(P023) DELAYED AWAKENING 22 DAYS AFTER OUT-OF-HOSPITAL CARDIAC ARREST

Case background: A 62-year-old female with diabetes and hypertension was admitted to the intensive care unit (ICU) after out of hospital cardiac arrest (OHCA). She had suffered an inferior STEMI complicated by ventricular fibrillation arrest 18 months prior, with complete neurological recovery within a few days. This time the patient was driving when she collapsed. She received bystander CPR, and EMS were on scene within 2 minutes. Rhythm analysis found ventricular fibrillation which was defibrillated twice. She reverted to normal sinus rhythm after the second, when return of spontaneous circulation (ROSC) was achieved. Downtime was approximately 10 minutes.

She was admitted without signs of shock. ECG showed anterior ST depression and T wave inversions. Initial troponin was approximately 900ng/L ( < 14 ng/L). The interventionalist on call deferred angiography. She had continuous temperature monitoring with maintenance of < 37.7°C for the first 4 days. Hepatic and renal function remained normal throughout her admission. After 11 days, the patient continued to be hemodynamically stable but was not waking after discontinuation of sedation.

Brainstem reflexes were preserved. The patient opened her eyes spontaneously but not to voice or pain. Her pupils had asymmetrical responses, but it is unclear if asymmetry was in relation to facial fractures from the original vehicle collision. Slight movement was noted in the extremities, but pain did not elicit motor response. CT head was normal and brain MRI revealed non-specific, symmetric abnormal signal in bilateral thalami unlikely to be related to recent ischemia. Repeat MRI 2 weeks later showed improvement in the abnormal thalamic signal. EEG showed diffuse intermixed slowing of all frequencies and inconsistent reactivity to stimuli without epileptiform activity. The patient did not have evoked potentials tested, as this test was not available locally.

Management Challenges: Guidelines recommend waiting 3-5 days after ROSC before performing multimodal neuroprognostication. Neuroprognostication involves clinical examination, neuroimaging, electroencephalography, evoked potentials, and/ or serological biomarkers. No definitive test or combination of tests is sufficient or superior based on available evidence, so a multimodal approach is recommended.

Clinical exam should include evaluation of alertness, ability to verbalize and follow commands as well as brainstem reflexes, pain, and motor response. Absence of brainstem reflexes, particularly the pupillary light reflex, and absent/extensor motor response to pain are predictors of poor outcome.

Brain CT rules out other causes of coma such as subarachnoid hemorrhage or herniation and can identify anoxic brain injury, linked to poor prognosis. MRI of the brain allows for improved evaluation of affected tissue and can categorize good and poor outcome with a specificity of up to 100%.

EEG can detect seizures, discontinuous patterns, and reactivity to physical stimuli. Status epilepticus, generalized periodic discharges, suppressed background, and burst suppression are frequently linked to poor outcomes. Aggressive management of post-anoxic status epilepticus is recommended for up to 14 days before prognostication, if other markers are favorable, as good neurological recovery is still possible.

Evoked potentials follow central responses to small electrical signals applied peripherally. Somatosensory evoked potentials (SSEP) are most common, which involve recording signal through electrodes on the scalp after a peripheral nerve is stimulated. Bilateral absence of cortical reactivity with SSEP is almost always associated with poor neurological outcome post cardiac arrest and is one of the most robust predictors.

Serum biomarkers are promising tools in demarcating neurological outcome. The most common in cardiac arrest is neuron specific enolase (NSE) with levels >60μg/L at 72 hours post arrest and increasing values, associated with poor neurological outcome. Though value is limited in isolation, NSE can provide supportive evidence in association with other prognostication modalities.

Our patient’s results were indeterminate. Her brainstem reflexes were intact, but she did not have motor response to pain. Her CT head was normal, but her MRI brain showed improving non-specific abnormal signaling in the thalami. Her EEG showed diffuse intermixed slowing of frequencies but inconsistent reactivity to stimuli. If results of initial assessments are inconclusive or contradictory, extended observation and repeat assessments are recommended. Changes over time can provide additional evidence for neuroprognostication.

Prolonged observation up to 3 weeks was recommended. On day 21 post cardiac arrest, the patient was still unresponsive. To respect her wishes to not live in a persistent poor functional state, the family planned for withdrawal of life sustaining therapy (WLST) but waited until the next day for a family member to arrive. On Day 22 the patient had purposeful movements, recognized her family members, and was extubated. On day 45 she was discharged home neurologically intact.

Patients with prolonged coma and indeterminate prognostic testing after cardiac arrest, are clinically challenging. Published guidelines from the Canadian Cardiovascular Society, American Heart Association, and the European Resuscitation Council have clear recommendations for timing of neuroprognostication testing and suggest management be based on a multitude of assessments. The decision to WLST is unambiguous in patients with brain death or overwhelming evidence of poor neurological outcome. Guidelines do not clearly direct decision making for patients with persistent unresponsiveness after cardiac arrest that have indiscriminate assessments. In these cases, decisions are more nuanced and must be balanced against the pressures of overcrowded ICUs, health care human resources, as well as patient and family values. Multimodal and repeat assessments can help define trajectories over time and predict long-term outcomes. Sufficiently long observation periods are recommended to allow patients adequate time for recovery if they have the potential. Clinicians may be wary of prolonged observation due to perception of increased risk for persistent poor functional state, though studies have not shown any association. The “sufficient” time to wait is not well established, though research supports a longer observational period than what is currently common practice. Timing of withdrawal of life sustaining therapy should be individualized, considering clinical status and progression over time, medical history, and previous functional status as well as patient/family wishes and values.