TOP TEN SELECTED PAPERS - July 2009

1

J Am Coll Surg. 2009 Jul;209(1):89-99. Epub 2009 May 28.

Profound hypothermia decreases cardiac apoptosis through Akt survival pathway.

Shuja F, Tabbara M, Li Y, Liu B, Butt MU, Velmahos GC, DeMoya M, Alam HB.

Division of Trauma, Emergency Surgery, and Surgical Critical Care, Massachusetts 
General Hospital, Boston, MA 02114, USA.

BACKGROUND: Hypothermia increases the tolerable ischemia time for myocardium in
hemorrhagic shock, but precise mechanisms are not clearly established. Here we
studied activation of Akt cell survival pathway in a rodent model of emergency
preservation and delayed resuscitation. STUDY DESIGN: Wistar-Kyoto rats underwent
40% blood volume arterial hemorrhage during 10 minutes and were randomized into 2
groups based on core body temperatures (n = 7/group): hypothermia (15 degrees C) 
and normothermia (37 degrees C). Hypothermia was induced by infusing cold
isotonic solution using cardiopulmonary bypass (CPB) setup. After reaching target
body temperature, low-flow state (CPB flow rate of 20 mL/kg/min) was maintained
for 60 minutes. Hypothermic rats were rewarmed to baseline temperature; all rats 
were resuscitated on CPB and monitored for 3 hours. The normothermia group
underwent identical CPB management. Sham rats (no hemorrhage, no instrumentation)
were used as controls (n = 7). Tissues were harvested at the end of experiment.
RESULTS: Induction of hypothermia increased survival rates (100% versus 0% in
normothermia group). Western blot analysis of cardiac tissue revealed increased
levels of phospho-Akt (active) in hypothermia and sham groups compared with the
normothermia group (p < 0.05). Among downstream targets of Akt, phospho-GSK-3beta
(inactive), phospho-Bad (inactive), beta-catenin, and Bcl-2 were considerably
elevated in the hypothermia group compared with the normothermia group.
Hypothermia also showed decreased activity of caspase-3 protein compared with
normothermia (p < 0.05), suggesting decreased apoptosis. CONCLUSIONS: Profound
hypothermia increases survival in a rodent model of hemorrhagic shock and
prolonged low-flow state. Hypothermia preserves Akt signaling pathway in
cardiomyocytes with a concurrent decrease in cardiac apoptosis.

Paediatr Anaesth. 2009 Jul 24. [Epub ahead of print]

Hemodynamic effects of dobutamine and dopexamine after cardiopulmonary bypass in 
pediatric cardiac surgery*

Kwapisz MM, Neuhäuser C, Scholz S, Welters ID, Löhr T, Koch T, Valeske K,
Akintürk H, Thul J, Müller M.

Department of Anesthesia, Dalhousie University, Queen Elizabeth II Health
Sciences Centre, Halifax, NS, Canada.

Background: After surgical repair of congenital heart disease, inotropic support 
is sometimes necessary to wean from cardiopulmonary bypass. In pediatric cardiac 
surgery, dobutamine and dopamine are often used as inotropic support. Dopexamine 
is a synthetic catecholamine, which has positive inotropic and vasodilating
properties. Because the hemodynamic effects of catecholamines are modified after 
cardiopulmonary bypass, the aim of this study was to investigate the effects of
dobutamine and dopexamine on cardiac index and systemic vascular resistance index
after cardiopulmonary bypass in pediatric cardiac surgery. Methods: The study was
performed in a prospective, randomized, and double-blinded cross-over design. The
investigation included 11 children for elective, noncomplex congenital heart
surgery. After weaning from cardiopulmonary bypass and a 20-min period of steady 
state, children received either 2.5 mug.kg(-1).min(-1) dobutamine or 1
mug.kg(-1).min(-1) dopexamine for 20 min. Cardiac index (transpulmonary
thermodilution), mean arterial pressure, central venous pressure, stroke volume, 
systemic vascular resistance, and central venous oxygen saturation were
determined. The primary outcome variable was cardiac index. Results: No
difference in cardiac index was observed between the two groups (P = 0.594). Both
drugs increased cardiac index, dopexamine from 3.9 +/- 0.6 to 4.7 +/- 0.8
l.min(-1).m(-2) (P = 0.003) and dobutamine from 4.1 +/- 0.7 to 4.8 +/- 0.7
l.min(-1).m(-2) (P = 0.004). During treatment with dobutamine, children presented
with significantly higher mean arterial pressure (P = 0.003) and systemic
vascular resistance index (P = 0.026). Conclusions: This trial demonstrates that 
low-dose dobutamine and dopexamine both increase cardiac index during pediatric
cardiac surgery but with different hemodynamic effects.

Br J Anaesth. 2009 Jul 31. [Epub ahead of print]

Profound haemodilution during normothermic cardiopulmonary bypass influences
neither gastrointestinal permeability nor cytokine release in coronary artery
bypass graft surgery.

Berger K, Sander M, Spies CD, Weymann L, Bühner S, Lochs H, Wernecke KD, von
Heymann C.

Department of Anaesthesiology and Intensive Care Medicine,
Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité
Mitte, Augustenburger Platz 1, 13353 Berlin, Germany.

BACKGROUND: /st> Cardiopulmonary bypass (CPB) impairs intestinal barrier function
and induces systemic inflammation after cardiac surgery. The objective of this
study was to evaluate the effect of profound haemodilution (haematocrit 19-21%)
during normothermic CPB on gastrointestinal permeability and cytokine release in 
comparison with a standard haemodilution (haematocrit 24-26%). METHODS: /st> This
was a prospective, controlled, randomized pilot trial of 60 patients without
gastrointestinal disease undergoing normothermic CPB (35.5-36 degrees C) for
coronary artery bypass graft surgery. Gastrointestinal permeability was measured 
by the triple-sugar technique (sucrose, lactulose, and mannitol excretion in
urine) before and after CPB. Interleukin (IL)-6, IL-10, and tumour necrosis
factor alpha (TNFalpha) were quantified using enzyme-linked immunosorbent assays.
RESULTS: /st> Data from 59 patients (19-21% haematocrit, n=28; 24-26%
haematocrit, n=31) were analysed. Data on gastrointestinal permeability were
available for 47 patients (19-21% haematocrit, n=23; 24-26% haematocrit, n=24),
blood samples for cytokine analysis from 59 patients. Mannitol excretion was
normal before and after surgery without significant differences between the
groups (after operation: 5.4% vs 2.9%, P=0.193). Lactulose and sucrose excretion 
was within a normal range before surgery and increased afterwards without
differences between the groups. IL-6, IL-10, and TNFalpha were elevated after
surgery, but there was no difference between the groups [IL-6 (P=0.78), IL-10
(P=0.74), and TNFalpha (P=0.67)]. CONCLUSIONS: /st> Profound haemodilution during
normothermic CPB brought about significant changes neither in intestinal
permeability nor in cytokine release. It may be concluded that a haematocrit of
19-21% during normothermic CPB does not impair intestinal barrier function and
cytokine response in patients without gastrointestinal comorbidity.

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

Static blood-flow control during cardiopulmonary bypass is a compromise of oxygen
delivery.

Svenmarker S, Häggmark S, Hultin M, Holmgren A.

Department of Surgical and Perioperative Science, Heart Centre, Umeå University
Hospital, Umeå, Sweden.

Background: Blood-flow control during cardiopulmonary bypass (CPB) is by
tradition based on the patient's body surface area. Emergence of new techniques
enables dynamic blood-flow control based on online measurement of venous oxygen
saturation and oxygen consumption. Present investigation aimed to compare static 
versus dynamic blood-flow control with respect to use of oxygen and effects upon 
organ function. Methods: In this study, 100 coronary-artery-bypass surgical
patients were prospectively randomised to static or dynamic hypothermic
blood-flow control during CPB. In the static group, pump flow was set to 2.4
(litres per minute) times the patient's body surface area (m(2)) throughout the
procedure. Pump flow in the dynamic group was varied according to the reading of 
the venous oxygen saturation and maintained at >75%. CPB-specific information was
collected online. Blood samples were collected for analysis of haemoglobin,
lactate, amylase, creatinine and C-reactive protein: pre-CPB, at weaning from CPB
and on day 1 postoperatively. Results: Randomisation formed two uniform groups.
Choice of static or dynamic blood-flow control during CPB had no significant
effects on organ function as judged by lactate, amylase or creatinine levels. On 
increasing oxygen demand, oxygen balance was maintained by increasing venous
oxygen extraction rates in the static flow mode and by increasing the pump flow
rate in the dynamic group. Conclusions: Independent of the blood-flow control
mode, oxygen balance remained preserved. However, the dynamic mode provided
higher oxygen delivery, which may increase margins of safety and protection of
organ function.

Can J Anaesth. 2009 Jul 29. [Epub ahead of print]

Target-achieved propofol concentration during on-pump cardiac surgery: a pilot
dose-finding study.

Raedschelders K, Hui Y, Laferlita B, Luo T, Zhang H, Chen DD, Ansley DM.

Department of Anesthesiology, Pharmacology, and Therapeutics, The University of
British Columbia, Rm 3200 3rd Floor, JPP. 910 West 10th Ave, Vancouver, BC, V5Z
4E3, Canada.

PURPOSE: Propofol concentrations that produce laboratory-based cardioprotective
effects are generally greater than those produced under routine anesthesia during
cardiac surgery. It is unknown whether experimental cardioprotective propofol
concentrations can routinely be achieved during cardiopulmonary bypass (CPB)
using continuous infusion. METHODS: Twenty-four patients scheduled for primary
aortocoronary bypass grafting with CPB were allocated to receive one of three
propofol infusion rates; 50, 100, or 150 mug . kg(-1) . min(-1) in an open-label 
pilot study. Data were described using a line of best fit to derive an
experimental clinical maneuver predicted to produce a whole blood concentration
of 5 mug . mL(-1) at reperfusion. A predetermined interim analysis of 30 patients
who were receiving the derived maneuver in an ongoing study was used to evaluate 
the maneuver. Cardiac index (CI), systemic vascular resistance index (SVRI), and 
left ventricular stroke work index (LVSWI) were recorded. RESULTS: The infusion
rate-concentration curve had an equation of y = 0.215e (0.0279x ), where y
represents the whole blood concentration and x represents the infusion rate (r
(2) = 0.781). The predicted infusion rate to achieve a mean concentration of 5
mug . mL(-1) was 113 mug . kg(-1) . min(-1). The nearest practical rate is 120
mug . kg(-1) . min(-1), producing a concentration of 5.39 (1.45) mug . mL(-1).
The values for CI, SVRI, and LVSWI were similar between groups at corresponding
time periods. CONCLUSIONS: An infusion rate of 120 mug . kg(-1) . min(-1) is
clinically practical and capable of achieving experimental cardioprotective
propofol concentrations at reperfusion.

Cytokine. 2009 Jul 23. [Epub ahead of print]

Age-dependent mobilization of circulating endothelial progenitor cells in infants
and young children undergoing cardiac surgery with cardiopulmonary bypass.

Sun Y, Yi D, Wang Y, Zheng R, Sun G, Wang J, Liu Y, Ren J, Wang Y, Zhang S, Gu C,
Pei J.

Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical
University, Xi'an, 710032 Shaanxi, China.

This study was designed to find the effects of age on circulating endothelial
progenitor cells (EPCs) and their mobilization in infants and young children
following surgical correction of congenital heart defects. In 60 consecutive
infants and young children (1month to 3years old) undergoing repair of
atrial/ventricular septal defect, the numbers of EPCs and plasma levels of IL-6, 
-8, -10, TNF-alpha, VEGF and G-CSF were determined preoperatively, at the end of 
cardiopulmonary bypass (CPB), as well as 6, 12, 24, 48, 72 and 96h following
surgery. Preoperative EPCs were reduced with increased age, similar to changes in
plasma VEGF and G-CSF levels. Rapid mobilizations of EPCs and plasma VEGF, G-CSF 
were induced by cardiac surgery with CPB in all infants and young children, and
the increased volumes of EPCs, VEGF and G-CSF decreased with age decreasing. The 
increased volumes of IL-6, -8, -10 and TNF-alpha were similar in different age
groups. However, mobilization of EPCs, plasma VEGF and G-CSF were limited in
infants <6months old, which did not correlate with change in inflammatory IL
activation. Preoperative EPCs and plasma levels of VEGF and G-CSF were reduced
with increasing age in infants and young children. Although a significant
increase in EPCs and release of cytochemokines were observed in infants
undergoing CPB, the mobilization of EPCs of the infants <6months old are limited.

Masui. 2009 Jul;58(7):897-902.

[The effect of bicarbonated Ringer's solution for infants and children undergoing
open-heart surgery]

[Article in Japanese]

Asano M, Doi Y, Soen M, Minami T.

Department of Anesthesiology, Osaka Medical College, Takatsuki 569-8686.

BACKGROUND: There is no study on the use of bicarbonated Ringer's solution (BR)
for pediatric patients. We evaluated the effect of BR on infants and children
undergoing open-heart surgery, compared with acetated Ringer's solution (AR).
METHODS: The records of 18 pediatric patients with congenital heart disease who
had undergone elective open-heart surgeries with cardiopulmonary bypass (CPB)
were reviewed retrospectively. Eight patients received AR as infusion and CPB
priming solution, and ten patients received BR. The pH, HCO3-, base excess and
lactate were measured at seven points ; (1) after anesthesia induction, (2)
CPB-start, (3) before CPB withdrawal or 60-minute after CPB, (4) after CPB
withdrawal, (5) end of operation, (6) 6-hour after operation, and (7) 24-hour
after operation, and administered volume of sodium bicarbonate during surgery and
24-hour after surgery were evaluated. Data were compared between two groups.
RESULTS: There were no significant differences in values of pH, HCO3-, base
excess and lactate between the two groups at any measurement point. The
administered volume of sodium bicarbonate during the procedure in BR was
significantly smaller than that in AR. CONCLUSIONS: BR was useful as infusion
fluid and CPB priming solution for infants and children who underwent open-heart 
surgeries, and reduced the administration of sodium bicarbonate during surgery.

Anesth Analg. 2009 Aug;109(2):320-30.

The efficacy of an intraoperative cell saver during cardiac surgery: a
meta-analysis of randomized trials.

Wang G, Bainbridge D, Martin J, Cheng D.

Department of Anesthesia and Perioperative Medicine, London Health Sciences
Centre, University of Western Ontario, London, Ontario, Canada.

BACKGROUND: Cell salvage may be used during cardiac surgery to avoid allogeneic
blood transfusion. It has also been claimed to improve patient outcomes by
removing debris from shed blood, which may increase the risk of stroke or
neurocognitive dysfunction. In this study, we sought to determine the overall
safety and efficacy of cell salvage in cardiac surgery by performing a systematic
review and meta-analysis of published randomized controlled trials. METHODS: A
comprehensive search was undertaken to identify all randomized trials of cell
saver use during cardiac surgery. MEDLINE, Cochrane Library, EMBASE, and abstract
databases were searched up to November 2008. All randomized trials comparing cell
saver use and no cell saver use in cardiac surgery and reporting at least one
predefined clinical outcome were included. The random effects model was used to
calculate the odds ratios (OR, 95% confidence intervals [CI]) and the weighted
mean differences (WMD, 95% CI) for dichotomous and continuous variables,
respectively. RESULTS: Thirty-one randomized trials involving 2282 patients were 
included in the meta-analysis. During cardiac surgery, the use of an
intraoperative cell saver reduced the rate of exposure to any allogeneic blood
product (OR 0.63, 95% CI: 0.43-0.94, P = 0.02) and red blood cells (OR 0.60, 95% 
CI: 0.39-0.92, P = 0.02) and decreased the mean volume of total allogeneic blood 
products transfused per patient (WMD -256 mL, 95% CI: -416 to -95 mL, P = 0.002).
There was no difference in hospital mortality (OR 0.65, 95% CI: 0.25-1.68, P =
0.37), postoperative stroke or transient ischemia attack (OR 0.59, 95% CI:
0.20-1.76, P = 0.34), atrial fibrillation (OR 0.92, 95% CI: 0.69-1.23, P = 0.56),
renal dysfunction (OR 0.86, 95% CI: 0.41-1.80, P = 0.70), infection (OR 1.25, 95%
CI: 0.75-2.10, P = 0.39), patients requiring fresh frozen plasma (OR 1.16, 95%
CI: 0.82-1.66, P = 0.40), and patients requiring platelet transfusions (OR 0.90, 
95% CI: 0.63-1.28, P = 0.55) between cell saver and noncell saver groups.
CONCLUSIONS: Current evidence suggests that the use of a cell saver reduces
exposure to allogeneic blood products or red blood cell transfusion for patients 
undergoing cardiac surgery. Subanalyses suggest that a cell saver may be
beneficial only when it is used for shed blood and/or residual blood or during
the entire operative period. Processing cardiotomy suction blood with a cell
saver only during cardiopulmonary bypass has no significant effect on blood
conservation and increases fresh frozen plasma transfusion.

J Card Surg. 2009 Jul-Aug;24(4):397-403.

Influence of methylprednisolone on levels of neuron-specific enolase in cardiac
surgery: a corticosteroid derivative to decrease possible neuronal damage.

Demir T, Demir H, Tansel T, Kalko Y, Tireli E, Dayioglu E, Barlas S, Onursal E.

Department of Cardiovascular Surgery, Istanbul Medical Faculty, Istanbul
University, Capa, Istanbul, Turkey. dr.tolgademir@gmail.com

BACKGROUND: Cerebral injury is a well-known complication after cardiac surgery
with cardiopulmonary bypass (CPB), especially in adult patients. Specific
biochemical markers like neuron-specific enolase (NSE) and S-100beta protein were
developed previously for early detecting neuronal damage after CPB.
Corticosteroids are shown to reduce multisystemic deleterious effects of
cardiopulmonary bypass due to their anti-inflammatory characteristics. The aim of
this study is to demonstrate the decrease of serum neuron-specific enolase levels
in patients who received corticosteroids before CPB. METHODS: Thirty patients
scheduled for elective coronary bypass surgery were included in the study.
Patients were divided randomly into two groups as the control group (n = 15) who 
underwent a standard coronary bypass surgery without any additional medication
and the study group (n = 15) who received 1 gm of methylprednisolone before CPB. 
Blood samples for analysis of serum NSE, interleukin-6 (IL-6), and IL-10 were
drawn before CPB, 4 and 24 hours after the end of extracorporeal circulation.
RESULTS: Serum cytokine and NSE levels were significantly increased after CPB
above their normal range in both groups. In the study group, IL-6 and NSE levels 
were significantly reduced while IL-10 levels were much higher after CPB. High
NSE levels significantly correlated with IL-6 levels in the control group.
CONCLUSION: The lower levels of NSE in patients who received methylprednisolone
may suggest that corticosteroids might be useful in decreasing possible neuronal 
damage during heart surgery. However, we were not able to demonstrate an adverse 
neurological outcome.

Eur J Cardiothorac Surg. 2009 Jul 4. [Epub ahead of print]

Preoperative statin treatment reduces systemic inflammatory response and
myocardial damage in cardiac surgery.

Martínez-Comendador JM, Alvarez JR, Mosquera I, Sierra J, Adrio B, Carro JG,
Fernández A, Bengochea J.

Department of Cardiovascular Surgery, University Hospital Santiago de Compostela,
Spain.

Objective: To determine if preoperative statin treatment is associated with a
reduction in systemic inflammatory response (SIR) and myocardial damage markers
following cardiac surgery with cardiopulmonary bypass (CPB). Methods: We study a 
prospective cohort of 138 patients who underwent coronary and valvular surgery
with CPB. We differentiate two study groups: patients with (group A, n=72) or
without (group B, n=66) statins. Plasma levels of pro-inflammatory interleukins
(tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8 and IL-2R),
creatine phosphokinase (CPK), CPK-MB and troponin I were measured before and 1,
6, 24 and >72h after surgery. Results: The baseline, operative and postoperative 
morbidity and mortality characteristics were similar for both the groups. Group A
had significantly lower postoperative levels of IL-6 than group B at 6h
(68.8+/-5pgml(-1) vs 108.9+/-108pgml(-1), p=0.01), 24h (71.7+/-7pgml(-1) vs
110.4+/-106pgml(-1), p=0.01) and before hospital discharge (21.6+/-12pgml(-1) vs 
32.8+/-27pgml(-1), p=0.005), as well as significantly lower average IL-6 levels
in the first 24h following surgery (71.8+/-5 pgml(-1) vs 112.8+/-82pg ml(-1),
p=0.002). The postoperative CPK-MB at 24h (19.7+/-23ngml(-1) vs
33.1+/-32ngml(-1), p=0.02) and troponin I levels at the end of the intervention
(2.2+/-2.2ngml(-1) vs 3.3+/-3.1ngml(-1), p=0.03) and at 24h (4.1+/-3.5ngml(-1) vs
6.6+/-8ngml(-1), p=0.04) were also significantly lower in the group treated with 
statins prior to surgery. Conclusions: Preoperative treatment with statins is
associated with a lower biochemical parameters of SIR and myocardial damage
following cardiac surgery with CPB, regardless of it being coronary bypass
grafting (CABG) or valvular surgery.