Serum anion gap in the differential diagnosis of metabolic acidosis in critically ill newborns

Objectives: To determine in critically ill newborn infants (1) the range of the serum anion gap without metabolic acidosis and (2) whether the serum a nion gap can be used to distinguish newborns with lactic acidosis from thos e with hyperchloremic metabolic acidosis. Study design: Umbilical arterial blood gases and serum electrolyte and lact ate concentrations were measured simultaneously in 210 samples from 63 infa nts over the first week of life. Metabolic acidosis was defined as a blood base deficit (BD) >4 mmol/L. The anion gap was calculated as [Na+] - [Cl-] - [TCO2,]. Lactic acidosis was defined as a serum lactate concentration >2 SD above the mean serum lactate concentration in samples without metabolic acidosis. Results: In 89 blood samples with BD <4 mmol/L, serum lactate:concentration decreased with postnatal age (r = 0.51). The upper limit of,serum lactate concentration was 3.8 mmol/L at less than 48 hours, 2.4 mmol/L between 48 a nd 96 hours, and 1.5 mmol/L for infants greater than 96 hours of age. The m ean serum anion gap +/- 2 SD in 174 samples without lactic acidosis was 8 /- 4 mmol/L; in 36 samples with lactic acidosis it was 16 +/- 9 mmol/L (P < .0001). Serum anion gap and lactate concentration were poorly correlated f or samples without lactic acidosis (r = 0.04) but highly correlated in thos e with lactic acidosis (r = 0.81, P < .0001). None of the 85 samples with m etabolic acidosis but without lactic acidosis had an anion gap >16 mmol/L. Only 4 of 36 samples with lactic acidosis had an anion gap <8 meq/L. mmol/L ever, 25 of 36 samples with lactic acidosis had serum-anion gaps, of 8 to 16 mmol/L. Conclusion: In the presence of metabolic acidosis, a serum anion gap >16 mm ol/L is highly predictive of lactic acidosis; a serum anion gap <8 is highl y predictive of the absence of lactic acidosis; an anion gap = 8 - 16 mmol/ L has no use in the differential diagnosis of metabolic acidosis in the cri tically ill newborn.