Eur J Cardiothorac Surg. 2006 Aug 31; [Epub ahead of print] 

The role of leukocyte depleting filters in heart transplantation: early outcomes
in prospective, randomized clinical trial.

Dvorak L, Pirk J, Cerny S, Kovar J.

Department of Cardiovascular Surgery, Institute for Clinical and Experimental
Medicine, Prague, Czech Republic.

Objective: Leukocyte-mediated reperfusion injury to cardiac allograft in the
perioperative period is most likely associated with the early and late mortality
after heart transplantation (Htx). Our aim is to determine the efficacy and
safety of using leukocyte-depleting filters in a cardiopulmonary bypass (CPB)
and secondary blood cardioplegia (SBC) circuit in Htx. Methods: A prospective,
randomized trial was performed in 40 patients undergoing orthotopic Htx. These
patients were divided into two groups, to be treated with either
leukocyte-depleted (LD) reperfusion (n=20) in the LD group, or whole blood
reperfusion (n=20) in the Control group. The SBC was used in both groups.
Results: Intraoperatively, the LD group presented the reduced markers of
reperfusion injury. The course of the creatine kinase MB (CK-MB) releases was
significantly lower in the LD group (p<0.05). The LD hearts showed better
spontaneous rhythm resumption (60% vs 10%; p<0.001), and lower need for
isoprenaline (0.02+/-0.01mug/(kgmin) vs 0.03+/-0.02mug/(kgmin); p<0.05) and
epicardial pacing (25% vs 60%; p<0.05) for weaning off CPB. Postoperatively,
lower and shorter need for inotropic support (48+/-46, median=35h vs 131+/-68,
median=109h; p<0.001), shorter temporary epicardial pacing (6+/-14, median=0h vs
25+/-52, median=1h; p<0.01), and lower 24-h chest drainage (551+/-274,
median=500ml vs 973+/-836, median=665ml; p<0.05) in the LD group contributed to
the shorter mechanical ventilation time (8+/-3, median=7.5h vs 14+/-12,
median=8.5h; p<0.05) and the shorter stay at an intensive care unit (ICU)
(70+/-24h vs 116+/-73h; p<0.05). The 30-day mortality was zero in both groups.
Conclusions: The use of leukocyte depleting filters in heart transplantation is
an effective, easy and safe method of myocardial protection, reducing
significant myocardial reperfusion injury and improving posttransplant graft
functional recovery.

Med Biol Eng Comput. 2006 Aug;44(8):729-37. Epub 2006 Jul 21. 

Filtering techniques for the removal of ventilator artefact in oesophageal pulse
oximetry.

Shafqat K, Jones DP, Langford RM, Kyriacou PA.

School of Engineering and Mathematical Sciences, City University, London, ECIV
0HB, UK, P.Kyriacou@city.ac.uk.

The oesophagus has been shown to be a reliable site for monitoring blood oxygen
saturation (SpO(2)). However, the photoplethysmographic (PPG) signals from the
lower oesophagus are frequently contaminated by a ventilator artefact making the
estimation of SpO(2) impossible. A 776th order finite impulse response (FIR)
filter and a 695th order interpolated finite impulse response (IFIR) filter were
implemented to suppress the artefact. Both filters attenuated the ventilator
artefact satisfactorily without distorting the morphology of the PPG when
processing recorded data from ten cardiopulmonary bypass patients. The IFIR
filter was the better since it conformed more closely to the desired filter
specifications and allowed real-time processing. The average improvements in
signal-to-noise ratio (SNR) achieved by the FIR and IFIR filters for the
fundamental component of the red PPG signals with respect to the fundamental
component of the artefact were 57.96 and 60.60 dB, respectively. The
corresponding average improvements achieved by the FIR and IFIR filters for the
infrared PPG signals were 54.83 and 60.96 dB, respectively. Both filters were
also compared with their equivalent tenth order Butterworth filters. The average
SNR improvements for the FIR and IFIR filters were significantly higher than
those for the Butterworth filters.

Crit Care Med. 2006 Aug 22; [Epub ahead of print] 

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.

From the Critical Care Group-Portex Unit, Institute of Child Health, University
College London (MLA, MJP, AG, IJ); Infectious Diseases & Microbiology Unit,
Institute of Child Health, University College London (MLA, NJK); and
Cardiothoracic Surgery, Great Ormond Street Hospital for Children NHS Trust,
London, UK (JAH, ME).

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.

Anaesthesist. 2006 Aug 17; [Epub ahead of print] 

[The new 2005 resuscitation guidelines of the European Resuscitation Council :
Comments and supplements.]

[Article in German]

Wenzel V, Russo S, Arntz HR, Bahr J, Baubin MA, Bottiger BW, Dirks B, Dorges V,
Eich C, Fischer M, Wolcke B, Schwab S, Voelckel WG, Gervais HW.

Univ.-Klinik fur Anaesthesie und Allgemeine Intensivmedizin, Medizinische
Universitat, Anichstrasse 35, 6020, Innsbruck, Osterreich,
volker.wenzel@uibk.ac.at.

The new CPR guidelines are based on a scientific consensus which was reached by
281 international experts. Chest compressions (100/min, 4-5 cm deep) should be
performed in a ratio of 30:2 with ventilation (tidal volume 500 ml, Ti 1 s,
F(I)O(2) if possible 1.0). After a single defibrillation attempt (initially
biphasic 150-200 J, monophasic 360 J, subsequently with the respective highest
energy), chest compressions are initiated again immediately for 2 min.
Endotracheal intubation is the gold standard; other airway devices may be
employed as well depending on individual skills. Drug administration routes for
adults and children: first choice IV, second choice intraosseous, third choice
endobronchial [epinephrine dose 2-3x (adults) or 10x (pediatric patients) higher
than IV]. Vasopressors: 1 mg epinephrine every 3-5 min IV. After the third
unsuccessful defibrillation attempt amiodarone IV (300 mg); repetition (150 mg)
possible. Sodium bicarbonate (1 ml/kg 8.4%) only in excessive hyperkalemia,
metabolic acidosis, or intoxication with tricyclic antidepressants. Consider
atropine (3 mg) and aminophylline (5 mg/kg). Thrombolysis during spontaneous
circulation only in myocardial infarction or massive pulmonary embolism; during
CPR only during massive pulmonary embolism. Cardiopulmonary bypass only after
cardiac surgery, hypothermia or intoxication. Pediatrics: best improvement in
outcome by preventing cardiocirculatory collapse. Alternate chest thumps and
chest compression (infants), or abdominal compressions (>1-year-old) in foreign
body airway obstruction. Initially five breaths, followed by chest compressions
(100/min; ~1/3 of chest diameter): ventilation ratio 15:2. Treatment of
potentially reversible causes (4 "Hs", "HITS": hypoxia, hypovolemia, hypo- and
hyperkaliemia, hypothermia, cardiac tamponade, intoxication, thrombo-embolism,
tension pneumothorax). Epinephrine 10 microg/kg IV or intraosseously, or 100
microg (endobronchially) every 3-5 min. Defibrillation (4 J/kg; monophasic oder
biphasic) followed by 2 min CPR, then ECG and pulse check. Newborns: inflate the
lungs with bag-valve mask ventilation. If heart rate <60/min chest
compressions:ventilation ratio 3:1 (120 chest compressions/min).
Postresuscitation phase: initiate mild hypothermia [32-34 degrees C for 12-24 h;
slow rewarming (<0.5 degrees C/h)]. Prediction of CPR outcome is not possible at
the scene; determining neurological outcome within 72 h after cardiac arrest
with evoked potentials, biochemical tests and physical examination. Even during
low suspicion for an acute coronary syndrome, record a prehospital 12-lead ECG.
In parallel to pain therapy, aspirin (160-325 mg PO or IV) and in addition
clopidogrel (300 mg PO). As antithrombin, heparin (60 IU/kg, max. 4000 IU) or
enoxaparine. In ST-segment elevation myocardial infarction, define reperfusion
strategy depending on duration of symptoms until PCI (prevent delay >90 min
until PCI). Stroke is an emergency and needs to be treated in a stroke unit. A
CT scan is the most important evaluation, MRT may replace a CT scan. After
hemorrhage exclusion, thrombolysis within 3 h of symptom onset (0.9 mg/kg rt-PA
IV; max 90 mg within 60 min, 10% of the entire dosage as initial bolus, no
aspirin, no heparin within the first 24 h). In severe hemorrhagic shock,
definite control of bleeding is the most important goal. For successful CPR of
trauma patients, a minimal intravascular volume status and management of hypoxia
are essential. Aggressive fluid resuscitation, hyperventilation, and excessive
ventilation pressure may impair outcome in severe hemorrhagic shock. Despite bad
prognosis, CPR in trauma patients may be successful in select cases. Any CPR
training is better than nothing; simplification of contents and processes
remains important.

J Clin Endocrinol Metab. 2006 Aug 8; [Epub ahead of print] 

Differential effects of a perioperative hyperinsulinemic normoglycemic clamp on
the neurohumoral stress response during CABG.

van Wezel HB, Zuurbier CJ, de Jonge E, van Dam EW, van Dijk J, Endert E, de Mol
BA, Fliers E.

Departments of Anesthesiology, Endocrinology and Metabolism, Intensive Care
Medicine, Cardiac Surgery and Laboratory of Endocrinology and Radiochemistry.
Academic Medical Center, University of Amsterdam, Meibergdreff 9, 1105 AZ
Amsterdam, The Netherlands; Dept. of Internal Medicine, Free University Medical
Center, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands.

Background. Hyperglycemia in patients undergoing coronary artery bypass grafting
(CABG) is associated with adverse outcome. Although insulin infusion strategies
are increasingly used to improve outcome, a pathophysiologic rationale is
currently lacking. The present study was designed to quantify the effects of a
perioperative hyperinsulinemic normoglycemic clamp on the neurohumoral stress
response during CABG. Methods. 44 non-diabetic patients, scheduled for elective
CABG, were randomized to either a control group (n = 22) receiving standard care
or to a clamp group (n = 22) receiving additionally a perioperative
hyperinsulinemic (regular insulin at a fixed rate of 0.1 IU kg(-1) h(-1))
normoglycemic (plasma glucose between 3.0 and 6.0 mmol liter(-1)) clamp during
26 h. We measured the endocrine response of the hypothalamus-pituitary-adrenal
(HPA) axis, the sympathoadrenal axis and glucagon, as well as plasma glucose and
insulin at regular intervals from the induction of anesthesia at baseline
through the end of the second postoperative day (POD). Results. There were no
differences in clinical outcome between the groups. In the control group
hyperglycemia developed at the end of surgery and remained present until the
final measurement point on POD2 while plasma insulin levels remained unchanged
until the morning of POD1. In the intervention group normoglycemia was well
maintained during the clamp, while insulin levels ranged between 600 and 800
pmol.liter(-1). In both groups, plasma ACTH and cortisol increased from 6 h
after discontinuation of cardiopulmonary bypass onwards. However, during the
clamp period, a marked reduction in the HPA axis response was found in the
intervention group, as reflected by a 47% smaller increase in area under the
curve (AUC) in plasma ACTH (P = 0.035) and a 27% smaller increase in plasma
cortisol (P = 0.002) compared with the control group. Compared with baseline,
epinephrine and norepinephrine increased by the end of the clamp interval until
POD2 in both groups. Surprisingly, the AUC of epinephrine levels was 47% higher
(P = 0.026) after the clamp interval in the intervention group as compared with
the control group. Conclusion. A hyperinsulinemic normoglycemic clamp during
CABG delays and attenuates the HPA axis response during the first 18 h of the
myocardial reperfusion period, while after the clamp, plasma epinephrine is
higher. The impact of delaying cortisol responses on clinical outcome of CABG
remains to be elucidated.

Masui. 2006 Aug;55(8):977-82. 

[Prophylactic effects of neutrophil elastase inhibitor for patients undergoing
surgery for thoracic aortic aneurysm: a retrospective study]

[Article in Japanese]

Minami T, Kito K.

Department of Anesthesia, Shiga Medical Center for Adults, Moriyama 524-0014.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) can occur after
cardiac surgery under cardiopulmonary bypass (CPB), especially thoracic aortic
surgery. Several reports have suggested that the earlier neutrophil elastase
inhibitor (NEI) is used, the more dramatically the acute lung injury (ALI)
following SIRS can be improved. We therefore examined whether prophylactic
administration of NEI is effective in treating ALI following SIRS. METHODS: In a
retrospective study, 24 patients were divided into a control group and a NEI
group, for whom infusion of NEI 0.2 mg x kg(-1) x hr(-1) was started prior to
initiation of CPB. We compared PaO2/FIO2 (P/F) ratio, intubation time, ICU stay,
and numbers of intubated patients and patients admitted to the ICU between the
two groups. We also examined laboratory findings for the two groups related to
systemic inflammation and organ function. RESULTS: In the NEI group, P/F ratio
tended not to be exacerbated postoperatively, which might have been responsible
in part for the finding that intubation time and ICU stay were significantly
shorter and ratios of intubated patients and those staying in the ICU were
significantly lower in the NEI group. Laboratory findings in the two groups
fluctuated similarly. CONCLUSIONS: Prophylactic administration of NEI appears to
be useful for achieving early extubation and discharge from the ICU of patients
undergoing thoracic aortic surgery.

Surgery. 2006 Aug;140(2):221-6. 

C-Reactive protein and inflammatory response associated to neurocognitive
decline following cardiac surgery.

Ramlawi B, Rudolph JL, Mieno S, Feng J, Boodhwani M, Khabbaz K, Levkoff SE,
Marcantonio ER, Bianchi C, Sellke FW.

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

BACKGROUND: It has been recognized that neurocognitive decline (NCD) often
occurs as a complication in cardiac surgery. The early inflammatory response and
C-reactive protein (CRP) was examined in relation to NCD and to a marker of
axonal central nervous system (CNS) injury after cardiopulmonary bypass.
METHODS: A cohort of patients undergoing coronary artery bypass grafting and/or
valve procedures using cardiopulmonary bypass were administered a neurocognitive
battery preoperatively and postoperatively at 6 hours and day 4. CRP,
interleukin 1 beta, and interleukin 10 were quantified from serum. Increase of
serum tau protein after surgery was used as a marker of axonal CNS damage.
RESULTS: The rate of NCD was found to be 40.5% in this group. Surprisingly,
known predictors of NCD did not differ significantly between patients
with/without NCD. Patients with NCD had an early increase of CRP of a
significantly higher magnitude than those without NCD (38.01 +/- 11.4 vs 16.49
+/- 3.5 mg/L, P = .042), interleukin 1ss (2.35 +/- 0.3 vs 1.20 +/- 0.2 pg/mL, P
= .002), and interleukin 10 (29.77 +/- 4.7 vs 12.94 +/- 2.2 pg/mL, P < .001).
Increase in serum Tau protein was significantly correlated to NCD (r = 0.50, P =
.02). CONCLUSION: Perioperative increases in CRP and inflammatory cytokines are
associated with NCD in patients after cardiopulmonary bypass. Thus, it appears
that inflammation plays a key role in NCD pathophysiology, likely via axonal CNS
injury, and could become a target for prevention.

Thorac Cardiovasc Surg. 2006 Aug;54(5):317-23. 

The Na+/H+ exchange inhibitor cariporide is washed out of the myocardium by
crystalloid cardioplegia.

Bechtel JF, Eichler W, Toerber K, Weidtmann B, Hernandez M, Klotz KF, Sievers
HH, Bartels C.

Department of Cardiac Surgery, University of Lubeck, Lubeck, Germany.
bechtel@medinf.mu-luebeck.de

BACKGROUND: Inhibition of the Na (+)/H (+) exchanger (NHE) is cardioprotective,
but dosage and timing of NHE-inhibitors are critical for their efficacy. We
studied the effect of a new dosing regime of the NHE-inhibitor cariporide on
myocardial function and damage after cardioplegic arrest (CPA) and determined
its myocardial and serum concentrations. METHODS: 3 pigs received a bolus of 180
mg cariporide intravenously (i. v.) and were sacrified shortly thereafter to
allow measurement of the myocardial concentrations of cariporide. Subsequently,
10 pigs were randomized to receive either i. v. cariporide (bolus followed by an
infusion of 40 mg/h) or placebo. Cardiopulmonary bypass was initiated, and the
heart was arrested for 60 minutes by infusion of St. Thomas Hospital solution.
Left ventricular (LV) function was studied using microsonometry. Myocardial
damage was assessed by troponin T. Serum concentrations of cariporide were
measured throughout the study, and myocardial concentrations were measured
before the end of CPA and 180 minutes thereafter. RESULTS: Cariporide was
present in all myocardial specimens (median: 1.4 ng/mg) studied priorly. In the
main study, LV function or myocardial damage did not differ significantly
between the groups at any time point. Stable serum cariporide concentrations
were achieved (3.4 +/- 0.5 microg/ml). Cariporide was detectable in only one of
the myocardial biopsies obtained before the end of CPA, but 180 minutes
thereafter, the myocardial cariporide concentration was 2.5 +/- 0.3 ng/mg.
CONCLUSION: We observed no effect of i. v. cariporide on LV function or
myocardial damage after cardioplegic arrest. Our data suggest that cariporide is
washed out of the myocardium by repeated application of crystalloid
cardioplegia. Thus, the mode of delivery also appears to be critical for
cardioprotection with NHE-inhibitors.

Pediatr Nephrol. 2006 Oct;21(10):1446-51. Epub 2006 Aug 11. 

Renal function and cardiopulmonary bypass in pediatric cardiac surgical
patients.

Lema G, Vogel A, Canessa R, Jalil R, Carvajal C, Becker P, Jaque MP, Fajardo C,
Urzua J.

Department of Anaesthesiology, Pontificia Universidad Catolica de Chile, P.O.
Box 114-D, Santiago, Chile, glema@med.puc.cl.

We studied prospectively the perioperative changes of renal function in nine
children undergoing cardiac surgery with cardiopulmonary bypass (CPB).
Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were
measured with inulin and (131)I-hippuran clearances before CPB, during hypo and
normothermic CPB, following sternal closure and 1 h postoperatively. Urinary
alpha glutathione S-transferase (alpha GS-T) was measured pre- and
postoperatively as a marker for tubular cellular damage. Plasma and urine
creatinine and electrolytes were measured. Free water, osmolal and creatinine
clearances, as well as fractional excretion of sodium (FeNa) and potassium
transtubular gradient (TTKG) were calculated. GFR was normal before and after
surgery. ERPF was low before and after surgery; it increased significantly
immediately after CPB. Filtration fraction (FF) was abnormally elevated before
and after surgery; however, a significant decrease during normothermic CPB and
sternal closure was found. Alpha GS-T presented a moderate, but nonsignificant
increase postoperatively. FeNa also increased in this period, but not
significantly. Creatinine, osmolal, free water clearances, as well as TTKG, were
normal in all patients pre- and postoperatively. We conclude that there is no
evidence of clinically significant deterioration of renal function in children
undergoing repair of cardiac lesions under CPB. Minor increases of alpha GS-T in
urine postoperatively did not confirm cellular tubular damage. There was no
tubular dysfunction at that time.

Eur J Cardiothorac Surg. 2006 Aug 7; [Epub ahead of print] 

Evaluation of myocardial metabolism with microdialysis during bypass surgery
with cold blood- or Calafiore cardioplegia.

Poling J, Rees W, Mantovani V, Klaus S, Bahlmann L, Ziaukas V, Hubner N,
Warnecke H.

Department of Cardiac Surgery, Schuchtermann-Klinik Bad Rothenfelde, Ulmenallee
11, 49214 Bad Rothenfelde, Germany; Institut fur klinische und molekulare
Herz-Kreislaufforschung der Universitat Witten-Herdecke, Dortmund, Germany.

Background: For the first time, microdialysis was used to investigate in vivo
and online the myocardial metabolism during and after cardiac surgery in
patients treated with two different methods of myocardial protection. Methods:
Thirty patients underwent standard CABG with one of two different methods of
myocardial protection. The patients were randomised to receive either cold blood
(COLD group) or warm modified Calafiore cardioplegia (WARM group). Microdialysis
probes were implanted into the myocardium of left ventricular apical region of
the heart. Cardioplegia was given antegrade only. Microdialysis measurements
were performed at time intervals before, during and 24h after cardiopulmonary
bypass and analysed for glucose, lactate, pyruvate and glycerol. Results:
Myocardial lactate concentrations were significantly higher in the WARM group
compared with that of the COLD group, while serum lactate was comparable.
Glycerol was significantly higher at the end of the clamping time in the WARM
group. At the same time the glucose-lactate ratio as a marker of nutritional
disorder had significantly lower levels in the WARM group. The cumulative CK-MB
release over 24h was significantly higher in those hearts protected with warm
blood. Conclusions: The oxidative stress measured was significantly higher in
patients undergoing CABG using modified Calafiore cardioplegia, whereas the cold
cardioplegia minimised the effects of aortic clamping. The results indicate that
cold cardioplegia offers superior protection of the heart, in terms of more
rapid normalisation of myocardial metabolism. In elective myocardial
revascularisation, intermittent antegrade warm blood cardioplegia is a
comparable safe method of myocardial protection. However, in patients referring
to a long clamping time, advantages of cold cardioplegia for myocardial
revascularisation may be magnified.