Tuesday, August 25, 2009

H1N1 and the ICU

Intensive-Care Patients With Severe Novel Influenza A (H1N1) Virus Infection --- Michigan, June 2009

In April 2009, CDC reported the first two cases in the United States of human infection with a novel influenza A (H1N1) virus (1). As of July 6, a total of 122 countries had reported 94,512 cases of novel influenza A (H1N1) virus infection, 429 of which were fatal; in the United States, a total of 33,902 cases were reported, 170 of which were fatal.* Cases of novel influenza A (H1N1) virus infection have included rapidly progressive lower respiratory tract disease resulting in respiratory failure, development of acute respiratory distress syndrome (ARDS), and prolonged intensive care unit (ICU) admission (2). Since April 26, communitywide transmission of novel influenza A (H1N1) virus has occurred in Michigan, with 655 probable and confirmed cases reported as of June 18 (Michigan Department of Community Health [MDCH], unpublished data, 2009). This report summarizes the clinical characteristics of a series of 10 patients with novel influenza A (H1N1) virus infection and ARDS at a tertiary-care ICU in Michigan. Of the 10 patients, nine were obese (body mass index [BMI] ≥30), including seven who were extremely obese (BMI ≥40); five had pulmonary emboli; and nine had multiorgan dysfunction syndrome (MODS). Three patients died. Clinicians should be aware of the potential for severe complications of novel influenza A (H1N1) virus infection, particularly in extremely obese patients.

The surgical intensive care unit (SICU) at the University of Michigan Health System (UMHS) specializes in the evaluation of adult patients with severe ARDS for advanced mechanical ventilation and possible extracorporeal membrane oxygenation (ECMO). During May 26--June 18, the unit received 13 patients for evaluation from outlying hospitals, 10 of whom were confirmed to have novel influenza A (H1N1) virus infection by testing of respiratory specimens with real-time reverse transcription--polymerase chain reaction (rRT-PCR) at MDCH and CDC. Direct immunofluorescent antibody staining at UMHS was negative for influenza A in all 10 patients. Viral culture at UMHS was positive for influenza A in two patients. All 10 patients were referred to the SICU because of severe hypoxemia, ARDS, and an inability to achieve adequate oxygenation with conventional ventilation modalities. Medical records of all 10 patients were reviewed for demographics, case characteristics, clinical findings, and clinical course.

Illness onset of the 10 patients occurred during May 22--June 13. The median age was 46 years (range: 21--53 years); nine patients were obese, including seven who were extremely obese (Table). In the three fatal cases, the time from illness onset to death ranged from 17 to 30 days. Four patients received steroids during their illness before transfer to the SICU; two with asthma received oral steroids as outpatients during the initial evaluation and treatment of their acute respiratory illness (one was on chronic oral steroids for underlying lung disease, and one without chronic pulmonary disease was prescribed oral steroids and oral antimicrobials). Five patients received intravenous corticosteroids during their SICU hospitalization: four for treatment of severe vasopressor-dependent refractory septic shock, and one for continuation of therapy for chronic pulmonary disease.

All 10 patients required initial advanced mechanical ventilation (high-frequency oscillatory or bilevel ventilation with high mean airway pressures [32--55 cm H20]). Two patients required veno-venous ECMO support. Six required continuous renal replacement therapy (CRRT) for acute renal failure. Upon transfer to the SICU, five had elevated white blood cell counts, and one had a decreased white blood cell count. The median white blood cell count (WBC) was 9,500 cells/mm3 (range: 3,700--19,700 cells/mm3; normal: 4,000--10,000 cells/mm3). All ten patients had elevated aspartate transaminase (AST) levels. The median AST level was 83.5 IU/L (range: 41--109 IU/L; normal: 8--30 IU/L). Six of the nine patients who were tested had elevated creatine phosphokinase (CPK) levels. The median CPK level was 999 IU/L (range: 51-- 6,572 IU/L; normal: 38--240 IU/L). Nine patients were admitted to the SICU with MODS, and nine manifested septic shock requiring vasopressor support. All 10 patients required tracheostomy.

Chest radiograph findings in all 10 patients were abnormal, with bilateral infiltrates consistent with severe multilobar pneumonia or ARDS. Computed tomography (CT) of the chest confirmed pulmonary emboli in four patients at admission to the SICU and in one additional patient who deteriorated 6 days after admission to the SICU. A hypercoagulable state was evident in two additional patients. One of these patients had frequent clotting of the CRRT circuit despite regional citrate anticoagulation. Another patient had bilateral iliofemoral deep venous thromboses, necessitating systemic heparin anticoagulation. None of the 10 patients had evidence of concomitant disseminated intravascular coagulation by laboratory studies.

As of July 8, none of the 10 patients had evidence of bacterial infection after admission to the SICU or in subsequent blood, bronchoalveolar lavage, or urine cultures. All patients received antibiotic therapy upon admission to the initial hospitals, and broad spectrum antibiotics were continued upon transfer to the SICU.

The timing of antiviral treatment initiation was difficult to determine because patients were transferred from other hospitals; however, the estimated median number of days from illness onset to initiation of antiviral treatment was 8 days (range: 5--12 days). During their care at the SICU, all 10 patients were administered oseltamivir and amantadine beyond the standard 5-day course, including higher-dose oseltamivir (up to 150 mg orally twice a day), with dose adjustment for decreased renal function.

As of July 8, one patient remained in the SICU requiring ECMO, one remained on advanced mechanical ventilation, five were transferred back to the referring facility in stable condition, and three had died. Autopsies were performed on two patients; results in both patients confirmed bilateral severe hemorrhagic viral pneumonitis with interstitial inflammation and diffuse alveolar damage and concurrent bilateral pulmonary emboli.

Reported by: LM Napolitano, MD, PK Park, MD, KC Sihler, MD, T Papadimos, MD, Div of Acute Care Surgery, Univ of Michigan Health System; C Chenoweth, MD, S Cinti, MD, C Zalewski, MPH, Div of Infectious Diseases and Infection Control, Univ of Michigan Health System; R Sharangpani, MD, Univ of Michigan School of Public Health; P Somsel, DrPH, E Wells, MD, Michigan Dept of Community Health. AM Fry, MD, AE Fiore, MD, MPH, JM Villanueva, PhD, S Lindstrom, PhD, TM Uyeki, MD, Influenza Div, National Center for Immunization and Respiratory Diseases, CDC.

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