During the influenza season, almost one third of patients hospitalized in our adult ICUs and with suggestion of lower respiratory tract infection had influenza. Influenza was unsuspected in 48.4% and hospital acquired in 42%. Patients with unsuspected influenza were more frequently admitted to the ICU for surgery, had a localized infiltrate on chest radiograph, and stayed longer in the ICU before being diagnosed with influenza. Antiviral treatment was initiated later in patients with unsuspected influenza, although mortality was similar in both groups. Overall mortality at 30 days after the influenza diagnosis was 29%; however, it was lower in patients with nosocomial influenza. Severe respiratory failure as the cause of admission to the ICU was the only independent factor associated with poor outcome.
Acute febrile respiratory illness is a common cause of respiratory failure and admission to the ICU [2–4]. In most cases, the etiology is bacterial, although viruses have been implicated in almost 9% of cases . During the 2009 pandemic, the rate of ICU admission for respiratory failure among hospitalized patients with a confirmed diagnosis of influenza A (H1N1v) ranged from 15% to 34% [18–22]. However, no studies have investigated the rates of bacterial and viral etiologies among patients admitted to the ICU with suggestion of lower respiratory tract infection during the 2009 pandemic. Here, we demonstrated that, after the pandemic influenza season, the etiology was viral in 31.4% of patients admitted to the ICU with suggestion of lower respiratory tract infection. Influenza was detected in most of these cases (93.9%).
The etiology of acute febrile respiratory illness causing respiratory failure is often unknown at admission to the ICU . About half of the cases are diagnosed as bacterial pneumonia shortly after admission, with a small number of cases found to be viral pneumonia when the initial bacterial studies are negative . Detection of influenza virus often depends on specific epidemiologic risk factors and clinical suspicion. The combination of fever, malaise, and cough was shown to have a 79% positive predictive value during the pandemic and seasonal epidemics [23, 24]; however, these criteria may be not accurate in ICU patients, because other etiologies, or conditions like as postsurgery sedation, may confound the diagnosis . In our study, influenza was unsuspected in 48.4% of cases. Suspicion of influenza was lower in older patients, in those admitted to the ICU for surgical conditions, in those who stayed for a longer time in hospital and ICU, and in those who did not have a cough and diffuse pulmonary infiltrates. The direct consequence of overlooked influenza was a significant delay in the initiation of antiviral treatment.
Definitive diagnosis of influenza is by detection of the virus in culture or RT-PCR with a nasopharyngeal aspirate/swab or lower respiratory tract sample [23, 24]. Because viral shedding peaks at 48 hours after the onset of illness and declines thereafter, testing of lower respiratory tract samples in patients with compromised lung parenchyma may be more beneficial [23, 26, 27]. Accordingly, we found that the upper respiratory tract sample did not reveal influenza in 17.6% of cases. Diagnostic viral load tended to be higher in patients with suspected influenza, possibly as a result of the earlier diagnosis of influenza after onset of symptoms in this group compared with patients with unsuspected influenza.
Hospital-acquired influenza is a well-recognized problem [28, 29]. Nosocomial outbreaks of pandemic and seasonal influenza have been documented in various settings, including ICUs, pediatric wards, transplant units, medical wards, and surgical wards [28–32]. However, few sporadic cases of hospital-acquired influenza have been reported during surveillance activities . In a study including 1,520 patients hospitalized with the pandemic 2009 influenza A in 75 hospitals in the United Kingdom, the authors identified 30 (2%) cases of sporadic nosocomial influenza . These comprised 15 adults and 15 children. Most had serious underlying illnesses and were admitted to nonmedical areas, as in our study. Unexpectedly, we found that the 30-day mortality rate was lower in patients with hospital-acquired influenza. This figure can be associated with viral factors, such as lower virulence of the influenza strains circulating in the hospital, or with host factors, such as older age and surgical conditions.
Overall, 30-day mortality was high (29%), and admission to the ICU for severe respiratory failure was an independent risk factor for death. These data are consistent with those of Martin-Loeches et al. , who showed that patients from the postpandemic influenza pH1N1 period had an unexpectedly high mortality rate. Early administration of antiviral therapy has been associated with better outcome in critically ill patients . In our study, although the timing to initiation of antiviral treatment was longer among patients with unsuspected influenza, a trend to lower mortality was seen in this group compared with patients with suspected influenza. A possible explanation of this finding could be that: suspected and unsuspected groups were epidemiologically very different, and the median relative viral load was lower in the unsuspected group; thus, epidemiologic and viral factors could influence the outcome in the two groups independently of the timing of antiviral treatment. Conversely, the benefit of testing will not be necessarily to the patient in terms of improved outcome due to early therapy, but more likely to preventing the nosocomial transmission of influenza.
Our study is limited in that the small number and heterogeneity of patients diminishes the power of our data analysis. We performed the study during the postpandemic period (2010 to 2011), when the prevalence of the pandemic influenza A H1N1 strain was still high. Findings could vary between one influenza season and another, depending on the characteristics of the prevalent influenza virus stain. We did not perform a cost-effectiveness analysis, although the finding of a longer ICU and hospital stay in patients with unsuspected influenza suggests a potential favorable impact on care management. We could not perform an analysis of the possible routes of transmission of the nosocomial cases. However, we can exclude with sufficient certainty the occurrence of an outbreak for the following reasons: (a) the cases of hospital-acquired influenza were distributed uniformly between the three ICUs (postsurgery ICU, six; medical ICU, five; and postcardiosurgery ICU, two); (b) no case of influenza was recognized among the health-care staff during the study period; (c) the preventive measures included vaccination of staff, respiratory isolation, and droplet-contact precautions, as recommended by the Centers for Disease Control and Prevention .