Metoclopramide or domperidone improves post-pyloric placement of spiral nasojejunal tubes in critically ill patients: a prospective, multicenter, open-label, randomized, controlled clinical trial.

INTRODUCTION: The use of prokinetic agents on post-pyloric placement of spiral nasojejunal tubes is controversial. The aim of the present study was to examine if metoclopramide or domperidone can increase the success rate of post-pyloric placement of spiral nasojejunal tubes. METHODS: A multicenter, open-label, randomized, controlled trial was conducted in seven hospitals in China between April 2012 and February 2014. Patients admitted to the intensive care unit and requiring enteral nutrition for more than three days were randomly assigned to the metoclopramide, domperidone or control groups (1:1:1 ratio). The primary outcome was defined as the success rate of post-pyloric placement of spiral nasojejunal tubes, assessed 24 hours after initial placement. Secondary outcomes included success rate of post-D1, post-D2, post-D3 and proximal jejunum placement and tube migration distance. Safety of the study drugs and the tubes during the entire study period were recorded. RESULTS: In total, 307 patients were allocated to the metoclopramide (n = 103), domperidone (n = 100) or control group (n = 104). The success rate of post-pyloric placement after 24 hours in the metoclopramide, domperidone and control groups was 55.0%, 51.5% and 27.3%, respectively (P = 0.0001). Logistic regression analysis identified the use of prokinetic agents, Acute Physiology and Chronic Health Evaluation (APACHE) II score <20, Sequential Organ Failure Assessment (SOFA) score <12 and without vasopressor as independent factors influencing the success rate of post-pyloric placement. No serious drug-related adverse reaction was observed. CONCLUSIONS: Prokinetic agents, such as metoclopramide or domperidone, are effective at improving the success rate of post-pyloric placement of spiral nasojejunal tubes in critically ill patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-TRC-12001956 . Registered 21 February 2012.

[Amelioration of inflammatory reaction in patients with severe sepsis with inosine].

OBJECTIVE: To evaluate the therapeutic effect of inosine in patients with severe sepsis. METHODS: A prospective study was conducted. Eighty-five severe sepsis patients hospitalized in intensive care unit (ICU) from March 2011 to August 2012 were included and randomized into three groups: 25 cases as conventional therapy group, who were treated with routine treatments; 28 patients were given inosine within 6 hours besides routine treatments; 32 patients were given inosine after 6 hours together with routine treatments. Inosine was given in the latter two groups by intravenous infusion (600 mg twice a day) for 10-14 days or to the end of the research when patients died or discharged from ICU. Before or after the treatment, venous blood was collected for determination of pro-inflammatory factors and organ function parameters. Average duration of stay in ICU and mortality rate were analyzed. RESULTS: Compared with conventional therapy group, the levels of pro-inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were decreased in inosine in both within 6-hour and after 6-hour groups (TNF-α: 9.6 ± 4.1 ng/L, 10.8 ± 2.8 ng/L vs. 18.2 ± 3.3 ng/L, IL-6: 123.0 ± 10.1 ng/L, 132.0 ± 18.4 ng/L vs. 172.0 ± 17.9 ng/L, CRP: 42.0 ± 10.3 mg/L, 45.0 ± 8.6 mg/L vs. 61.0 ± 12.7 mg/L, all P<0.05), but there was no statistical significance in the content of IL-10 (53.0 ± 9.4 ng/L, 56.0 ± 10.8 ng/L vs. 58.0 ± 11.2 ng/L, both P>0.05). The lowering of alanine transaminase (ALT), total bilirubin, B-type natriuretic peptide (BNP), oxygenation index was more marked in inosine within 6-hour and after 6-hour groups than those of conventional therapy group (ALT: 42.0 ± 10.8 U/L, 46.0 ± 7.9 U/L vs. 63.0 ± 9.4 U/L, total bilirubin: 16.3 ± 6.7 µmol/L, 18.3 ± 7.3 µmol/L vs. 28.1 ± 8.5 µmol/L, BNP: 322.0 ± 28.7 ng/L, 347.0 ± 31.4 ng/L vs. 428.0 ± 43.2 ng/L, oxygenation index: 210.0 ± 23.8 mm Hg, 198.0 ± 21.4 mm Hg vs. 163.0 ± 15.2 mm Hg, all P<0.05). However, the difference of these values showed no significant difference between the two inosine groups (all P>0.05). There was no statistical significance in ICU stay days (22.4 ± 6.3 days, 19.8 ± 4.6 days, 23.1 ± 5.2 days) and mortality rate (36.0%, 32.1%, 34.4%) among three groups (all P>0.05). CONCLUSION: For severe sepsis patients, on the base of routine treatments, normal dose of inosine can lower the level of pro-inflammatory factors and ameliorate organ function, but it cannot decrease average ICU stay days and mortality rate.