In this retrospective study, we investigated the association between the quantity of diarrhea and in-hospital mortality in 231 patients with newly developed diarrhea in the ICU. Multivariable analysis revealed that diarrhea quantity was an independent predictor of in-hospital mortality. This association was consistent across several sensitivity analyses. Similarly, the greater the quantity of diarrhea, the higher the ICU 28-day and 90-day mortalities. To the best of our knowledge, this is the first study to show an association between the quantity of diarrhea and mortality.
Previous studies have reported an association between the presence of diarrhea and mortality; however, no studies have examined whether mortality increases with a greater quantity of diarrhea [14, 42]. A systematic review of 12 studies, most of which used the definition of diarrhea as three or more loose or liquid stools, showed an association between diarrhea and mortality (RR: 1.43; 95% CI: 1.03–1.98; I2 = 86.7%; n = 11,866) [14]. We focused on the quantity of diarrhea in this study and showed that mortality increased with increasing quantity of diarrhea according to the adjusted RR in patients with newly developed diarrhea in the ICU. More diarrhea leads to worse electrolyte imbalance, nutritional deficit, and hemodynamic instability owing to water loss [17, 18]. Clinicians need to correct electrolytes, adjust enteral nutrition, and increase fluid administration as diarrhea increases.
The reason for the higher mortality rate among patients with a greater quantity of diarrhea remains unclear. Patients with CDI or cytomegalovirus enteritis, which are common diseases causing diarrhea, have been reported to have higher mortality, but they were excluded from our study. Indeed, diarrhea can cause dehydration, electrolyte abnormalities, metabolic acidosis, malnutrition, device contamination, and wound contamination [1]. However, since dehydration and electrolyte abnormalities are carefully corrected in the ICU, it is questionable to assume that diarrhea directly contributes to mortality.
Possible explanations for the relationship between diarrhea and mortality are as follows. First, diarrhea can be a sign of gastrointestinal organ failure that is associated with a high risk of mortality [4, 14, 43]. Patients with diarrhea have higher severity scores than those without diarrhea [2, 6, 8–10, 14]. In our study, most patients received treatments that could cause diarrhea, such as enteral nutrition and antimicrobials. These interventions are part of the treatment regimen for critically ill patients. In addition, approximately 60% of patients were on ventilation and used vasopressors, which means that patients with diarrhea have a higher severity of illness. In our analysis, we adjusted for the SOFA score, an organ disorder score that does not include gastrointestinal function and showed that diarrhea is a risk factor for mortality independent of other organ disorders. The quantity of diarrhea may be a candidate when adjusting for organ dysfunction. Second, diarrhea can be a sign of a disorder of the gut microbiota, which is called dysbiosis. This dysbiosis is believed to increase vulnerability to nosocomial infections, sepsis, organ failure, and mortality [44, 45]. The development of diarrhea might be associated with dysbiosis in the gut microbiota of ICU patients [46]. However, our data and analyses are not sufficiently conclusive to prove them. Further research is needed to test these hypotheses.
This study had several limitations. First, the measurement of diarrhea was not completely accurate. If diarrhea spills out of the diaper, it may not be measured. In this case, this may have led to an underestimation of the quantity of diarrhea. However, we believe that this measurement of the quantity of diarrhea reflects real clinical practice. Second, the inter-rater reliability of BSCS was not confirmed in our study. The reliability of BSCS has been studied and widely used [26–32], and our nurses were trained to measure BSCS in clinical practice, which should have minimized the inter-rater variability. Third, we did not obtain information on urinary catheter insertion. However, we expect that most patients in this study had urinary catheters because only critically ill patients were admitted to our ICU (a median SOFA score of 9 and 63.6% of them were on ventilators). Finally, this was a single-center study, and the generalizability of the results is limited.