Perioperative Pulmonary Hypertension
It is estimated that pulmonary hypertension (PH) affects about 1% of the global population and as many as 10% of persons older than 65 years. [1, 2] Until relatively recently, patients with this condition were considered to be at prohibitively high risk for undergoing elective procedures. This situation has changed: Greater knowledge of the pathophysiology of PH and advances in its treatment have led to improvements in both functional status and life expectancy for these patients.
PH has been associated with an increase in perioperative morbidity and mortality, particularly when complicated by an acute pulmonary hypertensive crisis and a failing right ventricle (RV). [3, 4, 5] As data regarding the risks (and also safety) of noncardiac surgery in patients with PH continue to accumulate, it is imperative for anesthesiologists to educate themselves about PH. This article focuses on salient aspects of the perioperative management of patients with PH who present for noncardiac surgical procedures.
Key points in the management of a patient with PH include the following:
The functional capacity of the vital organs is entirely dependent on the presence of sufficient perfusion and oxygenation. Perfusion and oxygenation, in turn, depend on the heart’s ability to pump oxygenated blood throughout the body. The following two interlinking circulatory systems help accomplish this  :
In a steady state, the cardiac output through the two systems is equal, and Ohm’s law suggests that the pressure gradient required to pump through each system is inversely dependent on its individual resistance.
In a physiologically normal state, the heart is perfectly modeled to accommodate these different resistances. Whereas the left ventricle (LV) must generate a relatively high pressure gradient in order to overcome the high systemic vascular resistance (SVR), the RV needs to generate a lower pressure gradient to overcome the lower pulmonary vascular resistance (PVR). Furthermore, the reduced filling pressures in the RV lead to less wall stress than occurs in the LV. Accordingly, the wall of the LV is substantially thicker than that of the RV in a physiologically normal state. 
In a pathologic state, PH of all forms leads to an increase in resistance to flow across the pulmonary vascular bed. This creates an increased afterload for the RV, thereby impeding the ability of the RV to eject blood, and increases the end-systolic and end-diastolic volumes.  In most individuals with chronic PH, the progression is gradual, allowing the right heart time for remodeling and hypertrophy in response to the increased pressure. This compensation allows increased contractility and brings stroke volume closer to baseline despite the increases in pressure and afterload.
However, patients with PH are not always in a compensated steady state, particularly when undergoing anesthesia or surgery. When a pressure-naive RV encounters elevated pulmonary pressures for the first time, or when a chronically hypertrophic RV works against a resistance far in excess of what it usually faces, it may not be able to compensate, and failure may result.
In such cases, this pressure is then transmitted in a retrograde fashion back into the venous circulation, leading to symptoms of acute right-heart failure and organ dysfunction from venous congestion. Furthermore, the decrease in forward flow through the pulmonary circulation reduces LV preload and stroke volume, thereby causing decreases in cardiac output and consequently in mean arterial pressure (MAP). 
Although increases in SVR can partially compensate for the decreased MAP for the purpose of maintaining tissue perfusion, there is still a decrease in overall oxygen delivery. In particular, decreased perfusion pressure and decreased cardiac output in a patient with a hypertrophic RV can greatly impede oxygen delivery to the thickened ventricular wall, leading to endocardial ischemia and worsened cardiac dysfunction.
If this situation is left untreated, the RV begins to dilate in the face of corrected afterload increase. Such dilation leads to dilation of the tricuspid annulus and subsequently to tricuspid regurgitation. This worsens forward flow and leads to increased back-pressure to the end organs (eg, the kidneys and liver), which is dependent on the difference between MAP (which is low) and central venous pressure (CVP, which is elevated). [8, 9]
PH is defined by a mean pulmonary artery pressure (mPAP) of 25 mm Hg or higher, as measured at catheterization. This is the most basic definition of the condition, which, though correct, omits some important descriptive nuances. The 2013 Nice World Symposium on Pulmonary Hypertension classified PH into five groups on the basis of etiology and the pathologic changes that lead to increased pulmonary pressures.  This classification culminates in group-specific differences in management.
In addition, the groups can be broadly categorized as either precapillary PH, characterized by a pulmonary artery wedge pressure (PAWP) of 15 mm Hg or less and a PVR of more than 3 Woods units (groups 1, 3, 4, and 5), or postcapillary PH, characterized by a PAWP of 15 mm Hg or greater and a PVR of less than 3 Woods units (group 2).
World Health Organization (WHO) group 1 disease includes patients with idiopathic pulmonary arterial hypertension (PAH); heritable PAH; and arteriopathies related to connective tissue disease, HIV infection, portopulmonary hypertension, congenital heart disease, and drug-induced disease.
These conditions are forms of distal precapillary disease and result in an increase in resistance of the pulmonary arterial tree. The endothelial and smooth-muscle cells of the small pulmonary arteries proliferate abnormally, and these angioproliferative vascular changes lead to an increase in PAP and PVR, without affecting PAWP. Eventually, a fixed irreversible reduction in the cross-sectional area of the pulmonary vascular tree develops that is unresponsive to vasodilator therapy.
Group 2 PH, the only postcapillary form of the disease, is also the most common form. It is due to retrograde transmission of elevated left atrial pressure (LAP) from left-heart disease. Typically, this results from LV systolic or diastolic dysfunction or from aortic and mitral valvular pathologies. The elevated pressures of the left heart are transmitted back to the pulmonary capillary bed, the pulmonary arteries, and finally the right heart. Group 2 PH can also coexist with precapillary disease (group 1, 3, 4, or 5), constituting “mixed” PH.  .
Despite the frequency of group 2 PH, data on pathologic changes in the pulmonary vasculature are scarce, probably because of the heterogeneity of both the patients and the pathology in this varied group. 
Group 3 PH includes any etiology related to lung disease and hypoxia. Associated diseases include chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, and interstitial lung disease. In response to the resulting hypoxia associated with these pathologies, the smooth-muscle cells of the pulmonary artery become hypertrophic, thereby increasing both PVR and PAP. It is noteworthy that only a small minority of patients with sleep apnea progress to PH.
Group 4 disease is solely due to CTEPH, arising from the progression of fibrous dysplasia in response to unresolved thromboemboli. Notably, CTEPH does not respond to pharmacologic vasodilation as robustly as other forms of PH do.
Group 5 disease includes forms of PH due to multifactorial mechanisms involving hematologic, systemic, and metabolic disorders (eg, sarcoidosis, sickle cell disease, and myeloproliferative disorders).
The initial presentation of PH may be nonspecific, and thus diagnosis is often delayed. Exertional dyspnea, fatigue, and reduced exercise capacity are common initial complaints, which are usually slow both in onset and in progression. 
If the condition goes untreated, right-side failure results, manifested by clinical findings such as elevated jugular venous pressure, hepatomegaly, ascites, and lower-extremity edema, with cardiac examination revealing an RV lift, a loud P2, and a tricuspid regurgitation murmur. Electrocardiography (ECG) may display signs of PH, including a peaked P wave (P pulmonale), RV hypertrophy, RV strain, and an S1Q3T3 pattern. Signs of PH on chest radiography consist of RV enlargement, dilated pulmonary arteries, and peripheral pruning. 
Echocardiography is often used as a screening test for PH. Although this modality has the advantage of being noninvasive, it is relatively inaccurate for evaluating PAP. The primary value of echocardiography in PH lies in its ability to evaluate the function of the heart—specifically, the RV. It can help differentiate long-standing chronic disease that has been well compensated by RV hypertrophy from an acute exacerbation to which the RV is adapting poorly.
Classically, PH is evaluated by means of right-heart catheterization, which is the gold standard for obtaining accurate intracardiac pressures. Right-heart catheterization measures right atrial pressure (RAP), mPAP, PAWP, cardiac output by thermodilution, and mixed venous oxygen saturation (SmvO2). It also provides data for calculating PVR. This information is essential for disease severity assessment and accurate risk stratification. The roles of echocardiography and catheterization are expanded upon below (see Management).
The most notable risks for patients with PH are as follows  :
Key factors to consider in assessing a patient with PH include the following:
Patients with PH who undergo minor procedures (eg, endoscopy or breast surgery) have lower complication rates than similar patients who undergo high- or intermediate-risk procedures (eg, laparoscopic abdominal, thoracic, vascular, or emergency procedures). Increased disease severity, as suggested by elevations in systolic and mean PAP, has also been associated with a higher complication rate. [13, 14] Furthermore, the presence of comorbid conditions such as coronary artery disease (CAD) or chronic kidney disease has been associated with increased risk and by itself changes the American Society of Anesthesiologists (ASA) physical status score.
In the presence of heart failure, hypoxia, or acidosis that is amenable to optimization, it is perhaps best to give additional consideration to the decision to proceed with elective surgery.  Even when medical status is optimized, it is easy to imagine that patients with PH represent a high-risk subgroup when undergoing noncardiac surgery.  Predictors of adverse outcome include the following:
The presence of one or more of these red flag characteristics may warrant more invasive monitoring (eg, pulmonary artery catheterization or TEE) intraoperatively. Echocardiographic parameters that predict a poor outcome include the following:
To summarize, dyspnea at rest, low cardiac output in the face of severely elevated right-side filling pressures, metabolic acidosis, and marked hypoxia point toward severe and potentially life-threatening disease that should prompt reassessment of the need for surgery before further optimization.
Although PH is defined in terms of elevated pulmonary pressures, it is important to recognize that the elevated pressure, in and of itself, is probably much less directly harmful to patients than is the resulting impairment of the right heart’s ability to pump blood through the pulmonary circulation. Vigilant perioperative management of patients with PH is essential for keeping them safe and requires an understanding not only of the pathophysiology of PH but also of the effects of anesthetic agents and positive-pressure ventilation (PPV).
Ventilation and metabolic considerations
Patients with PH are exquisitely sensitive to the effects of both general anesthesia and PPV. It is well known that PPV increases intrathoracic pressure, thereby reducing venous return and decreasing RV preload. This effect can also be seen with the addition of excessive positive end-expiratory pressure (PEEP). 
However, increases in intrathoracic pressure also increase pulmonary artery transmural pressure, thus increasing RV systolic transmural pressure, RV wall stress, and RV afterload. This dual effect (ie, reducing preload and increasing afterload) can lead to a drastic reduction in the ability of the RV to pump blood through the pulmonary circulation.  PVR is lowest at functional residual capacity, with lower volumes resulting in atelectasis and hypoxia and higher volumes resulting in compression of alveolar vessels. 
On the other hand, it is also important to avoid oversedating and creating hypoxia and hypercarbia during spontaneous ventilation, either of which can raise PVR above the patient’s baseline. Pain and acidosis can lead to acute increases in pulmonary pressures as well, particularly in a patient in active labor or a septic patient with a severe acidosis. Everything possible should be done to minimize these exacerbating factors. Recognizing and treating volume overload is vital; unmonitored fluid challenges can be disastrous. Furthermore, certain medications and agents (eg, N2O) can vasoconstrict the pulmonary circulation and should be avoided.
Perfusion and oxygen demand
Patients with PH live with a relative oxygen deficit, not only because of increased demand from a hypertrophic ventricle but also because of decreased oxygen delivery resulting from compromised output. Like a hypertrophic LV, a hypertrophic RV is especially sensitive to decreased perfusion. Normally, the RV is perfused in both systole and diastole, but in a hypertrophic heart experiencing pressure overload, the smaller pressure gradient between the aortic root and the RV allows perfusion only when the pressure inside the RV is low—specifically, during diastole. This yields a perfusion situation similar to that in the LV. 
When perfusion pressure is low, a positive feedback loop can quickly develop whereby the reduced perfusion leads to decreases in function and cardiac output, further reducing perfusion pressure to the RV. Accordingly, optimizing perfusion pressure and limiting myocardial oxygen demand are key tenets of anesthesia for these patients.
A failing, dilated RV also results in a dilated tricuspid annulus, causing valvular regurgitation. This ultimately leads to further compromise of forward flow. Hypoperfusion of the kidneys leads to decreased urine output; however, it also results in increased renin-angiotensin activity, sodium and water retention, and release of vasopressin, thus worsening volume status and impairing contractile efficiency. 
Superficial myocardial fibers encircle both the LV and the RV, and the two chambers share a pericardium along with a septal wall. Consequently, changes that affect one ventricle eventually affect the other as well. In view of the importance of this ventricular interdependence to RV function, every effort should be made to avoid drops in SVR and LV afterload.
In a normal heart, the RV contracts circumferentially onto the septal wall, leading to efficient contraction and good systolic function. However, when PAP is elevated and the RV is overloaded, the septal wall shifts out into the LV, impairing both RV systolic efficiency and LV diastolic function.  This is one of the reasons why maintenance of sinus rhythm is essential for LV filling. Fortunately, if LV afterload is increased, LV end-diastolic pressure (LVEDP) increases, and this pressure pushes the septal wall back to midline, allowing efficient RV contraction. Phenylephrine or other predominantly alpha-agonist agents (eg, norepinephrine) can be given to help accomplish this.
Regional vs general anesthesia
The literature has not yet clarified whether regional or general anesthesia is preferable in patients with PH.  One small limited study showed a nonsignificant trend toward increased perioperative complications for those undergoing general anesthesia.  In view of the known effects of general anesthesia and PPV, a recommendation can be made to lean toward using regional or neuraxial techniques if possible. The benefit to be gained may be the result of blockade of increases in sympathetic tone, which prevent any resultant increases in PVR.
Neuraxial anesthesia must be used with caution because it has the potential to cause profound systemic hypotension, decreased cardiac perfusion, and subsequent hemodynamic collapse. Accordingly, epidural anesthesia, being readily titratable and having a gradual onset, carries less risk than a single-shot subarachnoid block does. It is also recommended that moderate or deep sedation not be used concurrently with these techniques; hypoxia and hypercarbia from hypoventilation can drastically increase PVR and trigger a pulmonary hypertensive crisis.
Regional or neuraxial catheter-based techniques have the advantage of reducing sympathetic tone through excellent pain control that extends into the postoperative period, without the respiratory depression that can occur with opiates. Anticoagulant therapy, which these patients may be receiving, is sometimes the prohibiting factor and must be considered in making the choice.
General anesthesia has the advantage of allowing control of the patient’s airway, oxygenation, and carbon dioxide levels; however, the provider must be prepared and vigilant and must use the appropriate pharmacologic therapy to minimize PVR.
A thorough preoperative evaluation should be performed to assess the severity of the disease process, with particular attention paid to functional status, comorbid conditions, and the proposed procedure. The approach to perioperative care of patients with PH is often a multidisciplinary one that includes input from PH experts, surgeons, intensivists, pharmacists, and nursing staff. A careful assessment of the need for surgery, with a focus on the risk-to-benefit ratio in each individual patient, is the difficult task that falls on this group of caregivers.
A detailed history and a thorough physical examination should be complemented by a review of vital investigations—namely ECG, chest radiography, pulmonary function tests, brain natriuretic peptide (BNP) or other markers of heart failure, functional assessment or stress testing, echocardiography, and right-heart catheterization.  Dyspnea and fatigue are nonspecific symptoms, but angina and syncope are ominous indicators of advanced disease.  Multimodal assessment of volume status can be vital in optimizing RV preload.
Echocardiography (either TEE or transthoracic echocardiography [TTE]) can provide an estimate of pulmonary artery pressures and right-heart function. It provides insight into the functional reserve of the RV, its degree of compensation, and the anticipated need for inotropic or pulmonary vasodilator support. RV functional parameters, such as TAPSE and RV fractional area change, can be extremely useful for this purpose. 
Typically, a right-heart catheterization is performed in patients with severe PH who are undergoing elective surgery; this is the gold standard for characterizing disease severity. An mPAP of 25-40 mm Hg signifies mild disease, an mPAP of 40-55 mm Hg signifies moderate disease, and an mPAP higher than 55 mm Hg signifies severe disease.
Evaluation of intracardiac pressures is also essential for characterizing the effects of pressure overload on the right heart and determining whether a patient is nearing the limits of compensation. Typically, normal RAP is lower than 5 mm Hg, RV systolic pressure is lower than 25 mm Hg, and RV diastolic pressure is lower than 5 mm Hg. A combination of high RAP with reduced cardiac output is more concerning than a pure elevation in PAP would be because it points toward right-side pump failure.
Vasoreactivity in response to a calcium-channel blocker may identify patients who will benefit from intraoperative pulmonary vasodilation, which is commonly achieved by administering iNO.  A left-heart catheterization may be performed if there are concerns about possible severe CAD, left-side valvular disease, or inaccuracy in the measurement of PAWP.
One of the central considerations in anesthesia for this patient population is appropriate monitoring. Patients who have severe disease or a decompensated clinical picture cannot be treated effectively if the developing problem is not recognized. To this end, standard ASA-recommended monitors are a prerequisite.
Real-time monitoring of arterial pressure is key to maintaining adequate perfusion pressure to the RV. In any patient with moderate or severe PH, invasive arterial monitoring is generally warranted for all but the shortest procedures. In addition to rapid detection of hemodynamic deterioration, such monitoring enables analysis of arterial blood gas values in order to facilitate normocarbia and adequate oxygenation. Pulse contour analysis can add valuable information regarding volume responsiveness and cardiac output. 
A central venous catheter can facilitate measurement of CVP, optimization of fluid status, and administration of vasoactive drugs (if needed). Placement of a pulmonary artery catheter, though invasive and of questionable value, can be useful for titrating therapy to reduce PAP.  The authors advocate placing a central venous catheter in cases where either the severity of PH or the surgical risk is greater than moderate.
Intraoperative TEE can be a useful aid for evaluating RV systolic function in real time and assessing the efficacy of inotropic therapy. At present, however, there are no specific indications for intraoperative echocardiography in this setting, nor are there any clear guidelines as to how it should be conducted. Insertion of a probe must be done carefully and only after the benefit is weighed against the risk.
Pharmacologic agents used perioperatively to treat PH include vasodilators, inodilators, inotropes, and vasopressors (see Table 1 below). 
Table 1. Perioperative Pharmacologic Therapy for Pulmonary Hypertension (Open Table in a new window)
Increased prostacyclin levels/effects
Increases NO levels
Pulmonary and systemic vasodilation; risk of cyanide toxicity; tachyphylaxis
Increases NO levels
Increases cGMP and cAMP
(investigational in US)
Intraoperatively, the hemodynamic goals are to minimize PVR while maintaining effective RV systolic function and a normal-to-high MAP so as to maintain perfusion to end organs.
Accordingly, the inotropic agent of choice is typically dobutamine, which, at dosages below 5 μg/kg/min, is known to increase contractility and decrease PVR.  Milrinone, a phosphodiesterase (PDE)-3 inhibitor, has similar effects on inotropy and PVR and can act synergistically with dobutamine; however, it is associated with tachyphylaxis and is usually given only for short periods. At higher dosages (eg, >10 μg/kg/min for dobutamine), increased heart rate–related oxygen consumption generally offsets the benefits from increased cardiac output.
Levosimendan is a novel calcium sensitizer that, so far, has only been used investigationally in the United States. It causes an increase in contractility and a reduction in PVR without a significant increase in oxygen consumption.  Levosimendan is not currently available for clinical use in the United States but has shown promise for reducing mortality in patients with heart failure as compared with dobutamine.
Alpha agonists such as phenylephrine and vasopressin are essential for increasing SVR and raising the perfusion pressure to the RV. Low dosages of vasopressin may also cause a degree of pulmonary vasodilation, which can be beneficial in this setting. 
Pulmonary vasodilators improve forward flow by reducing afterload and manipulating hypoxic vasoconstriction. They should be tried after RV perfusion and cardiac output have been optimized.  Only a small minority of patients with PH will respond to calcium-channel blockers with vasodilation, and these agents can cause systemic hypotension that leads to hemodynamic compromise. Although patients taking calcium-channel blockers should continue to do so perioperatively, these agents generally are not used intraoperatively for acute reduction of PVR.
PDE-5 inhibitors, of which sildenafil is the prototype, have been shown to reduce PVR, improve LV diastolic dysfunction, and enhance quality of life in patients with PH. These medications are among the few with proven benefit in WHO type II PH, though as with calcium-channel blockers, intraoperative use of this class of drugs is minimal.
Drugs administered via the inhalational route, such as iloprost (also known as prostacyclin) and iNO, have the benefit of improving ventilation/perfusion (V/Q) mismatch by causing vasodilation in only the well-ventilated areas of the lung. Because they have a short half-life and thus are easily titratable, they are particularly useful in the operating room (OR).  Iloprost is also available in an intravenous (IV) form (outside the United States), though it can cause systemic hypotension and inhibition of platelet aggregation. Rebound PH is a possibility with abrupt discontinuance of iNO; gradual withdrawal is therefore recommended.
The exception to standard therapy is CTEPH, which has been found to be minimally responsive to external mediators of pulmonary vasodilation. In this situation, providers must be especially vigilant to avoid perturbations that would increase pulmonary vascular tone, including hypoxia, hypercarbia, acidosis, and pain. Furthermore, dobutamine, milrinone, and iNO seem to have minimal effect on PVR, and thus it is the authors’ preference to use dopamine or epinephrine for inotropic support. This avoids compromising MAP and cardiac perfusion pressure (especially to the RV).
Although acute changes in hemodynamics are less likely during the postoperative period, unpredictable volume shifts and many commonly used medications can still worsen a patient’s PH and precipitate RV failure. As always, it is important to avoid hypoxia, hypercarbia, acidosis, and pain, all of which can lead to clamping down of the pulmonary vasculature and increase pulmonary artery pressures.
Accordingly, it is essential that extubated patients be able to spontaneously ventilate in an effective manner without obstruction or concern for respiratory compromise. Particularly with a long case (>12 hours) or in a patient with obstructive sleep apnea, there is a risk of oversedation, and continued intubation should be carefully considered until the patient is fully alert and capable of adequate ventilation.
Treatment of pain in the postanesthesia care unit (PACU) typically involves opioids. In a patient with PH, the concern is decreased respiratory drive in response to hypercarbia and minor episodes of hypoxia from hypoventilation. To avoid exacerbating PH, nonopioid pain control (eg, acetaminophen, ketorolac, injection of local anesthetic, regional blocks, or epidural anesthesia) may be used. If opioid use is unavoidable and respiratory compromise is likely, continued endotracheal intubation and mechanical ventilation in the intensive care unit (ICU) may be considered until alleviation of acute surgical pain allows administration of reduced doses of narcotics.
On one hand, fluid shifts can lead to decreases in preload and impaired flow through the pulmonary circulation; on the other hand, they can also lead to significant increases in intravascular volume. Patients with a positive fluid balance must be monitored closely, and if there is concern that increased intravascular volume may lead to acute exacerbation of right-heart dysfunction, they should remain intubated and undergo appropriate diuresis. Furthermore, any inotrope or vasodilator being given intraoperatively should be either continued into the postoperative setting if needed or carefully tapered. 
A 54-year-old, 5’4″ (163 cm), 70-kg female patient with a known history of severe PH presents for an elective laparoscopic cholecystectomy. A right-heart catheterization report in her chart from 4 months previously documents elevated RAP (12 mm Hg), as well as elevated RV pressure (42/15 mm Hg). TTE shows a severely dilated RV and a moderately dilated RA. However, the patient is in no apparent distress, and there is no evidence of jugular venous distention, hepatomegaly, or anasarca.
Before induction an arterial line is placed, and baseline blood pressure is 126/72 mm Hg. The patient is preoxygenated and induced with fentanyl, lidocaine, propofol, and rocuronium. The airway is secured, and the surgical procedure starts with the establishment of pneumoperitoneum. Tachycardia (to 128 beats/min) is noted, and blood pressure decreases dramatically (to 78/32 mm Hg). The anesthesia provider asks for release of abdominal insufflation, then administers ephedrine and phenylephrine, with subsequent improvement in MAP.
This clinical scenario is suggestive of a developing acute pulmonary hypertensive crisis. Laparoscopy can be extremely detrimental to the physiology of patients with PH. Insufflation of CO2 (a commonly used gas in laparoscopy) raises the intra-abdominal pressure, leads to decreased venous return, and pushes the diaphragm into the chest, thereby increasing the intrathoracic pressure. Furthermore, over time, absorption of CO2 leads to hypercarbia and acidosis.  When these changes occur in a state of sympathetic overdrive (such as may occur immediately after incision), mismatch of supply and demand to the RV can develop, resulting in potentially catastrophic RV failure.
The preoperative evaluation included severely elevated right-side pressures with only mildly elevated pulmonary arterial pressures, suggesting near-exhaustion of compensatory mechanisms. The provider in such cases must be vigilant to minimize any further exacerbation (such as may be caused by hypercarbia or pain) that will vasoconstrict the pulmonary circulation. In this case, it was appropriate to place an awake arterial line. In cases of severe disease, the authors recommend having an inotrope (eg, dobutamine, dopamine, or epinephrine) ready and available for immediate use. In some situations, it is appropriate to start inotropic support even before induction and to have iNO readily available.
Removal of acute exacerbating factors (abdominal desufflation, in this case) should be swift in order to restore homeostasis. It is important to maintain adequate perfusion to the RV, and it is equally important to ensure adequate contractility so as to overcome the increased PVR. In this situation, giving small boluses of phenylephrine and ephedrine in conjunction would improve forward flow and RV perfusion while one is waiting for the vasoactive infusion to kick in.
A 62-year-old male patient with known PAH is scheduled to undergo a revision right total knee arthroplasty (TKA). He has a history of tobacco use, hypertension, and CAD, which was treated with a stent placed 6 years ago. He does not know the severity of his PH, and there are no other records in the chart. He reports that he often feels short of breath, including while walking in the morning from the parking lot; however, he attributes this to his knee and states that he has not felt chest pain since receiving his stent. He has stopped taking his aspirin but did take his metoprolol this morning. His medical history is otherwise insignificant.
The anesthesia team acknowledges the shortness of breath but attributes it to deconditioning. The decision is made to proceed with surgery. Induction and intubation are uneventful; the lower-extremity tourniquet is inflated, and surgery proceeds as normal. The procedure is lengthy, with a 1 L blood loss necessitating transfusion, and the tourniquet remains in place for slightly more than 2 hours. When the procedure is finished, the tourniquet is finally deflated.
The patient becomes tachycardic (to 108 beats/min), and end-tidal CO2 (EtCO2) increases from 38 to 48 mm Hg. The anesthesia provider starts 50% nitrous oxide to prepare for emergence and cycles the blood pressure cuff. Blood pressure is found to have declined from 118/72 mm Hg to 78/48 mm Hg. The provider gives a small bolus of phenylephrine and restarts the blood pressure cuff. Tachycardia persists, and the patient remains hypotensive (82/50 mm Hg). Noting a mild ST depression in lead II, the provider then administers 1 unit of vasopressin IV, puts the patient on 100% fraction of inspired oxygen (FiO2), and begins drawing up dilute epinephrine.
This is a disaster averted. In this patient with undiagnosed PH presenting for elective surgery, an extensive preoperative evaluation is a must. His functional symptoms raise concerns about moderate-to-severe disease. In fact, the patient’s hypotension and associated tachycardia, against the background of uncharacterized CAD, could cause a myocardial oxygen deficit and subsequent inferior-wall ischemia as seen on ECG. A right-heart catheterization would have been useful for assessing the severity of his disease, and a recent echocardiogram would have been helpful for evaluating cardiac function (especially RV function).
In many cases, TKA is done with a subarachnoid block. However, spinal anesthesia does carry a risk of profound decrease in preload/perfusion and can trigger RV failure. It is acceptable to plan for general anesthesia. However, in view of this patient’s suspected PH and known cardiac history, further invasive monitoring is warranted; at a minimum, an arterial line should be considered. If the surgery had been urgent, intraoperative echocardiography or placement of a pulmonary artery (Swan-Ganz) catheter could be considered. Additionally, it would be beneficial to have dobutamine and phenylephrine infusions available and to use milrinone early in the setting of beta blockade.
It has been shown that deflation of a tourniquet, especially after prolonged inflation, causes a small decrease in blood pressure related to the increase in venous capacitance; it also causes an increase in CO2 and acid metabolites returning into the circulation from the ischemic limb. This, in turn, can trigger a steep increase in PVR, as well as decreased RV perfusion and contractility. This state, if neglected, can quickly escalate into acute pulmonary hypertensive crisis and cardiovascular collapse. In addition, nitrous oxide has been proved to increase PVR in patients with PH and thus should be avoided in all patients with suspected or proven PH who are undergoing general anesthesia. 
Fortunately, the crisis was averted in this case, but it would have been advantageous to have had a more extensive workup and a better intraoperative monitoring strategy, as well as to have avoided intraoperative use of nitrous oxide.
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Increased prostacyclin levels/effects
Increases NO levels
Pulmonary and systemic vasodilation; risk of cyanide toxicity; tachyphylaxis
Increases NO levels
Increases cGMP and cAMP
(investigational in US)
Swapnil Khoche, MBBS, DNB, FCARCSI Assistant Clinical Professor, Department of Anesthesiology, University of California, San Diego, School of Medicine
Swapnil Khoche, MBBS, DNB, FCARCSI is a member of the following medical societies: American Society of Echocardiography
Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Northwest Anesthesia Seminars.
Darrell R Tran, MD Resident Physician, Department of Anesthesiology, University of California, San Diego, School of Medicine
Darrell R Tran, MD is a member of the following medical societies: American Society of Anesthesiologists
Disclosure: Nothing to disclose.
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Nothing to disclose.
Sheela Pai Cole, MD Clinical Associate Professor of Cardiothoracic Anesthesiology and Critical Care Medicine, Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine
Sheela Pai Cole, MD is a member of the following medical societies: American Medical Association, American Society of Anesthesiologists, American Society of Echocardiography, California Society of Anesthesiologists, International Anesthesia Research Society, Pennsylvania Society of Anesthesiologists, Society of Cardiovascular Anesthesiologists, Society of Critical Care Anesthesiologists, Society of Critical Care Medicine
Disclosure: Nothing to disclose.
Perioperative Pulmonary Hypertension
Research & References of Perioperative Pulmonary Hypertension |A&C Accounting And Tax Services