Download Early Survival of Infants Weighing 2.5 Kilograms or

Early Survival of Infants Weighing 2.5 Kilograms or Less
Undergoing First-Stage Reconstruction for Hypoplastic
Left Heart Syndrome
Samuel Weinstein, MD; J. William Gaynor, MD; Nancy D. Bridges, MD; Gil Wernovsky, MD;
Lisa M. Montenegro, MD; Rodolfo I. Godinez, MD, PhD; Thomas L. Spray, MD
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Background—Results of staged palliation for hypoplastic left heart syndrome (HLHS) have improved in recent years;
however, certain risk factors have been associated with decreased survival rates.
Methods and Results—We retrospectively reviewed the medical records of 67 patients weighing #2.5 kg undergoing the
first stage of reconstructive surgery at our institution between January 1, 1990, and December 31, 1997. HLHS was
present in 45 patients, complex double-outlet right ventricle in 10, unbalanced AV canal in 5, tricuspid atresia with
transposition of the great vessels in 4, and other diagnoses in 3. Mean age at surgery was 10.1610.7 days (median, 8
days), and mean weight was 2.260.3 kg (median, 2.2 kg). Fourteen patients weighed #2.0 kg, and 2 patients weighed
#1.5 kg. Early mortality (death within 30 days or before hospital discharge) was 51% (34 of 67). No patient, procedural,
or time-related variables correlated with increased mortality. However, there was a trend toward increased mortality with
increased cardiopulmonary bypass time (P50.076) and decreased preoperative ventricular performance (P50.139).
Conclusions—These findings suggest that low weight alone in a patient with HLHS or an anatomic variant should not be
considered a contraindication to staged reconstructive surgery. (Circulation. 1999;100[suppl II]:II-167–II-170.)
Key Words: heart defects, congenital n surgery n risk factors
E
arly survival after the first stage of palliative surgical
reconstruction for hypoplastic left heart syndrome
(HLHS) has steadily improved since Norwood et al1 and Doty
et al2 first described the operation in 1979. In a recent
multi-institutional review from the Congenital Heart Surgeons Society (CHSS), 1-month survival for stage 1 palliation
for aortic atresia was 64%, with better results achieved at 2
“low-risk” institutions.3 Bove and colleagues4 from the University of Michigan recently reported hospital survival rate of
76% after stage 1 palliation. Results from our own institution
are similar, with an overall early survival rate of 73% in
.171 cases between January 1, 1995, and December 31,
1998.
Early survival for HLHS is significantly less than for other
cardiac defects requiring neonatal repair. Anatomic variation,
size of the ascending aorta, age at surgery, tricuspid valve
function, ventricular function, low birth weight, associated
noncardiac anomalies, and other variables have been suggested as possible predictors of mortality for patients undergoing staged reconstruction for HLHS.5–11 Identification of
such risk factors would ideally lead to increased survival,
either as a result of preoperative management strategies to
reduce these “high-risk” characteristics or by leading to
referral for cardiac transplantation rather than staged recon-
struction to the Fontan operation for a specific subset of
patients.
There have been only a few recent reports on the outcome
of low-weight (,2.5 or 2.0 kg) infants undergoing cardiac
surgery.12–15 The overall early survival rate for infants undergoing corrective or palliative surgery for congenital heart
defects in these studies was acceptable (80% to 87%) but still
lower than for babies of normal weight. These studies
included few patients with HLHS. Because of the potential
additive risks of low weight and complicated neonatal palliative cardiac surgery, we evaluated the results of first-stage
reconstruction in infants weighing #2.5 kg to describe this
population and to attempt to identify factors predictive of
early mortality.
Methods
The cardiopulmonary bypass (CPB) records of cardiac surgical cases
performed at the Children’s Hospital of Philadelphia between January 1990 and December 1997 were reviewed to identify babies
weighing #2.5 kg at the time of stage 1 reconstruction for HLHS or
an anatomic variant (see Table 1). Among the 69 patients identified,
67 had complete records and are included in this study. Patient data
were compiled by review of clinical records, preoperative echocardiographic reports, perfusion records, operative notes, and
autopsy reports.
From the Divisions of Pediatric Cardiothoracic Surgery and Pediatric Cardiology, Cardiac Center, Children’s Hospital of Philadelphia, Philadelphia,
Penn.
Correspondence to Thomas L. Spray, MD, Children’s Hospital of Philadelphia, Division of Cardiothoracic Surgery, 34th & Civic Center Blvd, Suite
8527, Philadelphia, PA 19104-4399. E-mail [email protected]
© 1999 American Heart Association, Inc.
Circulation is available at http://www.circulationaha.org
II-167
II-168
Circulation
November 9, 1999
TABLE 1. Characteristics Examined as Potential Predictors of
Mortality in Low-Birth-Weight Infants Undergoing Stage 1
Palliation Analyzed as Either Dichotomous or
Continuous Variables
TABLE 2. Characteristics of 67 Low-Birth-Weight Infants
Undergoing Stage 1 Palliation and Probability Values
P
Sex, F/M
Dichotomous variables
32/35
Anatomic diagnosis, n
Anatomic subtype
HLHS
Aortic atresia and/or mitral atresia or mitral stenosis
Aortic stenosis and/or mitral atresia or mitral stenosis
HLHS variants
Complex double-outlet right ventricle
Unbalanced AV canal
Transposition with tricuspid atresia
Critical aortic stenosis
Transposition with small left ventricle
Echocardiographic assessment of right ventricular performance
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Normal to mildly depressed
Moderately to severely depressed
Echocardiographic assessment of AV valve function
Normal or mildly regurgitant
Moderately or severely regurgitant
Continuous variables
Pulmonary venous drainage
HLHS
45
HLHS variants
22
Complex double-outlet right ventricle
Unbalanced AV canal
0.7
10
5
Transposition with tricuspid atresia
2
Critical aortic stenosis
2
Transposition with small left ventricle
1
Ventricular performance, n
Normal or mildly depressed
Moderately or severely depressed
64
0.139
3
AV valve function
Normal or mildly regurgitant
Moderately or severely regurgitant
63
0.95
4
Pulmonary veins
Unobstructed
55
Mildly or moderately obstructed
9
Severely obstructed or intact atrial septum
3
0.289
Gestational age, wk
Unobstructed
Mild or moderately obstructed
Severely obstructed or intact atrial septum
Birth weight
Mean
3662
Median
36
Range
29–40
0.5
Age at surgery, d
Weight at surgery
Mean
Gestational age at birth
Age at time of surgery
CPB time
10611
Median
8
Range
1–46
0.5
Shunt size, n
Circulatory arrest time
Year of surgery
Stage 1 reconstruction at our institution includes aortic arch
augmentation with cryopreserved homograft, creation of an aortopulmonary shunt, and an atrial septectomy when necessary to ensure
adequate interatrial mixing. Early mortality was defined as death
within 30 days or before hospital discharge. Prematurity was defined
as birth at a gestational age of ,37 weeks. Appropriateness of
weight for gestational age was assessed with the Growth Record for
Infants (Abbott Laboratories). Time on CPB was calculated as
circulatory arrest time plus time on CPB.
Characteristics examined as potential predictors of mortality are
shown in Table 1. Operations were performed by 4 surgeons, and
because the variable “operating surgeon” was essentially collinear
with “year of operation,” only the latter variable was analyzed.
Logistic regression or x2 was used to analyze the dichotomous
variables. The remaining characteristics were analyzed as continuous
variables. Results of univariate analysis did not support proceeding
to multivariate analysis. All statistical tests were carried out by use
of Stata 5.0 software.
3.0 mm
15
3.5 mm
28
4.0 mm
24
CPB time, min
Mean
100–19
Range
68–172
Characteristics and anatomic diagnoses of the 67 patients
who met study criteria are listed in Table 2. Premature birth
occurred in 39 of 67 patients (58%). Weight was appropriate
for gestational age in 44 patients (79%), low for gestational
0.5
Circulatory arrest time, min
Mean
61611
Range
32–84
0.466
Weight at surgery, kg
Mean
2.260.3
Range
1.4–2.5
0.368
Birth weight, kg
Mean
2.260.4
Range
1.39–2.6
Year of surgery
1990–1991
1992–1993
Results
0.5
1994–1995
1996–1997
0.285
0.537
Weinstein et al
TABLE 3.
Causes of Hospital Mortality
n
Cardiac
23
Noncardiac
11
Abdominal
Necrotizing enterocolitis
3
Perforated intestine
2
Pulmonary
Aspiration pneumonia
1
Pneumonia
3
Meningitis
2
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age in 11 (16%), and high for gestational age in only 2.
Fourteen patients (21%) weighed #2 kg at the time of
surgery. Even in patients in whom surgery was performed
after the median age, there was no appreciable weight gain or
loss before surgery. Specific genetic syndromes were identified in 5 patients, including 2 infants with Turner’s syndrome
and 1 each with Rubinstein-Taybi syndrome, 22Q deletion,
and CHARGE syndrome.
Early mortality was 51% (34 of 67). Causes of hospital
mortality are listed in Table 3. One patient died after
discharge but before 30 days of life. Two thirds of the deaths
were secondary to cardiac causes, defined as a chart description of cardiopulmonary arrest, arrhythmia, or pulmonary
overcirculation preceding death. Infection and sepsis were a
factor in all noncardiac deaths. Necrotizing enterocolitis was
present before surgery in 6 patients, and 3 survived to hospital
discharge. In addition, 2 patients died of perforated viscus (1
colon and 1 appendiceal) in the postoperative period. Pulmonary infections were the primary cause of death in 4 patients.
Evidence of meningitis at autopsy was present in 2 patients.
The median time of death from cardiac causes was 1 day after
surgery (range, 0 to 19 days); for noncardiac causes, it was 17
days (range, 4 to 160 days).
In univariate analysis, no patient, procedural, or time-related
variable was predictive of mortality in this cohort. However,
there was a trend toward higher mortality with longer CPB times
(P50.07). In addition, all 3 patients with severely decreased
ventricular function and all 3 patients with severely obstructed
pulmonary venous drainage died. Three of the 5 infants with
genetic syndromes, 2 with Turner’s syndrome, and 1 with
Rubinstein-Taybi syndrome died.
Discussion
Although improvements in surgical technique and perioperative care have led to increased survival after surgical
reconstruction for HLHS, operative mortality after the first
stage is still high (9% to 47%).4,6,10 Many investigators have
attempted to identify factors predictive of death after the
Norwood procedure. Identification of high-risk characteristics would aid in the management of these patients and may
help in deciding more precisely which patients should be
listed for transplantation and which should undergo staged
reconstruction.16 Prematurity and low weight in patients with
HLHS have been found to be risk factors for higher mortality
in some reports. However, contemporary reviews of low-
Low-Weight Infants and Stage 1 Reconstruction
II-169
weight neonates with a wide variety of lesions requiring CPB
for repair have suggested that low weight alone is not a
contraindication to early repair.12–14 In the present study,
survival was 47% for low-weight infants undergoing stage 1
reconstruction. Overall survival for stage 1 reconstruction at
our institution is 74%. Within the cohort of low-weight
infants, weight at the time of stage 1 reconstruction for HLHS
had no effect on survival. In addition, no statistically significant increase or decrease in weight was evident in patients in
whom surgery was delayed.
Only a few studies have focused on the influence of weight
on survival after CPB.12,14,17,18 Pawade and associates14 from
the Royal Children’s Hospital in Melbourne analyzed risk
factors for mortality in infants weighing ,2.5 kg undergoing
CPB and compared them with a similar group undergoing
CPB with weights .2.5 kg. There were 8 univentricular
repairs and 52 biventricular repairs. HLHS was present in
only 4 of the low-weight infants. There were 946 patients in
the control group. Early mortality in the low-weight group
was 16.5% compared with 7.5% for the overall population
(P,0.006). Predictors of mortality were preoperative metabolic acidosis, univentricular repair, and longer CPB time. Of
the 4 patients with HLHS, 2 were early survivors.14 Rossi and
colleagues13 recently reviewed the outcomes of cardiac operations in 30 infants weighing #2 kg at the Mount Sinai
Hospital in New York. Hospital survival was 83%, with no
difference in mortality rates based on age, weight, or type of
procedure. HLHS was present in 4 patients; 3 of these were
early survivors.
Bove and Lloyd3 reviewed 158 patients undergoing staged
reconstruction from 1990 through 1995 and identified several
risk factors for early death, including age .1 month, pulmonary venous obstruction, significant noncardiac congenital
anomalies, gestational age ,35 weeks, and birth weight ,2.5
kg. Hospital survival for the 31 patients with these high-risk
characteristics was 42%, which was significantly lower than
the 86% survival rate seen in the remaining 127 patients
(P50.0001).3
Forbess and colleagues17 reviewed 212 consecutive patients undergoing stage 1 reconstruction at the Children’s
Hospital of Boston between 1983 and 1993. Operative
mortality in this group was 46.2%. Patients weighing ,3 kg
were at higher risk for hospital death, and weight ,3 kg was
an independent risk factor for mortality in the multivariate
analysis. The authors suggested that low-weight patients
might be best served by referral for transplantation.17 However, in the CHSS study, low birth weight was found to be an
incremental risk factor for death in both staged reconstruction
and heart transplantation protocols.3 Overall experience of
transplantation in low-weight infants is limited. In the largest
series reported of infants transplanted for HLHS at Loma
Linda (142 patients of 176 listed), the average weight was
3.760.8 kg (range, 2.0 to 6.4 kg; median weight, 3.6 kg).19
Traditional experience with cardiac surgery in small infants has suggested that weight is indeed a risk factor for early
intervention.12–14,18 The reasons for the increased mortality
are probably multifactorial. The neonatal heart is less compliant that the mature heart and is thought to be less capable
of handling a volume load.20,21 The immature pulmonary
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Circulation
November 9, 1999
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vascular bed can make the postoperative course unpredictable, and underdeveloped renal and hepatic functions impair
fluid balance.12–15,22 Patients born prematurely may have
hyaline membrane disease and are at risk for necrotizing
enterocolitis.13,22 In addition, the germinal matrix of the
premature infant is more susceptible to hemorrhage and
neurological complications from heparinization and CPB.18
Newborns of small size undergoing the Norwood procedure
present the additional technical challenges of cannulation,
cerebral protection, aortic arch reconstruction for extremely
small vessels, and selection of an appropriate shunt size to
provide adequate but not excessive pulmonary blood flow
while allowing for sufficient growth.
While this may be the largest reported series of small
infants undergoing stage 1 reconstructive surgery, the statistical power to define significant predictors of mortality is
limited. For example, the influence of severely diminished
ventricular performance, obstructed pulmonary venous drainage, and prolonged CPB times may be underestimated because of the small number of patients in the series with those
characteristics. As in previous reports examining the influence of weight on cardiac surgery, weight differences within
this group had no effect on mortality.12–14 Because of the
entry criteria of the study, we did not identify patients who
might have been born at ,2.5 kg but grew preoperatively to
weigh more than this at the time of surgery or patients who
were not referred for surgery because of low birth weight. Yet
in this review, patients in whom surgery was delayed did not
experience a statistical increase or decrease in weight before
the date of surgery, similar to previous reports.13,14 This
finding suggests that a delay in surgery to allow weight gain
is not justified and exposes the patient to prolonged risks of
pulmonary overcirculation, long-term mechanical ventilation,
and other ICU-related complications.13,14 The study design
also does not reveal how many infants at various postgestational ages might have died before surgery. Within the
limitations of this study, however, age at operation did not
influence survival. Previous studies have not compared ageweight appropriateness and outcome in cardiac surgery, but in
this study, being born small for gestational age did not predict
a higher mortality.
Although low-birth-weight infants with congenital cardiac
defects, including HLHS, are likely to be at a higher risk for
postoperative death and complications than their normal-size
counterparts, current experience does not suggest that waiting
to obtain a minimum weight before surgery improves outcome. Therefore, a delay in surgical intervention in the hope
of somatic growth is not warranted. Survival for low-weight
infants undergoing stage 1 reconstruction in general is decreased compared with larger babies having the same operation at the same institution; however, the absolute survival
rates are acceptable by national standards. Weight alone
should not be considered a contraindication to staged surgical
reconstruction in infants with HLHS.
Acknowledgment
This work was supported in part by the Daniel M. Tabas Endowed
Chair in Cardiothoracic Surgery.
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Early Survival of Infants Weighing 2.5 Kilograms or Less Undergoing First-Stage
Reconstruction for Hypoplastic Left Heart Syndrome
Samuel Weinstein, J. William Gaynor, Nancy D. Bridges, Gil Wernovsky, Lisa M. Montenegro,
Rodolfo I. Godinez and Thomas L. Spray
Downloaded from http://circ.ahajournals.org/ by guest on June 14, 2017
Circulation. 1999;100:II-167-Ii-170
doi: 10.1161/01.CIR.100.suppl_2.II-167
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