Monday, July 09, 2012

The use of morphine in acute pulmonary edema: good or bad?

In med schools, we have often been taught that the treatment of acute pulmonary edema is LMNOP where L = Lasix, M = morphine, N = nitrates, O = oxygen, P = position/prop up the patients.

However, many recent studies have shown that the evidence of the use of morphine in acute pulmonary edema is not only weak, but is potentially harmful to the patients.

Here's some notes on the use of morphine in acute pulmonary edema:

1. Why morphine was initially advocated for APO? (a history question)
This is because animal studies suggest that morphine produces a significant peripheral venodilation and moves significant quantities of blood from the central to the peripheral circulation; and thus reduce the workload of the heart.

(Ref: Vasko JS, Henney RP, Oldham HN, Brawley RK, Morrow AG. Mechanisms of action of morphine in the treatment of experimental pulmonary edema. American Journal of Cardiology 1966; 18:876-83.)

2. However, subsequent studies (e.g., Vismara et al, 1976) of venous tone changes in normal subjects vs patients with mild stable APO demonstrate that magnitude of the venodilation induced by morphine is rather minimal, and the amount of blood that could be pooled in the limbs has been calculated to be quite small (70ml in normal subjects vs 116mls in patients with APO).  This in fact is insufficient to cause significant clinical improvement in patients’ with APO.

(Ref: Vismara LA, Leaman DM, Zelis R. The effects of morphine on venous tone in patients with acute pulmonary edema. Circulation 1976; 54:335-7.)

3. Also, some studies show that these effects are indeed mediated via the histamine receptors and has nothing to do with the opiate receptors. In other words, we are depending on the side-effects of morphine to exert the venodilation.

(Ref: Grossmann M, Abiose A, Tangphao O, et al. Morphine-induced venodilation in humans. Clinical Pharmacology and Therapeutics 1996;60:554)

4. As early as 1999, Sacchetti et al (1999) reported increased intubation rates and a longer stay in the ICU if morphine was used.

(Ref: Sacchetti A, Ramoska E, Moakes ME, et al. Effect of ED management on ICU use in acute pulmonary edema .Am J Emerg Med 1999;17:571–4)

5.  In a recent retrospective analysis of the Acute Decompensated Heart Failure National Registry (ADHERE), as compared to patients not on morphine, patients on morphine:
  • were more likely to require mechanical ventilation (15.4% vs 2.8%)
  • had a longer median hospitalisation (5.6 vs 4.2 days)
  • more ICU admissions (38.7% vs 14.4%), and
  • had greater mortality (13.0% vs 2.4%) (all with p<0.001).

Even after risk adjustment and exclusion of ventilated patients, morphine was an independent predictor of mortality (OR 4.84 (95% CI 4.52 to 5.18), p<0.001). 
(Ref: Peacock WF, Hollander JE, Diercks DB, Lopatin M, Fonarow G, Emerman CL. Morphine and outcomes in acute decompensated heart failure: an ADHERE analysis. Emerg Med J. 2008 Apr;25(4):205-9.)

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