The pulmonary circulation is normally a low pressure, low resistance circulation. In patients with pulmonary arterial hypertension, altered vascular endothelial and smooth muscle function lead to a combination of vasoconstriction, localized thrombosis, and vascular growth and remodeling. These processes increase pulmonary vascular resistance, resulting in right ventricular failure, inadequate oxygenation, and ultimately death. Pulmonary hypertension markedly increases morbidity and mortality among patients undergoing surgery.1 2 3 4 5 6 Understanding the pathophysiology and etiology of pulmonary hypertension in the individual patient allows accurate risk assessment, optimization prior to surgery, and rational intraoperative and postoperative treatment.7 8 9 10 11 12
An approach to understanding the pathophysiology of an individual patient with pulmonary hypertension is derived from the equation for pulmonary vascular resistance: PVR = (PAP - LAP) x 80/CO, where PVR represents pulmonary vascular resistance (in dynes·s·cm-5), PAP represents mean pulmonary artery pressure (in mmHg), LAP represents left atrial pressure (in mmHg), and CO represents cardiac output (in L·min-1). Rearranging this equation for PAP demonstrates that PAP = LAP + (CO x PVR)/80.
Thus, the three factors that account for increased PAP are increased left atrial pressure, increased cardiac output, and increased pulmonary vascular resistance. Therapy of the perioperative patient with pulmonary hypertension should involve an assessment of the quantitative contribution of each of these three components. For example, patients with mitral stenosis who have increased PAP due solely to increased left atrial pressure have uncomplicated perioperative courses, but patients with mitral stenosis who have increased PAP due to increased PVR from pulmonary vascular modeling commonly have severe right ventricular failure after mitral valve replacement and may not succeed in weaning from cardiopulmonary bypass. Pulmonary vasodilator therapy would be inappropriate in one patient but life-saving in the other.
Similarly, patients with chronic left ventricular failure who undergo heart transplantation tend to do well perioperatively if the pulmonary hypertension is due solely to elevated left atrial pressure but may have severe right ventricular failure after transplantation if there is also a significant component of increased PVR. In patients with pulmonary arterial hypertension, analyzing whether cardiac output is maintained or is markedly decreased has significant prognostic value in assessing perioperative risk (see section on risk assessment).
The current World Health Organization classification of pulmonary hypertension involves five major categories (pulmonary arterial hypertension, pulmonary venous hypertension, pulmonary hypertension associated with disorders of the respiratory system and/or hypoxemia, chronic thrombotic and/or embolic disease, and pulmonary hypertension due to disorders directly affecting the pulmonary vasculature). For the physician who is treating a perioperative patient with pulmonary hypertension, the equation for pulmonary artery pressure can be used to review the common etiologies. Increased left atrial pressure includes left ventricular failure and valvular heart disease (particularly mitral stenosis and/or regurgitation). Increased cardiac output includes patients with congenital heart disease with cardiac shunts such as ventricular septal defects. The major categories of chronically increased PVR are pulmonary disease (parenchymal or airway), hypoxia without pulmonary disease (hypoventilation syndromes, high altitude), pulmonary arterial obstruction (thromboembolism, schistosomiasis), and idiopathic pulmonary arterial hypertension. Because of pulmonary vascular remodeling, all these etiologies of pulmonary hypertension can result in increased PVR.
In addition to these etiologies of chronic pulmonary hypertension, acute increases in PVR may result from hypoxia, hypercarbia, acidosis, increased sympathetic tone, and endogenous or exogenous pulmonary vasoconstrictors such as catecholamines, serotonin, thromboxane, and endothelin.13 Most perioperative patients with decompensated pulmonary hypertension have a combination of chronic pulmonary hypertension with an acute increase in PVR and therapy should be directed at reversing this acute PVR increase.
In the face of increased impedance to right ventricular ejection, the compensatory reserves of the right ventricle are limited. Reduction in right ventricular stroke volume and cardiac output as well as ventricular interdependence, with decreased left ventricular filling and output, occur. In the patient with pulmonary hypertension, anesthesia and surgery may produce progressive hemodynamic deterioration and death due to additional increases in PVR combined with decreases in right ventricular function. For example, patients with pulmonary hypertension undergoing cardiac surgery may fail to wean off cardiopulmonary bypass due to inadequate myocardial right ventricular protection during the ischemic period of aortic cross-clamping, increased endogenous pulmonary vasoconstrictors, and decreased endogenous pulmonary vasodilators from pulmonary endothelial injury during cardiopulmonary bypass. Thus patients with pulmonary hypertension have markedly increased perioperative morbidity and mortality.14 15 16 17 18 19 For patients with Eisenmenger syndrome undergoing cesarean section, mortality is as high as 70%.20 Patients undergoing liver transplantation with pulmonary arterial hypertension have increased mortality related to the severity of the pulmonary hypertension, with mortality rates as high as 80% when mean PAP >45 mmHg.21 Reports of successful outcomes of surgery in patients with severe pulmonary hypertension include curative procedures such as lung or heartlung transplantation, cesarean section, and relatively brief procedures with minor blood loss such as lung biopsy, cholecystectomy, femoral artery repair, and laparoscopic tubal ligation.22 23 24 25 26 27
Survival in pulmonary arterial hypertension correlates with the ability of the right ventricle to compensate for the increased PVR as assessed by cardiac output, right atrial pressure, and functional status. These factors also appear to be major predictors of perioperative risk in the surgical patient. However, perioperative risk is also highly correlated to the surgical procedure.28 Major procedures that result in the systemic inflammatory response syndrome may exacerbate pulmonary hypertension and increase the perioperative risk. Procedures with rapid blood loss may result in fatal hypotension in the patient requiring adequate venous return as compensation for increased right ventricular afterload. Finally, some procedures may pose special risks for the patient with pulmonary hypertension. For example, hip replacement surgery commonly involves pulmonary embolization of air, bone marrow, and cement during placement of the femoral component. Overall, the risk assessment requires balancing the functional reserve of the patient against the anticipated increased demands of the surgical procedure.
Progressive or acute increases in pulmonary artery pressure leading to acute right heart failure are the major complications of anesthesia and surgery. A pulmonary vasodilator trial may provide additional prognostic information and guide therapy if perioperative right ventricular failure occurs. This approach is used in the evaluation for heart transplantation and has been advocated in occasional patients with pulmonary hypertension undergoing noncardiac surgery. Because of pulmonary selectivity inhaled nitric oxide is an ideal agent for screening for pulmonary vascular reactivity. In patients at an unacceptably high risk following optimization of therapy, consideration should be given to lung or heart-lung transplantation or chronic prostacyclin treatment to decrease the pulmonary hypertension to acceptable levels.29 30
Whichever anesthetic technique is chosen, surgery and anesthesia in patients with pulmonary hypertension are associated with significant morbidity and mortality. Prior to anesthesia and surgery such patients should be evaluated with electrocardiography, chest x-ray, arterial blood gas (ABG) measurement, and echocardiography. Evidence of significant right ventricular dysfunction should prompt reevaluation of the need for surgery. All attempts to reduce PAP prior to surgery should be performed, such as the administration of oxygen, bronchodilators, antibiotics, and steroids in the patient with lung disease, and vasodilators and inotropes in the patient with cardiac disease. Reduction of PAP is more likely to succeed prior to surgery than after the induction of anesthesia. Digoxin may have beneficial short-term effect on cardiac function and sympathetic activation in pulmonary arterial hypertension.31 Patients receiving chronic therapy for pulmonary arterial hypertension should continue such therapy throughout the perioperative period. Discontinuation of continuous epoprostenol infusion (Flolan) can precipitate an acute pulmonary hypertensive crisis. Although prostacyclin inhibits platelet aggregation, excess surgical bleeding is not usually a problem. It is important to coordinate continuation of the prostacyclin infusion with the nursing staff that will care for the patient after surgery. Patients receiving chronic prostacyclin infusion should have the infusion continued throughout the perioperative period, and management of hypotension should be with additional therapy rather than with discontinuation of the prostacyclin infusion.
The anesthetic management of patients with pulmonary hypertension undergoing noncardiac surgery has received relatively little attention in the literature.32 33 34 Most discussion has been limited to obstetrical anesthesia case reports in adults and case series of repair of congenital heart defects in pediatrics. Most authors agree that the management of a specific anesthetic technique is as important as the choice of the technique. In the absence of evidencebased recommendations anesthesiologists need to focus on basic hemodynamic principles.
The anesthetic plan for the patient with pulmonary hypertension is designed to account for the underlying pathophysiology. The major abnormality is the elevated PVR, which increases right ventricular afterload, thereby increasing right ventricular work and decreasing right ventricular, and thus left ventricular, output. Based on the underlying pathophysiology, the major anesthetic considerations include:
1) Preload: Maintenance of preload (intravascular volume) at normal or increased levels is essential to maintain cardiac output in the face of increased ventricular afterload.
2) Systemic vascular resistance: In normal hemodynamic states, this is a major determinant of left ventricular afterload (and, therefore, cardiac output). In pulmonary hypertension, cardiac output is limited by right ventricular function and is, therefore, independent of systemic vascular resistance. Since systemic blood pressure is related to the product of cardiac output and systemic vascular resistance, it is important to maintain systemic vascular resistance in the normal-to-high range, because cardiac output is unable to increase when systemic vascular resistance decreases.
3) Contractility: Maintenance of normal-to-high contractility is essential to maintain cardiac output in the face of increased right ventricular afterload.
4) Heart rate and rhythm: Sinus rhythm is important for adequate filling of a hypertrophied right ventricle. Stroke volume is limited by right ventricular afterload, so bradycardia should be avoided.
5) Avoidance of myocardial ischemia: Right ventricular subendocardial ischemia due to myocardial oxygen supplydemand imbalance is common in pulmonary hypertension. Systemic hypotension and excessive increases in preload, contractility, and heart rate must be avoided.
The above five physiologic considerations for pulmonary hypertension are similar to the considerations in the patient with aortic stenosis (since both situations involve excessive ventricular afterload, specifically right ventricular afterload in pulmonary hypertension and left ventricular afterload in aortic stenosis). Although many physicians are skilled at the management of aortic stenosis, a final consideration applies only in the case of pulmonary hypertension:
6) Pulmonary vascular resistance: In pulmonary hypertension, this is the major factor governing right ventricular afterload and cardiac output. Therefore, increases in pulmonary vascular resistance must be avoided and therapy to decrease pulmonary vascular resistance may be required.
Monitoring during anesthesia must be adequate to detect the causes and complications of increased pulmonary vascular resistance. Arterial oxygen saturation should be continuously monitored by pulse oximetry. Arterial catheterization is required both for beat-to-beat blood pressure monitoring and for frequent arterial blood gas measurements. Monitoring of preload requires consideration of the altered physiology in pulmonary hypertension. In the absence of pulmonary hypertension, cardiac output is determined by left ventricular function, and the relevant preload is left ventricular filling, which is usually monitored by pulmonary artery occlusion pressure (PAOP). However, with severe pulmonary hypertension, cardiac output is limited by right ventricular function, and the relevant preload is right ventricular filling, which may correspond to right atrial or central venous pressures. Therefore in severe pulmonary hypertension, volume administration should be governed by central venous pressure rather than PAOP. However, with moderate pulmonary hypertension, cardiac output varies with both left and right ventricular performance. In these cases, the normal relationships between central venous pressure and PAOP may be altered, so that central venous pressure is no longer an indicator of left ventricular preload. Monitoring both central venous pressure and PAOP and observing the response to volume administration is the best method for accurately assessing preload in patients with pulmonary hypertension. Intraoperative volume assessment can be performed with transesophageal echocardiography, which demonstrates the filling of both ventricles.
Pulmonary artery catheterization may be valuable for perioperative management of the pulmonary hypertension patient. First, it allows measurement of both central venous pressure and PAOP and determination of preload. Second, it allows measurement of cardiac output and calculation of pulmonary and systemic vascular resistance. Third, it allows measurement of pulmonary artery pressure, which is necessary for proper management of systemic hypotension or the use of pulmonary vasodilator therapy. The measurement of mixed venous oxygen saturation allows continuous assessment of arterial oxygenation and cardiac output in patients with pulmonary hypertension. The risk of pulmonary artery catheterization in patients with pulmonary hypertension is increased because of the high mortality of associated arrhythmias, pulmonary artery rupture, and venous air embolism or thromboembolism. In addition, thermodilution cardiac output determinations may be misleading when pulmonary hypertension is associated with anatomic shunting or significant tricuspid regurgitation. If there is a left-to-right shunt, thermodilution will measure pulmonary, rather than systemic, blood flow since the cold indicator will be diluted by shunted blood. If there is a right-to-left shunt, thermodilution will measure systemic rather than pulmonary blood flow, since some of the cold indicator will pass through the shunt. Pulmonary artery catheterization is usually not indicated in patients with intracardiac shunting because of the high risk of catheter misdirection and the limited additional information over measurement of central venous pressure alone.
All types of anesthetic techniques have been successfully used in individual pulmonary hypertension patients.35 The choice of anesthetic technique is usually based on pathophysiological considerations. Since general anesthesia in pulmonary hypertension patients has significant risks, limited regional anesthesia (eg, axillary block for upper extremity surgery, ankle block for foot surgery) should be considered when appropriate. The use of neuraxial regional techniques (spinal or epidural block) with sympatholytic effects may decrease systemic vascular resistance and produce systemic hypotension when cardiac output is fixed due to pulmonary hypertension. Thus, spinal anesthesia may be contraindicated in most patients. Epidural anesthesia has been successful in selected patients,36 particularly when the magnitude of the block is limited, eg, in management of labor. Epidural anesthesia allows a slow onset of block and titration of the extent of block so that adverse hemodynamic effects may be recognized early and corrected. However, extreme caution is mandatory to avoid excessive sympatholytic effects. Thoracic epidural blockade has only minor hemodynamic effects but must be titrated slowly to avoid bradycardia. Excess sedation, which may decrease systemic vascular resistance and produce respiratory depression, should be avoided when regional anesthesia is used. Intrathecal and epidural narcotics may provide excellent pain relief postoperatively or during labor without sympathetic blockade or respiratory depression.
General anesthesia remains the method of choice for major surgery in patients with pulmonary hypertension. Several techniques of general anesthesia are possible. Potent inhalational agents may decrease systemic vascular resistance, contractility, and heart rate, thereby producing hypotension and low cardiac output. The marked reduction in contractility and the increased incidence of dysrhythmias that occur with halothane are poorly tolerated. Isoflurane, sevoflurane, and desflurane have less effect on contractility and may result in beneficial pulmonary vasodilation; however, the marked reductions in systemic vascular resistance may result in systemic hypotension. In patients with adequate functional reserve sevoflurane can be used as it is shorter-acting and more readily titratable than isoflurane and unlike desflurane does not produced tachycardia during rapid increases in concentration. Narcotic-nitrous oxide techniques maintain systemic vascular resistance, but may produce hypoxia and decreased contractility; in addition, nitrous oxide increases pulmonary resistance in patients with pulmonary hypertension.
“Balanced” anesthetic techniques may have all the above disadvantages but are frequently chosen as a means of limiting the adverse effects of a single technique. One anesthetic technique that maintains preload, systemic afterload, and contractility without increasing pulmonary vascular resistance is the high-dose narcotic-oxygen technique used in cardiac anesthesia. This appears to be the technique of choice in the patient with severe pulmonary hypertension undergoing major surgery. In addition to producing hemodynamic stability, the use of 100% oxygen may produce pulmonary vasodilation in some patients. In patients undergoing short procedures with intense stimulation such as bronchoscopy a remifentanil infusion can provide short-acting analgesia. The choice of induction agents for general anesthesia is based on similar considerations. Anesthetic induction of the patient with pulmonary hypertension is an unstable period during which patients are prone to develop systemic hypotension and cardiovascular collapse. In addition, patients with right-to-left anatomic shunting have markedly increased responses to intravenous agents and delayed response to inhalation agents. For rapid-sequence induction etomidate maintains systemic hemodynamics without affecting pulmonary resistance. In contrast, pentothal and propofol may adversely affect systemic resistance, venous return, and contractility. Although ketamine maintains systemic hemodynamics, questions have been raised about possible increases in pulmonary vascular resistance with this agent. Studies suggest that there is little or no increase in pulmonary vascular resistance when ventilation is controlled, and that any increase that may occur with ketamine will be less than the increase in systemic vascular resistance. Ketamine is therefore unlikely to produce systemic hypotension or reverse a left-to-right anatomic shunt.
Ventilatory management may markedly affect pulmonary vascular resistance. Alveolar hypoxia is a potent pulmonary vasoconstrictor and use of high inspired oxygen concentrations may result in additional pulmonary vasodilation in some patients. Hypercarbia is a potent pulmonary vasoconstrictor, and hypocarbia is a pulmonary vasodilator. Hyperventilation may decrease the pulmonary hypertensive responses to various stimuli. Pulmonary vascular resistance is dependent on functional residual capacity (FRC), such that it is increased whenever FRC is increased from its normal value. Pulmonary vascular resistance increases when lung volumes above normal FRC result in compression of small intra-alveolar vessels. Pulmonary vascular resistance also increases when lung volumes below normal FRC produce increased large-vessel resistance due to hypoxic pulmonary vasoconstriction. Ventilatory parameters may affect both FRC and peak lung volume. FRC is usually decreased during general anesthesia. This reduction in FRC can be reversed with positive end-expiratory pressure (PEEP), resulting in a decrease in pulmonary vascular resistance. However, excessive PEEP will increase FRC above optimal values, and result in an increase in pulmonary vascular resistance. The effect of tidal volume on pulmonary vascular resistance may similarly be bimodal. At low tidal volumes increased resistance occurs due to alveolar hypoxia and hypercarbia. At high tidal volumes lung volume intermittently exceeds normal FRC, resulting in compression of intra-alveolar vessels and increased pulmonary vascular resistance. Therefore, ventilation of the patient with pulmonary hypertension should use high concentrations of oxygen, moderate tidal volumes, rates sufficient to achieve hypocarbia, and low levels of PEEP (5-10 cm H2O). Highfrequency ventilation has been advocated as a means of achieving adequate gas exchange, while maintaining lung volume continuously at normal FRC.
Management of emergence from anesthesia requires maintaining hemodynamic stability and adequate alveolar ventilation. The major factor responsible for hemodynamic stability is the ratio of pulmonary to systemic vascular tone. Extubation in a deep plane of anesthesia to avoid pulmonary vasoconstriction may be complicated by decreased systemic vascular resistance, decreased contractility, and inadequate ventilation (producing hypoxemia or hypercarbia and exacerbating pulmonary hypertension). In addition, reductions in FRC can increase pulmonary vascular resistance. Extubation in a light plane of anesthesia can result in marked sympathetic tone and severe pulmonary vasoconstriction. The addition of narcotics to a primarily inhalational technique may allow extubation in a light plane of anesthesia without increasing sympathetic tone. A narcotic-oxygen anesthetic technique followed by postoperative mechanical ventilation appears to be the safest technique for major surgery.
Pulmonary hypertension patients have limited ability to tolerate any further increase in pulmonary vascular resistance and it is important to avoid introduction of air or particulate matter (eg, precipitated drugs) into the venous system. In patients with anatomic shunting, such venous embolization may result in systemic embolization, as well as provoking hemodynamic decompensation.
Pulmonary hypertension patients should have hemodynamic therapy aimed at maintaining blood pressure, cardiac output, and low pulmonary vascular resistance. When inotropic therapy is required agents such as dobutamine and milrinone, which increase cardiac output, maintain systemic blood pressure, and decrease pulmonary vascular resistance, are indicated. The management of systemic hypotension in the patient with pulmonary hypertension is based on principles of hemodynamic management. As shown in Table 1, systemic hypotension may result from four etiologies, each of which has a specific hemodynamic pattern.
Pulmonary artery catheterization allows differentiation among these etiologies. Decreased preload is the only etiology that decreases central venous pressure; volume therapy is the appropriate treatment. But volume loading of a failing right ventricle can result in further distention and progressive dysfunction and therefore must be monitored closely. Decreased contractility is the only condition that results in an increase in central venous pressure with a decrease in pulmonary artery pressure; inotropic therapy is indicated. Decreased systemic vascular resistance is the only condition in which cardiac output is maintained. Appropriate therapy may be a combination of systemic vasoconstrictors, inotropic agents, and pulmonary vasodilators. The use of vasopressin as a systemic vasoconstrictor has been recommended in some reports.37 38 A combined inotropic-vasopressor agent such as epinephrine or norepinephrine may be useful. Finally, if pulmonary artery pressure has increased or remained the same during systemic hypotension, then the elevated pulmonary vascular resistance is preventing generation of adequate cardiac output. The initial approach should be to detect any correctable causes of increased pulmonary vascular resistance such as hypoxia, hypercarbia, acidosis, increased sympathetic tone, and endogenous or exogenous vasoconstrictors. Patients without correctable factors should be considered candidates for acute pulmonary vasodilator therapy. Therefore, arterial blood gases should be measured and acid-base status corrected to baseline. When systemic hypotension occurs without a decrease in pulmonary artery pressure, cardiac output measurement will differentiate between a primary fall in systemic resistance (cardiac output increased or unchanged with no change in pulmonary vascular resistance) and worsened pulmonary hypertension (cardiac output decreased with increased pulmonary vascular resistance). A primary fall in systemic vascular resistance may be treated by either increasing cardiac output with inotropic agents or by achieving selective systemic vasoconstriction with phenylephrine, norepinephrine, or vasopressin.
When an increase in pulmonary vascular resistance produces decreased cardiac output and systemic hypotension, pulmonary vasodilator therapy is required to interrupt the cycle of pulmonary hypertension. This cycle is characterized by low cardiac output, systemic hypotension, and decreased right ventricular coronary perfusion with a further decrease in cardiac output; similarly, low cardiac output produces desaturation of mixed venous blood and acidosis, which result in increased pulmonary vasoconstriction. The goals of pulmonary vasodilator therapy are twofold: first, to reduce pulmonary vascular resistance and thereby decrease pulmonary artery pressure and/or increase cardiac output, and, second, to reduce the PVR/SVR ratio so that the increase in cardiac output will prevent hypotension by compensating for any reduction in systemic vascular resistance. Essentially all agents with systemic vasodilator activity (alpha-blockers, beta-agonists, acetylcholine, direct smooth muscle vasodilators, calcium channel blockers, prostacyclin, prostaglandin E1) are capable of producing pulmonary vasodilation. However, use of these agents as pulmonary vasodilators has frequently resulted in systemic hypotension. In pulmonary hypertension, cardiac output varies with right heart function. Both the pulmonary and systemic vasodilator effects of drugs are dose-dependent. For the majority of drugs, systemic vasodilator effects occur at doses that do not produce pulmonary vasodilation. Thus, with a decrease in systemic and no change in pulmonary vascular resistance, cardiac output cannot rise and systemic blood pressure must fall (BP = CO x SVR).
Pulmonary vasodilators include direct-acting nitro vasodilators such as hydralazine, nitroglycerin, and nitroprusside; alpha-adrenergic blockers such as tolazoline and phentolamine; beta-adrenergic agents such as isoproterenol; calcium blockers such as nifedipine and diltiazem; prostaglandins such as prostaglandin E1 and prostacyclin; adenosine; and indirect-acting vasodilators such as acetylcholine which cause nitric oxide release. The ideal pulmonary vasodilator for the perioperative setting should produce preferential pulmonary vasodilation without other direct hemodynamic effects; in addition, the drug should be short-acting when used for acute treatment. A major principle of acute vasodilator drug therapy is that short-acting titratable agents should be used and the effects should be assessed at each dose before increasing to a higher dose.
For severe perioperative pulmonary hypertension resulting in right ventricular failure inhaled vasodilator therapy is the treatment of choice. This approach was first developed with inhaled nitric oxide,39 40 41 42 which diffuses from the alveoli to the adjacent pulmonary vascular smooth muscle cells to produce pulmonary vasodilation. Inhaled nitric oxide does not produce systemic vasodilation because any nitric oxide that is absorbed into the pulmonary circulation is inactivated by binding to hemoglobin. In addition, inhaled nitric oxide may improve ventilation-perfusion matching in lung disease. Unlike intravenous vasodilators, which may increase blood flow to poorly ventilated alveoli, inhaled vasodilators are preferentially distributed to ventilated alveoli. By increasing blood flow to ventilated alveoli, there is an improvement in ventilation-perfusion matching and gas exchange. Inhaled nitric oxide effectively decreases perioperative pulmonary hypertension in multiple settings, particularly following cardiopulmonary bypass when pulmonary vascular resistance may be elevated due to pulmonary endothelial dysfunction. Inhaled nitric oxide may be useful in patients with allograft dysfunction following lung transplantation since nitric oxide may decrease pulmonary hypertension, improve ventilation-perfusion mismatch, and decrease ischemia-reperfusion lung injury. Inhaled nitric oxide improves outcome in neonatal pulmonary hypertension with hypoxic respiratory failure as judged by a decreased frequency of death or extracorporeal membrane oxygenation use. Although inhaled nitric oxide improves oxygenation and decreases pulmonary hypertension in the acute respiratory distress syndrome, randomized studies have not demonstrated sustained improvement or improved outcome. Patients with hypoxemia may not improve oxygenation with inhaled nitric oxide if the vascular tone in well-ventilated segments is not increased above basal levels. In such cases, combination of inhaled nitric oxide with almitrine bis mesylate or possibly phenylephrine may improve hypoxemia without producing excessive pulmonary hypertension.
In general, the inhaled nitric oxide dose-response curve in patients with pulmonary hypertension demonstrates maximal responses at doses of 10 ppm or less and, in the perioperative setting, a trial of 20 ppm inhaled nitric oxide is usually sufficient to determine if the patient will have a beneficial response. Discontinuation of inhaled nitric oxide may produce rebound pulmonary hypertension, which limits its utility in the perioperative setting. Rebound pulmonary hypertension may be due to progression of underlying pulmonary hypertension, decreased endogenous nitric oxide synthesis, downregulation of guanylyl cyclase, or activation of endogenous vasoconstrictor pathways such as endothelin. Approximately one third of pulmonary hypertension patients have little or no response to inhaled nitric oxide. Possible explanations include an unreactive pulmonary circulation, rapid inactivation of nitric oxide, abnormalities in the guanylyl cyclase system, or rapid metabolism of cGMP. Inhibition of cGMP phosphodiesterase with sildenafil can increase the frequency, the magnitude, and the duration of response to inhaled nitric oxide.
Other inhaled vasodilators may also produce selective pulmonary vasodilation.43 44 45 46 47 These include nitro vasodilators (nitroglycerin, nitroprusside) and prostaglandin derivatives such as prostacyclin, prostaglandin E1, and iloprost. The use of a combination of agents that affect different mechanisms of vasodilation (eg, nitric oxide, which increases cGMP and prostacyclin, which increases cAMP) may produce additive pulmonary vasodilation.48 Patients undergoing cardiac surgery who develop intractable right ventricular failure due to pulmonary hypertension may be candidates for a right ventricular assist device, either on a temporary basis until right ventricular function recovers or as a bridge to transplantation.
Although the focus in the literature has been on intraoperative management of pulmonary hypertension, most patients who die in the perioperative period do so several days after surgery. Causes of death include progressive increases in pulmonary vascular resistance, progressive decreases in myocardial function, and sudden death. Patients should therefore be monitored in an appropriate setting. Deepening of the level of sedation/anesthesia may be effective in selected patients.49 The use of epidural narcotics, limited thoracic epidural local anesthetics, continuous regional anesthesia, and non-narcotic analgesic adjuvant should be considered for pain management when appropriate.
In summary, pulmonary hypertension patients have markedly increased morbidity and mortality during anesthesia and surgery. However, management based on physiologic principles can allow the majority of patients to safely undergo required surgical procedures.