Effect of Polymyxins on Anion Gap – A Retrospective Study

INTRODUCTION: Polymyxins are a class of antibiotics that have re-emerged into clinical practice after the development of multi-drug-resistant gram-negative bacteria. They were initially used in the 1970s but became unpopular due to systemic toxicities. Both Polymyxin B and Polymyxin E are used extensively to treat Carbapenem Resistant organisms. Polymyxin usage has been reported as a cause of negative anion gap.(1) The possible reason would be the polycationic structure of polymyxin, which would act as a strong polyvalent cation, leading to an increase in the concentration of unmeasured cations, leading to a falsely low value of anion gap or unmeasured anions.(2,3) In literature, Polymyxin has been always reported as a possible cause of low anion gap(4), but no observational studies look at the effect of polymyxin usage on anion gaps. Low anion gap is a common finding in the ICU.(5) This study aims to identify the association of polymyxin usage with a decrease in anion gap. OBJECTIVES: To study the change in corrected anion gap after polymyxin administration in critically ill patients admitted to medical and surgical ICU. MATERIALS AND METHODS: After approval by the Institutional Review Board, the study was done as a retrospective observational study. Patients admitted to the medical and surgical ICU who were treated with polymyxin and were fulfilling inclusion criteria with 2 arterial blood gas analyses done, one before and one after initiation within 48 hours, were included in the study. Patients with known confounders that can affect anion gap, like diabetic ketoacidosis and with acute clinical deterioration that could lead to a major accumulation of unmeasured anions, were excluded from the study. Data was collected from electronic medical records and were analyzed based on pre-determined statistical tools. RESULTS: 122 patients were screened and 70 patients were included in this study. This is an interim analysis of the study. The median age of the study group was 52(IQR 38-60). 39 patients were from the medical ICU, and 31 were from the surgical ICU. 57% of patients were men. Sepsis with organ failures was the most common cause of ICU admission. The mean corrected anion gap was 13.8(SD-5.9) before polymyxin administration and it was 12.2(SD-5.1) after polymyxin administration. This difference between the means was 1.63 and was compared by the paired sample T-test, which showed statistical significance with a p-value of 0.00 and a 95% confidence interval of the difference between the means ranging from 0.80 to 2.45. DISCUSSIONS/CONCLUSIONS: Polymyxins that are so frequently used in ICUs today significantly lower the anion gap by about 1–2.5. The clinical significance of this small change may frequently mask a high anion gap metabolic acidosis, especially in combination with hypoalbuminemia. We would recommend a prospective study to test the same along with serum polymyxin level correlation to strengthen the conclusions of this trial. Blood gas analysis taken during polymyxin administration before its distribution into its large volume of distribution may show a higher effect than what was shown in this study.