Br J Anaesth. 2005 Apr 15; [Epub ahead of print] 

Effect of three different anaesthetic agents on the postoperative production of
cardiac troponin T in paediatric cardiac surgery.

Malagon I, Hogenbirk K, van Pelt J, Hazekamp MG, Bovill JG.

Department of Anaesthesia, Leiden University Medical Centre, Albinusdreef 2, PO
Box 9600, 2300 RC Leiden, The Netherlands.

BACKGROUND: Paediatric cardiac surgery is associated with some degree of
myocardial injury. Ischaemic preconditioning (IP) has been investigated widely
in the adult population. Volatile agents have been shown to simulate IP
providing extra protection to the myocardium during adult cardiopulmonary bypass
(CPB) while propofol seems to act through different mechanisms. IP has not been
investigated in the paediatric population to the same extent. Cardiac troponin T
(cTnT) is a reliable marker of myocardial injury in neonates and children. We
have investigated the relationship between three anaesthetic agents, midazolam,
propofol, and sevoflurane, and postoperative production of cTnT. METHODS: Ninety
patients undergoing repair of congenital heart defect with CPB were investigated
in a prospective randomized study. cTnT was measured four times during the first
24 h following admission to the paediatric intensive care unit. Other variables
measured included arterial blood gases, lactate, fluid balance, use of inotropic
drugs, PaO2/FIO2 ratio and ventilator hours. RESULTS: cTnT was elevated in all
three groups throughout the study period. The differences between the three
groups were not statistically significant. Eight hours after admission to the
intensive care unit cTnT concentrations tended to be higher in the midazolam
group [mean (95% confidence intervals)]; 2.7 (1.9-3.5) ng ml(-1). Patients
receiving a propofol-based anaesthesia had similar concentrations 2.6 (1.7-3.5)
ng ml(-1) while those receiving sevoflurane tended to have a lower cTnT
production 1.7 (1.3-2.2) ng ml(-1). CONCLUSIONS: Midazolam, propofol, and
sevoflurane appear to provide equal myocardial protection in paediatric cardiac
surgery when using cTnT as a marker of myocardial damage.

Kyobu Geka. 2005 Apr;58(4):278-83. 

[Risk factors for the surgical repair of ventricular septal perforation; an
8-year multiinstitutional analysis]

[Article in Japanese]

Sugiki H, Murashita T, Kunihara T, Matsuzaki K, Shiiya N, Yasuda K.

Department of Cardiovascular Surgery, Hokkaido University School of Medicine,
Sapporo, Japan.

OBJECTIVE: The purpose of this study was to determine the surgical outcomes and
risk factors for surgical repair of the ventricular septal perforation (VSP).
METHOD: From 1995 to 2003, 41 patients with VSP underwent surgical repair. There
were 18 males and 23 females, with the mean age of 71.7 +/- 9.2. Sixteen
patients (39.0%) had the preoperative shock, while 30 patients received
intraaortic balloon pumping (IABP) assistance and 1 of those required
percutaneous cardiopulmonary support (PCPS). Mean durations from onset of
myocardial infarction and VSP to operation were 5.8 +/- 9.4 and 2.4 +/- 8.1
days, respectively. Twenty-six patients underwent infarct exclusion technique,
11 underwent patch closure, and 4 Daggett operation. Mean cardiopulmonary and
aortic cross-clamp time were 211 +/- 85 and 105 +/- 43 minutes, respectively.
RESULTS: Thirty days mortality was 11 (26.8%). Nine patients (22%) required PCPS
after repair, however, 2 weaned off the support and only 1 discharged the
hospital. Residual shunt was found in 12 patients (29.3%), and 4 underwent the
reclosure of the residual shunt 13 +/- 8.6 days after the initial operation,
whereas none of patients with PCPS had residual shunt. Univariate analysis
revealed the preoperative shock (p = 0.03), longer cardiopulmonary bypass time
(p < 0.01), and the need for PCPS after repair (p < 0.01) were the risk factors
for the early mortality. Multivariate analysis indicated the cardiopulmonary
time over 210 minutes and the need for PCPS to be the significant risk factors.
CONCLUSION: The long cardiopulmonary bypass support after repair and the
subsequent need for PCPS imply the poor left ventricular function. Since the
residual shunt was not the cause of PCPS, the surgical outcome for VSP may be
limited in patients with poor left ventricular function. In these patients,
other therapeutic strategies may be required, such as ventricular assisting
devices, transplantation, or regenerative therapy.

J Thorac Cardiovasc Surg. 2005 Apr;129(4):851-9. 

Activation of neutrophils and monocytes by a leukocyte-depleting filter used
throughout cardiopulmonary bypass.

Ilmakunnas M, Pesonen EJ, Ahonen J, Ramo J, Siitonen S, Repo H.

Department of Bacteriology and Immunology, Division of Infectious Diseases,
University of Helsinki, Helsinki, Finland.

OBJECTIVE: Cardiopulmonary bypass elicits systemic inflammation. Depletion of
circulating leukocytes might alleviate inflammatory response. We studied the
effects of a leukocyte-depleting filter on phagocyte activation during
cardiopulmonary bypass. METHODS: Fifty patients undergoing coronary artery
bypass grafting were randomly allocated into an arterial line leukocyte filter
group (n = 25) with a Pall LeukoGuard 6 leukocyte-depleting filter (LG6; Pall
Biomedical, Portsmouth, United Kingdom) and a control group without any filter
(n = 25). Blood sampling took place from arterial line at predetermined time
points. In the filter group, the sample was taken immediately before the filter;
to evaluate activation at the site, an additional sample was taken immediately
after the filter. CD11b/CD18 and L-selectin expressions and basal production of
hydrogen peroxide were determined with whole-blood flow cytometry, and plasma
lactoferrin level was determined with enzyme-linked immunosorbent assay.
RESULTS: Neutrophil CD11b expression was higher in the filter group than in the
control group (P < .001). Likewise, monocyte CD11b expression, neutrophil
hydrogen peroxide production, and lactoferrin plasma levels were all
significantly higher, whereas neutrophil and monocyte counts and neutrophil
L-selectin expression were all significantly lower in the filter group (all P <
.001). At 5 minutes of CPB, CD11b expression increased across the filter on
neutrophils (median difference 197 relative fluorescence units, range 45-431
relative fluorescence units, P < .001) and monocytes (median difference 26
relative fluorescence units, range -68-111 relative fluorescence units, P <
.001). CONCLUSION: The LG6 arterial line leukocyte filter is ineffective in its
principal task of diminishing phagocyte activation during cardiopulmonary
bypass.

J Thorac Cardiovasc Surg. 2005 Apr;129(4):782-90. 

Combined administration of nitric oxide gas and iloprost during cardiopulmonary
bypass reduces platelet dysfunction: a pilot clinical study.

Chung A, Wildhirt SM, Wang S, Koshal A, Radomski MW.

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

BACKGROUND: Thrombocytopenia and platelet dysfunction are major mechanisms of
cardiopulmonary bypass-induced postoperative hemorrhage. This study evaluated
the effects of low amounts of nitric oxide, iloprost (prostacyclin analog), and
their combination administered directly into the oxygenator on platelet
function, platelet-leukocyte interactions, and postoperative blood loss in
patients undergoing coronary artery bypass grafting. METHODS: Blood samples from
41 patients randomized to the control, nitric oxide (20 ppm), iloprost (2 ng x
kg -1 x min -1 ), or nitric oxide plus iloprost groups were collected during
cardiopulmonary bypass. Platelets and leukocytes were enumerated. Platelet
membrane glycoprotein Ib and glycoprotein IIb/IIIa, P-selectin, platelet-derived
microparticles, leukocyte CD11b/CD18 (Mac-1), and platelet-leukocyte aggregate
were quantified by means of flow cytometry. Collagen and thrombin
receptor-activating peptide-induced platelet aggregation in whole blood was
analyzed by means of aggregometry. RESULTS: Both nitric oxide or iloprost
attenuated cardiopulmonary bypass-induced thrombocytopenia, reduction of
glycoprotein Ib and glycoprotein IIb levels, translocation of P-selectin,
microparticle formation, Mac-1 upregulation, and suppression of collagen-induced
aggregation. Nitric oxide plus iloprost was significantly more effective in
preventing thrombocytopenia, microparticle formation, and P-selectin
translocation. Moreover, this treatment preserved thrombin receptor-activating
peptide-induced aggregation, which was not rescued by single treatments. Both
nitric oxide and nitric oxide plus iloprost attenuated postoperative blood loss.
CONCLUSIONS: Nitric oxide plus iloprost reduced the deleterious effects of
cardiopulmonary bypass, such as thrombocytopenia, platelet activation,
platelet-leukocyte aggregate formation, and suppression of platelet aggregative
responses. The reduced postoperative bleeding observed with this treatment
suggests that this is a new and clinically feasible therapeutic option for
patients subjected to cardiopulmonary bypass.

J Thorac Cardiovasc Surg. 2005 Apr;129(4):760-6. 

Surgical trauma affects the proinflammatory status after cardiac surgery to a
higher degree than cardiopulmonary bypass.

Prondzinsky R, Knupfer A, Loppnow H, Redling F, Lehmann DW, Stabenow I, Witthaut
R, Unverzagt S, Radke J, Zerkowski HR, Werdan K.

Department of Medicine III, Martin-Luther-University Halle-Wittenberg, Halle
(Salle), Germany. roland.prondzinsky@medizin.uni-halle.de

OBJECTIVES: Cytokines contribute to the development of the systemic inflammatory
response syndrome or multiple-organ failure frequently observed after
cardiopulmonary bypass-supported cardiac surgery. To quantify the contribution
of bypass-induced versus trauma-induced inflammatory response after coronary
artery bypass grafting, we examined plasma cytokine levels in 120 patients with
coronary artery disease who were treated with or without cardiopulmonary
bypass-assisted procedures. METHODS: Patients were treated in accordance with
one of the following protocols: (1) elective percutaneous coronary intervention
without cardiopulmonary bypass (n = 69), (2) cardiopulmonary bypass-supported
percutaneous coronary intervention (cardiopulmonary bypass-percutaneous coronary
intervention; n = 10), and (3) cardiopulmonary bypass-supported coronary artery
bypass grafting (cardiopulmonary bypass-coronary artery bypass grafting; n =
41). Cytokine levels (picograms/milliliter) were measured by enzyme-linked
immunosorbent assay from plasma samples obtained at various time points.
RESULTS: Interleukin-6 was measured in blood samples from all 3 patient
populations. The maximum interleukin-6 level was 13.6 +/- 22.3 pg/mL in the
percutaneous coronary intervention group, 170.4 +/- 165.4 pg/mL in the
cardiopulmonary bypass-percutaneous coronary intervention group, and 640.3 +/-
285.7 pg/mL in the cardiopulmonary bypass-coronary artery bypass grafting group.
Interleukin-6 levels were significantly different, and the 95% confidence
intervals did not overlap. In the cardiopulmonary bypass-percutaneous coronary
intervention group, bypass duration correlated well with interleukin-6
production ( r = 0.915; P < .001), whereas these parameters did not correlate in
patients who underwent cardiopulmonary bypass-coronary artery bypass grafting (
r = 0.307; P = .054). CONCLUSIONS: These findings support the suggestion that
surgical trauma and cardiopulmonary bypass contribute to the inflammatory
response after cardiac surgery, although trauma may contribute to a higher
degree.

Chest. 2005 Apr;127(4):1184-9. 

Plasma L-arginine and metabolites of nitric oxide synthase in patients with
left-to-right shunt after intracardiac repair.

Gorenflo M, Ullmann MV, Eitel K, Gross J, Fiehn W, Hagl S, Dreyhaupt J.

Department of Pediatric Cardiology, University Medical Center, INF 153, D-69120
Heidelberg, Germany. Matthias_Gorenflo@med.uni-heidelberg.de

STUDY OBJECTIVE: Human plasma L-arginine serves as a substrate pool for
endothelial-derived nitric oxide (NO) synthase. In this pilot study, we tested
the hypothesis that plasma L-arginine and other metabolites of the L-arginine NO
pathway could correlate with postoperative pulmonary hypertension after
cardiopulmonary bypass (CPB). DESIGN: Forty-two patients (median age, 0.5 years;
range, 0.1 to 28 years) with atrial septal defect (n = 15), ventricular septal
defect (n = 18), atrioventricular canal (n = 8), and aortopulmonary window (n =
1) were enrolled. The influence of patient age, preoperative pulmonary
hypertension, duration of CPB, plasma L-arginine, guanosine 3', 5'-cyclic
monophosphate (cGMP), and nitrate on postoperative pulmonary hypertension during
the first 24 h after CPB was studied by logistic regression. RESULTS: Nineteen
of 42 patients were found to have preoperative pulmonary hypertension. Thirteen
of 42 patients showed persistent pulmonary hypertension after intracardiac
repair with a mean pulmonary artery pressure (PAP) of 38 mm Hg (range, 23 to 55
mm Hg) at 24 h after CPB. L-arginine concentrations in plasma were significantly
lower 24 h after CPB than before: 52 mumol/L (range, 18 to 95 mumol/L) vs 79
mumol/L (range, 31 to 157 mumol/L). Plasma cGMP levels were higher and plasma
nitrate levels were lower immediately after weaning from CPB (p < 0.0033). On
logistic regression analysis, only patient age (p = 0.02) and preoperative PAP
(p = 0.01) were related to postoperative pulmonary hypertension. CONCLUSION: Low
plasma L-arginine does not relate to persistent pulmonary hypertension in
patients with left-to-right shunt after CPB and intracardiac repair.

Lancet. 2005 Apr;365(9466):1231-8. 

Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal
injury after cardiac surgery.

Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K,
Shao M, Bean J, Mori K, Barasch J, Devarajan P.

Division of Nephrology and Hypertension, Cincinnati Children's Hospital Medical
Center, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039,
USA.

BACKGROUND: The scarcity of early biomarkers for acute renal failure has
hindered our ability to launch preventive and therapeutic measures for this
disorder in a timely manner. We tested the hypothesis that neutrophil
gelatinase-associated lipocalin (NGAL) is an early biomarker for ischaemic renal
injury after cardiopulmonary bypass. METHODS: We studied 71 children undergoing
cardiopulmonary bypass. Serial urine and blood samples were analysed by western
blots and ELISA for NGAL expression. The primary outcome measure was acute renal
injury, defined as a 50% increase in serum creatinine from baseline. FINDINGS:
20 children (28%) developed acute renal injury, but diagnosis with serum
creatinine was only possible 1-3 days after cardiopulmonary bypass. By contrast,
urine concentrations of NGAL rose from a mean of 1.6 microg/L (SE 0.3) at
baseline to 147 microg/L (23) 2 h after cardiopulmonary bypass, and the amount
in serum increased from a mean of 3.2 microg/L (SE 0.5) at baseline to 61
microg/L (10) 2 h after the procedure. Univariate analysis showed a significant
correlation between acute renal injury and the following: urine and serum
concentrations of NGAL at 2 h, and cardiopulmonary bypass time. By multivariate
analysis, the amount of NGAL in urine at 2 h after cardiopulmonary bypass was
the most powerful independent predictor of acute renal injury. For concentration
in urine of NGAL at 2 h, the area under the receiver-operating characteristic
curve was 0.998, sensitivity was 1.00, and specificity was 0.98 for a cutoff
value of 50 microg/L. INTERPRETATION: Concentrations in urine and serum of NGAL
represent sensitive, specific, and highly predictive early biomarkers for acute
renal injury after cardiac surgery.

Ann Thorac Surg. 2005 Apr;79(4):1316-25. 

pH-stat versus alpha-stat acid-base management strategy during hypothermic
circulatory arrest combined with embolic brain injury.

Dahlbacka S, Heikkinen J, Kaakinen T, Laurila P, Vainionpaa V, Kiviluoma K,
Salomaki T, Tuominen H, Ohtonen P, Biancari F, Lepola P, Juvonen T.

Department of Surgery, Oulu University Hospital, University of Oulu, Oulu,
Finland.

BACKGROUND: There is some evidence of beneficial metabolic effects associated
with the pH-stat than with alpha-stat perfusion strategy, but this is tempered
by a likely increased risk of embolism to the brain, especially in adult
patients. We investigated this possible adverse effect in an experimental model
that combined hypothermic circulatory arrest (HCA) and embolic brain injury.
METHODS: Twenty-four female juvenile pigs undergoing 25 minutes of HCA at a
brain temperature of 18 degrees C were assigned to either alpha-stat (n = 12) or
pH-stat (n = 12) strategy during cardiopulmonary bypass. Before the initiation
of HCA, the descending aorta was clamped and 200 mg of albumin-coated
polystyrene microspheres (250 to 750 microm in diameter) were injected into the
isolated aortic arch in both groups. RESULTS: The 7-day survival rate was 75% in
the pH-stat group and 50% in the alpha-stat group (p = 0.40). The pH-stat group
had significantly better behavioral scores on postoperative days 5 (p = 0.03)
and 6 (p = 0.04). The pH-stat strategy was associated with better postoperative
intracranial pressures and histopathologic scores, but such differences did not
reach statistical significance. The alpha-stat group had lower brain glucose
concentrations postoperatively as well as higher brain lactate/glucose and
lactate/pyruvate ratios CONCLUSIONS: These results suggest that pH-stat strategy
does not cause any worse brain injury than the alpha-stat strategy. Indeed, the
pH-stat strategy is associated with a slightly better outcome compared with the
alpha-stat strategy, even in the setting of cerebral embolization. This
observation suggests that the pH-stat strategy could also be used in adults
during deep hypothermic cardiopulmonary bypass despite the increased risk of
intraoperative cerebral embolization.

Ann Thorac Surg. 2005 Apr;79(4):1303-6. 

Early experience with activated recombinant factor VII for intractable
hemorrhage after cardiovascular surgery.

Halkos ME, Levy JH, Chen E, Reddy VS, Lattouf OM, Guyton RA, Song HK.

Division of Cardiothoracic Surgery, Emory University School of Medicine,
Atlanta, Georgia, USA.

BACKGROUND: Intractable hemorrhage after complex cardiovascular operations is a
serious and potentially lethal complication. We report our experience with the
use of activated recombinant factor VIIa (rFVIIa) as rescue therapy for patients
with refractory postoperative hemorrhage. METHODS: From April 2002 through
December 2003, 9 patients received rFVIIa for intractable hemorrhage after
cardiovascular surgery. Patients underwent aortic surgery (2), coronary artery
bypass graft surgery (4), double valve operations (2), and mitral valve
replacement (1). Four of these procedures were reoperations. Intraoperative
aprotinin was used in all patients. All patients underwent standard
heparinization (300 IU/kg) before cardiopulmonary bypass and reversal with
protamine. RESULTS: Five patients underwent reexploration for mediastinal
hemorrhage before treatment; 2 were reexplored twice. The average transfusion
requirement before rFVIIa administration was 9 U of blood, 7 U of plasma, 22 U
of platelets, and 19 U of cryoprecipitate. rFVIIa was administered as an
intravenous bolus at 68 to 120 mug/kg. Mean time of administration from the
first operation was 10.9 +/- 7.2 hours. At the time of activated rFVIIa
administration, chest tube drainage averaged 640 mL/h. In all patients, chest
tube drainage was dramatically reduced to less than 100 mL/h within 5 hours
after drug delivery. None of the patients required reexploration after
treatment. There were no postoperative neurologic or cardiovascular
complications. CONCLUSIONS: When used as rescue therapy for intractable
hemorrhage after cardiovascular surgery, rFVIIa may be effective in promoting
hemostasis, preventing reexploration, and reducing transfusion requirements.

Artif Organs. 2005 Apr;29(4):300-5. 

Descending thoracic aortic aneurysm repair with the aid of partial
cardiopulmonary bypass: heparin-coated circuits versus nonheparin-coated
circuits.

Morishita K, Kawaharada N, Fukada J, Hachiro Y, Kurimoto Y, Fujisawa Y, Saito T,
Abe T.

Department of Thoracic and Cardiovascular Surgery, Sapporo Medical University
School of Medicine, South 1 West 16, Central Ward, Sapporo 060-8543, Japan.
kmori@sapmed.ac.jp

BACKGROUND: We have performed descending thoracic aortic aneurysm repairs with
partial cardiopulmonary bypass, including heparin-coated circuits. The aim of
this study was to evaluate (i) the impact of partial cardiopulmonary bypass on
distal organ function and surgical outcomes; and (ii) the effectiveness of using
heparin-coated circuits for preventing bleeding complications. METHODS: From
July 1980 to June 2004, 309 patients underwent descending thoracic aortic
aneurysm repairs using partial cardiopulmonary bypass. Their mean age was 61
years (range 19-81 years). One hundred of the 309 patients underwent repair of
descending thoracic aortic aneurysm with heparin-coated circuits. Blood data for
renal and hepatic function were collected on the day before the operation and
postoperative days. RESULTS: The in-hospital mortality was 15%. Distal organ
dysfunction included spinal cord dysfunction in 2 patients (0.7%) and renal
failure necessitating hemodialysis in 15 patients (5%, 15/297: excluded 12
dialysis patients). Multivariate analyses showed that preoperative hemodialysis
and emergency operation were risk factors for operative mortality and that
emergency operation was a risk factor for requiring hemodialysis. Renal and
hepatic function normalized by 2 weeks after surgery. There were no significant
differences between the heparin-coated group and nonheparin-coated group in
amounts of packed red cells, fresh frozen plasma, and platelets transfused
during the procedures. CONCLUSIONS: Our data showed that partial cardiopulmonary
bypass is a safe and effective method for distal perfusion. Using this
technique, descending thoracic aortic aneurysm repair can be performed with
acceptable mortality and morbidity. However, the superiority of heparin-coated
circuits over nonheparin-coated ones was not proved.