Managing acute pulmonary oedema with high or standard dose nitrate
Date First Published:
October 21, 2004
Last Updated:
May 1, 2009
Report by:
Henry Morriss, Consultant in Emergency Medicine (Manchester Royal Infirmary and University Hospital of North Staffordshire)
Search checked by:
Magnus Harrison, Manchester Royal Infirmary and University Hospital of North Staffordshire
Three-Part Question:
In [patients with acute pulmonary oedema] does [high dose versus standard dose nitrate (e.g. glyceryl trinitrate)] [decrease the need for intubation or length of hospital stay]?
Clinical Scenario:
A 75-year-old man presents to the emergency department at 06:00 hours sweaty, acutely short of breath and coughing pink frothy sputum. You diagnose acute left ventricular failure/acute pulmonary oedema. You know intravenous nitrates are part of first line therapy but wonder whether a high dose will provide increased benefit.
Search Strategy:
OvidSP MEDLINE 1950 to January Week 2 2009.
The Cochrane Library Issue 1 2009
The Cochrane Library Issue 1 2009
Search Details:
Medline:[exp Pulmonary Edema/OR pulmonary oedema.mp. OR exp Heart Failure/OR left ventricular dysfunction.mp.] AND [exp isosorbide dinitrate/or exp nitrates/OR exp Nitroglycerin/or GTN.mp.] AND [exp Infusions, Intravenous/OR exp Injections, Intravenous/] Limit to English language, Humans and abstracts.<br><br>Cochrane: [(pulmonary oedema): ti,ab,kw OR MeSH descriptor Pulmonary Edema explode all trees] AND [MeSH descriptor Nitrates explode all trees OR MeSH descriptor Isosorbide Dinitrate explode all trees OR MeSH descriptor Nitroglycerin explode all trees].
Outcome:
A total of 57 papers was found, of which 54 were either irrelevant or of insufficient quality for inclusion. The remaining three papers are shown in the table
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| High-Dose Intravenous Isosorbide-Dinitrate is safer and better than BIPAP combined with conventional treatment of severe pulmonary edema. Sharon A, Shpirer I, Kaluski , Moshkovitz Y, Milovanov O, Polak R, Blatt A, Simovitz A, Shaham O, Faigenberg Z, Metzger M, Stav D, Yogev R, Golik A. 2000 Israel | 40 consecutive patients with severe pulmonary oedema (oxygen saturation, 90% on room air prior to treatment). All patients received oxygen at a rate of 10 litres/min, intravenous (IV) furosemide 80 mg and IV morphine 3 mg. Repeated boluses of IV ISDN 4 mg every 4 min (n = 20) vs BiPAP ventilation and standard dose nitrate therapy (n = 20). All treatment was delivered by mobile intensive care units before hospital arrival. |
RCT | Death | 2 deaths in BIPAP group v 0 in the ISDN group | Pre-hospital trial Small numbers |
| Intubation | 16 in BIPAP group v 4 in ISDN | ||||
| AMI | 11 in BIPAP v 2 in ISDN | ||||
| Combined (death/AMI/IMMV) | 17 in BIPAP v 5 in ISDN | ||||
| Recovery rate (measured by respiratory rate, oxygen saturation and pulse) | Quicker improvement seen at 1 hour in high dose ISDN group | ||||
| 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. 1998 Israel | 110 adult patients presenting to mobile emergency units with signs of congestive heart failure were treated with oxygen 10 L/min, intravenous furosemide 40 mg, and morphine 3 mg bolus. ISDN (3 mg bolus administered IV every 5 min (n = 56) vs furosemide (80 mg bolus administered IV every 15 min) as ISDN 1 mg/h, increased every 10 min by 1 mg/h (n = 54). |
RCT | Need for mechanical ventilation | 9 in high-dose ISDN vs 21 in furosemide group p = 0.004 | Pre-hospital study. |
| AMI | 9 in high-dose ISDN vs 19 in furosemide p = 0.047 | ||||
| Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: a feasibility and outcome analysis. Levy P, Compton S, Welch R, et al. 2007, USA | 29 Patients in a convenience sample. All patients had failed conventional treatment of high–low oxygen, IV furosemide and sublingual or oral spray bitrates. All had a systolic BP >160 or a MAP >120. GTN infusion titrated on all patients. 2 mg boluses GTN given every 3 min up to 10 doses. Outcomes compared with a retrospectively identified cohort. |
Before and after study | Intubation within 6 h | 13.8% vs 29.5% | Small study with a retrospective comparator |
| BiPAP | 6.9% vs 20% | ||||
| ICU admission rate | 37.9% vs 80% | ||||
| LoS | 4.1 days vs 6.2 days | ||||
| Cardiovascular complications | 20.7% vs 28.9% |
Author Commentary:
There is no well designed study that answers this question directly. Overall, the best evidence available suggests that high-dose nitrates (bolus or infusion) plus low-dose furosemide are effective in acute cardiogenic pulmonary oedema.
Bottom Line:
High-dose glyceryl trinitrate is effective in acute cardiogenic pulmonary oedema.
References:
- Sharon A, Shpirer I, Kaluski , Moshkovitz Y, Milovanov O, Polak R, Blatt A, Simovitz A, Shaham O, Faigenberg Z, Metzger M, Stav D, Yogev R, Golik A.. High-Dose Intravenous Isosorbide-Dinitrate is safer and better than BIPAP combined with conventional treatment of severe pulmonary edema.
- Cotter G, Metzkor E, Kaluski E, Faigenberg Z, Miller R, Simovitz A ,Shaham O, Marghitay D.. Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus low-dose isosorbide dinitrate in severe pulmonary oedema.
- Levy P, Compton S, Welch R, et al.. Treatment of severe decompensated heart failure with high-dose intravenous nitroglycerin: a feasibility and outcome analysis.