Neonatal Sulfhemoglobinemia Treated With Exchange Transfusion: A Case Report

Gabilan Sivapatham, David Stammers, MD

Royal University Hospital, Department of Pediatrics, Saskatoon, Canada.

Background Neonatal Intensive Care Unit (NICU) Discussion N-acetylcysteine Intake • Day 0: NPO, TPN & OG tube intermittent suction. Several cases demonstrate ingestion of metoclopramide Sulfhemoglobinemia is a rare acquired hemoglobinopathy This case demonstrates the clinical course of a neonate alone or in combination with NAC as causes of that results from the irreversible binding of a sulfur atom to • Day 2: Contrast enema showed narrowing of the with cystic fibrosis who developed sulfhemoglobinemia in sulfhemoglobinemia. NAC is a biochemical precursor of the porphyrin ring of the heme group of hemoglobin. This ascending colon. the setting of both meconium ileus and use of NAC, and glutathione and a substrate for hydrogen sulfide, although oxidation reaction renders hemoglobin incapable of was successfully treated with exchange transfusion. most cases of NAC use do not result in carrying oxygen. It is not usually found in blood. • Day 4: Laparotomy & enterotomy showed significant sulfhemoglobinemia. Perhaps the combination of narrowing of the terminal ileum. Meconium plug was Sulfhemoglobinemia should be suspected when: constipation leading to the overgrowth of particular cleared. T-tube inserted for ongoing bowel irrigation  A cyanotic patient does not have a significantly bacterial species combined with NAC led to an optimal with 50/50 normal saline and 20% Mucomyst (NAC). environment for the production of sulfhemoglobin. depressed arterial PaO2 or Still no bowel movements.  The history suggests toxic exposure to a known etiologic agent. Exchange Transfusion Pediatric Intensive Care Unit (PICU) Gharahbaghian et al. (2009) discuss the treatment of two • Day 14/15: Oxygen desaturations noted by pulse In this case, it was thought that intestinal stasis and/or pediatric patients who developed sulfhemoglobinemia oximetry. Increasing oxygen requirements & tachypnea NAC led to the production of hydrogen sulfide and after ingestion of exogenous hydroxylamine sulfate with with a rate of 50 to 70. No sources for increased subsequent hemoglobinopathy. Oxidation of hemoglobin exchange transfusion and pRBC transfusion that oxygen requirement were identified, including a partial can form methemoglobin, which can react with hydrogen demonstrated a rapid improvement in their patients’ Known causes of sulfhemoglobinemia include: septic workup and an echocardiogram. sulfide to produce sulfhemoglobinemia. oxygen saturation. Due to ~120 day lifespan of the red  Phenacetin, dapsone, sulfonamides, metoclopramide, blood cell, exchange transfusion provides a method to remove hemoglobin that cannot bind oxygen. nitrates, acetanilide, Septra • No improvement in his pulse oximetry despite non- Intestinal Stasis Intestinal stasis is thought to foster an environment of  Constipation invasive ventilator support leading to intubation for enhanced sulfide production by bacterial flora. hypoxemia. His ABG showed a PaO2 of 500 on 100% Conclusions  Hydrogen-sulfide-producing bacteria FiO while his pulse oximetry remained 80-90%.  Tangerman et al. (2002) present a 3-year-old male with 2 sulfhemoglobin-induced cyanosis whose blood and While methemoglobinemia responds to methylene blue, the organs were invaded by hemolytic Escherichia coli. This case report is unique in its approach to treatment with lack of antidote for sulfhemoglobinemia makes its treatment  Murphy et al. (2015) describe a 7-year-old female with exchange transfusion in a neonate with cystic fibrosis and challenging. Its prevalence is also rare, particularly in the non-drug-induced sulfhemoglobinemia whose fecal sulfhemoglobinemia. This was likely secondary to neonatal population. samples revealed the 38% relative abundance of intestinal stasis with NAC ingestion. We present three key This case report discusses a neonate with cystic fibrosis Morganella morganii, an opportunistic pathogen messages: (CF) who develops sulfhemoglobinemia secondary to capable of producing hydrogen sulfide. 1. Consider sulfhemoglobinemia in patients presenting meconium ileus & N-acetylcysteine (NAC) administration, with both hypoxemia and intestinal pathology. with resolution through exchange transfusion. In contrast, George and Goetz (2017) describe a 7-year- 2. In suspected cases of hemoglobinopathy, pulse old female who developed sulfhemoglobinemia in the oximetry, capillary and venous blood gases may be setting of chronic constipation but had normal intestinal unreliable. Objective flora on stool cultures. 3. Sulfhemoglobinemia can be successfully treated through exchange transfusion. • To describe a successful treatment strategy for neonatal sulfhemoglobinemia in a neonate with Single volume exchange transfusion replaces ~60% of total neonatal volume. cystic fibrosis • 6.4% methemoglobin noted on capillary gas led to treatment with 1g/kg methylene blue. This was Case Description ineffective, and the lab subsequently recognized the presence of over 10% sulfhemoglobinemia. Patient Methemoglobin and sulfhemoglobin have Antenatal History: treated initially with a packed red blood cell transfusion similar peak spectral absorbance at 620nm. • 37+2 week male, induced vaginal delivery to a 31-year- then an exchange transfusion. The patient’s FiO2 old G9P4 insulin-dependent DMII mother. requirement based on pulse oximetry recovered rapidly. References

No sulfhemoglobinemia was identified on any 1. Agbeko, R., Semmekrot, B., Bongaerts, G., Neeleman, C., & Severijnen, R. (1998). A newborn with cyanosis. European Journal of Pediatrics, 157(12), 1026-1029. 2. Aravindhan, N., Chisholm, D.G. (2000). Sulfhemoglobinemia Presenting as Pulse Oximetry Desaturation. Anesthesiology, 93:883-4. • Both parents are known cystic fibrosis carriers alongside subsequent arterial gases. 3. Curry, S. C., & Kang, A. M. (2017). Toxicant-Induced Hematologic Syndromes. In J. Brent, K. Burkhart, P. Dargan, B. Hatten, B. Megarbane, R. Palmer, & J. White (Eds.), Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient (pp. 643-659). Cham: Springer International Publishing. 4. Farmer, Brenna M., and Lewis S. Nelson. (2016). "Dyshemoglobinemias." Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e Eds. Judith E. an affected older sister. Tintinalli, et al. New York, NY: McGraw-Hill. 5. George, A., Goetz, D. M., & Goetz, D. M. (2017). A case of sulfhemoglobinemia in a child with chronic constipation. Respiratory medicine case reports, 21, 21-24. 6. Gharahbaghian, L., Massoudian, B., DiMassa, G. (2009). Methemoglobinemia and Sulfhemoglobinemia in Two Pediatric Patients after Ingestion of Hydroxylamine Sulfate. West J Emerg Med. 10(3):197-201. • Day 17: The patient started stooling and made a full 7. Langford, J.S., Sheikh, S. (1999). An adolescent case of sulfhemoglobinemia associated with high-dose metoclopramide and N-acetylcysteine. Ann Emerg Med. • Prenatal ultrasound showed polyhydramnios & increased 34:538-41. 8. Lu, H.C. et al. (1998). Pseudomethemoglobinemia. Arch Pediatr Adolesc Med. 152:803-5. recovery. Genetic testing confirmed a diagnosis of CF 9. Murphy, K. et al. (2015). Neonatal Sulfhemoglobinemia and Hemolytic Anemia Associated With Intestinal Morganella morganii. Pediatrics, 136(6):e1641-5. bowel echogenicity suggestive of bowel obstruction. 10. Park, C.M., & Nagel, R.L. (1984). Sulfhemoglobinemia - Clinical and Molecular Aspects. N Engl J Med, 310:1579-1584. 11. Percy MJ, McFerran NV, Lappin TR: Disorders of oxidised haemoglobin. Blood Rev 19: 61, 2005. with mutations deltaF508/M1101K. 12. Sankoff, J., Louie, A.D. (2008). Clinicopathologic Conference: A 28-yaer-old Woman with Perioral Cyanosis and Low Oxygen Saturation. Acad Emerg Med, 15(4): 363-367. Meconium ileus. Case courtesy of Dr Michael Sargent, Radiopaedia.org, rID: 6009 13. Sathe, M., Roderick., Houwen. (2017). Meconium ileus in Cystic Fibrosis. Journal of Cystic Fibrosis. 16:S32-39. 14. Tangerman, A., Bongaerts, G., Agbeko, R., Semmekrot, B., & Severijnen, R. (2002). The origin of hydrogen sulfide in a newborn with sulfhaemoglobin induced • APGAR scores of 9 and 9 with a birth weight of 3160g. cyanosis. Journal of clinical pathology, 55(8), 631–633.