No Effect of Alkalosis on Mortality in ICU Patients With Sepsis

In the first study ever to evaluate the prevalence or outcomes of metabolic alkalosis in patients with severe sepsis or septic shock, metabolic alkalosis was found to be associated with decreased 30-day and 12-month mortalities. However, after multivariate analysis, the effect disappeared. Results were published January 3, 2017, in PLoS One.1

Alkalosis is the condition in which arterial pH is higher than the body’s normal pH (>7.45). In patients with sepsis and trauma, it most frequently occurs as a result of treatment for hypotension, shock, or acidosis. Alkalosis has been reported to be the most common acid-base disturbance encountered in hospitalized patients.2

To investigate the relationship between metabolic alkalosis and mortality, as well as the relationship between metabolic alkalosis and intensive care unit (ICU) length of stay, Simon Kreü, MD, from Lund University’s Institute for Clinical Sciences in Malmö, Sweden, and colleagues analyzed arterial blood gas values in patients with severe sepsis and/or septic shock admitted to the ICUs of Sweden’s Halmstad and Varberg county hospitals.

Results showed a protective effect of metabolic alkalosis for 30-day (P =.001) and 12-month (P =.011) mortality after bivariate analysis, correcting for age. However, that effect was lost after multivariate analysis correcting for age, sex, pH on admission, base excess (BE) on admission, and Simplified Acute Physiology Score III (SAPS III) and acute kidney injury. Contrary to the investigators’ hypothesis, metabolic alkalosis did not have a deleterious effect on 30-day and 12-month mortality. However, patients with metabolic alkalosis had a significantly longer ICU length of stay compared with those without metabolic alkalosis (6 [3-10] vs 2 [1-4] days; P <.001).

In an email interview, Dr Kreü told Infectious Disease Advisor that the results of the study do not suggest that metabolic alkalosis protects against mortality. “We speculate that the mortality curve is U-shaped, with extremes of pH associated with poor outcome,” he stated. “We would have liked to investigate subgroups based on admission pH; however, the study design and sample size did not allow for this. What our study shows is that there is no significant difference in mortality between patients with metabolic alkalosis and those with acidosis and normal pH.”

When asked about the clinical implications of the study, Dr Kreü noted that physicians should be aware that metabolic alkalosis is not a benign condition. “It is often iatrogenic and should be avoided. Theoretically the leftward shift of the [oxygen-hemoglobin] dissociation curve caused by alkalosis impairs tissue oxygen delivery, with all its implications.”

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  1. Kreü S, Jazrawi A, Miller J, Baigi A, Chew M. Alkalosis in critically ill patients with severe sepsis and septic shock. PLoS ONE. 2017;12:e0168563. doi:10.1371/journal.pone.0168563
  2. Hodgkin JE, Soeprono FF, Chan DM. Incidence of metabolic alkalemia in hospitalized patients. Crit Care Med. 1980;8:725-728.