Critically ill patients supported by respirators in ICUs may develop weakness from drug treatment, not illness

Findings suggest an association between use of vasopressors and onset of new weakness, according to a new study in the journal CHEST®

Glenview, IL, September 11, 2018

At least 25 percent of critically ill patients who receive mechanical ventilation in intensive care units (ICUs) develop muscular weakness severe enough to impair their quality of life. In a new study published in the journal CHEST® designed to investigate possible causes, researchers found that mechanically ventilated patients treated with vasopressor medications had a more than three-fold increase in the odds of developing ICU-associated weakness. These findings highlight the unintended adverse effects of treatment and suggest possible interventions or avoidance strategies.

Patients with shock, a life-threatening condition causing a decrease in blood flow to the body, often require treatment with vasopressor medications that raise the blood pressure and restore blood flow to vital organs.

“Survivorship from critical illness is improving; however, patients often inherit many burdens including severe persistent weakness. In order to work towards improving long-term outcomes of critical illness, it is imperative to first improve our understanding of why patients develop weakness, specifically whether it is solely due to the underlying illness or if the treatments provided during the course of critical illness also play a role,” explained lead investigator Krysta S. Wolfe, MD, of the University of Chicago, Department of Medicine, Section of Pulmonary and Critical Care, Chicago, IL, USA.

Dr. Wolfe and co-investigators conducted a retrospective analysis of data from two clinical trials that studied the effects of engaging in early versus late physical and occupational therapy on functional outcomes and the development of weakness, focusing on 172 mechanically ventilated patients, some of whom experienced shock. Of these, 80 demonstrated ICU-associated weakness when discharged from the hospital.

The researchers found that the use of vasoactive medications was associated with a greater than three-fold increase in the odds of developing weakness. Every day that a patient received a vasoactive medication, the odds of developing weakness increased by 35 percent.

To better understand how vasopressors might be causing weakness, the researchers divided the data according to whether the patients received vasopressors that stimulate beta-adrenergic receptors (norepinephrine, epinephrine, dopamine, and dobutamine) and those that do not (phenylephrine and vasopressin). They found only vasopressors that stimulate beta-adrenergic receptors were associated with weakness. In fact, the incidence of ICU-associated weakness increased along with the cumulative dose of norepinephrine, but not with vasopressin or phenylephrine.

Bar graph proportion of patients with ICU-acquired weakness significantly increases with increasing cumulative dose of norepinephrine
The proportion of patients with ICU-acquired weakness significantly increases with increasing cumulative dose of norepinephrine (Chi² for trend P value < .0001).

“Vasopressors are medications commonly used in the ICU that have not traditionally been thought to independently contribute to the development of weakness. Recognition of this potential effect of vasopressors is important and can help direct future study and targeted interventions, such as early physical therapy, to reduce the risk of developing weakness during critical illness,” commented senior investigator John P. Kress, MD, FCCP, the University of Chicago, Department of Medicine, Section of Pulmonary and Critical Care, Chicago, IL, USA.

The findings also suggest that noradrenergic vasopressors may not be the best choice for patients at heightened risk of ICU-associated weakness. The investigators recommend that the potential connection between vasopressors and weakness after critical illness merits further investigation.


Notes for editors
The article is “Impact of Vasoactive Medications on ICU-Acquired Weakness in Mechanically Ventilated Patients,” by Krysta S. Wolfe, MD; Bhakti K. Patel, MD; Erica L. MacKenzie, MD; Shewit P. Giovanni, MD; Anne S. Pohlman, MSN; Matthew M. Churpek, MD, MPH, PhD; Jesse B. Hall, MD, FCCP; and John P. Kress, MD, FCCP ( It will appear in the journal CHEST® volume 154, issue 4 (October 2018) published by Elsevier.

This study was funded in part by an NIH/NHLBI grant (T32 HL007605), a Research Training in Respiratory Biology T32 grant (HL007605, NIH/NHLBI), and the Parker B. Francis Fellowship.

Full text of this article and interviews with the authors are available to credentialed journalists upon request; contact Andrea Camino, American College of Chest Physicians, at +1 224 521 9513 or

About the journal CHEST®
The journal CHEST®, the official publication of the American College of Chest Physicians, features the best in peer-reviewed, cutting-edge original research in the multidisciplinary specialties of chest medicine: pulmonary, critical care, and sleep medicine; thoracic surgery; cardiorespiratory interactions; and related disciplines. Published since 1935, it is home to the highly regarded clinical practice guidelines and consensus statements. Readers find the latest research posted in the Online First section each week and access series that provide insight into relevant clinical areas, such as Recent Advances in Chest Medicine; Topics in Practice Management; Pulmonary, Critical Care and Sleep Pearls; Ultrasound Corner; Chest Imaging and Pathology for Clinicians; and Contemporary Reviews. Point/Counterpoint Editorials and the CHEST Podcasts address controversial issues, fostering discussion among physicians.

About American College of Chest Physicians® (CHEST)
CHEST is the global leader in advancing best patient outcomes through innovative chest medicine education, clinical research and team-based care. Its mission is to champion the prevention, diagnosis and treatment of chest diseases through education, communication and research. It serves as an essential connection to clinical knowledge and resources for its 19,000 members from around the world who provide patient care in pulmonary, critical care and sleep medicine. For information about the American College of Chest Physicians and its flagship journal CHEST®, visit

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Media contact  
Andrea Camino
American College of Chest Physicians (CHEST)
+1 224 521 9513