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Perioperative Management of PH:
Covering All Aspects From Risk Assessment to
Postoperative Considerations
 Ronald
G. Pearl, PhD, MD
Professor and Chair, Department of Anesthesia
Stanford University School of Medicine
Stanford, California |
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.1-6 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.7-12
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.
Perioperative Risk Assessment
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.1-6 For patients with Eisenmenger
syndrome undergoing cesarean section, mortality is as
high as 70%.14 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.5 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. 15-20
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.3
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. 1,21
Preparation of the Patient for Anesthesia and Surgery
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.22
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.
Anesthetic Management
The anesthetic management of patients with pulmonary hypertension
undergoing noncardiac surgery has received relatively
little attention in the literature.6,7,9
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.
Physiologic Considerations and Goals
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.
Perioperative Monitoring
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.
Choice of Anesthetic Technique
All types of anesthetic techniques have been successfully
used in individual pulmonary hypertension patients.7 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,2
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.
Treatment of Perioperative Hypotension
 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.23,24 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,23,25-27 which diffuses
from the alveoli to the adjacent pulmonary vascular smooth
muscle cells to produce pulmonary vasodilation. Inhaled
nitric oxidedoes 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.28-32 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.33
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.
Postoperative Management
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.12 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.
References
1 Krowka MJ, Mandell MS, Ramsay
MA, Kawut SM, Fallon MB, Manzarbeitia C, Pardo M Jr, Marotta
P, Uemoto S, Stoffel MP, Benson JT. Hepatopulmonary syndrome
and portopulmonary hypertension: a report of the multicenter
liver transplant database. Liver Transpl. 2004;10:174-82.
2 Martin JT, Tautz TJ, Antognini
JF. Safety of regional anesthesia in`Eisenmenger’s
syndrome. Reg Anesth Pain Med.2002;27:509-13.
3 Ramakrishna G, Sprung J,
Ravi BS, Chandrasekaran K, McGoon MD. Impact of pulmonary
hypertension on the outcomes of noncardiac surgery: predictors
of perioperative morbidity and mortality. J Am Coll Cardiol.
2005;45:1691-9.
4Roberts NV, Keast PJ. Pulmonary
hypertension and pregnancy—a lethal combination. Anaesth
Intensive Care. 1990;18:366-74
5 Tan HP, Markowitz JS, Montgomery
RA, Merritt WT, Klein AS, Thuluvath PJ, Poordad FF, Maley
WR, Winters B, Akinci SB, Gaine SP. Liver transplantation
in patients with severe portopulmonary hypertension treated
with preoperative chronic intravenous epoprostenol. Liver
Transpl. 2001;7:745-9.
6 Weiss BM, Atanassoff PG.
Cyanotic congenital heart disease and pregnancy: natural
selection, pulmonary hypertension, and anesthesia. J Clin
Anesth.1993;5:332-41.
7 Blaise G, Langleben D, Hubert
B. Pulmonary arterial hypertension: pathophysiology and
anesthetic approach . Anesthesiology. 2003;99: 1415-32.
8 Burrows FA, Klinck JR, Rabinovitch
M, Bohn DJ. Pulmonary hypertension in children: perioperative
management. Can Anaesth Soc J. 1986; 33:606-28.
9 Fischer LG, Van Aken H, Burkle
H. Management of pulmonary hypertension: physiological
and pharmacological considerations for anesthesiologists.
Anesth Analg. 2003;96:1603-16.
10 Kaul TK, Fields BL. Postoperative
acute refractory right ventricular failure: incidence,
pathogenesis, management and prognosis. Cardiovasc Surg.
2000;8:1-9.
11 Riedel B. The pathophysiology
and management of perioperative pulmonary hypertension
with specific emphasis on the period following cardiac
surgery. Int Anesthesiol Clin.1999;37:55-79.
12 Rodriguez RM, Pearl RG.
Pulmonary hypertension and major surgery. Anesth Analg.1998;87:812-5.
13 Via G, Braschi A. Pathophysiology
of severe pulmonary hypertension in the critically ill
patient. Minerva Anestesiol. 2004;70:233-7.
14 Kahn ML. Eisenmenger’s
syndrome in pregnancy . N Engl J Med. 1993; 329:887.
15 Armstrong P. Thoracic epidural
anaesthesia and primary pulmonary hypertension. Anaesthesia.1992;
47:496-9.
16 Hohn L, Schweizer A, Morel
DR, Spiliopoulos A, Licker M. Circulatory failure after
anesthesia induction in a patient with severe primary
pulmonary hypertension. Anesthesiology. 1999;91:1943-5.
17 Davies MJ, Beavis RE. Epidural
anaesthesia for vascular surgery in a patient with primary
pulmonary hypertension. Anaesth Intens Care. 1984;12:115-7.
18 Mallampati SR. Low thoracic
epidural anaesthesia for elective cholecystectomy in a
patient with congenital heart disease and pulmonary hypertension.
Can Anaesth Soc J. 1993;2:159-68.
19. Slomka F, Salmeron S, Zetlaoui P,
et al. Primary pulmonary hypertension and pregnancy: anesthetic
management for delivery. Anesthesiol.1988;69:959-61.
20. Stoddart P, O’Sullivan G. Eisenmenger’s
syndrome in pregnancy: a case report and review of the
literature. Int J Obstet Anaesth.1993; 2:159-68.
21. Minder S, Fischler M, Muellhaupt
B, Zalunardo MP, Jenni R, Clavien PA, Speich R. Intravenous
iloprost bridging to orthotopic liver transplantation
in portopulmonary hypertension. Eur Respir J. 2004; 24:703-7.
22. Rich S, Seidlitz M, Dodin E, Osimani
D, Judd D, Genthner D, McLaughlin V, Francis G. The short-term
effects of digoxin in patients with right ventricular
dysfunction from pulmonary hypertension. Chest. 1998;114:787-92.
23. Oz MC, Ardehali A. Collective review:
perioperative uses of inhaled nitric oxide in adults.
Heart Surg Forum.2004;7:E584-9.
24. Braun EB, Palin CA, Hogue CW. Vasopressin
during spinal anesthesia in a patient with primary pulmonary
hypertension treated with intravenous epoprostenol. Anesth
Analg.2004;99:36-7.
25. Ichinose F, Roberts JD Jr, Zapol
WM. Inhaled nitric oxide: a selective pulmonary vasodilator:
current uses and therapeutic potential. Circulation.2004;109:3106-11.
26. Kavanagh BP, Pearl RG. Inhaled nitric
oxide in anesthesia and critical care medicine . Int Anesthesiol
Clin.1995;33:181210.
27. Kawakami H, Ichinose F. Inhaled nitric
oxide in pediatric cardiac surgery. Int Anesthesiol Clin.2004;42:93-100.
28. Bildirici I, Shumway JB. Intravenous
and inhaled epoprostenol for primary pulmonary hypertension
during pregnancy and delivery. Obstet Gynecol. 2004;103:1102-5.
29. De Wet CJ, Affleck DG, Jacobsohn
E, Avidan MS, Tymkew H, Hill LL, Zanaboni PB, Moazami
N, Smith JR. Inhaled prostacyclin is safe, effective,
and affordable in patients with pulmonary hypertension,
right heart dysfunction, and refractory hypoxemia after
cardiothoracic surgery. J Thorac Cardiovasc Surg.2004;127:1058-67.
30. Fattouch K, Sbraga F, Bianco G, Speziale
G, Gucciardo M, Sampognaro R, Ruvolo G. Inhaled prostacyclin,
nitric oxide, and nitroprusside in pulmonary hypertension
after mitral valve replacement. J Card Surg.2005;20:171-6.
31. Lowson SM. Inhaled alternatives to
nitric oxide. Crit Care Med. 2005;33:S188-95.
32. Siobal M. Aerosolized prostacyclins.
Respir Care. 2004;49:640- 52.
33. Hill LL, Pearl RG. Combined inhaled
nitric oxide and inhaled prostacyclin during experimental
chronic pulmonary hypertension. J Appl Physiol. 1999;86:1160-4.
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