J Thromb Haemost. 2004 Nov;2(11):1882-8. 

Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary
bypass.

Lillo-Le Louet A, Boutouyrie P, Alhenc-Gelas M, Le Beller C, Gautier I, Aiach M,
Lasne D.

Centre Regional de Pharmacovigilance and Clinical Pharmacology Unit, Hopital
Europeen Georges Pompidou, Assistance Publique-Hopitaux de Paris, France.
PharmacoVigilance.Hegp@hop.egp.ap-hop-paris.fr

Heparin-induced thrombocytopenia (HIT) occurs in nearly 3% of patients treated
with heparin after cardiopulmonary bypass (CPB). HIT carries a risk of severe
thrombotic complications, and must be diagnosed rapidly. To identify simple
criteria for estimating the probability of HIT after CPB, we retrospectively
analyzed the files of 84 patients with suspected HIT after CPB and we analyzed
the usefulness of several variables collected at the time of HIT suspicion to
estimate HIT probability. HIT was confirmed in 35 cases and ruled out in 49
cases, on the basis of a platelet increment after heparin withdrawal, detection
of heparin-dependent antibodies, and absence of other clear cause of
thrombocytopenia. A biphasic platelet count from CPB to the first day of
suspected HIT, an interval of >/= 5 days from CPB to the first day of suspected
HIT, and a CPB duration of </= 118 min were independent risk factors for HIT.
These variables were combined to create a post-CPB HIT probability score. The
score correctly identified 34/35 HIT patients and 28/49-non-HIT patients. This
score, which can be applied as soon as HIT is suspected after CPB, has very good
negative predictive value (97%). Prospective studies are required to confirm
these findings.

Am J Surg. 2004 Nov;188(5):474-80. 

Intraoperative regional myocardial acidosis predicts the need for inotropic
support in cardiac surgery.

Kumbhani DJ, Healey NA, Birjiniuk V, Crittenden MD, Treanor PR, Al-Tabbaa AK,
Khuri SF.

Surgical Service (112), Veterans Affairs Boston Healthcare System, 1400 VFW
Pkwy, West Roxbury, MA 02132, USA.

OBJECTIVE: To determine the impact of regional myocardial acidosis encountered
during cardiac surgery on the need for inotropic and intra-aortic balloon (IAB)
support. METHODS: Intramyocardial tissue pH(37C) was measured in 247 patients
undergoing cardiopulmonary bypass (CPB). Inotropic support (INO) was defined as
requiring one or more of norepinephrine/epinephrine/amrinone/dobutamine/>2.5
mug/kg/min dopamine, for at least 45 minutes intraoperatively, and
intraoperative or postoperative IAB use. PH (corrected to 37 degrees C, pH(37C))
during surgery was compared in patients who needed INO versus those who did not.
Multivariate logistic regression models identified the determinants of INO.
RESULTS: Fifty patients (20.2%) required INO intraoperatively. pH(37C) was
significantly lower throughout reperfusion in patients needing INO. Preoperative
ejection fraction and pH(37C) during reperfusion were identified as independent
predictors of INO. CONCLUSIONS: This is the first study to show that
intraoperative regional myocardial acidosis, a preventable condition,
independently determines the need for intraoperative INO. Increased INO is
associated with greater postoperative mortality and morbidity.

Br J Anaesth. 2004 Nov 12; [Epub ahead of print] 

Exhaled nitric oxide before and after cardiac surgery with cardiopulmonary
bypass--response to acetylcholine and nitroglycerin.

Tornberg DC, Angdin M, Settergen G, Liska J, Lundberg JO, Weitzberg E.

Department of Surgical Sciences, Anaesthesiology and Intensive Care, Karolinska
Institute and Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden.

BACKGROUND: Pulmonary endothelial dysfunction may occur after
ischaemia-reperfusion injury and can be revealed as a reduced vasodilatory
response upon administration of acetylcholine (ACh). ACh also releases the
endothelium-derived vasodilator nitric oxide but direct measurements of this gas
are difficult to perform in vivo. We wanted to study the effects of i.v.
administration of ACh and the endothelium-independent vasodilator nitroglycerin
on exhaled nitric oxide in relation to pulmonary endothelial dysfunction after
open-heart surgery and cardiopulmonary bypass (CPB). METHODS: Basal exhaled
nitric oxide and the response in exhaled nitric oxide to i.v. injections of ACh
and nitroglycerin were measured with chemiluminescence in 10 patients before and
after open-heart surgery. RESULTS: Exhaled nitric oxide decreased significantly
after CPB. I.V. bolus injections of ACh induced a reproducible and
dose-dependent increase in exhaled nitric oxide that was unaltered after CPB. In
contrast, the increase in exhaled nitric oxide evoked by nitroglycerin was
attenuated after CPB. The response in pulmonary vascular resistance index (PVRI)
to an infusion of ACh decreased after CPB, indicating endothelial dysfunction.
The decrease in PVRI response to ACh correlated to the duration of CPB.
CONCLUSIONS: Interestingly, pulmonary vascular dysfunction after CPB was
accompanied by a reduction in the exhaled nitric oxide response to nitroglycerin
and lower levels of basal exhaled nitric oxide. The ACh-induced responses in
exhaled nitric oxide were unchanged, which could indicate nitric
oxide-independent mechanisms behind the endothelial dysfunction in this study.
The possibility of using exhaled nitric oxide dynamics to investigate pulmonary
endothelial dysfunction merits further studies.

J Heart Lung Transplant. 2004 Nov;23(11):1228-30. 

Previous thoracic surgery does not increase peri-operative mortality in
pediatric heart-lung transplant recipients.

Koulouri S, Woo MS, Horn MV, Wells WJ, Starnes VA, Szmuszkovicz JR.

Division of Cardiology, Los Angeles, California, USA.

BACKGROUND: Heart-lung transplant (HLT) is indicated in select children with
end-stage cardiopulmonary disease. We sought to determine whether previous
thoracic surgery increases peri-operative morbidity and mortality. METHODS:
Retrospective data were analyzed using unpaired Student's t-test and Fisher's
exact test. Results are reported as mean +/- SD. Peri-operative mortality was
defined as death at <==30 days post-transplant. RESULTS: From August 1993
through April 2001, 13 patients (mean age 7.9 +/- 5.3 years; 9 girls, 4 boys)
underwent HLT at our center. Eight of 13 (62%) had previous thoracic surgery and
5 of 13 (38%) did not. Interval of last surgery to transplant date was 45.5 +/-
26.4 months (range 6 to 79 months). We compared HLT patients who had previous
thoracic surgery to HLT recipients who did not. There was no significant
difference in weight (18.6 +/- 14.3 vs 36.5 +/- 20.7 kg, p = 0.09), age (6.5 +/-
4.5 vs 10.2 +/- 6.1 years, p = 0.23) or duration of intubation (14.1 +/- 12.9 vs
17.0 +/- 30.3 days, p = 0.83). There were no caval or tracheal anastomotic
stenoses in either group. There was no significant difference in blood products
transfused <==48 hours after HLT: packed red blood cells (p = 0.16); fresh
frozen plasma (p = 0.13); platelets (p = 0.59), and cryoprecipitate (p = 0.27).
There was no difference in cardiopulmonary bypass time (129.3 +/- 48.2 vs 160.6
+/- 73.9 minutes, p 0.39); post-operative diaphragm dysfunction (4 of 8 vs 0 of
5, p = 0.1); re-exploration for bleeding (2 of 8 vs 1 of 5, p = 1.0); or
peri-operative mortality (2 of 8 vs 0 of 5, p = 0.48). CONCLUSIONS: We conclude
that previous thoracic surgery in HLT recipients does not significantly increase
blood product transfusion, cardiopulmonary bypass time or peri-operative
mortality.

Pediatr Res. 2004 Nov 5; [Epub ahead of print] 

Identification of Pressure Passive Cerebral Perfusion and Its Mediators after
Infant Cardiac Surgery.

Bassan H, Gauvreau K, Newburger JW, Tsuji M, Limperopoulos C, Soul J, Walter G,
Laussen PC, Jonas RA, DU Plessis AJ.

Departments of Neurology, Cardiology, Anesthesia, and Cardiac Surgery,
Children's Hospital Boston and Harvard Medical School, Boston, Ma 02115; and
Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115.

Cerebrovascular pressure autoregulation (CPA) regulates cerebral blood flow
(CBF) in relation to changes in mean arterial blood pressure (MAP).
Identification of a pressure-passive cerebral perfusion and the potentially
modifiable physiologic factors underlying it has been difficult to achieve in
sick infants. We previously validated the near-infrared spectroscopy-derived
hemoglobin difference (HbD) signal (cerebral oxyhemoglobin - deoxyhemoglobin) as
a reliable measure of changes in CBF in animal models. We now sought to
determine whether continuous measurements of DeltaHbD would correlate to middle
cerebral artery flow velocity (CBFV), allow identification and quantification of
pressure-passive state, and help to delineate potentially modifiable factors. We
enrolled 43 infants (2 d to 7 mo old) who were undergoing open cardiac surgery
and cardiopulmonary bypass. At 6 and 20 h after surgery, we measured changes in
HbD, CBFV (by transcranial Doppler), and MAP at different end-tidal CO2 levels.
We assigned a pressure-passive index (PPI) to each study on the basis of the
relative duration of significant coherence between DeltaMAP and DeltaHbD. We
found a significant relationship between DeltaHbD and DeltaCBFV at both time
points. At 6 h after surgery, we showed high concordance (coherence >0.5; PPI
>/=41%) between DeltaMAP and DeltaHbD, consistent with disturbed CPA in 13% of
infants. End-tidal CO2 values >/=40 mm Hg and higher MAP variability both were
associated with increased odds (p < 0.001) of autoregulatory failure. This
approach provides a means to identify and quantify disturbances of CPA. High CO2
levels and fluctuating MAP are two important preventable factors associated with
disturbed CPA.

J Surg Res. 2004 Nov;122(1):113-20. 

Dose dependent effects of cardiac beta2 adrenoceptor gene therapy.

Jones JM, Wilson KH, Steenbergen C, Koch WJ, Milano CA.

Department of Surgery, Duke University Medical Center, Durham, North Carolina,
USA.

BACKGROUND: Adenoviral-mediated gene transfer during cardiopulmonary bypass
(CPB) achieves efficient myocardial transgene expression. The optimal vector
dose required to produce not only increased beta adrenoceptor (betaAR) density
but, more importantly, enhanced left ventricular (LV) function is unknown. In
addition, it is unclear if absent extracardiac expression in preliminary studies
represented cardiac specific, as opposed to selective gene delivery, as a
consequence of low vector doses. MATERIALS AND METHODS: Adenoviral vector
encoding the human beta(2) adrenoceptor (Adeno-beta(2)AR) was delivered to
cardioplegic arrested hearts of neonatal piglets during CPB in three doses
ranging from 5 x 10(11) total viral particles (tvp) to 2 x 10(12) tvp. Control
animals received adenoviral vector encoding beta galactosidase (Adeno-betagal)
or PBS (PBS). LV and liver betaAR density and in vivo LV function were assessed
5 days later. RESULTS: Elevated LV betaAR density was present after delivery of
Adeno-beta(2)AR at all doses. Piglets which received 5 x 10(11) tvp and 1 x
10(12) tvp Adeno-beta(2)AR demonstrated enhanced LV dP/dt(max) but in those
receiving 2 x 10(12) tvp LV dP/dt(max) was unchanged. Moreover, at this higher
dose of adenoviral vector the detrimental effects of cardiac inflammation and
extracardiac gene overexpression became apparent. CONCLUSIONS: Although the
highest increase in cardiac betaAR density occurred after high-dose
Adeno-beta(2)AR, LV dP/dt(max) was not enhanced. Moreover, significant
extracardiac gene expression was present at this dose, emphasizing the need for
careful dose response studies in gene therapy. However, cardiac selective
beta(2)AR overexpression does occur following adenoviral vector delivery during
CPB and cardioplegic arrest resulting in enhanced LV dP/dt(max).

Eur J Cardiothorac Surg. 2004 Nov;26(5):947-50. 

How much heparin do we really need to go on pump? A rethink of current
practices.

Shuhaibar MN, Hargrove M, Millat MH, O'Donnell A, Aherne T.

Cork University Hospital, Cork, Ireland. msampca@msn.com

OBJECTIVES: Patients undergoing myocardial revascularisation using
extracorporeal circulation require heparin anticoagulation. We aimed to evaluate
the effect of reducing heparin dosage on target activated clotting time (ACT)
and postoperative blood loss. METHODS: In a prospective randomised trial, 195
patients undergoing isolated primary CABG were randomised into four groups A, B,
C, and D receiving an initial heparin dosage of 100, 200, 250 and 300 iu/kg,
respectively. Extra incremental heparin (50 iu/kg) was added if required to
achieve a target ACT of 480 s before initiating cardiopulmonary bypass.
Postoperative blood loss was measured from the time of heparin reversal to drain
removal 24h later. RESULTS: Target ACT was achieved in 0, 63, 68.3 and 82.4% of
patients in groups A, B, C and D, respectively, after the initial dose of
heparin. In group B, of those not achieving target act a single increment of
heparin was sufficient to achieve target ACT in further 18.6%. The mean ACT
after the initial dose in groups B, C and D was 482.9, 519 and 588 s,
respectively (P<0.05). Postoperative blood loss in millilitre per kilogram was
directly proportional to preoperative heparin dose. CONCLUSIONS: Patients
receiving lower dose of heparin has lower postoperative blood loss. Of those
achieving the target ACT, group B was significantly the closest to the target
ACT. A starting dose of 200 iu/kg of heparin and if necessary one 50 iu/kg
increment achieved target ACT in 81.5% of patients. The added benefit of
significant drop in postoperative blood loss is evident.

Eur J Cardiothorac Surg. 2004 Nov;26(5):939-46. 

Red blood cell aggregation during cardiopulmonary bypass: a pathogenic cofactor
in endothelial cell activation?

Morariu AM, Gu YJ, Huet RC, Siemons WA, Rakhorst G, Oeveren WV.

Department of Biomedical Engineering, Division of Artificial Organs, University
of Medicine Groningen, Faculty of Medical Sciences, A. Deusinglaan 1, 9713 AV
Groningen, The Netherlands. a.m.morariu@med.rug.nl

OBJECTIVE: The bio-incompatibility of the cardiopulmonary bypass (CPB) circuit
and the use of artificial colloids trigger massive defense reaction that
involves endothelial cells and several blood cells: platelets, neutrophils,
monocytes, red blood cells (RBC) and lymphocytes. Investigating the effects on
RBC aggregation and endothelial cells activation, the present study addresses
two different prime solutions commonly used in the clinical practice. METHODS:
RBC aggregation was measured by means of Laser-assisted Optical Rotation Cell
Analyzer, in an in vitro study designed to mimic the human blood-material
interactions during extracorporeal circulation. A clinical study investigating
endothelial activation was conducted in 20 patients undergoing elective coronary
bypass surgery, randomly assigned for CPB using two different priming solutions:
HAES-steril 6% (HES 200/0.5) and Voluven 6% (HES 130/0.4). RESULTS: Circulation
trough a Chandler loop of HES-blood mixes altered significantly RBC
aggregability. The use of HES 130/0.4 resulted in marked decrease in RBC
aggregation (aggregation index (AI) before and after circulation was 23.5+/-3.8
and 18+/-2.9, respectively), no significant differences being found when
compared with Ringer's lactate group. The use of HES 200/0.5 resulted in better
maintained RBC aggregation (AI 39.7+/-5.9 and 29.7+/-4.7 before and after
circulation, respectively). The AI measured for the whole blood (control) sample
was 61.9+/-4.9 before circulation, and 58.1+/-4 after. Markers of endothelial
activation (von Willebrand factor (vWF), thrombomodulin (TM), tissue plasminogen
activator (tPA) and E-selectin) significantly increased during CPB. Differences
between HES treatment groups were evident post-bypass. While the markers of
endothelial activation returned to baseline in HES 200/0.5 group, HES 130/0.4
was associated on the first post-operative day with further increase of vWF and
tPA. CONCLUSION: RBC aggregation significantly drooped as consequence of blood
dilution and blood-material interaction. We reason that low RBC aggregation
added to plasma viscosity reduction and non-physiologic flow conditions during
extracorporeal circulation are important factors contributing to loss of shear
stress at the venous endothelial wall. The loss of shear stress triggers complex
signaling leading to endothelial activation. Additional fundamental research is
needed in order to verify the hypothesis introduced by the present study.
Characterizing the impact of rheologic parameters on endothelial function could
prove to be valuable in patients undergoing CPB.

J Thorac Cardiovasc Surg. 2004 Nov;128(5):655-61. 

Emergency conversion to cardiopulmonary bypass during attempted off-pump
revascularization results in increased morbidity and mortality.

Patel NC, Patel NU, Loulmet DF, McCabe JC, Subramanian VA.

Section of Cardiothoracic Surgery, Lenox Hill Hospital, 130 E 77th Street, New
York, NY 10021, USA. niravcpatel@aol.com

OBJECTIVE: We sought to evaluate outcomes and predictors of emergency conversion
to cardiopulmonary bypass during attempted off-pump coronary bypass surgery.
METHODS: From January 1999 through July 2002, 1678 consecutive isolated coronary
artery bypass operations were performed at Lenox Hill Hospital, with the
intention to treat all patients with off-pump coronary bypass surgery. Fifty
(2.97%) patients required urgent conversion to cardiopulmonary bypass. All the
preoperative, intraoperative, and postoperative variables were collected and
analyzed in accordance with the New York State Cardiac Surgery Reporting System.
Multivariate regression analysis was performed to determine predictors for
conversion. RESULTS: In-hospital mortality and major morbidity were
significantly lower in the nonconverted group compared with the converted
patients (mortality: 1.47% [n = 24] vs 12% [n = 6], P = .001; stroke: 1.1% [n =
18] vs 6% [n = 3], P = .02; renal failure: 1.23% [n = 20] vs 6% [n = 3], P =
.02; deep sternal wound infection: 1.54% [n = 25] vs 8% [n = 4], P = .009;
respiratory failure: 3.75% [n = 61] vs 28% [n = 14], P < .0001; nonconverted vs
converted patients, respectively). The annual incidence of conversion decreased
during the study period. There was a significant reduction in the incidence of
conversion after routine use of a cardiac positioning device to performing
lateral and inferior wall grafts (4.2% [n = 27] vs 2.3% [n = 23], P = .04). None
of the preoperative variables were independent predictors of conversion on
multivariate regression analysis. CONCLUSIONS: Because emergency conversion to
cardiopulmonary bypass during attempted off-pump coronary bypass surgery results
in significantly higher morbidity and mortality, studies comparing off-pump
coronary bypass surgery with conventional coronary artery surgery should include
converted patients in the off-pump group. In our experience, emergency
conversion is an unpredictable event. The incidence of conversion decreases with
increasing experience of surgeons in performing off-pump coronary surgery and
use of a cardiac positioning device.