Impact of Thiamine Supplementation on Mortality in Septic Shock. A Controlled Before-and-after Study.

Sponsor

Hospital Sao Domingos (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05840718

Collaborator

(none)

Enrollment

6.2

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

This controlled before-and-after study analyse the impact of thiamine supplementation on outcomes of patients with septic shock treated according to the surviving sepsis campaign 2021 guidelines

Condition or Disease	Intervention/Treatment	Phase
Septic Shock	Drug: Thiamin

Detailed Description

Vitamin B1 (Thiamine) is a water-soluble vitamin that plays an important role in various biological processes. The active form is thiamine pyrophosphate, an essential cofactor in enzyme systems involved in carbohydrate metabolism and energy production. Recently, the role of thiamine in critically ill patients has gained prominence and septic shock has deserved special attention (1,2). It is important to emphasize that in these situations the clinical syndromes have low sensitivity and specificity for clinical diagnosis, which means that a high level of suspicion must be exercised in these situations. Donnino et al (3) analyzed 88 patients with septic shock in a prospective, randomized, double-blind study. The study showed that the administration of thiamine at a dose of 200 mg every 12 hours for 7 days had a significant impact on mortality only in patients who had reduced serum levels of thiamine. Woolum et al (4 ) retrospectively analyzed the impact of a single dose of Thiamine administered in the 24 hours that preceded the diagnosis of septic shock and compared with patients who did not receive the vitamin and identified improvement in lactate clearance and reduction in 28-day mortality in the thiamine group. Petsakul et al (5) evaluated the effect of thiamine administration in patients with septic shock and need for vasopressors and showed a significant reduction in the vasopressor dose in addition to improvement in lactate clearance. A recent meta-analysis including 5 studies and 645 patients with septic shock analyzed the impact of thiamine use on mortality. The study included 3 prospective randomized studies and 2 retrospective observational studies. The result showed a borderline beneficial effect on mortality. Regarding to HAT (Hydrocortisone, ascorbic acid and thiamine) therapy after the initial study by Marik et al. (7 ) at least 3 prospective randomized studies failed to repeat the good results of the initial study (8,9,10).

The sepsis management protocol at the São Domingos hospital underwent important changes from December 2021 to October 2022. In December, changes were incorporated in the protocol based on the new version of the Surviving Sepsis Campaign 2021 that had been launched the previous month ( 11). In April 2022 the SOSD (salvage, optimization, stabilization and de-resuscitation) systematics (12) was incoporated in the management of septic shock and in October 2022 thiamine use was implemented. Thiamine was incorporated into the protocol, although there are still no robust studies to indicate its use because, despite the implementation of previous measures with exceptional results in sepsis, between January and September 2022, mortality from sepsis was 1.69%, in the septic shock we had evolved little or nothing with mortality in the same period of 70%. In October, thiamine was started in isolated cases and as of November 2022, the investigators started using thiamine systematically and in all cases of septic shock at a dose of 200 mg EV every 12 hours for 7 days. In this controlled before-and-after study, the investigators compared outcomes of patients treated for septic shock between November 2022 and March 2023 with patients diagnosed with septic shock treated between May and September 2022.

Study Design

Study Type:

Observational

Anticipated Enrollment :

80 participants

Observational Model:

Other

Time Perspective:

Retrospective

Official Title:

Impact of Thiamine Supplementation on Mortality in Septic Shock. A Controlled Before-and-after Study.

Anticipated Study Start Date :

May 25, 2023

Anticipated Primary Completion Date :

Sep 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Control group Septic shock patients treated according surviving sepsis campaign 2021 guidelines
Intervention group Septic shock patients treated according surviving sepsis campaign 2021 guidelines supplemented with thiamin 200 mg in 50 ml 5% dextrose twice daily for 7 days.	Drug: Thiamin Patients in thiamine group received two daily dosis of 200 mg of thiamin diluted in 50 ml of 5% dextrose during 7 days

Arm

Intervention/Treatment

Control group

Septic shock patients treated according surviving sepsis campaign 2021 guidelines

Intervention group

Septic shock patients treated according surviving sepsis campaign 2021 guidelines supplemented with thiamin 200 mg in 50 ml 5% dextrose twice daily for 7 days.

Drug: Thiamin

Patients in thiamine group received two daily dosis of 200 mg of thiamin diluted in 50 ml of 5% dextrose during 7 days

Outcome Measures

Primary Outcome Measures

Comparison of mortality rate between intervention (thiamine supplemented) and control group of patients with septic shock [30 days]
To determine the mortality rate (n %) of patients with septic shock that received thiamine supplementation 200 mg twice daily for 7 days (intervention group) compared to a group that did not receive thiamine. Both groups treated according to Surviving Sepsis Campaign version 2021.

Secondary Outcome Measures

Lactate clearance. Length of time to achieve serum lactate concentration < 19 mg/dl [30 days]
Compare the lactate clearance time between the patients with septic shock supplemented with thiamine (intervention group) compared to patients that did not receive thiamine
Comparison of vasopressor-free days during ICU stay between the groups intervention and control [30 days]
Compare the vasopressor-free days between the two groups during the ICU stay
Comparison of vantilation-free days during ICU stay between the groups intervention and control [30 days]
Compare ventilation-free days between the two groups during the ICU stay
Compare the use of renal replacement therapy, n (%), initiated after 48 hours of septic shock between the groups intervention (thiamine supplementation) and control group [30 days]
- Compare the use of renal replacement therapy initiated after 48 hours of septic shock between the two groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

age > 18 years
presence of documented or suspected infection, SOFA score ≥ 2, serum lactate levels > 18 mg/dL and hypotension, MAP < 65 mm Hg maintained after volume expansion of at least 30 ml/kg in the first 2 hours of treatment followed by noradrenaline vasopressor dependence (with or without vasopressin) during the first 6 hours of treatment.