Paracetamol therapy and outcome of critically ill patients: a multicenter retrospective observational study

Suzuki et al. Critical Care 2015; 19:162: 1-11 doi: 10.1186/s-015-0865-1

Clinical Question

  • Does the administration of paracetamol reduce mortality in critically ill patients on the Intensive Care Unit?


  • Retrospective observational study
  • Multicenter


  • Data from 4 ICU’s. All large tertiary centres, Australia
  • Data collection from Jan 2000 to September 2010 (varied across centres)


  • Inclusion: All adult patients admitted to ICUs during the period when electronic data capture of paracetamol and body temperature prescription was possible
  • Exclusion: Readmission episodes; patients for whom data were not available for temperature, admission diagnosis or vital status at hospital discharge; patients with insufficient data for illness severity assessment
  • 15,818 patients


  • Patients who received at least 1g of paracetamol (n=10,046)


  • Patients who did not receive paracetamol (n=5772)
Comparing patients who received paracetamol with patients who did not receive paracetamol
  • APACHE II Score:  16.5 vs. 17.7, p<0.001
  • SAPS II: 30.2 vs. 28.3, p<0.001
  • Mechanical ventilation within first 24 hours of admission: 74% vs. 70%, p<0.001
  • Acute renal failure: 5% vs. 8%, p> 0.001
  • Elective surgery: 55% vs. 37%, p<0.001
  • Infection as admission diagnosis: 9% vs. 9%, p=0.99
  • Temperature >38C: 34% vs. 18%, p<0.001


  • Comparing patients who received paracetamol with patients who did not receive paracetamol
    • Primary outcome: Hospital mortality
      • 9.9% vs. 20.1%, p<0.0001
    • Secondary outcomes:
      • ICU mortality
        • 5.3% vs. 14.9%, p<0.0001
      • Multivariate logistic regression analysis: paracetamol administration significantly and independently associated with reduced in-hospital mortality (adjusted OR 0.60, 95% C.I. 0.53-0.68, p<0.001)
    • Consistent findings in subgroup analysis:
      • In surgical patients (n=9,994), administration of paracetamol was a  predictor of better outcome
        • Adjusted OR 0.72 (95% CI 0.58 to 0.91), p=0.006 Adjusted HR 0.51 (95% CI 0.42-0.61), p= < 0.0001
      • In medical patients (n=5,824), administration of paracetamol was a  predictor of better outcome
        • Adjusted OR 0.56 (95% CI 0.48 to 0.66), p<0.001 Adjusted HR 0.51 (95% CI 0.45-0.57), p= < 0.0001

Authors’ Conclusions

  • Paracetamol administration in the ICU appears to be independently associated with reduced in-hospital mortality and time to death after adjustment for multiple potential confounders and propensity score. This association, however, was modified by the presence of fever, suspected infection and lesser illness severity and may represent the effect of indication bias


  • Multi-centre
  • Large number of patients studied


  • Retrospective
  • Observational
  • Significant differences between the groups. This included severity scores; number of patients requiring mechanical ventilation; incidence of acute kidney injury; elective surgical admissions; medical vs surgical presentations
  • Did not record if patients were treated with interventions  that would affect temperature (e.g therapeutic hypothermia)

The Bottom Line

  • In critically ill patients, paracetamol was associated with a decreased mortality. There are many potential confounding variables that may account for this. A RCT is required to determine any outcome benefit. I eagerly await the results of the HEAT trial

External Links


Summary author: @stevemathieu75
Summary date: 26th June 2015
Peer-review editor: @davidslessor

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