- Email: [email protected]
Intravenous Fluids versus Gastric-Tube Feeding in Hospitalized Infants with Viral Bronchiolitis: A Randomized, Prospective Pilot Study
Intravenous Fluids versus Gastric-Tube Feeding in Hospitalized Infants with Viral Bronchiolitis: A Randomized, Prospective Pilot Study Amir Kugelman, MD1, Karine Raibin, MD1, Husein Dabbah, MD2, Irina Chistyakov, MD1, Isaac Srugo, MD1, Lea Even, MD2, Nurit Bzezinsky, RN1, and Arieh Riskin, MD1 The American Academy of Pediatrics recommends intravenous fluids for infants with bronchiolitis who are unable to sustain oral feedings. Our randomized, prospective pilot study shows that gastric tube feeding (in 31 infants) is feasible and demonstrated comparable clinical outcomes with intravenous fluids (in 20 infants) among hospitalized infants #6 months of age with moderate bronchiolitis. (J Pediatr 2013;162:640-2).
I
nfants with viral bronchiolitis often are hospitalized for respiratory monitoring and supportive care. Infants with respiratory difficulty may be at increased risk of aspiration of feedings into the lungs.1 According to the American Academy of Pediatrics guidelines,2 children who have difficulty feeding safely because of respiratory distress should be given intravenous (IV) fluids. However, there are other approaches. In a large Scottish study on viral bronchiolitis,3 none of the infants received IV fluids and no complications related to nasogastric (NG) feeds were reported. NG tubes also were reported as the common mode of feeding in infants admitted with bronchiolitis in The Netherlands.4 Although the American Academy of Pediatrics recommends IV fluids for infants unable to sustain oral feedings, no study has evaluated the preferred method for nutritional and fluid support in these infants. Our study hypothesis was that better and more physiologic nutrition could be achieved by gastric tube (GT) feeding of breast milk or infant’s formula as opposed to the administration of clear IV fluids, which may, in turn, enhance recovery of infants with bronchiolitis. The aim of our study was to compare the clinical outcomes associated with GT feeding versus IV fluids among moderately ill infants hospitalized with acute viral bronchiolitis.
Methods This was a prospective, open, randomized, controlled clinical pilot study. The study was approved by the institutional review boards of the authors’ hospitals. All parents signed an informed consent. The trial is registered with ClinicalTrials. gov (NCT01189149). If the infant was not able to sustain oral feedings, the mode of fluid/nutritional support was randomly assigned as IV fluids (glucose 5%, NaCl 0.33%, and potassium supplementation) or NG/orogastric tube (5F) feeding (of breast milk or
infant formula). Both groups were allowed comfort nonnutritive sucking. Inclusion criteria were age <6 months, hospitalized with the clinical diagnosis of “moderate bronchiolitis,” and unable to sustain oral feeding. Infants with “moderate bronchiolitis” were defined as infants who could not sustain oral feedings but had no signs of severe respiratory distress or of impending respiratory failure. Criteria for not sustaining oral feeding were respiratory rate >60 breaths/min, supplemental O2 requirement, and difficulties in eating.2,3,5,6 Supplemental O2 was administered when the pulse oximetry O2 saturation (SpO2) was <93% in room air, respiratory rate was >60 breaths/min, or there were difficulties with breathing and feedings.5,6 Exclusion or study termination criteria were severe respiratory distress and signs of impending respiratory failure defined by clinical assessment (severe retractions, significant apnea or apathy), poor ventilation (single blood gas measurement with PCO2 >50 mm Hg and pH <7.25 or evidence of CO2 retention with PCO2 >45 mm Hg and pH <7.3 in repeat blood gas samples), or poor oxygenation (fraction of inspired O2 >0.4 with SpO2 <91%). The primary outcome measures were the duration of supplemental O2 (criteria to stop O2 were stable clinical situation for $4 hours with SpO2 >93% and tolerance of oral feeds) and length of stay (actual and theoretical [no or only mild retractions, able to tolerate oral feeds, no need for O2 for $10 hours]). Statistical Analyses We performed an “intention-to-treat” analysis. We estimated that there would be a >80% chance of detecting a 30% difference between the groups (a < 0.05) with a sample
From the 1Department of Pediatrics, Bnai Zion Medical Center, The B&R Rappaport Faculty of Medicine, Technion, Haifa, Israel; and 2Department of Pediatrics, Western Galilee Hospital, Nahariya, Faculty of Medicine, Bar-Ilan University, Galilee, Israel The authors declare no conflicts of interest.
GT IV NG SpO2
Gastric tube Intravenous Nasogastric Pulse oximetry O2 saturation
Trial is registered with ClinicalTrials.gov: NCT01189149. Portions of this study were presented at the Society of Pediatric Research Meeting in Boston, Massachusetts, April 28-May 1, 2012. 0022-3476/$ - see front matter. Copyright ª 2013 Mosby Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2012.10.057
640
Vol. 162, No. 3 March 2013
Figure. Infant enrollment in the study.
size of 25 patients for each mode of treatment based on our previous data.5 Two-sample unpaired t tests (Student t) were used for continuous variables with normal distribution, and Wilcoxon rank sum test was used where distribution was skewed. Differences for categorical variables were tested by use of c2 analysis. For all tests the level of significance was set at P < .05. Data are presented as mean SD or median (range). Statistical analysis was performed using Minitab version 12.23 (State College, Pennsylvania) and SigmaStat version 2.03 (Chicago, Illinois) software.
Results Study enrollment is described in the Figure. Of the 124 eligible infants, 73 were not included because of technical constraints (mostly related to heavy provider work load during winter). Finally, 31 infants were assigned to GT feeding and 20 infants to IV fluids. Three infants were switched from GT feeding to IV fluids (due to vomiting) and 2 infants were switched from IV to GT feedings (one because of failure to gain IV access and the other because of fluid extravasation into the tissue). The 2 groups differed only in the duration of illness before hospitalization, which was longer in those who received IV fluids (Table I). Both groups were comparable in disease severity at study enrollment (Table II; available at www. jpeds.com). There was no difference between the IV and GT feeding groups in the duration of supplemental O2 administration (53 59 vs 56 59 hours; P = .95), length of stay (actual 98 48 vs 119 55 hours; P = .12; theoretical 81 55 vs 92 51 hours; P = .28), time to resume full oral feeding (46 39 vs 58 44 hours; P = .18), or medications used during the hospitalization. No events of clinical aspiration were recorded. GT feeding was not associated with worsening of any measure of respiratory status of the infants.
Discussion Our pilot study showed that GT feeding is feasible and has comparable clinical outcomes with IV fluid adminis-
tration among hospitalized infants with moderate viral bronchiolitis. The theoretical advantages of IV fluids during bronchiolitis are ease on breathing and no risk of aspiration.1 The main disadvantage of IV fluids is the creation of a catabolic state (ie, decreased calorie intake with no provision of protein or lipids despite increased metabolic demands during infection and respiratory distress related to bronchiolitis).7,8 Currently, total parenteral nutrition is not the standard of care for inpatients with bronchiolitis. GT feeding may allow a better and more physiologic nutrition, including Table I. Demographic characteristics of study subjects Cohort IV feeding (n = 20)
GT feeding (n = 31)
P
Age, mo Weight, kg Male/female, n Gestation age at birth, wk Term/preterm, n* Perinatal morbidity, n
2.6 1.2 5.4 1.4 14/6 38.0 2.7
2.1 1.1 5.0 1.2 24/7 38.0 1.5
.18 .30 .79 .63
Background illness, n
1 (Gastroesophageal reflux) 2
Known asthma or atopy in family, n Smoking in close contacts, n Bronchiolitis data, n RSV positive RSV negative Unknown RSV status Duration of illness before hospitalization, d Medications before admission, n Medications during hospitalization, n† Pneumonia, n
18/2 1 (Perianal abscess)
26/5 2 (Transient tachypnea of the newborn) 0
.69 1.00
2
.64
2
1
.55
15 3 2 4.4 2.7
26 4 1 3.5 2.7
.48 1.00 .55 .04
8
7
.21
18
26
.69
4
7
1.00
.39
RSV, respiratory syncytial virus. Values given as n or mean SD. *Preterm <37 weeks’ gestational age. †Mostly hypertonic saline with inhaled bronchodilators.
641
THE JOURNAL OF PEDIATRICS
www.jpeds.com
provision of expressed breast milk. Better nutrition in critically ill patients was shown to enhance recovery9 and improve nitrogen balance in patients in intensive care units.7 While planning a larger study, we had only a small number of participants because of technical constraints, related to the heavy work load in the emergency department during the respiratory syncytial virus season. Thus, our study serves only as a pilot study. The mode of support assignment could not be blinded to the medical team. Use of objective criteria and management protocols reduced the possibility of a bias related to nonblinding. We conclude that GT feeding is feasible and has comparable clinical outcomes with IV fluid administration among hospitalized infants with moderate viral bronchiolitis. GT feeding was not associated with clinical aspiration events or with any worsening of the infants’ respiratory status. Larger trials are warranted before it can be concluded that GT feeding is an optional treatment in infants with moderate bronchiolitis. n
Submitted for publication Jul 7, 2012; last revision received Sep 4, 2012; accepted Oct 26, 2012. Reprint requests: Amir Kugelman, MD, Bnai Zion Medical Center, Pediatric Pulmonary Unit and Department of Pediatrics, 47 Golomb Street, Haifa, 31048, Israel. E-mail: [email protected], [email protected]
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Vol. 162, No. 3
References 1. Khoshoo V, Edell D. Previously healthy infants may have increased risk of aspiration during respiratory syncytial viral bronchiolitis. Pediatrics 1999; 104:1389-90. 2. American Academy of Pediatrics. Diagnosis and management of bronchiolitis. Pediatrics 2006;118:1774-93. 3. Unger S, Cunningham S. Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis. Pediatrics 2008;121:470-5. 4. Brand PL, Vaessen-Verberne AA. Differences in management of bronchiolitis between hospitals in The Netherlands. Dutch Paediatric Respiratory Society. Eur J Padiatr 2000;159:343-7. 5. Bar A, Srugo I, Amirav I, Tzverling C, Naftali G, Kugelman A. Inhaled furosemide in hospitalized infants with viral bronchiolitis: a randomized, double-blind, placebo-controlled pilot study. Pediatr Pulmonol 2008; 43:261-7. 6. Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S, Price D. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med 2003;349:27-35. 7. de Betue CT, van Waardenburg DA, Deutz NE, van Eijk HM, van Goudoever JB, Luiking YC, et al. Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: a double-blind randomised controlled trial. Arch Dis Child 2011;96:817-22. 8. Hulst JM, van Goudoever JB, Zimmermann LJ, Hop WC, Albers MJ, Tibboel D, et al. The effect of cumulative energy and protein deficiency on anthropometric parameters in a pediatric ICU population. Clin Nutr 2004;23:1381-9. 9. Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ. Multicenter, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). CMAJ 2004;170:197-204.
Kugelman et al
CLINICAL AND LABORATORY OBSERVATIONS
March 2013
Table II. Cardiorespiratory status at study enrollment Cohort
Heart rate, beats/min Respiratory rate, breaths/min Fraction of inspired O2 Spo2, % PCO2, mm Hg Sodium bicarbonate, mEq pH Retractions, n None Mild Moderate–severe
IV feeding (n = 20)
GT feeding (n = 31)
P
157 16 56 14 0.26 0.09 94.3 4.0 40.6 6.0 23.2 2.7 7.38 0.04
160 17 59 12 0.26 0.07 94.7 5.7 43.3 10.5 23.8 3.9 7.37 0.04
.46 .50 .87 .35 .78 .63 .64
6 7 7
7 9 15
.74 .76 .39
Values given as n or mean SD.
Intravenous Fluids versus Gastric-Tube Feeding in Hospitalized Infants with Viral Bronchiolitis: A Randomized, Prospective Pilot Study
642.e1
I
nfants with viral bronchiolitis often are hospitalized for respiratory monitoring and supportive care. Infants with respiratory difficulty may be at increased risk of aspiration of feedings into the lungs.1 According to the American Academy of Pediatrics guidelines,2 children who have difficulty feeding safely because of respiratory distress should be given intravenous (IV) fluids. However, there are other approaches. In a large Scottish study on viral bronchiolitis,3 none of the infants received IV fluids and no complications related to nasogastric (NG) feeds were reported. NG tubes also were reported as the common mode of feeding in infants admitted with bronchiolitis in The Netherlands.4 Although the American Academy of Pediatrics recommends IV fluids for infants unable to sustain oral feedings, no study has evaluated the preferred method for nutritional and fluid support in these infants. Our study hypothesis was that better and more physiologic nutrition could be achieved by gastric tube (GT) feeding of breast milk or infant’s formula as opposed to the administration of clear IV fluids, which may, in turn, enhance recovery of infants with bronchiolitis. The aim of our study was to compare the clinical outcomes associated with GT feeding versus IV fluids among moderately ill infants hospitalized with acute viral bronchiolitis.
Methods This was a prospective, open, randomized, controlled clinical pilot study. The study was approved by the institutional review boards of the authors’ hospitals. All parents signed an informed consent. The trial is registered with ClinicalTrials. gov (NCT01189149). If the infant was not able to sustain oral feedings, the mode of fluid/nutritional support was randomly assigned as IV fluids (glucose 5%, NaCl 0.33%, and potassium supplementation) or NG/orogastric tube (5F) feeding (of breast milk or
infant formula). Both groups were allowed comfort nonnutritive sucking. Inclusion criteria were age <6 months, hospitalized with the clinical diagnosis of “moderate bronchiolitis,” and unable to sustain oral feeding. Infants with “moderate bronchiolitis” were defined as infants who could not sustain oral feedings but had no signs of severe respiratory distress or of impending respiratory failure. Criteria for not sustaining oral feeding were respiratory rate >60 breaths/min, supplemental O2 requirement, and difficulties in eating.2,3,5,6 Supplemental O2 was administered when the pulse oximetry O2 saturation (SpO2) was <93% in room air, respiratory rate was >60 breaths/min, or there were difficulties with breathing and feedings.5,6 Exclusion or study termination criteria were severe respiratory distress and signs of impending respiratory failure defined by clinical assessment (severe retractions, significant apnea or apathy), poor ventilation (single blood gas measurement with PCO2 >50 mm Hg and pH <7.25 or evidence of CO2 retention with PCO2 >45 mm Hg and pH <7.3 in repeat blood gas samples), or poor oxygenation (fraction of inspired O2 >0.4 with SpO2 <91%). The primary outcome measures were the duration of supplemental O2 (criteria to stop O2 were stable clinical situation for $4 hours with SpO2 >93% and tolerance of oral feeds) and length of stay (actual and theoretical [no or only mild retractions, able to tolerate oral feeds, no need for O2 for $10 hours]). Statistical Analyses We performed an “intention-to-treat” analysis. We estimated that there would be a >80% chance of detecting a 30% difference between the groups (a < 0.05) with a sample
From the 1Department of Pediatrics, Bnai Zion Medical Center, The B&R Rappaport Faculty of Medicine, Technion, Haifa, Israel; and 2Department of Pediatrics, Western Galilee Hospital, Nahariya, Faculty of Medicine, Bar-Ilan University, Galilee, Israel The authors declare no conflicts of interest.
GT IV NG SpO2
Gastric tube Intravenous Nasogastric Pulse oximetry O2 saturation
Trial is registered with ClinicalTrials.gov: NCT01189149. Portions of this study were presented at the Society of Pediatric Research Meeting in Boston, Massachusetts, April 28-May 1, 2012. 0022-3476/$ - see front matter. Copyright ª 2013 Mosby Inc. All rights reserved. http://dx.doi.org/10.1016/j.jpeds.2012.10.057
640
Vol. 162, No. 3 March 2013
Figure. Infant enrollment in the study.
size of 25 patients for each mode of treatment based on our previous data.5 Two-sample unpaired t tests (Student t) were used for continuous variables with normal distribution, and Wilcoxon rank sum test was used where distribution was skewed. Differences for categorical variables were tested by use of c2 analysis. For all tests the level of significance was set at P < .05. Data are presented as mean SD or median (range). Statistical analysis was performed using Minitab version 12.23 (State College, Pennsylvania) and SigmaStat version 2.03 (Chicago, Illinois) software.
Results Study enrollment is described in the Figure. Of the 124 eligible infants, 73 were not included because of technical constraints (mostly related to heavy provider work load during winter). Finally, 31 infants were assigned to GT feeding and 20 infants to IV fluids. Three infants were switched from GT feeding to IV fluids (due to vomiting) and 2 infants were switched from IV to GT feedings (one because of failure to gain IV access and the other because of fluid extravasation into the tissue). The 2 groups differed only in the duration of illness before hospitalization, which was longer in those who received IV fluids (Table I). Both groups were comparable in disease severity at study enrollment (Table II; available at www. jpeds.com). There was no difference between the IV and GT feeding groups in the duration of supplemental O2 administration (53 59 vs 56 59 hours; P = .95), length of stay (actual 98 48 vs 119 55 hours; P = .12; theoretical 81 55 vs 92 51 hours; P = .28), time to resume full oral feeding (46 39 vs 58 44 hours; P = .18), or medications used during the hospitalization. No events of clinical aspiration were recorded. GT feeding was not associated with worsening of any measure of respiratory status of the infants.
Discussion Our pilot study showed that GT feeding is feasible and has comparable clinical outcomes with IV fluid adminis-
tration among hospitalized infants with moderate viral bronchiolitis. The theoretical advantages of IV fluids during bronchiolitis are ease on breathing and no risk of aspiration.1 The main disadvantage of IV fluids is the creation of a catabolic state (ie, decreased calorie intake with no provision of protein or lipids despite increased metabolic demands during infection and respiratory distress related to bronchiolitis).7,8 Currently, total parenteral nutrition is not the standard of care for inpatients with bronchiolitis. GT feeding may allow a better and more physiologic nutrition, including Table I. Demographic characteristics of study subjects Cohort IV feeding (n = 20)
GT feeding (n = 31)
P
Age, mo Weight, kg Male/female, n Gestation age at birth, wk Term/preterm, n* Perinatal morbidity, n
2.6 1.2 5.4 1.4 14/6 38.0 2.7
2.1 1.1 5.0 1.2 24/7 38.0 1.5
.18 .30 .79 .63
Background illness, n
1 (Gastroesophageal reflux) 2
Known asthma or atopy in family, n Smoking in close contacts, n Bronchiolitis data, n RSV positive RSV negative Unknown RSV status Duration of illness before hospitalization, d Medications before admission, n Medications during hospitalization, n† Pneumonia, n
18/2 1 (Perianal abscess)
26/5 2 (Transient tachypnea of the newborn) 0
.69 1.00
2
.64
2
1
.55
15 3 2 4.4 2.7
26 4 1 3.5 2.7
.48 1.00 .55 .04
8
7
.21
18
26
.69
4
7
1.00
.39
RSV, respiratory syncytial virus. Values given as n or mean SD. *Preterm <37 weeks’ gestational age. †Mostly hypertonic saline with inhaled bronchodilators.
641
THE JOURNAL OF PEDIATRICS
www.jpeds.com
provision of expressed breast milk. Better nutrition in critically ill patients was shown to enhance recovery9 and improve nitrogen balance in patients in intensive care units.7 While planning a larger study, we had only a small number of participants because of technical constraints, related to the heavy work load in the emergency department during the respiratory syncytial virus season. Thus, our study serves only as a pilot study. The mode of support assignment could not be blinded to the medical team. Use of objective criteria and management protocols reduced the possibility of a bias related to nonblinding. We conclude that GT feeding is feasible and has comparable clinical outcomes with IV fluid administration among hospitalized infants with moderate viral bronchiolitis. GT feeding was not associated with clinical aspiration events or with any worsening of the infants’ respiratory status. Larger trials are warranted before it can be concluded that GT feeding is an optional treatment in infants with moderate bronchiolitis. n
Submitted for publication Jul 7, 2012; last revision received Sep 4, 2012; accepted Oct 26, 2012. Reprint requests: Amir Kugelman, MD, Bnai Zion Medical Center, Pediatric Pulmonary Unit and Department of Pediatrics, 47 Golomb Street, Haifa, 31048, Israel. E-mail: [email protected], [email protected]
642
Vol. 162, No. 3
References 1. Khoshoo V, Edell D. Previously healthy infants may have increased risk of aspiration during respiratory syncytial viral bronchiolitis. Pediatrics 1999; 104:1389-90. 2. American Academy of Pediatrics. Diagnosis and management of bronchiolitis. Pediatrics 2006;118:1774-93. 3. Unger S, Cunningham S. Effect of oxygen supplementation on length of stay for infants hospitalized with acute viral bronchiolitis. Pediatrics 2008;121:470-5. 4. Brand PL, Vaessen-Verberne AA. Differences in management of bronchiolitis between hospitals in The Netherlands. Dutch Paediatric Respiratory Society. Eur J Padiatr 2000;159:343-7. 5. Bar A, Srugo I, Amirav I, Tzverling C, Naftali G, Kugelman A. Inhaled furosemide in hospitalized infants with viral bronchiolitis: a randomized, double-blind, placebo-controlled pilot study. Pediatr Pulmonol 2008; 43:261-7. 6. Wainwright C, Altamirano L, Cheney M, Cheney J, Barber S, Price D. A multicenter, randomized, double-blind, controlled trial of nebulized epinephrine in infants with acute bronchiolitis. N Engl J Med 2003;349:27-35. 7. de Betue CT, van Waardenburg DA, Deutz NE, van Eijk HM, van Goudoever JB, Luiking YC, et al. Increased protein-energy intake promotes anabolism in critically ill infants with viral bronchiolitis: a double-blind randomised controlled trial. Arch Dis Child 2011;96:817-22. 8. Hulst JM, van Goudoever JB, Zimmermann LJ, Hop WC, Albers MJ, Tibboel D, et al. The effect of cumulative energy and protein deficiency on anthropometric parameters in a pediatric ICU population. Clin Nutr 2004;23:1381-9. 9. Martin CM, Doig GS, Heyland DK, Morrison T, Sibbald WJ. Multicenter, cluster-randomized clinical trial of algorithms for critical-care enteral and parenteral therapy (ACCEPT). CMAJ 2004;170:197-204.
Kugelman et al
CLINICAL AND LABORATORY OBSERVATIONS
March 2013
Table II. Cardiorespiratory status at study enrollment Cohort
Heart rate, beats/min Respiratory rate, breaths/min Fraction of inspired O2 Spo2, % PCO2, mm Hg Sodium bicarbonate, mEq pH Retractions, n None Mild Moderate–severe
IV feeding (n = 20)
GT feeding (n = 31)
P
157 16 56 14 0.26 0.09 94.3 4.0 40.6 6.0 23.2 2.7 7.38 0.04
160 17 59 12 0.26 0.07 94.7 5.7 43.3 10.5 23.8 3.9 7.37 0.04
.46 .50 .87 .35 .78 .63 .64
6 7 7
7 9 15
.74 .76 .39
Values given as n or mean SD.
Intravenous Fluids versus Gastric-Tube Feeding in Hospitalized Infants with Viral Bronchiolitis: A Randomized, Prospective Pilot Study
642.e1