Crit Care Med. 2006 Oct;34(10):2658-65. 

Interleukin-10 and its role in clinical immunoparalysis following pediatric
cardiac surgery.

Allen ML, Hoschtitzky JA, Peters MJ, Elliott M, Goldman A, James I, Klein NJ.

Critical Care Group-Portex Unit, Institute of Child Health, University College
London, UK.

OBJECTIVE: A systemic insult is associated with subsequent hyporesponsiveness to
endotoxin (as measured by ex vivo tumor necrosis factor [TNF]-alpha production)
and an increased risk of late nosocomial infection in some patients. When
combined with low monocyte surface major histocompatibility complex class II
expression, this state of altered host defense is now commonly referred to as
immunoparalysis. This study was undertaken to delineate the relationship between
observed levels of the anti-inflammatory cytokine interleukin-10, common genetic
polymorphisms that influence these levels, and the occurrence and severity of
endotoxin hyporesponsiveness in children following elective cardiac surgery
requiring cardiopulmonary bypass. 

DESIGN: A prospective observational clinical
study. 

SETTING: A tertiary pediatric cardiac center. 

PATIENTS: Thirty-six infants and children <2 yrs of age undergoing elective cardiac surgery 
requiring cardiopulmonary bypass. 

INTERVENTIONS: None. 

MEASUREMENTS AND MAIN RESULTS: We investigated the production of TNF-alpha, 
interleukin-6, interleukin-8, interleukin-1 receptor antagonist, and interleukin-10 in whole blood 
in response to lipopolysaccharide (Neisseria meningitides 10 ng/mL) in samples drawn before,
during, and up to 48 hrs after surgery. Patients were genotyped for the -1082,
-819, and -592 interleukin-10 promoter polymorphisms. Whole blood cytokine
response to lipopolysaccharide was reduced postoperatively to 100 pg/mL) over the
first 48 hrs were more likely to have an uncomplicated short stay (odds ratio
4.7, 95% confidence interval 1-22). 

CONCLUSIONS: Immediately following cardiac surgery, many children become relatively refractory 
to lipopolysaccharide stimulation. This immunoparalysis appears to be related in part to high
circulating levels of interleukin-10 and places these patients at increased risk
of postoperative complications. Interleukin-10 genotype may be a risk factor for
immunoparalysis.

J Surg Res. 2006 Oct 18; [Epub ahead of print] 

In Vitro Restoration of Post-Operatively Decreased IFN-Gamma Levels After
Cardiac Surgery and Its Effect on Pro- and Anti-Inflammatory Mediators.

Franke A, Lante W, Markewitz A, Weinhold C.

Department of Cardiovascular Surgery, Bundeswehr Central Hospital, Koblenz,
Germany.

BACKGROUNDS: A decreased synthesis of interferon gamma (IFN-gamma) by TH 1
lymphocytes after cardiac operations with cardiopulmonary bypass (CPB) is part
of the inflammatory response to local operative and systemic traumas. The
consequences of this mechanism on the release of pro- and anti-inflammatory
cytokines remain unclear. To evaluate the role of IFN-gamma, we added
recombinant IFN-gamma to peripheral blood mononuclear cells (PBMCs) on the first
post-operative day in an attempt to restore pre-operative values and then
measured the release of pro- and anti-inflammatory cytokines in vitro. METHODS:
PBMCs of 10 patients scheduled for elective coronary artery bypass grafting
(CABG) were obtained pre-operatively (d0) and on the first (d1) and third (d3)
post-operative days. The release of IL-6, IL-8, TNF-alpha, IFN-gamma, IL-10,
IL-2, and IL-4 was studied after stimulation (48 h) with PHA
(phytohemagglutinin) and LPS (lipopolysaccharide) in the absence or presence of
recombinant human IFN-gamma. RESULTS: Endogenous IFN-gamma synthesis was
suppressed on d1. Adding exogenous IFN-gamma restored IFN-gamma levels to normal
on d1 and doubled IFN-gamma levels on d0 and d3. The addition of IFN-gamma
increased TNF-alpha levels up to 250% on d1 and IL-2 synthesis by 75% on d1 and
d3; the IL-2 levels, however, were still significantly depressed. The addition
of recombinant IFN-gamma did not affect the synthesis of IL-6, IL-8, IL-10, and
IL-4. CONCLUSIONS: Contrary to our expectations, the in vitro release of IL-6
and IL-8 as well as IL-10 and IL-4 was not influenced by the addition of
IFN-gamma. However, TNF-alpha production in isolated PBMC cultures increased
significantly on the first post-operative day. This may indicate a
hyper-reactivity of PBMCs to IFN-gamma and suggests that the decrease in
IFN-gamma synthesis might prevent an excessive stimulation of the non-specific
immune system by high TNF-alpha levels after cardiac surgery.

Eur J Anaesthesiol. 2006 Oct 23;:1-6 [Epub ahead of print] 

The outcome of patients requiring emergency conversion from off-pump to on-pump
coronary artery bypass grafting.

Landoni G, Pappalardo F, Crescenzi G, Aletti G, Marchetti C, Poli D, Franco A,
Rosica C, Zangrillo A.

Universita Vita-Salute San Raffaele, Italia e Istituto Scientifico San Raffaele,
Italy.

SummaryBackground and objective: Patients undergoing off-pump coronary artery
bypass grafting (CABG) may need emergent institution of cardiopulmonary bypass
(CPB) for circulatory collapse during the operation. Our aim was to evaluate
outcome in such patients and identify preoperative and intraoperative risk
factors. Methods: This is an observational study in a University Hospital
setting. In the period June 2001-July 2003, data from 988 consecutive patients
undergoing CABG in our institution were prospectively collected. No
interventions were made. Prolonged hospital stay (>7 days), hospital mortality,
temporal trends and risk factors for conversion from off-pump to on-pump surgery
were studied. Results: Fifty-four patients with emergency operations and six
with associated carotid artery surgery were excluded. Of the remaining 928
patients, 450 (48.5%) were planned for off-pump surgery. Thirty-seven (8.2%) of
them required conversion to CPB on an emergency basis. These patients had higher
mortality (5.4%) than the off-pump group (1.5%) and the CPB group (0.4%), P =
0.02. The incidence of prolonged hospital stay was also higher (conversion group
= 27%, off-pump group = 12.3%, CPB group = 17.6%; P = 0.02). We did not identify
any perioperative characteristics significantly associated with the risk of
requiring conversion. The conversion rate was uniformly distributed over the
study period. Conclusions: Patients who are emergently converted to CPB during
attempted off-pump procedures are at higher risk of death and prolonged hospital
stay; this population should be included in comparative studies as 'intention to
treat' in the off-pump group.

Thromb Res. 2006 Oct 3; [Epub ahead of print] 

An alternative pathway for fibrinolysis is activated in patients who have
undergone cardiopulmonary bypass surgery and major abdominal surgery.

Gando S, Kameue T, Sawamura A, Hayakawa M, Hoshino H, Kubota N.

Division of Acute and Critical Care Medicine, Department of Anesthesiology and
Critical Care Medicine, Hokkaido University Graduate School of Medicine, N17 W5,
Kita-ku, Sapporo 060, Japan.

INTRODUCTION: We conducted this prospective study in order to investigate the
hypotheses that an alternative pathway for fibrinolysis is activated in patients
who have undergone cardiopulmonary bypass (CPB) surgery and major abdominal
surgery and that the levels of fibrin degradation products digested by
polymorphonuclear neutrophil elastase (elastase-XDP) and the D-dimer increase in
the patients' plasma. MATERIALS AND METHODS: We studied a total of 77 patients
who were scheduled to undergo either CPB surgery (36 patients) or major
abdominal surgery (41 patients) and then measured the elastase-XDP and D-dimer
levels at several time points both during and after the surgeries. The CPB
surgery was divided into surgery for aortic dissection (AD) and cardiac surgery.
The major abdominal surgery consists of hepatic resection and esophagectomy.
RESULTS: The elastase-XDP and D-dimer levels significantly increased in the
patients who underwent both CPB surgery and major abdominal surgery. The
elastase-XDP levels in AD surgery showed highest values at the end of the CPB,
while the levels in the other surgeries reached their peak on the day after the
surgery. Statistical difference was seen in the levels of elastase-XDP among the
three subgroups undergoing a hepatic resection. While we found significant
correlations between the levels of elastase-XDP and D-dimer in patients
undergoing CPB surgery and a subsegmentectomy of a cirrhotic liver, the
correlation coefficients were markedly low in comparison to those of the other
surgeries. CONCLUSIONS: Our findings demonstrated that the elastase-mediated
pathway of fibrinolysis is activated to varying degrees depending on the surgery
performed. Variations in the correlation coefficients between the levels of
elastase-XDP and D-dimer may suggest that elastase-mediated fibrinolysis play a
different role from the physiological fibrinolysis mediated by plasmin.

Scand Cardiovasc J. 2006 Oct;40(5):305-11. 

What is a normal lactate level during cardiopulmonary bypass?

Svenmarker S, Haggmark S, Ostman M.

Department of Surgical & Perioperative Science, Umea University Hospital,
Sweden. staffan.svenmarker@vll.se

Blood lactate levels during cardiopulmonary bypass are often used to verify
adequacy of perfusion. The present investigation aimed to propose a threshold
for hyperlactatemia. Blood lactate levels in 5 121 cardiac surgical patients
were retrospectively analysed by a review of database records. Hyperlactatemia
was defined as a value equal to the 90th percentile of the identified lactate
distribution at weaning from cardiopulmonary bypass. Patient demographics,
background and outcome statistics were performed stratified on presence of
hyperlactatemia. The threshold for hyperlactatemia was found to equal 2 mmol/l.
Significant predictors of hyperlactatemia based on logistic regression modelling
were age, complex surgery, duration of cardiopulmonary bypass, blood
transfusion, acid base level, emergency operations, diabetes, vasoactive
intervention, venous-blood-return to the heart-lung machine and renal function.
Patients with hyperlactatemia required longer intensive care and postoperative
ventilatory support. Complications were more frequent, especially: renal
dysfunction, infections, respiratory and circulatory disorders. Hospital
mortality was 13.3% compared to an overall level at 2.2%. The threshold for
hyperlactatemia during cardiopulmonary bypass attained 2 mmol/l and predicted
increased morbidity and mortality.

J Thorac Cardiovasc Surg. 2006 Oct;132(4):948-53. 

Aprotinin improves cerebral protection: evidence from a survival porcine model.

Anttila V, Hagino I, Iwata Y, Mettler BA, Lidov HG, Zurakowski D, Jonas RA.

Department of Cardiovascular Surgery, Children's Hospital Boston, Harvard
Medical School, Boston, Mass, USA.

OBJECTIVE: Aprotinin is a serine protease inhibitor used during cardiac surgery
to reduce blood loss and preserve platelet function. It has also been shown to
reduce leukocyte activation during and after cardiopulmonary bypass. The goal of
the study was to test the hypothesis that aprotinin could reduce cerebral injury
after low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest.
METHODS: Sixteen piglets (mean weight, 13.6 +/- 1.3 kg) were randomly assigned
to receive aprotinin or placebo (8 animals per group) before a 120-minute period
of deep hypothermic circulatory arrest (15 degrees C) or 25 mL x kg(-1) x
min(-1) low-flow cardiopulmonary bypass (25 degrees C or 34 degrees C). Piglets
had a cranial window placed over the parietal cerebral cortex for direct
examination of the microcirculation by means of intravital microscopy.
Rhodamine-stained leukocytes were observed in postcapillary venules, with
analysis for adhesion and rolling. Plasma was labeled with fluorescein
isothiocyanate-dextran for assessment of functional capillary density.
Neurologic and histologic scores were used as the primary outcome measures.
RESULTS: During rewarming, the mean number of both rolling and adherent
leukocytes was significantly lower after aprotinin administration (P < .05). At
5 and 15 minutes of rewarming, functional capillary density recovered faster
with aprotinin treatment (P < .05). Functional outcome (neurologic deficit
score) on postoperative day 1 was significantly improved in aprotinin-treated
piglets (P < .05). CONCLUSIONS: Aprotinin reduces inflammation and improves
neurologic outcome after a prolonged period of deep hypothermic circulatory
arrest or low-flow cardiopulmonary bypass.

J Thorac Cardiovasc Surg. 2006 Oct;132(4):845-52. 

Intermediate-term outcomes of the arterial switch operation for transposition of
great arteries in neonates: alive but well?

Freed DH, Robertson CM, Sauve RS, Joffe AR, Rebeyka IM, Ross DB, Dyck JD;
Western Canadian Complex Pediatric Therapies Project Follow-up Group.

Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.

OBJECTIVES: This interprovincial inception cohort study outlines the operative
and intermediate outcomes of all neonates at a single institution with a broad
referral area who underwent the arterial switch operation for transposition of
great arteries, including complex types. Predictors of outcome are explored.
METHODS: A total of 88 consecutive neonates underwent the arterial switch
operation between 1996 and 2004 with full-flow (150 mg/kg/min) cardiopulmonary
bypass with selective deep hypothermic circulatory arrest. Overall and
event-free survivals were calculated. Health and neurodevelopment (Bayley Scales
of Infant Development II) were assessed at 18 to 24 months of age. Univariate
and multivariate analyses, sensitivity, and specificity were determined to
identify preoperative, intraoperative, and postoperative factors associated with
mental and/or motor delay. RESULTS: There was 1 operative mortality (1.1%). At
the average 4-year follow-up, survival was 98.9% and freedom from reintervention
was 93.2%. Eighty-five children were assessed. Three were excluded because of
unrelated postoperative diagnoses. For the remaining 82, mean scores were 89 +/-
17 (49-118) for mental skills and 92 +/- 15 (49-125) for motor skills. Anatomic
complexity, cardiopulmonary bypass, and deep hypothermic circulatory arrest
times were not associated with developmental outcome. Preoperative variables of
low gestational age and high preoperative lactate correctly classified 84.1% of
mentally and/or motor-delayed children. CONCLUSION: Transposition of great
arteries, including complex types, can be corrected with low surgical risk and
good intermediate survival; however, neurodevelopmental outcome is a concern.
These data suggest that although anatomic complexity may not affect late
outcome, there may be potentially modifiable preoperative factors that can be
optimized to improve developmental outcomes.

Ann Surg. 2006 Oct;244(4):593-601. 

Serologic markers of brain injury and cognitive function after cardiopulmonary
bypass.

Ramlawi B, Rudolph JL, Mieno S, Khabbaz K, Sodha NR, Boodhwani M, Levkoff SE,
Marcantonio ER, Sellke FW.

Division of Cardiothoracic Surgery, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA 02215, USA.

OBJECTIVE: To examine the association between biochemical markers of brain
injury (MBI) and the inflammatory response in relation to neurocognitive
deficiency (NCD) after cardiopulmonary bypass (CPB). SUMMARY BACKGROUND DATA: In
cardiac surgery, NCD is a common but underdiagnosed complication with an unclear
pathophysiology leading to significant morbidity. Despite extensive
investigation, identification of a MBI for clinical use and clarifying the
pathophysiology of NCD have not been achieved. METHODS: Forty patients
undergoing CABG and/or valve procedures using CPB were administered a validated
neurocognitive battery preoperatively and postoperatively at day 4 and 3 months.
S-100b, neuron specific enolase (NSE), and tau protein were assayed as MBIs
preoperatively and postoperatively at 6 hours and day 4. C-reactive protein
(CRP), interleukin (IL)-6, C3a, and total peroxide levels were also quantified
from serum. Impact of cardiotomy suction and antifibrinolytics on markers of
brain injury was assessed. RESULTS: The incidence of early NCD was 40% (16 of
40). NSE and tau protein at the 6-hour time point were both significantly
elevated in the presence of NCD (NCD group) compared with those without NCD
(NORM group) (8.69 +/- 0.82 vs. 5.98 +/- 0.61; P = 0.018 and 68.8 vs. 29.2%; P =
0.015; respectively). S-100b increase was not different between the NCD and NORM
groups. Cardiotomy suction significantly elevated S-100b levels, whereas NSE and
tau were not significantly influenced. Aprotinin did not have an effect on NCD
or levels of MBIs. Also, the NCD group had significantly elevated CRP and
peroxide levels compared with the NORM group at postoperative day 4 while C3a
was significantly elevated at 6 hours. CONCLUSION: NSE and tau are better
associated with NCD and less influenced by cardiotomy suction compared with
S-100beta. Inflammatory and oxidative stress is associated with NCD post-CPB.

Ann Thorac Surg. 2006 Oct;82(4):1436-44. 

Patterns of postoperative systemic vascular resistance in a randomized trial of
conventional on-pump versus off-pump coronary artery bypass graft surgery.

Tatoulis J, Rice S, Davis P, Goldblatt JC, Marasco S.

Department of Cardiothoracic Surgery, Royal Melbourne Hospital, University of
Melbourne, Parkville, Victoria, Australia. james.tatoulis@mh.org.au

BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) is associated with
a less intense systemic inflammatory response according to biochemical markers.
We studied systemic vascular resistance (SVR) as a physiologic response to
systemic inflammatory response to determine any differences between OPCAB and
on-pump coronary artery bypass grafting (ONCAB) in a prospective randomized
trial. METHODS: One hundred consecutive patients were randomized to OPCAB or
ONCAB, 50 in each group. Antifibrinolytics and steroids were not used. All
protocols were identical except for cardiopulmonary bypass. Temperature, SVR
index, cardiac index, and blood pressure were measured continuously for the
first 24 hours postoperatively. All patients were reviewed at 30 days. RESULTS:
There was no 30-day mortality, no stroke, and no acute renal failure. Mean
temperature peaked at 37.5 degrees C at 12 hours (p = 0.700 between groups).
Mean SVR index fell to 1,900 dyne x cm(-5) x m(-2) at 12 to 18 hours; 42% of
OPCAB and 32% of ONCAB patients developed very low SVR index (<1,500 dyne x
cm(-5) x m(-2)). The incidence of high SVR (>2,500 dyne x cm(-5) x m(-2)) fell
from 20% to 2% by 12 to 18 hours. The extent and pattern of SVR index responses
were similar in both groups (p = 0.840). Mean cardiac index peaked at 3.0 L x
min(-1) x m(-2), 12 to 18 hours postoperatively (p = 0.815 between groups); 84%
of OPCAB and 90% of ONCAB had cardiac index greater than 2.2 L x min(-1) x m(-2)
at all times. Only 10% of patients required vasopressors. Blood pressure
responses were also similar (p = 0.314). CONCLUSIONS: The incidence of low SVR,
and patterns of SVR changes were similar in ONCAB and OPCAB, and were clinically
unimportant as few patients required vasopressor support. Cardiac outputs and
clinical outcomes were excellent in both groups.

Cardiol Young. 2006 Oct;16(5):455-62. 

Experience with intraoperative ultrasound in paediatric cardiac surgery.

Balmer C, Barron D, Wright JG, de Giovanni JV, Miller P, Dhillon R, Brawn WJ,
Stumper O.

The Heart Unit, Birmingham Children's Hospital-NHS Trust, Birmingham, United
Kingdom.

OBJECTIVE: Intraoperative ultrasound was introduced to evaluate the adequacy of
repair after surgical repair of congenital cardiac malformations. Our purpose
was to review the evolution of this technique at our centre. METHODS: We
evaluated all intraoperative ultrasound studies undertaken between 1997 and
2002, reviewing the data from 1997 through 2001 retrospectively, but undertaking
a prospective audit of studies undertaken from 2002 onwards. In all, we carried
out a total number of 639 intraoperative ultrasound studies, from a possible
2737 cardiac operations (23.3%), using the epicardial approach in 580 (90.7%),
and transoesophageal ultrasound in the other 59 patients (9.3%). Median age was
0.6 years, with an interquartile range from 0.06 to 3.6 years. RESULTS: The
findings obtained using intraoperative ultrasound influenced the surgical
management in 63 of the 639 patients (9.9%), suggesting the need for additional
surgery in 26, adjustment of the band placed round the pulmonary trunk in 16,
preoperative assessment of the cardiac malformation in 5, and confirming the
need for prolonged support with cardiopulmonary bypass for impaired ventricular
function in 16. There were 18 early reoperations, 5 of which may have been
predicted by intraoperative ultrasound. Of the 183 studies reviewed
prospectively in 2002, it was not possible to obtain the complete range of views
in 8 (4.4%), while in 27 patients (14.7%), the postoperative findings using
transthoracic interrogation differed from the findings obtained immediately
following bypass. CONCLUSION: Intraoperative ultrasound is an important
technique for monitoring the results of complex congenital cardiac surgery. The
immediate recognition of significant lesions, together with multidisciplinary
discussion, allows for improved management and prevention of early surgical
reintervention.