The management of pulmonary hypertension and right ventricular dysfunction in critically ill patients presents many challenges, but current evidence suggests several clear and effective approaches. According to a systematic review of the literature, use of vasopressors had a moderate to high level of supporting evidence. Studies invest igating inotropic drugs and pulmonary vasodilators also demonstrated efficacy for levosimendan and selective phosphodiesterase inhibitors.
“This systematic review confirms that management of right heart function is multifaceted and problematic, but several key messages emerged from the analysis,” said Johnny J. Kenth, MBBS, academic clinical fellow at the National Institute for Health Research, in London. “If your center doesn’t regularly handle complex cases, early referral to specialized centers is recommended.
“Our findings also echoed what previous reviews have suggested regarding vasopressors,” Dr. Kenth said. “Norepinephrine at higher doses can increase pulmonary vascular resistance, which leads to worse outcomes. Vasopressin has emerged as a promising alternative to norepinephrine and is associated with fewer adverse outcomes.”
As Dr. Kenth explained, pulmonary hypertension, right ventricular dysfunction and right heart failure are all independent prognostic indices for poor outcomes, but there is limited consensus on the acute management of these conditions in cardiothoracic ICUs across Europe. Although pulmonary hypertension may be common in ICU patients, when it is associated with right ventricular dysfunction and right heart failure, the nuances of specialist management in optimizing right heart function have been shown to improve survival, Dr. Kenth said. The foundation of such treatment typically involves vasopressors, inotropes and/or specific pulmonary vasodilators.
Demanding Inclusion Criteria
To assess the efficacy of vasoactive drugs in the management of pulmonary hypertension, right ventricular dysfunction and right heart failure in adult ICU patients, Dr. Kenth undertook a systematic review of the literature as part of his academic clinical fellowship. He searched PubMed/Medline, EMBASE, CINAHL, Cochrane Central Register and Google Scholar for randomized controlled trials in English with a predefined protocol and reported prior specified outcome measures. Primary outcome measures of the trials included continuous variables such as hemodynamic indexes, markers of right ventricular function and dichotomous data, including morbidity, mortality, hospital length of stay and adverse events.
As Dr. Kenth reported at the 2017 annual meeting of the International Anesthesia Research Society (abstract 1557), 38 of 1,275 studies satisfied the inclusion criteria, for a total of 5,874 patients (mean age, 47.5 years). Some details of the studies are as follows:
Nine studies assessed the efficacy of vasopressors in the management of pulmonary hypertension and right ventricular failure. Although low-dose norepinephrine was found to improve hemodynamic parameters, higher doses were associated with inferior outcomes. In addition, vasopressin demonstrated superiority to norepinephrine, with minimal changes to pulmonary vascular resistance and fewer adverse events. Patients with low blood pressure should start with vasopressors to improve their hemodynamic parameters, Dr. Kenth said.
Thirteen studies investigated inotropic drugs, in which Dr. Kenth observed “strong evidence to support their use across all patient groups.” Phosphodiesterase inhibitors and levosimendan were found to be superior to dobutamine, as high doses of dobutamine were associated with increased pulmonary vascular resistance and right ventricular dysfunction. Moreover, Dr. Kenth said, both dopamine and epinephrine were strongly associated with increases in pulmonary vascular resistance.
Sixteen studies of pulmonary vasodilators identified a benefit for patients with preexisting pulmonary hypertension and after cardiothoracic or hepatic surgery. Selective PDE5 inhibitors (e.g., sildenafil) were highly effective at reducing pulmonary hypertension and improving right ventricular dysfunction, according to Dr. Kenth, and inhaled pulmonary vasodilators were equally as effective as IV agents with fewer side effects. In patients with acute respiratory distress syndrome, however, inconsistent efficacy was reported.
Despite these conclusions, additional assessment of the studies revealed uncertainty in the risk for bias across several domains.
“This review demonstrated the paucity of high-quality, multicenter randomized controlled trials with a low propensity for bias,” Dr. Kenth said. “Future trials would benefit from collaborating with other centers to increase sample sizes, reduce bias and improve the strength of associations.”
Dr. Kenth and his colleagues plan to update this review by incorporating studies of mechanical heart–lung support in treating pulmonary hypertension and right ventricular dysfunction, as either primary therapy or a rescue measure.
Moderator of the session Ruben Azocar, MD, FCCM, professor and chair of the Department of Anesthesiology and Perioperative Medicine at Tufts University School of Medicine, in Boston, noted that despite the reduction in adverse outcomes associated with vasopressin, its high cost poses a potential barrier for prescribers in the United States.
“In the U.K., especially being a trainee, cost is not frequently considered, but vasopressin, which is a newer drug, is extremely expensive,” Dr. Kenth said. “Nevertheless, it’s a much better drug with much less effect on pulmonary vascular resistance.”