The Daily Dose • Tuesday, May 1

Management of Patients with Pulmonary Hypertension

By Amanda Decimo, Nurse Anesthetist, from the IARS 2018 Annual Meeting*

Pulmonary hypertension (PH) incidence is on the rise. Dr. Ronald Pearl of Stanford University School of Medicine opens this panel discussion with the reminder that as these patients receive better treatment, they are living longer. Anesthesiologists will see more pulmonary hypertension patients coming for elective and emergent surgeries.

Dr. Neil Goldenberg, The Hospital for Sick Children, University of Toronto, discusses the pathologic mechanisms and novel therapies used in the treatment of chronic PH. Traditionally PH pathogenesis focused on pulmonary vascular resistance and vasoconstriction. Current research demonstrates how PH involves remodeling of pulmonary vessels: a more oncogenic, or cancer based, process.

The cancer model of PH describes pulmonary vascular endothelial damage, with surviving endothelial cells that undergo phenotypic change, causing growth in a disregulated fashion. Dr. Goldenberg notes the similarities in the pathways of cellular metabolism, cellular replication, and inflammation for cancer and PH pathophysiology.

Changes in the mitochondria occur from cellular stress in PH. These changes shut down glucose oxidation and up regulate extra mitochondrial glycolytic pathways. This is known as the Warburg Effect, which leads to cellular proliferation. Dichloroacetate (DCA) is one example of a new therapy that aims to regulate flow through the oxidative metabolic pathways in PH.

Cellular proliferation in PH involves the thickening of pulmonary vessels in smooth muscle and endothelial cells. Endothelin receptor antagonists (bosentan, macitentan) shut down proliferative pathways hence preventing vascular lesion formation.

Current therapies are being developed with specific anti-inflammatory properties. Plasma antibodies also cause cellular proliferation in PH, demonstrating the autoimmune component. Rituximab targets autoimmune processes in scleroderma related pulmonary hypertension. Regenerative medicine and immune cellular therapies use a patient’s own t-cells to disrupt the disease process. Targets in these pathways are promising for new treatment development.

Dr. Harish Ramakrishna of the Mayo Clinic College of Medicine and Science discusses the preoperative assessment for pulmonary hypertension (PH) patients for non-cardiac surgery. WHO PH classes are discussed (I-V). Class I (pulmonary arterial hypertension) is severe and can be idiopathic or as a result of other disease processes. These patients have the highest rate of perioperative morbidity and mortality. Class II (due to left heart disease) cases are seen most commonly.

Dr. Ramakrishna advises that during preoperative assessment, patients with newly diagnosed or suspected PH deserve extra caution and addition workup. Signs to evaluate for systemic disease include shortness of breath, jugular distention, and abdominal distention. Ramakrishna mentions the 6-minute walk test as a revealing diagnostic test for pulmonary arterial hypertension. Other important preoperative risk factors to consider: type of surgery (lung, orthopedic, laparoscopic), age greater than 50, and BMI greater than 30. All of these are associated with higher perioperative risk in PH.

Echocardiography is an important first line diagnostic test for evaluating PH. Tricuspid regurgitation peak velocity (TRV) value <2.8 indicates a low probability of PH, and TRV >3.4 indicate PA pressures of 50mgHg or greater. Right cardiac catheterization is the gold standard for diagnosing PH. It gives the severity of PH and right heart function.

Dr. Pearl discusses anesthetic choice, monitors, and how to treat right ventricular decompensation if it occurs. The cycle of right ventricular failure (RVF) in PH patients involves an increase in an already high pulmonary vascular resistance that rapidly leads to decompensation. Management involves avoiding increases in pulmonary vascular resistance. This is challenging and at times beyond the anesthesiologist’s control-such as laparoscopy.

General, neuraxial, and regional anesthesia are all acceptable choices when managed properly. The key is judicious use of opioids, avoiding respiratory depression and elevated CO2. Respiratory depression will rapidly lead to decompensation. Etomidate maintains stable hemodynamics; it is an ideal induction agent. Dexmedetomide works well as sedative. Pearl cautions that PH patients have a high vagal tone. Dexmedetomide associated bradycarded should be avoided. Pearl also recommends arterial and pulmonary artery catheter to guide management.

In the setting of pulmonary hypertension (PH) and systemic hypotension, vasopressors effectively increase perfusion to the right heart, eliminating ischemia. Vasopressin is the best choice, as it selectively raises SVR and will not increase pulmonary vascular resistance. Pulmonary vasodilators should be continued throughout the perioperative period. Finally, consider RVAD or VA-ECMO when all else fails.

Dr. André Denault of Université de Montréal describes right heart failure (RHF) treatment with the use of inhaled agents. Inhaled agents reach their target more effectively than IV agents in patients with a failing right ventricle. External administration of inhaled pulmonary vasodilators (such as nasal cannula) can even be used after extubation, in the ICU setting. He also uses right ventricular waveform monitoring or CVP to guide treatment.

The first rule in treating RHF: don’t make it worse! Fluid administration will further overload these patients. Be sure the patient is not ischemic or experiencing left ventricular dysfunction. In this scenario inhaled prostacyclin and nitric oxide can worsen their condition. Pharmacologic management includes: maintaining adequate perfusion pressure with vasopressors (vasopression), decreasing RV afterload with inhaled pulmonary vasodilators, increasing right ventricular contractility, and mechanical support if needed.

Dr. Denault also discusses the effectiveness of intratracheal milrinone in the setting of acute right ventricular failure: peak concentration is reached in 4 minutes, with rapid reversal of RHF.

As pulmonary hypertension progresses to right heart failure, cardio-intestinal syndrome develops. This is followed by gut edema and bacterial translocation. Portal hypertension and reversed portal flow are ominous signs that predict development of multisystem failure. The cycle demonstrates exactly why the mortality rate is so high.

*Coverage from the Panel session, Management of Patients with Pulmonary Hypertension

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