Transplantation.  2004 May 15;77(9):1389-94.  

Abo-incompatible heart transplantation in infants: the Freeman Hospital
experience.

Rao JN, Hasan A, Hamilton JR, Bolton D, Haynes S, Smith JH, Wallis J, Kesteven
P, Khattak K, O'Sullivan J, Dark JH.

Department of Cardiothoracic Surgery, Freeman Hospital, Newcastle upon Tyne,
United Kingdom. jagan.rao@nuth.northy.nhs.uk

BACKGROUND: Incompatibility of the major blood groups A, B, and O has been an
absolute contraindication for heart transplantation. However, because of
immunologic immaturity, infants may have relative protection from hyperacute
rejection and thus could undergo transplantation with ABO-mismatched organs.
METHODS: Since January 2000, the authors have adopted a policy of considering
infants for ABO-incompatible heart transplantation. Serum isohemagglutinin
titers were measured before, during, and after transplantation. Two infants (3
and 2 months old) and a 21-month-old child underwent ABO-incompatible heart
transplantation. During cardiopulmonary bypass, plasma exchange was performed.
No other antibody-removal procedures were performed. A routine immunosuppressive
regimen was used, and rejection was monitored by endomyocardial biopsies. An
additional two patients (31 and 18 months old) were worked up but were
unsuitable for ABO-incompatible transplantation because of high isohemagglutinin
titers. They were successfully bridged to transplantation and received heart
transplants from ABO-compatible donors. RESULTS: All three infants with
ABO-incompatible heart transplants are fit and well, 40 months, 30 months, and
12 months postoperatively. All three had serum antibodies to antigens of the
donor's blood group before transplantation. No hyperacute rejection occurred. No
morbidity attributable to the ABO incompatibility has been observed.
CONCLUSIONS: ABO-mismatched heart transplantation may be undertaken safely and
without any short-term adverse consequences in infants and young children in
whom isohemagglutinin production is not yet established.

J Card Surg.  2004 May-Jun;19(3):260-3.  

Brachial artery cannulation facilitates lower ministernotomy cardiac surgery.

Demirkilic U, Kuralay E, Cingoz F, Bingol H, Gunay C, Yildirim V, Kilic S, Tatar
H.

Department of Cardiovascular Surgery, Gulhane Military Medical Academy, Etlik,
Ankara, Turkey.

Abstract Background: Lower ministernotomy has become a more popular approach for
many heart operations. However, cannulation of the ascending aorta may cause
serious complications. Femoral and brachial arteries have been used for
alternative arterial cannulation sites. Materials and Methods: The lower
ministernotomy approach was used in 65 patients. Ascending aortic cannulation
was performed in group 1 (n = 38), femoral cannulation in group 2 (n = 12), and
brachial cannulation in group 3 (n = 15) patients. Brachial artery diameter was
measured preoperatively by Doppler ultrasound in the preoperative period.
Results: Average cross-clamp time for femoral and brachial artery cannulated
patients was significantly shorter than in patients in group 1 (31 +/- 9 and 35
+/- 6 minutes, respectively) (p = 0.034). Total cardiopulmonary bypass (CPB)
time was 56 +/- 11 minutes for group 1, 39 +/- 7 minutes for group 2, and 41 +/-
5.4 minutes for group 3 (p = 0.041). Operation time was 112 +/- 24, 88 +/- 12,
and 91 +/- 11 minutes for the groups 1, 2, and 3, respectively. There was also
statistically significant difference between group 1 and group 3 comparisons
with regard to CPB time (p = 0.041). Difficult exposure from many cannulas
impedes access and lengthens the operation in group I. Superficial wound
infection developed in seven patients in group 1, one patient in group 2, and
one patient in group 3. Conclusion: Cannulation of the brachial artery is
superior to the femoral due to possible infection and lymph leakage with the
latter and both are superior to central cannulation when lower ministernotomy is
performed. By avoiding the difficulties of central aortic cannula placement the
operative time is decreased and possible wound edge is protected as lesser
exposure is required. (J Card Surg 2004;19:260-263)

J Card Surg.  2004 May-Jun;19(3):221-5.  

N-acetylcysteine Reduces Lung Reperfusion Injury After Deep Hypothermia and
Total Circulatory Arrest.

Cakir O, Oruc A, Kaya S, Eren N, Yildiz F, Erdinc L.

Department of Cardiovascular Surgery, Dicle University, School of Medicine,
Diyarbakir, Turkey.

Abstract Objective: We hypothesized that the use of N-acetylcysteine would
ameliorate the lung reperfusion injury observed after deep hypothermia and total
circulatory arrest (DHTSA). Methods: Experiments were carried out on 12 adult
mongrel dogs of either sex weighing 25 to 30 kg. The animals were randomly
divided into two groups of six animals each. All animals were cooled to an
esophageal temperature of 15 degrees C during 30 minutes and underwent 60
minutes of DHTSA, followed by the reinstitution of cardiopulmonary bypass (CPB)
and rewarming. Before rewarming, while 100 mL physiologic saline solution was
added into the pump in group I, 50 mg/kg N-acetylcysteine(NAC) was given in
group II. Heart rate, mean arterial pressure, pulmonar arterial pressure, left
atrial pressure, central venous pressure, and cardiac output were recorded. To
measure lung tissue malondialdehyde (MDA), water content and polymorphonuclear
leukocytes (PMNs) count, lung tissue samples were taken before CPB and after
weaning CPB. In addition, alveolar-arterial oxygen difference (AaDO(2))()for
tissue oxygenation was calculated by obtaining arterial blood gas samples.
Dynamic lung compliance (DLC) was measured before CPB and after CPB. Results:
MDA levels before CPB of 44.2 +/- 3.9 nmol/g tissue rose to 76.6 +/- 5.6 nmol/g
tissue after weaning CPB in group I (p = 0.004). In group II also, the MDA
levels increased from 43.5 +/- 4.2 to 57.4 +/- 5.6 nmol MDA/g tissue after
weaning CPB (p = 0.006). The MDA increase in group II after CPB was found to be
significantly lower than in group I (p = 0.006). The wet-to-dry lung weight
ratio in the NAC group was 5.1 +/- 0.2, significantly less than in the control
group (5.9 +/- 0.3), (p = 0.004). AaDO(2) significantly increased in the group I
and II (p = 0.002 and p = 0.002, respectively); this elevation in group I was
significant than in group II (p = 0.044). In histopathological examination, it
was observed that neutrophil counts in the lung parenchyma rose significantly
after CPB in both groups (p < 0.001). The increase in group I was significantly
larger than group II (p < 0.001). Conclusions: Results represented in our study
indicate that addition of NAC into the pump after DHTSA can reduce lung
reperfusion injury. (J Card Surg 2004;19:221-225)

Expert Rev Cardiovasc Ther.  2004 May;2(3):339-57.  

Lepirudin: a bivalent direct thrombin inhibitor for anticoagulation therapy.

Greinacher A.

Ernst-Moritz-Arndt Universitat, Institut fur Immunologie und Transfusionmedizin,
Klinikum/Sauerbruchstrasse, 17489 Greifswald, Germany.
greinach@uni-greifswald.de

Lepirudin (Refludan((R)), Berlex Laboratories, USA and Canada; Pharmion((R)),
all other countries), a recombinant derivative of the naturally occurring leech
anticoagulant hirudin, was the first direct thrombin inhibitor to be approved by
the European Agency for the Evaluation of Medicinal Products and the US Food and
Drug Administration for the treatment of heparin-induced thrombocytopenia. Since
its introduction into Europe and the USA, it has been studied in over 7000
patients requiring anticoagulation in conditions including acute coronary
syndromes, percutaneous coronary intervention, cardiopulmonary bypass and
heparin-induced thrombocytopenia. Three European clinical trials, designated
Heparin-Associated Thrombocytopenia (HAT)-1, -2 and -3, demonstrated the
efficacy and safety of lepirudin in the prevention and treatment of thrombosis
in patients with antibody-confirmed heparin-induced thrombocytopenia. A
postmarketing, observational study, termed the Drug-Monitoring Program,
evaluated lepirudin in over 1000 patients with heparin-induced thrombocytopenia
in the setting of routine clinical practice. In the Drug-Monitoring Program,
adverse events were substantially reduced compared with clinical trials, while
clinical efficacy was maintained; suggesting that insight gained through
clinical experience was translated into improved safety. Here, pharmacotherapy
using lepirudin is reviewed, with particular reference to clinical studies in
heparin-induced thrombocytopenia, and some recommendations based on this
extensive clinical experience with lepirudin are provided. Although only
approved for the treatment of heparin-induced thrombocytopenia, the use of
lepirudin in acute coronary syndromes, percutaneous coronary intervention,
vascular surgery and coronary artery bypass grafting is also discussed. The
review concludes with a discussion of pharmacokinetic and clinical data
supporting the potential for subcutaneous administration of lepirudin.

JAMA.  2004 May 19;291(19):2319-27.  

Terminal complement blockade with pexelizumab during coronary artery bypass
graft surgery requiring cardiopulmonary bypass: a randomized trial.

Verrier ED, Shernan SK, Taylor KM, Van de Werf F, Newman MF, Chen JC, Carrier M,
Haverich A, Malloy KJ, Adams PX, Todaro TG, Mojcik CF, Rollins SA, Levy JH;
PRIMO-CABG Investigators.

Division of Cardiothoracic Surgery, University of Washington School of Medicine,
Seattle 98195-6310, USA. edver@u.wash.edu

CONTEXT: Inflammation and ischemia-reperfusion injury during coronary artery
bypass graft (CABG) surgery requiring cardiopulmonary bypass are associated with
postoperative myocardial infarction (MI) and mortality. OBJECTIVE: To determine
the efficacy and safety of pexelizumab, a C5 complement inhibitor, in reducing
perioperative MI and mortality in CABG surgery. DESIGN, SETTING, AND
PARTICIPANTS: A randomized, double-blind, placebo-controlled trial, including
3099 patients (> or = 18 years) undergoing CABG surgery with or without valve
surgery at 205 hospitals in North America and Western Europe from January 2002
to February 2003. INTERVENTIONS: Patients were randomly assigned to receive
intravenous pexelizumab (2.0 mg/kg bolus plus 0.05 mg/kg per hour for 24 hours;
n = 1553) or placebo (n = 1546) 10 minutes before undergoing the procedure. MAIN
OUTCOME MEASURES: The primary composite end point was the incidence of death or
MI within 30 days of randomization in those undergoing CABG surgery only (n =
2746). Secondary analyses included the intent-to-treat analyses of death or MI
composite at days 4 and 30 in all 3099 study patients. RESULTS: After 30 days,
134 (9.8%) of 1373 of patients receiving pexelizumab vs 161 (11.8%) of 1359 of
patients receiving placebo (relative risk, 0.82; 95% confidence interval,
0.66-1.02; P =.07) died or experienced MI in the CABG surgery only population.
In the intent-to-treat analyses, 178 (11.5%) of 1547 patients receiving
pexelizumab vs 215 (14.0%) of 1535 receiving placebo died or experienced MI
(relative risk, 0.82; 95% confidence interval, 0.68-0.99; P =.03). The trial was
not powered to detect a reduction in mortality alone. CONCLUSIONS: Compared with
placebo, pexelizumab was not associated with a significant reduction in the risk
of the composite end point of death or MI in 2746 patients who had undergone
CABG surgery only but was associated with a statistically significant risk
reduction 30 days after the procedure among all 3099 patients undergoing CABG
with or without valve surgery.

Blood Purif.  2004 May 12;22(3):249-255.  

Continuous Renal Replacement Therapy after Cardiac Surgery. Review of 85 Cases.

Lugones F, Chiotti G, Carrier M, Parent D, Thibodeau J, Ducharme B, Cardinal J,
Leblanc M.

Department of Nephrology and Intensive Care, Maisonneuve-Rosemont Hospital,
Montreal, Quebec, Canada.

Background/Aims: To evaluate the outcome of patients who require continuous
renal replacement therapy (CRRT) following cardiac surgery. Methods: All
patients who received CRRT after cardiac surgery over more than 4 years at the
Surgical Intensive Care Unit of the Montreal Heart Institute were reviewed.
Among 5,564 consecutive patients, 85 underwent CRRT postoperatively. Results:
The mean delay between surgery and CRRT initiation was 5 days, and the duration
of CRRT was 9 days, without a difference between survivors and non-survivors.
Delivered clearances with CRRT were estimated at 25-28 ml/min ( approximately 40
liters/day), 29-32 ml/min ( approximately 46 liters/day) and 17 ml/min (
approximately 25 liters/day) for continuous veno-venous hemofiltration,
continuous veno-venous hemodiafiltration and continuous veno-venous
hemodialysis, respectively. In-hospital mortality was 43.5%. No difference in
mortality was observed between patients with normal renal function at baseline
and those with pre-operative renal dysfunction. Mortality was 33.3% after a
coronary artery bypass graft (CABG), 57.1% after CABG and valve surgery, 60%
after valve surgery, and 72.7% for redo-CABG or redo-valve surgery. 79% of
survivors and 86% of non-survivors had received a cardiopulmonary bypass (p =
NS). The Simplified Acute Physiology Score II upon intensive care unit (ICU)
admission and the requirement of an intra-aortic balloon pump were higher in
non-survivors (p < 0.05). The mean length of ICU and hospital stay was 27.4 and
34.2 days for survivors and 17.9 and 22.3 days for non-survivors, respectively
(p < 0.05). Conclusions: Renal impairment is relatively common after cardiac
surgery. The mortality of patients who required CRRT after cardiac surgery was
43.5% and was particularly influenced by the type of surgery. Copyright 2004 S.
Karger AG, Basel

 World J Surg. 2004 May 6   [Epub ahead of print] 

Liver Transplantation Techniques with Preservation of the Natural Venovenous
Bypass: Effect on Surgical Resection of Renal Cell Carcinoma Invading the
Inferior Vena Cava.

Delis S, Dervenis C, Lytras D, Avgerinos C, Soloway M, Ciancio G.

Unit of Liver Surgery, 1st Surgical Department, Agia Olga Hospital, 3-5 Agias
Olgas Street, 14233, Athens, Greece.

Although renal tumors invading the inferior vena cava (IVC) are unusual, they
represent a challenge to the surgical team because their accessibility is
difficult. Liver transplantation techniques have been developed that preserve
the venous collaterals, enhance the exposure, increase the safety of the
resection, and avoid cardiopulmonary bypass. We describe our technique for
dealing with renal tumors that have invaded the IVC, a combined experience of
two centers, and the safety of the procedure and subsequent low morbidity.
Between May 1997 and February 2003, a total of 45 patients (mean age 60.7 years)
underwent surgical resection of a renal tumor extending into the IVC by
techniques developed from liver transplantation, with the intention to avoid
sternotomy and cardiopulmonary bypass. In 42 patients (93.3%) surgical resection
of the tumor and thrombus was successful using the transabdominal approach while
preserving the venous collaterals; 3 patients with a level IV tumor thrombus
required cardiopulmonary bypass. The mean operating time was 342 minutes, and
the mean estimated blood loss was 1442 cc. Postoperative ileus in one patient
required laparoscopic lysis of the adhesions, and 2 patients (4.4%) died owing
to multiple system organ failure and massive pulmonary embolism. The median
follow-up was 36 months, during which time 6 patients developed metastatic
disease and 37 were disease-free. We concluded that liver transplantation
techniques enhance the surgical management of complicated urologic tumors.
Patients with tumor thrombus extending to the IVC can be treated while avoiding
thoracotomy and cardiopulmonary bypass.

J Thorac Cardiovasc Surg.  2004 May;127(5):1270-5.  

Safety of deliberate intraoperative and postoperative hypothermia for patients
undergoing coronary artery surgery: a randomized trial.

Nathan HJ, Parlea L, Dupuis JY, Hendry P, Williams KA, Rubens FD, Wells GA.

Division of Cardiac Anaesthesia, University of Ottawa Heart Institute, Ottawa,
Ontario, Canada. hnathan@ottawaheart.ca

BACKGROUND: Hypothermia in the perioperative period is associated with adverse
effects, particularly bleeding. Before termination of cardiopulmonary bypass,
rewarming times and perfusion temperatures are often increased to avoid
post-cardiopulmonary bypass hypothermia and the presumed complications. This
practice may, however, also have adverse effects, particularly cerebral
hyperthermia. We present safety outcomes from a trial in which patients
undergoing coronary artery surgery were randomly assigned to normothermia or
hypothermia for the entire surgical procedure. METHODS: Consenting patients over
the age of 60 years presenting for a first, elective coronary artery surgery
with cardiopulmonary bypass were randomly assigned to having their
nasopharyngeal temperature maintained at either 37 degrees C (group N; 73
patients) or 34 degrees C (group H; 71 patients) throughout the intraoperative
period, with no rewarming before arrival in the intensive care unit. All
received tranexamic acid. RESULTS: There was no clinically important difference
in intraoperative blood product or inotrope use. Temperatures on arrival in the
intensive care unit were 36.7 degrees C +/- 0.38 degrees C and 34.3 degrees C
+/- 0.38 degrees C in groups N and H, respectively. Blood loss during the first
12 postoperative hours was 596 +/- 356 mL in group N and 666 +/- 405 mL in group
H (mean difference +/- 95% confidence interval, 70 +/- 126 mL; P =.28). There
was no significant difference in blood product utilization, intubation time,
time in the hospital, myocardial infarction, or mortality. The mean time in the
intensive care unit was 8.4 hours less in the hypothermic group (P =.02).
CONCLUSIONS: Our data support the safety of perioperative mild hypothermia in
patients undergoing elective nonreoperative coronary artery surgery with
cardiopulmonary bypass. These findings suggest that complete rewarming after
hypothermic cardiopulmonary bypass is not necessary in all cases.

Pediatr Crit Care Med.  2004 May;5(3):246-50.  

The use of recombinant coagulation factor VIIa in uncontrolled postoperative
bleeding in children undergoing cardiac surgery with cardiopulmonary bypass.

Pychynska-Pokorska M, Moll JJ, Krajewski W, Jarosik P.

Department of Anesthesiology and Intensive Care (MP-P, WK) and the Clinic of
Cardiosurgery (JJM, PJ), Polish Mother Memorial Hospital Research Institute,
Lodz, Poland.

OBJECTIVE: To assess the hemostatic efficacy of recombinant coagulation factor
VIIa (rFVIIa) in the management of uncontrolled bleeding in postcardiac surgery
with cardiopulmonary bypass in children. DESIGN: An open-label study. SETTING: A
postoperative intensive care unit. PATIENTS: Eight consecutive pediatric
patients with excessive bleeding after cardiac surgery with cardiopulmonary
bypass that met the criteria for reexploration and did not respond to optimal
transfusions of platelets and fresh frozen plasma. INTERVENTIONS: rFVIIa 30
microg/kg was given as a bolus injection. A higher dose of 60 microg/kg was used
if a patient had preoperative coagulopathy, preoperative multiple-organ failure,
or indications that required an emergency operation. The same dose was repeated
15 mins after the previous injection if the bleeding had not decreased. If the
bleeding had decreased but still exceeded 10 mL/hr for body weight </=5 kg or
exceeded 2 mL.kg(-1).hr(-1) for body weight >5 kg, the same dose was repeated 2
hrs after the previous injection. A maximum of four doses could be given before
rFVIIa was considered ineffective and a reexploration was needed. MEASUREMENTS
AND MAIN RESULTS: Postoperative blood loss was estimated from the volume of
chest tube drainage. rFVIIa successfully controlled bleeding and prevented
reexploration in all seven patients who received treatment according to the
protocol. One patient who received only one dose of rFVIIa required
reexploration because a second dose was not available. No adverse events related
to rFVIIa were seen. CONCLUSIONS: rFVIIa may be useful in preventing
reexploration in uncontrolled postoperative bleeding in children undergoing
cardiac surgery with cardiopulmonary bypass. Randomized, placebo-controlled
studies are needed to confirm the safety and efficacy of rFVIIa in this clinical
setting.