Perfusion  2001 Sep;16(5):411-6

Alternatives to unfractioned heparin for anticoagulation in cardiopulmonary
bypass.

von Segesser LK, Mueller X, Marty B, Horisberger J, Corno A.

Department of Cardiovascular Surgery, CHUV, Centre Hospitalier Universitaire
Vaudois, Lausanne, Switzerland. Ludwig.von_Segesser@chuv.hospvd.ch

Despite the progress made in the development of cardiopulmonary bypass (CPB)
equipment, systemic anticoagulation with unfractioned heparin and post-bypass
neutralization with protamine are still used in most perfusion procedures.
However, there are a number of situations where unfractioned heparin, protamine
or both cannot be used for various reasons. Intolerance of protamine can be
addressed with extracorporeal heparin removal devices, perfusion with (no) low
systemic heparinization and, to some degree, by perfusion with alternative
anticoagulants. Various alternative anticoagulation regimens have been used in
cases of intolerance to unfractioned heparin, including extreme hemodilution,
low molecular weight heparins, danaparoid, ancrod, r-hirudin, abciximab,
tirofiban, argatoban and others. In the presence of heparin-induced
thrombocytopenia (HIT) and thrombosis, the use of r-hirudin appears to be an
acceptable solution which has been well studied. The main issue with r-hirudin
is the difficulty in monitoring its activity during CPB, despite the fact that
ecarin coagulation time assessment is now available. A more recent approach is
based on selective blockage of platelet aggregation by means of monoclonal
antibodies directed to GPIIb/IIIa receptors (abciximab) or the use of a
GPIIb/IIIa inhibitor (tirofiban). An 80% blockage of the GPIIb/IIIa receptors
and suppression of platelet aggregation to less than 20% allows the giving of
unfractioned heparin and running CPB in a standard fashion despite HIT and
thrombosis. Likewise, at the end of the procedure, unfractioned heparin is
neutralized with protamine as usual and donor platelets are transfused if
necessary. GPIIb/IIIa inhibitors are frequently used in interventional
cardiology and, therefore, are available in most hospitals.

Perfusion  2001 Sep;16(5):353-60
Systemic inflammation and cardiac surgery: an update.

Asimakopoulos G.

Cardiothoracic Department, Imperial College  School of Medicine at Hammersmith
Hospital, London, UK. geoasi@hotmail.com

Cardiac surgery with cardiopulmonary bypass (CPB) is associated with the
development of a systemic inflammatory response that can often lead to
dysfunction of major organs. The systemic inflammation can be assessed intra-
and postoperatively by measuring concentrations of inflammatory mediators in
plasma and tissues. These concentrations, however, do not always correlate with
the degree of observed organ dysfunction. Various strategies have been used to
reduce inflammatory phenomena in patients undergoing CPB. Cardiac surgery
without CPB has been performed increasingly with satisfactory results over the
past few years. Attenuation of systemic inflammation and improved outcome in
high risk patients are potential benefits of this technique. The emergence and
expanding performance of cardiac surgical procedures without the use of CPB has
given us an excellent tool to investigate the relative importance of CPB as a
cause of systemic inflammation. Aprotinin is a protease inhibitor which is used
in cardiac surgical patients for its haemostatic effects. Aprotinin has
anti-inflammatory properties, the nature of which have not been completely
clarified. This article presents a summary of the published literature
investigating inflammatory response and organ dysfunction in patients who have
cardiac surgery without CPB. It also presents an overview of recent data on the
anti-inflammatory action mechanisms of aprotinin.

Ann Thorac Surg  2001 Sep;72(3):850-3

Is the use of albumin in colloid prime solution of cardiopulmonary bypass
circuit justified?

Boks RH, van Herwerden LA, Takkenberg JJ, van Oeveren W, Gu YJ, Wijers MJ,
Bogers AJ.

Department of Cardiothoracic Surgery, Erasmus Medical Center Rotterdam, The
Netherlands. boks@thch.azr.nl

BACKGROUND: Albumin in the priming solution precoats the surface of the
cardiopulmonary bypass circuit, supposedly causing delayed adsorption of
fibrinogen and reduced activation and adhesion of platelets. This action may
result in lower transoxygenator resistance. Because our institution uses a
colloidal prime solution (Gelofusine), questions were raised about the value of
albumin in the prime solution. We decided to focus on the clinical effects of
transoxygenator resistance. METHODS: Sixty adults undergoing elective cardiac
operations were randomly divided into three groups: a group with 20-g albumin (n
= 20), a group with 2-g albumin (n = 20), and a group with no albumin (n = 20)
in the 1,600-mL colloidal prime. Patients older than 75 years and patients with
a preoperative serum albumin level of 30 g/L or less were excluded. The
transoxygenator resistance was measured throughout cardiopulmonary bypass.
Beta-thromboglobulin levels were used to study contact activation of platelets.
Measures of prothrombin F1,2 fragments were used as a marker of thrombin
generation. Body surface area, age, preoperative albumin, hematocrit,
hemoglobin, fibrinogen, platelet count, and colloid osmotic pressure levels were
compared between groups. RESULTS: Base line characteristics and chosen control
measurements were similar for all three populations. When comparing the observed
transoxygenator resistance among the three different groups, no significant
differences were noted. Prothrombin F1.2 fragments remained low for all the
groups without significant differences. In the no-albumin group the level of
beta-thromboglobulin appeared to be higher, but the difference was not
statistically significant. CONCLUSIONS: Addition of albumin to prime solution in
a cardiopulmonary bypass circuit that already contains colloids does not affect
the transoxygenator resistance of the COBE Duo flat sheet oxygenator and does
not affect prothrombin F1.2 and beta-thromboglobulin levels. Therefore
additional costs for the albumin are not justified. Measurement of
transoxygenator resistance is a reliable, simple method to determine the effects
of a prime solution on the oxygenator surface in vivo.

J Heart Lung Transplant  2001 Sep;20(9):1005-9

The changing profile of the cardiac donor.

Brock MV, Salazar JD, Cameron DE, Baumgartner WA, Conte JV.

Johns Hopkins Medical Institutions, Divisions of Cardiac and Thoracic Surgery,
Baltimore, Maryland, USA

Background: Expansion of traditional donor criteria has become standard in most
centers. To determine how this has affected donor profiles, at our institution,
we reviewed all adult (age >/= 16) cardiac donors of the past 15 years.Methods:
We separated 261 cardiac donors into 2 groups based on time periods: Group I,
1983 to 1991 (n = 131), and Group II, 1991 to 1998 (n = 130).Results: The groups
differed significantly in mean donor age (26.2 years vs 30.9; p < 0.001),
percent older than 40 years (6% vs 27%; p < 0.001), percent female (23% vs 35%;
p = 0.04), percent distant procurement (54% vs 22%; p < 0.001), and percent
minority donors (14% vs 29%; p < 0.001). We found an increase in non-traumatic
deaths (24% vs 40%; p = 0.008). Older donors had significantly more
non-traumatic deaths than younger donors (79% vs 13%; p < 0.001). Overall 5-year
survival of recipients was 64% and was not significantly different between our
early and late experiences (60% vs 68%; p = not significant [NS]). Recipients
with hearts from older donors had a 5-year survival similar to recipients with
younger donor hearts (61% vs 64%; p = NS). Traumatic and non-traumatic donors
had similar 5-year survivals (64% vs 63%, p = NS). A stepwise multivariate
analysis of the entire cohort identified donor age, donor weight, recipient
United Network for Organ Sharing status, and cardiopulmonary bypass time as
significant independent risk factors for recipient survival. Recipients of
hearts from donors < 90 kg had significantly better 5-year survivals than
recipients from donors >/= 90 kg (66% vs 48%; p = 0.01).Conclusions: Our
evolving cardiac donor pool now has more minorities, women, and older donors
whose deaths are often non-traumatic. At our institution, donor pool expansion
has had no adverse effect on the long-term survival of recipients.

Chest  2001 Sep;120(3):860-5

Cardioprotective effect of adenosine pretreatment in coronary artery bypass
grafting.

Wei M, Kuukasjarvi P, Laurikka J, Honkonen EL, Kaukinen S, Laine S, Tarkka M.

Division of Cardiovascular Surgery, Tampere University Hospital, Tampere,
Finland.

OBJECTIVE: There are several reports of the use of adenosine as a
cardioprotective agent during cardiac surgery. Adenosine treatment might affect
neutrophils and inflammatory mediators. The present prospective randomized study
was designed to investigate the effect of adenosine pretreatment on myocardial
recovery and inflammatory response in patients undergoing elective coronary
artery bypass surgery. DESIGN: A prospective, randomized, controlled study.
SETTING: Operative unit and ICU in a university hospital in Finland. PATIENTS:
Thirty male patients undergoing primary, elective coronary revascularization.
INTERVENTIONS: Patients in the adenosine group received a 7-min infusion of
adenosine (total, 650 microg/kg) before the initiation of cardiopulmonary
bypass. MEASUREMENTS: Postoperative creatine kinase (CK)-MB release and
hemodynamics were recorded. Perioperative leukocyte and cytokine release were
measured. RESULTS: Adenosine pretreatment resulted in less CK-MB release and an
improved postbypass cardiac index. Similar leukocyte counts and cytokine
responses were seen in both groups perioperatively. Neutrophil counts were
similar between the groups before and after myocardial ischemia when measured
simultaneously in arterial and coronary sinus blood. CONCLUSIONS: The present
results support the hypothesis that adenosine pretreatment is cardioprotective
in humans, but the present dose failed to regulate the inflammatory responses
after coronary artery bypass grafting.

Kyobu Geka  2001 Sep;54(10):835-8

[Blood transfusion under cardiopulmonary bypass is a possible inducer for
inflammation]?

[Article in Japanese]

Hamada Y, Kohtani T, Nakata T, Takano S, Tsunooka N, Kawachi K, Kadota M.

Department of Surgery II, Ehime University School of Medicine, Ehime, Japan.

To investigate that blood transfusion under cardiopulmonary bypass is a possible
inducer for inflammation, a retrospective study was made with 20 adult patients
who underwent coronary artery bypass grafting. The subjects were divided into
two groups; transfusion group (group T) including 9 patients who received blood
transfusion during cardiopulmonary bypass and the control group (group C)
including 11 patients who did not undergo perioperative transfusion. Respiratory
index as an indicator of respiratory functions was determined before and
immediately after cardiopulmonary bypass, at the end of surgery and 4 hours
thereafter. Cardiac index and arterial pressure were determined as the indicator
of cardiac function. Moreover, interleukin 6 and 8 (IL-6 and IL-8), inflammatory
cytokines were measured and compared between the two groups. The mean amount of
blood transfusion was 2.1 units per individual of group T. The minimum value of
hematocrit during cardiopulmonary bypass was significantly lower in group T
(15.8 +/- 1.8%) than group C (19.1 +/- 1.4%), but the difference became not
significant after cardiopulmonary bypass. There were no significant differences
either in aortic pressure or cardiac index between two groups. The respiratory
index at the end of surgery was higher in group T but the difference was not
significant. Meanwhile IL-8 level at the end of cardiopulmonary bypass was
significantly higher in group T (67.9 +/- 36 pg/ml) than group C (35.1 +/- 21
pg/ml). However, there was no difference in IL-6 level between the two. These
results suggested that inflammation might be aggravated by an increase of IL-8
induced by blood transfusion.

Eur J Anaesthesiol  2001 Sep;18(9):576-84

What factors are associated with hyperlactatemia after cardiac surgery
characterized by well-maintained oxygen delivery and a normal postoperative
course? A retrospective study.

Inoue S, Kuro M, Furuya H.

Department of Anesthesiology, National Cardiovascular Center, 5-7-1
Fujishirodai, Suita, Osaka 565, Japan.

BACKGROUND: and objective The purpose of this study was to investigate
retrospectively what factors contribute to the development of the type of
hyperlactatemia which may follow cardiopulmonary bypass despite well-maintained
oxygen delivery and a normal perioperative course. METHODS: The medical records
of 124 patients undergoing elective cardiac surgery using cardiopulmonary bypass
were reviewed. The patients were divided into a hyperlactatemia group (n=34),
where the serum lactate concentration was > 5.0 mmol L-1 perioperatively, and a
normal lactatemia group (n=90), which comprised the remaining patients. RESULTS:
The duration of cardiopulmonary bypass in the hyperlactatemia group was
significantly longer than for the normal lactatemia group. Significant
differences of lactate concentrations between the groups, and significant
elevations of serum lactate had been observed after the start of cardiopulmonary
bypass. Oxygen extraction rates were significantly reduced during the period of
cardiopulmonary bypass but, on the contrary, increased in the hyperlactatemia
group after surgery. The area under the curve of mean arterial pressure
consisted of 5-min interval plots during the initial period of cardiopulmonary
bypass in the hyperlactatemia group. This was significantly smaller than for the
normal lactatemia group. Weakly significant correlations between maximal lactate
and duration of cardiopulmonary bypass, and especially the area under the curve,
were observed. CONCLUSIONS: It is suggested that the pathophysiology observed is
based on impairment of tissue oxygen utilization. The duration of
cardiopulmonary bypass and especially the occurrence of hypotension at the start
of the bypass period appears to be related to the development of lactic
acidosis.

J Thorac Cardiovasc Surg  2001 Sep;122(3):457-63

Low-dose postoperative aprotinin reduces mediastinal drainage and blood product
use in patients undergoing primary coronary artery bypass grafting who are
taking aspirin: A prospective, randomized, double-blind, placebo-controlled
trial.

Alvarez JM, Jackson LR, Chatwin C, Smolich JJ.

Cardiothoracic Surgery Unit, Monash Medical Centre, and the Centre for Heart and
Chest Research, Departments of Medicine and Surgery, Monash University, Clayton,
Victoria, Australia.

BACKGROUND: Although low-dose aprotinin administered after cardiopulmonary
bypass has been reported to reduce mediastinal blood loss and blood product
requirements in patients not taking aspirin, it is unknown whether low-dose
postoperative aprotinin has any beneficial effects in patients undergoing
coronary artery bypass operations who are at high risk of excessive
postoperative bleeding and increased transfusion requirements because of aspirin
use until just before the operation. METHODS: Fifty-five patients undergoing
primary coronary artery operations with cardiopulmonary bypass who continued
taking aspirin (150 mg/d) until the day before the operation were enrolled in a
prospective, randomized, double-blind trial to receive a single dose of either
placebo (n = 29) or 2 x 10(6) kallikrein inhibiting units of aprotinin (n = 26)
at the time of sternal skin closure. RESULTS: Patients in the aprotinin group
had a lower rate (28 +/- 18 vs 43 +/- 21 mL/h [mean +/- standard deviation], P
<.005) and total volume of mediastinal drainage (955 +/- 615 vs 1570 +/- 955 mL,
P <.007), as well as a shorter duration of mediastinal drain tube insertion
(24.4 +/- 13.8 vs 31.3 +/- 16.5 hours, P <.05). In addition, a smaller
proportion of patients receiving aprotinin required a blood product (31% vs 62%,
P =.03), resulting in a reduction in the use of packed cells by 47% (P =.05),
platelets by 77% (P =.01), fresh frozen plasma by 88% (P =.03), and total blood
products by 68% (P =.01) in this group. CONCLUSIONS: These results suggest that
postoperative administration of low-dose aprotinin in patients taking aspirin
until just before primary coronary artery operations with cardiopulmonary bypass
not only reduces the rate and total amount of postoperative mediastinal blood
loss but also lowers postoperative blood product use.

J Thorac Cardiovasc Surg  2001 Sep;122(3):449-56

Prime solutions for cardiopulmonary bypass in neonates: Antioxidant capacity of
prime based on albumin or fresh frozen plasma.

Molicki JS, Draaisma AM, Verbeet N, Munneke R, Huysmans HA, Hazekamp MG, Berger
HM.

Department of Pediatrics, Division of Neonatology, Department of Extracorporeal
Circulation, and the Department of Cardiothoracic Surgery, Leiden University
Medical Center, Leiden, The Netherlands.

OBJECTIVE: Oxidative damage and inflammation are believed to play an important
role in postoperative complications after cardiopulmonary bypass. During bypass,
a prime solution with a high antioxidant capacity may reduce the oxidative
damage and inflammation. We investigated total antioxidant capacity and
individual scavengers during the preparation of 2 different prime solutions.
METHODS: The prime solutions were prepared with either pasteurized human albumin
or fresh frozen plasma. The total antioxidant capacity was measured with the
total radical antioxidant parameter assay and with the ferric-reducing ability
of plasma assay. The individual scavengers vitamin C, sulfhydryl groups, uric
acid, and total protein were measured before, during, and after the prime
preparation. Malondialdehyde was measured as a parameter for lipid peroxidation.
RESULTS: Neither prime solution showed a total radical antioxidant parameter
value. The ferric-reducing ability of plasma value of prime solutions was lower
than that of undiluted human albumin or fresh frozen plasma. Addition of
mannitol did not increase the ferric-reducing ability of plasma value. Vitamin C
was only found in the fresh frozen plasma prime. Both prime solutions contained
sulfhydryl groups and uric acid in low concentrations. During ultrafiltration,
low-molecular-weight antioxidants were lost into the ultrafiltrate. CONCLUSIONS:
We showed that prime solutions based on either albumin or fresh frozen plasma
had very low antioxidant capacity and that ultrafiltration of the prime solution
further lowers this capacity. A prime solution with a low antioxidant capacity
may increase oxidative stress in neonates undergoing cardiopulmonary bypass.