Transfusion. 2007 Oct;47(4 Suppl):206S-248S.

Nonsurgical bleeding diathesis in anemic thrombocytopenic patients: role of
temperature, red blood cells, platelets, and plasma-clotting proteins.

Valeri CR, Khuri S, Ragno G.

NBRL, Inc., and Boston VA Healthcare System, Boston, Massachusetts, USA.
navblood@nbrl.org

Research at the Naval Blood Research Laboratory (Boston, MA) for the past four
decades has focused on the preservation of red blood cells (RBCs), platelets
(PLTs), and plasma-clotting proteins to treat wounded servicemen suffering blood 
loss. We have studied the survival and function of fresh and preserved RBCs and
PLTs and the function of fresh and frozen plasma-clotting proteins. This report
summarizes our peer-reviewed publications on the effects of temperature, RBCs,
PLTs, and plasma-clotting proteins on the bleeding time (BT) and nonsurgical
blood loss. The term nonsurgical blood loss refers to generalized, systemic
bleeding that is not corrected by surgical interventions. We observed that the BT
correlated with the volume of shed blood collected at the BT site and to the
nonsurgical blood loss in anemic thrombocytopenic patients after cardiopulmonary 
bypass surgery. Many factors influence the BT, including temperature; hematocrit 
(Hct); PLT count; PLT size; PLT function; and the plasma-clotting proteins factor
(F)VIII, von Willebrand factor, and fibrinogen level. Our laboratory has studied 
temperature, Hct, PLT count, PLT size, and PLT function in studies performed in
non-aspirin-treated and aspirin-treated volunteers, in aspirin-treated baboons,
and in anemic thrombocytopenic patients. This monograph discusses the role of
RBCs and PLTs in the restoration of hemostasis, in the hope that a better
understanding of the hemostatic mechanism might improve the treatment of anemic
thrombocytopenic patients. Data from our studies have demonstrated that it is
important to transfuse anemic thrombocytopenic patients with RBCs that have
satisfactory viability and function to achieve a Hct level of 35 vol percent
before transfusing viable and functional PLTs. The Biomedical Excellence for
Safer Transfusion (BEST) Collaborative recommends that preserved PLTs have an in 
vivo recovery of 66 percent of that of fresh PLTs and a life span that is at
least 50 percent that of fresh PLTs. Their recommendation does not include any
indication that preserved PLTs must be able to function to reduce the BT and
reduce or prevent nonsurgical blood loss. One of the hemostatic effects of RBC is
to scavenge endothelial cell nitric oxide, a vasodilating agent that inhibits PLT
function. In addition, endothelin may be released from endothelial cells, a
potent vasoconstrictor substance,to reduce blood flow at the BT site. RBCs, like 
PLTs at the BT site, may provide arachidonic acid and adenosine diphosphate to
stimulate the PLTs to make thromboxane, another potent vasoconstrictor substance 
and a PLT-aggregating substance. At the BT site, the PLTs and RBCs are activated 
and phosphatidyl serine is exposed on both the PLTs and the RBCs. FVa and FXa,
which generate prothrombinase activity to produce thrombin, accumulate on the
PLTs and RBCs. A Hct level of 35 vol percent at the BT site minimizes shear
stress and reduces nitric oxide produced by endothelial cells. The transfusion
trigger for prophylactic PLT transfusion should consider both the Hct and the PLT
count. The transfusion of RBCs that are both viable and functional to anemic
thrombocytopenic patients may reduce the need for prophylactic leukoreduced PLTs,
the alloimmunization of the patients, and the associated adverse events related
to transfusion-related acute lung injury. The cost for RBC transfusions will be
significantly less than the cost for the prophylactic PLT transfusions.

Anesthesiology. 2007 Oct;107(4):577-84.

Effects of extreme hemodilution during cardiac surgery on cognitive function in
the elderly.

Mathew JP, Mackensen GB, Phillips-Bute B, Stafford-Smith M, Podgoreanu MV,
Grocott HP, Hill SE, Smith PK, Blumenthal JA, Reves JG, Newman MF; Neurologic
Outcome Research Group (NORG) of the Duke Heart Center.

Department of Anesthesiology, Duke University Medical Center, Durham, North
Carolina 27710, USA. mathe014@mc.duke.edu

BACKGROUND: Strategies for neuroprotection including hypothermia and hemodilution
have been routinely practiced since the inception of cardiopulmonary bypass. Yet 
postoperative neurocognitive deficits that diminish the quality of life of
cardiac surgery patients are frequent. Because there is uncertainty regarding the
impact of hemodilution on perioperative organ function, the authors hypothesized 
that extreme hemodilution during cardiac surgery would increase the frequency and
severity of postoperative neurocognitive deficits. METHODS: Patients undergoing
coronary artery bypass grafting surgery were randomly assigned to either moderate
hemodilution (hematocrit on cardiopulmonary bypass >or=27%) or profound
hemodilution (hematocrit on cardiopulmonary bypass of 15-18%). Cognitive function
was measured preoperatively and 6 weeks postoperatively. The effect of
hemodilution on postoperative cognition was tested using multivariable modeling
accounting for age, years of education, and baseline levels of cognition.
RESULTS: After randomization of 108 patients, the trial was terminated by the
Data Safety and Monitoring Board due to the significant occurrence of adverse
events, which primarily involved pulmonary complications in the moderate
hemodilution group. Multivariable analysis revealed an interaction between
hemodilution and age wherein older patients in the profound hemodilution group
experienced greater neurocognitive decline (P = 0.03). CONCLUSIONS: In this
prospective, randomized study of hemodilution during cardiac surgery with
cardiopulmonary bypass in adults, the authors report an early termination of the 
study because of an increase in adverse events. They also observed greater
neurocognitive impairment among older patients receiving extreme hemodilution.

Eur J Cardiothorac Surg. 2007 Dec;32(6):882-7. Epub 2007 Sep 29.

Pulmonary lactate release following cardiopulmonary bypass.

Gasparovic H, Plestina S, Sutlic Z, Husedzinovic I, Coric V, Ivancan V, Jelic I.

Department of Cardiac Surgery, University Hospital Rebro Zagreb, Zagreb, Croatia.

Objective: The etiology of lung injury following cardiopulmonary bypass (CPB) is 
multifactorial. Our study focused on quantifying the lactate release from the
lungs precipitated by extracorporeal circulation at different time points after
the insult. This was complemented by an evaluation of the gas exchange at the
level of the alveolar-capillary membrane. Methods: Forty consecutive patients
(age 61+/-11 years, EuroScore 4.7+/-2.7) undergoing CABG were prospectively
analyzed. The data are presented as medians and the interquartile range. Results:
The pulmonary lactate release (PLR) increased from a baseline value of 0.033
(range -0.077 to 0.170) to 0.465mmol/min/m(2) (range 0.113-0.922), which was seen
6h postoperatively (P<0.001). The A-a O(2) gradient increased from 12.7 (range
8.8-15) to 39.1kPa (range 30.3-46.5) upon discontinuation of CPB (P<0.001). The
systemic arterial lactate (L(S)) concentration increased from 1.22 (range 1-1.44)
to 3.03mmol/l (range 2.29-4.76) 6h after surgery (P<0.001). The veno-arterial
pCO(2) difference (V-A dpCO(2)) rose from 0.6 (range 0.5-0.9) to 0.9kPa (range
0.7-1) (P=0.014). The mortality in the studied group was 5% (2/40). Conclusions: 
The lungs were found to be a significant source of lactate, and this pulmonary
lactate flux was accentuated by CPB. The PLR correlated with systemic
hyperlactatemia as well as the A-a O(2) gradient, and was found to be higher in
patients requiring prolonged mechanical ventilatory support. The duration of CPB 
had a significant impact on the systemic lactate concentrations, V-A dpCO(2) and 
the A-a O(2) gradient, but not on the PLR.

J Cardiothorac Vasc Anesth. 2007 Oct;21(5):683-9. Epub 2007 Mar 9.

Isoflurane, 0.5 minimum alveolar concentration administered through the
precardiopulmonary bypass period, reduces postoperative dobutamine requirements
of cardiac surgery patients: a randomized study.

Ndoko SK, Tual L, Ait Mamar B, Sauvat S, Jabre P, Zakhouri M, Rosanval O, Abdi M,
Kirsch M, Pouzet B, Loisance D, Dhonneur G.

Department of Anesthesiology and Surgical Intensive Care, Paris XII, University
Hospital Henri Mondor, Créteil, France. serge.ndoko@jvr.aphp.fr

OBJECTIVE: Cardioprotective properties have been shown with halogenated volatile 
agents. It was hypothesized that low-dose isoflurane administered before aortic
cross-clamping may reduce the amount of dobutamine required to improve impaired
postoperative cardiac function after various types of cardiac surgery. DESIGN: A 
prospective, randomized trial. SETTING: An anesthesia and intensive care unit,
university hospital. PARTICIPANTS: Two hundred eighty cardiac surgery patients.
INTERVENTIONS: All patients allocated to either isoflurane treatment (T) or no
treatment (control group [C]) received total intravenous anesthesia. In the
treatment group, isoflurane was administered at a 0.5 minimum alveolar
concentration (MAC) from tracheal intubation to initiation of cardiopulmonary
bypass (CPB). During weaning from CPB, dobutamine was introduced by using a
hemodynamically driven decision tree. MEASUREMENTS AND MAIN RESULTS: The number
of patients receiving dobutamine was comparable (66 v 78, p = 0.07, in T and C
groups, respectively). The total amount of postoperative dobutamine indexed to
patient weight, considered as the primary endpoint, was reduced in the
isoflurane-treated group (4.2 +/- 8 v 7.2 +/- 15, p < 0.02, in T and C,
respectively). Isoflurane was identified as an independent variable significantly
(odds ratio [confidence interval]) influencing the total amount of postoperative 
dobutamine (0.53 [0.31-0.92], p < 0.02). Postoperative troponin I release at 20
hours was not affected by isoflurane treatment. CONCLUSIONS: This study revealed 
that exposure to 0.5 MAC isoflurane before CPB reduced the total amount of
dobutamine required to normalize postoperative cardiac dysfunction in various
types of cardiac surgical patients.

Circulation. 2007 Oct 23;116(17):1888-95. Epub 2007 Oct 8.

Continuous-flow cell saver reduces cognitive decline in elderly patients after
coronary bypass surgery.

Djaiani G, Fedorko L, Borger MA, Green R, Carroll J, Marcon M, Karski J.

Department of Anesthesia, Toronto General Hospital, University Health Network,
200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. george.djaiani@uhn.on.ca

BACKGROUND: Cerebral microembolization during cardiopulmonary bypass may lead to 
cognitive decline after cardiac surgery. Transfusion of the unprocessed shed
blood (major source of lipid microparticulates) into the patient during
cardiopulmonary bypass is common practice to reduce blood loss and blood
transfusion. Processing of shed blood with cell saver before transfusion may
limit cerebral microembolization and reduce cognitive decline after surgery.
METHODS AND RESULTS: A total of 226 elderly patients were randomly allocated to
either cell saver or control groups. Anesthesia and surgical management were
standardized. Epiaortic scanning of the proximal thoracic aorta was performed in 
all patients. Transcranial Doppler was used to measure cerebral embolic rates.
Standardized neuropsychological testing was conducted 1 week before and 6 weeks
after surgery. The raw scores for each test were converted to Z scores, and then 
a combined Z score of 10 main variables was calculated for both study groups. The
primary analysis was based on dichotomous composite cognitive outcome with a 1-SD
rule. Cognitive dysfunction was present in 6% (95% confidence interval, 1.3% to
10.7%) of patients in the cell saver group and 15% (95% confidence interval, 8%
to 22%) of patients in the control group 6 weeks after surgery (P=0.038). The
severity of aortic atheroma and cerebral embolic count were similar between the 2
groups. CONCLUSIONS: The present report demonstrates that processing of shed
blood with cell saver results in clinically significant reduction in
postoperative cognitive dysfunction after cardiac surgery. These findings
emphasize the clinical importance of lipid embolization in contributing to
postoperative cognitive decline in patients exposed to cardiopulmonary bypass.

J Inflamm (Lond). 2007 Oct 10;4(1):21 [Epub ahead of print]

Inhibition of neutrophil activity improves cardiac function after cardiopulmonary
bypass.

Abdel-Rahman U, Margraf S, Aybek T, Loegters T, Moreno JB, Francischetti I,
Kranert T, Gruenwald F, Windolf J, Moritz A, Scholz M.

ABSTRACT: BACKGROUND: The arterial in line application of the leukocyte
inhibition module (LIM) in the cardiopulmonary bypass (CPB) limits overshooting
leukocyte activity during cardiac surgery. We now studied in a porcine model
whether LIM may have beneficial effects on cardiac function after CPB. METHODS:
German landrace pigs underwent CPB (60 min myocardial ischemia; 30 min
reperfusion)without (group I; n=6) or with LIM (group II; n=6). The cardiac
indices (CI) and cardiac function were analyzed pre and post CPB with a Swan-Ganz
catheter and the cardiac function analyzer. Neutrophil labeling with technetium, 
scintigraphy, and histological analyses were done to track activated neutrophils 
within the organs. RESULTS: LIM prevented CPB-associated increase of neutrophil
counts in peripheral blood. In group I, the CI significantly declined post CPB
(post: 3.26 +/- 0.31; pre: 4.05 +/- 0.45 l/min/m2; p<0.01). In group II, the CI
was only slightly reduced (post: 3.86 +/- 0.49; pre 4.21 +/- 1.32 l/min/m2;
p=0.23). Post CPB, the intergroup difference showed significantly higher CI
values in the LIM group (p<0.05) which was in conjunction with higher pre-load
independent endsystolic pressure volume relationship (ESPVR) values (group I:
1.57 +/- 0.18; group II: 1.93 +/- 0.16; p<0.001). Moreover, the systemic vascular
resistance and pulmonary vascular resistance were lower in the LIM group. LIM
appeared to accelerate the sequestration of hyperactivated neutrophils in the
spleen and to reduce neutrophil infiltration of heart and lung. CONCLUSIONS: Our 
data provide strong evidence that LIM improves perioperative hemodynamics and
cardiac function after CPB by limiting neutrophil activity and inducing
accelerated sequestration of neutrophils in the spleen.

Anaesth Intensive Care. 2007 Oct;35(5):714-9.

Efficacy of risperidone for prevention of postoperative delirium in cardiac
surgery.

Prakanrattana U, Prapaitrakool S.

Department of Anaesthesiology, Siriraj Hospital, Mahidol University, Bangkok,
Thailand.

This randomised, double-blinded, placebo-controlled study was primarily aimed to 
evaluate the potential of risperidone to prevent postoperative delirium following
cardiac surgery with cardiopulmonary bypass and the secondary objective was to
explore clinical factors associated with postoperative delirium.
One-hundred-and-twenty-six adult patients undergoing elective cardiac surgery
with cardiopulmonary bypass were randomly assigned to receive either 1 mg of
risperidone or placebo sublingually when they regained consciousness. Delirium
and other outcomes were assessed. The confusion assessment method for intensive
care unit was used to assess postoperative delirium. The incidence of
postoperative delirium in the risperidone group was lower than the placebo group 
(11.1% vs. 31.7% respectively, P=0.009, relative risk = 0.35, 95% confidence
interval [CI] = 0.16-0.77). Other postoperative outcomes were not statistically
different between the groups. In exploring the factors associated with delirium, 
univariate analysis showed many factors were associated with postoperative
delirium. However multiple logistic regression analysis showed a lapse of 70
minutes from the time of opening eyes to following commands and postoperative
respiratory failure were independent risk factors (P=0.003, odds ratio [OR] =
4.57, 95% CI = 1.66-12.59 and P=0.038, OR = 13.78, 95% CI = 1.15-165.18
respectively). A single dose of risperidone administered soon after cardiac
surgery with cardiopulmonary bypass reduces the incidence of postoperative
delirium. Multiple factors tended to be associated with postoperative delirium,
but only the time from opening eyes to following commands and postoperative
respiratory failure were independent risk factors in this study.

Anaesth Intensive Care. 2007 Oct;35(5):792-5.

Perioperative management of sickle cell disease in paediatric cardiac surgery.

Bhatt K, Cherian S, Agarwal R, Jose S, Cherian KM.

Department of Cardiac Anaesthesiology, Frontier Lifeline, Chennai, Mogappair,
India.

In sickle cell disease, cardiopulmonary bypass may induce red cell sickling.
Partial exchange transfusion reduces the circulating haemoglobin S level. We
report the management of a child with sickle cell disease who required surgical
closure of a ventricular septal defect. Preoperative exchange transfusion of 50% 
of the total blood volume was performed with fresh packed red cells over three
days. Further exchange transfusion was performed as cardiopulmonary bypass
commenced. The haemoglobin S level was reduced from 76% to 37%. The blood removed
from the patient during the exchanges was processed allowing storage and
re-infusion of the patient's plasma and platelets. Combined preoperative and
intraoperative exchange transfusions, instead of a single stage 50% volume
exchange, was effective and potentially avoids larger haemodynamic effects.
Cardiopulmonary bypass was conducted at normothermia and cold cardioplegia was
avoided (fibrillatory arrest was used during the surgical repair).

Interact Cardiovasc Thorac Surg. 2007 Oct 12; [Epub ahead of print]

A study assessing the potential benefit of continued ventilation during
cardiopulmonary bypass.

John LC, Ervine IM.

Kings College Hospital, London, UK.

It has been suggested that maintaining ventilation during bypass might reduce
lung injury, which is a common complication of cardiac surgery. In order to
assess this, a study is being undertaken to examine the effect upon a number of
parameters that may be indicative of lung injury, of continued ventilation
compared with discontinued ventilation whilst on bypass. The following parameters
have been assessed: extravascular lung water, static and dynamic compliance,
ratio of left atrialyright atrial white blood count, alveolar arterial oxygen
gradient and the respiratory index together with clinical end points. Provisional
results are reported. Twenty-three elective patients for coronary artery surgery 
have to date been randomised to either ventilation (VB) (n=12) or non-ventilation
on bypass (NVB) (n=11). The post-bypass extravascular lung water was
significantly smaller in the VB group compared to the NVB group (530+/-50 ml vs. 
672+/-32 ml; P=0.028). Extubation time was also significantly shorter in the VB
group (3.6+/-0.3 h vs. 4.8+/-0.4 h; P=0.038). The provisional results of this
work in progress are suggestive that continued ventilation during bypass may
reduce lung injury. Keywords: Acute lung injury; Cardiac surgery; Cardiopulmonary
bypass; Ventilation; Extravascular lung water.

Br J Pharmacol. 2007 Oct 22; [Epub ahead of print]

Inflammatory response and cardioprotection during open-heart surgery: the
importance of anaesthetics.

Suleiman MS, Zacharowski K, Angelini GD.

1Bristol Heart Institute and Department of Anaesthesia, Faculty of Medicine and
Dentistry, University of Bristol, Bristol, UK.

Open-heart surgery triggers an inflammatory response that is largely the result
of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g.
heart). The heart sustains injury triggered by ischaemia and reperfusion and also
as a result of the effects of systemic inflammatory mediators. In addition, the
heart itself is a source of inflammatory mediators and reactive oxygen species
that are likely to contribute to the impairment of cardiac pump function.
Formulating strategies to protect the heart during open heart surgery by
attenuating reperfusion injury and systemic inflammatory response is essential to
reduce morbidity. Although many anaesthetic drugs have cardioprotective actions, 
the diversity of the proposed mechanisms for protection (e.g. attenuating Ca(2+) 
overload, anti-inflammatory and antioxidant effects, pre- and
post-conditioning-like protection) may have contributed to the slow adoption of
anaesthetics as cardioprotective agents during open heart surgery. Clinical
trials have suggested at least some cardioprotective effects of volatile
anaesthetics. Whether these benefits are relevant in terms of morbidity and
mortality is unclear and needs further investigation. This review describes the
main mediators of myocardial injury during open heart surgery, explores available
evidence of anaesthetics induced cardioprotection and addresses the efforts made 
to translate bench work into clinical practice.British Journal of Pharmacology
advance online publication, 22 October 2007; doi:10.1038/sj.bjp.0707526.