TOP TEN SELECTED PAPERS - September 2009

1

J Thorac Cardiovasc Surg. 2009 Sep 8. [Epub ahead of print]

Predictive value of the National Institutes of Health Stroke Scale and the
Mini-Mental State Examination for neurologic outcome after coronary artery bypass
graft surgery.

Nussmeier NA, Miao Y, Roach GW, Wolman RL, Mora-Mangano C, Fox M, Szekely A,
Tommasino C, Schwann NM, Mangano DT; for the Investigators of the Ischemia and
Education Foundation and the Multicenter Study of Perioperative Ischemia Research
Group.

Department of Anesthesiology, SUNY Upstate Medical University, Syracuse, NY.

OBJECTIVE: We intended to define the role of the National Institutes of Health
Stroke Scale and the Mini-Mental State Examination in identifying adverse
neurologic outcomes in a large international sample of patients undergoing
cardiac surgery. METHODS: We evaluated 4707 patients undergoing cardiac surgery
with cardiopulmonary bypass at 72 centers in 17 countries between November 1996
and June 2000. Prespecified overt neurologic outcomes were categorized as type I 
(clinically diagnosed stroke, transient ischemic attack, encephalopathy, or coma)
or type II (deterioration of intellectual function). The National Institutes of
Health Stroke Scale and Mini-Mental State Examination were administered
preoperatively and on postoperative day 3, 4, or 5. Receiver operating
characteristic curves were plotted to determine the predictive value of worsening
in National Institutes of Health Stroke Scale and Mini-Mental State Examination
scores with respect to type I and II outcomes. RESULTS: The receiver operating
characteristic area under the curve for changes in National Institutes of Health 
Stroke Scale score (n = 4620) was 0.89 for type I outcomes and 0.66 for type II
outcomes. A 1-point worsening in National Institutes of Health Stroke Scale score
provided excellent discrimination (86% specificity; 84% sensitivity) of type I
outcomes. The receiver operating characteristic area under the curve for changes 
in Mini-Mental State Examination score (n = 4707) was 0.75 for type I outcomes
and 0.71 for type II outcomes. A 2-point worsening in Mini-Mental State
Examination score provided only fair discrimination (73% specificity; 62%
sensitivity) of type II outcomes. CONCLUSION: We used baseline controls and
postoperative worsening in National Institutes of Health Stroke Scale and
Mini-Mental State Examination scores to predict both serious adverse neurologic
outcome and deterioration of intellectual function. Our findings provide the only
reference for evaluating these tests that are used in cardiac surgical clinical
trials.

J Card Surg. 2009 Sep-Oct;24(5):606-10.

Deep brain hyperthermia while rewarming from hypothermic circulatory arrest.

Amir G, Ramamoorthy C, Riemer RK, Hanley FL, Reddy VM.

Department of Cardiothoracic Surgery, Pediatric Division, Schneider Children's
Medical Center of Israel, Rabin Medical Center, Petach Tikva, Israel.
GabrielA@clalit.org.il

BACKGROUND: Neurologic injury is a feared and serious long-term complication of
cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA).
Postoperative hyperthermia was found to enhance postischemic neurologic injury.
The use of core temperature as the reference point through CPB assumes parallel
changes in brain temperature. We tested the hypothesis that regional and deep
brain temperature (DBT) differ during cooling, DHCA, and rewarming. METHODS:
Neonatal piglets (n = 9) were subject to CPB and cooled to rectal temperature
(RT) of 18 degrees C, 30 minutes of DHCA were initiated, and subsequently the
piglets were rewarmed to RT of 36.5 degrees C and weaned from CPB. Temperature
probes were inserted into the DBT targeting the caudate and thalamic nuclei,
their position confirmed by pathology. Superficial brain temperature was measured
by a temperature probe inserted extradurally. RT, nasopharyngeal (NPT), and
tympanic (TT) temperatures were recorded. RESULTS: During cooling the deep brain 
cooled faster and to lower temperatures compared to RT and TT; NPT reflected DBT 
accurately. During rewarming DBT was significantly higher than RT and TT. By the 
end of rewarming the difference between the deep brain and the RT reached
statistical significance (30 minutes: 35.1 +/- 0.7 vs. 32.3 +/- 0.7 p < 0.05,
respectively, 40 minutes: 37.5 +/- 0.3 vs. 34.7 +/- 0.8 p < 0.05, respectively). 
CONCLUSION: Deep brain hyperthermia routinely occurs during the last stages of
rewarming following DHCA. DBT is accurately reflected by NPT and is directly
correlated with inflow temperature. Therefore, during rewarming inflow
temperatures should not exceed 36 degrees C and NPT should be closely monitored.

Thromb Res. 2009 Sep 3. [Epub ahead of print]

The combination of recombinant factor VIIa and fibrinogen correct clotting ex
vivo in patient samples obtained following cardiopulmonary bypass surgery.

Sørensen B, Asvaldsdottir HS, Gudmundsdottir BR, Onundarson PT.

Center for Haemophilia and Thrombosis, Aarhus University Hospital, Skejby,
Denmark; Haemostasis Research Unit, Centre for Haemophilia and Thrombosis, Guy's 
and St Thomas Hospital & NHS Trust Foundation, King's College Londong School of
Medicine, London, United Kingdom.

Cardiac surgery involving cardio pulmonary bypass (CPB) may be associated with
development of a coagulopathy that increases risk of bleeding. In the present ex 
vivo study we investigated the influence of fibrinogen and rFVIIa, alone or in
combination, on whole blood coagulation thromboelastometry using pre- and
postoperative blood samples from 18 consecutive adult patients undergoing CPB
surgery. Dynamic thromboelastometric clotting profiles were recorded using
citrated whole blood activated with trace amounts of tissue factor (Innovin(R),
final dilution 1:17000). Blood samples were collected before surgery (control)
and postoperative samples were obtained following in vivo neutralization of
heparin with protamine sulphate. All blood samples were treated with heparinase
to ensure neutralization of possible residual heparin effect. The post-operative 
blood samples were spiked with buffer, rFVIIa (2 microg/mL), fibrinogen (1
mg/mL), or the combination of rFVIIa and fibrinogen. Despite neutralization of
heparin, CPB surgery left a measurable coagulopathy that was
thromboelastometrically characterized by prolonged onset of clotting, reduced
maximum velocity of clot formation (MaxVel), and decreased maximum clot firmness 
(MCF). Ex vivo spiking of the postoperative samples with rFVIIa shortened the
clotting time. Fibrinogen also shortened the clotting time and, in addition,
improved the MaxVel, and MCF. Finally, adding the combination of rFVIIa and
fibrinogen to the postoperative samples corrected all thromboelastometric
parameters to the preoperative range. In conclusion, the correction of whole
blood clotting abnormalities that occurs with rFVIIa and/or fibrinogen suggests
that future clinical trials on treatment of bleeding during CPB surgery should
study the haemostatic effect of fibrinogen or possibly the combination of rFVIIa 
and fibrinogen.

Ann Thorac Surg. 2009 Sep;88(3):823-9.

Comment in:
    Ann Thorac Surg. 2009 Sep;88(3):829.

Perioperative stroke in infants undergoing open heart operations for congenital
heart disease.

Chen J, Zimmerman RA, Jarvik GP, Nord AS, Clancy RR, Wernovsky G, Montenegro LM, 
Hartman DM, Nicolson SC, Spray TL, Gaynor JW, Ichord R.

Division of Pediatric Cardiology, Department of Pediatrics, The Children's
Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
chenjo@email.chop.edu

BACKGROUND: The prevalence of perioperative stroke in infants undergoing
operations for congenital heart disease has not been well described. The
objectives of this study were to determine the prevalence of stroke as assessed
by postoperative brain magnetic resonance imaging (MRI), characterize the
neuroanatomic features of focal ischemic injury, and identify risk factors for
its development. METHODS: Brain MRI was performed in 122 infants 3 to 14 days
after cardiac operation with cardiopulmonary bypass, with or without deep
hypothermic circulatory arrest. Preoperative, intraoperative, and postoperative
data were collected. Risk factors were tested by logistic regression for
univariate and multivariate associations with stroke. RESULTS: Stroke was
identified in 12 of 122 patients (10%). Strokes were preoperative in 6 patients
and possibly intraoperative or postoperative in the other 6 patients, and were
clinically silent except in 1 patient who had clinical seizures.
Arterial-occlusive and watershed infarcts were identified with equal distribution
in both hemispheres. Multivariate analysis identified lower birth weight,
preoperative intubation, lower intraoperative hematocrit, and higher blood
pressure at admission to the cardiac intensive care unit postoperatively as
significant factors associated with stroke. Prematurity, younger age at
operation, duration of cardiopulmonary bypass, and use of deep hypothermic
circulatory arrest were not significantly associated with stroke. CONCLUSIONS:
The prevalence of stroke in infants undergoing operations for congenital heart
disease was 10%, half of which occurred preoperatively. Most were clinically
silent and undetected without neuroimaging. Mechanisms included thromboembolism
and hypoperfusion, with patient-specific, procedure-specific, and postoperative
contributions to increased risk.

J Thorac Cardiovasc Surg. 2009 Sep;138(3):703-11. Epub 2009 May 27.

Hetastarch increases the risk of bleeding complications in patients after
off-pump coronary bypass surgery: a randomized clinical trial.

Hecht-Dolnik M, Barkan H, Taharka A, Loftus J.

Kaiser Permanente Medical Center, Oakland, Calif, USA. howardbarkan@cs.com

OBJECTIVE: Hetastarch is an artificial colloid widely used intraoperatively in
fluid-replacement regimens. Previous studies have found that the intraoperative
administration of hetastarch may increase the risk of postoperative bleeding in
patients who undergo coronary artery bypass graft surgery with cardiopulmonary
bypass. Previous published reports have not examined this risk in patients who
underwent coronary artery bypass grafting without cardiopulmonary bypass.
METHODS: In a randomized clinical trial, 156 patients undergoing off-pump
coronary artery bypass grafting were assigned to receive either 1 liter of
hetastarch or 1 liter of albumin as part of intraoperative volume replacement.
Sample recruitment was halted in a review per protocol by the study's Data Safety
Monitoring Committee. We assessed the rate of postoperative bleeding by
monitoring the number of units of blood products transfused in the first 24
postoperative hours in the intensive care unit and the hourly chest tube drainage
in the first 12 postoperative hours. RESULTS: Intraoperative administration of 1 
liter of hetastarch was associated with statistically significant increases in 3 
measures: transfusion requirements on postoperative day 1 (red blood cells, 1.14 
vs 0.40 units, P = .017; fresh-frozen plasma, 0.57 vs 0.15, P = .009; platelets, 
0.35 vs 0.10, P = .013); the overall likelihood of receiving transfusion on
postoperative day 1 (46.2% vs 25.6%, P = .012); and the volume of chest tube
drainage in the first 12 hours postoperatively (732.0 vs 563.6 mL, P < .001).
CONCLUSION: In patients undergoing off-pump coronary artery bypass, the
intraoperative administration of hetastarch increases the postoperative
transfusion requirement and the volume of blood drained postoperatively.

Paediatr Anaesth. 2009 Sep;19(9):854-61.

Hemostatic consequences of a non-fresh or reconstituted whole blood small volume 
cardiopulmonary bypass prime in neonates and infants.

Hornykewycz S, Odegard KC, Castro RA, Zurakowski D, Pigula F, DiNardo JA.

Division of Cardiac Anesthesia, Children's Hospital Boston and Harvard Medical
School, Boston, MA 02115, USA.

OBJECTIVES: Despite aggressive measures to miniaturize the cardiopulmonary bypass
(CPB) circuit in neonates and infants, the CPB prime volume is often at least as 
large as the patients' blood volume. We conducted an observational study to
characterize the hemostatic consequences of a CPB prime consisting of either
non-fresh or reconstituted whole blood. METHODS: Hematocrit, fibrinogen, platelet
count, plasminogen, anti-thrombin III (AT-III), and factors (F) II, V, VII, IX,
and X of 30 neonates and infants undergoing cardiac surgery with CPB utilizing
either a non-fresh or reconstituted whole blood prime were prospectively
evaluated at eight time points. Following protamine administration, microvascular
bleeding was treated by protocol. RESULTS: The hemostatic composition of the CPB 
prime was the same following the use of either non-fresh or reconstituted whole
blood. The CPB prime platelet count (mean +/- SD) was 5.87 +/- 2.84 x 10(3)
microl(-1) when compared to a preoperative platelet count of 298 +/- 142 x 10(3) 
microl(-1) (P < 0.0001). Twenty patients received 17.3 +/- 9.2 ml x kg(-1) (0.86 
+/- 0.46 units x kg(-1)) of platelets with significant improvement in platelet
count. Nine patients received 16.7 +/- 13.4 ml x kg(-1) (0.84 +/- 0.67 units x
kg(-1)) of cryoprecipitate with significant improvements in FVIII and fibrinogen.
CONCLUSIONS: Non-fresh or reconstituted whole blood as a component of a small
volume CPB prime in neonates and infants induces clinically significant
dilutional thrombocytopenia in conjunction with less significant reductions in
fibrinogen, FII, FV, FVII, FVIII, FIX, FX, plasminogen, and AT-III.

Interact Cardiovasc Thorac Surg. 2009 Aug 11. [Epub ahead of print]

Minimal extracorporeal circulation and off-pump compared to conventional
cardiopulmonary bypass in coronary surgery.

Panday GF, Fischer S, Bauer A, Metz D, Schubel J, El Shouki N, Eberle T, Hausmann
H.

Mediclin Coswig Heart Center, Germany.

Objectives: Although minimal extracorporeal circulation (MECC) and off-pump
surgery are equal or better alternatives to conventional cardiopulmonary bypass
(CCPB) regarding perioperative morbidity, use of blood and blood products and
completeness of revascularization, CCPB is still being used in the majority of
coronary artery bypass grafting (CABG) operations. Methods and Results: We
investigated 1472 CABG operations in our center. 1143 CABG operations were
performed using CCPB, 220 using MECC and 109 were performed as off-pump coronary 
artery bypass (OPCAB). All patients were recorded prospectively. Perioperative
follow-up was focused on the occurrence of arrhythmia, neurocognitive disorders
and the need of blood and blood products. Operative mortality rates were
comparable in all 3 groups. The mean number of distal anastomoses was 3.2+/-0.6
in the MECC group, 3.4+/-0.7 in the CCPB group and 1.9+/-0.8 in the OPCAB group
(p=0.01). Arrhythmia occurred in 25% of the MECC group and in 35.6% off the CCPB 
group (p=0.05). Arrhythmia occurred in 21.7% of the OPCAB group. Seven patients
(3%) of the MECC group suffered neurocognitive disorders perioperatively compared
to 74 (7%) patients off the CCPB group (p=0.05) and 3 patients of the OPCAB group
(3%). The median number of blood transfusions per patient was 0.8 in the MECC
group, 1.8 in the CCPB group and 0.8 in the OPCAB group (p<0.0001). Conclusions: 
Perioperative morbidity of MECC and OPCAB is comparable to or even less in
comparison to CCPB. MECC allows CABG surgery in cardiac arrest so that
completeness of revascularization is being warranted and longer patency rates can
be guaranteed. Furthermore the use of blood and blood products is significantly
less in MECC surgery so that MECC should be considered first choice in CABG
surgery over CCPB and OPCAB. Keywords: Coronary artery disease; Minimal
extracorporeal circulation; Off-pump coronary artery bypass; Conventional
cardiopulmonary bypass; Coronary artery bypass grafting.

Eur J Cardiothorac Surg. 2009 Jul 28. [Epub ahead of print]

Static blood-flow control during cardiopulmonary bypass is a compromise of oxygen
delivery.

Svenmarker S, Häggmark S, Hultin M, Holmgren A.

Department of Surgical and Perioperative Science, Heart Centre, Umeå University
Hospital, Umeå, Sweden.

Background: Blood-flow control during cardiopulmonary bypass (CPB) is by
tradition based on the patient's body surface area. Emergence of new techniques
enables dynamic blood-flow control based on online measurement of venous oxygen
saturation and oxygen consumption. Present investigation aimed to compare static 
versus dynamic blood-flow control with respect to use of oxygen and effects upon 
organ function. Methods: In this study, 100 coronary-artery-bypass surgical
patients were prospectively randomised to static or dynamic hypothermic
blood-flow control during CPB. In the static group, pump flow was set to 2.4
(litres per minute) times the patient's body surface area (m(2)) throughout the
procedure. Pump flow in the dynamic group was varied according to the reading of 
the venous oxygen saturation and maintained at >75%. CPB-specific information was
collected online. Blood samples were collected for analysis of haemoglobin,
lactate, amylase, creatinine and C-reactive protein: pre-CPB, at weaning from CPB
and on day 1 postoperatively. Results: Randomisation formed two uniform groups.
Choice of static or dynamic blood-flow control during CPB had no significant
effects on organ function as judged by lactate, amylase or creatinine levels. On 
increasing oxygen demand, oxygen balance was maintained by increasing venous
oxygen extraction rates in the static flow mode and by increasing the pump flow
rate in the dynamic group. Conclusions: Independent of the blood-flow control
mode, oxygen balance remained preserved. However, the dynamic mode provided
higher oxygen delivery, which may increase margins of safety and protection of
organ function.

Can J Anaesth. 2009 Sep;56(9):658-66. Epub 2009 Jul 29.

Target-achieved propofol concentration during on-pump cardiac surgery: a pilot
dose-finding study.

Raedschelders K, Hui Y, Laferlita B, Luo T, Zhang H, Chen DD, Ansley DM.

Department of Anesthesiology, Pharmacology, and Therapeutics, The University of
British Columbia, Rm 3200 3rd Floor, JPP. 910 West 10th Ave, Vancouver, BC V5Z
4E3, Canada.

PURPOSE: Propofol concentrations that produce laboratory-based cardioprotective
effects are generally greater than those produced under routine anesthesia during
cardiac surgery. It is unknown whether experimental cardioprotective propofol
concentrations can routinely be achieved during cardiopulmonary bypass (CPB)
using continuous infusion. METHODS: Twenty-four patients scheduled for primary
aortocoronary bypass grafting with CPB were allocated to receive one of three
propofol infusion rates; 50, 100, or 150 microg x kg(-1) x min(-1) in an
open-label pilot study. Data were described using a line of best fit to derive an
experimental clinical maneuver predicted to produce a whole blood concentration
of 5 microg x mL(-1) at reperfusion. A predetermined interim analysis of 30
patients who were receiving the derived maneuver in an ongoing study was used to 
evaluate the maneuver. Cardiac index (CI), systemic vascular resistance index
(SVRI), and left ventricular stroke work index (LVSWI) were recorded. RESULTS:
The infusion rate-concentration curve had an equation of y = 0.215e (0.0279x ),
where y represents the whole blood concentration and x represents the infusion
rate (r (2) = 0.781). The predicted infusion rate to achieve a mean concentration
of 5 microg x mL(-1) was 113 microg x kg(-1) x min(-1). The nearest practical
rate is 120 microg x kg(-1) x min(-1), producing a concentration of 5.39 (1.45)
microg x mL(-1). The values for CI, SVRI, and LVSWI were similar between groups
at corresponding time periods. CONCLUSIONS: An infusion rate of 120 microg x
kg(-1) x min(-1) is clinically practical and capable of achieving experimental
cardioprotective propofol concentrations at reperfusion.

Cytokine. 2009 Sep;47(3):206-13. Epub 2009 Jul 24.

Age-dependent mobilization of circulating endothelial progenitor cells in infants
and young children undergoing cardiac surgery with cardiopulmonary bypass.

Sun Y, Yi D, Wang Y, Zheng R, Sun G, Wang J, Liu Y, Ren J, Wang Y, Zhang S, Gu C,
Pei J.

Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical
University, Xi'an, 710032 Shaanxi, China.

This study was designed to find the effects of age on circulating endothelial
progenitor cells (EPCs) and their mobilization in infants and young children
following surgical correction of congenital heart defects. In 60 consecutive
infants and young children (1month to 3years old) undergoing repair of
atrial/ventricular septal defect, the numbers of EPCs and plasma levels of IL-6, 
-8, -10, TNF-alpha, VEGF and G-CSF were determined preoperatively, at the end of 
cardiopulmonary bypass (CPB), as well as 6, 12, 24, 48, 72 and 96h following
surgery. Preoperative EPCs were reduced with increased age, similar to changes in
plasma VEGF and G-CSF levels. Rapid mobilizations of EPCs and plasma VEGF, G-CSF 
were induced by cardiac surgery with CPB in all infants and young children, and
the increased volumes of EPCs, VEGF and G-CSF decreased with age decreasing. The 
increased volumes of IL-6, -8, -10 and TNF-alpha were similar in different age
groups. However, mobilization of EPCs, plasma VEGF and G-CSF were limited in
infants <6months old, which did not correlate with change in inflammatory IL
activation. Preoperative EPCs and plasma levels of VEGF and G-CSF were reduced
with increasing age in infants and young children. Although a significant
increase in EPCs and release of cytochemokines were observed in infants
undergoing CPB, the mobilization of EPCs of the infants <6months old are limited.