Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09

Abstract

Background: Neuraminidase inhibitor (NAI) antiviral drugs can shorten the duration of uncomplicated influenza when administered early (<48 hours after illness onset) to otherwise healthy outpatients, but the optimal timing of effective therapy for critically ill patients is not well established.

Methods: We analyzed California surveillance data to characterize the outcomes of patients in intensive care units (ICUs) treated with NAIs for influenza A(H1N1)pdm09 (pH1N1). Demographic and clinical data were abstracted from medical records, using standardized case report forms.

Results: From 3 April 2009 through 10 August 2010, 1950 pH1N1 cases hospitalized in ICUs were reported. Of 1859 (95%) with information available, 1676 (90%) received NAI treatment, and 183 (10%) did not. The median age was 37 years (range, 1 week-93 years), 1473 (79%) had ≥1 comorbidity, and 492 (26%) died. The median time from symptom onset to starting NAI treatment was 4 days (range, 0-52 days). NAI treatment was associated with survival: 107 of 183 untreated case patients (58%) survived, compared with 1260 of 1676 treated case patients (75%; P ≤ .0001). There was a trend toward improved survival for those treated earliest (P < .0001). Treatment initiated within 5 days after symptom onset was associated with improved survival compared to those never treated (P < .05).

Conclusions: NAI treatment of critically ill pH1N1 patients improves survival. While earlier treatment conveyed the most benefit, patients who started treatment up to 5 days after symptom onset also were more likely to survive. Further research is needed about whether starting NAI treatment >5 days after symptom onset may also convey benefit.

Figure 1.

Survival comparison of critically ill case patients with influenza A(H1N1)pdm09 in California, with and without antiviral treatment, April 2009–August 2010. ^aIncludes all cases with known treatment information, regardless of whether the date of symptom onset or start of antiviral treatment was known. ^bBy using “Never treated” as the reference group, the proportion of case patients who survived when treated on these days is significantly higher, at P < .05. ^cDay 0 is defined as the date of symptom onset. ^dThe Cochran-Armitage test for trend was used to assess the time from onset of symptoms to initiation of antiviral treatment and survival (P < .0001). The error bars represent 95% confidence intervals.