Eur J Cardiothorac Surg. 2007 Mar 30; [Epub ahead of print] 

Preliminary experience with inhaled milrinone in cardiac surgery.

Lamarche Y, Perrault LP, Maltais S, Tetreault K, Lambert J, Denault AY.

Research Center, Montreal Heart Institute and Universite de Montreal, 5000
Belanger Street, Montreal, Quebec H, Canada; Department of Cardiac Surgery,
Montreal Heart Institute and Universite de Montreal, 5000 Belanger Street,
Montreal, Quebec H, Canada.

Background: Inhaled administration of milrinone reduces pulmonary artery
pressure. Pulmonary hypertension (PH) and right heart failure are associated
with difficult separation from cardiopulmonary bypass (CPB). Therefore, inhaled
milrinone could facilitate separation from CPB. Objective: To determine the
impact and timing of administration of inhaled milrinone. Methods: A
retrospective analysis of our experience on high-risk patients receiving inhaled
milrinone was conducted to evaluate the postoperative course after
administration of the drug. Results: Seventy-three patients received inhaled
milrinone from June 2002 to February 2005. Mean age was 64+/-13 years, with a
mean preoperative Parsonnet score of 27+/-14. Inhaled milrinone (5mg) was
administered before (n=30) or after (n=40) CPB, three patients had off-pump
procedures and were excluded. CPB time was 145+/-78min with cross-clamping times
of 91+/-56min without any significant difference between groups. Fifty-four
patients (74%) had difficult separation from CPB, 14 patients (19%) required an
intra-aortic balloon pump and 10 patients (14%) needed emergency reinitiation of
CPB for hemodynamic instability. Ten patients died in the perioperative period
(13.7%). Patients receiving inhaled milrinone prior to CPB initiation had a
lowering pulmonary artery pressure after CPB (p<.01) and had less emergency
reinitiation of CPB after weaning (3% vs 23%, p=.02) as compared to those with
administration after CPB. No detectable side effects were directly linked to the
administration of the drug. Conclusion: In this high-risk cohort, use of inhaled
milrinone was well tolerated. Administration before initiation of CPB could help
weaning from CPB.

Crit Care. 2007 Mar 12;11(2):207 [Epub ahead of print] 

Clinical review: Aggressive management and extracorporeal support for
drug-induced cardiotoxicity.

Baud FJ, Megarbane B, Deye N, Leprince P.

Medical and Toxicological Intensive Care Unit, Assistance Publique-Hopitaux de
Paris, University Paris 7, Hopital Lariboisiere, 75010 Paris, France.
frederic.baud@lrb.aphp.fr.

ABSTRACT: Poisoning may induce failure in multiple organs, leading to death.
Supportive treatments and supplementation of failing organs are usually
efficient. In contrast, the usefulness of cardiopulmonary bypass in drug-induced
shock remains a matter of debate. The majority of deaths results from poisoning
with membrane stabilising agents and calcium channel blockers. There is a need
for more aggressive treatment in patients not responding to conventional
treatments. The development of new antidotes is limited. In contrast,
experimental studies support the hypothesis that cardiopulmonary bypass is
life-saving. A review of the literature shows that cardiopulmonary bypass of the
poisoned heart is feasible. The largest experience has resulted from the use of
peripheral cardiopulmonary bypass. However, a literature review does not allow
any conclusions regarding the efficiency and indications for this invasive
method. Indeed, the majority of reports are single cases, with only one series
of seven patients. Appealing results suggest that further studies are needed.
Determination of prognostic factors predictive of refractoriness to conventional
treatment for cardiotoxic poisonings is mandatory. These prognostic factors are
specific for a toxicant or a class of toxicants. Knowledge of them will result
in clarification of the indications for cardiopulmonary bypass in poisonings.

Clin Chem. 2007 Mar 15; [Epub ahead of print] 

Perioperative Activin A Concentrations as a Predictive Marker of Neurologic
Abnormalities in Children after Open Heart Surgery.

Florio P, Felipe Abella R, de la Torre T, Giamberti A, Luisi S, Bufera G,
Cazzaniga A, Frigiola A, Petraglia F, Gazzolo D.

Department of Pediatrics, Obstetrics and Reproductive Medicine, University of
Siena, Siena, Italy.

BACKGROUND: Ischemic-reperfusion injury of the brain is a major adverse event
after cardiac surgery, especially when extracorporeal circuits are used. Because
brain injury induces local overproduction of activin A, we measured plasma
concentrations in children after open heart surgery with cardiopulmonary bypass
(CPB) to investigate the potential of measuring activin A for early
identification of infants at risk for brain damage. METHODS: We evaluated 45
infants (age <1 year) with congenital heart defects: 36 without overt neurologic
injury, and 9 with neurologic injury on day 7 after the surgical procedure.
Blood samples were taken before surgery, during surgery before CPB, at the end
of CPB, at the end of surgery, and at 12 h after surgery. Neurologic development
was assessed before surgery and on postoperative day 7. RESULTS: Activin A
concentrations increased significantly during surgery (P <0.0001) to a maximum
at the end of CPB. Infants who developed abnormal neurologic sequelae had
concentrations significantly higher (P <0.0001, all comparisons) than patients
with normal neurologic outcome at all evaluated times, but not before surgery.
Activin A had a sensitivity of 100% [95% confidence interval (CI), 66%-100%] and
a specificity of 100% (95% CI, 90%-100%) as a single marker for predicting
neurologic abnormalities (area under the ROC curve, 1.0). CONCLUSIONS: Activin A
increases in children who experience poor neurologic outcomes after open heart
surgery, and its assay may help in early identification of infants at risk for
brain damage.

Heart Lung Circ. 2007 Mar 12; [Epub ahead of print] 

What is the Role of Leukocyte Depletion in Cardiac Surgery?

Lim HK, Anderson J, Leong JY, Pepe S, Salamonsen RF, Rosenfeldt FL.

Cardiac Surgical Research Unit, Alfred Hospital, Melbourne, Australia; Monash
University Department of Surgery, Alfred Hospital, Melbourne, Australia.

Leukocytes play an important pathogenic role in ischaemia-reperfusion injury.
During cardiopulmonary bypass, leukocyte filters have the potential to remove
leukocytes, thereby reducing contact of activated leukocytes with the
endothelium of target organs. Improvement in the safety and efficacy of
commercially available leukocyte filters in recent years has led to their
increasing use in cardiac surgery. However, the benefits have been inconsistent.
Current evidence suggests that leukocyte depletion may not have a significant
impact in low risk elective coronary artery bypass grafting but may be
beneficial in valve surgery and high-risk cardiac surgery. High-risk surgical
groups that may benefit from leukocyte filtration are those with left
ventricular hypertrophy (LV mass>300g), poor ejection fraction (EF<40%), chronic
obstructive airways disease (predicted FEV1<75%), prolonged ischaemia (cross
clamp time>120min or cardiac transplantation), paediatric cardiac surgery and
patients in cardiogenic shock requiring emergency coronary artery bypass
grafting. Future trials should be powered to detect important clinical end
points and be designed to avoid premature exhaustion of the filter.

Eur J Cardiothorac Surg. 2007 Mar 9; [Epub ahead of print] 

Retransfusion of pericardial blood does not trigger systemic coagulation during
cardiopulmonary bypass.

van den Goor JM, Nieuwland R, Rutten PM, Tijssen JG, Hau C, Sturk A, Eijsman L,
de Mol BA.

Department of Cardio-thoracic Surgery, Academic Medical Center of the University
of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.

Objective: During cardiopulmonary bypass (CPB), systemic coagulation is believed
to become activated by blood contact with the extracorporeal circuit and by
retransfusion of pericardial blood. To which extent retransfusion activates
systemic coagulation, however, is unknown. We investigated to which extent
retransfusion of pericardial blood triggers systemic coagulation during CPB.
Methods: Thirteen patients undergoing elective coronary artery bypass grafting
surgery were included. Pericardial blood was retransfused into nine patients and
retained in four patients. Systemic samples were collected before, during and
after CPB, and pericardial samples before retransfusion. Levels of prothrombin
fragment F(1+2) (ELISA), microparticles (flow cytometry) and non-cell bound
(soluble) tissue factor (sTF; ELISA) were determined. Results: Compared to
systemic blood, pericardial blood contained elevated levels of F(1+2),
microparticles and sTF. During CPB, systemic levels of F(1+2) increased from
0.28 (0.25-0.37; median, interquartile range) to 1.10 (0.49-1.55) nmol/l
(p=0.001). This observed increase was similar to the estimated (calculated)
increase (p=0.424), and differed significantly between retransfused and
non-retransfused patients (1.12nmol/l vs 0.02nmol/l, p=0.001). Also, the
observed systemic increases of platelet- and erythrocyte-derived microparticles
and sTF were in line with predicted increases (p=0.868, p=0.778 and p=0.205,
respectively). Before neutralization of heparin, microparticles and other
coagulant phospholipids decreased from 464mug/ml (287-701) to 163mug/ml
(121-389) in retransfused patients (p=0.001), indicating rapid clearance after
retransfusion. Conclusion: Retransfusion of pericardial blood does not activate
systemic coagulation under heparinization. The observed increases in systemic
levels of F(1+2), microparticles and sTF during CPB are explained by dilution of
retransfused pericardial blood.

Am J Cardiol. 2007 Mar 15;99(6):771-3. Epub 2007 Jan 22. 

Elective high-risk percutaneous coronary interventions supported by
extracorporeal life support.

Vainer J, van Ommen V, Maessen J, Geskes G, Lamerichs L, Waltenberger J.

Department of Cardiology, University Hospital, Maastricht, The Netherlands.

This study investigated the feasibility of high-risk percutaneous coronary
intervention (PCI) in hemodynamically unstable patients supported by modified
cardiopulmonary bypass (extracorporeal life support [ELS]). Over a 38-month
period, 15 patients (10 men, 5 women, mean age 72 +/- 9 years, mean ejection
fraction 34 +/- 15%, angina pectoris New York Heart Association class III to IV)
who were not eligible for coronary artery bypass grafting because of high
co-morbidity underwent elective high-risk PCI supported by ELS. All lesions were
technically challenging. ELS perfusion cannulas in the femoral artery and vein
were surgically inserted and removed. Procedural success was achieved in 14 of
15 patients. After a mean perfusion duration of 88 +/- 37 minutes, all patients
were weaned from the ELS in the catheterization laboratory. The patients were
ventilated for 5.1 +/- 3.3 hours. Blood transfusion was given to 8 patients.
Apart from 2 groin bleedings, no other complications occurred. Patients left our
hospital after 3.2 +/- 2.8 days. Of the 4 patients who died during the 15 +/-
12-month follow-up, 1 died of a noncardiac cause. In conclusion, in highly
selected patients ineligible for bypass surgery, ELS-supported PCI can be
performed with promising short- and long-term clinical outcomes. This complex
procedure is a safe alternative whenever other options for revascularization are
exhausted.

Ann Thorac Surg. 2007 Mar;83(3):895-901. 

Hawley H. Seiler Resident Award paper. The use of a miniaturized circuit and
bloodless prime to avoid cerebral no-reflow after neonatal cardiopulmonary
bypass.

Hickey E, Karamlou T, You X, Komanapalli C, Person T, Wehrley K, Ungerleider R.

Oregon Health and Sciences University, Portland, Oregon, USA.
edward.hickey@sickkids.ca

BACKGROUND: Our miniaturized bloodless prime circuit for neonatal
cardiopulmonary bypass (CPB) has previously been shown to elicit significantly
reduced systemic inflammation. We studied the effects of this circuit on
cerebral reperfusion because the pathophysiology of "no-reflow" is believed to
have an inflammatory component. METHODS: Twenty neonatal piglets were randomized
to CPB with miniaturized circuitry using either blood (group 1) or bloodless
(group 2) prime. At 18 degrees C, piglets underwent 60 minutes of either (A)
deep hypothermic circulatory arrest (DHCA) or (B) continuous low-flow bypass
(DHCLF). Analysis of cerebral blood flow (CBF) was undertaken before and after
CPB in addition to quantification of circulating tumor necrosis factor-alpha
(TNFalpha) and intracerebral TNFalpha messenger RNA (mRNA). RESULTS: The final
hematocrit in group 2 was 22% versus 28% (p < 0.05). The CBF fell in every
animal in group 1A, but increased in every animal in group 2A (p < 0.001),
despite no overall change in total cardiac output. The use of DHCLF was not
associated with pronounced trends in either prime group. Final serum TNFalpha
concentrations were significantly higher in group 1B (3166 +/- 843 pg/mL) than
group 2B (439 +/- 192 pg/mL; p < 0.05). Irrespective of the CPB strategy used,
the use of a blood prime generated significantly higher levels of intracerebral
TNFalpha mRNA. CONCLUSIONS: We attribute the hyperemic cerebrovascular response
to reduced inflammation through avoiding allogeneic whole blood. The analysis of
circulating and intracerebral TNFalpha in this study suggests that DHCLF in
conjunction with a bloodless prime might offer advantages through avoiding
ischemia, no-reflow, and in addition, resulting in a significantly reduced
cerebral inflammatory response.

Eur J Cardiothorac Surg. 2007 Apr;31(4):659-64. Epub 2007 Feb 8. 

Washing of irradiated red blood cells prevents hyperkalaemia during
cardiopulmonary bypass in neonates and infants undergoing surgery for complex
congenital heart disease.

Swindell CG, Barker TA, McGuirk SP, Jones TJ, Barron DJ, Brawn WJ, Horsburgh A,
Willetts RG.

Birmingham Children's Hospital, Birmingham, United Kingdom.

Objective: High concentrations of potassium and lactate in irradiated red cells
transfused during cardiopulmonary bypass may have detrimental effects on infants
and neonates undergoing cardiac surgery. The effects of receiving washed and
unwashed irradiated red cells from the cardiopulmonary circuit on serum
potassium and lactate concentrations were compared. Methods: The study
population included neonates and infants undergoing heart surgery for complex
congenital heart disease. A control group (n=11) received unwashed irradiated
red cells and the study group (n=11) received irradiated red cells washed in a
cell saver (Dideco Electa) using 900ml of 0.9% saline prior to pump priming.
Potassium and lactate concentrations were compared before, during and after
bypass. Results: Washing irradiated red cells reduced donor blood [potassium]
from>20 to 0.8+/-0.1mmol/l, and [lactate] from 13.7+/-0.5 to 5.0+/-0.3mmol/l
(p<0.001). The resulting prime had significantly lower [potassium] and [lactate]
than the unwashed group (potassium 2.6+/-0.1 vs 8.1+/-0.4mmol/l, p<0.001;
lactate 2.6+/-0.2 vs 4.6+/-0.3mmol/l, p<0.001). Peak [potassium] in the unwashed
group occurred 3 minutes after going on bypass (4.9+/-0.3mmol/l) and during
rewarming (4.9+/-0.4mmol/l). These were significantly higher than the washed
group (3.1+/-0.1, p<0.001 and 3.0+/-0.1mmol/l, p<0.001). The [potassium] was
greater than 6.0mmol/l for 4 out of these 11 unwashed patients compared with
none of the washed group. Immediately post-bypass the washed group had
significantly lower serum [potassium] (3.2+/-0.1 vs 4.2+/-0.2mmol/l, p=0.002).
There was no significant difference in [lactate] between groups during and after
cardiopulmonary bypass. Conclusions: The washing of irradiated red cells reduces
potassium and lactate loads and prevents hyperkalaemia during cardiopulmonary
bypass. The washing of irradiated red cells should be considered in neonates and
infants undergoing cardiac surgery for complex congenital heart disease.

J Thorac Cardiovasc Surg. 2007 Mar;133(3):704-9. 

The effect of mannitol on oxygenation and creatine kinase MB release in patients
undergoing multivessel off-pump coronary artery bypass surgery.

Shim JK, Choi SH, Oh YJ, Kim CS, Yoo KJ, Kwak YL.

Department of Anesthesiology and Pain Medicine, Yonsei University College of
Medicine, Seoul, South Korea.

OBJECTIVES: Despite avoiding cardiopulmonary bypass, off-pump coronary artery
bypass surgery is associated with reduction in PaO2 and postoperative
respiratory compliance. Also, transient interruption of coronary flow is
necessary during distal anastomoses and may impose ischemia-reperfusion
myocardial injury. Mannitol is an osmotic diuretic with free radical scavenging
properties, and we have evaluated the effects of mannitol on oxygenation and
cardiac enzyme release in patients undergoing multivessel off-pump bypass
surgery in a prospective, randomized, controlled, double-blind trial. METHODS:
Fifty patients were randomly allocated to receive either 20% mannitol 0.5 g/kg
(n = 25) or normal saline 2.5 mL/kg (n = 25) during Y-graft construction.
Pulmonary variables and serum sodium concentrations were measured 15 minutes
after induction of anesthesia and sternum closure. Creatine kinase MB was
measured before and after the operation. Intraoperative and postoperative fluid
input and output, time to extubation, and intraoperative hemodynamic variables
were also recorded. RESULTS: PaO2 after sternum closure was significantly higher
in the mannitol group, with faster time to extubation and shorter length of stay
in the intensive care unit. Intraoperative urine output was significantly
greater in the mannitol group, without significant differences in fluid input,
serum sodium concentration, and hemodynamic variables. Number of patients with a
creatine kinase MB level more than 3 times the upper limit of normal was
significantly higher in the control group. CONCLUSION: Mannitol could be safely
used without adverse side effects in patients undergoing multivessel off-pump
bypass surgery with beneficial effects in terms of preserving oxygenation,
earlier extubation, and fewer patients with significant creatine kinase MB
elevation.

J Thorac Cardiovasc Surg. 2007 Mar;133(3):632-9. Epub 2007 Jan 29. 

Over two decades of pediatric heart transplantation: how has survival changed?

Morales DL, Dreyer WJ, Denfield SW, Heinle JS, McKenzie ED, Graves DE, Price JF,
Towbin JA, Frazier OH, Cooley DA, Fraser CD Jr.

Michael E. DeBakey Department of Surgery, Division of Congenital Heart Surgery,
Baylor College of Medicine, Houston, Tex, USA.
dlmorale@texaschildrenshospital.org

OBJECTIVE: In 1984, the first successful infant heart transplant was performed
at Texas Children's Hospital. This study analyzes the 21-year experience with
pediatric heart transplantation at Texas Children's Hospital to assess whether
and how survival has changed over time. METHODS: Between November 1, 1984, and
October 3, 2005, 164 consecutive orthotopic heart transplants were performed on
154 patients. Characteristics: mean age 7.1 +/- 6.0 years, mean body surface
area 0.8 +/- 0.5 m(2). Diagnosis at transplant: cardiomyopathy 53.0% (n = 87),
congenital heart defect 39.0% (n = 64), retransplant 7.9% (n = 13). Multivariate
risk factor analysis of 32 variables was completed by Cox proportional hazards
regression models. RESULTS: Mean follow-up was 5.9 +/- 4.8 years. Overall
Kaplan-Meier survival was 82% at 1 year, 65% at 5 years, and 54% at 10 years.
After 1995, Kaplan-Meier survival (91% at 1 year and 71% at 5 years) was
significantly improved over pre-1995 survival (71% at 1 year, 57% at 5 years,
and 48% at 10 years; P =.026). Hospital survival improved in the post-1995 era
(96%) compared with the pre-1995 era (77%; P < .001). Life-table analysis by
yearly increments demonstrates only an improved survival (pre-1995, 71%
-->post-1995, 91%) in the first posttransplant year (P = .001); every subsequent
year the mortality rates are the same (P = .92). Risk factors for overall
mortality are prolonged postoperative intubation (>5 days) and longer
cardiopulmonary bypass time. CONCLUSIONS: Primarily attributable to an increase
in early survival, overall pediatric heart transplant survival is improved.
However, after the first posttransplant year, the rate of mortality has not
changed in 21 years. This highlights the need for new therapies to treat
children both with or in need of a heart transplant.