Considerations for N e u ro p ro t e c t i o n i n t h e Tra uma tic B r ai n I n j u r y P o pul a ti on Karen Bergman, PhD, RN, CNRNa,b,*, Valerie Beekmans, Jeff Stromswold, RN, BSN, CCRNc
RN, BSN
c
,
KEYWORDS Trauma Brain injury Neuroprotection Cooling Craniectomy KEY POINTS The brain undergoes complex pathophysiologic changes following a traumatic injury, and efforts should be made to decrease the amount of secondary injury. There is evidence to support the use of cooling, craniectomy, and medications as neuroprotective measures to save the brain following traumatic injury. Cooling for all persons with severe traumatic brain injury is not supported in the evidence; however, cooling may be beneficial to reduce intracranial pressure. Craniectomy may be beneficial in the management of increased intracranial pressure; however, current research does not support improved outcomes for patients, and further research is needed. Severe traumatic brain injury is associated with a high rate of death or disability; nurses are key in monitoring and treating secondary brain injury in efforts to save the brain. Further research is needed to improve knowledge of neuroprotection following traumatic brain injury.
INTRODUCTION
Traumatic brain injury (TBI) is a contributing factor in approximately 30% of all injuryrelated deaths in the United States.1 The Centers for Disease Control and Prevention estimated the direct and indirect cost of TBI in 2010 to be $76.5 billion, with the medical care for those with severe TBI accounting for 90% of those costs. Approximately 5.3 million Americans are living with a disability as a result of TBI, affecting all aspects of their life and their ability to function as contributing members of society.1
Disclosures: The authors have nothing to disclose and no conflicts of interest. a Department of Professional Practice, Bronson Hospital, Western Michigan University, 601 John Street, Box 88, Kalamazoo, MI 49007, USA; b School of Nursing, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo MI 49008, USA; c Neuro Critical Care, Bronson Hospital, 601 John Street, Box 88, Kalamazoo, MI 49007, USA * Corresponding author. E-mail address: [email protected] Crit Care Nurs Clin N Am - (2015) -–http://dx.doi.org/10.1016/j.cnc.2015.02.009 ccnursing.theclinics.com 0899-5885/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
2
Bergman et al
TBI damages the neurons of the brain in both direct and indirect ways. Direct damage is caused by the initial injury compressing, twisting, or otherwise damaging the neuron, resulting in neuronal dysfunction or neuronal death. The aims of medical and nursing therapies for management of brain injury are to limit the effects of secondary brain injury, which is caused by a myriad of cellular and pathophysiologic mechanisms. Secondary injury is triggered by the initial injury and then leads to further brain damage as a result of altered cerebral blood flow, altered cerebrovascular autoregulation, changes in cerebral metabolism, and low cerebral oxygenation. Further damage to neurons can occur by excessive release of glutamate, an excitatory neurotransmitter, and the influx of calcium and sodium into the intracellular space.2 Minimizing the effects of the secondary injury to the brain following the initial injury is the focus of nursing care in the days to weeks following the trauma. Neuroprotection is a concept that health care providers use to optimize treatments in such a way that the neuronal damage or loss is minimized, and patient outcomes are improved. This article summarizes areas in which research has previously supported or refuted the brain-protecting efforts of procedures or medications. COOLING
Therapeutic hypothermia has been studied for more than a decade as a neuroprotective strategy for patients after cardiac arrest.3 The 2011 National Institute for Health and Clinical Excellence guidelines support the use of hypothermia to 32 C to 34 C for 12 to 24 hours following cardiac arrest with slow rewarming to improve neurologic outcome for comatose patients with return of spontaneous circulation.4 The pathophysiology of cooling as a neuroprotective mechanism is complex and involves a multitude of responses at the cellular level to the ischemia or injury. This article provide an overview of the pathophysiology in order for nurses to better understand the background of why cooling brain-injured patients may or may not be beneficial. Ischemia or injury to the brain causes the release of excitatory amino acids and glutamate. Neuronal exposure to the excess levels of these substances causes inflammation, edema, and accelerated cell death. In addition, ischemia or injury to the neuron causes a deficit in the oxygen, ATP, and glucose needed for normal cellular function. Hypothermia is able to decrease cerebral metabolic rate as well as reduce the inflammatory response, thus protecting the brain by decreasing the secondary injury.5,6 With the promising trials supporting the use of therapeutic hypothermia for the postarrest population, it became an area of interest to determine whether the TBI population would also have improved outcomes with the use of cooling. Several factors come into play when assessing the quality of studies supporting or refuting the effects of therapeutic hypothermia in the brain-injured population, such as when to cool (prophylactic vs targeted management if intracranial pressure [ICP] is increased), what methods to use to cool (superficial vs intravascular), how long to cool, what temperature is best, how to rewarm, and which combinations of these factors produce the best outcomes. This article uses the therapeutic moderate hypothermia range of 32 C to 35 C, because most studies are within this range. Two large multicenter trials were conducted to determine the effect on early hypothermia after severe brain injury, targeting overall hypothermia as a neuroprotectant and not as a treatment of ICP. These trials were the North American Brain Injury Study: Hypothermia I and II.7,8 Patients were randomized to cooling to 35 C, 33 C, or normothermia with standard of care for severe TBI. Patients were cooled quickly (20 mm Hg), removing a large portion of the skull on 1 or both sides, along with opening of the dura, allows the cerebral edema to expand outside the limits of the cranial vault.16,17 Allowing the brain to swell outside of the
3
4
Bergman et al
normally enclosed cranial vault prevents cerebral herniation and should reduce ICP and improve cerebral blood flow.18 A meta-analysis of the outcomes of ICP and cerebral perfusion pressure (CPP) following DC found that DC effectively decreases ICP and increases CPP in persons with refractory increases of ICP.19 An RCT published by Cooper and colleagues20 (2011) compared outcomes at 6 months between persons after early bifrontotemporoparietal DC and standard care for management of intracranial hypertension. They randomized 155 adults with severe TBI, and those with craniectomy had better controlled ICP and fewer days in the intensive care unit; however, there was an equal rate of death between groups, and at 6 months the odds for having a worse outcome on the Glasgow Outcomes Score–Extended were worse for the craniectomy group (odds ratio, 1.84; P 5 .03). Despite the unpromising results of this study, clinicians continue to use DC as a method to treat refractory intracranial hypertension. There may be other factors to consider, such as bilateral versus unilateral craniectomy, timing of craniectomy, and differences in patient characteristics, that may not have been reflected in this trail. With regard to timing of DC, most clinicians agree that craniectomy should be performed as a secondary approach, meaning that the patient has failed conservative methods to decrease or control ICP. Nirula and colleagues21 (2014) evaluated DC performed as a primary treatment versus as a secondary therapy, assessing the timing of the DC. Their findings for 264 patients who received craniectomies showed no survival benefit with early primary DC (relative risk, 1.07; P 5 .77). Chibbaro and colleagues22 (2011) studied 147 patients with severe TBI and found younger age and earlier DC (within 9 hours from trauma) to have a significant effect on Glasgow Outcomes Score (P
RN, BSN
c
,
KEYWORDS Trauma Brain injury Neuroprotection Cooling Craniectomy KEY POINTS The brain undergoes complex pathophysiologic changes following a traumatic injury, and efforts should be made to decrease the amount of secondary injury. There is evidence to support the use of cooling, craniectomy, and medications as neuroprotective measures to save the brain following traumatic injury. Cooling for all persons with severe traumatic brain injury is not supported in the evidence; however, cooling may be beneficial to reduce intracranial pressure. Craniectomy may be beneficial in the management of increased intracranial pressure; however, current research does not support improved outcomes for patients, and further research is needed. Severe traumatic brain injury is associated with a high rate of death or disability; nurses are key in monitoring and treating secondary brain injury in efforts to save the brain. Further research is needed to improve knowledge of neuroprotection following traumatic brain injury.
INTRODUCTION
Traumatic brain injury (TBI) is a contributing factor in approximately 30% of all injuryrelated deaths in the United States.1 The Centers for Disease Control and Prevention estimated the direct and indirect cost of TBI in 2010 to be $76.5 billion, with the medical care for those with severe TBI accounting for 90% of those costs. Approximately 5.3 million Americans are living with a disability as a result of TBI, affecting all aspects of their life and their ability to function as contributing members of society.1
Disclosures: The authors have nothing to disclose and no conflicts of interest. a Department of Professional Practice, Bronson Hospital, Western Michigan University, 601 John Street, Box 88, Kalamazoo, MI 49007, USA; b School of Nursing, Western Michigan University, 1903 West Michigan Avenue, Kalamazoo MI 49008, USA; c Neuro Critical Care, Bronson Hospital, 601 John Street, Box 88, Kalamazoo, MI 49007, USA * Corresponding author. E-mail address: [email protected] Crit Care Nurs Clin N Am - (2015) -–http://dx.doi.org/10.1016/j.cnc.2015.02.009 ccnursing.theclinics.com 0899-5885/15/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved.
2
Bergman et al
TBI damages the neurons of the brain in both direct and indirect ways. Direct damage is caused by the initial injury compressing, twisting, or otherwise damaging the neuron, resulting in neuronal dysfunction or neuronal death. The aims of medical and nursing therapies for management of brain injury are to limit the effects of secondary brain injury, which is caused by a myriad of cellular and pathophysiologic mechanisms. Secondary injury is triggered by the initial injury and then leads to further brain damage as a result of altered cerebral blood flow, altered cerebrovascular autoregulation, changes in cerebral metabolism, and low cerebral oxygenation. Further damage to neurons can occur by excessive release of glutamate, an excitatory neurotransmitter, and the influx of calcium and sodium into the intracellular space.2 Minimizing the effects of the secondary injury to the brain following the initial injury is the focus of nursing care in the days to weeks following the trauma. Neuroprotection is a concept that health care providers use to optimize treatments in such a way that the neuronal damage or loss is minimized, and patient outcomes are improved. This article summarizes areas in which research has previously supported or refuted the brain-protecting efforts of procedures or medications. COOLING
Therapeutic hypothermia has been studied for more than a decade as a neuroprotective strategy for patients after cardiac arrest.3 The 2011 National Institute for Health and Clinical Excellence guidelines support the use of hypothermia to 32 C to 34 C for 12 to 24 hours following cardiac arrest with slow rewarming to improve neurologic outcome for comatose patients with return of spontaneous circulation.4 The pathophysiology of cooling as a neuroprotective mechanism is complex and involves a multitude of responses at the cellular level to the ischemia or injury. This article provide an overview of the pathophysiology in order for nurses to better understand the background of why cooling brain-injured patients may or may not be beneficial. Ischemia or injury to the brain causes the release of excitatory amino acids and glutamate. Neuronal exposure to the excess levels of these substances causes inflammation, edema, and accelerated cell death. In addition, ischemia or injury to the neuron causes a deficit in the oxygen, ATP, and glucose needed for normal cellular function. Hypothermia is able to decrease cerebral metabolic rate as well as reduce the inflammatory response, thus protecting the brain by decreasing the secondary injury.5,6 With the promising trials supporting the use of therapeutic hypothermia for the postarrest population, it became an area of interest to determine whether the TBI population would also have improved outcomes with the use of cooling. Several factors come into play when assessing the quality of studies supporting or refuting the effects of therapeutic hypothermia in the brain-injured population, such as when to cool (prophylactic vs targeted management if intracranial pressure [ICP] is increased), what methods to use to cool (superficial vs intravascular), how long to cool, what temperature is best, how to rewarm, and which combinations of these factors produce the best outcomes. This article uses the therapeutic moderate hypothermia range of 32 C to 35 C, because most studies are within this range. Two large multicenter trials were conducted to determine the effect on early hypothermia after severe brain injury, targeting overall hypothermia as a neuroprotectant and not as a treatment of ICP. These trials were the North American Brain Injury Study: Hypothermia I and II.7,8 Patients were randomized to cooling to 35 C, 33 C, or normothermia with standard of care for severe TBI. Patients were cooled quickly (20 mm Hg), removing a large portion of the skull on 1 or both sides, along with opening of the dura, allows the cerebral edema to expand outside the limits of the cranial vault.16,17 Allowing the brain to swell outside of the
3
4
Bergman et al
normally enclosed cranial vault prevents cerebral herniation and should reduce ICP and improve cerebral blood flow.18 A meta-analysis of the outcomes of ICP and cerebral perfusion pressure (CPP) following DC found that DC effectively decreases ICP and increases CPP in persons with refractory increases of ICP.19 An RCT published by Cooper and colleagues20 (2011) compared outcomes at 6 months between persons after early bifrontotemporoparietal DC and standard care for management of intracranial hypertension. They randomized 155 adults with severe TBI, and those with craniectomy had better controlled ICP and fewer days in the intensive care unit; however, there was an equal rate of death between groups, and at 6 months the odds for having a worse outcome on the Glasgow Outcomes Score–Extended were worse for the craniectomy group (odds ratio, 1.84; P 5 .03). Despite the unpromising results of this study, clinicians continue to use DC as a method to treat refractory intracranial hypertension. There may be other factors to consider, such as bilateral versus unilateral craniectomy, timing of craniectomy, and differences in patient characteristics, that may not have been reflected in this trail. With regard to timing of DC, most clinicians agree that craniectomy should be performed as a secondary approach, meaning that the patient has failed conservative methods to decrease or control ICP. Nirula and colleagues21 (2014) evaluated DC performed as a primary treatment versus as a secondary therapy, assessing the timing of the DC. Their findings for 264 patients who received craniectomies showed no survival benefit with early primary DC (relative risk, 1.07; P 5 .77). Chibbaro and colleagues22 (2011) studied 147 patients with severe TBI and found younger age and earlier DC (within 9 hours from trauma) to have a significant effect on Glasgow Outcomes Score (P
