Psychosom Med. 2007 Aug 27; [Epub ahead of print]

Anxiety Predicts Mortality and Morbidity After Coronary Artery and Valve Surgery 
A 4-Year Follow-Up Study.

Székely A, Balog P, Benkö E, Breuer T, Székely J, Kertai MD, Horkay F, Kopp MS,
Thayer JF.

Department of Anesthesia and Intensive Care (A.S.), Department of Rehabilitation 
Care (E.B.), Research Department (T.B.), Department of Cardiac Surgery (F.H.),
Gottsegen György Hungarian Institute of Cardiology, Budapest, Hungary; Institute 
of Behavioral Sciences (P.B., M.S.K.), School of Ph.D. Studies (T.B.), Department
of Anesthesia (M.D.K.), Semmelweis University, Budapest, Hungary; Department of
Radiotherapy (J.S.), Mannheim Institute of Public Health, Heidelburg University, 
Mannheim, Germany; and Department of Psychology (F.H., J.F.T.), Ohio State
University, Columbus, Ohio.

Objective: To explore the long-term effect of anxiety and depression on outcome
after cardiac surgery. To date, the relationship between psychosocial factors and
future cardiac events has been investigated mainly in population-based studies,
in patients after cardiac catheterization or myocardial infarction. Methods: In
total, 180 patients who underwent cardiac surgery using cardiopulmonary bypass
were prospectively studied and followed up for 4 years. Anxiety (Spielberger
State-Trait Anxiety Inventory, STAI-S/STAI-T), depression (Beck Depression
Inventory, BDI), living alone, and education level along with clinical risk
factors and perioperative characteristics were assessed. Psychological
self-report questionnaires were completed preoperatively and 6, 12, 24, 36, and
48 months after discharge. Clinical end-points were mortality and cardiac events 
requiring hospitalization during follow-up. Results: Average preoperative STAI-T 
score was 44.6 +/- 10. Kaplan-Meier analysis showed a significant effect of
preoperative STAI-T >45 points (p = .008) on mortality. In multivariate models,
postoperative congestive heart failure (OR: 10.8; 95% confidence interval
[CI]:2.9-40.1; p = .009) and preoperative STAI-T (score OR: 1.07; 95% CI:
1.01-1.15; p = .05) were independently associated with mortality. The occurrence 
of cardiovascular hospitalization was independently associated with postoperative
intensive care unit days (OR: 1.41; 95% CI: 1.01-1.96; p = .045) and post
discharge 6th month STAI-T (OR: 1.06; 95% CI:1.01-1.13; p = .03). Conclusions:
The results of the present study suggest that the assessment of psychosocial
factors, particularly the ongoing assessment of anxiety, could help in risk
stratification and identification of patients at risk of mortality and
cardiovascular morbidity after cardiac surgery.

Thromb Haemost. 2007 Aug;98(2):385-391.

Platelet dysfunction after normothermic cardiopulmonary bypass in children:
Effect of high-dose aprotinin.

Flaujac C, Pouard P, Boutouyrie P, Emmerich J, Bachelot-Loza C, Lasne D.

Département d’hématologie Biologique, Hôpital Necker, 149 rue de Sèvres, 75743
Paris cedex 15, France. E-mail: dom.lasne@nck.aphp.fr.

Platelet dysfunction after cardiopulmonary bypass (CPB) can contribute to
excessive post-operative bleeding. Most trials of the protective effect of
aprotinin in this setting have involved hypothermic CPB, which is more
deleterious for platelets than normothermic CPB. Here we investigated the effect 
of aprotinin on platelet function during normothermic CPB in pediatric patients. 
Twenty patients (9 newborns [<1 month old] and 11 infants [<36 month old]),
weighting less than 15 kg and undergoing normothermic CPB (35-36 degrees C) were 
randomly assigned to two equal groups, one of which received high-dose aprotinin.
Platelet function was assessed by flow cytometry just before CPB and 5 minutes
after heparin neutralization. F1 + 2 fragments were measured by ELISA before and 
5 minutes after CPB. Platelet activation marker expression (CD62P and activated
alphaIIbbeta3) induced by ADP or TRAP was lower after CPB than before CPB,
suggesting a deleterious effect of normothermic CPB on platelet function.
Prothrombin fragment F1 + 2 levels increased after CPB. Aprotinin administration 
did not influence the level of prothrombin fragments or platelet marker
expression measured in basal condition. However, after CPB, the capacity for
platelet activation was higher in the aprotinin group, as shown by measuring
CD62P expression after TRAP activation (p = 0.05). This study suggests that
pediatric normothermic CPB causes platelet dysfunction, and that high-dose
aprotinin has a protective effect.

Acta Anaesthesiol Scand. 2007 Aug 20; [Epub ahead of print]

Limitations of arterial pulse pressure variation and left ventricular stroke
volume variation in estimating cardiac pre-load during open heart surgery*

Rex S, Schälte G, Schroth S, de Waal EE, Metzelder S, Overbeck Y, Rossaint R,
Buhre W.

Department of Anaesthesiology, University Hospital, Rheinisch-Westfälische
Technische Hochschule Aachen, Aachen, Germany.

Background: In addition to their well-known ability to predict fluid
responsiveness, functional pre-load parameters, such as the left ventricular
stroke volume variation (SVV) and pulse pressure variation (PPV), have been
proposed to allow real-time monitoring of cardiac pre-load. SVV and PPV result
from complex heart-lung interactions during mechanical ventilation. It was
hypothesized that, under open-chest conditions, when cyclic changes in pleural
pressures during positive-pressure ventilation are less pronounced, functional
pre-load indicators may be deceptive in the estimation of ventricular pre-load.
Methods: Forty-five patients undergoing coronary artery bypass grafting
participated in this prospective, observational study. PPV and SVV were assessed 
by pulse contour analysis. The thermodilution technique was used to measure the
stroke volume index and global and right ventricular end-diastolic volume index. 
Trans-oesophageal echocardiography was used to determine the left ventricular
end-diastolic area index. All parameters were assessed before and after
sternotomy, and, in addition, after weaning from cardiopulmonary bypass before
and after chest closure (pericardium left open). Patients were ventilated with
constant tidal volumes (8 +/- 2 ml/kg) throughout the study period using pressure
control. Results: SVV and PPV decreased after sternotomy and increased after
chest closure. However, these changes could not be related to concomitant changes
in the ventricular pre-load. The stroke volume index was correlated with SVV and 
PPV in closed-chest conditions only, whereas volumetric indices reflected cardiac
pre-load in both closed- and open-chest conditions. SVV and PPV were correlated
with left and right ventricular pre-load in closed-chest-closed-pericardium
conditions only (with the best correlation found for the right ventricular
end-diastolic volume index). Conclusions: SVV and PPV may be misleading when
estimating cardiac pre-load during open heart surgery.

Crit Care. 2007 Aug 14;11(4):R87 [Epub ahead of print]

Influence of dextran-70 on systemic inflammatory response and myocardial
ischaemia - reperfusion following cardiac operations.

Gombocz K, Beledi A, Alotti N, Kecskes G, Gabor V, Bogar L, Koszegi T, Garai J.

ABSTRACT: INTRODUCTION: Experimental studies have justified that dextran-70
reduces the leukocyte - endothelium interaction, but clinical evidence is still
lacking. Our objective was to justify its anti-inflammatory effect following
cardiac operations. METHODS: Forty patients undergoing coronary bypass surgery
(n=32) or aortic valve replacement (n=8) had been enrolled in this prospective,
randomized, double blind study. Two groups were formed. In group A (n=20),
dextran-70 infusion was administered at a dose of 7.5 ml/kg before the
initiation, and of 12.5 ml/kg after the cessation of cardiopulmonary bypass.
Group B served as a control with identical amounts of gelatin infusion (n=20).
Plasma concentration of procalcitonin, C-reactive protein, interleukin 6,
interleukin 6r, interleukin 8, interleukin 10, soluble endothelial leukocyte
adhesion molecule-1, soluble intercellular adhesion molecule-1, cardiac
troponin-I and various haemodynamic parameters were measured in the perioperative
period. Multivariate methods were used for statistical analysis. RESULTS: In
group A lower peak (median) plasma levels of procalcitonin (0.2 vs.1.4; p<0.001),
interleukin 8 (5.6 vs. 94.8; p<0.001), interleukin 10 (47.2 vs. 209.7; p=0.001), 
endothelial leukocyte adhesion molecule-1 (88.5 vs. 130.6; p=0.033),
intercellular adhesion molecule-1 (806.7 vs. 1375.7; p=0.001) and troponin-I
(0.22 vs. 0.66; p=0.018) were found. There was no significant difference in
interleukin 6, interleukin -6r and C-reactive protein values, between groups.
Higher figures of cardiac index (p=0.010) along with reduced systemic vascular
resistance (p=0.005) were noted in group A. CONCLUSION: Our investigation has
demonstrated that the use of dextran-70 reduces the systemic inflammatory
response and cardiac troponin-I release following cardiac operation. Trial
registration: ISRCTN38289094.

J Heart Lung Transplant. 2007 Aug;26(8):850-6.

Resolution of severe ischemia-reperfusion injury post-lung transplantation after 
administration of endobronchial surfactant.

Kermeen FD, McNeil KD, Fraser JF, McCarthy J, Ziegenfuss MD, Mullany D, Dunning
J, Hopkins PM.

Queensland Heart-Lung Transplant Unit, The Prince Charles Hospital, Brisbane,
Queensland, Australia. fiona_keerman@health.qld.gov.au

BACKGROUND: Ischemia-reperfusion injury (IRI) is a prominent cause of primary
graft failure after lung transplantation and is associated with an altered
surfactant profile. Experimental animal studies have found that replacement with 
exogenous surfactant administered via fiber-optic bronchoscopy (FOB) enhanced
recovery from IRI with improved pulmonary compliance and gas exchange after lung 
transplantation. We report our clinical experience with FOB instillation of
surfactant in severe IRI after human lung transplantation. METHODS: This study is
a retrospective review of 106 consecutive lung or heart-lung transplants
performed at a single institution. Severe IRI was defined as diffuse
roentgenographic alveolar infiltrates, worsening hypoxemia and decreased lung
compliance within 72 hours of lung transplantation. One vial of surfactant (20
mg/ml phospholipid) was instilled into each segmental bronchus upon diagnosis of 
IRI. RESULTS: Six patients (5 bilateral sequential and 1 re-do heart-lung
transplant), mean age 46 years, were diagnosed with IRI and surfactant was
administered at a mean of 37 hours (range 2.3 to 98) post-transplant. Mean graft 
ischemia time was 376 minutes (range 187 to 625) and cardiopulmonary bypass time 
174 minutes (range 0 to 210). Mean Pao(2) [mm Hg]/Fio(2) ratio before and 48
hours after surfactant instillation was 70 and 223, respectively. Significant
resolution of radiologic infiltrates was evident in all cases within 24 hours.
Successful extubation occurred at a mean of 13.5 days and survival is presently
100% at 19 months (range 3 to 54). CONCLUSIONS: Bronchoscopic instillation of
surfactant improves oxygenation and prognosis after severe IRI in lung transplant
recipients. It represents a cost-effective, relatively non-invasive therapeutic
alternative to extracorporeal membrane oxygenation.

Eur J Cardiothorac Surg. 2007 Aug 7; [Epub ahead of print]

Glycopeptide pharmacokinetics in current paediatric cardiac surgery practice.

Shime N, Kato Y, Kosaka T, Kokufu T, Yamagishi M, Fujita N.

Department of Intensive Care and Anaesthesiology, Kyoto Prefectural University of
Medicine, Kyoto, Japan; Department of Infection Control and Prevention, Kyoto
Prefectural University of Medicine, Kyoto, Japan.

Objective: To examine the evolution of serum concentrations of prophylactic
glycopeptides administered during state-of-the-art cardiopulmonary bypass (CPB)
and vigorous haemodiafiltration in paediatric patients undergoing cardiac
surgery. Methods: We enrolled infants and children <3 years of age who, based on 
the preoperative microbiological screening, age and surgical complexity, were at 
high risk of methicillin-resistant Staphylococcus aureus (MRSA) infection.
Antimicrobial prophylaxis with glycopeptides was administered to 22 patients,
randomly assigned to vancomycin (VAN; n=11) versus teicoplanin (TEC; n=11). Fixed
doses of each drug (15mg/kg for VAN and 8mg/kg for TEC) were administered
immediately before the operation, at the time of priming of the extracorporeal
circuit, upon admission to the intensive care unit and for 48h thereafter, q. 8h 
for VAN, and once daily for TEC. Vigorous haemodiafiltration was applied during
and briefly after CPB. Results: The second dose of drug added to the prime
prevented a fall in serum drug concentrations at the onset of CPB in both groups.
A 77% decrease in VAN, versus 53% in TEC concentrations, was observed after the
conclusion of CPB. Serum concentrations of TEC>10mug/ml were observed throughout 
the treatment period in 91% of patients, while 55% of patients assigned to VAN
had serum concentrations consistently >5mug/ml (p=0.08). Therapeutic serum
concentrations were maintained throughout the intraoperative period, particularly
with TEC, administered before the first surgical incision, followed by a
supplemental bolus in the priming fluid of CPB. Postoperative surgical wound
infections occurred in neither group. Conclusions: The prophylactic use of
glycopeptides in paediatric patients at high risk of MRSA infection undergoing
cardiac surgery was safe and effective. TEC might be the drug of choice, since
stable, therapeutic serum concentrations were easily maintained throughout the
treatment period.

J Cardiothorac Vasc Anesth. 2007 Aug;21(4):529-34. Epub 2007 Apr 5.

Improved neurologic outcome after implementing evidence-based guidelines for
cardiac surgery.

Suojaranta-Ylinen RT, Roine RO, Vento AE, Niskanen MM, Salmenperä MT.

Department of Anesthesia and Intensive Care Medicine, Helsinki University
Hospital, Helsinki, Finland.

Objective: A high incidence of neurologic complications was observed in the year 
2001 in cardiac surgical patients in this department. This article attempts to
show the impact of changing and optimizing management protocols on the incidence 
of neurologic morbidity after cardiac surgery. Design: An observational study of 
cardiac surgical patients. Setting: University hospital. Participants: All
cardiac surgical patients treated postoperatively in the cardiac surgical ICU in 
2001 (n = 1,165, control group) and in 2003 (n = 1,222, intervention group) were 
evaluated. Interventions: A quality improvement program started at the beginning 
of 2002, based on the Task Force Committee Guidelines, included surgical and
cardiopulmonary bypass recommendations as well as peri- and postoperative care
(eg, use of epiaortic echo and strict perfusion protocol, avoidance of
hyperthermia and hyperglycemia, and minimization of cerebral edema). Results: The
number of neurologic complications decreased from 78 (6.7%) in 2001 to 33 (2.7%) 
in 2003 (p < 0.01), and corresponding numbers for ICU mortality were 44 (3.8%)
and 24 (2.0%) (p < 0.01). The length of ICU stay also decreased (3.2 +/- 4.5 days
in 2001 v 2.9 +/- 5.5 days in 2003, p < 0.001). In 2001, patients with neurologic
complications consumed 853 ICU patient days (23% of all ICU patient days) and, in
2003, 549 (15% of all ICU patient days). According to logistic regression
analysis that included 11 independent variables (treatment year, EuroSCORE,
diabetes mellitus, history of stroke, and 7 different types of surgery),
treatment in 2003 was independently associated with decreased risk for neurologic
complications (odds ratio 0.30, 95% confidence intervals 0.19-0.47, p < 0.001).
Conclusions: The occurrences of neurologic complications, mortality, and ICU
resource consumption by this patient group decreased after implementation of an
optimized management protocol and evidence-based guidelines.

Ann Surg. 2007 Aug;246(2):323-9.

Predictors and outcome of gastrointestinal complications in patients undergoing
cardiac surgery.

Filsoufi F, Rahmanian PB, Castillo JG, Scurlock C, Legnani PE, Adams DH.

Department of Cardiothoracic Surgery, Mount Sinai School of Medicine, New York,
NY 10029, USA. farzan.filsoufi@mountsinai.org

OBJECTIVE: To determine the incidence and independent predictors of
gastrointestinal complications (GICs) following cardiac surgery. SUMMARY
BACKGROUND DATA: Gastrointestinal ischemia and hemorrhage represent a rare but
devastating complication following heart surgery. The profile of patients
referred for cardiac surgery has changed during the last decade, questioning the 
validity of previously reported incidence and risk factors. METHODS: We
retrospectively analyzed prospectively collected data from 4819 patients
undergoing cardiac surgery between 1998 and 2004. Patients with GICs were
compared with the entire patient population. Study endpoints were mortality,
postoperative morbidities, and long-term survival. RESULTS: GICs occurred in 51
(1.1%) patients. Etiologies were intestinal ischemia (n = 30; 59%) and hemorrhage
(n = 21; 41%). The incidence decreased during the study period (1998-2001: 1.3%, 
2002-2004: 0.7%; P = 0.04). The incidence per type of procedure was as follows:
coronary artery bypass grafting (CABG)/valve (2.4%), aortic surgery (1.7%), valve
surgery (1.0%), and CABG (0.5%; P = 0.001). Multivariate analysis revealed age
(odds ratio [OR] = 2.1), myocardial infarction (OR = 2.5), CHF (OR = 2.4),
hemodynamic instability (OR = 2.8), cardiopulmonary bypass time >120 minutes (OR 
= 6.2), peripheral vascular disease (OR = 2.2), renal (OR = 3.2), and hepatic
failure (OR = 10.8) as independent predictors of GICs. The overall hospital
mortality among patients with GICs was 33%. Long-term survival was significantly 
decreased in patients with GICs compared with the control group. CONCLUSIONS:
Gastrointestinal complications following cardiac surgery remain rare with an
incidence <1% in a contemporary series. The key to a lower incidence of GICs lies
in systematic application of preventive measures and new advances in
intraoperative management. Identification of independent risk factors would
facilitate the determination of patients who would benefit from additional
perioperative monitoring. Future resources should therefore be redirected to
mitigate GICs in high-risk patients.

J Thorac Cardiovasc Surg. 2007 Aug;134(2):319-26.

Pharmacokinetics and safety of intravenously administered citrulline in children 
undergoing congenital heart surgery: potential therapy for postoperative
pulmonary hypertension.

Barr FE, Tirona RG, Taylor MB, Rice G, Arnold J, Cunningham G, Smith HA, Campbell
A, Canter JA, Christian KG, Drinkwater DC, Scholl F, Kavanaugh-McHugh A, Summar
ML.

Department of Pediatrics, Pediatric Critical Care, Vanderbilt Children's
Hospital, Vanderbilt University Medical Center, Nashville, Tenn, USA.
rick.barr@vanderbilt.edu

OBJECTIVE: Pulmonary hypertension may complicate surgical correction of
congenital heart defects, resulting in increased morbidity and mortality. We have
previously shown that plasma levels of the nitric oxide precursors citrulline and
arginine drop precipitously after congenital cardiac surgery and that oral
citrulline supplementation may be protective against the development of pulmonary
hypertension. In this study, we assessed the safety and pharmacokinetic profile
of intravenous citrulline as a potential therapy for postoperative pulmonary
hypertension. METHODS: The initial phase of this investigation was a
dose-escalation study of intravenously administered citrulline in infants and
children undergoing one of five congenital cardiac surgical procedures (phase 1).
The primary safety outcome was a 20% drop in mean arterial blood pressure from
the baseline pressure recorded after admission to the intensive care unit. Based 
on our previous work, the target circulating plasma citrulline trough was 80 to
100 micromol/L. Each patient was given two separate doses of citrulline: the
first in the operating room immediately after initiation of cardiopulmonary
bypass and the second 4 hours later in the pediatric intensive care unit.
Stepwise dose escalations included 50 mg/kg, 100 mg/kg, and 150 mg/kg. After
model-dependent pharmacokinetic analysis, we enrolled an additional 9 patients
(phase 2) in an optimized dosing protocol that replaced the postoperative dose
with a continuous infusion of citrulline at 9 mg/(kg.h) for 48 hours
postoperatively. RESULTS: The initial stepwise escalation protocol (phase 1)
revealed that an intravenous citrulline dose of 150 mg/kg given after initiation 
of cardiopulmonary bypass yielded a trough level of in the target range of
approximately 80 to 100 micromol/L 4 hours later. The postoperative dose revealed
that the clearance of intravenously administered citrulline was 0.6 L/(h.kg),
with a volume of distribution of 0.9 L/kg and estimated half-life of 60 minutes. 
Because of the short half-life, we altered the protocol to replace the
postoperative dose with a continuous infusion of 9 mg/(kg.h). An additional 9
patients were studied with this continuous infusion protocol (phase 2). Mean
plasma citrulline levels were maintained at approximately 125 mumol/L, with a
calculated clearance of 0.52 L/(h.kg). None of the 17 patients studied had a 20% 
drop in mean arterial blood pressure from baseline. CONCLUSIONS: In this first
report of the use of intravenous citrulline in humans, we found citrulline to be 
both safe and well tolerated in infants and young children undergoing congenital 
cardiac surgery. Because of the rapid clearance, the optimal dosing regimen was
identified as an initial bolus of 150 mg/kg given at the initiation of
cardiopulmonary bypass, followed 4 hours later by a postoperative infusion of 9
mg/(kg.h) continued up to 48 hours. Using this regimen, plasma arginine,
citrulline, and nitric oxide metabolite levels were well maintained. Intravenous 
citrulline needs to be studied further as a potential therapy for postoperative
pulmonary hypertension.

Anesth Analg. 2007 Aug;105(2):335-43.

Comment in:
    Anesth Analg. 2007 Aug;105(2):301-3.

The frequency of anesthesia-related cardiac arrests in patients with congenital
heart disease undergoing cardiac surgery.

Odegard KC, DiNardo JA, Kussman BD, Shukla A, Harrington J, Casta A, McGowan FX
Jr, Hickey PR, Bacha EA, Thiagarajan RR, Laussen PC.

Department of Anesthesiology, Perioperative and Pain Medicine, Children's
Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
kirsten.odegard@childrens.harvard.edu

BACKGROUND: The frequency of anesthesia-related cardiac arrests during pediatric 
anesthesia has been reported between 1.4 and 4.6 per 10,000 anesthetics. ASA
physical status >III and younger age are risk factors. Patients with congenital
cardiac disease may also be at increased risk. Therefore, in this study, we
evaluated the frequency of cardiac arrest in patients with congenital heart
disease undergoing cardiac surgery at a large pediatric tertiary referral center.
METHODS: Using an established data registry, all cardiac arrests from January
2000 through December 2005 occurring in the cardiac operating rooms were
reviewed. A cardiac arrest was defined as any event requiring external or
internal chest compressions, with or without direct cardioversion. Events
determined to be anesthesia-related were classified as likely related or possibly
related. RESULTS: There were 41 cardiac arrests in 40 patients (median age, 2.9
mo; range, 2 days to 23 yr) during 5213 anesthetics over the time period, for an 
overall frequency of 0.79%; 78% were open procedures requiring cardiopulmonary
bypass and 22% closed procedures not requiring cardiopulmonary bypass. Eleven
cardiac arrests (26.8%) were classified as either likely (n = 6) or possibly
related (n = 5) to anesthesia, (21.1 per 10,000 anesthetics) but with no
mortality; 30 were categorized as procedure-related. The incidence of
anesthesia-related and procedure-related cardiac arrests was highest in neonates 
(P < 0.001). There was no association with year of event or experience of the
anesthesiologist. CONCLUSION: The frequency of anesthesia-related cardiac arrest 
in patients undergoing cardiac surgery is increased, but is not associated with
an increase in mortality. Neonates and infants are at higher risk. Careful
preparation and anticipation is important to ensure timely and effective
resuscitation.