Thiamine Administration and Prevalence of Delirium in the Intensive Care Unit: A Before-after Study

Delirium is a very common condition among ICU-admitted patients, and its prevalence is estimated between 30-40%. Delirium is associated with increased morbidity and mortality and future cognitive decline, along with increased ventilation-dependency and other complications.

There are multiple risk factors for delirium, including deficiencies of micronutrients. Thiamine deficiency is associated with specific neurological syndromes, including Wernicke and Korsakoff syndromes and Delirium Tremens. Several studies demonstrated significant thiamine deficiency among ICU-admitted patients (prevalence of 30-70%) without known risk factors, such as alcohol dependency. Thiamine deficiency may cause delirium in those patients.

Intravenous thiamine had been safely used for decades, for several indications. Lately, thiamine has been advocated for therapy in patients with septic shock, and its use in intensive care units has increased worldwide.

Since 2016, thiamine has been routinely administered in our intensive care unit. Considering the theoretical association between thiamine deficiency and ICU-related delirium, the investigators aim to investigate whether the routine use of thiamine has been associated with decreased prevalence of delirium among ICU patients when compared to the pre-routine thiamine administration era.

Study Overview

• Status: Completed
• Conditions: Delirium
• Intervention / Treatment: Drug: intravenous Thiamine

Detailed Description

Delirium is a very common condition among ICU-admitted patients, and its prevalence is estimated between 30-40%. Delirium is associated with increased morbidity and mortality and future cognitive decline, along with increased ventilation-dependency and other complications.

There are multiple risk factors for delirium, including deficiencies of micronutrients. Thiamine deficiency is associated with specific neurological syndromes, including Wernicke and Korsakoff syndromes and Delirium Tremens. Several studies demonstrated significant thiamine deficiency among ICU-admitted patients (prevalence of 30-70%) without known risk factors, such as alcohol dependency. Thiamine deficiency may cause delirium in those patients.

Intravenous thiamine had been safely used for decades, for several indications. Lately, thiamine has been advocated for therapy in patients with septic shock, and its use in intensive care units has increased worldwide.

Since 2016, thiamine has been routinely administered in our intensive care unit. Considering the theoretical association between thiamine deficiency and ICU-related delirium, the investigators aim to investigate whether the routine use of thiamine has been associated with decreased prevalence of delirium among ICU patients when compared to the pre-routine thiamine administration era.

Primary endpoint: Average delirium score during ICU-hospitalization before and after the routine intravenous thiamine administration.

Secondary endpoints: ICU and hospital admission times, duration of ventilation, need for tracheostomy, need for anti-delirium therapy and 28-day mortality.

Study design: Retrospective before-after interventional study. Inclusion criteria: All patients, aged 18-99, admitted to the intensive care unit in our medical facility between the years 2014-2018 (two years before and after intervention).

Exclusion criteria: Patients who were treated with thiamine prior to ICU admission, and patients who did not receive thiamine in the ICU.

Data collection: Data will be collected from the patients' electronic management file (iMD soft, Ofek and Chameleon software). Data collection will be anonymous.

Data: Age, gender, ICU and hospital admission times, duration of ventilation, 28-day mortality, need for tracheostomy. Need for anti-delirium therapy, cause for ICU admission, medical history, regular medication therapy, APACHE-2 score, SOFA score, lactate levels, need for inotropic or vasopressor support, need for physical restraints, need for renal replacement therapy, use of medication which may increase risk for delirium, RASS score.

Cohort size: 1000 patients overall, 500 in each study group (before and after intervention).

• Study Type: Observational
• Enrollment (Actual): 1000

Contacts and Locations

Study Locations

• Israel
  • Kfar Saba, Israel
    • Meir medical center Kfar Saba

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All patients, aged 18-99, admitted to the intensive care unit in our medical facility between the years 2014-2018 (two years before and after intervention).

Description

Inclusion Criteria:

• All patients, aged 18-99, admitted to the intensive care unit in our medical facility between the years 2014-2018 (two years before and after intervention).

Exclusion Criteria:

• Patients who were treated with thiamine prior to ICU admission, and patients who did not receive thiamine in the ICU.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Thiamine group; group 1: ICU patients who did not receive IV thiamine
Non-thiamine group; group 2: ICU patients who received IV thiamine,100-500 mg/day for at least one day	Drug: intravenous Thiamine; patients who received Thiamine,100-500 mg/day for at least one day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delirium score	RASS score (Richmond agitation-sedation scale, from minus 5 to plus 4, desirable score 0)	Average RASS score during ICU-hospitalization, through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Meir Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): January 1, 2021

Study Registration Dates

• First Submitted: December 8, 2019
• First Submitted That Met QC Criteria: December 25, 2019
• First Posted (Actual): January 2, 2020

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Thiamine
• Other Study ID Numbers: 0277-19-MMC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No