1. Pulmonary Artery Hypertension and Anesthesia
Greg Latham, MD
Assistant Professor
Seattle Children’s Hospital
Updated 4/2017

2. Disclosures
No disclosures to report

3. Objectives Define pulmonary arterial hypertension (PAH)
Describe pulmonary hypertensive crisis and its causes
Discuss intraoperative treatment of pulmonary hypertensive crisis
Discuss anesthetics techniques to minimize risk of intraoperative morbidity and mortality
Review pharmaceutical management of PAH

4. Pulmonary Arterial Hypertension (PAH)
CT angiography showing massive dilation of main and branch pulmonary arteries, especially when compared to ascending aorta (to the left of the pulmonary artery calipers) and the descending aorta (adjacent to the vertebral body)
Open Access License: Hoette S, Figueiredo C, Dias B, et al. Pulmonary artery enlargement in schistosomiasis associated pulmonary arterial hypertension. BMC Pulmonary Medicine. 2015;15:118. (

5. PAH Definition PVR calculation = 80 (mPAP-PCWP)/CO
Normal PVR = 70 (range ) dyn.sec/cm5
Normal PVR = 1 (range ) Woods units
Woods unit is just another unit of resistance and is calculated as = 80 x dyn.sec/cm5

6. Why Does PAH Occur in Children?
 pLA
LV systolic/diastolic dysfunction
MV or AV stenosis/regurgitation
Pulmonary vein obstruction
 pulmonary blood flow
Congenital heart disease with L  R shunt
 PVR
Pulmonary parenchymal disease
Thromboembolic disease
This simply describes the most common mechanical principles behind the etiology of PAH in children.
pLA = left atrial pressure; LV = left ventricle; MV = mitral valve; AV = aortic valve; PVR = pulmonary vascular resistance

7. Eisenmenger Syndrome (ES)
The most severe form of CHD-associated PAH
Definition:
“CHD with an initial large systemic-to-pulmonary shunt that induces progressive pulmonary vascular disease and PAH, with resultant reversal of the shunt and central cyanosis”
When shunt reversal occurs, symptoms include:
Cyanosis, dyspnea, fatigue, dizziness, syncope, and arrhythmia
Poor exercise tolerance
Life expectancy is markedly reduced

8. Pulmonary Hypertensive Crisis

9. Open Access License: Galiè N, Palazzini M, Manes A
Open Access License: Galiè N, Palazzini M, Manes A. Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses. European Heart Journal. 2010;31(17): (

10. Pulmonary Hypertensive Crisis
DEFINITION: A potentially fatal complication, characterized by a rapid increase in PVR to the point where PAP exceeds systemic blood pressure
RV ejection fraction decreases acutely and can rapidly progress to right ventricular failure
Pulmonary hypertensive crisis is a feared complication of anesthetizing children with PAH. It is associated with morbidity and mortality.

11. Pulmonary Hypertensive Crisis
If no PFO or ASD:
RV failure  decreased pulmonary blood flow  decreased cardiac output  hypoxia, acidosis, hypercarbia  biventricular failure  vicious cycle!
If PFO or ASD:
Intra-atrial RL shunt augments LA filling and supports cardiac output
But… at the expense of hypoxia, hypercarbia & acidosis  decreased cardiac output/cyanosis  vicious cycle!
The presence of in intra-atrial communication makes a difference with how and how quickly the patient decompensates during a pulmonary hypertensive crisis. The presence of a PFO or ASD is protective at first by supporting preload to the left side of the heart, but continued R  L shunt and the subsequent cyanosis and hypercarbia it produces can cause bradycardia, cardiac ischemia and arrest.

12. Pulmonary Hypertensive Crisis
Awake symptoms of a PAH crisis include:
Syncope, dyspnea, cyanosis, pallor, bradycardia, right ventricular heave, and bronchospasm
Anesthetized symptoms of a PAH crisis include:
Decreased ETCO2, hypoxia, hypotension, other signs of depressed cardiac output

13. PAH Crisis – How Bad Is It?
This table demonstrates that while the risk of cardiac arrest (~3:10,000) and death (4:100,000) is rare during anesthesia of children as a whole, the risk of cardiac arrest and death is up to 100-fold increased in children with PAH.
Friesen, R. H., & Williams, G. D. (2008). Anesthetic management of children with pulmonary arterial hypertension. Pediatric Anesthesia, 18(3), 208–216.

14. PAH and Anesthesia

15. PAH and Anesthesia Goals of anesthesia:
Minimize stress and maintain hemodynamic conditions as close to baseline by providing adequate anesthesia and analgesia for the operative procedure
Prevent any stimuli that may trigger a PAH crisis
Maintain hemodynamic stability such that the risk of RV ischemia is minimized
Avoid interruption of any medication currently being used to control pulmonary pressures (e.g., epoprostenol)
Minimize preoperative hypovolemia

16. PAH and Anesthesia Two patient categories to consider:
Newly diagnosed PAH
At increased risk for life-threatening PAH crisis, cardiac arrest
The younger the child, the more reactive the airway is  the risk of crisis may be increased
The primary objective is to prevent any stimuli from triggering this crisis
Idiopathic PAH may have a higher risk of cardiac arrest
Ongoing or chronic PAH
Likely to have chronically increased PVR with a hypertrophied RV
This group seems more likely to succumb to RV ischemia and arrhythmias and develop ventricular failure, rather than an acute PAH crisis
Although there may be some overlap, this distinction allows the anesthesiologist to plan accordingly.

17. PAH and Anesthesia Preop sedation Monitoring
Efficacious to provide calm induction
Midazolam and/or ketamine do not impact PVR, as long as hypoventilation does not occur
Monitoring
As dictated by specifics of the patient, anesthetic plan, and procedure
May need to monitor ABGs/VBGs for accurate pH, pO2, and pCO2 control
Preop sedation may be beneficial to reduce crying, screaming, or struggling that can lead to increased PVR and exacerbate PAH.

18. Induction Pts with fixed PVRs:
Prevent any further increase in PVR, at the same time maintain RV function and avoiding a reduction in SVR
Any increase in PVR will reduce pulmonary blood flow  reduce LV preload and CO  increased RV EDP causes septal deviation leftward  impair LV function  decrease CO
At the same time, decreased SVR  decreased coronary blood flow to the hypertrophied right ventricle  rapid ischemia due to exquisite sensitivity to coronary hypoperfusion
Consider availability of inotropic support and iNO
Consider a bolus of 5-10 mL/kg of fluid before induction to protect RV preload

19. End-diastolic End-systolic
(A) End-diastolic and (B) end-systolic cardiac short axis slice in PAH patient. This demonstrates septal bowing into the LV and the diminshment of LV cavity size.
End-diastolic
End-systolic
Open Access License: Mauritz G-J, Marcus JT, Boonstra A, Postmus PE, Westerhof N, Vonk-Noordegraaf A. Non-invasive stroke volume assessment in patients with pulmonary arterial hypertension: left-sided data mandatory. Journal of Cardiovascular Magnetic Resonance. 2008;10(1):51. (

20. Induction Pts with reactive PAH
Minimize stress, maintain hemodynamics, prevent any stimuli that may trigger a PAH crisis
Triggers of PAH crisis:
Hypoxia
Hypercarbia
Acidosis
Hypothermia
Noxious stimulus
While a deep level of anesthesia to prevent noxious stimulus is certainly a goal, specifics of the child’s associated CHD may impact how a deep plane of anesthesia is achieved. A high-dose opiate technique, which provides significant analgesia while typically maintaining hemodynamic stability, may be warranted.

21. Treatment of PAH Crisis
Administer 100% oxygen; hyperventilate moderately
Administer opiate and deepen anesthesia
Institute inotropic support; treat bradycardia
Initiate nitric oxide therapy (fastest Rx)
Correct metabolic and respiratory acidosis, if present
Treat hypothermia, if present
As a PAH crisis becomes apparent, it can be a tough decision whether to deepen anesthesia or not if the cardiac output is starting to fall. If the PAH crisis may be from light anesthesia and noxious stimulus, deepening anesthesia may be beneficial, even if vasopressor support is needed to counteract any hypotensive affect of deepening anesthesia. Again, opiates can provide analgesia with less hemodynamic affects compared to propofol, sevoflurane, etc.

22. Anesthetic Drugs and Maintenance of Anesthesia
There is no specific anesthetic technique that is “best” for patients with PAH; tailor according to the underlying hemodynamic stability and the planned procedure
Balanced technique is advocated in some papers
In a review of 156 children with PAH undergoing 256 procedures, the incidence of complications was not different between sedation vs. GA
Carmosino MJ, Friesen RH, Doran A et al. Perioperative complications in children with pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. Anesth Analg 2007; 104: 521–527

23. Anesthetic Drugs and Maintenance of Anesthesia
The goal is to maintain pulmonary blood flow, prevent any additional workload for the right ventricle, and maintain coronary artery perfusion…
…whichever technique accomplishes this is the “right” technique!

24. Anesthetic Drugs and Maintenance of Anesthesia
Ventilation strategy is important:
Over-aggressive ventilation can reduce RV filling and increase PVR
Inadequate ventilation (spontaneous or mechanical) will reduce minute ventilation and increase atelectasis, hypoxia, hypercarbia, and thus PVR
Aggressive mechanical ventilation with high tidal volumes, inspiratory pressure, and inspiratory times can reduce RV filling, reduce RV output, and increase PVR.
i.e., adjust vent settings to ensure adequate pulmonary blood flow is maintained without signs of increased RV strain

25. PAH Medication Therapy
Pulmonary Vasodilators

26. Open Access License: Baldi F, Fuso L, Arrighi E, Valente S
Open Access License: Baldi F, Fuso L, Arrighi E, Valente S. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course. Therapeutics and Clinical Risk Management. 2014;10: doi: /TCRM.S48920.

27. Pulmonary Vasodilators
Inhaled nitric oxide (iNO)
Very rapid onset – best Rx for rescue of PAH crisis
Selective pulmonary vasodilation
Diffuses into pulmonary vascular smooth muscle cells  activates soluble guanylate cyclase  increases cGMP  vasodilation
iNO if rapid-acting and can rescue a PAH crisis rather quickly. If anesthetizing a patient at increased risk for PAH crisis or supra-systemic PAH at baseline, immediate availability of iNO in the operating room may be warranted.

28. Pulmonary Vasodilators
Inhaled nitric oxide (iNO)
Rebound PAH is possible, especially after high or chronic therapy
Administering iNO when PAH is secondary to downstream obstruction can lead to acute pulmonary edema
An example of “downstream obstruction” would be pulmonary vein stenosis. In this case, administering iNO increases pulmonary blood flow (especially in children with left-to-right shunt), and downstream resistance from pulmonary venous hypertension risks pulmonary congestion and edema.

29. Pulmonary Vasodilators
Phosphodiesterase (PDE) inhibitors
Block hydrolysis of cGMP  increases cGMP  vasodilation
Sildenafil and dipyridamole – short acting oral Rx
Milrinone (less selective pulmonary vasodilator)

30. Pulmonary Vasodilators
Prostacyclin analogs
Increases cGMP through stimulation of adenylate cyclase
Rapid onset of action and short half-life
Epoprostenol (Flolan) – continuous IV therapy
Iloprost (Ventavis) - inhaled analog
Treprostinil (Remodulin) - subcutaneous or intravenous
Beraprost - oral

31. Pulmonary Vasodilators
Others
Bosentan - endothelin antagonist; promising for chronic Rx
Calcium channel blockers – promising for chronic Rx of reactive PAH

32. References
Friesen, R. H., & Williams, G. D. (2008). Anesthetic management of children with pulmonary arterial hypertension. Pediatric Anesthesia, 18(3), 208–216
Carmosino MJ, Friesen RH, Doran A et al. Perioperative complications in children with pulmonary hypertension undergoing noncardiac surgery or cardiac catheterization. Anesth Analg 2007; 104: 521–527
Suggested Reading:
Shukla, A. C., & Almodovar, M. C. (2010). Anesthesia considerations for children with pulmonary hypertension. Pediatric Critical Care Medicine, 11(2), S70–S73
Beghetti, M., & Tissot, C. (2009). Pulmonary Arterial Hypertension in Congenital Heart Diseases. Seminars in Respiratory and Critical Care Medicine, 30(04), 421–428