Myths in Heart Failure: Part II – ED Management
- Aug 6th, 2018
- Brit Long
Author: Brit Long, MD (@long_brit, EM Attending Physician, San Antonio, TX) // Edited by: Alex Koyfman, MD (@EMHighAK)
A 62-year-old male presents with significant dyspnea at rest and with exertion. He has a history of heart disease, hypertension, and hyperlipidemia, but no known diabetes or heart failure. He has not seen a physician in over 5 years. He is hypertensive on exam, 192/110 mm Hg, hypoxic at 90% on RA, and breathing at 25 times per minutes. He is sitting upright with retractions. You detect bibasilar rales and +2 pitting edema bilaterally. This is a vastly different patient from Part 1, as this patient appears to be in hypertensive pulmonary edema. What are your next steps? Should we provide diuretics right away? What about high dose nitroglycerin? Is morphine efficacious?
Part I looked at myths and misconceptions in the evaluation of acute heart failure (AHF) exacerbation, including labs such as BNP, the association between worsening renal function and mortality, and the importance of ultrasound. Part II will evaluate ED management.
Myth #1: Diuretics are your mainstay in management in AHF and essential in all cases of AHF.
Yes, diuretics are a key part of therapy for acutely decompensated and chronic heart failure and are an important factor in guidelines.1-8 Guidelines place diuretics as primary means of improving congestion and reducing hypervolemia, with the most common medications including furosemide, torsemide, and bumetanide.2-5,8.9 Furosemide is eliminated via the renal system, while torsemide and bumetanide undergo elimination through the liver.9,10 Administration via the IV route is typical in the ED, which provides higher bioavailability in systemic hypervolemia. Diuresis typically begins within 30-60 minutes. Guidelines recommend an IV dose equal to or greater than the patient’s daily maintenance dose.1-5 ACEP’s clinical policy on heart failure provides Level B recommendations stating: “Treat patients with moderate-to-severe pulmonary edema resulting from acute heart failure with furosemide in combination with nitrate therapy”, and a Level C recommendation that “(1) Aggressive diuretic monotherapy is unlikely to prevent the need for endotracheal intubation compared with aggressive nitrate monotherapy. (2) Diuretics should be administered judiciously, given the potential association between diuretics, worsening renal function, and the known association between worsening renal function at index hospitalization and long-term mortality.”1
One major part of treatment is considering AHF as a syndrome, rather than one distinct disease entity. Patients in heart failure present in a variety of ways based on hemodynamic status and systemic versus pulmonary congestion.1-5,8,9 Diuretics can be beneficial in that chronically hypervolemic patient who presents with weeks of worsening,1-5 but that patient who presents with hypertensive pulmonary edema is a whole different situation.
Pearl #1: In acute pulmonary edema with hypertension, nitroglycerin and noninvasive positive pressure ventilation should be your first-line therapies, before diuretics.
Greater than 50% of patients do not have true volume overload in hypertensive pulmonary edema, with fluid primarily in the pulmonary system.11-13 Studies have suggested little, if any change (typically < 2 pounds) from dry weight in these patients, suggesting volume redistribution, not overload.12,13 This disease is associated with fluid shifts from the splanchnic circulation into the pulmonary circulation, resulting in pulmonary edema. Diuretics such as furosemide can reduce LV function, worsen LV filling pressures, and increase systemic vascular resistance once administered by activating the neurohormonal system.11-17 This can actually reduce blood flow to the kidneys and reduce GFR.14-17 If the patient is not truly volume overloaded, then diuretic therapy may harm, rather than help, the patient.
Is there a patient population that does benefit from diuretics? In patients who are systemically volume overloaded, including peripheral edema or ascites, which has occurred over a more extended period, diuretics should be given.1-5 In acute pulmonary edema patients who are hypertensive, start with nitroglycerin and noninvasive positive pressure ventilation, which improve respiratory status, decrease preload, decrease afterload (with nitroglycerin at higher doses).1,17-20 NIPPV reduces need for intubation (NNT 8) and mortality (NNT 13).17-20
Pearl #2: In patients with volume overload, you have multiple avenues for diuresis, and ultrafiltration may improve diuresis in patients refractory to IV diuretics.
In patients with normal blood pressure and volume overload, diuretics should be provided. IV diuretics have short half-lives, and you may need to repeat doses (furosemide can be repeated every 4-6 hours).1-5,8,9 Start out with an IV dose equivalent or greater than the home dose, which can be provided in bolus form or infusion (per the AHA/ACCF Heart Failure Guidelines).2-4,8 If diuresis is not adequate, a higher dose can be used, or add a second diuretic (such as a thiazide).2-5 Whether you provide bolus or continuous infusion is controversial in terms of diuresis. High dose loop diuretics may improve symptoms faster but also increase serum creatinine. However, continuous versus intermittent IV doses do not demonstrate a significant difference in clinical outcomes.21,22 Ultrafiltration is an alternative in patients refractory to IV diuretics, with literature suggesting greater net weight and fluid loss, but no change in mortality.24-27
Myth #2: The safest way of providing nitroglycerin IV is to start with small doses and titrate to relief of symptoms in those with pulmonary edema.
Nitrates cause vasodilation by activating guanylyl cyclase on nitrate-derived nitric oxide, increasing cGMP action.28,29 Nitroglycerin vasodilates venous and arterial vasculature, reducing pulmonary vascular resistance, biventricular filling pressures, and systemic arterial blood pressure.30,31 The most common nitrates we use are nitroglycerin and nitroprusside. Nitroglycerin is more commonly used in heart failure, improving coronary blood flow and reducing myocardial ischemia, with relatively no effect on neurohormones.7-9,28-33 Nitroprusside reduces coronary blood flow, increases myocardial ischemia, and increases neurohormones.32,33
Nitroglycerin’s greatest benefit in pulmonary edema is improving preload and redistributing fluid from the pulmonary system. The AHA recommends using vasodilators in addition to diuretics in patients who fail diuretics alone, or patients with fluid overload but no hypotension.2-5,8 The ESC, Heart Failure Association of the ESC, European Society of Emergency Medicine and Society of Academic Emergency Medicine recommend providing nitroglycerin to those with SBP > 100-110 mm Hg.2-5,34,35 ACEP recommends “administer intravenous nitrate therapy to patients with acute heart failure syndromes and associated dyspnea”, which is a Level B recommendation.1 You have several means of providing nitroglycerin (SL, IV, paste, etc.). You can start with sublingual nitroglycerin with a 400 mcg tablet. Classic IV dosing is to start with 10-20 mcg/min IV, which is increased by 10-20 mcg/min until symptom improvement.1-5,8,20 Keep in mind that nitroglycerin is contraindicated in hypotension, LV outflow obstruction, recent phosphodiesterase inhibitor use, and conditions similar to AHF where vasodilation is not beneficial (COPD). Side effects such as headache (20% of patients) and nitrate resistance and tolerance may occur.36-39
Pearl #3: Nitroglycerin IV is safe at higher doses, including bolus or infusion, which will rapidly improve symptoms.
Nitrates do not decrease mortality rates, but they do significantly improve symptoms and hemodynamics.40-42 Multiple studies have evaluated higher dose nitrates provided IV, bolus or infusion.43-45 One study from 1998 included 110 patients and found bolus dose isosorbide-nitrate 3 mg IV every 5 minutes to be safe and reduce pulmonary edema, need for mechanical ventilation, and rate of myocardial infarction, compared with 1 mg/hr infusion.20 A study from 2000 evaluating isosorbide-nitrate 4 mg IV every 4 minutes in patients with pulmonary edema found reduced need for intubation and mortality rate, though this study included only 40 patients.44 What about the more commonly used nitroglycerin? A 2007 nonrandomized study including patients with pulmonary edema and SBP > 160 mm Hg found nitroglycerin 2 mg IV every 3 minutes reduced need for intubation, need for NIPPV, and ICU admission.43 A 2017 retrospective study found nitroglycerin bolus (500-2000 mcg every 3-5 minutes compared with 20-35 mcg/min infusion and bolus plus infusion) to be associated with reduced need for ICU admission.45 Length of stay (a secondary outcome) was also shorter, but there were no differences in need for intubation.45 What’s your take to work key? Nitroglycerin at higher doses is likely safe with reduced intubation rates and ICU admission. However, it probably does not improve mortality.
Myth #3: Morphine is safe in AHF and should be provided to most patients with AHF.
Many of us were taught the importance of morphine in heart failure and ACS, with its reported effects of preload and heart rate reduction, anxiolysis, and reducing myocardial oxygen demand.46-50 Morphine can decrease sympathetic nervous system activity and reduce central nervous system activity. According to older studies, it produces anxiolysis and reduces cardiac filling and arterial pressures. These suggestions come from older trials, which evaluated 12 dogs, 12 patients with mild pulmonary edema, and 12 patients with myocardial infarction (let’s just say not the strongest literature support).47-49 One study from 1994 suggested venous and arterial vasodilation in dog vasculature (in vitro), and a 2008 study conducted in cats found dose-dependent pulmonary vessel vasodilation with morphine.51 A study in 1979 conducted in post cardiac bypass surgery patients found 0.5 mg/kg IV caused a large reduction in peripheral vascular resistance.52 But what about the patients we are looking at for this post, or heart failure?
Guidelines vary concerning morphine. The ESC supports opioid use in heart failure, with morphine 4-8 mg in patients with pulmonary edema and severe anxiety; however, the HFSA does not include morphine in its recommendations from 2010 and states morphine should be used with caution if provided.4,5,8,53 The ACC/AHA 2013 guidelines do not discuss morphine.2
Pearl #4: In AHF, morphine may be harmful and does not improve patient outcomes.
In patients with AHF, evidence suggests morphine is harmful, as it can induce myocardial depression, reduce heart rate, decrease cardiac output, and result in respiratory depression.54-56 This is likely dose-dependent, with higher doses reducing tidal volume and respiratory rate.55,56 A prehospital study found patients receiving morphine and furosemide to have greater risk of deterioration, compared with groups not receiving medication regimens not including morphine.14 Four other studies suggest harm with morphine, further discussed in a 2008 review article that emphasizes the association of morphine with further deterioration.57-61 A study from the ADHERE registry suggested morphine in decompensated AHF was associated with increased mechanical ventilation, greater length of stay, increased need for ICU admission, and higher risk-adjusted mortality.62 A retrospective study released in 2011 (2336 patients) found morphine was associated with higher mortality; however, with propensity score matching, the association was not significant.63 A study with 6516 patients found greater mortality at 30 days (20% vs. 12.7%), but in-hospital mortality and length of stay were not different.64
Most of the literature consists of observational studies with many confounders (morphine may have been more commonly given in patients with severe heart failure). Determining if morphine is actually associated with increased intubation, compared to its use as a sedative post-intubation, is difficult to determine.65 Let’s face it: if you want to reduce preload and afterload in these patients, you can use NIPPV and nitroglycerin, which are safer and more efficacious.14,17,18
Myth #4: Almost all patients with heart failure require admission, as risk stratification tools offer little benefit.
As we all know, disposition is key in the ED. In patients with AHF, this decision is complex, as AHF is a heterogenous syndrome with a variety of presentations. Other factors include comorbidities, social factors, patient education, and follow up.1-5,66,67 Patients may not improve with initial therapy and need a little more prolonged therapy, such as in an observation unit. However, not all ED’s have an observation unit, which further makes disposition decisions difficult.68,69
Patients with AHF in the U.S. are more often admitted (approximately 80%), though more patients are discharged in Canada and Europe.70-75 A key question is whether patients discharged from the ED with AHF have higher rates of adverse events, compared with admitted patients. Mortality varies widely across studies (4% at one month, reaching 20% at one year).71-76 One study found higher rates of adverse outcomes at 30 days in patients discharged directly from the ED, but adverse events at 90 days were similar.72 A separate study found similar mortality rates at 7 and 30 days for patients discharged directly from the ED, though past this point, adverse event rates were higher in patients discharged.73 However, these studies have many confounders, and close evaluation of these studies reveal poor compliance with guideline-directed therapy and poor patient follow up as major predictors of adverse events.2-5,67 AHF return rates range from 20%-35% within a 30 day period, and more than 75% of these returns result in hospitalization.74,77-81
Pearl #5: Risk stratification tools can assist, but disposition remains challenging. Several factors should be considered in the disposition decision.
Sure, there are several validated risk stratification tools for conditions such as pneumonia and pulmonary embolism, but what about heart failure. Though several scores have been evaluated for use in AHF, most of these have been evaluated in admitted patients.82-90 However, two scores have been evaluated in ED patients: the Ottawa Heart Failure Risk Scale (OHFRS), based on 9 or 10 clinical variables, and the Emergency Heart Failure Mortality Risk Grade (EHMRG).83,91-93
The OHFRS classifies adverse events as 30-day all cause mortality or several outcomes within 14 days of the ED visit (intubation, ICU admission, myocardial infarction, major cardiovascular procedure, or hospital admission).91,92 The derivation study included 559 patients in 6 ED’s, followed by validation. Scores of 1, 2, and 3 as threshold for admission demonstrated sensitivities of 95.2%, 80.6%, and 64.5%, respectively, for adverse events.91 A 2017 prospective study with 1100 patients found scores >2 demonstrated sensitivity of 91.8% for adverse event, but this increased admission rates.92 If scores > 2 are used as criteria for admission, admission rate is reduced, but sensitivity for adverse events remains approximately the same. The EHMRG attempts to predict 7-day mortality.93 The score does not take into account ejection fraction or patients with ESRD. Derivation and validation studies are promising. As discussed, other scores have been derived from hospitalized patients, which fail to consider patients who are discharged and take into account factors that may not be available in the ED.83-90
These scores are promising, but several other factors should be considered. Patients with hemodynamic instability, ischemia on ECG or biomarkers, or those who require IV nitroglycerin or respiratory support require admission (probably to the ICU). Patients should also have normal blood pressures, normal sodium (135-145 mmol/L), renal function at patient baseline, and room air saturation greater than 92% if considering discharge.2-5,83 Patients should be stable, subjectively feel improved, and have the ability to follow up within 7 days. These factors, along with the OHFRS or EHMRG scale, may allow for safe discharge.83,91-93
– A variety of misconceptions are present concerning the ED evaluation and management of AHF.
– Patients with hypertensive pulmonary edema require nitroglycerin and NIPPV. Diuretics before these therapies can be harmful.
– Diuretics can be beneficial in patients with more subacute decompensation and systemic volume overload.
– Nitroglycerin in bolus doses is safe and can reduce need for ICU admission. It probably does not improve mortality.
– Morphine can be harmful; you have safer options to reduce preload and afterload (nitroglycerin and NIPPV).
– Disposition is a complex decision, but combining assessment of patient hemodynamic status, ability to follow up, lab markers/ECG, and risk stratification toolsmay allow patient discharge.
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