Anesthesia and Pulmonary Hypertension

Transcription

Progress in Cardiovascular Diseases 55 (2012) 199 – 217
www.onlinepcd.com
Anesthesia and Pulmonary Hypertension
Dana McGlothlin a,⁎, Natalia Ivascu b , Paul M. Heerdt b, c
a
Division of Cardiology, University of California San Francisco, CA
Department of Anesthesiology, Weill Cornell Medical College, New York, NY
c
Department of Pharmacology, Weill Cornell Medical College, New York, NY
b
Abstract
Anesthesia and surgery are associated with significantly increased morbidity and mortality in
patients with pulmonary hypertension due mainly to right ventricular failure, arrhythmias,
postoperative hypoxemia, and myocardial ischemia. Preoperative risk assessment and
successful management of patients with pulmonary hypertension undergoing cardiac surgery
involve an understanding of the pathophysiology of the disease, screening of patients at-risk for
pulmonary arterial hypertension, analysis of preoperative and operative risk factors, thorough
multidisciplinary planning, careful intraoperative management, and early recognition and
treatment of postoperative complications. This article will cover each of these aspects with
particular focus on the anesthetic approach for non-cardiothoracic surgeries. (Prog Cardiovasc
Dis 2012;55:199-217)
© 2012 Elsevier Inc. All rights reserved.
Keywords:
Pulmonary hypertension; Pulmonary arterial hypertension; Anesthesia; Anesthetics; General anesthesia; Surgery; Non-cardiac
surgery; Right ventricular failure; Right heart failure; Heart failure; Mechanical ventilation
Introduction
Advances in the understanding of the pathogenesis and
pathophysiology of pulmonary hypertension (PH) and the
availability of new drug therapies for pulmonary arterial
hypertension (PAH) have led to improved survival and
increased awareness of this life-threatening condition. It
has been known for many years that non-cardiac surgery,
particularly Cesarean section for parturient woman with
Eisenmenger's Syndrome (ES), has been associated with
high mortality of up to 70%. 1-3 PH is also well known to
complicate heart disease, and morbidity and mortality with
cardiac surgery in such patients are increased. 4-9 Conversely, data regarding the risk factors and outcomes of PH
patients undergoing non-cardiac surgery have been scarce,
probably because PH may have been occult or overlooked
pre-operatively, whereas the presence of PH before cardiac
Statement of Conflict of Interest: See page 215.
⁎ Address reprint requests to Dana McGlothlin, MD, Division of
Cardiology, University of California San Francisco, California.
E-mail address: [email protected] (D. McGlothlin).
0033-0620/$ – see front matter © 2012 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.pcad.2012.08.002
surgeries is often identified with routine pre-operative
testing. Data are now mounting about the risks of
anesthesia and surgery in patients with PH, and this article
will focus on the peri-operative management of patients
with PH undergoing non-cardiac surgery.
To date, there have been five retrospective studies
reporting outcomes following non-cardiac surgery in
patients with PH. Each of the studies varied in the diagnostic
methods and definitions of PH used, the causes and severity
of PH, and whether or not a control population was
included. 10-14 Perioperative morbidity occurred in 15%–
42% of patients, and included post-operative respiratory
failure (7%–28%), 10,13 heart failure (10%–13.5%), 10,11,13
hemodynamic instability (8%), 10 dysrhythmias (12%), 13
renal insufficiency (7%), 13 sepsis (7%–10%), 10,13 ischemia/myocardial infarction (4%), delayed tracheal extubation
(8%–21%), 10,11 longer ICU 10 and total hospital length of
stays, 10 and a trend towards greater 30 day readmissions
(16.7% and 7.8% in PH vs non-PH patients, respectively;
p = 0.08, OR 2.4). 10 In-hospital mortality was as low as
1% 10 in a study that included mostly patients with PH
related to left heart failure, however mortality rates in the
199
200
D. McGlothlin et al. / Progress in Cardiovascular Diseases 55 (2012) 199–217
Abbreviations and Acronyms
ADRVF = Acute
decompensated right
ventricular failure
ASA = American Society of
Anesthesiology
BIPAP = Bi-level positive
airway pressure
CAD = Coronary artery
disease
CHF = Congestive heart
failure
CI = Cardiac index
CKD = Chronic kidney
disease
CO = Cardiac output
CO2 = Carbon dioxide
COPD = Chronic obstructive
pulmonary disease
CPAP = Continuous positive
airway pressure
C-section = Cesarean section
CTEPH = Chronic
thromboembolic pulmonary
hypertension
CVP = Central venous
pressure
ECG = Electrocardiogram
ERA = Endothelin receptor
antagonist
ES = Eisenmenger's
Syndrome
FiO2 = Fraction of inspired
oxygen
FRC = Functional reserve
capacity
HFpEF = Heart failure with
preserved ejection fraction
HFrEF = Heart failure with
reduced ejection fraction
HIV = Human
immunodeficiency virus
HPV = Hypoxic pulmonary
vasoconstriction
iNO = Inhaled nitric oxide
LAP = Left atrial pressure
remaining four studies
were between 7% and
10%. 11-14 Interestingly,
perioperative mortality
with non-cardiac surgery
was the same (7%) in a
study that included only
patients with mild–moderate pre-capillary PH 12
as it was in another study
of patients with severe
PAH (Eisenmenger's
syndrome), 14 however
both studies were small.
It now seems clear that
patients with PH of any
etiology and severity, not
just the rare disease PAH,
have increased risk of
perioperative morbidity
and mortality with both
cardiac and non-cardiac
surgeries. Importantly,
however, is that the perioperative management of
patients with PH varies
drastically, depending
upon the etiology and
severity of the disease.
Successful management of the perioperative
patient with PH is complex and requires a thorough understanding of
the pathophysiology of
PH and right ventricular
(RV) function along with
multiple steps that need
to be taken, including
recognition of the disorder, especially in patients
at-risk for developing
PAH (e.g. connective tissue disease, portal hypertension, congenital heart
disease, and HIV infection), identification of the
underlying cause(s), assessment of the severity
of disease, assessment
of the risks versus benefits of anesthesia and
surgery, development of
an anesthetic plan, and
vigilant monitoring in the
critical care setting for the
LHF = Left heart failure
LV = Left ventricular
LVEDP = Left ventricular
end-diastolic pressure
MAP = Mean arterial pressure
MPAP = Mean pulmonary
artery pressure
NYHA = New York Heart
Association
MRI = Magnetic resonance
imaging
OSA = Obstructive sleep
apnea
PA = Pulmonary artery
PAH = Pulmonary arterial
hypertension
PAP = Pulmonary artery
pressure
PASP = Pulmonary artery
systolic pressure
PCWP = Pulmonary capillary
wedge pressure
PDE5I = Phosphodiesterase
type-5 inhibitors
PE = Pulmonary embolism
PEEP = Positive endexpiratory pressure
PFT = Pulmonary function
test
PH = Pulmonary hypertension
PVR = Pulmonary vascular
resistance
RAD = Right axis deviation
RAP = Right atrial pressure
RHC = Right heart
catheterization
RV = Right ventricle
RVH = Right ventricular
hypertrophy
RVMPI = Right ventricular
myocardial performance index
RVSP = Right ventricular
systolic pressure
SBP = Systolic blood pressure
SVR = Systemic vascular
resistance
early recognition and
treatment of any postoperative complications.
Understanding
pulmonary
hypertension:
definitions and
classification
PH is defined with
direct, invasive measurement via right heart catheterization as an elevated
mean pulmonary artery
pressure (MPAP) N 25
mm Hg. It is important
to understand that PH is a
disorder associated with
many potential etiologies
in which there is elevation of the pulmonary
artery pressure (PAP)
that results from an increase in: 1) resistance to
blood flow within the
pulmonary arteries (i.e.
pulmonary vascular resistance, PVR), 2) pulmonary venous pressure
from left heart disease, 3)
pulmonary blood flow or
4) a combination of these
elements.
Hemodynamic
classification of PH
In hemodynamic
terms (Table 1), PH related to increased PVR ≥
3.0 Wood units (WU)
without significant elevation of the left atrial
pressure (LAP) or its
surrogate, pulmonary
capillary wedge pressure
(PCWP) (i.e. PCWP ≤
15 mmHg), is referred
to as “pre-capillary” PH
because the location of
pressure elevation lies
proximal to the pulmonary capillary bed within
the pulmonary arteries. 15
“Post-capillary” PH (also
TAPSE = Tricuspid annular
plane excursion
known as “pulmonary
venous”, “passive”, or
“congestive” PH) is the
TEE = Transesophageal
hemodynamic profile
echocardiogram
resulting from left atrial
TPG = Transpulmonary
pressure (LAP) elevation
gradient
related to any cause of
V/Q = Ventilation/perfusion
left heart failure (LHF).
In pure post-capillary PH,
WHO = World Health
the elevated LAP is pasOrganization
sively transmitted backWU = Wood units
wards into the pulmonary
veins and arteries, leading to elevated pulmonary artery pressure (PAP), and it is
characterized by a PCWP N 15 mmHg with normal PVR
and transpulmonary gradient (TPG; TPG = MPAP −
PCWP). “Mixed” PH (i.e. mixed pre- and post-capillary),
also known as “reactive” PH, results from chronic
pulmonary venous hypertension that is nearly always related
to left heart failure (LHF) and leads to pulmonary arterial
vasoconstriction and vascular remodeling 15-20 and rise in
PVR. This type of PH is characterized by an increased
PCWP N 15 mmHg (often N 18 mmHg), PVR to ≥ 2.5–
3.0 WU and a TPG of ≥ 12–15 mmHg. In these cases, the
elevation in MPAP is out of proportion to the degree of
PCWP elevation, hence the popular term “PH out of
proportion to left heart disease” that is also often used to
describe this condition. Mixed PH may further be described
as “vasoreactive” or “fixed,” depending on the reversal of
TPG and PVR with vasodilators and diuretics (or a left
ventricular assist device). Rarely, increased pulmonary
blood flow from a systemic-to-pulmonary shunt or high
cardiac output state (e.g. anemia, sepsis, portal hypertension,
thyrotoxicosis, chronic hemodialysis for end-stage renal
disease, and some chronic myeloproliferative disorders)
leads to PH without an elevation in PCWP or PVR. 15
201
The severity of PAP elevation on the basis of the
MPAP is characterized as mild (25–40 mmHg), moderate
(41–55 mmHg), or severe (N 55 mmHg). 21 Key measures
for evaluating PH are right atrial pressure (RAP), central
venous pressure (CVP), PAP, PCWP, cardiac output (CO),
cardiac index (CI), mixed venous O2 saturation, and
pulmonary and systemic vascular resistance calculations.
The CVP and CI are very important parameters to assess
during RHC, as markedly elevated CVP and reduced CI
are indicative of right ventricular failure and poor survival
in patients with PAH. 22
WHO clinical classification of pulmonary hypertension
Table 2 outlines the updated World Health Organization (WHO) clinical classification of PH from the Dana
Point meeting in 2008. 23 It is important to note that WHO
Group 2 PH from LHF is managed very differently than
PAH and other etiologies of pre-capillary PH, and it can
easily be distinguished hemodynamically with heart
catheterization by the presence of elevated PCWP and/or
LVEDP. Thus, the measurement of left ventricular filling
pressure (PCWP and/or directly measured LVEDP)
becomes the most critical aspect of defining the nature
of PH and its treatment, and for this reason pressure
tracings during heart catheterization should be reviewed
independently by the interpreter for accuracy (endexpiratory rather than digitized mean PCWP). 24,25
Although many principles in the peri-operative management of RV failure and PH are common to any etiology
of PH, there are critical differences that should be
understood and recognized when it comes to the use of
PAH therapies. One of the most important aspects relates
to the effects of pulmonary vasodilators therapies in
certain types of PH. While pulmonary vasodilators can
have favorable responses and have been proven to be
Table 1
Hemodynamic definitions of pulmonary hypertension.
Definition
Hemodynamic Characteristics
WHO Clinical Groups 25
PH
MPAP N 25 mmHg
CO normal, reduced, or high⁎
PCWP/LVEDP ≤ 15 mmHg
TPG ≥ 12–15 mmHg
ALL
Pre-capillary PH
Post-capillary PH
Mixed PH
“Reactive” †
“Non-reactive”/“fixed” ‡
PCWP/LVEDP N 15 mmHg, PVR ≤ 3 WU
TPG b 12 mmHg
PCWP/LVEDP N 15 mmHg, PVR N 3 WU
TPG ≥ 12–15 mmHg
1. PAH
3. PH due to lung disease and/or hypoxemia
4. CTEPH
5. PH with unclear or multifactorial mechanisms
2. PH owing to LHD
2. PH owing to LHD
All values measured at rest. PH = pulmonary hypertension; MPAP = mean pulmonary artery pressure; WHO = World Health Organization; CO = cardiac
output; PCWP = pulmonary capillary wedge pressure; LVEDP = left ventricular end diastolic pressure; PVR = pulmonary vascular resistance; TPG =
transpulmonary gradient; WU = Wood Units; PAH = pulmonary arterial hypertension; CTEPH = chronic thromboembolic PH; LHD = left heart disease.
⁎ High CO can be present in cases of portal hypertension (PoPH; portopulmonary hypertension), hyperthyroidism, anemia, sepsis, systemic-topulmonary shunts (pulmonary circulation only), etc.
†
PVR and TPG reverse with vasodilators and/or normalization of PCWP/LVEDP.
‡
PVR and TPG remain elevated despite normalization of PCWP/LVEDP with vasodilators, diuretics, and/or ventricular assist devices.
202
Table 2
WHO clinical classification of pulmonary hypertension (Dana Point,
2008). 25
1. Pulmonary arterial hypertension (PAH)
1.1 Idiopathic PAH (IPAH)
1.2 Heritable
1.2.1 BMPR2
1.2.2 ALK, endoglin (with or without hereditary
hemorrhagic telangiectasia
1.2.3 Unknown
1.3 Drug and toxin induced
1.4. Associated with:
1.4.1 Connective tissue diseases
1.4.2 HIV infection
1.4.3 Portal hypertension
1.4.4 Congenital heart diseases
1.4.5 Schistosomiasis
1.4.6 Chronic hemolytic anemia
1.5. Persistent pulmonary hypertension of the newborn
1′. Pulmonary veno-occlusive disease (PVOD) and/or
pulmonary capillary hemangiomatosis (PCH)
2. Pulmonary hypertension owing to left heart disease
2.1. Systolic dysfunction
2.2. Diastolic dysfunction
2.3. Valvular disease
3. Pulmonary hypertension owing to lung diseases and/or hypoxemia
3.1. Chronic obstructive pulmonary disease
3.2. Interstitial lung disease
3.3. Other pulmonary diseases with mixed restrictive and
obstructive pattern
3.4. Sleep-disordered breathing
3.5. Alveolar hypoventilation disorders
3.6. Chronic exposure to high altitude
3.7. Developmental abnormalities
4. Chronic thromboembolic pulmonary hypertension (CTEPH)
5. Pulmonary hypertension with unclear multifactorial mechanisms
5.1. Hematologic disorders: myeloproliferative disorders, splenectomy
5.2. Systemic disorders: sarcoidosis, pulmonary Langerhans
cell histiocytosis: lymphangioleiomyomatosis,
neurofibromatosis, vasculitis
5.3. Metabolic disorders: glycogen storage disease, Gaucher
disease, thyroid disorders
5.4. Other: tumoral obstruction, fibrosing mediastinitis,
chronic renal failure on dialysis
Sarcoidosis, histiocytosis X, lymphangiomatosis, compression of
pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis)
beneficial in treating patients with PAH, they can have
deleterious consequences when used in patients with nonPAH PH. For example, pulmonary vasodilator therapies
can lead to a rise in pulmonary venous pressure and
precipitate pulmonary edema when they are administered
to patients with post-capillary PH from heart failure with
preserved ejection fraction (HFpEF) or heart failure with
reduced ejection fraction (HFrEF) (WHO Group II PH)
perhaps with the exception of phosphodiesterase type-5
inhibitors (PDE5I), which are showing some promise in
this group. 26 In addition, systemically administered
pulmonary vasodilators when given to hypoxic patients
with parenchymal lung disease can increase perfusion to
poorly ventilated lung regions and increase ventilation–
perfusion mismatching, resulting in worsened hypoxemia.
Pre-operative evaluation and management
When contemplating surgery in a patient with PH, the
perioperative evaluation should include an assessment of
risk that takes into consideration the type of surgery,
patient's functional status, severity of disease including
right ventricular function, and the patient's comorbidities.
In addition, patients without a history who are at high risk
for PH (e.g. scleroderma spectrum of diseases, obesity and
obstructive sleep apnea, and HFpEF) should be screened
for symptoms and signs of PH, particularly if they are
being considered for intermediate- or high-risk surgery.
High-risk surgical procedures include those that are
associated with the potential for rapid blood loss,
significant perioperative systemic inflammatory response
(e.g. cardiopulmonary bypass), venous air embolism,
carbon dioxide (CO2) (e.g. laparoscopic surgery), fat or
cement emboli (e.g. orthopedic surgery), and loss of
lung blood vessels (e.g. lung resection). Emergency
procedures, 11,12 ASA class ≥ 2, 10 intermediate or high
risk surgery, 11-13 longer duration of surgery and anesthesia
(N 3 h), 12,13 coronary artery disease (CAD), 11 chronic
renal insufficiency, 10 history of pulmonary embolism
(PE), 13 NYHA functional classification ≥ II, 13 and
PAP 10,11 have all been identified as independent predictors
of morbidity and/or mortality in patients with PH
undergoing non-cardiac surgery (Table 3). Additionally,
markers of RV strain, including right-axis deviation (RAD)
(p = 0.02), RV hypertrophy (RVH) (p = 0.04), RV index of
myocardial performance index (RVMPI) ≥ 0.075 (p =
0.03), RV systolic pressure/systolic blood pressure
ratio ≥ 0.66 (p = 0.01), as well as the intra-operative use
of vasopressors (p = b 0.01), were predictors of post-
Table 3
Risk factors for morbidity and mortality in non-cardiac surgery.
Patient factors
• History of PE, 13 CAD, 11 CKD 10
• NYHA/WHO FC ≥ II 13
• RAD on ECG 13
• Echo parameters: RVH, 13 RVMPI ≥ 0.75 13
• Hemodynamics: higher PAP, 10,11 RVSP/SBP ratio N 0.66 13
Operative factors
• Emergency surgery 12,13
• Intermediate or high risk operations 11–13
• Higher ASA class 11
• Longer duration of anesthesia 12,13
• Intra-operative vasopressor use 13
This table summarizes the risk factors identified from studies of patients
with pulmonary hypertension undergoing non-cardiac surgery.
PE = pulmonary embolism, CAD = coronary artery disease, CKD =
chronic kidney disease, NYHA = New York Heart Association,
WHO = World Health Organization, RAD = right axis deviation,
ECG = electrocardiogram, RVH = right ventricular hypertrophy,
RVMPI = right ventricular myocardial performance index, PAP = pulmonary artery pressure, SBP = systolic blood pressure, ASA = American
Surgical Association
operative mortality on univariate analysis in one study by
Ramakrishna et al. 13 In a study by Kaw et al., which
included 96 patients with PH and 77 patients without PH
who underwent diagnostic heart catheterization and
hemodynamic classification prior to non-cardiac surgery,
25 of 27 patients (92.5%) who had peri-operative
complications were patients with PH. The only death in
the study occurred in a patient whose MPAP was N 45 mm
Hg undergoing an intermediate-risk operation, and he/she
developed post-operative congestive heart failure (CHF). 10
Patients with pre-capillary PH had greater post-operative
morbidity (41%) compared to patients with pure pulmonary venous or mixed PH from LHF (16% and 24%,
respectively), 10 although these differences were not
statistically significant. Moreover, PA pulse pressure
(p = 0.003) and PVR (p = 0.008) were associated with
worse perioperative outcomes on univariate analysis, 10
and recent reports have suggested that assessments
of increased pulmonary vascular stiffness, decreased
pulmonary compliance, which may be measured noninvasively by cardiac output divided by pulmonary artery pulse
pressure, 27,28 relative area change on cardiac magnetic
resonance imaging (MRI) 29 may be an indicator of
poor outcomes in patients with PH. These results suggest
that patients with an increased pulmonary artery pulsatile
load are at greater risk for right ventricular pulmonary
artery mismatch. It is notable, however, that in the study
by Kaw and colleagues, the perioperative morbidity
was high even among patients with purely pulmonary
venous hypertension.
Evaluation
The pre-operative evaluation should include a thorough
history and physical examination with special attention to
signs and symptoms of right ventricular dysfunction.
While dyspnea and generalized fatigue are the most
common symptoms in patients with PAH, angina, near
syncope and syncope are symptoms of advanced PAH
disease. 30 Syncope is a particularly ominous sign that
portends a poor prognosis in PAH. 30,31 Important exam
findings to note include signs of right ventricular failure
such as elevated jugular venous pressure (prominent Vwaves are indicative of severe tricuspid regurgitation),
right ventricular S3 gallop, hepatomegaly, abdominal
swelling from ascites, and peripheral edema. Pulmonary
crackles are indicative of either left-sided heart failure or
interstitial lung disease rather than PAH.
Routine pre-operative tests include basic laboratory
studies, electrocardiography, echocardiography, chest
radiography, and consideration of right heart catheterization. If the etiology of PH has not already been established,
additional studies should be considered in order to guide
perioperative management. 32 These include pulmonary
function tests (PFT) and arterial blood gas analysis to
evaluate for respiratory disease, ventilation/perfusion (V/
203
Q) scan to exclude chronic thromboembolic PH (CTEPH),
liver function tests, serologic studies for connective tissue
disease and HIV infection to evaluate for diseases
associated with PAH, and thyroid function testing.
Transthoracic echocardiography is an essential test to
obtain pre-operatively, as it is the most useful and readily
available noninvasive tool to evaluate right ventricular
function in patients with PH. Anatomical and functional
data, including both right and left ventricular size and
function, valvular abnormalities, PAP estimate, and
intracardiac shunts can be assessed. Depending on the
severity of disease, patients with significant PH exhibit
varying degrees of right ventricular enlargement and
reduced systolic function. Intuitively, patients with
marked right heart chamber enlargement and small,
compressed left heart chambers have worse disease and
are greater perioperative risk than patients with near
normal RV size and function. Objective measures of RV
function that are useful include tricuspid plane annular
excursion (TAPSE), right ventricular fractional area
change, and the RV myocardial performance index.
Paradoxical ventricular septal flattening occurring during
systole is an indication of RV pressure overload, and it is a
common finding in patients with significant PH. However,
ventricular septal flattening during diastole indicates right
ventricular volume overload, usually from RV failure and/
or severe tricuspid regurgitation in patients with PH.
Reduced LV systolic function and left atrial enlargement
on echocardiography in patients with PH usually indicate
that the PH is likely related to pulmonary venous
hypertension. On the other hand, PH related to HFpEF
can be a challenging diagnosis to make non-invasively and
usually requires heart catheterization to assess the PCWP.
However, many patients with significant pre-capillary PH
from PAH, parenchymal lung disease, or CTEPH will
have impairment of LV filling from ventricular interaction
that manifests as Grade I LV diastolic dysfunction
(impaired LV relaxation). On the other hand, moderate
to severe LV diastolic dysfunction (i.e. pseudonormal or
restrictive diastolic filling patterns) correlates with high
left atrial pressure and strongly suggests that PH is related
to left heart failure. The PA systolic pressure (PASP) can
be estimated by using Doppler to measure the peak
tricuspid regurgitant jet velocity. However, echo-Doppler
estimates of PASP in PH patients can lead to both a
significant under- or over-estimation of the true PAP when
compared with catheterization. 33 Agitated saline contrast
not only aids in the estimation of PASP when the TR jet is
incomplete and in the diagnosis of intracardiac congenital
systemic-to-pulmonary shunts, but may also detect a
patent foramen ovale, which can lead to right-to-left
shunting in PH patients when the right atrial pressure is
elevated. Echocardiographic predictors of a poor prognosis in patients with PAH include a severe right atrial
enlargement, reduced TAPSE, higher Doppler global right
ventricular index, left ventricular (LV) eccentricity index
204
(degree of interventricular septal flattening), and the
presence of a pericardial effusion. 34-36
Pre-operative heart catheterization
In cases where the patient has greater than mild PH by
history and/or non-invasive assessment or if the patient is
being considered for an intermediate- to high-risk
operation, serious consideration should be given to
performing a right heart catheterization for hemodynamic
assessment of disease severity pre-operatively in order to
guide perioperative management. In addition, RHC should
be considered in patients who have evidence of significant
PH (eg PASP > 50 mm Hg and/or RV enlargement) and
who are at risk for both pre- and post-capillary PH, such as
those with obesity, obstructive sleep apnea, scleroderma, or
other risk factors for HFpEF (e.g. elderly, male gender,
atrial fibrillation, left atrial enlargement), since the
presence of pulmonary venous hypertension and severity
of disease will alter perioperative management, particularly
as it relates to the use of pulmonary vasodilators,
inodilators and fluid management. Left heart catheterization should also be considered in patients suspected of
having LHF, because many patients whose PCWP is not
elevated actually have elevated LVEDP when measured
directly, and they may be misclassified as having PAH. 37
Depending on the urgency of surgery, the RHC can be done
several weeks in advance so that PAH therapies in
appropriate candidates can be initiated or optimized. For
example, patients with idiopathic or associated PAH may
benefit from pre-operative RHC followed by the initiation
of intravenous prostanoid therapy if poor prognostic
findings are demonstrated (e.g. high RAP, low CI, severely
elevated PAP/PVR) prior to a higher risk surgery that can
be delayed, such as orthopedic surgery. Patients with
severe pulmonary venous hypertension may be optimized
with appropriate diuresis, systemic vasodilators, and
inodilators. In some cases, based mainly upon discussions
between the PH specialist and anesthesiologist, a RHC may
be done on the day of surgery with plans to defer surgery if
severe hemodynamics are found versus retain the PA
catheter to guide intra-operative management or remove
the PA line if the hemodynamics are reassuring.
Acute vasoreactivity testing is routinely performed
during the diagnostic right heart catheterization in patients
with PAH in order to identify “vasoresponders” who are
candidates for calcium channel blocker monotherapy. 38,39
Pre-operative vasoreactivity testing may also be useful for
perioperative planning in order to determine the degree of
vasoreactivity and to predict the perioperative effectiveness of vasodilators such as inhaled nitric oxide. If the
PVR does not decrease at all during testing, the pulmonary
vascular disease is largely fixed/non-responsive and limits
our perioperative interventions. Inhaled nitric oxide (iNO)
is the preferred agent for acute vasodilator testing, but
adenosine, epoprostenol, and inhaled iloprost can also be
used. The efficacy of iNO depends on the baseline PVR
and vasoreactivity, with greater response in patients with
higher PVR, greater degree of vascular reactivity and
worse RV function. 40-42 Responsiveness to iNO may also
reflect improved V/Q mismatch and improvement in
hypoxic pulmonary vasoconstriction (HPV) in patients
with parenchymal lung disease and a component of
hypoxic PH (e.g., interstitial lung disease that is prevalent
in the scleroderma patient population).
Dyspnea at rest, syncope, hemodynamic findings of
severe RV failure (low CI, high RAP N 15 mmHg),
metabolic acidosis, and marked hypoxemia are all signs of
advanced, unstable disease and serious consideration should
be given to cancelling or postponing the surgery until/unless
improvement and stabilization can be achieved.
Pre-operative hemodynamic optimization
All attempts to lower PVR and improve RV function
should be done prior to surgery, including maximizing
medical therapy for PAH and heart failure, and preventing
conditions that may cause acute deterioration. Examples
include the initiation or augmentation of PAH specific
therapies for patients with WHO Group I PH; administration
of oxygen, bronchodilators, antibiotics, and steroids for
patients with chronic obstructive pulmonary disease
(COPD); use of BIPAP for patients with obstructive sleep
apnea (OSA) and, diuretics, systemic vasodilators and other
appropriate HF therapies for patients with WHO Group II
PH. As a guide for management, Table 4 outlines the
hemodynamic goals, which should be strived for throughout
the perioperative period. If a patient has newly identified PH
and the surgery cannot be delayed in order to establish the
etiology and best treatment, a PDE5I such as sildenafil 20–
40 mg three times daily, can be started pre-operatively as it
has acute vasodilatory effects, right ventricular inotropy and
has been safely administered to a broad spectrum of PH
disease etiologies, although this has not been studied
specifically for most non-PAH PH etiologies.
Table 4
Perioperative hemodynamic goals.
• MAP ≥ 55 to 60 mmHg
• SBP ≥ 80 mmHg
• SvO2 saturation 92% to 100%
• RAP b 10 mmHg
• MPAP b 35 mmHg
• PVR/SVR ratio b 0.5 (if possible)
• PCWP 8 to 12 mmHg
• CI ≥ 2.2 L/min/m 2
This table summarizes optimal perioperative hemodynamic conditions.
Not all of these hemodynamics are achievable in patients with pulmonary
hypertension, however they represent goals for the medical management
of patients during the perioperative period.
MAP = mean arterial pressure, SBP = systolic blood pressure, SvO2 =
systemic venous oxygen saturation, RAP = right atrial pressure, MPAP =
mean pulmonary arterial pressure, PVR = pulmonary vascular resistance;
SVR = systemic vascular resistance, PCWP = pulmonary capillary wedge
pressure, CI = cardiac index.
205
Fig 1. Representative Hemodynamic Tracings During Positive Pressure Ventilation and Changes in Positive End Expiratory Pressure Representative
tracings of right (RV) and left (LV) ventricular pressures along with RV volume and aortic blood flow during positive pressure ventilation and variations in
positive end-expiratory pressure (PEEP) in a an experimental animal (dog). Marked respiratory variation in RV volume and aortic flow is evident,
particularly with increased levels of PEEP.
Multidisciplinary planning for surgery
Owing to the complexity of most PH treatment
protocols, pre-operative coordination among the patient's
care team is vital and can take considerable time. The
perioperative management of PH patients frequently
involves a multidisciplinary team approach that includes
physician subspecialists such as anesthesiologists, cardiologists, and pulmonary/critical care physicians, in addition to allied healthcare team members (nurses, respiratory
therapists, and pharmacists). For all except the lowest risk
PH patients and procedures, one of the most critical aspects
of the pre-operative planning involves the identification of
a highly qualified anesthesiologist with experience in
managing patients with PAH, complex hemodynamics,
and transesophageal echocardiography (TEE), such as a
cardiovascular or critical care anesthesiologist. Generally
speaking, patients with PH, particularly those with PAH,
should be referred to a tertiary care center for procedures
requiring anesthesia. Moreover, in patients with severe PH,
RV failure, and chronic hypoxemia requiring moderate or
deep sedation for procedures (e.g. endoscopy, TEE, teeth
extraction), consideration should be given to having the
procedure done with an experienced anesthesiologist
present. Also extremely important is the post-operative
“hand-off” from the intra-operative team (surgeon and
anesthesiologist) to the post-operative team (usually the
critical care physician and PH specialist).
Chronic PAH therapies, including PDE5I, endothelin
receptor antagonists (ERA), and prostanoids, should be
continued throughout the perioperative period. Patients on
chronic inhaled prostacyclin analogues should receive
treatment before surgery, and if they are unable to continue
inhaled therapy after surgery (e.g. intubated), consideration should be given to the administration of iNO,
intermittent nebulized prostacyclin, continuously inhaled
Flolan, versus intravenous prostanoids. Although prostanoids cause platelet inhibition, their use does not cause
significant bleeding complications with surgery. Coumadin should be discontinued before the procedure without
the need for bridging with heparin unless there is another
indication (e.g. history of PE, hypercoagulable state,
mechanical heart valve, etc.). Patients should receive
prophylactic anticoagulation perioperatively to prevent
deep vein thrombosis and pulmonary thromboembolism.
Intra-operative management
General principles: RV–PA mechanical coupling
As with both pre- and post-operative management, the
primary intra-operative goal for patients suffering from PH is
to maintain optimal mechanical matching between the RV
and pulmonary circulation. Ultimately, this requires an
understanding of intra-operative events that can affect RV
afterload, inotropy, and oxygen supply/demand relationships.
RV afterload
It is conceptually clear that chronic PH opposes
ejection from the RV leading to chamber dilation,
hypertrophy, increased wall stress, and reduced ejection
fraction. Less apparent, however, is the fact that a variety
of common intra-operative events can acutely alter both
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the magnitude and nature of this load. For example, the
seemingly simple transition from spontaneous respiration
to positive pressure mechanical ventilation produces
cyclic changes in RV afterload that affect volume and
pressure (Fig 1). This effect can be amplified by patient
position (Trendelenburg, prone), the addition of positive
end-expiratory pressure (PEEP), and surgical manipulations such as pneumoperitoneum (see below). Ultimately,
ventilatory changes in afterload can have clear effects on
RV preload, stroke volume and ejection fraction (Fig 1).
The relationship between lung volume and PVR during
mechanical ventilation is U-shaped with PVR being
minimal at functional residual capacity and increased at
both large and small lung volumes. At low lung volumes,
alveolar hypoxia and hypercarbia cause HPV whereas
hyperinflation of the lungs leads to compression of the
intra-alveolar vessels with marked increases in PVR. 43
Likewise, PEEP N 15 mm Hg increases PVR. In addition
to the acute pulmonary vascular effects of hypoxia and/or
hypercarbia, patients can also be subjected to venous
emboli arising from air, thrombi, or particulate matter
forced into the circulation (particularly during orthopedic
surgery) intra-operatively. 44 Finally, surgical procedures
involving the lung can have direct effects on both the
pulmonary circulation and myocardial contractile reserve
that persist postoperatively. 45
It is important to appreciate that while RV afterload is
often summarized as PVR, this steady-state variable (i.e.,
defined by mean pressure and mean flow) is largely
dictated by small vessels and may not adequately
incorporate the added pulsatile load presented to the RV
by anesthetics or intraoperative manipulation of large
elastic vessels. 46,47 Furthermore, intra-operative events
such as positive pressure ventilation, position, or surgical
techniques may augment the underlying impact of
vasoconstriction and vascular remodeling on pressure
and flow wave reflection, thus imposing a greater reflective
component to RV afterload as well. For example, as shown
in Fig 2, while compressing the left branch of the PA – as
may be done during surgery in the chest– has only a modest
acute effect on the absolute value for maximal RV pressure,
it does produce a distinct qualitative change in the RV
pressure waveform, indicative of changes in load not
summarized by PVR. While the highest pressure is attained
early in systole at baseline, during left PA compression the
highest pressure is late in systole suggesting the enhanced
contribution of reflected waves (“late phase load”).
Consistent with a predominant effect on large vessels,
there is a relatively greater increase in characteristic
impedance (Zc), an index of large vessel pulsatile load,
than PVR. However, also evident in Fig 2 is the fact that
simultaneously measured PA pressure does not as clearly
reflect the qualitative shift to a late-phase load evident in
the RV pressure waveform. The potential clinical implication of this observation is that when a PA catheter
positioned more distally in the circulation is used to
monitor pressure intra-operatively, its ability to appreciate
acute qualitative changes in RV pressure that reflect more
than just alterations in PVR may be dampened or lost.
RV inotropy
Two main aspects of intra-operative care can affect
myocardial contractile performance via both direct and
Fig 2. Right Ventricular and Pulmonary Arterial Pressures Before and During Compression of the Left Pulmonary Artery. Top panel. Right ventricular
(RV) and pulmonary arterial (PA) pressures before and after compression of the left PA in an experimental animal (swine). Changes in both the amplitude
and morphology of the pressure waveforms are evident along with calculated changes in pulmonary vascular resistance (PVR) and characteristic impedance
(Zc). Bottom panel. Changes in the RV pressure-–volume relationship produced by compression of the left PA are depicted.
indirect mechanisms: 1) depression by anesthetics and 2)
acute changes in sympathetic/parasympathetic tone.
Anesthetic-induced myocardial depression
Many of the drugs used both for induction and
maintenance of anesthesia have well-described direct
effects on inotropy. 48,49 In general, anesthetic drugs
have been found to directly affect either calcium cycling
by the myocyte, or the sensitivity of contractile proteins to
the amount of calcium released into the cytoplasm during
systole. In addition, anesthetics tend to have depressive
effects on the autonomic nervous system that can
indirectly influence contractility. The direct negative
inotropic effects of inhaled anesthetics in particular are
dose related, and potency for this response varies among
different drugs; halothane – now rarely used – produces
the greatest effect. To date, the literature focuses primarily
on the effects of anesthetic drugs on the LV and suggests
that the overall hemodynamic impact of decreased
contractility is offset to some degree by a simultaneous
decline in afterload. However, studies evaluating the
effects of inhaled anesthetics such as isoflurane, sevoflurane, and desflurane on the RV have provided a
different picture. 46,50,51 For example, as shown in Fig 3,
207
while isoflurane has similar potency for depressing
contractility in both ventricles, it has disparate effects on
afterload, particularly when pulsatile components are
assessed. Ultimately this produces different dose-dependent effects on the total work each ventricle has to perform
in order to move blood into the circulation. Complicating
things further are data showing regional differences in the
negative inotropic effects of volatile anesthetics on the
RV, i.e. greater relative depression of the outflow than
inflow tract. 51,52
Experimental data also indicate that two commonly used
intravenous anesthetics, propofol and etomidate, can have
direct depressive effects on myocardial contractility, albeit at
relatively high concentrations. 48,53 The clinical significance
of these observations remain somewhat controversial,
particularly as they apply to patients with PH. 54 Alternatively, concerns have been raised about the use of ketamine,
not because of negative inotropic effects (direct effects are
modest), but due to the possibility of sympathetic
stimulation and pulmonary vasoconstriction. 54 However,
there are clinical data to suggest that when ventilation is
maintained to prevent hypercarbia and optimize acid–base
balance, this effect is negated, 55 and that ketamine may, in
fact, have pulmonary vasodilating properties. 56
Fig 3. The Comparative Dose-related Effects of Isoflurane on Biventricular Function. 50 Preload recruitable stroke work (PRSW) was used as an index of
contractility, and steady-state (frequency independent) and characteristic impedance (frequency dependent) regarded as indices of afterload. The disparity
of effects on each ventricle is evident, with there ultimately being a marked difference in relationship between total chamber work (WT) and cardiac output
(CO). (Data adapted from Price et al. 12).
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Sympatho-vagal balance
Neuraxial anesthesia (spinal, epidural) has been safely
used in patients with PH and may have advantages in some
populations, (i.e. obstetrics). Nonetheless, autonomic
nervous fibers are more sensitive to blockade by local
anesthetics than sensory or motor fibers, and there is
always the possibility that the level of autonomic blockade
could include cardiac innervation arising from the upper
thoracic portion of the spinal cord. 57 At the same time,
since cardiac parasympathetic innervation originates in the
cranial region, function of these fibers can remain intact.
Ultimately, an acute shift in sympatho-vagal balance can
occur. While relatively well tolerated in normal patients,
the consequences may be more profound in those
dependent upon high sympathetic tone for inotropic and/
or chronotropic augmentation. 57
Acute changes in myocardial oxygen supply/demand
Relative to the RV stresses imposed by everyday life
(i.e., exercise, fever), perhaps the most unique challenge
encountered intra-operatively is the combination of
increased RV afterload and transient systemic hypotension. Between the direct cardiovascular effects of
anesthetic drugs, the indirect impact of withdrawing
sympathetic tone, effects of mechanical ventilation, and
intraoperative manipulation of the heart and/or great
vessels, periods of transient hypotension are common
during anesthesia and surgery. While these effects are
generally treated rapidly and have less global impact on
the LV – where vasodilation and myocardial depression
tend to decrease mechanical work and oxygen consumption – similar unloading is not as prominent for the RV;
most anesthetic drugs produce less pulmonary than
systemic vasodilation, and as noted above, the imposition
of positive pressure ventilation tends to augment afterload
during the ventilatory cycle. Changes in coronary
perfusion patterns in the setting of PH and RV
hypertrophy 58 and the propensity for RV ischemia even
in the absence of significant coronary disease 59 have been
well described. Of particular note is the transition to
greater dependence upon diastolic coronary flow as RV
pressures and systolic wall tension rise. It is in this context
of increased load and altered coronary perfusion patterns
that systemic arterial hypotension may have greater impact
on the RV than LV in the setting of PH.
Fundamentals of anesthetic management
There are obviously a variety of anesthetic techniques
available — local, conscious sedation, regional (i.e.,
axillary block for surgery in the upper extremity),
neuraxial (spinal, epidural), general. The decision of
which one to use is dictated by a combination of the
planned surgery, patient preference, and comorbidities.
For the PH patient, there is the added dimension of a low
tolerance for any degree of hypoxia and/or hypercarbia,
which can complicate conscious sedation, and the
possibility of intra-operative events that may acutely
worsen PH and disrupt what was a compensated state at
baseline. For example, while many orthopedic procedures
are amenable to neuraxial anesthesia, during surgery such
as hip replacement there is substantial risk of intraoperative pulmonary emboli that can potentially precipitate instability and necessitate emergent tracheal intubation under suboptimal conditions. As such, a controlled
general anesthetic with careful airway management and
elective tracheal intubation is often preferred. Similarly,
for patients with PH secondary to chronic hypoxia from
intrinsic lung disease, obesity, or obstructive sleep apnea,
careful consideration of a technique that optimizes airway
patency and gas exchange is essential.
Regardless of technique, there are fundamental components of any anesthetic that must be considered in the
patient with PH:
Basic preparation
For all PH patients, intravenous lines and syringes must
be meticulously de-aired. The hypertensive pulmonary
circulation is particularly sensitive to even small amounts
of air that would generally be tolerated in a normal
patient. 54 In addition, patients with a patent foramen ovale
are at risk for passage of air into the systemic arterial
circulation as right atrial pressure may exceed that in the
left atrium. Forced air-warming blankets, heat and moisture
exchangers in the breathing circuit, and warmed IV fluids
are all helpful in preventing hypothermia, which can inhibit
physiologic HPV and lead to V/Q mismatching.
Airway management and ventilation
Whether administered by nasal cannula, face mask,
laryngeal mask airway, or an endotracheal tube, all
anesthetics should include supplemental oxygen. In
addition to preventing hypoxemia, oxygen acts as a direct
pulmonary vasodilator, 60 and is frequently administered in
high concentration. When using anesthetic techniques
other than general, it is extremely important to assure
airway patency and easy access to the airway should
ventilation become compromised in any way. For general
anesthesia, the initial induction represents a period of
vulnerability since ventilation can become uncontrolled,
and there is the potential for intense sympathetic
stimulation if laryngoscopy is performed prior to achieving
a deep level of anesthesia. As such, application of 100%
oxygen by mask to fill the lung functional reserve capacity
(FRC) prior to induction of anesthesia, and careful
attention to anesthetic depth prior to laryngoscopy and
tracheal intubation are especially important in patients with
PH. An additional challenge is presented by the PH patient
with obstructive sleep apnea or intrinsic lung disease with
low FRC and diffusing capacity. In these situations, the
airway must be very carefully evaluated pre-operatively,
and the risks of sympathetic stimulation from “awake
Table 5
Perioperative ventilatory conditions to avoid and promote.
Avoid pulmonary vasoconstrictors:
• Hypoxemia
• Inspiratory pressure N 30 mm Hg
• High PEEP (N 15 mmHg)
• Hypercapnia
• Acidosis
Promote pulmonary vasodilation:
• Improve oxygenation (e.g. FiO2 1.0)
• Permissive hypocapnia (pCO2 ≤ 30–35 mmHg)
• Alkalosis (pH N 7.4)
• Optimal ventilatory volume
This table summarizes the conditions to avoid or promote during
mechanical ventilation in patients with pulmonary hypertension.
PEEP = positive end-expiratory pressure, FiO2 = fraction of inspired oxygen.
intubation” with fiberoptic bronchoscopy balanced against
the benefit of avoiding a period of poor ventilation and
possible hypoxia-induced pulmonary vasoconstriction.
After the airway is secured, ventilator management of
the patient with PH should entail the use of higher FiO2,
hyperventilation when necessary to achieve a PaCO2 of 30
to 35 mmHg or less, PEEP b 15 mmHg (preferably
between 5 and 10 cm H2 O), and maintenance of lung
volumes at normal functional residual capacity. 43,60,61
Table 5 outlines the perioperative ventilatory conditions to
avoid and promote. 54
Monitoring
Invasive arterial pressure monitoring is indicated for most
procedures to allow for rapid hemodynamic control and
blood sampling for gas analysis. While standard end-tidal
CO2 analysis is useful as a trend, it is not an accurate
reflection of PaCO2 in patients with increased dead space
ventilation. As such, arterial blood gas sampling can be
beneficial for assuring adequate ventilation and normocarbia.
Pulmonary artery catheters are not generally indicated
for low-risk procedures as the risks probably outweigh the
benefits. However, as noted below, even seemingly simple
minimally invasive procedures can impose acute intraoperative challenges to the RV, and these need to be
considered when planning intra-operative monitoring and
possible pharmacotherapy. An introducer catheter for
central venous access may be placed at the start of a
procedure so that CVP can be monitored and a PA catheter
subsequently added intra-operatively, if needed. This also
allows for venous blood sampling to assess oxygen
saturation as an index of cardiac output adequacy. In
cases where significant blood loss or changes in RV
afterload are anticipated, PA catheter insertion prior to
beginning the procedure may be helpful in guiding perioperative fluid and vasomodulating therapies. 62 During
the intra-operative period, maintenance of euvolemia is
particularly challenging because intravascular volume is
constantly in flux due to the combination of blood loss and
209
evaporation from the skin, breathing circuit, and surgical
field (especially in open abdominal surgery). PA catheters
with the ability to monitor continuous mixed venous
saturation offer real-time assessment of oxygen extraction
and global cardiac performance as well as monitoring
trends. However, thermodilution measurement of cardiac
output based either upon cold bolus injection via a PA
catheter or continuous “reverse” heat pulses from a coil
may have questionable utility in the setting of RV dilation,
due to concurrent tricuspid regurgitation. 63 Accuracy of
newer devices based upon arterial pulse contour analysis
in PH patients remains unclear, but has been questioned. 64
A more accurate measurement may be obtained by the
Fick method, but this technique is relatively slow and
tedious, and provides only a snapshot that may not be of
great value in guiding acute therapy intra-operatively.
Recent studies suggest that a new “Bioreactance” method
for continuously measuring cardiac output non-invasively
in ambulatory patients with PH provides data that are
remarkably similar to intermittent Fick measurements. 65
However, intraoperative accuracy of this device in PH
patients remains to be determined.
An adjunct or alternative to intraoperative PA catheter
monitoring is transesophageal echocardiography (TEE). 66
While routine use is not clearly indicated, in cases
involving significant blood loss and rapid intravenous
fluid administration, TEE can be helpful in evaluating
right heart size and function, as well as stroke volume. In
the setting of systemic hypotension, the combination of
TEE and CVP can rapidly distinguish between hypovolemia and right heart failure. In addition, acute changes in
systolic PA pressure can be estimated when a jet of
tricuspid regurgitation is present, and estimation of the
mean PA pressure has also been described. 67,68 Finally,
continuous qualitative evaluation of biventricular function
and ventricular interdependence can best be assessed with
TEE during times of intra-operative stress.
Hemodynamics
During anesthesia and surgery, pharmacological maintenance of systemic and coronary artery perfusion pressure
is often needed to compensate for anesthetic or procedureinduced hypotension. The challenge of evaluating and
maintaining euvolemia was previously discussed. Apart
from hypovolemia, management of hypotension in PH
patients should be primarily directed toward vasopressor
therapy rather than downward titration of any IV
pulmonary vasodilator the patient may be receiving. As
noted above, chronic PH leads to remodeling of the right
heart and changes in the pattern of coronary perfusion,
making it particularly prone to ischemia in the setting of
systemic hypotension. In general, the vasoconstrictors
phenylephrine and vasopressin can restore adequate aortic
root pressure without marked increases in PVR. Vasopressin in particular has been noted in experimental
models to bind to peripheral V1 receptors and cause
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Special Intra-operative Case Considerations
Orthopedics
Debilitating arthritis and trauma are common indications for orthopedic surgery in all patients including those
with PH. Peripheral nerve blocks can provide excellent
anesthesia for surgery on the feet and upper extremities,
without the hemodynamic complexities of general anesthesia. Conscious sedation is usually used to augment
patient comfort during surgery, but as noted above,
particular attention must be paid to insure adequate
ventilation during sedation since even mild hypercapnia
and hypoxia can lead to significant increases in PVR. 72The highest risk orthopedic procedures for PH patients
include hip and knee joint replacements, and hip fracture
repairs. Joint replacements in the setting of PH of all
etiologies carry a very high morbidity and mortality. 44
Accordingly, the risks and benefits of this essentially
elective surgery must be carefully weighed. In contrast,
hip surgery in the setting of fracture is an urgent procedure
with few acceptable alternatives.
Although pre-operative discussion prior to these procedures is often focused upon the type of anesthesia
(regional versus general anesthesia), the greater risk is
actually related to surgical technique. In addition to
common risks such as bleeding, hip or knee replacement
surgery carry the added potential for pulmonary emboli due
to preparation of the femoral canal for prosthesis insertion.
The initial process of reaming the bone results in extremely
high intramedullary pressures that transfer bone fragments,
marrow, fat, air and inflammatory mediators into the
circulation. 73,74 In addition, the surgeon may elect to use
bone cement to fix the prosthesis in place. During
cementing, an exothermic reaction occurs in the compound
causing it to expend in the intramedullary space; pressures
as high as 5000 mmHg have been measured in cadaveric
studies, 75 increasing the potential for air and/or other
medullary components to enter the circulation and create
potentially lethal pulmonary emboli. Consistent with this
prospect, intra-operative echocardiography studies indicate that cementing leads to a larger embolic load than uncemented arthroplasty, 73 with emboli as large as 5 cm
reported. 76 Embolic loads have also been described during
final reduction of the hip joint. Ultimately these embolic
“showers” can lead to acute changes in RV afterload not
only by physical effects on the pulmonary circulation, but
also by release of pro-inflammatory mediators that may
further increase PVR. 73 Hypotension should be quickly
treated with vasoconstrictors. Preemptive inotropic support
can be considered in patients with severely compromised
right heart function in anticipation of an embolic load.
Dobutamine may be a preferable inotropic choice since it
causes less systemic vasodilation than milrinone. 77
In addition to the general practices just described,
certain surgical procedures present additional challenges
for PH patients. The following is a brief overview of the
perioperative implications of such procedures.
Laparoscopy
Some “minimally invasive” surgical procedures
designed to be less stressful may, in fact, present
significant physiological challenges to the PH patient.
systemic vasoconstriction while stimulating nitric oxide
release and vasodilation in the pulmonary circulation, 69
thus lowering the pulmonary to systemic vascular
resistance (PVR/SVR) ratio. For patients with frank RV
dysfunction, vasopressor agents with inotropic properties
(e.g. norepinephrine or epinephrine) are generally preferred. RV afterload reduction using pulmonary dilator
therapy can also be helpful to improve RV function. While
systemically administered vasodilators such as IV prostanoids, sodium nitroprusside, and nitroglycerin reduce
PVR (the former being most appropriate in PAH patients
and the latter two reserved for patients with left heart
failure), systemic effects limit their use in patients
receiving anesthesia. Inhaled prostanoids and nitric oxide
are more suitable for use in the operating room because of
their pulmonary selectivity. 70,71 iNO is rapidly inactivated
by hemoglobin and has no systemic effects. It has the
added potential benefit of increasing PaO2 by reaching
well-ventilated regions of the lung and improving
ventilation–perfusion matching, which can be beneficial
not only in PAH patients but also in patients with
parenchymal lung disease. Although there are reports of
inhaled prostanoids and iNO being used successfully to
reduce PVR in patients with left ventricular dysfunction,
they should generally be used with caution in such patients
because of the risk of precipitating pulmonary edema.
The immediate post-operative period
For patients that have undergone a general anesthetic,
the risks and benefits of extubation in the operating room
must be considered on a case-by-case basis. After a
lengthy procedure requiring a large volume of intravenous
fluid or in the presence of any indication of right heart
failure, it is advisable to delay extubation until effective
diuresis can occur. Post-operatively, PH patients require a
well-planned pain management strategy to minimize
sympathetic activation and increases in PVR and immediate post-operative monitoring in an intensive care unit.
Epidural analgesia, peripheral nerve blocks, and nonopiate pain medications are useful post-operative pain
management strategies. In addition to pain, immediate
post-operative care should include close attention to body
temperature since hypothermia and shivering can acutely
increase PVR. Patients with OSA should have their home
positive pressure airway device readily available in the
post-anesthesia care unit. While recovering from general
anesthesia, OSA patients may benefit from augmentation
of their minute ventilation with CPAP or BIPAP. Arterial
blood pressure and PA catheter monitoring can be very
useful to follow acute hemodynamic changes.
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Fig 4. The Hemodynamic Effects of Pneumoperitoneum. The representative effect of inducing pneumoperitoneum on pulmonary arterial (PA) pressure,
diameter, flow, pulse wave velocity (PWV), and characteristic impedance (Zc). The data indicate an acute increase in right ventricular afterload in terms of
effects on both pulmonary vascular resistance (PVR, primary determined by small vessels) and Zc (primarily determined by large vessels). In addition, the
increase in PWV suggests that pressure waves will be reflected from the distal pulmonary circulation more rapidly potentially contributing to increased afterload.
Laparoscopy has become widely used for a variety of
abdominal procedures, and is clearly beneficial in terms of
post-operative pain and recovery time. Less well appreciated, however, is the fact that laparoscopy – which
involves pressurized distension of the abdomen with
carbon dioxide, diaphragmatic displacement, increased
inspiratory pressures, mesenteric and aortic compression,
and often hypercarbia – can have substantial acute impact
on biventricular load and pump function. 78 For the RV in
particular, the combination of pneumoperitoneum and the
increased inspiratory pressure required for mechanical
ventilation and prevention of atelectasis has marked
effects on both the magnitude and character of RV
afterload. As shown in Fig 4, with the increasing airway
pressures associated with pneumoperitoneum, there is not
only a progressive rise in PA pressure, but a compression
of the PA that results in decreased diameter, increased
pulse wave velocity, and rapid augmentation of pulsatile
components of RV afterload.
Clinical data based upon PA catheter measurements have
indicated that even in otherwise healthy individuals,
laparoscopy can have marked effects on cardiac output,
particularly when the patient is in the “head up” position, 79
and that these effects can lead to compromised hemodynamics in patients with pre-existing cardiac disease. 80 Not
surprisingly, the acute hemodynamic consequences of
laparoscopy in patients with PH are less well described. 81,82
Clinical data also indicate that the increases in PA pressure
induced by laparoscopy may not be immediately reversed
when the pneumoperitoneum is relieved. 83 In that the
abdomen is distended with pressurized CO2, it is
relatively common for there to be a degree of subcutaneous emphysema — and hypercarbia as this CO2 is
absorbed — in the immediate post-operative period. The
persistent increase in PA pressure, probably from
pulmonary vasoconstriction, has been linked to this
hypercarbia, and while seemingly well tolerated in normal
subjects, may have deleterious effects in patients with PH
and poorly compensated RV function.
It is important to appreciate that not all procedures
involving laparoscopy present the same physiological
perturbations. For example, robotic-assisted procedures in
the lower abdomen, used in particular for pelvic surgery
such as radical prostatectomy or hysterectomy, can have
different hemodynamic implications than upper abdominal
procedures (i.e., cholecystectomy), largely due to patient
position. Commonly, extreme Trendelenburg positioning
(up to 45°) will be maintained for several hours, further
augmenting the impact of pneumoperitoneum on inspiratory pressure, pulmonary compliance, and RV afterload. In
a study of otherwise healthy patients, invasive monitoring
revealed that right and left heart filling pressures were
increased 2–3 fold. 83 PH (defined as a PASP N 35 mmHg)
was present in 75% of these normal patients. In this
population, both right and left heart pressures proportionally increased, as did the mean arterial pressure. The CO
was unchanged. Even moderate (30°) head down position
led to a 50% increase in CVP. Right ventricular stroke
work index increased 65%, although echocardiography
indicated that there were no signs of right ventricular
pressure overload in this healthy population. 84 This
technique has not been carefully studied in patients with
PH, but it is expected that steep positioning in roboticassisted laparoscopy would be poorly tolerated.
Thoracic surgery
Another minimally invasive surgical technique associated with acute challenges to mechanical coupling between
the RV and pulmonary circulation is thoracoscopy for lung
biopsy or resection. While the long-term benefits of
thoracoscopy are becoming increasingly clear, particularly
in elderly subjects or those with significant co-morbidities, 85
the short-term stresses on the RV can be profound. Although
thoracoscopy does not involve a sustained pressurization of
the chest similar to that produced in the abdomen during
laparoscopy, it does require non-ventilation and prolonged
atelectasis of the operative lung. There are two features of
this intentional lung collapse that are particularly relevant to
212
Fig 5. Effect of Single Lung Ventilation on PAP and CVP in a Patient with PAH. The effect of initiating single lung ventilation (SLV) on pulmonary arterial
(PAP) and central venous (CVP) pressure in a patient with pre-existing PAH.
the PH patient: a) the increase in PA pressure and RV load
produced by HPV and b) the potential for systemic hypoxia.
Following the initiation of single lung ventilation, there
are an acute rise in airway pressure as the tidal volume is
shifted to one lung, and a progressive redistribution of
blood flow away from the non-ventilated lung as alveolar
oxygen is absorbed and HPV occurs. While this
redistribution of pulmonary blood flow has only a modest
effect on PA pressure in normal subjects, 86 the effect is
more pronounced in those with pre-existing PAH (Fig 5).
Accordingly, it has become relatively common to use iNO
or intravenous (IV) epoprostenol intra-operatively to
optimize vasodilation in the ventilated lung thus reducing
PA pressure while maximizing ventilation/perfusion
matching and lessening the risk of systemic hypoxia. 87
Confounding this approach to some degree has been the
increasing pre-operative use of IV pulmonary vasodilators
that may affect HPV intra-operatively. In this setting
(Fig 5), there may be benefit to also instituting inhaled
pulmonary vasodilators during single lung ventilation to
Fig 6. Representative Tracings of Systemic and Pulmonary Arterial Pressures During Lung Lobectomy in a Patient with Pre-existing PAH. Representative
simultaneous tracings of systemic arterial and pulmonary arterial (PA) pressures during lung lobectomy in a patient with pre-existing PAH who was
receiving intravenous (IV) Flolan (epoprostenol) preoperatively. With the transition from double lung ventilation (DLV) to single lung ventilation (SLV),
the IV Flolan dose was decreased and inhaled Flolan initiated in order to maximize vascular dilation of the ventilated lung and potentially lessen and
deleterious effects of systemic Flolan on hypoxic pulmonary vasoconstriction. Following lung resection and resumption of the preoperative Flolan dose,
PA pressure remained elevated relative to baseline.
allow for limiting or even discontinuing intravenous
therapy, lessening potential inhibition of HPV and
promotion of systemic hypoxia.
Finally, it is important to note that even when normal
double lung ventilation is resumed upon conclusion of the
procedure, PA pressure may not return to pre-operative
levels despite increased doses of intravenous and/or
inhaled pulmonary vasodilator, particularly if an anatomic
resection (i.e. lobectomy) was performed (Fig 6).
Post-operatively, epidural analgesia is commonly used
following lung resection and other non-cardiac surgery in
the chest. As noted above, sympathetic blockade at the
thoracic level can lead to dampening of cardiac sympathetic tone and systemic hypotension when high concentrations of local anesthetics are administered in the
epidural space. Accordingly, in light of the fact that PA
pressure may remain elevated following lung resection
despite increased doses of pulmonary vasodilators, using a
dilute local anesthetic solution, careful monitoring of
systemic arterial pressure, and rapid intervention for
hypotension are warranted.
Obstetrics
PH and pregnancy are well known to be a potential lethal
combination. Outcome statistics are primarily derived from
case studies and small case series, but perioperative
mortality rates have been reported to be between 30% and
70%. 1-3,13,88 A recent review of the literature sought to
compare more recent outcome data (1997–2007) with
previous reports (1978–1996). 88 The more recent mortality
rate declined among patients with IPAH to 17%, compared
with 30% in previous decades. On the other hand, congenital
heart disease associated PAH and other PH cases are still
213
associated with mortality of 28%–33%. As such, avoidance
of pregnancy or termination is still strongly advocated.
For pregnant patients presenting with newly diagnosed
or established PAH who present at a stage where the risk
of termination is similar to delivery of the fetus or who
refuse to terminate pregnancy, successful maternal–fetal
outcomes have been reported with an aggressive and
multidisciplinary management approach. 89 Vaginal delivery, often with an assisted 2nd stage, is preferred unless
there is a recognized obstetrical indication for a Cesarean
section (C-section). Advantages to vaginal delivery over
C-section include less fluid shifts, decreased bleeding
complications and a lower rates of infection. 88 Slow
epidural analgesia is strongly advised for the laboring
parturient patient to minimize the risk of hypotension and
also to avoid sympathetic stimulation associated with
painful labor contractions. Invasive monitoring is necessary with an arterial line and either a CVP or PA catheter.
If needed for inotropic support of a failing right ventricle,
low dose dobutamine is often effective, however vasopressin is preferred if a pressor is needed.
Post-operative management
An algorithm for the post-operative management of
patients with PH and RV failure is proposed in Fig 7.
Patients with PH warrant ICU monitoring in the postoperative period. Death, when it occurs, can be sudden and
often occurs within the first few days after surgery.
Frequent serial examinations should be performed in order
to promptly identify and treat factors that may precipitate
acute decompensated right ventricular failure (ADRVF).
Fig 7. Post-operative Management Algorithm for Patients with PH and RV failure. This figure provides an algorithm for the management of patients with
pulmonary hypertension in the post-operative period.
214
Invasive monitoring (arterial line, central venous or
pulmonary artery catheter), and echocardiography are
essential to determine causes of hemodynamic instability.
Post-operative clinical deterioration and death are often
due to fluid shifts, increased sympathetic tone, increased
pulmonary vasoconstriction (e.g. acidosis, hypoxia, hypothermia), and pulmonary thromboembolism that lead to
worsened RV failure, sometimes with arrhythmias. 90-92
The most dangerous perioperative complication is systemic hypotension due to RV failure from exacerbation
of PH. 93
Atrial tachyarrhythmias should be slowed with digoxin,
amiodarone, or cautious use of diltiazem or beta-blockers.
The calcium channel blocker verapamil should be avoided
because of negative inotropic and vasodilatory properties
that may exacerbate hypotension. Caution should be
taken with the use of beta-blockers and diltiazem in
patients with severe RV failure due to their negative
inotropic properties. If the patient is hypotensive, electrical
cardioversion is indicated.
Infection is poorly tolerated in patients with PH in
whom RV contractile reserve is limited. Anemia also
increases RV work and should be corrected if significant.
Oxygen is a pulmonary vasodilator and maintenance of
adequate oxygenation is of paramount importance in
patients with PH and RV failure. Acidemia increases PVR
and therefore acidosis should be aggressively treated. In
fact, small degrees of alkalemia appear to be beneficial. 94
Respiratory acidosis should be avoided (goal pCO2
is ≤ 30–35 mmHg) and the prompt correction of metabolic acidosis is also indicated (goal pH is ≥ 7.4).
Avoidance of hypothermia and shivering is accomplished
by maintenance of a body temperature around 37 °C. 43
The hypertrophied right ventricle in PH is somewhat
“preload dependent” and may not tolerate volume
depletion such as bleeding. On the other hand, the RV is
less fluid responsive than the left ventricle, and excessive
volume loading is also detrimental as discussed previously. For diuretic resistant patients, introduction of ultrafiltration by various modalities may be appropriate.
Excessive RV dilation may adversely impact on LV
filling via shift of the interventricular septum (i.e.
ventricular interdependence). Maintenance of adequate
systemic blood pressure with vasopressors and inotropes
in addition to the replacement of blood volume loss when
necessary is of paramount importance. For most spontaneously breathing patients, a CVP of 5–10 mm Hg is
optimal. However, in an intubated patient, the level of
PEEP should be taken into account when assessing the
CVP. The effectiveness of fluid administration in a
hypotensive patient with PH and a CVP ≤ 10 mm Hg
can be estimated by lifting the patient's legs and if the
MAP increases, small bolus(es) of intravenous fluids
should be considered. Conversely, if the CVP is ≥ 15 mm
Hg and/or there is no increase in MAP with the leg raising
maneuver, diuretics may be more appropriate.
The most suitable vasodilators for use in the perioperative
setting to reduce PVR in patients who develop ADRVF are
the inhaled agents, such as iNO, as discussed previously.
Drawbacks to the use of iNO include the potential for toxic
metabolites and rebound PH during weaning. The oral or
intravenous (at reduced doses) PDE5I sildenafil can help
wean iNO. Alternatives to iNO include inhaled iloprost and
the more recently available inhaled treprostinil. Much less
commonly, inhaled preparations of other prostanoids (e.g.
epoprostenol and prostaglandin E1), phosphodiesterase-3
inhibitors (eg, milrinone), 95,96 and calcium sensitizers (eg,
levosimendan, available in Europe) have been used to treat
PH in the perioperative setting with most reports in the
cardiothoracic surgery literature. Intravenous prostanoid
therapies (e.g. epoprostenol and treprostinil) are appropriate
agents for patients with severe PAH and ADRVF who are
candidates for chronic therapy, whereas the combined
systemic and pulmonary vasodilators sodium nitroprusside,
nitroglycerin, nesiritide, milrinone, and levosimendan are
reserved for patients with PH related to decompensated left
heart failure. Several principles regarding pulmonary
vasodilator therapies must be kept in mind: 1) prostanoids
are generally only appropriate for patients with PAH (WHO
group 1 PH), 2) selective pulmonary vasodilators (oral,
inhaled and IV), with the exception of PDE5I, can worsen
left heart failure and pulmonary venous hypertension, and 3)
systemically administered pulmonary vasodilators can
worsen hypoxemia via V/Q mismatching and also potentiate
hypotension; thus, they should generally be avoided in
patients at risk.
As discussed previously, when indicated for hypotension
in PH patients with overt RV dysfunction, vasopressin and
norepinephrine are generally preferred over the pure alpha
agonist phenylephrine. 43,97-106 Epinephrine is typically
reserved for patients in severe shock. In normotensive
patients who need inotropic support for RV failure,
dobutamine is the preferred agent to improve RV contractility
and CO, and it is sometimes used in combination with
vasopressin to maintain adequate systemic blood pressure. 107
Dopamine has less potential for causing hypotension than
dobutamine, however it may cause more tachycardia and is
not generally considered a first-line agent for managing
patients with PH and RV failure. The inodilator milrinone is
very useful for patients with systolic LV failure and PH,
however its systemic vasodilator effects can overwhelm the
pulmonary vascular effects in PAH and its use should
therefore be avoided in these patients.
Summary
Anesthesia and surgery in patients with PH are
associated with high perioperative morbidity and mortality, and elective surgeries should generally be avoided.
Successful perioperative management requires a multidisciplinary approach involving the PH specialist,
anesthesiologists, critical care physicians, and allied
healthcare team members. Pre-operative planning should
include a careful risk assessment, taking into account the
type of surgery as well as the etiology and hemodynamic
severity of PH, patient functional status, and other medical
comorbidities. If possible, optimization of hemodynamics
and management of comorbidities should be attempted
prior to surgery. Anesthetic agents, mechanical ventilation, and conditions related to specific surgeries have
profound effects on pulmonary arterial and right ventricular coupling, and a thorough understanding of these
physiologic effects, as well as having an experienced
anesthesiologist, are of paramount importance for the
successful perioperative management of patients with PH.
Post-operative management must include vigilant hemodynamic monitoring with serial assessment, optimization
of hemodynamics, avoidance of factors known to cause
pulmonary vasoconstriction, and when necessary, the
administration of inopressors and pulmonary vasodilators,
the choice of which is based largely upon the etiology of
PH. In the future, studies of patients with PH undergoing
anesthesia and surgery should provide greater understanding of the risk factors and optimal perioperative management of these complex patients.
Statement of Conflict of Interest
Dana McGlothlin, MD has received research support/
grants from Actelion Pharmaceuticals, Inc., United
Therapeutics Co.; and has served on speakers’ bureaus/
received honoraria from Gilead Sciences, Inc., Actelion
Pharmaceuticals, Inc., and United Therapeutics, Co.
Paul Heerdt, MD, PhD has served as a consultant and
has received honoraria from Cheetah Medical.
Natalia Ivascu, MD has no conflicts of interest
to report.
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