Asian Cardiovasc Thorac Ann. 2007 Jan;15(1):39-44. 

Antithrombin and protein C in systemic inflammatory response syndrome.

Massad I, Abu-Ali H, Biron-Andreani C, Picot MC, Trinh-Duc P.

, Department of Anesthesia and Intensive Care, Jordan University Hospital, PO
Box 13046, Amman 11942, Jordan. islam_wafa@yahoo.com.

Coronary artery bypass grafting with cardiopulmonary bypass can induce systemic
inflammatory response syndrome. To assess the prevalence of preoperative
antithrombin and protein C deficiencies in relation to the incidence of this
syndrome, antithrombin and protein C levels were measured in 130 patients
undergoing coronary artery bypass grafting with cardiopulmonary bypass. Systemic
inflammatory response syndrome developed in 36 (27.7%) patients who were
predominantly male, had a lower EuroSCORE, longer cardiopulmonary bypass time,
higher pre-bypass temperature, and shorter activated coagulation time. Logistic
regression showed that predictive factors included bypass duration and
pre-bypass temperature; however, low antithrombin levels appeared to be a
negative predictive factor. Antithrombin levels were < 80% in 33.8% of patients,
and 11.6% had protein C levels < 80%. Postoperative antithrombin and protein C
deficiencies are not uncommon in adults undergoing cardiac surgery with
cardiopulmonary bypass, but detection of these deficits did not identify
patients at increased risk of systemic inflammatory response syndrome.

Anesth Analg. 2007 Feb;104(2):378-83. 

A phase II, double-blind, placebo-controlled, ascending-dose study of Eritoran
(E5564), a lipid A antagonist, in patients undergoing cardiac surgery with
cardiopulmonary bypass.

Bennett-Guerrero E, Grocott HP, Levy JH, Stierer KA, Hogue CW, Cheung AT, Newman
MF, Carter AA, Rossignol DP, Collard CD.

Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710,
USA. elliott.bennettguerrero@duke.edu

BACKGROUND: Lipid A, the toxic moiety of endotoxin, is linked to multiple
complications after cardiac surgery, including fever, vasodilation, and
pulmonary and renal dysfunction. The lipid A antagonist eritoran (or E5564)
prevents endotoxin-induced systemic inflammation in animals and humans. In this
study we assessed the safety of eritoran administration in patients undergoing
cardiac surgery and obtained preliminary efficacy data for the prophylaxis of
endotoxin-mediated surgical complications. METHODS: A double-blind, randomized,
ascending-dose, placebo-controlled study was conducted at nine hospitals.
Patients undergoing coronary artery bypass graft and/or cardiac valvular surgery
with cardiopulmonary bypass were enrolled. Patients received a 4-h infusion of
placebo (n = 78) vs 2 mg (n = 24), 12 mg (n = 26), or 28 mg (n = 24) of eritoran
initiated approximately 1 h before cardiopulmonary bypass. RESULTS: No
significant safety concerns were identified with continuous safety monitoring,
and enrollment continued to the highest prespecified dose (28 mg). No
statistically significant differences were observed in most variables related to
systemic inflammation or organ dysfunction/injury. CONCLUSIONS: This Phase II
safety study suggests that the administration of the novel lipid A antagonist,
eritoran, is not associated with overt toxicity in cardiac surgical patients.
Blocking lipid A with eritoran does not appear to confer any clear benefit to
elective cardiac surgical patients.

Eur J Anaesthesiol. 2007 Jan 23;:1-10 [Epub ahead of print] 

Bispectral index and electroencephalographic entropy in patients undergoing
aortocoronary bypass grafting.

Lehmann A, Schmidt M, Zeitler C, Kiessling AH, Isgro F, Boldt J.

Klinikum der Stadt Ludwigshafen, Department of Anaesthesiology and Intensive
Care Medicine, Ludwigshafen, Germany.

SummaryBackground and objective: This study was conducted to compare bispectral
index, state entropy and response entropy in patients undergoing coronary artery
bypass grafting. Methods: In 66 patients, anaesthesia was maintained at two
different levels using bispectral index. Doses of sufentanil and midazolam were
adjusted to achieve a bispectral index in the range of 45-55 in 33 patients (BIS
50 group) and 35-44 in another 33 patients (BIS 40 group). Simultaneously, state
entropy and response entropy were recorded. Results: The targeted values of
bispectral index were achieved in both groups and the bispectral index values
differed significantly during whole anaesthesia. Median response entropy and
state entropy fell to 19-26 during anaesthesia in both groups. Response entropy
and state entropy values in the two groups differed significantly only after
induction of anaesthesia and did not differ during further anaesthesia. There
was no explicit intraoperative recall in both groups. Patients in Group BIS 40
received significantly (P < 0.05) more sufentanil than the BIS 50 group (704 +/-
181 mug vs. 490 +/- 107 mug, respectively) and midazolam (18.5 +/- 6.1 mg vs.
15.6 +/- 3.8 mg, respectively). After cardiopulmonary bypass, significantly (P <
0.05) more patients in Group BIS40 needed inotropic support with dobutamine
(79%) than in the BIS50 group (52%). Time to extubation did not differ between
the two groups. Conclusion: In patients undergoing coronary artery bypass
grafting, no relationship was found between bispectral index levels and state
entropy and response entropy at two different stages of a sufentanil-midazolam
anaesthesia. A bispectral index level of 45-55 reduced anaesthetic medications
used and the need for inotropic support.

J Cardiothorac Surg. 2007 Jan 23;2:7. 

Influence of hypothermia on right atrial cardiomyocyte apoptosis in patients
undergoing aortic valve replacement.

Castedo E, Castejon R, Monguio E, Ramis S, Montero CG, Serrano-Fiz S, Burgos R,
Escudero C, Ugarte J.

Department of Cardiothoracic Surgery, Clinica Puerta de Hierro, Madrid, Spain.
evaristocm@terra.es.

ABSTRACT: BACKGROUND: There is increasing evidence that programmed cell death
can be triggered during cardiopulmonary bypass (CPB) and may be involved in
postoperative complications. The purpose of this study was to investigate
whether apoptosis occurs during aortic valve surgery and whether modifying
temperature during CPB has any influence on cardiomyocyte apoptotic death rate.
METHODS: 20 patients undergoing elective aortic valve replacement for aortic
stenosis were randomly assigned to either moderate hypothermic (ModHT group, n =
10, 28 degrees C) or mild hypothermic (MiHT group, n = 10, 34 degrees C) CPB.
Myocardial samples were obtained from the right atrium before and after weaning
from CPB. Specimens were examined for apoptosis by flow cytometry analysis of
annexin V-propidium iodide (PI) and Fas death receptor staining. RESULTS: In the
ModHT group, non apoptotic non necrotic cells (annexin negative, PI negative)
decreased after CPB, while early apoptotic (annexin positive, PI negative) and
late apoptotic or necrotic (PI positive) cells increased. In contrast, no change
in the different cell populations was observed over time in the MiHT group. Fas
expression rose after reperfusion in the ModHT group but not in MiHT patients,
in which there was even a trend for a lower Fas staining after CPB (p = 0.08).
In ModHT patients, a prolonged ischemic time tended to induce a higher increase
of Fas (p = 0.061). CONCLUSION: Our data suggest that apoptosis signal cascade
is activated at early stages during aortic valve replacement under ModHT CPB.
This apoptosis induction can effectively be attenuated by a more normothermic
procedure.

Eur J Cardiothorac Surg. 2007 Jan 18; [Epub ahead of print] 

The effects of various leukocyte filtration strategies in cardiac surgery.

Warren O, Alexiou C, Massey R, Leff D, Purkayastha S, Kinross J, Darzi A,
Athanasiou T.

Department of BioSurgery and Surgical Technology, Imperial College, St. Mary's
Hospital, Praed Street, London W2 1NY, United Kingdom.

It is known that cardiopulmonary bypass causes an inflammatory reaction with an
associated morbidity and mortality. Several anti-inflammatory strategies have
been implemented to reduce this response, including leukocyte removal from the
circulation using specialised filters. The aim of this study is to
systematically review the available evidence on leukocyte filtration in cardiac
surgery, focusing on its effect on systemic inflammation and whether this has
influenced clinical outcomes. Five electronic databases were systematically
searched for studies reporting the effect of leukocyte filtration at any point
within the cardiopulmonary bypass circuit in humans. Reference lists of all
identified studies were checked for any missing publications. Two authors
independently extracted the data from the included studies. Whilst systemic
leukodepleting filters do not appear to consistently lower leukocyte counts,
they may preferentially remove activated leukocytes. Small improvements in early
post-operative lung function in patients receiving systemic leukodepletion have
been reported, but this does not lead to reduced hospital stay or decreased
mortality. There is substantial evidence that cardioplegic leukocyte filtration
attenuates the reperfusion injury at a cellular level, but this has not been
translated into clinical improvements. Finally, whilst various strategies
involving multiple leukocyte filters, or the incorporation of pharmacological
agents into leukocyte-depleting protocols have been evaluated, the current
available results are not conclusive. Our study suggests that there is not
enough high quality or consistent evidence to draw guidelines regarding the use
of leukocyte-depleting filters within routine cardiac surgical practice.

ASAIO J. 2007 Jan-Feb;53(1):32-5. 

Minimizing cardiopulmonary bypass attenuates myocardial damage after cardiac
surgery.

Skrabal CA, Steinhoff G, Liebold A.

University of Rostock, Department of Cardiac Surgery, Schillingallee 35, 18057
Rostock, Germany.

The standard heart-lung machine is deemed a major trigger of systemic
inflammatory reactions, potentially inducing organ failure. The strict reduction
of blood-artificial surface and blood-air contact might represent meaningful
improvements of the extracorporeal technology with respect to organ
preservation. In this study, we assessed perioperative myocardial damage by
using a novel minimal extracorporeal circuit (MECC) and a conventional
cardiopulmonary bypass (CPB) system.Sixty patients scheduled for coronary artery
bypass surgery were randomly assigned to either the MECC or the standard CPB
system. Myocardial markers were determined by specific immunoassays 6, 12, and
24 hours after CPB initiation. Results were corrected for
hemodilution.Demographics, hemodynamics, the number of anastomoses, CPB, and
cross-clamp time were comparable between the groups. MECC patients demonstrated
significantly lower levels of Troponin T (ng/ml) at 6, 12, and 24 hours (0.07
+/- 0.01 vs. 0.16 +/- 0.04, p < 0.005; 0.12 +/- 0.03 vs. 0.28 +/- 0.08, p <
0.008; 0.21 +/- 0.05 vs. 0.35 +/- 0.09, p < 0.03, respectively) and creatine
kinase-MB (U/l) at 6 and 12 hours (22.5 +/- 1.5 vs. 40.6 +/- 3.3, p < 0.0001;
23.3 +/- 3.4 vs. 40.8 +/- 8.0, p < 0.001, respectively). Creatine kinase-MB at
24 hours tended to lower values in the MECC group but did not quite reach
statistical significance.The MECC system may not only provide a less invasive
solution to meet the requirements during cardiac surgery but also a more
organ-preserving alternative to standard CPB.

 J Cardiothorac Surg. 2007 Jan 11;2(1):4 [Epub ahead of print] 

Factors influencing the outcome of paediatric cardiac surgical patients during
extracorporeal circulatory support.

Balasubramanian SK, Tiruvoipati R, Amin M, Aabideen KK, Peek GJ, Sosnowski AW,
Firmin RK.

ABSTRACT: BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (ECMO)
is a common modality of circulatory assist device used in children. We assessed
the outcome of children who had ECMO following repair of congenital cardiac
defects (CCD) and identified the risk factors associated with hospital
mortality. METHODS: From April 1990 to December 2003, 53 patients required ECMO
following surgical correction of CCD. Retrospectively collected data was
analyzed with univariate and multivariate logistic regression analysis. RESULTS:
Median age and weight of the patients were 150 days and 5.4 kgs respectively.
The indications for ECMO were low cardiac output in 16, failure to wean
cardiopulmonary bypass in 13, cardiac arrest in 10 and cardio-respiratory
failure in 14 patients. The mean duration of ECMO was 143 hours. Weaning off
from ECMO was successful in 66% and of these 83% were survival to
hospital-discharge. 37.7% of patients were alive for the mean follow-up period
of 75 months. On univariate analysis, arrhythmias, ECMO duration >168 hours,
bleeding complications, renal replacement therapy on ECMO, arrhythmias and
cardiac arrest after ECMO were associated with hospital mortality. On
multivariate analysis, abnormal neurology, bleeding complications and
arrhythmias after ECMO were associated with hospital mortality. Extra and
intra-thoracic cannulations were used in 79% and 21% of patients respectively
and extra-thoracic cannulation had significantly less bleeding complications (p
= 0.031). CONCLUSIONS: ECMO provides an effective circulatory support following
surgical repair of CCD in children. Extra-thoracic cannulation is associated
with less bleeding complications. Abnormal neurology, bleeding complications on
ECMO and arrhythmias after ECMO are poor prognostic indicators for hospital
survival.

 Artif Organs. 2007 Jan;31(1):23-30. 

A novel device for reducing hemolysis provoked by cardiotomy suction during open
heart cardiopulmonary bypass surgery: a randomized prospective study.

Jegger D, Horisberger J, Jachertz M, Seigneul I, Tozzi P, Delay D, von Segesser
LK.

Department of Cardiovascular Surgery, Centre Hospitalier Universitaire Vaudois,
Lausanne, Switzerland.

Since the inception of cardiopulmonary bypass (CPB), little progress has been
made concerning the design of cardiotomy suction (CS). Because this is a major
source of hemolysis, we decided to test a novel device (Smartsuction [SS])
specifically aimed at minimizing hemolysis during CPB in a clinical setting.
Block randomization was carried out on a treated group (SS, n = 28) and a
control group (CTRL, n = 26). Biochemical parameters were taken pre-, peri-, and
post CPB and were compared between the two groups using the Student's t-test
with statistical significance when P < 0.05. No significant differences in
patient demographics were observed between the two groups. Lactate dehydrogenase
(LDH) and plasma free hemoglobin (PFH) pre-CPB were comparable for the CTRL and
SS groups, respectively. LDH peri-CPB was 275 +/- 100 U/L versus 207 +/- 83 U/L
for the CTRL and SS groups, respectively (P < 0.05). PFH was 486 +/- 204 mg/L
versus 351 +/- 176 mg/L for the CTRL and SS groups, respectively (P < 0.05). LDH
post CPB was 354 +/- 116 U/L versus 275 +/- 89 U/L for the CTRL and SS groups,
respectively (P < 0.05). PFH was 549 +/- 271 mg/L versus 460 +/- 254 mg/L for
the CTRL and SS groups, respectively (P < 0.05). Preoperative hematocrit (Hct)
of 43 +/- 5% (CTRL) versus 37 +/- 5% (SS), and hemoglobin (Hb) of 141 +/- 16 g/L
(CTRL) versus 122 +/- 17 g/L (SS) were significantly lower in the SS group.
However, when normalized (N), the SS was capable of conserving Hct, Hb, and
erythrocyte count perioperatively. Erythrocytes (N) were 59 +/- 5% (CTRL) versus
67 +/- 9% (SS); Hct (N) was 59 +/- 6% (CTRL) versus 68 +/- 9% (SS), and Hb (N)
was 61 +/- 6% (CTRL) versus 70 +/- 10% (SS) (all P < 0.05). This novel SS device
evokes significantly lowered blood PFH and LDH values peri- and post CPB
compared with the CTRL blood using a CS system. The SS may be a valuable
alternative compared to traditional CS techniques.

Saudi Med J. 2007 Jan;28(1):49-53. 

Ultra-low dose aprotinin effects on reducing the need for blood transfusion in
cardiac surgery.

Parvizi R, Azarfarin R, Hassanzadeh S.

Associate Professor in Cardiac Surgery, Cardiovascular Research Center of Tabriz
University of Medical Sciences, Tabriz, Iran. Tel. +98 (411) 3361175. Fax. +98
(411) 3344021. E-mail: drparvizir@yahoo.com.

OBJECTIVE: To assess the effects of ultra-low dose one million kallikrein
inhibitor units (KIU) of aprotinin on bleeding and the need for transfusion
after cardiac surgery. METHODS: We carried out this randomized clinical trial on
162 cardiac surgery patients in Shahid Madani Hospital, Tabriz, Iran from April
2004 to December 2005. The patients were randomly divided into 2 groups of 81
individuals. In the aprotinin group, 0.5 million KIU infused before and 0.5
million KIU during cardiopulmonary bypass. In the placebo group, 100 ml normal
saline was infused as above. The need to use fresh frozen plasma (FFP), packed
red blood cells (PRBCs) transfusion during, after operation, the rate of chest
tubes drainage at 6, 12 and 24 hours after surgery were measured in 2 groups.
RESULTS: Chest tubes drainage at 6 hours after surgery was 190 +/- 24 ml in the
aprotinin group and 266 +/- 33 ml in the placebo group (p=0.066). The amount of
bleeding at 12 and 24 hours was significantly different between 2 groups
(p=0.048, p=0.009). The frequency of blood products transfusion in the aprotinin
group was 68% and in the placebo group was 75% (p=0.02). The number of PRBCs and
FFP units transfused were significantly lower in the aprotinin group (p=0.000,
p=0.005). Total amount of blood and products transfusion in the aprotinin group
was 2.56 +/- 0.27 units and in placebo group it was 4.37 +/- 0.27 units
(p=0.0001). CONCLUSION: Results indicate that the use of one million KIU of
aprotinin in cardiac surgery is effective in reducing postoperative bleeding and
transfusion requirements.

J Thorac Cardiovasc Surg. 2007 Jan;133(1):44-51. 

Activation of protein C and hemodynamic recovery after coronary artery bypass
surgery.

Raivio P, Fernandez JA, Kuitunen A, Griffin JH, Lassila R, Petaja J.

Department of Cardiothoracic Surgery, Helsinki University Central Hospital,
Helsinki, Finland. peter.raivio@hus.fi

OBJECTIVES: Activated protein C is a physiologic anticoagulant that is activated
by thrombin and upregulated during coronary artery bypass grafting. We studied
the balance between thrombin generation and activated protein C levels during
coronary artery bypass grafting and hypothesized that protein C activation
during reperfusion is associated with hemodynamic recovery or postoperative
myocardial damage. METHODS: One hundred patients undergoing elective on-pump
coronary artery bypass grafting were prospectively studied. Activated protein C,
protein C, prothrombin fragment F1+2 (a marker of thrombin generation), and
D-dimer (a marker of fibrinolysis) levels were measured preoperatively and at 7
time points during cardiopulmonary bypass and reperfusion and postoperatively.
Hemodynamic parameters were measured serially. Cardiac biomarkers (mass of the
Mb fraction of creatine kinase and troponin T) were measured postoperatively.
RESULTS: Reperfusion induced a significant increase in thrombin generation.
Activated protein C levels peaked after heparin neutralization, when they
increased more than 3-fold. Activated protein C levels correlated with F1+2 and
D-dimer levels during cardiopulmonary bypass and reperfusion. Even though this
correlation peaked during early reperfusion (r = 0.55, P < .001), the ratio of
activated protein C to F1+2 decreased during surgical intervention and early
reperfusion by 70% from the preoperative level, indicating a marked delay in
protein C activation in relation to thrombin generation. Patients in the highest
quintile of activated protein C levels during this period had a higher
postoperative cardiac index (mean, 3.1 vs 2.5 L x min(-1) x m(-2); P < .05) and
lower systemic vascular resistance (mean, 2137 vs 2429 dyne x s x cm(-5) x
m(-2); P < .05). Conversely, levels of preoperative activated protein C and
activated protein C measured after heparin neutralization were associated with
unfavorable hemodynamic recovery postoperatively. Activated protein C or protein
C levels were not associated with increased postoperative cardiac biomarkers.
CONCLUSIONS: Reperfusion caused significant thrombin generation that was
followed by activation of protein C. The balance of activated protein C with
thrombin is associated dynamically with postoperative hemodynamic recovery.