Here’s the scene:
A 60 year-old man with a recent NSTEMI is admitted for pneumonia. The nurse suddenly calls you to the bedside, because the patient is unresponsive. He has no pulse, so you start chest compressions. Initial rhythm is PEA so you give epinephrine and continue compressions as the patient is successfully intubated. The second rhythm shows ventricular fibrillation (VF). You think to yourself, “Great this guy might actually have a chance!” You’re feeling pretty good as you administer a shock and then resume compressions. It’s time for the next rhythm and pulse check, and the rhythm is still VF. You shock again, resume CPR, give epinephrine, and ask the nurse to pull up amiodarone 300mg as you anxiously await the next check. Rhythm is still VF. You give another shock, resume CPR, and give your first bolus of amiodarone. After yet another shock and CPR, the VF persists. You give 150mg of amiodarone and then later another shock, but still, VF. You think you’re pretty clever and you pull up lidocaine.
Quick pause: Is there any literature comparing lidocaine to amiodarone for VF?
In 2002 Dorian et al published a double-blinded, randomized, controlled trial of 347 patients comparing lidocaine and amiodarone for resistant VF in out-of-hospital cardiac arrest. Of those treated with amiodarone 22.8% survived to hospital ADMISSION compared to 12% of those treated with lidocaine (P=0.009; odds ratio, 2.17; 95 percent confidence interval, 1.21 to 3.83) (1). This “ALIVE” trial was the study that first began all the hype about amiodarone for VT/VF arrest.
However, in 2016, Kudenchuk et al. performed a double-blinded, randomized, controlled trial of 3026 patients with initial rhythms of VT/VF to receive amiodarone, lidocaine or placebo and found that 24.4%, 23.7%, and 21.0%, respectively, survived to hospital DISCHARGE. Neither drug had greater rates of favorable neurologic outcome compared to each other or placebo!! (2)
Back to the case… so you recall lidocaine may be just as ineffective as amiodarone, but you reason that those pre-hospital studies may not apply to your patient. Andddd the Kudenchuk study additionally reported that patients with WITNESSED arrests had better survival when treated with either drug compared to placebo (28% vs. 23%) (2). You figure that because this was a witnessed arrest, there may be actual benefit to giving meds. So you administer lidocaine 1mg/kg and shock again, but the patient continues to have VF. You defibrillate again and give more lidocaine.
You’re starting to feel less clever until you remember that magnesium is a miracle drug! What if this is Torsades? You give magnesium. No response.
Side note: Hassan et al. performed a double blind, placebo controlled trial comparing magnesium (2-4mg) administration to patients with refractory VF and found no increase in ROSC or survival to hospital discharge compared to placebo (3). Allegra et al. also did a placebo controlled RCT comparing 2g magnesium sulfate versus placebo and also found no benefit in terms of ROSC or survival to hospital admission or discharge (4).
You’re starting to get anxious. This guy is still in VF. Are there any other drugs in your back pocket?
Esmo who? Esmolol!
Driver et al. performed a retrospective study in 2014 analyzing 25 patients with cardiac arrest with initial VT/VF rhythms, 9 of whom received esmolol. They found that significantly more patients in the esmolol group (50%) survived to hospital discharge compared to those who did not receive esmolol (16%); and 50% in the esmolol group compared to 11% in the “no esmolol group” survived to discharge with a favorable neurologic outcome (5).
EM cardiology expert Dr. Steve Smith states that esmolol or beta-blockade can result in less electrical instability. He argues that relaxing the LV and mitral stenosis (which are both negatively affected by epinephrine) may actually lead to increased LV filling and outflow, and as a result, increased inotropy (6).
You’re waiting for esmolol to come from the pharmacy, and you’re running out of ideas. You’ve shocked this guy 4-5 times and he still has VF and occasionally what looks like pulseless VT. Do you just keep shocking this guy?!
Answer: = Yes.. and maybe even give a double shock. DOUBLE SHOCK????
Hoch et al. performed a retrospective review of 2990 patients who had VF during electrophysiologic studies. Of those patients, 5 had refractory VF and underwent double sequential shocks 0.5-4.5 seconds apart by means of two defibrillators each with separate pairs of electrodes. All of them achieved ROSC (7).
However, Cabanas et al. performed a retrospective review of 10 patients who underwent double sequential external defibrillation (DSED) in the pre-hospital setting and found less success. They evaluated patients with refractory VF (defined as more than 5 defibrillations) who then had a second set of pads placed and received 2 simultaneous shocks. They found VF broke in 70%, but only 30% had ROSC and no patients survived to discharge (8).
But there may stil be hope for our double shock! This year (2016), Merlin et al. performed another retrospective case series of patients who received double simultaneous defibrillation (DSD). They placed one set of pads in the anterior-posterior position and an additional set in the anterior-lateral position. They analyzed 7 patients who had an average of 5 shocks prior to DSD and a mean of 2 DSD shocks each and found VF converted in 5 patients (57%). Four patients (43%) survived to hospital admission and 3 patients survived to discharge with minimal or no neurologic deficits (9).
What does the future look like?
What if we could oxygenate and remove carbon dioxide from the blood without doing CPR and without ROSC? Wait, we can! Extracorporeal membrane oxygenation ECMO!
But is it useful in our patient with refractory VF?
More prospective studies are definitely needed, but it looks like the answer is YES:
In 2015, Siao et al. published an ED based retrospective review of 60 patients with refractory VF and compared clinical outcomes of those who received traditional CPR with medications versus those who received extracorporeal CPR (E-CPR). Refractory VF was defined as ventricular fibrillation resistant to at least three defibrillations, 3 mg of epinephrine, 300 mg of amiodarone, and no ROSC achieved after CPR for more than 10 min. They found that CPR was much longer for those placed on ECMO (69.90 ± 49.6 min vs 34.3 ± 17.7 min, p = 0.0001), but that they also had much higher sustained rates of ROSC (95.0 vs 47.5%). More importantly, they had much higher rates of good neurologic function at discharge (40 vs. 7.5%). Survival one year after discharge was 50% in the E-CPR group vs. 20% in the traditional CPR group (10).
Also in 2015, The Minnesota Resuscitation Consortium implemented a protocol for patients with out-of-hospital refractory VF/VT arrest. In the first 3 months, 18 patients met criteria. Of these, 83% were immediately placed on ECMO and 67% sent for emergent percutaneous coronary intervention. Fifty five percent of patients survived to hospital discharge with 50% (9 patients) achieving good neurologic function! (11).
Conclusions: It takes longer to perform and requires resources, but ECMO may bridge the patient until he can undergo PCI. From these two very small and very recent studies, it appears that survival to hospital discharge with good neurologic function for patients undergoing E-CPR is significantly higher (40 – 50%) than refractory VF patients receiving only traditional CPR (5.6% reported in 2006) (12).
TAKE HOME POINTS:
- Lidocaine and amiodarone have not been shown to be superior to placebo, but keep in mind that these studies were in pre-hospital arrests. There may be a benefit for monitored inpatient arrests, where they are discovered early and defibrillation/CPR can be initiated immediately.
- I love magnesium, and it’ll never hurt to give it, but there’s also no data to support its use for our VF storm patients.
- Esmolol seems counterintuitive in a code situation, but it may combat some of epi’s negative effects. And if you’ve already shocked 5 times and exhausted your other meds which studies don’t support, why not give it a try? Esmolol was given as a loading dose of 500 mcg/kg, followed by infusions of 0, 50, or 100 mcg/kg/min.
- If all else fails, give a double shock.. twice.
- The future is now. If you want your patient to walk out of the hospital, get them on ECMO and open up those coronaries.
- Dorian P, et al. Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation [published erratum appears in N Engl J Med 2002;347(12):955]. N Engl J Med 2002;346(12):884–90.
- Kudenchuk PJ, et al.Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. N Engl J Med. 2016 May 5; 374(18):1711-22. Epub 2016 Apr 4.
- Hassan et al. A randomised trial to investigate the efficacy of magnesium sulphate for refractory ventricular fibrillation. Emerg Med J.2002 Jan;19(1):57-62.
- Allegra, J et al. Magnesium sulfate in the treatment of refractory ventricular fibrillation in the prehospital setting. Resuscitation.2001 Jun;49(3):245-9.
- Driver et al. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation.2014 Oct;85(10):1337-41. doi: 10.1016/j.resuscitation.2014.06.032. Epub 2014 Jul 14.
- Smith, S. (2013, April 6). 68 minutes with chest compressions, full recovery. Plus recommendations from a 5-member panel on cardiac arrest. [Web log post] Retrieved from http://hqmeded-ecg.blogspot.com/2013/04/68-minutes-with-chest-compressions-full.html
- Hoch DH et al. Double Sequential External Shocks for Refractory Ventricular fibrillation. JACC 1994; 23: 1141 – 5.
- Cabanas, JG, et al. Double Sequential External Defibrillation in Out-of-Hospital Refractory Ventricular Fibrillation: A Report of Ten Cases. Prehosp Emerg Care.2015 January-March;19(1):126-130. Epub 2014 Sep 22.
- Merlin et al. A Case Series of Double Sequence Defibrillation. Prehosp Emerg Care.2016 Jul-Aug;20(4):550-3. doi: 10.3109/10903127.2015.1128026. Epub 2016 Feb 5.
- Siao et. al. Managing cardiac arrest with refractory ventricular fibrillation in the emergency department: Conventional cardiopulmonary resuscitation versus extracorporeal cardiopulmonary resuscitation. Resuscitation.2015 Jul;92:70-6. doi: 10.1016/j.resuscitation.2015.04.016. Epub 2015 Apr 29.
- Yannopoulos, D. et al. Minnesota Resuscitation Consortium’s Advanced Perfusion and Reperfusion Cardiac Life Support Strategy for Out-of-HospitalRefractoryVentricular Fibrillation. J Am Heart Assoc. 2016 Jun 13;5(6). pii: e003732. doi: 10.1161/JAHA.116.003732.
- Sakai, T., Iwami, T., Tasaki, O. et al. Incidence and outcomes of out-of-hospital cardiac arrest with shock-resistant ventricular fibrillation: data from a large population-based cohort. Resuscitation. 2010; 81: 956–961