Daily laxative therapy reduces organ dysfunction in mechanically ventilated patients: a phase II randomized controlled trial

Rodrigo Palacio de Azevedo, Flávio Geraldo Resende Freitas, Elaine Maria Ferreira, Luciano Cesar Pontes de Azevedo, Flávia Ribeiro Machado, Rodrigo Palacio de Azevedo, Flávio Geraldo Resende Freitas, Elaine Maria Ferreira, Luciano Cesar Pontes de Azevedo, Flávia Ribeiro Machado

Abstract

Introduction: Constipation is a common problem in intensive care units. We assessed the efficacy and safety of laxative therapy aiming to promote daily defecation in reducing organ dysfunction in mechanically ventilated patients.

Methods: We conducted a prospective, randomized, controlled, nonblinded phase II clinical trial at two general intensive care units. Patients expected to remain ventilated for over 3 days were randomly assigned to daily defecation or control groups. The intervention group received lactulose and enemas to produce 1-2 defecations per day. In the control group, absence of defecation was tolerated up to 5 days. Primary outcome was the change in Sequential Organ Failure Assessment (SOFA) score between the date of enrollment and intensive care unit discharge, death or day 14.

Results: We included 88 patients. Patients in the treatment group had a higher number of defecations per day (1.3 ± 0.42 versus 0.7 ± 0.56, p < 0.0001) and lower percentage of days without defecation (33.1 ± 15.7% versus 62.3 ± 24.5%, p < 0.0001). Patients in the intervention group had a greater reduction in SOFA score (-4.0 (-6.0 to 0) versus -1.0 (-4.0 to 1.0), p = 0.036) with no difference in mortality rates or in survival time. Adverse events were more frequent in the treatment group (4.5 (3.0-8.0) versus 3.0 (1.0-5.7), p = 0.016), including more days with diarrhea (2.0 (1.0-4.0) versus 1.0 (0-2.0) days, p < 0.0001). Serious adverse events were rare and did not significantly differ between groups.

Conclusions: Laxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score.

Trial registration: Clinical Trials.gov NCT01607060, registered 24 May 2012.

Figures

Fig. 1
Fig. 1
Study flow chart. GI gastrointestinal, ICU intensive care unit
Fig. 2
Fig. 2
Kaplan-Meier curve demonstrating the 28-day survival of the ICU patients according to their group allocation. Cox proportional hazards analysis results following adjustment for the category of admission, APACHE score, age and SOFA score (hazard ratio 1.772, 95 % confidence interval 0.789 to 3.978.51; p = 0.166) are shown. Dotted line intervention group; filled line control group

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