The American Heart Association cardiopulmonary resuscitation guidelines have been updated for 2015! There are some interesting changes to the guidelines that pharmacists should know about and I’ll summarize them for you in this episode.
Web-based guidelines with continuous updates
The Guidelines will transition from a 5-year cycle of periodic revisions and updates to a Web-based format that is continuously updated. The first release of the Web-based integrated Guidelines, now available online at ECCguidelines.heart.org is based on the comprehensive 2010 Guidelines plus the 2015 Guidelines Update. Moving forward, these Guidelines will be updated by using a continuous evidence evaluation process to facilitate more rapid translation of new scientific discoveries into daily patient care.
This is certainly an exciting change! I hope other organizations take note and do the same.
ILCOR adopted the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) process for evidence evaluation.
The 2015 AHA Guidelines Update for CPR and ECC contains 315 classified recommendations. There are 78 Class I recommendations (25%), 217 Class II recommendations (68%), and 20 Class III recommendations (7%). Overall, 3 (1%) are based on Level of Evidence (LOE) A, 50 (15%) are based on LOE B-R (randomized studies), 46 (15%) are based on LOE B-NR (nonrandomized studies), 145 (46%) are based on LOE C-LD (limited data), and 73 (23%) are based on LOE C-EO (consensus of expert opinion).
It is important to know the level of evidence behind each guideline recommendation before deciding on whether to apply the recommendation to your patient.
I think it is fascinating that the majority of the recommendations in these guidelines are level II or lower and are based on either limited data or concensus opinion.
Upper limit on rate of compressions
In adult victims of cardiac arrest, it is reasonable for rescuers to perform chest compressions at a rate of 100 to 120/min (Class IIa, LOE C-LD). The addition of an upper limit of compression rate is the result of 1 large registry study associating extremely rapid compression rates with inadequate compression depth.
I have yet to give chest compressions in a code (and I hope to keep it that way – there are always many people that respond!) but you can be sure this upper limit of compression rate will be in any recertification course.
Give epinephrine sooner
The recommendations for timing of epinephrine administration were updated and stratified based on the initial presenting rhythm, recognizing the potential difference in pathophysiologic disease. For those with a nonshockable rhythm, it may be reasonable to administer epinephrine as soon as feasible.
This appears to be building common sense into the guidelines, and that is always a good thing!
Vasopressin is gone…or is it?
Vasopressin was removed from the ACLS Cardiac Arrest Algorithm as a vasopressor therapy in recognition of equivalence of effect with other available interventions (eg, epinephrine). This modification valued the simplicity of approach toward cardiac arrest when 2 therapies were found to be equivalent.
With the recent price increase of vasopressin this is a very interesting change. Nothing has changed in terms of evidence to support vasopressin, it was removed purely to keep the algorithm simple. Very rarely is vasopressin requested at my institution to replace the first dose of epinephrine.
I estimate we have about $25,000 worth of vasopressin stocked in our code carts throughout my institution. This change in the guidelines should help free up some of the drug budget to spend on something more effective.
Vasopressin with steroids and epinephrine
The combination of intra-arrest vasopressin, epinephrine, and methylprednisolone and postarrest hydrocortisone as described by Mentzelopoulos et al may be considered; however, further studies are needed before the routine use of this therapeutic strategy can be recommended (Class IIb, LOE C-LD).
A pair of studies were published in 2009 & 2013 looking at vasopressin + epinephrine + methylprednisolone versus epinephrine + placebo given in cardiac arrest. Both studies had positive outcomes. The second study found significantly improved survival to discharge with good neurologic outcome compared with only epinephrine and placebo.
I found it puzzling – with two randomized controlled trials (albeit most of the patients in the 2013 study were at the same center as the 2009 one) why is this recommendation so weak and buried in the update? So I emailed the lead author of the studies, Dr. Spyros D. Mentzelopoulos, to ask his opinion.
I got a response within 8 hours. It never fails – every time I email a study author (each article has a correspondence email listed) I get a prompt response. I got this idea from my wife who is an elementary reading teacher. She will have her students write the author of a book and they always write back. Corresponding with authors of studies is so educational & effective I call it “PharmacyJoe-ism #18: For questions about green eggs and ham, email Dr. Suess.”
Here is my email to Dr. Spyros D. Mentzelopoulos:
I read your studies with great interest when they were published. I’m surprised given that you have 2 RCT supporting giving vasopressin+epinephrine+methylprednisolone that the updated ACLS guidelines do not include this as a stronger recommendation. Why do you think this is? Do you use the combination of medications in your study routinely in your hospital? Thank you for your great work!
In case you haven’t seen it yet, here is what they said:
In IHCA, the combination of intra-arrest vasopressin, epinephrine, and methylprednisolone and post-arrest hydrocortisone as described by Mentzelopoulos et al may be considered; however, further studies are needed before recommending the routine use of this therapeutic strategy (Class IIb, LOE C-LD).
Here is the response I received 8 hours later!
Thank you so much for your interest and positive comments on our work. Regarding critical long-term outcomes: The first randomized clinical trial (RCT) had favorable results on survival to hospital discharge and the second RCT had favorable results on survival to hospital discharge with good neurological recovery. These critical outcomes do not coincide; that is, they are not the same: survival to discharge does not necessarily mean leaving the hospital at a good functional status. Consequently, there has actually been 1 small favorable RCT showing better “survival to discharge” and 1 larger favorable RCT showing better “survival to discharge with good neurological (i.e. functional) outcome”.
These studies have been conducted within the Greek National Health System (NHS) and the generalizability of their results to other NHSs still remains to be shown – An important difference among NHSs across the world pertains to the efficacy of infection control measures, especially in the intensive care environment – More generally speaking, it is widely acceptable that differences in the quality of care (including postresuscitation care) can potentially impact patient outcomes. In addition, it should be noted that several critical care interventions such as Activated Protein C, Tight Glucose Control with Insulin, and Early Goal Directed Therapy initially supported by substantially larger studies were not subsequently validated by follow-up multicenter/multinational trials. Therefore, I would say that the AHA recommendation regarding the results of our studies is both fair and prudent. I would strongly support the conduct of a definitive multinational study on the vasopressin-steroids-epinephrine (VSE) combination; of course, I would expect/predict positive results.
In our hospital, we do apply the VSE protocol; nevertheless, lately, we have been facing a shortage in vasopressin supply secondary to the Economic Crisis-related Capital Controls. Even so, intensivists most frequently choose to prescribe stress dose hydrocortisone for postresuscitation shock.
Thank you again for your interest.
Spyros D. Mentzelopoulos, MD
Targeted temperature management
A high-quality randomized controlled trial did not identify any superiority of targeted temperature management at 36°C compared with management at 33°C. Excellent outcomes are possible when patients are actively managed at either temperature. All comatose (ie, lack of meaningful response to verbal commands) adult patients with ROSC after cardiac arrest should have targeted temperature management, with providers selecting and maintaining a constant temperature between 32°C and 36°C for at least 24 hours after achieving target temperature. It is also reasonable to actively prevent fever in comatose patients after targeted temperature management.
I’ll have to check with my cardiologists on this to see if we will change our temperature range. I believe we are still aiming for 33°C at my institution.
Naloxone added to Basic Life Support (BLS) interventions
For patients with known or suspected opioid addiction who have a definite pulse but no normal breathing or only gasping (ie, a respiratory arrest), in addition to providing standard BLS care, it is reasonable for appropriately trained BLS providers to administer intramuscular or intranasal naloxone (Class IIa, LOE C-LD). It is reasonable to provide opioid overdose response education with or without naloxone distribution to persons at risk for opioid overdose in any setting (Class IIa, LOE C-LD).
Naloxone in this context refers to use outside of the hospital. For naloxone dosing in the hospital, listen to episode 25.
Intravenous lipid emulsion (ILE) makes the cut!
Administration of ILE for the treatment of local anesthetic systemic toxicity (LAST), particularly from bupivacaine, is supported by extensive animal research and human case reports. In the 2015 Guidelines Update, this science was reviewed and a weak recommendation supporting use of ILE for treatment of LAST was reaffirmed. Since 2010, animal studies and human case reports have been published that examined the use of ILE for patients with other forms of drug toxicity, with mixed results. The 2015 Guidelines Update contains a new recommendation that ILE may be considered in patients with cardiac arrest due to drug toxicity other than LAST who are failing standard resuscitative measures.
Intravenous lipid emulsion definitely deserves to be a podcast topic on it’s own! I’m glad to see ILE make it into the guidelines. An emergency medicine physician I work with showed me a successful case study about ILE in overdose many years ago.
As a result, I had ILE placed in the automated dispensing cabinets in all the critical care and surgical areas. Wouldn’t you know it, on my day off there was a cardiac arrest in the preop area, 40 minutes after a ropivicaine nerve block was administered. The patient had VTach resistant to multiple shocks & amiodarone. ILE was given and within 1 minute the patient had return of spontaneous circulation. They were later discharged neurologically intact.
Update: Since this episode was published, a very detailed review of the VSE evidence was posted here. I recommend you check it out!
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.