Written by: Kaitlin Ray, MD (NUEM PGY-3) Edited by: Mitali Parmar, MD (NUEM alum '18) Expert commentary by: Colin McCloskey, MD (NUEM alum '16)
ED Management of Pulmonary Hypertension
Pulmonary hypertension (PH) is rare disease associated with high morbidity and mortality. Given the non-specific nature of pulmonary hypertension in its early stages, it is often only diagnosed once patients have reached an advanced stage of disease . Given the low physiologic reserve of these patients, any superimposed illness, change in volume status, tachyarrhythmias, or changes in oxygenation or ventilation can tip the patient’s homeostatic balance and precipitate a life threatening situation . Presently, no set guidelines exist regarding the management of critically ill patients with pulmonary hypertension in the emergency department (ED). As emergency physicians, we must have a sound understanding of pulmonary hypertension because although a rare disease, management is based on efficiently and effectively addressing and optimizing the underlying pathophysiology . Below is a quick review of the etiology and pathophysiology of pulmonary hypertension, followed by management goals in the ED with regards to optimizing oxygenation, ventilation and volume status, as well as guidelines for resuscitative efforts.
Definition/Etiology of PH:
The pulmonary vascular system is a high flow, low resistance circuit. Pulmonary hypertension is defined as mean pulmonary arterial pressure > 25 mmHg at rest (>30 mmHg during exertion) as diagnosed by right heart catheterization. Note that an RV systolic pressure >35mmHg on echo is highly suggestive of PH, however is not diagnostic .
Understanding the etiology of PH is critical as it guides treatment. For example, PH secondary to COPD may be addressed by treating the COPD itself. The WHO has classified PH into five groups based on etiology as below :
- Group 1: Pulmonary arterial hypertension (PAH): may be idiopathic or inherited; secondary to connective tissue disease (scleroderma), HIV, sickle cell disease, etc
- Group 2: Pulmonary venous hypertension due to left heart disease:
- Most common cause of PH
- 2/2 cardiomyopathy, diastolic dysfunction, MS, MR, AS, AR
- Group 3: Chronic hypoxemic lung disease: COPD, ILD, OSA
- Group 4: Thromboembolic disease
- Group 5: Miscellaneous: systemic disorders (sarcoidosis, neurofibromatosis), lymphatic obstruction, hematologic disorders (myeloproliferative)
The exact pathophysiology of PH is unknown; however PAH is thought to be secondary to endothelial dysfunction with an imbalance between endogenous vasodilators (ie prostacyclin) and vasoconstrictors (endothelin-1)—resulting in a net effect of vasoconstriction and thrombus formation, leading to elevated pulmonary vascular resistance and impaired blood flow .
When pulmonary vascular resistance (PVR) is high, the right ventricle (RV) dilates in order to maintain preload and stroke volume . Over time, displacement of the RV leads to increased ventricular wall tension and inhibits left ventricular filling, causing decreased cardiac output and systemic perfusion . Additionally, the RV is typically perfused during both systole and diastole because of low RV wall tension . However in chronic PH, RV remodeling leads to elevated transmural pressures, thus impairing RCA perfusion such that it occurs only in diastole. This ultimately leads to RV ischemia and potentially RV failure3.
Patients with PH often present with fairly non-specific complaints, with dyspnea (both at rest and with exertion) being the most common. Other complaints include chest pain, fatigue, presyncope/syncope, and exertional lightheadedness. While physical exam findings may be normal early in the course of disease, in more advanced disease assess for signs of RV failure including tricuspid regurgitation, JVD, hepatomegaly, ascites, lower extremity edema, and increased P2 on auscultation.
Workup of suspected or confirmed pulmonary hypertension will vary based on the patient, however below are a few easily obtained diagnostics that may assist in your assessment and treatment of the patient.
- Most common EKG finding in PH: Right axis deviation 
- Most common dysrhythmias: Atrial fibrillation, atrial flutter, and AVNRT1
- Look for RVH, RBBB, rsR’ in V1, qR in V1, large inferior P waves, ST depression or TWI in V1 or inferior leads (indicating R heart strain) 
- Chest XR:
- Evaluate for enlarged RA, RV, and hilar pulmonary arteries
- Depending on etiology of PH—pulmonary edema, hyperinflation, ILD 
- Bedside echo:
- Assess the RV—evaluate for RA/RV dilation, RV:LV ratio > 1.0 (normal <0.6) on apical 4-chamber view
- “D” sign indicating RV pressure overload
- RV free wall thickening (vs. RV strain due to PE which would result in a thin free wall) 
- Troponin: if elevated, concern for ischemia due to poor RCA perfusion, associated with increased morbidity and mortality 
- BNP: typically does not impact ED management however can reflect degree of myocardial stretch; can be useful if you also have a baseline for comparison
- Avoid hypoxemia
- Goal SpO2 > 90% 
- Provide supplemental oxygen as needed
- Hypoxemia/hypercapnea --> vasoconstriction in lungs --> worsening pulmonary vascular resistance 
- Avoid intubation…
- Increased risk of rapid cardiovascular collapse with intubation 
- Increased intrathoracic pressure from positive pressure ventilation --> decreases preload --> worsening cardiac output.
- Avoid NIPPV in the setting of hypotension as this will also increase intrathoracic pressure and therefore decrease preload 
- …but if you must intubate:
- Etomidate for induction: minimal effects of systemic vascular resistances, pulmonary vascular resistance, and cardiac contractility 
- Use lung protective settings (TV of 6ml/kg ideal body weight, lowest PEEP to maintain O2 >90%)
- Monitor serial plateau pressures (<30cm H20)
- Avoid hypercapnea: adjust respiratory rate as needed 
- Recall that hypercapnea increases pulmonary vascular resistance, pulmonary artery pressure, and RV strain
- Optimize intravascular volume:
- Assess volume status: Physical exam is often unreliable in patients with PH; trends in CVP may be useful so consider early placement of a central line 
- If clearly hypovolemic: give serial 250cc boluses with close monitoring. Start low and go slow! 
- If clearly hypervolemic: cautiously diurese (furosemide, bumetanide) and titrate to patient’s response
- Hypervolemia --> RV dilation --> displaced intraventricular septum --> decreased LV volume --> decreased cardiac output --> decreased systemic perfusion 
- Pulmonary artery catheters: most reliable method to manage fluid balance in an ICU but has not been shown to improve mortality 
- If patient proves refractory to volume management:
- Consider RV assist device
- Consider inhaled NO
- Consider VA ECMO (biventricular support and respiratory support 
- Augment RV function:
- Dobutamine: drug of choice!
- Beta-2 mediated systemic vasodilation
- Increases contractility, reduces pulmonary and systemic vascular resistance 
- Avoid > 10 micrograms/kg/min --> may increase PVR, cause tachydysrhythmias, or hypotension! 
- If hypotensive on dobutamine --> start norepinephrine! 
- Milrinone: 2nd line
- PDE-3 inhibitor --> reduces PVR to augment RV function
- Avoid high doses --> may cause hypotension 
- If hypotensive on milrinone --> start norepinephrine! 
- Dobutamine: drug of choice!
- Maintain RCA perfusion:
- Norepinephrine: drug of choice!
- Alpha-1/alpha-2 properties increase systemic vascular resistance --> augments RV function and CO
- Reduces 28-day mortality from cardiogenic shock 
- Avoid dopamine and phenylephrine due to increased risk of tachydysrhythmias and elevation in PVR and pulmonary artery pressure 
- Norepinephrine: drug of choice!
- Rate control dysrhythmias:
- Most common arrhythmias = atrial fibrillation/atrial flutter
- If uncontrolled can precipitate acute decompensation
- Treat aggressively: if unstable, low threshold to cardiovert
- Caution with beta-blockers/calcium-channel blockers: impair contractility and may cause cardiogenic shock 
- Decreased RV afterload:
- Pulmonary vasodilators: decreasing pulmonary arterial pressure will decrease RV afterload 
- Most commonly used pulmonary vasodilators :
- Prostanoids: rarely started in ED, often given via ongoing infusion
- Endothelin receptor antagonists: PO, not typically used in acutely ill
- PDE-5 inhibitors: PO, not typically used in acutely ill
- Troubleshoot: Avoid disruptions in medication!
- If patient prescribed PO medication but is unable to receive it in the ED, start an inhaled or IV therapy while consulting with patient’s PH specialist 
- If patient has continuous prostanoid infusion via central venous catheter with a portable infusion pump, do not discontinue the pump!
- If pump is malfunctioning, consider this a life-threatening emergency! Patient is at increased risk of RV failure, rebound pulmonary hypertension and death.
- Place IV line and reinitiate the pump while simultaneously calling a PH specialist
- Do NOT interrupt the infusion for any circumstance
- Do NOT turn off the pump
- Do NOT prime or flush the IV line—a bolus with too much medication can be just as dangerous as lack of medication
- Do NOT infuse other medications where the PH medication is infusing (obtain 2nd peripheral IV if needed) 
- If patient presents with adverse effects associated with medication due to systemic vasodilation (ie flushing, headache, diarrhea, jaw discomfort), do NOT stop or decrease dose of medication! 
The majority of these patients will be admitted to the hospital for continued management. For those in acute RV failure, admission to the ICU is more appropriate. If patient is well appearing and you are considering discharge, obtain a walking O2 saturation. If patient desats, they should likely be admitted.
Pulmonary hypertension can be difficult to manage as these patients have little physiologic reserve and volume status can be difficult to assess. Realizing that there are no specific guidelines for ED management in critically ill patients with PH, we must guide our treatment based on the pathophysiology of the disease. Keeping in mind these basic principles as listed below, we can more efficiently and effectively treat patients with PH.
- Treat the underlying cause if able!
- Avoid hypoxemia
- Avoid intubation, but if you must, use etomidate for induction and place vent on lung protective settings
- Optimize intravascular volume: Give small 250cc boluses if hypovolemic and cautiously diurese if hypervolemic—constantly titrate your efforts towards the patient’s hemodynamic response
- Augment RV function: 1st line = dobutamine, 2nd line = milrinone
- Maintain RCA perfusion: 1st line = norepinephrine
- Rate control dysrhythmias: low threshold to cardiovert patients in uncontrolled atrial fibrillation or flutter
- Decrease RV afterload: pulmonary vasodilators
- Avoid any kind of disruption in medication delivery (whether PO or via continuous infusion via central venous catheter with portable pump)
This is an excellent overview of pulmonary hypertension for the emergency physician. Several points of emphasis include:
- Pulmonary hypertension, and its therapeutic considerations, is not as rare as it may seem. Although WHO class 1 pulmonary arterial hypertension (PAH) has an incidence of 15 per 1 million patients, pathologies featuring right ventricular (RV) dysfunction are common. 10-30% of patients with COPD have elevated pulmonary artery pressures . The prevalence of echocardiographic right ventricular dysfunction in ARDS is 22-50% . Sepsis can cause right ventricular dysfunction itself , and infection is the most common cause of acute RV failure in patients with PAH . Thus, patients with right heart dysfunction, either from primary PAH as described above, or secondary to a concomitant pathology are omnipresent in the emergency department.
- Echocardiography is essential in evaluating these patients: For one, it can rule out physiologic mimics of right heart dysfunction, such as cardiac tamponade. It can also reliably show systolic dysfunction of RV, with use of the tricuspid angular plane systolic excursion (TAPSE). A TAPSE < 15 mm yielded high specificity to distinguish abnormal from normal RV EF [5,6]. Further, if there is a question on if right heart dysfunction is acute or chronic, measurement of the RV free wall (normal 3-5 mm) correlate with chronicity of elevated right sided pressures .
- In addition to BNP and troponin, abnormal liver function in conjunction with concern for RV failure has a negative prognostic implication [8,9]. LFT elevation with hypoxia and a clean chest x-ray should prime concern for RV pathology.
- Volume status: As you cogently point out, volume status is an essential consideration in these patients. Both high and low filling pressures may result in reduced cardiac output . My approach in the patient with acute heart failure is to perform a passive leg raise or mini bolus of fluid, and do an ultrasound or other assessment of cardiac output. If responsive, then repeat with gentle fluid loading. More often, especially in chronic pulmonary hypertensive patients, diuresis is more often required.
- Inotropes: Dobutamine, milrinone and digoxin are all acceptable. Milrinone may be novel to most EPs; it is a PDE 3 inhibitor given as a loading bolus followed by an infusion. Evidence exists that it lowers pulmonary vascular resistance to a greater extent than dobutamine [11,12]. Similar to dobutamine, it can cause systemic hypotension, and may require a vasopressor or inopressor. An oft forgotten inotropic agent that is useful in these patients is digoxin . It offers RV systolic support with benign effects on heart rate. A digoxin load (500 mcg q2 hrs up to 1.5 mg) can be effective in the tachycardic patient who needs right sided inotropic support.
- If systolic blood pressure requires augmentation, norepinephrine is preferred . RV mechanics improved with NE infusion vs fluid challenge in basic science studies , and familiarity of use to EP makes it attractive. Vasopressin at low doses (<0.03 units/min) causes pulmonary vasodilation , though at higher doses can increase PVR and cause coronary vasoconstriction. Thus, in a patient in which arrhythmia is a concern this agent is a reasonable choice.
- With obvious exception of patients dependent on vasodilator medications via pump, inhaled pulmonary vasodilators are preferred to systemic vasodilators. Pulmonary vasodilators, such as inhaled NO or iloprost, can improve oxygenation in the short term, though are not associated with improvement in mortality . They are preferred to IV vasodilators which can cause systemic hypotension and worsen shunt. Nicely, iNO can be administered via BiPAP or heated high flow nasal cannula.
- Intubating these patients is dangerous . RV failure patients should not be intubated solely due to signs of shock, as this can be reversed with aforementioned strategies. Non-invasive forms of ventilation CPAP/BiPAP/HHFNC are all excellent options, perhaps with concomitant inhaled pulmonary vasodilators. Hemodynamic optimization prior to intubation attempt (Resuscitate before intubate), induction with cardiac stable medications (etomidate, ketamine), and lung protective ventilation strategies that allow the least PEEP to ensure adequate oxygenation. However, unlike the ARDSnet protocol, permissive hypercapnia should not be tolerated.
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- Vallabhajosyula S, Kashyap R, Geske J, Kumar M, Kashani K, Jentzer J. 28: Right ventricular dysfunction in sepsis and septic shock an eight-year analysis. Crit Care Med. 2016;44(12):93.
- Hoeper MM, Granton J. Intensive care unit management of patients with severe pulmonary hypertension and right heart failure. American journal of respiratory and critical care medicine. 2011;184(10):1114-1124.
- Tamborini G, Pepi M, Galli CA, et al. Feasibility and accuracy of a routine echocardiographic assessment of right ventricular function. Int J Cardiol. 2007;115(1):86-89.
- Jurcut R, Giusca S, La Gerche A, Vasile S, Ginghina C, Voigt J. The echocardiographic assessment of the right ventricle: What to do in 2010? European Journal of Echocardiography. 2010;11(2):81-96.
- Ho SY, Nihoyannopoulos P. Anatomy, echocardiography, and normal right ventricular dimensions. Heart. 2006;92 Suppl 1:i2-13.
- Abe S, Yoshihisa A, Takiguchi M, et al. Liver dysfunction assessed by model for end-stage liver disease excluding INR (MELD-XI) scoring system predicts adverse prognosis in heart failure. PloS one. 2014;9(6):e100618.
- van Deursen VM, Damman K, Hillege HL, van Beek AP, van Veldhuisen DJ, Voors AA. Abnormal liver function in relation to hemodynamic profile in heart failure patients. J Card Fail. 2010;16(1):84-90.
- Goldstein JA, Harada A, Yagi Y, Barzilai B, Cox JL. Hemodynamic importance of systolic ventricular interaction, augmented right atrial contractility and atrioventricular synchorny in acute right ventricular dysfunction. J Am Coll Cardiol. 1990;16(1):181-189.
- Eichhorn EJ, Konstam MA, Weiland DS, et al. Differential effects of milrinone and dobutamine on right ventricular preload, afterload and systolic performance in congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol. 1987;60(16):1329-1333.
- Feneck RO, Sherry KM, Withington PS, Oduro-Dominah A, European Milrinone Multicenter Trial Group. Comparison of the hemodynamic effects of milrinone with dobutamine in patients after cardiac surgery. J Cardiothorac Vasc Anesth. 2001;15(3):306-315.
- Rich S, Seidlitz M, Dodin E, et al. The short-term effects of digoxin in patients with right ventricular dysfunction from pulmonary hypertension. Chest. 1998;114(3):787-792.
- Harjola V, Mebazaa A, Čelutkienė J, et al. Contemporary management of acute right ventricular failure: A statement from the heart failure association and the working group on pulmonary circulation and right ventricular function of the european society of cardiology. European journal of heart failure. 2016;18(3):226-241.
- Ghignone M, Girling L, Prewitt RM. Volume expansion versus norepinephrine in treatment of a low cardiac output complicating an acute increase in right ventricular afterload in dogs. Anesthesiology. 1984;60(2):132-135.
- Tayama E, Ueda T, Shojima T, et al. Arginine vasopressin is an ideal drug after cardiac surgery for the management of low systemic vascular resistant hypotension concomitant with pulmonary hypertension. Interactive cardiovascular and thoracic surgery. 2007;6(6):715-719.
- Adhikari NK, Dellinger RP, Lundin S, et al. Inhaled nitric oxide does not reduce mortality in patients with acute respiratory distress syndrome regardless of severity: Systematic review and meta-analysis. Crit Care Med. 2014;42(2):404-412.
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Colin McCloskey, MD
University of Michigan, Critical Care Fellow
How to Cite this Post
[Peer-Reviewed, Web Publication] Ray K, Parmar M (2018, August 13). Pulmonary hypertension in the ED. [NUEM Blog. Expert Commentary by McCloskey C]. Retrieved from http://www.nuemblog.com/blog/PH
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- Bright, Justin. “The Crashing Pulmonary Hypertension Patient.” EmDOCs.net - Emergency Medicine Education, 16 Oct. 2015, www.emdocs.net/the-crashing-pulmonary-hypertension-patient/.