Abstract
Should continuous electroencephalographic monitoring be used during hypothermia? If so, how long should the patient be monitored?
Electroencephalography (EEG) measures cortical synaptic activity. The cerebral cortex is particularly vulnerable to the anoxic injury that may occur as a result of cardiac arrest. At a critical cerebral blood flow threshold of ∼10–18 mL/100 g/min or less, changes in the frequency of the electrical activity as demonstrated by EEG may reflect ischemia or permanent injury (Sinha and Parnia, 2017; Muhlhofer and Szaflarski, 2018; Nguyen et al., 2018).
The rationale for EEG monitoring during the postcardiac arrest period is twofold: the detection of seizures and prognostication. Although guidelines for the past 10–15 years have recommended the use of EEG after the return of spontaneous circulation (ROSC) and at 72 hours or longer after ROSC, with or without targeted temperature management (TTM), recommendations regarding timing and duration of EEG monitoring have been inconsistent or lacking (Wijdicks et al., 2006; Callaway et al., 2015; Nolan et al., 2015). The guidelines primarily address prognostication, with specific EEG patterns reflecting poor and good outcomes. EEG patterns prognostic for poor outcomes include low-voltage EEG and generalized suppression; a burst-suppression pattern, particularly with malignant bursts; discontinuous background; alpha/theta and spindle coma; generalized periodic discharges; and status epilepticus (Calloway et al., 2015; Westhall, 2017; Muhlhofer and Szaflarski, 2018). EEG patterns predictive of good outcomes include continuous background and rhythmic activity and the absence of seizure activity (Muhlhofer and Szaflarski, 2018; Westhall, 2017). Intermittent myoclonic jerks are neither myoclonic seizures or myoclonic status and should not be interpreted as a strong consistent predictor of poor prognosis (Tacone et al., 2014; Nolan et al., 2015; Sandroni and D'Arrigo, 2017).
If seizures are detected on EEG, they should be treated. Seizures and postanoxic status epilepticus occur in up to 40% of patients postcardiac arrest (Tacone et al., 2014; Oddo and Friberg, 2017). Prolonged seizures may become increasingly resistant to treatment and result in secondary neurological injury related to the increased release of toxic excitatory neurotransmitters, increased metabolic activity, increased intracranial pressure, lipid peroxidation with disruption of the neuronal membrane, and ultimately cell death (Muhlhofer and Szaflarski, 2018). However, EEG has limitations. EEG may be affected by sedation, muscle artifact as a result of shivering, mechanical ventilation, and electrical equipment interference. Sedation may result in burst suppression (Westhall et al., 2016; Westhall, 2017). In addition, therapeutic hypothermia slows the activity of hepatic enzymes by 7–22% with each degree centigrade decrease <37°C, resulting in persistent higher levels of sedation and neuromuscular blockade (Muhlhofer and Szaflarski, 2018). Interpretation of EEG is complex and time consuming and a skill set not easily acquired. In addition, until more recently, a lack of standardization around interpretation has been cited in the literature as a limiting factor of EEG postcardiac arrest (Hirsch et al., 2013; Tacone et al., 2014; Nguyen et al., 2015; Oddo and Friberg, 2017; Hawkes and Rabinsten, 2019). Some discussion in the literature exists around the use of continuous versus intermittent EEG monitoring related to increased use of resources, technology, and staffing associated with continuous EEG, which may not be available at all hospitals (Creapeau et al., 2014). Continuous EEG, when adequate resources are available, is preferred by many as EEG may be most helpful in evaluating brain function over time (Tacone et al., 2014; Nguyen et al., 2018). Intermittent EEGs at specified times, such as a baseline as soon as possible after ROSC or at 12–24 hours after ROSC may or may not be as helpful as continuous EEG. Although EEG during the first 12–72 hours may demonstrate high specificity and low false positive rates, many of the studies are not blinded, which adds bias. Therapeutic hypothermia down to 32–33°C does not affect EEG interpretation. However, seizure activity during hypothermia is often associated with a worse prognosis. After hypothermia, rewarming is a particularly vulnerable time for risk of seizures and status epileptics related to increased irritability of the cortex (Muhlhofer and Szaflarski, 2018).
Evidence for the use of EEG alone in prognostication is low and a multimodal approach is currently recommended. The multimodal approach includes not only EEG, but the clinical examination after a minimum of 72 hours post-ROSC with or without hypothermia/TTM, in addition to evoked potentials, imaging, and blood biomarkers (Calloway, 2015; Muhlhofer and Szaflarski, 2018). Somatosensory evoked potentials, particularly the bilateral N20 median nerve sensory waveform, are thought to be less affected by sedation than EEG (Fugate, 2017). If the patient does not awaken after the removal of sedation at 72 hours or more, subclinical seizures must be ruled out by EEG. A time at which to end EEG monitoring, intermittent or continuous, in the absence of seizure activity is not known. The recommendation to obtain an EEG at 72 or more hours has been found to be congruent with the changes in EEG associated with cardiac arrest patients treated with normothermia (Muhlhofer and Szaflarski, 2018).
EEG is diagnostic for seizures after ROSC and provides information for prognostication around ROSC postcardiac arrest, therapeutic hypothermia, and rewarming, particularly at 72 hours or more. However, its efficacy may be affected by a number of factors, including the patient's physiological state and the physician's expertise in EEG interpretation. Questions remain regarding optimal timing of the EEG, continuous versus intermittent monitoring, and duration.
Authored by:
Patricia A. Blissitt, PhD, ARNP-CNS, CCRN, CNRN, SCRN, CCNS, CCM, ACNS-BC
Neuroscience Clinical Nurse Specialist
Harborview Medical Center and Swedish Medical Center
Associate Professor, Clinical Faculty
University of Washington School of Nursing
Seattle, Washington
References
Callaway CW, Donnino MW, Fink EL, et al. Part B: post cardiac arrest care. 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 2015;132 (18 Suppl 2):S465–S482.
Creapeau AZ, Fugate JE, Mandrekar J, et al. Value analysis of continuous EEG in patients during therapeutic hypothermia after cardiac arrest. Resuscitation 2014;85:785–789.
Fugate J. Anoxic-ischemic brain injury. Neurol Clin 2017;36:601–611.
Hawkes MA, Rabinsten AA. Neurologic prognostication after cardiac arrest in the era of targeted temperature management. Curr Neurol Neurosci Rep 2019;10:10.
Hirsch LJ, LaRoche SM, Gaspard N, et al. American Clinical Neurophysiology Society's standardized critical care EEG terminology: 2012 version. J Clin Neurophysiol 2013;125:2397–2404.
Muhlhofer W, Szaflarski JP. Prognostic value of EEG in patients after cardiac arrest—an updated review. Curr Neurol Neurosci Rep 2018;18:16.
Nguyen KPL, Pai V, Rashid S, et al. Prognostication in anoxic brain injury. Am J Hosp Palliat Care Med 2018;35. DOI: 10.1177/1049909118767881
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Oddo M, Friberg H. Neuroprognostication after cardiac arrest in the light of target temperature management. Curr Opin Crit Care 2017;23:244–250.
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Taccone FS, Cronberg T, Friberg H, et al. How to assess prognosis after cardiac arrest and therapeutic hypothermia. Crit Care 2014;18:202.
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Our intensivist orders buspirone on our hypothermia and normothermia management patients. How does it work? Does it stop the shivering?
The exact mechanism of action for buspirone is unknown, although it has a strong affinity and is a partial agonist at serotonin 5-HT1A receptors and has a moderate affinity for dopamine D2 receptors (Mokhtarani et al., 2001). In a report from 1963, it was suggested that the balance of serotonin and norepinephrine in the hypothalamus helps to control the body's temperature set point (Weant et al., 2010). Thus, effects by medications on serotonin should help with the body's temperature and shivering threshold.
One trial studied the use of buspirone with meperidine in eight healthy volunteers who were cooled to a mean skin temperature of 32°C (Mokhtarani et al., 2001). Cooled infusions of lactated Ringer's were administered until the shivering threshold was identified. The volunteers were studied on four separate days, where they received either no medication, meperidine to a target concentration of 0.8 mcg/mL, meperidine at 0.4 mcg/mL and buspirone 30 mg, or buspirone 60 mg. Buspirone alone reduced the shivering threshold by close to 1°C, but the combination of meperidine and buspirone reduced the shivering threshold to 33.4°C ± 0.7°C, an ∼2°C reduction (Mokhtarani et al., 2001).
Another study of 22 healthy volunteers was conducted where patients received meperidine alone, meperidine plus buspirone 30–60 mg, meperidine plus ondansetron, or a combination of meperidine, ondansetron, and magnesium sulfate (Zweifler et al., 2004). Target temperature goal was 34.5°C. Patients receiving the combination of meperidine, ondansetron, and magnesium sulfate experienced an increased cooling rate and comfort level (Zweifler et al., 2004).
Lenhardt et al. (2009) published another study of eight healthy patients who received no medication, buspirone 60 mg, dexmedetomidine alone, or buspirone plus dexmedetomidine. Buspirone reduced the shivering threshold from 36.6°C to 35.9°C, whereas the combination of buspirone plus dexmedetomidine reduced the threshold from 36.6°C to 34.1°C.
A case report by Honasoge et al. (2016) describes the administration of buspirone to a patient undergoing TTM after cardiac arrest. This patient received buspirone and acetaminophen through a rectal device as this patient also was experiencing a gastrointestinal bleed. The use of rectal buspirone led to a cessation in shivering and decreased his previously rising core temperature (Honasoge et al., 2016).
As meperidine often has more serious adverse effects, such as seizures and hypotension, buspirone can be a useful option to lower shivering threshold, either monotherapy or in combination with other agents. Unfortunately, much of the literature surrounding buspirone use is in healthy patients, although many institutions routinely include buspirone in their antishivering protocols. Further research should be conducted as to ideal dosage and frequency of buspirone.
Authored by:
Leslie A. Hamilton, PharmD, FCCP, FCCM, BCPS, BCCCP
Associate Professor of Clinical Pharmacy and Translational Science
College of Pharmacy
University of Tennessee Health Science Center
Knoxville, Tennessee
References
Honasoge A, Parker B, Wesselhoff K, et al. (2016). First Use of a New Device for Administration of Buspirone and Acetaminophen to suppress shivering during therapeutic hypothermia. Ther Hypothermia Temp Manag 2016;6:48–51.
Lenhardt R, Orhan-Sungur M, Komatsu R, et al. Suppression of shivering during hypothermia using a novel drug combination in healthy volunteers. Anesthesiology 2009;111:110–115.
Mokhtarani M, Mahgoub AN, Morioka N, et al. Buspirone and mepiridine synergistically reduce the shivering threshold. Anesth Analg 2001;93:1233–1239.
Weant KA, Martin JE, Humphries RL, et al. pharmacologic options for reducing the shivering response to therapeutic hypothermia. Pharmacother 2010;30:830–841.
Zweifler RM, Voorhees ME, Mahmood MA, et al. Magnesium sulfate increases the rate of hypothermia via surface cooling and improves comfort. Stroke 2004;35:2331–2334.
How do you institute TTM/hypothermia postcardiac arrest in the emergency department (ED) if the patient is experiencing an ST elevation myocardial infarction and must go to the catheterization laboratory immediately?
There are multiple priorities in the immediate postcardiac arrest resuscitation phase. Reassessment of airway, stabilizing the blood pressure, and ECG rhythm are done immediately. Most experts in the field of postcardiac arrest management advocate for early implementation of TTM. In addition, revascularizing the patient with a suspected coronary artery occlusion or narrowing is the top priority and should not be delayed for any reason. The American Heart Association (AHA) (2015) recommends performing coronary angiography emergently for OHCA with ST elevation myocardial infarction (STEMI) (AHA). (Class I, LOE B-NR) If you work in a facility where STEMI alerts are activated by Emergency Medical System (EMS), the ED will be bypassed and cooling initiated in the catheterization laboratory.
If the patient is experiencing a STEMI postcardiac arrest and is in the emergency department, cooling should be initiated in a timely manner. Mooney et al. (2011) reported a 20% increase in risk of death for every hour of delay in starting TTM. Patients going to the cardiac catheterization laboratory can receive TTM through surface, esophageal, or endovascular catheter methods.
Surface cooling can be implemented quickly by placing the external pads on the patient and initiating TTM before leaving the ED. Many cardiac catheterization laboratories have cooling console devices available, so the patient can be connected on arrival to the laboratory. The same is true for esophageal temperature management. If endovascular cooling catheters are used, many cardiologists prefer to place them in the catheterization laboratory during the procedure. If this is the case, the TTM protocol would be initiated in the catheterization laboratory.
Iced saline infusions were studied in the prehospital setting and did not show mortality benefit. Kim et al. (2014) discovered there was a higher incidence of pulmonary edema and rearrest when iced saline was administered. Iced saline to “kick-start” cooling is not recommended by the AHA.
Authored by:
Nicole Kupchik, MN, RN, CCNS, CCRN-K, PCCN-CMC
CEO and Independent CNS
Nicole Kupchik Consulting, Inc.
Seattle, Washington
References
American Heart Association. (2015). Web-based integrated guidelines for cardiopulmonary resuscitation and emergency cardiovascular care—part 8: post-cardiac arrest care. ECCguidelines.heart.org https://eccguidelines.heart.org/index.php/circulation/cpr-ecc-guidelines-2/part-8-post-cardiac-arrest-care (accessed April 1, 2019).
Kim F, Nichol G, Maynard C, et al. Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial. JAMA 2014;311:45–52.
Mooney M, Unger B, Boland L, et al. Therapeutic hypothermia after out of hospital cardiac arrest: evaluation of a Regional System to increase access to cooling. Circulation 2011;124: 206–214.
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