Treating Neurologic Injury With Hypothermia

NASHVILLE—Therapeutic hypothermia is being used with increasing frequency to treat patients with neurologic injury from conditions such as stroke, cardiac arrest, and traumatic brain injury (TBI). “Induced hypothermia can sometimes be risky, but it’s potentially highly rewarding,” said Kees H. Polderman, MD, PhD, at the Society of Critical Care Medicine’s 38th Critical Care Congress. Effective use of hypothermia is strongly dependent on the quality of other aspects of ICU care; therefore, he recommended that clinicians give careful attention to all of these factors.

When interpreting findings from studies examining therapeutic hypothermia, “you should always look at where it’s being performed, the context in which this treatment is taking place, and what other aspects of care are similar to your own and which ones are different; then you can assess if you can reproduce those results in your own center, or if you need to adapt your policy a bit,” commented Dr. Polderman, Professor in Intensive Care Medicine at the Department of Critical Care, University of Pittsburgh Medical Center.

Goals of Therapeutic Hypothermia
Stroke, cardiac arrest, and, to a lesser extent, TBI are characterized by ischemia and reperfusion injury. After a period of ischemia, a series of destructive processes takes place in the injured cells of the brain. “The damage is ongoing while the patient is in your ICU or your emergency room,” said Dr. Polderman.

Therefore, the first goal of treatment with hypothermia is to try to limit this injury. “Hypothermia acts as a sort of blanket therapy,” he said. “It can interrupt every single one of these harmful processes, in contrast to many other therapies that we’ve tried in the past.”

Another goal is to treat brain edema, which may also play a role in some disease states—TBI being one example. For patients with brain edema, the approach to treatment is slightly different, requiring a longer period of cooling.

Controlling Brain Temperature
When using hypothermia for patients with neurologic injury, physicians should do their best to prevent fever, Dr. Polderman advised. “Most of our patients in the neurocritical care units develop fever at some point in their ICU stay. The more severe the injury, the more likely the chance that [the patient] will develop fever,” he said.

Fever is associated with longer length of stay, worse neurologic outcome, and higher mortality. In two studies involving patients with subarachnoid hemorrhage and intracerebral hemorrhage, researchers reported that even a minimal elevation in temperature to slightly greater than 37.5°C—not considered a real fever by some—had a significant adverse effect on outcome.

One explanation for this could be that brain temperature exceeds core temperature. “The destructive processes triggered by ischemia generate heat. Local brain edema makes it difficult to get rid of the excess heat, and this leads to overheating of the brain,” explained Dr. Polderman. “So fever after neurologic injury seems to be extremely harmful, and hypothermia seems to be really protective.”

Proven Efficacy
Three randomized controlled trials have assessed neurologic outcome in patients who underwent therapeutic hypothermia following witnessed cardiac arrest, with significant improvement seen in patients treated with hypothermia across all three studies, said Dr. Polderman. In addition, a number of nonrandomized studies have reported good outcomes following treatment with induced hypothermia.

Dr. Polderman and his colleagues conducted a prospective, multicenter study in which 64 patients with witnessed cardiac arrest underwent therapeutic hypothermia. The results have not yet been published as a full paper. In this study, 60% of patients with ventricular tachycardia/ventricular fibrillation (VT/VF) had a good neurologic outcome (defined as return to their home situation with no or only minimal neurologic impairment). In addition, 50% of patients with an initial rhythm of asystole who reached the hospital alive also had a good neurologic outcome.

“We should lose the pessimism surrounding patients with witnessed cardiac arrest, because the good outcome rates can be better than 50% in this category of patients when hypothermia has been used,” commented Dr. Polderman. “We need to get the cardiologist to do the appropriate intervention, even when the patient is comatose. We need to promote bystander CPR, because the chances of this therapy helping the patient are much better if basic CPR has been performed.”

Some studies have also reported good outcome following therapeutic cooling in patients with severe TBI. Meta-analyses have reported a 22% to 48% reduction in the risk for adverse neurologic outcome in patients with severe TBI treated with therapeutic hypothermia, although not all these differences were statistically significant.

However, the treatment looks highly promising, according to Dr. Polderman. He pointed out for comparison that data on the use of barbiturates and mannitol do not show any benefit on neurologic outcome in patients with TBI.

Cooling in the Right Context
Although hypothermia has beneficial effects on neurologic outcome, “a treatment can only be effective if the other aspects of intensive care are good,” cautioned Dr. Polderman. Therefore, “context matters. It’s not just about cooling.”

When using hypothermia, temperature should be lowered rapidly, but rewarming should be done very slowly, noted Dr. Polderman. “If you do it rapidly, you could lose some or all of the protective effects of hypothermia,” he warned.

In addition, physicians should consider other aspects of ICU treatment, such as prevention of hypo- and hypercapnia, electrolyte disorders, hyperglycemia, and hypoglycemia. “All these things matter, and they may make all the difference,” he said. “Without getting that right, hypothermia can be an ineffective or even dangerous therapy.”

“The idea of context applies even more strongly to areas like severe TBI,” he asserted. “Speed and duration of cooling are important.” For patients with TBI who receive hypothermia, longer duration of cooling (ie, greater than 48 hours) and slow rewarming protocols are associated with better outcome. He noted that one way to determine the optimal duration of cooling in individual patients is to measure intracranial pressure. Intracranial pressure is both a marker of ongoing brain injury and a potential cause of additional injury.

“The use of hypothermia is not risk-free. There are severe side effects, which we should take into account, but the good news is that these can be fairly easily managed,” concluded Dr. Polderman.   

NASHVILLE—Therapeutic hypothermia is being used with increasing frequency to treat patients with neurologic injury from conditions such as stroke, cardiac arrest, and traumatic brain injury (TBI). “Induced hypothermia can sometimes be risky, but it’s potentially highly rewarding,” said Kees H. Polderman, MD, PhD, at the Society of Critical Care Medicine’s 38th Critical Care Congress. Effective use of hypothermia is strongly dependent on the quality of other aspects of ICU care; therefore, he recommended that clinicians give careful attention to all of these factors.

When interpreting findings from studies examining therapeutic hypothermia, “you should always look at where it’s being performed, the context in which this treatment is taking place, and what other aspects of care are similar to your own and which ones are different; then you can assess if you can reproduce those results in your own center, or if you need to adapt your policy a bit,” commented Dr. Polderman, Professor in Intensive Care Medicine at the Department of Critical Care, University of Pittsburgh Medical Center.

Goals of Therapeutic Hypothermia
Stroke, cardiac arrest, and, to a lesser extent, TBI are characterized by ischemia and reperfusion injury. After a period of ischemia, a series of destructive processes takes place in the injured cells of the brain. “The damage is ongoing while the patient is in your ICU or your emergency room,” said Dr. Polderman.

Therefore, the first goal of treatment with hypothermia is to try to limit this injury. “Hypothermia acts as a sort of blanket therapy,” he said. “It can interrupt every single one of these harmful processes, in contrast to many other therapies that we’ve tried in the past.”

Another goal is to treat brain edema, which may also play a role in some disease states—TBI being one example. For patients with brain edema, the approach to treatment is slightly different, requiring a longer period of cooling.

Controlling Brain Temperature
When using hypothermia for patients with neurologic injury, physicians should do their best to prevent fever, Dr. Polderman advised. “Most of our patients in the neurocritical care units develop fever at some point in their ICU stay. The more severe the injury, the more likely the chance that [the patient] will develop fever,” he said.

Fever is associated with longer length of stay, worse neurologic outcome, and higher mortality. In two studies involving patients with subarachnoid hemorrhage and intracerebral hemorrhage, researchers reported that even a minimal elevation in temperature to slightly greater than 37.5°C—not considered a real fever by some—had a significant adverse effect on outcome.

One explanation for this could be that brain temperature exceeds core temperature. “The destructive processes triggered by ischemia generate heat. Local brain edema makes it difficult to get rid of the excess heat, and this leads to overheating of the brain,” explained Dr. Polderman. “So fever after neurologic injury seems to be extremely harmful, and hypothermia seems to be really protective.”

Proven Efficacy
Three randomized controlled trials have assessed neurologic outcome in patients who underwent therapeutic hypothermia following witnessed cardiac arrest, with significant improvement seen in patients treated with hypothermia across all three studies, said Dr. Polderman. In addition, a number of nonrandomized studies have reported good outcomes following treatment with induced hypothermia.

Dr. Polderman and his colleagues conducted a prospective, multicenter study in which 64 patients with witnessed cardiac arrest underwent therapeutic hypothermia. The results have not yet been published as a full paper. In this study, 60% of patients with ventricular tachycardia/ventricular fibrillation (VT/VF) had a good neurologic outcome (defined as return to their home situation with no or only minimal neurologic impairment). In addition, 50% of patients with an initial rhythm of asystole who reached the hospital alive also had a good neurologic outcome.

“We should lose the pessimism surrounding patients with witnessed cardiac arrest, because the good outcome rates can be better than 50% in this category of patients when hypothermia has been used,” commented Dr. Polderman. “We need to get the cardiologist to do the appropriate intervention, even when the patient is comatose. We need to promote bystander CPR, because the chances of this therapy helping the patient are much better if basic CPR has been performed.”

Some studies have also reported good outcome following therapeutic cooling in patients with severe TBI. Meta-analyses have reported a 22% to 48% reduction in the risk for adverse neurologic outcome in patients with severe TBI treated with therapeutic hypothermia, although not all these differences were statistically significant.

However, the treatment looks highly promising, according to Dr. Polderman. He pointed out for comparison that data on the use of barbiturates and mannitol do not show any benefit on neurologic outcome in patients with TBI.

Cooling in the Right Context
Although hypothermia has beneficial effects on neurologic outcome, “a treatment can only be effective if the other aspects of intensive care are good,” cautioned Dr. Polderman. Therefore, “context matters. It’s not just about cooling.”

When using hypothermia, temperature should be lowered rapidly, but rewarming should be done very slowly, noted Dr. Polderman. “If you do it rapidly, you could lose some or all of the protective effects of hypothermia,” he warned.

In addition, physicians should consider other aspects of ICU treatment, such as prevention of hypo- and hypercapnia, electrolyte disorders, hyperglycemia, and hypoglycemia. “All these things matter, and they may make all the difference,” he said. “Without getting that right, hypothermia can be an ineffective or even dangerous therapy.”

“The idea of context applies even more strongly to areas like severe TBI,” he asserted. “Speed and duration of cooling are important.” For patients with TBI who receive hypothermia, longer duration of cooling (ie, greater than 48 hours) and slow rewarming protocols are associated with better outcome. He noted that one way to determine the optimal duration of cooling in individual patients is to measure intracranial pressure. Intracranial pressure is both a marker of ongoing brain injury and a potential cause of additional injury.

“The use of hypothermia is not risk-free. There are severe side effects, which we should take into account, but the good news is that these can be fairly easily managed,” concluded Dr. Polderman.   

NASHVILLE—Therapeutic hypothermia is being used with increasing frequency to treat patients with neurologic injury from conditions such as stroke, cardiac arrest, and traumatic brain injury (TBI). “Induced hypothermia can sometimes be risky, but it’s potentially highly rewarding,” said Kees H. Polderman, MD, PhD, at the Society of Critical Care Medicine’s 38th Critical Care Congress. Effective use of hypothermia is strongly dependent on the quality of other aspects of ICU care; therefore, he recommended that clinicians give careful attention to all of these factors.

When interpreting findings from studies examining therapeutic hypothermia, “you should always look at where it’s being performed, the context in which this treatment is taking place, and what other aspects of care are similar to your own and which ones are different; then you can assess if you can reproduce those results in your own center, or if you need to adapt your policy a bit,” commented Dr. Polderman, Professor in Intensive Care Medicine at the Department of Critical Care, University of Pittsburgh Medical Center.

Goals of Therapeutic Hypothermia
Stroke, cardiac arrest, and, to a lesser extent, TBI are characterized by ischemia and reperfusion injury. After a period of ischemia, a series of destructive processes takes place in the injured cells of the brain. “The damage is ongoing while the patient is in your ICU or your emergency room,” said Dr. Polderman.

Therefore, the first goal of treatment with hypothermia is to try to limit this injury. “Hypothermia acts as a sort of blanket therapy,” he said. “It can interrupt every single one of these harmful processes, in contrast to many other therapies that we’ve tried in the past.”

Another goal is to treat brain edema, which may also play a role in some disease states—TBI being one example. For patients with brain edema, the approach to treatment is slightly different, requiring a longer period of cooling.

Controlling Brain Temperature
When using hypothermia for patients with neurologic injury, physicians should do their best to prevent fever, Dr. Polderman advised. “Most of our patients in the neurocritical care units develop fever at some point in their ICU stay. The more severe the injury, the more likely the chance that [the patient] will develop fever,” he said.

Fever is associated with longer length of stay, worse neurologic outcome, and higher mortality. In two studies involving patients with subarachnoid hemorrhage and intracerebral hemorrhage, researchers reported that even a minimal elevation in temperature to slightly greater than 37.5°C—not considered a real fever by some—had a significant adverse effect on outcome.

One explanation for this could be that brain temperature exceeds core temperature. “The destructive processes triggered by ischemia generate heat. Local brain edema makes it difficult to get rid of the excess heat, and this leads to overheating of the brain,” explained Dr. Polderman. “So fever after neurologic injury seems to be extremely harmful, and hypothermia seems to be really protective.”

Proven Efficacy
Three randomized controlled trials have assessed neurologic outcome in patients who underwent therapeutic hypothermia following witnessed cardiac arrest, with significant improvement seen in patients treated with hypothermia across all three studies, said Dr. Polderman. In addition, a number of nonrandomized studies have reported good outcomes following treatment with induced hypothermia.

Dr. Polderman and his colleagues conducted a prospective, multicenter study in which 64 patients with witnessed cardiac arrest underwent therapeutic hypothermia. The results have not yet been published as a full paper. In this study, 60% of patients with ventricular tachycardia/ventricular fibrillation (VT/VF) had a good neurologic outcome (defined as return to their home situation with no or only minimal neurologic impairment). In addition, 50% of patients with an initial rhythm of asystole who reached the hospital alive also had a good neurologic outcome.

“We should lose the pessimism surrounding patients with witnessed cardiac arrest, because the good outcome rates can be better than 50% in this category of patients when hypothermia has been used,” commented Dr. Polderman. “We need to get the cardiologist to do the appropriate intervention, even when the patient is comatose. We need to promote bystander CPR, because the chances of this therapy helping the patient are much better if basic CPR has been performed.”

Some studies have also reported good outcome following therapeutic cooling in patients with severe TBI. Meta-analyses have reported a 22% to 48% reduction in the risk for adverse neurologic outcome in patients with severe TBI treated with therapeutic hypothermia, although not all these differences were statistically significant.

However, the treatment looks highly promising, according to Dr. Polderman. He pointed out for comparison that data on the use of barbiturates and mannitol do not show any benefit on neurologic outcome in patients with TBI.

Cooling in the Right Context
Although hypothermia has beneficial effects on neurologic outcome, “a treatment can only be effective if the other aspects of intensive care are good,” cautioned Dr. Polderman. Therefore, “context matters. It’s not just about cooling.”

When using hypothermia, temperature should be lowered rapidly, but rewarming should be done very slowly, noted Dr. Polderman. “If you do it rapidly, you could lose some or all of the protective effects of hypothermia,” he warned.

In addition, physicians should consider other aspects of ICU treatment, such as prevention of hypo- and hypercapnia, electrolyte disorders, hyperglycemia, and hypoglycemia. “All these things matter, and they may make all the difference,” he said. “Without getting that right, hypothermia can be an ineffective or even dangerous therapy.”

“The idea of context applies even more strongly to areas like severe TBI,” he asserted. “Speed and duration of cooling are important.” For patients with TBI who receive hypothermia, longer duration of cooling (ie, greater than 48 hours) and slow rewarming protocols are associated with better outcome. He noted that one way to determine the optimal duration of cooling in individual patients is to measure intracranial pressure. Intracranial pressure is both a marker of ongoing brain injury and a potential cause of additional injury.

“The use of hypothermia is not risk-free. There are severe side effects, which we should take into account, but the good news is that these can be fairly easily managed,” concluded Dr. Polderman.