Journal Club Synopsis September, 2015:  O2 in MI; O2 Delivery in Hypoxemic Respiratory Failure; ROSC and the Cath Lab.

Many thanks to Mike Marynowski for hosting (skyline views and an outdoor big screenTV-what??).  Outstanding synopses by Braden, Elise, Franklin, Dr. Ede, Rachel and Dr. Burns.

Article 1:  We should think of oxygen as a drug, with benefits and harms. There has been suggestion since the 1970s that O2 may be harmful in ACS, through the reduction of coronary blood flow,  increase in coronary vascular resistance, and generation of reactive oxygen species. The latest AHA STEMI guidelines give no clear recommendation for O2 therapy in normoxic patients.

Stub D et al. Air Versus Oxygen in ST-Segment-Elevation Myocardial Infarction. Circulation  2015;131(24):2143-50.   AVOID Trial.

Editorial:  Nedeljkovic ZS, Jacobs AK:  Oxygen for ST-Segment–Elevation Myocardial Infarction Still Up in the Air.  Circulation  2015;131:2101-3.

In this multicenter, prospective, RCT from Australia, 441 normoxic patients with STEMI received O2 (8 L/min by facemask) or no O2, pre-hospital until admission to cardiac care ward.  Primary outcome was MI size as assessed by degree of cardiac enzyme elevation-troponin and CPK.  Secondary outcomes included recurrent MI, arrhythmia, and MI size assessed by cardiac MRI at 6 months.  There was no significant difference in troponin elevation between the two groups, although there was a significant increase in mean peak CPK in the O2 group compared to the no O2 group.  Rate of recurrent MI was significantly higher in the O2 group (5.5% vs. 0.9%, p=0.006).  The O2 group also had a trend towards higher frequency of cardiac arrhythmias (40% vs. 31%) and significantly increased MI size on cardiac MRI.  The kicker was mortality.  Six-month mortality was 3.8 with O2 vs. 5.9 with air (NNtoKill=48).  This was non-significant statistically, but a concerning trend, and engendered significant discussion at JC, especially as the study’s primary outcome was not clinical/patient oriented.  Troponin/CPK elevation are disease oriented outcomes, and very rough surrogates for outcome and prognosis.  Unfortunately, the trial was not powered for clinical outcomes.  Authors are to be congratulated for completing a challenging study involving delayed consent initiated in the field, but statistical methods were controversial, involving “imputation”, or presumption of results when data were missing (statistics on made up data).  The amount of O2 provided was also questioned, as nasal cannula rather than mask is more the norm in the USA.  The accompanying editorial states that the routine use of oxygen for patients with STEMI remains “up in the air”, and the concerning mortality trend led the majority of folks at JC to vote to continue providing routine O2 to this patient population.  Stay tuned:  a large Swedish Registry randomized trial examining this question is currently enrolling patients, and is powered for both morbidity and mortality.

Article 2:  We all love us some BIPAP in respiratory failure due to COPD or CHF, as noninvasive positive-pressure ventilation reduces intubation and mortality rates in these patients.  However, in patients with non-hypercapnic acute hypoxemic respiratory failure (think really bad pneumonia), noninvasive ventilation is associated with high failure rates and particularly high mortality.  Maybe not such a great idea to always reach for the Darth Vader mask...what’s the optimal O2 delivery in acute hypoxemic respiratory failure?

Frat JP, et al: High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.  N Engl J Med  2015;372:2185-2196.

In this multicenter, open label RCT trial of 310 ICU pts with non-hypercapnic acute hypoxemic respiratory failure, which excluded patients with CHF, asthma, and COPD, patients received 1 of 3 treatments: high flow O2 via nasal cannula (HFNC), noninvasive positive-pressure ventilation, or standard oxygen therapy via face mask.  Respiratory failure criteria were defined, as were criteria for intubation.  Primary outcome was proportion of patients intubated at 28 days; secondary outcomes included all-cause ICU and 90 mortality rates.  Twenty-eight day intubation rates were 38% vs. 50% vs. 47%, respectively; a non-significant trend favoring HFNC.  Ninety-day all-cause mortality was significantly lower for HFNC (12% vs. 28% vs. 23%, NNT=6 or 9).  ICU complication rates did not significantly differ between the three groups.

This study supports the superiority of HFNC in acute hypoxemic respiratory failure, compared with noninvasive ventilation or O2 by face mask.  Noninvasive ventilation performed poorly.  Caveats?  This was an ICU, rather than an ED study.  We don’t see many patients with respiratory failure from pure pneumonia.  However, for this patient cohort, consider high-flow O2 via NC instead of BIPAP.  Yes, we have it in the ED.  Need to dial in flow rate (max 60 liters/minute, this study used 50 L/min), and FiO2.  HFNC is comfortable, well tolerated, and allows patient to eat, drink, and communicate. 

Article 3:  You have ROSC after cardiac arrest!  Patient is hemodynamically optimized and cooling, O2 sat is 94%, and the ECG shows.....not a STEMI L.    2010 AHA guidelines state: “consideration of emergent coronary angiography may be reasonable even in the absence of STEMI” in post-arrest patients.  Should you push for cardiology to take them to the cath lab?

Kern KB, et al: Outcomes of Comatose Cardiac Arrest Survivors With and Without ST-Segment Elevation Myocardial Infarction: Importance of Coronary Angiography.  JACC Cardiovasc Interv  2015 Jul;8(8):1031-40. 

In this retrospective review of 746 comatose post-cardiac arrest patients including 198 with STEMI (26.5%) and 548 without STEMI (73.5%), overall survival was greater in those with STEMI compared with those without (55% vs. 41%; p = 0.001). However, in all patients who underwent immediate coronary angiography, survival was similar between those with and without STEMI (55% vs. 58%; p = 0.60). A culprit vessel was more frequently identified in those with STEMI, but also in one-third of patients without STEMI. The majority of culprit vessels were occluded (STEMI, 93%; no STEMI, 69%).  An occluded culprit vessel was found in 74% of STEMI patients and in 23% of non-STEMI patients. Among cardiac arrest survivors discharged from the hospital who had presented without STEMI, coronary angiography was associated with better functional outcome (93% vs. 79%; p < 0.003, NNT=7).

Basically, this study attempts to show that early coronary angiography is associated with improved outcomes, regardless if STEMI is present on ECG.  An occluded culprit vessel was found in 23% of non-STEMI patients who went to cath lab.  This is aligned with prior studies demonstrating up to 50% of patients with ROSC after cardiac arrest having an acutely occluded coronary vessel, not well predicted by the presence of STEMI on ECG (Spaulding, 1997, NEJM).

So what’s the problem?  First, this was a study of 6 hospitals, with widely variable cath lab protocols, and additional individual cardiologist variability.  Coronary angiography was only performed in 45% of non-STEMI patients.   The non-STEMI patients who went to cath lab are likely very different from those who didn’t-the fatal flaw of this study.  It’s also a retrospective registry trial, therefore lots of other limitations.  A quarter of the non-STEMI patients who went to cath lab went in a delayed fashion, which has been shown to be of no significant benefit in stable, asymptomatic patients (OAT trial NEJM 2006; 2013 AHA STEMI guidelines).  The AHA STEMI guidelines specifically classify PCI of a non-infarct artery at the time of PCI for STEMI as “Class III-harm”; in other words, PCI should be not be driven by an interventionalist’s oculo-occluded reflex.  If the occluded vessels identified in the 23% of the non-STEMI patients are truly culprit, then positive outcomes may be expected, but the study’s conclusions are not supported by its methodology.  How to improve?  Publish the data for hospitals who take all ROSC patients (STEMI and non-STEMI) to cath lab.