Successful exchange transfusion in extremely preterm infant after symptomatic lipid overdose

1 Background

Lipid emulsion is an important component of parenteral nutrition (PN), both as a source of energy substrate and a supplier of essential fatty acids [1]. Since the introduction of 20% lipid solutions containing predominantly soybean oil, complications of intravenous (i.v.) lipid administration have been relatively uncommon [2]; however inadvertent rapid infusion of IVFE is an inherent risk when fats are infused separately from the dextrose-amino acid solution [3].

In most cases, patients simply experienced hypertriglyceridemia that disappeared upon discontinuation of the IVFE. In other cases, serious complications such as respiratory failure, metabolic acidosis and even death have been linked to rapid infusion of IVFE [2, 4]. We report a case of an extremely preterm newborn who inadvertently received a massive overdose of IVFE that illustrates the characteristics and successful management of this complication of PN.

2 Case report

The patient was the “A” twin of a dizygotic pregnancy, born at 25 weeks and 6 days of gestation weighing 920 g. He was delivered by emergency cesarean section because of abruptio placentae. Apgar scores were 5/8.

The initial course involved mechanical ventilation and surfactant therapy before extubation to continuous positive airway pressure at three hours of life. Caffeine citrate was started and he was also being treated with ampicillin and gentamicin until sepsis was ruled out.

Under stable conditions PN and 20% lipid emulsion were started at eight hours of life through an umbilical line. Lipid emulsion was ordered to be infused at 0.4 ml/hour (2 g of lipid/kg/day).

Few hours later the infant presented with lethargy, frequent episodes of apnea and hypotension. He required mechanical ventilation with increasing FiO₂ needs and inotropic support (dobutamine up to 10 microgram/kg/min).

His chest X-ray was normal but blood sample obtained was grossly lipemic. Lipid emulsion was then checked, finding out that, due to a device failure, the infant inadvertently received 60 ml of 20% fat emulsion (13 g/kg) during an eight hour period. Patient's arterial blood gas revealed metabolic acidosis (pH 7.18; PaCO₂ 37 mmHg; PaO₂ 54 mmHg and base deficit – 14.6 mmol/L), hyperglycemia (145 mg/dl) and hyponatraemia (Na 128 mmol/L). Other studies including triglyceride levels, cholesterol, alanine aminotransferase, aspartate aminotransferase, total and direct bilirubin, complete blood count and coagulation could not be performed by our laboratory because of extreme lipemia. Despite discontinuation of IVFE and supportive care, clinical course and metabolic acidosis worsened, so we decided to perform a double- volume exchange transfusion. The procedure was well tolerated, without complications. Serum triglyceride concentration immediately after the exchange-transfusion was 1652 mg/dl, and 24 hours later it was 19 mg/dl so fat emulsion was restarted. Other laboratory data also normalized immediately after the exchange transfusion except platelet count, being necessary a platelet transfusion. Clinical outcome was also positive. The patient was extubated to continuous positive airway pressure and inotropic support was discontinued 24 hours after the procedure. Neurological signs as well as cerebral ultrasound were normal. Enteral feedings were restarted on the fourth day of life and were well tolerated. He was discharged at home at corrected age of 40 weeks with normal magnetic resonance imaging and ophthalmologic examination. He will attend our neurodevelopmental follow-up clinic.

3 Discussion

Fat emulsions are a critical part of PN therapy given to infants who cannot yet, for developmental or medical reasons, use their enteral organ system for nutritional intake. It's use is essential to provide infants with the necessary calories, essential fatty acids and fat soluble vitamins for growth and energy expenditure. This applies especially to preterm infants with low energy stores and high metabolic and neurodevelopmental needs [1, 5]. Complications of i.v. lipid administration are relatively uncommon. However, inadvertent rapid infusion of IVFE is an inherent risk when fats are infused separately from the dextrose-amino acid solution. Often it is a result of human error, of infusion pump programming errors, misconnection of tubing or simply device failure [2, 3] as occurred in our patient. In most cases infants simply experienced triglyceridemia that completely reverse after the lipid infusion is discontinued [3, 4]. Unfortunately our patient experienced serious complications that illustrate the metabolic and physiologic side effects of hypertriglyceridemia.

It is known that acute severe hypertriglyceridemia can reduce pulmonary function, cause hemolysis, liver dysfunction and increase the chance for infection [5]. According to one report it could even worsen bronchopulmonary dysplasia in premature infants [6]. Our patient presented with lethargy, oxygen desaturation and apnea shortly after the lipid overdose.

Regarding respiratory symptoms, an underlying mechanism may relate to fat embolism in pulmonary microvessels with a decrease in diffusion capacity. Other possible explanation includes a diminished bioavailability of endothelial derived vascular relaxant nitric oxide and an increased production of prostaglandins and thromboxane [1, 5] which would increase pulmonary vascular resistance causing right-left shunting and reducing oxygenation.

The neurologic symptoms suggested an effect of hypertriglyceridemia on cerebral perfusion. Pathologic studies have revealed accumulations of fat in the cerebral vasculature [2]. In our patient head imaging studies were normal with no apparent short-term sequelae. However because of the potential long-term sequelae of severe hypertriglyceridemia he will attend our neurodevelopmental follow-up clinic.

Laboratory abnormalities found in our patient included metabolic acidosis, hyponatremia and mild hyperglycemia. The metabolic acidosis could be related to a poor tissue perfusion from sludging of lipids in the microvessels. The hyponatremia may have been an artefact due to the hypertriglyceridemia. Finally, it is known a mild glycemic response linked to IVFE.

In such cases of serious complications, there is scarce information about specific therapy, management and outcome of i.v. lipid overdose in the neonate and even less in the extremely preterm newborn. Standard management consists of removing the source of fat and giving supportive care. However, regarding our patient's clinical course who continued worsening despite supportive care we believed that he could benefit of double volume exchange transfusion. Therapeutic exchange transfusion has been previously used with varying success in the management of hyperbilirubinemia in very low birth weight infants [7] and in one case of lipid overdose in an infant of 32 weeks of gestational age [2]; however, to our knowledge, this is the first report of successful exchange transfusion in an extremely preterm newborn after accidental lipid overdose.

Despite advances in neonatal intensive care, exchange transfusion remains a high-risk procedure. Most reports suggest that sick, preterm infants, are more likely than term infants to experience serious complications from exchange transfusion as cardio-respiratory arrest, arrhythmias, thrombosis, thrombocytopenia, hypothermia, necrotizing enterocolitis and infection [8, 9]. The most common adverse events however, are asymptomatic, transient and treatable laboratory abnormalities such as thrombocytopenia, hypocalcemia and metabolic acidosis [8].

In our patient the procedure was well tolerated, without complications. Clinical symptoms and laboratory data normalized immediately after the exchange transfusion except platelet count as previously mentioned and clinical outcome was also positive.

Despite this positive outcome, prevention of inadvertent overdose of IVFE is of the utmost importance. To lessen the chance of overdose, our institution prepares now sterile syringes with appropriate volumes of IVFE for individual patients and all health care workers pay close attention to the hourly rate of infusion.

4 Conclusions

The use of IVFE is essential to providing optimum nutrition for sick neonates, and most adverse events associated with this therapy are related to high rates of infusion that exceed triglyceride clearance mechanisms. The use of individual doses will minimize the risk of potential overdose. In cases of profound, symptomatic hypertriglyceridemia due to lipid overdose, double-volume exchange transfusion should be considered.

Funding source

No external funding was secured for this study.

Financial disclosure

Authors have no financial relationships relevant to this article to disclose.

Conflict of interest

Authors have no conflicts of interest to disclose.

Informed consent

Written informed consent was obtained. The Hospital Ethics Committee approved the publication of this case.