Effects of intravenous paracetamol on mean arterial pressure in critically ill patients: A systematic review and meta-analysis with trial sequential analysis

Background: Intravenous administration of paracetamol to critically ill patients may have negative hemodynamic effects. However, such effects have not been adequately quantified. Methods: We conducted a systematic review and meta-analysis of observational studies (published in English language in PubMed and/or EMBASE) conducted on intensive care unit (ICU) patients, reporting hemodynamic changes within 30 min of intravenous paracetamol administration for fever and/or analgesia. The primary outcome was the mean difference (MD) with 95% confidence interval [95%CI] in mean arterial pressure (MAP). Secondary outcomes were systolic and diastolic arterial pressure (SAP and DAP), heart rate (HR), and incidence of hypotension. Trial sequential analysis (TSA) was conducted to ascertain the robustness of findings. Results: Eight studies were included. We observed significant reduction after paracetamol of MAP (5 studies, MD: −6.75 mmHg [−10.68; −2.82]; p = 0.0008; I2 = 74%), SAP (5 studies, MD: −11.55 mmHg [−20.55; −2.55]; p = 0.01; I2 = 78%) and DAP (5 studies, MD: −5.29 mmHg [−8.53; −2.05]; p = 0.001; I2 = 42%). No effects were seen for HR (4 studies, MD: −3.08 bpm [−7.09;0.93]; p = 0.13; I2 = 0%). Subgroup analyses were hampered by the small number of studies. MAP reduction appeared consistent when paracetamol was administered for fever. TSAs showed that results on MAP and DAP were robust; SAP and HR were not. The grade of evidence was very low. The occurrence of hypotension after intravenous paracetamol was 45.5% (n = 143/314, 4 studies). Conclusions: Hypotension after intravenous paracetamol is frequent in the ICU, with significant reduction in MAP, SAP, and DAP but no effects on HR. Effects seem more pronounced in patients with fever. More advanced hemodynamic studies are needed to understand the mechanisms of paracetamol-induced hypotension. Registration: PROSPERO (CRD number 42024574919).