Top Recent Articles: One ED Professor's View

An analysis of time trends in pulmonary embolism (PE) in the United States nicely captured his frustration on this score, thereby making his ‘best-of’ list. The investigators compared national rates of PE and treatment outcomes before and after 1988, the year that CT pulmonary angiography became widely available. After 1988, the incidence of PE climbed by 81% through 2006, and the rate of in-hospital anticoagulation-related complications rose by 71%, from 3.1 to 5.3 cases per 100,000. Yet there was no significant reduction in the death rate due to PE (Arch. Intern. Med. 2011;171:831-7).

"Ouch! All we’ve done is harm a lot more people without a lot of evidence that we’ve saved more people," Dr. Mallon commented.

"I remember when I was in medical school I was told this: If a person has a PE of significance, they will have the diagnostic duet of tachypnea and tachycardia. They’ll be sick from their PE. And PE morphed from that life-threatening thing to us finding these small, subsegmental little things we don’t even really know the meaning of in a person with a totally normal ECG who maybe had a twinge of chest pain and couldn’t catch their breath for 5 minutes," he said. "I think there’s compelling evidence that what we used to think a PE was is not what PE is today, and that the need for treatment of these newer PEs isn’t being talked about in a sensible way. There’s room for that discussion."

• Hyperbaric oxygen therapy for carbon monoxide poisoning: The hyperbaric oxygen chamber is well accepted as standard therapy for divers with the bends, but its utility in cases of domestic acute carbon monoxide toxicity has been highly controversial. A pair of recent French prospective randomized trials concluded it is ineffective and possibly harmful.

One study randomized 179 noncomatose patients with transient loss of consciousness to a real or sham hyperbaric oxygen therapy session. There was no difference in outcomes.

The other trial involved 206 comatose carbon monoxide overdose patients randomized to one or two sessions of hyperbaric oxygen therapy. It was halted early because the group that received more hyperbaric oxygen had less complete recovery, worse delayed neurologic symptoms, and more persistent sequelae (Intensive Care Med. 2011;37:486-92).

• Nonsurgical hemorrhage control: Hyperfibrinolysis is present in 10%-15% of trauma patients and is associated with sharply higher 6- and 24-hour mortality. It can now be detected in 15 minutes at the bedside using thromboelastogram measurement. And, in several recent studies, early administration of tranexamic acid to trauma patients in order to block hyperfibrinolysis has demonstrated improved survival.

The most recent of these studies, MATTERS, (Military Application of Tranexamic Acid in Trauma Emergency Resuscitation), was a retrospective observational study that included 896 trauma patients who received packed red blood cells, 293 of whom also received tranexamic acid.

Unadjusted mortality was significantly lower in tranexamic acid recipients by a margin of 17.4%, compared with 23.9%, even though they had higher mean Injury Severity Scores and thus should have done worse.

The survival benefit associated with tranexamic acid was greatest in the subgroup who received massive transfusions. Their mortality rate was 14.4% compared to 28.1% in controls. In a multivariate analysis, administration of tranexamic acid in this subgroup was associated with a 7.2-fold increased likelihood of survival (Arch. Surg. 2012;147:113-9).

Tranexamic acid is a relatively inexpensive, Food and Drug Administration–approved synthetic blocker of the conversion of plasminogen to plasmin. It has a reasonable safety profile. Remaining questions regarding its incorporation into trauma management protocols include optimal dosing and whether thromboelastogram measurement should be used to guide therapy such that only those patients with hyperfibrinolysis would get tranexamic acid.

Look for answers to come from two ongoing major randomized trials: CRASH-3 (Clinical Randomisation of an Antifibrinolytic in Significant Head Injury) and PROPPR (Pragmatic, Randomized Optimal Platelets and Plasma Ratios), Dr. Mallon said.

• ‘ARDS, acronyms, and the Pinocchio effect’: This was the title of an essay by British physicians (Anaesthesia 2010; 65: 976-9) who argued that the medical world has gone acronym-crazy, with vast research money being spent trying to find cures for ARDS (acute respiratory distress syndrome), SIRS (systemic inflammatory response syndrome), ARF (acute respiratory failure), and the like.

"This is the oldest paper in the series, but I thought it was important enough to bring up," Dr. Mallon explained. "The Pinocchio effect is an important new concept in medicine. The authors point out that these aren’t diseases, they’re just acronyms. When you look at ARDS or SIRS, there are dozens of causes of each of them. Why on earth would we think there’s going to be a magic bullet therapy when there’s such tremendous underlying heterogeneity in the cause? Yet, we keep doing research trials trying to find a treatment for SIRS or ARDS."