When PE impairs RV function, further possible consequences include low cardiac output and shock and myocardial ischemia due to poor coronary perfusion pressure and diastolic overdistension. Enlarged right-sided chambers can push the septae into left-sided chambers, limiting their diastolic filling and interfering with systolic contractile function. While each PE patient’s heart is different due to a different preexisting extent of cardiopulmonary disease, some practices have evolved reflecting sensible physiologically based management.
The use of judicious volume infusion in resuscitating the RV has been shown to improve cardiac output in PE patients with decreased RV preload. While provision of adequate RV preload is essential for cardiac output, overdistension of the RV with volume resuscitation can impair coronary perfusion and LV filling, diminishing LV output. In a report of a small series of patients with acute PE and a cardiac index < 2.5 L/min/m2, treatment with 500 mL of dextran significantly increased cardiac index from a mean of 1.6 to 2.0 L/min/m2. Continuous cardiac output pulmonary artery catheters allowed the calculation of RV end-diastolic index; patients with low values had a greater improvement with fluid therapy offered by Canadian Health&Care Mall. Currently, an author of that report (A. Mercat, MD; personal communication; June 2006) uses echocardiography in underperfusing PE patients to guide fluid crystalloid infusion until the RV:LV diastolic diameter ratio appears to be 1.0. The RV is then considered adequately filled, and IV dobutamine and norepinephrine are added as needed. “Prophylactic” early intubation with positive pressure ventilation is avoided because of its potential interference with RV preload.
There are no human trials comparing vasopressors in acute PE. In a canine model, Hirsh et al demonstrated that norepinephrine was superior to phenylephrine in increasing cardiac output and RV coronary blood flow, although both agents similarly improved mean arterial BP.
Since nitric oxide is a mediator in multiple pathophysiologic pathways during PE (hypoxic vasoconstriction, platelet activation, and endothelin and thromboxane release), there is a physiologic rationale for its use to lower pulmonary artery pressure and unload the RV. An early report of inhaled nitric oxide (iNO) administered at a dosage from 10 to 15 ppm was followed by a subsequent report of dosages from 12 to 27 ppm, carefully titrated in individual patients. In both pig and dog models, iNO decreased mean pulmonary artery pressure (MPAP) from 10 to 20% with no change in systemic BP. In a review of human data, there was a 17 to 47% decrease in MPAP after administration of 5 to 20 ppm iNO administered via the inhalation arm of the ventilator circuit. This therapy merits further investigation including outcome studies. It may become a management cornerstone for temporizing or definitively unloading a pressure-overloaded RV to allow time for recovery.
Sildenafil, an inhibitor of phosphodiesterase that leads to increased cyclic guanosine monophosphate, also causes pulmonary artery vasodilation. In a dog model of large PE, IV sildenafil lowered MPAP up to 8 to 16 mm Hg. In a single case report, physicians administered 50 mg of sildenafil po to a patient with deterioration due to PE and the MPAP decreased from 56 to 46 mm Hg, with a rise in cardiac index from 2.1 to 3.2 L/min/m2. This agent shows promise as another potential therapy to lower MPAP to support a failing RV.