Title: Early Acetaminophen Administration and Mortality Outcomes in Critically Ill Patients
with Cirrhosis: A Retrospective Analysis from the MIMIC-IV Database
Version: 0 Date: 21 Mar 2025
Reviewer:  Tarana Gupta
Reviewer's report:
1. In Fig 1, 3020 patients included in IPW cohort which are further subdivided without and with
APAP use (3126 and 3205) respectively. Please explain how this subgrouping numbers exceed
main group.
2. Authors have not mentioned the cumulative dose of APAP in patients. They have not
mentioned the indication for which APAP was used in cirrhosis as this is indicated for fever
and pain only.
3. APAP is a dose dependent hepatotoxic drug which may be cumulative if used over several
days in a patient with cirrhosis.
4. They should also mention the formulation and route like intravenous or oral APAP which was
used in these patients as bioavailability and dose differs significantly among different routes.
5. The discussion mentions higher mortality in patients with bilirubin >10 mg/dL. however,
supplementary table shows upper bound of bilirubin at 5 or 7 mg/dL. Please explain.
6. In routine clinical practice, APAP has a relative contraindication in patients with
decompensated cirrhosis with jaundice. The study should check as to why so many patients were
receiving APAP in this high risk population.
Title: Early Acetaminophen Administration and Mortality Outcomes in Critically Ill Patients
with Cirrhosis: A Retrospective Analysis from the MIMIC-IV Database
Version: 0 Date: 21 Mar 2025
Reviewer:  Tarana Gupta
Reviewer's report:
1. In Fig 1, 3020 patients included in IPW cohort which are further subdivided without and with
APAP use (3126 and 3205) respectively. Please explain how this subgrouping numbers exceed
main group.
2. Authors have not mentioned the cumulative dose of APAP in patients. They have not
mentioned the indication for which APAP was used in cirrhosis as this is indicated for fever
and pain only.
3. APAP is a dose dependent hepatotoxic drug which may be cumulative if used over several
days in a patient with cirrhosis.
4. They should also mention the formulation and route like intravenous or oral APAP which was
used in these patients as bioavailability and dose differs significantly among different routes.
5. The discussion mentions higher mortality in patients with bilirubin >10 mg/dL. however,
supplementary table shows upper bound of bilirubin at 5 or 7 mg/dL. Please explain.
6. In routine clinical practice, APAP has a relative contraindication in patients with
decompensated cirrhosis with jaundice. The study should check as to why so many patients were
receiving APAP in this high risk population.
Please review this paper.
user
Title: Early Acetaminophen Administration and Mortality Outcomes in Critically Ill Patients
with Cirrhosis: A Retrospective Analysis from the MIMIC-IV Database
Version: 0 Date: 21 Mar 2025
Reviewer:  Tarana Gupta
Reviewer's report:
1. In Fig 1, 3020 patients included in IPW cohort which are further subdivided without and with
APAP use (3126 and 3205) respectively. Please explain how this subgrouping numbers exceed
main group.
2. Authors have not mentioned the cumulative dose of APAP in patients. They have not
mentioned the indication for which APAP was used in cirrhosis as this is indicated for fever
and pain only.
3. APAP is a dose dependent hepatotoxic drug which may be cumulative if used over several
days in a patient with cirrhosis.
4. They should also mention the formulation and route like intravenous or oral APAP which was
used in these patients as bioavailability and dose differs significantly among different routes.
5. The discussion mentions higher mortality in patients with bilirubin >10 mg/dL. however,
supplementary table shows upper bound of bilirubin at 5 or 7 mg/dL. Please explain.
6. In routine clinical practice, APAP has a relative contraindication in patients with
decompensated cirrhosis with jaundice. The study should check as to why so many patients were
receiving APAP in this high risk population.
assistant