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Critical Care of H1N1 Influenza A Patients

By Amesh A. Adalja, MD, October 16, 2009

Australia and New Zealand | Mexico | Canada | Michigan |

The scenario most feared in planning for pandemic influenza involves shortages—of ventilators, intensive care unit (ICU) beds, antiviral drugs, and vaccines. Reports now emerging from the Southern Hemisphere, where the flu season is over, and a few other areas, are beginning to paint a clearer picture of both the clinical manifestations of severe H1N1 influenza disease and actual utilization of critical care resources. This picture suggests that as H1N1 influenza spreads in the U.S., the best approach for managing ICU resources may be to create regional centers equipped to deal with the minority of patients who are too ill to be managed by conventional ICU measures.

Utilization of Critical Care Services in the Southern Hemisphere

A report on all 2009 H1N1 Influenza A ICU admissions in Australia and New Zealand, which are just emerging from their winter flu season, has just been published in NEJM.1 The experience in these 2 countries provides the following details about ICU patients with H1N1 influenza:

  • 92.7% were under 65 years of age; this confirms the known age distribution of infection

  • 9.1% were pregnant women

  • 65% required mechanical ventilation

  • 20% had a bacterial co-infection

  • 14% died and 16% remained hospitalized, as of September 7, 2009

  • Median length of stay was 8 days.

A separate report, published in JAMA, details the experience in Australia and New Zealand with 68 influenza patients who were treated with extra corporeal membrane oxygenation (ECMO).2 These patients were the most severely ill, and 14 (21%) succumbed to their illness—a mortality rate lower than the 30% to 48% mortality rate seen in other ARDS cases requiring ECMO.

The Mexican ICU Experience

An observational study of 58 critically ill Mexican patients—comprising 6.5% of hospitalized patients at 6 centers—was also published in JAMA.4 As with other studies, several features in common were noted, including a median patient age of 48 years and obesity in 36% of patients. Medical histories revealed the following:

  • 95% of patients received antibiotics; 78% received targeted antiviral therapy

  • 2 patients received activated protein C

  • 54 of 58 patients (93%) required mechanical ventilation; 2 patients required prone positioning

  • 1 patient required HFOV (other rescue therapies were not used)

  • 4 patients had secondary bacterial pneumonia

  • Excluding those who died within 72 hours, survivors were 7.4 times more likely to receive appropriate antiviral therapy

  • 41% of patients had died by 60 days from admission.

The Canadian ICU Experience

In addition to the data from Mexico, JAMA also published details on 168 critically ill patients with probable and confirmed cases of 2009 H1N1 influenza A disease from 38 Canadian ICUs.5 Important features include the following:

  • Median age was 32 years

  • 25% of patients were Aboriginal Canadians, a community that was similarly disproportionately affected by the 1918 influenza pandemic

  • 24% of patients were morbidly obese

  • 81% required mechanical ventilation on the first day of ICU admission

  • 31% were administered inhaled nitric oxide; 12% required HFOV; 4% required EMCO, and 3% prone positioning

  • 33% of patients were administered vasopressors on their first day in the ICU

  • 91% received antiviral therapy; 99% received antibiotics

  • 51% received corticosteroids

  • 17% (29) of patients died.

The Michigan ICU Experience

In July, the MMWR reported on the University of Michigan’s experience with 10 patients with ARDS due to 2009 H1N1 influenza virus.3 Important aspects of these cases include:

  • All patients initially required sophisticated mechanical ventilation strategies, including bilevel ventilation or high frequency oscillatory ventilation (HFOV). ECMO was initiated in 2 of those patients

  • 60% required continuous renal replacement therapy

  • 100% required tracheostomy

  • 90% required vasopressors

  • No bacterial co-infections were identified

  • 30% of case patients died.

How Will Critical Care be Delivered?

These studies illustrate the propensity of 2009 H1N1 influenza A to induce severe respiratory disease in a small fraction of those infected. Most of the patients reported on in these articles required mechanical ventilation, and an unexpectedly large percentage required the most advanced rescue therapies (ECMO or HFOV). The good news is that, among patients treated with these advanced techniques, fatality rates have been lower than expected. Unfortunately, as Derek Angus, UPMC’s Chairman of Critical Care Medicine, points out in an accompanying JAMA editorial,6 because of potential selection bias and confounding factors in these studies, it is too early to conclude with certainty that the better-than-expected outcomes can be attributed to these rescue therapies. And many ICUs are not equipped with such advanced capabilities. Therefore, Dr. Angus proposes that the best strategy for dealing with a surge of severe cases of influenza may be to develop regional centers of expertise that consult with smaller facilities and possibly accept transfer of patients who require adept critical care management.

References

  1. The ANZIC Investigators. Critical care services and 2009 H1N1 influenza in Australia and New Zealand. NEJM 2009; 361. http://content.nejm.org/cgi/content/full/NEJMoa0908481. Accessed October 12, 2009.

  2. The Australia and New Zealand extracorporeal membrane oxygenation (ANZ ECMO) influenza investigators. Extracorporeal membrane oxygenation for 2009 influenza A(H1N1) acute respiratory distress syndrome [published online October 12, 2009]. JAMA. 2009; 302(17). http://jama.ama-assn.org/cgi/content/full/2009.1535. Accessed October 12, 2009.

  3. CDC. Intensive-care patients with severe novel influenza A (H1N1) virus infection---Michigan, June 2009. MMWR 2009; 58:749-752. http://www.cdc.gov/mmwr/preview/mmwrhtml/
    mm5827a4.htm
    . Accessed October 12, 2009.

  4. Domínguez-Cherit G, Lapinsky SE, Macias AE, et al. Critically ill patients with 2009 influenza A(H1N1) in Mexico [published online October 12, 2009]. JAMAhttp://jama.ama-assn.org/cgi/content/full/2009.1536v1. Accessed October 12, 2009.

  5. Kumar A, Zarychanski R, Pinto R; et al. Canadian Critical Care Trials Group H1N1 Collaborative. Critically ill patients with 2009 influenza A(H1N1) infection in Canada [published online October 12, 2009]. JAMA. 2009; 302(17). http://jama.ama-assn.org/cgi/content/full/2009.1496v1. Accessed October 12, 2009.

  6. White DB, Angus DC. Preparing for the sickest patients with 2009 influenza A(H1N1)[published online October 12, 2009]. JAMA. doi:10.1001/jama.2009.1539. http://jama.ama-assn.org/cgi/content/full/2009.1539. Accessed October 12, 2009.