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Multicenter Study
. 2022 Dec 27;22(1):1000.
doi: 10.1186/s12877-022-03709-w.

The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial

Philipp Heinrich Baldia  1 , Bernhard Wernly  2 , Hans Flaatten  3 , Jesper Fjølner  4 , Antonio Artigas  5 , Bernardo Bollen Pinto  6 , Joerg C Schefold  7 , Malte Kelm  1 , Michael Beil  8 , Raphael Romano Bruno  1 , Stephan Binnebößel  1 , Georg Wolff  1 , Ralf Erkens  1 , Sviri Sigal  8 , Peter Vernon van Heerden  8 , Wojciech Szczeklik  9 , Muhammed Elhadi  10 , Michael Joannidis  11 , Sandra Oeyen  12 , Brian Marsh  13 , Finn H Andersen  14 , Rui Moreno  15 , Susannah Leaver  16 , Dylan W De Lange  17 , Bertrand Guidet  18 , Christian Jung  19 ; COVIP study group
Collaborators, Affiliations
Multicenter Study

The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial

Philipp Heinrich Baldia et al. BMC Geriatr. .

Abstract

Background: In the early COVID-19 pandemic concerns about the correct choice of analgesics in patients with COVID-19 were raised. Little data was available on potential usefulness or harmfulness of prescription free analgesics, such as paracetamol. This international multicentre study addresses that lack of evidence regarding the usefulness or potential harm of paracetamol intake prior to ICU admission in a setting of COVID-19 disease within a large, prospectively enrolled cohort of critically ill and frail intensive care unit (ICU) patients.

Methods: This prospective international observation study (The COVIP study) recruited ICU patients ≥ 70 years admitted with COVID-19. Data on Sequential Organ Failure Assessment (SOFA) score, prior paracetamol intake within 10 days before admission, ICU therapy, limitations of care and survival during the ICU stay, at 30 days, and 3 months. Paracetamol intake was analysed for associations with ICU-, 30-day- and 3-month-mortality using Kaplan Meier analysis. Furthermore, sensitivity analyses were used to stratify 30-day-mortality in subgroups for patient-specific characteristics using logistic regression.

Results: 44% of the 2,646 patients with data recorded regarding paracetamol intake within 10 days prior to ICU admission took paracetamol. There was no difference in age between patients with and without paracetamol intake. Patients taking paracetamol suffered from more co-morbidities, namely diabetes mellitus (43% versus 34%, p < 0.001), arterial hypertension (70% versus 65%, p = 0.006) and had a higher score on Clinical Frailty Scale (CFS; IQR 2-5 versus IQR 2-4, p < 0.001). Patients under prior paracetamol treatment were less often subjected to intubation and vasopressor use, compared to patients without paracetamol intake (65 versus 71%, p < 0.001; 63 versus 69%, p = 0.007). Paracetamol intake was not associated with ICU-, 30-day- and 3-month-mortality, remaining true after multivariate adjusted analysis.

Conclusion: Paracetamol intake prior to ICU admission was not associated with short-term and 3-month mortality in old, critically ill intensive care patients suffering from COVID-19.

Trial registration: This prospective international multicentre study was registered on ClinicalTrials.gov with the identifier "NCT04321265" on March 25, 2020.

Keywords: Analgesics; COVID-19; Frailty; ICU; Paracetamol.

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Conflict of interest statement

The authors declare that they have no competing interests. JCS reports grants (full departmental disclosure) from Orion Pharma, Abbott Nutrition International, B. Braun Medical AG, CSEM AG, Edwards Lifesciences Services GmbH, Kenta Biotech Ltd, Maquet Critical Care AB, Omnicare Clinical Research AG, Nestle, Pierre Fabre Pharma AG, Pfizer, Bard Medica S.A., Abbott AG, Anandic Medical Systems, Pan Gas AG Healthcare, Bracco, Hamilton Medical AG, Fresenius Kabi, Getinge Group Maquet AG, Dräger AG, Teleflex Medical GmbH, Glaxo Smith Kline, Merck Sharp and Dohme AG, Eli Lilly and Company, Baxter, Astellas, Astra Zeneca, CSL Behring, Novartis, Covidien, Philips Medical, Phagenesis Ltd, Prolong Pharmaceuticals and Nycomed outside the submitted work. The money went into departmental funds. No personal financial gain applied.

Figures

Fig. 1
Fig. 1
Kaplan–Meier curve for patients with (red) and without (blue) paracetamol intake prior to up to ten days before admission to intensive care units for COVID-19 (with 95% confidence interval)
Fig. 2
Fig. 2
Sensitivity analyses stratifying 30-day-mortality in subgroups for patient-specific characteristics using logistic regression producing univariate odds ratios. The 30-day-mortality was similar between patients with and without paracetamol intake regardless of treatment limitations, the use of NIV, age strata and the time from symptom onset until admission. Patients categorized as vulnerable according to CFS (OR 0.36) and without endotracheal intubation and vasopressor use (OR 0.62, respectively) were more likely to take paracetamol
See this image and copyright information in PMC

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