Hirsch – neuroprognostication after arrest 3-23-17

Brain Injury after Cardiac Arrest: Management, Prognosis and Controversies

Summary written by Dr. Kamel Gharaibeh

Epidemiology

• Over 500,000 cases of cardiac arrest per year in USA (75% are out of hospital)
• Most morbidity & mortality in those with ROSC results from neurologic injury
• 60-80% of patients who survive ROSC die from withdrawal of care due to neurologic status
• Up to 60% of those with ROSC ultimately survive, but with significant functional limitations & ~80% remain comatose

Post-cardiac arrest syndrome

• Focus has changed from cardio-pulmonary resuscitation to cardio-cerebral resuscitation
• De-emphasize ventilation & focus on cardiac and cerebral perfusion

Pathophysiology

• Complex but includes global ischemia (no flow) à global hypoperfusion (low flow) à gross reperfusion (reperfusion)

Critical care management

• Regional systems of care – balance transport time with clinical expertise
• Early goal-directed therapy with hemodynamic optimization
• Therapeutic hypothermia
• Early intervention to address underlying cause

Hemodynamics after cardiac arrest

• Early goal-directed therapy
• The problem with algorithm is that it does not include neuromonitoring – not guided by cerebral pressure perfusion
• Among patients with cardiac arrest requiring vasopressors, combined vasopressin-methylprednisolone-epinephrine (VSE) during CPR, and stress-dose hydrocortisone in post-resuscitation shock, (compared with epinephrine/saline placebo) resulted in improved survival to hospital discharge with favorable neurological status; however, patients in VSE group had a higher blood pressure and higher SVO₂, which may have affected the results. (Mentzelopoulos et al. JAMA 2013)
• A prospective observation analysis showed that time-weighted average MAP was associated with good neurologic outcome at a threshold of MAP >70mmHg (Kilgannon et al. CCM in 2014)

Therapeutic Hypothermia

• In patients with ROSC s/p V-fib arrest, therapeutic mild hypothermia increased favorable neurologic outcome & reduced mortality. However, some of the normothermic group was actually hyperthermic, which could have affected the results. (NEJM 2002)
• TTM trial showed in unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C (Nielsen et al., NEJM 2013)
• Guidelines recommend maintaining a constant temperature between 32^oC-36^oC during TTM
• TTM-2 trial is looking at 33^oC vs < 37.5^oC
• ICE-CAP Trial à assessing influence of cooling duration on efficacy in cardiac arrest patients

Prognostication

• We should never talk about prognosis in the first 24 hours after cardiac arrest. Premature documentation of poor prognosis may contribute to early decisions to withdraw care.
• Some clinical features should be interpreted with more caution after cardiac arrest. EEG background reactivity is useful in determining the prognosis after CA treated with therapeutic hypothermia.
• Motor response, brainstem reflexes, myoclonus, absent pupil & corneal reflexes are unreliable prognostic measures, especially in the first 24 hours. Some patients with extensor posturing had a good outcome.
• Clinical examination (i.e., brainstem reflexes, motor response, presence of myoclonus) at day #3 after cardiac arrest remains an accurate predictor of outcome after therapeutic hypothermia (Fugate et al, Ann Neurol 2010). Sedative medications in both hypothermic and non-hypothermic patients may confound the clinical exam.
• MRI is not very helpful in first 24 hours. It is helpful on day #2 to day #5.
• In the absence of clear guidance from patient/surrogate, irreversible management decisions should not be made on the basis of a single parameter or early in the clinical course.

Though not perfect, the Outcome Algorithm should look something like this

References

• White BC, Sullivan JM, DeGracia DJ, et al. Brain ischemia and reperfusion: molecular mechanisms of neuronal injury. J Neurol Sci. 2000; 179(1-2):1-33.
• Gaieski DF, Band RA, Abella BS, et al. Early goal-directed hemodynamic optimization combined with therapeutic hypothermia in comatose survivors of out-of-hospital cardiac arrest. Resuscitation. 2009; 80(4):418-24.
• Mentzelopoulos SD, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013 Jul 17; 310(3):270-9
• Kilgannon JH, Roberts BW, Jones AE, et al. Arterial blood pressure and neurologic outcome after resuscitation from cardiac arrest. Crit Care Med. 2014 Sep; 42(9):2083-91.
• The Hypothermia after Cardiac Arrest Study Group. Mild Therapeutic Hypothermia to Improve the Neurologic Outcome after Cardiac Arrest. N Engl J Med 2002; 346:549-56.
• Neilsen N, Wetterslev J, Cronberg T, et al. Targeted Temperature Management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013.
• Perman SM, Kirkpatrick JN, Reitsma AM, et al. Timing of neuroprognostication in postcardiac arrest therapeutic hypothermia. Crit Care Med. 2012.
• Fugate JE, Wijdicks EF, Mandrekar J, et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol. 2010.