Inflammatory Basis of Pulmonary Arterial Hypertension

Implications for Perioperative and Critical Care Medicine

Neil M. Goldenberg, M.D., Ph.D.; Marlene Rabinovitch, M.D.; Benjamin E. Steinberg, M.D., Ph.D.


Anesthesiology. 2019;131(4):898-907. 

In This Article

Inflammation in Pulmonary Arterial Hypertension: Implications for the Anesthesiologist

Our evolving understanding of the pathobiology of pulmonary arterial hypertension and the development of new treatment paradigms will have implications for anesthesiologists and critical care physicians. Hopefully such treatments will result in improved preoperative optimization of these high-risk patients. However, as with any new therapies, their interactions with anesthetic drugs and the operative environment will have to be studied and accounted for. It stands to reason that some of these experimental agents will result in some degree of immunosuppression, which will necessitate vigilance and aggressive treatment of infection and sepsis. The overall inflammatory milieu in this population may predispose them to further insults. For instance, pulmonary arterial hypertension may serve as a first hit, increasing susceptibility to ventilator-induced lung injury and acute respiratory distress syndrome. In fact, several of the biomarkers and inflammatory mediators seen in pulmonary arterial hypertension are also found in acute respiratory distress syndrome and correlate with poor outcome.[65]

There is a broad base of evidence showing that the perioperative period is a time of immune dysregulation and inflammation, and that anesthesia can have a meaningful impact on this state.[66] One could speculate that anesthetic techniques that serve to minimize these insults—including regional anesthesia, and pre-emptive analgesia—may benefit patients with pulmonary arterial hypertension coming for surgery. As new treatments emerge for pulmonary arterial hypertension patients, and our understanding of disease pathogenesis deepens, this will represent an important field of study for perioperative and critical care physicians. Until such agents are approved for use, it is unlikely that specific perioperative data will be available to guide anesthetic care. For a discussion of the interactions of pulmonary vasodilators with the operative setting, please see the Perioperative Management of Patients with Pulmonary Arterial Hypertension section above, and other publications.[9] As an example of the potential for immunotherapy for pulmonary arterial hypertension in the critical care setting, an instructional case series using tacrolimus has been published.[67] Having identified tacrolimus as an agent that modulates pathways important in pulmonary arterial hypertension,[68] a series of three patients with end-stage, treatment-refractory pulmonary arterial hypertension were given low-dose tacrolimus. One patient was subsequently delisted from the lung transplant registry because of her improvement to low-risk status within 2 months of treatment initiation. A second patient had substantial recovery of RV function within 3 months, with concomitant improvements in her functional status. A third patient improved, voluntarily discontinued tacrolimus and worsened, only to again improve following reinstitution of therapy.[67] A randomized trial of tacrolimus for pulmonary arterial hypertension is currently underway to systematically assess its utility in pulmonary arterial hypertension (NCT01647945), but this small series of patients may offer a glimpse into the future of pulmonary arterial hypertension management in the clinic and the intensive care unit. The fact that palliative disease was improved suggests that this strategy may become useful in the acute setting.