Standing on the corner, minding my own business in the ER

Evidence Based Management of Acute Heart Failure: Forget LMNOP, think POND!

KimJong

Case:

Imagine you are an attending ED physician supervising a learner.

A 72 year old female presents to the ED with cough and shortness of breath worsening over a week.  She has a history of Afib, previous MI, diabetes and dyslipidemia.  She has recently been non-compliant with her meds and has been taking some ketorolac (damn you ketorolac) for her arthritis pain.  Tachycardic and hypertensive, the patient is in distress, but not about to die this second.

You’re medical student/resident assesses the patient and concludes the patient is suffering from acute decompensated heart failure (ADHF).

You ask what they would like to do, and it sounds something like this:

Lasix, morphine, nitroglycerin, oxygen, position (sit them upright).

The LMNOP mnemonic for acute CHF must be one of the all time most cited medical mnemonics. Most 1st and 2nd year medical students can rattle this one off without much difficulty (thanks a bunch, Toronto Notes!), but is LMNOP really all its cracked up to be?

LMNOP-CHFMeme

In this post,  I’m going to propose we replace the old LMNOP acronym with “POND”.   It’s shorter, it’s a word, and it puts the interventions in their actual order of benefit, as opposed to LMNOP which starts with crappy lasix and morphine.  Let’s talk about the evidence based management of acute heart failure.

POND

Positive Pressure/Position

Oxygen

Nitrates

Diuretics (Lasix)

The primary reference for this post is this article by Paul Marik (He of the famous “Seven Mares” CVP article and central line infection meta-analysis.  See my post on CVLs here) and Mark Flemmer in the Journal of Intensive Care Medicine. I would highly suggest everyone read this article!

Let’s look at the old LMNOP mnemonic letter by letter.

L – Lasix (furosemide)

First, some critical ward pimping trivia: Why is lasix called lasix?

Because it lasts six hours.  (True of po lasix.  IV is more like 2 hours)

More important clinically relevant question:

What level of evidence is the use of diuretics in ADHF?

Level C – Expert opinion! 2006 Heart Failure Society of America (HFSA) guidelines.

In the words of Joe Lex, lasix is “GOBSAT” – Good ole’ boys sitting around a table.

The biggest study of lasix in ADHF comes from Peacock et al. who looked at the ADHERE (Acute Decompensated Heart Failure National Registry – A registry of over 100,000 patients treated for ADHF) data in 2009.  They found patients receiving <160 mg furosemide in the first 24 hours in hospital had significantly less decline in renal function, length of stay, and in-hospital mortality (OR 0.87, 95% CI 0.78-0.97 p=0.01) when compared with patients receiving > 160 mg in the first 24 hours.

In a smaller but cooler study of 110 patients, Cotter et al. randomized 110 patients with cardiogenic pulmonary edema to high dose nitrates vs. high dose lasix, and found much higher rates of mechanical ventilation (21 in lasix group vs. 7 in nitrate group, p=0.0041) and MI (19 in lasix group vs. 9 in nitrate group, p=0.047) in the lasix group.  Admittedly, the lasix dosing in this study was very high, but as a proof of principle, I think this article helps provide the leeway to get studies using less diuretics past ethics review boards.

Below is a quote from Marik’s paper in which he details why lasix is unlikely to be beneficial in heart failure.

“It has been erroneously suggested that diuretic-induced changes in preload increase ventricular performance by 2 mechanisms, namely (i) by shifting the ventricle to a “more optimal position on the descending limb on the Starling Curve” or (ii) by reducing LV size and thereby reducing systolic wall stress (afterload) by the LaPlace effect. However, high-dose loop diuretics have a number of adverse effects in patients with HF, which include direct activation of the RAAS, increased arginine vasopressin (AVP), increased norepinephrine levels, decreased glomerular filtration rate (GFR), increased systemic vascular resistance, and electrolyte disturbances.”

There are many more references in Marik’s paper supporting nitrates in place of diuresis, going as far back as 1983.

So, am I proposing we stop diuresing ADHF patients?  No. 

Lasix stays in the acronym, but based on the above data, you can see why it now moves to last place in the POND (D for Diuresis) acronym.  There are other interventions that will work more rapidly, effectively and have more benefit for the patient.

M – Morphine

While lasix is a slightly controversial therapy, morphine is downright dangerous.  We’ll keep this short and sweet.

Again looking at the ADHERE registry data, morphine is an independent predictor of mortality (OR 4.84) and also carries an increased risk of intubation.  There is a reason morphine is a good drug for dyspnea in end-of-life care, it blunts the respiratory drive.  So don’t blunt the respiratory drive of your acutely ill heart failure patients. (Unless of course you want to palliate them, which is an appropriate conversation you should be having.)

N – Nitrates

Now were getting to the good stuff.  Nitrates are a mainstay of ADHF management, but unfortunately get way, way, way less love than lasix.  Whether it is spray, patch, tablet or infusion, getting nitro on board right away is a critical intervention for your heart failure patients.  To hear the virtues and practical use of nitrates espoused further, take a stroll down memory lane with EMCrit Podcast #1 by Mr. ED Critical Care, Scott Weingart. Holy crap, that was 4 years ago!

When looking at the literature, there are numerous articles referencing what are considered huge doses of iv nitrates, 200-400 mcg/min.  I find that practically, this is impossible if you ask a nurse to do it, as the rates are about 4x higher than what they are comfortable with.  The concept of a nitro infusion alone is unfortunately fraught with trepidation among many staff, including nurses, medical students, residents, etc. because of concerns about a precipitous drop in blood pressure.  However, many decompensated HF patients have a massive catecholamine surge, and have blood pressure to spare.  If you have a hypotensive HF patient, well, that kinda sucks.

As an example, earlier this year I had a nurse setup a nitro infusion, then I asked him to turn away while I blasted it at 200 mcg/min for a couple of minutes before turning it down.  Worked like magic, but there was no way the nurse would have done this for me.

I think the more practical way to do this is to spray 1-2 pumps of sublingual spray (400 mcg/spray) q5mins while setting up the infusion.  Nurses will have no problem doing this, and at that point you can start the infusion at a lower rate after your sublingual “boluses”.

O – Oxygen

There are no randomized controlled trials studying oxygen vs. no oxygen for ADHF!

I think we’ll all agree that it’s probably a good idea :)

P – Position AND more importantly, Positive Pressure Ventilation

However, this does lead into the two P’s, Position (upright) and Positive Pressure Ventilation, where there is evidence for CPAP over standard oxygen therapy.

This 2008 Cochrane Review included 1071 patients and found that NIPPV significantly reduced hospital mortality (RR 0.6, 95% CI 0.45 to 0.84) and endotracheal intubation (RR 0.53, 95% CI 0.34 to 0.83) with numbers needed to treat of 13 and 8, respectively.

Those are ridiculously good numbers, which is why CPAP is my #1 treatment for ADHF patients.  On my last CCU rotation, I was called every night about some crashing ward patient with hypoxemic respiratory failure from ADHF.  Every single time I would go to the ward, discuss code status, call a respiratory therapist and start CPAP.  Not one of those patients was intubated.  NIPPV rocks!

Note that CPAP is as good or better than BiPAP for heart failure because it is a problem of oxygenation.  BiPAP is only needed if there is concurrent hypercarbic respiratory failure, such as in combo CHF/COPD patients.

Note: As an aside, you should be aware that while hypoxia is bad, hyperoxia also has deleterious effects.  So, you don’t need to get that PaO2 up to 500 and blast those lungs with free radicals.

If you want to learn more about oxygen physiology, do a PubMed search for Daniel Davis from the University of San Diego.  You can also hear him discuss pulse oximetry lag on EMCrit episode 88 and the May 2012 EM:RAP podcast where he discusses hyperoxia in traumatic brain injury.

Post-publishing edit: Thanks to one of my readers who points out that NIPPV may not be quite as awesome as this Cochrane review suggests.  However, when applied early it is still an integral part of preventing intubation in these patients.

 

Bottom Line: Forget LMNOP, use POND instead!

Bond'sPond-Bellagio

Positive Pressure/Position

Oxygen

Nitrates

Diuretics (Lasix)

If you like POND, tweet the hell out of it!

Below is a table from Marik’s paper listing the evidence based beneficial and harmful therapies in ADHF.  There’s a lot more to discuss, particularly inotropes and beta-blockers, I’ll try to get to those in the future.

Cheers,

Chris

@socmobem

 

Pre-pub peer review by Brent Thoma (@boringem), Nadim Lalani (@ermentor), Danica Kindrachuk @Want2BeMD

 

References:

Marik PE, Flemmer M.  Narrative Review: The Management of Acute Decompensated Heart Failure. J Intensive Care Med. 2012 Nov-Dec;27(6):343-53

Cotter G, Metzkor E, Kaluski E, Faigenberg Z, Miller R, Simovitz A, Shaham O, Marghitay D, Koren M, Blatt A, Moshkovitz Y, Zaidenstein R, Golik A.Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema. Lancet. 1998 Feb 7;351(9100):389-93.

Peacock WF, Costanzo MR, De MT, et al. Impact of intravenous loop diuretics on outcomes of patients hospitalized with acute decompensated heart failure: insights from the ADHERE registry. Cardiology. 2009;113(5):12–19.

Vital FMR, Saconato H, Ladeira MT, Sen A, Hawkes CA, Soares B, Burns KEA, Atallah ÁN. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary edema. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD005351. DOI: 10.1002/14651858.CD005351.pub2.

EMCrit Podcast #1 http://emcrit.org/podcasts/scape/

EMCrit Podcast #88 http://emcrit.org/podcasts/oxygen-physiology/

EM:RAP May 2012 http://www.emrap.org/episode/2012/may/airwaycorner

Comments

  1. Hang on. You’re citing a Cochrane review that is essentially combines some shockingly bad studies. However, there is much crisper evidence to show: The C3PO study. A proper experiment – http://www.nejm.org/doi/full/10.1056/NEJMoa0707992

    Very notably, there are very few mortality-improving interventions in this patient group, that stand up to any scrutiny.

  2. Great post! I’ll be referring the medical registrars to this post and I think I’ll be saying to my juniors ‘POND for APO/CHF, but remember, the D is silent’ :)

  3. Seth Trueger says:

    Great post!

    I would add that if you are considering diuresis, at least wait until you get the creatinine back — after all, D comes after C

    • Good point, Seth. As Chris Edwards and Amal Mattu said, the D in POND is silent :)
      The question for us in the ER is whether we should even be using lasix in the acute stage?

      Chris

      • Seth Trueger says:

        I don’t think so. by the time it’s time to give lasix either it’s time to admit and the admitting docs can manage their fluid balance, which is appropriate because it’s a longer-term issue. Or, it’s time to go home, and if we dose em now they’ll pee themselves on the way home, so give an extra PO tab to take at home (tip from my chair in residency)

        Which brings me to:
        https://twitter.com/epmonthly/status/321641782926524417

  4. Chris,
    great post and nice review!
    High bolus-dose nitrates gets nurses queasy but please insist!
    Has been my usual approach these last years (ever since discovered on emcrit) if feasible in high BPs together with NIPPV.
    Usual bolus dose about 0,01 mg / kg i.e. 0,8 mg for 80 kg patient, delivered in 2-10 mins with rate depending on initial stability. Just tell them that it’s same dose as given po / sl and they’ll accept more easily and after succesfully repeating a few times they will start to insist with your collegues!
    Not sure about definite Lasix solution: certainly should be eradicated prehospital and that lasix-on-admission reflex. If used probably lower doses as usual and lateron, as you wrote, and only if fluid overload. Hard work ahead to continue convincing to change old habits!
    As far as Morphine is concerned:
    Evidence is clear for not using it. But as second step in bad adaption to NIV and bad cooperation because of subjective anxiety and dyspnea I sometimes used Fentanyl, microdoses of Midazolam and once or twice a small dose of Ketamine in the mix. Worked a treat! Everything second options, but goes for better adaption. Shortacting Fentanyl probably safe because of duration and really scarcely resp depressive.
    Any thoughts on these practices?

  5. Damon Tedford says:

    Started studying for our exam. I’ve now come back to this post and the references a few times. Thanks for sharing your work.

    Damon

  6. The Cotter 1998 study cited here isn’t really a great study to base management on. It didn’t just compare high-dose nitrates vs. high-dose diuretics. Nitrates were administered per protocol in both arms, so there’s no real control group in this study. The most recent Cochrane review on the topic of nitrates for acute heart failure syndromes (Cochrane Database Syst Rev. 2013 Aug 6;8:) couldn’t find strong evidence that they meaningfully improve symptoms or hemodynamic parameters. The other big study of nitrates was by Levy in 2007 (Ann Emerg Med. 2007 Aug;50(2):144-52.) was non-randomized. Not that they shouldn’t be used, but don’t think the evidence is as robust as some like to make it.

    • Hey ORA,

      Thanks for the comment. I agree with you, Cotter is not a direct comparison, although one group did receive a much bigger initial nitrate dose than the other. When it comes to robust evidence, you could argue that it doesn’t exist for many/all of the treatments in CHF. At least for nitrates there is some supportive evidence and better than evidence for early furosemide or morphine. Unfortunately the study of nitrates vs. no nitrates with no furosemide for either group probably wouldn’t pass ethics, and that really just leaves us with supplemental O2/NIPPV as a stand alone treatment. Cotter’s group was required to use furosemide for the study to be approved by ethics. At least we could probably do a study omitting furosemide now.

      The key point I’m trying to emphasize is that first line furosemide is archaic and the combination of initial NIPPV and nitrates will save countless intubations and probably lives. Diuretics and ACE inhibitors can be considered on an individual basis after the initial resus has taken place.

      Chris

  7. chris turner says:

    Hi- just been reading the new NICE guidelines for acute HF management and dismayed (and I know this is an inappropriately emotional response to a set of guidelines…) to see that furosemide is top of the list again. I strongly suspect this will be in part due to the Felker 2011 NEJM paper (low to high dose furosemide) which was given level 1B evidence status in the European Society of Cardiology guidelines 2012 for the use of furosemide in pulmonary oedema, despite it being a trial of furosemide vs furosemide (the study already assumes that furosemide is the daddy with the statement “Intravenous loop diuretics are an essential component of current treatment and are administered to approximately 90% of patients who are hospitalized with heart failure”). The references to the NICE guidance are not yet available but in the event that this is another set of guidelines using this paper as high level evidence we should be spreading the word….

    • Thanks for the comment. I think it’s time for a study without loop diuretics in the ED to see what happens when these patients just get NIPPV and nitrates. It could probably pass ethics now, and would be very helpful in clarifying this whole thing. For me, I’ll continue to avoid the initial lasix unless truly intravasc overload after nitro.

      Cheers,

      Chris

Trackbacks

  1. […] post on Acute Heart Failure has it all, evidence based medicine, a new treatment mnemonic and plenty of well placed humour (and […]

  2. […] Evidence Based Management of Acute Heart Failure: Forget LMNOP, think POND! The new pneumonic  in managing ACPE is: POND – Positive pressure/position, Oxygen, Nitrates, Diuretics – glad the evidence is starting to catch up.  […]

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