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The Burden of Influenza-Associated Critical Illness Hospitalizations*

Ortiz, Justin R. MD; Neuzil, Kathleen M. MD; Shay, David K. MD; Rue, Tessa C. MS; Neradilek, Moni B. MS; Zhou, Hong MS; Seymour, Christopher W. MD; Hooper, Laura G. MD; Cheng, Po-Yung PhD; Goss, Christopher H. MD; Cooke, Colin R. MD

doi: 10.1097/CCM.0000000000000545
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Objective: Influenza is the most common vaccine-preventable disease in the United States; however, little is known about the burden of critical illness due to influenza virus infection. Our primary objective was to estimate the proportion of all critical illness hospitalizations that are attributable to seasonal influenza.

Design: Retrospective cohort study.

Setting: Arizona, California, and Washington from January 2003 to March 2009.

Patients: All adults hospitalized with critical illness, defined by International Classification of Diseases, 9th Edition, Clinical Modification diagnosis and procedure codes for acute respiratory failure, severe sepsis, or in-hospital death.

Measurements and Main Results: We combined the complete hospitalization discharge databases for three U.S. states, regional influenza virus surveillance, and state census data. Using negative binomial regression models, we estimated the incidence rates of adult influenza-associated critical illness hospitalizations and compared them with all-cause event rates. We also compared modeled outcomes to International Classification of Diseases, 9th Edition, Clinical Modification–coded influenza hospitalizations to assess potential underrecognition of severe influenza disease. During the study period, we estimated that 26,760 influenza-associated critical illness hospitalizations (95% CI, 14,541, 47,464) occurred. The population-based incidence estimate for influenza-associated critical illness was 12.0 per 100,000 person-years (95% CI, 6.6, 21.6) or 1.3% of all critical illness hospitalizations (95% CI, 0.7%, 2.3%). During the influenza season, 3.4% of all critical illness hospitalizations (95% CI, 1.9%, 5.8%) were attributable to influenza. There were only 2,612 critical illness hospitalizations with International Classification of Diseases, 9th Edition, Clinical Modification–coded influenza diagnoses, suggesting influenza is either undiagnosed or undercoded in a substantial proportion of critical illness.

Conclusions: Extrapolating our data to the 2010 U.S. population, we estimate that about 28,000 adults are hospitalized for influenza-associated critical illness annually. Influenza in many of these critically ill patients may be undiagnosed. Critical care physicians should have a high index of suspicion for influenza in the ICU, particularly when influenza is known to be circulating in their communities.

Supplemental Digital Content is available in the text.

1Department of Medicine, University of Washington, Seattle, WA.

2Department of Global Health, University of Washington, Seattle, WA.

3Vaccine Access and Delivery Global Program, PATH, Seattle, WA.

4Influenza Division, Centers for Disease Control and Prevention, Centers for Disease Prevention and Control, Atlanta, GA.

5Department of Biostatistics, University of Washington, Seattle, WA.

6The Mountain-Whisper-Light Statistics, Seattle, WA.

7Division of Health Informatics and Surveillance (proposed), Centers for Disease Prevention and Control, Atlanta, GA.

8Departments of Critical Care and Emergency Medicine, University of Pittsburgh, Pittsburgh, PA.

9Department of Medicine, University of Michigan, Ann Arbor, MI.

* See also p. 2441.

This work was performed at the University of Washington.

The opinions expressed by authors do not necessarily reflect the opinions of the Centers for Disease Control and Prevention or the institutions with which the authors are affiliated.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Dr. Ortiz receives funding from the Robert Wood Johnson Harold Amos Medical Faculty Development Program. His institution received grant support from Robert Wood Johnson. Dr. Shay has disclosed government work. Ms. Rue’s institution received grant support from Robert Wood Johnson. Mr. Neradilek has disclosed work for hire. Her institution received support for participation in review activities and support for manuscript writing/review. Dr. Seymour received support for article research from the National Institutes of Health (NIH). His institution received grant support from the NIH. Dr. Goss receives funding from the Cystic Fibrosis Foundation (CFF), the NIH (R01HL103965, R01HL113382, R01AI101307, U M1HL119073, and P30DK089507), and the Food and Drug Administration (R01FD003704). He served as a board member for Transave (no fee paid) and KaloBios Pharmaceuticals (fee donated to cystic fibrosis [CF] clinical research), received grant support from Transave (grant to analyze symptom score data in a clinical trial) and Vertex Pharmaceuticals (grant to perform analysis using multiple existing datasets), lectured for F. Hoffmann-La Roche (honoraria for preparing and giving symposium talk), and received support for manuscript preparation from Johns Hopkins University (honoraria for preparing and giving Continuing Medical Education talks). His institution received grant support from the CFF (grants to conduct clinical trials in methicillin-resistant Staphylococcus aureus eradication, home monitoring, and use of IV Gallium all in CF; grant to Chair CFF Patient Registry Committee), the NIH (grants to conduct clinical trials in home monitoring in CF and the use of IV gallium in CF), and the Food and Drug Administration (grants to conduct a clinical trial in the use of IV gallium in CF). Dr. Cooke is supported by a Mentored Clinical Scientist Research Career Development Award from the Agency for Healthcare Research and Quality (AHRQ) (K08HS020672). He received support for article research from the AHRQ. His institution received grant support from the AHRQ. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: jrortiz@uw.edu

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