1. What is the basic pathophysiology of acute pulmonary edema (APE)? How does this differ from a CHF exacerbation?
APE is defined as the leakage of fluid from the pulmonary capillaries into the alveolar space due to increased hydrostatic pressure, resulting from the inability of the left ventricle (LV) to adequately handle pulmonary venous return. Poor LV function leads to congestion and resultant poor right ventricular function. In addition, leakage of fluid into the alveolar space washes away pulmonary surfactant.
During APE, the sympathetic nervous system becomes stimulated leading to increased heart rate and attempts to increase contractility (usually, these patients’ hearts cannot increase contractility so only HR is increased). In addition, sympathetic activation, along with renin-angiotensin system activation, leads to venous constriction and increased preload. Effective circulating volume is also increased as antidiuretic hormone (ADH) increases in response to decreased splanchnic blood flow (i.e. decreased renal perfusion).
In CHF, there is also leakage of fluid into the alveolar space, but these other systems are not quite as activated as in APE, and so you don’t see as much vasoconstriction or decreased organ perfusion. Basically, these two entities lie on a spectrum, with CHF on one end and APE on the other.
2. What medications do you use for immediate management of APE and why?
Medical intervention must focus on both preload and afterload reduction. Decreasing preload leads to decreased RV filling and decreased pulmonary venous congestion. It is generally accepted that nitrates are the most effective preload reducing agents. They can be given sublingually, transdermally and intravenously making them both easy to administer and titrate to effect. Often, doses of upward of 200 mcg/min are required to effectively reduce preload. The key is to rapidly titrate IV nitro infusions as the patient’s BP tolerates. At high doses, nitro also reduces afterload.
Improving LV emptying with afterload reduction can also reduce the hydrostatic pressure. Decreasing the afterload, or the amount of pressure work the left ventricle must do, results in “unloading” the heart and decreasing pulmonary hydrostatic pressure.
A number of different interventions have been suggested to decrease afterload, including morphine, furosemide, angiotensin-converting enzyme inhibitors (ACEI) and non-invasive positive pressure ventilation by mask.
There is a great deal of evidence with regards to each of these agents and reviewing it all here would be difficult. Here is a summary:
Morphine, although long a part of the APE algorithm is not effective in afterload reduction, and has been shown in observational and retrospective studies (e.g., Peacock, et al, for the ADHERE registry) to increase morbidity and mortality. It should no longer be part of our treatment package.
Furosemide is also rarely necessary in treatment. First of all, roughly 50% of patients presenting with APE are not volume overloaded. If you are not volume overloaded, you don’t need diuresis. Secondly, there is no immediate improvement in either preload or afterload when furosemide is used (Kraus, et al.). In fact, afterload undergoes a mild increase in the first 15 minutes after furosemide is given. Lastly, remember that many patients with APE have ESRD and so you can’t diures them with furosemide, even if you think they need it.
ACEI are an interesting modality in that they have been shown (albeit in small studies) to reduce afterload. Angiotensin II is a potent vasoconstrictor and sympathetic agonist; it also increases sodium absorption and promotes aldosterone release, thereby increasing the blood volume. All of these actions lead to an increased afterload and worsening cardiac function. ACEI attenuate this reaction by blocking the critical conversion of angiotensin I to angiotensin II. In addition, ACEI increase circulating levels of bradykinin, a potent vasodilator. Hamilton, et al, found a reduction in the need for mechanical ventilation in patients receiving ACEI. Sacchetti, et al, showed that ACEI use in APE patients was associated with a lower ICU admission rate (OR = 0.29) and lower intubation rates (OR = 0.16). The major downside to ACEI is that they last for a long time, so if you get into trouble with blood pressure, you are stuck with their effects (as opposed to nitro, which wears off quickly).
3. What is the role of non-invasive positive pressure ventilation (NIPPV) in APE? Which is preferred: CPAP or BiPAP?
NIPPV can be applied either via continuous positive airway pressure (CPAP), or bilevel positive airway pressure (BiPAP). Both are effective at decreasing the work of breathing. APE patients have decreased lung compliance because they have washed away their surfactant and have atelectatic lungs and/or alveolar collapse. The “threshold work,” or energy necessary to open these alveoli, is dramatically higher in APE (over 25% consumption of energy, compared to less than 3-4% in the normal lungs). CPAP and BiPAP reduce the work of breathing by “stenting” the alveoli open during expiration and thus diminishing the energy consumption needed to open the alveoli during each inspiration. The resultant decrease in work of breathing allows for a greater amount of energy to be devoted to cardiac work and thus potentially increases LV function
To date, the data on superiority of CPAP or BiPAP is inconclusive but tends to favor BiPAP (Mehta, et al). This advantage may be due to the fact that BiPAP decreases afterload and leads to improved cardiac output, while CPAP does not.
4. When do you intubate?
As with all critical disease processes, the decision to intubate is a clinical one. There are no guidelines, lab values, or vital signs that can give you this answer. In general, these patients are older and have less cardio-pulmonary reserve and as a result, tend to tire quickly. Failure to oxygenate or ventilate, evidence of tiring, and failure to tolerate NIPPV are just some of the criteria used to consider intubation. It is important to note that intubation and mechanical ventilation will relieve a patient of much of the work of breathing, and increase the available energy for myocardial demand, which may improve cardiac function.
References and Further Reading
Ferguson C and Redford A. Towards evidence based emergency medicine: best BETS from the Manchester Royal Infirmary. BET 4: ACE inhibitors in addition to standard treatments in acute heart failure. Emerg Med J. 2010 Jan; 27(1): 57-58.
Mebazaa A, et al. Practical recommendations for prehospital and early in-hospital management of patients presenting with acute heart failure syndromes. Crit Care Med. 2008 Jan; 36 (1 Suppl): S129-139.