TOP TEN SELECTED PAPERS - April 2009

1

Eur J Cardiothorac Surg. 2009 Apr 28. [Epub ahead of print]

The effect of fenoldopam and dopexamine on hepatic blood flow and hepatic
function following coronary artery bypass grafting with hypothermic
cardiopulmonary bypass.

Adluri RK, Singh AV, Skoyles J, Robins A, Hitch A, Baker M, Mitchell IM.

Department of Cardiac Surgery, Cardiac Anaesthesia and Clinical Perfusion,
Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, United Kingdom.

Background: Hypothermic cardiopulmonary bypass is associated with low perfusion
state causing a mismatch between demand and supply to various organs such as gut,
kidneys and brain. The consequences are thought to be responsible for
postoperative complications like systemic inflammatory response, renal failure,
neurological injury, etc. Pharmacological agents like dopamine, dopexamine and
dobutamine have been used in an attempt to reduce hypoperfusion and hence
complications. Fenoldopam, a dopamine analog (DA-1 receptor agonist), has
recently been shown to be specific reno-splanchnic vasodilator in animal studies.
We studied the haemodynamic effects of fenoldopam and its effect on hepatic blood
flow (HBF) during and after cardiopulmonary bypass and compared these with
dopexamine. Methods: Ethics committee approval was obtained. Forty-two
consecutive patients with good/moderate left ventricular function undergoing
either elective/urgent coronary artery bypass grafting were included in the
study. Patients were randomised to receive either fenoldopam (0.2mug/kgmin) (F;
n=14) or dopexamine (2.0mug/kgmin) (Dx; n=14) normal saline (NS; n=14)
continuously after induction of anaesthesia for 24h following completion of
surgery. HBF was measured using the Indocyanine green dye disappearance rate
method, before, during and after cardiopulmonary bypass. Data were collected
pre-, intra- and postoperatively. Serum liver enzymes were measured during the
perioperative period. Repeated measures ANOVA test was used to compare timed
samples in both groups. Results: The study groups were comparable in pre- and
intraoperative variables. In the fenoldopam and dopexamine groups there was a
significant increase in heart rate 15min following the commencement of the
infusion (NS:F:DX::-2.0+/-7.8beats/min:13.6+/-8.1beats/min
(p=0.007):18.36+/-20.2beats/min (p=0.004)). However the change in mean arterial
blood pressure was similar (NS:F:DX::-12.7+/-14.9:-4.0+/-23.1
(p=0.699):-2.6+/-22.3) (p=0.235). Cardiac index increased and systemic vascular
resistance decreased (requiring noradrenaline infusion) in the fenoldopam group, 
however this did not reach statistical significance. Hepatic blood flow reduced
during CPB and returned to near preoperative levels in all three groups with no
statistical difference between groups. Conclusions: Fenoldopam infusion induced
transient tachycardia, with no augmentation of hepatic blood flow whereas
dopexamine induced tachycardia and did not augment hepatic blood flow. Fenoldopam
and dopexamine may have hepato-protective effect.

Can J Surg. 2009 Apr;52(2):125-8.

Comparison of gastrointestinal complications in on-pump versus off-pump coronary 
artery bypass grafting.

Croome KP, Kiaii B, Fox S, Quantz M, McKenzie N, Novick RJ.

Division of Cardiac Surgery, University of Western Ontario, London, Ont.
krisbelize@hotmail.com

BACKGROUND: Gastrointestinal (GI) complications following coronary artery bypass 
grafting (CABG), although infrequent, are associated with significant morbidity
and mortality. It has been suggested that systemic inflammatory response plays an
important role in these complications. Cardiopulmonary bypass (CPB) is well known
to cause increased systemic inflammation, and therefore it has been proposed that
performing CABG using an off-pump technique could substantially minimize the risk
of GI complications. Prolonged CPB duration has been shown to be an independent
predictor of GI complications; however, the effect of avoiding CPB altogether
through off-pump procedures has not been thoroughly examined. We sought to
compare the incidence of GI complications in patients undergoing on-pump and
off-pump CABG. METHODS: We analyzed prospectively entered data on 2451 patients
who underwent isolated CABG between January 2000 and October 2004. We compared GI
complication rates in 5 predetermined areas (GI bleed, ileus, pancreatitis,
ischemic bowel and cholecystitis) among patients who had on-pump CABG with those 
of patients who had off-pump CABG. We also compared in-hospital mortality due to 
these complications between the 2 groups. RESULTS: We compared data for a total
of 2010 patients in the on-pump group and 441 in the off-pump group. In the
on-pump group, 30 (1.49%) patients experienced GI complications compared with 4
(0.91%) in the off-pump group (p = 0.34). Gastrointestinal bleed was the most
common complication in the off-pump group. Eight patients in the on-pump group
experienced ischemic bowels compared with no patients in the off-pump group. Six 
patients (0.3%) in the on-pump group died from GI complications, whereas no
patients in the off-pump group died from such complications (p = 0.25).
CONCLUSION: We found no significant difference in the total number of GI
complications between the off-pump and on-pump groups; however, trends could be
seen in the types of GI complications that occurred in the 2 groups. Owing to the
relatively infrequent occurrence of GI complications, a larger scale study would 
be beneficial to determine whether the differences observed would be significant.

J Cardiothorac Vasc Anesth. 2009 Apr 24. [Epub ahead of print]

Cardiopulmonary Bypass Increases Endogenous Carbon Monoxide Production.

Schober P, Kalmanowicz M, Schwarte LA, Loer SA.

Department of Anesthesiology, VU University Medical Center, Amsterdam, The
Netherlands.

OBJECTIVE: Endogenous carbon monoxide (CO) production results from heme
metabolism catalyzed by heme oxygenase (HO) enzymes of which HO-1 is inducible by
oxidative stress. Cardiopulmonary bypass provokes oxidative stress associated
with systemic and pulmonary inflammatory responses. Therefore, the authors
hypothesized that cardiopulmonary bypass is associated with an increase in
endogenous carbon monoxide production. DESIGN: A prospective, observational
study. SETTING: A cardiothoracic operating room. PARTICIPANTS: Forty patients
undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: End-tidal CO levels and arterial carboxyhemoglobin
concentrations were measured before and after cardiopulmonary bypass. End-tidal
CO concentrations and carboxyhemoglobin levels were increased significantly after
cardiopulmonary bypass as compared with prebypass values (median [interquartile
range]: end-tidal CO levels: 33 [20-42] ppm v 22 [16-32] ppm, p < 0.01;
carboxyhemoglobin 1.3% [1.0%-1.3%] v 0.9% [0.6%-1.0%], p < 0.01). To exclude that
the observed increases were caused by CO accumulation during CPB, the authors
also assessed carboxyhemoglobin concentrations in the arterial and venous limb of
the oxygenator, indicating that CO is eliminated across the membrane oxygenator
during CPB. CONCLUSIONS: Cardiac surgery with cardiopulmonary bypass is
associated with an increase in endogenous CO production.

Eur J Cardiothorac Surg. 2009 Apr 24. [Epub ahead of print]

Predictors of impaired neurodevelopmental outcomes at one year of age after
infant cardiac surgery.

Fuller S, Nord AS, Gerdes M, Wernovsky G, Jarvik GP, Bernbaum J, Zackai E, Gaynor
JW.

Division of Pediatric Cardiothoracic Surgery, The Children's Hospital of
Philadelphia, Philadelphia, PA, USA.

Objective: For most newborns, congenital heart defects (CHD) appear to be
isolated anomalies and the brain is presumed to have normal developmental
potential. Most studies of neurodevelopmental outcomes have focused on operative 
management strategies. Methods: Infants with complex CHD and no identified
syndromes other than 22q11 microdeletions enrolled in a study of apolipoprotein E
(APOE) polymorphisms and developmental outcome were evaluated at one year of age;
including genetic evaluation and the Bayley Scales of Infant Development-II
[mental (MDI) and psychomotor developmental indices (PDI)]. Results: Five hundred
and fifty infants enrolled and 359 (20 with 22q11) of 501 survivors (72%)
returned. Mean MDI was 90+/-15 and PDI was 78+/-18. Genetic syndromes not
identified at birth were confirmed in 28 (8.1%) and suspected in 51 (15.0%). By
multivariable analysis, suspected/confirmed genetic syndromes and APOE
varepsilon2 allele predicted lower MDI and PDI, all p<0.04. Lower birth weight
(p<0.001) and preoperative intubation (p=0.012) predicted lower MDI. Higher
hematocrit during the initial operation was associated with higher MDI (p=0.007).
Longer postoperative length of stay was predictive of lower PDI (p=0.002).
Additional operations with cardiopulmonary bypass were associated with lower MDI 
and PDI (both p<0.002), but use of deep hypothermic circulatory arrest was not.
Conclusions: Patient factors (birth weight and preoperative status) are
significant determinants of neurodevelopmental outcomes as opposed to operative
management strategies. In this cohort, genetic syndromes unsuspected at birth
were surprisingly common and correlate with poor neurodevelopmental outcomes.
Without multiple congenital anomalies, syndromes may be missed in infancy.
Genetic evaluation should be considered in all infants with CHD.

Heart Surg Forum. 2009 Apr;12(2):E75-8.

Continuous arterial pressure waveform analysis accurately detects cardiac output 
in cardiac surgery: a prospective comparison with thermodilution,
echocardiography, and magnetic resonance techniques.

Senay S, Toraman F, Gelmez S, Dagdelen S, Karabulut H, Alhan C.

Department of Cardiovascular Surgery, Acibadem University School of Medicine,
Acibadem Kadikoy Hospital, Istanbul, Turkey. sahinsenay@gmail.com

OBJECTIVE: The aim of this study was to compare the accuracy of cardiac output
(CO) measurements of noninvasive continuous arterial pressure waveform analysis, 
thermodilution technique and echocardiography with magnetic resonance (MRI)
imaging. METHODS: Eleven patients who underwent coronary bypass surgery under
cardiopulmonary bypass were prospectively enrolled in this study in 2008.
Repeated arterial pressure based, thermodilution, echocardiography, and MRI
cardiac output measurements were performed at the postoperative 24th hour.
RESULTS: Mean CO values were 5.58 +/- 0.98, 5.97 +/- 0.8, 5.31 +/- 0.52, and 5.32
+/- 0.92 measured with MRI, echocardiography, arterial pressure waveform
analysis, and thermodilution techniques, respectively. Bland-Altman analysis
showed good overall agreement between the MRI vs arterial waveform analysis and
MRI vs thermodilution; values for bias +/- SD were -0.27 +/- 1.06 (95% confidence
interval [CI] [-2.3 to 1.8]; P = .42) and -0.26 +/- 0.89 (95% CI [-2.0 to 1.5]; P
= .34), respectively. Poor agreement was defined between MRI and
echocardiography: bias +/- SD, 0.39 +/- 1.28 (95% CI [-2.1 to 2.9]; P = .34).
CONCLUSIONS: Arterial pressure-based and thermodilution CO measurement systems
yielded results comparable to those obtained with cardiac MRI assessment after
cardiac surgery. Arterial pressure wave-form analysis systems for CO measurement 
may be feasible, noninvasive methods for use in cardiac surgery.

Heart Surg Forum. 2009 Apr;12(2):E65-9.

Comparison of unilateral antegrade cerebral perfusion at 16 degrees C and 22
degrees C systemic temperature.

Sanioglu S, Sokullu O, Arslan IY, Sargin M, Yilmaz M, Ozay B, Tokoz H, Bilgen F.

Department of Cardiovascular Surgery, Dr Siyami Ersek Thoracic and Cardiovascular
Surgery Training and Research Hospital, Istanbul, Turkey. sanioglu@gmail.com

OBJECTIVES: Unilateral antegrade cerebral perfusion can be performed with minimal
manipulations to arch arteries, but whether it provides adequate brain perfusion 
remains unclear. Some authors believe that this technique can be inadequate
without deep hypothermia. We investigated the reliability of unilateral cerebral 
perfusion at 22 degrees C hypothermia and the advantages of avoiding deep
hypothermia. METHODS: Study participants were 55 patients who underwent surgery
with unilateral cerebral perfusion. Patients were divided into 2 groups; 18
patients underwent surgery at 16 degrees C hypothermia (group I) and 37 patients 
at 22 degrees C hypothermia (group II). The mean age of the patients was 59 +/-
10 years in group I and 55 +/- 14 years in group II. Supracoronary ascending
aorta replacement was performed in 25 and hemiarch replacement in 15 patients.
Nine patients underwent surgery for a Bentall procedure. Total arch replacement
was performed in 4 patients and total thoracic aorta replacement in 2 patients.
RESULTS: The hospital mortality was 11% in group I and 5.4% in group II (P =
.59). Transient neurologic deficits were not detected in any of the patients. The
rate of permanent neurologic deficits was 5.9% in group I and 2.8% in group II (P
= .54). Although mean aortic cross-clamp and antegrade cerebral perfusion times
were not significantly different, mean cardiopulmonary bypass time was longer in 
group I than group II (174 +/- 38 vs 142 +/- 37 minutes, P = .005). Postoperative
bleeding, blood product usage, serum creatinine and hepatic enzyme level changes,
inotrope usage, and arrhythmia occurrence were not different between the 2
groups. Mean mechanical ventilation time was longer in group I than group II (24 
+/- 17 vs 16 +/- 6 hours, P = .02). CONCLUSIONS: Unilateral antegrade cerebral
perfusion at 22 degrees C systemic hypothermia appears to be safe and reliable
for brain protection. Advantages of this technique are avoidance of deep
hypothermia and reduced cardiopulmonary bypass and mechanical ventilation times
in patients undergoing aortic surgery.

Adv Ther. 2009 Apr 16. [Epub ahead of print]

Comparison of inhaled and intravenous milrinone in patients with pulmonary
hypertension undergoing mitral valve surgery.

Wang H, Gong M, Zhou B, Dai A.

Department of Anesthesiology, Second Affiliated Hospital, School of Medicine,
Zhejiang University, Hangzhou, 310009, China.

INTRODUCTION: Increased pulmonary vascular resistance (PVR) is detrimental to
cardiac output in postoperative cardiac-surgery patients. The aim of this study
was to investigate the postoperative hemodynamic effects of milrinone inhalation,
and determine whether it has a selective effect of pulmonary vasodilation in
patients with pulmonary hypertension undergoing mitral valve replacement surgery.
METHODS: In this study, 48 patients with pulmonary hypertension who underwent
mitral valve replacement surgery were included. Patients were randomly divided
into two groups with 24 patients in each: the inhaled group and the control group
(intravenous [i.v.] milrinone). In the inhaled group, milrinone was administered 
with a jet nebulizer, and nebulized for 4 hours. In the control group, patients
received a bolus of 50 mug/kg i.v. milrinone, then received a continuous
milrinone infusion, 0.5 mug/kg/min, for 4 hours. A number of hemodynamic changes 
in all patients were evaluated. RESULTS: With milrinone administration, mean
pulmonary artery pressure (MPAP) and PVR showed a comparable decrease in both
groups. However, after initiation of milrinone, both mean arterial pressure and
systemic vascular resistance in the inhaled group were significantly higher than 
in the control group. MPAP and PVR returned to baseline values 60 minutes after
termination of milrinone inhalation. In addition, in the inhaled group, there was
a reduction in intrapulmonary shunt fraction (Qs/Qt), with an improvement in
PaO(2)/FiO(2) (arterial oxygen tension/fraction of inspired oxygen). CONCLUSION: 
The major advantage of inhaled milrinone is its pulmonary selectivity, thereby
avoiding systemic side effects and ventilationperfusion mismatch. Inhaled
milrinone is an effective pulmonary vasodilator and appears to be an alternative 
promising approach in addressing the problem of right-ventricular decompensation 
following cardiopulmonary bypass.

J Thorac Cardiovasc Surg. 2009 May;137(5):1154-62. Epub 2009 Feb 23.

Myocardial membrane injury in pediatric cardiac surgery: An animal model.

Egan JR, Butler TL, Cole AD, Abraham S, Murala JS, Baines D, Street N, Thompson
L, Biecker O, Dittmer J, Cooper S, Au CG, North KN, Winlaw DS.

Kids Heart Research, The Children's Hospital at Westmead, Sydney, Australia.

OBJECTIVE: Reduced myocardial performance invariably follows pediatric cardiac
surgery and is manifested by a low cardiac output state in its severest form. The
role of myocardial membrane proteins in this setting is unknown. Dystrophin and
dysferlin are involved in membrane integrity, whereas aquaporins selectively
transport water. These proteins were examined in a model of pediatric cardiac
surgery, together with a trial of poloxamer 188, which may reduce membrane
injury. METHODS: Eight lambs were randomized to saline with or without poloxamer 
188. Lambs underwent 2 hours of cardiopulmonary bypass and aortic crossclamping. 
After a further 9 hours of monitoring, the hearts were assessed for water
content, capillary leak, and protein expression. RESULTS: Dystrophin expression
was unaffected by ischemia/reperfusion, but dysferlin expression was reduced.
Aquaporin 1 protein increased after ischemia/reperfusion. Poloxamer 188
administration was associated with supranormal levels of dystrophin, preservation
of dysferlin expression, and normalization of aquaporin 1 expression. Poloxamer
188 was associated with less capillary leak, maintained colloid osmotic pressure,
and less hemodilution. Poloxamer 188 was associated with an improved hemodynamic 
profile (higher blood pressure, higher venous saturation, and lower lactate),
although the heart rate tended to be higher. CONCLUSIONS: Changes in protein
expression within the myocardial membrane were found in a clinically relevant
model of pediatric cardiac surgery. Indicators of reduced performance, such as
lower blood pressure and lower oxygen delivery, were lessened in association with
the administration of the membrane protecting poloxamer 188. Poloxamer 188 was
also associated with potentially beneficial changes in membrane protein
expression, reduced capillary leakage, and less hemodilution.

Extra-corporeal life support following cardiac surgery in children: analysis in a
single institution.

Alsoufi B, Al-Radi OO, Gruenwald C, Lean L, Williams WG, McCrindle BW, Caldarone 
CA, Van Arsdell GS.

King Faisal Heart Institute, King Faisal Specialist Hospital and Research Centre,
Riyadh, Saudi Arabia.

Objective: Application of extra-corporeal life support (ECLS) following pediatric
cardiac surgery varies between different institutions based on manpower
availability and philosophy towards ECLS utilization. We examined a large single 
institution experience with postoperative ECLS in children aiming to identify
outcome predictors. Methods: Hospital records of all children who required
postoperative ECLS at our institution were reviewed. Patients' demographics,
cardiac anatomy, surgical and ECLS support details were entered into a
multivariable regression analysis to determine factors associated with survival. 
Results: Between 1990 and 2007, 180 consecutive children, median age 109 days
(range: 1 day-16.9 years), required postoperative ECLS. Sixty-nine children (38%)
had undergone palliative treatment for single ventricle pathology. ECLS support
was required for failure to separate from cardiopulmonary bypass (n=83) or for
postoperative low cardiac output state (n=97). Forty-eight patients (27%)
received rescue extra-corporeal membrane oxygenation (ECMO) support during active
chest compression for refractory cardiac arrest. Under ECLS support, 37 patients 
required surgical revision and 20 received orthotopic heart transplantation. One 
hundred and nine patients (61%) survived >24h following ECLS discontinuation and 
68 (38%) were discharged alive. Hospital survivors required shorter ECLS support 
duration compared to non-survivors (median 3 vs 5 days, respectively, p=0.05)
however survival occurred after up to 16 days of ECLS support. ECLS indication
(OR: 0.85 for failure to separate from bypass vs postoperative low cardiac output
95% CI (0.47-1.56), p=0.62) and rescue ECMO (OR: 0.63 for rescue ECMO vs not
95%CI (0.32-1.24), p=0.18) were not associated with risk of mortality. In a
multivariable logistic regression model, neurological complications (p=0.0007),
prolonged ECLS duration (p=0.003), repeat ECLS requirement (p=0.02), renal
dysfunction (p=0.04) and not performing heart transplantation (p=0.04) were
significant factors for hospital death. Conclusion: ECLS plays a valuable role in
children with low cardiac output state following cardiac surgery. More than one
third of those patients, including young neonates, older children, patients with 
single ventricle, or those requiring rescue ECMO can be salvaged. Although
prognosis worsens with prolonged ECLS duration, survival can be noted up to 16
days of support. Heart transplantation is often an important ECLS exit strategy
and should be considered early in selected children. Patients' survival could
improve if renal and neurological complications are avoided.

Crit Care. 2009 Apr 3;13(2):R48. [Epub ahead of print]

Haemofiltration in newborns treated with extracorporeal membrane oxygenation: a
case-comparison study.

Blijdorp K, Cransberg K, Wildschut ED, Gischler SJ, Jan Houmes R, Wolff ED,
Tibboel D.

Department of Intensive Care, Erasmus MC Sophia Children's Hospital, Dr
Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. d.tibboel@erasmusmc.nl.

ABSTRACT: INTRODUCTION: Extracorporeal membrane oxygenation is a supportive
cardiopulmonary bypass technique for patients with acute reversible
cardiovascular or respiratory failure. Favourable effects of haemofiltration
during cardiopulmonary bypass instigated the use of this technique in infants on 
extracorporeal membrane oxygenation. The current study aimed at comparing
clinical outcomes of newborns on extracorporeal membrane oxygenation with and
without continuous haemofiltration. METHODS: Demographic data of newborns treated
with haemofiltration during extracorporeal membrane oxygenation were compared
with those of patients treated without haemofiltration in a retrospective 1:3
case-comparison study. Primary outcome parameters were time on extracorporeal
membrane oxygenation, time until extubation after decannulation, mortality and
potential cost reduction. Secondary outcome parameters were total and mean fluid 
balance, urine output in mL/kg/day, dose of vasopressors, blood products and
fluid bolus infusions, serum creatinin, urea and albumin levels. RESULTS: Fifteen
patients with haemofiltration (HF group) were compared with 46 patients without
haemofiltration (control group). Time on extracorporeal membrane oxygenation was 
significantly shorter in the HF group: 98 hours (interquartile range (IQR) = 48
to 187 hours) versus 126 hours (IQR = 24 to 403 hours) in the control group (P = 
0.02). Time from decannulation until extubation was shorter as well: 2.5 days
(IQR = 0 to 6.4 days) versus 4.8 days (IQR = 0 to 121.5 days; P = 0.04). The
calculated cost reduction was euro5000 per extracorporeal membrane oxygenation
run. There were no significant differences in mortality. Patients in the HF group
needed fewer blood transfusions: 0.9 mL/kg/day (IQR = 0.2 to 2.7 mL/kg/day)
versus 1.8 mL/kg/day (IQR = 0.8 to 2.9 mL/kg/day) in the control group (P<
0.001). Consequently the number of blood units used was significantly lower in
the HF group (P< 0.001). There was no significant difference in inotropic support
or other fluid resuscitation. CONCLUSIONS: Adding continuous haemofiltration to
the extracorporeal membrane oxygenation circuit in newborns improves outcome by
significantly reducing time on extracorporeal membrane oxygenation and on
mechanical ventilation, because of better fluid management and a possible
reduction of capillary leakage syndrome. Fewer blood transfusions are needed. All
in all, overall costs per extracorporeal membrane oxygenation run will be lower.