Give It Some Time! Plug Pulled Too Soon in Hypothermia-Treated Cardiac-Arrest Patients

November 14, 2010

November 14, 2010 (Chicago, Illinois) — New data from multiple studies suggest that clinicians are pulling the plug too early in patients who suffer an out-of-hospital cardiac arrest, especially among patients treated with therapeutic hypothermia. In one study, investigators showed that arbitrarily withdrawing life support 72 hours after an out-of-hospital cardiac arrest prematurely "terminates life" in as much as 10% of patients.

"What is challenging for me, as a clinician who has spent 20 years trying to increase survival rates and to get people alive to the hospital, is to think that we are losing them because we don't know what to do with them," lead investigator Dr Keith Lurie (University of Minnesota, Minneapolis) told heartwire . "It suggests there is a huge opportunity to improve survival. I'm thinking, in absolute terms, of 5% to 10% for any patient who comes into the hospital with a pulse--they have a 5% to 10% greater likelihood of walking out intact if we give them time."

To withdraw support, or the idea of making a pronouncement about the degree of neurologic recovery on day three, needs to be revisited.

In addition to that report, Drs Shaker Eid and Nisha Chandra (John Hopkins University School of Medicine, Baltimore, MD) also provide data suggesting that care for cardiac-arrest patients treated with therapeutic hypothermia is withdrawn too soon. In that analysis, no cardiac-arrest patient who was treated with hypothermia was alert and conscious after 72 hours, whereas one-third of these patients had regained alertness by day seven.

"At this stage, the data are too premature to make any formal recommendations, but we do believe there needs to be a deliberate evaluation of these patients," Chandra told heartwire . "To withdraw support, or the idea of making a pronouncement about the degree of neurologic recovery on day three, needs to be revisited."

A Clinical Disagreement Leads to Study

The results of both investigations were presented this week here at the American Heart Association (AHA) 2010 Resuscitation Science Symposium. In the first trial, Lurie said the small retrospective study emerged from a disagreement about when to withdraw care for a comatose patient who had an out-of-hospital cardiac arrest. Another patient, not alert and unconscious 72 hours following cardiac arrest, was sent to a nursing home, only to wake up two weeks later "feeling fine," but confused about his surroundings.

With the lack of certitude about when to withdraw care and the disagreements that can arise among experienced clinicians, Lurie analyzed the existing data at his center, trying to determine whether clinicians might be giving up on patients too soon and to seek out clinical predictors that might be used to identify patients who wake up late, such as those who awoke 72 hours or more after rewarming from therapeutic hypothermia.

In total, 66 cardiac-arrest patients presented to the hospital between 2007 and 2009 and were cooled to 33ºC for 24 hours. Of these, six patients awoke after 72 hours and had "good neurological function" within 30 days of cardiac arrest. In a multivariate analysis examining predictors of late awakening, those who presented in ventricular fibrillation, those who received bystander-initiated cardiopulmonary resuscitation (CPR) and had witnessed arrests, and those with longer times from the 911 call to advanced life support were more likely to awaken after 72 hours.

To heartwire , Lurie said these late-awakening patients are "slipping through the survival cracks," and the study challenges clinicians by showing them that patients can wake up late, and they need to be more judicious in their recommendations and discussions with family members.

I think we ought to support them and we think we should tell the family there is still a possibility that they'll wake up.

In Minnesota, comatose patients are generally treated after hypothermia for at least 48 hours before any decision to withdraw supportive care. However, once patients are rewarmed to 37ºC, the decision to continue or withdraw support is not standardized and is typically made after consulting with family members. Usually, if a patient is younger, Lurie said he encouraged waiting at least 72 hours before making a decision. Based on this research, his recommendation is to wait at least six or seven days for all patients.

"By day seven, if the patient is still intubated and on a ventilator, that means they're probably not going to do well," said Lurie. "If they're extubated, and breathing on their own, but they just haven't woken up, then I think we ought to support them, and we think we should tell the family there is still a possibility that they'll wake up."

Hypothermia Changes the Game

In an interview with heartwire , Chandra explained that the three-day threshold is a holdover from another era, from a paper published 25 years ago showing that most patients who "wake up" will do so by 72 hours. However, as she and Eid pointed out, treatment following cardiac arrest, particularly the use of therapeutic hypothermia, has changed since then.

In their study, Eid, Chandra, and colleagues wanted to examine the prognosis for recovery in the hypothermia era. They evaluated 47 consecutive patients who survived out-of-hospital cardiac arrest and were admitted to an academic medical center. Of these, 15 patients received therapeutic hypothermia and were cooled to 33ºC, with seven of these individuals surviving until discharge. The remaining patients did not undergo hypothermia, and 13 of these 32 patients survived until discharge.

After 72 hours, 38.5% of patients treated without hypothermia were alert after resuscitation and had mild cognitive defects, as assessed by the cerebral performance category (CPC) score, whereas no cardiac-arrest patient cooled was alert or conscious after three days. By day seven, one-third of the hypothermia patients regained alertness, with mild cognitive deficits, while 83% were recovered by discharge. The average length of hospital stay was 13 days for those undergoing hypothermia compared with four days for those treated without cooling.

"Looking at their neurological recovery, we saw that in those patients who were treated with hypothermia, their recovery was actually delayed," Eid told heartwire . "So you'd have a small number that would have some type of neurologic recovery at day three, but most recover around five to seven days, mostly at seven days."

Dr. David Greer (Yale Medical School, New Haven) is senior author on new brain death guidelines released in June by the American Academy of Neurology.

Asked for comment on the Johns Hopkins study, he said he applauds the findings, "with great enthusiasm. It provides good evidence for what we already expected, that the usual timing for determining prognosis after cardiac arrest needs to be completely rethought when a patient has received therapeutic hypothermia."

In his own experience, he has seen a patient treated with hypothermia after cardiac arrest who woke after 13 days and is now living independently.

"Many of the studies to date of comatose patients have been biased by early withdrawal of care, regardless of whether the patients underwent therapeutic hypothermia or not," he added. "Physicians, and neurologists in particular, need to be extremely diligent in using all of the tools available to make an accurate prognosis, including the use of neuroimaging ([magnetic resonance imaging] and [computed tomography] scan) and electrophysiology (evoked potentials and [electroencephalography]) when assessing a cardiac arrest patient for prognosis. And the most important rule is, when in doubt, give more time!"

The use of therapeutic hypothermia for unconscious patients who have been successfully resuscitated from out-of-hospital cardiac arrest has been endorsed by the AHA since 2003. Collectively, said Chandra, the data presented this week are gratifying in that they all show similar results--hypothermia patients take longer to wake up--but are also concerning, because it means clinicians have been pulling the plug too soon. A third study, also presented during the Resuscitation Science Symposium by Dr Kyle McCarty (Maricopa Medical Center, Phoenix, AZ), suggested that care is withdrawn too early in cardiac-arrest patients who underwent therapeutic hypothermia. In that trial, care was withdrawn in 33% of patients within 24 hours and in 30% of patients within 25 hours to 72 hours.

Lurie, Eid, and Chandra report no conflicts of interest. Dr. Greer receives funding from Boehringer Ingelheim, reports royalties from the publication of Acute Ischemic Stroke: An Evidence-Based Approach, and has served as a consultant in a medicolegal case.

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