Relationship of Admission Serum Anion Gap and Prognosis of Critically Ill Patients: A Large Multicenter Cohort Study
Ruohan Li, Xuting Jin, Jiajia Ren, Guorong Deng, Jiamei Li, Ya Gao, Jingjing Zhang, Linyun Du, Jueheng Liu, Xiu Liu, Xiaochuang Wang, Gang Wang
Abstract
Background. There were controversies over the relationship between Anion gap (AG) and mortality in critically ill patients. Therefore, a large multicenter cohort study was conducted to evaluate the association of AG and mortality in large-scale intensive care units (ICUs) patients. Methods. This retrospective cohort study included adult ICU patients enrolled from eICU Collaborative Research Database. According to initial serum AG upon ICU admission, patients were divided into three groups: <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:mtext>AG</a:mtext> <a:mo><</a:mo> <a:mn>8</a:mn> <a:mtext> </a:mtext> <a:mtext>mmol</a:mtext> <a:mo>/</a:mo> <a:mtext>L</a:mtext> </a:math> , <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mn>8</c:mn> <c:mo>≤</c:mo> <c:mtext>AG</c:mtext> <c:mo>≤</c:mo> <c:mn>16</c:mn> <c:mtext> </c:mtext> <c:mtext>mmol</c:mtext> <c:mo>/</c:mo> <c:mtext>L</c:mtext> </c:math> , and <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mtext>AG</e:mtext> <e:mo>></e:mo> <e:mn>16</e:mn> <e:mtext> </e:mtext> <e:mtext>mmol</e:mtext> <e:mo>/</e:mo> <e:mtext>L</e:mtext> </e:math> . Logistic regression models were built to investigate the association between serum AG and ICU and hospital mortalities. Serum AG was added into Acute Physiology and Chronic Health Evaluation (APACHE) IV score and the model discrimination was assessed by the area under the curve (AUC) of receiver operating characteristic curves. The relationship between serum AG and mortalities in patients with different acid-base status and serum lactate were also evaluated. An external validation was performed with the Critical care database comprising patients with infection at Zigong Fourth People’s Hospital. Results. A total of 8520 patients entered the final cohort. There are 42 patients with <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mtext>serum</g:mtext> <g:mtext> </g:mtext> <g:mtext>AG</g:mtext> <g:mo><</g:mo> <g:mn>8</g:mn> <g:mtext> </g:mtext> <g:mtext>mmol</g:mtext> <g:mo>/</g:mo> <g:mtext>L</g:mtext> </g:math> , 3238 patients with <i:math xmlns:i="http://www.w3.org/1998/Math/MathML" id="M5"> <i:mn>8</i:mn> <i:mo>≤</i:mo> <i:mtext>AG</i:mtext> <i:mo>≤</i:mo> <i:mn>16</i:mn> <i:mtext> </i:mtext> <i:mtext>mmol</i:mtext> <i:mo>/</i:mo> <i:mtext>L</i:mtext> </i:math> , and 5240 patients with <k:math xmlns:k="http://www.w3.org/1998/Math/MathML" id="M6"> <k:mtext>AG</k:mtext> <k:mo>></k:mo> <k:mn>16</k:mn> <k:mtext> </k:mtext> <k:mtext>mmol</k:mtext> <k:mo>/</k:mo> <k:mtext>L</k:mtext> </k:math> . <m:math xmlns:m="http://www.w3.org/1998/Math/MathML" id="M7"> <m:mtext>Serum</m:mtext> <m:mtext> </m:mtext> <m:mtext>AG</m:mtext> <m:mo>></m:mo> <m:mn>16</m:mn> <m:mtext> </m:mtext> <m:mtext>mmol</m:mtext> <m:mo>/</m:mo> <m:mtext>L</m:mtext> </m:math> is related with increased ICU mortality (odds ratio [OR], 1.530; 95% confidence interval [CI], 1.305–1.794) and hospital mortality (OR, 1.618; 95% CI, 1.415–1.849), compared with <o:math xmlns:o="http://www.w3.org/1998/Math/MathML" id="M8"> <o:mn>8</o:mn> <o:mo>≤</o:mo> <o:mtext>AG</o:mtext> <o:mo>≤</o:mo> <o:mn>16</o:mn> <o:mtext> </o:mtext> <o:mtext>mmol</o:mtext> <o:mo>/</o:mo> <o:mtext>L</o:mtext> </o:math> . Adding Serum AG to APACHE IV score could statistically improve the prediction of ICU (0.770 [0.761–0.779] to 0.774 [0.765–0.783], <q:math xmlns:q="http://www.w3.org/1998/Math/MathML" id="M9"> <q:mi>P</q:mi> <q:mo>=</q:mo> <q:mn>0.001</q:mn> </q:math> ) and hospital mortalities (0.756 [0.747–0.765] to 0.761 [0.751–0.770], <s:math xmlns:s="http://www.w3.org/1998/Math/MathML" id="M10"> <s:mi>P</s:mi> <s:mo>=</s:mo> <s:mn>0.012</s:mn> </s:math> ). The associations between serum AG and mortalities remain robust in patients with different acid-base statuses and serum lactate. The findings are validated in the external cohort. Conclusions. Initial <u:math xmlns:u="http://www.w3.org/1998/Math/MathML" id="M11"> <u:mtext>serum</u:mtext> <u:mtext> </u:mtext> <u:mtext>AG</u:mtext> <u:mo>></u:mo> <u:mn>16</u:mn> <u:mtext> </u:mtext> <u:mtext>mmol</u:mtext> <u:mo>/</u:mo> <u:mtext>L</u:mtext> </u:math> after ICU admission is associated with increased mortality in critically ill patients.