Cardiovasc Drugs Ther. 2005 Sep 20; [Epub ahead of print] 

Propionyl-L-Carnitine Improves Hemodynamics and Metabolic Markers of Cardiac
Perfusion during Coronary Surgery in Diabetic Patients.

Lango R, Smolenski RT, Rogowski J, Siebert J, Wujtewicz M, Slominska EM,
Lysiak-Szydlowska W, Yacoub MH.

Department of Anesthesiology and Intensive Care, Medical University of Gdansk,
Debinki, 7 80-211, Poland, rlango@amg.gda.pl.

Diabetic hearts are particularly vulnerable to ischemia-reperfusion injury
during cardiac surgery. Application of carnitine derivatives could be beneficial
not only because of metabolic effects but also by protecting vasculature. This
study aimed to evaluate hemodynamic changes associated with
propionyl-L-carnitine and L-carnitine administration and its correlation with
biochemical markers of cardiac vascular function.Methods: Sixty-eight diabetic
patients undergoing cardiopulmonary bypass coronary operation were given
intravenously 20 mg/kg b.w. L-carnitine (LC), 24 mg/kg b.w.
propionyl-L-carnitine (PC), or placebo (Cont). Endothelin and nucleotide
metabolites were determined intraoperatively in arterial and coronary sinus
blood and heart biopsies.Results: Cardiac index at 6 and 12 h after
cardiopulmonary bypass was significantly higher in PC (3.30 +/- 0.12 and 3.47
+/- 0.15 L/min/m(2)) as compared to Cont (2.92 +/- 0.13 and 2.91 +/- 0.16
L/min/m(2); P = 0.04 and P = 0.01, respectively). Mean pulmonary artery pressure
was lower in PC at 6 (20.8 +/- 0.91 mmHg) and 12 h (20.7 +/- 0.81 mmHg) in
comparison to Cont (23.5 +/- 0.75 and 23.4 +/- 0.75 mmHg; P = 0.03 and P = 0.02,
respectively). Trans-cardiac endothelin difference on reperfusion was higher in
Cont (0.33 +/- 0.26 pmol/L) than in LC (-0.61 +/- 0.24 pmol/L, P = 0.012) and
tended to be higher than in PC (-0.29 +/- 0.17 pmol/L, P = 0.056). Trans-cardiac
hypoxanthine difference after 10 min reperfusion was significantly higher in
Cont (6.22 +/- 1.08 mumol/L) in comparison to LC (3.17 +/- 0.66 mumol/L, P =
0.025) and PC (2.36 +/- 0.73 mumol/L, P = 0.006). Myocardial hypoxanthine
concentration was lowest in PC.Conclusions: Significant improvement of
hemodynamics following propionyl-L-carnitine administration in diabetic patients
undergoing on-bypass coronary surgery was accompanied by reduced trans-cardiac
endothelin difference and rapid hypoxanthine washout during reperfusion
suggesting improvement of metabolism or vascular function.

Eur J Anaesthesiol. 2005 Sep;22(9):666-71. 

Kidney-specific proteins in patients receiving aprotinin at high- and low-dose
regimens during coronary artery bypass graft with cardiopulmonary bypass.

Fauli A, Gomar C, Campistol JM, Alvarez L, Manig AM, Matute P.

University of Barcelona, Hospital Clinic, Department of Anesthesiology,
Barcelona, Spain. afauli@clinic.ub.es

BACKGROUND AND OBJECTIVE: The aim was to determine whether the administration of
aprotinin can cause deleterious effects on renal function in cardiac surgery
with cardiopulmonary bypass (CPB). METHODS: Sixty consecutive patients with
normal preoperative renal function undergoing elective coronary artery bypass
surgery with CPB using the same anaesthetic; CPB and surgical protocols were
randomized into three groups. Patients received placebo (Group 1), low-dose
aprotinin (Group 2) or high-dose aprotinin (Group 3). Renal parameters measured
were plasma creatinine, alpha1-microglobulin and beta-glucosaminidase (beta-NAG)
excretion. Measurements were performed before surgery, during CPB and 24 and 72
h, and 7 and 40 days postoperatively. RESULTS: In the three groups,
alpha1-microglobulin and beta-NAG excretions significantly increased during CPB,
at 24 and 72 h, and 7 days postoperatively (P < 0.05) and had returned to
preoperative levels at postoperative day 40. Plasma creatinine levels were
within normal values at times recorded. In Groups 2 and 3, alpha1-microglobulin
excretion during CPB was significantly higher than in Group 1 (P < 0.001), and
24h after surgery it still remained significantly higher in Group 3 compared to
Groups 1 and 2 (P < 0.05). CONCLUSIONS: Aprotinin caused a significant increase
in alpha1-microglobulin excretion but not in beta-NAG excretion during CPB,
which may be interpreted as a greater renal tubular overload without tubular
damage. This effect persisted for 24 h after surgery when high-dose aprotinin
doses had been administered. Creatinine plasma levels were not sensitive to
detect these prolonged renal effects in our study.

Arch Dis Child. 2005 Sep 13; [Epub ahead of print] 

Hyperchloraemic metabolic acidosis following open cardiac surgery.

Hatherill M, Salie S, Waggie Z, Lawrenson J, Hewitson J, Reynolds L, Argent A.

University of Cape Town, South Africa.

OBJECTIVES: To describe acid-base derangements in children following open
cardiac surgery on cardiopulmonary bypass (CPB), using the Fencl-Stewart strong
ion approach. METHODS: Prospective observational study set in the paediatric
intensive care unit (PICU) of a university children's hospital. Arterial blood
gas parameters, serum electrolytes, strong ion difference, strong ion gap (SIG),
and partitioned base excess (BE) were measured and calculated on admission to
PICU. RESULTS: 97 children, median age 57 months (0.03- 166), median weight 14
kg (2.1-50), were studied. Median CPB time was 80 min (17-232). Predicted
mortality was 2% and there was a single nonsurvivor. These children demonstrated
mild metabolic acidosis (median standard bicarbonate 20.1 mmol/L and BE -5.1
mEq/L) characterised by hyperchloraemia (median corrected Cl 113 mmol/L), and
hypoalbuminaemia (median albumin 30 g/L), but no significant excess unmeasured
anions or cations (median SIG 0.7 mEq/L). The major determinants of the net BE
were the chloride and albumin components (chloride effect -4.8 mEq/L and albumin
effect +3.4 mEq/L). Metabolic acidosis occurred in 72 children (74%) but was not
associated with increased morbidity. Hyperchloraemia was a causative factor in
53 children (74%) with metabolic acidosis. Three (4%) hyperchloraemic children
required adrenaline for inotropic support, compared to 8 children (28%) without
hyperchloraemia (p=0.005). Hypoalbuminaemia was associated with longer duration
of inotropic support (p=0.047) and PICU stay (p=0.009). CONCLUSIONS: In these
children with low mortality following open cardiac surgery, hypoalbuminaemia and
hyperchloraemia were the predominant acid-base abnormalities. Hyperchloraemia
was associated with reduced requirement for adrenaline therapy. We suggest that
hyperchloraemic metabolic acidosis is a benign phenomenon that should not prompt
escalation of haemodynamic support. By contrast, hypoalbuminaemia, an
alkalinizing force, was associated with prolonged requirement for intensive
care.

J Thorac Cardiovasc Surg. 2005 Sep;130(3):822-829. 

Effect of cardiopulmonary bypass and surgical intervention on the natriuretic
hormone system in children.

Costello JM, Backer CL, Checchia PA, Mavroudis C, Seipelt RG, Goodman DM.

Division of Cardiology, Childrens Memorial Hospital, The Feinberg School of
Medicine at Northwestern University, Chicago, Ill; Division of Critical Care
Medicine, Childrens Memorial Hospital, The Feinberg School of Medicine at
Northwestern University, Chicago, Ill.

OBJECTIVES: We sought to determine the effect of cardiopulmonary bypass and
surgical intervention on the natriuretic hormone system in children and to
assess whether such changes are associated with morbidity. METHODS: At 6
perioperative time points in 25 patients, plasma levels of atrial natriuretic
peptide, brain natriuretic peptide, and guanosine 3', 5'-monophosphate were
measured, and the biologic activity of the natriuretic hormone system was
quantified. Relationships were sought between changes in brain natriuretic
peptide levels, biologic activity, and a number of morbidity indicators.
RESULTS: There was a significant change in atrial natriuretic peptide levels (P
= .037), brain natriuretic peptide levels (P = .001), and biologic activity of
the natriuretic hormone system (P = .009) over the first 4 time points in the
study. Atrial natriuretic peptide levels transiently decreased from baseline to
12 hours after surgical intervention. Compared with baseline values, brain
natriuretic peptide levels were increased at 12 hours after surgical
intervention and on postoperative day 1. The increase in brain natriuretic
peptide levels from baseline to 12 hours after surgical intervention was
associated with cardiopulmonary bypass time (r(s) = 0.4, P = .047). The biologic
activity transiently decreased from baseline to intensive care unit admission
but was not associated with any morbidity indicators. CONCLUSIONS: Increased
postoperative brain natriuretic peptide levels are associated with longer bypass
times. The biologic activity of the natriuretic hormone system is transiently
impaired. Larger studies should investigate brain natriuretic peptide as a
predictor of postoperative morbidity and the potential for natriuretic hormone
infusions to improve postoperative hemodynamics and urine output.

J Thorac Cardiovasc Surg. 2005 Sep;130(3):712-8. 

Hypothermic circulatory arrest is not a risk factor for neurologic morbidity in
aortic surgery: A propensity score analysis.

Kunihara T, Grun T, Aicher D, Langer F, Adam O, Wendler O, Saijo Y, Schafers HJ.

Department of Thoracic and Cardiovascular Surgery, University Hospital Homburg,
Homburg, Germany.

OBJECTIVE: Hypothermic circulatory arrest has been an important tool in aortic
arch surgery, even though its use has recently been discussed controversially.
We sought to clarify the role of hypothermic circulatory arrest as a risk factor
for mortality and neurologic morbidity in aortic surgery by using a propensity
score-matching analysis. METHODS: Five hundred eleven patients (60 +/- 13 years,
349 male patients) who underwent replacement of the ascending aorta with (n =
273) or without (n = 238) arch involvement were analyzed by means of
multivariate analysis. Using propensity score matching, we identified comparable
patient groups: HCA(+) group and HCA(-) group (n = 110 each). For aortic arch
replacement, hypothermic circulatory arrest was used with a mean duration of 14
+/- 9 minutes: 12 +/- 7 minutes or 26 +/- 8 minutes for partial or total arch
replacement, respectively. RESULTS: In the entire cohort multivariate analysis
identified acute dissection and duration of cardiopulmonary bypass as
significant predictors for hospital death. Predictors for stroke were acute
dissection, diabetes mellitus, peripheral arterial disease, and concomitant
mitral valve surgery, and predictors for temporary neurologic dysfunction were
peripheral arterial disease and age. After propensity score matching, the
incidence of death (HCA[+]: 0.9% vs HCA[-]: 2.7%), stroke (0% vs 1.8%,
respectively), and temporary neurologic dysfunction (15.5% vs 13.6%,
respectively) was comparable between the 2 groups. Multivariate analysis
identified age, diabetes mellitus, peripheral arterial disease, and concomitant
coronary artery bypass grafting as the independent risk factors for temporary
neurologic dysfunction. CONCLUSIONS: In a standard clinical setting (hypothermic
circulatory arrest of <30 minutes and nasopharyngeal temperature of <20 degrees
C), hypothermic circulatory arrest constitutes no significant risk for mortality
or neurologic morbidity and thus appears clinically safe. Patient-related risk
factors primarily determine clinical outcome.

Ann Thorac Surg. 2005 Sep;80(3):982-8. 

Randomized comparison between normothermic and hypothermic cardiopulmonary
bypass in pediatric open-heart surgery.

Caputo M, Bays S, Rogers CA, Pawade A, Parry AJ, Suleiman S, Angelini GD.

Bristol Heart Institute, University of Bristol, Bristol Royal Infirmary,
Bristol, United Kingdom.

BACKGROUND: The purpose of this study is to investigate the effect of
cardiopulmonary bypass (CPB) temperature on myocardial reperfusion injury,
oxidative stress, and inflammatory response in pediatric open heart surgery.
METHODS: Fifty-nine children (median age 78 months; interquartile range, 39-130)
undergoing correction of simple congenital heart defects were randomized to
receive either hypothermic (28 degrees C) or normothermic (35-37 degrees C) CPB.
Troponin I and 8-isoprostane, complement activation C3a, interleukin (IL) -6,
-8, and -10, were measured preoperatively, on removal of the aortic cross clamp,
30 minutes, 6, and 24 hours postoperatively. RESULTS: Troponin I and
8-isoprostane were significantly raised, compared to baseline, in both groups,
and remained high at 24 hours. Overall, troponin I and 8-isoprostane levels were
37% and 84% higher in the hypothermic than in the normothermic group,
respectively (ratio 1.37, 95% CI 1.00 to 1.88, p = 0.053 and 1.84, 95% CI 1.22
to 2.78, p = 0.0045, respectively), and there was no evidence to suggest the
treatment effect changed significantly over the time points measured (p = 0.63).
Adjusting for aortic cross-clamp time reduced the effect of hypothermia on
troponin (p = 0.18) but not on 8-isoprostane levels (p = 0.0028). The C3a, IL-6,
and IL-8 release was similar in the two groups. The IL-10 release between the
groups changed over time (p = 0.059) and examining differences at individual
time points highlighted a statistically significant difference at the end of the
cross-clamp time (p = 0.0079). CONCLUSIONS: Normothermic CPB is associated with
reduced oxidative stress compared with hypothermic CPB, and similar myocardial
reperfusion injury and whole body inflammatory response, in children undergoing
open heart surgery. A larger study with clinical outcomes as primary end points
is now warranted.

Am J Surg. 2005 Sep;190(3):401-5. 

Risk factors and outcomes of pancreatitis after open heart surgery.

Perez A, Ito H, Farivar RS, Cohn LH, Byrne JG, Rawn JD, Aranki SF, Zinner MJ,
Tilney NL, Brooks DC, Ashley SW, Banks PA, Whang EE.

Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Harvard
Medical School, Boston, MA 02115, USA.

BACKGROUND: We sought to analyze the risk factors and natural history associated
with post-cardiac surgery acute pancreatitis. METHODS: Retrospective analysis of
all patients having undergone cardiac surgery at our hospital between January 1,
1992, and October 1, 2001. RESULTS: A total of 10,249 cardiac operations were
performed. Thirty-nine (0.4%) patients developed postoperative pancreatitis.
There was a higher incidence during the period spanning 1992 through 1996 than
1997 through 2001 (0.6% versus 0.2%, P< .05). Patients with pancreatitis had
longer postoperative length of stay (51+/-5 days versus 10+/-1 days, P<.05) and
a greater in-hospital mortality rate (28% versus 4%, P<.05) than patients who
did not develop pancreatitis. A history of alcohol abuse, cardiac surgery
performed during 1992 to 1996, increased cardiopulmonary bypass time, and
increased cross-clamp time were independent risk factors for the development of
pancreatitis. Multiple-organ failure was an independent predictor for death
among patients with pancreatitis. CONCLUSIONS: Although the frequency of
post-cardiac surgery pancreatitis is diminishing, it is still associated with
significant mortality.

Exp Brain Res. 2005 Sep;165(3):343-350. Epub 2005 Jun 7. 

Cerebral oxygen saturation and electrical brain activity before, during, and up
to 36 hours after arterial switch procedure in neonates without pre-existing
brain damage: its relationship to neurodevelopmental outcome.

Toet MC, Flinterman A, Laar IV, Vries JW, Bennink GB, Uiterwaal CS, Bel FV.

Department of Neonatology, KE 04.123.1, University Medical Center Utrecht/
Wilhelmina Children's Hospital, P.B. 85090, 3508, Utrecht, The Netherlands,
M.Toet@WKZ.AZU.nl.

Objective: To monitor the pattern of cerebral oxygen saturation (rSat), by use
of NIRS, in term infants before, during and after the arterial switch operation
and to evaluate its relation to neurodevelopmental outcome. Methods: In 20
neonates without pre-existing brain damage hemodynamics and arterial oxygen
saturation (AO(2)-Sat) were monitored simultaneously with rSat and
amplitude-integrated EEG (aEEG) from 4 h to 12 h before up to 36 h after
cardiopulmonary bypass (CPB) and short duration of cardiac arrest during deep
hypothermia (DHCA). The Bayleys developmental scale was performed at 30 months.
Results: Before surgery rSat was <50% in 16 patients. During CPB rSat increased
to normal values, with a sharp decrease during brief CA (median 6.5 min).
Post-CPB rSat showed a transient decrease (30-45%) despite normal PaO(2) with
sustained normalization after 6-26 h. Recovery time of the rSat seemed longer
when pre-operative rSat was below 35%, and for lower minimum nasopharyngeal
temperature and longer duration of CPB and of DHCA. Recovery time of the aEEG
varied and did not correlate with normalization of rSat. Neurodevelopmental
outcome was normal in all but two patients. Patients with lower pre-operative
rSat (<35%) tended to have lower DQ (developmental quotient) scores at 30-36
months. (median: mental 102 and motor 101 (range 58-125) compared with mental
100 and motor 110 (range 83-125)) Conclusion: Despite prompt normalization of
circulation and oxygenation after surgery, recovery of rSat of the brain took
6-26 h, probably because of higher energy demand after CPB. Pre-operative
cerebral oxygenation may be underestimated as a possible cause of adverse
post-operative outcome.

Eur J Cardiothorac Surg. 2005 Sep 2; [Epub ahead of print] 

Vasoplegic syndrome-the role of methylene blue.

Shanmugam G.

Department of Cardiac Surgery, Royal Hospital for Sick Children, Dalnair Street,
Glasgow G3 8SJ, UK.

Vasoplegic syndrome is a recognized complication following cardiac surgery using
cardiopulmonary bypass and is associated with increased morbidity and mortality.
In several patients profound post-operative vasodilatation does not respond to
conventional vasoconstrictor therapy. Methylene blue has been advocated as an
adjunct to conventional vasoconstrictors in such situations. There is limited
data pertaining to the use of methylene blue and a number of reports have been
anecdotal observations. This article reviews the incidence and problems
associated with the vasoplegic syndrome, the mechanism of action of methylene
blue, its effects and adverse reactions and the literature supporting its
intra-operative and post-operative use. In cases where first-line therapy fails,
the use of methylene blue seems to be a potent approach to refractory
vasoplegia. The early use of methylene blue may halt the progression of low
systemic vascular resistance even in patients responsive to norepinephrine and
mitigate the need for prolonged vasoconstrictor use. However, dosing regimens
and protocols need to be clearly defined before widespread routine use. Whether
methylene blue should be the first line of therapy in patients with vasoplegia
is a matter of debate, and there is inadequate evidence to support its use as a
first line drug. More scientific evidence is needed to define the role of MB in
the treatment of catecholamine refractory vasoplegia.

Intensive Care Med. 2005 Sep 16; [Epub ahead of print] 

Effect of dexamethasone on postoperative cardiac troponin T production in
pediatric cardiac surgery.

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

Department of Anesthesia, Leiden University Medical Center, Albinusdreef 2, P.O.
Box 9600, 2300 RC, Leiden, The Netherlands, jmalagon@lumc.nl.

OBJECTIVE: Pediatric cardiac surgery is associated with a temporary rise in
cardiac troponin T (cTnT) during the postoperative period. We examined whether
dexamethasone given before cardiopulmonary bypass has myocardial protective
effects as assessed by the postoperative production of cTnT.DESIGN AND SETTING:
Prospective randomized interventional study in the pediatric intensive care unit
in a university hospital.INTERVENTIONS: Patients were randomly allocated to act
as controls or receive a single dose of dexamethasone (1 mg/kg) during induction
of anesthesia.MEASUREMENTS AND RESULTS: cTnT was measured four times
postoperatively: immediately after admission to the pediatric intensive care
unit (PICU) and 8, 15, and 24 h thereafter. The two groups had similar mean cTnT
concentrations on PICU admission: those receiving dexamethasone 1.85 ng/ml
(1.55-2.15) and those not receiving it 2 ng/ml (95% confidence interval
1.56-2.51). Concentrations of cTnT 8 h after admission to the PICU differed
significantly after 8 h: 1.99 ng/ml (1.53-2.45) in those receiving dexamethasone
and 3.08 ng/ml (2.46-3.69) in those not receiving it. After subgroup statistical
analysis differences between the two groups remained significant only at 8 h,
not those after 15 or 24 h.CONCLUSIONS: The use of dexamethasone (1 mg/kg)
before cardiopulmonary bypass is associated with a brief but significant
reduction in postoperative cTnT production. The clinical significance of this
effect is unclear.