Highlights:
Introduction
The Review
What It Means for You
Introduction
You respond to a report of an unconscious person in the front yard of a home several blocks away. After a short response interval, you arrive on the scene to find bystanders performing cardiopulmonary resuscitation on a man lying in the grass. One of the bystanders says that Mr. Burks was mowing the yard, turned off the mower, and was walking back to the porch when he collapsed. After quickly verifying pulselessness, firefighters take over CPR.
Your partner quickly attaches the monitor/defibrillator and discovers ventricular fibrillation. After two-minutes of high quality CPR, you charge the defibrillator to 150-joules, deliver a countershock, and direct the firefighters to resume CPR.
Without interrupting chest compressions, your partner easily inserts a supraglottic airway while you establish IV access. You finish administering 1-milligram of epinephrine as the two-minute cycle of CPR ends. Mr. Burks’ electrocardiogram continues to display VF, you deliver an additional 150-joule countershock, and the firefighters resume chest compressions.
During the next two-minute period of CPR, your partner administers 300-mg amiodarone. As the period expires, the patient’s ECG continues to show VF and you deliver a third 150-joule countershock followed immediately by chest compressions.
At the end of the next two-minute period of CPR, the ECG shows asystole, which you verify in more than one lead. The resuscitation attempt continues on scene for an additional 20 minutes with no change in the patient’s condition. At that point, Mr. Burks meets the termination of resuscitation criteria established by your protocol.
Later in the day, you and the other responders discuss the call. Your partner says the last department she worked for used escalating energy doses for refractory VF patients. She wonders if Mr. Burks’ outcome would have been different had the team delivered higher energy doses for the second and third shocks.
The Review
Utilizing three emergency medical service systems in Canada, serving a population of approximately 3.2 million people, researchers examined the electrical, clinical, and adverse effects that delivery of fixed or escalating biphasic energy doses from an automated external defibrillator have on out-of-hospital patients suffering from cardiac arrest (Stiell, 2007).
During the investigation, the researchers hypothesized that patients requiring more than one defibrillation attempt would have higher conversion rates if rescuers increased the energy level with each shock.
During the planning stage of this investigation, researchers agreed on a triple-blinding procedure, meaning that no one directly involved with the study (patients, health care providers, or researchers) knew which patient received which therapy.
If the researchers had not designed the study this way, EMS personnel would know which AEDs delivered fixed energies and which ones delivered escalating energies.
With that knowledge, firefighters and medics could unintentionally develop a performance bias for one group of patients, thereby altering the outcome of the investigation.
Likewise, emergency department staff might treat one group differently because of preconceived attitudes about how well one defibrillation strategy works. Blinding places everyone in the dark (except for the independent safety monitoring committee assigned to the trial) and reduces the possibility of unregulated influence.
For the study, researchers used biphasic waveform AEDs programmed to deliver one of two energy configurations. The fixed lower-energy configuration delivered a 150-joule charge for each defibrillation attempt. The escalating-energy configuration delivered a 200-joule initial shock, a 300-joule second shock, and a 360-joule shock for all subsequent defibrillation attempts.
Researchers deactivated the AED energy display function to prevent EMS personnel from seeing the delivered energy level. A randomization process selected patients to receive either the fixed-energy shocks or the escalating energy shocks. After each use, EMS supervisors blindly and randomly reset the AED for the next patient encounter, thereby maintaining the integrity of the selection process.
The population sample for this study included all adult patients who required a defibrillation attempt after suffering a bystander or EMS-witnessed cardiac arrest in the out-of-hospital environment. This includes patients who presented in non-shockable rhythms but later required a shock during the resuscitation attempt.
The researchers further restricted inclusion to only those patients receiving shocks by first responders with one of the study AEDs. The researchers excluded:
• Pediatric patients — defined as less than 8 years of age
• Patients with a documented terminal illness
• Anyone without basic CPR for a period of 10 minutes
• Patients suffering cardiac arrest secondary to acute trauma or exsanguination
• Patients suffering cardiac arrest as an inpatient at an acute care hospital
• Patients receiving an initial defibrillation attempt by a paramedic equipped with ALS and a conventional monitor/defibrillator.
As the primary outcome measure, the research team chose successful conversion, which they defined as the establishment of an organized rhythm within 60 seconds of the termination of VF.
The team predefined an organized rhythm as having at least two QRS complexes separated by no more than five seconds. In addition, the researchers chose a number of secondary outcome measures including:
• Termination of VF — defined as the absence of re-fibrillation for at least five seconds regardless of any resulting rhythm
• Return of spontaneous circulation (ROSC), regardless of the duration
• ROSC with continuous pulse and measurable blood pressure for at least one hour
• Survival to 24 hours
• Survival to hospital discharge
• Functional status of those who survived to hospital discharge.
The team was also interested in determining if either defibrillation strategy was associated with an increase in myocardial damage. To determine this, the researchers measured:
• ECG evidence of infarction or ischemia within the first six hours following defibrillation
• Cardiac enzyme levels (creatinine kinase and troponin) within the first six hours
• Left ventricular ejection fraction (percentage of blood pumped out of a filled left ventricle during a single contraction [Grogan, 2008]) below a predetermined threshold measured at hospital admission.
Over a three-and a-half year period, 256 patients received at least one shock using a study AED. Of those, researchers excluded 35 cases because they did not meet the inclusion criteria, including 26 cases where the AED delivered a shock to an asystolic patient. The researchers theorize that motion artifact or ongoing chest compressions could have caused these inappropriate shocks.
The researchers set the criteria for statistical significance, or p value, at 0.05. A p value, also called the alpha, represents the probability of making an error in the data interpretation.
After measuring a single characteristic in each group, analysts calculate the p value for that characteristic and compare it to their predetermined critical value. If the calculated p value is less than the predetermined value (0.05, in this case), the researcher considers the difference statistically significant with less than 5 percent chance of a data interpretation error. If the p value is greater than 0.05, the differences are not statistically significant and could be the result of chance alone.
The randomization process subdivided the remaining 221 patients into two categories, those who received a single shock (n = 115) and those who received more than one shock (n = 106).
There were no significant differences between the groups with respect to demographic or clinical characteristics. Forty-eight percent required more than one defibrillation attempt either because the first attempt failed to convert the VF or because of subsequent refibrillation.
Since the primary outcome measure for this study (higher conversion rates with increased energy levels) was electrical in nature, the researchers compared the shocks between the two groups instead of comparing the patients.
With this perspective, the 221 patients received 498 shocks. Of those, 114 patients received 292 shocks from the fixed energy AEDs (150-joule) and 107 patients received 206 shocks from the escalating energy AEDs (200-joule, 300-joule, 360-joule).
Researchers found that the escalating energy strategy did produce statistically improved conversion rates in patients requiring more than one shock (fixed energy, 24.7 percent; escalating energy, 36.6 percent; p = 0.035; absolute difference, 11.9 percent; 95 percent CI, 1.2 to 24.4) (Table 1).
The escalating energy strategy also produced statistically significant improvement in the secondary electrical outcome measure, termination of VF (fixed energy, 71.2 percent; escalating energy, 82.5 percent; p = 0.027; absolute difference, 11.3 percent; 95 percent CI, 1.6 to 20.9).
Table 1 | Fixed Energy | Escalating Energy | p value |
Successful conversion |
|
|
|
Shocks in multishock patients | 24.7% | 36.6% | 0.035 |
First shocks only | 38.4% | 36.7% | 0.92 |
Termination of VF |
|
|
|
Shocks in multishock patients | 71.2% | 82.5% | 0.027 |
First shocks only | 86.8% | 88.8% | 0.81 |
Neither defibrillation strategy resulted in statistically improved ROSC, survival to one hour, survival to 24 hours, survival to hospital discharge, or median Cerebral Performance Category scores. There was also no difference in adverse events between the two groups.
What it means for you
Due to the lack of compelling evidence, the 2005 American Heart Association ACLS Guidelines failed to make a definitive energy level recommendation for first and subsequent defibrillation attempts with biphasic AEDs. This study continues to try to identify an optimal defibrillation strategy.
During this investigation, the researchers categorized outcomes as being either electrical or clinical in nature. The electrical outcomes demonstrated that for patients requiring more than one defibrillation attempt, increasing the energy levels for second and third shock delivery resulted in higher conversion rates. Unfortunately, these conversion rates did not translate into improved clinical outcomes, such as survival.
However, clinical benefit may actually exist in spite of the results, depending on the study design. Competent researchers attempt to answer one question at a time — this is the reason for a study hypothesis and a primary outcome measure.
This one question determines all of the research methodology, e.g., inclusion and exclusion criteria, sample size, and the specific statistical test used in the analysis. Researchers often measure additional characteristics or secondary outcomes during the data collection process in an attempt to learn more about the subject. Unfortunately, because these additional outcomes are not the primary focus of the research, they may not have sufficient power to detect differences.
In this case, the researchers designed the study to address electrical outcome, i.e., arrhythmia conversion rates following fixed or increasing energy level countershocks.
The researchers arbitrarily chose a sample size of 200 patients, as they believed it would provide reasonable power to detect electrical outcome events but not clinical outcome events. In fact, to detect a 50 percent increase in survival, the researchers estimated that they would need 10 times as many patients as they had.
Another limitation of this study is in the inherent difficulty of using clinical outcome measures for cardiac arrest research. The average time from call received until the patient arrived at the hospital was approximately 42 minutes.
The average time that the rescue team used the AED before switching to a manual defibrillator was about four minutes, or about one-tenth of the total out-of-hospital interval.
Clearly, there are many opportunities during the resuscitation attempt for health care providers to perform a host of other interventions that could influence the survival of patients suffering a cardiac arrest. The researchers did measure the frequency of some of these interventions, like intubation and drug administration and found both groups to be similar.
However, the researchers did not measure the quality of chest compressions or other variables in the mechanics of CPR. One could assume that the randomization process helps to evenly distribute any variability in CPR technique, but without measurement, one can never be sure. Attempting to prove a cause and effect relationship between defibrillation energy levels and survival is extremely difficult, if not impossible.
In the scenario presented at the beginning of this review, employing an escalating energy strategy may have resulted in earlier conversion of the patient’s VF.
Although one may argue that conversion must occur before there can be ROSC and improved survival, achieving the former does not ensure the later. Because of that, it is not unreasonable for the department to continue to use a fixed energy delivery strategy for patients with refractory VF.
References
American Heart Association. (2005). 2005 AHA guidelines for CPR and ECC, Part 5: electrical therapies: automated external defibrillators, defibrillation, cardioversion, and pacing. Circulation, 112, IV-35-IV-46. doi: 10.1161/CIRCULATIONAHA.105.166554
Grogan, M. (2008). Ejection fraction: What does it measure. Retrieved from www.mayoclinic.com/health/ejection-fraction/AN00360
Stiell, I. G., Walker, R. G., Nesbitt, L. P., Chapman, F. W., Cousineau, D., Christenson, J., Bradford, P., Sookram, S., Berringer, R., Lank, P., & Wells, G. A. (2007). BIPHASIC Trial: A randomized comparison of fixed lower versus escalating higher energy levels for defibrillation in out-of-hospital cardiac arrest. Circulation, 115, 1511-1517. doi: 10.1161/CIRCULATIONAHA.106.648204
The author has no financial interest, arrangement, or direct affiliation with any corporation that has a direct interest in the subject matter of this presentation, including manufacturer(s) of any products or provider(s) of services mentioned.
