Background

Intravenous (IV) nitroglycerin (NTG) infusion is one of the mainstay treatments in acute pulmonary edema (aka acute decompensated heart failure (ADHF)), but is associated with increased hospital length of stay (LOS) and health care costs. Optimal NTG dosing isn’t established though physiologically, higher infusion doses (> 100 mcg/min) are helpful as they affect both afterload and preload. Recent studies suggest that intermittent high-dose bolus therapy may be as or more effective than infusions, however the impact on ICU admissions has not been studied.

Clinical Question

Does high-dose NTG bolus therapy prevent ICU admissions in patients with acute hypertensive heart failure when compared to IV infusion therapy?

Population

All patients older than 18 years who were treated for AHF with IV NTG in the emergency department (ED), as documented in the medical record, between January 2007 and July 2011.

Intervention

NTG Bolus (500 - 2000 mcg q3-5 min) vs. NTG infusion (20-35 mcg/min) vs. NTG Bolus + Infusion

Outcomes

Primary: Need for ICU admission
Secondary: Hospital LOS and adverse outcomes (hypotensive episodes, cardiac injury as identified by positive troponin, and renal dysfunction).

Design

Single center retrospective observational cohort study

Excluded

Patients who had IV NTG orders but not documented as given in the electronic medical record
Patients who received NTG for other indications, such as acute coronary syndrome, blood pressure management, or hypertensive urgency without heart failure
Pregnant patients

Primary Results

  • 1227 patients received IV NTG and 845 were excluded who received therapy for non-AFH indications.
  • Those included were divided into 3 groups:
    • Intermittent bolus group (n=124)
    • Continuous infusion group (n=182)
    • Intermittent bolus + continuous infusion (n=89)
  • Groups were similar with respect to age, gender and race, as well as markers of illness severity (initial vital signs, ejection fraction, baseline brain natriuretic peptide)
  • The average NTG bolus dose was 2000 mcg

ICU Admissions By Group (Primary Outcome)

  • Bolus: 48%
  • Infusion: 67%
  • Combination: 79%

Secondary outcomes

  • Total hospital LOS was shorter in the bolus group (3.7 days) vs infusion (4.7 days) vs combination group (5.0 days).
  • Overall there were no differences in adverse outcomes between the groups. Rates of intubation and non-invasive respiratory support were the same among the groups.

Strengths

  • Investigates a critical presentation with minimal current evidence
  • Large study with patient centered outcomes
  • Although not prospective or randomized, the 3 treatment groups seem to have similar characteristics

Limitations

  • This study took place at a single inner-city hospital. The results may not be applicable to populations different than that in this study
  • Retrospective cohort chart review design means the intervention was not randomized or blinded, which may bias investigators
  • This hospital had a policy that all patients on NTG drips must go to the ICU, which is  problematic toward this study’s outcome evaluation
  • Although patients had similar characteristics in each group, it is unclear why different treatment modalities were chosen for different patients
  • The study did not control for the use of NIPPV or other medications (i.e. ACE inhibitors)
  • Average starting infusion rate was low at 20 mcg/min with the maximum dose averaging just 35 mcg/min. Doses this low are unlikely to be effective

Author's Conclusions

“In ED patients with acute heart failure, IV NTG by intermittent bolus was associated with a lower ICU admission rate and a shorter hospital LOS compared to continuous infusion.”

Our Conclusions

Although this retrospective study has significant limitations, it provides evidence for the safety of intermittent high-dose bolus therapy, and suggests superiority over low-dose infusion therapy. These results warrant further prospective research for corroboration.

Potential Impact To Current Practice

Emergency providers may consider using high-dose NTG therapy in patients with APE in order to break the neurohormonal mediator cycle that causes the emergent presentation.

Bottom Line

Early high-dose NTG therapy in AHF appears safe, but a prospective, randomized trial will be needed to further compare bolus therapy to infusion therapy.

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