Which medications are used in the perioperative management of pulmonary hypertension (PH)?

Updated: Sep 11, 2019
  • Author: Swapnil Khoche, MBBS, DNB, FCARCSI; Chief Editor: Sheela Pai Cole, MD  more...
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Pharmacologic therapy

Pharmacologic agents used perioperatively to treat PH include vasodilators, inodilators, inotropes, and vasopressors (see Table 1 below). [20]

Table 1. Perioperative Pharmacologic Therapy for Pulmonary Hypertension (Open Table in a new window)

  Starting Dosage Mechanism of Action Effects
    Epoprostenol 2 ng/kg/min IV

Increased prostacyclin levels/effects

Increases cAMP

Pulmonary and systemic vasodilation; decreased platelet function; rebound pulmonary hypertension after discontinuance
    Treprostinil 2 ng/kg/min SC/IV
    Sildenafil 10 mg IV tid

PDE-5 inhibitor

Increases cGMP

Pulmonary vasodilation; improves erectile dysfunction
    Nesiritide  2 μg/kg IV bolus, then 0.01-0.03 μg/kg/min 

Recombinant BNP

Increases cGMP

Systemic vasodilation; natriuresis and diuresis; increased capillary permeability
    Nitroprusside 0.2-2 μg/kg/min IV

Increases NO levels

Increases cGMP

Pulmonary and systemic vasodilation; risk of cyanide toxicity; tachyphylaxis

    Nitroglycerin  0.5-2.5 μg/kg/min IV

Increases NO levels

Increases cGMP

Pulmonary and systemic vasodilation
    Nicardipine 5-15 mg/hr IV CCB; ↓intracellular calcium Pulmonary and systemic vasodilation
    Dobutamine 5-20 μg/kg/min IV Beta1 > beta2 agonist Inotropy and chronotropy (beta1); pulmonary and systemic vasodilation (beta2); increased HR can lead to increased oxygen demand
    Milrinone 50 μg/kg IV bolus, then 0.25-0.5 μg/kg/min

PDE-3 inhibitor

Increases cGMP and cAMP

Inotropy; pulmonary and systemic vasodilation


(investigational in US)

6-12 μg/kg IV bolus, then 0.1-0.3 μg/kg/min Sensitizes myocyte contractile proteins to calcium and inhibits vascular potassium channels Inotropy and lusitropy; pulmonary and systemic vasodilation
    Epinephrine 0.03-0.1 μg/kg/min IV Beta1, beta2, and alpha1 agonist  Inotropy and chronotropy (beta1); systemic and pulmonary vasoconstriction (alpha1)
    Dopamine 2-20 μg/kg/min IV D1 agonist (2-5 μg/kg/min), beta1 agonist (5-10 μg/kg/min), alpha1 agonist (10-20 μg/kg/min)  Inotropy and chronotropy at lower doses (beta1); high doses primarily vasoconstrict (alpha1)
    Isoproterenol 0.025-0.5 μg/kg/min IV Beta1 and beta2 agonist  Inotropy and chronotropy (beta1); pulmonary and systemic vasodilation (beta2)
    Vasopressin 0.01-0.04 U/min IV V1 and V2 agonist; ↑Ca via activation of phospholipase C Systemic vasoconstriction in peripheral tissues; coronary, renal, cerebral, and pulmonary blood flow preserved
    Phenylephrine 20-200 μg/min IV Alpha1 agonist  Systemic vasoconstriction (alpha1)
    Norepinephrine 0.02-0.05 μg/kg/min IV Alpha1 > beta agonist  Systemic vasoconstriction (alpha1); minor inotropy (beta1) 
BNP = brain natriuretic peptide; cAMP = cyclic adenosine monophosphate; CCB = calcium-channel blocker; cGMP = cyclic adenosine monophosphate; NO = nitric oxide; PDE = phosphodiesterase.

Intraoperatively, the hemodynamic goals are to minimize PVR while maintaining effective RV systolic function and a normal-to-high MAP so as to maintain perfusion to end organs.

Accordingly, the inotropic agent of choice is typically dobutamine, which, at dosages below 5 μg/kg/min, is known to increase contractility and decrease PVR. [21]  Milrinone, a phosphodiesterase (PDE)-3 inhibitor, has similar effects on inotropy and PVR and can act synergistically with dobutamine; however, it is associated with tachyphylaxis and is usually given only for short periods. At higher dosages (eg, >10 μg/kg/min for dobutamine), increased heart rate–related oxygen consumption generally offsets the benefits from increased cardiac output.

Levosimendan is a novel calcium sensitizer that, so far, has only been used investigationally in the United States. It causes an increase in contractility and a reduction in PVR without a significant increase in oxygen consumption. [8]  Levosimendan is not currently available for clinical use in the United States but has shown promise for reducing mortality in patients with heart failure as compared with dobutamine. 

Alpha agonists such as phenylephrine and vasopressin are essential for increasing SVR and raising the perfusion pressure to the RV. Low dosages of vasopressin may also cause a degree of pulmonary vasodilation, which can be beneficial in this setting. [4]

Pulmonary vasodilators improve forward flow by reducing afterload and manipulating hypoxic vasoconstriction. They should be tried after RV perfusion and cardiac output have been optimized. [4]  Only a small minority of patients with PH will respond to calcium-channel blockers with vasodilation, and these agents can cause systemic hypotension that leads to hemodynamic compromise. Although patients taking calcium-channel blockers should continue to do so perioperatively, these agents generally are not used intraoperatively for acute reduction of PVR.

PDE-5 inhibitors, of which sildenafil is the prototype, have been shown to reduce PVR, improve LV diastolic dysfunction, and enhance quality of life in patients with PH. These medications are among the few with proven benefit in WHO type II PH, though as with calcium-channel blockers, intraoperative use of this class of drugs is minimal.

Drugs administered via the inhalational route, such as iloprost (also known as prostacyclin) and iNO, have the benefit of improving ventilation/perfusion (V/Q) mismatch by causing vasodilation in only the well-ventilated areas of the lung. Because they have a short half-life and thus are easily titratable, they are particularly useful in the operating room (OR). [4]  Iloprost is also available in an intravenous (IV) form (outside the United States), though it can cause systemic hypotension and inhibition of platelet aggregation. Rebound PH is a possibility with abrupt discontinuance of iNO; gradual withdrawal is therefore recommended.

The exception to standard therapy is CTEPH, which has been found to be minimally responsive to external mediators of pulmonary vasodilation. In this situation, providers must be especially vigilant to avoid perturbations that would increase pulmonary vascular tone, including hypoxia, hypercarbia, acidosis, and pain. Furthermore, dobutamine, milrinone, and iNO seem to have minimal effect on PVR, and thus it is the authors' preference to use dopamine or epinephrine for inotropic support. This avoids compromising MAP and cardiac perfusion pressure (especially to the RV).

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