Download Managing low cardiac output syndrome after congenital heart surgery

Managing low cardiac output syndrome after congenital heart
surgery
David L. Wessel, MD
P
atients with congenital or acquired heart disease comprise
a major diagnostic category for
admissions in large pediatric
intensive care units (ICUs) across the
country, compromising 30% to 40% or
more of admissions in many centers. Obviously, assessment and treatment of low
cardiac output states among patients
with heart disease can be life saving. Although some causes of low cardiac output after cardiopulmonary bypass (CPB)
are attributable to residual or undiagnosed structural lesions, progressive low
cardiac output states do occur (1). A
number of factors have been implicated
in the development of myocardial dysfunction after CPB, including the following: 1) the inflammatory response associated with CPB; 2) the effects of
myocardial ischemia from aortic crossclamping; 3) hypothermia; 4) reperfusion
injury; 5) inadequate myocardial protection; and 6) ventriculotomy (when performed). The expression and prevention
of reperfusion injury after aortic crossclamping on CPB is currently the subject
of intense investigation. Figure 1 shows
the typical decrease in cardiac index in
newborns after an arterial switch operation. In this group of 122 newborns, the
median maximal decrease in cardiac index, which occurred typically 6-12 hrs
after separation from CPB, was 32% (2). A
quarter of all these newborns reached a
nadir of cardiac index that was ⬍2
From Cardiac Intensive Care, Children’s Hospital,
and Harvard Medical School, Boston, MA.
Key Words: catecholamines; phosphodiesterase
inhibitors; extracorporeal membrane oxygenation; cardiopulmonary bypass; milrinone; pulmonary hypertension
Address requests for reprints to: David L. Wessel,
MD, Director, CICU Office, Children’s Hospital, 300
Longwood Avenue, Boston, MA 02115. E-mail:
[email protected]
Copyright © 2001 by the Society of Critical Care
Medicine
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L/min/m 2 on the first postoperative
night. Low cardiac output states do occur
in the postoperative patient, but appropriate anticipation and intervention can
do much to avert morbidity or the need
for mechanical support (Table 1).
Volume Adjustments
After CPB, the factors that influence
cardiac output, preload, afterload, myocardial contractility, heart rate, and
rhythm must be assessed and manipulated. Volume therapy (increased preload)
is commonly necessary, followed by appropriate use of inotropic and afterloadreducing agents (3). Atrial pressure and
the ventricular response to changes in
atrial pressure must be evaluated. Ventricular response is judged by observing
systemic arterial pressure and waveform,
heart rate, skin color and peripheral extremity temperature, peripheral pulse
magnitude, urine flow, core body temperature, and acid-base balance.
Preserving and Creating Rightto-Left Shunts
Selected children with low cardiac
output may benefit from strategies that
allow right-to-left shunting at the atrial
level in the face of postoperative right
ventricular dysfunction. A typical example is early repair of tetralogy of Fallot,
when the moderately hypertrophied,
noncompliant right ventricle has undergone a ventriculotomy and may be further compromised by an increased volume load from pulmonary regurgitation
secondary to a transannular patch on the
right ventricular outflow tract. In these
children it is very useful to leave the
foramen ovale patent to permit right-toleft shunting of blood, thus preserving
cardiac output and oxygen delivery, despite the attendant transient cyanosis. If
the foramen is not patent or is surgically
closed, right ventricular dysfunction can
lead to reduced left ventricular filling,
low cardiac output, and ultimately, left
ventricular dysfunction. In infants and
neonates with repaired truncus arteriosus, the same concerns apply and may
even be exaggerated if right ventricular
afterload is elevated because of pulmonary artery hypertension (4). This concept has been extended to older patients
with single-ventricle physiology who are
at high risk for Fontan operations. The
Fontan circulation relies on passive flow
of blood through the pulmonary circulation, without benefit of a pulmonary ventricle. If an atrial septal communication
or fenestration is left at the time of the
Fontan procedure, the resulting right-toleft shunt helps to preserve cardiac output. These children have fewer postoperative complications (5). It is better to
shunt blood right to left, accept some
decrement in oxygen saturation, but
maintain ventricular filling and cardiac
output than to have high oxygen saturation but low blood pressure and cardiac
output.
Other Strategies
Newer strategies to support low cardiac output associated with cardiac surgery in children include the use of atriobiventricular pacing for patients with
complete heart block or prolonged interventricular conduction delays and asynchronous contraction. Appreciation of
the hemodynamic effects of positive and
negative pressure ventilation may facilitate cardiac output. Avoidance of hyperthermia and even induced hypothermia
may provide end organ protection during
periods of low cardiac output. Finally,
anti-inflammatory agents including
monoclonal antibodies, competitive receptor blockers, inhibitors of compliment
activation, and preoperative preparation
with steroids are being actively investiCrit Care Med 2001 Vol. 29, No. 10 (Suppl.)
Table 1. Managing low cardiac output syndrome after congenital heart surgery
Figure 1. Typical decrease in cardiac index in
newborns after an arterial switch operation.
gated in an effort to prevent and protect
major organs from ischemic injury imposed by CPB and the reperfusion injury
associated with the recovery period.
Pharmacologic Support
Catecholamines. Failure to improve
cardiac output after volume adjustments
requires the additional use of an inotropic drug (3, 6 –9). Table 2 lists commonly
used vasoactive drugs and their actions.
Many prefer to use dopamine first in
doses of 3–10 ␮g/kg/min. One rarely uses
⬎15 ␮g/kg/min because of the known
vasoconstrictor and chronotropic properties of dopamine at very high doses. However, extreme biologic variability in pharmacokinetics and pharmacodynamics
defies placing narrow limits on recommended dosages. Dobutamine’s chronotropic and vasodilatory advantages recognized in adults with coronary artery
disease have not always proved equally
efficacious in clinical studies in children.
In fact, dobutamine has fewer, or no, dopaminergic advantages for the kidney.
This may be an especially important limitation in infants with excess total body
water and interstitial edema. The significant chronotropic effect and increased
oxygen consumption induced by isoproterenol have also increasingly limited its
use in neonates and infants. Epinephrine
is occasionally useful for short-term therapy when high systemic pressures are
sought, provided the temporary increase
in peripheral vascular resistance can be
tolerated. High doses of epinephrine are
occasionally necessary to increase pulmonary blood flow across significantly narrowed systemic-to-pulmonary artery
shunts when oxygen saturations are low
and falling. Arginine vasopressin has
been advocated for states of refractory
vasodilation associated with low circulating vasopressin levels as may rarely occur
after CPB in children (10).
Crit Care Med 2001 Vol. 29, No. 10 (Suppl.)
I. Extent of the problem
A. One quarter of newborns will decrease their cardiac index to ⬍2.0 L/min/m2 after CPB
II. Exclude residual disease
A. Transesophageal echocardiography and intracardiac catheters provide important
anatomic and physiologic data for planning the need for reintervention
III. Optimize preload
A. Monitor filling pressure and interpret values in light of underlying cardiac disease
IV. Enable R3L shunting for right heart failure
A. Newborn after right ventriculotomy (TOF and truncus arteriosus)
B. Baffle fenestration in patients undergoing a Fontan operation helps preserve cardiac
output and oxygen delivery and reduces right atrial pressure
C. Preserving a R3L shunt in patients with known elevation in pulmonary vascular
resistance may preserve cardiac output during postoperative pulmonary hypertensive
crises or during CPR
V. Pharmacologic support
A. Catecholamines
1. Dopamine (5–15 ␮g/kg/min) supports cardiac output and preserves aortic perfusion
pressure during weaning from CPB; dobutamine may reduce afterload
2. Prolonged high-dose epinephrine after CPB in neonates is associated with myocardial
necrosis and marked diastolic dysfunction and is increasingly avoided
B. Afterload reduction
1. Milrinone, a phosphodiesterase inhibitor, increases cardiac output and lowers filling
pressures; nitrates are commonly employed as vasodilators
2. Phenoxybenzamine is a potent ␣-blocker and has been advocated as part of the
postoperative management of patients with hypoplastic left heart syndrome but has a
long duration of action
3. Nitric oxide is a selective pulmonary vasodilator that will reduce afterload on the
right heart
VI. Rhythm
A. A-V sequential pacing is important for arrhythmias, such as JET or complete heart
block
B. Atrio-biventricular pacing may improve hemodynamics substantially in patients with
complete right or left bundle branch block
VII. Ventilation/cardiorespiratory interactions
A. Positive pressure ventilation reduces left ventricular afterload but decreases preload and
may raise pulmonary vascular resistance and RV afterload
B. Negative pressure ventilation (Hayek oscillator) may augment R heart function
VIII. Hypothermia
A. There is renewed interest in lowering core body temperature to 34–35°C for patients in
low cardiac output states in an effort to reduce oxygen consumption and to optimize
oxygen delivery
IX. Ischemia reperfusion injury
A. Anti-inflammatory agents including monoclonal antibodies, competitive receptor
blockers, inhibitors of compliment activation, and preoperative preparation with
steroids are being actively investigated in an effort to prevent and protect major organs
from ischemic injury imposed by cardiopulmonary bypass and the reperfusion injury
associated with the recovery period
X. Mechanical support
A. Extracorporeal membrane oxygenation
B. Ventricular assist device
CPB, cardiopulmonary bypass; R, right; L, left; TOF, tetralogy of Fallot; CPR, cardiopulmonary
resuscitation; A-V, atrioventricular; JET, junctional ectopic tachycardia; RV, right ventricular.
In the past, the side effects of inotropic
support of the heart with catecholamines
seemed a lesser concern in children than in
adults with an ischemic, noncompliant
heart. Tachycardia, an increased enddiastolic pressure and afterload, or increased myocardial oxygen consumption,
despite their undesirable side effects, was
tolerated by most children in need of inotropic support after CPB. However, with
increasing perioperative experience in neonates and young infants, the adverse effects
of vasoactive drugs have become more ev-
ident. The less compliant neonatal myocardium, like the ischemic adult heart, may
raise its end-diastolic pressure during
higher doses of dopamine infusion or may
develop even more extreme noncompliance. Actual myocardial necrosis caused by
high doses of epinephrine infusions has
been identified in neonatal animal models
after CPB (11, 12). Although these agents
do increase the cardiac output, the concomitant increase in ventricular filling
pressure is less well tolerated by the immature myocardium than it is in older chilS221
Table 2. Summary of selected vasoactive agents
Agent
Noncatecholamines
Digoxin (total
digitalizing dose)
Doses (IV)
Peripheral Vascular Effect
Cardiac Effect
Conduction System Effect
Increases peripheral vascular
resistance 1–2⫹; acts directly
on vascular smooth muscle
Inotropic effect 3–4⫹;
acts directly on
myocardium
Slows sinus node slightly;
decreases A-V
conduction more
Calcium chloride
Calcium gluconate
20 ␮g/kg premature
30 ␮g/kg neonate (0–1 mo)
40 ␮g/kg infant (⬍2 yrs)
30 ␮g/kg child (2–5 yrs)
20 ␮g/kg child (⬎5 yrs)
10–20 mg/kg/dose (slowly)
50–100 mg/kg/dose (slowly)
Variable; age dependent;
vasoconstrictor
Inotropic effect 3⫹;
depends on ionized
Ca2⫹
Slows sinus node;
decreases A-V
conduction
Nitroprusside
0.5–5 ␮g/kg/min
0.5–10 ␮/kg/min
Amrinone
1–3 mg/kg loading dose
5–20 ␮g/kg/min
maintenance
50 ␮g/kg loading dose
0.25–1.0 ␮/kg/min
maintenance
0.003–0.002 U/kg/min
Indirectly increases
cardiac output by
decreasing afterload
Decreases preload, may
decrease afterload;
reduces myocardial
work related to
change in wall stress
Diastolic relaxation
(lusitropy)
Reflex tachycardia
Nitroglycerin
Donates nitric oxide group to
relax smooth muscle and dilate
pulmonary and systemic vessels
Primarily venodilator; as a nitric
oxide donor may cause
pulmonary vasodilation and
enhance coronary vasoreactivity
after aortic cross-clamping
Systemic and pulmonary
vasodilator; thrombocytopenia
As above; shorter half-life
As above
As above
Potent vasoconstrictor
No direct effect
None known
Milrinone
Vasopressin
Peripheral Vascular Effect
Agent
Dose Range
Alpha
Beta2
Delta
Beta1
Beta2
Catecholamines
Phenylephrine
0.1–0.5 ␮g/kg/min
4⫹
0
0
0
0
Isoproterenol
0.05–0.5 ␮g/kg/min
0
4⫹
0
4⫹
4⫹
Norepinephrine
0.1–0.5 ␮g/kg/min
4⫹
0
0
2⫹
0
Epinephrine
0.03–0.1 ␮g/kg/min
0.2–0.5 ␮g/kg/min
2⫹
4⫹
1–2⫹
0
0
0
2–3⫹
4⫹
2⫹
3⫹
Dopamine
2–4 ␮g/kg/min
4–8 ␮g/kg/min
⬎10 ␮g/kg/min
2–10 ␮g/kg/min
0
0
2–4⫹
1⫹
0
2⫹
0
2⫹
2⫹
2⫹
0
0
0
1–2⫹
1–2⫹
3–4⫹
0
1⫹
2⫹
1–2⫹
Dobutamine
Minimal
Minimal tachycardia
Cardiac Effect
Comment
Increases systemic resistance, no inotropy; may cause
renal ischemia; useful for treatment of TOF spells
Strong inotropic and chronotropic agent; peripheral
vasodilator; reduces preload; pulmonary
vasodilator; limited by tachycardia and oxygen
consumption
Increases systemic resistance; moderately inotropic;
may cause renal ischemia
Beta2 effect with lower doses; best for blood pressure
in anaphylaxis and drug toxicity
Splanchnic and renal vasodilator; may be used with
isoproterenol; increasing doses produce increasing
␣-effect
Less chronotropy and arrhythmias at lower doses;
effects vary with dose similar to dopamine;
chronotropic advantage compared with dopamine
may not be apparent in neonates
A-V, atrioventricular; TOF, tetralogy of Fallot.
dren. Many of the complex corrective procedures performed in neonates and small
infants are accompanied by transient postoperative arrhythmias that are either induced or exacerbated by catecholamines,
which can have a profound adverse effect
on the patient’s recovery after surgery. Diastolic function is crucial in older patients
with single ventricles and can be adversely
affected by catecholamines. Nevertheless,
the predictable and often significant decrease in cardiac output documented by
many investigators after CPB in infants and
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older children continues to justify the practice of judiciously using inotropic agents to
support the heart and circulation while
weaning them from CPB and during the
immediate postoperative period (6).
Phosphodiesterase III Inhibitors. Amrinone and milrinone have emerged as
important inotropic agents for use in
children after open heart surgery. They
are nonglycosidic, noncatecholamine
inotropic agent with additional vasodilatory and lusitropic properties. They have
been used extensively in adults for the
treatment of chronic congestive heart
failure and, more recently, introduced to
pediatric practice (5, 13, 14). These drugs
exert their principal effects by inhibiting
phosphodiesterase, the enzyme that metabolizes cyclic adenosine monophosphate (cAMP). By increasing intracellular
cAMP, calcium transport into the cell is
favored, and the increased intracellular
calcium stores enhance the contractile
state of the myocyte. In addition, the reuptake of calcium is a cAMP-dependent
process, and these agents may, therefore,
Crit Care Med 2001 Vol. 29, No. 10 (Suppl.)
enhance diastolic relaxation of the myocardium by increasing the rate of calcium
re-uptake after systole (lusitropy). The
drug also appears to work synergistically
with low doses of ß-agonists and has
fewer side effects than other catecholamine vasodilators, such as isoproterenol. Although the use of amrinone, beginning in the operating room, has
become more commonplace in many cardiovascular centers (9, 15), the half-life of
2– 4 hrs rather than minutes and its potential toxicity in the face of hepatic and
renal failure have discouraged some from
using this drug more frequently. Milrinone has the advantage of a shorter halflife and may, therefore, be more titratable
in the face of hemodynamic instability
(16, 17). It also may have a lower incidence of thrombocytopenia and is preferable when longer term use of a phosphodiesterase inhibitor is indicated.
Other Afterload-Reducing Agents.
When systemic blood pressure is elevated
and cardiac output appears low or normal, a primary vasodilator is indicated to
normalize blood pressure and to decrease
the afterload on the left ventricle. This is
especially true for the newborn myocardium, which is especially sensitive to
changes in afterload and tolerates elevated systemic resistances poorly. Although nitroprusside has no known direct inotropic effects, this potent
vasodilator has the advantage of being
readily titratable and possessing a short
biologic half-life. Use of nitroglycerin
avoids the toxic metabolites, cyanide and
thiocyanate, associated with nitroprusside use (especially in hepatic and renal
insufficiency), but its potency as a vasodilator is less than that of nitroprusside.
Inhibitors of angiotensin-converting enzyme have proven to be important adjuvants to chronic anticongestive therapy
in pediatric patients. Intravenous forms
are available and may be useful in the
treatment of systemic hypertension immediately after coarctation repair or
when afterload reduction with these inhibitors would benefit patients unable to
receive oral medications (18).
control of right ventricular afterload (21–
24).
Although it is understandable to presume that postoperative patients with
pulmonary hypertension have active and
reversible pulmonary vasoconstriction as
the source of their pathophysiology, the
critical care physician is obligated to explore anatomical causes of mechanical
obstruction that impose a barrier to pulmonary blood flow. Elevated left atrial
pressure, pulmonary venous obstruction,
branch pulmonary artery stenosis, or surgically induced loss of the vascular tree
all will raise right ventricular pressure
and impose an unnecessary burden on
the right heart. Similarly, a residual or
undiagnosed left-to-right shunt will raise
pulmonary artery pressure postoperatively and must be addressed surgically.
Extended use of pulmonary vasodilator
strategies will only augment residual or
undiagnosed shunts and increase the volume load on the heart
Several factors peculiar to CPB may
raise pulmonary vascular resistance:
microemboli, pulmonary leukosequestration, excess thromboxane production, atelectasis, hypoxic pulmonary vasoconstriction, and adrenergic events
have all been suggested to play a role in
postoperative pulmonary hypertension
(23, 25). Postoperative pulmonary vascular reactivity has been related not
only to the presence of preoperative
pulmonary hypertension and left-toright shunts (19, 22, 26), but also to the
duration of total CPB (27, 28). Treatment of postoperative pulmonary hypertensive crises has been partially addressed by surgery at earlier ages,
pharmacologic intervention, and other
postoperative management strategies
(Table 3). However, recent developments in vascular biology offer new insights into the possible causes and cor-
Pulmonary Hypertension
3.
4.
5.
6.
7.
8.
9.
10.
Anatomical Considerations. Children
with many forms of congenital heart disease are prone to develop perioperative
elevations in pulmonary vascular resistance (19, 20). This may complicate the
postoperative course, when transient
myocardial dysfunction requires optimal
Crit Care Med 2001 Vol. 29, No. 10 (Suppl.)
rection of post-CPB pulmonary
hypertension.
Pulmonary Vasodilators. Success with
vasodilators for the treatment of pulmonary hypertension caused by pulmonary
vasoconstriction has had mixed results
because of systemic vasodilating effects
that may predominate and limit effectiveness. Tolazine, prostaglandin E1, and
prostacyclin have all been suggested as
useful pharmacologic treatments for this
condition (Table 4) (29 –32). Nitric oxide
(NO) is a selective pulmonary vasodilator
that can be breathed as a gas and distributed across the alveoli to the pulmonary
vascular smooth muscle. Nitric oxide is
formed by the endothelium from L arginine and molecular oxygen in a reaction catalyzed by NO synthase. It then
diffuses to the adjacent vascular smooth
muscle cells where it induces vasodilation through a cyclic guanosine monophosphate-dependent pathway (33–37).
Because NO exists as a gas it can be
delivered by inhalation to the alveoli and
then to the blood vessels that lie in close
proximity to the ventilated lung. Because
of its rapid inactivation by hemoglobin,
inhaled NO may achieve selective pulmonary vasodilation when pulmonary vasoconstriction exists. It has advantages over
intravenously administered vasodilators
that cause systemic hypotension and increase intrapulmonary shunting. Inhaled
NO lowers pulmonary artery pressure in a
number of diseases without the unwanted
effect of systemic hypotension. This is
especially dramatic in children with cardiovascular disorders and postoperative
patients with pulmonary hypertensive
crises.
Pulmonary vascular endothelial dysfunction may be a contributing factor in
post-CPB pulmonary hypertension.
Structural damage to the pulmonary endothelium is demonstrable after CPB,
Table 3. Critical care strategies for treatment of pulmonary hypertension
Encourage
1.
2.
Anatomic investigation
Opportunities for right-to-left shunt
as “pop off” in right heart failure
Sedation/anesthesia
Moderate hyperventilation
Moderate alkalosis
Adequate inspired oxygen
Normal lung volumes
Optimal hematocrit
Inotropic support
Vasodilators
Avoid
1. Residual anatomic disease
2. Intact atrial septum in right heart
3.
4.
5.
6.
7.
8.
9.
10.
Agitation/pain
Respiratory acidosis
Metabolic acidosis
Alveolar hypoxia
Atelectasis or overdistention
Excessive hematocrit
Low output and coronary perfusion
Vasoconstrictors/increased afterload
See text for explanation and detail.
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Table 4. Pharmacologic agents available as pulmonary vasodilators during acute illness
Drug Class
Advantages
Nitrates
Easily titratable, rapid onset and offset
␣-Antagonists
Powerful, dense blockade
Angiotensin converting enzyme
inhibitors
Calcium channel blockers
Orally active, facilitates myocardial remodeling
Prostaglandins (e.g., prostacyclin)
Good afterload reduction, increases cardiac output,
some pulmonary selectivity, titratable, long-term
benefit for remodeling, antiplatelet, and
cytoprotective effect
Effective for disease states with high endothelin
levels; may be tailored to have some pulmonary
specificity
Increases cardiac output, titratable
Endothelin receptor blockers
␤-Agonists
Phosphodiesterase inhibitors type III
Phosphodiesterase inhibitors type V
Inhaled nitric oxide
Orally active, best defined role in primary pulmonary
hypertension
Increases contractile function, reduces afterload,
lowers filling pressures, acts synergistically with
catecholamines, not arrhythmogenic
Orally active, acts synergistically with inhaled nitric
oxide to raise cGMP, attenuates withdrawal
response to nitric oxide, may have utility as
single-agent pulmonary vasodilator
Selective potent pulmonary vasodilator, rapid onset,
improves intrapulmonary shunt, no myocardial
depression, may have benefit from selected longterm applications
Disadvantages
Nonspecific, tachycardia, tachyphylaxis, cyanide
toxicity
Nonspecific, very long duration of action, serious
systemic hypotension
Little effect on pulmonary circulation
Myocardial depression, raises end-diastolic
pressure, bradycardia, sudden death,
hypotension in infants
Systemic hypotension, increases intrapulmonary
shunt, value in acute illness unproven, longterm administration, requires central vascular
access, expensive
Clinical experience is preliminary, range of
applicable disease states may be limited
Nonspecific, tachycardia, increases myocardial
oxygen demand, maldistribution of cardiac
output, arrhythmogenic
Nonspecific, hypotension at high doses for
refractory pulmonary hypertension, slightly
long duration of action (1–3 hrs)
Clinical experience is preliminary, may be
nonspecific vasodilator, longer acting oral or
intravenous forms under development,
concomitant nitrate therapy contraindicated
(hypotension)
Methemoglobin, nitrogen dioxide, complex
delivery, rebound effects, short acting,
expensive
cGMP, cyclic guanine monophosphate.
and the degree of pulmonary hypertension is correlated with the extent of endothelial damage after CPB (27, 28). The
decreased pulmonary blood flow on CPB
may result in postoperative impairment
of endothelial function and the inability
to release nitric oxide. Transient pulmonary vascular endothelial cell dysfunction
has been demonstrated in neonates and
older children by documenting the transient loss of endothelium-dependent vasodilation immediately after CPB (38).
NO production measured by exhaled NO
is reduced postoperatively (39). This and
other evidence provides a theoretical basis for administering NO after surgery.
Therapeutic uses of inhaled NO in
children with congenital heart disease
abound. For example, newborns with total anomalous pulmonary venous connection (TAPVC) frequently have obstruction of the pulmonary venous pathway as
it connects anomalously to the systemic
venous circulation. When pulmonary venous return is obstructed preoperatively,
pulmonary hypertension is severe and demands urgent surgical relief. Increased
neonatal pulmonary vasoreactivity, endoS224
thelial injury induced by CPB, and intrauterine anatomical changes in the pulmonary vascular bed in this disease (40)
contribute to postoperative pulmonary
hypertension. In one study, 20 infants
presenting with isolated TAPVC were
monitored for pulmonary hypertension.
A mean percentage decrease of 42% in
pulmonary vascular resistance and 32%
in mean pulmonary artery pressure was
demonstrated with 80 ppm of NO. There
was no significant change in heart rate,
systemic blood pressure, or vascular resistance (41).
Inhaled NO can also be used diagnostically in neonates with right ventricular
hypertension after cardiac surgery to discern those with reversible vasoconstriction. Failure of the postoperative newborn with pulmonary hypertension to
respond to NO successfully discriminated
anatomical obstruction to pulmonary
blood flow from pulmonary vasoconstriction (42). Failure of the postoperative
newborn to respond to NO should be regarded as strong evidence of anatomical
and possibly surgically remediable obstruction.
Patients with TAPVC, congenital mitral stenosis, and other pulmonary venous hypertensive disorders associated
with low cardiac output appear to be
among the most responsive to NO. These
infants are born with significantly increased amounts of smooth muscle in
their pulmonary veins. Histologic evidence of muscularized pulmonary veins
as well as pulmonary arteries suggest the
presence of vascular tone and capacity for
change in resistance at both the arterial
and venous sites. The increased responsiveness seen in younger patients with
pulmonary venous hypertension to NO
may result from pulmonary vasorelaxation at a combination of pre- and postcapillary vessels.
Successful use of inhaled NO in a variety of congenital heart defects after cardiac surgery has been reported by several
groups (43– 46). It may be especially
helpful when administered during a pulmonary hypertensive crisis. Descriptions
of use after Fontan procedures (47) and
after ventricular septal defect repair have
been reported, along with a variety of
other anatomical lesions. Very young inCrit Care Med 2001 Vol. 29, No. 10 (Suppl.)
fants who are excessively cyanotic after a
bidirectional Glenn anastomosis do not
generally improve oxygen saturation in
response to inhaled NO.
At the relatively low levels of NO used
therapeutically (1– 80 ppm), the metabolic fate of inhaled NO is an accumulation of nitrate and nitrite in plasma, a
small increase in methemoglobin but little detectable nitrosylhemoglobin (48).
Possible toxicities of inhaled NO include
methemoglobinemia because of the intravascular binding to hemoglobin (49),
cytotoxic effects in the lung resulting
from free radical formation, development
of excess nitrogen dioxide, peroxynitrite
production, or injury to the pulmonary
surfactant system (50). Carcinogenic and
teratogenic potential of inhaled NO exist,
as well as effects on glutathione metabolism, unknown effects on the immature
or immunocompromised lung, potential
interaction with other heme containing
proteins, and effects on platelet function
and hemostasis.
Caution should be exercised when administering NO to patients with severe
left ventricular dysfunction and pulmonary hypertension. In adults with ischemic cardiomyopathy, sudden pulmonary
vasodilation may occasionally unload the
right ventricle sufficiently to increase
pulmonary blood flow and harmfully augment preload in a compromised left ventricle (51, 52). The attendant rise in left
atrial pressure may produce pulmonary
edema (53). This is not likely to arise
from any negative inotropic effect of NO
(54) and may be ameliorated with vasodilators or diuretics. Clinicians should be
cognizant of this potential adverse effect
during acute testing of unstable patients
during cardiac catheterization, even
though it has not been reported to occur
in children with congenital heart disease.
Abrupt withdrawal effects of NO or even
rebound pulmonary hypertension are important issues. Appreciation of the transient characteristics of withdrawal of NO
may facilitate weaning from NO and has
important implications for patients with
persistent pulmonary hypertensive disorders when interruption of NO is necessary (41, 55). If the underlying pulmonary hypertensive process has not
resolved, then the tendency for an abrupt
increase in pulmonary artery pressure
may be hazardous when NO therapy is
withdrawn or interrupted (56, 57). If
withdrawal of NO is necessary before resolution of the pathologic process, hemodynamic instability may be expected. If a
Crit Care Med 2001 Vol. 29, No. 10 (Suppl.)
labile patient with pulmonary hypertension is stabilized with NO before transfer
to a specialized center for further management, NO should be available during
patient transport. Recent work suggests
that the withdrawal response to inhaled
NO can be attenuated by pretreatment
with the type V phosphodiesterase inhibitor, sildenafil (Viagra) (58).
Diastolic Dysfunction
Occasionally, there is an alteration of
ventricular relaxation, an active energydependent process, which reduces ventricular compliance. This is particularly
problematic in patients with a hypertrophied ventricle undergoing surgical repair, e.g., tetralogy of Fallot, and after
CPB in some neonates when myocardial
edema may significantly restrict diastolic
function (i.e., “restrictive physiology”).
The ventricular cavity size is small, and
the stroke volume is decreased. ßAdrenergic antagonists and calcium
channel blockers add little to the treatment of this condition. In fact, hypotension or myocardial depression produced
by these agents frequently outweighs any
gain from slowing the heart rate. Calcium channel blockers are relatively contraindicated in neonates and small infants because of their dependence on
transsarcolemmal flux of calcium both to
initiate and sustain contraction.
A gradual increase in intravascular
volume to augment ventricular capacity,
in addition to the use of low doses of
inotropic agents, has proven to provide a
modest benefit in patients with diastolic
dysfunction. Tachycardia must be
avoided to optimize diastolic filling time
and to decrease myocardial oxygen demands. If low cardiac output continues
despite the above-outlined treatment,
therapy with vasodilators can be attempted to alter systolic wall tension (afterload) and, thus, decrease the impediment to ventricular ejection. Although,
intuitively, one may hesitate to use vasodilators in the presence of marginal systemic arterial blood pressure because
blood pressure is the product of cardiac
output and systemic vascular resistance,
a decrease in systemic vascular resistance
could increase flow with no undesirable
changes in pressure (3). Because the capacity of the vascular bed increases after
vasodilation, simultaneous volume replacement is indicated. Amrinone, milrinone, or enoximone are useful under
these circumstances because these agents
are non-catecholamine so-called inodilators with vasodilating and lusitropic (improved diastolic state) properties, in contrast to other inotropic agents (59 – 64).
Mechanical Support
For more refractory but potentially reversible ventricular dysfunction, ventricular assist devices may be useful when
gas exchange appears satisfactory (65).
Although this technique offers potential
advantages for selected patients over extracorporeal membrane oxygenation
(ECMO), ECMO is indicated when pulmonary function is also significantly impaired (66, 67). It is also more reliable
therapy for biventricular dysfunction. In
our experience, which is similar to many
other centers, mechanical support is necessary in ⬍2% of all patients who undergo CPB (68).
The availability of extracorporeal cardiorespiratory support for children with
congenital heart disease has had a dramatic impact on a broad range of issues
in the ICU (66, 69 –78). Prolonging intraoperative CPB for cardiac surgical patients returning to the ICU was an early
and obvious extension of CPB technology. The effect on hospital mortality is
unequivocal and even more obvious when
used as rescue therapy during cardiopulmonary resuscitation (CPR) (79, 80).
However, the impact is felt across many
disciplines, including medicine, surgery,
nursing, pharmacy, and respiratory therapy, and involves cardiovascular surgeons, cardiologists, intensivists, anesthesiologists, neonatologists, and ECMO
specialists. Extracorporeal cardiorespiratory support has expanded our options for
supporting reversible heart failure and
utilizing organ transplantation (81, 82).
It has enabled us to perform difficult
catheter interventions in unstable patients and allowed treatment of lifethreatening arrhythmias with catheter
ablation techniques. It has altered the
way intensive care physicians select patients for intervention and conduct CPR,
and it has made clinicians confront practical issues of informed consent for starting and stopping potentially life-saving
treatment. This in turn has challenged
the medical ethicists to opine on study
designs involving ECMO and the important issues of parental input and consent.
The technology has confused the clergy
by introducing ambiguities about the
temporal domains of life and death in the
ICU. It has put extraordinary demands on
S225
administrators and ECMO specialists to
provide more time and personnel during
an era of cost reduction. The care of these
patients provides intellectual challenges
in understanding unique pathophysiology and requires expertise that physicians
and other healthcare professionals seek
to obtain. The intensity and experience
associated with using the ultimate resuscitative tool to achieve sudden shifts from
near certain death to dramatic recovery is
highly motivating and enormously gratifying.
Tables 5 and 6 show the cumulative
activity through 1999 in the Extracorporeal Life Support Organization registry
with survival by diagnostic category.
With the advent of high-frequency oscillatory ventilation, use of surfactant, inhaled NO, and other advances in critical
care of the newborn, the need for ECMO
for hypoxemic respiratory failure has declined since its peak in 1992. Cardiac
ECMO (including adults) seems to have
declined more recently as adult use of
ventricular assist devices (including implantable) has gained acceptance. In contrast, the proportion of children who received ECMO support for congenital or
acquired heart disease at Children’s Hospital (Boston, MA) has steadily increased;
this is typical of the pediatric experience
in many large cardiac centers. More than
half of all ECMO runs in our institution
are now for cardiovascular support rather
than respiratory support. Survival for patients on ECMO after cardiac surgery has
also steadily improved but has not
reached the survival rates of neonates on
ECMO for respiratory failure (Table 6).
Substantial institutional variability in patient selection for ECMO makes comparison with published experience difficult.
Even within institutions, practice has
substantially evolved, and this confounds
the interpretation of trends over time.
Overall, one can propose that the use of
ECMO for cardiovascular support is increasing, and results are improving; however, there is room for further progress
(83). Refinement of ECMO personnel and
organization to include an in-hospital
team for rapid resuscitation may improve
outcome (80). During the past year at
Children’s Hospital, Boston, ⬎20 patients
have been cannulated for cardiovascular
support during resuscitation for cardiac
arrest; hospital survival exceeds 60%.
Survivors among neonates has dramatically improved to 70%, including those
patients with hypoplastic left heart synS226
Table 5. Cumulative Extracorporeal Life Support Organization (ELSO) registry data through 1999
Neonatal
Respiratory
Cardiac
Pediatric
Respiratory
Cardiac
Adult
Respiratory
Cardiac
Total Patients
Survived ECMO, %
Survived to
Discharge, %
14,543
1,085
84
55
79
40
1,711
1,642
62
52
55
39
483
244
52
36
49
32
ECMO, extracorporeal membrane oxygenation.
Table 6. Cumulative Extracorporeal Life Support Organization registry data through 1999 for
neonatal respiratory failure by diagnostic category
MAS
CD hernia
Sepsis
PPHN/PFC
RDS
Pneumonia
Other
Total Runs
Average Run Time
Percent Survived
5177
3132
2088
2065
1268
151
740
127
216
138
137
132
216
164
94
55
76
80
80
55
68
MAS, meconium aspiration syndrome; CD, congenital diaphragmatic; PPHN/PFC, persistent pulmonary hypertension of newborn/persistent fetal circulation; RDS, respiratory distress syndrome.
drome who have undergone a Norwood
operation.
Indications for ECMO. General indications for the use of mechanical support in
patients with heart disease include inadequate oxygen delivery or a requirement for
temporary support during cardiac catheterization interventions. Inadequate oxygen
delivery is caused most commonly by low
cardiac output, profound cyanosis with intracardiac shunting and cardiovascular collapse, or profound hypoxemia from associate lung disease (Table 7).
The most common cause of inadequate
oxygen delivery in a pediatric cardiac ICU
stems from low cardiac output, which is
usually a result of myocardial dysfunction.
Ventricular dysfunction may occur as a
component of chronic cardiomyopathy or
from other causes of congestive heart failure. It may occur more dramatically with
acute decompensation, typified by acute
fulminant viral myocarditis.
Patients who fail to wean from CPB
may be converted to an ECMO circuit in
the operating room and brought to the
ICU in hopes of recovering myocardial
function (84). These children typically
have poorer survival rates for multifactorial reasons, including severity and complexity of disease, as well as increased
bleeding. Other children have progressive
myocardial failure after successful weaning from CPB. This typically occurs during the first 24 hrs after cardiac surgery,
and subsequent survival may be better in
this group of patients after a period of
myocardial rest and decompression.
Pulmonary hypertensive crises after
CPB may be refractory to therapy and
necessitate mechanical support of the
right heart. These patients are notoriously difficult to resuscitate after cardiac
arrest if they have advanced pulmonary
vascular obstructive disease. Resuscitation is facilitated if a small right-to-left
communication is created or left in place
at the time of surgical intervention.
Refractory arrhythmias are occasionally controlled only after the heart has
been decompressed on ECMO and sufficient time has been gained to achieve
adequate pharmacologic control of the
arrhythmia.
Cardiac arrest may occur suddenly in
the postoperative period, without substantial warning. It may also occur as the
culmination of progressive postoperative
myocardial dysfunction, resistant to therapy. Although anticipation of this event
with timely preparation for ECMO is preferable, cannulation during CPR is not
uncommon (83).
Crit Care Med 2001 Vol. 29, No. 10 (Suppl.)
Table 7. Indications and relative contraindications for extracorporeal membrane oxygenation (ECMO)
Typical indications for ECMO
I. Inadequate oxygen delivery
A. Low cardiac output
1. Chronic (cardiomyopathy)
2. Acute (myocarditis)
3. Weaning from CPB
4. Progressive postoperative failure
5. Pulmonary hypertension
6. Refractory arrhythmias
7. Cardiac arrest
B. Profound cyanosis
1. Intracardiac shunting and cardiovascular collapse
C. Profound hypoxemia
1. Child
a) pneumonia or acute respiratory failure exaggerated by underlying heart disease
2. Newborn
b) CHD, complicated by other newborn indications for ECMO, such as meconium
aspiration syndrome, PPHN, pneumonia, sepsis, respiratory distress syndrome, etc.
II. Support for intervention during cardiac catheterization
A. Ablation
B. Dilation
C. Device closure
Relative contraindications for ECMO
I. End-stage, irreversible, or inoperable disease
II. Family, patient directives to limit resuscitation
III. Significant neurologic impairment
IV. Uncontrolled bleeding within major organs
V. Extremes of size and weight
VI. Inaccessible vessels during CPR
VII. Residual, operable, anatomic lesion (reoperation rather than ECMO)
CPB, cardiopulmonary bypass; CHD, congestive heart disease; PPHN, persistent pulmonary hypertension of newborn; CPR, cardiopulmonary resuscitation.
Relative Contraindications to ECMO.
Although there may be few structural
heart defects that preclude the use of
ECMO, there are some potentially important contraindications that should be
considered (Table 7). Obviously, if the
underlying disease is felt to be irreversible or inoperable, common sense may
dictate that mechanical support of the
circulation merely prolongs a terminal
illness that is destined to have a fatal
outcome in the near future. However,
perspective on the term “inoperable” may
vary among healthcare professionals and
is closely tied to the parents’ perception
of the likelihood of survival and the quality of life during survival.
Significant central nervous system
disease or injury may also preclude the
use of ECMO. Chromosomal abnormalities associated with central nervous system impairment may complicate the assessment of patients and affect
predictions about the quality of life. Generally speaking, the presence of Trisomy
21 has not been considered recently to be
a contraindication to ECMO after cardiac
surgery. However, most families and
practitioners believe that the severe limitation in cognitive function and predicted life span associated with Trisomy
Crit Care Med 2001 Vol. 29, No. 10 (Suppl.)
13 or 18 would not be consistent with the
guideline that the underlying disease or
diseases must be reversible to merit consideration for ECMO.
Active bleeding from relatively inaccessible locations such as the brain or
abdominal structures before initiation of
ECMO may also present a relative contraindication, because heparinization would
in all likelihood aggravate previously existing disease. Extremes of size and
weight may pose limitations on ECMO
technology, but those limits expand each
year.
Unattainable vascular access may deter ECMO cannulation during CPR. Occasionally, a child with congenital heart
disease will have had surgery many weeks
or months before an in-hospital cardiopulmonary arrest that would otherwise
prompt consideration for ECMO as part
of the resuscitative maneuvers. However,
if the jugular veins or superior vena cava
are known to be obstructed from previous
interventions and there are anatomical
limitations (size or previous procedures)
to cannulating through the groin, then
the notion of continuing CPR through a
prolonged procedure to reopen the sternum through extensive scar tissue may
be inadvisable.
A
ggressive identification and treatment of low car-
diac output conditions after
cardiac surgery is central to
the critical care of children
with
congenital
heart
disease.
Finally, if progressive myocardial dysfunction characterizes the postoperative
course of a patient who is identified as
having significant residual anatomical
disease, then the temptation to support
the child with ECMO must be balanced
against the more prudent need to return
to the operating room and to address
directly the residual anatomical lesion.
Identifying Residual Disease. The importance of identifying residual or previously undiagnosed anatomical disease in
the postoperative patient with progressive myocardial dysfunction and low cardiac output cannot be underestimated.
This is one of the prime responsibilities of
those who participate in postoperative
management (85, 86). Intracardiac catheters to measure pressure and to sample
blood for oxygen saturation will help assess the adequacy of diagnosis and repair.
Transthoracic and transesophageal echocardiography are valuable in the postoperative evaluation of the child with low
cardiac output. When acoustic windows
are limited with echocardiography, the
patient may benefit from cardiac catheterization, including physiologic assessment and angiographic imaging. Aggressive diagnostic intervention is a critical
component in the assessment of low cardiac output in the postoperative patient.
This is especially appealing if suspected
residual lesions can be addressed with
interventional catheterization techniques.
Optimizing Cardiac Output Before
and After Mechanical Support. Physicians in the ICU bare the responsibility of
anticipating changes in cardiac output
after cardiac surgery, excluding residual
disease as a causative factor and optimizing physiologic conditions that will
achieve optimal cardiac output. The need
S227
for mechanical support of the circulation
can often be averted by an experienced
appreciation of therapeutic modalities to
support oxygen delivery short of ECMO
(85, 87). However, even if these therapies
are inadequate to sustain the patient before invoking ECMO, they must again be
thoughtfully applied in the effort to wean
the patient from mechanical support as
soon as possible after myocardial function has returned and adequate organ
perfusion can be guaranteed (Table 1).
Institution of Mechanical Circulatory
Support. Initiation of ECMO requires the
prompt and coordinated efforts of the entire mechanical support team. Algorithms for action to proceed will vary
among institutions. In the authors’ experience, the decision to proceed with
ECMO is usually made at the bedside by
those attending the patient: cardiac surgeon, cardiac intensivist, bedside nurse,
and nurse in charge. Cross-trained personnel, such as ECMO specialists who are
also respiratory therapy staff, facilitate
communication and streamline personnel requirements. As the ECMO specialist
is notified, the transfusion service is contacted and a blood prime is planned. The
operating room nursing staff are called,
and a scrub nurse is made available
whenever possible. The precise moment
of the procedure start time may vary according to the availability of personnel
and necessary components when resuscitation is not impending or under way.
Rapid-Deployment ECMO for Resuscitation. When ECMO is utilized during an
ongoing resuscitation, the goal is to have
a circuit ready in 15 mins and cannulation complete in ⬍30 mins after cardiac
arrest. Since 1996, we have utilized an
in-hospital rapid deployment team to respond to an emergency need for ECMO
cannulation during cardiopulmonary arrest and resuscitation at a variety of locations throughout the hospital (80).
These include the ICU, cardiac catheterization laboratory, emergency department, inpatient wards (rarely), and noncardiac operating rooms.
Hospital survival of pulseless patients
resuscitated with ECMO now exceeds
60%. Obviously, the effectiveness of
ECMO as a tool to achieve successful resuscitation of cardiac patients will depend
on the nature of the underlying disease
and the efficiency of the technique. Typically, we now wait only 5 mins (or one
round of medication administration) before determining that return of cardiovascular stability during CPR is unlikely
S228
and the ECMO circuit should be primed.
A circuit prepared and primed with crystalloid but unused can be maintained in
readiness for 24 hrs but will usually be
discarded after that time. Delay in cannulation during CPR is rarely the result of
prolonged circuit preparation time.
A parallel consideration involves the
decision process for determining suitability for ECMO. This must occur before
cardiac arrest whenever possible. Institutions may adopt general philosophies
about rapid resuscitation ECMO for broad
categories of patients in the ICU. For example, infants with two ventricles and
uncomplicated repair of congenital heart
disease who have no other underlying
disease may all be candidates for ECMO
should they have a sudden, unexpected
cardiac arrest in the early postoperative
period. In contrast, it may be generally
inadvisable to impose ECMO on an older
patient with end-stage heart disease or
severe neurologic disease who declines or
is not otherwise a candidate for transplantation but has an acute decompensation and cardiac arrest. In between these
extremes is an area that requires discussion and individualization of care plans
that must be accomplished before any
anticipated or unanticipated decompensation. Thus, daily patient rounds in the
ICU must now incorporate a dialogue
among physicians, nurses, family, and
support staff that addresses the patient’s
suitability for ECMO. The moment after
cardiac arrest is not the time to initiate
discussions about the appropriateness of
invasive, potentially life-prolonging technology. Addressing these issues during
rounds and fully discussing the appropriate limitation of technology is an important new responsibility.
SUMMARY
Aggressive identification and treatment of low cardiac output conditions
after cardiac surgery are central to the
critical care of children with congenital
heart disease. Successful application of
these strategies has undoubtedly contributed to the remarkable decline in mortality associated with congenital heart surgery in the past two decades.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
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