Table 1.

Clinical studies evaluating single thiamine supplementation in septic shock.

Authors	Diagnosis, number of patients and design	Dose and time	Results
Donnino et al. (13). Crit Care Med	Septic shock n = 88 Randomized, double-blind clinical trial Primary outcome: lactate levels 24 hours after the first dose Secondary outcomes: time to shock reversal, severity of illness and mortality	Thiamine 200 mg IV or placebo twice daily for 7 days or until hospital discharge	35% of the patients were thiamine deficient There was no difference in lactate levels at 24 hours (median: 2.5 mmol/L [1.5 - 3.4] vs. 2.6 mmol/L [1.6 - 5.1], p = 0.40) Overall mortality was 43% There was no difference in the proportion of patients with shock reversal between the thiamine and placebo groups (74% vs. 71%, p = 0.81) and mortality was also similar in both groups (42% vs 44%, p=1.00) There was no difference in APACHE II score (p = 0.15) and SOFA score (p= 0.41) between the groups Among thiamine deficient patients, those in the thiamine group had statistically significantly lower lactate levels at 24 hours (median 2.1 mmol/L [1.4 - 2.5] vs. 3.1 [1.9 - 8.3], p = 0.03)
Moskowitz et al. (50). Ann Am Thorac Soc	Septic shock n = 70 Secondary analysis of a randomized, double-blind trial Primary outcome: requirement for renal replacement therapy	Thiamine 200 mg IV or placebo twice daily for 7 days or until hospital discharge	32.8% of patients were deficient in thiamine Mortality of 37.1% (32.2% in the thiamine group and 41% in the placebo group; p=0.45) Lower serum creatinine levels (p=0.05) and a lower need for renal replacement therapy in the thiamine-treated group compared to placebo (3% vs. 21%, p=0.04) No differences regarding APACHE II, SOFA score, time of MV and other clinicals and demographics variables between the groups.
Holmberg et al. (48). J Crit Care	Septic shock with alcohol use disorders n = 53 Retrospective Primary outcomes: Mortality and practice patterns relating to thiamine administration in patients with alcohol use disorders	Low-dose (100 mg) was the most frequently ordered dose. Median time to administration was 9 (4–18) h	Thiamine deficiency was not evaluated 64% of the patients received thiamine at hospital admission Thiamine administration was associated with decreased mortality (44% vs. 79%, p = 0.02) No differences regarding SOFA score, hospital, and ICU-free days and other clinicals and demographics variables between the groups
Woolum et al. (14). Crit Care Med	Septic shock n = 1,049 Retrospective Primary outcomes: lactate clearance Secondary outcomes: 28-days mortality, change in SOFA score, AKI or RRT within the ICU, vasopressor-free, ventilator-free, and ICU-free days within the 28 days following ICU admission	High-dose thiamine (500 mg) was the most frequently ordered dose. Thiamine was administered for a median of 3 days	Thiamine deficiency not evaluated The median time from hospital admission to thiamine administration was 6.4 hours Thiamine administration was associated with improved lactate clearance (hazard ratio, 1.307; 95% CI, 1.002–1.704) and a reduction in 28-day mortality (hazard ratio, 0.666; 95% CI, 0.490–0.905) There were no differences in any other secondary outcomes
Harun et al. (15). Crit Care and Shock	Septic shock n = 72 Randomized clinical trial Primary outcome: lactate clearance	Thiamine 200 mg IV or placebo twice daily for 3 days	Thiamine deficiency not evaluated Supplementation was not associated with relative lactate changes (p= 0.091) No differences regarding SOFA score, ICU LOS and ICU mortality
Miyamoto et al. (46). Crit Care Med	Septic shock n = 68,571 Retrospective Primary outcome: 28-day mortality	Low-dose (100 mg and 200 mg) were the most frequently ordered doses within 2 days of admission	Thiamine deficiency not evaluated No significant differences between the 100-mg thiamine group and the control group (risk difference, 0.6%; 95% CI, −0.3% to 1.4%) and the 200-mg thiamine group and the control group (risk difference, −0.3%; 95% CI, −1.3% to 0.8%) regarding mortality
Petsakul et al. (49). BMC Anesthesiology	Septic shock n = 50 Randomized clinical trial Primary outcome: decrease in vasopressor requirement within 7 days	Thiamine 200 mg IV or placebo twice daily for 7 days or until hospital discharge.	Thiamine deficiency was not evaluated No difference in vasopressor-free days between the thiamine and placebo groups (p = 0.197) There was a reduction in the dependence index on vasopressors (0.14 mmHg−1 vs.0.03 mmHg−1, p = 0.02) and in the serum lactate concentration at 24 h (1.0 mmol/L vs. 0.5 mmol/L, p = 0.024) after initial supplementation No difference was observed in SOFA score within 7 days, vasopressor dependency index within 4 days and 7 days, or 28-day mortality

AKI, Acute kidney injury; APACHE II, Acute Physiology And Chronic Health Evaluation; IV, intravenous; ICU, intensive care unit; LOS, length of stay; MV, Mechanical ventilation; RRT, Renal replacement treatment; SOFA, sequential organ failure assessment.