Biomarkers. 2009 Feb;14(1):38-42.

Increased ischaemia modified albumin following coronary artery bypass grafting.

Sbarouni E, Georgiadou P, Panagiotakos D, Alivizatos PA, Voudris V.

2nd Department of Cardiology, Onassis Cardiac Surgery Center, Athens, Greece.
esbarouni@yahoo.gr

BACKGROUND: Any increase of cardiac biomarkers after coronary artery bypass
grafting (CABG) indicates myocyte necrosis and is likely to be related to an
impaired outcome. We investigated whether ischaemia-modified albumin (IMA), a
biomarker of ischaemia, is also raised following CABG. METHODS: We studied 50
stable consecutive patients undergoing elective isolated CABG on cardiopulmonary 
bypass, of whom 46 were men and four women, aged 64 +/- 9 years. Blood samples
were obtained the day before the operation (pre-op) as well as immediately after 
the operation, 24 h postoperatively (post-op) and the fourth day post-op and
assayed for creatine kinase, the MB isoenzyme of creatine kinase, cardiac
troponin-I, albumin and IMA. RESULTS: The typical rising and falling pattern of
myocardial necrosis of all three cardiac enzymes was observed post-op (p
<0.0001). IMA increased significantly following CABG at all three time points
(113 +/- 43, 106.7 +/- 22.6 and 110.2 +/- 12.5 U ml(-1), respectively) compared
with pre-op values (91.7 +/- 10.5 U ml(-1)), (p <0.0001); the sample immediately 
post-op was significantly higher compared with the following samples (immediately
post-op vs 24 h, p = 0.008 and immediately post-op vs 4 days, p = 0.03, with no
significant difference between the last two). IMA level changes during the study 
course were independent of the albumin changes. Haemoglobin decreased
significantly post-op (p <0.0001 vs baseline) whereas serum creatinine did not
differ during the study period. CONCLUSIONS: IMA increases significantly
following CABG but whether or not this carries a prognostic significance remains 
to be elucidated.

Eur J Cardiothorac Surg. 2009 Feb 26. [Epub ahead of print]

Tranexamic acid and aprotinin in low- and intermediate-risk cardiac surgery: a
non-sponsored, double-blind, randomised, placebo-controlled trial.

Later AF, Maas JJ, Engbers FH, Versteegh MI, Bruggemans EF, Dion RA, Klautz RJ.

Department of Cardiothoracic Surgery, Leids Universitair Medisch Centrum,
Albinusdreef 2, Postbus 9600, 2300 RC Leiden, The Netherlands.

Objective: Tranexamic acid has been suggested to be as effective as aprotinin in 
reducing blood loss and transfusion requirements after cardiac surgery. Previous 
studies directly comparing both antifibrinolytics focus on high-risk cardiac
surgery patients only or suffer from methodological problems. We wanted to
compare the effectiveness of tranexamic acid versus aprotinin in reducing
postoperative blood loss and transfusion requirements in the patient group
representing the majority of cardiac surgery patients: low- and intermediate-risk
patients. Methods: We conducted a non-sponsored, double-blind, randomised,
placebo-controlled trial in which 298 patients scheduled for low- or
intermediate-risk (mean logistic EuroSCORE 4.1) first-time heart surgery with use
of cardiopulmonary bypass were randomised to receive either tranexamic acid,
high-dose aprotinin, or placebo. All patients had preoperative normal renal
function. End points of the study were monitored from the time of surgery until
patient discharge. This trial was executed between June 2004 and October 2006.
Results: Both antifibrinolytics significantly reduced blood loss and transfusion 
requirements when compared with placebo. Aprotinin was about twice as effective
as tranexamic acid in reducing total postoperative blood loss (estimated median
difference 155ml, 95% confidence interval (CI) 60-260; p<0.001). Accordingly,
aprotinin reduced packed red blood cell transfusions more than tranexamic acid,
although the difference did not reach statistical significance. Only aprotinin
significantly reduced the proportion of transfused patients when compared with
placebo (mean difference -20.9%, 95% CI 7.3-33.5; p=0.013), and only aprotinin
completely abolished bleeding-related re-explorations (mean difference 6.8%, 95% 
CI 1.6-13.4%; p=0.004). Neither antifibrinolytic agent increased the incidence of
mortality (mean difference tranexamic acid -0.4%, 95% CI -4.6 to 4.4; p=0.79,
mean difference aprotinin -1.3%, 95% CI -6.2 to 3.5; p=0.62) or other serious
adverse events when compared with placebo. Conclusion: Aprotinin has clinically
significant advantages over tranexamic acid in patients with normal renal
function scheduled for low- or intermediate-risk cardiac surgery.

J Cardiovasc Pharmacol. 2009 Feb 25. [Epub ahead of print]

Rapid Detection of Acute Kidney Injury by Plasma and Urinary Neutrophil
Gelatinase-associated Lipocalin After Cardiopulmonary Bypass.

Tuladhar SM, Püntmann VO, Soni M, Punjabi PP, Bogle RG.

From the *Department of Cardiothoracic Surgery, Imperial College Healthcare NHS
Trust, London, United Kingdom; and daggerCardiovascular Section, Department of
Experimental Medicine and Toxicology, Division of Investigative Sciences,
Imperial College London, Hammersmith Campus, London, United Kingdom.

BACKGROUND:: Cardiopulmonary bypass (CPB) is associated with a significant risk
of postoperative renal dysfunction. We studied the utility of a novel biomarker
in predicting acute kidney injury (AKI) in adult patients undergoing cardiac
surgery. METHODS AND RESULTS:: Blood and urine were obtained from 50 patients
undergoing CPB-requiring surgery. Patients were divided into group A (n = 41)
with normal creatinine pre-bypass and post-bypass and group B (n = 9) who
developed an increase in serum creatinine of >0.5 mg/dL within the first 48 hours
post CPB. Plasma and urinary neutrophil gelatinase-associated lipocalin (NGAL)
was determined at baseline and 2 hours after CPB.Plasma levels of NGAL were
higher in patients who developed AKI [214 +/- 16.7 ng/mL (95% CI 176.9-252.9)]
compared with those who did not [149.5 +/- 13.5 ng/mL (95% CI 122.1-175.7); P =
0.035]. Two hours after CPB, there was a significant increase (P = 0.0003) in
NGAL levels, greater in those patients who developed AKI [476.1 +/- 41.1 ng/mL
(95% CI 380.6-571.6); P = 0.0003] compared with those who did not [278.4 +/- 22
ng/mL (95% CI 233.9-323.0)]. In the AKI group, urinary NGAL increased from 7.13
+/- 2.30 ng/mL (95% CI 2.5-11.8) to 2924 +/- 786 ng/mL (95% CI 1110-4739). In the
non-AKI group, there was an increase from 1.6 +/- 0.6 (95% CI 0.3-3.0) to 749 +/-
179 ng/mL (95% CI 386-1113). The post-CPB levels of urinary NGAL were
significantly different in the AKI group (P < 0.0001) such that a suitable
threshold for use as a diagnostic test could be determined. Receiver operating
characteristics were determined for plasma and urinary NGAL with area under the
curve (AUC) of 0.80 and 0.96, respectively. For a threshold of 433 ng/mmol
creatinine, the test had 90% sensitivity and 78% specificity for the detection of
post-CPB renal dysfunction. CONCLUSIONS:: Measurement of this novel biomarker in 
the urine or plasma of patients in the first hours after CPB is predictive of
subsequent renal injury. Although the AUC for plasma NGAL seemed inferior to
urine, even an AUC of 0.8 as reported compares very favorably to that for other
"outstanding" biomarkers (eg, AUCs in the 0.7 range for troponin).

Br J Anaesth. 2009 Feb 25. [Epub ahead of print]

Effects of phenylephrine on the sublingual microcirculation during
cardiopulmonary bypass.

Maier S, Hasibeder WR, Hengl C, Pajk W, Schwarz B, Margreiter J, Ulmer H, Engl J,
Knotzer H.

Department of Anaesthesiology and Critical Care Medicine.

BACKGROUND: /st> The objective of the present study was to investigate sublingual
microvascular blood flow and microcirculatory haemoglobin oxygen saturation
(Smc(o(2))) during cardiopulmonary bypass (CPB) using constant systemic blood
flow but different perfusion pressures achieved by phenylephrine administration. 
METHODS: /st> Fifteen patients undergoing coronary artery bypass grafting were
enrolled in this pilot study. Systemic haemodynamics, oxygen transport variables,
arterial and mixed venous blood gas analysis, and microcirculatory variables were
determined after initiation of general anaesthesia, during CPB (systemic blood
flow=2.4 litre m(-2)), after increasing perfusion pressure by 20 mm Hg with a
continuous infusion of phenylephrine, and after termination of phenylephrine
infusion. RESULTS: /st> CPB immediately resulted in a significant (P<0.05)
decrease in systemic oxygen transport without alterations in sublingual
microcirculatory blood flow and Smc(o(2)). Increasing perfusion pressure from 47 
(sd 9) to 68 (7) mm Hg using phenylephrine=1.4 (1.0) microg kg(-1) min(-1)
resulted in a significant decrease in sublingual small vessel blood flow (from
median 2.5 to 1.8 arbitrary units) representing mostly capillary blood flow, but 
not in medium-sized vessels (median 3 to 2.8 arbitrary units). Concurrently,
global tissue blood flow from 110 (54) to 197 (100) perfusion units and Smc(o(2))
increased from 72 (11)% to 84 (7)%, suggesting significant microcirculatory blood
flow shunting in vessels with diameters >25 microm. CONCLUSIONS: /st> Our data
demonstrate that an increased perfusion pressure produced by phenylephrine at
constant CPB flow may decrease microcirculatory blood flow in the sublingual
mucosal microcirculation due to microvascular blood flow shunting.

J Anesth. 2009;23(1):87-92. Epub 2009 Feb 22.

An individualized recruitment maneuver for mechanically ventilated patients after
cardiac surgery.

Serita R, Morisaki H, Takeda J.

Department of Anesthesiology, Tokyo Dental College Ichikawa General Hospital,
5-11-13 Sugano, Ichikawa, 272-8513, Japan.

PURPOSE: The recruitment maneuver (RM) has been shown to improve oxygenation for 
post-cardiopulmonary bypass (CPB) patients; however, sustained inflation of the
lung gives rise to hypotension. The primary goal of our study was to evaluate the
safety and efficacy of our proposed RM, defined on the basis of dynamic lung
compliance (Cdyn). METHODS: Twenty-eight patients undergoing elective cardiac
surgery with CPB were assigned to two treatment groups: an individualized RM
group, in which a pressure equal to 15 ml x real body weight/Cdyn + positive
end-expiratory pressure (PEEP) cmH(2)O was applied for 15 s; and a control RM
group, in which a pressure of 20 cmH(2)O was applied for 25 s. Arterial blood
pressure, cardiac output, pulmonary artery pressure, and heart rate (HR) were
monitored. Tidal volume (V(T)), and airway pressure were continuously obtained
from an expiratory flow meter and pressure monitor. Blood samples were obtained
and analyzed with a blood gas analyzer. RESULTS: The changes in HR, mean arterial
pressure, mean pulmonary artery pressure, and cardiac index at the end of the RM 
were not significantly different between the two groups. The mean airway pressure
of sustained inflation was 28.3 +/- 1.3 cmH(2)O in the individualized RM group.
The individualized RM significantly improved the Cdyn and partial pressure
arterial oxygen/inspiratory fraction of oxygen (P/F) ratio compared with values
in the control RM group (P = 0.026 and P = 0.012, respectively). CONCLUSION: The 
present study indicates that the individualized RM resulted in minimum changes of
hemodynamics and brought about improvement in oxygenation and lung compliance.

J Pediatr Surg. 2009 Feb;44(2):325-8.

Congenital tracheal stenosis: the prognostic significance of associated
cardiovascular anomalies and the optimal timing of surgical treatment.

Okamoto T, Nishijima E, Maruo A, Yokoi A, Takamizawa S, Satoh S, Oshima Y.

Department of Pediatric Surgery, Kobe Children's Hospital, Kobe, Japan.

BACKGROUND/PURPOSE: Cardiovascular anomalies (CA) are frequently associated with 
congenital tracheal stenosis (CTS), but their prognostic impact on CTS and the
optimal timing of surgical treatment remain uncertain. The aim of this study was 
to explore the prognostic factors and the optimal timing of surgical treatment in
CTS patients with CA. METHODS: After obtaining institutional review board
approval, a retrospective review of 42 patients who underwent surgical repair of 
CTS between 1996 and 2006 was conducted. The patients were divided into 3 groups:
CTS without CA (n = 10, group A), CTS with CA repaired simultaneously (n = 27,
group B), and CTS with CA repaired in stages (n = 5, group C). Seven clinical
characteristics, including gestational week and weight at birth, the age and body
weight at operation, the length of tracheal stenosis (%), the duration of
cardiopulmonary bypass (CPB) during surgery, and operation time were compared
among the groups using analysis of variance, Fisher's Exact test, and Student's t
test. RESULTS: Although no operative mortalities occurred in groups A and C,
there were 3 early deaths and 1 late death in group B. The deaths occurred in
cases with associated complex CA (critical pulmonary stenosis, tetralogy of
Fallot with an absent pulmonary valve, right ventricular outflow block, and cor
triatrium). The duration of CPB was significantly different between groups A and 
B (P = .017), and furthermore, CPB time was significantly longer in early death
cases than in surviving cases in group B (318.3 +/- .71.1 vs 204.0 +/- 67.8
minutes; P = .012). CONCLUSIONS: Complex CA and long CPB duration would be
prognostic factors for the outcome of surgical management for CTS and CA.
Simultaneous reconstruction of CTS and simple CA appears to be a reasonable
method of surgical intervention, but patients with long segment CTS with complex 
CA may still be difficult to cure using this strategy, and staged correction may 
be considered.

Int J Clin Pharmacol Ther. 2009 Feb;47(2):78-88.

Inflammatory response to cardiopulmonary bypass with enoximone or steroids in
patients undergoing myocardial revascularization: a preliminary report study.

Santarpino G, Caroleo S, Onorati F, Dimastromatteo G, Abdalla K, Amantea B,
Santangelo E, Gulletta E, Renzulli A.

Cardiac Surgery Unit, Magna Graecia University of Catanzaro, Italy.

OBJECTIVE: Recent reports have showed an antiinflammatory effect of
phosphodiesterase III inhibitors (PDEi) in patients undergoing cardiopulmonary
bypass (CPB). We sought to evaluate the immunological and hemodynamic response to
enoximone and methylprednisolone in patients undergoing CABG. DESIGN:
Prospective, randomized, controlled study. Setting: Cardiac surgery unit in a
university hospital. PATIENTS: 40 patients undergoing CPB-CABG. INTERVENTIONS:
Patients receive enoximone (20, Group A) or methylprednisolone (20, Group B).
MEASUREMENTS AND MAIN RESULTS: Hemodynamic response was evaluated by Swan-Ganz
catheter serial measurements and perioperative Lactate and Troponin I leakage,
immunological response was analyzed by IL-2, IL-4, IL-6, TNF-alpah, IFN-gamma,
IL-10 before anesthetic induction (T0), at aortic-declamping (T1), at the end of 
surgery (T2), ITU admission (T3), 24 hs (T4) postoperatively. Morbidity and
mortality were comparable between the two groups. Group A demonstrated higher
cardiac index at T2 (2.93 l/min m2 vs 2.06, p < 0.001), at T3 (3.01 vs 2.18, p < 
0.001), lower indexed systemic vascular resistance at T2 (2,044 dyne s cm-5 m-2
vs 3,132, p < 0.001). Except for higher TNF-alpha in Group B at T2 (15.89 vs
22.68, p = 0.005) proinflammatory cytokines were comparable. IL-10 was higher in 
Group B at any postoperative time (IL-10: T1 80.74 vs 143.3, p < 0.001, T2 165.7 
vs 377.4, p < 0.001, T3 203.4 vs 443.5, p < 0,001, T4 251.8 vs 437.1, p < 0.001),
whereas IL-4 and IFN-gamma proved higher in Group A at all time-points (IL-4: T1 
45.9 vs 31.2, p = 0.008, T2 67.2 vs 39.7, p < 0.001, T3 77.9 vs 39.2, p < 0.001, 
T4 102.9 vs 42.2, p < 0.001. IFN-gamma: T1 25.8 vs 15.8, p < 0.001, T2 52.2 vs
30.3, p < 0.001, T3 78.4 vs 40.8, p < 0.001, T4 159.9 vs 67.4, p < 0.001).
CONCLUSIONS: Despite comparable major clinical endpoints enoximone showed a
different antiinflammatory pattern compared to methylprednisolone, however, the
better hemodynamic response in enoximone compared to methylprednisolone suggests 
enoximone as a potential antiinflammatory tool to improve the outcome in cardiac 
surgery.

J Cardiothorac Vasc Anesth. 2009 Feb 6. [Epub ahead of print]

Is C-Reactive Protein a Biomarker for Immediate Clinical Outcome After Cardiac
Surgery?

Corral L, Carrió ML, Ventura JL, Torrado H, Javierre C, Rodriguez-Castro D,
Farrero E, Valero J, Ortiz D.

Department of Intensive Care, Hospital Universitari de Bellvitge, Barcelona,
Spain;

OBJECTIVE: The purpose of this study was to determine the possible correlation
between inflammatory activation after cardiac surgery with cardiopulmonary
bypass, measured by postoperative C-reactive protein concentrations, and
immediate intensive care unit outcome. DESIGN: A prospective, clinical cohort
study. SETTING: A 10-bed surgical intensive care unit at a tertiary university
hospital. PATIENTS: Two hundred sixteen consecutive patients undergoing
nonemergency cardiac surgery with cardiopulmonary bypass. MEASUREMENTS AND MAIN
RESULTS: Parsonnet and Acute Physiology and Chronic Health Evaluation scores,
characteristics of the surgical intervention, intensive care unit length of stay,
and mortality were recorded along with the following variables: cardiac (hours
requiring inotropic support and new atrial fibrillation), respiratory
(oxygenation index and hours requiring intubation), renal (difference between
serum creatinine at admission and maximum creatinine), and analytic (C-reactive
protein at admission and 6, 24, and 48 hours later; troponin I; CK-MB; and
lactate). RESULTS: Postoperative C-reactive protein concentrations did not
correlate with variables such as time requiring inotropic support or intubation, 
oxygenation index, delta serum creatinine, and intensive care unit length of stay
(with the exception of cardiopulmonary bypass time and the more frequent
norepinephrine requirement in patients with higher C-reactive protein
concentration at 48 hours); nor did C-reactive protein correlate with the
analytic variables (with the exception of the lactate peak and C-reactive protein
concentrations at 24 and 48 hours). There was no correlation between C-reactive
protein and postoperative variables for coronary artery bypass graft surgery and 
valvular groups analyzed separately. CONCLUSION: Postoperative C-reactive protein
does not seem to be a useful marker in predicting outcome after 48 hours in the
intensive care unit.

J Intensive Care Med. 2009 Feb 2. [Epub ahead of print]

Recombinat Activated Factor VII Following Pediatric Cardiac Surgery.

Kylasam S, Mos K, Fijtin S, Webster B, Chard R, Egan J.

Pediatric ICU, The Children's Hospital at Westmead.

Objective: Review the use of recombinant activated Factor VII following cardiac
surgery. Specifically, we sought to define our current therapeutic practice
indications and outcomes to assess the impact of recombinant activated factor VII
on postoperative bleeding. Design: Retrospective case series. Setting: The study 
was conducted at the University affiliated pediatric intensive care unit.
Patients and participants: All postcardiac surgical patients who received
recombinant activated Factor VII between June 2002 and July 2006. Results:
Cardiac surgery requiring cardiopulmonary bypass was performed on 1010 children
during this period. In all, 25 (2.5%) children received recombinant activated
factor VII for excessive bleeding. A single dose (180 microg/kg) of recombinant
activated factor VII was given to 11 patients and 2 doses of 180 microg/kg to 14 
patients. Intercostal drain losses were reduced from 12 (6.7-20.8) mL/kg/h to 3
(1-4.1) mL/kg/h, P = .018 following 1 dose of recombinant activated factor VII.
In those receiving 2 doses; initial losses were 19.1 (7.5-31.7) mL/kg/h, after
the first dose were 7.5 (3.6-13.7) mL/kg/h, P = .046, and after the second dose
were 2 (1-2.9) mL/kg/h, P = .008. The plasma prothrombin time decreased in both
the 1 dose, P = .003 and 2 dose, P = .009 groups. The activated partial
thromboplastin time also decreased in the 1 dose group, P = .007 and 2 dose
group, P = .03. There were no side effects attributable to recombinant activated 
factor VII. Annual rates of return to the operating theatre for excessive
bleeding were coincidentally reduced in association with the routine use of
recombinant activated factor VII from 4.3% to 1.5%, P = .019. Conclusions:
Hemostasis occurred in 25 postoperative pediatric cardiac patients after
recombinant activated Factor VII was given. In this setting, once conventional
hemostatic therapy was optimized, recombinant activated Factor VII 180 microg/kg 
initially with intercostal losses greater than 10 mL/kg/h and a repeat dose after
2 hours if losses remained greater than 5 mL/kg/h was effective. No complications
were found to have occurred and there was a coincidental reduction in annual
returns to theatre for excessive bleeding.

Anesth Analg. 2009 Feb;108(2):448-55.

The impact of aprotinin on postoperative renal dysfunction in neonates undergoing
cardiopulmonary bypass: a retrospective analysis.

Guzzetta NA, Evans FM, Rosenberg ES, Fazlollah TM, Baker MJ, Wilson EC, Kaiser
AM, Tosone SR, Miller BE.

Department of Anesthesiology, Emory University School of Medicine, Children's
Healthcare of Atlanta, GA 30322, USA. nina.guzzetta@emoryhealthcare.org

BACKGROUND: Recent concern about the safety of aprotinin administration to adults
has led to its suspension from worldwide markets. However, few studies have
examined its safety in pediatric patients. Studies in children evaluating
aprotinin's safety have been hindered by the heterogeneity of pediatric patients 
and the inconsistency of clinical protocols. In this investigation, we
retrospectively reviewed 200 neonatal cardiac surgical cases performed at our
institution to examine the safety of aprotinin, focusing on postoperative renal
dysfunction, using a consistent aprotinin dosing protocol. METHODS: Two-hundred
consecutive neonates scheduled for palliative or corrective congenital cardiac
surgery requiring cardiopulmonary bypass (CPB) from January 1, 2005 through
February 28, 2007 were included in this retrospective investigation.
Preoperative, intraoperative and postoperative data were collected and analyzed. 
Markers of safety included 72-h postoperative renal dysfunction, need for
dialysis (peritoneal or hemodialysis), thrombosis and in-hospital mortality.
RESULTS: Neonates were divided into those who received aprotinin (aprotinin
group; n = 156) and those who did not (no aprotinin group; n = 44). Twenty-four
and 72-h postoperative serum creatinine levels were significantly greater than
baseline levels in both groups. The degree of change in creatinine levels was
highly significant and similar between the two groups. A larger percentage of
neonates in the aprotinin group developed renal dysfunction, although this
difference was not statistically significant. Stepwise logistic regression,
assessing the impact on renal dysfunction of all variables that indicated
significance between neonates who did or did not receive aprotinin and between
neonates who did or did not develop renal dysfunction, identified CPB time and
age as significant predictors of postoperative renal dysfunction. All neonates
who developed postoperative renal dysfunction had a CPB time of more than 100 min
regardless of the use of aprotinin. Additionally, using this subset, similar
percentages of renal dysfunction occurred in both groups. A second multivariable 
regression analysis to simultaneously account for the predictors of CPB time, age
and aprotinin administration found CPB time to be the only significant predictor 
of renal dysfunction. Incidences of postoperative dialysis, postoperative
thrombosis and in-hospital mortality were not statistically significantly
different between the aprotinin and the no aprotinin groups. CONCLUSION: The
occurrence of postoperative renal dysfunction in neonates was more significantly 
predicted by the duration of CPB than by the intraoperative administration of
aprotinin. CPB times of more than 100 min appeared to be a critical marker for
the development of postoperative renal dysfunction. Randomized prospective trials
are needed to confirm the validity of our retrospective findings.