The Use of Hypothermia for Severe Traumatic Brain Injury in Adults

Nancy Kelly, RNUCLA Ronald Reagan

Neuroscience/Trauma Intensive Care Unit

Presentation Outline

• Case Study• Burden/Cost• Physiology of TBI• Stages of Injury• Cooling Categories

1. Prophylactic2. Refractory ICPs

• Guidelines• Complications• Suggested Reading• Future Research

Case Study

• 44 y/o male• Motorcycle accident on freeway• Complex hospitalization/Prolonged ICU stay• Severe TBI with refractory intracranial HTN• Therapeutic hypothermia in addition to mult.

standard interventions• Walked out of hospital grossly intact

Public Health Burden of TBI in the United States: Approximately 1.7M TBIs Annually

Faul, M et al. Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2010

1,365,000 Emergency Departments Visits

275,000 Hospitalizations

52,000 Deaths

Estimated Economic Costs of TBI $76.3 Billion in 2010

Finkelstein, E at al. The Incidence and Economic Burden of Injuries in the United States. New York (NY): Oxford University Press, 2006 Coronado, VG et al. The epidemiology and prevention of TBI, in press, 2012

Med-ical

$11.50

Indirect $64.80

~15%

~85%B

B

What is a TBI?

Traumatic brain injury (TBI) occurs when a sudden trauma, often a blow or jolt to the head, causes damage to the brain. The severity of TBI can range from mild (concussion), moderate (lethargic) to severe (coma).

• A TBI does not include a stroke, an infection in the brain or a brain tumor.

Brain Trauma Foundation. https://www.braintrauma.org/tbi-faqs/

What Happens to the Brain

• Primary Injury: Initial damage from impact• Secondary Injury: Complex neurotoxic

cascade, difficult to control, can worsen outcome

Complex Neurotoxic Cascade after TBISecondary Pathological Insults

TBI

Ischemia

Excitotoxicity

Cell Death cascade

Energy Failure

Blood brain barrier disruption

Cell Death cascades

Free radicals &lipid peroxidation

Cerebral edema

Apoptosis

Blood brain barrier disruption

Demyelination

Stages of Secondary Injury

• Early Phase (minutes–hours)

• Intermediate Phase (24hrs-7 days)

• Late (weeks to months)

Urbano, L. A., Oddo, Mauro (2012). Therapeutic Hypothermia for Traumatic Brain Injury. Current Neurology and Neuroscience Report, DOI: 10.1007/s11910-012-0304-5

How Hypothermia May Reduce Secondary Injury

Early Phase

• Decreases cerebral blood flow & lowers metabolic rate of oxygen (5-7% per 1c) Reducing risk of hypoxemia/ischemia

• Decreases cerebral glucose consumption Reducing risk of energy crisis

• Reduction in cerebral thermopooling Reduce temp gradient between injury site and surrounding tissue

• Inhibition of excitotoxicity Reducing Ca influx & damaging excitatory amino acids/free radicals

• Suppresses early cellular stress responses preventing mitochondrial damage, DNA alteration & cell death

How Hypothermia May Reduce Secondary Injury

Intermediate Phase

• Reduced permeability of blood brain barrier & minimize brain swelling lower ICPs

• Inhibition of Epileptic Activity

How Hypothermia May Reduce Secondary Injury

Late Phase

• Reduced extent of injury and enhance neuronal growth and activity

Clinical Utility

Hypothermia has long been suggested as a therapeutic strategy after TBI. Clinical trials evaluating hypothermia can be divided into two categories according to the therapeutic aims:

1) Hypothermia applied in the early phase of TBI, as a prophylactic neuroprotectant

2) Hypothermia applied in the intermediate phase of TBI to control elevated ICP

Hypothermia applied in the earlyphase of TBI, as a prophylactic

neuroprotectant

Controversial treatment: Questionableefficacy & impact on mortality

Prophylactic Hypothermia: Varying Results

• A number of animal models have repeatedly demonstrated the benefit of early cooling. However, the translation of these positive data into clinical human studies has proven difficult and not clearly demonstrated.

• Conflicting studies on TBI – Single center studies produced more favorable results than multi-center randomized control trials (RCT)– Lesser expertise with the management of hypothermia

associated with more complications

National Acute Brain Injury Study

• A multi center RCT including patients who were 16-45 years old, had severe, non-penetrating TBI, treated with hypothermia within 2-5 hours. Patients were cooled to 33 deg. for 48hrs. Trail was stopped in 2009 for lack of effect. Data suggesting no benefit from early cooling

• Sub group analysis:– Evacuated hematoma +– Diffuse brain injury -Data suggesting different effects of hypothermia depending on the type of TBI

Meta Analyses

Given discrepancy between single center and multi-center RCTs, many meta analyses have attempted to

further examine the impact of prophylactic cooling on patient outcome after TBI

Meta-analysis: a statistical technique for combining the findings from independent studies. It does this by combining data from two or more randomized control trials.

Brain Trauma Foundation Analysis• Meta Analysis of 6 Class II studies of induced

prophylactic hypothermia

• Selection criteria– Pts with TBI >= 14 yrs– Hypothermia used as prophylaxis, regardless of ICP– Assessed mortality

• Statistical MethodsTarget cooling temp (32-33 or >33)Cooling duration (<48h, 48h, or >48h)Rate of warming (1C/hr, 1C per day, or slower)

Brain Trauma Foundation Guidelines

Level III recommendation (weak)

Insufficient data to support a Level I or Level II recommendation

• Prophylactic hypothermia is not significantly associated with

decreased mortality when compared with normothermic controls

Preliminary findings suggest patients treated with hypothermia are more likely to have favorable neurological outcomes when cooling is maintained for more than 48 hours

Current RecommendationsNormothermia is currently recommended in head injury

although this is subject to change depending on current trials

Prophylactic cooling is not supported by clinical evidence

Hypothermia applied in the intermediate phase of TBI to control elevated ICP

Clinical trials are showing promising results

Hypothermia for Elevated ICPs

In 17 controlled trials moderate induced hypothermia (32-35c) was tested in severe TBI patients with refractory intracranial hypertension. Compared to normothermia, moderate cooling was associated with significant reduction in elevated ICP & improved outcomes

Type of TBI is relevant: Focal TBI may respond better than those with diffuse injury. Data suggesting different effects of hypothermia depending on the type of TBI

Urbano, L. A., Oddo, Mauro (2012). Therapeutic Hypothermia for Traumatic Brain Injury. Current Neurology and Neuroscience Report, DOI: 10.1007/s11910-012-0304-5

Current Recommendations

When used to control brain edema mild hypothermia is effective in reducing elevated ICP and is a valid therapy for refractory intracranial

hypertension in TBI patients.

Temperatures for ICP ControlOptimal target temperatures are not precisely defined

Suggestions

• 35c - 35.5c effectively treats ICP, while maintaining sufficient CPP without cardiac dysfunction or oxygen debt

• Temp. between 32-35c have been used

• <35 may reduce cerebral perfusion pressure, oxygen delivery and increase side effects

• Hypothermia targeted on an individual basis titrating temperature to maintain ICP <20mmHg.

Duration of Cooling

• Suggestions

– Optimal duration of hypothermia depends on the severity of the ICP

– Hypothermia should be individualized and may need to be continued for more than 48hs and up to 4-5 days until the peak period of ICP subsides

– Importantly, adverse effects of cooling have been observed principally in the initial phase, and duration has not been demonstrated to significantly increase the rate of pneumonia and other complications

Rewarming• Withdraw of hypothermia should be slow, using controlled

rewarming for maximal neuroprotective effect. Rapid rewarming not only reverses the protective effects, may worsen cerebral damage

• Suggestions– 0.1 - 0.2 C/hr.

• Reperfusion Injury/HyperemiaUncontrolled rewarming may offset benefits of hypothermia, causing rebound cerebral edema and intracranial hypertension

Systemic Complications: Temperature Related

Shivering

Increased oxygen consumption & energy use – brain tissue oxygenation

Sedation (propofol) & analgesia (demerol)

Immune SystemImpaired leukocyte,

macrophage function--Increased risk of sepsis & pneumonia

Regular microbiological sampling & f/u on infection biomarkers (procalcitonin)

CardiovascularBradycardia/

TachycardiaReduced cardiac output

Arrhythmias

Monitor K+ levels, continuous cardiac monitoring

HematologicProlonged partial

thromboplastin time, low platelets

Monitor coagulation lab values,

assess skin for signs of bleeding

Systemic Complications: Technique Related

• Wraps/pads (Artic Sun, Cooling blanket) Skin injury

– Apply immediately– Nurse driven– Covers large area of skin

• Intravascular Catheters (Coolguard) Thrombosis

– Efficient– Cools rapidly– MD/NP to place

Nursing Interventions

• Familiar with hypothermia protocol

• Familiar with systemic complications

• Educate patient and family

Current Research

• Prophylactic Hypothermia– Polar Study: Australian & New Zealand Intensive Care RCT to

determine whether early cooling of patients with severe TBI is associated with better outcomes. Patient recruitment began mid 2010

• Hypothermia for Elevated ICP– Eurotherm Trial: An International, multicenter, RCT will examine

the effects of mild hypothermia (32-35c) as a treatment for ICP reduction after TBI. Recruitment continue until Jan 2013.

Suggestions forNursing Research

• Develop evidence based cooling protocols

• Research most effective cooling devices

• Research best interventions to reduce complications

References

• Urbano, L. A., Oddo, Mauro (2012). Therapeutic Hypothermia for Traumatic Brain Injury. Current Neurology and Neuroscience Report, DOI: 10.1007/s11910-012-0304-5

• Brain Trauma Foundation. Inhospital Severe TBI Guidelines / Prophylactic Hypothermia. Accessed 4 Sept. 2012. http://tbiguidelines.org/glHome.aspx?gl=1

• Wavra, T., Bader, M.K., (2009). AACN 2009 NTI & Critical Care Exposition. Chill Out: The Use of Mild Hypothermia in Cardiac and Neuro Populations. [PowerPoint Slides] Retrieved from http://www.aacn.org:88/WD/NTI/NTI2009/nti_cd/data/papers/main/30990.pdf

References• Mcilvoy, L., Meyer K., (2011) Nursing Management of Adults with Severe

Traumatic Brain Injury. Inducing Moderate Hypothermia May Decrease ICP in Refractory Intracranial Hypertension (Level 2) AANN Clinical Practice Guideline Series

• Wright, D. W. (2011) Center for Disease Control and Prevention. Public Health Grand Rounds, Archives. Traumatic Brain Injury: From Guidelines to Novel Therapy [Power Point Slides] Retrieved from http://www.cdc.gov/about/grand-rounds/archives/2011/pdfsGRTBI20Sep2011.pdf

• McGuire, L. C. (2011) Center for Disease Control and Prevention. Public Health Grand Rounds, Archives. Severe Traumatic Brain Injury in the United States and the Role of Public Health [Power Point Slides] Retrieved from http://www.cdc.gov/about/grand-rounds/archives/2011/pdfsGRTBI20Sep2011.pdf

Thank you!