Hap review 2011

Pulmonary Hypertension: A Review of

Pathophysiology and Anesthetic Management

Ali Salehi, MD

Pulmonary hypertension is a condition that can result in serious complications in patientsundergoing any type of anesthesia during the perioperative period. By definition, pulmonary arteryhypertension is caused by a persistent rise in mean pulmonary artery pressure $25 mm Hg withPulmonary capillary wedge pressure # 15 mm Hg or exercise mean pulmonary artery pressure $35mm Hg and pulmonary vascular resistance $ 3 wood unit’s. The severity of the complicationsdepends on the severity of the underlying condition, other comorbidities, and type of procedure,anesthetic technique, and anesthetic drugs. In this article, we briefly review the pulmonary vascularphysiology, pathophysiology of the disease, clinical assessment and diagnosis, treatment options,and the anesthetic management of these patients.

Keywords: pulmonary hypertension, pulmonary vasoconstriction/dilatation, nitric oxide, prostacy-cline, phosphodiesterase-3, phosphodiesterase-5, anesthetic agents, anesthetic management

PHYSIOLOGY

A pulmonary vascular bed is a high flow, low pressuresystem. Normal PA pressure is about one-fifth of thesystemic pressure.1 It has a lower resistance comparedwith systemic vasculature (40–120 vs. 800–1200dyn�s/cm5)1 due to thinner media and less smoothmuscle. Factors that can affect the pulmonary vascularresistance (PVR) include oxygenation, hypercarbia andacidosis, cardiac output, lung volumes and airwaypressure, gravity, pulmonary vascular endotheliumand vascular mediators.2–4 Pulmonary vasculatureconstricts in response to hypoxia (Euler–Liljestrandreflex) and dilates in response to hyperoxia. PVR risesas the PO2 decreases below 60 mm Hg.5

Hypercarbia does not directly affect PVR. It increasesPVR through an increase in H+ ion and resulting acidosis.Hypoxia and acidosis have a synergistic effect on PVR.5

Increase in cardiac output enrolls the closed bloodvessels and dilates the open vessels in the lungresulting in a net increase in pulmonary circulationarea and hence a decrease in PVR. An increase in left

artrial (LA) pressures also has the same effect.

Clinically, the use of inotropes or enhanced blood

volume will passively decrease PVR.4

VR is maximum with small lung volumes (vasocon-

striction of alveolar blood vessels) and large lung

volumes (compression of extraalveolar vessels), and it

is minimum at functional residual capacity. This results

in a ‘‘U’’ shape relationship (Fig. 1) between PVR and

lung volumes.4 High positive end expiratory pressure

(PEEP) also compresses the vasculature in the well-

ventilated areas of the lung and diverts the flow to less

ventilated areas resulting in [PVR and YPaO2. Hence,

in clinical practice, one should avoid hypo/hyperven-

tilation and high PEEP in patients with pulmonary

hypertension.Gravity increases the blood flow to the dependent

parts of the lung. This is important in patients with

unilateral lung disease. To obtain the best gas

Ronald Regan UCLA Medical Center, Department of Anesthesi-ology, Division of Cardiothoracic Anesthesia, David Geffen Schoolof Medicine at UCLA, Los Angeles, CA.Address for correspondence: Ronald Regan UCLA Medical Center,Department of Anesthesiology, Division of Cardiothoracic Anes-thesia, David Geffen School of Medicine at UCLA, 757 WestwoodPlaza, Suite 3325, Los Angeles, CA 90095-7403. E-mail: [email protected]

American Journal of Therapeutics 0, 000–000 (2011)

1075–2765 � 2011 Lippincott Williams & Wilkins www.americantherapeutics.com

exchange, these patients should be ventilated with theirdiseased side up.6

There are 2 main mechanisms in the pulmonaryvascular endothelium that affect the pulmonaryvascular tone and PVR: The first mechanism initiatedin the endothelium is the activation of nitric oxide (NO)syntase. NO syntase converts L-Argenine to L-Citrulinand release of NO. NO diffuses to the smooth muscleand increases the activity of the enzyme Guanylatesynthase, which converts guanosine triphosphate tocGMP resulting in vasodilatation. Phosphodiesterase-5(PDE-5) catalyzes the breakdown of cGMP limiting theduration of vasodilatation (Fig. 2). The second mech-anism initiated in the endothelium involves the activa-tion of the enzyme Cyclooxygenase. This results inproduction of prostacycline (PGI2) from arachidonicacid. PGI2 diffuses to the smooth muscle and increasesthe activity of the enzyme Adenylate syntase, whichconverts adenosine triphosphate (ATP) to cyclic aden-osine monophosphate (cAMP). PDE-3 catalyzes thebreakdown of cAMP (Fig. 2). These mechanisms arestimulated by O2, shear force, ATP, and vascular endo-thelial growth factor.3,7 PGF2a, endothelin (ET-1), angio-tensin, serotonin result in pulmonary vasoconstriction.

Pulmonary vascular response to autonomic nervoussystem depends on the baseline vascular tone.b-Receptors mediate the response when PVR is low(vasodilatation), and a receptors mediate the responsewhen PVR is high (vasoconstriction).

PATHOPHYSIOLOGY

The natural history of the disease consists of 3 stages:

1. Endothelial dysfunction and vasoconstriction. In thisstage, there is a decrease in the endothelial-derivedNO and PGI2 and an increase in thromboxane

A2 and ET-1, which result in pulmonary vasocon-striction, smooth muscle (SM) proliferation, andplatelet aggregation. Platelet aggregation leads to insitu thrombosis and further releases of endothelialderived factors.1,3,8–10

2. Vascular remodeling and in situ thrombosis. Chronichypoxia, inflammation (due to acute respiratorydistress syndrome, chronic obstructive pulmonarydisease, and sepsis) leads to endothelial damage andfailure of these cells to eliminate the factors thatinitiate SM proliferation: Angiotensin 2, ET-1,Thromboxane A2, Superoxide radicals. SM pro-liferation occurs in both muscular and nonmuscularvessels. There is also an increase in the activity ofProtein kinase C, which mediates fibroblast pro-liferation and collagen deposition in the adventitialayer.1,8,9

3. The last stage is the formation of plexiform lesionsthat irreversibly obliterate the pulmonary arterioles.This is seen in late pulmonary artery hypertension

FIGURE 2. Mechanism of endothelium-dependent vaso-dilation in the pulmonary artery. Endothelial nitric oxidesynthase (eNOS) and cyclooxygenase (COX) are stimu-lated by physiologic agonists ATP and vascular endothelialgrowth factor (VEGF) and directly by oxygen and shearstress. NO and PGI2 diffuse to vascular smooth muscle,where they activate soluble guanylate cyclase (sGG) andadenylate cyclase, respectively, to increase the levels ofcGMP and cAMP. These cyclic nucleotides initiate smoothmuscle relaxation. Specific PDEs promote breakdown ofthe cyclic nucleotides. The arginine analog, asymmetricdimethyl arginine (ADMA), superoxide (O�2 ), and ET-1decrease NO release and cause vasoconstriction. NSAID,nonsteroidal anti-inflammatory drug; PGIS, prostacyclinsynthase.7

FIGURE 1. Relationship between lung volume and PVR.RV, residual volume, FRC, functional residual capacity,TLC, total lung capacity.4

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2 Salehi

(idiopathic pulmonary hypertension, scleroderma,Eisenmenger’s syn).1

There are factors that can accelerate the progressionof the disease in either acute or chronic setting. Thesefactors include hypoxia, acidosis, increased cardiacoutput (pregnancy, obesity, anemia, hyperthyroid-ism). Progression of the disease increases the rightventricular (RV) afterload and RV dilation andeventually RV failure. The slower the rate of pro-gression, the higher the chances for RV to adapt andbetter prognosis.

CLINICAL ASSESSMENT ANDDIAGNOSIS

Pulmonary hypertension in the past was classified intoprimary and secondary pulmonary arterial hypertension(PAHTN). In 1998, the World Health Organizationintroduced a new classification based upon categoriessharing similar pathophysiology, clinical presentation,and treatment options. WHO classified PAHTN into 5categories: (1) Pulmonary artery hypertension, (2) Pul-monary hypertension with left heart disease, (3) Pulmo-nary hypertension with respiratory disease, (4)Pulmonary hypertension caused by chronic embolic/thrombotic disease, and (5) Miscellaneous.

Symptoms vary based on the severity of the disease.Patients could be asymptomatic in the mild form of thedisease to demonstrating fatigue, weakness, dyspnea,leg swelling, abdominal fullness, palpitations, angina,syncope, and cyanosis in more advanced stages.4

Frequent signs of pulmonary hypertension duringphysical examination include normal to low bloodpressure (BP), jugular vein distention with prominent‘‘a’’ wave, left parasternal heave, loud P2 with splitsecond heart sound, S3 and/or S4 of RVorigin, crackles

on lung auscultation, and signs of R. heart failure(hepatomegaly, ascites, leg edema).2

The WHO has classified patients suffering frompulmonary hypertension based on their functionalclass into 4 classes. Class I patients are those in whomregular activity does not cause undue dyspnea, fatigue,or chest pain; class II patients have slight limitation ofphysical activity; class III patients have markedlimitations of physical activity; and class IV patientsare those who cannot carry out any physical activitywithout inducing any symptoms.

A series of laboratory tests are needed to confirm thediagnosis and assess the severity of the disease and itsunderlying pathology. These include chest x-ray, elec-trocardiogram (ECG), complete blood count, urinalysis,coagulation profile, Echocardiogram (presence of RVhypertrophy and dilatation, severity of tricuspidregurgitation, flattening of the intraventricular septum),pulmonary function tests, ventilation/perfusion scan,chest computed tomography/magnetic resonance im-aging, stress test, 6-minute walk test, right and left heartcatheterization including acute vasodilator response test(administering NO at a concentration of 20–40 ppm ifthe PVR decreases by 20% and CO is unchanged orincreased the patient is an acute responder),7 and liverfunction tests (LFTs; Table 1).

TREATMENT

Treatment of pulmonary hypertension consists ofa general and a specific approach. General treatmentfor patients with PAHTN consists of supplementaloxygen to keep SaO2 . 90% at rest or during activity. Ithas been shown that supplemental O2 can improvesurvival in these patients. Diuretics are given toprevent volume overload and treat ascites and edema.Salt restriction is recommended. Digoxin is given totreat heart failure. Proper nutrition is required to

Table 1. Diagnostic work-up.8

Diagnostic test Associated condition

Echocardiogram LV/RV dysfunction, valvular heart disease, CHDChest radiography Underlying pulmonary diseasePulmonary function tests COPD, restrictive lung diseaseV/Q scan, pulmonary angiography, spiral CT scan Chronic thromboembolic diseaseSleep study Sleep apneaBlood tests (CBC, chemistry panel, serology,

coagulation tests)Connective tissue disease,

hypercoagulable statesLFTs Portopulmonary hypertensionCardiac catheterization with vasodilator testingElectrocardiogram Arrhythmias, right axis deviation, heart block

COPD, chronic obstructive pulmonary disease; LFTs, liver function tests.

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Pulmonary Hypertension: A Review 3

maintain ideal body weight. Exercise is to be done astolerated. Anticoagulation with warfarin is recommen-ded to prevent in situ thrombi. Goal INR is 2–3, and itsdose needs to be adjusted if used with prostacylin.

Specific treatment includes the use of the differentclasses of pulmonary vasodilator medications. Wereview them briefly as follows:

Calcium channel blockers

These are only used in patients with a positivevasodilatory response. Their major side effects arehypotension and right heart failure. Nifedipine,Diltiazem, and Amlodipine are commonly used.2,4,7

Prostacycline analogs

These are analogs of PGI2, a product of endothelialarachidonic acid, which causes smooth muscle relaxationvia [cAMP. They improve outcome and long-termsurvival. The Most common drugs from this group areEpoprostenol a nonselective IV PGI2 analog with a half lifeof 4–6 minutes, unstable at room temperature with highpH requiring central access for administration. Iloprost isa selective inhaled PGI2 analog with a half life of 20–30minutes. It has a simple delivery system and can be usedin nonintubated patients. Treprostinil is a nonselectiveSQ/IV PGI2 analog with a half life of 3 hours. It wasapproved for use in 2002. It is stable at room temperatureand has a neutral pH. Beraprost is an oral PGI2 analog,which is still under investigation.2,11

Inhaled nitric oxide

Inhaled nitric oxide (INO) is a selective pulmonaryvasodilator through activation of cGMP. It is delivered tothe well-ventilated areas of the lung, thus improvingthe V/Q matching and decreasing intrapulmonaryshunting. It has a half life of 2–6 minutes and israpidly deactivated by oxyhemoglobin and haptoglobin–hemoglobin complexes. It produces methemoglobin inreactiontooxyhemoglobin,so its levelsshouldbecheckedevery q6 hours to keep it below 3–5%. It can be deliveredvia a nasal cannula, face mask, endotracheal tube. It hasa complicated delivery system and is expensive. Its usualdose is 10–40 ppm. High flow rates should be used duringits administration to prevent the accumulation ofNitrogen Dioxide (toxic byproduct of INO). INO shouldnever be abruptly discontinued because it can result inrebound pulmonary hypertension.2,8,11

Endothelin receptor blockers

ET-1 is a direct pulmonary vasoconstrictor by aug-menting smooth muscle proliferation and fibrosis. Ithas 2 receptors, ETa responsible for SM proliferationand vasoconstriction and ETb responsible for clearance

of endothelin and production of NO and PGI2 from theendothelium. This group of drugs has been shown toimprove hemodynamics, exercise tolerance, and symp-toms. Bosentan is a nonselective oral Eta blocker witha half life of 5 hours approved for patients with WHOfunctional classes III and IV. It can cause hepatotoxicity;therefore, monthly LFTs are recommended. Ambrisen-tan is a selective Eta antagonist approved for patientswith WHO functional classes II and III. It is admin-istered orally and can cause hepatic toxicity and birthdefects. Sitaxsentan is under investigation in the UnitedStates. It is 6000 times more selective for Eta thanbosentan is.8,11

Phosphodiesterase-5 inhibitors

This group of drugs inhibits phosphodiesterase-5and thus increases the cGMP levels leading to smoothmuscle relaxation and vasodilatation. Sildenafil isapproved for treatment of pulmonary hypertensionregardless of functional class. It is safe to use with Etablockers, PGI2 analogs, and INO. It prolongs INOeffect and attenuates the rebound PAHTN when INO isdiscontinued. Sildenafil improves functional class andexercise tolerance in 12 weeks and 1-year follow-upwith good safety profile.12,13 It is orally administeredand can be given via a nasogastric tube intraoper-atively. Its use is contraindicated with nitrates due tohigh risk of developing profound hypotension.

Phosphodiesterase-3 inhibitors

By inhibiting phosphodiesterase-3, these inhibitorsincrease the cAMP levels, which in return cause smoothmuscle relaxation and nonselective vasodilatation. Theyalso have a positive inotropic effect. Most importantdrugs from this group are Amrinone and Milrinone.Milrinone comes in both inhaled and IV forms. IVmilrinone and INO have a more pronounced effect inreducing pulmonary artery pressure than when they areused alone. It also attenuates the rebound pulmonaryhypertension when INO is being weaned. Inhaledmilrinone has an additive effect with inhaled PGI2. Itsmost important side effect is hypotension.4,14

ANESTHETIC MANAGEMENT

Assessment of patients with pulmonary hypertensionundergoing anesthesia should include obtaining thehistory and performing a thorough physical examina-tion, obtaining the recent ECG, chest x-ray, echocardio-gram, right heart catheterization, and an arterial bloodgas sample. All treatments need to be continued to theday of surgery with few considerations. SubcutaneousTrepostinil should be converted to IV Epoprostenol. Oral


4 Salehi

Anticoagulation can be converted to short acting IVagents and be discontinued at the time of surgery. Anysign of worsening of pulmonary hypertension or RVfunction should necessitate further work up and treat-ment, and delay of the intended procedure if possible.8

MORTALITY AND MORBIDITY

Noncardiac surgery in patients with pulmonaryhypertension is associated with considerable morbidityand mortality even in patients that are stable and wellmanaged. Ramakrishna et al15 showed a 7% mortalityand 42% morbidity in patients undergoing majornoncardiac surgery (Orthopedic, Thoracic, Vascular,Laparoscopic, etc). The risk is even higher withC-section and liver transplantation. Factors predictingperioperative morbidity risk include New York HeartAssociation class II or greater, history of PE, Surgery.3 hours, Intermediate to high risk surgery. Factorspredicting perioperative mortality risk include rightaxis deviation on the ECG, RV hypertrophy, RV systolicpressure/Systolic BP $ 0.66, use of intraoperativevasopressors, and history of PE. (Table 2).

ANESTHETIC GOALS

Formulating an appropriate anesthetic plan requiresa clear vision into the general and hemodynamic goalsfor these patients. General goals include avoidinghypoxia, hypercarbia, acidosis (respiratory or meta-bolic), Hypo or Hypervolemia, hypothermia, provid-ing adequate anesthesia and pain control. Hypoxia,hypercarbia and acidosis directly or indirectly increasePVR, which in turn can cause a rapid rise in the PApressures leading to a pulmonary hypertensive crisisand RV failure. Hypovolemia leads to systemichypotension and impairment of RV perfusion andRV failure. Hypervolemia depending on the presenceor absence of left ventricular (LV) dysfunction canresult in pulmonary congestion, RV overload, elevationof central venous pressure, and end organ congestion(Liver, Kidney). Providing adequate anesthesia and

pain control are essential because pain leads tosympathetic stimulation, which in the context ofincreased pulmonary vascular tone in these patientscan result in pulmonary hypertensive crisis.

Hemodynamic goals include maintenance of preloadto maintain ventricular filling, maintaining afterload tosustain adequate ventricular perfusion pressure, nor-mal to high contractility to preserve cardiac output andforward flow, maintaining sinus rhythm and normalheart rate (avoiding extremes) to sustain adequateventricular filling and preserving stroke volume andcardiac output.

PREMEDICATION

Control of anxiety is important in these patients.Benzodiazepines should be titrated carefully to preventoversedation and hypoventilation, which can bedetrimental. Bronchodilators should be considered ifindicated. All pulmonary hypertension specific treat-ments should be continued in the perioperative period.Specific changes may be needed as mentioned before.

MONITORING

In addition to standard American Society of Anes-thesiologists monitors, selection of invasive monitorsdepends on the severity of the disease and the risksassociated with the procedure (fluid shifts, blood loss,acidosis, and swings in BP). Patients with mildpulmonary hypertension usually do not need invasivemonitoring. In patients with moderate to severepulmonary hypertension, an arterial line is indicatedto monitor beat to beat BP changes and blood gasmonitoring to detect acid/base imbalances and oxy-genation. Central venous pressure monitoring usuallyis adequate to guide fluid management in the setting ofnormal RV function. Pulmonary artery catheters areusually indicated when the procedure is associatedwith significant fluid shifts, BP swings or in patientswith compromised RV function. It should be noted thatfloating PA catheters is associated with higher risk of

Table 2. Perioperative considerations.8

Predictors of morbidity Predictors of mortality

History of PE History of PENYHA class II or greater Right axis deviationIntermediate to high risk surgery Right ventricular hypertrophySurgery duration . 3 hrs RV systolic pressure/systolic blood pressure $ 0.66

Intraoperative vasopressor use

NYHA, New York Heart Association.



PA rupture, and arrhythmias in this patient popula-tion.8 Transesophageal echocardiography can also beused to assess RV and LV function, calculate PApressures, and cardiac output. It could be an alternativein patients with high risk of PA rupture or arrhythmias.Its use depends on the practitioner’s comfort inobtaining and interpreting images.

ANESTHETIC TECHNIQUES

A Specific Anesthetic technique is less important thanthe attention to the anesthetic goals and prevention oftriggers that cause PAHTN crisis. An appropriateanesthetic technique should be based on the type ofprocedure, risks associated with the procedure,patients’ comorbidities, and severity of disease. Be-cause any airway instrumentation can precipitatepulmonary hypertensive crisis in patients with mod-erate to severe PAHTN, local anesthesia or conscioussedation may be preferred considering that the pro-cedure allows the use of such techniques. If conscioussedation is chosen, end tidal carbon dioxide (ETCO2)administered via a nasal cannula should be carefullymonitored because it reflects adequate pulmonaryblood flow and RV function, Sudden drop in ETCO2

can be a sign of increase in PVR and RV failure.Anesthesiologists should be ready to assist or controlventilation.14 If it is determined that the patient maynot be able to maintain adequate ventilation (morbidobesity, sleep apnea, high anesthetic requirements)under sedation or the procedure will not permitspontaneous ventilation, general anesthesia withlaryngeal mask airway or endotracheal intubationshould be considered. Carmosino et al16 showed thatIncidence of complications in children with pulmonaryhypertension is independent of the method of airwaymanagement. If mechanical ventilation is considered,moderate tidal volumes and low PEEP should beconsidered to optimize lung recruitment and pulmo-nary blood flow and minimize atelectasis.8

Neuraxial anesthesia and regional blocks can be usedin this patient population if not contraindicated (anti-coagulation). Spinal anesthesia should be avoided dueto profound sympathetic blockade, decrease in venousreturn, and bradycardia. Lumbar epidural anesthesiawith careful titration is the method of choice ifneuraxial anesthesia is considered, although thesuccessful use of combined spinal epidural anesthesiaduring delivery has been reported.17 Thoracic epiduralanesthesia should be considered with caution becauseit blocks the efferent cardiac sympathetic nerve fibers,which results in negative inotropic response to suddenrise of PA pressures and RV failure.18

ANESTHETIC AGENTS

There is conflicting evidence in the literature regardingthe effects of anesthetic agents on the pulmonaryvasculature. IV anesthetics have little effect on PVR. Theycause less intrapulmonary shunting than inhalationalagents do because they do not blunt the hypoxic vaso-constriction in the lungs.19,20 Propofol and Thiopentaldecrease PVR and pulmonary artery pressure (PAP) andmean arterial pressure and myocardial contractility,which are not desirable. The effect of Etomidate onpulmonary vasculature is not well studied. It has minimaleffect on the systemic hemodynamics. Benzodiazepinesand Narcotics have minimal systemic and pulmonaryhemodynamic effect. There is no consensus on thepulmonary effects of Ketamine. It can increase PVRand PAP depending on their baseline values with themost profound effect when baseline PVR and PAP arehigh.21 Ketamine does not increase PVR when used withpulmonary vasodilators while maintaining its systemiceffects [maintenance of systemic vascular resistance (SVR)and BP] which makes its use desirable in this setting.4

Inhalational agents impair hypoxic vasoconstrictionin the lungs and hence increase intrapulmonaryshunting. They cause dose-dependent depression ofmyocardial contractility and decrease SVR, which maycause RV dysfunction. Desflurane augments vaso-contrictive response to a1 adrenergic activity andincreases PVR and PAP. Isoflurane and Sevoflurane areacceptable components of a balanced anesthetictechnique. NO increases PVR in adults but has littleeffect in infants with pulmonary hypertension.22

Pulmonary vascular response to N2O is dependenton the perioperative degree of PVR.23

A balanced anesthesia technique is preferred forgeneral anesthesia. Combination of Midazolam, Fentan-yl, low-dose Propofol, or Etomidate/low concentrationof Sevoflurane can be used for induction. Anesthesia canbe maintained with low-dose inhalational agents andintermittent doses of narcotics. If Neuromuscular re-laxation is desired, agents with low hemodynamic effectsare preferable (Rocuronium, Vecuronium).

POSTOPERATIVE CARE

These patients need a monitored bed or an intensivecare unit postoperatively to provide adequate ventila-tion and oxygenation, pain control, fluid managementand to monitor hemodynamics. Pulmonary vasodila-tory therapies should continue in the postoperativeperiod. In most patients, morbidity and mortality occurseveral days after surgery due to progressive [PVR,RV dysfunction, and sudden death.


6 Salehi

MANAGEMENT OF PULMONARYHYPERTENSIVE CRISIS

Management of pulmonary hypertensive crisis is basedon the principles discussed before: administration of100% O2 to increase PAO2 and PaO2 and decrease PVR;hyperventilation to induce a respiratory alkalosis;reduction of PAP by YPaCO2

14; correction of metabolicacidosis. PVR is directly related to the H+ concentra-tion. Management also involves starting INO or otherpulmonary vasodilators; supporting myocardial con-tractility and cardiac output with inotropic support.Epinephrine and Milrinone are preferred. If systemichypotension and vasodilatation occur, the use ofvasopressors is recommended. Norepinephrine is pre-ferred because of its wider ratio of systemic to pulmo-nary effects (more systemic vasoconstriction thanpulmonary). Adequate pain management to eliminatenoxious stimuli, which can cause an increase in PAP.14

CONCLUSIONS

In managing patients with pulmonary hypertension,anesthesiologists face many challenges. One shouldcarefully assess these patients, obtain all the necessarystudies, consult with the surgeon and other specialtiesinvolved in the care of these patients, and devise a well-thought anesthetic plan.

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