Evaluation of Thiamine as Adjunctive Therapy in COVID-19 Critically Ill Patients

A Two-Center Propensity Score Matched Study

Khalid Al Sulaiman; Ohoud Aljuhani; Maram Al Dossari; Asma Alshahrani; Aisha Alharbi; Rahmah Algarni; Majed Al Jeraisy; Shmeylan Al Harbi; Abdulmalik Al Katheri; Fahad Al Eidan; Abdulkareem M. Al Bekairy; Nouf Al Qahtani; Mashael Al Muqrin; Ramesh Vishwakarma; Ghassan Al Ghamdi

Disclosures

Crit Care. 2021;25(223) 

In This Article

Discussion

Our study is a two-center, non-interventional retrospective study of critically ill patients admitted to ICUs with a confirmed diagnosis of COVID-19. It investigates the correlation between thiamine use as adjunctive therapy and the clinical outcomes. The 30-day mortality rate was significantly lower in the thiamine group with a P value of (P = 0.009) after using propensity score matching that takes into consideration the use of the corticosteroid since it showed survival benefits in the recovery trial.[26]

Our findings agree with a substantial number of studies published over the past decades and reported a survival benefit with thiamine in non-COVID19 critically ill patients. However, there are no current trials that directly investigate the effect of thiamine in critically ill COVID-19 patients. Woolum et al. proved the relation between early thiamine administration to critically ill patients with septic shock during the first 24 hours of admission with rapid lactate clearance and decreased 28-day mortality rates.[14] However, the recent VITAMINS trial tested the HAT protocol (hydrocortisone, ascorbic acid and thiamine) in critically ill patients with septic shock and found no survival benefit.[21]

Severe COVID-19-infected patients may develop malnutrition and risk for refeeding syndrome due to low food intake prior to ICU admission.[22] Thiamine deficiency plays a major role in malnutrition in critically ill patients, which leads to the inability to create adenosine triphosphate (ATP), inability to use oxygen, high-output cardiac failure, cardiovascular collapse and death when untreated.[23] One retrospective observational study conducted in Wuhan found that critically ill COVID-19 patients with higher Nutritional Risk Screening 2002 (NRS) had a higher risk of mortality and longer hospital stay.[22] Preadmission nutritional status in our patients has been assessed using NUTRIC score due to the unavailability of NRS-2002-related information (e.g., weight loss history, food intake history prior to ICU admission). Moreover, phosphorus levels were evaluated in our cohort for further nutrition assessment, the mean phosphorus level was 1.05 (0.36) mmol/L and 1.16 (0.38) mmol/L in control and thiamine group (P = 0.07), respectively. The preadmission low nutrition status due to COVID-19 infection combined with the known low intake of some micronutrients (such as zinc and selenium) in the Saudi population might explain the benefits of thiamine observed in our study.[11,24]

The ICU length of stay was not statistically significant between the groups (P-value = 0.48), with a median duration of eight days. A lack of studies assessed the thiamine's impact on ICU LOS in COVID-19 critically ill patients. Conversely, a retrospective study by Mitchell et al. investigates the benefits of thiamine, vitamin C, and hydrocortisone as a combination in septic patients and found a significant difference in the ICU LOS.[25]

In our data, the incidence of AKI was lower in the thiamine group, which may explain a kidney protective effect but was not statistically significant. Acute kidney injury is one of the most frequent complications during critical illness and could contribute to a malnutrition state and impaired patients' immunity.[27] A randomized, double-blind, placebo-controlled trial found that serum creatinine levels were lower in patients who received a high dose of thiamine and were less likely to have kidney failure requiring renal replacement therapy (RRT).[13]

Interestingly, thiamine use was found to be associated with a statistically significant reduction in thrombosis by 81% compared to the control group [OR (95% CI) 0.19 (0.040, 0.884), P value = 0.03]. The exact mechanism for thrombosis reduction observed in our cohort with thiamine use is unknown. This finding worth further investigation and should trigger future research to address the precise impact of thiamine on the prevention of thrombosis in COVID-19 critically ill patients.

Our study's uniqueness lies in the lack of extensive well-conducted studies connecting thiamine administration's effect directly to a positive impact on mortality rates in COVID 19 critically ill patients. However, the study may have been affected by several limitations, including our design observational nature, and some residual confounding factors are still possible. Therefore, we conducted several analyses to control these variables using multivariable regression adjustment after propensity score matching. Additionally, thiamine initiation in our centers was primarily based on clinical judgment; thus, treating physicians' bias toward using one treatment regimen versus another cannot be ruled out. Also, thiamine levels were not measured for patients neither initially on admission nor during ICU stay.

Thiamine has a good safety profile, and readily available at low cost; therefore, it can be considered as a part of COVID-19 critically ill patients' therapeutic management protocols. Further interventional studies are required to confirm our findings.

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