|Year : 2020 | Volume
| Issue : 4 | Page : 261-265
Clinical outcome of enteral nutrition versus IV fluids in newborns on inotropes: A randomized study
Yashwant Kumar Rao1, Rachit Saxena1, Tanu Midha2, Neeraj Rao1, Vivek Saxena3
1 Department of Paediatrics, GSVM Medical College, Kanpur, Uttar Pradesh, India
2 Department of Preventive and Social Medicine Government Medical College, Kannauj, Uttar Pradesh, India
3 Department of Pediatrics, Vatsalya Hospital, Kanpur, Uttar Pradesh, India
|Date of Submission||22-Apr-2020|
|Date of Decision||10-Jul-2020|
|Date of Acceptance||10-Jul-2020|
|Date of Web Publication||01-Oct-2020|
Yashwant Kumar Rao
Department of Paediatrics, GSVM Medical College, Swaroop Nagar, Kanpur - 208 002, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Benefits of early enteral nutrition in neonates are well established, but the effects of enteral nutrition in neonates with inotropic support for hemodynamic instability are not well studied. A study was planned to compare the clinical outcome in terms of morbidity, mortality, and hospital stay in the neonates with enteral feed versus intravenous (IV) fluid group with inotropes and to evaluate the safety of enteral nutrition in neonates with inotropic support as well as to determine the cutoff levels of the inotropes at which enteral feed is well tolerated. Methods: A randomized control trial was conducted in a tertiary care neonatal intensive care unit, Kanpur, and included 200 neonates on inotropes who were allotted randomly 100 each in enteral feed and IV fluid group. Results: Demographic characteristics were comparable in both the groups, mean gestational age being 36.09 ± 0.4 weeks and 35.96 ± 0.3 weeks, and mean weight on admission being 2321.60 ± 73.9 g and 2214.30 ± 53.1 g for the enteral feed group and IV fluid group, respectively. In enterally fed neonates, 88.3% were discharged and 11.7% were expired, while in the IV fluid group, 69.6% were discharged and 30.4% were expired. There was a significant difference in the mean duration of hospital stay (13.4 ± 5.0 days and 15.5 ± 5.1 days in enteral feed and IV fluid group, respectively). No complications were observed in 88.2% of enterally fed neonates versus 93.5% of neonates in the IV fluid group. There was no significant difference between complications in two groups (P = 0.245). When receiver operating characteristic(ROC) curve analysis was done to find out the cutoff level of inotropes to predict feed tolerance, at cutoff level of dopamine 10 μ/kg/min + dobutamine 7.5 μ/kg/min, the sensitivity and specificity to predict feed tolerance were found to be 61.5% and 77%, respectively.Conclusions: Enteral nutrition in neonates with inotropic support is associated with shorter duration of hospital stay and better survival rate. Neonates can tolerate enteral feed up to dopamine 10 μ/kg/min and dobutamine 7.5 μ/kg/min.
Keywords: Enteral nutrition, inotrope, neonatal shock
|How to cite this article:|
Rao YK, Saxena R, Midha T, Rao N, Saxena V. Clinical outcome of enteral nutrition versus IV fluids in newborns on inotropes: A randomized study. J Clin Neonatol 2020;9:261-5
|How to cite this URL:|
Rao YK, Saxena R, Midha T, Rao N, Saxena V. Clinical outcome of enteral nutrition versus IV fluids in newborns on inotropes: A randomized study. J Clin Neonatol [serial online] 2020 [cited 2021 Jan 28];9:261-5. Available from: https://www.jcnonweb.com/text.asp?2020/9/4/261/297002
| Introduction|| |
Malnutrition has been associated with poor clinical outcomes, particularly in the developing nations where the prevalence of malnutrition is high and the disease process makes the situation worse; thus, nutritional support is of at most importance and should be initiated as early as possible. In patients with a functional gut, enteral route should always be preferred, as the evidence suggests that critically ill patients on parenteral nutrition had longer duration of stay, greater chances of sepsis and complications associated with luminal starvation including mucosal thinning, flattening of villi and bacterial translocation. Secondly, high price for parenteral nutrition makes it unaffordable. On the other hand, favorable effects of enteral nutrition include better substrate utilization and early establishment of gut flora along with numerous advantages of breast milk.
Therefore, feeding in newborns should be started as soon as possible. The lack of systematic research and clinical trials on various aspects of enteral feeding in the newborns on inotropes makes it challenging to compile evidence-based practice guidelines, thus making it a topic of special interest.
| Methods|| |
A pilot study was conducted with 20 newborns on inotropes with 10 patients each allocated randomly in enteral feed and intravenous (IV) fluid group. The results were analyzed, and mortality of the group on enteral feed was found to be 2 (20%) while that in the group on IV fluid was 4 (40%) (P = 0.952).
Applying the formula for calculation of sample size for difference between two proportions (at level of significance = 5%, power = 80%, type of test = two sided) on the above data, the minimum sample size for the study was calculated to be 78 in each group. The minimum sample size for the study was calculated at 78 in each group. Taking in account the loss of follow-up occurring during the study at approximately 20%, the study was planned to be started with 100 patients in each group. The study was approved by the Institutional Ethical Committee, GSVM Medical College, Kanpur.
After taking detailed history and thorough clinical examination, patients with signs of decreased perfusion/shock (lethargic or comatose/hypothermic or temperature instability/respiratory distress/tachypnea or apnea/pallor, mottled, cyanosed color/limp or increased tone/convulsions/tachycardia or bradycardia/capillary refill time ≥3 s/low or poor pulse volume/low mean blood pressure/decreased oxygen saturation/decreased urine output) were identified. The inclusion criteria for the study were fluid nonresponsive shock, whereas the exclusion criteria were associated with comorbid conditions of gastrointestinal tract (GIT), birth weight <1000 g, or gestation age <28 weeks.
Volume resuscitation was done using NS bolus 10 ml/kg up to a maximum of 60 ml/kg as per the requirement with continuous monitoring of the signs of fluid overload. Thereafter, reassessment of the hemodynamic status of the newborn was done and if shock was non-responsive to fluids, the newborn was included in the study [Figure 1].
|Figure 1: Flow of participants through each stage of a randomized trial (CONSORT)|
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Written consent was taken from the parents/guardians of both the groups included in the study.
This was a single-blinded study as neither the patient nor the participants' attendant knew which group they had been allotted in the study. The newborn was randomly assigned (using computer-generated block randomization list) into one of the two study groups by the investigator; the particulars were then recorded in a predesigned pro forma. The patient was put into one of the typical clinical scenarios of shock in the neonates and was continuously assessed for the requirement to upgrade the inotropes. Once the patient maintained a stable circulation for 6 h, the tube feeding was started in the enteral group using expressed breast milk. Expressed breast milk was used for feeding in all babies as per the guideline.
The initial volume was administered for at least 24 h prior to any increase. The guidelines were individualized based on the infant's clinical status, birth weight, and gestational age. Once feeding volume has reached approximately 80 mL/kg/day, infants weighing <1250 g were fed at intervals of every 2 h or 3 h, as opposed to every 4 h. Feed volumes were advanced more rapidly than the above guidelines once the tolerance of >100 mL/kg/day was established but did not exceed increments of 15 mL/kg every 12 h in most infants weighing <1500 g. The recommended volume goal for feedings was 140–160 mL/kg/day. The newborns in the IV fluid group were not given any feed.
Both the groups were monitored (follow-up) continuously for worsening hemodynamic status; inotropes were tapered slowly over 6–12 h once newborn maintained a stable circulation. Signs of feed intolerance (abdominal distension >2 cm/vomiting/blood-stained residues/residual feed >50%) and other complications were looked for.
The patients were closely monitored till one of the predefined outcomes was met (discharged/death/discharged on personal request/left against medical advice).
Data was compiled and analyzed using SPSS 20.0 (IBM. SPSS Statistics for Windows, Armonk, NY: IBM Corp). Categorical variables were analyzed using percentages and Chi Square test and quantitative variables were analyzed using mean, standard deviation and Student's t- test. Receiver operating characteristic (ROC) curve analysis was done in the enteral group only to find out the cutoff dose of inotropes to predict feed intolerance.
| Results|| |
In the present study, both the groups had no significant difference on the baseline characteristics such as gestational age, sex distribution, weight on admission, and other clinical scenarios (P > 0.05). In the enteral feed group, 32 (32%) neonates were very low/low birth weight in immediate postnatal period, 47 (47%) had perinatal depression, 18 (18%) had septic shock, and 3 (3%) had heart disease. In the IV fluid group, 26 (26%) neonates were very low/low birth weight in immediate postnatal period, 62 (62%) had perinatal depression, 9 (9%) had septic shock, and 3 (3%) had heart disease. The distribution was uniform with no significant difference and P = 0.13 [Table 1].
The discharge rate was significantly higher in the enteral feed group as compared to IV fluid group (P < 0.001), whereas the mortality in the IV fluid group was significantly higher than that in the enteral group (P = 0.002) [Table 2].
|Table 2: Clinical Outcome in terms of mortality, morbidity and duration of stay in the Enteral Feed and IV Fluid group|
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There was a significant difference in the mean duration of hospital stay among the two groups (13.4 ± 5 days and 15.5 ± 5.1 days in the enteral feed group and IV fluids, respectively; P = 0.013).
No complication was observed in 83 (88.2%) neonates of the enteral feed group and 86 (93.5%) neonates of the IV fluid group, whereas 7 (7.5%) enterally fed neonates reported minor problems such as vomiting/feed intolerance/abdominal distension against 2 (2.2%) neonates of the IV fluid group. Necrotizing enterocolitis developed in 4.3% and 4.4% neonates of the enteral feed and IV fluid group, respectively. Statistical analysis showed no significant difference in the complications among two groups (P = 0.245).
[Table 3] depicts the relationship between the dosages of various inotropes and feed tolerance by the neonates at the respective inotrope infusion dose level. ROC curve analysis was done to find out the cutoff level of inotropes to predict feed tolerance [Figure 2]. Area under the curve was 0.763. At a cutoff level of dopamine 10 μ/kg/min + dobutamine 7.5 μ/kg/min, sensitivity and specificity to predict feed tolerance were 61.5% and 77%, respectively. Therefore, it can be said that neonates can tolerate enteral feed up to dopamine 10 μ/kg/min and dobutamine 7.5 μ/kg/min.
| Discussion|| |
This is the pioneer randomized controlled trial in the newborns in this field. Similar studies have been carried out in adults and have yielded favorable results. The studies conducted on adults have to undergo extrapolative research and analysis before its data could be applied to the neonatal population, thus making it a topic of special interest.
In the present study, the association between inotropes and feed tolerance was found to be statistically significant, concluding that enteral feed can be given safely in hemodynamically unstable patients on inotropes. This was similar to the findings in adults reported by Revelly et al. who concluded that introduction of enteral nutrition in these postoperative patients increased cardiac index and splanchnic blood flow, while the metabolic response indicated that nutrients were utilized. These preliminary results suggest that the hemodynamic response to early enteral nutrition may be adequate after cardiac surgery even in patients requiring inotropes.
Yang et al. gave an evidence-based review and practical advice on early enteral nutrition in critically ill patients with hemodynamic instability. They stated that early enteral nutrition is able to safely restore splanchnic perfusion/oxygenation in hemodynamically unstable patients; the consensus is that inotropes are not a contraindication in carefully monitored early enteral nutrition.
In the present study, in cases given dopamine at 5 μ/kg/min, 30 (96.6%) showed feed tolerance and 1 (3.4%) showed no tolerance to feeds. Among cases requiring dopamine at 10 μ/kg/min, 14 (82.4%) showed feed tolerance and 3 (17.6%) showed no tolerance to feeds. The cases requiring both dopamine 10 μ/kg/min and dobutamine 5 μ/kg/min showed tolerance to feed in 12 (75%)cases, while 4 (25%) cases showed feed intolerance. Among the cases given dopamine at 10 μ/kg/min and dobutamine at 10 μ/kg/min, 14 (66.6%) showed tolerance to feed, while 7 (33.3%) showed feed intolerance. Of patients given both dopamine at 10 μ/kg/min and dobutamine at 15 μ/kg/min, 2 (50%) were tolerant and 2 (50%) were intolerant to feed. On a combination of both dopamine/dobutamine and adrenaline (0.01–0.03 mg/kg/min), only 1 (12.5%) case showed feed tolerance and 7 (87.5%) cases were intolerant to feed. The association between dosage of inotropes and feed tolerance was found to be statistically significant. This was in concordance with the findings of Mancl et al. (2013) who, in an urban medical academic center under multidisciplinary team, observed that enteral nutrition is relatively well tolerated in patients receiving inotropes. Tolerability was less likely in patients receiving higher dose of inotropes or the combination of two inotropes.
In our study, we found that among patients allotted to enteral feed and IV fluid group, 83 (88.3%) were discharged successfully and 11 (11.7%) patients expired in enteral feeding, while 64 (69.6%) were discharged successfully and 28 (30.4%) patients expired on IV fluids, indicating that fluid group had significantly higher mortality than that in the enteral group (P = 0.002). This was similar to the findings of Imran Khalid et al. who observed that hospital mortality was lower in the early enteral nutrition group in adults. The beneficial effect of early enteral feeding was more evident in the sickest of the patients, that is, those treated with multiple inotropes
Hadfield et al. preferred the use of enteral nutrition over TPN. They reported that the use of total parenteral nutrition (TPN) in the critically ill may be associated with the translocation of bacteria and their products from the lumen of the GIT to the systemic circulation. This study demonstrated that GIT dysfunction is evident in critically ill patients and suggests that loss of GIT mucosal integrity is reversed by the institution of EN.
Our findings are similar to the study of Zaloga et al. who advocated the initiation of enteral feeding at low rates even if the patient requires continued inotropes/inotropic support. They concluded that enteral nutrition restores splanchnic perfusion and oxygenation in the hemodynamically unstable patients and in cases receiving inotropes/inotropic support.
In our study, we found that in the group on enteral feed, 83 (88.30%) cases had no complications as compared to 86 (93.47%) cases in the group on iv fluids. Around 7 (7.45%) cases reported minor problems as vomiting/feed intolerance/abdominal distension against 2 (2.18%) cases in the IV fluid group. Around 4% of the patients in both the groups (4.25% in enteral feed group and 4.35% in IV group) had necrotising enterocolitis. Wells et al. reviewed the effects of inotropes on gastrointestinal blood flow, discussed complications associated with inotrope use during enteral nutrition, and proposed important considerations to determine the safety of EN in hemodynamically unstable patients requiring inotrope support. They concluded that bowel necrosis is a rare complication that has been most often described in patients receiving enteral nutrition. Although studies regarding the effects of inotropes on gut perfusion yield inconsistent results, there have been very few documented cases of concomitant enteral nutrition and inotropes use, leading to bowel necrosis. Therefore, in the majority of intensive care unit patients, administration of enteral nutrition into the stomach during the provision of low, stable doses of inotropes with close monitoring for signs of intolerance or worsening hemodynamic stability poses very little risk for bowel necrosis.
One limitation of the study is that the cases on IV fluids were not given TPN because affordability of TPN is very low. A multicentric study with larger number of patients in each subgroup would help improve generalizability.
| Conclusion|| |
Therefore, we conclude that enteral feeding is well tolerated in neonates and poses no major risk. The mortality was less in the enteral feed group and the mean duration of stay was shorter as compared to the IV fluid group.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]