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Meta-analysis finds vasopressor use in critically ill COVID-19 patients linked to higher mortality

Vasopressor use for critically ill COVID-19 patients in either intensive care or high dependency units leads to a higher risk of mortality, according to a recent study

Vasopressor use in critically ill COVID-19 patients is associated with an increased risk of death according to the results of a meta-analysis by a team of Greek and US researchers.

All critically ill patients, including those with COVID-19, often require haemodynamic support. In a 2020 statement, the Surviving Sepsis Campaign COVID-19 panel advocated that for adults who experience shock, norepinephrine should be the first-line vasoactive agent. Vasopressor use is designed to increase vascular tone and required in critically ill patients with profound haemodynamic impairment when tissue blood flow is insufficient to meet metabolic requirements. Vasopressors are commonly used and in one survey of critical care staff managing patients with COVID-19, it was found that overall, 56% reported (combined very frequent/frequent use) vasopressor use in COVID-19 patients. Despite the impact on haemodynamic stability, vasopressors have several adverse cardiovascular effects. For instance, in one study, new-onset tachyarrhythmias, prolonged elevation of heart rate and myocardial cell damage were frequently observed such that overall, adverse cardiac events occurred in 48.2% of all intensive care patients.

Although current guidelines recommend the use of catecholamines as the drug of first choice for their haemodynamic effects, the drugs have numerous other biological effects in shock states including aggravation of hyper-metabolism by promoting hyperglycaemia, which further increase oxygen demands and can contribute to further organ damage. It is possible therefore that vasopressor use in critically ill COVID-19 patients could also have a deleterious effect although this has not been fully examined.

For the present study (which is available as a preprint), the researchers systematically reviewed the literature for studies in which adult critically ill patients were given vasopressors. They set the primary outcome of interest as all-cause mortality at 28 or 30 days but where this specific time-point was not stated, the researchers simply quoted the level of all-cause mortality reported. A secondary outcome considered was the level of acute kidney injury.

Vasopressor use and all-cause mortality

A total of 33 observational studies were included in the final analysis although only 30 included a direct comparison of vasopressor use vs no use. The remaining three studies examined either use of angiotensin-II use only (1 study) or angiotensin-II vs vasopressor use.

The primary outcome could be assessed from 21 of the studies with 7,900 patients. The analysis revealed that vasopressor use was associated with a statistically significant increased risk of mortality (relative risk, RR = 4.26, 95% CI 3.15 – 5.76,p < 0.001). In subgroup analysis by department of admission, i.e., intensive care (RR = 3.45) or high dependency unit (RR = 6.25) also revealed a significant increased mortality risk (p < 0.001 in both cases).

For the secondary outcome of acute kidney injury, vasopressor use was significantly associated with a greater risk of the outcome (RR = 3.17, 95% CI 2.21 – 4.54, p < 0.001).

The authors concluded that vasopressor use was associated with a higher level of mortality in critically ill COVID-19 patients and called for further studies to estimate the correlation of specific vasopressor agents with adverse effects and mortality.

Mermiri M et al. The effect of vasopressors on mortality in critically ill patients with COVID-19: A systematic review and meta-analysis Med Rxiv 2022

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