Putting Therapeutic Hypothermia into Practice
Abstract & Commentary
By Saadia R. Akhtar, MD, MSc, Idaho Pulmonary Associates, Boise, is Associate Editor for Critical Care Alert.
Dr. Akhtar does research for Eli Lilly.
Synopsis: This retrospective 'real-life' single-center study found that therapeutic hypothermia could be readily implemented and that it improved outcomes in patients with out-of-hospital cardiac arrest.
Source: Oddo M, et al. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med. 2006;34:1865-1873.
Previous large, randomized studies have demonstrated improved neurological outcome in comatose patients with out-of-hospital cardiac arrest due to ventricular fibrillation (VF) who are managed with therapeutic hypothermia (TH): those with other arrhythmias or shock were excluded.1,2 General acceptance and implementation of TH however have been slow to occur.3 Oddo et al performed a retrospective, single-center trial to assess ease of implementation of TH and its impact on outcomes in patients with out-of-hospital cardiac arrest of all etiologies. At a Swiss medical intensive care unit, consecutive patients with coma after out-of-hospital cardiac arrest were enrolled over an approximately 2-year period during which TH was being used: data were also collected on a similar number of historical controls. Standard resuscitation and care were provided to all patients. TH consisted of external cooling (ice bags and cooling mattress, started in the emergency department) to 33° for 24 hours, followed by passive rewarming. Outcome was determined by blinded review of patients' neurological examination at the time of discharge. 'Good' outcome was defined as 1 or 2 on the Glasgow-Pittsburgh Cerebral Performance categories: 1 is total recovery and 2 is moderate disability but able to work part-time and be independent in activities of daily living. Standard statistical methods were used.
The study included 109 patients, 55 treated with TH and 54 historical controls. The groups were similar in terms of demographics, comorbidities, time from collapse to return of pulse, and initial arterial pH. A similar number of patients in each group had an initial rhythm other than VF: these patients had longer time to return of pulse, lower initial pH, and more shock. Goal temperature of 33° was achieved in a median time of 5 hours, and this time interval decreased with experience. There was no relationship between time-to-goal temperature and outcome. Of the patients with cardiac arrest due to VF, good outcome was noted in 55.8% of those managed with TH vs 25.6% of controls. The numbers of patients with other initial arrhythmias were small and their outcomes extremely poor (mortality > 80%) thus it was difficult to comment on impact of TH. In contrast, those patients with shock at presentation also had high mortality.
TH did appear to improve outcomes compared to standard care alone. In comparing the treatment groups, the authors noted that patients receiving TH had greater fluid resuscitation and use of vasopressors and higher mean arterial pressures. Multivariate analysis using these and other predictors defined a priori revealed that these differences did not appear to account for the improved outcomes in the TH group. Only time to return of spontaneous circulation (< 30 minutes) was significant. Finally, incidence of infections or new arrhythmias was no different between the 2 groups.
Oddo et al's work provides further support for what has thus far been published about TH in out-of-hospital cardiac arrest. That is, TH is an effective means of significantly improving neurological outcome in patients who suffer out-of-hospital cardiac arrest due to VF.1,2 This study shows that TH can be applied safely to all patients (rather than just to a specially selected, screened population as was done in the larger randomized trials). Using simple and universally available methods of external cooling, goal temperatures were able to be achieved in a short period of time (≤ 5 hours) and maintained for 24 hours: we see that this is something any hospital could do.
The authors observed rates of improved outcomes with TH that were similar to those in previously published large randomized trials. (There was an approximately 2-fold difference between the TH group and the control group.) As in prior studies, the time to return of spontaneous circulation related to outcome even in those patients receiving TH. These authors added to our knowledge by observing the impact of TH on patient populations excluded from prior large studies of TH: they demonstrated that TH may be beneficial in patients with persistent shock after cardiac arrest. Their results also suggest that TH may not add much to the care of those with cardiac arrest due to arrhythmias other than VF. This is at least partly because those patients have extremely high mortality: perhaps studies to assess earlier interventions (eg, cooling in the field) in these populations are warranted.
This study has several limitations which the authors acknowledge. It is a single-center study with somewhat small numbers and this may limit its generalizability. It is non-randomized and retrospective and it relies on historical controls. All of these factors make it likely that some bias is introduced and that there may be significant unmeasured differences between the 2 comparison groups. Thus, although the study's findings offer limited support for the already-available strong evidence for TH and suggest new hypotheses for areas not well-investigated (such as TH for out-of-hospital cardiac arrest with prolonged shock), they do not in themselves provide substantial new scientific information.
I suggest to you that the importance of this study should not be measured by its ability or inability to prove the benefits of TH: that has already been done by prior large randomized trials.1,2 Rather, this work is valuable because it clearly and completely meets its primary objective: it demonstrates that what was accomplished in large, randomized clinical trials can be readily reproduced in our own institutions. If we can absorb this and follow Oddo et al's example, we will significantly improve outcomes for our patients with out-of-hospital cardiac arrest.
- The Hypothermia After Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002; 346:549-556; Erratum in: N Engl J Med. 2002;346:1756.
- Bernard SA, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002;346:557-563.
- Merchant RM, et al. Therapeutic hypothermia utilization among physicians after resuscitation from cardiac arrest. Crit Care Med. 2006;34:1935-1940.