Impact of early oseltamivir treatment on outcome in critically ill patients with 2009 pandemic influenza A.

OBJECTIVES: The impact of oseltamivir on mortality in critically ill patients with 2009 pandemic influenza A (2009 H1N1) is not clear. The main objective of this study was to investigate the relationship between the timing of antiviral administration and intensive care unit (ICU) outcomes. METHODS: Prospective, observational study of a cohort of ICU patients with confirmed 2009 H1N1 infection. Clinical data, treatment and outcome were compared between patients receiving early treatment (ET) with oseltamivir, initiated within 2 days, and patients administered late treatment (LT), initiated after this timepoint. Multivariate analysis and propensity score were used to determine the effect of oseltamivir on ICU mortality. RESULTS: Six hundred and fifty-seven patients were enrolled. Four hundred and four (61.5%) patients required mechanical ventilation (MV; mortality 32.6%). Among them, 385 received effective antiviral therapy and were included in the study group. All patients received oseltamivir for a median duration of 10 days (interquartile range 8-14 days). Seventy-nine (20.5%) ET patients were compared with 306 LT patients. The two groups were comparable in terms of main clinical variables. ICU length of stay (22.7 ±â€Š16.7 versus 18.4 ±â€Š14.2 days; P = 0.03), hospital length of stay (34.0 ±â€Š20.3 versus 27.2 ±â€Š18.2 days; P = 0.001) and MV days (17.4 ±â€Š15.2 versus 14.0 ±â€Š12.4; P = 0.04) were higher in the LT group. ICU mortality was also higher in LT (34.3%) than in ET (21.5%; OR = 1.9; 95% CI 1.06-3.41). A multivariate model identified ET (OR = 0.44; 95% CI 0.21-0.87) as an independent variable associated with reduced ICU mortality. These results were confirmed by propensity score analysis (OR = 0.44; 95% CI 0.22-0.90; P < 0.001). CONCLUSIONS: Our findings suggest that early oseltamivir administration was associated with favourable outcomes among critically ill ventilated patients with 2009 H1N1 virus infection.

Severe pandemic (H1N1)v influenza A infection: report on the first deaths in Spain.

BACKGROUND AND OBJECTIVE: The impact of pandemic influenza A (H1N1)v infection is still unknown but it is associated with a high case-fatality rate. METHODS: This was a prospective, observational, multicentre study conducted in 144 Spanish intensive care units. Demographic and clinical data were reviewed for all cases of pandemic influenza A (H1N1)v infection reported from 23 June 2009 through 11 February 2010 and confirmed by reverse transcriptase PCR assay. RESULTS: Out of 872 cases reported by statewide surveillance, data for the first 131 deceased patients were analysed. Thirty-seven patients (28.2%) died within the first 14 days. The median age of these patients was 46 years (interquartile range 35-58) and 60.3% were male. Twenty-eight patients (21.4%) did not present with any comorbidities on admission. Forty-six per cent of patients were reported to be obese and 22 (16.8%) had COPD. The vast majority of the patients (72.5%) had viral pneumonia; 95.4% of these had bilateral patchy alveolar opacities (predominantly basal), affecting three or four quadrants. One hundred and fifteen patients (87.8%) developed multi-organ dysfunction syndrome. Ninety-seven patients (74%) required vasopressor drugs, 37 (27.2%) received renal replacement therapy, and 47 (35.1%) received intravenous corticosteroids on admission to the intensive care unit. Only 68 patients (51.9%) received empirical antiviral treatment. CONCLUSIONS: One-third of patients with pandemic influenza A (H1N1)v infection died within the first two weeks and these were young patients, with rapidly progressive viral pneumonia as the primary cause of admission. Obese patients were at high risk but one in four patients did not present with any risk factors on admission. Only half the patients received empirical antiviral therapy and this was administered late.

Intensive care adult patients with severe respiratory failure caused by Influenza A (H1N1)v in Spain.

INTRODUCTION: Patients with influenza A (H1N1)v infection have developed rapidly progressive lower respiratory tract disease resulting in respiratory failure. We describe the clinical and epidemiologic characteristics of the first 32 persons reported to be admitted to the intensive care unit (ICU) due to influenza A (H1N1)v infection in Spain. METHODS: We used medical chart reviews to collect data on ICU adult patients reported in a standardized form. Influenza A (H1N1)v infection was confirmed in specimens using real-time reverse transcriptase-polymerase-chain-reaction (RT PCR) assay. RESULTS: Illness onset of the 32 patients occurred between 23 June and 31 July, 2009. The median age was 36 years (IQR = 31 - 52). Ten (31.2%) were obese, 2 (6.3%) pregnant and 16 (50%) had pre-existing medical complications. Twenty-nine (90.6%) had primary viral pneumonitis, 2 (6.3%) exacerbation of structural respiratory disease and 1 (3.1%) secondary bacterial pneumonia. Twenty-four patients (75.0%) developed multiorgan dysfunction, 7 (21.9%) received renal replacement techniques and 24 (75.0%) required mechanical ventilation. Six patients died within 28 days, with two additional late deaths. Oseltamivir administration delay ranged from 2 to 8 days after illness onset, 31.2% received high-dose (300 mg/day), and treatment duration ranged from 5 to 10 days (mean 8.0 +/- 3.3). CONCLUSIONS: Over a 5-week period, influenza A (H1N1)v infection led to ICU admission in 32 adult patients, with frequently observed severe hypoxemia and a relatively high case-fatality rate. Clinicians should be aware of pulmonary complications of influenza A (H1N1)v infection, particularly in pregnant and young obese but previously healthy persons.