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Neonatal Intensive Care Units (NICUs) often encounter the challenge of hypoxia, a commonly faced problem. Among the various causes, methemoglobinemia stands out as one of the rarest and most life-threatening complications that can arise. It is a medical condition characterized by elevated levels of methemoglobin in the blood, which impairs the ability of red blood cells to effectively oxygenate tissues [1]. Methemoglobin contains oxidized hemoglobin in the ferric state, which cannot effectively bind and transport oxygen [2-6]. This condition can be either acquired or congenital, with the acquired form often resulting from exposure to some known substances like dapsone, benzocaine, nitrates, and aniline derivatives [7].

We report a case of hypoxia due to methemoglobinemia in an extreme preterm (24 weeks) weighing 555 grams being treated with carbapenem (meropenem) for Burkholderia cepacia sepsis. This case also possibly represents the youngest reported instance of methemoglobinemia in neonates [8].

An extreme preterm born at 24 weeks of period of gestation with birth weight of 555gram was noted to have an increased FIO₂ requirement to 88% suddenly while earlier on 25% Heated Humidified High Flow Nasal Cannula (HHHFNC) on day 20 of life. This baby girl was born to an elderly G3P1L1E1 (IVF Pregnancy) mother by emergency Lower Segment Caesarean Section (LSCS) for severe oligohydramnios due to pPROM of 72 hours at 24 weeks of gestation with a birth weight of 555 grams.

The baby needed nasal CPAP and LISA for RDS at birth and was switched to HHHFNC on day 12 of life. Other standard cares in NICU were given. However, clinical sepsis on day 15 of life with blood culture sensitivity of Burkholderia cepacia indicated need for addition of IV Meropenem as per sensitivity.

On day 20 of life, a sudden increase in FIO₂ requirement was noted, and respiratory support was hence stepped up to CPAP mode (5 cm H₂O). However, over the next 48 hours, the FIO₂ requirement still went up to 100% to reach the target SPO₂ of 90%. There was no increase in distress/retractions as well as no apnea and child was very active, euthermic, normotensive, euglycemic and well perfused with no significant change in chest x-ray, repeat CRP was negative, CBC parameters were in normal range except for hemoglobin of 7.2 g/dl, for which she was given irradiated, leucodepleted packed red blood cells (15 ml/kg), and 2D ECHO showed a tiny PDA of 0.9 mm with a leftto-right shunt, no PAH. As she required still 100% FIO₂ without any suggestion of cardio-pulmonary involvement and no other clinical or hemodynamical deterioration, the possibility of methemoglobinemia and abnormal hemoglobin variants were considered in the differential diagnosis. Arterial blood gas done using the Radiometer ABL 800 FLEX showed pH 7.43, PCO₂ 35.9 mmhg, PO₂ 137 mmhg, HCO3 24, BE 0.1, Lactate 5.7 mmol/L. Hence, based on the clinical condition since SPO₂ being on the lower side (88-90%) despite FIO₂ 100% and a PAO₂ being 137 mmHg a methemoglobin level was checked and found to be 10.2%. A diagnosis of possible methemoglobinemia was made, and blood was sent for reconfirmation of methemoglobin and was reported as 38.7%.

She was started immediately on intravenous methylene blue 1 mg/ kg (0.5 mg) and intravenous ascorbic acid 500 mg twice a day after making sure serum G6PD levels were normal and other supportive care continued. We looked into the possible cause of methemoglobinemia; Congenital methemoglobinemia cause was unlikely as baby till 20 days of age was stable and maintained oxygenation well with respiratory support as expected of any extreme preterm. Acquired causes of methemoglobinemia were looked into, and the only medication she was receiving was intravenous meropenem for Burkholderia cepacia, apart from supplement. Based on an earlier case report by Andrade et al. 8 in which they reported a case of methemoglobinemia in a newborn possible due to intravenous Meropenem treated for Burkholderia cepacia since no other causes for methemoglobinemia was found hence intravenous Meropenem was stopped for our patient and intravenous Ceftazidime was used based on our blood culture report. Over the next few days, good clinical improvement was seen. Baby was given 4 doses of intravenous methylene blue and intravenous ascorbic acid for 8 days. Serial arterial blood measurements showed a decreasing trend in methemoglobin levels, which normalized after 10 days (day 29 of life) and the baby’s FIO2 need reduced to 25% on HHHNC support (Figure 1).

 

Figure 1: An extreme preterm born at 24 weeks of period of gestation.

The majority of cases of neonatal methemoglobinemia documented in the literature attribute congenital factors as the root cause. However, there have been recent reports of acquired methemoglobinemia linked to specific drugs such as prilocaine, benzocaine, and nitrate solutions, as highlighted in various reports [9]. Also, Andrade et al. have reported a possible cause of methemoglobinemia due to intravenous meropenem treated for Burkholderia cepacia.

Methemoglobinemia is typically caused by drugs containing a free nitrate group that can convert hemoglobin from ferrous to ferric form. Unlike broad-spectrum antibiotics such as meropenem, which lack a free nitrate group. The methemoglobinemia in our case could be due to intravenous meropenem as also reported by Andrade et al. Also, low levels of methemoglobin reductase enzyme (50% of adult value) could be a contributing factor in our case.

With advances in medical sciences and with time, the medical fraternity will understand the disease in a better way. As of now, we know certain drugs and conditions that cause methemoglobinemia, which are mentioned earlier in the course. There has been case reports of IV Meropenem being implicated in causing methemoglobinemia. The clinical response seen in our patient on withdrawal of the drug throws a high index of suspicion to consider Meropenem as the cause of methemoglobinemia.

A high index of suspicion is required to diagnose methemoglobinemia, considering its rarity, especially in extreme preterm infants. Our case report also highlights the importance of reviewing the drug history of the patient to look for acquired causes of methemoglobinemia after congenital methemoglobinemia and cyanosis due to cardiopulmonary causes are ruled out.

We sincerely thank parents for accepting and giving consent to publish this data

None

Written informed consent taken from parents

The first and corresponding author were involved in the writing of the manuscript. All six authors were involved in finalising the manuscript.

1. Johnson SF (2019) . Curr Probl Pediatr Adolesc Health Care 49: 57-67.

   [] [] []

2. Da-Silva SS, Sajan IS, Underwood JP (2003) Pediatrics 112: 158–161.

   [] [] []

3. Schwartz L, Franck P, Debruille C, Olivier JL, Vigneron C (2005) Congenital methemoglobinemia: A rare case of cyanosis in the newborn. Ann BiolClin 63: 314–316.
4. Glader BE (1989) . Pediatrics 83: 792–793. [Crossref] [Google Scholar] [PubMed]
5. Viršilas E, Timukien臈 L, Liubšys A (2019) Clin Pract 9:1188.

   [] [] []

6. Ash-Bernal R, Wise R, Wright SM (2004) Medicine 83: 265–273.

   [] [] []

7. Andrade SJ, Raj KA, Lewis LE (2019) Indian J Pediatr 86: 663.

   [] [] []

8. Chou TD, Gibran NS, Urdahl K, Lin EY, Heimbach DM, et al. (1999) Burns 25: 549–552.

   [] [] []

9. Couper RT (2000) J Paediatr Child Health 36: 406–407.

   [] [] []