Nitrate bolus in acute heart failure

Despite intravenous nitrate boluses being used in original studies demonstrating benefit in acute heart failure1,2, I regularly meet reluctance from both physicians and nurses in the emergency department to give them.

Their resistance seems to be based on a concern for inducing hypotension, and they prefer to ‘titrate up’ an infusion.

iv nitrate options include nitroglycerin (GTN), and isosorbide dinitrate (ISDN). Studies have used ISDN 4mg every 4 mins, ISDN 3mg every 5 mins, and GTN 2mg every 3 mins3.

There are a number of reasons to avoid starting with a low rate infusion in a sick heart failure patient.

Matthew Reed highlighted cannula size as an important factor4:

If a GTN infusion is commenced at a rate of 1 ml/h, a critically unwell patient with a large cannula—for example, a grey cannula (16G) — will have to wait over 6 min for the drug to enter the body. This compares with 1.5 min for a pink cannula (20G) at the same infusion rate. If a large-diameter cannula is chosen for these patients, then a fast initial infusion rate should also be chosen to ensure that the GTN begins to act quickly.

Alistair Steel subsequently pointed out further reasons to avoid slow infusions5:

(1) mechanical slack within an infusion device may mean an infusion set at 1 ml/h will take many minutes for the driver to contact and advance the syringe plunger. For this reason, infusions should be purged before patient connection.

(2) the pharmacokinetics of the drug should be considered. At low infusion rates it will take significant time for a steady state to be achieved (a drug such as GTN, with a half-life of 2 min, would require 10 min to achieve steady state). For clinical effects to be seen quickly, a bolus should be given before commencing infusions.

(3) the use of 1 ml/h infusions (8 µg/min using a 0.5% solution) may be excessively cautious – the British National Formulary recommends a therapeutic dose range from 10 to 200 µg/min. Furthermore, there is emerging evidence that, when used for decompensated heart failure, higher doses of GTN are associated with more favourable outcomes.

(4) at low infusion rates any obstruction in the intravenous system will take a proportionally longer time to become apparent, as it will take longer for the pressure to build up and trigger the syringe pump’s high pressure alarm.

Now a recent study confirms such a regimen can be used safely in the elderly. ISDN 3mg bolus treatment was not associated with higher rates of hypotension in the elderly population treated for heart failure in the emergency department. Despite a small study and a retrospective design, this lends support to the practice of iv bolus nitrate therapy for acute heart failure, even in the elderly.

1. 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

2. High-doses intravenous isosorbide dinitrate is safer and better than Bi-PAP ventilation combined with conventional treatment for severe pulmonary edema
J Am Coll Cardiol. 2000 Sep;36(3):832-7 Free Full Text

3. Managing acute pulmonary oedema with high or standard dose nitrate
Emerg Med J. 2009 May;26(5):357-8

4. Administering a glyceryl trinitrate infusion: big is not always best
Emerg Med J 2007;24:423-424

5. Administering a glyceryl trinitrate infusion: faster is better than slower
Emerg Med J. 2008 Jan;25(1):60

6. Isosorbide dinitrate bolus for heart failure in elderly emergency patients: a retrospective study
Eur J Emerg Med. 2011 Oct;18(5):272-5