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Is octreotide a risk factor in necrotizing enterocolitis?
Journal of Pediatric Surgery (2008) 43, 1209–1210
www.elsevier.com/locate/jpedsurg
Is octreotide a risk factor in necrotizing enterocolitis? Carlos A. Reck-Burneo⁎, Aruna Parekh, Francisca T. Velcek Long Island College Hospital, Brooklyn, NY 11201, USA Received 30 August 2007; revised 14 February 2008; accepted 15 February 2008
Key words: Octreotide; Necrotizing enterocolitis; Neonatal hypoglycemia; Insulinoma; Nesidioblastosis
Abstract Octreotide is used as a second-line treatment for hyerinsulinemic hypoglycemia in neonates who do not respond to diazoxide. We present a case of a full-term newborn with massive enterocolitis that developed after octreotide was started for the treatment of refractory hypoglycemia. Multiple intestinal resections were necessary to save intestinal length and restore intestinal function. One case has previously been reported linking the use of octreotide to the development of necrotizing enterocolitis in an infant. © 2008 Elsevier Inc. All rights reserved.
1. Case report A 22-day-old full-term neonate developed abdominal distension and vomiting 3 days after institution of octreotide treatment for refractory hypoglycemia. The baby was born by normal spontaneous vaginal delivery to a healthy mother. There was no maternal history of diabetes or medication use during pregnancy. Birth weight was 3.1 kg and Apgar scores 9 and 9 at 1 and 5 minutes, respectively. At 1 hour of life while in the nursery, the patient developed apnea and hypotonia and required bag and mask resuscitation. A chemstrip showed severe hypoglycemia with a glucose level of 12 mg/dL. Symptoms resolved immediately after intravenous glucose administration was started. The baby was otherwise stable. The patient was afebrile with no respiratory distress. Bacterial, viral, and fungal cultures remained negative after 5 days and on repeated occasions. Further laboratory examinations revealed an elevated insulin level with the remaining tests including a complete blood ⁎ Corresponding author. Tel.: +1 3474200879; fax: +1 8665404123. E-mail addresses: [email protected] (C.A. Reck-Burneo), [email protected] (A. Parekh), [email protected] (F.T. Velcek). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.02.062
count, HgbA1c, electrolytes, and liver function studies within normal limits. Urine analysis was normal and negative for ketones. Feedings with breast milk and a neonatal formula were started and were well tolerated. Bowel movements were normal at all times. Except for ampicillin and gentamicin started on admission to the neonatal intensive care unit, no other medications were instituted. The newborn screening was later reported to be negative for cystic fibrosis and metabolic syndromes. Hypoglycemia returned on every attempt to wean the patient of intravenous glucose so that diazoxide treatment was started on day of life 8 at a dose of 10 mg/kg per day. For the next 10 days diazoxide was titrated to a maximum of 20 mg/kg per day with no response at maximum dose. Ultrasound and computed tomographic scan of the pancreas were normal. Octreotide therapy was decided upon and started on day of life 20. The initial dose used was 10 μg/kg per day administered every 6 hours and further titrated to 15 μg/kg per day within 48 hours. Within 72 hours of treatment with octreotide, the patient developed significant abdominal distension, vomiting, and feeding intolerance. Laboratory examinations were significant for metabolic acidosis. Abdominal x-rays showed generalized gaseous distension, pneumatosis intestinalis, and portal venous
1210
C.A. Reck-Burneo et al. constipation, or other complications related to the necrotizing enterocolitis have been noted.
2. Discussion
Fig. 1 Intraoperative findings were consistent with necrotizing enterocolitis involving extensive areas of jejunum, ileum and colon.
gas. Blood and urine cultures remained negative. Liver function tests were normal. No respiratory distress was present at the time, and the patient was on room air. After initial stabilization, the patient was taken to the operating room for an exploratory laparotomy. Intraoperative findings were consistent with massive necrotizing enterocolitis involving the entire jejunum, ileum, and colon. (Fig. 1) Intestinal decompression was done and, because of the extent of the affected intestine, a second look operation 24 hours later was decided upon to allow possible recovery and demarcation of the necrotic bowel. Subsequently, 4 resections of grossly necrotic small bowel (2.5, 4, 5, and 6 cm) amounting to approximately 17.5 cm and a proximal jejunostomy and mucous fistula were performed. There were 7 areas of partially infarcted bowel that were repaired. A proximal viable small intestinal segment of 23 cm and a distal segment of 89 cm were left behind. Two further laparotomies for necrotic breakdown of the bowel and subsequent reestablishment of intestinal continuity were required. Hypoglycemia was treated with glucose infusion rates of up to 16 mg/kg per minute. Since then and after a long and complicated hospitalization, the patient was weaned of intravenous glucose and started on enteral g-tube carbohydrate caloric supplement in addition to a regular diet. Glucagon injections are administered as needed for rescue treatment of hypoglycemia. Glucose management continues to be difficult because of poor glycemic control and bouts of hypoglycemia. The patient also currently has morbid obesity and feeding difficulties. Plans for future pancreatectomy are being considered as glycemic control continues to be challenging. One year postoperatively, no signs of intestinal obstruction,
Octreotide, a somatostatin analog is currently being advocated for the treatment of pancreatitis, enterocutaneous fistulas, chylothorax, and nesidioblastosis [1,2]. Wellestablished prospective studies in neonates are lacking, and the safety profile and side effects of this medication remain to be studied. Our literature search showed one previous report of octreotide causing necrotizing enterocolitis [3]. The present case further supports growing evidence for this important side effect of octreotide. Although transient gastrointestinal symptoms such as abdominal distension, vomiting, and steatorrhea may be more common side effects [2,4], a high index of suspicion for necrotizing enterocolitis needs to exist when a neonate is treated with this medication. Octreotide increases splanchnic vascular resistance reducing gut blood flow [4], and this could provide an explanation for the development of this illness. Other important side effects unrelated to this case but reported with octreotide are pulmonary hypertension [5,6] and the development of gallstones [2] when used on a prolonged period of time. Suggested uses for this medication have not been evaluated extensively in neonates and when used, attention should be paid for early gastrointestinal signs so that aggressive management can be instituted timely to assure a better outcome. Aggressive management in this case resulted in survival of this very sick infant. Octreotide in the meanwhile should only be considered as a second-line treatment of hyperinsulinemia in neonates.
References [1] Lam JC, Aters S, Tobias JD. Initial experience with octreotide in the pediatric population. Am J Ther 2001;8:409-15. [2] Roehr CC, Jung A, Proquitté H, et al. Somatostatin or octreotide as treatment options for chylothorax in young children: a systemic review. Intensive Care Med 2006;32:650-7. [3] Mohseni-Bod H, Macrae D, Slavik Z. Somatostatin analog (octreotide) in management of neonatal postoperative chylothorax: is it safe. Pediatr Crit Care Med 2004;5:257-356. [4] Stajich GV, Ashworth L. Octreotide. Neonatal Netw 2006;25:365-9. [5] Arevalo RP, Bullabh P, Krauss AN, et al. Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates. J Pediatr Surg 2003;38:251-3. [6] Silvani P, Camporesi A. Drug-induced pulmonary hypertension in newborns: a review. Curr Vasc Pharmacol 2007;5:129-33.
www.elsevier.com/locate/jpedsurg
Is octreotide a risk factor in necrotizing enterocolitis? Carlos A. Reck-Burneo⁎, Aruna Parekh, Francisca T. Velcek Long Island College Hospital, Brooklyn, NY 11201, USA Received 30 August 2007; revised 14 February 2008; accepted 15 February 2008
Key words: Octreotide; Necrotizing enterocolitis; Neonatal hypoglycemia; Insulinoma; Nesidioblastosis
Abstract Octreotide is used as a second-line treatment for hyerinsulinemic hypoglycemia in neonates who do not respond to diazoxide. We present a case of a full-term newborn with massive enterocolitis that developed after octreotide was started for the treatment of refractory hypoglycemia. Multiple intestinal resections were necessary to save intestinal length and restore intestinal function. One case has previously been reported linking the use of octreotide to the development of necrotizing enterocolitis in an infant. © 2008 Elsevier Inc. All rights reserved.
1. Case report A 22-day-old full-term neonate developed abdominal distension and vomiting 3 days after institution of octreotide treatment for refractory hypoglycemia. The baby was born by normal spontaneous vaginal delivery to a healthy mother. There was no maternal history of diabetes or medication use during pregnancy. Birth weight was 3.1 kg and Apgar scores 9 and 9 at 1 and 5 minutes, respectively. At 1 hour of life while in the nursery, the patient developed apnea and hypotonia and required bag and mask resuscitation. A chemstrip showed severe hypoglycemia with a glucose level of 12 mg/dL. Symptoms resolved immediately after intravenous glucose administration was started. The baby was otherwise stable. The patient was afebrile with no respiratory distress. Bacterial, viral, and fungal cultures remained negative after 5 days and on repeated occasions. Further laboratory examinations revealed an elevated insulin level with the remaining tests including a complete blood ⁎ Corresponding author. Tel.: +1 3474200879; fax: +1 8665404123. E-mail addresses: [email protected] (C.A. Reck-Burneo), [email protected] (A. Parekh), [email protected] (F.T. Velcek). 0022-3468/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.jpedsurg.2008.02.062
count, HgbA1c, electrolytes, and liver function studies within normal limits. Urine analysis was normal and negative for ketones. Feedings with breast milk and a neonatal formula were started and were well tolerated. Bowel movements were normal at all times. Except for ampicillin and gentamicin started on admission to the neonatal intensive care unit, no other medications were instituted. The newborn screening was later reported to be negative for cystic fibrosis and metabolic syndromes. Hypoglycemia returned on every attempt to wean the patient of intravenous glucose so that diazoxide treatment was started on day of life 8 at a dose of 10 mg/kg per day. For the next 10 days diazoxide was titrated to a maximum of 20 mg/kg per day with no response at maximum dose. Ultrasound and computed tomographic scan of the pancreas were normal. Octreotide therapy was decided upon and started on day of life 20. The initial dose used was 10 μg/kg per day administered every 6 hours and further titrated to 15 μg/kg per day within 48 hours. Within 72 hours of treatment with octreotide, the patient developed significant abdominal distension, vomiting, and feeding intolerance. Laboratory examinations were significant for metabolic acidosis. Abdominal x-rays showed generalized gaseous distension, pneumatosis intestinalis, and portal venous
1210
C.A. Reck-Burneo et al. constipation, or other complications related to the necrotizing enterocolitis have been noted.
2. Discussion
Fig. 1 Intraoperative findings were consistent with necrotizing enterocolitis involving extensive areas of jejunum, ileum and colon.
gas. Blood and urine cultures remained negative. Liver function tests were normal. No respiratory distress was present at the time, and the patient was on room air. After initial stabilization, the patient was taken to the operating room for an exploratory laparotomy. Intraoperative findings were consistent with massive necrotizing enterocolitis involving the entire jejunum, ileum, and colon. (Fig. 1) Intestinal decompression was done and, because of the extent of the affected intestine, a second look operation 24 hours later was decided upon to allow possible recovery and demarcation of the necrotic bowel. Subsequently, 4 resections of grossly necrotic small bowel (2.5, 4, 5, and 6 cm) amounting to approximately 17.5 cm and a proximal jejunostomy and mucous fistula were performed. There were 7 areas of partially infarcted bowel that were repaired. A proximal viable small intestinal segment of 23 cm and a distal segment of 89 cm were left behind. Two further laparotomies for necrotic breakdown of the bowel and subsequent reestablishment of intestinal continuity were required. Hypoglycemia was treated with glucose infusion rates of up to 16 mg/kg per minute. Since then and after a long and complicated hospitalization, the patient was weaned of intravenous glucose and started on enteral g-tube carbohydrate caloric supplement in addition to a regular diet. Glucagon injections are administered as needed for rescue treatment of hypoglycemia. Glucose management continues to be difficult because of poor glycemic control and bouts of hypoglycemia. The patient also currently has morbid obesity and feeding difficulties. Plans for future pancreatectomy are being considered as glycemic control continues to be challenging. One year postoperatively, no signs of intestinal obstruction,
Octreotide, a somatostatin analog is currently being advocated for the treatment of pancreatitis, enterocutaneous fistulas, chylothorax, and nesidioblastosis [1,2]. Wellestablished prospective studies in neonates are lacking, and the safety profile and side effects of this medication remain to be studied. Our literature search showed one previous report of octreotide causing necrotizing enterocolitis [3]. The present case further supports growing evidence for this important side effect of octreotide. Although transient gastrointestinal symptoms such as abdominal distension, vomiting, and steatorrhea may be more common side effects [2,4], a high index of suspicion for necrotizing enterocolitis needs to exist when a neonate is treated with this medication. Octreotide increases splanchnic vascular resistance reducing gut blood flow [4], and this could provide an explanation for the development of this illness. Other important side effects unrelated to this case but reported with octreotide are pulmonary hypertension [5,6] and the development of gallstones [2] when used on a prolonged period of time. Suggested uses for this medication have not been evaluated extensively in neonates and when used, attention should be paid for early gastrointestinal signs so that aggressive management can be instituted timely to assure a better outcome. Aggressive management in this case resulted in survival of this very sick infant. Octreotide in the meanwhile should only be considered as a second-line treatment of hyperinsulinemia in neonates.
References [1] Lam JC, Aters S, Tobias JD. Initial experience with octreotide in the pediatric population. Am J Ther 2001;8:409-15. [2] Roehr CC, Jung A, Proquitté H, et al. Somatostatin or octreotide as treatment options for chylothorax in young children: a systemic review. Intensive Care Med 2006;32:650-7. [3] Mohseni-Bod H, Macrae D, Slavik Z. Somatostatin analog (octreotide) in management of neonatal postoperative chylothorax: is it safe. Pediatr Crit Care Med 2004;5:257-356. [4] Stajich GV, Ashworth L. Octreotide. Neonatal Netw 2006;25:365-9. [5] Arevalo RP, Bullabh P, Krauss AN, et al. Octreotide-induced hypoxemia and pulmonary hypertension in premature neonates. J Pediatr Surg 2003;38:251-3. [6] Silvani P, Camporesi A. Drug-induced pulmonary hypertension in newborns: a review. Curr Vasc Pharmacol 2007;5:129-33.