A close examination of this rare disease with high morbidity and mortality
Case – A 38-year-old female is brought in by ambulance for chief complaint of severe dyspnea. As you put down your coffee by your computer and step into the room, you see a patient in respiratory distress doing her best to breathe. Her vital signs include RR 28, HR 112, T 37.2oC, oxygen saturation 87% on room air, and blood pressure 82/55 mm Hg. You quickly ask the nurse to obtain bilateral IVs and start oxygen, and you then turn to the EMS crew to ask what’s going on. They state they were called to the scene by the patient due to severe shortness of breath and some mild chest pain, located centrally. “Oh yeah, she has something called pulmonary hypertension.” Suddenly, you wish it was time for the new provider to show up as you try to calm the knot in your stomach. You know this resuscitation could be rocky…
Pulmonary hypertension is a condition with significant morbidity and mortality. Primary pulmonary hypertension (just one group of the condition) is rare with 5 to 15 cases per 1 million adults, though patients with the disease accounted for 64,400 ED visits over a 5-year period in one study [1-4]. Patients are often on complex medication regimens, and managing these patients is difficult due to the heterogeneous nature of the disease. Unfortunately, despite the potential for severe disease, up to 21% of patients have symptoms over two years before diagnosis [4-6]. These patients in particular have greater functional disability and risk of mortality.
Normally, the pulmonary circulation is under low pressure with low resistance. Pulmonary artery pressure is usually less than 15 mm Hg, and pressures greater than 25 mm Hg on right heart catheterization and 35 mm Hg on echocardiogram define pulmonary hypertension [1,2,7-9]. Normal pulmonary vessels and the right ventricle are thin and can accommodate significant changes in preload, but often cannot overcome increases in obstruction or afterload due to limited contractile reserves. Ultimately, the duration and degree of pulmonary vascular resistance impact the severity of pulmonary hypertension [9-14]. Increased pulmonary system pressure results in decreased right ventricular (RV) stroke volume and output. Increased RV volume leads to the interventricular septum bulging into the left ventricle (LV), decreasing cardiac output. RV failure can occur in acute or chronic pulmonary hypertension. Chronic pulmonary hypertension allows for gradual compensation by the RV due to the slow increase in pulmonary vascular resistance, whereas acute decompensation does not allow for this compensation. Once a certain pressure is reached, the RV is unable to function, reducing cardiac output and causing shock [1,2,10-14].
Coronary blood flow is an important aspect to understand. The LV receives coronary flow only during diastole, while the RV under normal pressures receives flow throughout systole and diastole [1,2,12-16]. In pulmonary hypertension, the increased RV wall pressure leads to decreased blood flow, specifically when pulmonary artery pressures are greater than systemic pressures. This leads to ischemia, decreasing RV function, increasing RV overload, and ultimately reducing total cardiac output due to obstruction [12-17]. This tenuous physiologic reserve allows any illness, tachydysrhythmia, volume change, or oxygenation/ventilation perturbation to precipitate acute on chronic RV failure [18,19].
The condition is broken into 5 different groups by the World Health Organization (WHO) [1,2,8,9]. This is important to understand, as patients in different classes may be managed differently. These separate groups, with diseases, are demonstrated below in Table 1. Group 2 is the most common cause of pulmonary hypertension. Of note, the majority of cases are not diagnosed in the ED, as official diagnosis requires right heart catheterization.
Patients present in a variety of ways: complaints related to pulmonary hypertension, complaints related to the underlying condition, and complaints unrelated to pulmonary hypertension. The most important part of the history is the past medical history – a patient with diagnosed pulmonary hypertension will likely tell you about the disease. On the other hand, pulmonary hypertension not diagnosed presents a challenge, as its presentation mimics many other diseases. The most common symptom associated with pulmonary hypertension is dyspnea with exertion, occurring in 60% to 99% of patients [1-4,20,21]. Patients may also experience chest pain due to impaired RV perfusion. Emergency providers must focus on asking about exertional dyspnea and chest pain, as well as syncope which signifies more advanced disease [1,2,20-23]. Patients with syncope could be experiencing obstruction in output, dysrhythmia, or ischemia. Palpitations, general fatigue, edema, and near syncope are other symptoms. Certain medications are associated with pulmonary hypertension including appetite suppressants, selective serotonin reuptake inhibitors, St. John’s wort, interferon, and illicit drugs such as stimulants (up to 30% of patients with disease admit to stimulant use) [24,25].
Physical exam is often normal in early stages. However, later stages with decompensation may demonstrate peripheral edema, midsystolic murmur, early systolic click, parasternal lift, and prominent jugular pulsation. A loud P2 is heard in up to 90% of patients at some point during their course [7,21-23]. However, in a loud ED, the cardiac exam listening for murmurs and clicks is not always reliable. Oxygen saturation is often normal in early disease, but in severe stages or in exacerbation, oxygen saturation will first drop with ambulation and then at rest [1,2]. Another important aspect is evaluating the medication pump function and line for any signs of obstruction. Evaluate for any sign of poor perfusion or shock such as cool extremities, altered mental status, end organ damage, and hypotension, as these are all signs of impending cardiovascular collapse [1,2,7,23]. Evaluation Tips are shown in Table 2.
Your patient demonstrates respiratory distress, and you notice pronounced JVD with a parasternal lift. It’s too loud to hear any murmurs. You don’t see any edema. Through one to two word sentences, she tells you her Treprostinil pump started beeping several hours ago, after which she began to experience shortness of breath which worsens with walking. Her extremities are cool to touch with decreased pulses distally, and her pump is flashing red…
Providers should obtain several investigations for the patient with known or suspected pulmonary hypertension. Testing includes laboratory markers, electrocardiogram (ECG), and imaging, shown in Table 3.
Laboratory findings include troponin and brain natriuretic peptide (BNP) elevation with RV strain and ischemia. In particular, NT-proBNP elevation greater than 1,500 pg/mL is associated with increased mortality, while levels less than 300 pg/mL correlate with low mortality risk.26 Lactate may elevate with systemic hypoperfusion. Other abnormalities may include electrolyte disturbances, anemia, coagulopathy, and liver dysfunction. These findings offer prognostic information, as well as providing clues to potentially reversible conditions [1,2,27,28].
The ECG is a vital diagnostic tool, as it is cheap, reliable, and rapid. Approximately 70% of patients show right axis deviation, as well as signs of RV hypertrophy including right bundle branch block.29 Tall p waves in the inferior ECG leads suggests enlargement of the right atrium. ST depressions and T wave inversion in the inferior and right precordial leads indicate RV strain.29,30 Supraventricular tachycardia including AV nodal reentrant tachycardia, atrial fibrillation, and atrial flutter must be recognized early, specifically atrial fibrillation which has a mortality rate approaching 80% due to loss of atrial kick [1,29,31,32].
Imaging includes chest X-ray, chest CT, and echocardiogram. These tests offer valuable information for the emergency provider. Chest X-ray may demonstrate several key findings, but the absence of findings does not exclude pulmonary hypertension.21 Bedside US is indispensable in the initial evaluation and management of these patients [1,2,33]. Chest CT is warranted for patients with new cardiopulmonary symptoms and known disease . Imaging findings are demonstrated in Table 4.
For those with no formal diagnosis, a pearl is to consider pulmonary hypertension in patients with shortness of breath, chest pain, or syncope with negative workups . Patients with known current PE or prior PE are also at risk for pulmonary hypertension. An outpatient follow-up with pulmonology and complete echocardiogram may diagnose pulmonary hypertension.
Your initial labs return, and the patient has a NT-proBNP of 1700 pg/mL, negative troponin, and lactate of 3.5 mmol/L. The rest of her labs are normal. As an US guru, you are able to obtain a great cardiac window demonstrating RV:LV ratio of 1 with RV bowing. The portable chest X-ray shows large pulmonary arteries. You think you have a diagnosis, but what now?
Pulmonary hypertension patients in the ED with acute decompensation or any severe illness present numerous challenges to resuscitation, as assessment and management are often difficult. An overview of the treatment priorities is shown below in Table 5.
The first important aspect is understanding the cause of pulmonary hypertension if possible, followed by treating this cause. Second, consult the pulmonologist. Cautious use of any medication that may depress cardiopulmonary status is important (sedatives, narcotics) [1,19].
Fluid optimization is key, as the goal is adequate RV preload [14,15]. Assessment of volume status is difficult, as the physical exam is usually not reliable. Other measures including central venous pressure, pulse pressure variation, and stroke volume variation are not accurate either [35-37]. The overall goal is to optimize preload of the RV, while avoiding overload and decreased total cardiac output. A pulmonary artery catheter may be required, which the literature suggests is one of the better means of evaluating RV function and fluid balance [37-39]. However, this is not often feasible in the ED. Fluid overload will cause increased RV pressure and LV obstruction, while not enough preload decreases output [14,15,17]. If volume depletion is suspected, low volume boluses of 250-500 ml should be used. If fluid overload is suspected in stable pulmonary hypertension patients, diuretics can be used with furosemide [14,15]. All interventions require continued reassessment of mental status, capillary refill, blood pressure, urine output, and lactate.
RV Systolic Function and Perfusion
RV systolic function is a target, as well as enhancing RV perfusion through systemic vascular pressure. If the patient is normotensive, dobutamine can be used starting at 2 mcg/kg/min IV (titrating up to 10 mcg/kg/min) to increase RV systolic function. Milrinone may be utilized in the ICU but is not available in many ED’s [15,40-42]. Hypotension must be avoided, as these patients experience a set level of pulmonary vascular tone. Any drop in blood pressure will not be matched by a decrease in pulmonary arterial pressure, worsening RV ischemia [18,19]. Vasopressors may be needed to improve cardiac contractility and systemic vascular tone. If the patient is hypotensive, norepinephrine is the first line vasopressor. This medication can improve coronary perfusion pressure, systemic perfusion, and isotropy [14,15,44,45]. Dosing begins at 0.05 mcg/kg/min, titrating to improved mean arterial pressure. Phenylephrine should be avoided as it can increase pulmonary resistance [45-47]. Vasopressin is a valid option as it increases systemic arterial pressure while decreasing pulmonary vascular pressure through nitric-oxide production [1,2,17].
RV Afterload Reduction
An increase in RV afterload due to increased pulmonary artery pressures often causes acute decompensation. This can be avoided through ensuring adequate oxygenation and absence of hypercarbia and acidosis [48-52]. Oxygen saturations of greater than 90% are the target, which will improve pulmonary pressures [14,15,32,37]. In patients with group 2 and 3 pulmonary hypertension, positive pressure ventilation may assist the patient [1,2]. However, other groups may demonstrate hemodynamic decompensation with positive pressure ventilation, especially if decreased preload/hypovolemia is present [51,52]. If the patient is in respiratory distress, positive pressure ventilation can be started at low levels while resuscitation continues with constant monitoring for decompensation. Endotracheal intubation and mechanical ventilation should be avoided if possible [51,52]. These measures increase pulmonary vascular resistance and reduce preload. If intubation is required, use etomidate, which has less effect on hemodynamic status . Lung-protective ventilator strategies should be utilized if intubated, while avoiding permissive hypercapnia and keeping plateau pressures < 30 cm H20 [1,2,17,32].
Pulmonary vasodilators include nitric oxide, prostanoids (epoprostenol, treprostinil), endothelin receptor antagonists, and phosphodiesterase inhibitors (sildenafil) [14,15,32,37]. Pulmonary vasodilators should not be used in a hemodynamically unstable patient or one naïve to these medications [1,2]. However, many patients with known disease will be on these medications. If the medication was suddenly stopped, decompensation will rapidly follow. The medication should be started in the ED, and if the peripheral pump is not working, the infusion can continue through a peripheral IV, as withdrawal of these medications will cause rapid decompensation [1,2,14,15,32,37].
Of note, dysrhythmias are not tolerated well due to need for atrial kick. Beta and calcium channel blockers are not recommended due to worsening RV function.1,37,52 Cardioversion is the best option, with etomidate providing optimal sedation [1,37].
The patient is saturating 92% on 8L nasal cannula. You give her a 500 cc bolus of NS while starting norepinephrine. Her pressures improve to 102/62, and your favorite pharmacist is able to rapidly provide a Treprostinil infusion, which you begin peripherally. Her pulmonologist runs down, who thanks you for the treatment you started and asks you to start dobutamine as well. The patient is admitted to the ICU, and you breathe a huge sigh of relief.
Pulmonary hypertension is a rare disease with high morbidity and mortality. Five groups are present, based on the underlying disease. Ask the patient about prior pulmonary vasodilator treatment, chest pain, exertional dyspnea, and syncope. Key studies include cardiac biomarkers, electrolytes, and imaging (chest X-ray, bedside US, and chest CT). Management requires focus on treating the underlying cause of the exacerbation, consulting pulmonology, continuing pulmonary vasodilator treatment, optimizing volume, optimizing RV systolic function and perfusion, and rapidly treating dysrhythmias. Patients with negative prior workups for cardiovascular/pulmonary complaints should be referred for pulmonology follow-up and echocardiogram.
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Fantastic review. Thank you!
Challenging patients to manage in acute setting. Thanks for clinical pearls!!
Nice simplification of complicated disease.
I am a physician with pulmonary hypertension and I am pleased to see someone bring attention to this condition. As a patient, one of my major fears is being brought to an ER where I am not able to inform the staff about my condition and not receiving the correct treatment.
I used to have a subcutaneous pump for treprostinil. One nurse insisted it was an insulin pump and tried to switch me over to insulin when I was in the hospital for testing. This is a really bad idea.
It can be life threatening to stop treprostinil. As far as I know, all pulmonary hypertension patients on this treatment will have back-up supplies. Ask them or their family about this because many small hospitals do not have this in stock. They should have a second pump in case the first stops working.
Unfortunately, PAH patients are not supposed to bring their medications and supplies into the hospital due to Insurance requirements. If the patient is admitted, they will need to have the pump and medication sent in from the pharmacy.
Also, many PAH patients are on Sildenafil (Viagra). Do not stop this either. I had a patient on Sildenafil and her entire supply was stolen from the hospital cart. I think this medication should be locked up like narcotics because it has a high risk of theft. It is also expensive to replace. The hospital administration did not want to replace the missing drug. They thought she could just wait until the next week’s shipment of regular meds arrived. I asked them if that is how they would handle missing drugs for a diabetic or heart patient and they quickly realized they needed to get it refilled right away despite the cost.
Another important item is fluids. it is really easy to cause fluid overload for a patient with pulmonary hypertension. Be careful about adding the IV fluids.
Finally realize that not every PAH patient has regular dyspnea and low oxygen sats. After I was in a car accident and I had the air bags go off, I had several broken ribs. The doctors and nurses attributed my O2 of 90% and my breathlessness to the PAH. It took six weeks and multiple complaints from me for anyone to check. I had fluid filling the lower lobe of my right lung from the accident and my symptoms went away when it was tapped.