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Treatment with vasopressor medications was associated markedly increased risk for developing intensive care unit (ICU)-associated weakness among critically ill patients on mechanical ventilation, researchers said.

This increase, with an odds ratio of 3.2 (P=0.01) relative to patients not receiving such medications, was independent of all other established risk factors for weakness. Specifically:

• Norepinephrine was the most commonly used drug, with 60% of patients with ICU-acquired weakness receiving norepinephrine compared with 24% of patients without ICU-acquired weakness (P<0.0001)
• Patients with ICU-acquired weakness were also treated with vasopressin (48% versus 22%; P=0.0002) and phenylephrine (31% versus 5%; P<0.0001) more frequently than patients without ICU-acquired weakness
• Dobutamine, dopamine, and epinephrine were used less often, and no significant difference was seen in weakness between the two groups

"We show in a population of critically ill, mechanically ventilated patients that the use of vasoactive medications is independently associated with the diagnosis of ICU-associated weakness at hospital discharge," wrote Krysta Wolfe, MD, of the University of Chicago, and colleagues in . "Importantly, the use of steroids and neuromuscular blockers did not differ between the groups."

Vasopressor drugs are commonly given to patients with shock in the ICU to raise blood pressure and restore blood flow to vital organs. ICU-associated muscle weakness often increases hospital stays and can persist for years after discharge,

"Many risk factors for the development of ICU-acquired weakness have been described, including pharmacologic interventions used in the treatment of critically ill patients, such as glucocorticoids and neuromuscular blocking agents. It is unclear what role other pharmacologic agents used in the ICU, such as vasoactive medications, have in the development of ICU-acquired weakness," the researchers wrote.

"The effect of vasoactive medication use remained significant when evaluating the subgroup of patients that survived to hospital discharge. This suggests that vasoactive medications, above and beyond being a marker for other risk factors associated with ICU-acquired weakness, may have a direct and independent effect on the development of neuromuscular weakness."

The study was a retrospective analysis that included data from a randomized trial designed to examine the impact of early versus late occupational and physical therapy on functional outcomes and the development of weakness in the ICU setting.

Patients in the trial (n=172) were originally randomized to receive early occupational and physical therapy (within 72 hours of mechanical ventilation) versus conventional therapy, with the endpoint being ICU-acquired weakness on hospital discharge. All patients had bedside muscle strength testing performed by a therapist blinded to study allocation to evaluate ICU-acquired weakness.

All patients received daily assessment for sepsis, and the initiation and choice of vasoactive drugs were determined by the primary medical service. The type and dose of vasoactive medications given were recorded daily for all patients.

A total of 80 patients had ICU-acquired weakness on hospital discharge. Patients with ICU-acquired weakness tended to be older and have higher APACHE (Acute Physiology and Chronic Health Evaluation) II scores, higher incidence of sepsis, longer hospital stays, and a longer duration of mechanical ventilation.

Study limitations, the team noted, included the retrospective design and the fact that patients were recruited from a single treatment center.