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

Abstract

IntroductionConstipation 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.MethodsWe 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.ResultsWe 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.ConclusionsLaxative therapy improved daily defecation in ventilated patients and was associated with a greater reduction in SOFA score.Trial registrationClinical Trials.gov NCT01607060, registered 24 May 2012.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-1047-x) contains supplementary material, which is available to authorized users.

Constipation Occurrence among Critically Ill patients

“…Our findings were congruent with De Azevedo et al (19) who reported that laxative therapy enhanced the daily defecation for the mechanically ventilated patients. Also, these data was stressed by Van der Spoel et al (20) who mentioned that patients who received both lactulose and polyethylene glycol were defecating promptly and effectively than placebo.…”

Factors associated with time to defecate and outcomes in critically ill patients: a prospective, multicentre, observational study

“…We studied 396 out of 2037 (19%) patients admitted to ICU ( Fig. 1 and Table 1 intensive care stay of 6 (4-8 [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]) days (Fig. 2).…”

“…The association of laxatives with shorter times to defecate is unsurprising and has been described [2,11,22].…”

“…Constipation has been inconsistently associated with mortality, with studies reporting little association [1,3,5,11,25] whereas others have reported an association of ≥ 3 days' constipation with mortality [4,18,19]. It is difficult to reach a conclusion, particularly as time to defecate is associated with observation time (on ICU), which in turn is a consequence of critical illness that increases mortality [1,4,5,[9][10][11]25].…”

Efficacy of daiokanzoto in chronic constipation refractory to first-line laxatives

“…In a previous study, it was observed that preventing constipation improved multi-organ failure in critically ill patients (7). Therefore, it is important that evidence of the clinical effects of the treatment of constipation are accumulated to improve the care of patients.…”