Getting to the core of H1N1 flu deaths

Lung inflammation and respiratory failure are largely responsible for the fatal cases of H1N1 (swine) flu seen so far, three new studies show. The findings also confirm observations that the influenza hits young adults the hardest but can be fought off in many cases with the use of antiviral flu drugs and a mechanical ventilator to aid breathing.

The new studies offer the first large-scale analyses of how the H1N1 flu causes life-threatening illness. All three reports find a consistent pattern of oxygen deprivation in the blood of critically ill patients, a dangerous condition that in the worst-case scenario leads to shock, organ failure and death, the researchers report online October 12 in the Journal of the American Medical Association. The studies were conducted between early March and late August in Canada, Mexico and Australia and New Zealand.

“The data suggests it starts as a diffuse viral pneumonia,” says physician Anand Kumar of the University of Manitoba in Winnipeg, who coauthored the Canadian study. By the time a person becomes critically ill, he says, it’s no longer clear whether it’s still pneumonia or has developed into a more severe respiratory distress syndrome.

In such severely ill patients, H1N1 causes massive inflammation in the lungs, which leads to fluid build-up in airways and lung tissues and even bleeding in lung tissues, says physician and epidemiologist Robert Fowler of the University of Toronto, who coauthored the studies in Canada and Mexico. These changes hamper the transfer of oxygen from inhaled air to the blood stream.

“Most patients are still able to take breaths, but these breaths are ineffective,” he says. Blood pressure can crash, disrupting circulation. While oxygen deprivation can cause widespread damage, “the lungs are the organs most visibly affected,” Fowler says.

In the largest of the three studies, Fowler and a team of scientists in Canada monitored the course of 168 patients deemed critically ill with H1N1 flu. Although the patients averaged only 32 years of age and received intensive-care-unit treatment, 17 percent died.

Doctors in the study conducted in Australia and New Zealand identified 68 patients critically ill with flu symptoms, most of whom were eventually confirmed to have H1N1. Despite having a median age of 34 years, their fatality rate was 21 percent. Six of the survivors were still in intensive care units when the data were reported.

In the study done in Mexico, scientists examined the records of 58 critically ill H1N1 patients who had a median age of 44 years, finding a fatality rate of 41 percent.

The vast majority of patients in the studies in Canada and Mexico received mechanical ventilation, which typically lasted 10 to 12 days. But the respiratory crash occurred too rapidly in some patients for ventilation to help. In Mexico, for example, four patients died before healthcare workers could get them into an intensive care unit. In Australia and New Zealand, doctors used a treatment called extracorporeal membrane oxygenation, in which blood is extracted from each patient and passed through a machine that adds oxygen. The blood is then returned to the patient.

Many patients in all three regions were also given the flu medication oseltamivir phosphate (Tamiflu), with apparent benefit. In the Mexican analysis, critically ill patients who survived were seven times more likely to have received the drug than those who died.

All three groups of critically ill patients included very few people over the age of 60 and few young children. The numbers support a widespread hypothesis that older people carry some residual immunity against H1N1 flu, Fowler says. The new data don’t explain why very young children were underrepresented in these critically ill groups.

On the other hand, the data fail to explain why people in the prime of life would be most susceptible to the lethal effects of H1N1, a trend eerily reminiscent of the 1918 flu pandemic, which was also caused by an H1N1 strain.

But the studies do provide much-needed empirical knowledge about the H1N1 flu, physicians Douglas White and Derek Angus of the University of Pittsburgh note in an editorial also released by JAMA.  “It is remarkable to have any data so early in the course of the influenza pandemic, let alone the systematically collected data present in these reports,” they observe. “These studies provide important signals about what clinicians and hospitals may confront in the coming months.”

Fowler adds: “These papers teach us that in the subset of patients with critical illness due to H1N1, the patients can deteriorate very quickly,” he says. “But with early recognition of the disease, prompt treatment and capacity for aggressive life-support and rescue therapies for oxygenation failure, mortality can be limited.”