Low volume status linked to adverse outcomes in shiga-toxin producing Eschericia coli illness

1. Based on a systematic review and meta-analysis, low volume status (as estimated with clinical judgement or hematocrit values) in children presenting with shiga-toxin producing Escherichia coli (STEC) diarrheal illness was associated with increased risk of complications from hemolytic uremic syndrome (HUS).

2. Intravenous fluid (IVF) administration given prior to the diagnosis of HUS was linked to lower risk of central nervous system sequelae and need for renal replacement therapy.

Evidence Rating Level: 2 (Good)       

Study Rundown: Shiga-toxin producing E. coli (STEC) is a cause of infectious diarrhea, and 10-15% of children afflicted with this can develop hemolytic-uremic syndrome (HUS). HUS is characterized by hemolytic anemia, renal failure, and thrombocytopenia. Many patients with HUS develop oligo-anuric renal failure, CNS involvement, and require renal replacement therapy (RRT). Close to one-third of patients who recover will have ongoing chronic kidney disease as a result of HUS. Intravenous fluids are used conservatively due to concern for volume overload during the oligo-anuric phase. The current study sought to evaluate the effects of clinical hypovolemia and intravenous fluid therapy during the initial presentation of STEC and the risk of HUS and its consequences.

In this meta-analysis, which used pooled data from 8 studies, low volume status/elevated hematocrit was associated with oligo-anuric renal failure, need for RRT, and death. The risk of HUS development specifically was not able to be assessed using these studies. Use of intravenous fluids from time of medical presentation to diagnosis of HUS was linked to lower risk of need for RRT. IVF administration within the first 4 days of diarrhea onset was also associated with lower risk of oligo-anuric renal failure. The strength of the study was the meta-analysis, however it did rely on a mix of prospective and retrospective data from several different countries. Also, the clinical relevance of using hematocrit as a marker for volume resuscitation is questionable in a disease state with hemolysis.

Click to read the study, published in JAMA Pediatrics

Relevant Reading: Relative Nephroprotection During Escherichia coli O157:H7 Infections: Association With Intravenous Volume Expansion

In-Depth [meta-analysis]: This study included 8 studies (3 retrospective cohort, 3 prospective cohort, 2 case-control) that evaluated STEC infections and HUS presentations. Exposures under study included intravenous fluids (either from time of presentation to diagnosis of HUS, or within 4 days of symptom onset), and low hydration status (from hematocrit at presentation greater than 23% or clinical judgement). Studies were excluded if the outcomes could not be correlated to fluid/hydration status, all participants underwent the same fluid administration protocol, all patients developed outcomes of interest, or if volume status was evaluated after administration of fluids.

A total of 1511 children were included in the combined analysis. Patients with low hydration status were at increased risk of oligo-anuric renal failure (OARF) (OR 2.38; 95%CI 1.30-4.35), need for RRT (OR 1.90; 95% CI 1.25-1.90), and death (OR 5.13; 95%CI 1.50-17.57). Intravenous fluids given from presentation to HUS diagnosis was associated with reduced need for RRT (OR 0.26; 95%CI 0.11-0.60), and CNS involvement (OR 0.48; 95%CI 0.07-0.91). IVF within 4 days of diarrhea onset demonstrated lower risk of OARF (OR 0.16; 95%CI 0.05-0.51).

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