Objective: Stewart's physicochemical approach to acid-base balance defines
the aetiology of a metabolic acidosis by quantifying anions of tissue acids
(TA), which consist of unmeasured anions (UMA) and/orlactate. We hypothesi
sed that an increase in TA during metabolic acidosis would lead to a compen
satory fail in the plasma chloride (C1) relative to sodium (Cl:Na ratio) in
order to preserve electro-neutrality. Thus, the Cl:Na ratio could be used
as a simple alternative to the anion gap in identifying raised TA.
Patients: Two hundred and eighty two consecutive patients who were admitted
to our Paediatric Intensive Care were enrolled in the study.
Interventions: We obtained 540 samples (admission n = 282, 24 h n = 258) fo
r analysis of blood chemistry, lactate and quantification of TA and UMA. Sa
mples were subgrouped into those with metabolic acidosis (standard bicarbon
ale < 22 mmol/l) either with or without increased UMA (> 3 mEq/l).
Measurements and results: Metabolic acidosis occurred in 46 % of samples, o
f which 52.3 % (120/230) had increased UMA. The dominant component of TA wa
s UMA rather than lactate, and these two components did not always rise in
tandem. Our hypothesis of relative hypochloraemia was supported by a lower
Cr:Na ratio (P < 0.0001) but not a lower absolute C1 (P = 0.5) in the acido
tic subgroup with raised UMA, and by the inverse relationship between TA an
d the Cl:Na ratio. (coefficient of determination (r(2)) = -0.37, P < 0.0001
). The best discriminator for the presence of raised TA was the albumin-cor
rected anion gap (AG(corr)), however, this could not track changes in TA wi
th clinical accuracy. The Cl:Na ratio discriminated reasonably well, a rati
o of < 0.75 identified TA (positive predictive value (PPV) 88 %) with a lik
elihood ratio (LR) similar to the AG (7.8 vs 7.4). Conversely, a high ratio
(> 0.79) excluded TA (PPV 81%, LR 4.5). Base deficit (BD) and lactate perf
Conclusion: In metabolic acidosis due to TA, plasma C1 concentration decrea
ses relative to sodium. The Cl:Na ratio is a simple alternative to the AG f
or detecting TA in this setting.