Acta Anaesthesiol Scand. 2006 Jan;50(1):108-11. 

Effects of intravascular volume therapy using hydroxyethyl starch (130/0.4) on
post-operative bleeding and transfusion requirements in children undergoing
cardiac surgery: a randomized clinical trial.

Chong Sung K, Kum Suk P, Mi Ja Y, Kyoung Ok K.

Department of Anesthesiology and Pain Medicine, Seoul National University
Hospital, Seoul, Korea.

Background: Hydroxyethyl starch (HES) used for intravascular volume expansion
may cause coagulation abnormalities, especially in cardiac patients. Although
low molecular weight HES (130/0.4) has been developed to minimize its influence
on coagulation, experience with HES (130/0.4) in children is limited. Therefore,
we evaluated the effects of a HES (130/0.4) infusion on post-operative blood
loss in children undergoing cardiac surgery. Methods: Forty-two children
undergoing cardiac surgery were assigned at random to receive either 10 ml/kg
fresh frozen plasma (FFP group; n = 21) or HES (130/0.4) (HES group; n = 21)
shortly after cardiopulmonary bypass termination. Activated partial
thromboplastin time (aPTT) and international normalization ratio (INR) were
measured. In addition, post-operative transfusion requirements and blood loss
until the end of the first post-operative day were compared. Results: INR was
significantly prolonged after HES infusion in comparison to the FFP group (P <
0.05). During the first 24 h after surgery, post-operative blood loss, the use
of allogenic blood/blood products and aPTT were similar in all children.
Conclusions: Our study shows that the administration of a moderate dose of HES
(130/0.4) in children undergoing cardiac surgery does not cause more bleeding or
a higher transfusion requirement than a FFP infusion, and suggests that the
administration of 10 ml/kg HES (130/0.4) is a safe alternative to plasma for
intravascular volume replacement in this patient population.

Heart Vessels. 2006 Jan;21(1):42-47. 

Effects of N-acetylcysteine on myocardial ischemia-reperfusion injury in bypass
surgery.

Orhan G, Yapici N, Yuksel M, Sargin M, Senay S, Yalcin AS, Aykac Z, Aka SA.

Department of Cardiovascular Surgery, Siyami Ersek Thoracic and Cardiovascular
Surgery Center, Istanbul, Turkey, gokcenorhan@hotmail.com.

Myocardial ischemia-reperfusion injury may complicate coronary artery bypass
grafting (CABG) operations. N-Acertylcysteine (NAC) had antioxidant and
microcirculatory effects, and inhibits neutrophil aggregation. The aim of this
study was to determine the effects of NAC in limiting myocardial
ischemia-reperfusion injury in CABG operations. Twenty patients undergoing
elective coronary bypass operation with cardiopulmonary bypass were enrolled and
randomly assigned to two groups: a control group operated with a routine CABG
protocol, and one where NAC was administered intravenously during the operation
(NAC group). Blood samples from coronary sinus for tumor necrosis factor-alpha
assay, myocardial biopsy specimens for chemiluminescent luminol, and lucigenin
measurements of reactive oxygen species were taken. The luminol (specific for
(*)OH, H(2)O(2), and HOCl(-) radicals) and lucigenin (specific for O(2) (*-))
levels and the difference ratios after reperfusion were significantly lower in
the NAC group. Tumor necrosis factor-alpha levels increased in the control group
but, in contrast, a significant decrease was detected in the NAC group (P <
0.01). Creatine kinase-MB levels at 6 and 12 hours were singnificantly lower in
the NAC group (P = 0.02). N-Acetylcysteine has potential effects to limit
ischemia reperfusion injury during CABG operations. We believe that its effects
on clinical outcome may be more apparent in patients prone to
ischemia-reperfusion injury.

Eur J Anaesthesiol. 2006 Jan 27;:1-4 [Epub ahead of print] 

Axillary and tympanic membrane temperature measurements are unreliable early
after cardiopulmonary bypass.

Khan TA, Vohra HA, Paul S, Rosin MD, Patel RL.

University Hospitals Coventry and Warwickshire NHS Trust, Walsgrave Hospital,
Department of Cardiothoracic Surgery, Coventry, UK.

SummaryBackground and objective: Inaccurate measurements of body temperature
following cardiopulmonary bypass may be associated with serious complications.
The purpose of this study was to determine whether axillary and tympanic
temperature measurements correlate with the urinary bladder temperature in the
early postcardiac surgery period. Methods: Forty-nine adult patients who
underwent cardiac surgery under cardiopulmonary bypass at our institution were
prospectively studied. Urinary bladder, right axillary, right tympanic and left
tympanic temperature measurements were simultaneously recorded at 0, 6, 12 and
18 h following cardiopulmonary bypass. Patients had one to four sets of
recordings and a total of 629 temperature measurements were recorded. The mean
difference (bias) between the bladder and each of the other methods and limits
of agreement were calculated using Bland and Altman method. Results: The mean
core body temperature recorded from the bladder on admission to the intensive
care unit was 36.4 degrees C. After 6, 12 and 18 h the mean core body
temperature was 37.4 degrees C (range: 35.2-39.0), 37.5 degrees C and 37.45
degrees C, respectively. The mean differences (bias) between the bladder
temperature and the other three methods were: left tympanic, 0.65 degrees C (95%
CI: -0.24 to 1.58); right tympanic, 0.57 degrees C (95% CI: -0.48 to 1.63) and
right axillary, 0.55 degrees C (95% CI: -0.27 to 1.36). Conclusions: The axilla
and tympanic membrane are unreliable sites for core body temperature measurement
early after cardiopulmonary bypass in adult patients and clinical decisions
should be based on more reliable methods.

ASAIO J. 2006 Jan-Feb;52(1):96-9. 

Deterioration of Body Oxygen Metabolism by Vasodilator and/or Vasoconstrictor
Administration during Cardiopulmonary Bypass.

Sato K, Sogawa M, Namura O, Hayashi J.

From the Division of Thoracic and Cardiovascular Surgery, Niigata University
Graduate School of Medical and Dental Sciences, Niigata, Japan.

During cardiopulmonary bypass (CPB), tissue perfusion injury occurs even if
perfusion pressure is maintained. Although a vasodilator and a vasoconstrictor
are clinically administered if bypass flow is maintained, they may restore
perfusion pressure without improving tissue perfusion. We evaluated the
influence of vasodilators and vasoconstrictors on the whole body during CPB.
Fifty-six patients with valvular disease who received moderately hypothermic CPB
without blood transfusion were divided into four groups, depending upon whether
a vasodilator and/or a vasoconstrictor was administered, and postoperative data
were compared. Bypass flow and aortic pressure were maintained at 2.4 l/min/m
and 5090 mm Hg. Body weight, dilution, hematocrit level, CPB, and aortic clamp
duration, blood temperature, bypass flow, perfusion pressure, base excess levels
during CPB, cardiac index, arterial and mixed venous oxygen pressure, and
alveolar-arterial oxygen distribution after CPB were comparable among the four
groups. However, the time to extubation was significantly longer. Blood lactate
levels, measured for patients returned to the ward, were significantly higher in
the agent-administered groups than in the no-agent group, whereas blood lactate
levels on extubation and blood creatinine levels on postoperative day 1 were
comparable among the groups. Vasodilator and/or vasoconstrictor administration
during CPB may deteriorate the body oxygen metabolism, which might imply tissue
perfusion and worsen the complications induced by hypoperfusion during CPB.

J Thorac Cardiovasc Surg. 2006 Feb;131(2):268-76. Epub 2006 Jan 18. 

Effect of closed minimized cardiopulmonary bypass on cerebral tissue oxygenation
and microembolization.

Liebold A, Khosravi A, Westphal B, Skrabal C, Choi YH, Stamm C, Kaminski A, Alms
A, Birken T, Zurakowski D, Steinhoff G.

Department of Cardiac Surgery, University of Rostock, Rostock, Germany.
andreas.liebold@med.uni-rostock.de

OBJECTIVE: Coronary artery bypass grafting with cardiopulmonary bypass carries a
risk for neurologic complications because of cerebral hypoperfusion and
microembolization. The basic goals of a novel closed minimized extracorporeal
circulation are to prevent excessive hemodilution and to avoid blood-air
interface. The aim of this prospective randomized study was to determine the
effect of using the minimized extracorporeal circulation system compared with
open conventional extracorporeal circulation on cerebral tissue oxygenation and
microembolization. METHODS: Forty patients undergoing coronary artery bypass
grafting (20 in each group) were continuously monitored for changes in cerebral
oxygenated hemoglobin and tissue oxygenation index by using near-infrared
spectroscopy. Total microembolic count and gaseous embolic count in both median
cerebral arteries were monitored with multifrequency transcranial Doppler
instrumentation. RESULTS: In the conventional extracorporeal circulation group
there was a highly significant reduction in both cerebral oxygenated hemoglobin
and tissue oxygenation index from the start to the end of cardiopulmonary bypass
(P < .01). The rate of decrease in cerebral oxygenated hemoglobin after aortic
cannulation was faster in the conventional extracorporeal circulation group (F
test = 9.03, P < .001). No significant changes with respect to cerebral
oxygenated hemoglobin or tissue oxygenation index occurred in the minimized
extracorporeal circulation group, except at the beginning of rewarming (P <
.01). Total embolic count, as well as gaseous embolic count, in the left and
right median cerebral arteries was significantly lower in the minimized
extracorporeal circulation group (all P < .05). Postoperative bleeding was
greater (P < .05) and the transfusion rate was higher (P < .05) in the
conventional extracorporeal circulation group. CONCLUSIONS: Use of closed
minimized cardiopulmonary bypass compared with conventional open cardiopulmonary
bypass preserves cerebral tissue oxygenation and reduces cerebral
microembolization.

J Card Surg. 2006 Jan-Feb;21(1):57-61. 

The effects of pentoxifylline on the myocardial inflammation and
ischemia-reperfusion injury during cardiopulmonary bypass.

Ustunsoy H, Sivrikoz MC, Tarakcioglu M, Bakir K, Guldur E, Celkan MA.

Department of Cardiovascular Surgery, Gaziantep University Medical Faculty,
Gaziantep, Turkey.

Background: Pentoxifylline (Ptx) decreases necessity of cell energy and
inflammatory reactions via inhibition of 5'-nucleotidase (5'-NT). The aim of
this study is to investigate whether the addition of Ptx into the cardioplegic
solutions avoids myocardial inflammatory reactions and ischemia/reperfusion
(I/R) injury during extracorpereal circulation. Methods: Between December 1999
and February 2002, we operated 75 patients with the diagnoses of atrial septal
defect (ASD), ventricular septal defect (VSD), valve disease, and coronary
disease. The average age of patients was 42.4 and male-female ratio was 1: 1.5.
The patients were divided into two groups, which were the study group (n = 40)
and the control group (n = 35). We used cold blood cardioplegia mixed with St.
Thomas' Hospital II cardioplegic solution for both of the groups. Ptx was added
into the cardioplegic solution (500 mg/L) in the study group. Interleukin-6
(IL-6), interleukin-8 (IL-8), and tumor necrotisis factor-alpha (TNF-alpha)
levels in coronary sinus blood samples during cross-clamp time (X-clamp) and
after releasing of it and tissue TNF-alpha in the right atrial appendix biopsy
material that was taken after X-clamp were studied to compare the both groups.
Results: After releasing X-clamp, results of blood TNF-alpha, IL-6, and IL-8 of
both groups were statistically significant (p < 0.005). At the pathological
examination, we also observed that the amount of tissue TNF-alpha in the control
group (66 +/- 17.1) was much higher than the study group (16.6 +/- 5.9, p
<0.005). Conclusions: These results show that Ptx may be added into cardioplegic
solution to avoid the myocardial inflammation and I/R injury during open heart
surgery.

Heart Surg Forum. 2006;9(1):E543-8. 

The use of Minimized Extracorporeal Circulation System has a Beneficial Effect
on Hemostasis--A Randomized Clinical Study.

Abdel-Rahman U, Martens S, Risteski P, Ozaslan F, Riaz M, Moritz A,
Wimmer-Greinecker G.

Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe
University, Frankfurt/Main, Germany.

Background. Conventional cardiopulmonary bypass (CPB) is associated with
increased coagulation and fibrinolytic activity. A closed miniaturized bypass
circuit (CorX) features a significantly reduced tubing set, an integrated pump,
and an air removal system without a cardiotomy reservoir. In a prospective
randomized trial, the effects on hemostasis were investigated while comparing
CorX with conventional CPB in patients undergoing coronary artery bypass
grafting. Methods. Over a period of 1 year, 81 patients were randomly assigned
either to the CorX system (n = 39, group A) or standard CPB system (n = 42,
group B). Primary endpoints were platelet count, plasmin-antiplasmin complex
(PAP), prothrombin fragments 1+2 (F1+F2), D-dimers, and fibrinogen. Secondary
end-points were hematocrit, blood loss in the first 12 hours postoperatively,
transfused packed red blood cells, and fresh frozen plasma in the first 24 hours
postoperatively. In addition, we analyzed partial thromboplastin time,
prothrombin time, and antithrombin III. Results. After aortic declamping, PAP
complex and prothrombin F1+F2 were significantly lower in group A than in group
B. The difference in D-dimers between groups reached significance at 1 hour
post-CPB. Hematocrit values at the end of CPB measured 26 +/- 6% in group A
versus 22 +/- 4% in group B (P = .01). The rest of the observed parameters did
not significantly differ between groups. Conclusion. Postoperative blood loss
was not reduced in the present study. However, the use of the CorX system leads
to a significant suppression of activation of coagulation and fibrinolytic
cascades compared to conventional CPB, suggesting that miniaturized
extracorporeal circuits are a step forward toward reduced imbalance of
hemostasis in cardiac surgery.

J Am Coll Surg. 2006 Jan;202(1):131-8. Epub 2005 Nov 10. 

Transfusion increases the risk of postoperative infection after cardiovascular
surgery.

Banbury MK, Brizzio ME, Rajeswaran J, Lytle BW, Blackstone EH.

Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic
Foundation, Cleveland, OH 44195, USA.

BACKGROUND: Because of the immunomodulatory effects of transfusion, we attempted
to identify factors associated with blood product use and determine the
association of transfusion quantity with postoperative infection. STUDY DESIGN:
We studied total perioperative transfusion of blood products for 15,592
cardiovascular operations performed from July 1998 to May 2003. Infection end
points were septicemia/bacteremia (n=351, 2.2%) and superficial (n=353, 2.3%)
and deep (n=212, 1.4%) sternal wound infections. Factors associated with blood
product administration were used to form balancing scores to adjust for
differences in patient characteristics among those receiving and not receiving
blood products. RESULTS: Fifty-five percent of patients received packed red
blood cells (RBC), 21% received platelets, 13% got fresh frozen plasma (FFP),
and 3% got cryoprecipitate. Factors associated with RBC use included older age,
female gender, higher New York Heart Association class, lower hematocrit,
reoperation, and longer cardiopulmonary bypass time--all indicative of
higher-risk patients. The more RBC units transfused, the higher was the
occurrence of septicemia/bacteremia (p < 0.0001) and superficial (p=0.0007) and
deep (p < 0.0001) sternal wound infection. Use of FFP (septicemia/bacteremia)
and platelets (septicemia/bacteremia and deep sternal wound infection) mitigated
against this association only slightly. CONCLUSIONS: Blood products tended to be
used in the sickest patients. But after accounting for this, risk of infection
increased incrementally with each unit of blood transfused. Although cause and
effect cannot be established, results suggested that blood product transfusion
is an independent risk factor for postoperative infection in cardiac surgical
patients, blood products are more likely to be used in the sickest patients, and
no amount of blood loss treated by transfusion is innocuous.

Eur J Cardiothorac Surg. 2006 Feb;29(2):168-74. Epub 2006 Jan 11. 

Brain oxygenation and metabolism during selective cerebral perfusion in
neonates.

Schears G, Zaitseva T, Schultz S, Greeley W, Antoni D, Wilson DF, Pastuszko A.

Department of Anesthesiology and Critical Care, Mayo Clinic, Rochester, MN, USA.

Objective: To investigate the possible neuroprotective effects of selective
cerebral perfusion (SCP) during deep hypothermic circulatory arrest on brain
oxygenation and metabolism in newborn piglets. Methods: Newborn piglets 2-4 days
of age, anesthetized and mechanically ventilated, were used for the study. The
animals were placed on cardiopulmonary bypass, cooled to 18 degrees C and put on
SCP (20ml/(kgmin)) for 90min. After rewarming, the animals were monitored
through 2h of recovery. Oxygen pressure in the microvasculature of the cortex
was measured by oxygen-dependent quenching of phosphorescence. The extracellular
level of dopamine in striatum was measured by microdialysis and hydroxyl
radicals by ortho-tyrosine levels. Levels of phosphorylated cAMP response
element binding protein (pCREB) in striatal tissue were measured by Western
blots using antibodies specific for phosphorylated CREB. The results are
presented as mean+/-SD (p<0.05 was significant). Results: Pre-bypass cortical
oxygen pressure was 48.9+/-11.3mmHg and during the first 5min of SCP, the peak
of the histogram, corrected to 18 degrees C, decreased to 11.2+/-3.8mmHg
(p<0.001) and stayed near that value to the end of bypass. The mean value for
the peak of the histograms measured at the end of SCP was 8+/-3mmHg (p<0.001).
SCP completely prevented the deep hypothermic circulatory arrest-dependent
increase in extracellular dopamine and hydroxyl radicals. After SCP, there was a
statistically significant increase in pCREB immunoreactivity (534+/-60%)
compared to the sham-operated group (100+/-63%, p<0.005). Measurements of total
CREB showed that SCP did induce a statistically significant increase in CREB as
compared to sham-operated animals (168+/-31%, p<0.05). Conclusion: SCP, as
compared to DHCA, improved cortical oxygenation and prevented increases in the
extracellular dopamine and hydroxyl radicals. The increase in pCREB in the
striatum following SCP may contribute to improved cellular recovery after this
procedure.

The New Engl J Med Volume 354:353-365
The Risk Associated with Aprotinin in Cardiac Surgery

Dennis T. Mangano, Ph.D., M.D., Iulia C. Tudor, Ph.D., Cynthia Dietzel, M.D., for the 
Multicenter Study of Perioperative Ischemia Research Group and the Ischemia 
Research and Education Foundation 


Background: The majority of patients undergoing surgical treatment for 
ST-elevation myocardial infarction receive antifibrinolytic therapy to limit blood loss. 
This approach appears counterintuitive to the accepted 
medical treatment of the same condition — namely, fibrinolysis to limit thrombosis. 
Despite this concern, no independent, large-scale safety assessment has been undertaken. 

Methods: In this observational study involving 4374 patients undergoing revascularization, 
we prospectively assessed three agents (aprotinin [1295 patients], 
aminocaproic acid [883], and tranexamic acid [822]) as compared with no agent (1374 patients)
 with regard to serious outcomes by propensity and multivariable methods. 
 (Although aprotinin is a serine protease inhibitor, here we use the term antifibrinolytic therapy to
  include all three agents.) 

Results: In propensity-adjusted, multivariable logistic regression (C-index, 0.72), 
use of aprotinin was associated with a doubling in the risk of renal failure requiring dialysis 
among patients undergoing complex coronary-artery surgery (odds ratio, 2.59; 95 percent 
confidence interval, 1.36 to 4.95) or primary surgery (odds ratio, 2.34; 95 percent 
confidence interval, 1.27 to 4.31). Similarly, use of aprotinin in the latter group was associated 
with a 55 percent increase in the risk of myocardial infarction or heart failure (P<0.001) and a 181 
percent increase in the risk of stroke or encephalopathy (P=0.001). 
Neither aminocaproic acid nor tranexamic acid was associated with an increased risk of renal, 
cardiac, or cerebral events. Adjustment according to propensity score for the 
use of any one of the three agents as compared with no agent yielded nearly identical findings. 
All the agents reduced blood loss. 

Conclusions: The association between aprotinin and serious end-organ damage indicates that 
continued use is not prudent. In contrast, the less expensive generic medications aminocaproic 
acid and tranexamic acid are safe alternatives.