Effect of Thiamine Administration on Lactate Clearance and Mortality in Patients With Septic Shock
Woolum JA. Crit Care Med 2018; 46:1747–1752
doi: 10.1097/CCM.0000000000003311
Clinical Question: Does the administration of thiamine lead to more rapid lactate clearance and improved clinical outcomes in patients with septic shock?
Background: Septic shock is characterized by a hypermetabolic state that resembles thiamine deficiency. Thiamine deficiency is common in critically ill patients. A previous pilot randomized controlled trial had shown significantly lower lactate levels and improved mortality over time in patients with septic shock who were thiamine deficient.
Design: Retrospective, matched cohort study, based on data collected from electronic medical records. Regression analysis was performed with mortality as competing event (if the patient died with a lactate level of more than 2 mmol/l, clearance was considered not achieved). Three models were constructed: (1) with lactate levels alone, (2) after adjustment for age, sex, and race, and (3) with age, sex, race, and other likely factors that influence mortality and lactate clearance. A Cox proportional hazards model was constructed along the same lines for 28-day mortality.
Setting: A single academic center in the US. The study covered a 4-year period between January 1, 2013, and January 1, 2017.
Population: An electronic medical database was queried based on the diagnostic code for septic shock according to 9thor 10thedition of the International Classification of Diseases (ICD).
Inclusion criteria:
- Patients who were coded as septic shock on the electronic medical database
- 18 years and older
- Admission to medical or surgical services
Exclusion criteria:
- Less than 18 years of age
- Septic shock not present at admission
After validation using the Sepsis-3 criteria, 1049 patients were included out of the 2270 patients who were initially screened. Out of this cohort, 123 patients who received thiamine were matched with 246 patients who did not.
Intervention: Intravenous administration of thiamine in any dose within the first 24 hours of hospital admission.
Control: Patients who received thiamine were matched with a cohort who did not receive thiamine in a 1:2 ratio.
Outcomes:
Primary outcome: Patients who were administered intravenous thiamine in the first 24 hours of hospital admission had more rapid lactate clearance. All three regression models revealed improved lactate clearance with thiamine administration. The subdistribution hazard ratios in the three models ranged between 1.292–1.339. The effect of thiamine on lactate clearance was significantly more in female patients on a gender-based interaction model.
Secondary outcomes: Thiamine was found to significantly reduce 28-day mortality on the three Cox’s proportional hazards models. Similar to lactate clearance, the benefit was more evident in female patients. There was no significant difference in other secondary outcomes including change in SOFA scores on day 5 compared to baseline, vasopressor-free days, ventilator-free days, ICU-free days, incidence of AKI, and the requirement for renal replacement therapy.
Authors’ conclusions:
In patients with septic shock, intravenous thiamine, administered within 24 hours of ICU admission resulted in more rapid lactate clearance and a significantly reduced 28-day mortality.
Strengths:
- This is the largest study so far to evaluate the effect of thiamine on lactate clearance and mortality in patients with patients with septic shock.
- Matching was carried out between patients who had thiamine and those who did not.
- Regression analysis was performed with mortality as the competing event.
Weaknesses:
- This a retrospective observational study based on data derived from electronic medical records. Although matching was carried out between patients who received thiamine and those who did not, there may be confounders that have not been accounted for.
- The dose of thiamine was variable and ranged between 100–500 mg per day.
- Thiamine levels were not measured; it is unclear whether the benefit may be related to thiamine deficiency.
- Lactate measurements were presumably carried out at random intervals; this may have led to miscalculation of time to lactate clearance.
- The mortality of the cohort was high compared to contemporaneous studies (54%) which the authors attribute to a relatively large number of patients with cirrhosis.
My take:
This study adds to the growing body of evidence that intravenous thiamine may improve outcomes in patients with sepsis and septic shock. However, no prospective, controlled trial has evaluated the effect of thiamine in sepsis. In my opinion, given that harmful effects are unlikely, intravenous thiamine may be considered in critically ill patients with sepsis.
References
- [Abstract]Effect of Thiamine Administration on Lactate Clearance and Mortality in Patients With Septic Shock by Woolum JA et al.
- [Abstract]Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study by Marik PE et al.
- [Abstract]Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study by Donnino MW et al.
