Download causes of right ventricular failure

07 February 2014
No. 04
ANAESTHESIA AND
RIGHT VENTRICULAR FAILURE
CL Chellan
Moderator: B Daya
School of Medicine
Anaesthetics and Critical Care
CONTENTS
INTRODUCTION ................................................................................................... 3
ANATOMY OF THE RIGHT VENTRICLE ............................................................. 5
PHYSIOLOGY OF THE RIGHT VENTRICLE ....................................................... 7
CAUSES OF RIGHT VENTRICULAR FAILURE................................................. 10
A. Pressure Overload ................................................................................... 11
Pulmonary Hypertension .................................................................................. 11
1.
Volume Overload ..................................................................................... 13
2.
Right Ventricular Dysfunction ................................................................... 14
PATHOPHYSIOLOGY ........................................................................................ 14
CLINICAL SYNDROME OF RIGHT VENTRICULAR FAILURE ......................... 17
DIAGNOSTIC TESTING ..................................................................................... 18
PERI-OPERATIVE MANAGEMENT ................................................................... 24
A. Pre-operative Assessment ....................................................................... 24
B. Anaesthetic Goals .................................................................................... 25
C. Choice of Anaesthetic .............................................................................. 26
D. Intra-operative Monitoring ........................................................................ 27
E. Management of peri-operative right ventricular failure .............................. 28
1.
General Measures.................................................................................... 28
II.
Preload Management ............................................................................... 28
III. Optimisation of RV Rate and Rhythm ....................................................... 29
IV. Pulmonary Vasodilators ........................................................................... 29
V. Vasopressors ........................................................................................... 31
VI. Inotropes .................................................................................................. 31
VII. Mechanical Support of the Right Ventricle................................................ 34
F. Post-operative considerations .................................................................. 34
CONCLUSION .................................................................................................... 35
Page 2 of 37
ANAESTHESIA AND RIGHT VENTRICULAR FAILURE
INTRODUCTION
For many years, the right ventricle (RV) of the heart has received little attention [1];
with the emphasis in cardiology being placed on the left ventricle (LV),
overshadowing the importance of RV function. Before the 1970s, the RV was
viewed as little more than a passive conduit for blood[2]; and the RV was thought
to play a minor, sub-serviant role to the LV[3]. More recently, the importance of the
RV in maintaining haemodynamic stability and organ function has been
recognised. Since the RV has received much less interest in research, right
ventricular failure (RVF) is less well understood, and there is limited outcomes
data with regards to available therapy[1].
In contrast to left ventricular failure (LVF), there are no practice guidelines for its
management[4]. The RV is different from the LV, and these differences may
influence the assessment and treatment of patients with predominantly right, left
or biventricular failure – hence RVF cannot be understood simply by extrapolating
data and experience from LVF[5].RVF is a major public health problem[1]. It is
estimated to account for 3% of all acute heart failure admissions, and may confer
increased mortality compared to acutely decompensated LVF. It may also be an
independent risk factor for morbidity and mortality in patients with left heart failure.
Pulmonary hypertension (PH) in itself carries increased risk of adverse events
(24%) and in-hospital deaths (9.7%); and PH and RHF is more common than
previously thought[6]. In a retrospective study conducted by Ramakrishna and
colleagues at the Mayo Clinic[7], RVF was found to be a contributing cause of
death in 50% of patients with PH, with a mortality rate of 7% for patients
undergoing non-cardiac surgery, during the study period 1991 – 2003. 1 in 2000
of the 10-15 million people with COPD will develop RVF[1], and RVF has been
found to be the primary cause of death in most of the 50000 fatal cases of PE in
the US each year[6].
Acute RV decompensation may be sudden and unpredictable and often responds
poorly to treatment[8]. Unfortunately, it is becoming increasingly common, due to
the growing prevalence of its predisposing conditions which include LV
dysfunction, PE, PH, adult congenital heart disease and coronary ischaemia. In
RVF, it has come to attention that RV function plays an important role in heart
physiology. The importance of RVF in patients with cardiac and pulmonary
disease and its impact in the peri-operative period and critical care is felt every
day in clinical practice[9]. The aim of this talk is to provide an overview of the
anatomy and physiology of the right ventricle, pathophysiology and diagnosis of
RVF; and to discuss the treatment options that may be used when peri-operative
RVF is encountered.
Page 3 of 37
LIST OF ABBREVIATIONS
RV: Right ventricle
LV: Left ventricle
RA: Right atrium
LA: Left atrium
RVF: Right ventricular failure
LVF: Left ventricular failure
RVEF: Right ventricular ejection
fraction
CO: Cardiac output
LVEF: Left ventricular ejection
fraction
MAP: Mean arterial pressure
PA: Pulmonary artery
PAP: Pulmonary artery pressure
RHC: Right heart catheterisation
PV: Pressure-Volume
mPAP: Mean pulmonary artery
pressure
RAP: Right atrial pressure
PAC: Pulmonary artery catheter
EDV: End diastolic volume
PAWP: Pulmonary artery wedge
pressure
CVP: Central venous pressure
SVR: Systemic vascular
resistance
AV: Atrio-ventricular
PVR: Pulmonary vascular
resistance
IV: Interventricular
TV: Tricuspid valve
PV: Pulmonary valve
PH: Pulmonary hypertension
HPV: Hypoxic pulmonary
vasoconstriction
LVAD: Left ventricular assist
device
COPD: Chronic obstructive
pulmonary disease
PDE: Phosphodiesterase
CPB: Cardio-Pulmonary Bypass
PE: Pulmonary embolism
iNO: Inhaled nitric oxide
RVMI: Right ventricular
myocardial infarction
BNP: Brain natriuretic peptide
Page 4 of 37
ANATOMY OF THE RIGHT VENTRICLE
In the normal heart, the RV is situated anteriorly in the chest, lying behind the
sternum; and is bordered by the annulus of the tricuspid and pulmonary valves
and the IV septum. The anatomy of the RV has been described as being unique
and complex[10]. The RV appears triangular when viewed laterally and crescentshaped in cross-section, in contrast to the ellipsoidal LV. The RV shape is
influenced by the position of the IV septum, with the septum being concave toward
the LV in normal loading conditions[11]. The RV is thin-walled, usually 1-3mm;
hence RV mass is about 1/6th that of the LV in the mature child and adult. The RV
volume is greater than that of the LV; the normal range of RVEDV (based on MRI)
is 49 – 100 mL/m2 and LVEDV is 44 – 89 mL/m2 [12].
The RV is therefore well designed to accommodate increases in preload, but
poorly designed to accommodate increases in afterload[13]. The RV can be divided
into 2 components, the sinus or inflow region – extending from the TV and
includes the trabeculated apical portion; and the conus or outflow tract (also called
the infundibulum) – extending from the septo-marginal band to the PV. Three
prominent muscular bands are present in the RV: parietal, septal and moderator
bands. The parietal band and infundibular septum makes up the crista
supraventricularis, which separates the sinus and conus regions [10, 11]. The septomarginal band extends inferiorly and becomes continuous with the moderator
band, which extends from the anterior papillary muscle to the IV septum.
The moderator band was so named as it was initially thought to moderate RV
distension, but it actually transmits the right branch of the AV bundle of the
conduction system[13]. The RV can also be divided into anterior, lateral and
inferior walls; as well as basal, mid and apical sections[11]. Both ventricles are
composed of multiple muscle layers, that form a 3D network of fibres[11]. In the RV,
the superficial layer fibres are arranged circumferentially – parallel to the AV
groove – and continue into the superficial myofibrils of the LV. RV deep layers are
aligned longitudinally from base to apex. The RV and LV are functionally bound
due to the continuity of muscle fibres, IV septum and pericardium – these
contribute to ventricular interdependence[11]; the concept that the size, shape and
compliance of one ventricle can influence that of the other ventricle.
The RV is supplied mostly by the right coronary artery – in a right dominant
system. The lateral wall is supplied by the marginal branches, the posterior wall
and infero-septal region by the posterior descending artery, the anterior wall and
antero-septal region by branches of the left anterior descending artery, and the
infundibulum by the conal artery[11]. The RV drains into the anterior cardiac veins
which empty into the RA[14]. In the LV, myocardial perfusion occurs mostly in
diastole, when intramyocardial tissue pressure is less than that of the aortic root.
In the RV, under normal loading conditions, intramyocardial pressure remain low
throughout the cardiac cycle, allowing continuous coronary flow.
Page 5 of 37
Figure1. Segmental anatomy of the RV[10]
Page 6 of 37
PHYSIOLOGY OF THE RIGHT VENTRICLE
RV contraction is sequential- contraction starts with the inlet and trabeculated
myocardium, and moves in a wave, ending with the infundibulum[6, 11].
The RV contracts by three mechanisms:
- Inward movement of the free wall
- Contraction of the longitudinal fibres which shortens the long axis, bringing the
tricuspid annulus towards the apex
- Traction of the free wall secondary to contraction of the LV – this may
contribute up to 40% of systolic RV function due to ventricular
interdependence
This bellows like contraction (vs. the “wringing” motion of the LV) results in a
greater ratio of RV volume change to RV free wall surface area change –
producing a greater RVEF with little change in RV wall stretch[1]. This type of
contraction is optimal for moving large, varying volumes of blood; but poorly
adapted to generating high pressure – ie. the RV performs mainly volume, rather
than pressure work[13]. RV systolic function is determined by preload, contractility
and afterload[11]. RV performance is also influenced by rhythm, ventricular
synchrony, RV free-interval relationship and ventricular interdependence. The
relationship between preload and afterload is well demonstrated in the PressureVolume loops of the RV (illustrated in Figure 2) – where the triangular shape
illustrates the short period of isovolumetric contraction and increased
compliance[15].
Figure 2. Pressure-Volume loops of RV and LV[13]
Page 7 of 37
One important finding from examination of PV loops is that the RV follows a timevarying elastance model[10, 11]; where ventricular elastance is the relationship
between systolic pressure and volume under varying conditions. RV maximal
elastance can be approximated by a linear relationship, and can be used as an
index of contractility. Some limitations in the time-elastance model include nonlinearity, variability in slope values and afterload dependency[11] RV preload
represents the load present before contraction. RV filling starts before and finishes
after the LV, and RV filling velocities and the E/A ratio are lower[11].
Factors that influence RV filling are: intravascular volume status, ventricular
relaxation, ventricular chamber compliance, heart rate, passive and active atrial
characteristics, and pericardial constraint. The RV is able to accommodate
dramatic alterations in venous return which may be caused by changes in volume
status, position, and respiration. Despite these changes, the RV maintains a
somewhat constant CO[1], largely due to its unique geometry. RV afterload is
chiefly determined by the pulmonary circulation, which has a low pressure and
resistance (1/10th that of SVR)[9] and is highly compliant.The cross-sectional area
of the pulmonary vascular bed is large.
The pulmonary vasculature is highly distensible, and is able to accommodate
increases in flow because its vessels are recruitable. PVR can be regulated by
many factors[4, 16]: hypoxia and hypercarbia ( vasoconstriction), cardiac output
(distends open vessels and recruits previously closed vessels  ↓PVR), gravity
(influences distribution of blood flow in the pulmonary circulation), pulmonary
volume (increased flow  mechanical stress  activation of endothelial cells) and
pressure, and specific molecular pathways such as nitric oxide (vasodilatation),
prostaglandins (vasodilatation), and the endothelin pathway (vasoconstriction).
Under physiological conditions, pulmonary arterioles are thin walled, with thin
media (only about 7% of wall thickness), and few smooth muscle cells, however
endothelial dysfunction, chronic hypoxia, and inflammation can lead vascular
remodelling which can cause and worsen pulmonary hypertension[16].
Page 8 of 37
Table 1 summarises the important anatomic and physiologic characteristics of the RV and LV.
TABLE 1. COMPARISON OF NORMAL RV AND LV STRUCTURE AND FUNCTION[11]
CHARACTERISTICS
RV
LV
Structure
Inflow region, trabeculated
myocardium, infundibulum
Inflow region and
myocardium, no
infundibulum
Shape
From the side: triangular
Cross section: crescentic
Elliptic
EDV (mL/m2)
75 + 13 (49 – 101)
66 + 12 (44 – 89)
Mass (g/m2)
26 + 5 (17 – 34)
87 + 12 (64 – 109)
Thickness of ventricular wall (mm)
2–5
7 – 11
Ventricular pressures (mmHg)
25 / 4 [(15 – 30)/(1 – 7)]
130 / 8 [(90 – 140)/(5 – 12)]
RVEF (%)
61 + 7 (47 – 76)
67 + 5 (57 – 78)
Ventricular elastance - Emax
(mmHg/mL)
1.30 + 0.84
5.48 + 1.23
Compliance at end diastole
(mmHg-1)
Higher than LV
5.0 + 0.52 x 10-2
Filling profiles
Starts earlier and finishes
later, lower filling velocities
Starts later & finishes
earlier, higher filling
velocities
PVR vs. SVR (dyne.s.cm-5)
70 (20 – 130)
1110 (700 – 1600)
Stoke work index (g.m2/beat)
8 + 2 (1/6 of LV stroke
work)
50 + 20
Exercise reserve
↑ RVEF > 5%
↑ LVEF > 5%
Resistance to ischaemia
Greater resistance
More susceptible
Adaptation to disease state
Better adapted to volume
overload
Better adapted to pressure
overload
Page 9 of 37
CAUSES OF RIGHT VENTRICULAR FAILURE
The common causes of RVF as illustrated in Table 2 are broadly divided based on
the underlying pathophysiological mechanisms[4, 13, 14]:
- RV pressure overload / RVF secondary to increased afterload
- RVF secondary to volume overload
- Intrinsic RVF (in the absence of PH)
TABLE 2 : CAUSES OF RVF[13]
1. RVF with normal afterload
Cardiomyopathy
RV Infarction
Sepsis
Arrhythmogenic RV dysplasia
2. RVF secondary to increased afterload
Mitral valve disease with PH
Pulmonary embolus
Obstructive sleep apnoea
ARDS
Pulmonary stenosis
RV outflow tract obstruction
Tetralogy of Fallot
Double-chambered RV
Transposition of great vessels
Increased afterload following cardiac
surgery
- Inflammatory effects of CPB
- Protamine
Increased afterload following thoracic
surgery
- Excessive lung resection
- LVAD
3. RVF secondary to volume overload
Ventricular septal defect
Atrial septal defect
Pulmonary regurgitation
Tricuspid regurgitation
Anomalous pulmonary venous return
Sinus valsalva rupture into the RA
Coronary artery fistula to RA or RV
Rheumatic valvulitis
Page 10 of 37
Carcinoid syndrome
A.
Pressure Overload
This is the most common cause of RVF, due to its anatomical and physiological
properties[14]. RV pressure overload is caused by any condition impeding blood
flow between the RV and LV such as PH, RV outflow tract obstruction and PV
stenosis. Peri-operative causes of acutely elevated PVR include[4, 16]: hypoxia,
hypoventilation, atelectasis, high ventilating pressures, CPB (due to endothelial
injury), protamine reactions, acute pulmonary thromboembolism, CO2 or air
embolism, bone cement and ischaemia-reperfusion syndromes.
Pulmonary Hypertension [4, 15, 17-21]
PH is defined as mPAP (mPAP = PVR X CO + LAP) of >25mmHg at rest, as
assessed by RHC. Pre-capillary PH occurs in the setting of normal PAWP of
<15mmHg, PVR of >3 wood units and normal or reduced CO; whereas in postcapillary PH, the PAWP is >15mmHg. The previous additional definition of
mPAP>30mmHg during exercise is no longer used[20]. PH may be further
classified as mild (mPAP 25 – 40mmHg), moderate (41-55mmHg), or severe
(>55mmHg)[4].
The additional classification is useful as mild PH rarely impacts anaesthetic
management[17] , whereas moderate and severe PH can precipitate acute
decompensation of the RV, necessitating specific anaesthetic plans and therapy.
The American College of Chest Physicians recommends that all patients who are
suspected to have PH undergo RHC so that a precise diagnosis can be made [15].
RHC remains the gold standard for the diagnosis of PH as Echocardiography may
have technical limitations, even under optimal conditions.
Haemodynamic variables measured during RHC (which include RAP, PVR and
RV performance) can also be used to assess prognosis and predict survival [15].
The diagnosis of PH relies on a high index of suspicion as symptoms are nonspecific and it may not be easy to differentiate them from symptoms of other
pulmonary and/or cardiovascular disease – which may also co-exist.
The mean interval from onset of symptoms to diagnosis has been noted to be
around 2 years[19]. The classification of PH has undergone many changes since it
was 1st proposed in 1973[20]. At the 4th World Symposium on Pulmonary
Hypertension held in Dana Point, California in 2008; an updated clinical
classification directed at the underlying clinical causes was developed – as
illustrated in Table 3[18, 22].
Page 11 of 37
TABLE 3 : Clinical Classification of Pulmonary Hypertension developed by
the
4th World Symposium on Pulmonary Hypertension at Dana Point, CA[22]
1. Pulmonary arterial hypertension (PAH)
1.1 Idiopathic (IPAH)
1.2 Heritable
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 disease
1.4.5 Schistosomiasis
1.4.6 Chronic haemolytic anaemia
1.5 Persistent pulmonary hypertension of the newborn
1.6 Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary
haemangiomatosis
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 disease and/or hypoxia
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 multi-factorial mechanisms
5.1 Haematologic disorders: myeloproliferative disorders, splenectomy
5.2 Systemic disorders: sarcoidosis, pulmonary Langerhans cell
histiocytosis
5.3 Metabolic disorders: glycogen storage disease, Gaucher disease,
thyroid disease
5.4 Others: tumoral obstruction, fibrosing mediastinitis, chronic renal
failure on dialysis
Page 12 of 37
PAH[20]: can occur in association with many other disorders. The incidence of PAH
in HIV is approximately 0.5% - 6–12X higher than the general population, and this
incidence is not decreased with ARV therapy. It is characterised by the presence
of pre-capillary hypertension. Histological examination has demonstrated a panvasculopathy affecting predominantly small ‘resistance’ pulmonary arteries,
involving intimal hyperplasia, medial hypertrophy, adventitial proliferation,
thrombus in situ, varying degrees of inflammation and plexiform arteriopathy.
PH due to LH Disease[6, 21, 23]: is a post-capillary PH, and includes LV systolic
dysfunction, LV dysfunction with preserved EF and Valvular diseases. LH disease
may cause passive backward transmission of increased LAP, leading to raised
PAP. In some patients, the observed rise in PAP is out of proportion to the
increased LAP, and the trans-pulmonary gradient is also increased – indicating
remodelling of the pulmonary circulation or an abnormal vasoconstrictor response.
PH due to LH disease, particularly LV systolic dysfunction is one of the most
common causes of PH and these patients are at higher risk for morbidity and
mortality. Therapy in this group is mainly directed toward the underlying condition.
Although theoretical “reversal” of the PH may be possible if the underlying
pathology is corrected, the increased PVR becomes irreversible in many
conditions, PH due to lung diseases[18]: is mainly caused by alveolar hypoxia,
impaired control of breathing, or high altitude. In most patients, the PH is modest.
CTEPH: is a frequent cause of PH and occurs in up to 4% of patients after acute
PE.
Treatment goals in PH include[20]: improving symptoms and functional capacity,
decreasing mPAP, normalising CO, and reversal or slowing down the rate of
progression of the underlying disease. With the increasing availability of diseasemodifying therapies, median survival for patients with PH has increased –
resulting in more of these patients undergoing anaesthesia and surgery.
Factors predicting poor prognosis and increased risk of illness after non-cardiac
surgery include[15, 18]: poor functional status (NYHA II or higher), elevated RAP,
significant RV dysfunction (which may be more significant than the severity of PH)
or evidence of RVF, increased BNP and CRP, underlying scleroderma, history of
PE, intermediate or high risk surgery, and anaesthesia lasting longer than 3 hours.
The overall mortality from massive PE is 6 – 8%, increasing to 30% if complicated
by systemic hypotension. Total peri-operative mortality is about 30% with mortality
rates approaching 60% in patients where pre-operative cardio-pulmonary
resuscitation was necessary[24].
1. Volume Overload[1, 4, 25]
Acute volume overload may be caused by atrial or ventricular septal defects,
acute tricuspid regurgitation, volume overload, and ruptured sinus of Valsalva
aneurysm. Although volume overload is commonly considered as a cause, it
generally will not cause acute RVF in the absence of increased PAP.
Page 13 of 37
This is because the RV adapts better to volume than to pressure overload and
may be able to tolerate volume overloaded states for a long time before significant
decline in RV systolic function become evident.
2. Right Ventricular Dysfunction[1, 4, 13, 14, 25]
RV ischaemia can be caused directly by RVMI, or indirectly by systemic
hypotension. The RV is usually less prone to ischaemia due to its thin wall,
continuous coronary perfusion, low oxygen extraction (about 50%) and
consumption under resting conditions. RV infarction often occurs in association
with LV infarction but can also occur as an isolated event. RVMI is often
unrecognised. Most clinically evident cases occur in the setting of inferior MI, and
although instability with hypotension occurs in less than 10% of patients, it is
associated with high mortality – up to 75%. Acute RVF may be caused by RV
myocardial injury itself, LV dysfunction, or loss of atrio-ventricular synchrony. RV
dysfunction occurs commonly after cardiac surgery, and may be due to:
myocardial stunning, intracoronary air embolism, decompensation of pre-existing
RV dysfunction, as well as the effects of CPB or cardioplegic arrest.
PATHOPHYSIOLOGY
The most important factors determining RV adaptation to disease is the type and
severity of myocardial injury or stress, the time-course of the disease
(acute/chronic), and the time of onset of the disease(newborn/paediatric/adult)[25].
Other factors that may have a role include: neuro-hormonal activation, altered
gene expression, and the pattern of ventricular remodelling; with interactions
occurring between the factors.
A. Response of the RV to increased volume[1, 4, 6, 14]
Generally, RV volume overload is well tolerated because it is optimised to
accommodate large changes in volume[6]. Indeed, the RV may tolerate longstanding volume overload, as seen in ASD and TR, without significant decreases
in RV systolic function[25].Like the LV, the RV uses the Frank Starling Mechanism
to increase stoke volume in response to increased wall stretch[1]. Thus, RV
dilatation leads to greater recruitment of function. This response is usually minimal
at baseline, but once the RV has dilated into a more circular form, a steeper
relationship between volume and stretch develops[4].
Global function of the RV is dependent on its free wall and IV septum, with both
the RV and LV making a contribution towards RV output. In isolated volume
overload, the RV can still use ventricular interaction. Although the IV septum is
shifted towards the left in diastole, it returns to normal position in systole – adding
to RV systolic function[14]. With severe RV dilatation, minimal increase in RV free
wall contraction can occur in response to further increases in volume, leading to
increasing RV pressure; further increases in RV volume then occurs at the
expense of the RV[6], and this may have a negative effect on CO.
Page 14 of 37
B. Response of the RV to increased pressure[6]
In comparison to the LV, the RV has limited ability to produce elevated pressure
work[6]: RV functions worsens parallel to increases in PAP[9]. The thinner free wall
faces higher rise in wall tension with increased pressure (LaPlace relation). There
also appears to be biochemical differences allowing the RV to be optimised more
for rapid contraction[6]. Two examples of well tolerated pressure overloaded states
include Eisenmenger Syndrome and Congenital Pulmonary Stenosis. The initial
response to modest pressure overload is accomplished by homeometric
autoregulation – The Anrep Phenomenon[1, 4].
This rapidly increases contractile function to maintain CO, and is mediated
through alterations in calcium dynamics. Although RV hypertrophy may initially be
adaptive, it is also the initial step in the process of remodelling, which is ultimately
damaging[5]. As afterload increases, endogenous catecholamines may allow
further increases in inotropy. With further increases in PVR, the EDV increases
and functional recruitment via the Frank Starling mechanism occurs –
heterometric autoregulation[14]. Once the mechanisms of contractile reserve are
exhausted, further increases in afterload can lead to sudden haemodynamic
collapse, which is often associated with the onset of RV ischaemia[4].
Progressive RV dilatation leads to increased IV septal shift and tricuspid
regurgitation, causing decreased LV compliance and preload, which causes
decreased CO and systemic hypotension. The dynamics of RV coronary perfusion
is also altered due to increased RV pressure and decreased aortic root
pressure[1]. RV ischaemia leads to further decreases in RV stroke volume, LV
preload and MAP  a catastrophic downward spiral – as illustrated in figure 3[14].
Page 15 of 37
C. Response of the RV to decreased contractility[1, 4]
If the pulmonary driving pressure can be maintained, and the PVR remains low,
decreases in RV contractility may not result in RVF. In this situation, an elevated
CVP can provide enough driving force to maintain flow across the pulmonary
circulation. When PVR or LAP is elevated, ie. when RV demand increases; RVF
will occur. Ischaemia caused by RCA occlusion can lead to varying degrees of RV
ischaemia, which explains why there may be varying degrees of haemodynamic
instability[9].
Grade 1: necrosis of <50% of the posterior wall
Grade 2: necrosis limited to, but not involving >50% of the posterior wall
Grade 3: necrosis of the posterior wall and <50% of the anterolateral wall
Grade 4: necrosis of the RV posterior wall and >50% of the anterolateral wall
RV MI has been reported to occur more in the setting of previous RV hypertrophy.
D. The RV in LVF[5]
The hypothesis that LV enlargement can lead to RV dysfunction was first made in
1910. RVF may develop in association with LV dysfunction or failure through
many different mechanisms:
LVF causes increased RV afterload due to increased pulmonary venous and
ultimately pulmonary arterial pressure. This is illustrated in Figure 4[26]
If LV dysfunction is due to cardiomyopathy, the same process may also affect the
RV
Myocardial infarction may affect both ventricles
LV dysfunction may cause decreased aortic root pressure, decreasing RV
coronary perfusion which may lead to significant RV dysfunction
Ventricular interdependence may play a role
LV dilatation may cause RV diastolic function by a limited pericardial component
Page 16 of 37
CLINICAL SYNDROME OF RIGHT VENTRICULAR FAILURE
The American College of Cardiology/American Heart Association guidelines[27]
define Heart Failure as “a complex clinical syndrome that can result from any
structural of functional cardiac disorder that impairs the ability of the ventricle to fill
with or eject blood.” In these guidelines, the RV is barely mentioned. In patients
with an LVAD, the Interagency Registry for Mechanically Assisted Circulatory
Support (INTERMACS) proposes an inclusive definition for RVF as[1]: “symptoms
and signs of persistent RV dysfunction (RAP >18mmHg with cardiac index
<2.0l/min/m2) [in the absence of elevated LAP/PCWP (greater than 18mmHg),
tamponade, ventricular arrhythmias or pneumothorax]; any RVF requiring Right
ventricular assist device implantation; or any RVF requiring iNO or inotropic
therapy for a duration of more than 1 week at any time after LVAD implantation.”
For the peri-operative period, no consensus definition of RVF has yet been
established. Greyson CR suggests that RVF be defined as[1]: “the clinical
syndrome resulting from the rights heart’s inability to provide adequate blood flow
to the pulmonary circulation at a normal central venous pressure.” The symptoms
of RVF are non-specific and they may vary depending on the severity of and the
underlying precipitant of RVF[8]. Patients with conditions causing increased
afterload, may complain of dyspnoea, presyncope, syncope or fatigue.
In both RV infarction and PE, chestpain or discomfort may be an important
presenting symptom. In acute on chronic RVF, lower limb swelling, and RUQ
discomfort may be present. Signs of RVF include: systemic hypotension,
tachycardia, tachypnoea, cyanosis, elevated jugular venous pressure, a
parasternal heave, right sided 3rd heart sound, TR, hepatomegaly and peripheral
oedema. The signs of PH may also be present: increased splitting of the 2 nd heart
sound, loud pulmonary component of the 2nd heart sound – although these may
be lost as RVF worsens and PAP decreases.
The signs and symptoms of acute RVF may be superimposed on those of chronic
RVF, and may also co-exist with LVF, valvular lesions, and chronic pulmonary
diseases.No single sign or symptom can perfectly identify all episodes of RVF, but
in general, decompensated RVF is not present if the JVP is normal – this may be
a predicament in the setting of RVF with intravascular volume depletion. The
absence of pulmonary congestion with raised CVP + hypotension has often been
quoted as being the most specific findings in isolated RVF[1]. Peri-operative
limitations of these key elements in diagnosing RVF include:
- Co-existence of RVF with LV systolic or diastolic failure
- Increased RAP from increased intrathoracic or intraabdominal pressure without
any RV dysfunction.PH – is a risk factor for developing RVF (initial PAP will be
high, but will pseudonormalise in RVF due to decreased CO)
Page 17 of 37
DIAGNOSTIC TESTING
The current options for diagnosis include ECG, CXR, cardiac biomarkers, ECHO,
cardiac MRI and RHC. Figure 5 illustrates an integrated approach to the
assessment in a patient with acutely decompensated RVF.
Page 18 of 37
Electrocardiograph[8, 13]: is often normal. Patients may have evidence of
infarction or signs suggestive of PE. Possible changes include:
- Sinus tachycardia
- T wave inversion in leads III and aVF or leads V1-4
- RBBB – incomplete or complete
- QRS axis >90 or indeterminate
- SIQIIITIII pattern
- Qr pattern in lead VI
- S waves in lead I and aVL >1.5mm
- Q waves in lead III and aVF but not in lead II
- Transition zone shifted to V5
- Low limb lead voltage
- Atrial fibrillation
Chest Radiograph (CXR)[8]: has limited ability to identify RVF. Once signs
suggestive of RVF are shown, it is usually advanced. Due to its anatomic location,
the RV is poorly visualised on conventional CXR. PE may be suggested by
enlargement of the main PAs, distended azygous vein, and oligaemia of a lobe.
RV dilatation may be suggested by changes in heart position, cardiac silhouette
(filling of retrosternal space), and adjacent structures. RA dilatation may be
suggested by increased curvature of the right heart border.
Cardiac Biomarkers: will aid in the diagnosis of RVF, and suggest possible
causes[8]. Elevated levels of serum troponins, BNP and pro-BNP have been seen
in RV dysfunction, especially in the setting of underlying PE. Troponins may be
elevated due to ischaemia or micro-infarction secondary to increased wall tension,
increased oxygen demand and decreased coronary perfusion. BNP is secreted by
the myocardium secondary to increased RV shear stress. In general, the cut-off
values for troponins and prognostication in PE are similar to those used in
diagnosing MI. In PE, troponins and BNP have negative predictive values for in
hospital death between 97-100%.
In acute PE and RVF though, the positive predictive value is low, there is a wide
range of sensitivities, and specificity is also low for adverse events, including inhospital deaths[8]. In a study by Nagaya and colleagues[28], in patients with
volume overload secondary to ASD and pressure overload secondary to PAH or
thromboembolic PH; rising BNP levels correlated with increases in mPAP, PVR,
mRAP, RVEDP and RV mass, and decreases in CO and RVEF. In another study,
the same authors showed that elevated baseline and post treatment BNP were
independent prognostic markers of mortality, in patients with PAH[29].
Echocardiography (ECHO/Echo) [8, 14, 30-32]
This is quoted by some as being the preferred diagnostic tool due to its availability
at the bedside and non-invasive nature; and by others as being inferior to RHC
due to intrinsic and operator dependent limitations.
Page 19 of 37
ECHO can be useful in determining RV dimensions and function, PAPs, and
allows for real-time analysis of RV shape – with particular attention to septum,
convexity, RV dimension and TR[9]. It may also help diagnose the cause of RV
dysfunction, and diagnose other conditions such as valvular heart disease,
congenital heart disease, LV outflow tract obstruction, LV systolic or diastolic
dysfunction, acute PE, pulmonary disease and pericardial diseases. Although
Trans-Thoracic Echo (TTE) provides direct visualisation of the RV, technical and
anatomic limitations may decrease its sensitivity and reproducibility; and TransOesophageal Echo(TOE) may then provide better assessment[8].
Echocardiography assessment of the RV may be more challenging than that of
the LV because of its complex shape, difficulty in endocardial surface recognition,
and marked dependence on loading conditions[33]. Although challenging, it
remains the mainstay of peri-operative RV functional assessment. Because RV
dysfunction is associated with morbidity and mortality, especially after cardiac
surgery, its assessment during intra-operative TOE is vital[33]. In the near future,
3D technology may enable better assessment of RV volumes.
Echocardiographic findings associated with RVF include[8]:
- RV dilatation (ratio of RVEDV:LVEDV of >0.6, if severe then >1.0)
- RV hypokinesis
- Change to a more concentric RV morphology
- Paradoxical septal motion
- Impaired LV diastolic function (suggested by alterations in Doppler mitral flow
such that A wave> E wave)
- RA enlargement
- TR
- PAP as estimated by the modified Bernoulli equation (p=4V2)
- PA dilatation
- Lack of inspiratory collapse of the IVC
- Pericardial effusions
Other useful Echo derived measures of RV loading conditions and performance
are[13]:
- RV free wall motion
- Thickness of free wall >15mm at end-diastole  hypertrophy
- Dilatation: as assessed by examining the apex in long-axis view – when the
RV forms the apex then dilatation is present
- Tissue Doppler tissue velocity: quantitative index of RV free wall motion and
function
- Hepatic venous flow pattern: demonstrates systolic flow reversal - occurs in
severe RVF
- Doppler echo: allows assessment of severity of PH
Page 20 of 37
Figure 6 Views used to perform comprehensive evaluation of the right heart [34]
Page 21 of 37
In 2010, the American Society of Echocardiography published their guidelines for
the assessment of the Right Heart in adults[34]. The purposes of their guidelines
are to:
- Describe acoustic windows required to evaluate the right heart (14 views are
described and illustrated – as in Figure 6)
- Describe echo parameters required to assess RV size and function
- Present advantages and disadvantages of each measure/technique described
by critical assessment of the literature
- Recommend measures to be included in the standard echo report
- Provide reference values of right-sided measurements based on literature
reviews
Table 4 gives a summary of the echocardiograph indices of the RV.
Table 4: Echocardiographic indices of the right ventricle[33]
FUNCTIONAL PARAMETER
NORMAL VALUE
LOAD DEPENDENCY
RV Fractional Area Change (RVFAC) (%)
32 – 60
+++
RVEF (%)
45 – 68
+++
>15
+++
1.4 + 0.5
+
Systolic Performance Variables
Tricuspid Annular Plane Systolic Excursion (TAPSE) (mm)
Isovolumetric Acceleration using Doppler tissue
imaging (IVA) (m/s2)
Tricuspid annular plane maximal systolic velocity
(using spectral pulsed wave tissue Doppler) (cm/s)
>12
++
Diastolic Parameters
IVC dimension (cm), collapse index (%)
Tricuspid early (E) to late (A) filling velocity ratio
< 1.7, CI > 50
+++
1.5 + 0.3
+++
S/D velocity ratio >1
no S reversal
atrial reversal< 50% S
Hepatic vein profile (S: systolic, D: diastolic)
+++
Isovolumetric Relaxation Time (IVRT) (ms)
< 60
+++
Rapid myocardial filling velocity (E1) (cm/s)
E1: 15.6 + 3.9
+++
Late diastolic myocardial filling velocity, A1 (cm/s)
A1: 15.4 + 4.5
+++
0.28 + 0.04
++
Combined Systolic and Diastolic Parameter
RV myocardial performance index
The severity of RV systolic dysfunction may be graded using RVFAC and RVEF
Using RVFAC: mild dysfunction: 25-31%, moderate dysfunction 18-24%, severe dysfunction <17%
Using RVEF: mild dysfunction: 35-44%, moderate dysfunction 26-34%, severe dysfunction <25%
Page 22 of 37
Radionuclide Ventriculography[9, 35]: allows for non-invasive assessment of RV
function. In this procedure, RBCs are radiolabeled and ECG-gated cardiac
scintigraphy is obtained. Alternative names for this technique includes gated
cardiac blood pool imaging, multigated acquisition (MUGA), and gated equilibrium
radionuclide angiography (RNA). This method can be used to assess regional and
global wall motion, cardiac chamber size and morphology, ventricular systolic and
diastolic function – including LVEF and RVEF. An RVG may be acquired at rest,
during exercise, and after therapeutic interventions.
Cardiac Magnetic Resonance Imaging (MRI)[14, 30]: allows measurements of RV
mass and volume. With the use of gadolinium, it can detect ischaemia vs.
infarction. It is particularly helpful in patients with complex congenital lesions, for
planning complex cardiac surgery, and for research purposes. Currently, its use is
limited.
Right Heart Catheterisation (RHC): with end-expiratory measurements of PA,
right-sided and left-sided pressures, is the gold standard for the diagnosis of PH.
Although it has not been shown to affect outcomes, RHC provides essential
haemodynamic information in acute RVF[32], especially in combination with Echo,
or in cases where Echo studies are technically limited; or when continuous
haemodynamic monitoring is required[8].
Thermodilution using the PAC allows RV output to be determined: 𝐸𝐹 =
𝐸𝐷𝑉−𝐸𝑆𝑉
× 100%. It also allows measurement of right-side pressures, RVEF and
𝐸𝐷𝑉
RV volumes – providing valuable information into RV function or dysfunction and
allows for risk stratification as well. It can also be used to evaluate response to
pharmacological therapy and allows drugs to be titrated to specific end-points[32].
Important limitations include unreliable measuring of CO using thermodilution in
the face of significant TR, the risks associated with balloon inflation in patients
with severe PH, and the potential complications associated with central venous
catheterisation.
Page 23 of 37
PERI-OPERATIVE MANAGEMENT
A. Pre-operative Assessment[4, 14, 18]
A pre-operative management plan should be formulated in association with the
relevant attending physicians and the surgeons. The pre-operative assessment[18]
should include:
o Type of surgery:
o Thoracic surgery: changes in intrathoracic pressures, lung volumes and
oxygenation may cause acute increases in PVR and decreased RV function
o Laparascopic procedures: pneumoperitoneum is usually poorly tolerated
due to decreased preload and increased afterload
o Procedures with rapid blood loss: poorly tolerated especially in patients with
RV systolic and diastolic dysfunction
o Other high risk surgeries: include those with significant perioperative
systemic inflammatory response (eg. CPB); and those with a high possibility
of venous air, CO2, fat, or cement emboli
- Functional status of the patient
- Severity of PH
- RV function
- Co-morbidities
- Pregnancy: even though mortality has decreased from 38 to 25% with
current therapies, it is still high; and pregnancy is still discouraged in
patients with severe PH, and RV dysfunction
Merits of surgery must be carefully assessed and discussed with the patient,
especially in a patient with significant RV dysfunction as this may be a significant
peri-operative risk factor. In patients with unacceptably high risk, consideration
should be given to chronic treatment or corrective surgery (eg. Valve repair or
thrombectomy/pulmonary endarterectomy); prior to elective or non-urgent surgery,
in order to decrease PH and improve RV performance[4]. Pre-operative
assessment of RV dysfunction can be aided by the investigations described
earlier. Other investigations that may be clinically indicated include: arterial blood
gases, lung function tests and liver function tests[4].
In certain cases - ie. moderate to severe RV dysfunction with severe PH, RHC
may be performed to evaluate the patients response to pulmonary vasodilators[14].
This aids with the planning for intra-operative pulmonary vasodilator therapy.
Premedication[4]: should be individualised. It is aimed at providing anxiolysis
without respiratory depression. Chronic therapy should be continued perioperatively (with a few exceptions such as warfarin). Pre-operative pulmonary
vasodilator therapy (oral sildenalfil, Ca-channel blockers, iNO, and nebulised
iloprost) should be considered as they may decrease the adverse effect of perioperative factors that increase PVR.
Page 24 of 37
B. Anaesthetic Goals[12, 20, 32]
Acute decompensation in the perioperative period is relatively common. No
algorithms exist, but principles of management include:
- Optimisation of RV rate and rhythm
- Augmentation of cardiac output
o Optimisation of RV preload
o Optimisation of RV systolic function (Categorisation of interventions aimed
at improving RV performance is depicted in Figure 7)
o Reduction in afterload by decreasing PVR
 Treat reversible factors that increase PVR
 Use pulmonary vasodilators
- Avoiding RV hypoperfusion
o Maintenance of aortic root pressure to ensure adequate RCA filling
pressure
o Prevention of systemic hypotension
Page 25 of 37
C. Choice of Anaesthetic
Both general and regional anaesthesia has been safely conducted in patients with
high risk of RV decompensation[4], eg. patients with severe PH secondary to
valvular heart disease undergoing Caesarean section. Large sympathetic
haemodynamic responses to pain, surgery, and laryngoscopy should be avoided,
as they will increase PVR.
If a neuraxial technique is performed, it should be introduced slowly (such as in a
graded epidural or intrathecal catheter), invasive monitoring should be used and
vasopressor agents must be immediately available.
If general anaesthesia is performed, ventilator factors that increase PVR should
be avoided:
- Avoid hypoventilation: as hypercapnia will increase the PAP independently of
the presence of hypoxia – SPAP increases up to 1mmHg for every 1mmHg
increase in PCO2
- Avoid hypoxia: which leads to localised pulmonary vasoconstriction. HPV
usually becomes active when the alveolar PO2 decreases less than 60mmHg,
and in response to decrease in mixed venous PaO2
- Avoid atelectasis: Decreased FRC may be prevented by using PEEP, but high
levels of PEEP must also be avoided as it will also increase PVR
- Avoid high ventilating pressures: including Valsalva manoeuvres, high
inflating pressures and high PEEP. These cause RV dilatation which leads to IV
septal shift, and decreased RV output. In patients with poor respiratory function,
it may be difficult to achieve these goals and if possible and not contraindicated, neuraxial anaesthesia is recommended[4].
Influence of anaesthetic drugs on PVR and RHF
Anaesthetic drugs can cause changes in PVR, RV afterload, and intracardiac
shunting[16]. Many agents have direct and indirect agents on PVR. IV Agents:
Many authors advocate Etomidate as the IV induction agent of choice [4, 18] – but
there are no comparative data to support this. Ketamine increases PVR in adults,
but this has not been observed in infants or children with PH[4].
There have been conflicting findings regarding the effects of Propofol: some
studies showing decreased RV contractility[4, 16] and others showing increased
PaO2 and lower shunt fraction values with Propofol vs. Iso/Sevoflurane in onelung-ventilation, and another showed decreased mean cardiac index and
RVEF[36].
Inhalational Agents[16]: All volatiles may worsen RV dysfunction due to
decreased preload, contractility and afterload.
Halothane, Isoflurane and
Sevoflurane do not adversely affect PVR, but Desflurane and Nitrous Oxide cause
increases in PVR.
Opiates[4]: Fentanyl and Sufentanil have minimal effects on pulmonary
haemodynamics. Remifentanyl produces minor pulmonary vasodilatation.
Page 26 of 37
D. Intra-operative Monitoring[4, 14]
An individualised approach is important, and choice of monitors should be dictated
by the severity of RV dysfunction and PH, intra-operative mode of ventilation, and
type of procedure[14].
- Invasive arterial blood pressure: facilitates haemodynamic management as
systemic hypotension can be detected earlier and vasopressor/inotropic
therapy can be initiated. Frequent sampling of blood gases can also be
undertaken, especially in cases where ventilation is difficult and
hypoventilation may be a problem.
- Central Venous Pressure: In the absence of hypovolaemia, acute RVF will
cause an increase in CVP and jugular venous engorgement. The onset of
TR can also be detected by prominent CV waves on the CVP waveform.
- Pulmonary Artery Catheter: is a useful monitor of RV function. It can aid with
assessing severity or worsening of PH and RVF; monitor the effects of PH
and RVF; and monitor the effects of interventions that may be undertaken,
especially in cases of acute deterioration. An acute increase in PAP –
provides a warning that PVR may be increasing and acute RVF may be
suspected if this is concurrent with increasing CVP and decreasing CO. It
should be kept in mind that pressure measurements alone provide less
information than measurement of PVR and that severe PH is a risk factor for
catheter induced rupture of the PA.
- Trans-Oesophageal Echocardiograph: is quoted as being mandatory by
some authors[4,8]. It is a practical investigative tool that can be used to
confirm the intra-operative diagnosis of acute decompensated RVF.
Technical limitations may adversely affect intra-operative assessment of RV
function.
Page 27 of 37
Table 5 summarises the anaesthetic recommendations for patients at risk of RV decompensation as
illustrated by Forrest and colleagues[4].
TABLE 5. Recommendations for patients at risk for intra-operative RV
decompensation[4]
INTERVENTION
- PH, + RVF Severe PH, - Severe PH, +
RVF
RVF
Premedication and Pre-induction
+
Sildenafil 25 – 50mg po
+/+
Iloprost 10mcg via neb
Monitoring
CVP : Spontaneous Ventilation
IPPV
IABP: Spontaneous Ventilation
IPPV
CO:
Spontaneous Ventilation
IPPV
TOE
Neuraxial Anaesthesia
Ventilation
High FiO2
Mild Hyperventilation
Low Ventilating Pressures
Anaesthetic Agents
+
+
+/+
+
+
+
+
+
+
+
+/+
+
+
+
+
+
+
+
+
+
Ketamine: Children
Adults
Thiopentone / Etomidate
Propofol
N2O
Isoflurane/Sevoflurane/Halothane
Desflurane
+
+/+
+
+
-
+
+
+
+
-
+
+
+
-
Fentanyl/Sufentanyl/Remifentanil
+
+
+
E. Management of peri-operative right ventricular failure
1. General Measures
Supportive measures should be instituted immediately; usually while urgent
ECHO is being organised[4].
- Ensure adequate oxygenation: use of high FiO2 and mild hyperventilation may
decrease RV afterload[14]
- Optimize ventilation: correct hypoventilation, recruitment manoeuvres and
PEEP can help to minimise atelectasis
- Treat hypotension
II. Preload Management
Determining optimal preload in the face of RVF can be problematic[4].
Hypovolaemia will decrease RV output and an inappropriate fluid challenge or
volume overload will worsen RV dysfunction by resulting in acute RV distension,
increased TR, IV septal shift, impairment of LVED filling, systemic hypotension
Page 28 of 37
and decreased RV perfusion  a progressive downward spiral[20]. CVP and Pulse
pressure variation cannot be used reliably in patients with RVF[25].
Echo guided volume assessment (eg. IVC diameters) and response to challenges
may be useful. Optimal filling can be assessed with cautious fluid boluses or by
elevation of the patient’s legs. Vigorous fluid administration is discouraged[32], and
liberal transfusion strategies are associated with increased morbidity and
mortality[25]. Forrest and colleagues suggest that if the CVP is < 10cmH20 and
raising the legs produces an increase in MAP – then IV fluids are indicated; if the
CVP is <20 and there is no increase in MAP – then diuresis may be more
appropriate[4]. RV volume overload may also be recognised by a rising V wave on
CVP, increasing TR seen at ECHO, or pulmonary oedema – Fluid withdrawal with
diuretics or ultrafiltration is then indicated[32].
III. Optimisation of RV Rate and Rhythm[20, 25]
Sinus rhythm and ventricular synchrony are important for optimal filling of the RV.
AV block or atrial fibrillation may have profound haemodynamic effects, and may
require sequential AV pacing or cardioversion. A study of RV synchronisation is
still in its early stages and further studies are still needed to determine optimal site
of pacing, optimal outcome variables and long term effects[25]. Because of the
association between RV and TR, slightly increased heart rate (80 – 100bpm) are
advantageous, in order to decrease EDV. Bradycardia causes decrease in CO as
SV is already limited by the increased afterload. Tachycardia may increase RV
ischaemia.
IV. Pulmonary Vasodilators
Perioperative RVF is usually associated with increased PVR, either as the
underlying cause or the precipitant. Since the RV is poorly adapted to tolerate
acute changes in afterload, vasodilator therapy aims to decrease RV afterload,
thereby improving physiological coupling between the RV and pulmonary
circulation and leading to increased CO[12]. Pulmonary vasodilators have been
described as being the cornerstone of RVF treatment[32]. Specific pulmonary
vasodilators help by decreasing afterload, and contain HPV. In the chronic setting,
they may also influence remodelling of pulmonary vessels[12]. These beneficial
effects may come at the expense of decreased SVR, hypotension and can
potentially worsen RV preload and ischaemia – especially with non-selective
agents and in unstable patients. Pulmonary vasodilators should therefore be used
after optimisation of RV perfusion and CO, or in conjunction with
vasopressors/inotropic agents[12].
- Intravenous Pulmonary Vasodilators [4, 16]: such as Ca channel blockers,
adenosine, Mg, Nitroglycerin and PDE inhibitors reduce PVR. Besides the
potential haemodynamic side effects, their non-selective actions may also
worsen ventilation/perfusion matching.
- Prostanoids [4, 8, 12]: include prostaglandin I2 (Prostacyclin, PGI2) and its
analogues – iloprost, and prostaglandin E1 (Alprostadil). An important difference
between the different preparations is their half-lives. Prostacyclin is derived from
Page 29 of 37
endothelial cells and is a potent systemic and pulmonary vasodilator, with
antiplatelet and antiproliferative effects. It has been shown to improve survival in
patients with Idiopathic PAH and is effective in decreasing PVR and ARDS and
following mitral valve surgery[4].
- These agents may worsen ventilation/perfusion mismatching or increase PAWP
in patients with severe LV dysfunction. Their potent anticoagulant effects must
also be kept in mind, especially in patients post-surgery, those on heparin
infusions, and those in whom neuraxial anaesthesia is planned.
- PDE5 Inhibitors [12, 13, 30]: including Sildenafil, inhibit breakdown of cyclic GMP by
the PDE V isoenzyme, potentiating the beneficial effects of Nitric Oxide (NO),
ie. Pulmonary vasodilatation – thereby acutely decreasing PVR, increasing CO,
and decreasing PAWP. PDE5 inhibitors may also exert Milrinone like effects
through PDE3 inhibition, augmenting RV function[12]. Adverse effects include
decreased SVR and hence decreased RV performance.
- Inhaled Pulmonary Vasodilators [4, 12, 30, 32]: Inhaled prostacyclin and iNO cause
selective pulmonary vasodilatation in well ventilated areas, decreasing PVR and
improving ventilation/perfusion matching.
iNO is a potent pulmonary vasodilator with a short half-life due to inactivation by
haemoglobin – which decreases its systemic effects. It does require continuous
delivery into the ventilator circuit, which is practically difficult. Other limitations
include: accumulation of toxic metabolites leading to methaemoglobinaemia and
rebound PH after weaning. iNO decreases PVR and improves CO in PAH,
secondary PH, acute PE, ischaemic RV dysfunction and postsurgical PH[12]. It
has also been shown to benefit patients with acute RVF secondary to ARDS, and
to decrease inflammatory cytokine production[32]. The use of iNO prophylactically
in patients with PH undergoing cardiac surgery is controversial.
Inhaled Iloprost is more convenient to administer due to its longer half-life and
comparable efficacy. Continuous nebulisation is not required. It has been shown
to be more effective than NO in decreasing PVR and improving CO in patients
with PH after CPB, and in PAH[12]. Other advantages include decreased systemic
effects and no need for additional equipment or monitoring.
Selective Oral Pulmonary Vasodilators [4, 12]: Sildenafil as already mentioned is a
potent pulmonary vasodilator and leads to decreased PVR. It maintains SVR and
improved myocardial perfusion and has been used effectively in selected patients
-eg. post CABG, and children undergoing congenital heart surgery. It has
lusitropic and inotropic effects in the hypertrophied RV and decreases RV mass in
patients with PAH. It can also be used to improve pulmonary haemodynamics and
exercise capacity in patients with systolic LV dysfunction. It may improve
myocardial perfusion, reduce platelet activation, and decrease endothelial
dysfunction post CPB[12]. In one study, 25-50 mg was shown to produce a
49%decrease in PVR within 30min of administration[4], and some authors quote
that even a single dose may facilitate weaning from NO[12].
Page 30 of 37
Bosentan – an endothelin II antagonist, also produces selective pulmonary
vasodilatation and is effective in management of Primary PPPH, CTEPH,
Congenital heart disease and Eisenmengers syndrome[4]. Its use is contraindicated in pregnancy and there is still limited experience in its peri-operative
use[13]. Several combinations of pulmonary vasodilators have been shown to
produce greater effects than single agents, eg. Inhaled iloprost + iNO; oral
sildenafil + inhaled iloprost.
V. Vasopressors
Vasopressors increase coronary perfusion pressure by increased SVR. This may
also benefit ventricular interdependence by shifting the IV septum back towards
the RV. This leads to improved LV output, and may improve and even reverse RV
ischaemia[4]. Vasopressors may also be initiated to compensate for systemic
hypotension caused by systemic side effects of pulmonary vasodilators or
inodilators. The ideal agent would increase SVR without affecting PVR and
without causing a tachycardia.
Vasopressin has been shown in animal studies to cause vasoconstriction and
pulmonary vasodilatation due to stimulation of NO release. In humans, the effects
have been variable, and it should be considered especially in refractory cases[4].
Phenylephrine is a direct alpha-1 agonist and improves right coronary perfusion
without causing tachycardia. It may cause increased PVR and hence worsen RV
function. It may be less effective than noradrenaline in treating hypotension post
induction of anaesthesia in patients with RVF[4].
Noradrenaline exerts its vasopressor effects through alpha-1 agonism and is also
positively inotropic through beta-1 stimulation – it can therefore improve RV-PA
coupling, CO, and RV performance; but it may have adverse effects on PVR at
high doses (ie. >0.5mcg/kg/min) [12].
VI. Inotropes
Inotropes are indicated in patients with acute RVF and decreased CO, as it
improves myocardial function. There is limited data available to guide which agent
is best.
Adrenaline decreases PVR, PAP, and the PVR/SVR ratio.
Dobutamine at doses up to 5mcg/kg/min, has been considered the drug of choice
in patients with RV infarction[4]. It is also useful in patients with RVF due to acute
pressure overload as it increases myocardial contractility, decreases PVR and
SVR. It has been shown to have synergistic effects when used with NO in patients
with PH[12]. It can induce tachycardia, especially at higher doses, and is therefore
not ideal in patients with tachyarrhythmia[30].
PDE3 Inhibitors increase intracellular cAMP and augment myocardial
contractility[12]. It also produces systemic and pulmonary vasodilatation.
Page 31 of 37
The selective agents include enoximone, milrinone and amrinone. Milrinone[12] is
most frequently used and has been shown to decrease pulmonary pressures and
augment RV function. Nebulised milrinone has been used to manage PH crises –
through pulmonary selectivity, it causes less systemic hypotension and less V/Q
mismatching compared to intravenous use. When combined with iNO, it produces
greater decrease in PAP than either agent alone. In animal studies, when
combined with oral sildenafil, it was also shown to decrease PVR significantly
more than either agent alone, without causing any further decrease in SVR[12].
Due to the side effects of systemic hypotension, it is often co-administered with
vasopressors: Milrinone+Vasopressin is superior to Milrinone+Noradrenaline in
RV dysfunction[12]. Levosimendan sensitises troponin C in the myocardium to
calcium, leading to improved diastolic function and myocardial contractility. It also
has global vasodilatory and anti-ischaemic properties - through K+ channel
opening in vascular smooth muscle cells and endothelin1 inhibition; and specific
pulmonary vasodilatory properties - through PDE3 inhibition[32]. By decreasing
PVR, it appears to improve RV-PA coupling, hence overall improving RV
function[12].
Most of the studies have been conducted on animals in an experimental RVF
setting and although there is some evidence of the benefits of Levosimendan in
clinical situations – such as RV ischaemia, ARDS and post mitral valve
replacement, further studies in acute RVF are needed[32]. In a systematic review
and analysis of research from 1980-2010, Price and colleagues make
recommendations based on the GRADE method, to guide the management of
pulmonary vascular and pulmonary dysfunction[12]. The breakdown of articles
incorporated into the systematic search is shown in Table 6.
Page 32 of 37
Table 6. Breakdown of Clinical Articles in Systematic review by Price and
Colleagues[12]
Subtype of treatment
Number of studies in initial
search
Number of suitable studies
included in the review
Volume therapy
113
5
Vasopressors
388
28
Sympathetic Inotropes
565
8
Inodilators
280
17
Levosimendan
172
12
Pulmonary Vasodilators
586
121
Mechanical Devices
47
19
Their recommendations based on the quality of evidence (STRONG/WEAK) were:
- WEAK: Close monitoring of fluid status according to effects on RV function
- WEAK: Noradrenaline may be an effective systemic pressor in patients with
acute RV dysfunction and RV failure
- WEAK: Low dose Vasopressin may be useful in difficult cases that are
resistant to usual treatments
- WEAK: Low dose Dobutamine improves RV function, it may reduce SVR
- STRONG: Dopamine may increase tachyarrhythmias, and it is not
recommended
- WEAK: Levosimendan may be considered for short term improvements in
RV performance
- STRONG: Pulmonary vasodilators decrease PVR, improve CO, and
oxygenation
- STRONG: Consideration should be given to use of inhaled rather than
systemic agents when systemic hypotension is likely, and concomitant
vasopressor use should be anticipated
- STRONG: Give consideration for use of NO as a short term therapy
- WEAK: Oral Sildenafil may decrease PVR and facilitate weaning from NO in
selected patients, without adverse effects on systemic blood pressure.
Page 33 of 37
VII. Mechanical Support of the Right Ventricle
Mechanical support of the RV can be considered in patients with severe RVF
refractory to medical therapy: if there is a potentially reversible cause, if the
patient is awaiting corrective surgery, or if the patient is a candidate for heart-lung
transplantation.
An intra-aortic balloon pump may improve RV perfusion by augmenting right
coronary artery perfusion, but this does not necessarily mean that RV function will
improve[4], and it is generally only used for short term support. It may also be used
to allow for weaning of vasopressors[8]. Extracorporeal Membrane Oxygenation
has been used in severe PH as a bridge to transplantation, and after
endarterectomy or massive PE[32]. Atrial Septostomy: has evolved from the
observation that patients with PH and a patent foramen ovale survived longer than
those without[24].
In this surgical procedure, a shunt is created between the atria, allowing for
decompression of the right side, a decrease in RVEDP, decrease wall tension,
and increased contractility. The resulting desaturation caused by the right to left
shunt can be controlled with supplemental oxygen[8]. This procedure is generally
only considered when all other interventions have failed – it is considered
palliative[25]. It may also be used as a bridge to transplantation.
F. Post-operative considerations [37]
Understanding of the impact that PH and RV dysfunction have on peri-operative
outcome in non-cardiac surgery is still incomplete[38]. Post-operative complications
include: heart failure, respiratory failure (delayed extubation, re-intubation),
myocardial ischemia or infarction, stroke, dysrrhythmias, and in-hospital death.
In a study investigating postoperative outcomes in non-cardiac surgery by Lai and
colleagues[38], most post-operative deaths were preceded by refractory
hypoxaemia and cardio-pulmonary failure. The authors suggest that surgical
stress, pain, fluid shifts, nutritional insufficiency, sympathetic activation and
potential infection; compromise pulmonary oxygenation and CO. Therefore,
careful postoperative management is necessary to prevent worsening RV
dysfunction and failure.
Attention should be paid to volume status, ventilation and oxygenation levels,
acid-base status, blood pressure, and heart rate. Continued administration of
vasopressors/pulmonary vasodilators/inotropes may be necessary. Adequate
analgesia is important to prevent sympathetic stimulation – which worsens PH; but
this must be balanced against the negative effects of analgesics (especially
opioids) on cardiopulmonary function.
Good postoperative management depends on:
- A thorough preoperative assessment (to risk stratify the patient)
- Communication between the surgeon, anaesthesiologist, physician, and
intensivist
- Prior planning for postoperative care including level of care (ICU vs. high care
vs. general ward)
Page 34 of 37
CONCLUSION
The peri-operative management of patients with RV dysfunction is complex and
requires multiple steps:
- Recognising the disorder
- Diagnosing the cause
- Assessing disease severity
- Evaluating risks and benefits of anaesthesia and surgery
- Formulating an anaesthetic plan and
- Managing the peri-operative complications that may arise
Minimizing PVR and maintaining MAP, ie. “RV Protection,” are of major
importance in the prevention of decompensated RVF – which is characterised by
rising CVP and falling CO. Thus, the anaesthesiologist must have knowledge of
RV physiology, the underlying pathophysiology of perioperative RV dysfunction,
and the potential treatment strategies available including optimising physiological
parameters, use of selective pulmonary vasodilators, and vasopressor and
inotropic support.
.
Improved understanding of the complex RV may also increase interest in the
neglected disorder of RVF and may facilitate research. This need for further
research has been highlighted by the National Heart, Lung and Blood Institute
Working Group on Cellular and Molecular Mechanisms of Right Heart Failure [5],
as they recognise the pivotal impact that the right ventricle has on the outcome of
various disease states, both common and rare. They state that further research
should be a high priority.
Page 35 of 37
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