Case Presentation

A 54-year-old, 72-kg woman with severe idiopathic pulmonary arterial hypertension presented for emergent exploratory laparotomy for a perforated viscus. She was treated with oxygen via nasal cannula, a continuous infusion of epoprostenol via a tunneled peripherally inserted central catheter, and warfarin. Transthoracic echocardiography (TEE) revealed a severely hypertrophied right ventricle (RV), moderate tricuspid regurgitation, and norma l left ventricular (LV) systolic function.

Emergent mechanical circulatory support was prepared. A radial arterial line was placed, and a central venous pressure (CVP) of 18 mm Hg was noted when transduced from the central catheter. Her epoprostenol infusion was continued, and a bolus of 2 units of vasopressin was administered before intubation. After induction of general anesthesia with etomidate, fentanyl, and rocuronium, her CVP increased to 28 mm Hg, and her mean arterial pressure decreased to 46 mm Hg.

Intraoperative TEE revealed a hyperkinetic underfilled LV; a dilated, hypertrophied, hypokinetic RV; severe tricuspid regurgitation; and systolic shift of the interventricular septum into the LV cavity. An additional bolus of 2 units of vasopressin was administered.

Mechanical ventilation was initiated with 100% oxygen, and inhaled nitric oxide (iNO) was started at 20 ppm. Milrinone and vasopressin were administered as continuous infusions. The CVP gradually decreased to 10 mm Hg while the mean arterial pressure increased to 72 mm Hg. On TEE, the tricuspid regurgitation improved dramatically, and the interventricular septal shift resolved. The RV appeared to be less distended with improved contractility, while the LV appeared to be better filled. Four-factor prothrombin complex concentrate was administered for warfarin reversal.

At the conclusion of surgery, the patient was transferred to the ICU intubated on 20 ppm iNO. Before leaving the OR, a pulmonary artery catheter was inserted and the initial pulmonary artery pressure (PAP) measurement was 83/42 mm Hg. Ultrasound-guided transversus abdominis plane blocks were performed. She was successfully extubated the following day after judicious weaning of iNO and vasoactive support. She was discharged to the floor the next day and to home 3 days later on her prehospital medical regimen.

The main goal of anesthetic care in patients with pulmonary hypertension is to maintain hemodynamic stability and prevent RV failure. Use of a pulmonary artery catheter allows direct monitoring of PAP, while TEE allows direct global assessment of RV function as well as Doppler monitoring of the cardiac output.1 Care must be exercised during the insertion of a pulmonary artery catheter, as patients with pulmonary hypertension are dependent on sequential atrial–ventricular contraction and do not tolerate ectopy well.2 An arterial line should be placed before induction to allow monitoring of acute hemodynamic changes.

Regional anesthetic techniques have the advantage of preserving spontaneous breathing and avoiding elevated PAP resulting from positive pressure ventilation. Continuous regional anesthetic techniques provide distinct advantages for pain management in the postoperative period. Thoracic epidural anesthesia has no significant impact on oxygenation or pulmonary vascular tension; however, high thoracic levels of sympathetic blockade may result in decreased cardiac inotropy and chronotropy.1

Advantages of general anesthesia include controlled oxygenation and ventilation, as well as the implementation of a direct conduit for the administration of inhaled pulmonary vasodilators. Disadvantages lie in the administration of positive pressure ventilation and the potential for blood pressure variation from the anesthetic agents. A significant drop in diastolic arterial pressure has the potential to reduce coronary perfusion pressure to the RV, setting up a vicious cycle of RV ischemia, impaired RV contractility, and hemodynamic collapse.1

Volatile anesthetic agents at concentrations up to 1 minimum alveolar concentration may be administered without negative effects on PVR. Avoidance of ketamine and N2O is recommended, due to the potential to increase PVR.

Hypoxia is one of the single strongest inducers of pulmonary vasoconstriction, and higher fractions of inspired oxygen should be maintained. Very judicious use of positive end-expiratory pressure and recruitment maneuvers may help maintain ventilation–perfusion matching. However, alveolar overdistention must be avoided to limit increases in PVR. Acidosis and hypercarbia also are contributors to pulmonary vasoconstriction, so adequate minute ventilation must be maintained. Adequate depth of anesthesia will help limit sympathetic pulmonary vasoconstriction. Hypothermia must be avoided, as shivering can significantly increase pulmonary pressures. Judicious fluid management also is essential to maintain adequate LV stroke volume while avoiding overload of the RV.1

Continuous IV medication must be continued in the intra- and postoperative periods. Abrupt discontinuation of IV epoprostenol can result in acute decompensation and RV failure.3 The goal of intraoperative pharmacotherapy is to dilate the pulmonary arterial bed to reduce RV afterload, while maintaining adequate RV contractility. However, IV vasodilators dilate both the pulmonary and systemic circulation, risking a dangerous drop in RV perfusion pressure. The phosphodiesterase type 3 inhibitor milrinone is a potent inotropic agent that also reduces both PVR and SVR.1 Vasopressin has the unique property of having little to no pulmonary vasoconstrictive effects while having potent systemic vasoconstrictive effects. The combination of milrinone and vasopressin allows maintenance of RV contractility, reduction of PVR, and maintenance of SVR.4 Dobutamine also combines inotropic effects with reduced PVR, but its use is often limited by the resultant tachycardia.1

iNO easily crosses from the alveolus to smooth muscle cells, where it directly stimulates soluble guanylate cyclase to cause vascular relaxation. iNO will produce pulmonary vasodilation at concentrations from 5 to 40 ppm, leading to reduced PVR, PAP, and RV afterload without impact on SVR. iNO significantly improves cardiac output and mixed venous oxygen saturation in critically ill patients with circulatory shock secondary to RV failure.5

The use of iNO is limited by both the high cost and potential toxicity. Nitric oxide forms methemoglobin and nitrate when exposed to oxyhemoglobin in the pulmonary circulation. In the absence of methemoglobin reductase deficiency, doses less than 40 ppm generally do not cause clinical methemoglobinemia. However, lung injury may occur if large amounts of NO are oxidized to nitrogen dioxide (NO2), a pulmonary irritant that may cause bronchospasm and pulmonary edema. Modern systems in use for the delivery of iNO include monitors for NO and NO2 levels.5

In patients with acute RV failure refractory to medical management, mechanical circulatory support, such as extracorporeal membrane oxygenation, may be used to help unload the RV.6

Conclusion

A balanced anesthetic technique that includes inhalational agents, regional anesthetics, and opioids may provide for the smoothest hemodynamic profile in these patients. Postoperative recovery of patients with significant pulmonary hypertension should be in an ICU. Continuance of the intraoperative vasoactive agents is usually necessary in the postoperative period. Slow-controlled de-escalation of these agents with intense physiologic monitoring is the safest way to proceed.

Dr Klick is the director of cardiovascular anesthesia and an associate professor of anesthesiology and perioperative medicine; Dr Cios is an assistant professor of anesthesiology and perioperative medicine; Dr Malhotra is an associate professor of anesthesiology and perioperative medicine; and Dr Roberts is an assistant professor of anesthesiology and perioperative medicine, Department of Anesthesiology and Perioperative Medicine, Penn State Health Milton S. Hershey Medical Center, in Hershey, Pennsylvania. Dr Vaida is a professor of anesthesiology, obstetrics, and gynecology; the vice chair for research; and the director of obstetric anesthesia at Penn State Health Milton S. Hershey Medical Center. The authors and reviewer reported no relevant financial disclosures.

References

  1. Gille J, Seyfarth H-J, Gerlach S, et al. Perioperative anesthesiological management of patients with pulmonary hypertension. Anesthesiol Res Pract. 2012;2012:356982.
  2. Liu H, Kalarickal PL, Tong Y, et al. Perioperative considerations of patients with pulmonary hypertension. In: Elwing J, Panos RJ, eds. Pulmonary Hypertension. IntechOpen. 2013. www.intechopen.com/ books/ pulmonary-hypertension/ perioperative-considerations-of-patients-with-pulmonary-hypertension. Accessed March 2, 2019.
  3. Calcaianu G, Calcaianu M, Canuet M, et al. Withdrawal of long-term epoprostenol therapy in pulmonary arterial hypertension (PAH). Pulm Circ. 2017;7(2):439-447.
  4. Currigan DA, Hughes RJ, Wright CE, et al. Vasoconstrictor responses to vasopressor agents in human pulmonary and radial arteries: an in vitro study. Anesthesiology. 2014;121(5):930-936.
  5. Thunberg CA, Morozowich ST, Ramakrishna H. Inhaled therapy for the management of perioperative pulmonary hypertension. Ann Card Anaesth. 2015;18(3):394-402.
  6. Kumar A, Neema PK. Severe pulmonary hypertension and right ventricular failure. Indian J Anaesth. 2017;61(9):753-759.