A cluster of new studies examining intensive care unit (ICU) cases of 2009 Influenza A(H1N1) swine flu in the initial outbreak of the disease in Mexico, Canada, and then later in Australia and New Zealand, has once again pointed to the unusual propensity for the most severely affected patients to be relatively healthy adolescents and young adults. The studies also highlight the sudden demand and burden placed on critical care resources during such an outbreak, raising questions about whether they are equipped to cope with a similar demand this fall and winter, should it occur.

The three studies and an accompanying editorial appear in the 12 October issue of JAMA, Journal of the American Medical Association.

In the first study, researchers observed 58 patients with H1N1-related disease admitted to 6 ICUs in Mexico City during spring 2009, and in the second study, researchers observed 168 similarly ill patients admitted to 38 ICUs throughout Canada.

Both studies show strikingly similar results: patients were in the main relatively healthy adolescents and young adults who had a brief period of illness with no specific symptoms followed by rapidly progressive respiratory failure, and in many cases, shock and multisystem organ failure too.

For these ICU patients, hypoxemia (where there is not enough oxygen in the blood) was prolonged and severe, and on average they needed 12 days of mechanical ventilation and, as explained in the editorial accompanying the studies, the ICU staff frequently had to administer rescue therapies such as high-frequency oscillatory ventilation, prone positioning, neuromuscular blockade, and inhaled nitric oxide.

About 17 per cent of the patients in Canada and 41 per cent of the patients in Mexico died. Of the 24 Mexican patients who died, 21 of them were aged 20 to 50, as were 14 of the 29 Canadian patients who died.

Although the spring outbreak lasted about 3 months in Mexico and Canada, the peak was only a few weeks and hospitals and ICUs struggled to meet the increase in admissions. In Mexico, four patients died waiting for ICU beds.

The third study analyzed data from all medical centers in Australia and New Zealand that provided extracorporeal membrane oxygenation (ECMO) for patients admitted with H1N1-related disease during the winter months of 2009 in the Southern hemisphere.

Again, most of the patients were young adults with hardly any other underlying medical conditions, who also developed severe hypoxemia and multisystem organ failure. The patients had about 10 days of ECMO and 21 per cent of them died.

In their accompanying editorial, Drs Douglas B White and Derek C Angus of the Department of Critical Care Medicine at the University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania (Angus is also a Contributing Editor for JAMA), suggest that the three studies together:

“Represent important efforts within the intensive care medicine and clinical research communities to rapidly gather, analyze, and disseminate data in response to a new public health threat.”

They said it was remarkable to get data so early in a pandemic, and the approaches used, which built on the experience of the 2003 SARS outbreak, stand as a model for the future.

But they point to several limitations of the studies. One is the difficulty, as with the study of any disease that has a range of symptoms and severity, to establish for certain the incidence of H1N1 in the population and thus work out accurately what proportion needed hospitalization, ICU treatment and rescue therapy like ECMO.

The other difficulty is trying to work out the benefits of certain therapies because there is always the potential for selection bias and the inevitable confounding variables that arise when you have differences between groups that did and did not receive treatment. For this and other reasons, despite the use of standard report forms, it does not make sense to compare the reasons behind the marked differences in mortality between the patients in Mexico and Canada.

Where it does make sense, suggest the editors, is to use the content of the reports to help predict the burden of the H1N1 pandemic, and as these studies suggest, particularly with respect to peak strains on critical care services.

But there is a snag: the unpredictability of the virus, in that if it mutates, as many flu viruses do, then will the impact this fall and winter follow the same pattern as before and result in similar rates and severity of clinical infection or will it go in a completely different direction?

However, the editors suggest that despite these limitations and questions, the studies offer important and helpful information about how hospitals and medical staff can prepare for the months ahead.

“H1N1 can produce a rapidly progressive respiratory failure that is refractory to conventional mechanical ventilation, often in young, healthy patients — a group who are not currently a priority group for H1N1 vaccination,” wrote the editors, warning that:

“The rapid onset of refractory hypoxemia, together with multisystem organ failure and hypotension, suggests that clinical outcomes will depend on clinicians’ ability to apply sophisticated mechanical ventilatory support and adjunct therapies.”

They also warned that health professionals and hospitals need to take care with rescue therapies, in that those used in these studies can cause harm if not used in the right way.

“Many US hospitals may not have adequate numbers of physicians with this expertise, or staffing structures to facilitate timely treatment at any time of day or night,” they warned.

The editors suggest that one way to meet the possible challenge posed by a resurgence of the H1N1 pattern this fall and winter is to regionalize the care of patients with advanced respiratory failure, so that a few centers can accumulate experience managing the sickest patients, while outlying hospitals can then focus on other patients.

Such an approach would make best use of accumulated experience and offer the potential for streamlining clinical trials of promising treatments, they added.

Another approach might me to use “telemedicine”, where the doctors in the outlying hospitals consult with the regional professionals who are accumulating experience of dealing with the sickest patients.

“Critically Ill Patients With 2009 Influenza A(H1N1) in Mexico.”
Guillermo Dominguez-Cherit; Stephen E. Lapinsky; Alejandro E. Macias; Ruxandra Pinto; Lourdes Espinosa-Perez; Alethse de la Torre; Manuel Poblano-Morales; Jose A. Baltazar-Torres; Edgar Bautista; Abril Martinez; Marco A. Martinez; Eduardo Rivero; Rafael Valdez; Guillermo Ruiz- Palacios; Martin Hernandez; Thomas E. Stewart; Robert A. Fowler.
JAMA: 2009;302(17)
Published online 12 October 2009.

“Critically Ill Patients With 2009 Influenza A(H1N1) Infection in Canada.”
Anand Kumar; Ryan Zarychanski; Ruxandra Pinto; Deborah J. Cook; John Marshall; Jacques Lacroix; Tom Stelfox; Sean Bagshaw; Karen Choong; Francois Lamontagne; Alexis F. Turgeon; Stephen Lapinsky; Stephane P. Ahern; Orla Smith; Faisal Siddiqui; Philippe Jouvet; Kosar Khwaja; Lauralyn McIntyre; Kusum Menon; Jamie Hutchison; David Hornstein; Ari Joffe; Francois Lauzier; Jeffrey Singh; Tim Karachi; Kim Wiebe; Kendiss Olafson; Clare Ramsey; Satendra Sharma; Peter Dodek; Maureen Meade; Richard Hall; Robert Fowler; for the Canadian Critical Care Trials Group H1N1 Collaborative.
JAMA: 2009;302(17)
Published online 12 October 2009.

“Extracorporeal Membrane Oxygenation for 2009 Influenza A(H1N1) Acute Respiratory Distress Syndrome.”
The Australia and New Zealand Extracorporeal Membrane Oxygenation (ANZ ECMO) Influenza Investigators.
JAMA: 2009;302(17).
Published online 12 October 2009.

“Preparing for the Sickest Patients With 2009 Influenza A(H1N1).”
Douglas B. White; Derek C. Angus
JAMA: 2009;302(17)
Published online 12 October 2009.

Source: JAMA & Archives Journals.

Written by: Catharine Paddock, PhD