of extracorporeal membrane oxygenation (ECMO) is becoming increasingly common in pediatric patients with severe respiratory or heart failure (1). Critically ill patients on ECMO support are at a high risk of developing digestive problems, since splanchnic circulation may be impaired favoring intestinal ischemia (2) and sepsis due to bacterial translocation (3).
Undernutrition is prevalent among pediatric patients on ECMO (4,5) and may have negative effects on prognosis (6–8), therefore, an adequate nutritional support is essential in these patients (5,9,10). EN support is common but not uniform among neonatal and pediatric patients receiving ECLS (11). Parenteral nutrition (PN) or late enteral nutrition (EN) is often administered to critically ill children on ECMO to prevent potential digestive complications.
Some recent studies suggest that early EN (EEN) is safe in adult patients on ECMO support (12–15), but the evidence about its safety in neonates (16) and pediatric patients (17) is scarce. Moreover, the nutritional status of these patients and the development of gastrointestinal complications associated with EN, has not been assessed in any of the studies published so far.
The primary outcome of this study was to assess the development of gastrointestinal complications and mortality associated with the use of EN, including enteral nutrition started within the first 48 hours of ECMO support, in children on ECMO. The secondary outcomes were to analyze the nutritional status and type of nutritional support including the caloric and protein intake in this population.
PATIENTS AND METHODS
A retrospective study was carried out in the Pediatric Intensive Care Unit (PICU) of a tertiary hospital between September 2006 and 2016. All patients, neonates and children <18 years receiving ECMO in the pediatric intensive care unit were previously included in a prospective registry. The registry was approved by the Gregorio Marañon Institutional Review Board. Informed consent from the parents was obtained for all the patients included in the registry. The local Ethics Committee approved also this retrospective review.
The data collected included demographic and anthropometric data, nutritional status before ECMO support, diagnosis, length of PICU stay and mortality. Other data included were the reason for indication and type of ECMO, duration of therapy and data related to artificial nutrition support (ANS): type of ANS, type of formula administered, time to initiation of ANS, route of EN administration and use of EN within the first 48 hours of ECMO support (48HEN).
Moreover, information about digestive complications (abdominal distension, gastric residual volume, constipation, diarrhea, vomits, gastrointestinal bleeding, and intestinal ischemia) was collected.
Anthropometric (weight and height/length) was registered at PICU admission and nutritional status was assessed using an online tool (https://www.seghnp.org/) certified by the Spanish Society of Pediatric Gastroenterology to calculate the following scores: weight-for-height (WH) z score for children <2 years and body mass index (BMI) z score for children >2 years. Undernutrition was defined as a z score <−2 in any of these scores and overweight was defined as a z score >2. This cut-off point was selected following the American and European guidelines (18,19).
Energy targets were calculated using Schofield equations for basal metabolic rate and protein targets were taken as the lower range of requirement for age in critically ill children (18).
The following variables were collected: caloric and protein intake at the beginning and at day 7 of EN, time to nutrition initiation (hours), time to maximum nutrition delivery (hours) and maximum caloric (kcal kg–1 d–1) and protein intake (g kg–1 d–1).
Long-term ECMO support was defined as a duration of ECMO >7 days.
High gastric residual volume was considered when gastric content was >50% the volume of enteral nutrition administered in the previous 4 hours (20). Diarrhea was defined as the presence of >8 liquid stools in infants <3 months of age, >4 liquid stools in 3−12-month-old children, and more than two liquid stools in children >12 months (20). Constipation was defined as the absence of bowel movements 72 hours after the start of EN (21). Abdominal distension was considered if abdominal circumference on the sagittal plane was increased (22). Intestinal ischemia was defined as the occurrence of clinical signs of low digestive bleeding and/or poor abdominal wall perfusion concurrent to pathological findings on ultrasound or CT scan.
Categorical variables were expressed as frequencies and percentages. Continuous variables were presented as mean and standard deviation in case of normal distribution or as median and interquartile range when the variable was not normally distributed. Comparison of categorical variables was performed using χ2 and Fisher exact test. Continuous variables were compared with Student t-test and median test for not normally distributed variables. Univariate and multivariate logistic regression models were performed to study the strength of the association with complications and mortality. As independent variables, we considered those that are clinically significant. After a first statistical evaluation, we limited the covariates to three in the complications model (ECMO duration, enteral nutrition, and high morphic dose). In the mortality model, five covariates (malnutrition, low cardiac output, ECMO duration, enteral nutrition, digestive complications) were necessary to maintain an adequate area under the receiver operator characteristic curve (area under curve = 0.85). Significance was set at a P value of <0.05. IBM SPSS Statistics 21.0 system (SPSS Inc, Chicago, USA) was used for statistical analysis.
RESULTS
During the study period, 100 critically ill children required ECMO support. Sixty-seven percent of them were male. The median age at the onset of ECMO therapy was 9.7 months (interquartile range [IQR] 3.9–63.1 months). Detailed demographic and clinical characteristics of the cohort are highlighted in Table 1.
TABLE 1.
Total group median [IQR] | Enteral nutrition, N = 64 | No enteral nutrition, N = 36 | P | |
Age (mo) | 9.7 [3.9–63.1] | 7.2 [3.6–35.4] | 22 [4.2–127] | 0.145 |
Weight (kg) | 7.3 [4.8–16.7] | 7.2[4.7–12] | 8.7 [4.8–32] | 0.532 |
Height (cm) | 69 [58–102] | 67 [57–95] | 79 [61–123] | 0.200 |
% Total group | % Enteral nutrition | % No enteral nutrition | P | |
Cardiac disease | 93% | 91% | 97% | 0.213 |
Postoperatory period | 65% | 65.6% | 63.9% | 0.515 |
Cardiac arrest | 24% | 15.6% | 38.9% | 0.014 |
Undernutrition | 33.3% | 36.2% | 28.6% | 0.615 |
Exitus | 49% | 43.8% | 58.3% | 0.120 |
ECMO = extracorporeal membrane oxygenation; IQR = interquartile range.
The most prevalent diagnosis at admission was cardiac disease (93%), followed by respiratory failure (5%) and septic shock (2%).
ECMO therapy was veno-arterial in 98% of the cases. The most frequent reasons for ECMO support were inability to wean from extracorporeal membrane oxygenation after cardiac surgery (28%) and non-postoperative low cardiac output (25%), followed by postoperative low cardiac output (17%), hypoxemia (13%), resuscitation (11%), arrhythmia (5%), and shock (1%). As many as 24% of children required ECMO in the setting of a cardiac arrest.
ECMO was performed with a centrifugal pump (Jostra Rotaflow HL20, Maquet, Germany) and hollow fiber oxygenators Quadrox-D and Quadrox-iD Pediatr (Jostra, Germany).
In 31 patients, ECMO support was necessary before PICU admission and was started in the operating room or catheterization laboratory. In the remaining 69 cases, the median time from PICU admission to ECMO therapy was 2 days (IQR 0.5–8 days). The median duration of ECMO therapy was 137.8 hours (IQR 73.9–226.1 hours) and the median length of PICU stay for survivors was 30 days (IQR 19.2–54.4 days).
The mortality rate of children requiring ECMO support was 49%. The leading cause of death was multiorganic failure (42.9%) followed by neurological complications (18.4%), adequacy of therapeutic effort (16.3%), massive bleeding (12.2%), cardiogenic shock (4.1%), arrhythmia after ECMO weaning (4.1%), and sepsis (2%). The use of EN was not associated with mortality (P = 0.43).
Nutritional Status of Children on Extracorporeal Membrane Oxygenation Support
The median weight at admission was 7.3 kg (IQR 4.8–16.7 kg) [median weight for age z score −1.4 (IQR −2.4/−0.4)]. Undernutrition was prevalent among children on ECMO at the onset of the therapy (33.3%) [median WH z score −1.9 (IQR −2.8/−0.9); median BMI z score −0.35 (IQR −1.9/0.9)] and was severe in 16% of the patients.
Undernutrition was more frequent in children <2 years as compared to older patients (P = 0.042).
Being undernourished was not associated with the development of gastrointestinal complications (P = 0.68), mortality (P = 0.51), or the need for prolonged ECMO support (P = 0.32).
Few children (5.3%) were overweight at the ECMO therapy onset. Being overweight was not associated with the development of gastrointestinal complications (P = 0.37), mortality (P = 0.89), or prolonged ECMO (P = 0.1).
Characteristics of the Artificial Nutritional Support of Children on Extracorporeal Membrane Oxygenation
At the onset of the ECMO support, 92% of patients were on intravenous fluid therapy. EN was used as the initial ANS in 45% of patients and PN in 47%. Eight percent of patients did not receive any nutritional support during ECMO therapy.
Most children (64%) received EN at some point during ECMO therapy (34% of them were on exclusive EN and 30% received supplementary PN) and 28% of patients received PN as a sole mode of nutritional support. 48HEN was administered to 60.3% of children on EN.
Mean time from ECMO onset to the initiation of EN was 46.5 ± 40 hours and mean time to achieve total EN was 1.41 ± 2.13 days (Table 2).
TABLE 2.
Enteral nutrition, N = 64, mean (SD) | Parenteral nutrition N = 28, mean (SD) | P | |
Time to nutrition initiation (h) | 46.5 (40) | 26.7 (24) | 0.220 |
Time to maximum nutrition delivery (h) | 33.8 (51.1) | 60 (57.6) | 0.097 |
Maximum caloric intake (kcal kg–1 d–1) | 53 (16) | 49 (18) | 0.311 |
Maximum protein intake (g kg–1 d–1) | 1.8 (0.85) | 1.9 (0.88) | 0.722 |
% Schofield | 92 (35) | 110 (36) | 0.08 |
ECMO = extracorporeal membrane oxygenation; SD = standard deviation.
Transpyloric tube was the preferred method for EN delivery in these patients (97%) followed by continuous nasogastric tube (3% of the children).
The formulas used were Isosource Junior in 25% of the patients, standard artificial formula in 20.3%, hypercaloric formulas (Infatrini) in 14% and breast milk administered by feeding tube in 10.9% of the patients.
The mean of the maximum caloric and protein intake administered by the enteral and parenteral route within the first week after ECMO support initiation are detailed in Table 2. There were no statistically significant differences in the maximum caloric supply (P = 0.31) nor in the maximum protein delivery (P = 0.72) between fed children compared with patients on parenteral nutrition (Table 2).
Children on EN achieved 92% of the energy target calculated using Schofield equations while children on PN received 110% of the target. There were no statistically significant differences in the caloric intake measured as percentage of Schofield achieved between enteral and parenteral nutrition.
Outcomes
Twenty-six patients (26%) died during the ECMO therapy. Seventy-four patients (74%) were able to survive to ECMO weaning but 23 of them (31%) died during PICU admission. Mean survival of these patients was 36 (SD 62) days after ECMO weaning.
Mortality rate in the PICU was lower in patients who received EN as the initial ANS as compared to PN (37.7% vs 51%, P = 0.005). 48HEN was also associated with a lower mortality rate, as compared to enteral nutrition initiated after 48 hours of ECMO support (34% vs 50%, P = 0.04).
In the logistic regression analysis, duration of ECMO support and low cardiac output were the only factors associated with mortality in the PICU. More details are summarized in Table 3.
TABLE 3.
Variable | Odds ratio | 95% CI | P |
Malnutrition | 1.99 | 0.58–6.85 | 0.273 |
Low cardiac output | 9.5 | 2.2–41.6 | 0.003 |
ECMO Duration | 1.01 | 1.003–1.013 | 0.001 |
Enteral Nutrition | 0.35 | 0.13- 0.98 | 0.044 |
Digestive complications | 1.36 | 0.49–3.81 | 0.557 |
95% CI = 95% confidence interval; CEC = extracorporeal circulation; ECMO = extracorporeal membrane oxygenation; PICU = Pediatric Intensive Care Unit.
Gastrointestinal Complications
Forty-five patients on ECMO (45%) developed digestive complications, mostly mild. The most prevalent complication was constipation in 31 patients (33%), followed by high gastric residual volume in 16 children (16.5%), abdominal distension in 13 children (13.4%), gastrointestinal bleeding in 10 patients (10.3%), and intestinal ischemia in 3 of them (5.3%). Two patients developed diarrhea and one presented with vomiting.
There was an association between the use of EN and the development of constipation [24 patients with enteral (44.4%) vs 7 without EN (17.5%); P = 0.006] and high gastric residual volume [13 (22.8%) vs 3 (7.5%) without EN; P = 0.046]. There were no statistically significant differences between the use of EN and the occurrence of other digestive complications (Table 4).
TABLE 4.
GI complication | Patients without EN | Patients with EN | P value |
Constipation | 7 (17.5%) | 24 (44.4%) | 0.006 |
High gastric residual volume | 3 (7.5%) | 13 (22.8%) | 0.046 |
Abdominal distension | 4 (9.7%) | 9 (16.1%) | 0.367 |
Gastrointestinal bleeding | 3 (7.5%) | 7 (12.3%) | 0.446 |
Intestinal ischemia | 1 (2.5%) | 2 (3.6%) | 0.755 |
Diarrhea | 0 (0%) | 2 (3.5%) | 0.226 |
Vomiting | 0 (0%) | 1 (1.8%) | 0.390 |
ECMO = extracorporeal membrane oxygenation; EN = enteral nutrition; GI = gastrointestinal.
48HEN in children on ECMO was not associated with an increase in the incidence of gastrointestinal complications (P = 0.13). Patients who developed digestive complications needed more time to reach total EN as compared to patients without gastrointestinal symptoms (P = 0.028). Gastrointestinal complications in children on ECMO receiving enteral nutrition within de first 48 hours and after 48 hours of ECMO initiation are detailed in Table 5.
TABLE 5.
GI complication | Patients with 48HEN | Patients with late EN | P |
Constipation | 13 (35.1%) | 12 (50%) | 0.249 |
High gastric residual volume | 7 (18.4%) | 6 (24%) | 0.592 |
Abdominal distension | 4 (10.8%) | 6 (24%) | 0.166 |
Digestive bleeding | 4 (10.5%) | 5 (20.8%) | 0.262 |
Intestinal ischemia | 1 (2.7%) | 1 (4.1%) | 0.754 |
Diarrhea | 2 (5.2%) | 0 (0%) | 0.244 |
Vomiting | 1 (2.7%) | 0 (0%) | 0.407 |
48HEN = enteral nutrition initiation in the first 48 hours on extracorporeal membrane oxygenation support; EN = enteral nutrition; GI = gastrointestinal.
The need for prolonged ECMO was associated with constipation (43.9% vs 24.5%; P = 0.048) but not with other types of gastrointestinal complications. Children who required muscle relaxants had also more constipation, although the differences were not statistically significant (35.9% vs 12.5%, P = 0.056).
The use of high doses of opioids did not increase the risk for gastrointestinal complications in patients on ECMO in univariate (46% vs 41%; P = 0.67) or logistic regression (95% confidence interval [CI] 0.26–2.13; P = 0.586).
Abdominal distension was more prevalent in patients who died (P = 0.033).
In the multivariable study (Table 6), the only factor affecting complications was the ECMO duration (95% CI 1.01–1.011; P = 0.023).
TABLE 6.
Variable | Odds ratio | 95% CI | P |
ECMO duration | 1.006 | 1.01–1.011 | 0.023 |
Enteral nutrition | 0.45 | 0.18–1.14 | 0.093 |
High morphic dose | 0.75 | 0.26–2.13 | 0.586 |
95% CI = 95% confidence interval; ECMO = extracorporeal membrane oxygenation.
DISCUSSION
There is scarce data about the nutritional status, characteristics of nutritional support and the development of digestive complications in pediatric patients requiring ECMO support. To our knowledge, this is the largest study that has analyzed these factors in a large cohort of critically ill children on ECMO showing that undernutrition is prevalent and that enteral nutrition may be safe and beneficial in this population. Although it is a retrospective study, it provides interesting results that should be confirmed in future prospective studies.
The primary outcome of the present study was to describe the relationship between nutrition support and complications including mortality. Our data reflects that children on ECMO receiving EN did not develop severe gastrointestinal complications or higher mortality.
Historically, EN used to be avoided in patients with shock, as splanchnic circulation can be compromised resulting in mesenteric ischemia, necrotizing enterocolitis, gastrointestinal perforation, or gastrointestinal bleeding (23); however, most patients on ECMO stabilize within a few hours and inotropes can be withdrawn being considered as stable patients who can be fed (24).
Few studies suggest that EN can be safe in adult patients on ECMO (10,13–15) even when used early (14,25–27). In the pediatric field, there is scant data, although results seem to be favorable for neonates and infants (16,17,28,29). Indeed, the use of EN at day 5 during ECMO therapy has been associated with higher survival rates at discharge, as compared to exclusive PN (30). On the other hand, a recent retrospective study reported that EEN in ECMO patients reduced in-hospital and at 28-day mortality (31). Our results are consistent with previous studies (28–30) highlighting that EN is not only safe in children on ECMO but it can also decrease mortality when it is used as the initial type of ANS. Moreover, EN initiated within the first 48 hours of ECMO onset may also be beneficial as it was associated with lower mortality but not with a higher incidence of gastrointestinal complications.
EN may be associated with gastrointestinal complications (20,32–39) but they are usually not severe (40). Mild digestive complications have been reported in adult ECMO patients on EN (abdominal distension, high gastric residual volume, diarrhea, and constipation) (13,14).
The gastrointestinal complications in pediatric patients on ECMO are scarcely described in the literature. A study conducted by Hanekamp in neonates assisted with ECMO (16) revealed that the most frequent complication was high gastric residual volume. In pediatric patients, there is only one study that has analyzed it (17), showing that abdominal distension and high gastric residual volume were the most prevalent complications.
In our study, 45% of patients developed gastrointestinal complications, mainly constipation, high gastric residual volume, and abdominal distension. High gastric residual volume and constipation were more frequent in the children who received EN. The incidence of high gastric residual volume and abdominal distension observed in our study was consistent with the one reported in previous studies (16,17), but higher than the one reported in other series of critically ill patients without ECMO (32,33). This inconsistency may be explained by the fact that ECMO patients are at a higher risk of developing gastrointestinal complications.
Our data reflects that children on ECMO receiving EN did not develop severe gastrointestinal complications or higher mortality suggesting that EN in these patients is safe and should be the preferred nutritional support if not contraindicated.
Transpyloric enteral nutrition can be useful for managing feeding intolerance in critically ill children (20,32,41–43) and can be used in patients receiving ECMO support (26,29,44,45). In our experience, transpyloric EN was used in most patients without complications. Therefore, it can be an alternative for pediatric ECMO patients with feeding intolerance.
The secondary outcome of our study was to describe the nutritional status of children on ECMO and to assess the caloric and protein delivery administered to these patients.
Our data are consistent with previous studies (5), showing that undernutrition is prevalent in pediatric patients on ECMO, especially in infants under the age of two. Therefore, close monitoring of the nutritional status of these patients and individualized nutritional support should be performed in this population.
Although undernutrition in critically ill children, and more specifically in children requiring ECMO support, has been associated with a poor prognosis (6–8), in our study, undernutrition was not associated with higher mortality or more gastrointestinal problems. Only children who needed prolonged ECMO support had more complications as reflected in the multivariable study. Nevertheless, prospective studies are needed to confirm these results.
Adequate nutritional support may contribute to improve the prognosis of critically ill children including those on ECMO (5,9). Enteral route is the preferred method to deliver artificial nutrition in PICU since it has multiple advantages (18), but due to a variety of barriers, parenteral nutrition is often employed as a sole mode of nutrient delivery or as supplementary. In our study, most children (64%) received EN at some point during ECMO therapy being the initial ANS in 45% of them. Thirty-four of the patients were on exclusive enteral nutrition and 30% received supplementary parenteral nutrition. Few patients (28%) were on exclusive PN. These results contrast with a previous report where only 44% of the children received EN at day 7 of ECMO being most of them (85%) on a combination of EN and PN (46).
In our study, mean time from ECMO onset to the initiation of ANS was 46.5 hours for EN and 26.7 hours for PN. Early administration of ANS after ECMO onset allowed patients to achieve total enteral or parenteral nutrition fast. This is an important fact as early nutrition support, may prevent cumulative and protein-energy deficit that can worsen outcomes in these populations.
Armstrong et al reported a median time of 6 days to the initiation of EN versus 1 day to the onset of PN (46). According to our results, time to ANS initiation was shorter in children on parenteral nutrition than in children on enteral nutrition reflecting the reluctance of PICU caregivers to fed children on ECMO for the risk of complications.
Energy requirements during ECMO remain unclear as the presence of more than one site of gas exchange makes indirect calorimetry technically challenging. Following the international guidelines, we estimated resting energy expenditure using the Schofield equation. In our cohort, energy delivery was similar to the target in both enteral and parenteral group and superior to previous reports (5,46). On the other hand, we did not find any differences in the maximum caloric and protein intake between the enteral and the parenteral group contrasting with previous data where PN provided the majority of calories and proteins (5).
Limitations
Our study has some limitations. First, it is a retrospective, single-center study so prospective, multicenter studies are needed to confirm our results. In addition, the influence of some factors such as the diagnosis, the severity of critical illness, and the use of vasoactive drugs on nutrition tolerance and the development of digestive complications were not assessed in this study.
CONCLUSIONS
Undernutrition is prevalent among pediatric patients on ECMO, mainly in patients under the age of two. Close monitoring of their nutritional status and individualized nutritional support may be crucial. EN, may be safe and beneficial in this population.
Footnotes
Source of Funding: This work was supported by Carlos III Health Institute (PI17/00248): Mother-Child Health and Development Network (Red SAMID)–RETICS funded by the PN I+D+I 2008–2011 (Spain), ISCIIISub-Directorate General for Research Assessment and Promotion, and the European Regional Development Fund (ERDF), ref. RD16/0022/0007.
The authors report no conflicts of interest.
REFERENCES
- 1.Rehder KJ, Turner DA, Bonadonna D, et al. Technological advances in extracorporeal membrane oxygenation for respiratory failure. Expert Rev Respir Med 2012; 6:377–384. [DOI] [PubMed] [Google Scholar]
- 2.Koning NJ, Vonk ABA, Van Barneveld LJ, et al. Pulsatile flow during cardiopulmonary bypass preserves postoperative microcirculatory perfusion irrespective of systemic hemodynamics. J Appl Physiol 2012; 112:1727–1734. [DOI] [PubMed] [Google Scholar]
- 3.Kurundkar AR, Killingsworth CR, McIlwain RB, et al. Extracorporeal membrane oxygenation causes loss of intestinal epithelial barrier in the newborn piglet. Pediatr Res 2010; 68:128–133. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.De Souza Menezes F, Leite HP, Koch Nogueira PC. Malnutrition as an independent predictor of clinical outcome in critically illchildren. Nutrition 2012; 28:267–270. [DOI] [PubMed] [Google Scholar]
- 5.Ong C, Mok YH, Tan ZH, et al. Nutritional practices and adequacy in children supported on extracorporeal membrane oxygenation. Clin Nutr ESPEN 2018; 26:21–26. [DOI] [PubMed] [Google Scholar]
- 6.Anton-Martin P, Papacostas M, Lee E, et al. Underweight status is an independent predictor of in-hospital mortality in pediatric patients on extracorporeal membrane oxygenation. J Parenter Enter Nutr 2018; 42:104–111. [DOI] [PubMed] [Google Scholar]
- 7.Costa CAD, Tonial CT, Garcia PCR. Association between nutritional status and outcomes in critically-ill pediatric patients – a systematic review. J Pediatr (Rio J) 2016; 92:223–229. [DOI] [PubMed] [Google Scholar]
- 8.Chen MY, Yang YJ. Being underweight is an independent risk factor for poor outcomes among acutely critically ill children. Nutr Clin Pract 2018; 33:433–438. [DOI] [PubMed] [Google Scholar]
- 9.Farr BJ, Rice-Townsend SE, Mehta NM. Nutrition support during pediatric extracorporeal membrane oxygenation. Nutr Clin Pract 2018; 33:747–753. [DOI] [PubMed] [Google Scholar]
- 10.Lu MC, Yang MD, Li PC, et al. Effects of nutritional intervention on the survival of patients with cardiopulmonary failure undergoing extracorporeal membrane oxygenation therapy. In Vivo (Brooklyn) 2018; 32:829–834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Desmarais TJ, Yan Y, Keller MS, et al. Enteral nutrition in neonatal and pediatric extracorporeal life support: a survey of current practice. J Pediatr Surg 2015; 50:60–63. [DOI] [PubMed] [Google Scholar]
- 12.Bear DE, Smith E, Barrett NA. Nutrition support in adult patients receiving extracorporeal membrane oxygenation. Nutr Clin Pract 2018; 33:738–746. [DOI] [PubMed] [Google Scholar]
- 13.Umezawa Makikado LD, Flordelís Lasierra JL, Pérez-Vela JL, et al. Early enteral nutrition in adults receiving venoarterial extracorporeal membrane oxygenation: an observational case series. J Parenter Enter Nutr 2013; 37:281–284. [DOI] [PubMed] [Google Scholar]
- 14.Ferrie S, Herkes R, Forrest P. Nutrition support during extracorporeal membrane oxygenation (ECMO) in adults: a retrospective audit of 86 patients. Intensive Care Med 2013; 39:1989–1994. [DOI] [PubMed] [Google Scholar]
- 15.Keith Scott L, Boudreaux K, Thaljeh F, et al. Early enteral feedings in adults receiving venovenous extracorporeal membrane oxygenation. J Parenter Enter Nutr 2004; 28:295–300. [DOI] [PubMed] [Google Scholar]
- 16.Hanekamp MN, Spoel M, Sharman-Koendjbiharie I, et al. Routine enteral nutrition in neonates on extracorporeal membrane oxygenation. Pediatr Crit Care Med 2005; 6:275–279. [DOI] [PubMed] [Google Scholar]
- 17.Pettignano R, Heard M, Davis R, et al. Total enteral nutrition versus total parenteral nutrition during pediatric extracorporeal membrane oxygenation. Crit Care Med 1998; 26:358–363. [DOI] [PubMed] [Google Scholar]
- 18.Mehta NM, Skillman HE, Irving SY, et al. Guidelines for the provision and assessment of nutrition support therapy in the pediatric critically ill patient: Society of Critical Care Medicine and American Society for Parenteral and Enteral Nutrition. Pediatr Crit Care Med 2017; 18:675–715. [DOI] [PubMed] [Google Scholar]
- 19.Tume LN, Valla FV, Joosten K, et al. Nutritional support for children during critical illness: European Society of Pediatric and Neonatal Intensive Care (ESPNIC) metabolism, endocrine and nutrition section position statement and clinical recommendations. Intensive Care Med 2020; 46:411–425. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Santiago Lozano MJ, Alonso Álvarez C, Álvarez Heidbüchel C, et al. Nutrition in children with continuous renal replacement therapy. An Pediatr 2020; 92:208–214. [DOI] [PubMed] [Google Scholar]
- 21.López J, Botrán M, García A, et al. Constipation in the critically ill child: frequency and related factors. J Pediatr 2015; 167:857.e1–861.e1. [DOI] [PubMed] [Google Scholar]
- 22.López J. Complicaciones digestivas en el niño críticamente enfermo. 2019; Manual de Cuidados Intensivos Pediátricos, Madrid: Publimed, p. 378. [Google Scholar]
- 23.Singer P, Berger MM, Van den Berghe G, et al. ESPEN guidelines on parenteral nutrition: intensive care. Clin Nutr 2009; 28:387–400. [DOI] [PubMed] [Google Scholar]
- 24.Brown G, Moynihan KM, Deatrick KB, et al. Extracorporeal Life Support Organization (ELSO): guidelines for pediatric cardiac failure. ASAIO J 2021; 67:463–475. [DOI] [PubMed] [Google Scholar]
- 25.Ridley EJ, Davies AR, Robins EJ, et al. Nutrition therapy in adult patients receiving extracorporeal membrane oxygenation: a prospective, multicentre, observational study. Crit Care Resusc 2015; 17:183–189. [PubMed] [Google Scholar]
- 26.MacGowan L, Smith E, Elliott-Hammond C, et al. Adequacy of nutrition support during extracorporeal membrane oxygenation. Clin Nutr 2019; 38:324–331. [DOI] [PubMed] [Google Scholar]
- 27.Davis RC, Durham LA, Kiraly L, et al. Safety, tolerability, and outcomes of enteral nutrition in extracorporeal membrane oxygenation. Nutr Clin Pract 2020; 0:1–7. [DOI] [PubMed] [Google Scholar]
- 28.Wertheim HFL, Albers MJIJ, Piena-Spoel M, et al. The incidence of septic complications in newborns on extracorporeal membrane oxygenation is not affected by feeding route. J Pediatr Surg 2001; 36:1485–1489. [DOI] [PubMed] [Google Scholar]
- 29.Piena M, Albers MJIJ, Haard PMM Van, et al. Introduction of enteral feeding in neonates on extracorporeal membrane oxygenation after evaluation of intestinal permeability changes. J Pediatr Surg 1998; 33:30–34. [DOI] [PubMed] [Google Scholar]
- 30.Greathouse KC, Sakellaris KT, Tumin D, et al. Impact of early initiation of enteral nutrition on survival during pediatric extracorporeal membrane oxygenation. J Parenter Enter Nutr 2018; 42:205–211. [DOI] [PubMed] [Google Scholar]
- 31.Ohbe H, Jo T, Yamana H, et al. Early enteral nutrition for cardiogenic or obstructive shock requiring venoarterial extracorporeal membrane oxygenation: a nationwide inpatient database study. Intensive Care Med 2018; 44:1258–1265. [DOI] [PubMed] [Google Scholar]
- 32.López-Herce J, Santiago MJ, Sánchez C, et al. Risk factors for gastrointestinal complications in critically ill children with transpyloric enteral nutrition. Eur J Clin Nutr 2008; 62:395–400. [DOI] [PubMed] [Google Scholar]
- 33.Pérez-Navero JL, Dorao Martínez-Romillo P, López-Herce Cid J, et al. Artificial nutrition in pediatric intensive care units. An Pediatr 2005; 62:105–112. [DOI] [PubMed] [Google Scholar]
- 34.López-Herce J. Gastrointestinal complications in critically ill patients: what differs between adults and children? Curr Opin Clin Nutr Metab Care 2009; 12:180–185. [DOI] [PubMed] [Google Scholar]
- 35.Montejo González JC, Montiel BE. Complicaciones gastrointestinales en el paciente crítico [Gastrointestinal complications in critically ill patients]. Nutr Hosp 2007; 22: (Suppl 2): 56–62. [PubMed] [Google Scholar]
- 36.Mutlu G, Mutlu E, Factor P. GI complications in patients receiving mechanical ventilation. Chest 2001; 119:1222–1241. [DOI] [PubMed] [Google Scholar]
- 37.Mentec H, Dupont H, Bocchetti M, et al. Upper digestive intolerance during enteral nutrition in critically ill patients: frequency, risk factors, and complications. Crit Care Med 2001; 29:1955–1961. [DOI] [PubMed] [Google Scholar]
- 38.Reintam A, Parm P, Kitus R, et al. Gastrointestinal symptoms in intensive care patients. Acta Anaesthesiol Scand 2009; 53:318–324. [DOI] [PubMed] [Google Scholar]
- 39.Ho KM, Dobb GJ, Webb SAR. A comparison of early gastric and post-pyloric feeding in critically ill patients: a meta-analysis. Intensive Care Med 2006; 32:639–649. [DOI] [PubMed] [Google Scholar]
- 40.Solana MJ, Manrique G, Fernández R, et al. Nutritional status and nutrition support in critically ill children in Spain: results of a multicentric study. Nutrition 2021; 84:110993. [DOI] [PubMed] [Google Scholar]
- 41.Sánchez C, López-Herce J, Carrillo A, et al. Early transpyloric enteral nutrition in critically ill children. Nutrition 2007; 23:16–22. [DOI] [PubMed] [Google Scholar]
- 42.López-Herce J, Mencía S, Sánchez C, et al. Postpyloric enteral nutrition in the critically ill child with shock: a prospective observational study. Nutr J 2008; 7:6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Solana MJ, López-Herce J, López J. Feed intolerance and postpyloric feeding in the critically ill child. Pediatr Med 2020; 3:19–119. [Google Scholar]
- 44.Bear D, Haslam J, Camporota L, et al. An international survey of nutrition practices in adult patients receiving veno-venous ECMO. Intensive Care Med Exp 2015; 3:A295. [Google Scholar]
- 45.Lukas G, Hilton AK, Health A, et al. Nutritional support in adult patients receiving extracorporeal membrane oxygenation. Crit Care Resusc 2010; 12:230–234. [PubMed] [Google Scholar]
- 46.Armstrong LB, Ariagno K, Smallwood CD, et al. Nutrition delivery during pediatric extracorporeal membrane oxygenation therapy. J Parenter Enter Nutr 2018; 42:1133–1138. [DOI] [PubMed] [Google Scholar]