French study profiles ICU patients with H1N1

Oct 26, 2010 (CIDRAP News) – A thorough surveillance study from France reinforces findings from other countries about obesity and delayed antiviral treatment as risk factors for severe 2009 H1N1 influenza, while indicating that the pandemic put a greater burden on intensive care units (ICUs) than seasonal flu typically does.

Writing in Epidemiology and Infection, investigators from France's National Institute for Public Health Surveillance report that 1,065 French patients aged 15 years and older required intensive care for confirmed H1N1 infections from July 2009 through mid February of this year and that 20% of them died.

The researchers found that for ICU patients the risk of a severe outcome—death or the need for mechanical ventilation—increased with age, obesity, and late antiviral treatment. "This study confirms the main results published in the literature and highlights the role of obesity as an independent risk factor for severe disease and the protective role of rapid antiviral treatment," they write.

They also report that the number of patients admitted to French ICUs with a flu diagnosis from October 2009 to January 2010 was several times the numbers admitted during the same period in the previous 3 years.

National surveillance set up
The article explains that France set up a national surveillance system to count all hospitalized H1N1 patients starting Jul 1, 2009. Because of surging numbers of cases, the surveillance was narrowed in November to include only the patients admitted to ICUs.

From Jul 1, 2009, through Feb 15, 2010, 1,297 patients were reported to have been admitted to an ICU for pandemic flu in France. Of those, 1,117 were 15 or older, and 1,065 had lab-confirmed cases.

Only 13% of the ICU patients were 65 years or older. Thirty-five percent of the patients were between 50 and 64 years old, though this age-group made up only 18% of the general population. Another 20% of the patients were between 40 and 49 years old, 12% were 30 to 39, 14% were 20 to 29, and 5% were 15 to 19.

Eighty-two percent of the patients had an underlying health condition, including 33% with a chronic respiratory disease, with asthma accounting for 13%. Another 6% were pregnant (versus a 1% pregnancy rate in the general population), while 20% were obese (versus 12% in the general population) and 6% were morbidly obese. Sixteen patients had been vaccinated against the pandemic virus, but 15 of them had been vaccinated less than a week before getting sick.

Of the 1,065 patients, 217 (20%) died, the report says. Sixty-seven percent of the patients required mechanical ventilation, 49% suffered from acute respiratory distress syndrome, and 7% were treated with extra-corporeal membrane oxygenation (ECMO).

A multivariate analysis showed that age led the list of significant independent risk factors for a severe outcome (mechanical ventilation or death). Compared with younger patients, the adjusted odds ratio (OR) for those aged 40 to 64 was 2.4, and the ratio for those 65 and older was 3.5. Antiviral therapy that was delayed more than 48 hours after illness onset was a significant risk factor for those with predisposing risk factors (OR, 2.0), but not in those without such risk factors, the researchers found.

They also found that pregnancy was not associated with an increased risk of a severe outcome, while chronic respiratory disease was actually linked to a lower risk of such an outcome (OR, 0.4).

More ICU cases than with seasonal flu
The authors further report that the French national hospital discharge database shows that 1,748 patients were admitted to ICUs with a flu diagnosis (confirmed or unconfirmed) in the 13 weeks from mid October 2009 to mid January 2010. By comparison, the numbers for the same periods during the three previous flu seasons were 148, 172, and 344.

"This increase reflects the H1N1 severity compared to seasonal influenza," even though increased testing during the pandemic may have contributed to the higher number, the report states.

The investigators say their findings are consistent with reports from other countries. For example, in Australia and New Zealand, the rate of ICU admission was low in the elderly, but the risk of death for ICU patients increased with age, they report, citing a November 2009 article in the New England Journal of Medicine.

"This first large series of severe cases in Europe confirms the high contribution of young adults, aged 30-64 years, to A(H1N1) mortality," the researchers say. They add that their analysis doesn’t include all French deaths related to the virus, because it included only lab-confirmed ICU cases, and there were 76 deaths related to probable or confirmed H1N1 that occurred in other hospital wards.

The authors observe that the number of deaths during the pandemic "appears less than predicted for a pandemic virus." They suggest several factors that may help explain this, including the virus's "moderate virulence," its sensitivity to antiviral drugs, the relative protection enjoyed by elderly people because of previous flu exposures, the widespread use of antivirals, and the vaccination of high-risk groups (though vaccine uptake in France was below 20%).

Another factor, they write, is that the French population has rapid access to hospital care, with no financial barrier: "The median time from onset of symptoms to hospital admission of 3 days illustrates this very high accessibility to hospital for severe . . . cases." And because the virus was moderate in virulence, critical care services did not become overloaded, they add.

Furhman C, Bonmarin I, Bitar D, et al. Adult intensive-care patients with 2009 pandemic influenza A(H1N1) infection. Epidemiol Infect 2010 (published online Oct 26) [Abstract]

See also:

Nov 12, 2009, N Engl J Med article on severe H1N1 in New Zealand, Australia

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