J Thorac Cardiovasc Surg.  2004 Jan;127(1):213-22.  

Arterial switch with full-flow cardiopulmonary bypass and limited circulatory
arrest: Neurodevelopmental outcome.

Karl TR, Hall S, Ford G, Kelly EA, Brizard CP, Mee RB, Weintraub RG, Cochrane
AD, Glidden D.

OBJECTIVES: Neonatal cardiac surgery has been associated with unfavorable
neurodevelopmental events. We investigated a patient cohort operated on
predominantly with full-flow cardiopulmonary bypass (150 mL. kg(-1). min(-1),
alpha-stat, alpha-blockade, median arrest = 6 minutes, temperature of 22 degrees
C) as the major support strategy for neonatal arterial switch operations
(transposition of the great arteries and intact ventricular septum). METHODS:
Seventy-four patients and "best-friend" control subjects were assessed 109
months (range, 48-166 months) postoperatively with general medical and
neurologic evaluation, IQ testing, formal movement scores, and detailed
parent-teacher behavioral-social reports. Fetal, neonatal, and perioperative
data were collated. RESULTS: The prevalence of perioperative seizures was 6.8%
(4/5 cases occurring preoperatively). The incidence of all perioperative
neurologic abnormalities was 20%. Patients who had a neurologic event were (as a
group) older at the time of operation and had a lower arterial blood pH before
the operation. Selected perioperative factors (not related directly to
cardiopulmonary bypass variables) predicted early (before discharge) neurologic
outcome in a multivariate model. At late assessment, patients were more likely
than control subjects to have a mild neurologic abnormality (P = 0.002).
Full-scale IQ scores (Wechsler Preschool and Primary Scale of Intelligence and
Wechsler Intelligence Scale for Children-Third Edition) were higher in control
subjects (101.9 [SD = 13] vs 108.6 [SD = 12], P =.0007), with both groups having
scores greater than the population-based test means. Full-scale IQ scores
related most significantly to years of paternal education (beta = 1.51, P
=.0078) but were also influenced by perioperative neurologic abnormalities,
birth weight, and circulatory arrest time. Patients had higher motor impairment
scores (Movement Assessment Battery) than control subjects (P =.0004). Parents
(Achenbach Child Development Checklist) assigned higher total social-behavioral
competence scores to control subjects (P =.05). Teachers (Achenbach Teacher
Report Form) suggested that patients were more likely to be perceived as having
various speech and expressive language problems, as well as minor behavioral
problems. CONCLUSION: With the perioperative strategies used, not all survivors
can be considered (neurodevelopmentally) normal at late follow-up, although the
risk of important impairment is low. Perioperative events might have long-term
prognostic value. On the basis of this study and published data regarding other
strategies, continued application of full-flow cardiopulmonary bypass is
justified, with the proviso that further investigation is required.

J Thorac Cardiovasc Surg.  2004 Jan;127(1):44-50.  

Supplemental nitric oxide and its effect on myocardial injury and function in
patients undergoing cardiac surgery with extracorporeal circulation.

Gianetti J, Del Sarto P, Bevilacqua S, Vassalle C, De Filippis R, Kacila M,
Farneti PA, Clerico A, Glauber M, Biagini A.

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory response that
may contribute to clinical morbidity. Gaseous nitric oxide at relatively low
concentrations may elicit peripheral anti-inflammatory effects in addition to a
reduction of pulmonary resistances. We examined the effects of 20 ppm of inhaled
nitric oxide administered for 8 hours during and after cardiopulmonary
bypass.Methods and results Twenty-nine consecutive patients undergoing aortic
valve replacement combined with aortocoronary bypass were randomly allocated to
either 20 ppm of inhaled nitric oxide (n = 14) or no additional inhalatory
treatment (n = 15). Blood samples for total creatine kinase, creatine kinase MB
fraction, and troponin I measurements were collected at 4, 12, 24, and 48 hours
postsurgery. In addition, we collected perioperative blood samples for
measurements of circulating nitric oxide by-products and brain natriuretic
peptide. Soluble P-selectin was analyzed in blood samples withdrawn from the
coronary sinus before and after aortic clamping. The area under the curve of
creatine kinase MB fraction (P =.03), total creatine kinase (P =.04), and
troponin I (P =.04) levels were significantly decreased in the nitric
oxide-treated patients. Moreover, in the same group we observed blunted
P-selectin and brain natriuretic peptide release (P =.01 and P =.02,
respectively). Nitric oxide inhalation consistently enhanced nitric oxide
metabolite levels (P =.01). CONCLUSIONS: Nitric oxide, when administered as a
gas at low concentration, is able to blunt the release of markers of myocardial
injury and to antagonize the left ventricular subclinical dysfunction during and
immediately after cardiopulmonary bypass. The organ protection could be
mediated, at least in part, by its anti-inflammatory properties.

Curr Med Res Opin.  2004 Jan;20(1):121-6.  

Impact of tranexamic acid vs. aprotinin on blood loss and transfusion
requirements after cardiopulmonary bypass: a prospective, randomised,
double-blind trial.

Hekmat K, Zimmermann T, Kampe S, Kasper SM, Weber HJ, Geissler HJ, Mehlhorn U.

Department of Thoracic and Cardiovascular Surgery, University of Cologne,
Germany.

INTRODUCTION: Aprotinin (AP) reduces blood loss and transfusions after
cardiopulmonary bypass (CPB), but may sensitise patients and is expensive.
Tranexamic acid (TA) has less side-effects, but data regarding its efficacy are
controversial. The aim of our prospective, randomised, double-blind study was to
compare the impact of AP vs. TA on drainage blood loss and transfusion
requirements in patients undergoing first time CABG on CPB. MATERIALS AND
METHODS: One hundred and twenty adult patients were randomised to receive either
high-dose AP according to Hammersmith or a total of 2 g TA. Perioperative blood
products were transfused in a standardised fashion. Blood loss was measured up
to 24 h. Demographic and clinical patient data were collected until hospital
discharge. RESULTS: The data from 118 patients (TA: n = 58, TA appears to be a
cost-effective alternative to AP AP: n = 60) who completed the study according
to protocol were analysed. Blood loss at 24 h postoperation in TA patients was
significantly higher (896 +/- 354 ml) as compared to AP patients (756 +/- 347ml;
p = 0.03). TA patients received 1.5 +/- 1.5 units of red blood cells (AP: 1.5
+/- 1.7, p = 1.0), 1.3 +/- 2.0 units of fresh frozen plasma (AP: 1.0 +/- 2.0, p
= 0.38) and 0.5 +/- 1.4 units of platelets (AP: 0.2 +/- 0.7, p = 0.15). Clinical
data, including perioperative myocardial infarction rate, acute renal failure,
mechanical ventilation, hospital stay and mortality, were not significantly
different between either group. CONCLUSION: Our data show a difference in blood
loss between TA and high-dose AP. Although statistically significant, it has
little clinical relevance, because perioperative transfusion requirements were
similar for both groups. Thus, in primary CABG patients.

Pediatr Cardiol. 2004 Jan 23 

Alterations in the Natriuretic Hormone System Related to Cardiopulmonary Bypass
in Infants with Congestive Heart Failure.

Costello JM, Backer CL, Checchia PA, Mavroudis C, Seipelt RG, Goodman DM.

Division of Cardiology, Children's Memorial Hospital, The Feinberg School of
Medicine at Northwestern University, 2300 Children's Plaza, #73, Chicago, IL
60614-3394, USA.

This study examined changes in the natriuretic hormone system in five infants
with congestive heart failure (CHF) due to intracardiac left-to-right shunting
who were exposed to cardiopulmonary bypass (CPB) during surgical repair. Plasma
concentrations of three hormones [atrial natriuretic peptide (ANP), brain
natriuretic peptide (BNP), and dendroaspis natriuretic peptide (DNP)] and their
secondary messenger, guanosine 3', 5'-monophosphate (cGMP), were measured, and
the biological activity of the system was quantified. At baseline, BNP and DNP
concentrations were normal in our patients, a finding that is strikingly
different from that of adult CHF patients, whereas ANP concentrations were
elevated. Following CPB, ANP concentrations decreased (median, 175 vs 44 pg/ml;
p = 0.043) and BNP concentrations increased (median, 25 vs 66 pg/ml; p = 0.043),
whereas DNP concentrations did not change. Following modified ultrafiltration,
BNP concentrations increased ( p = 0.043), but other natriuretic peptide
concentrations did not change. The calculated biological activity of the
natriuretic hormone system decreased following CPB [molar ratio, cGMP / (ANP +
BNP + DNP); median, 213 vs 127; p = 0.043)]. Additional studies are needed to
expand on these findings and identify patients with other types of congenital
heart disease who have perioperative disturbances in the natriuretic hormone
system and thus might benefit from pharmacologic intervention.

Ann Thorac Surg.  2004 Jan;77(1):220-5.  

Sonoclot analysis in cardiac surgery in dialysis-dependent patients.

Shibata T, Sasaki Y, Hattori K, Hirai H, Hosono M, Fujii H, Suehiro S.

Department of Cardiovascular Surgery, Osaka City University Medical School,
Osaka, Japan. shibata@msic.med.osaka-cu.ac.jp

BACKGROUND: Dialysis-dependent patients have multiple disorders of hemostasis;
however, there are no reports of viscoelastic changes during cardiac surgery in
such patients. METHODS: Hemostasis in dialysis-dependent patients during cardiac
operations was evaluated. Thirty patients who underwent cardiopulmonary bypass
(CPB) were studied: 6 with chronic renal failure undergoing dialysis (HD group),
and 24 without hemodialysis. Blood samples were obtained at four points: before
sternotomy, 30 and 90 minutes after the start of CPB, and after protamine
administration. RESULTS: Activated clotting time (ACT) measured with Sonoclot
analyzer was significantly correlated with ACT measured traditionally (r = 0.92;
p < 0.001; y = 36.1 + 0.95x). Values for ACT measured with Sonoclot analyzer as
well as traditional ACT increased significantly during CPB. Values for ACT
measured with Sonoclot analyzer in the HD group were significantly longer than
those in the control group. Before CPB, both ACT measured with Sonoclot analyzer
and traditional ACT in the HD group were significantly longer than those in the
control group; however, there were no significant differences in ACT measured
with Sonoclot analyzer between the groups after CPB. Clot rates and peak signal
values were significantly decreased during CPB in both groups, and returned to
preoperative values after protamine administration. There were no significant
differences in clot rate and peak signal values between the two groups. There
were no differences between the two groups in changes of time to peak. Platelet
counts in the HD group were significantly higher (p < 0.05) than those in the
control group. There were no differences in platelet counts after CPB between
the two groups. Antithrombin III levels decreased below 50% during and after
CPB. Antithrombin III in the HD group was significantly lower (p < 0.01) than
those in the control group. A significant time-group interaction was observed in
antithrombin III levels. CONCLUSIONS: Sonoclot signatures in HD patients showed
no significant differences in viscoelastic changes compared with non-HD
patients.

Ann Thorac Surg.  2004 Jan;77(1):214-9.  

Markers for endothelial activation during open heart surgery.

Eikemo H, Sellevold OF, Videm V.

Department of Immunology and Transfusion Medicine, Trondheim, Norway.

BACKGROUND: Reliable markers for endothelial activation are needed when studying
biocompatibility of cardiopulmonary bypass. METHODS: Blood samples from 21
patients undergoing combined valve and coronary artery bypass surgery were
collected before anesthesia (T1), after re-transfusion of blood from the
heart-lung machine (T2), and on the first postoperative morning (T3).
Concentrations of soluble markers were determined using sandwich enzyme-linked
immunoadsorbent assay for sICAM-1, sVCAM-1, and sE-selectin. The sera were also
used to stimulate human umbilical vein endothelial cells (HUVEC) in culture for
6 hours, in which activation was measured using cell enzyme immunoassay for
mICAM-1 and mVCAM-1. RESULTS: The concentrations of sICAM-1 and sVCAM-1
increased during both measurement intervals (p < 0.05). The sICAM-1 T1 was 311.0
ng/mL (range, 271.0 to 350.7 ng/mL); the sICAM-1 T2 was 341.6 ng/mL (range,
322.0 to 422.0 ng/mL), and the sICAM-1 T3 was 400.2 ng/mL (range, 348.0 to 556.4
ng/mL; the sVCAM-1 T1 was 607.5 ng/mL (range, 497.8 to 813.8 ng/mL), the sVCAM-1
T2 was 755.3 ng/mL (range, 660.6 to 834.4 ng/mL), and the sVCAM-1 T3 was 1149.0
ng/mL (946.0 to 1406.0 ng/mL); whereas the sE-selectin increased from T1 to T3
(p < 0.01). Both the mICAM-1 (p < 0.002) and the mVCAM-1 (p < 0.005) increased
on the human umbilical vein endothelial cells in culture after stimulation with
the patient sera. The amounts of soluble markers in vivo were not correlated
with the degree of endothelial activation in vitro, but were correlated with
various operative variables including age, medication, and time of aortic
cross-clamping. CONCLUSIONS: Endothelial cells were activated during
cardiopulmonary bypass. The soluble adhesion molecules sICAM-1, sVCAM-1, and
sE-selectin displayed different kinetics, rendering it difficult to determine a
simple expression for the degree of endothelial cell activation. Clinically,
sVCAM-1 seemed to be the best-suited marker for endothelial cell activation,
because it was only associated with aortic cross-clamping and heparin and
protamine doses, and it also showed the largest numerical changes.

Ann Thorac Surg.  2004 Jan;77(1):61-5.  

Predictors of mortality at initiation of peritoneal dialysis in children after
cardiac surgery.

Boigner H, Brannath W, Hermon M, Stoll E, Burda G, Trittenwein G, Golej J.

Department of Neonatology and Pediatric Intensive Care, University Children's
Hospital of Vienna, Vienna, Austria. harald.boigner@akh-wien.ac.at

BACKGROUND: The development of renal dysfunction in the postoperative course of
cardiac surgery is still associated with high mortality in pediatric patients.
In particular for small infants peritoneal dialysis offers a secure and useful
treatment option. The aim of the present study was to investigate if routinely
used laboratory and clinical variables could help predict mortality at
initiation of peritoneal dialysis. METHODS: We performed a retrospective chart
analysis of pediatric intensive care unit patients with renal dysfunction who
were treated with peritoneal dialysis after cardiac surgery between 1993 and
2001 and analyzed variables obtained 3 hours or less before starting peritoneal
dialysis. RESULTS: Results are documented as means and standard errors. A total
of 1141 children underwent a cardiac operation on cardiopulmonary bypass.
Sixty-two children (5.4%) were treated with peritoneal dialysis. Mortality was
40.3% (37 survivors, 25 nonsurvivors). The pH in survivors was 7.35 (0.01); in
nonsurvivors it was 7.23 (0.03; p = 0.0037). Base excess in survivors was -1.37
mmol/L (0.61); in nonsurvivors it was -7.17 mmol/L (1.49; p = 0.0026). Lactate
in survivors was 4.5 mmol/L (0.60); in nonsurvivors it was 10.5 mmol/L (1.78; p
= 0.0089). Positive inspiratory pressure in survivors was 24.6 cm H(2)O (0.78);
in nonsurvivors it was 28.9 cm H(2)O (1.08; p = 0.0274). Tidal volume per
kilogram bodyweight in survivors was 11.0 mL/kg (0.48); in nonsurvivors it was
8.7 mL/kg (0.50; p = 0.0493). CONCLUSIONS: We conclude from our data that the
consideration of pH, base excess, lactate, positive inspiratory pressure, and
tidal volume per kilogram bodyweight help predict mortality at initiation of
peritoneal dialysis. We were able to observe significant differences between
survivors and nonsurvivors using these variables.

Pediatr Crit Care Med.  2004 Jan;5(1):28-34.  

Glucocorticoids reduce cardiac dysfunction after cardiopulmonary bypass and
circulatory arrest in neonatal piglets.

Duffy JY, Nelson DP, Schwartz SM, Wagner CJ, Bauer SM, Lyons JM, McNamara JL,
Pearl JM.

Divisions of Cardiothoracic Surgery (JYD, CJW, JML, JLM, JMP) and Cardiology
(DPN, SMS, SMB), Cincinnati Children's Hospital Medical Center, Cincinnati, OH;
and the Departments of Surgery (JYD, JML, JMP) and Pediatrics (JYD, DPN, SMS),
University of Cincinnati School of Medicine, Cincinnati, OH.

OBJECTIVE: The hypotheses were that glucocorticoid administration could improve
ventricular recovery by reducing cardiopulmonary bypass (CPB)-induced
inflammatory response and that presurgical administration might be more
effective than intraoperative dosing. DESIGN: Animal case study. SUBJECTS:
Crossbred piglets (5-7 kg). INTERVENTIONS: Piglets were cooled with CPB,
followed by 120 mins of deep hypothermic circulatory arrest (DHCA). Animals were
rewarmed to 38 degrees C, removed from CPB, and maintained for 120 mins.
Methylprednisolone (60 mg/kg) was administered in the CPB pump prime
(intraoperative glucocorticoid [intraop GC]) or 6 hrs before CPB (30 mg/kg) in
addition to the intraoperative dose (30 mg/kg; pre- and intraop GC). Controls
(no GC) received saline. MEASUREMENTS AND MAIN RESULTS: In no GC, left ventricle
(LV) positive change in pressure in time (+dP/dt) (mm Hg/sec) had a mean +/- sd
of 1555 +/- 194 at baseline vs. 958 +/- 463 at 120 mins after CPB, p =.01). LV
+dP/dt was maintained in glucocorticoid-treated animals (1262 +/- 229 at
baseline vs. 1212 +/- 386 in intraop GC and 1471 +/- 118 vs. 1393 +/- 374 in
pre-intraop GC). Glucocorticoids reduced myocardial interleukin-6 messenger RNA
expression, measured by ribonuclease protection assay, at 120 mins after CPB
compared with animals receiving saline (p <.05), although interleukin-6 plasma
and LV protein concentrations were not affected. Interleukin-10 myocardial
protein concentrations were elevated after CPB-DHCA with higher concentrations
in glucocorticoid-treated animals (p <.05). Glucocorticoid treatment maintained
myocardial concentrations of the inhibitor of nuclear factor-kappaB in the
cytosol and decreased nuclear factor-kappaB concentrations detected in the
nucleus in a DNA/protein interaction array. CONCLUSIONS: Glucocorticoids
improved recovery of LV systolic function in neonatal animals undergoing
CPB-DHCA. Animals receiving glucocorticoids before CPB had better postoperative
oxygen delivery than those receiving only intraoperative treatment. Maintenance
of cardiac function after glucocorticoids might be due, in part, to alterations
in the balance of pro- and anti-inflammatory proteins, possibly through nuclear
factor-kappaB-dependent pathways.

Am Heart J.  2004 Jan;147(1):173-80.  

Pharmacokinetics and safety of TP10, soluble complement receptor 1, in infants
undergoing cardiopulmonary bypass.

Li JS, Sanders SP, Perry AE, Stinnett SS, Jaggers J, Bokesch P, Reynolds L,
Nassar R, Anderson PA.

Department of Pediatrics, Division of Cardiology, Duke University Medical
Center, Durham, NC 27710, USA. li000001@mc.duke.edu

BACKGROUND: Increase in vascular permeability and multiorgan dysfunction after
cardiopulmonary bypass (CPB) are barriers to successful cardiac surgery in
infants. Complement inhibition with TP10, a C3/C5 convertase inhibitor (AVANT
Immunotherapeutics, Needham, Mass), blunts post-CPB organ dysfunction in the
neonatal pig.Methods and results The pharmacokinetics and safety of TP10 in
infants (age <1 year, n = 15) undergoing CPB were examined in a phase I/II
open-label prospective trial. TP10 (10 mg/kg) was given intravenously before CPB
and also added (10 mg/100 mL prime volume) to the CPB circuit. TP10 plasma
levels correlated with C3a levels and measures of clinical course. All infants
survived. No adverse events were attributed to TP10. TP10 plasma concentration
fell to < or =60 microg/mL 12 hours after CPB. A 2-compartment model was fit to
the TP10 blood levels as a function of time. Based on this model, an initial
dose of 10 mg/kg over 0.5 hours followed by 10 mg/kg over 23.5 hours is the most
appropriate for maintaining TP10 concentration between 100 microg/mL and 160
microg/mL for 24 hours after CPB. C3a was lower 12 hours after CPB than before
CPB and still lower 24 hours after CPB. TP10 concentration was inversely
correlated with the 12-hour post-CPB to pre-CPB ratio of C3a (Spearman rho
-0.76, P = -.016), and with total (rho -0.56, P =.047) and net (rho -0.85, P
=.0016) fluid and blood product administration/kg >24 hours after CPB.
CONCLUSIONS: TP10 administration to infants appears safe. Pharmacokinetic
analysis generated an optimal dosing strategy to achieve effective TP10 levels
for 24 hours after CPB. In the infant, TP10 appears to decrease CPB-induced
complement activation and protect vascular function. These results support a
phase III trial of TP10 in infants requiring CPB.