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

- Rogue Medic

Nitroglycerin for Treatment of Acute, Hypertensive Heart Failure – Bolus, Drip or Both?


If standard doses of nitrate – NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries), ISDN (IsoSorbide DiNitrate), or ISMN (IsoSorbide MonoNitrate) improve outcomes for CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure) patients, and larger IV (IntraVenous) doses are more effective than standard doses,[1],[2],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12] what method(s) of drug delivery works best?

High dose IV drip?

High dose IV bolus?

A high dose IV bolus combined with a high dose IV drip?

We performed a retrospective cohort study of patients who presented to the emergency department (ED) of an urban, teaching hospital with severe, acute hypertensive heart failure between Jan 2007 and July 2011 and received intravenous nitroglycerin. 3 subgroups were defined: 1) those given nitroglycerin by higher dose (≥ 0.5 mg) bolus alone (higher dose nitroglycerin); 2) those given nitroglycerin by continuous intravenous infusion alone (intravenous nitroglycerin); and 3) those given nitroglycerin by concurrent higher dose bolus and continuous IV infusion (higher dose intravenous nitroglycerin).[13]


At least half a milligram at a time means at least 25% more than the standard bolus dose with a NTG tab/spray.


Click on images to make them larger.

With bolus dosing the blood pressure dropped more quickly.

The sooner we drop the patient’s blood pressure, as long as we do not drop it too much, the better for the patient.

Do we really have a problem with dropping the pressure too much with high doses of bolus IV NTG?


Almost every severely hypotensive patient in this study received more than 1 mg/minute IV NTG, which would be boluses of at least 5 mg IV NTG every 5 minutes until they improved – and most did improve dramatically.[14]



Conclusion: In this single-center, retrospective, unadjusted analysis of primarily African-American patients with acute hypertensive heart failure, nitroglycerin administered by higher dose bolus without concurrent intravenous infusion was associated with a significant decrease in ICU admissions and hospital length of stay. Based on our findings, bolus higher dose nitroglycerin appears to be a viable option for the management of such patients.[13]


There are some important questions about IV bolus dosing of NTG for CHF/ADHF.

How aggressive should our initial bolus dose be?

How often should we repeat the dosing?

NTG is metabolized very quickly, so these boluses are only to treat the initial emergency, then the patient will be switched to an infusion of NTG.

We do need more research, but we also need research that does not include furosemide, or compares furosemide with a placebo.

This evidence is much better than any evidence used to justify epinephrine in cardiac arrest. If any CHF/ADHF patients have a cardiac arrest and they are not immediately resuscitated, they are supposed to be treated with epinephrine according to the current ACLS (Advanced Cardiac Life Support) guidelines.

These patients do not arrest due to any deficiency of adrenaline (epinephrine).

These patients improve with treatment that is essentially the opposite of epinephrine.


[1] [The efficacy of isosorbide dinitrate administered in an intravenous bolus in acute cardiogenic pulmonary edema].
Rabaçal C, Ribeiro H, Nuno L, Mendonça C, Linder J, Pereira D, Carvalho E, Afonso JS, Fernandes JS.
Rev Port Cardiol. 1993 Dec;12(12):1029-35, 1000. Portuguese.
PMID: 8117456 [PubMed – indexed for MEDLINE]

[2] Intravenous nitroglycerin boluses in treating patients with cardiogenic pulmonary edema.
Nashed AH, Allegra JR.
Am J Emerg Med. 1995 Sep;13(5):612-3. No abstract available.
PMID: 7662071 [PubMed – indexed for MEDLINE]

[3] Intravenous nitrates in the prehospital management of acute pulmonary edema.
Bertini G, Giglioli C, Biggeri A, Margheri M, Simonetti I, Sica ML, Russo L, Gensini G.
Ann Emerg Med. 1997 Oct;30(4):493-9.
PMID: 9326864 [PubMed – indexed for MEDLINE]

[4] Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema.
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.
Lancet. 1998 Feb 7;351(9100):389-93.
PMID: 9482291 [PubMed – indexed for MEDLINE]

[5] High-dose intravenous isosorbide-dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema.
Sharon A, Shpirer I, Kaluski E, Moshkovitz Y, Milovanov O, Polak R, Blatt A, Simovitz A, Shaham O, Faigenberg Z, Metzger M, Stav D, Yogev R, Golik A, Krakover R, Vered Z, Cotter G.
J Am Coll Cardiol. 2000 Sep;36(3):832-7.
PMID: 10987607 [PubMed – indexed for MEDLINE]

Free Full Text and Free PDF Download from ScienceDirect

[6] Administering a glyceryl trinitrate infusion: big is not always best.
Reed MJ.
Emerg Med J. 2007 Jun;24(6):423-4.
PMID: 17513541 [PubMed – indexed for MEDLINE]

Free Full Text from PubMed Central

[7] Administering a glyceryl trinitrate infusion: faster is better than slower.
Steel A, Varley J.
Emerg Med J. 2008 Jan;25(1):60. No abstract available.
PMID: 18156558 [PubMed – indexed for MEDLINE]

[8] Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: a feasibility and outcome analysis.
Levy P, Compton S, Welch R, Delgado G, Jennett A, Penugonda N, Dunne R, Zalenski R.
Ann Emerg Med. 2007 Aug;50(2):144-52. Epub 2007 May 23.
PMID: 17509731 [PubMed – indexed for MEDLINE]

Free Full Text PDF Download from Ferne.org

[9] High dose nitroglycerin treatment in a patient with cardiac arrest: a case report.
Guglin M, Postler G.
J Med Case Reports. 2009 Aug 10;3:8782.
PMID: 19830240 [PubMed]

Free Full Text from PubMed Central

[10] A Protocol of Bolus-Dose Nitroglycerin and Non-Invasive Ventilation to Avert Intubation in Emergency Department Acute Pulmonary Edema
Piyush Mallick, Surjya Upadhyay, TS Senthilnathan, El Matit Waleed , Al Jahra Hospital, Scott Weingart, Mount Sinai School of Medicine
Prepublication abstract
PDF Download of page at EMCrit

[11] EMCrit Podcast 1-Sympathetic Crashing Acute Pulmonary Edema
by EMCRIT on April 25, 2009
Link to Podcast page

Link to page with other evidence supporting this treatment

[12] Isosorbide dinitrate bolus for heart failure in elderly emergency patients: a retrospective study.
Freund Y, Delerme S, Boddaert J, Baker E, Riou B, Ray P.
Eur J Emerg Med. 2011 Oct;18(5):272-5.
PMID: 21499108 [PubMed – indexed for MEDLINE]

[13] Nitroglycerin for Treatment of Acute, Hypertensive Heart Failure: Bolus, Drip or Both?
Kwiatkowski GM, Saely S, Purakal J, Mahajan A, Levy PD/Detroit Receiving Hospital, Detroit, MI; Wayne State University School of Medicine, Detroit, MI
Annals of Emergency Medicine, Volume 60, issue 4 (October, 2012), p. S9.
ISSN: 0196-0644 DOI: 10.1016/j.annemergmed.2012.06.049
Abstract 22 Indexed with OhioLINK Journal Article Locator

[14] What is the basis for post-resuscitation treatment recommendations?
Rogue Medic
Mon, 15 Oct 2012

Kwiatkowski, G.M.; Saely, S.; Purakal, J.; Mahajan, A.; Levy, P.D. (2012). Nitroglycerin for Treatment of Acute, Hypertensive Heart Failure – Bolus, Drip or Both? Annals of Emergency Medicine, 60 (4), 59-59


CHF Treatment: Is Furosemide on the Way Out?

There si a discussion of the inevitable elimination of furosemide from the emergency drug list for CHF/ADHF (Congestive Heart Failure/Acute Decompensated Heart Failure). The only real surprise is that it has taken this long. The problems with furosemide have been documented since the 1970s.

This isn’t just a problem with CFH/ADHF. With the treatment of spontaneous pneumothorax, the problem has persisted, in spite of evidence, for even longer.

What is crucially needed here is what should have been done 40 years ago, which is a randomized controlled study of conservative observational management of primary spontaneous pneumothorax against what is currently the best evidenced intervention which is pleural aspiration.[1]

Nitro, morphine and furosemide: they’ve been the Holy Trinity of emergent treatment of acute CHF since the 1960s, but does this cocktail actually work?[2]

Déjà vu all over again?

Whatever the cause, CHFers rarely call EMS because their feet are swollen. They call because they can’t breathe, which is why we have traditionally considered CHF a cardiac disease disguised as a respiratory condition. The bulk of prehospital treatment of CHF is aimed at treating the primary clinical manifestation of left heart failure: cardiogenic acute pulmonary edema (APE).[2]

When their CHF/ADHF improves, their ankles will begin to improve, too. But we should not worry about their ankles when they can’t breathe. They don’t breathe through their feet.

Clinical presentation of acute pulmonary edema almost always manifests itself as severe respiratory distress, often accompanied by a constellation of associated signs and symptoms, including:

Profound hypertension (hallmark sign)[2]

This is why it is safe to use huge doses of NTG (NiTroGlycerin – GTN GlycerylTriNitrate in Commonwealth countries) for these patients, when they are hypertensive.

However, it also became apparent that higher doses of nitroglycerin resulted in significant dilation of the arterial system as well, reducing peripheral vascular resistance, increasing forward flow and, ultimately, decreasing workload for the weak and damaged left ventricle. This global vasodilatory effect of nitroglycerin has been shown to significantly reduce mortality in APE patients treated in the prehospital setting, and even hypotensive patients (systolic BP < 100) were shown to benefit from intravenous nitroglycerin.2 [2]

A systolic pressure less than 100? But we’ll kill the patients!

Actually, NTG is safe in much more hypotensive patients.

How hypotensive?

Is a blood pressure of 0/0 low enough?[3] 😯

Huge doses are safe.

We are supposed to be terrified of giving IV bolus NTG to hypotensive CHF/ADHF patients, but the death rate for hypotensive patients was cut in half by IV bolus NTG in this study.[4] NTG is not a new drug, we have just been too afraid to use enough.

Acute pulmonary edema, therefore, may likely be less of a fluid volume problem than a fluid distribution problem. There may be no excess accumulation of fluid needing to be diuresed; it is simply in the wrong place and needs to be distributed properly.[2]

Furosemide removes fluid, but only after the circulation returns to the kidneys. During critical illness, the body shunts circulation away from the kidneys. As with high-flow oxygen for chest pain, if the blood isn’t getting to the heart muscle, it does not matter how much oxygen is in the blood that isn’t getting where we want it. Like being in a traffic jam honking the horn, it may feel as if we are doing something, but we are only making things worse.

I prefer to keep treatment simple. Giving a bunch of drugs in a short period of time is a good way to make things a lot worse. This is kind of like the person who makes large adjustments to four different settings on a ventilator, but without reassessing at any point until after adjusting everything. Several drugs with varying durations of effect can also be a bad idea.

A lot of NTG. If you are uncomfortable, start off slowly, but if the blood pressure does not start to drop, keep increasing the dose. If this is CHF, small doses of NTG will probably have no effect on blood pressure. Expect the blood pressure to rise.

CPAP (Continuous Positive Airway Pressure), which makes it difficult to give sublingual NTG, but does not stop us from giving IV NTG – either as an infusion, which requires a pump, or boluses of the same doses we give under the tongue.

1 mg to 2 mg at a time – repeated every 3 to 5 minutes until symptoms improve.


This IS safe.


Go read the full article. Kelly and Gene know what they are writing about.


[1] Spontaneous pneumothorax: time for some fresh air.
Simpson G.
Intern Med J. 2010 Mar;40(3):231-4. Review.
PMID: 20446970 [PubMed – indexed for MEDLINE]

An excellent, but mostly unappreciated, review of the problems with the Standard Of Care for spontaneous pneumothorax. Not that much different from the mythological treatment that persists in so many other areas of medicine.

[2] CHF Treatment: Is Furosemide on the Way Out?
Created: June 1, 2012
by Steven “Kelly” Grayson, NREMT-P, CCEMT-P and William E. (Gene) Gandy, JD, LP,
EMS World

[3] High dose nitroglycerin treatment in a patient with cardiac arrest: a case report.
Guglin M, Postler G.
J Med Case Rep. 2009 Aug 10;3:8782.
PMID: 19830240 [PubMed]

Free Full Text from PubMed Central

[4] Intravenous nitrates in the prehospital management of acute pulmonary edema.
Bertini G, Giglioli C, Biggeri A, Margheri M, Simonetti I, Sica ML, Russo L, Gensini G.
Ann Emerg Med. 1997 Oct;30(4):493-9.
PMID: 9326864 [PubMed – indexed for MEDLINE]


Drug Shortages Affect Those Still in the Dark Ages – Furosemide


Also posted over at Paramedicine 101 and at Research Blogging.

Go check out the excellent material at both sites.

In the current JEMS, there is an embarrassing article. Drug Shortage Possible in N.Y.

It seems that the drugs that people are worried about are lidocaine, furosemide, 50% dextrose, and epinephrine 1:10,000 preloaded syringes. Here, I will discuss furosemide.

Furosemide is not appropriate for EMS patients, because there are more appropriate drugs, more appropriate other treatments, and it is too often given to patients who have pneumonia.

Fluid accumulation in the lungs associated with APE, until recently, was attributed to excess accumulation of total body fluid. Accordingly, treatment of APE was aimed at removing excess fluid from the lungs by promoting massive diuresis. However, this explanation for APE could not reconcile the fact that APE typically occurs during early morning hours when fluid intake is minimal. The current explanation is that APE results from fluid redistribution within the body whereby a part of the intravascular volume is redistributed to the lungs as a consequence of increased intravascular pressure as outlined above.13 Primary objectives for the treatment of acute CHF are to reduce pulmonary capillary pressure, to redistribute pulmonary fluid, and to improve forward flow.12,13 These may be achieved by reducing LV preload and afterload, providing ventilatory and inotropic supports, and identifying and treating the underlying etiology of the syndrome (Table 3). It should be recognized that these treatment measures are intended for APE patients who are normotensive or hypertensive and not those who are hypotensive. The latter comprises cardiogenic shock secondary to severe LV systolic dysfunction; treatment of these critically ill patients is beyond the scope of this review.[1]

That is a big paragraph, but there is a lot of information in there. Enough to convince us that we should not be using furosemide to treat an acute onset/exacerbation of heart failure.

In the chart below, before furosemide in treatment there are plenty of other treatments. Notice that only oxygen comes before NTG (NiTroGlycerin) and the more severe the symptoms, the more NTG is given.

Mild symptoms – One 0.4 mg NTG spray/tab – repeated every 4 to 5 minutes.

Moderate symptoms – High-dose NTG, which is explained below.

Severe symptoms – Two to five 0.4 mg sprays/tabs at a time – repeated every 3 to 5 minutes.

But, but, but, but, but, . . . . . we can only give a maximum of 3 NTG – ever.

Then you need to get a better medical director, because your medical director has you killing patients.

Am I being too subtle?

Another treatment that is very effective is CPAP (Continuous Positive Airway Pressure) which is a BLS (Basic Life Support) skill, except where medical directors like to kill patients. When using CPAP (a form of NIPPV – Non-Invasive Positive Pressure Ventilation), NTG paste can be applied. Do not be shy with the paste, because nothing is absorbed well through the skin when the skin is pale. Pale means a lack of circulation. Also, since the appropriate dose is much more than standard NTG dosing, there is not much reason to hold back.

I disagree about the placement of CPAP at the bottom. CPAP should be started right away. This was published in 2003, so it is kind of old and conservative.

You call that NTG use conservative?!?!?

I do. I have given dozens of NTG in a period of 10 to 20 minutes and never had a patient experience any adverse effects while in my care or at the hospital. I have written elsewhere about the superstitious way we approach NTG.

Furosemide is in there, but only if the patient has peripheral edema. If there is no peripheral edema, is fluid overload the problem? That is a fluid redistribution problem. There is fluid in the wrong place, but that does not mean that the whole body is overloaded with fluid or that putting a bunch of fluid in the bladder is going to make things better. Moving fluid to the bladder does not mean that we are removing it from the lungs any more than we are removing fluid from anywhere else.

Click on the chart to make it bigger. I know I can’t read any of it at this size. This is from the same paper as the paragraph above.

Well, that is just one paper. Nobody else would be so irresponsible as to recommend such large doses of NTG.

Then let’s read about what they do in the ED (Emergency Department).

Most patients who experience CPE, however, do not have ECG evidence of an acute dysrhythmia or AMI. Treatment should therefore be aimed at redistributing the excessive pulmonary interstitial fluid into the systemic circulation, which improves alveolar oxygen-carbon dioxide exchange and hypoxia; therefore, pharmacologic agents that provide preload reduction and afterload reduction should be administered. In some cases, inotropic support is required also.[2]

What drugs do we use to provide preload reduction and afterload reduction?

The most effective and rapidly-acting preload-reducing medication is nitroglycerin (NTG) [21–25]. Multiple studies have demonstrated the superiority of NTG over furosemide [21,24,26–28] and morphine sulfate [28–30] for preload reduction, symptomatic improvement, and safety. NTG can be administered in sublingual, IV, or transdermal form, although the transdermal absorption can be erratic in the patient in extremis. NTG also has the benefit of a short half-life; therefore, if the patient develops a precipitous fall in blood pressure (generally uncommon in CPE {Cardiogenic Pulmonary Edema} patients), the blood pressure should return to previous values within 5 to 10 minutes of discontinuation of administration.[2]

But what about the dose?

In one study [26], 3 mg IV boluses of NTG were administered every 5 minutes to patients who had developed CPE, a dose equivalent to a 600 mg/min infusion. This protocol was found to be safe, well-tolerated, and effective for these patients and associated with reduced need for mechanical ventilation and more rapid resolution of symptoms. Standard anti-anginal dosages of sublingual NTG with which most physicians are comfortable (ie, 400 µg every 5 minutes), has the bioequivalence of an IV NTG infusion of 60 to 80 µg/min. Physicians should, therefore, be comfortable with the safety of even higher dosages of NTG for patients who experience CPE and usually present in a hyper-adrenergic state with moderately-to-severely elevated blood pressures.[2]

That is 7 1/2 times to 10 times the standard dose of NTG – with no problems.

Maybe that maximum of 3 NTG is something that should be ignored. The AHA (American Heart Association) seems to be ignoring it. Just try to find a limit on NTG administration in the current ACLS, which is from 2005.

These papers are available in PDF format, so you can print them out and hand them to your medical director and/or to the other doctors in the ED.

These are important papers. Both are review articles. One is written for EMS, while the other is written for the ED.

If you are feeling aggressive, maybe you can write on the bottom, Call me about improving the protocols we use to treat our patients.

There is one problem with this. This will lead to fewer intubations.

The best intubation is the intubation that is prevented by excellent patient care.


[1] Prehospital therapy for acute congestive heart failure: state of the art.
Mosesso VN Jr, Dunford J, Blackwell T, Griswell JK.
Prehosp Emerg Care. 2003 Jan-Mar;7(1):13-23. Review.
PMID: 12540139 [PubMed – indexed for MEDLINE]

Free Full Text PDF

[2] Modern management of cardiogenic pulmonary edema.
Mattu A, Martinez JP, Kelly BS.
Emerg Med Clin North Am. 2005 Nov;23(4):1105-25. Review.
PMID: 16199340 [PubMed – indexed for MEDLINE]

Free Full Text PDF

Mosesso VN Jr, Dunford J, Blackwell T, & Griswell JK (2003). Prehospital therapy for acute congestive heart failure: state of the art. Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors, 7 (1), 13-23 PMID: 12540139

Mattu A, Martinez JP, & Kelly BS (2005). Modern management of cardiogenic pulmonary edema. Emergency medicine clinics of North America, 23 (4), 1105-25 PMID: 16199340