Page 446 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

316 PART 3: Cardiovascular Disorders

Vasopressin: The role of vasopressin (and its longer acting congener, ter- By contrast, in a small controlled study of 14 patients with acute PE and
lipressin) remains controversial and incompletely evaluated. Vasopressin mild RV dysfunction, parenteral PGI was no more effective than placebo
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clearly functions as a systemic vasoconstrictor at high doses. In patients in improving RV dilation or other measures of RV pressure overload. 131
with septic shock, replacement of acutely depleted endogenous vaso- Although not conclusively demonstrated, inhaled prostacyclin has
pressin with a low-dose infusion (0.04 U/min) is thought to improve been used with some success in perioperative acute RHS.
catecholamine sensitivity via the functionally vasoconstricting V receptor.
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The pulmonary vasculature has been shown by some investigators to Inodilators Phosphodiesterase Inhibitors: Amrinone is an inotrope and
express V receptors, but that vasopressinergic stimuli may paradoxi- vasodilator with potential in the acute right heart syndromes. In a canine
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cally mediate pulmonary vasodilation. 124,125 This might suggest a salutary model of massive embolism, amrinone (0.75 mg/kg bolus followed
potential for vasopressin therapy in acute right heart syndromes. In a by 7.5 µg/kg per minute) lowered pulmonary artery pressure, raised
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canine model, however, vasopressin caused both systemic and pulmo- cardiac output, and raised systemic blood pressure. Limited data are
nary vasoconstriction while impairing RV contractility. Our present available for the use of milrinone in acute RHS and its use is limited by
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practice is to avoid vasopressin for acute right heart syndromes unless a long half-life and limited ability of titration. Additionally, milrinone
catecholamine-dependent septic shock is present. has been shown to be less efficacious than inhaled NO in treating
pulmonary hypertension post-cardiac surgery. Administration of
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Calcium Sensitizers: Levosimendan is widely used in acute left heart inhaled milrinone in perioperative severe pulmonary hypertension
failure episodes and is approved for use in Europe and countries other demonstrated a preferential pulmonary selective effect in reducing PVR
than the United States. Levosimendan appears to have unique phar- and mean Pa pressures compared with parenteral administration thus
macologic properties that recommend its potential value in acute RH avoiding systemic adverse effects. Another phosphodiesterase inhibi-
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syndromes. 109,110,126,127 Experience in acute right heart syndromes is less tor, dipyridamole, has been evaluated as an adjunct to NO in pediatric
well described. In a porcine acute PE model of RV failure levosimendan patients with acute RHF, and shown to have some additional pulmonary
was effective in improving RV contractility, decreasing RV afterload vasodilatory effects. 133,134
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and improving right ventriculovascular coupling. In a canine model Significant interest has arisen in the therapeutic potential of the selec-
of acute RV failure induced by Pa constriction, levosimendan was more tive type 5 PDE inhibitors, sildenafil, tadalafil, and vardenafil, initially
effective than dobutamine at equivalent inotropic levels at restoring approved for male erectile dysfunction. Impressive acute reductions in
right ventriculovascular coupling efficiency through direct effects on the pulmonary arterial pressures have been demonstrated with oral and
pulmonary vasculature. 109 intravenous administration in animal models of acute lung injury
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and RHS, in patients with established pulmonary hypertension, 136-138
Antiarrhythmics: Atrial tachycardias (atrial flutter and fibrillation) are and in pulmonary hypertension complicating pulmonary fibrosis.
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an important exacerbating factor in patients with acute-on-chronic Additionally, synergistic effects of selective PDE inhibitors in combina-
PH with RV diastolic dysfunction and a frequent occurrence in tion with inhaled and intravenous vasodilators has been demonstrated
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patients with sepsis and ARDS associated acute cor pulmonale. in acute lung injury–associated right heart syndromes. 140-142 We have
Since rate control alone may be insufficient to reverse acute cor pul- used sildenafil for synergistic effects with dobutamine and inhaled PGI
monale, reestablishment of normal sinus rhythm is often necessary. in patients with severe RV dysfunction. Lastly, sildenafil through its
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Our approach is to initiate antiarrhythmics (loading with intravenous effects on cGMP metabolism, appears to be effective in ameliorating the
amiodarone in preference to β-blockers or digoxin) and perform potentially morbid rebound effects of inhaled NO withdrawal in patients
prompt electrical cardioversion in acutely unstable patients. Tachycardia with acute RH syndrome. 143
mapping and radiofrequency ablation, while often definitive, is rarely
tolerated in acutely ill patients. Nitric Oxide: Inhaled nitric oxide (iNO) combines the physiological
■ REDUCE RIGHT VENTRICLE AFTERLOAD AND RV ISCHEMIA potential for hemodynamic as well as gas exchange improvement in
acute right heart syndromes. iNO is widely prescribed in North America
Prostanoids: Prostaglandin E (PGE , alprostadil) is a potent pulmonary and Europe for adults in the intra- and perioperative and critical care
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vasodilator that exhibited promise in the treatment of ARDS. When environments with acute and acute-on-chronic right heart syndromes,
infused at a dose of 0.02 to 0.04 µg/kg per minute to patients with severe including ARDS and neonatal acute hypoxemic respiratory failure.
ARDS and mean Pa pressure greater than 20 mm Hg, Pa pressure fell Acute improvements in gas exchange and pulmonary vascular resistance
15% despite an increase in cardiac output. At the same time, however, and flows have been documented in a substantial number of patients
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systemic blood pressure fell to a similar degree, and intrapulmonary (reviewed by Siobal and Hess ). In term newborns with severe acute
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shunting rose significantly. In an oleic acid model of porcine ARDS, hypoxemic respiratory failure (from conditions other than congenital
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PGE lowered pulmonary artery pressure, but stroke volume and stroke diaphragmatic hernia), evidence supports early initiation of iNO at a
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work did not improve significantly. 112 flow rate of 20 ppm. However, there has to date been no prospective
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When inhaled, prostacyclin (PGI , epoprostenol) is a potent and demonstration of meaningful improvements in outcomes, resource
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selective pulmonary vasodilator. In a porcine hypoxia-induced acute PH utilization or long-term performance/quality of life for any adult
model, inhaled PGI doubled cardiac output and halved RV afterload. patient group with acute right heart syndrome alone or in conjunction
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In patients with ARDS given prostacyclin (PGI , 4 ng/kg per minute), with primary hypoxemic respiratory failure or PE. 144-146 Remarkably in
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pulmonary artery pressure fell, RV ejection fraction rose, and cardiac meta-analysis of 4 RCTs of iNO studies reporting pulmonary vascular
output increased significantly. When compared for acute hemody- pressures in ARDS, despite improvements in oxygenation and mean
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namic effects in patients with primary pulmonary hypertension (PPH), PAP, there was no different on either day 1 or day 4 of therapy amongst
aerosolized prostacyclin (approximately 14 ng/kg per minute over iNO treated patients versus controls. Day 1 to 4 studies (165 patients),
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15 minutes) was demonstrated to be a pharmacologically more potent treatment effect favoring iNO; 0.95 (95% CI [0.88-1.03] P = 0.24); day 4
acute vasodilator than inhaled NO (NO 40 ppm for 15 minutes). 129 to 3 studies (130 patients), treatment effect favoring iNO; 0.94 (95% CI
In a similar comparison in ARDS patients, gas exchange parameters were [0.88-1.01] P = 0.08).
comparably improved when inhaled PGI (7.5 ± 2.5 ng/kg per minute) was Concerns regarding the use of iNO in RHS relate to risks for platelet
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compared with inhaled NO at a dose lower than that in the PPH study dysfunction, renal failure, left-shift of the dose-response curve with
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(17.8 ± 2.7 ppm). This may suggest that in patients with right heart continued use and potential for accumulation of toxic reactive oxygen
syndromes and long-standing pulmonary hypertension, inhaled prosta- and nitrogen species, including s-nitrosothiols and peroxynitrite as
cyclin may afford greater efficacy. well as the potential for methemoglobinemia. Taken together, the lack of
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