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Without evidence of benefit, an intervention should not be presumed to be beneficial or safe.

- Rogue Medic

The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia

Wed, 17 Aug 2016 13:30:50 -0400 by
ResearchBlogging.org
 

This is a very interesting trial that may surprise the many outspoken amiodarone advocates, but it should not surprise anyone who pays attention to research.

ALPS showed that we should stop giving amiodarone for unwitnessed shockable cardiac arrest. The lead researcher is still trying to spin amiodarone for witnessed shockable cardiac arrest, even though the results do not show improvement in the one outcome that matters – leaving the hospital with a brain that still works.[1],[2],[3]

There is an excellent discussion of the study on the podcast by Dr. Salim Rezaie and Dr. Anand Swaminathan REBELCast: The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia.

One problem with the study that they do not address on the podcast is that the patients in the study appear to have had time to watch Casablanca before treatment started. Here’s looking at you, while we’re waiting, kid. This is apparently unintentional one way of doing a placebo washout. If we wait long enough . . . .
 

Time from arrival to start of infusion was 87 ± 21 min for procainamide and 115 ± 36 min for amiodarone patients (P = 0.58).[4]

 

If nothing else, this demonstrates how little we need to worry about immediately pushing drugs for stable monomorphic VT (V Tach or Ventricular Tachycardia). Should we expect much from antiarrhythmic treatment?

Research shows that for stable monomorphic VT (V Tach or Ventricular Tachycardia) amiodarone is not very likely to be followed by an improvement. Only 29%[5] or only 25%[6] or only 15% within 20 minutes, but if we don’t mind waiting an hour it can be as much as 29%.[7] For those of you who are not good at math, that means amiodarone is about the same as doing nothing, only it comes in a syringe. Even though these poor outcomes ignore the side effects, they are the best evidence in favor of amiodarone, so what Kool-Aid are the advocates drinking?

Adenosine, yes adenosine the SVT (SupraVentricular Tachycardia) drug, appears to be more effective at treating ventricular tachycardia than amiodarone – and adenosine is faster and safer than amiodarone.[8]

What if the patient becomes unstable? First start an IV (IntraVenous) line. Then sedate the patient. Then apply defibrillator pads. After the patient is adequately sedated, then cardiovert. We do not need the pads on the patient first. If it takes a while to put the pads on, that is a problem with the ability of the doctors and nurses, not a medical problem.

It does not appear as if any patient received amiodarone or procainamide until after waiting in the ED (Emergency Department) for over an hour. Were some patients cardioverted in well under an hour? Probably. The important consideration is that the doctors and nurses be able to apply the defibrillator pads properly and quickly and deliver a synchronized cardioversion in less than a minute. If the patient has not yet been sedated, the cardioversion should be delayed until after the patient is adequately sedated, so the intervention that depends most on time is the sedation of the patient.
 

VT + Amiodarone Cardioversion
 

Is there a better treatment than amiodarone? Sedate the patient before the patient becomes unstable, then cardiovert. How do the MACEs (Major Adverse Cardiac Events) compare with sedation and cardioversion vs. antiarrhythmic treatment.
 

5.4 Proarrhythmia
Amiodarone may cause a worsening of existing arrhythmias or precipitate a new arrhythmia. Proarrhythmia, primarily torsade de pointes (TdP), has been associated with prolongation, by intravenous amiodarone, of the QTc interval to 500 ms or greater. Although QTc prolongation occurred frequently in patients receiving intravenous amiodarone, TdP or new-onset VF occurred infrequently (less than 2%). Monitor patients for QTc prolongation during infusion with amiodarone. Reserve the combination of amiodarone with other antiarrhythmic therapies that prolong the QTc to patients with life-threatening ventricular arrhythmias who are incompletely responsive to a single agent.[9]

 

All antiarrhythmic drugs can cause arrhythmias. In the absence of information about a specific problem that is best addressed by a specific drug (amiodarone is the opposite of specific), we should avoid treatments that have such a high potential for harm.

Amiodarone doesn’t even do a good job of preventing arrhythmias.
 

Intravenous amiodarone did not prevent induction of sustained ventricular tachycardia in any of five patients inducible at baseline. Of six patients with non-sustained ventricular tachycardia, five had sustained ventricular tachycardia or fibrillation induced after amiodarone infusion.[10]

 

Is anything worse than amiodarone? Even epinephrine, yes epinephrine the inadequately tested cardiac arrest drug, has been followed by improved outcomes from V Tach after amiodarone failed.[11]
 

What is best for the patient?

Sedation, search for reversible causes, apply defibrillator pads, and be prepared to cardiovert.

Maybe sedation isn’t that important? This is by Dr. Peter Kowey, one of the top cardiologists in the world.
 

The man’s very first utterance was, “If it happens again, just let me die.”

As I discovered, the reason for this patient’s terror was that he had been cardioverted in an awake state. Ventricular tachycardia had been relatively slow, he had not lost consciousness, and the physicians, in the heat of the moment, had not administered adequate anesthesia. Although the 5 mg of intravenous diazepam had made him a bit drowsy, he felt the electric current on his chest and remembered the event clearly.

The patient’s mental state complicated the case considerably.[12]

 

How unimportant is sedation? How unimportant is consent?

For sedation, I would recommend ketamine, but etomidate was recommended in the podcast. Both work quickly and the most important obstacle to immediate treatment of a patient who suddenly deteriorates is the time to effect of sedation. Neither drug is expected to interfere with perfusion, which is the main excuse given for avoiding sedation for cardioversion.

This study is very small (not the fault of the authors), but it adds to the evidence that amiodarone is not a good first treatment for the patient.
 

Go listen to the podcast by Dr. Salim Rezaie and Dr. Anand Swaminathan REBELCast: The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia

 

Over the years, I have written a bit about cardioversion and the importance of sedation –

Cardioversion – I’m not doing that, you do it! – Mon, 24 Mar 2008

Cardioversion – 2010 ACLS – Part I – Mon, 25 Oct 2010

Cardioversion – 2010 ACLS – Part II – Sun, 31 Oct 2010

Cardioversion – 2010 ACLS – Part III – Thu, 11 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part I – Thu, 11 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part II – Fri, 12 Nov 2010

Synchronized Cardioversion Without Sedation – Part II Scallywag’s Response – Sun, 14 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part III – Tue, 16 Nov 2010

On the relative wisdom of synchronized cardioversion without sedation – Part IV – Wed, 24 Nov 2010

Comments on Cardioversion – 2010 ACLS – Part II – Mon, 16 Apr 2012
 

I have also written a bit about amiodarone –

Merit Badge Courses, Amiodarone, and tPA – Fri, 17 Sep 2010

Amiodarone for Cardiac Arrest in the 2010 ACLS – Part I – Wed, 01 Dec 2010

Amiodarone for Cardiac Arrest in the 2010 ACLS – Part II – Fri, 03 Dec 2010

Is Nexterone the Next Amiodarone? – Sat, 04 Dec 2010

Amiodarone for Cardiac Arrest in the 2010 ACLS – Part III – Mon, 06 Dec 2010

Where are the Black Box Warnings on These Drugs – I – Mon, 05 Dec 2011

Where are the Black Box Warnings on These Drugs – II – Sun, 11 Dec 2011

Is Amiodarone the Best Drug for Stable Ventricular Tachycardia – Wed, 14 Dec 2011

V Tach Storm – Part I – Wed, 28 Dec 2011

V Tach Storm – Part II – Thu, 29 Dec 2011

Nifekalant versus lidocaine for in-hospital shock-resistant ventricular fibrillation or tachycardia – Wed, 04 Jan 2012

NIH launches trials to evaluate CPR and drugs after sudden cardiac arrest – Sun, 29 Jan 2012

What Will Be the Next Standard Of Care We Eliminate – Wed, 28 Mar 2012

Happy Adenosine Day – Tue, 12 Jun 2012

Too Much Medicine and Evidence-Based Guidelines – Part I – Tue, 26 Jun 2012

Too Much Medicine and Evidence-Based Guidelines – Part II – Tue, 03 Jul 2012

Ondansetron (Zofran) Warning for QT Prolongation – is Amiodarone next? – Part I – Mon, 02 Jul 2012

Ondansetron (Zofran) Warning for QT Prolongation – is Amiodarone next? – Part II – Thu, 05 Jul 2012

Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium – Part I – Mon, 17 Sep 2012

Wide variability in drug use in out-of-hospital cardiac arrest: A report from the resuscitation outcomes consortium – Part II – Tue, 18 Sep 2012

How do we measure the QT segment when there are prominent U waves? – Thu, 13 Dec 2012

Woman with Risks for Torsades de Pointes Dying within Hours of Leaving the Emergency Department – Wed, 02 Jan 2013

Examples of Ventricular Tachycardia Caused by Amiodarone – Part I – Tue, 28 May 2013

Publication Bias – The Lit Whisperers – Tue, 11 Jun 2013

Standards Of Care – Ventricular Tachycardia – Wed, 31 Jul 2013

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Footnotes:

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[1] Dr. Kudenchuk is Misrepresenting ALPS as ‘Significant’
Tue, 12 Apr 2016
Rogue Medic
Article

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[2] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest
Mon, 04 Apr 2016
Rogue Medic
Article

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[3] Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest.
Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P; Resuscitation Outcomes Consortium Investigators.
N Engl J Med. 2016 May 5;374(18):1711-22. doi: 10.1056/NEJMoa1514204. Epub 2016 Apr 4.
PMID: 27043165

CONCLUSIONS
Overall, neither amiodarone nor lidocaine resulted in a significantly higher rate of survival or favorable neurologic outcome than the rate with placebo among patients with out-of-hospital cardiac arrest due to initial shock-refractory ventricular fibrillation or pulseless ventricular tachycardia.

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[4] Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study.
Ortiz M, Martín A, Arribas F, Coll-Vinent B, Del Arco C, Peinado R, Almendral J; PROCAMIO Study Investigators.
Eur Heart J. 2016 Jun 28. pii: ehw230. [Epub ahead of print]
PMID: 27354046

Free Full Text from European Heart Journal.

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[5] Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison.
Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, Ellinor PT.
Acad Emerg Med. 2010 Mar;17(3):297-306.
PMID: 20370763 [PubMed – indexed for MEDLINE]

Free Full Text from Academic Emergency Medicine.

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[6] Amiodarone is poorly effective for the acute termination of ventricular tachycardia.
Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, Ruskin JN.
Ann Emerg Med. 2006 Mar;47(3):217-24. Epub 2005 Nov 21.
PMID: 16492484 [PubMed – indexed for MEDLINE]

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[7] Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment?
Tomlinson DR, Cherian P, Betts TR, Bashir Y.
Emerg Med J. 2008 Jan;25(1):15-8.
PMID: 18156531 [PubMed – indexed for MEDLINE]

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[8] Adenosine for wide-complex tachycardia – diagnostic?
Thu, 23 Aug 2012
Rogue Medic
Article

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[9] AMIODARONE HYDROCHLORIDE- amiodarone hydrochloride injection, solution
DailyMed
5 WARNINGS AND PRECAUTIONS
FDA Label

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[10] Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction.
Kułakowski P, Karczmarewicz S, Karpiński G, Soszyńska M, Ceremuzyński L.
Europace. 2000 Jul;2(3):207-15.
PMID: 11227590 [PubMed – indexed for MEDLINE]

Free Full Text PDF + HTML from Europace

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[11] Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia.
Bonny A, De Sisti A, Márquez MF, Megbemado R, Hidden-Lucet F, Fontaine G.
World J Cardiol. 2012 Oct 26;4(10):296-301. doi: 10.4330/wjc.v4.i10.296.
PMID: 23110246 [PubMed]

Free Full Text from PubMed Central.

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[12] The calamity of cardioversion of conscious patients.
Kowey PR.
Am J Cardiol. 1988 May 1;61(13):1106-7. No abstract available.
PMID: 3364364

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Kudenchuk PJ, Brown SP, Daya M, Rea T, Nichol G, Morrison LJ, Leroux B, Vaillancourt C, Wittwer L, Callaway CW, Christenson J, Egan D, Ornato JP, Weisfeldt ML, Stiell IG, Idris AH, Aufderheide TP, Dunford JV, Colella MR, Vilke GM, Brienza AM, Desvigne-Nickens P, Gray PC, Gray R, Seals N, Straight R, Dorian P, & Resuscitation Outcomes Consortium Investigators (2016). Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Cardiac Arrest. The New England journal of medicine, 374 (18), 1711-22 PMID: 27043165

Ortiz M, Martín A, Arribas F, Coll-Vinent B, Del Arco C, Peinado R, Almendral J, & PROCAMIO Study Investigators (2016). Randomized comparison of intravenous procainamide vs. intravenous amiodarone for the acute treatment of tolerated wide QRS tachycardia: the PROCAMIO study. European heart journal PMID: 27354046

Marill KA, deSouza IS, Nishijima DK, Senecal EL, Setnik GS, Stair TO, Ruskin JN, & Ellinor PT (2010). Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison. Academic emergency medicine : official journal of the Society for Academic Emergency Medicine, 17 (3), 297-306 PMID: 20370763

Marill KA, deSouza IS, Nishijima DK, Stair TO, Setnik GS, & Ruskin JN (2006). Amiodarone is poorly effective for the acute termination of ventricular tachycardia. Annals of emergency medicine, 47 (3), 217-24 PMID: 16492484

Tomlinson DR, Cherian P, Betts TR, & Bashir Y (2008). Intravenous amiodarone for the pharmacological termination of haemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emergency medicine journal : EMJ, 25 (1), 15-8 PMID: 18156531

Kułakowski P, Karczmarewicz S, Karpiński G, Soszyńska M, & Ceremuzyński L (2000). Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2 (3), 207-15 PMID: 11227590

Bonny A, De Sisti A, Márquez MF, Megbemado R, Hidden-Lucet F, & Fontaine G (2012). Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia. World journal of cardiology, 4 (10), 296-301 PMID: 23110246

Kowey PR (1988). The calamity of cardioversion of conscious patients. The American journal of cardiology, 61 (13), 1106-7 PMID: 3364364

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Filed Under: ACLS, Adenosine, Assessment, Cardioversion, Critical Judgment, Ethics, Ketamine, Pharmacology, Research Blogging, Sedation, Toxicology, V Tach

Adenosine for wide-complex tachycardia – diagnostic?

Thu, 23 Aug 2012 14:00:33 -0400 by
ResearchBlogging.org
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Adenosine is a drug that wears off very quickly, so that its side effect of asystole is not really a problem. The metabolism of adenosine takes place in the cells. If you remember the Krebs cycle, you remember how important adenosine is for the production of energy. Almost every cell has a constant demand for adenosine for energy. No circulation is needed for metabolism, as long as the person was alive when the adenosine was given (or in the few minutes before adenosine was given).
 


Image credit. Click on images to make them larger.
 

This study looks at the efficacy and safety of adenosine as a diagnostic tool for WCT (Wide Complex Tachycardia) WCT is a fast rhythm with prolonged ventricular conduction that has not had its cause diagnosed, yet. The W in WCT is its Width on an ECG (ElectroCardioGram), which is a measure of time.

The authors claim that a lack of response to adenosine will identify VT (V Tach – Ventricular Tachycardia). At least, that is what they claim that their study demonstrates.
 


WCT image from EMS 12 Lead. To find out more about this WCT, read about it at EMS 12 Lead.
 

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It is expected that adenosine will 1) terminate the majority of supraventricular tachycardias (SVTs) that rely on the AV node to form a reentrant circuit; 2) cause transient AV block to permit the accurate diagnosis of atrial flutter; and 3) be unlikely to terminate most ventricular tachycardias (VTs).[1]

This is a multicenter retrospective observational study of administration of adenosine to patients with WCT (Wide Complex Tachycardia) WCT is a fast rhythm with prolonged ventricular conduction that has not had its cause diagnosed, yet. The W in WCT is its Width on an ECG (ElectroCardioGram), which is a measure of time.

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A sustained rhythm was defined as continuous for at least 2 mins to minimize the risk of mislabeling spontaneous termination of a transient WCT as a response to adenosine.[1]

It often takes a couple of minutes to get everything ready to give adenosine and it is a good idea to observe a stable rhythm and to get a 12 lead ECG. Unstable patients are often cardioverted, but I will use adenosine for unstable SVT (SupraVentricular Tachycardia) rather than shock the patient without sedation.

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A regular rhythm was defined as having ≤ 5% beat-to-beat variability in R-to-R interval for contiguous beats. Wide QRS tachycardia was defined as a QRS width ≥ 120 msecs and a heart rate (HR) of at least 120 beats/min.[1]

Patients who responded to 6 mg adenosine, or who received 12 mg adenosine were included. If the patient only received 6 mg adenosine, but there was no response, the patient was not included.

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The underlying mechanism of the WCT rhythm was determined by the investigators using the following methods and criteria in descending order, as available: ECG evidence of AV dissociation demonstrating VT, review of the tachydysrhythmia from ICD recordings, reproduction of the dysrhythmia during an electrophysiologic study, diagnostic response to carotid massage or adenosine, such as transient AV block revealing atrial flutter waves, ECG analysis by the treating cardiology team with clear evidence of the diagnosed rhythm confirmed by the investigators, or if necessary, ECG analysis using standard criteria by an electrophysiologist investigator blinded to all clinical data.[1]

 

Let’s look at those diagnostic criteria –

1. ECG evidence of AV dissociation demonstrating VT,

That is my favorite way of identifying VT. Some people see P waves and say that is evidence of an atrial rhythm, but if the P waves are dissociated, that is evidence that the rhythm is not atrial.

2. review of the tachydysrhythmia from ICD recordings,

Meaning that this review of rhythms included a review of older rhythms and the onset of the rhythms. However, if the previous diagnosis was based on response to adenosine, is this a valid criterion?

3. reproduction of the dysrhythmia during an electrophysiologic study,

EP (ElectroPhysiologic) studies are important for patients who have had WCT, because it is sometimes difficult to identify VT.

4. diagnostic response to carotid massage or adenosine, such as transient AV block revealing atrial flutter waves,

Is adenosine diagnostic for SVT vs. VT?

Of course it is.

How do you know?

A response to adenosine was assumed to be diagnostic for SVT.

Am I being unfair to the authors?

They did include other criteria before response to adenosine or CSM (Carotid Sinus Massage – an adenosine analogue and not something that is accurately described by the word massage).

That was their last resort, so their only option was to not answer the question.

That would have been more honest/less biased, but this was not the last resort. they had other diagnostic criteria that were trumped by response to adenosine or CSM.

5. ECG analysis by the treating cardiology team with clear evidence of the diagnosed rhythm confirmed by the investigators,

Do I want to trust a response to adenosine for diagnosis or do I want to trust a team of cardiologists?

We joke that if we give an ECG to five cardiologists, we will get six interpretations.

If the cardiologists agree, should we ignore the consensus of the experts in rhythm interpretation because of a drug response that agrees with our biases?

While I do not automatically trust experts, I have much greater distrust for people who allow their biases to guide them.

Why do you believe X?

Because I want to believe X.

Or, more honestly –

Because X is consistent with my biases.

But wait.

There’s more.

Not only was that not the last resort, it wasn’t even the second to last resort.

The authors also felt that response to adenosine or CSM was better at diagnosing SVT vs. VT than the electrophysiologists.

6. or if necessary, ECG analysis using standard criteria by an electrophysiologist investigator blinded to all clinical data.

Being blinded to the clinical data may seem like a bad idea to them, but does any of it help to identify the rhythm correctly?

No.

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Maybe they are correct.

Maybe a response to adenosine does prove that the rhythm is not VT.

There were no cases of VT being terminated by adenosine, so that is a reasonable conclusion.

No.

There were cases of VT terminated by adenosine in this study.
 


 

If 2 of the patients diagnosed as VT responded to adenosine, how many of the 102 tachycardia patients diagnosed as supraventricular (the SV of SVT) were diagnosed based only on response to adenosine and could have actually been ventricular (VT)?
 


 

49%
 

Allow me to round off a teens-weensy bit.

Half of the SVT diagnosed patients were diagnosed based on the response to adenosine or to CSM.

Only 1% were diagnosed based on CSM response and 48% were diagnosed based on adenosine response.

Allow me to round off a teens-weensy bit more.

Half of the SVT diagnosed patients were diagnosed based on the response to adenosine.

Patients regularly receive antibiotics for viral infections, even though the doctors know that the antibiotics will not treat a viral infection. A lot of these patients get better after they take antibiotics, no matter how non-compliant they are with the directions for taking the medication.

Do any of these doctors write papers claiming that this is evidence that the patients had bacterial infections?

I have not done a search for this, but I hope not. If they do, I hope they receive plenty of criticism.

A response to adenosine has never been demonstrated to be diagnostic.

A response to a treatment that has never been demonstrated to be diagnostic should never be used to confirm the ability of that treatment to diagnose.

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Footnotes:

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[1] Adenosine for wide-complex tachycardia: efficacy and safety.
Marill KA, Wolfram S, Desouza IS, Nishijima DK, Kay D, Setnik GS, Stair TO, Ellinor PT.
Crit Care Med. 2009 Sep;37(9):2512-8.
PMID: 19623049 [PubMed – indexed for MEDLINE]

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Marill KA, Wolfram S, Desouza IS, Nishijima DK, Kay D, Setnik GS, Stair TO, & Ellinor PT (2009). Adenosine for wide-complex tachycardia: efficacy and safety. Critical care medicine, 37 (9), 2512-8 PMID: 19623049

Filed Under: Adenosine, Cardiology, Heresy, Pharmacology, Research Blogging

FDA Safety Alert Adenosine Prefilled Glass Syringes

Fri, 19 Nov 2010 06:30:59 -0500 by
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The FDA (Food and Drug Administration) sent out a safety alert about malfunctions of adenosine pre-filled glass syringes when used with needleless IV (IntraVenous) tubing.

AUDIENCE: Critical Care Medicine, Emergency Medicine, Cardiology, Risk Manager[1]

I don’t think it is unreasonable to assume that they mean to include EMS, as well.

Most of the reports have been related to pre-filled needleless glass syringes that contain adenosine, often when attempting to connect to some pin activated needleless IV access systems.[1]

Healthcare organizations currently using glass prefilled syringes should consider stocking adenosine supplied in vials or pre-filled plastic syringes as a back up measure.[1]

This does not mean that we should replace all prefilled adenosine, but that we should have another method of giving adenosine if the prefilled syringe is not working.

FDA is interested in receiving information on the type, manufacturer and NDC numbers of the prefilled syringes and type and manufacturer of needless IV access devices. FDA is especially interested in any description of the nature of the syringe failure, any adverse patient outcomes, and any mitigation strategies that have been identified or implemented by users of these products.[1]

The U.S. Food and Drug Administration (FDA) is seeking your help in communicating an important safety message about pre-filled needleless glass syringes to people affiliated with your organization. We hope you will share this information to ensure they are aware of this issue and can take steps to remedy the problem.

The FDA has received reports of compatibility problems when certain needleless pre-filled glass syringes are used with some needleless intravenous (IV) access systems. These syringes may malfunction, break, or become clogged during the process of attempting to connect to needleless IV access systems. In some cases, the syringe may damage the IV tubing and/or the needleless connector and require reestablishment of intravenous access.[2]

This is much more of a problem with adenosine than with most other drugs, because we act in a somewhat civilized manner, when giving other drugs. Not with adenosine for SVT (SupraVentricular Tachycardia).

Adenosine is SLAMMED in.

The reason adenosine is given through a large bore IV as close to the central circulation, is that adenosine is metabolized very quickly.

How quickly adenosine is metabolized depends on the patient being treated. Anyone who tells us any specific time frame is exaggerating their understanding of adenosine. Does it matter if the half life is 10 seconds, 14 seconds, 30 seconds, or something else? It only matters for someone trying to come up with test questions.

How do they know what they are telling us? They read it somewhere. As with everything else about the human body, there is a range of normal and there are even plenty of abnormal presentations. One specific number is supposed to apply to all of them? Real life does not work that way.

Adenosine is metabolized very quickly, so we do want IV access in a vein that will not blow when we forcefully push the adenosine and immediately follow that with a 20 ml flush. The 20 ml syringe can contain 0.9% Saline, or D5W, or Lactated Ringers, any other IV solution that is handy, as long as there is no dose of medication in it. Draw this up before you begin to give the adenosine, otherwise it doesn’t do anything good for the patient.

I miss the old 2 needle in one port method, but with a needleless system, we need to either immediately switch syringes or have the flush syringe in another port. If those are not possible, clamp the IV line above the port we are using for the adenosine, put a blood pressure cuff around the IV bag, inflate it to over 200 mmHg, and release the clamp immediately after pushing the adenosine. This is not a great method, but it is much faster than the run the IV wide open method used by people who do not understand what they are doing.

The faster we SLAM the adenosine in, the more likely that 6 mg will be effective. The slower we push the adenosine in, the more likely that even 12 mg will not be effective.

And most important of all – don’t treat asystole that appears right after adenosine. Wait at least a minute. If we give epinephrine or atropine (not in the new asystole algorithm) expect the patient to regain a rhythm and pulse just the same way they would have if we had given a healthy dose of benign neglect, but now the tachycardia that we were treating may be a lethal rhythm.

How fast was the heart rate before the adenosine?

Adenosine almost always wears off in less than a minute. Then the rhythm breaks or the tachycardia returns.

Assume that the patient had a heart rate of over 200 beats per minute without epinephrine – how fast will the heart rate be after being hit with a dead person dose of epinephrine?

If we want to give atropine, we should first consider our initial treatment for SVT.

Vagal maneuvers.

The quickest way to break the rhythm is with a vagal maneuver. Atropine is an anti-vagal drug. The vagal nerve keeps the vital signs under control. We were using the vagal maneuvers and the adenosine because the vital signs were not under control. Now the vital signs are even less likely to be controlled any time soon.

Following adenosine with epinephrine or atropine is a clear case of a malignant intervention.

But the patient is in asystole!

Don’t worry. It will wear off.

Consider how adenosine is metabolized. All cells use adenosine to make energy. This is one drug that does not need to be circulated through the liver or kidneys to be metabolized. A dead patient with red blood cells that have not yet clotted, is still metabolizing the adenosine. If the blood in the patient’s veins has clotted, then epinephrine and atropine will not matter. This is the reason for pushing adenosine so quickly.

Treat the patient – not the monitor.

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Given all of that – it is very important that the adenosine syringe function properly. The ones listed below might not.

Below is the information about the specific syringes from the FDA Safety Alert.[2]

Adenosine             Teva                               00703-8781-23
Adenosine             Sagent                           25021-0301-72
Adenosine             Baxter                           10019-0063-08(07)
Adenosine             Wockhardt                   64679-0630-01(02)
Amiodarone         Sagent/Gland             25021-0302-73

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Adenosine Teva

1 0703-8781-23 10 SYRINGE In 1 TRAY contains a SYRINGE (0703-8781-21)
1 0703-8781-21 2 mL In 1 SYRINGE This package is contained within the TRAY (0703-8781-23)[3]

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Adenosine Sagent

1 25021-301-72 10 CARTON In 1 BOX contains a CARTON
1 1 SYRINGE In 1 CARTON This package is contained within the BOX (25021-301-72) and contains a SYRINGE
1 2 mL In 1 SYRINGE This package is contained within a CARTON and a BOX (25021-301-72)[4]

Sagent also makes a 12 mg syringe, but that is not included in the lot numbers provided in the FDA Safety Alert.[1] No explanation is given. We should expect the same thing to happen with their 12 mg syringe. Not including the 12 mg syringe is probably a clerical error, not a sign that everyone needs 12 mg. Below is the information on the 12 mg syringe.

2 25021-301-76 10 CARTON In 1 BOX contains a CARTON
2 1 SYRINGE In 1 CARTON This package is contained within the BOX (25021-301-76) and contains a SYRINGE
2 4 mL In 1 SYRINGE This package is contained within a CARTON and a BOX (25021-301-76)[4]

–

Adenosine Baxter

1 10019-063-08 10 BOX In 1 PACKAGE contains a BOX (10019-063-07)
1 10019-063-07 1 SYRINGE In 1 BOX This package is contained within the PACKAGE (10019-063-08) and contains a SYRINGE, GLASS (10019-063-34)
1 10019-063-34 2 mL In 1 SYRINGE, GLASS This package is contained within a BOX (10019-063-07) and a PACKAGE (10019-063-08)[5]

–

Adenosine Wockhardt

1 55648-630-07 10 SYRINGE In 1 CARTON contains a SYRINGE, GLASS (55648-630-01)
1 55648-630-01 2 mL In 1 SYRINGE, GLASS This package is contained within the CARTON (55648-630-07)
2 55648-630-08 10 SYRINGE In 1 CARTON contains a SYRINGE, GLASS (55648-630-02)
2 55648-630-02 4 mL In 1 SYRINGE, GLASS This package is contained within the CARTON (55648-630-08)[6]


–

And –

Amiodarone Sagent

1 25021-302-73 10 SYRINGE In 1 CARTON contains a SYRINGE
1 3 mL In 1 SYRINGE This package is contained within the CARTON (25021-302-73)[7]

No picture

–

Footnotes:

–

[1] Needleless Pre-filled Glass Syringes: Stakeholder Advisory – Compatibility Problems with Needleless Intravenous Access Systems
Reports Received on Adenosine and Amiodarone Products
[Posted 11/17/2010]
FDA Safety Alert

–

[2] Letter to Stakeholders: Communication on certain needleless pre-filled glass syringes
Drug Safety and Availability
November 17, 2010
FDA
Letter

–

[3] ADENOSINE injection
[Teva Parenteral Medicines, Inc]
FDA Label
DailyMed
Label with link to PDF download of FDA Label

–

[4] ADENOSINE injection
[Sagent Pharmaceuticals, Inc]
FDA Label
DailyMed
Label with link to PDF download of FDA Label

–

[5] ADENOSINE injection, solution
[Baxter Healthcare Corporation]
FDA Label
DailyMed
Label with link to PDF download of FDA Label

–

[6] ADENOSINE injection
[WOCKHARDT LIMITED]
FDA Label
DailyMed
Label with link to PDF download of FDA Label

–

[7] AMIODARONE HYDROCHLORIDE injection, solution
[Sagent Pharmaceuticals]
FDA Label
DailyMed
Label with link to PDF download of FDA Label

.

Filed Under: 2010 AHA Guidelines, ACLS, Adenosine, FDA, Heresy

Up to a Maximum of X Times vs. Titration

Fri, 11 Jul 2008 00:30:00 -0400 by
Over at Ridin’ the Bus, Gertrude was writing Who’s teaching the teachers? Well, my answer is that the teaching jobs are often as political as the desirable EMS jobs. Squad Y is a bunch of people friendly with So-and-So. Squad B is a bunch of people friendly with Whojamacallit. Whether these are 911 jobs, critical care jobs, flight medic/nurse jobs, or anything else does not matter. There is more of an old boy network involved than a critical examination of the qualifications of a job candidate. Teaching is no different.

The current teachers are not necessarily those who excelled in medic school, or EMT school, when they attended. They might not have learned things all that well, when they were in school. The instructor may have modified his understanding since then, but that does not mean that it was for any medical reason. A lot of what is taught is pure speculation.

I described this in several posts A, B, C, D, and E. I reference it in several others. We are poorly educated. The educators often do not know what they are doing well enough to be teaching it.

An excellent example of this is cardioversion. I have never seen anyone else do a good job of teaching cardioversion. That does not mean that it does not happen, but it is not encouraging that I do not see it taught well. ACLS (Advanced Cardiac Life Support) encourages us to just review the material, since the students are already supposed to be familiar with everything. How many nurses going to their first ACLS class have any experience with cardioversion? This is not something that you learn to do well from a book or a blog. You learn it by using the paddles, turning on the synchronizer, and delivering shocks to a mannequin or to a patient. Too many people learn, during their first cardioversion, that they never really understood cardioversion.

Anyway, the topic of Gertrude’s post was the rules that are taught to us. Her example is when a student asked her for the maximum number of times a patient can be suctioned.

Think about this.

Why do we suction patients?

We suction them because there is something in the airway that may interfere with ventilation. It may be a potential obstruction. It may be a partial obstruction. It may be a complete obstruction.

As long as we do what we can to maintain oxygenation, there is no maximum. For the complete obstruction, there is no reason to pause and ventilate in between suction attempts, or to limit the length of suctioning, unless there is the possibility that you have cleared, or partially cleared, the obstruction.

One of the other instructors had given them a number. What is a good number for this? 3? 5? 23? The patients weight in kilograms, divided by their SpO2 percent, multiplied by the number of synapses actually transmitting information in that instructor’s brain?

How about until the portable battery runs out? But remember there are other ways of creating suction – a large syringe, a bulb syringe from the OB kit, scooping things out of the airway, gravity, a vacuum cleaner in the residence. Who really cares how you do it, if you are able to provide the airway the patient needs?

Why do we feel the need to have a number? A limit on what we can do?

People like externally imposed limits. The idea of being responsible for making intelligent decisions is something that many people flee from.

“Responsibility? Just tell me what I have to do to avoid getting in trouble.”

“As long as I follow the protocol, I won’t get in trouble.”

Of course, if the protocol does not apply to your patient, or if you follow the wrong protocol (because you ignored assessment in favor of memorization of protocols) you might kill your patient in your devotion to keeping out of trouble.

Maximum of 3 NTG (NiTroGlycerin, overseas GTN – GlycerylTriNitrate).

Why?

Most likely because the AHA wants you to switch the patient to IV NTG as soon as possible. Not exactly common in the prehospital setting, but a very good idea. NTG is a drug that needs to be titrated. A maximum number prevents titration, so people teaching these maximums should not be teaching. Titration is adjusting the dose based on the response of the patient. Almost all EMS drugs need to be titrated.

Does a response mean that you stop? No, but you take that information into consideration in your continuing doses. Sometimes it will mean to stop. NTG + Syncope is more than a subtle hint to stop NTG. After blood pressure returns, then you may resume cautiously (perhaps after running a liter into the patient) or you may decide not to give any more, but initially your response should be to stop.

Atropine is not a titration drug. Fast push, a minimum adult dose of 0.5 mg and a maximum dose of 0.03 mg/kg if stable, 0.04 mg/kg if unstable. With atropine, you may get the opposite result of what you want, if you give it slowly or if you do not give enough. Another non-titration drug is adenosine. Also fast push. Maximum of 3 doses – 6 mg, 12 mg, and another dose of 12 mg. Glucagon is another drug not generally titrated (many places do not even carry more than one dose).

Some titration drugs:

Oxygen – titrate to adequate oxygenation.

Dextrose 50% in Water – titrate to adequate saccharinity.

Dopamine and dobutamine are given as drips, the dosage formula is for calculating a starting dose and for understanding the maximum dose rate, which does not mean that you stop, only that you stop increasing the dose rate.

NTG – I have given over 50 sprays (over 20 mg) to a single CHF patient on one call and the blood pressure never dropped below 200 mm/hg systolic. Maximum of 3? Not a chance.

Albuterol (Salbutamol overseas)- if the patient is not able to breathe adequately, we continue giving albuterol, but we add other beta 2 agonists, maybe some magnesium and methylprednisolone. There are some who will even tell you that you may not give albuterol to a tachycardic or hypertensive patient, since it is not completely selective for beta 2 and might make things worse. Yes, it will stimulate the heart to work harder, but if it opens the airways, the pressure and heart rate will come down in spite of that stimulus. If it doesn’t open the airways, the side effects are not the patient’s primary concern, not even a secondary concern.

Fentanyl/dilaudid/morphine – no minimum dose and no maximum dose. Only the response to treatment matters. No maximum of 6 mg, or 10 mg, or 20 mg, or even 100 mg of morphine (about 60 mcg/100 mcg/200 mcg/1 mg for fentanyl; 0.75 mg/1.25 mg/2.5 mg/12.5 mg for dilaudid). Anyone who tells you otherwise is a liar and/or incompetent.

Midazolam/lorazepam/diazepam – no minimum dose and no maximum dose. Only the response to treatment matters. No maximum of 5 mg, or 10 mg, or 20 mg, or even 100 mg of midazolam . . . .

Diltiazem is a slow push medication that has standard doses (0.25 mg/kg for the initial dose and 0.35 mg/kg for a repeat). If you are giving it slowly it isn’t just to minimize the side effects, but also to observe for side effects that would discourage you from continuing with the dose. Diltiazem is often given to little old people, who may not give much warning before dropping their blood pressure significantly. I like to keep them sitting up and talking to me while I slowly (over 5 minutes, not the recommended 2 minutes) push the diltiazem. If they are sitting up, the part of the body most likely to show signs of decreased perfusion is the brain – sooner than a repeat blood pressure, sooner than skin sign changes. If the behavior changes in any way, I stop and I do not give any more until after I have satisfied myself that this is not a sign of an adverse reaction. I can always give more later, but most likely it is an adverse reaction.

Naloxone – no minimum dose and no maximum dose. I like to give 20 mcg to 40 mcg at a time. Response is what tells me when to stop.

These are just some of the drugs that are only appropriately given when titrated.

.

By Rogue Medic
Filed Under: ACLS, Adenosine, Airway Management, Assessment, Atropine, Cardioversion, Critical Judgment, Fentanyl, GTN, Heresy, Math, Midazolam, Morphine, Naloxone, NTG