Intensive Care Med  2002 Aug;28(8):1094-102 

Early increase of procalcitonin after cardiovascular surgery in patients with
postoperative complications.

Meisner M, Rauschmayer C, Schmidt J, Feyrer R, Cesnjevar R, Bredle D,
Tschaikowsky K.

Department of Anaesthesiology and Intensive Care Medicine,
Friedrich-Schiller-Universitat Jena, Bachstrasse 18, 07743 Jena, Germany,
michael.meisner@t-online.de

OBJECTIVE. Type and frequency of postoperative abnormalities were registered
after cardiovascular surgery to evaluate the aetiology and diagnostic value of
increased concentrations of procalcitonin (PCT) and C-reactive protein (CRP)
during the early postoperative period. DESIGN. Prospective, observational study.
PATIENTS. Two hundred and eight patients undergoing coronary artery bypass
grafting or valve replacement requiring cardiopulmonary bypass were monitored
for 7 days postoperatively for various types of infectious or non-infectious
complications. Plasma PCT and CRP levels were measured on day 1 and day 2 after
surgery and, when increased, until day 7. 
RESULTS. More patients with PCT above
2 ng/ml on day 1 or 2 ( n=55) had postoperative abnormalities (95%) than
patients with lower PCT (59%). Specifically, the incidence of three or more
criteria of the "systemic inflammatory response syndrome" was 45% versus 4%
(area under the curve of the receiver operating characteristic 0.866); positive
inotropic support was needed in 65% versus 9% (0.870); respiratory insufficiency
(PaO(2)/FIO(2)<200) 38% versus 12% (0.704); proven and suspected bacterial
infection 9% versus 1% (0.900) and 24% versus 1% (0.897), respectively. For CRP,
the respective areas under the curve were all below 0.63, while all patients had
elevated CRP levels, whether they had a complication or not. 
CONCLUSIONS.
Elevated PCT, but not CRP, correlates with evidence of systemic inflammation and
other complications early postoperatively after cardiac surgery. Although the
PCT levels do not rise as quickly as the criteria of the systemic inflammatory
response syndrome appear, they do reflect systemic inflammation. Early
identification and quantification of a systemic inflammatory response may help
reduce postoperative complications.

Ann Thorac Surg  2002 Aug;74(2):426-31; discussion 431 

Influence of retrograde cerebral perfusion during aortic arch procedures.

Moon MR, Sundt TM 3rd.

Division of Cardiothoracic Surgery, Washington University School of Medicine,
St. Louis, Missouri 63110-1013, USA. moonm@msnotes.wustl.edu

BACKGROUND: Recent reports suggest dramatic improvement in outcome using
retrograde cerebral perfusion (RCP) during operations on the arch; however, most
investigators have compared contemporary results with historic controls. The
purpose of this study was to determine the impact of RCP within the same patient
population and time period. 
METHODS: From 1996 to 2000, 72 consecutive patients
underwent an aortic arch procedure using hypothermic circulatory arrest (HCA)
(31 acute dissection or rupture, 41 chronic dissection or aneurysm).
Supplemental RCP was used in 36 patients, whereas 36 patients had HCA alone. The
groups were similar in age, emergent status, and cardiopulmonary bypass time (p
> 0.08), but HCA time was higher with RCP (40 +/- 15 minutes versus 29 +/- 14
minutes; p < 0.001). 
RESULTS: Operative mortality was 10% +/- 4% (+/- 70%
confidence limit), and adverse outcomes (death or cerebrovascular accident)
occurred in 14% +/- 4%, but there was no difference between HCA alone (8% +/-
5%, 14% +/- 6%) and HCA with RCP (11% +/- 5%, 14% +/- 6%) (p > 0.73). The
incidence of transient neurologic dysfunction was also similar (HCA alone, 11%
+/- 5%; HCA with RCP, 17% +/- 6%; p > 0.73). Multivariate risk factors for
mortality included emergency operation and HCA time (p < 0.02). Risk factors for
adverse outcome included emergency operation and atheromatous ascending aorta (p
< 0.03). Risk factors for transient neurologic dysfunction included preexisting
cerebrovascular disease and rewarming retrograde (femoral) rather than antegrade
(through the graft) (p < 0.03). 
CONCLUSIONS: Supplemental RCP during HCA did not
decrease mortality or neurologic complications. Retrograde rewarming through the
femoral artery after completion of the distal anastomosis increased transient
neurologic dysfunction. Therefore, RCP remains optional, but reperfusion should
be antegrade to improve neurologic recovery.

Ann Thorac Surg  2002 Aug;74(2):394-9 

Stroke after conventional versus minimally invasive coronary artery bypass.

Stamou SC, Jablonski KA, Pfister AJ, Hill PC, Dullum MK, Bafi AS, Boyce SW,
Petro KR, Corso PJ.

Department of Surgery, Washington Hospital Center, and MedStar Research
Institute, DC 20010, USA.

BACKGROUND: Postoperative stroke is a serious complication after coronary artery
bypass grafting with cardiopulmonary bypass (on-pump), and portends higher
morbidity and mortality. It is unknown whether an off-pump cardiopulmonary
bypass (OPCAB) approach may yield a lower stroke rate over conventional on-pump
coronary artery bypass grafting. 
METHODS: From June 1994 to December 2000, OPCAB
was performed in 2,320 patients and compared with 8,069 patients who had on-pump
coronary artery bypass grafting, during the same period of time. The patients
undergoing OPCAB were randomly matched to on-pump patients by propensity score.
A logistic regression model was used to test the difference in the postoperative
stroke rate between OPCAB and on-pump procedures controlling for the correlation
between matched sets. A multiple logistic regression model predicting the risk
of stroke adjusted by stroke risk factors and operation type was also computed.
RESULTS: Matches by propensity score were found for 72% of the patients
undergoing OPCAB. Patients undergoing on-pump coronary artery bypass grafting
were 1.8 (95% confidence interval 1.0 to 3.1, p = 0.03) times more likely to
suffer a stroke postoperatively than OPCAB patients after controlling for
preoperative risk factors through matching. Independent predictors of stroke
identified from the multiple logistic model included on-pump operation (versus
OPCAB operation), female gender, 4 to 6 vessels grafted (versus <4 grafts),
hypertension, history of previous cerebrovascular accident, carotid artery
disease, chronic obstructive pulmonary disease, and depressed ejection fraction.
CONCLUSIONS: Off-pump cardiopulmonary bypass avoids the risks of cardiopulmonary
bypass and atrial trauma. A substantially lower stroke rate suggests that OPCAB
is a neurologically safe treatment option for revascularization.

Ann Thorac Surg  2002 Aug;74(2):390-3; discussion 393 

Is the kaolin or celite activated clotting time affected by tranexamic acid?

Bechtel JF, Prosch J, Sievers HH, Bartels C.

Department of Cardiac Surgery, University Hospital of Luebeck, Germany.

BACKGROUND: During cardiopulmonary bypass, the activated clotting time is
frequently used for determination of anticoagulation, and either Celite or
kaolin are used as activators. If aprotinin is administered concomitantly, the
Celite activated clotting time (C-ACT) becomes significantly higher than the
kaolin activated clotting time (K-ACT). Therefore, insufficient anticoagulation
using C-ACT in the presence of aprotinin is a major concern. Whether the
application of tranexamic acid (TA), a pharmacologic alternative to aprotinin,
has similar effects has not been studied before. 
METHODS: An in vitro study
using the blood of healthy volunteers was performed. Both C-ACT and K-ACT were
measured at baseline, after adding TA, and after adding TA and heparin. In
addition, 30 patients undergoing primary cardiac operations had simultaneous
measurements of C-ACT and K-ACT after skin-incision, 5 minutes after the
application of heparin and TA, every 30 minutes during cardiopulmonary bypass,
and 10 minutes after the application of protamine. 
RESULTS: In vitro, C-ACT and
K-ACT correlated significantly at each measurement. Tranexamic acid had no
influence on the activated clotting time. In vivo, C-ACT and K-ACT did not
differ significantly, but at each time C-ACT tended to be greater than K-ACT (p
= 0.086). The average difference between K-ACT and C-ACT was stable before and
after the application of TA (p = 0.85) but the variability of the differences
significantly increased during cardiopulmonary bypass (p < 0.001). 
CONCLUSIONS:
Application of TA does not seem to differentially affect the mean C-ACT and
K-ACT. No recommendation seems warranted to prefer one activator over the other
in patients receiving TA.

Crit Care Med  2002 Aug;30(8):1712-6 

Soluble tumor necrosis factor receptor p55 predicts cytokinemia and systemic
inflammatory response after cardiopulmonary bypass.

ElBarbary M, Khabar KS.

Departments of Cardiovascular Diseases (MEB).

OBJECTIVES: To examine the behavior of soluble tumor necrosis factor (TNF)
receptors in circulation before and after cardiopulmonary bypass and the
relationship to the development of cytokinemia and acute complications
comprising systemic inflammatory response syndrome (SIRS) and multiple organ
dysfunction syndrome (MODS). The predictive value of soluble TNF receptor is
assessed herein. 
DESIGN: Prospective study comparing prebypass and postbypass
levels in patients with and without complications indicative of SIRS and MODS.
SETTING: Cardiac surgical intensive care unit in a tertiary care hospital.
PATIENTS: A total of 20 pediatric patients who underwent cardiopulmonary bypass
during open heart surgery. 
INTERVENTIONS: Blood samples were collected from
catheters before and 2 hrs and 24 hrs after the onset of bypass. 
MEASUREMENTS
AND MAIN RESULTS: We measured plasma levels of soluble TNF receptors by using
enzyme-linked immunosorbent assay in 20 patients before and after
cardiopulmonary bypass. Clinical data, including duration of bypass and tests or
signs indicative of SIRS/MODS, were collected. Soluble TNF receptor I (p55 sR),
significantly increased (2241 +/- 312 pg/mL) at 2 hrs after bypass (p <.0005)
and remained elevated (2826 +/- 695 pg/mL) at 1 day after bypass (p <.005) when
compared with prebypass levels (725 +/- 130 pg/mL). Patients with the acute
complications of SIRS/MODS had a higher ratio of postbypass to prebypass p55 sR
levels (5.0-fold, p <.001) when compared with patients with no SIRS/MODS
(1.75-fold). Remarkably, before surgery, levels of TNF p55 sR predict both
cytokinemia (r =.67 to.73, p <.05) and SIRS/MODS (p <.01). The prebypass levels
of TNF p55 sR were consistently higher (range, 1000-1400 pg/mL) in patients who
subsequently developed SIRS/MODS than the levels (range, 400-570 pg/mL) in
patients who did not develop SIRS/MODS. Hypotension, respiratory dysfunctions,
and coagulopathy were particularly more prevailing (p <.005) among the
complications that were associated with high prebypass levels of TNF p55 sR.
CONCLUSIONS: Soluble TNF receptor p55 can be employed as a predictive marker for
cytokinemia and the development of SIRS/MODS that may arise from a major insult
to the body such as cardiopulmonary bypass.

J Cardiothorac Vasc Anesth  2002 Aug;16(4):431-436 

Change in plasma glutamate concentration during cardiac surgery is a poor
predictor of cognitive outcome.

Reynolds JD, Amory DW, Grocott HP, White WD, Newman MF.

Department of Anesthesiology, Duke University Medical Center, Durham, NC.

OBJECTIVE: To develop a simple and reliable method for quantitating plasma
glutamate concentration and apply this method to monitor systemic glutamate
levels during coronary artery bypass graft (CABG) surgery, a procedure
associated with neurologic deficits. 
DESIGN: Prospective serial investigation of
cardiac surgery patients. 
SETTING: Tertiary-care university teaching hospital.
PARTICIPANTS: Patients undergoing CABG surgery (n = 33). 
INTERVENTIONS:
Preoperative and postoperative neurologic and neurocognitive testing were done.
Intraoperative blood samples for glutamate quantitation were obtained from
jugular bulb and pulmonary artery catheters before, during, and after
cardiopulmonary bypass. Measurements and Main Results: Glutamate concentrations
were determined using a reverse-phase high-pressure liquid chromatography method
coupled to precolumn derivatization of the analyte with o-phthalaldehyde. The
mean prebypass plasma glutamate concentration was 79.4 +/- 41.8 &mgr;mol/L.
Plasma glutamate levels fluctuated during surgery with considerable degrees of
temporal and quantitative interpatient variability. Neurologic and
neurocognitive deficits were observed after CABG surgery. However, neither the
occurrence nor the severity of cognitive decline could be predicted by the
magnitude of increase in plasma glutamate concentration. 
CONCLUSION:
Fluctuations in intraoperative systemic glutamate levels do not predict
post-CABG surgery neurologic outcome. Copyright 2002, Elsevier Science (USA).
All rights reserved.

J Cardiothorac Vasc Anesth  2002 Aug;16(4):405-12 

Intraoperative insulin therapy does not reduce the need for inotropic or
antiarrhythmic therapy after cardiopulmonary bypass.

Groban L, Butterworth J, Legault C, Rogers AT, Kon ND, Hammon JW.

Departments of Anesthesiology, Public Health Sciences, and Cardiothoracic
Surgery, Wake Forest University School of Medicine, Winston-Salem, NC.

OBJECTIVE: To determine whether attempted glucose control through intraoperative
insulin therapy reduces the need for inotropic or antiarrhythmic therapy after
cardiopulmonary bypass (CPB). 
DESIGN: Post hoc analysis of a randomized, masked
clinical trial of insulin therapy for prevention of neurobehavioral deficits.
SETTING: Single university hospital. PARTICIPANTS: Nondiabetic patients
undergoing elective coronary artery bypass graft surgery (n = 381).
INTERVENTIONS: Patients received either insulin infusions in an attempt to
maintain blood glucose at 80 to 120 mg/dL (n = 188) or placebo (saline; n =
193). Inotropic therapy was defined as the initiation of vasoactive support with
epinephrine or amrinone infusions or mechanical support with the initiation of
an intra-aortic balloon pump in the operating room or within 12 hours
postoperatively. Antiarrhythmic therapy was defined as cardioversion,
antiarrhythmic medications, or pacing. Measurements and Main Results: Of
patients, 64 in the placebo group and 71 in the insulin group required inotropic
support after CPB (p = not significant). The use of cardioversion (55 in placebo
group v 61 in insulin group), antiarrhythmic medications (64 in placebo group v
76 in insulin group), and pacing (118 in placebo group v 117 in insulin group)
was similar between groups. Inotropic drug support was associated with age >60
years, female gender, reduced preoperative ejection fraction, history of angina,
and increased duration of CPB. 
CONCLUSION: Intraoperative insulin therapy did
not reduce the use of inotropic or antiarrhythmic support after cardiac surgery
with CPB. The lack of benefit may be due to the inability to prevent
hyperglycemia during the physiologic stress of CPB or a tribute to the
effectiveness of modern myocardial preservation techniques. Copyright 2002,
Elsevier Science (USA). All rights reserved.

Anesthesiology  2002 Aug;97(2):405-11 

Cardiac Troponin I Is an Independent Predictor of In-hospital Death after Adult
Cardiac Surgery.

Lasocki S, Provenchere S, Benessiano J, Vicaut E, Lecharny JB, Desmonts JM,
Dehoux M, Philip I.

Departement d'Anesthesie-Reanimation, Hopital Bichat, Paris, France.

BACKGROUND: Although myocardial injury during cardiac surgery is associated with
impaired clinical outcome, little is known about the prognostic value of cardiac
troponin I (cTnI), a cardiac-specific biologic marker. The purpose of this
prospective study was to evaluate the prognostic value of cTnI concentrations
measured 20 h after the end of surgery in adult patients undergoing coronary
artery bypass grafting or conventional valve surgery. 
METHODS: Baseline and
perioperative characteristics of 502 consecutive patients undergoing
conventional heart surgery during a 1-yr period were collected. In-hospital
death (n = 28) and major clinical outcomes, e.g., low cardiac output,
ventricular arrhythmia, and renal failure, were recorded. 
RESULTS: Multivariate
analysis, using a stepwise logistic regression, showed that cTnI concentration
was an independent predictor of in-hospital mortality (for cTnI concentration >
13 ng/ml, odds ratio = 6.7 [95% confidence interval, 2.3-19.3]), as were
diabetes, altered preoperative cardiac function, emergent surgery,
cardiopulmonary bypass duration, postoperative Pao2 level and total chest
drainage volume. Further, elevated cTnI concentrations were associated with a
cardiac cause of death and with major clinical outcomes. 
CONCLUSIONS: Our
results demonstrated that cTnI concentration measured 20 h after the end of
surgery is an independent predictor of in-hospital death after cardiac surgery.
In addition, elevated concentrations of cTnI are associated with a cardiac cause
of death and with major postoperative complications.

Anesthesiology  2002 Aug;97(2):390-9 

Pharmacokinetics of tranexamic acid during cardiopulmonary bypass.

Dowd NP, Karski JM, Cheng DC, Carroll JA, Lin Y, James RL, Butterworth J.

Division of Cardiac Anesthesia and Intensive Care, Toronto General Hospital,
University Health Network, University of Toronto, Toronto, Ontario, Canada.

BACKGROUND: Tranexamic acid (TA) reduces blood loss and blood transfusion during
heart surgery with cardiopulmonary bypass (CPB). TA dosing has been empiric
because only limited pharmacokinetic studies have been reported, and CPB effects
have not been characterized. We hypothesized that many of the published TA
dosing techniques would prove, with pharmacokinetic modeling and simulation, to
yield unstable TA concentrations. 
METHODS: Thirty adult patients undergoing
elective coronary artery bypass grafting, valve surgery, or repair of atrial
septal defect received after induction of anesthesia: TA 50 mg/kg (n = 11), TA
100 mg/kg (n = 10), or TA 10 mg/kg (n = 10) over 15 min, with 1 mg x kg(-1) x
hr(-1) maintenance infusion for 10 h. TA was measured in plasma using high
performance liquid chromatography. Pharmacokinetic modeling was accomplished
using a mixed effects technique. Models of increasing complexity were compared
using Schwarz-Bayesian Criterion (SBC). 
RESULTS: Tranexamic acid concentrations
rapidly fell in all three groups. Data were well fit to a 2-compartment model,
and adjustments for CPB were supported by SBC. Assuming a body weight of 80 kg,
our model estimates V1 = 10.3 l before CPB and 11.9 l during and after CPB; V2 =
8.5 l before CPB and 9.8 l during and after CPB; Cl1 = 0.15 l/s before CPB, 0.11
l/s during CPB, and 0.17 l/s after CPB; and Cl2 = 0.18 l/s before CPB and 0.21
l/s during and after CPB. Based on simulation of previous studies of TA
efficacy, we estimate that a 30-min loading dose of 12.5 mg/kg with a
maintenance infusion of 6.5 mg x kg(-1) x hr(-1) and 1 mg/kg added to the pump
prime will maintain TA concentration greater than 334 microm, and a higher dose
based on 30 mg/kg loading dose plus 16 mg x kg(-1) x h(-1) continuous infusion
and 2 mg/kg added to the pump prime would maintain TA concentrations greater
than 800 microm. 
CONCLUSIONS: Tranexamic acid pharmacokinetics are influenced by
CPB. Our TA pharmacokinetic model does not provide support for the wide range of
TA dosing techniques that have been reported. Variation in TA efficacy from
study to study and confusion about the optimal duration of TA treatment may be
the result of dosing techniques that do not maintain stable, therapeutic TA
concentrations.