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

- Rogue Medic

2016 – Amiodarone is Useless, but Ketamine Gets Another Use

amiodarone-edit-1
 

I didn’t write a lot in 2016, but 2016 may have been the year we put the final nail in the coffin of amiodarone. Two major studies were published and both were very negative for amiodarone.

If we give enough amiodarone to have an effect on ventricular tachycardia, it will usually be a negative effect.[1]

Only 38% of ventricular tachycardia patients improved after amiodarone, but 48% had major adverse cardiac events after amiodarone.

There are better drugs, including adenosine, sotalol, procainamide, and ketamine for ventricular tachycardia. Sedation and cardioversion is a much better choice. Cardioversion is actually expected after giving amiodarone.

For cardiac arrest, amiodarone is not any better than placebo or lidocaine. What ever happened to the study of amiodarone that was showing such wonderful results over a decade ago? It still hasn’t been published, so it is reasonable to conclude that the results were negative for amiodarone. It is time to make room in the drug bag for something that works.[2],[3]

On the other hand, now that we have improved the quality of CPR by focusing on compressions, rather than drugs, more patients are waking up while chest compressions are being performed, but without spontaneous circulation, so ketamine has another promising use. And ketamine is still good for sedation for intubation, for getting a patient to tolerate high flow oxygen, for agitated delirium, for pain management, . . . .[4],[5]

Masimo’s RAD 57 still doesn’t have any evidence that it works well on real patients.[6]

When intubating, breathe. Breathing is good. Isn’t inability to breathe the reason for intubation?[7]

Footnotes:

[1] The PROCAMIO Trial – IV Procainamide vs IV Amiodarone for the Acute Treatment of Stable Wide Complex Tachycardia
Wed, 17 Aug 2016
Rogue Medic
Article

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

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

[4] What do you do when a patient wakes up during CPR?
Tue, 08 Mar 2016
Rogue Medic
Article

[5] Ketamine For Anger Management
Sun, 06 Mar 2016
Rogue Medic
Article

[6] The RAD-57 – Still Unsafe?
Wed, 03 Feb 2016
Rogue Medic
Article

[7] Should you hold your breath while intubating?
Tue, 19 Jan 2016
Rogue Medic
Article

.

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

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

Footnotes:

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

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

[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.

[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.

[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.

[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]

[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]

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

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

[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

[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.

[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

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

.

Is mixing Mountain Dew and racing fuel a new trend?

 

Is Dewshine (mixing Mountain Dew and racing fuel) what all the cool kids are doing?

Will it make me cool?
 
DewAndFuel_1453815893474_30645234_ver1.0_640_480
Image credit.
 

According to one article, one recent case of four teens getting together to drink this bad idea of a cocktail may be just the tip of some sort of epidemic iceberg –
 

And that’s just one state, and the just the cases that have been reported.[1]

 

While that is correct, it is also much more than an exaggeration of the facts.
 

She (Tennessee Poison Center Medical Director Donna Seger) says this is the first time she has seen this type of poisoning. The four cases are the only ones reported in Tennessee, and Seger is not aware of any cases in other states.[2]

 

Nationally, there was only one methanol poisoning fatality reported among teens aged 13-19 by the American Association of Poison Control Centers’ National Poison Data System in 2014, the most recent year data is available.[3]

 

Rudy Eugene was shot while eating the face of another person. This was supposed to be the beginning of a wave of attacks by abusers of bath salts, but . . .
 

Lab tests detected only marijuana in the system of a Florida man shot while chewing another man’s face, the medical examiner said Wednesday, ruling out other street drugs including the components typically found in the stimulants known as bath salts.[4]

 

We are still waiting for the bath salts zombie apocalypse.

What did I write about it at the time?[5]
 

This appears to be the first time that mixing Mountain Dew and racing fuel has been reported, so is it the tip of an iceberg or just an example of click bait?

Why mix racing fuel with anything and drink it? Racing fuel contains methanol, a type of alcohol that is much more poisonous to humans than ethanol (the type of alcohol that is sold for to be drunk by humans).

Why drink methanol, rather than ethanol? The dead were both 16 years old. Suppose that you are 16 and you want alcohol. Ethanol is not legally available. You probably do not know much about chemistry or toxicology. You may know that methanol is a form of alcohol. You skip right by due diligence. You draw the wrong conclusion. Four of you are hospitalized, but only two survive.

Teens tend to choose to experiment with marijuana, rather than methanol. Both are much easier to obtain than ethanol, but the dangers of marijuana are more likely to be legal, while the dangers of methanol are more likely to be medical.[6]

Mixing products containing methanol with Mountain Dew may be new, but the use of methanol for intoxication is not new, accidental ingestion of methanol by smaller children is also not new, and inhalation of products containing methanol (such as huffing carburetor cleaner) appears to be more even more common than ingestion of methanol.

The hospital treatment for methanol toxicity is hemodialysis and fomepizole (Antizol) and/or 10% ethanol. The EMS treatment is supportive care.[7]

Patients with initial blood sugar measurements above 140 mg/dL appear to be much more likely to die, which means that we should be especially vigilant with these patients, not that those with blood sugar measurements below 140 mg/dL will not die.[8]

Breath alcohol analyzers may mistake methanol for ethanol, so do not conclude that a positive breath test means drunk, rather than methanol poisoning.[9],[10],[11]

Don’t drink, or inhale, methanol. Methanol is neither fashionable nor healthy.

I hope you don’t come here for fashion advice, but I have provided valid evidence for my health advice.

Footnotes:

[1] Kids Are Dying From Drinking Racing Fuel Because For Fuck’s Sake, Don’t Drink Racing Fuel
Jason Torchinsky
Yesterday (01/27/2016?) 10:00pm
Article

[2] 2 teens die after drinking racing fuel, soda – The teens evidently thought they could drink methanol, which is extremely toxic, as a substitute for ethanol
EMS1.com
Yesterday (01/27/2016?) at 12:56 PM
AP
Article

[3] No ‘dewshine’ trend, Tennessee officials say
Anita Wadhwani
11:42 p.m. CST January 27, 2016
The Tennessean
Article

[4] Tests find only marijuana in face-chewer’s system
Boston Globe
Suzette Laboy
June 28, 2012
AP
Article

[5] Police fatally shot a naked man chewing on the face of another naked man
Tue, 29 May 2012
Rogue Medic
Article

 

Will I be surprised if the lab results show drugs in his system? No.

Will I be surprised if the lab results do not show drugs in his system? No.

There are other causes of excited delirium. Drugs are most common, so a wise bet would be to bet on there being drugs in his system, but enough patients experience excited delirium without drugs that we would be behaving inappropriately if we did not consider other causes of altered mental status, such as hypoglycemia, head injury, either a clot or a bleed in the brain, or any of the other possible causes of excited delirium.

We do not know what caused this.

 

[6] Cannabis-related hospitalizations: unexpected serious events identified through hospital databases.
Jouanjus E, Leymarie F, Tubery M, Lapeyre-Mestre M.
Br J Clin Pharmacol. 2011 May;71(5):758-65. doi: 10.1111/j.1365-2125.2010.03897.x.
PMID: 21204913

Free Full Text from PubMed Central
 

We estimated that in 2007 the incidence of cannabis-related AEs in the Midi-Pyrenees region ranged from 1.2 per 1000 regular cannabis users (95% confidence interval (CI) 0.7, 1.6) to 3.2 (95% CI 2.5, 3.9).

 

[7] American Academy of Clinical Toxicology practice guidelines on the treatment of methanol poisoning.
Barceloux DG, Bond GR, Krenzelok EP, Cooper H, Vale JA; American Academy of Clinical Toxicology Ad Hoc Committee on the Treatment Guidelines for Methanol Poisoning.
J Toxicol Clin Toxicol. 2002;40(4):415-46. Review.
PMID: 12216995
 

CONCLUSION:
The management of methanol poisoning includes standard supportive care, the correction of metabolic acidosis, the administration of folinic acid, the provision of an antidote to inhibit the metabolism of methanol to formate, and selective hemodialysis to correct severe metabolic abnormalities and to enhance methanol and formate elimination. Although both ethanol and fomepizole are effective, fomepizole is the preferred antidote for methanol poisoning.

 

[8] Hyperglycemia is a strong prognostic factor of lethality in methanol poisoning.
Sanaei-Zadeh H, Esfeh SK, Zamani N, Jamshidi F, Shadnia S.
J Med Toxicol. 2011 Sep;7(3):189-94. doi: 10.1007/s13181-011-0142-x.
PMID: 21336799

Free Full Text from PubMed Central
 

Considering the cutoff level of 140 mg/dL for blood glucose and using logistic regression analysis, and adjusting according to the admission data with significant statistical difference in the two study groups, the odds ratio for hyperglycemia as a risk factor for death was 6.5 (95% confidence interval = 1.59-26.4). Our study showed that blood glucose levels were high in methanol poisoning and even higher in those who died in comparison with the survivors. Therefore, hyperglycemia might be a new prognostic factor in methanol poisoning, but further studies are needed to determine whether controlling hyperglycemia has therapeutic consequences.

 

Don’t make the mistake of treating the blood sugar in the belief that you are improving outcomes. There is no evidence to support that hypothesis. In the absence of evidence of benefit or safety, we should expect that treating the blood sugar would be more harmful than beneficial.

[9] Breath alcohol analyzer mistakes methanol poisoning for alcohol intoxication.
Caravati EM, Anderson KT.
Ann Emerg Med. 2010 Feb;55(2):198-200. doi: 10.1016/j.annemergmed.2009.07.021. Epub 2009 Oct 14.
PMID: 19833410
 

A 47-year-old-man was found in a public park, acting intoxicated. A breath analyzer test (Intoxilyzer 5000EN) measured 0.288 g/210 L breath ethanol, without an interferent noted. In the emergency department, the patient admitted to drinking HEET Gas-Line antifreeze, which contains 99% methanol. Two to three hours after ingestion, serum and urine toxicology screen results were negative for ethanol and multiple other substances. His serum methanol concentration was 589 mg/dL,

 

[10] Methanol ingestion: prevention of toxic sequelae after massive ingestion.
Lushine KA, Harris CR, Holger JS.
J Emerg Med. 2003 May;24(4):433-6.
PMID: 12745047

[11] Observations on the specificity of breath-alcohol analyzers used for clinical and medicolegal purposes.
Jones AW.
J Forensic Sci. 1989 Jul;34(4):842-7.
PMID: 2760587
 

Three different methods of alcohol analysis are reported: semiconductor sensing (Alcotest 7310), electrochemical fuel cell (Alcolmeter SM-1), and infrared (IR) absorptiometry (IR Intoximeter 3000). Methanol could not be distinguished from ethanol with any of these breath-test instruments. When nonspecific techniques of ethanol analysis are used, the results must be considered with caution when interfering substances expelled in breath cannot be excluded.

 

.

Dextrose in Cardiac Arrest – More Kitchen Sink Medicine

 
Should we treat hypoglycemia in a dead person?

How do we determine hypoglycemia in a dead person?

Is there any evidence that giving dextrose, in any concentration, will help to resuscitate a dead person?

Should we treat patients based on the philosophy of Who knows? Maybe it could work? Bleach enemas are currently in fashion among the alternative to medicine crowd,[1] so we could use the same reasoning to give bleach enemas in cardiac arrest. Who knows? Maybe it could work.

Is Kitchen Sink Medicine significantly different from any other alternative to medicine?

The dead person is not breathing, so we have to provide ventilations.[2], [3], [4]

The dead person is dead, so we have to do something.

We do compressions and (when indicated) defibrillation, because those are the only treatments that have been demonstrated to work.

 


 
 

The foundation of successful ACLS is high-quality CPR, and, for VF/pulseless VT, attempted defibrillation within minutes of collapse. For victims of witnessed VF arrest, early CPR and rapid defibrillation can significantly increase the chance for survival to hospital discharge.128–133 In comparison, other ACLS therapies such as some medications and advanced airways, although associated with an increased rate of ROSC, have not been shown to increase the rate of survival to hospital discharge.31,33,134–138 [5]

 

Ventilations are only a part of high-quality CPR for children and people who have a respiratory cause of cardiac arrest.

But what about dextrose for hypoglycemic cardiac arrest?

We may already be raising the blood sugar with epinephrine.
 

Epinephrine causes a prompt increase in blood glucose concentration in the postabsorptive state. This effect is mediated by a transient increase in hepatic glucose production and an inhibition of glucose disposal by insulin-dependent tissues.[6]

 

We seem to have trouble understanding that dead people do not respond to treatments the same way that living people do.
 

Pharmacologic insults are just so massive and normal metabolism and physiology so deranged that no mere mortal can make a meaningful intervention. The seriously poisoned who maintain vital signs in the ED have the best, albeit never guaranteed, chance of rescue from a modicum of antidotes and intensive supportive care.[7]

 

Maybe we should find out what we are doing and not blindly throw kitchen sinks at dead people based on hunches.

Dr. Brooks Walsh gave a good review of the evidence in his article written three years ago.[8]
 

What about my original questions?

Should we treat hypoglycemia in a dead person?

There is no evidence that giving dextrose is safe or effective for any cardiac arrest patients.

How do we determine hypoglycemia in a dead person?

We guess or check a capillary blood sugar, which is not reliable.

Is there any evidence that giving dextrose, in any concentration, resuscitates a dead person?

No.
 

Go read Using Dextrose in Cardiac Arrest at Mill Hill Ave Command.
 

Footnotes:

[1] Bleaching away what ails you
Science-Based Medicine
David Gorski
May 28, 2012
Article

[2] Cardiocerebral Resuscitation: An Approach to Improving Survival of Patients With Primary Cardiac Arrest.
Ewy GA, Bobrow BJ.
J Intensive Care Med. 2014 Jul 30. pii: 0885066614544450. [Epub ahead of print]
PMID: 25077491 [PubMed – as supplied by publisher]

[3] Cardiocerebral resuscitation is associated with improved survival and neurologic outcome from out-of-hospital cardiac arrest in elders.
Mosier J, Itty A, Sanders A, Mohler J, Wendel C, Poulsen J, Shellenberger J, Clark L, Bobrow B.
Acad Emerg Med. 2010 Mar;17(3):269-75.
PMID: 20370759 [PubMed – indexed for MEDLINE]

Free Full Text from Academic Emergency Medicine.

[4] Cardiac Arrest Management is an EMT-Basic Skill – The Hands Only Evidence
Fri, 09 Dec 2011
Rogue Medic
Article

[5] Management of Cardiac Arrest
2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science
Part 8.2: Management of Cardiac Arrest
Overview
Free Full Text from Circulation.

[6] Effect of epinephrine on glucose metabolism in humans: contribution of the liver.
Sherwin RS, Saccà L.
Am J Physiol. 1984 Aug;247(2 Pt 1):E157-65.
PMID: 6380304 [PubMed – indexed for MEDLINE]

[7] Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Emergency Medicine News:
October 2011 – Volume 33 – Issue 10 – pp 16-18
doi: 10.1097/01.EEM.0000406945.05619.ca
InFocus
Roberts, James R. MD
Article

[8] Using Dextrose in Cardiac Arrest
Wednesday, March 14, 2012
Mill Hill Ave Command
Dr. Brooks Walsh
Article

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Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest

ResearchBlogging.org
 

This study is interesting for several reasons.

In a system that claims excellence, the most consistent way to identify the study group is by documentation of a protocol violation – but it is not intended as a study of protocol violations.

This may hint at some benefit from epinephrine (Adrenaline in Commonwealth countries), but that would require some study and we just don’t study epinephrine. We only make excuses for not studying epinephrine.

The atropine results suggest that the epinephrine data may be just due to small numbers, or that we may want to consider atropine for drug overdose cardiac arrest patients, or . . . .

The Sodium Bicarbonate (bicarb – NaHCO3) results suggest a flaw in EMS education (probably testing, too). If the patient is acidotic, this is one type of cardiac arrest where hyperventilation may be beneficial. Bicarb is the part of the drug that doesn’t do much, especially if the patient is dead. The sodium is what works, such as when the patient has taken too much of a sodium channel blocker, such as a tricyclic antidepressant or a class I antiarrhythmic. Acidosis is treated by hyperventilation. Use capnography.

Most important – antidotes probably don’t work as expected during cardiac arrest. Not even naloxone (Narcan).
 

Despite clear differences in the etiology of suspected OD [OverDose] and non-OD OHCA [Out of Hospital Cardiac Arrest], the International Liaison Committee on Resuscitation guidelines published in 2010 do not specify different treatments for suspected OD-OHCA patients during resuscitation,and state that there is no evidence promoting the intra-arrest administration of the opioid antagonist naloxone.8 [1]

 

What did they find in the study?

They may have located the highest concentration of heroin overdose in the country. 93% of OD-OHCA patients were treated with naloxone.
 

We relied on either naloxone administration or clear description of circumstantial evidence in the PCR [Patient Care Recod] to identify a suspected OD. Clear descriptions are also rare, and most (93%) of the cases were identified by naloxone administration. Naloxone during cardiac arrest is not part of any regional protocol, and all of these administrations are deviations from recommended practice. There may be other cases in which paramedics suspected OD, but did not deviate from protocol to administer naloxone. Therefore, it is impossible to be certain whether the actual number of OD cases is larger or smaller than the reported number. However, the use of naloxone as a proxy indicator of suspected OD has been supported in the literature.11 [1]

 

The EMS approach to naloxone still appears to be –
 


Image credits – 123
 

These results seem to show better response to the prehospital drugs in the OD-OHCA patients, but that ignores the ROSC (Return Of Spontaneous Circulation) rates.
 


Click on images to make them larger.
 

Why would OD-OHCA patients do better than non-OD-OHCA patients if they get a pulse back?

The average non-OD-OHCA patient is 20+ years older. These older patients may not be as capable of recovery nor as capable of tolerating the toxicity of the drugs they were treated with.

The change after ROSC is dramatic. Is that the important point of this study?

Are they doing anything special for OD patients in the hospital, or is it just a matter of That which does not kill me by anoxic brain damage, may allow me to recover twice as often as a typical cardiac arrest patient.
 

Do drugs (antidotes, antiarrhythmics, . . . ) work the same way in dead people as in living people?
 

Pharmacologic insults are just so massive and normal metabolism and physiology so deranged that no mere mortal can make a meaningful intervention. The seriously poisoned who maintain vital signs in the ED have the best, albeit never guaranteed, chance of rescue from a modicum of antidotes and intensive supportive care.[2]

 

We should understand that normal metabolism is irrelevant to cardiac arrest.

We should understand that we do not need to ventilate adult cardiac arrest patients, when the cause is cardiac. An absence of ventilation would not be appropriate in a living adult, but dead metabolism is not normal. If something as basic as oxygen changes, when the patient is dead, how much less do we understand the behavior of other drugs in dead patients?

Footnotes:

[1] Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest.
Koller AC, Salcido DD, Callaway CW, Menegazzi JJ.
Resuscitation. 2014 Jun 26. pii: S0300-9572(14)00581-4. doi: 10.1016/j.resuscitation.2014.05.036. [Epub ahead of print]
PMID: 24973558 [PubMed – as supplied by publisher]

[2] Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions
Emergency Medicine News:
October 2011 – Volume 33 – Issue 10 – pp 16-18
doi: 10.1097/01.EEM.0000406945.05619.ca
InFocus
Roberts, James R. MD
Article

Roberts, J. (2011). InFocus: Dissecting the ACLS Guidelines on Cardiac Arrest from Toxic Ingestions Emergency Medicine News, 33 (10), 16-18 DOI: 10.1097/01.EEM.0000406945.05619.ca

Koller, A., Salcido, D., Callaway, C., & Menegazzi, J. (2014). Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest Resuscitation DOI: 10.1016/j.resuscitation.2014.05.036

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Is It Wrong To Medicate To The Point Of Needing Ventilation – Question from mpatk


Image credit.
 

In the comments to Where is the Line Between Good Pain Management and Bad, mpatk write the following –
 

To clarify, would you consider it acceptable to sedate to the point of requiring assisted ventilation for a sufficiently painful injury (e.g. multiple long bone fx’s)?

 

I have not needed to ventilate any of these patients, but I have added oxygen to keep some patients’ oxygen saturation above 93%.

Would it be wrong to medicate to the point of needing to ventilate?

There was a time when I would have taken the position that this is an indication of bad pain management/bad sedation, but I no longer agree with that.

We are there to provide appropriate care for the patient, not appropriate care for the patient up to the point of needing to assist with ventilation.

Most medical directors will probably disagree with me, but medical directors are getting better at encouraging appropriate pain management and sedation.

You, and I, do not have access to ketamine, but ketamine would be the ideal drug for many painful injuries. Ketamine provides sedation, analgesia, and dissociation, but generally does not cause any respiratory depression. Ketamine can occasionally cause laryngospasm, but that is easy to manage. I need to follow up on some earlier posts on ketamine and laryngospasm.[1],[2],[3]

But we do not have ketamine. should our patients suffer because we do not have the best drug for these patients?

No.

What is going to happen in the hospital?

The patient is going to need surgery, which generally involves ventilation through an endotracheal tube, or an LMA (Laryngeal Mask Airway). We could anticipate that and place an airway for ventilation.

We could give tiny titrated doses of naloxone (for suspected opioid-induced hypoventilation) and/or tiny titrated doses of flumazenil (for suspected benzodiazepine-induced hypoventilation).

This problem is not a lack of oxygenation, because we could treat that with a higher concentration of oxygen. This is a problem of inadequate removal of CO2 (Carbon DiOxide), or it is a combined problem of hypoxia and hypercarbia.

There is a discussion of procedural sedation by Dr. Al Sacchetti that is essential listening for anyone who provides sedation and/or pain management.[4]

Why should paramedics listen to this? Because this is important material to understand to be good at sedation and pain management.

Pay attention to the whole presentation, because Dr. Sacchetti makes some excellent points.

Most relevant to what I am writing is what he says from 27:00 to 28:15.

Would an LMA have been more appropriate? Maybe. Maybe not.

At 29:30 Dr. Sacchetti says –
 

The medication with the lowest complication rate is . . .
 
Propofol (Diprivan)?

Midazolam (Versed)?

Ketamine (Ketalar)?

Morphine?

Hydromorphone (Dilaudid)?

Fentanyl (Sublimaze)?

What do you think was the safest drug (lowest complication rate)?
 

 

 

 

 

 

 

 

 

 

ketamine.
 

Zero major complications.
 

At 30:00 he puts the safety of fentanyl and etomidate (EMS medications) in perspective, when compared with ketamine and propofol, which are often considered too dangerous for EMS.
 

Fentanyl has the highest complication rate followed by etomidate.
 


This list is in alphabetical order, not in order of complications, or number of patients, or . . . .
 

Perspective is important.

Airway management skill is essential.

Limiting EMS to the least safe medications does not protect patients.

Footnotes:

[1] Laryngospasm, hypoxia, excited delirium, and ketamine – Part I
Thu, 21 Jun 2012
Rogue Medic
Article

[2] Laryngospasm, hypoxia, excited delirium, and ketamine – Part I
Mon, 25 Jun 2012
Rogue Medic
Article

[3] Serious adverse events during procedural sedation with ketamine – Part I
Thu, 27 Sep 2012
Rogue Medic
Article

[4] Al Sacchetti: Procedural Sedation in the Community ED
April 28, 2010
Free Emergency Medicine Talks
Al Sacchetti
Page with free download of presentation in mp3 format.

The reference is to the ProSCED registry, which is described in the papers below – both are free.

Procedural sedation in the community emergency department: initial results of the ProSCED registry.
Sacchetti A, Senula G, Strickland J, Dubin R.
Acad Emerg Med. 2007 Jan;14(1):41-6. Epub 2006 Aug 31.
PMID: 16946280 [PubMed – indexed for MEDLINE]

Page With Free Full Text in PDF Download format from Academic Emergency Medicine. Click on Get PDF (97K).
 

The safety of single-physician procedural sedation in the emergency department.
Hogan K, Sacchetti A, Aman L, Opiela D.
Emerg Med J. 2006 Dec;23(12):922-3.
PMID: 17130600 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central.

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Is that Aspirin or Acetaminophen? Recall Due to Wrong Drug in Packages

 

Last week the FDA (Food and Drug Administration) sent out a safety announcement about a recall of Rugby label Enteric Coated Aspirin Tablets, 81 mg, Lot 13A026.
 


 

The package does not contain 81 mg aspirin, but actually contains 500 mg acetaminophen (Tylenol), which is a much larger dose and is in many other over the counter medicines, such as cough and cold medicines. Almost all of these medicines contain a full adult dose of acetaminophen in addition to whatever the active ingredient is (guaifenesin, dextromethorphan, et cetera).
 

Consumers may be inadvertently taking Acetaminophen 500 mg instead of Enteric Coated Aspirin 81 mg which may cause severe liver damage to those who take other drugs containing acetaminophen, consumers who take 3 or more alcoholic drinks every day, or those who have liver disease. The labeled directions instructs patients to take 4-8 tablets every 4 hours, but not more than 48 tablets in 24 hours. Consumers who take 48 tablets daily of the defective product may be ingesting up to 24,000 mg of Acetaminophen, which is about six times the maximum recommended daily dose of acetaminophen (4,000 mg).[1]

 

Taking more acetaminophen than needed is not safe because of this duplication of doses. The liver may be able to remove the current amount of acetaminophen we are consuming (intentionally and unintentionally), but an extra half gram of acetaminophen may result in a toxic dose.

Some people only take 81 mg enteric coated aspirin on a daily basis for its antiplatelet effects, but the package recommends a lot more.

 

“It’s not an uncommon overdose,” said Dr. Corey Slovis, who heads the department of emergent medicine at Vanderbilt University Medical Center in Tennessee. “We hate Tylenol overdose because they’re the silent overdoses.”

Slovis said patients who overdose on acetaminophen often don’t feel sick right away, unless they’ve taken a massive dose that induces vomiting within six hours. Instead, many patients who overdose on acetaminophen don’t see a doctor for more than two days because they feel fine at first. When they finally get to Slovis, they’re often jaundiced and experiencing the early signs of liver failure.

As such, this kind of overdose could result in liver failure, the need for a transplant or death, Slovis said.[2]

 

The pills are probably larger than the normal aspirin pills, but if you are unfamiliar with the product, you would not recognize the difference. Taking a handful (4-8 tablets every 4 hours, but not more than 48 tablets in 24 hours) of pills at a time is probably not a good idea, regardless of the label instructions.

“Did he take six pills or only five?” Well, to tell you the truth, in all this excitement I kind of lost track myself.[2]

We have trouble counting beyond three.

Footnotes:

[1] Advance Pharmaceutical Inc. Issues Voluntary Recall of One Lot of Enteric Coated Aspirin Tablets, 81 mg, Due to Health Risk
Recall – Firm Press Release
FDA
Recall notice

[2] Aspirin Recalled Over Bottle Mix-Up
Sydney Lupkin (@slupkin)
ABC News
Article

[3] Dirty Harry (1971)
Quotes
IMDb.com
Quote

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Looks Like Anaphylaxis, But Isn’t

ResearchBlogging.org
 

Half an hour after lunch, a 67 year old man passes out.

He regains consciousness, as often happens with syncope.

He is not quite back to normal, blood pressure is 80/60 mm Hg, heart rate is 110, respiratory rate is 25, oxygen saturation is 99% on room air, with a temperature of 96.8° Fahrenheit.

If we tilt him, we will probably get a worsening of his vital signs, but there is no need to actually obtain the numbers if the assessment is causing deterioration.
 

Medical examination was only remarkable for diffuse erythema on his chest and face, without mucosal swelling or pruritus. Anaphylaxis was nonetheless suspected, and the patient immediately received intravenous epinephrine (0.1 mg) and aggressive intravenous fluid resuscitation.[1]

 

It reads as if this looks like a sunburn, which anaphylaxis sometimes does. He was treated for anaphylaxis. As it turns out, this is not anaphylaxis, but the treatment is not much different.
 

Worsening circulatory failure required high-dose (0.8 μg/kg per minute) norepinephrine infusion.[1]

 

His 12 lead also shows that his body is not happy.
 


 
Click on the image to make it larger/clearer.
 

ST segment depression almost everywhere. ACS (Acute Coronary syndrome)?

Catecholamines (epinephrine, norepinephrine, dopamine, dobutamine, isoproterenol, metaproterenol, albuterol, . . . ) can increase the stress on an infarcting heart and make an ACS worse, but he had no other indications of a heart attack.
 

Further interrogation revealed that the patient erratically self-medicated with disulfiram and that he had ingested 500 mg of disulfiram 1 hour before alcohol intake.[1]

 

Disulfiram (Antabuse) is used by some people with problems avoiding alcohol as a means to discourage consumption of alcohol. This patient consumed 500 ml (a little more than a quart) of wine with his lunch, so there may be a lack of understanding of how the medication works.
 

The patient was discharged home the day after, without any medication. The diagnosis of severe “disulfiram ethanol reaction” (DER) was retained.[1]

 

Direct alcohol consumption is not the only way that DER (Disulfiram Ethanol Reaction) can present.
 

The detailed personal history revealed that he was an alcoholic of 5 years and was started on disulfiram 100 mg daily for deaddiction since 9 months. His previous medical report revealed frequent medical consultation for palpitation, chest discomfort, paresthesia, and easy fatigability after initiation of deaddiction. His old records showed no detectable blood alcohol levels. On further interrogation, it was noticed that he was exposed to variety of solvents such as metal paints, thinners, varnish removers, and polish containing methanol, ethanol, isopropyl alcohol, and toluene for about 8 to 12 hours a day and 6 days a week in view of his occupation.[2]

 

There are other documented cases of occupational exposure leading to DER. An explanation of the way occupational exposure with disulfiram works is available in the discussion of another case from Oxford Journals.[3]
 

Our case emphasizes the need to include drug interaction in the differential diagnosis of any shock, to avoid unnecessary and invasive procedures or therapeutics. Especially, DER should be suspected in an alcoholic patient presenting with miscellaneous manifestations mimicking anaphylaxis, complicated myocardial infarction, or toxinic shock.[1]

 

The authors finish with a statement that is extremely important.
 

the potential severity of adverse side effects of drugs indicates that any medication should be carefully scrutinized for potential pharmacokinetic and pharmacodynamic interactions that may result.[1]

 

How many of us understand the possible drug interactions we are creating when reflexively treating patients according to protocol?

Footnotes:

[1] Disulfiram ethanol reaction mimicking anaphylactic, cardiogenic, and septic shock.
Bourcier S, Mongardon N, Daviaud F, Moachon L, Arnould MA, Perruche F, Pène F, Cariou A.
Am J Emerg Med. 2013 Jan;31(1):270.e1-3. doi: 10.1016/j.ajem.2012.05.002. Epub 2012 Jul 16.
PMID: 22809767 [PubMed – indexed for MEDLINE]

[2] Antabuse reaction due to occupational exposure-an another road on the map?
Senthilkumaran S, Menezes RG, Ravindra G, Jena NN, Thirumalaikolundusubramanian P.
Am J Emerg Med. 2013 Jun 18. doi:pii: S0735-6757(13)00297-0. 10.1016/j.ajem.2013.05.022. [Epub ahead of print] No abstract available.
PMID: 23791458 [PubMed – as supplied by publisher]

[3] Disulfiram reaction in an artist exposed to solvents.
Ehrlich RI, Woolf DC, Kibel DA.
Occup Med (Lond). 2012 Jan;62(1):64-6. doi: 10.1093/occmed/kqr172. Epub 2011 Nov 7.
PMID: 22068046 [PubMed – indexed for MEDLINE]

Free Full Text from Oxford Journals.

Bourcier S, Mongardon N, Daviaud F, Moachon L, Arnould MA, Perruche F, Pène F, & Cariou A (2013). Disulfiram ethanol reaction mimicking anaphylactic, cardiogenic, and septic shock. The American journal of emergency medicine, 31 (1), 2700-3 PMID: 22809767

Senthilkumaran S, Menezes RG, Ravindra G, Jena NN, & Thirumalaikolundusubramanian P (2013). Antabuse reaction due to occupational exposure-an another road on the map? The American journal of emergency medicine PMID: 23791458

Ehrlich RI, Woolf DC, Kibel DA. (2012). Disulfiram reaction in an artist exposed to solvents Occup Med (Lond)., 62 (1), 64-66 DOI: 10.1093/occmed/kqr172

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