Mechanism of paracetamol-induced hypotension in critically ill patients: A prospective observational cross-over study

Krajčová, Adéla; Matoušek, Vojtěch; Duška, František

doi:10.1016/j.aucc.2012.02.002

Cited by 44 publications

(56 citation statements)

References 18 publications

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“…Recently, Krajcova et al . performed a non‐blinded, non‐randomized study on six intensive care patients who received 48 paracetamol and 35 control drug administrations . These authors reported that i.v.…”

Section: Discussioncontrasting

confidence: 63%

“…Recently, in the context of critical illness, clinical studies have suggested that i.v. paracetamol may cause hypotension [1][2][3][4][5][6][7][8]. Most of these studies did not report on the possible mechanism for the hypotension observed [1,3,[5][6][7].…”

Section: Relationship To Previous Studiesmentioning

confidence: 99%

“…However, with growing use, concerns have developed in critical care literature, which suggest that i.v. formulations may be associated with transient hypotension [1][2][3][4][5][6][7][8]. Additionally, studies examining the haemodynamic effects of i.v.…”

Section: Introductionmentioning

confidence: 99%

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The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

Chiam

Weinberg

Bailey

et al. 2016

Brit J Clinical Pharma

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Aim The haemodynamic effects of intravenous paracetamol have not been systematically investigated. We compared the physiological effects of intravenous mannitol‐containing paracetamol, and an equivalent dosage of mannitol, and normal saline 0.9% in healthy volunteers. Methods We performed a blinded, triple crossover, randomized trial of 24 adult healthy volunteers. Participants received i.v. paracetamol (1 g paracetamol +3.91 g mannitol 100 ml–1), i.v. mannitol (3.91 g mannitol 100 ml–1) and i.v. normal saline (100 ml). Composite primary end points were changes in mean arterial pressure (MAP), systolic blood pressure (SBP) and diastolic blood pressure (DBP) measured pre‐infusion, during a 15 min infusion period and over a 45 min observation period. Systemic vascular resistance index (SVRI) and cardiac index were measured at the same time points. Results Infusion of paracetamol induced a transient yet significant decrease in blood pressures from pre‐infusion values (MAP –1.85 mmHg, 95% CI –2.6, –1.1, SBP –0.54 mmHg, 95% CI –1.7, 0.6 and DBP −1.92 mmHg, 95% CI –2.6, –1.2, P < 0.0001), associated with a transient reduction in SVRI and an increase in cardiac index. Changes were observed, but to a lesser extent with normal saline (MAP –0.15 mmHg, SBP +1.44 mmHg, DBP −–0.73 mmHg, P < 0.0001), but not with mannitol (MAP +1.47 mmHg, SBP +4.03 mmHg, DBP +0.48 mmHg, P < 0.0001). Conclusions I.v. paracetamol caused a transient decrease in blood pressure immediately after infusion. These effects were not seen with mannitol or normal saline. The physiological mechanism was consistent with vasodilatation. This study provides plausible physiological data in a healthy volunteer setting, supporting transient changes in haemodynamic variables with i.v. paracetamol and justifies controlled studies in the peri‐operative and critical care setting.

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Section: Discussioncontrasting

confidence: 63%

Section: Relationship To Previous Studiesmentioning

confidence: 99%

See 1 more Smart Citation

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

Chiam

Weinberg

Bailey

et al. 2016

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Paracetamol reduces both HR and SV, as well as SVR. The reduction in cardiac index associated with paracetamol has been described previously 6 . The mechanism behind this is unknown: Chiam et al hypothesised that this reduction may be due to SV changes secondary to mannitol used as a stabilizer in most intravenous paracetamol formulations.…”

Section: Discussionmentioning

confidence: 99%

“…The haemodynamic mechanism for this blood pressure decrease has been explored using various methods. Some authors have reported a reduction in cardiac output -either due to a reduction in heart rate 6 , or due to the diuretic effect of mannitol present in intravenous paracetamol preparations 7 . However, there is also evidence to suggest that the reduction in blood pressure is related to a decrease in the systemic vascular resistance (SVR): (a) peripheral blood flow increases when measured using laser Doppler flowmetry in febrile patients 8 ; and (b) a reduction in SVR has been observed following paracetamol administration when measured in a randomised controlled trial of healthy volunteers, but not after an equivalent dose of mannitol alone was given 7 .…”

Section: Introductionmentioning

confidence: 99%

Haemodynamic changes with paracetamol in critically-ill children

Ray

Brick

Raman

et al. 2017

Journal of Critical Care

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Purpose: Paracetamol has been associated with a reduction in blood pressure, especially in febrile, critically-ill adults. We hypothesised that blood pressure would fall following administration of paracetamol in critically-ill children and this effect would be greater during fever and among children with a high body surface area to weight ratio. Methods:A 12-month prospective observational study of children (0-16 years) admitted to paediatric intensive care, who underwent pulse contour analysis and received paracetamol concurrently. Results:Mean arterial blood pressure decreased significantly by 4.7% from baseline (95% CI 1.75-8.07%) in 31 children following 148 doses of paracetamol. The nadir was 2-hours postdose. The effect was pronounced in children with fever at baseline (6.4%, 95% CI 2.8-10%), although this was not statistically significant. There was no simple relationship between this effect and body surface area to weight ratio. The association between a change in blood pressure and changes in heart rate or measured stroke volume was poor; therefore it was likely that a change in the systemic vascular resistance contributes most to this effect. Conclusion:There is a significant but modest reduction in blood pressure post-paracetamol in critically-ill children. This is likely related to a change in systemic vascular resistance.

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A narrative review of paracetamol‐induced hypotension: Keeping the patient safe

Young

2021

Nursing Open

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Nurses are required to escalate concerns about the quality and safety of care and are accountable for incidents that occur on their watch. Nurses have reported paracetamol-induced hypotension, through monitoring and surveillance (Lee et al., 2018). Nevertheless, paracetamol continues to be marketed and prescribed as a presumed safe and harmless drug. This poses a risk that paracetamol will cause haemodynamic instability, which vastly goes undetected, even in high-risk patient populations (Bae et al., 2017;Kang et al., 2018).The risk warnings of current paracetamol manufacturers are questionable, because they do not compel clinical governors to regulate the administration of paracetamol in the hospital environment. This narrative review combines the nurse's voice with the scientific evidence presented in the literature, which demonstrates that paracetamol-induced hypotension is a real-world problem and identifies high-risk patients. Through narrative synthesis, we suggest methods of early detection and prevention of paracetamol-induced hypotension, wherever paracetamol is prescribed in the hospital environment. | BACKG ROU N DTo treat fever or not remains a perennial debate (Mohr and Doerschuk, 2013). The benefits of reducing the oxygen and energy consumption

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Mechanism of paracetamol-induced hypotension in critically ill patients: A prospective observational cross-over study

Cited by 44 publications

References 18 publications

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

The haemodynamic effects of intravenous paracetamol (acetaminophen) in healthy volunteers: a double‐blind, randomized, triple crossover trial

Haemodynamic changes with paracetamol in critically-ill children

A narrative review of paracetamol‐induced hypotension: Keeping the patient safe

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