Eur J Cardiothorac Surg. 2005 Dec 28; [Epub ahead of print] 

Aprotinin decreases reperfusion injury and allograft dysfunction in clinical
lung transplantation.

Bittner HB, Richter M, Kuntze T, Rahmel A, Dahlberg P, Hertz M, Mohr FW.

Division of Thoracic and Cardiovascular Surgery, Heart Center Leipzig of the
University of Leipzig, Struempell Str. 39, 04289 Leipzig, Germany.

Objective: Primary graft dysfunction caused by ischemia-reperfusion injury is
one of the most frequent causes of early morbidity and death after lung
transplantation. We hypothesized that the perioperative management with
aprotinin decreases the incidence of allograft reperfusion injury and
dysfunction after clinical lung transplantation. Methods: Lung transplant
databases of two transplant centers were used to investigate the incidence of
severe post-transplant reperfusion injury (PTRI). We examined data of 142
patients who underwent either single lung (81) or bilateral sequential lung (61)
transplantation for COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and
miscellaneous lung disorders between 1997 and 2000. Thirty patients were
excluded due to heart-lung transplantation or lung transplantation for
Eisenmenger's disease, re-transplantation, rejection, or deviation from the
standardized triple immunosuppression protocol. The data of remaining 112
patients (control group, 64% single lung, 36% sequential bilateral lung
transplants) were compared to the prospectively collected data of 59 lung
transplant patients over the last 5 years. All of these 59 patients were managed
perioperatively with aprotinin infusion. In addition, Euro-Collins-aprotinin
procurement solution (Apt-EC group) was used for 50 donor lungs (58% single
lung, 42% sequential bilateral lung transplants). Aprotinin in combination with
low-potassium dextran (LPD) flush solution (Apt-LPD group) was used for the
procurement of 34 lungs (59% single lung, 41% sequential bilateral lung
transplants). The International Society of Heart and Lung Transplantation
(ISHLT) grade III injury score was used for the diagnosis of severe PTRI, which
is based on a PaO(2)-FIO(2) ratio of less than 200mmHg. Results: Severe
reperfusion injury grade III was observed in 18% of the control group. ECMO
support was required in 25% of these patients. The associated mortality rate was
40%. Correlating factors for PTRI were donor age greater than 35 years (45%,
p=0.01, mean age 38+/-8) and recipient pulmonary artery systolic pressure
greater than 60mmHg (48%, p<0.05). Lung graft ischemic times (231+/-14min) and
intraoperative techniques (cardiopulmonary bypass in 12%) were not associated
with negative outcomes. Despite longer ischemic times (258+/-36min and
317+/-85min, respectively) and older donors (42+/-12 years and 46+/-12 years,
respectively) in the aprotinin patient groups (Apt-EC and Apt-LPD group), the
incidence of PTRI was markedly lower (6% and 9%, respectively). There was no
mortality in the Apt-EC group and one patient died in the Apt-LPD group due to
PTRI-induced graft failure. Conclusions: Severe PTRI increased short-term
morbidity and mortality. The incidence of reperfusion injury was not dependent
upon the duration of donor organ ischemia. The use of aprotinin in the
perioperative patient management in lung transplantation had strong beneficial
effects on the patient outcomes and decreased the incidence of post-transplant
ischemia-reperfusion injury significantly.

Eur J Cardiothorac Surg. 2005 Dec 20; [Epub ahead of print] 

Brain oxygenation and metabolism during selective cerebral perfusion in
neonates.

Schears G, Zaitseva T, Schultz S, Greeley W, Antoni D, Wilson DF, Pastuszko A.

Department of Anesthesiology and Critical Care, Mayo Clinic, Rochester, MN, USA.

Objective: To investigate the possible neuroprotective effects of selective
cerebral perfusion (SCP) during deep hypothermic circulatory arrest on brain
oxygenation and metabolism in newborn piglets. Methods: Newborn piglets 2-4 days
of age, anesthetized and mechanically ventilated, were used for the study. The
animals were placed on cardiopulmonary bypass, cooled to 18 degrees C and put on
SCP (20ml/(kgmin)) for 90min. After rewarming, the animals were monitored
through 2h of recovery. Oxygen pressure in the microvasculature of the cortex
was measured by oxygen-dependent quenching of phosphorescence. The extracellular
level of dopamine in striatum was measured by microdialysis and hydroxyl
radicals by ortho-tyrosine levels. Levels of phosphorylated cAMP response
element binding protein (pCREB) in striatal tissue were measured by Western
blots using antibodies specific for phosphorylated CREB. The results are
presented as mean+/-SD (p<0.05 was significant). Results: Pre-bypass cortical
oxygen pressure was 48.9+/-11.3mmHg and during the first 5min of SCP, the peak
of the histogram, corrected to 18 degrees C, decreased to 11.2+/-3.8mmHg
(p<0.001) and stayed near that value to the end of bypass. The mean value for
the peak of the histograms measured at the end of SCP was 8+/-3mmHg (p<0.001).
SCP completely prevented the deep hypothermic circulatory arrest-dependent
increase in extracellular dopamine and hydroxyl radicals. After SCP, there was a
statistically significant increase in pCREB immunoreactivity (534+/-60%)
compared to the sham-operated group (100+/-63%, p<0.005). Measurements of total
CREB showed that SCP did induce a statistically significant increase in CREB as
compared to sham-operated animals (168+/-31%, p<0.05). Conclusion: SCP, as
compared to DHCA, improved cortical oxygenation and prevented increases in the
extracellular dopamine and hydroxyl radicals. The increase in pCREB in the
striatum following SCP may contribute to improved cellular recovery after this
procedure.

Heart Lung Circ. 2005 Dec;14(4):255-61. Epub 2005 Jul 20. 

Minimally Invasive Surgery for Cardiac Myxomas using an Upper Hemi-Sternotomy
and Biatrial Septal Approach.

Nordstrand IA, Tam RK.

Department of Cardiac Surgery, The Prince Charles Hospital, Rode Road,
CHERMSIDE, Qld 4032, Australia.

BACKGROUND: Minimally invasive surgery is pervading all fields of surgery with
the principal benefits being: reduced pain, smaller incision, faster recovery,
shorter hospital stay and reduced cost. Cardiac surgery is no different. Cardiac
myxoma morbidity and mortality depends on early diagnosis, adequate exposure,
complete resection, minimal manipulation and unifocal presence. We reviewed our
cases of cardiac myxoma excised via an upper hemi-sternotomy with a biatrial
septal cardiac approach, to demonstrate this technique as a valid alternative to
a full-length median sternotomy. METHODS: From April 1997 to March 1999, one
surgeon excised two cardiac myxomas via this minimal technique. Upper
hemi-sternotomy was midline without transverse sternal transection. Standard
aortobicaval cardiopulmonary bypass and myocardial protection were established
with complete tumour excision via a biatrial septal approach commenced in the
left atrial dome and extended to the right atrial appendage. RESULTS: Inpatient
care was prolonged with cardiorespiratory morbidity a consequence of
preoperative co-morbidities. Neither patient required return to theatre and
hospital mortality was nil. Patients demonstrated reduced sternal wound pain,
reduced length of incision, excellent healing and improvement in New York Heart
Association functional class with no evidence of recurrence. CONCLUSIONS: Most
proposed benefits of minimally invasive surgery were demonstrated in cardiac
myxoma application without significant compromise to patient care and recovery
using upper hemi-sternotomy and biatrial septal approach. Cardiac myxoma
excision via upper hemi-sternotomy and biatrial septal approach can be achieved
without compromise to patient care.

Br J Anaesth. 2005 Dec 9; [Epub ahead of print] 

Changes in the effect of propofol in response to altered plasma protein binding
during normothermic cardiopulmonary bypass.

Takizawa E, Hiraoka H, Takizawa D, Goto F.

Department of Anaesthesiology, Saitama Cardiovascular and Pulmonary Centre, 1696
Itai Konan-machi Osato-gun, Saitama 360-0105, Japan.

BACKGROUND: During normothermic cardiopulmonary bypass (CPB), the effect on
propofol pharmacokinetics of changes in its binding to plasma proteins is
consistent with the predictions of the well-stirred model of hepatic elimination
for nonrestrictively cleared drug. However, whether changes in binding lead to
clinically significant changes in the drug effect remains unclear. The purpose
of this study was to assess changes in the drug effect of propofol in response
to altered plasma binding using quantitative EEG measurements. METHODS: Thirty
patients undergoing cardiac surgery were assigned randomly to receive propofol
infusions at 4 (Group P-4) or 6 (Group P-6) mg kg(-1) h(-1) during surgery. The
concentration of propofol in blood samples, collected from the radial artery at
predetermined intervals, was determined by HPLC. The unbound fraction of drug in
plasma was estimated using equilibrium dialysis. Bispectral index (BIS) and
burst suppression ratio (BSR) were measured at the time blood samples were
collected. RESULTS: The total concentration of propofol in blood was unchanged
during CPB relative to the pre-CPB value in both groups. However, the fraction
of unbound propofol in blood increased by 2-fold during CPB. While BIS values
were unchanged during CPB in Group P-4, there was a slight, but significant,
decrease in Group P-6. In both groups, BSR significantly increased during CPB.
BIS values showed a weak correlation with the concentration of unbound propofol
(r(2)=0.19, P<0.001). BSR showed a moderate correlation with the concentration
of unbound propofol (r(2)=0.56, P<0.001). CONCLUSIONS: The anaesthetic effect of
propofol significantly increased during CPB without any alteration in the total
drug concentration. The enhanced efficacy may be caused by a reduction in plasma
binding of the drug.

Arch Dis Child. 2005 Dec 2; [Epub ahead of print] 

Procalcitonin does discriminate between sepsis and systemic inflammatory
response syndrome.

Arkader R, Troster EJ, Lopes MR, Junior RR, Carcillo J, Leoni C, Okay TS.

University of Sao Paulo, Brazil.

OBJECTIVE: to evaluate whether procalcitonin (PCT) and C reactive protein (CRP)
are able to discriminate between sepsis and systemic inflammatory response
syndrome (SIRS) in critically ill pediatric patients. Design and SETTING:
Prospective, observational study in a pediatric intensive care unit. The study
was divided in two parts: I) kinetics of PCT and CRP in patients undergoing open
heart surgery with cardiopulmonary bypass (CPB), representing the SIRS model
(group I) [1]. II) Kinetics of PCT and CRP in patients with confirmed bacterial
sepsis (group II). Patients: Fourteen patients with confirmed bacterial sepsis
(group II). Measurements and main RESULTS: In group I PCT and CRP concentrations
were determined in five different times: before CPB; immediately after CPB; 24h;
48h and 72h after the procedure. Although all 14 patients of group I had
negative cultures, the sampling time "before CPB" was obtained in order to
ensure that baseline laboratory markers were within reference values, but these
results were not used in statistical analyses between groups. PCT median
concentration was 0.24 ng/mL thus confirming that patients were not infected
(reference value < 2.0 ng/mL). There was an increment of PCT concentrations
which peaked immediately after CPB (median 0.58 ng/mL), then decreased to 0.47
ng/mL at 24 h; 0.33 ng/mL at 48h and 0.22 ng/mL at 72 h. CRP median
concentrations remained high on POD1 (36.6 mg/L) and POD2 (13.0 mg/L). In septic
children (group II), PCT and CRP were measured four times: at admission; 24 h,
48 h and 72 h after hospitalization. PCT concentrations were high at admission
(median 9.15 ng/mL) and unlikely CRP, decreased afterwards in 11 of 14 patients
who evolved favorably (median 0.31 ng/mL). Conversely, CRP levels were high in
only 11 out of 14 patients at admission. CRP persisted high in 13 of 14 patients
at 24 h; in 12 of 14 at 48 h; and finally in 10 of 14 patients at 72 h. Median
values were: 95.0 mg/L; 50.9 mg/L 86.0 mg/L and 20.3 mg/L, respectively. The
area under the receiver operating characteristic curve (ROC) was 0.99 for PCT
and 0.54 for CRP. Cut off concentrations to differentiate SIRS from sepsis were
> 2 ng/mL for PCT and > 79 mg/L for CRP. CONCLUSION: PCT is able to
differentiate between SIRS and sepsis. CRP lacked sensitivity as it did not
detect 3 septic patients at admission. Moreover, CRP did not modulate according
to patients outcome as did PCT. The latter returned to reference values in 11 of
14 patients who evolved favorably, persisting high in the 3 patients who died.

Thorac Cardiovasc Surg. 2005 Dec;53(6):341-5. 

Aspirin and clopidogrel taken until 2 days prior to coronary artery bypass graft
surgery is associated with increased postoperative drainage loss.

von Heymann C, Redlich U, Moritz M, Sander M, Vargas Hein O, Grubitzsch H,
Konertz WF, Spies C.

Department of Anesthesiology and Intensive Care Medicine, Charite - University
Hospital Berlin, Berlin, Germany. christian.von_heymann@charite.de

OBJECTIVE: Platelet aggregation inhibitors, such as aspirin and clopidogrel, are
associated with increased bleeding in patients undergoing cardiac surgery with
cardiopulmonary bypass. We investigated the impact of time between the last
intake of aspirin and clopidogrel before CABG surgery and drainage loss,
transfusion requirements and rate of reoperation. PATIENTS AND METHODS: The
records of patients who had coronary artery bypass graft surgery (CABG) were
reviewed for intake of aspirin and clopidogrel within 7 days prior to surgery.
Drainage loss, transfusion requirements and rate of reoperation for bleeding
within 5 days after the operation, were recorded. RESULTS: Out of 261 analysed
patients, 225 patients (86.2 %) had no anti-platelet medication and 36 patients
(13.8 %) were on aspirin and clopidogrel. Aspirin and clopidogrel, taken all
until 2 days prior to operation, were associated with a significantly higher
postoperative blood loss (1840 mL [1230 - 3710] vs. 280 mL [185 - 765], p =
0.005 for one day and 850 mL [345 - 1725] vs. 277 mL [165 - 778], p = 0.026, for
2 days prior to surgery). The trend showed that patients in the study group
received more platelet concentrates (PC: 5.3 % vs. 13.9 %, p = 0.067). The rate
of reoperation for bleeding was not different ( p = 0.25). CONCLUSION: Aspirin
and clopidogrel up to 2 days prior to CABG were associated with a significantly
higher postoperative drainage loss.

J Thorac Cardiovasc Surg. 2005 Dec;130(6):1537-41. 

Simultaneous management of congenital tracheal stenosis and cardiac anomalies in
infants.

Loukanov T, Sebening C, Springer W, Ulmer H, Hagl S.

Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
tsloukanov@abv.bg

OBJECTIVE: The present article aims to describe our experience with patients who
underwent simultaneous repair of congenital tracheal stenosis and cardiac
anomalies. METHODS: Between January 2000 and December 2003, 9 infants underwent
simultaneous surgical repair of a congenital tracheal stenosis and congenital
heart disease. The intraoperative findings revealed localized tracheal stenosis
in 3 patients. The funnel-type tracheal stenosis was present in 6 patients.
Associated cardiac anomalies included ostium secundum atrial septal defect in 5
patients and ventricular septal defect in 2 patients, pulmonary artery sling in
4 patients, patent ductus arteriosus in 6 patients, atrioventricular septal
defect in 1 patient, aortic arch hypoplasia in 1 patient, coarctation of the
aorta in 1 patient, and partial anomalous pulmonary venous connection in 2
patients, one of them with "scimitar syndrome." Tracheal origin of the right
upper lobe was diagnosed in 2 of the patients. A right aberrant subclavian
artery (lusoria) was found in one patient. All patients were operated on through
a median sternotomy and with cardiopulmonary bypass. Tracheal resection with
direct end-to-end anastomosis was performed in all cases. RESULTS: There was no
operative mortality. One patient died 6 weeks postoperatively. Eight patients
were extubated between the 14th and 30th postoperative days under bronchoscopic
monitoring. The extubation was performed after a stepwise respirator-weaning
program. Postoperative endoscopic examination showed adequate airway dimensions
and patency in every case. The midterm results after a mean follow-up of 37
months (range, 16-58 months) of the entire group demonstrate a stabile and
complication-free clinical outcome. CONCLUSIONS: We advocate our current
strategy for infants with congenital tracheal stenosis: resection with
end-to-end anastomosis and simultaneous repair of associated intracardiac
anomalies.

Acta Neuropathol (Berl). 2005 Dec;110(6):563-578. Epub 2005 Oct 22. 

Hypoxic-ischemic brain injury in infants with congenital heart disease dying
after cardiac surgery.

Kinney HC, Panigrahy A, Newburger JW, Jonas RA, Sleeper LA.

Department of Pathology, Children's Hospital and Harvard Medical School, Enders
1112, 300 Longwood Avenue, Boston, MA, 02115, USA.

Cardiac surgery for congenital heart disease is performed increasingly earlier
in infancy, including in the neonatal period. With increased survival of
infants, there is growing concern about the long-term neurological sequelae of
hypoxic-ischemic injury due to congenital heart disease itself prior to surgery,
corrective surgery with the use of low-flow cardiopulmonary bypass (CPB) and/or
deep hypothermic circulatory arrest (DHCA), and/or unstable hemodynamic factors
postoperatively. In analyzing the neuropathology of 38 infants dying after
cardiac surgery, we tested a set of questions related to the severity and
patterns of brain injury, CPB, DHCA, and age of the infants at the time of
surgery. In all infants dying after cardiac surgery, irrespective of the
modality, cerebral white matter damage [periventricular leukomalacia (PVL) or
diffuse white matter gliosis] was the most significant lesion in terms of
severity and incidence, followed by a spectrum of gray matter lesions. There was
no significant association between the duration of deep hypothermic circulatory
arrest and the degree of severity of overall brain injury, and the pattern of
brain injury was similar irrespective of the modality of cardiac surgery. There
was no significant association between the age at the time of surgery (neonatal
versus postneonatal) and the severity of overall brain injury. The patterns of
brain injury were not age-related in the limited time-frame analyzed, except
that infants who developed acute PVL after both closed and DHCA/CPB surgery
(14/38 infants, 34%) were significantly younger at death (median age 13.0 days)
compared to unaffected infants (median age at death 42.5 days) (P=0.031). This
observation suggests that neonatal (<30 postnatal days), but not postneonatal
(>30 postnatal days), brains are at risk for acute PVL, and likely reflects the
vulnerability of immature (pre-myelinating) white matter to hypoxia-ischemia.

Eur J Vasc Endovasc Surg. 2005 Dec;30(6):624-31. Epub 2005 Jul 14. 

Thoracoabdominal aortic aneurysm repair: interplay of spinal cord protecting
modalities.

Weigang E, Hartert M, von Samson P, Sircar R, Pitzer K, Genstorfer J, Zentner J,
Beyersdorf F.

Department of Cardiovascular Surgery, University Hospital, Freiburg, Germany.
weigang@ch11.ukl.uni-freiburg.de

BACKGROUND: The purpose of this study was to assess the complementary use of
different methods of measuring spinal cord perfusion during thoracoabdominal
aortic surgery. METHODS: The spinal cords of 28 patients undergoing surgery on
the thoracoabdominal aorta were monitored with transcranial electrical
stimulation (tcMEP) and somatosensory-evoked potentials (SSEP). Available
approaches of spinal cord-protection included: Moderate systemic hypothermia,
constant cerebrospinal fluid (CSF) drainage and pressure monitoring,
reimplantation of segmental arteries, cardiopulmonary bypass (CPB), and staged
clamping. RESULTS: Fourteen of 19 patients (75%) undergoing open surgical
treatment (Group I) exhibited loss of tcMEP after proximal aortic clamping. In
nine cases (47%), we observed recovery of tcMEP after intraoperative
interventions, while two patients subsequently developed paraplegia and three
died. Seventeen of 19 patients showed loss of SSEP, with recovery in 12 cases
(63%). During stent-graft implantation (Group II), one of nine patients (11%)
demonstrated tcMEP loss with intraoperative, intervention-related recovery. The
SSEP-recording course remained stable. CONCLUSIONS: tcMEP/SSEP monitoring has
proved to be an excellent means of detecting spinal cord ischaemia during
surgery on thoracoabdominal aortic aneurysms. The prognostic value of tcMEP
monitoring should be considered superior to that of SSEP measurements, because
of its direct and rapid response to spinal malperfusion. Through combined
neurophysiological monitoring, vital parameter balancing and intraoperative
interventions, spinal cord perfusion improves and recovery of tcMEP and SSEP is
achievable, reducing the prevalence of postoperative paraplegia.

Arch Dis Child. 2005 Dec;90(12):1288-92. Epub 2005 Sep 13. 

Hyperchloraemic metabolic acidosis following open cardiac surgery.

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

Division of Critical Care & Children's Heart Disease, School of Child &
Adolescent Health, University of Cape Town, South Africa. mark@rmh.uct.ac.za

AIMS: 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: A total of 97 children, median age 57 months (range 0.03-166),
median weight 14 kg (range 2.1-50), were studied. Median CPB time was 80 minutes
(range 17-232). Predicted mortality was 2% and there was a single non-survivor.
These children showed mild metabolic acidosis (median standard bicarbonate 20.1
mmol/l, 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,
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 eight children
(28%) without hyperchloraemia. Hypoalbuminaemia was associated with longer
duration of inotropic support and PICU stay. 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. It is suggested
that hyperchloraemic metabolic acidosis is a benign phenomenon that should not
prompt escalation of haemodynamic support. By contrast, hypoalbuminaemia, an
alkalinising force, was associated with prolonged requirement for intensive
care.