Without High Tech Care, H1N1 Death Toll Could Soar, Experts Say

[indigo girl]

http://www.google.com/hostednews/canadianpress/article/ALeqM5g3sRrDAviQQ0bfvr0gEBvYl7Foew

Good article from Medical Reporter, Helen Branswell:

Developing countries with limited access to advanced health-care facilities may be in for a rough ride with swine flu and even countries with high-tech ICUs may find themselves pushed to the limit as their hospitals struggle to save gravely ill H1N1 patients, new studies suggest.

The studies, which compare outcomes among H1N1 patients admitted to intensive care units in Canada and Mexico, showed the death rate in the latter was more than double that seen among Canadian patients. Just over 40 per cent of critically ill Mexican patients succumbed to their illness by day 60, compared to 17.3 per cent of Canadian patients by day 90.

"I think this H1N1 (virus), it's not going to be the one that people would say 'Oh, my God, that killed off X per cent of our population'," said Dr. Rob Fowler, a critical care specialist and senior author of both studies. "But we're going to see large numbers of patients that have illness, a subset that are critically ill and in different parts of the world it's actually going to translate into lots of people dying that wouldn't have otherwise died - especially so if you can't support them (medically)."

The studies were published online Monday by the Journal of the American Medical Association. Their publication was timed to coincide with Fowler's presentation of the data at a conference staged by the European Society of Critical Care Medicine.

Dr. Michael Osterholm, an infectious diseases expert at the University of Minnesota, said the findings should serve as an eye-opener for the large segment of the public that has dismissed swine flu as a mild form of influenza. For many it is, but "for a very small number of patients, this illness is hell," said Osterholm, director of the Center for Infectious Diseases Research and Policy.

An editorial that accompanied the package said saving that group of patients depends on the ability of medical teams to employ sophisticated mechanical ventilatory support. There may not be enough of these beds available or the trained staff needed to deliver this kind of care, the authors warned.

"Clinicians and hospitals should take note that the rescue therapies used in these studies have the potential to cause harm if not implemented in a co-ordinated manner," noted Dr. Douglas White and Dr. Derek Angus, critical care physicians at the University of Pittsburgh. They suggested hospitals need to make plans for how they will handle an influx of severely ill cases, noting that while the number of such cases during the spring wave was modest, the burden they place on hospitals in both Canada and Mexico was "sobering." "Any deaths from 2009 influenza A (H1N1) will be regrettable, but those that result from insufficient planning and inadequate preparation will be especially tragic," Angus and White said.

As they and many others have noted, this pandemic is not triggering the volume of severe disease experts feared the world might see with the first pandemic of the century. While it's not currently possible to estimate what percentage of people who catch the virus need to be hospitalized, it is clear that for most people, H1N1 is indistinguishable from regular influenza. But a small proportion of patients became profoundly ill and did so quickly. Fowler said those who went into this sharp decline generally ended up in the ICU within about 24 hours of entering hospital.

There medical teams battled to save their lives, hooking these patients up to ventilators that breathed for them or even the types of bypass machines - called extracorporeal membrane oxygenation, or ECMO - used in cardiac surgery. These patients are far younger than those hospitals generally see dying from flu or the complications of flu, said Dr. Anand Kumar, an intensivist who treated many of these patients in Winnipeg hospitals this spring and the lead author on the Canadian study. He said any loss of life in an ICU is difficult, but it is especially hard when the cases are like those this virus often kills - younger adults and middle-aged people who were relatively healthy before they contracted the virus.

"To lose somebody 24, 25, 30, 40 years old - it's just not their time," Kumar said. He said he's gotten emails from intensivists all over asking why public health authorities are calling this flu mild, "because it's certainly not mild from an ICU context." The World Health Organization also objects to the use of the term mild to describe this pandemic, calling it moderate.

Where resource-intensive therapies are available, chances are decent that H1N1 patients will pull through, these and other recently published studies have found. But where they are not, the death toll will be higher, said Fowler, a critical care specialist at Toronto's Sunnybrook Health Sciences Centre.

"This is a young, relatively healthy group of patients that has their lungs fail. And if you can throw the book at them to get their lungs through this, then you have a pretty good shot at keeping them alive," Fowler said. "And I think in places that aren't able to do that, well ... you have a much lesser likelihood of making it."

The comparison of the outcomes between the two patient groups - 168 confirmed or probable cases in Canada, 58 in Mexico - provided some other important information. Fewer of the patients from Mexico were treated with antiviral drugs like Tamiflu, allowing the authors to compare the outcomes of the patients who received the drugs and those who did not. Antiviral treatment is recommended for all patients sick enough to require hospitalization, even if treatment is commenced later than the 48-hour window in which therapy is supposed to start for best results. In Canada most of the patients would have received the drugs, so there would be no way to assess whether they were helping or not. But by comparing the data from the two countries, the authors showed that people who received the drugs were seven times more likely to survive than those who did not.

"People should get these drugs," Fowler said.

The Canadian study also found a disproportionately high percentage of the severely ill cases were women - 67.3 per cent. The virus is especially tough on pregnant women, but the pregnancy doesn't account for all of the excess in women, Fowler said.

He admitted the gender imbalance among severe cases is puzzling. "I have no idea why that could be the case," Fowler said. "But that does seem to be something that has been consistently reported ... that critically ill women are over-represented relative to critically ill men."

Article reformatted.

(hat tip Crofsblog)

[indigo girl]

Preparing for the Sickest Patients with 2009 Influenza A (H1N1)

http://jama.ama-assn.org/cgi/content/full/2009.1539

Despite an enormous global investment in preparing for the reemergence of 2009 influenza A(H1N1), preparations proceeded largely without empirical data about the nature and severity of disease. This paucity of data is particularly problematic for clinicians in intensive care units (ICUs), who will shoulder a heavy burden for the clinical response to H1N1. In this issue of JAMA, 3 reports provide data that begin to fill this empirical void.

Domínguez-Cherit and colleagues1 conducted an observational study of 58 patients admitted to 6 ICUs in Mexico City with H1N1-related disease during the initial outbreak in spring 2009. Kumar and colleagues2 conducted a similar study of 168 critically ill patients in 38 Canadian ICUs. There were striking similarities in the main findings. Patients tended to be relatively healthy adolescents and young adults who developed a brief prodromal illness followed by rapidly progressive respiratory failure. Shock and multisystem organ failure were common. Hypoxemia was prolonged and severe, requiring on average 12 days of mechanical ventilation and frequent use of rescue therapies such as high-frequency oscillatory ventilation, prone positioning, neuromuscular blockade, and inhaled nitric oxide. The influenza outbreak lasted about 3 months in both countries, but the peak lasted just a few weeks, during which time hospitals struggled to accommodate the increased patient load, with 4 Mexican patients dying while awaiting ICU beds. Notably, the Mexican cohort incurred a mortality rate twice as high as that in Canada. In contrast to the high rates of health care worker infections during severe acute respiratory syndrome (SARS) outbreaks,3 there were no documented cases of nosocomial transmission in either series.

The third article, by Davies and colleagues,4 is based on data from all centers providing extracorporeal membrane oxygenation (ECMO) for H1N1-related disease in Australia and New Zealand during the 2009 Southern hemisphere winter. The cases were typically young adults with little underlying comorbid disease who developed severe hypoxemia and multisystem organ failure. The median duration of ECMO support was 10 days, and the case-fatality rate was 21%.

In aggregate, these studies 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. It is remarkable to have any data so early in the course of the influenza pandemic, let alone the systematically collected data presented in these reports. Investigators achieved this by using existing clinical research networks and standardized data collection forms developed after the 2003 SARS outbreak. This approach is a model for the future.

Nonetheless, each of these studies has substantial epidemiological limitations. As with all diseases that manifest with a range of symptoms and severity, it is difficult to ascertain the incidence of H1N1 infection in the population and hence the true proportion of affected patients who require hospitalization, ICU admission, or rescue therapies such as ECMO. It is also difficult to infer benefits of certain therapeutic maneuvers because of the potential for selection bias and residual confounding related to differences between groups that did and did not receive treatment. Although the use of standardized case report forms increases the ability to compare results within and across studies, baseline differences in usual care confound causal inferences. This is particularly relevant when trying to reconcile the marked differences in mortality between patients in Mexico and Canada. Much of the value of these reports lies in the extent to which they will help predict the burden of the H1N1 pandemic. However, the ability of the influenza virus to mutate raises questions about whether the virus that will emerge this fall will produce similar rates and severity of clinical infection.

Despite these limitations, these studies1-2,4 provide important signals about what clinicians and hospitals may confront in the coming months. 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.5 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. Clinicians and hospitals should take note that the rescue therapies used in these studies have the potential to cause harm if not implemented in a coordinated manner. 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.

How then might hospitals within a given region respond to the unique needs of the sickest patients with H1N1? One possibility is regionalization of care for patients with advanced respiratory failure. This would allow a few centers to accumulate experience managing the sickest patients, while preserving the resources at outlying hospitals for other patients. Strengths of this approach are the possibility for improved outcomes due to accumulated experience and the potential for streamlined conduct of clinical trials of promising treatments.6 A second possibility is the development of telemedicine consultation for clinicians at outlying hospitals who may benefit from expert clinical advice for such tenuous patients. Demonstration projects are ongoing for telemedicine during a public health emergency.7 A third possibility is for hospitals to make temporary staffing changes to ensure the continuous presence of clinicians competent to handle these cases. This approach lacks some of the potential benefits of regionalization and may be infeasible because of foreseeable workforce shortages during a severe influenza outbreak.

The case series by Davies and colleagues4 raises a particularly critical question: will the use of ECMO decrease mortality in patients with H1N1 who have refractory respiratory failure? Of course, causal inferences should not be drawn from an uncontrolled case series. In theory, however, if ECMO were only initiated in patients who were judged to be certain (or nearly certain) to die without it, a substantial portion of the observed survival may plausibly be attributed to treatment with ECMO. However, there are insufficient details about inclusion and exclusion criteria to conclude that ECMO use was restricted in this way. Recent data suggest that patients who might be considered for ECMO often may survive without it.8 Nonetheless, based on the data presented, it seems likely that the mortality rate without ECMO would have been higher than the observed 21%. A final caution about generalizability of the high survival rate observed in this study: not all patients who died from H1N1-related illness were offered ECMO. It is therefore likely that the outcomes were in part due to careful selection of patients.

The large proportion of critically ill patients with H1N1 who survived is an important reminder that the medical response to a respiratory pandemic is very different today than it was for the 1918 influenza pandemic. The widespread availability of antibiotics, antiviral agents, vasopressors, and mechanical ventilation makes it possible to save many patients who would not have survived in 1918.9 With this potential comes an obligation for hospitals and public health systems to collaboratively develop strategies to ensure that, if there is a resurgence of 2009 influenza A(H1N1), the benefits of intensive care medicine can be offered to the maximum number of patients. Although guidelines and recommendations exist for augmenting hospital surge capacity, their implementation in individual hospitals is far from complete. The investigators from both Mexico and Canada noted that the health care systems struggled to meet the demands created by the increased patient volume, a sobering observation given that the absolute number of excess ICU admissions was modest.

Hospitals must develop explicit policies to equitably determine who will and will not receive life support should absolute scarcity occur. The controversy that erupted around triage decisions during Hurricane Katrina highlights the importance of advance planning and clear guidelines.10 Several groups have provided recommendations for allocating scarce therapies during the influenza pandemic.11-13 Any deaths from 2009 influenza A(H1N1) will be regrettable, but those that result from insufficient planning and inadequate preparation will be especially tragic.

(hat tip Avian Flu Diary)

[jennifer0702]

It is scary to think they will have to decide who can and cannot receive care. It sounds like that is what it is going to come down to though. How are they going to create a criteria of who will get care first?