Loop diuretics in Acute Pulmonary Edema; Necessary..Evil…or Necessary Evil?

4 Feb

Welcome back on EMDutch, the blog by Dutch emergency physicians, for emergency physicians worldwide!

So far we have discussed morphine and NTG in Acute Heart Failure (AHF) and now it’s diuretics’ turn! And before we go on I want to make clear that we are discussing patients with Acute Pulmonary Edema (APE) without hypotension and not the patients with swollen ankles and no severe dyspnea or the patients in cardiogenic shock.

Diuretics in APE for me as a resident was something you didn’t think about and clearly works, just like thrombolysis in ischemic stroke, steroids in sepsis and acenocoumarol in small PE (YEAH…RIGHT!). But when you join the #FOAMed family and really start thinking about (evidence-based) medicine nothing is what it seemed to be.

Ok, loop diuretics in APE! Off course a lot has been written about it, but a good, blinded, prospective study looking at diuretics vs no diuretics is lacking. But….when comparing high-dose ISDN with low dose furosemide vs high-dose furosemide with low dose ISDN, the high-dose ISDN was more effective in terms of need for mechanical ventilation, frequency of MI, any adverse events and the SpO2 rose much faster in the first 50 minutes. (1) This at least questions the use of diuretics in APE.

So why do we still use it and what is the idea behind it? Just think about your goals in the treatment of APE: Preload reduction, Afterload reduction and Improvement of LV-function. Furosemide was thought to reduce the preload, due to rapid diuresis, thereby reducing plasma volume and pulmonary capillary wedge pressure (PCWP). After some conflicting data regarding this preload effect of furosemide, Kraus, et al studied the effect of i.v. furosemide on PCWP in their ICU. (2) They found that furosemide alone or combined with preload reduction vasodilator (= low dose NTG) had an initial 15 minutes rise of PCWP(!), while a combination of furosemide + pre- & afterload reduction (= high dose NTG or captopril) showed an immediate fall in PCWP. Nelson, et al (3) already found in 1983 that in patients suffering from AHF after MI both ISDN and frusemide decreased the pressures in pulmonary vasculature, but the venodilation by ISDN was more rapid and effective than the diuresis by frusemide. Moreover, frusemide was followed by an decrease in cardiac output (CO) and an increase in systemic vascular resistance, implying an increase in peripheral vasoconstriction, which can lead to impairment of tissue perfusion. ISDN reduced the systemic vascular resistance without lowering CO and without increase in peripheral vasoconstriction.

So, nitrates show great benefit over loop diuretics! If you still want to give furosemide to decrease the preload, furosemide alone is not the way to go and it should be given after high dose NTG or ACE-inhibitors.

As said above, furosemide alone doesn’t reduce the preload immediately, but  i.v. administration results in prompt diuresic effect (4),  so it must work in an overload state as APE, right???? Wrong! The cause of the APE is probably insufficient systolic and often diastolic myocardial functional reserve (5), rather than volume overload. (6) Most well-managed CHF patients are euvolemic or slightly dehydrated, and most incidences occur in the early morning hours, when intake is the lowest. (7) This would also explain why loop diuretics is a predictor of worsening of renal function (WRF).

Worsening of renal function is frequently observed in both chronic and acute heart failure. Diuretic doses has been shown to be related with changes in renal function and mortality but there is conflicting data and the data out there is mostly retrospective. (8) This makes it possible that sicker patients got more diuretics, which would be an important confounder. Metra, et al (9) were the first to look prospectively and guess what they found: severity of HF and daily furosemide dose were the most important predictors of the occurrence of WRF. But how strong is this data. They say that WRF is a strong predictor of a powerful predictor of mortality and HF hospitalization and I want to believe that…..but what was the influence of furosemide??? Well, not that strong. The odds ratio of ‘furosemide i.v.daily dose at admission’ as a predictor for WRF was 1.001! That’s nothing! When >100mg/day was given the Odds ratio was 2.18, but in this article the dosis of furosemide was not preset. So probably the higher doses are a consequence of more advanced HF a coexcisting renal failure, rather than the cause.


Most of the evidence out there shows a trend towards not using furosemide, I would say. APE is related to an increase in systemic vascular resistance, due to insufficient myocardial functional reserve. This is different from what we used to believe, a state of volume overload and low cardiac output. Therefore the treatment should be an agent that rapidly reduces PCWP and causes venous and arterial dilatation, rather than a diuretic…..Nitroglycerin.

Since there is no good study looking at different regiments of furosemide in APE we don’t know for sure. Maybe it is good, but probably not as good as we ones thought. If you’re are planning on giving furosemide…..give the high dose nitroglycerin first! Otherwise the PCWP will initially rice.

In the Netherlands the ambulance personnel gives O2, morphine, furosemide  (and sometimes NTG s.l. ones or twice) to patients with APE. I think this post clearly shows that this is not the way to go! Furosemide is NOT the first-line treatment for APE and this protocol needs to be re-evaluated! NTG beats furosemide easily and I don’t understand that the Task Force of the European Society of Cardiology puts it as the nr. 1 treatment for APE in their 2012 guideline?! Even in low blood pressure an ACE-inhibitor is probably better, but that is something for a later post.

Next time: Non Invasive Ventilation in APE!

See you than……and please let me know if you have any comments!

Egon Zwets

References on loop diuretics in AHF


8 Responses to “Loop diuretics in Acute Pulmonary Edema; Necessary..Evil…or Necessary Evil?”

  1. Sean Scott February 5, 2013 at 08:51 #

    Hey Egon,

    Keep up the good work debunking cardiological myths.

    Could you link your references to abstracts of the articles through medline?

    Have you thought about doing a podcast on this stuff?

    • Egon February 5, 2013 at 10:11 #

      Hi Sean, thanx for following us! We really enjoy working on EMDutch (Me, Laura, Linda & Roger) and in May I will give a presentation on the Dutch Congres of EM. Hopefully more people in Holland will start following the website than.
      I will try to link the references next time!
      I saw your website! Congratulations!!!
      Maybe see you on Skype soon?

      Grtz Egon

  2. prehospitalpro February 5, 2013 at 10:35 #

    Reblogged this on prehospitalpro.

  3. Kirsty Challen (@KirstyChallen) February 5, 2013 at 10:38 #

    Hello Egon

    There is also a secondary publication from the 3CPO trial about medical therapies – obviously not an RCT of those therapies but still failed to find an effect for furosemide.

    Gray, A., S. Goodacre, et al. (2010). “Diuretic, opiate and nitrate use in severe acidotic acute cardiogenic pulmonary oedema: analysis from the 3CPO trial.” Quarterly Journal of Medicine 103: 573-581.

    I end up wondering what it is that makes these patients appear to get better, as it doesn’t seem related to anything we do!

    BW, Kirsty

  4. Laura February 5, 2013 at 13:26 #

    Hi Egon,

    It would be interesting to ask our colleagues to upload (via the webmasters) their AHF Guidelines, for sharing.


  5. Femke February 6, 2013 at 12:53 #

    Hi Egon,

    Strongly and very clearly put, with some great underlying arguments. Maybe you should think about forwarding this post to ambulance medical directors; just in case they haven’t heard of EMDutch yet?
    Keep up the good work!!!


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  7. Patrickcen April 28, 2019 at 22:16 #


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