ARTICLE IN BRIEF
Investigators reported that awakening after therapeutic hypothermia is usually evident within three days of cardiac arrest and not delayed compared with those who did not undergo the treatment.
Cardiac arrest patients who are treated with hypothermia tend to awaken within three days, timing similar to what is experienced by patients who do not get therapeutic hypothermia.
A new study from Mayo Clinic researchers adds some clarity to a debated issue — whether the use of hypothermia lengthens the time to awakening after cardiac arrest, in part because of the sedatives needed for the therapy.
Mayo researchers studied 227 cardiac arrest patients, 128 of whom were treated with induced hypothermia. While the study wasn't done to study the efficacy of hypothermia, the results confirm that the therapy works well.
“Median day of awakening was day two for both groups and most (91 percent hypothermic and 79 percent non-hypothermic) awakened within three days,” the researchers concluded in a report published in the Sept. 7 online edition of Neurology.
Jennifer E. Fugate, DO, a fellow in the Division of Critical Care Neurology at the Mayo Clinic in Rochester, MN, and colleagues found that a minority of cardiac arrest patients in both hypothermic and non-hypothermic groups may have delayed awakenings due to lingering sedation or critical systemic illness, but that hypothermia itself does not appear to be a major factor.
The study authors noted that the AAN practice parameter that is used to predict outcomes in survivors of cardiopulmonary arrest — published in Neurology in 2006 — was developed with data collected before the era of therapeutic hypothermia.
“The degree to which hypothermia influences the reliability of predictors has been studied with conflicting results,” the researchers wrote. “Two recent studies concluded that neurologic examination (the motor response in particular) after hypothermia may no longer reliably predict outcome. In contrast, in a large prospective study we found that in the absence of cofounders, the clinical examination retains its predictive value after hypothermia. Different use of sedative medication (more frequently used in hypothermia protocols) likely contributes to the discrepancy of findings regarding the reliability of clinical examination predictors.”
The researchers noted that because of “these inconsistent findings, some have suggested that those treated with hypothermia may take longer to ‘awaken’ and more provocatively have raised concern that life-sustaining treatments may be withdrawn prematurely in this population.”
They wrote that “further research with prospective, multicenter studies using well-defined prognostic protocols and strict reporting of the factors leading to WLST [withdrawal of life-sustaining treatments] are needed.”
The study included 227 survivors, 152 of them men, who were on average 62 years old. Of the 128 patients who received hypothermia therapy, 82 — or 64 percent — survived to discharge. Survival was considerably lower in the non-hypothermia group: Just 24 of 99 patients — 24 percent — made it to discharge. Of the hypothermia patients awho survived to discharge, 88 percent had a favorable functional outcome — a CPC score of at least 2 — compared to 67 percent of those who survived in the non-hypothermic group. In both groups, most patients awakened by the third day.
“While some patients in each group awakened after the fifth day, clinical examinations were confounded by complications of critical systemic illness and persistent pharmacological sedation,” the study authors noted. “This reinforces the importance of obtaining a reliable examination and excluding confounders of the clinical assessment in cardiac arrest survivors, regardless of the use of therapeutic hypothermia.”
The researchers acknowledged that their results did not square with some previous research, in particular a recent small study that found that most patients treated with hypothermia did not awaken until at least day seven after cardiac arrest. Dr. Fugate said that differences in sedation protocols from one hospital to the next may help explain the varied timing.
“Our institutional protocol uses relatively small doses of sedative medications during therapeutic hypothermia,” she said. Her team plans to do further research looking at longer-term cognitive outcomes in patients and sedative use and serum drug levels during and after induced hypothermia.
The study could provide some guidance for families who find themselves in the difficult position of deciding whether to continue or end treatment for someone who is comatose after suffering a major heart attack, said Gene Sung, MD, director of critical care and stroke at the University of Southern California. On the one hand, families want to have hope and make certain that doctors do everything possible to save their loved one's life. At the same time, they don't want to subject their loved one to the burden of futile therapy leading to permanent vegetative state.
“This study may help both clinicians and patient family members to make better and more efficient decisions for the patient,” said Dr. Sung, who was not involved with the study.
In an editorial accompanying the study, Andrea O. Rossetti, MD, of University Hospital (CHUV) in Lausanne, Switzerland, and Matthew A. Koenig, MD, of the John A. Burns School of Medicine in Honolulu, said the study results should be interpreted with caution.
“Hypothermia and non-hypothermia-treated patients were not randomized, and indeed represented different populations in terms of type and location of cardiac arrest and prognosis,” they wrote. “It is possible, for example, that some patients having a potentially less favorable prognosis ended up in the non-hypothermia protocol — and thus were less affected by sedation — while they would have needed a longer time to awaken in the other treatment group.”
They added that “disparities in sedation protocols at other centers and lingering concerns for delayed metabolism of sedative agents in the setting of hypothermia raise concerns about the generalizability of these findings.”
Julius Gene Latorre, MD, MPH, assistant professor of neurology at SUNY Upstate, told Neurology Today that the study results from the Mayo Clinic researchers underscore the benefits of hypothermia for cardiac arrest patients.
“Patient mortality is significantly lower in patients who received hypothermia,” he said, “and of survivors, more patients had a very good functional outcome.”
Dr. Latorre said his institution considers hypothermia to be “the standard of care,” but some hospitals have not embraced the therapy because “it takes a lot of infrastructure to implement,” including having trained personnel and the necessary equipment.
Dr. Latorre noted that making a decision on the prognosis of a patient following a severe heart attack is not always easy. “Families most of the time would like a definitive answer,” he said. “Unfortunately, most of the time we can't be definitive but we can give them a general idea of what's going on with the patient.”
Dr. Latorre said this latest finding that awakening time for hypothermia patients is not usually delayed should help doctors provide better information to families grappling with whether to continue or discontinue life support. “You want to honor the dignity of patients and make them comfortable in their last days. At the same time, you don't want to prematurely withdraw care if patients have a chance at good recovery.”
* Researchers reviewed the records of adult survivors of cardiac arrest and cardiopulmonary resuscitation who were admitted to St. Mary's Hospital in Rochester, MN, from June 2006 to December 2010.
* Patients with out-of-hospital ventricular fibrillation cardiac arrest were candidates for therapeutic hypothermia at the hospital, while patients with rhythms other than ventricular fibrillation or patients with in-hospital cardiac arrests were generally not candidates.
* The hospital used this hypothermia protocol: Sedation with a bolus of intravenous midazolam at 0.03 mg/kg followed by an infusion starting at 1 mg/hour. Analgesia was provided by an intravenous infusion of fentanyl of 25 mcg/hour, and paralysis with atracurium 0.4 mg/kg bolus followed by an initial infusion of 4 mcg/kg/minute.
* The researchers reviewed patient records for details on time to regaining consciousness, systemic complications, primary cause of mortality, and circumstances of withdrawing life-sustaining therapies.
* Patients were considered to have regained consciousness when they met both of these criteria: eyelids opened spontaneously or to voice; and patients followed commands or visually tracked moving objects. Results of somatosensory evoked potentials (SSEP), serum neuron specific enolase (NSE) measurements, and electroencephalogram (EEG) were recorded.
* A “poor prognosticator” was defined as any of the following: absent pupillary or corneal reflexes or absent or extensor motor response to noxious stimulation; myoclonic status epilepticus; absent N20 cortical responses measured with SSEP; NSE > 33 mg/mL; or EEG demonstrating status epilepticus or a nonreactive background. Survival and neurologic outcome according to the Glasgow-Pittsburgh Cerebral Performance Categories (CPC) Scale were assessed at hospital discharge.
Fugate JE, Wijdicks EFM, Rabinstein AA, et al. Does therapeutic hypothermia affect time to awakening in cardiac arrest survivors? Neurology 2011; E-pub 2011 Sept 7.
Rossetti AO, Koenig MA. Editorial: Prognostication after cardiac arrest: A tale of timing, confounders and self-fulfillment. Neurology 2011; E-pub 2011 Sept 7.
Wijdicks EFM, Hijdra A, Young GB, et al. Practice parameter: Prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review): Report of the Quality Standards Subcommittee of the American
Academy of Neurology. Neurology 2006; 67:203–210