An Assessment of H1N1 Influenza-Associated Acute Respiratory Distress Syndrome Severity after Adjustment for Treatment Characteristics

Pandemic influenza caused significant increases in healthcare utilization across several continents including the use of high-intensity rescue therapies like extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation (HFOV). The severity of illness observed with pandemic influenza in 2009 strained healthcare resources. Because lung injury in ARDS can be influenced by daily management and multiple organ failure, we performed a retrospective cohort study to understand the severity of H1N1 associated ARDS after adjustment for treatment. Sixty subjects were identified in our hospital with ARDS from “direct injury” within 24 hours of ICU admission over a three month period. Twenty-three subjects (38.3%) were positive for H1N1 within 72 hours of hospitalization. These cases of H1N1-associated ARDS were compared to non-H1N1 associated ARDS patients. Subjects with H1N1-associated ARDS were younger and more likely to have a higher body mass index (BMI), present more rapidly and have worse oxygenation. Severity of illness (SOFA score) was directly related to worse oxygenation. Management was similar between the two groups on the day of admission and subsequent five days with respect to tidal volumes used, fluid balance and transfusion practices. There was, however, more frequent use of “rescue” therapy like prone ventilation, HFOV or ECMO in H1N1 patients. First morning set tidal volumes and BMI were significantly associated with increased severity of lung injury (Lung injury score, LIS) at presentation and over time while prior prescription of statins was protective. After assessment of the effect of these co-interventions LIS was significantly higher in H1N1 patients. Patients with pandemic influenza-associated ARDS had higher LIS both at presentation and over the course of the first six days of treatment when compared to non-H1N1 associated ARDS controls. The difference in LIS persisted over the duration of observation in patients with H1N1 possibly explaining the increased duration of mechanical ventilation

Adjusted lung injury score by influenza status.

<p>Analyses adjusted for significant covariates (change of risk factor coefficient by ±15%) which included BMI, statin use and daily tidal volume used in addition to age and SOFA score.</p

Treatment variables over the first six days of therapy and outcomes.

<p>All values represent means ± SD unless otherwise specified.</p>1<p><i>p</i>-values based on the following tests: <i>t-</i>test for variables presented as means, Wilcoxon rank-sum test for variables presented as the median, Fisher's exact test of association for categorical variables.</p

ARDS-related pulmonary measures over the first six days of treatment.

<p>All variables [A) PaO₂/FiO₂ ratio; B) positive end expiratory pressure; C) pulmonary compliance; D) lung injury (Murray) score] are recorded from the first complete data point after 8am on each day of observation while on conventional mechanical ventilation. Values from subjects requiring ECMO were dropped on days this modality was utilized. Bars represent box plots for each variable by day and cause of ARDS (H1N1-associated vs non H1N1). Center line represents the median; edges of each box represent the 75^th and 25^th percentiles and whiskers the maximum and minimum values. Dots indicate outliers. (n, for H1N1 associated ARDS is 23, 20, 18, 17, 16 and 14 and non-H1N1 is 30, 33, 34, 30, 29 and 22 for day 0–5).</p

Cohort enrollment diagram.

<p>Cohort enrollment diagram.</p

Unadjusted lung injury score by influenza status.

<p>AUC, area under the curve for first daily lung injury scores.</p