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Introduction

Acute ischemic stroke treatment has advanced significantly with early thrombolytic treatment when indicated and with revascularization interventions. Over the last decade, stroke mortality and morbidity have moved from the second leading cause of death to the fifth.  

Targeted temperature management (TTM) is a method to quickly reduce body temperature to induce a therapeutic hypothermic state to preserve neurological function. Through cooling pads or invasive, endovascular procedures, the body temperature is reduced to between 32 and 36 °C, to sustain this temperature for 24 to 72 hours. Outcomes are optimal when cooling is initiated within six hours of the onset of symptoms (1).  

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Pathophysiology 

At 80% of total strokes, ischemic is the most common cerebrovascular accident. Globally, it is still the leading cause of death. During an ischemic stroke, one or multiple of the three branches of cerebral blood vessels become occluded. These vessels are the anterior cerebral arteries, middle cerebral arteries, and posterior cerebral arteries. Their function is to supply blood to the cerebral parenchyma. Occlusions may be embolic or thrombotic and may be due to blood clots, debris, or atherosclerotic deposits of plaque. Plaque is comprised of fibrin, cholesterol, fatty substances, calcium, and other cellular matter (1, 2, 6).  

The ischemic effects of a stroke caused by interruption of blood supply to cerebral tissue occur suddenly, within minutes of the event onset. The most common cause of stroke stemming from an embolic source is blood clots manifested by blood pooling in the atria due to atrial fibrillation. Thrombus sources are typically from vascular formations of atherosclerotic plaque. The area of tissue damage is referred to as the ischemic core. As the stroke progresses, the lack of blood flow results in oxygen deprivation and insufficient nutrients causing necrotic tissue. This area of death is responsible for physical and mental changes such as balance issues, hemiplegia, dysarthria, paraplegia, and aphasias (6).  

Surrounding this core is the ischemic penumbra. This area is the target for reperfusion and restoration of function. Patients who seek treatment within 3 hours of the onset of symptoms may be candidates for thrombolytic. This medication aims at breaking up the fibrin threads that bind a clot, often referred to as a ‘clot buster’. A common thrombolytic used in an emergency setting is tissue plasminogen activator (tPA) (3, 4). 

Returning blood flow promptly is essential to reducing the amount of permanent damage that can affect speech, movement, coordination, and cognitive acumen. For patients who qualify, percutaneous thrombectomy has been shown to improve clinical outcomes versus standard care. Even with successful reflow, ischemic damage triggers an inflammatory cascade along with biochemical changes that result in hyperthermia (3, 4).  

Indications and Contraindications 

Targeted temperature management has been utilized for applications beyond the treatment of ischemic cerebrovascular events. Its use has also been applied to cardiac arrest, supportive care during cardiac surgery, brain injury, and encephalopathies of various origins. As the application of targeted temperature management for ischemic stroke is relatively new, suggested guidelines follow similar criteria for those used in patients who have cardiac arrest with the return of spontaneous circulation.  

These guidelines and criteria include (all from 15): 

• Absolute contraindications: Hemorrhage, uncontrolled arrhythmia, cardiac arrest from trauma, GCS > 8 

• Relative contraindications: coagulopathy, cardiac arrest > 60 minutes, refractory hypotension, thrombocytopenia 

• Other contraindications: Pregnancy, severe sepsis, terminal illness, Do Not Resuscitate status 

Identification 

Time is essential in preventing nervous tissue death that results in rapid and permanent deterioration of health and quality of life. Campaigns are aimed at informing the public of the emergent need for expeditious medical intervention when signs and symptoms are suspected.  

Building upon the initial FAST campaign of 1998, this has expanded to the nationally recognized and adopted BEFAST due to a 40% misdiagnosis rate when ataxia and visual changes were prominent symptoms (7). 

BEFAST:  

Balance – Sudden loss of balance or coordination 

Eyes – Sudden difficulty seeing out of one or both eyes 

Fast – Sudden drooling on one side of the face 

Arms – Sudden weakness in one arm or leg 

Speech – Sudden trouble with speech or understanding. 

Time – Time to call 911 

Upon arrival at the emergency department, staff must work quickly to confirm or rule out a stroke. Many hospitals partner with the emergency medical services (EMS) to receive a pre-notification of a possible cerebrovascular event to decrease the ED door-to-stroke team activation. The intervention window for an acute stroke is limited with timely identification critical to guide treatment via a stat computed tomography (8, 9).  

These metrics aim to guide quick identification and intervention with a door-to-CT time of less than 25 minutes and a door-to-intervention time of less than 60 minutes. Standardized forms used to screen patients for stroke must be accessible and intuitive for staff.  

The following documentation is comprehensive and meaningful to elicit valuable clinical decision-making information to neurology and promote data gathering for further metric analysis (all from 9): 

• Mode of arrival (EMS versus non-EMS) 

• Prehospital stroke activation 

• Initial vital signs to include: 

• Respiratory rate 

• Blood pressure 

• Heart rate 

• Pulse oxygen saturation. 

• Need for supplemental oxygen and delivery method. 

• Glasgow Coma Scale 

• Cognitive assessment and level of orientation (person, place, time) 

• National Institutes of Health Stroke Scale (NIHSS) score 

• Blood glucose level 

• Elapsed time since the patient was last known well. 

• Previous stroke or transient ischemic attack history 

• Previous history of hypertension 

Based on the clinical information and presentation of the patient, the interventional neurologist may elect to treat via intravenous thrombolysis or endovascular thrombolysis to achieve reperfusion. When large vessel occlusions are identified, mechanical thrombectomy is highly successful in achieving immediate recanalization with rates of 85%; however, further studies have shown that at three months post-intervention, roughly half of the patients have not met goals for functional independence (6).  

To combat poor vascular outcomes, adjunctive therapy including anti-thrombotic treatment is used to increase angiographic perfusion. In addition, management with anticoagulants and neuroprotective targeted therapies such as temperature regulation has shown promising long-term outcomes (10). 

Case Study 

EMS has contacted the nearest emergency department to notify them that they are bringing in a patient who is 64 years old and was found stumbling in their driveway and is now confused with slurred speech. The neighbor called 911 because this was not normal behavior for this individual.  

Methods of Targeted Temperature Management 

Initial targeted temperature management may be accomplished via antipyretics and watchful monitoring of signs of infection. When pyrexia is evident, established as a temperature above 37.5°C, the cause is investigated.  

Possible signs used to evaluate for infection include blood and fluid tests that result positive for leukocytosis, identification of an infectious agent, and visualization of fluid collections or suspicious tissue that would indicate the presence of bacterial infection (5).  

Admission temperature did not have a significant factor in the severity of the stroke; however, there is a school of thought that promotes the association that an increased temperature factors into an increase in permeability within the blood-brain barrier. This factor increases the likelihood of extracellular edema, and restriction of capillary flow to the ischemic core and penumbra, all of which perpetuate the progression of increased ischemic infarct.  

Compromise begins early at 4-6 hours post-ischemic event, then a delay and reopening at 2-3 days post-stroke (5). In addition, management of the ischemic cascade prevents excitotoxicity related to neurotransmitter production, promotes anti-inflammatory action, delays apoptosis, and reduces the release of oxygen derivative free radicals. Multiple studies have shown that TTM is the most effective method for neuroprotective therapy to reduce hypoxic and ischemic encephalopathy, that initiates this unique cascade event. 

There are three main phases to TTM: induction, target, and rewarming.  

The initial stage is induction, which is accomplished through the use of a cooling device. This may be via a non-invasive targeted temperature system that uses pads adhered to the patient’s skin. Cool water is circulated through these pads and skin temperature is monitored to induce hypothermia. The alternative method is with an endovascular balloon catheter that contains an internal cooling circuit. As blood circulates past this catheter, the blood is cooled. The catheter contains a sensor for temperature control (10, 11). Both of these methods may be coupled with an infusion of cooled normal saline delivered intravenously at a bolus rate of 20ml/kg over 30 to 60 minutes.  

The goal is to quickly reduce the temperature to typically between 32-34◦C; although, some studies have found that reducing the temperature to 36◦C or for shorter durations of time does offer some protective benefits when lower target temperatures are not tolerated. Care must be taken when cooling to control shivering. For target temperatures below 35.5◦C, the standard of care includes mechanical ventilation and sedation. These types of patients have higher acuity and require an intensive care team to manage (13). 

Reducing the temperature quickly takes approximately 12 hours. Another neurotoxic mechanism that is prevented is the sharp rise in calcium and accumulation of glutamate that occurs with cerebral ischemia (12). When the target goal is met, oxygen consumption is reduced while mild hypothermia at these temperatures is maintained for approximately 36 hours. Once the target temperature has been maintained, the body is rewarmed slowly to prevent a rebound increase in intracerebral pressure (12). 

Case Study 

The patient was assessed in the emergency department and immediately sent for a head CT which revealed a large vessel occlusion. As the last known well time was 2 hours ago, the patient was given thrombolytics, received percutaneous thrombectomy with successful recanalization, and is being admitted to the intensive care unit. The patient has slurred speech but is oriented to time, place, and self with some intermittent lapses in memory. 

Adverse Effects and Interventions 

Whole-body cooling has the disadvantage of leading to systemic adverse effects and complications. Many can be medically treated when anticipated by experienced staff. The most common adverse effect of targeted temperature is the management of shivering. A standardized tool is used by all nursing staff monitoring the patient to assess and trend the occurrence of shivering. A higher score may indicate increased occurrence of shivering is present in the patient. 

The Bedside Shivering Assessment Score rates rigors on a scale of 0 to 3 as follows (13): 

0 – None: no evidence of shivers 

1 – Mild: shivering that is localized to the neck and thorax; may cause ECG artifact or be felt via palpation 

2 – Moderate: Intermittent rigors involving the upper extremities, with or without thorax 

3 – Severe: Shivering is generalized or sustained affecting upper and lower extremities 

This scoring is used to guide pharmacological treatment and intervention. Mismanagement of identification and treatment to control shivering can have significant clinical detriments to outcomes. Shivering occurs in approximately 40% of patients undergoing targeted temperature management.  

The following multimodal interventions are commonly used to provide relief from potential and actual shivering (all from 13): 

• Active cutaneous counter warming with forced air (Bair Hugger, etc.) 

• Passive cutaneous (heated blankets) 

• Electroacupuncture 

• Non-opioid Analgesics 

• Non-steroidal anti-inflammatory drugs (NSAIDs) 

• Vasodilators 

• Intravenous magnesium sulfate infusions 

• Neuromuscular blockade agents 

Neuromuscular blockage agents, such as vecuronium, are high-alert medications that should be used stringently and only when necessary. There are adverse effects related to the administration of this medication, such as the need for mechanical ventilation, prolonged stay in an ICU level of care, and an increased risk of developing ventilator-associated pneumonia (14). 

Sinus bradycardia, indicated by a heart rate of less than 50 beats per minute, is a common side effect of targeted temperature management. This occurs most frequently during the maintenance phase of treatment. While this may appear concerning nursing staff who are unfamiliar with the pathophysiological cascade during hypothermia, it is an induced, normal physiological response and is not typically associated with hemodynamic changes (2).  

Hypovolemia due to diuresis can occur as hypothermia elicits an excretory state in the kidneys leading to water loss and volume reduction. This can also lead to a loss of potassium. Potassium may also be decreased as intracellular shift occurs during the maintenance phase. Electrolyte lab values should be monitored closely for hypokalemia (2).  

Pneumonia may not only be associated with paralytics combined with mechanical ventilation but also due to a decrease in immune function (12). Any signs of infection should be closely monitored and treated promptly to reduce the likelihood of progression to systemic inflammatory response syndrome (SIRS), sepsis, or septic shock. 

Case Study 

The patient is mechanically ventilated and cooled to the maintenance phase. The nurse assesses the patient utilizing the Bedside Shivering Assessment Score tool. The nurse documents the assessment as a 2. The previous score was a 3 and was effectively treated with a neuromuscular blockade agent. The nurse is considering what agent to use to treat the shivering. 

Conclusion

Induced hypothermia through targeted temperature management has been used to protect neurological function post-cardiac arrest for nearly two decades. The use of this treatment has been expanded to include preventing pyrexia and the inflammatory process that follows successful thrombolysis in cerebral infarction. A specialized, intensive care team is required to manage treatment as the adverse effects that may occur with cooling need prompt action to ensure the benefits versus risks are balanced.  

Although more research is needed to assess the widespread use of targeted temperature management as a standard of care post-stroke, this is currently an effective method to reduce the probability of increased cranial pressure and expanse of the ischemic area in the presence of an acute ischemic stroke with reperfusion. 

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