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Vasopressor use in critically ill COVID-19 patients associated with higher mortality

Vasopressor use in patients with COVID-19 admitted to an intensive care unit due to critical illness increases the risk of mortality

Vasopressor use in COVID-19 patients who become critically ill is linked to an increased risk of death compared to those not given such drugs according to the results of a meta-analysis by a team of Greek and US researchers.

Patients who are critically ill with not only COVID-19 but any illness, require haemodynamic support. In 2020, the Surviving Sepsis Campaign COVID-19 panel issued a number of statements regarding the management of COVID-19. In relation to COVID-19 and shock, the panel advocated that for adults who experience shock, use of norepinephrine should be used as the first-line vasoactive agent.

Vasopressor use is designed to increase vascular tone and is necessary in critically ill patients with profound haemodynamic impairment such that tissue blood flow is not sufficient to meet metabolic requirements. Vasopressors are commonly used, in fact, one survey of critical care staff managing patients with COVID-19 found that overall, 56% reported (combined very frequent/frequent use) vasopressor use in COVID-19 patients.

Despite the impact on haemodynamic stability, vasopressors are known to have several adverse cardiovascular effects. For example, in one study, new-onset tachyarrhythmias, prolonged elevation of heart rate and myocardial cell damage were frequently observed and that overall, adverse cardiac events occurred in 48.2 % of all intensive care patients.

Although current guidelines recommend the use of catecholamines for their haemodynamic effects, these 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 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 days 28 or 30 but if this data was missing, simply referred to the level of all-cause mortality reported. A secondary outcome considered was the level of acute kidney injury.

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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 also 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