Supplemental Digital Content
Effect of Thiamine Administration on Lactate Clearance and Mortality in Patients with Septic Shock
Jordan A Woolum, Pharm.D., Erin L Abner, Ph.D., M.P.H., Andrew Kelly, M.A.S., M.S., Melissa L. Thompson Bastin, Pharm.D., BCPS, Peter E. Morris, M.D.,
Alexander H. Flannery, Pharm.D., BCCCP, BCPS
Appendix. STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) Checklist eTable 1. ICD-9 and -10 Codes Used in Data Query
eTable 2. Baseline Demographics in Unmatched Cohort
eTable 3. Cox Proportional Hazards Models for 28-Day Mortality eTable 4. Secondary Outcomes
eFigure 1. Probability of Lactate Clearance Over Time with Thiamine-Sex Interaction eFigure 2. Cumulative Hazard of Death Over Time with Thiamine-Sex Interaction eFigure 3. Frequency Distribution of Vasopressor Free Days by Thiamine Exposure eFigure 4. Frequency Distribution of Ventilator Free Days by Thiamine Exposure eFigure 5. Frequency Distribution of ICU-Free Days by Thiamine Exposure
Appendix. STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) Checklist
Item No. Recommendation Page
Number(s) Title and abstract
1 (a) Indicate the study’s design with a commonly used term in the title or the abstract
1 (b) Provide in the abstract an informative and balanced
summary of what was done and what was found
2 Introduction
Background/
rationale
2 Explain the scientific background and rationale for the investigation being reported
3 Objectives 3 State specific objectives, including any prespecified hypotheses 3-5 Methods
Study design 4 Present key elements of study design early in the paper 3-5 Setting 5 Describe the setting, locations, and relevant dates, including
periods of recruitment, exposure, follow-up, and data collection 3-5 Participants 6 (a) Give the eligibility criteria, and the sources and methods of
selection of participants. Describe methods of follow-up
3-4 (b) For matched studies, give matching criteria and number of
exposed and unexposed
4 Variables 7 Clearly define all outcomes, exposures, predictors, potential
confounders, and effect modifiers. Give diagnostic criteria, if applicable
3-5
Data
sources/measurement
8 For each variable of interest, give sources of data and details of methods of assessment (measurement). Describe comparability of assessment methods if there is more than one group
3-5
Bias 9 Describe any efforts to address potential sources of bias 4
Study size 10 Explain how the study size was arrived at 5
Quantitative variables 11 Explain how quantitative variables were handled in the analyses. If applicable, describe which groupings were chosen and why
4-5
Statistical methods 12 (a) Describe all statistical methods, including those used to control for confounding
4-5 (b) Describe any methods used to examine subgroups and
interactions
4-5 (c) Explain how missing data were addressed 4 (d) If applicable, explain how loss to follow-up was addressed N/A
(e) Describe any sensitivity analyses N/A
Results
Participants 13 (a) Report numbers of individuals at each stage of study—eg numbers potentially eligible, examined for eligibility, confirmed eligible, included in the study, completing follow- up, and analysed
5
(b) Give reasons for non-participation at each stage 5
(c) Consider use of a flow diagram 5
Descriptive data 14 (a) Give characteristics of study participants (eg demographic, clinical, social) and information on exposures and potential confounders
5
(b) Indicate number of participants with missing data for each variable of interest
5 (c) Summarise follow-up time (eg, average and total amount) 5-6 Outcome data 15 Report numbers of outcome events or summary measures over
time
5-6 Main results 16 (a) Give unadjusted estimates and, if applicable, confounder-
adjusted estimates and their precision (eg, 95% confidence interval). Make clear which confounders were adjusted for and why they were included
5-6
(b) Report category boundaries when continuous variables were categorized
5-6 (c) If relevant, consider translating estimates of relative risk
into absolute risk for a meaningful time period
N/A Other analyses 17 Report other analyses done—eg analyses of subgroups and
interactions, and sensitivity analyses
6 Discussion
Key results 18 Summarise key results with reference to study objectives 6-8 Limitations 19 Discuss limitations of the study, taking into account sources of
potential bias or imprecision. Discuss both direction and magnitude of any potential bias
8
Interpretation 20 Give a cautious overall interpretation of results considering objectives, limitations, multiplicity of analyses, results from similar studies, and other relevant evidence
6-8
Generalisability 21 Discuss the generalisability (external validity) of the study results
6-8 Other information
Funding 22 Give the source of funding and the role of the funders for the present study and, if applicable, for the original study on which the present article is based
N/A
Adapted from reference 6 in manuscript: von Elm E, Altman DG, Egger M, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Epidemiology. 2007 Nov;18(6):800-4.
eTable 1. ICD-9 and -10 Codes Used in Data Query Septic Shock Diagnosis Codes
ICD9 785.52 ICD10 R65.21
Liver Disease Diagnosis Codes
ICD9 571.5
ICD9 571.6
ICD9 571.8
ICD9 571.9
ICD9 572
ICD9 572.1
ICD9 572.2
ICD9 572.3
ICD9 572.4
ICD9 572.8
ICD9 573
ICD9 573.4
ICD9 573.5
ICD9 573.8
ICD9 573.9
ICD9 782.4
ICD9 789.1
ICD9 789.5
ICD9 789.59
ICD9 790.4
ICD9 790.5
ICD9 794.8
ICD10 K70.41 ICD10 K71.10 ICD10 K71.8 ICD10 K71.9 ICD10 K72.00 ICD10 K72.01 ICD10 K72.10 ICD10 K72.11 ICD10 K72.90 ICD10 K72.91 ICD10 K74.0 ICD10 K74.3 ICD10 K74.5
ICD10 K74.60 ICD10 K74.69 ICD10 K75.0 ICD10 K75.89 ICD10 K75.9 ICD10 K76.0 ICD10 K76.1 ICD10 K76.3 ICD10 K76.5 ICD10 K76.6 ICD10 K76.7 ICD10 K76.9
ICD10 K77
ICD10 R16.0 ICD10 R16.2
ICD10 R17
ICD10 R74.0 ICD10 R74.8 ICD10 R74.9 ICD10 Z94.4
eTable 2. Baseline Demographics in Unmatched Cohort
No thiamine (n=926) Thiamine (n=123) p-value Baseline Demographics
Age (years) 60 (50-69) 52 (43-61) <0.001
Sex (% male) 51.50% 56.10% 0.339
Race (% white) 92.70% 91.90% 0.755
Liver Disease (%) 34.20% 65.00% <0.001
Elixhauser Comorbidity Index 4 (3-5) 4 (2-5) 0.451
Service (% medical) 82.60% 96.80% <0.001
SOFA Score on ICU Admission 9 (7-11) 10 (8-12) <0.001
Stress Dose Steroids (%) 47.10% 52.90% 0.229
Peak Lactate 5.2 (3.2-9.1) 6.1 (3.3-12.2) 0.048
eTable 3. Cox Proportional Hazards Models for 28-Day Mortality
Primary Models 95% Hazard Ratio
Thiamine only 0.806 (0.596-1.090)
Thiamine, age, sex, and race 0.797 (0.589-1.079)
Thiamine, age, sex, race, and clinical factorsa 0.666 (0.490-0.905)
Interaction Models with Sex
Thiamine, age, sex, and race with thiamine-sex interaction term
Female: 0.453 (0.277-0.741) Male: 1.229 (0.831-1.815) Thiamine, age, sex, race, and clinical factorsa with
thiamine-sex interaction term
Female: 0.363 (0.221-0.596) Male: 1.063 (0.716-1.575)
eTable4. Secondary Outcomes
No thiamine (n=246) Thiamine (n=123) p-value Secondary Outcomes
SOFA Change 0 (-3 to +2) 0 (-2 to +3) 0.384
Vasopressor-Free Days 2.97(0.2-10.9) 4.6(0.2-11.9) 0.427
AKI 0.891
None 76.80% 73.20%
Risk 8.90% 10.60%
Injury 8.10% 8.90%
Failure 6.10% 7.30%
Renal Replacement Therapy (%) 20.70% 20.30% 0.927
Ventilator-Free Days 0.94 (0-6.2) 0 (0-5.2) 0.186
ICU-Free Days 0.5 (0-5.4) 0.04 (0-6.4) 0.319
28-Day Mortality 56.1% 51.2% 0.375
eFigure 1. Probability of Lactate Clearance Over Time with Thiamine-Sex Interaction
eFigure 2. Cumulative Hazard of Death Over Time with Thiamine-Sex Interaction
eFigure 3. Frequency Distribution of Vasopressor Free Days by Thiamine Exposure
050100
0 10 20 30 0 10 20 30
No Thiamine Thiamine
Frequency
Vasopressor-Free Days
eFigure 4. Frequency Distribution of Ventilator Free Days by Thiamine Exposure
050100150
0 10 20 30 0 10 20 30
No Thiamine Thiamine
Frequency
Ventilator-Free Days
eFigure 5. Frequency Distribution of ICU-Free Days by Thiamine Exposure
050100150
0 10 20 30 0 10 20 30
No Thiamine Thiamine
Frequency
ICU-Free Days
