Episode 35 - Neurological Care After Cardiac Arrest

(upbeat music) - Welcome back everyone. My name is Safah Tahakim. I'm the PGY4 resident at Yale University. We have a special episode today about neurologic care after cardiac arrest. By Dr. Rachel Deakman, who's one of our neuro ICU attendings, with great interest in cardiac arrest. We also have one of our PGY4 residents, Gabriela Garcia, who's going into neuro ICU, who will be interviewing Dr. Beakman today, because she is very interested in passionate about cardiac arrest, and it will be a wonderful episode that I'm very excited about. Welcome Dr. Beakman and welcome Gabriela. Thank you for being with us here today. - Thanks Safah. Dr. Beakman, could you walk us through the impact of cardiac arrest in this country, and also the neurologist crucial role in management, post-arrest? - Of course, thank you so much for having me. Cardiac arrest is one of the leading causes of morbidity and mortality worldwide. The incidence of cardiac arrest in the United States is about 600,000 patients per year. Despite advances in pre-hospital care and hospital management, the prognosis unfortunately remains poor, with only 10 to 20% of patients surviving to hospital discharge. The primary determinant of mortality after cardiac arrest is hypoxic ischemic brain injury, and withdrawal of life-sustaining therapy due to perceived poor neurologic prognosis. Many question why a neurologist is important in the treatment of cardiac arrest patients. But you should think of cardiac arrest as the largest stroke anyone can have. Cardiac arrest causes global brain ischemia. Neurologist can improve care by identifying and preventing secondary brain injury, identifying patients at risk for brain death, which occurs enough to 10% of cardiac arrest patients, and guiding the medical team and the patient's family in prognostication and shared decision-making, as the vast majority of these patients remain comatose. - Awesome, thanks for that excellent topic introduction. In this episode, we will also cover the role of the neurological assessment immediately post-return of spontaneous circulation, indications to use targeted temperature management or TTM. How TTM is implemented, the effective secondary brain injury, and also details on multimodal prognostic assessments. So let's start with the case. This is a 67 year old man brought to the emergency department after a witness cardiac arrest at home. Family reports he was clutching his chest shortly before becoming unresponsive. And upon arrival to the ED, he's actively getting CPR and estimated downtime of about 20 minutes. Once they achieve return of spontaneous circulation, neurology, resonance paged. So what does his initial assessment by the neuroresident consist of and why is it valuable? - At our institution, a chill alert is called once the patient with a cardiac arrest receives return of spontaneous circulation. A chill alert notifies the neurology and cardiology consultants for prompt evaluation, but also informs the ICU charge nurses bed management that an ICU bed will be needed as soon as possible. Your role in the acute evaluation is to gather critical information that helps to identify the degree of primary brain injury. To evaluate if targeted temperature management is indicated, to evaluate the need and urgency for brain imaging, to facilitate the connection to EEG, to evaluate the patient's hemodynamics, ventilator settings, and labs. All which help you identify brain sensor or cessetation goals. Upon walking into the resuscitation room, you may see that CPR is ongoing, as a real arrest is not uncommon. There will be many people in the room, including nursing, emergency department staff, students, pharmacy technicians, social work, and other consultants. In the hallway outside of the resuscitation room, EMS will be present. EMS has invaluable information regarding arrest details. If they are still present, it is critical to talk to them about the time they were called, the time they arrived. If there is bystander CPR, the time CPR was started, and the time of risk. They also may have information regarding pro-dromal symptoms, like clutching of the chest, seen in our patient, or worse headache of life, which may point to a neurogenic etiology of RS. If EMS has already left, they typically leave an ambulance record. And this information gets scanned into the media tab. This information is vital determining the no flow and low flow of times, which impact neurologic prognosis. In addition to gathering critical information regarding the arrest, it is important to document an initial examination to determine the eligibility for TTM. It is important to recognize that this exam is limited and non-reactive pupils on the initial assessment may not be indicative of irrecoverable brain injury. The two most important examination features to pay attention to are the GCS motor score and the pupil exam. Fixed and dilated pupils, but not fixed in small pupils, may indicate the degree of primary brain injury. In patients with fixed and dilated pupils, would they prolong to no flow or low flow time, especially if it's a non-shockable rhythm? You should consider an early head CT to determine the extent of primary brain injury as this patient may not benefit from target temperature management. Patients who can follow commands after cardiac arrest should not be treated at target temperature management. Patients who are purposeful, like sitting up in the bed and trying to self-extubate, may improve to an exam where they're following commands in the setting of holding sedation. And these are patients we may want to reassess when sedation is held to determine their eligibility of TTM. Lastly, the initial six to 12 hours is the most critical period for development of secondary brain injury. Although the heart is restarted, cerebral blood flow is not normal. Microcirculatory dysfunction and inflammation can result in ongoing ischemia. It is important to assess the hemodynamics, labs, ventilator settings, all to optimize cerebral physiology and minimize secondary brain injury. We'll talk more about this later, but it is important to recognize that patients are often not admitted to the ICU and seen by an attending neurologist until the following day. And it is important to make sure that some of these physiologic parameters are optimized before that time point. You kind of got into part of the neurological exam, but can we delve into more detail about what are important features to keep in mind when doing a neuro exam? - Yeah, the clinical examination in cardiac arrest patients is a standard coma exam. Prior to starting the examination, you should assess if the patient is on sedation or if the patient has recently received any neuromuscular blockade. At the beginning of the examination, you should say the patient's name softly, followed by loudly. If there is no response to verbal stimulation, you should try tactile stimulation. First softly and then vigorously with either bilateral trapezius squeeze or sernal rub. You should then ask the patient to do a task such as open your eyes or wiggle your toes. It should be loud and firm. If patients are unable to follow commands, you should see if they can localize the painful stimuli. You can start with deep trapezius pressure. Localization means that they can find the painful stimulus. In patients who do not localize, you should proceed with proximal and distal knock to stimuli, typically done in the medial arm, medial thigh, and nail bed pressure in the hands and feet. You must assess if the motor response is a withdrawal, flexion, extension, or triple flexion. Next, you should assess the brain's temporary flexes. The pupil exam should be done in dark light when feasible. And it is important to recognize that with small pupils, pupil amatry is more likely to detect reactivity than your naked eye assessment. Coronel reflexes should be done with saline drops and if no response is identified, you should move onto a cotton swab or direct pressure. It is important to touch the swabs to the lateral aspect of the cornea, which is the colored portion of the eye, and not the conjectiva, which is the white portion of the eye. Aculosophalic reflexes should only be tested in patients without injuries to the cervical spine. Cough should be assessed with deep suctioning. Prior to the assessment of cough, you should evaluate if a patient is breathing above the rate set on the ventilator. The exam features may be used to determine the Glasgow coma scale score, the GCS score, or the full outline of unresponsiveness score, which is the four score. Lastly, it is important to identify myoclonus, which may be subtle, such as eyelid movement or chin movement, and may be indicative of status ethylapsicus. This requires urgent connection to EEG. - So the immunology of primary brain injury and cardiac arrest, patients, is mainly ischemia, secondary to global hyperperfusion. But what can you tell us about secondary brain injury post-arrest? - The primary brain injury depends on many factors that, unfortunately, we can't control once the patient is already seen in the hospital. Secondary brain injury is notifiable, and aggressive treatment may yield improved outcomes. Secondary brain injury is caused by an imbalance between cerebral metabolic demands and the energy substrates. There are many causes of secondary brain injury after cardiac arrest, including microcirculatory dysfunction, excitotoxicity, inflammation, cerebral edema, impaired auto-regulation, fever, shivering, and seizures just to name a few. While many of these mechanisms might not be readily identifiable, fever, shivering, and seizures can be easily recognized at the bedside and aggressive management is important to prevent secondary brain injury. - Speaking of preventing secondary brain injury, what ways do we have to prevent it? - It's important to recognize risk factors for secondary brain injury, including things that increase cerebral metabolic demands, like seizures, fevers, or shivering. But it's also important to recognize that there's no one-size-fits-all approach in cardiac arrest management. For example, while math over 65 is recommended by the guidelines, it's likely insufficient for the vast majority of cardiac arrest patients, auto-regulatory failure, or the inability to maintain cerebral blood flow despite changes in blood pressure, is common after cardiac arrest, and will contribute to a patient's optimal blood pressure goals. There are several basic things that we can do to minimize brain injury, including avoiding hypotension, avoiding hypoglycemia, avoiding hypotonic fluid, or large electrolyte shifts, like you might see in dialysis or the treatment of DKA, aggressively treating fevers and shivering, avoiding hypocaphnea, which causes cerebral vasoconstriction and therefore, can worsen ongoing ischemia, and hypoxemia, which decreases the cerebral oxygen supply. It is also important to aggressively treat seizures. While the impact of seizure treatment on outcomes has yet to be elucidated, we do know that seizures, and some epilepsy form patterns, can cause a state of cerebral metabolic crisis in other acute brain injury. And for this reason, it might yield ongoing brain injury. The goal of TTM is really to reduce the cerebral metabolic demands and prevent fever. Inadequate treatment of shivering will increase the cerebral oxygen consumption and counteract the benefit of TTM. - You mentioned seizure treatment, possibly improving outcomes. So does this mean we should provide anti-seger herbal access to cardiac respitions? - There is no role for prophylaxis with anti-seger medication. However, if you, you know, sites have the ability to connect EEG as soon as possible, but it should be connected and seizure should be treated. As up to 30% of patients have non-compulsive seizures after cardiac arrest, and aggressive treatment may improve outcomes that's still an ongoing topic of interest. - Let's get into one very crucial component of postcardic arrest care, which is targeted temperature management or TTM. Can you first explain what TTM is? - Induced hypothermia dates back to Hippocrates, who actually observed that infants exposed to the open survived longer in winter than summer, and that packing patients with acute brain injury in the snow improves their survival. Many centuries later, animal studies confirmed the benefits of induced hypothermia in hypoxic escape and brain injury. The first studies that evaluated therapeutic hypothermia and cardiac arrest patients were in the 1960s, and they found that the patients that were subjected to hypothermia had improved survival. The first randomized trials involving therapeutic hypothermia actually didn't happen until 2002, and that's the Haka and the Bernard study, which both showed significant improvement in functional recovery for the hypothermia group. After the publication of these trials, guidelines began recommending the use of therapeutic hypothermia and cardiac arrest patients, but it took many years to become common practice. In 2013, the TTM trial evaluated cooling to 33 versus 36 with the hypothesis that maybe fever prevention was more important than hypothermia. This trial showed no difference in outcomes, and prompted many sites to shift to using 36 degrees. The current guidelines recommend cooling to any temperature between 32 and 36 degrees. Target temperature management involves four phases, induction, maintenance, rewarding, and control normalthermia. - So when is TTM recommended? - Patients with sustained risk, which means that their heartbeat remains 20 minutes after achieving risk, and who are unable to follow commands should be treated with targeted temperature management. The most recent guidelines are the AHA guidelines from 2020, which recommends any temperature between 32 and 36 for 24 hours for any cardiac rhythm. But these guidelines will need to be updated to incorporate the recent findings of the largest TTM trial, TTM 2. - And are there any contraindications to TTM? - There are a few absolute contraindications, and each patient needs to be evaluated for eligibility. The two most common contraindications to TTM are hemodynamic instability and life-threatening bleeding. It is important to recognize that your initial evaluation is just a snapshot in time. For example, a patient who's hemodynamically unstable with a rapidly escalating press or requirement, but due to respiratory acidosis may be more stable after adjustment of ventilator settings. A patient with hemorrhagic shock due to anticoagulation may become more stable after transfusion and a reversal of coagulopathy. A patient with renal failure who's not a candidate for dialysis, however, is unlikely to improve their hemodynamics rapidly. Pregnant patients are excluded from TTM as the effects on the fetus are unknown. And patients with pre-morbid dependency or a life expectancy less than six months are unlikely to benefit from TTM and should be excluded. - Do we need brain imaging before initiating TTM? And for example, for our case, would you recommend brain imaging? - Early head CT can be particularly helpful in patients with a prolonged unwitnessed or a non-shockable rhythm arrest with brings them a reflexia to identify devastating injury that may not benefit from target asymmetry management. Head CT may also be indicated in patients where there is either concern for trauma or a neurologic pro-drone, but it is important to recognize that in the United States, a neurogenic etiology arrest is extremely rare less than five percent. And that earlier initiation of TTM likely drives the improvement in outcomes. And for this reason, head CT should not delay the initiation of TTM. In the case you presented, it's a witness cardiac arrest with clear proceeding chest pain. And for this reason, there's no specific benefit to an early head CT in this patient. - I know each institution's TTM guidelines differ slightly, but could you walk us through how TTM is generally implemented? - Yeah, so I was mentioning before, there's four phases of TTM. The first phase is induction. Our hospital algorithm uses an initial core temperature to guide the target temperature. For patients who present with a core temperature of 36 or higher, they're cooled to 36. For patients whose core temperature is anywhere between 33 and 36, they're kept at their core temperature. For patients who present with a core temperature below 33, they are slowly re-warmed, no greater than 0.25 degrees Celsius per hour, to a goal of 33 degrees. It is crucial to start the induction phase with connection to a definitive device, so whether that's Artexan or IBM, as soon as possible. There is likely minimal benefit of starting TTM beyond six hours after cardiac arrest. Phase two is maintenance, and once the target temperature is reached, this should be maintained for 24 hours. Phase three is re-warming, which should occur on a standard patient at 0.25 degrees Celsius per hour. We sometimes recommend slowing the re-warming to 0.1 degrees Celsius per hour and special circumstances, such as hemodynamic instability or a concern for cerebral edema. And lastly, phase four is controlled normal thermania. The patient should be maintained at a temperature of less than 37.5, for about two days, ranging anywhere from 33 to 44 hours, depending on the timing of a re-warming, for a total TCM duration of 72 hours. - You mentioned earlier the publication of the TTM to trial on how that might change guidelines, but briefly, they essentially showed that targeted hypothermia after cardiac arrest did not seem to confer survival benefits when compared to normal thermia. So given this new trial, does this mean that we should no longer induce hypothermia in cardiac arrest patients? - This is a great question, and a question that many are asking around the country. The TTM-2 trial evaluated TTM to 33 degrees versus controlled normal thermia. In cardiac arrest patients with a cardiac ideology, it is a very well done study and the largest TTM trial to date. While the results of the TTM-2 trial are valid for the population studied, it is important to recognize the differences between the population we see and those who are enrolled in TTM-2. In the TTM-2 trial, 91% had a witness cardiac arrest, 82% had by a standard CPR, and 72% had a shock of over them. This vastly differs from the patients we see at our hospital, which 65% have a witness arrest, 40% have by a standard CPR, and less than 30% have a shock of over them. The overall survival in the TTM-2 trial was 50%, and 42% had good neurologic outcomes. Compare this to the survival rate we see of 25%, and a good neurologic outcome rate of only 8%. The TTM-2 trial showed that controlled normal thermia was equivalent to cooling in a population with overall a lower risk of severe hypopsychyschemic brain injury. This study is not generalizable to all cardiac arrest patients, specifically in the US, whereby standard CPR rates are significantly lower. It's important also to recognize that the pragmatic design of this study resulted in target temperatures being achieved six to eight hours after return of spontaneous circulation. We know from animal models that the benefit of TTM is reduced as chymalapses, and that it is possible that ultra-early cooling, like being done in the ice cap trial, which is specifically achieving a target temperature less than 34, within four hours from the 9-1-1 call, may show different results. Lastly, the controlled normal thermia group was maintained with temperatures below 37.8, and almost 40% of those in the controlled normal thermia group actually needed definitive cooling devices, such as Arctic Sun or IBTM, to achieve this goal. It is important to recognize that controlled normal thermia requires the use of a cooling device in the vast majority of patients, and it does not mean that patients do not get treated at all. The most important point from this trial, the individualization matters. A target temperature somewhere between 33 and 37.8 degrees is probably appropriate. We know from other studies that the Pittsburgh cardiac arrest category score, which grades patients based on the initial degree of neurologic injury and cardiopulmonary failure, may help to identify which patients benefit from moderate hypothermia closer to a normal thermia. We also know from other studies that initial lactate over 12 may suggest benefit from 33 degrees. Going forward, it's really important to identify biomarkers that help target the goal temperature in each individual patient. - Let's pivot a little bit here and talk about next steps that the neurologist might be involved in after targeted temperature management and after cardiac arrest. A really common question that we get is now that my loved one has had a cardiac arrest, will they be neurologically different if they make it through this critical stage and stabilize? So in other words, we're asked to neuropagnosticate. What can you tell us about the types of deficits experienced by cardiac arrest survivors? - Yeah, more than half of cardiac arrest survivors are gonna have some measurable neurocognitive dysfunction. And somewhere between 20 to 50% will have persistent deficits in memory of earning or executive function even after three months. Unfortunately, the majority of the tools that we have to predict neurologic outcome fail to predict functional outcomes that are relevant to patients and their families. We often in research studies define good outcome by the cerebral Pittsburgh category score. And this defines patients with good outcomes as those who have mild neurologic or psychological deficits and patients who are able to work in a sheltered environment with moderate cerebral disability. - You mentioned that we have some tools that we can use to neuropagnosticate. Can you elaborate on these? - The most common tools used for prognostication after cardiac arrests are the clinical examination, EEG, CAT scan of the head, MRI of the brain, somatic sensory evoked potentials, and biomarkers such as neuron-specific inhalase. The neurologic examination is performed daily and the examination 72 hours after normal thermia, discontinuation of oxidation and confounding variables is the exam that's used in the prognostic assessment. On neurologic examination, absence of pupillary-like reflex and corneal reflex is the most specific for poor outcomes. EEG should be connected as soon as feasible and should remain on for the completion of TTM. The EEG backgrounds, the presence or absence of reactivity and the presence or absence of epilepsy formed discharges and seizures is helpful for determining neurologic prognosis. Early EEG patterns, days one through three, are more helpful for prognostication than later findings. Neuron-specific inhalase is a biomarker of neuronal injury. While false positives are seen in the setting of the molasses, renal and liver failure, a rise in neuron-specific inhalase over the first three days is a predictor of poor outcomes. Brain imaging, including head CT and MRI, are very helpful tools, but it is important to recognize that these tools are very subjective. Somatic sensory evoked potentials assess the integrity of the phylamacortical circuit and bilateral absence of the N20 potential is very specific for poor outcomes. - What are some of the challenges and pitfalls of neuroprimestication that we should be aware of? - It's very important to recognize that withdrawal of life sustaining therapy occurs in approximately 60% of cardiac arrest patients. Our prognostic tools are heavily subject to self-fulfilling prophecy bias. Delayed awakening is common and risk factors include advanced age, renal insufficiency, shock liver, status epilepticus, and the use of long-acting sedatives. When determining a patient's prognosis, it is important to use multimodal prognostication. And by that, I mean incorporating your findings from multiple assessments. When the studies do not align, it is important to recognize the limitations of our assessments and express some level of prognostic uncertainty to the family. - So let's go back to the case I presented at the start. Let's say that on day five, therapy had intact pupil and corneal reflexes, but no motor response. And as EEG showed, myoclonic status epilepticus, which required four anti-seedrum medications and the use of a birthed drip for two days. His MRI showed mild diffusion restriction in the cortex. His N20 on SSEP were present bilaterally. NSE was 60 on day one, but dropped to 25 by day three. So taking all of this into consideration, how would you go about determining his prognosis? - So this is a great example with mixed prognostic features. Although myoclonic status epilepticus is notoriously associated with poor prognosis, there are actually two different variants with dissimilar prognostic significance. Myoclonic status epilepticus with a birth suppression pattern has a high specificity for poor outcome. While continuous backgrounds with central predominance spike wave discharges can be associated with a good prognosis and up to 50% of cases. In this case, given some of the mixed features, I would recommend continuing aggressive care for up to two weeks and being honest with the family about the level of prognostic uncertainty. - Thank you so much for sharing your expertise on this topic, Dr. Beakman. And thanks to Safa and Dr. Moller for having us on. - Thank you so much. - What a wonderful episode. Thank you so much for sharing your knowledge with us. This was exceptionally informative for me, and I hope it was helpful for our listeners. Thank you for your time today. Bye, everyone. (upbeat music)