Asian Cardiovasc Thorac Ann  2002 Jun;10(2):115-118 

Is Hyperamylasemia After Cardiac Surgery Due to Cardiopulmonary Bypass?

Wan S, Arifi AA, Chan CS, Ng CS, Wan IY, Lee TW, Yim AP.

Division of Cardiothoracic Surgery Department of Surgery The Chinese University
of Hong Kong Prince of Wales Hospital Shatin, New Territories, Hong Kong
People's Republic of China.

Although hyperamylasemia has been reported in a large proportion of patients
undergoing cardiac surgery with cardiopulmonary bypass, its clinical
significance and pathogenetic mechanisms remain poorly understood. The study was
designed to investigate whether avoidance of cardiopulmonary bypass would limit
amylase elevation. Serum levels of amylase and lipase were measured
preoperatively as well as 24 and 48 hours postoperatively in 58 patients
undergoing elective coronary artery bypass grafting. Three surgical approaches
were used: cardiopulmonary bypass (n = 32) and off-pump through a median
sternotomy (n = 14) or a left minithoracotomy (n = 12). There was no hospital
mortality or postoperative abdominal complications. Transient hyperamylasemia
occurred in 14 patients: 7 (22%), 5 (36%), and 2 (17%) in the respective groups.
The increase in amylase levels was similar among the groups. However, no lipase
elevation was detected in any patient. There was no clear correlation between
hyperamylasemia and increased creatinine levels. Perioperative plasma calcium
levels were normal in patients who had hyperamylasemia. Our results indicate
that hyperamylasemia after bypass surgery is not related to the use of
cardiopulmonary bypass or the mode of surgical access.

Ann Thorac Surg  2002 Jun;73(6):1905-9; discussion 1910-1 

Lactic acidosis after cardiac surgery is associated with polymorphisms in tumor
necrosis factor and interleukin 10 genes.

Ryan T, Balding J, McGovern EM, Hinchion J, Livingstone W, Chughtai Z, Smith OP.

Department of Anaesthesia, St. James's Hospital, Dublin, Ireland. ryants@iol.ie

BACKGROUND: Lactic acidosis after cardiac surgery is a manifestation of excess
cytokine production. Cytokine-related genetic polymorphisms account for
variability in cytokine response and may predispose to the development of lactic
acidosis after cardiac surgery. METHODS: Routine postoperative cardiac surgery
patients were studied. Lactic acid levels were greater than 4 mmol/L in study
patients and less than 4 mmol/L in controls. Polymerase chain reaction-based
techniques were used to examine carriage of tumor necrosis factor beta
(TNF-beta), TNF G-308A, and interleukin 10 (IL-10) G-1082A alleles. RESULTS:
Demographic characteristics and details of surgery were similar for 30 control
and 21 study patients. Lactic acid levels after intensive care admission changed
over time and were related to both TNF-beta and IL-10 G-1082A polymorphisms. All
4 study patients homozygous for TNF-beta1 and carrying an IL-10-1082A allele
developed lactic acidosis (p = 0.02). There was no relation between the rate of
epinephrine infusion or duration of cardiopulmonary bypass and lactic acid
levels. CONCLUSIONS: Genetic factors have a role in the development of lactic
acidosis after cardiac surgery.

Ann Thorac Surg  2002 Jun;73(6):1897-904 

Aprotinin in coronary operation with cardiopulmonary bypass: does "low-dose"
aprotinin inhibit the inflammatory response?

Englberger L, Kipfer B, Berdat PA, Nydegger UE, Carrel TP.

Department of Cardiovascular Surgery, University Hospital (Inselspital), Berne,
Switzerland. lars.englberger@insel.ch

BACKGROUND: Cardiopulmonary bypass induces a systemic inflammatory response.
Aprotinin, a nonspecific proteinase inhibitor is known to improve postoperative
hemostasis and may modify the inflammatory reaction. This study evaluates the
effects of low-dose aprotinin on inflammatory markers in patients scheduled for
elective coronary artery bypass grafting. METHODS: Patients were prospectively
randomized into two groups: the control group (C) (n = 14) and the low-dose
aprotinin group (A) (n = 15) with (2 x 10(6) KIU = 280 mg) aprotinin added to
the pump prime. Cytokine response (interleukin-6, soluble TNF II receptor),
terminal complement production (SC5b-9), and neutrophil activation (lactoferrin)
were assessed up to 6 hours postoperatively. Clinical data and hemostatic
factors including fibrinopeptide A, thrombin-antithrombin complex, D-dimer, and
plasmin/alpha2-antiplasmin were investigated. RESULTS: In both study groups, a
significant increase of all inflammatory markers was seen (IL-6, sTNF-IIR,
SC5b-9, lactoferrin), p less than 0.001. Peak levels of complement production
occurred after protamine administration, whereas cytokine increases were more
pronounced postoperatively with marked elevation up to 6 hours. The markers did
not differ significantly between groups throughout the study period (p > 0.05 at
each time of determination). However, after protamine administration reduced
fibrinolysis (D-dimer, plasmin/alpha2-antiplasmin) was detected in group A.
Measurements for coagulation (fibrinopeptide A, thrombin-antithrombin complex)
were not significantly influenced by aprotinin. The total amount of blood loss
during the first 24 hours was significantly reduced in group A (p < 0.02).
CONCLUSIONS: Low-dose aprotinin added to the pump prime does not inhibit the
inflammatory response caused by cardiopulmonary bypass, but improves
postoperative hemostasis. A potential effect of high-dose aprotinin on
inflammatory markers remains to be elucidated.

Thorac Cardiovasc Surg  2002 Jun;50(3):136-40 

Elastase Release Following Myocardial Ischemia during Extracorporeal Circulation
(ECC) - Marker of Ongoing Systemic Inflammation?

Boeken U, Feindt P, Schulte HD, Gams E.

Department of Thoracic and Cardiovascular Surgery, Heinrich Heine University
Hospital, Dusseldorf, Germany.

BACKGROUND: 'Post-Perfusion Syndrome' (PPS) after cardiopulmonary bypass (CPB)
is known to be evoked by inflammatory reactions. The hypothesis of a
pathogenetic role for the neutrophil granulocytes in this inflammation would be
strengthened if elevated concentrations of a neutrophil product such as elastase
could be demonstrated, particularly in case of a PPS or a systemic inflammatory
response syndrome (SIRS). METHODS: In a randomized prospective double-blind
study, 40 patients undergoing aortocoronary bypass grafting (CABG) were divided
into 4 groups of 10 patients each. One group served as the control group, one
received prostacyclin (PGl 2 ), the third group was substituted with high-dosed
aprotinin and the last group was treated with a combination of PGl 2 and
aprotinin. 6 blood samples were taken from every patient perioperatively, and
plasma elastase (PE), procalcitonin (PCT), C 1 -esterase inhibitor (CEI) and
parameters of coagulation and fibrinolysis were determined. RESULTS: Levels of
elastase increased significantly in all intra- and postoperative blood samples
compared to the preoperative baseline values (< 30 microg/l, p < 0.05). The
elastase release was even more pronounced in the control and aprotinin group
(170 +/- 23 microg/l; 175 +/- 14 microg/l during ECC) compared to patients who
received prostacyclin (142 = 21 microg/l, p < 0.05). Duration of myocardial
ischemia could be directly correlated to elastase levels at the end of CPB. 10
of the 40 patients suffered postoperatively from a PPS or a SIRS; in these
patients, elastase levels at the end of CPB were significantly higher (188 +/-
26 microg/l vs. 138 +/- 22 microg/l, p < 0.05). Immediately after the operation,
these 10 patients also showed significant changes in the cascades of coagulation
and fibrinolysis resulting in a hypercoagulatory state. Levels of PCT and CEI
did not change significantly during and after ECC. CONCLUSIONS: Our results
indicate that CPB initiates an elastase release that can be suppressed by
prostacyclin. Increased intraoperative elastase levels in patients with PPS show
that elastase may be an indicator of ongoing systemic inflammation, possibly
causing complications due to a hypercoagulatory state. Myocardial ischemia seems
to be one reason for this elastase release. It can be speculated that early
PGl2-infusion could be a therapeutic option in inflammatory diseases caused by
ECC.

Jpn J Thorac Cardiovasc Surg  2002 Jun;50(6):241-5 

Effects of chlorpromazine as a systemic vasodilator during cardiopulmonary
bypass in neonates.

Imoto Y, Kado H, Masuda M, Yasui H.

Department of Cardiovascular Surgery, Fukuoka Children's Hospital, Fukuoka,
Japan.

OBJECTIVES: Vasodilator use during cardiopulmonary bypass is important in
pediatric cardiac surgery, but the full range of their effects on hemodynamics
remains to be clarified. We studied the effects of chlorpromazine, a potent
alpha-blocking agent, in neonates. METHODS: Subjects were 60 neonates undergoing
arterial switch operations for complete transposition of the great arteries with
an intact ventricular septum. Of these, 37 received 2.1 to 6.5 mg/kg of
chlorpromazine during cardiopulmonary bypass (CPZ group) and 23 received no
vasodilator (control group). We then compared hemodynamic parameters between
groups during and early after surgery. RESULTS: The systemic vascular resistance
index and mean arterial pressure during cardiopulmonary bypass were
significantly lower in the CPZ group (p < 0.05), but systolic pressure 15
minutes after cessation of cardiopulmonary bypass did not differ between groups.
The rise in peripheral temperature during rewarming after hypothermia was
significantly higher and the acid-base status 40 minutes after cardiopulmonary
bypass less acidotic in the CPZ group. Urine output during cardiopulmonary
bypass was higher in the CPZ group. CONCLUSIONS: Chlorpromazine effectively
counteracts systemic vasoconstriction induced by cardiopulmonary bypass without
serious side effects in neonatal cardiac surgery.

J Cardiothorac Vasc Anesth  2002 Jun;16(3):330-3 

Does normoxemic cardiopulmonary bypass prevent myocardial reoxygenation injury
in cyanotic children?

Bulutcu FS, Bayindir O, Polat B, Yalcin Y, oZbek U, Cakali E.

Departments of Anesthesiology and Reanimation, Cardiothoracic and Vascular
Surgery, and Pediatric Cardiology, Kadir Has University, Florence Nightingale
Hospital, Istanbul, Turkey.

OBJECTIVE: To evaluate whether the deleterious effect of cardiopulmonary bypass
(CPB) can be prevented by controlling PaO(2) in cyanotic children. DESIGN:
Prospective, randomized, clinical study. SETTING: Single university hospital.
PARTICIPANTS: Pediatric patients undergoing cardiac surgery for repair of
congenital heart disease (n = 24). INTERVENTIONS: Patients were randomly
allocated into 3 groups. Patients in the acyanotic group (group I, n = 10) had
CPB initiated at a fraction of inspired oxygen (F(I)O(2)) of 1.0 (PO(2), 300 to
350 mmHg). Cyanotic patients were subdivided as follows: Group II (n = 7) had
CPB initiated at an F(I)O(2) of 1.0, and group III (n = 7) had CPB initiated at
an F(I)O(2) of 0.21 (PO(2), 90 to 110 mmHg). A biopsy specimen of right atrial
tissue was removed during venous cannulation, and another sample was removed
after CPB before aortic cross-clamping. The tissue was incubated in 4 mmol/L of
t-butylhydroperoxide, and the malondialdehyde (MDA) level was measured to
determine the antioxidant reserve capacity. Blood samples for cytokine levels,
tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 response to CPB were
collected after induction of anesthesia and at the end of CPB before protamine
administration. Measurements and Main Results: After initiation of CPB, MDA
level rose markedly in the cyanotic groups compared with the acyanotic group
(210 +/- 118% v 52 +/- 34%, p < 0.05), which indicated the depletion of
antioxidants. After initiation of CPB, TNF-alpha and IL-6 levels of the cyanotic
groups were higher than for the acyanotic group (168 +/- 77 v 85 +/- 57, p <
0.001; 249 +/- 131 v 52 +/- 40; p < 0.001). When a comparison between the
cyanotic groups was performed, group II (initiating CPB at an F(I)O(2) of 1.0)
had significantly increased MDA production compared with group III (initiating
CPB at an F(I)O(2) of 0.21) (302 +/- 134% v 133 +/- 74%, p < 0.05). Group II had
higher TNF-alpha and IL-6 levels than group III (204 +/- 81 v 131 +/- 52, p <
0.001; 308 +/- 147 v 191 +/- 81, p < 0.01). CONCLUSION: Conventional clinical
methods of initiating CPB at a hyperoxemic PO(2) may increase the possibility of
myocardial reoxygenation injury in cyanotic children. This deleterious effect of
reoxygenation can be modified by initiating CPB at a lower level of oxygen
concentration. Subsequent long-term studies are needed to determine the best
method of decreasing the oxygen concentration of the CPB circuit. Copyright
2002, Elsevier Science (USA). All rights reserved.

Artif Organs  2002 Jun;26(6):564-6 

Is roller pump induced tubing rupture a clinical possibility?

Kim WG, Chung CI, Cho SR.

Department of Thoracic and Cardiovascular Surgery and Heart Research Institute,
Seoul National University College of Medicine; and Clinical Research Center,
Seoul National University Hospital, Kangnam General Hospital, Seoul, Korea.

We analyzed the effects of variations in the diameter of silicone rubber and
polyvinyl chloride (PVC) tubings on the likelihood of tubing rupture during
modeling of accidental arterial line clamping in cardiopulmonary bypass (CPB)
with a roller pump. A closed CPB circuit constructed with a roller pump was
tested with both PVC and silicone rubber tubings of 1/2, 3/8, and 1/4 inch
internal diameter. Arterial line pressure was monitored, and an occlusive clamp
was placed across the tubing distal to the pressure monitor site to model an
accidental arterial line occlusion. A charge coupled device camera with 512
(horizontal) x 492 (vertical) pixels was installed above the roller pump to
measure tubing diameters at pump outlet where the maximum deformations
(distension) of the tubings occurred. Quantitative measurement of the changes of
tubing diameters with the change of arterial line pressure was performed using
computerized image processing techniques. A visible change of tubing diameter
was generally noticeable by around 250 psi of arterial line pressure, which was
already very high. By 1,500 psi, the PVC tubings showed an increase of diameter
between 5% to 10% while the silicone rubber tubings showed an increase between
20% to 25%. Silicone rubber tubings of all sizes showed greater distensibility
than PVC tubings of equivalent size. In conclusion, although roller pump induced
tubing rupture remains a theoretical problem during CPB in terms of the inherent
mechanism of the pump, in reality such an occurrence is impossible in real
clinical conditions.

Circulation  2002 Jun 18;105(24):2849-54 

Cardiopulmonary Bypass Induces Release of Soluble CD40 Ligand.

Nannizzi-Alaimo L, Rubenstein MH, Alves VL, Leong GY, Phillips DR, Gold HK.

COR Therapeutics, South San Francisco, Calif.

BACKGROUND: Cardiopulmonary bypass (CPB) is known to induce platelet activation,
thrombosis, thrombocytopenia, and a systemic inflammatory response. It is known
that CD40 ligand (CD40L) exists in platelets, that a soluble form of this
protein (sCD40L) is released on platelet activation, that platelets are the
primary source of sCD40L in blood, and that sCD40L is involved in thrombosis and
inflammation. The present study was designed to determine whether sCD40L is
released during CPB. Methods and Results- Blood was obtained from patients
undergoing CPB-requiring surgery and analyzed for sCD40L, interleukin-6, and
platelet factor 4 and beta-thromboglobulin (markers of platelet activation).
Platelets were also isolated and analyzed for their levels of CD40L. Plasma
levels of sCD40L increased >1.7-fold (from 0.29 to 0.51 ng/mL, P=0.001) within 1
hour on CPB and increased further to 3.7-fold (to 1.08 ng/mL, P=0.03) 2 hours
after the procedure. Half of the released sCD40L was cleared in 2 hours, which
allowed the sCD40L to return to approximately baseline levels 8 hours after the
procedure. The platelet content of CD40L was decreased by 40% (2.675 to 1.64
ng/10(8) platelets, P=0.001) 1 hour after initiation of CPB and was similar to
that observed for platelet factor 4 and beta-thromboglobulin. Interleukin-6, a
marker of inflammation, also increased during CPB. CONCLUSIONS: The present
study demonstrates that CPB causes an increase in the concentration of plasma
sCD40L. The corresponding decrease in platelet CD40L suggests that this
prothrombotic and proinflammatory protein was derived primarily from platelets
and may contribute to the thrombotic and inflammatory complications associated
with CPB.

Anesth Analg  2002 Jun;94(6):1402-8, table of contents 

Mortality and adverse events after protamine administration in patients
undergoing cardiopulmonary bypass.

Kimmel SE, Sekeres M, Berlin JA, Ellison N.

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
School of Medicine, 717 Blockley Hall, 423 Guardian Drive, Philadelphia, PA
19104-6021, USA. skimmel@cceb.med.upenn.edu

We designed this study to determine whether adverse hemodynamic events after a
protamine administration increase the risk of in-hospital mortality. Using a
retrospective cohort study design, medical and anesthesia records of patients
undergoing cardiopulmonary bypass (CPB) at the Hospital of the University of
Pennsylvania, Philadelphia, between 1990 and 1994 were reviewed. Adverse events
after a protamine administration were determined using strict, predefined
criteria, and in-hospital mortality was assessed without knowledge of exposure
status. Mortality was more frequent among the 53 patients with adverse events
(13.2%) than the 223 patients without events (2.7%; crude odds ratio 5.50; 95%
confidence interval, 1.49-20.6). After adjusting for confounders, the odds ratio
was 6.98 (95% confidence interval, 1.36-35.9; P = 0.017). Those suffering severe
events had the highest mortality (23.5% compared with 8.3% among those with less
severe events versus 2.7% among those without any event, P = 0.001 for trend).
In addition, the odds ratio was largest when using the strictest definition for
protamine-related events. In conclusion, patients undergoing CPB who experience
adverse events after a protamine administration have an increased risk of
in-hospital mortality. Further studies to confirm these findings and development
and testing of protamine alternatives or prophylactic therapies are required to
determine if mortality can be reduced. IMPLICATIONS: A retrospective cohort
study demonstrated an association between adverse events after a protamine
administration and increased in-hospital mortality.