Effects of thiamine on vasopressor requirements in patients with septic shock: a prospective randomized controlled trial.

BACKGROUND: Thiamine, an essential vitamin for aerobic metabolism and glutathione cycling, may decrease the effects of critical illnesses. The objective of this study was to determine whether intravenous thiamine administration can reduce vasopressor requirements in patients with septic shock. METHODS: This study was a prospective randomized double-blind placebo-controlled trial. We included adult patients with septic shock who required a vasopressor within 1-24 h after admission between March 2018 and January 2019 at a tertiary hospital in Thailand. Patients were divided into two groups: those who received 200 mg thiamine or those receiving a placebo every 12 h for 7 days or until hospital discharge. The primary outcome was the number of vasopressor-free days over 7 days. The pre-defined sample size was 31 patients per group, and the study was terminated early due to difficult recruitment. RESULTS: Sixty-two patients were screened and 50 patients were finally enrolled in the study, 25 in each group. There was no difference in the primary outcome of vasopressor-free days within the 7-day period between the thiamine and placebo groups (mean: 4.9 days (1.9) vs. 4.0 days (2.7), p = 0.197, mean difference - 0.9, 95% CI (- 2.9 to 0.5)). However, the reductions in lactate (p = 0.024) and in the vasopressor dependency index (p = 0.02) at 24 h were greater among subjects who received thiamine repletion vs. the placebo. No statistically significant difference was observed in SOFA scores within 7 days, vasopressor dependency index within 4 days and 7 days, or 28-day mortality. CONCLUSIONS: Thiamine was not associated to a significant reduction in vasopressor-free days over 7-days in comparison to placebo in patients with septic shock. Administration of thiamine could be associated with a reduction in vasopressor dependency index and lactate level within 24 h. The study is limited by early stopping and low sample size. TRIAL REGISTRATION: TCTR, TCTR20180310001. Registered 8 March 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=3330 .

Temperature Dependence of Plasmodium falciparum Erythrocytic Stage Development.

Plasmodium falciparum infection causes febrile illness and severe disease with multiple organ failure and death when treatment is delayed. Antipyretic treatment is standard, and inducing hypothermia has been proposed to protect the brain in cerebral malaria. Here, we investigated the temperature dependence of asexual-stage parasite development and parasite multiplication in vitro. Plasmodium falciparum laboratory strain TM267 was incubated for 2 hours (short exposure) or 48 hours (continuous exposure) at different temperatures (32°C, 34°C, 35°C, 38°C, 39°C, and 40°C). The starting parasite developmental stage (ring, trophozoite, or schizont) varied between experiments. The parasite multiplication rate (PMR) was reduced under both hyper- and hypothermic conditions; after continuous exposure, the mean PMR ± SD was 9.1 ± 1.2 at 37°C compared with 2.4 ± 1.8 at 32°C, 2.3 ± 0.4 at 34°C, and 0.4 ± 0.1 at 40°C (P < 0.01). Changes in PMR were not significant after 2-hour exposure at temperatures ranging from 32°C to 40°C. Morphological changes in parasite cytoplasm and nucleus could be observed after long exposure to low or high temperature. After 48-hour incubation, rosette formation (≥ 2 uninfected red blood cells bound to infected red blood cells) was decreased at 34°C or 39°C compared with that at 37°C. In conclusion, both hyper- and hypothermia reduce PMR and delay erythrocytic stage development of P. falciparum, subsequently reducing rosette formation.