Clinical trial NCT05840718: Supplemental Thiamine in Septic Shock: A Before-after Study
Official title: Impact of Thiamine Supplementation on Clinical Outcomes of Patients With Septic Shock: a Retrospective Before-after Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Septic Shock
Keywords: Septic shock
Thiamin
Critically ill patients
Mortality
Surviving sepsis campaign
Lead sponsor: Hospital Sao Domingos
Sponsor class: OTHER
First posted: 2023-05-03
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: OTHER
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: This is a retrospective before-after study. Included were all patients with inclusion criteria admitted to a 13-bed surgical ICU, a 12-bed medical and a 12-bed high-complexity surgical and trauma ICU .during the 2 study periods: May 1 to September 30, 2022, control group and November 1, 2022 to March 31, 2023, study group.

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

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.

Eligibility criteria: 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.

Exclusion Criteria:

* pregnant women
* patients treated only with comfort measures.

Primary outcomes:
measure: Compare lactate clearance between intervention (thiamine supplemented) and control group.
timeFrame: 30 days
Secondary outcomes:
measure: Comparison of mortality rate between intervention (thiamine supplemented) and control
timeFrame: 30 days
measure: Comparison of vasopressor-free days during ICU stay between the groups intervention and control
timeFrame: 30 days
measure: Comparison of vantilation-free days during ICU stay between the groups intervention and control
timeFrame: 30 days
measure: Compare the use of renal replacement therapy, n (%), initiated after 48 hours of septic shock between the groups intervention (thiamine supplementation) and control group
timeFrame: 30 days
Other outcomes:
Locations:
city: São Luís
country: Brazil
facility: Hospital São Domingos
state: Maranhão
city: Sao Luis
country: Brazil
facility: Hospital Sao Domingos
state: MA
Study officials:
affiliation: Hospital Sao Domingos
name: ISNARA S CARVALHO, RN
role: PRINCIPAL_INVESTIGATOR
References:
citation: Cruickshank AM, Telfer AB, Shenkin A. Thiamine deficiency in the critically ill. Intensive Care Med. 1988;14(4):384-7. doi: 10.1007/BF00262893.
citation: Costa NA, Gut AL, de Souza Dorna M, Pimentel JA, Cozzolino SM, Azevedo PS, Fernandes AA, Zornoff LA, de Paiva SA, Minicucci MF. Serum thiamine concentration and oxidative stress as predictors of mortality in patients with septic shock. J Crit Care. 2014 Apr;29(2):249-52. doi: 10.1016/j.jcrc.2013.12.004. Epub 2013 Dec 14.
citation: Donnino MW, Andersen LW, Chase M, Berg KM, Tidswell M, Giberson T, Wolfe R, Moskowitz A, Smithline H, Ngo L, Cocchi MN; Center for Resuscitation Science Research Group. Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. Crit Care Med. 2016 Feb;44(2):360-7. doi: 10.1097/CCM.0000000000001572.
citation: Woolum JA, Abner EL, Kelly A, Thompson Bastin ML, Morris PE, Flannery AH. Effect of Thiamine Administration on Lactate Clearance and Mortality in Patients With Septic Shock. Crit Care Med. 2018 Nov;46(11):1747-1752. doi: 10.1097/CCM.0000000000003311.
citation: Petsakul S, Morakul S, Tangsujaritvijit V, Kunawut P, Singhatas P, Sanguanwit P. Effects of thiamine on vasopressor requirements in patients with septic shock: a prospective randomized controlled trial. BMC Anesthesiol. 2020 Nov 9;20(1):280. doi: 10.1186/s12871-020-01195-4.
citation: Kanchanasurakit S, Suthumpoung P, Santimaleeworagun W, Nakaranurack C, Huynh NS, Srisawat C, Nunta M, Chirakan V, Saokaew S. Effectiveness of thiamine therapy in mortality rate in patients with septic shock: A systematic review and meta-analysis. Int J Crit Illn Inj Sci. 2021 Apr-Jun;11(2):86-94. doi: 10.4103/IJCIIS.IJCIIS_159_20. Epub 2021 Jun 29.
citation: Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017 Jun;151(6):1229-1238. doi: 10.1016/j.chest.2016.11.036. Epub 2016 Dec 6.
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