While being sick at home and still working on diuretics in Acute Pulmonary Edema I thought to myself, why not post something I have already finished but never put on the internet. (Better lazy then tired as we say in Holland ) Sadly I found that most of it has to be translated into English, except for the following “poster”.

One of my great residents (Annemarie v/d/ Velden) was interested in morphine and benzodiazepines for the relief of acute dyspnea. Opiates have traditionally been used as one of the main treatments of acute dyspnea and are still recognized as such. Most current textbooks and official guidelines advise the use of morphine as one of the first-line treatments for patients in acute dyspnea and a majority of physicians accept it to be the case. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. For me this was something you never think about and it just works….but does it really???

Here is what we did and the results we found:

We performed an extensive literature search in order to validate the evidence for the use of opiates and benzodiazepines in acute dyspnea. An electronic search was carried out of Medline, Embase and The Cochrane Library. The primary search key used was dyspnea, the secondary and tertiary were morphine and benzodiazepine. Limits were set to Humans and Adults, and articles had to be published in English, German or Dutch. Review articles and reference lists of retrieved articles were hand searched. A total of four papers, all in English, were found that directly investigated or reported the clinically important outcomes of treatment of acute dyspnea. Two of these papers were Cochrane Collaboration Review Articles, both relatively recently updated. The full text of the relevant studies were retrieved and data were independently extracted by the authors. Studies were quality scored according to the Oxford Quality Scale.

Author, date Patient group Study type Key Results Study weaknesses
and country

Jennings AL 293 patients with review article The meta-analysis showed Retrospective.
2002, GB dyspnea of any cause (Cochrane) statistically significant No comment on potential
(18 RCT included) positive effect of benefit of opioids in
non-nebulised opioids on relation to the causes
the sensation of breathlessness.
breathlessness. Small doses of morphine
The clinical effect appears
to be relatively small.

Simon ST et al., 200 patients with review article No beneficial effect of Retrospective
2010, Germany advanced stages of (Cochrane) benzodiazepines for relief 1 study was not included cancer, COPD, CHF*, (7 RCT were included) of breathlessness in in meta-analysis because
MND* and IPF* patients with advanced of inappropriate
cancer or COPD presentation of data
Different studies studied
different benzodiazepines

Sosnowski MA, 589 patients with review article There is no evidence Retrospective
2008, Australia APO* (5 studies were included) supporting the use of Heterogeneous groups opiates in the treatment
of APO.

Peacock WF et al., 147362 patients with retrospective analysis Morphine is associated with Retrospective
2008, USA ADHF* increase adverse events in Heterogeneous groups
ADHF** Unclear when morphine
was given
No follow up

PPP Blood gassesHi everyone,

Last week our ED registrars hosted a really good day of education for their colleagues in the surrounding hospitals. I was asked to give a workshop on blood gas. During the MNSHA masterclass I enjoyed the discussion about arterial versus venous, and decided to share that with our colleagues-to-be. Just for starters, hope I made some of them curious enough to search for details. But I started with the alveolar gas equation, to explain how we can assess if the lungs are properly transferring oxygen into the blood.
I have put my slides on our website so you can use them.

Gr. Laura

Hello, I ‘caught’ a really cool ECG last week..don’t want to withhold you this one. Post your ideas and I will give you the patient story later on..

Greetings, Dorien

Hi everybody, welcome back on EMDutch. As promised I am working on “diuretics in AHF” right now. To be honest, it doesn’t seem to be the cornerstone of treatment in my mind, but that will be discussed in my next post. Because these CAT’s (“critical approved topics”) take a lot of time I thought it would nice to present a case for you today!
Every doctor in his career will encounter patients he or she will never forget. Sometimes because of their appearance, attitude or disease, but in this case it was the outcome……DEAD! And off course we often see people die in the ED. And off course you kind of get used to it. And off course it’s part of the job. But when an otherwise healthy men, 50 years of age, dies a couple of hours after you have seen him it tends to stick! Getting interested??? Just read the case below. Hopefully you will learn something from it and otherwise you can always e-mail/tweet/post me what a bad job I did! Please don’t scroll to the end, but test yourself and try to find what I missed, while reading the case!

So this 50 year old men was seen by one of my colleagues in the ED with acute onset of chest pain without radiation. He has hypertension in his medical history and had no prior episode of chest pain. He was hemodynamically stable. His ECG showed minimal ST-elevation in V2-V3 and an inverted T-wave in III and aVF. On the chest X-ray a slightly widened mediastinum was found which was explained by the technique of the photo. The cardiac enzymes were negative and he was admitted for chest pain with low molecule heparin and ASA.
The ergometric stress test showed no ischemic response and ultrasound of the heart showed a slighty widened aorta ascendens (44mm) and a bicuspid aorta valve. He developed abdominal pain with fever and an elevated WBC and CRP and was transferred to internal medicine. The abdominal ultrasound performed showed no pathology.
On the 3rd day he got a second episode of severe chest pain, which was almost gone when I came to take a look at the patient. I was in my first year and did my rotations in cardiology. Like with every chest pain patient in the house I was called to take a look at the patient. He looked fine and was hemodynamically stable. There were new changes on the EKG this time (see below). And because I was in Emergency Medicine I knew Amal Mattu (really, who doesn’t???)….and when you know him, you know EKG’s…and in this case pericarditis. The EKG showed ST-elevations in multiple leads, so I asked myself the 3 questions to differentiate between pericarditis and MI:
1.) Is there any ST-depression (beyond aVR & V1)  No (we can debate about lead III & aVF, but it was exactly the same as in the 1st EKG.)
2.) Is there ST-elevation covex upwards or horizontal  No
3.) ST-elevation III>II  No
THIS MEANS NO MI, IT MEANS PERICARDITIS!

SR, 65/min, 1st degree AV-block, concave ST elevation I, aVL, V2-V5, inverted T wave III, aVF and aVR

He got NSAID’s next to the antibiotics he already was given and his symptoms disappeared. But….In the 5th night the patient suddenly died.
So what did I miss? I had no idea! Was it a MI after all, was it a PE….or was it something else??? Well, it was something else! Autopsy showed an aortic dissection type A with massive hemopericardium.

So where did I go wrong and what were the clues I missed? In retrospect there were 3 (and if you more, please let me know!):
1.) 1 diagnosis is just 1 diagnosis, but maybe not the whole diagnosis. Pericarditis may present as a sudden sharp pain, but other causes like MI, PE, GERD and dissection has to be in your mind. It wasn’t in mine. I stopped at the 1st diagnosis! Boy, did I learn my lesson!
2.) In 1987 Saner He, et al (1) already describes 5 cases in which pericarditis was the 1st sign of aortic dissection (type A). The hypothesis is that slow pentration of blood into the pericardial space causes inflammation. It’s striking that 2 of these cases had a bicuspid aortic valve, just like our patient. Even before 1987 Edwards (in 1978) already describes the relation between dissection and bicuspid valve (2) In my defence….at the time I had no knowledge of this and it’s sad to figure this out when it’s too late for the patient.

3.) This patient had chest- and abdominal pain. So he had pain above and below the diaphragma. Like somebody recently told me (I know…too little too late!)….think dissection ! One article showed that in dissection 67% has chest pain, 84% had sudden onset of any pain and 23% had abdominal pain (and 64% has a history of hypertension !!!) (3)

In conclusion:
An aortic dissection is a difficult diagnosis to make. That’s why it is important to know it can initially present as a pericarditis. There is often a ‘therapeutic window of treatment’, which means you have time on your side to get to the correct diagnosis in time.
This case doesn’t justify a CT with every patient presenting in the ED with a pericarditis, but in retrospect our patients had some signs which could have led to the correct diagnosis. He had a widened mediastinum and a bicuspid aortic valve which is a known risk factor for aortic dissection. Futhermore he has chest- and abdominal pain !

Ok….hopefully you have enjoyed reading this case and remember….aortic dissection is ‘the great masquerader’ and you will miss some in your carreer, but maybe this can help you to find more aortic dissection in your carreer! Good luck!

Until next time !

Egon Zwets

References:
1.)
Chest. 1987 Jan;91(1):71-4.
Aortic dissection presenting as pericarditis.
Saner HE, Gobel FL, Nicoloff DM, Edwards JE.

2.)
Circulation. 1978 May;57(5):1022-5.
Dissecting aortic aneurysm associated with congenital bicuspid aortic valve.
Edwards WD, Leaf DS, Edwards JE.

3.)
JAMA. 2002 May 1;287(17):2262-72.
Does this patient have an acute thoracic aortic dissection?
Klompas M.

Welcome back on the EMDutch website….the website talking about emergency medicine below sealevel. And because we, the people living below sealevel (It sound more scary than it is), use nitroglycerin (NTG) for acute decompensated heart failure, that is what we will be mainly talking about. I know there are other vasodilators out there, like nitroprusside and nesiritide, but for us NTG is the vasodilator/nitrate of choice!

Nitroglycerin is a nitrate that causes venodilation at low doses and arterial dilation at higher doses. (1) There is little doubt about its effectiveness in AHF and it lacks significant side effects (2), but its use is limited by marked underdosing in clinical practice. (3) And this is so true in my own hospital! Nurses and fellow doctors are used to giving 150ug/h in stable chest pain patients, which they can titrate up to 500 ug/h. In acute heart failure (with a normal-high blood pressure) this is just not enough. You have to be aggressive, don’t be scared and treat your patient! They want to be treated…fast! An infusion rate I found in the literature (4) is: start at 10-20 ug/min and titrate upward in stepwise fashion using 10-60 ug/min, looking at improvement of symptoms, development of side effects, change of blood pressure, or a maximum dose of 200-500ug/min!!! Elkayam, et al (5) found…and I quote: “The potential benefit of nitroglycerin seems to be limited by a decreased vasodilatory response in patients with heart failure, which requires an active titration of the drug and the use of high doses (>120 ug/min). In addition, the initial beneficial hemodynamic effect achieved with the appropriate dose of nitroglycerin is associated with neurohumoral activation and limited by an early development of nitrate tolerance that leads to a marked attenuation of the initial effect.”

As been said above, there is little doubt about its effectiveness in AHF. Why is that? Most studies of the role of NTG in AHF are limited to small-cohort hemodynamic evaluations without cardiovascular outcome data. (1) These studies showed benefit from nitrate therapy in terms of decreased pulmonary capillary wedge pressure, increased cardiac output and increased cardiac index. (6) But is this where I am really interested in? No! I am interested in 2 things, does it cause symptom relieve and does it decrease mortality/morbidity?

First the symptom relieve:
Cottor, et al (7) found and improvement in pulse rate, respiratory rate and O2-saturation in the high dose nitrate + low dose furosemide group, when compared to the high-dose furosemide + low dose nitrate group, indicating that these patients (probably) feel better and less dyspnoeic. On the other hand, the VMAC trial of nesiritide (8), which used relative low doses of NTG!! (mean 41 +/- 61 ug/min) resulted in a decrease of 3.8 mmHg of PCWP, but no significant improvement of dyspnea was found when compared with placebo.

On mortality and morbidity a good powered study is still lacking. The study by Cottor did show a lower rate in death (and mechanical ventilation and MI) in the high-dose nitrates + lowe-dose furosemide group.

So where do we stand on NTG (nitrates) in AHF?A lot of its use has been based on small-cohort hemodynamic evaluations and the ESC guideline states that only 2 (I could only find the article by Cottor, et al, but apparently there is another trial) randomized trials have established the efficacy of i.v. nitrates in combination with furosemide and have demonstrated that dose titration to the highest haemodynamically tolerable dose of nitrates is superior to furosemide alone. There are no outcome trials with NTG vs placebo, and given the low cost and availability of NTG, it is unlikely that a study like this will be preformed.

In conclusion, I couldn’t find the evidence I was hoping for. In my mind NTG is a incredibly good medication for AHF without hypotension. Like all you folks out there I have seen it work and would expect to find tons of evidence supporting it. I did find the article by Cottor, indicating that high-dose nitrates with low-dose furosemide is better than the other way around and this what I was expecting to find!
In my mind, based on 5 years of clinical practice (yes, yes, only 5 years, I am still pretty young) and what I have read about it, NTG (along with NIV) is the cornerstone of treatment and maybe, just maybe, furosemide shouldn’t even be in there, but that will be discussed next time!

So remember, in normo-/hypertensive patients with AHF, be aggressive with the NTG and titrate upward fast!

Until next time and let me know if you have any comments!

Egon Zwets

List of references

For all our national and international colleagues, wishing you a lot of love for 2013.

I want to ask you to put links in comments to this post for the EP’s that appeared in a radio or tv interview about new-years eve events on your ED!

Laura Kater

Radio 1: 1 jan 05.06h RKZ Beverwijk: http://www.radio1.nl/terugluisteren/tijd?terugluisteren_dag=2013-01-01&terugluisteren_hour=5

The next post is written by one of my great assistants, who is really an EKG-nerd! I hope you like it! Please respond if you have any comments and myself (Egon) and Iwan will take a look at it!

—–

Have a look at this EKG. Go on, you know you want to!

What is the rhythm and what would be your treatment ?

At first glance it looked like an AVNRT (atrioventricular nodal reentrant tachycardia) to me and I had adenosine drawn up. But let’s be a good boy and follow the diagnostic tree from the ESC guidelines:

- Narrow ? Check.
- Tachycardia ? Yup.
- Visible P waves ? Hum, that’s a little tricky… Have a closer look:

Hey, what would you know, there do appear to be some funny looking p waves!

Atrial rate greater than ventricular rate ? It would seem so

Guess that makes it atrial flutter or atrial tachycardia.

Before we could do anything the rhythm spontaneously changed:

So what is the rhythm now? The computer seems to think it’s atrial flutter with a 2:1 atrioventricular block. (And we all know artificial intelligence beats natural stupidity.)

P waves are best seen in V2. Check it out:

2:1 block indeed but the PP segment is fairly straight, so no flutter.

And so my dear Watson, when all else is excluded the rhythm that remains must be the truth:

Paroxysmal atrial tachycardia (PAT) with block!!!
Although non sustained atrial tachycardia (AT) is frequently seen on Holter, sustained focal AT is actually relative rare.

In 1960 Lown. et al established following diagnostic criteria for PAT:

- abnormal P waves with a different morphology from the sinus P waves
- atrial rate between 150 and 250 bpm
- isoelectric intervals between P waves in all leads

The location of the ectopic atrial focus can be surmised from the P wave morphology:

a positive or biphasic P wave in aVL usually indicates a right atrial focus
a positive P wave in V1 usually indicates a left atrial focus

Mechanism:
increased automaticity of an ectopic atrial focus (gradual onset and termination)
triggered by ‘delayed afterdepolarization’ (especially seen digitalis intoxication)
micro reentry

Precipitating factors:
cardiac abnormalities
digitalis intoxication (especially AT with AV block)
hypokaliemia

Treatment:
Our patient received iv metoprolol which reduced the rate only marginally and because of persistent symptoms we ended up electrically cardioverting the patient back to sinus rhythm.
I wonder what would have happened if we had given the adenosine I had drawn up initially ? At the very least it would have slowed AV conduction and thereby revealing the atrial tachycardia, but apparently it could also have converted the patient. In fact, it is a IIa recommended treatment for AT according to the ESC as can be seen in the table below:

But hold on there for one freaking minute, young Padawan! I thought adenosine only caused a short AV block and surely the AV node is not part of an atrial tachycardia! How could it possibly convert AT ?

Adenosine has 2 mechanisms of action:
- it interacts with A1 receptors which increases potassium conductance, shortens the action potential and hyperpolarizes the membrane. This effect happens in both atrial and AV node tissue, but is absent in ventricular tissue.
- an indirect anti-adrenergic effect which decreases intracellular cAMP and inhibits calcium influx.

Triggered arrhythmias are thought to arise because of intracellular calcium overload and cAMP dependent. This is why adenosine can terminate triggered AT (and some forms of VT, since the anti-adrenergic effect is not tissue specific!). AT due to enhanced automaticity usually will only be transiently suppressed in response to adenosine.

Prognosis of AT is usually excellent but persistent forms may lead to tachycardia induced cardiomyopathy.

Hope you enjoyed this EKG case and remember: life will not break your heart, it will crush it!

Iwan Dierckx

Casus1

Anybody any other suggestions?