Can J Anaesth  2001 Oct;48(9):902-10

Reproductibilite et interchangeabilite du Thromboelastographe(R), Sonoclot(R) et
du temps de coagulation active (Hemochron(R)), en chirurgie cardiaque :
[Reproducibility and interchangeability of the Thromboelastograph(R),
Sonoclot(R) and Hemochron(R) activated coagulation time in cardiac surgery].

Forestier F, Belisle S, Contant C, Harel F, Janvier G, Hardy JF.

Des departements D'anesthesiologie, Et De Biostatistiques, Institut de
Cardiologie de Montreal, Montreal, Quebec, Canada. C.H.U de Bordeaux, Pessac,
France.

PURPOSE: Despite their common use in cardiac surgery, few studies have evaluated
the reproducibility of the Thromboelastograph(R) (TEG), of the Sonoclot(R)
(SCT), and of the activated coagulation time with celite (ACT-C) or kaolin
(ACT-K) measured with the Hemochron(R), in clinical conditions of on-site
monitoring of hemostasis. This study determined the reproducibility of those
measurements, and evaluated the ability of various devices to substitute for the
ACT-C. METHODS: Blood samples collected from 20 volunteers and 21 patients
undergoing myocardial revascularization were analyzed in the two channels of the
TEG, in two SCT and four Hemochron(R) analyzers. The overall of TEG and SCT
coagulation profiles were analyzed by a computerized TEG and an experienced
observer respectively. The variation rate (V%) was calculated for each variable.
The ability of ACT-K and SCT to substitute for ACT-C under different clinical
conditions was evaluated. RESULTS: ACT-C and ACT-K V% ranged between 5.6% and
10.8% and between 6.7% and 12.4% respectively. TEG and SCT V% ranged between
3.1% and 9.5% and between 5.8% and 33.6% respectively, according to different
conditions and parameters. In volunteers and non-heparinized patients, the ACT-C
and ACT-K were interchangeable. No other test can substitute for the ACT-C when
patients are heparinized during cardiopulmonary bypass (CPB). CONCLUSIONS: In
the clinical conditions of use, on-site hemostasis monitoring devices providing
the most reproducible measurements are, in decreasing order, the TEG, the
Hemochron(R) and the SCT. In heparinized patients and during CPB, results from
different tests are not interchangeable, stressing the importance of
establishing appropriate instrument-specific values for monitoring
anticoagulation during cardiac surgery.

Anesthesiology  2001 Oct;95(4):842-8

Changes in plasma creatinine concentration after cardiac anesthesia with
isoflurane, propofol, or sevoflurane: a randomized clinical trial.

Story DA, Poustie S, Liu G, McNicol PL.

Department of Anaesthesia, Austin and Repatriation Medical Centre, Heidelberg,
Victoria, Australia. davids@austin.unimelb.edu

BACKGROUND: Renal impairment often follows cardiac surgery. The authors
investigated whether sevoflurane produces greater increases in plasma creatinine
concentration than isoflurane or propofol after elective coronary artery
surgery. METHODS: As part of maintenance anesthesia, including during
cardiopulmonary bypass, patients were randomly allocated to receive one of three
agents: isoflurane (n = 118), sevoflurane (n = 118), or propofol (n = 118).
Fresh gas flows were 3 l/min. The preoperative plasma creatinine concentration
was subtracted from the highest creatinine concentration in the first 3
postoperative days. A median maximum increase greater than 44 microM (0.5 mg/dl)
was regarded as clinically important. Data were analyzed on an
intention-to-treat basis. Subgroup analyses were performed on per-protocol
patients and those with preoperative renal impairment (creatinine concentration
> 130 microM [1.47 mg/dl] or urea > 7.7 mM [blood urea nitrogen, 21.6 mg/dl]).
RESULTS: The differences between the groups were small, clinically unimportant,
and not statistically significant for the primary analysis and subgroups. The
proportions of patients with creatinine increases greater than 44 microM were
15% in the isoflurane group, 17% in the sevoflurane group, and 11% in the
propofol group (P = 0.45). The median increases were 8 microM in the isoflurane
group, 4 microM in the sevoflurane group, and 6 microM in the propofol group.
The differences between the three median maximum increases were 1-4 microM (P >
0.45). In the subgroup with preoperative renal impairment, the median increases
were 10 microM in the isoflurane group, 15 microM in the sevoflurane group, and
5 microM in the propofol group (P = 0.72). CONCLUSIONS: Sevoflurane did not
produce greater increases in creatinine than isoflurane or propofol after
elective coronary artery surgery.

Thorac Cardiovasc Surg  2001 Oct;49(5):273-8

Lipopolysaccharide-Binding Protein (LBP) and Markers of Acute-Phase Response in
Patients with Multiple Organ Dysfunction Syndrome (MODS) following open heart
surgery.

Sablotzki A, Borgermann J, Baulig W, Friedrich I, Spillner J, Silber RE,
Czeslick E.

Clinic of Anesthesiology and Intensive Care Medicine, MLU Halle/Wittenberg,
Germany.

Cardiopulmonary bypass (CPB) is associated with an immunological injury that may
cause pathophysiological alterations in the form of a systemic inflammatory
response syndrome (SIRS) or a multiple organ dysfunction syndrome (MODS).
Previous studies on this issue have reported different changes of immunological
parameters during and after CPB, but there are no reports about the
lipopolysaccharide-binding protein (LBP) in relationship to other markers of
inflammation in patients with MODS following cardiovascular surgery. In the
present study, we investigated the acute-phase response of patients with MODS of
infectious and non-infectious origin following open-heart-surgery. Plasma levels
of procalcitonin (PCT), c-reactive protein (CRP), interleukin-6 (IL-6), and LBP
were measured in the first four postoperative days in 12 adult male patients
with the signs of SIRS and two or more organ dysfunctions after myocardial
revascularization (MODS-group), and 12 patients without organ insufficiencies
(SIRS-group). There were no significant differences regarding age, weight,
height, preoperative NYHA-classification, preoperative LVEDP, or the number of
anastomosis. Patients with MODS had a significantly longer operation time,
duration of ischemia, and duration of extracorporeal circulation. None of the
patients in the SIRS group died, whereas in the MODS group, 4 patients died due
to septic multiorgan failure. Plasma PCT and IL-6 concentrations were
significantly elevated in all MODS patients. CRP and LBP showed no differences
between the MODS and the SIRS group. Comparing the MODS patients with and
without positive microbial findings, we found significantly elevated levels of
PCT and LBP in those patients with documented infections. Our results indicate
that LBP may be a new marker for the differentiation between a severe
non-infectious SIRS and an ongoing bacterial sepsis in the early postoperative
course following CPB, while a microbiological result is still missing.

Ann Thorac Surg  2001 Oct;72(4):1331-5

Carbon dioxide management and the cerebral response to hemodilution during
hypothermic cardiopulmonary bypass in dogs.

Cook DJ, Boston US, Orszulak TA, Slater JM.

Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota
55905, USA. cook.david@mayo.edu

BACKGROUND: Increases in blood flow support oxygen (O2) delivery with
hemodilution. However, with alpha-stat management, the cerebral response to
hemodilution is blunted. We tested the hypothesis that carbon dioxide (CO2)
management is a primary determinant of the cerebral blood flow (CBF) response to
hemodilution during hypothermic bypass. METHODS: Following Animal Care Committee
approval, 15 dogs underwent bypass at 18 degrees C (pH-stat, n = 7 or
alpha-stat, n = 8). Measurements were obtained after progressive hemodilution,
and cerebral blood flow was determined by sagittal sinus outflow. Arterial
pressure was maintained at 60 to 70 mm Hg. The CBF response to hemodilution and
cerebral metabolic rate were compared in the two groups of animals. RESULTS: In
both groups, hemodilution increased CBF. At every hematocrit, CBF and O2
delivery in the pH-stat group exceeded that of alpha-stat group, although O2
demand did not differ between groups. While absolute CBF in the pH-stat group
was greater at every hematocrit, the relative change in CBF from control and the
slope of the CBF-Hct relationship did not differ between groups. CONCLUSIONS:
pH-stat management is associated with a greater absolute CBF and a greater ratio
of cerebral O2 supply to demand for any degree of hemodilution. However, over
the range of hematocrits common in practice, CO2 management per se does not
determine the cerebral response to hemodilution.

Ann Thorac Surg  2001 Oct;72(4):1316-20

Preoperative administration of steroids: influence on adhesion molecules and
cytokines after cardiopulmonary bypass.

Schurr UP, Zund G, Hoerstrup SP, Grunenfelder J, Maly FE, Vogt PR, Turina MI.

Clinic for Cardiovascular Surgery, University Hospital Zurich, Switzerland.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with tissue damage
mediated by adhesion molecules and cytokines. Prebypass steroid administration
may modulate the inflammatory response, resulting in improved postoperative
recovery. METHODS: Fifty patients undergoing elective coronary operations under
normothermic CPB were randomized into two groups: group A (n = 24) received
intravenous methylprednisolone (10 mg/kg) 4 hours preoperatively, and group B (n
= 26) served as controls. Cytokines (tumor necrosis factor-alpha [TNF-alpha],
interleukin-2R [IL-2R], IL-6, IL-8), soluble adhesion molecules (sE-selectin,
sICAM-1), C-reactive protein, and leukocytes were measured before steroid
application, then 24 and 48 hours, and 6 days postoperatively. Adhesion
molecules were measured by enzyme-linked immunosorbent assay, cytokines by
chemiluminescent immunoassay. Postoperatively, hemodynamic measurements,
inotropic agent requirements, blood loss, duration of mechanical ventilation,
and intensive care unit stay were compared. RESULTS: Aortic cross-clamp and CPB
time was similar in both groups. Prednisolone administration reduced
postoperative levels of IL-6 (611 versus 92.7 pg/mL; p = 0.003), TNF-alpha (24.4
versus 11.0 pg/L, p = 0.02), and E-selectin (327 versus 107 ng/mL, p = 0.02).
Postoperative recovery did not differ between groups. CONCLUSIONS: Preoperative
administration of methylprednisolone blunted the increase of IL-6, TNF-alpha,
and E-selectin levels after CPB but had no measurable effect on postoperative
recovery.

Ann Thorac Surg  2001 Oct;72(4):1256-61; discussion 1261-2

Magnesium infusion dramatically decreases the incidence of atrial fibrillation
after coronary artery bypass grafting.

Toraman F, Karabulut EH, Alhan HC, Dagdelen S, Tarcan S.

Department of Cardiovascular Surgery, Acibadem Hospital, Istanbul, Turkey.

BACKGROUND: Atrial fibrillation (AF) is one of the most common complications of
cardiac surgery. Magnesium, like several other pharmacologic agents, has been
used in the prophylaxis of postoperative AF with varying degrees of success.
However, the dose and the timing of magnesium prophylaxis need to be clarified.
The purpose of this study was to assess the effect of intermittent magnesium
infusion on postoperative AF. METHODS: A total of 200 consecutive patients who
had elective, isolated, first-time coronary artery bypass grafting were
prospectively randomized to two groups. Patients in the magnesium group (n =
100) received 6 mmol MgSO4 infusion in 100 mL 0.9% NaCl solution (25 mL/h) the
day before surgery, just after cardiopulmonary bypass, and once daily for 4 days
after surgery. Patients in the control group (n = 100) received only 100 mL 0.9%
NaCl solution (25 mL/h) at the same time points. RESULTS: Postoperative AF
occurred in 2 (2%) patients in the magnesium group and in 21 (21%) patients in
the control group (p < 0.001). Atrial fibrillation started, on average, 49.4 +/-
16.8 hours postoperatively. The postoperative length of hospital stay was not
significantly different in patients with AF (7.4 +/- 8.0 days) compared with
patients without AF (5.4 +/- 1.1 days; p = 0.236). CONCLUSIONS: The use of
magnesium in the preoperative and early postoperative periods is highly
effective in reducing the incidence of AF after coronary artery bypass grafting.

Crit Care Med  2001 Oct;29(10):1903-9

Effects of normothermia versus hypothermia on extravascular lung water and serum
cytokines during cardiopulmonary bypass: a randomized, controlled trial.

Honore PM, Jacquet LM, Beale RJ, Renauld JC, Valadi D, Noirhomme P, Goenen M.

Cardiothoracic Intensive Care Unit, St-Luc Teaching Hospital, Brussels, Belgium.
Pathonor@skynet.be

OBJECTIVE: To evaluate the influence of perfusion temperature on the systemic
effects of cardiopulmonary bypass (CPB), including extravascular lung water
index (EVLWI), and serum cytokines. DESIGN: Prospective, randomized, controlled
study. SETTING: Cardiothoracic intensive care unit of a university hospital.
PATIENTS: Patients undergoing elective coronary artery bypass grafting.
INTERVENTIONS: Twenty-one patients undergoing elective coronary artery bypass
grafting were randomly assigned to receive either normothermic bypass (36
degrees C, n = 8) with intermittent antegrade warm blood cardioplegia (IAWBC),
or hypothermic (32 degrees C, n = 13) CPB with cold crystalloid cardioplegia.
MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, heart rate, cardiac
output, systemic vascular resistance, mean pulmonary arterial pressure, and
pulmonary vascular resistance were determined at baseline, i.e., after induction
of anesthesia but before sternal opening (T-1), at arrival in the intensive care
unit (T0), and 4 hrs (T4), 8 hrs (T8), and 24 hrs (T24) after surgery. EVLWI,
intrathoracic blood volume index (ITBVI), and EVLW/ITBV ratio were obtained by
using thermal dye dilution utilizing an arterial thermistor-tipped fiberoptic
catheter and were recorded at T-1, T0, T4, T8, and T24. Serial blood samples for
cytokine measurements were obtained at each hemodynamic measurement time point.
Before, during, and after CPB, there were no differences in the conventional
hemodynamic measurements between the groups. There were no changes in EVLWI up
to T8 in either group. Furthermore, no change in the ratio EVLW/ITBW was
observed between the groups at any time, further indicating the absence of a
change in pulmonary permeability. Plasma levels of interleukin-6, tumor necrosis
factor-alpha, and interleukin-10 increased during and after CPB, independently
of the perfusion temperature. CONCLUSION: Normothermic CPB is not associated
with additional inflammatory and related systemic adverse effects regarding
cytokine production and EVLWI as compared with mild hypothermia. The potential
temperature-dependent release of cytokines and subsequent inflammation has not
been observed and normothermic CPB may be seen as a safe technique regarding
this issue.

J Am Coll Cardiol  2001 Oct;38(4):1216-23

Moderate hypothermia during cardiopulmonary bypass reduces myocardial cell
damage and myocardial cell death related to cardiac surgery.

Vazquez-Jimenez JF, Qing M, Hermanns B, Klosterhalfen B, Woltje M, Chakupurakal
R, Schumacher K, Messmer BJ, von Bernuth G, Seghaye MC.

Department of Thoracic and Cardiovascular Surgery, Aachen, Germany.
jvazquez-jimenez@post.klinikum.rwth-aachen.de

OBJECTIVES: The goal of this study was to test the hypothesis that moderate
hypothermia during cardiopulmonary bypass (CPB) provides myocardial protection
by enhancing intra-myocardial anti-inflammatory cytokine balance. BACKGROUND:
Moderate hypothermia during experimental CPB stimulates production of
interleukin-10 (IL10) and blunts release of tumor necrosis factor-alpha
(TNFalpha). METHODS: Twelve young pigs were assigned to a temperature (T degrees
) regimen during CPB: moderate hypothermia (T degrees : 28 degrees C; n = 6) and
normothermia (T degrees : 37 degrees C; n = 6). Intra-myocardial TNFalpha- and
IL10-messenger RNA were detected by competitive reverse transcriptase polymerase
chain reaction and quantification of cytokine synthesis by Western blot. Levels
of cardiac troponin I (cTnI) in cardiac lymph and in arterial and coronary
venous blood were examined during and after CPB. Myocardial cell damage was
assessed by histologic and ultrastructural anomalies of tissue probes taken 6 h
after CPB. RESULTS: Synthesis of IL10 was significantly higher, while that of
TNFalpha was significantly lower, in pigs that were in moderate hypothermia
during surgery than in the others. In contrast with normothermia, moderate
hypothermia was also associated with significantly lower cumulative cardiac
lymphatic flow during and after CPB, significantly lower lymphatic cTnI
concentrations after CPB, significantly lower percentages of myocardial cell
necrosis and a significantly lower score of ultrastructural anomalies of
myocardial cells. While the percentage of apoptotic cells was not different
between groups, the apoptosis/necrosis ratio tended to be higher in animals that
were in moderate hypothermia during surgery. In all animals, TNFalpha synthesis
correlated positively while IL10 production correlated negatively with necrosis
and total cell death, respectively. CONCLUSIONS: Our results suggest that
moderate hypothermia during CPB provides myocardial protection by enhancing
intra-myocardial anti-inflammatory cytokine balance.

J Thorac Cardiovasc Surg  2001 Oct;122(4):753-8

Is hyperglycemia seen in children during cardiopulmonary bypass a result of
hyperoxia?

Bandali KS, Belanger MP, Wittnich C.

Departments of Physiology and Surgery, The Hospital for Sick Children,
University of Toronto, Toronto, Ontario, Canada.

OBJECTIVE: We sought to identify whether elevated PaO (2) itself can directly
cause hyperglycemia in newborns and to document any additional effects of
cardiopulmonary bypass on this response. METHODS: Piglets were exposed to either
normoxia (88 +/- 6 mm Hg) or hyperoxia (470 +/- 28 mm Hg) in the following
studies. Anesthetized 3-day-old neonatal pigs were either ventilated for 2 hours
of normoxia (n = 5) or hyperoxia (n = 5) or placed on normothermic, normoxic
cardiopulmonary bypass (n = 6) and then randomly assigned to either undergo a
2-hour normoxic period or a 1-hour hyperoxic episode, followed by a return to
normoxia for an additional hour. Blood glucose levels were measured in all
animals. RESULTS: No significant changes were observed in blood glucose levels
in neonatal pigs that underwent 2 hours of normoxic ventilation (5.0 +/- 0.6
mmol/L) or cardiopulmonary bypass (6.6 +/- 1.6 mmol/L). However, the ventilatory
model showed a significant and sustained (P <.001) hyperglycemic response after
both 1 hour (8.6 +/- 1.0 mmol/L) and 2 hours (9.8 +/- 1.6 mmol/L) of hyperoxia.
In the cardiopulmonary bypass model, exposure to 1 hour of hyperoxia elicited a
significant (P <.05) hyperglycemic response (10.3 +/- 1.2 mmol/L), followed by a
return to normal blood glucose levels (6.6 +/- 1.6 mmol/L) with a return to
normoxia. This hyperoxia-mediated hyperglycemic response was confirmed when data
examined from children undergoing cardiopulmonary bypass for primary repair of
their congenital defects also identified a significant positive correlation (r =
0.72, P =.02) between oxygen levels and blood glucose levels measured before and
at the end of cardiopulmonary bypass. CONCLUSIONS: Hyperoxia triggers a
hyperglycemic response in both ventilatory and bypass models. Cardiopulmonary
bypass does not exacerbate this response, as shown by the similar levels of
hyperglycemia sustained for the duration of the hyperoxic exposure in both
experimental models. Therefore, not only may hyperoxia play a crucial role in
the hyperglycemic response seen during neonatal cardiopulmonary bypass, but its
effect on glucose homeostasis should be considered whenever children are exposed
to hyperoxia.