Perfusion  2002 May;17 Suppl:53-62 

A review of leukofiltration in cardiac surgery: the time course of reperfusion
injury may facilitate study design of anti-inflammatory effects.

Ortolano GA, Aldea GS, Lilly K, O'Gara P, Alkon JD, Mader F, Murad T, Altenbern
CP, Tritt CS, Capetandes A, Gikakis NS, Wenz B, Shemin RJ, Downey FX 3rd.

Pall Medical, Pall Corporation, East Hills, New York, USA.
jerry_ortolano@pall.com

The systemic inflammatory response syndrome (SIRS) is a well-recognized
phenomenon attending cardiopulmonary bypass (CPB) surgery. SIRS leads to costly
complications and several strategies intended to ameliorate the symptoms have
been studied, including leukocyte reduction using filtration. Although the body
of work suggests that leukoreduction attenuates SIRS, discrepancies remain
within the literature. The recent literature is reviewed, highlighting the areas
where concordance is lacking. Investigations into many promising device-related
technologies are often deterred by the high costs of clinical trials. Adding to
costs is the fact that clinical end points generally require large sample sizes.
An understanding, however, of the pathogenesis of reperfusion injury can guide
the investigator to choose physiologic response measures that correlate well
with clinical outcome, but feature low inherent variability, allowing for
clinical trials with smaller sample sizes. With this goal in mind, a model for
the pathogenesis of reperfusion injury is described. Using a model of
reperfusion injury as underpinnings for the design of prospective pilot studies,
we show that salvaged blood reinfused following CPB elicits time-dependent
effects on pulmonary function as predicted by the model. Data are illustrative
of principles that could expand the scope of clinical investigations designed to
validate the use of physiologic response measures as correlates of clinical
outcome. Such investigations would target surrogate markers of clinical outcome,
measured at clinically relevant times. Once validated, these surrogate markers
would, thereafter, become economical screening tools for clinical studies of
device-related or pharmacological anti- inflammatory interventions.

Crit Care Med  2002 May;30(5):1140-5 

Early postoperative monocyte deactivation predicts systemic inflammation and
prolonged stay in pediatric cardiac intensive care.

Allen ML, Peters MJ, Goldman A, Elliott M, James I, Callard R, Klein NJ.

Immunobiology Unit, Great Ormond Street Hospital for Children NHS Trust, London,
UK. m.allen@ich.ucl.ac.uk

OBJECTIVE: Sepsis and systemic inflammatory response syndrome (SIRS) are major
causes of morbidity and mortality after cardiopulmonary bypass. Attempts to
suppress proinflammatory mediators have failed to improve outcomes in sepsis or
in patients undergoing cardiopulmonary bypass. Recent work in adult patients has
suggested that the balance between pro- and anti-inflammatory mediators is more
important than the level of proinflammatory response alone. This balance may be
reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with
low concentrations indicating an excess of anti-inflammatory stimuli and
relative immunodeficiency. We investigated the relationship between monocyte
HLA-DR expression and the subsequent development of sepsis/SIRS in children
undergoing cardiopulmonary bypass. 

DESIGN: A prospective, observational,
clinical study. 

SETTING: A tertiary pediatric cardiac center. 

PATIENTS:
Eighty-two infants and children undergoing elective cardiac surgery between
March and December 1999. 

MEASUREMENTS AND MAIN RESULTS: Monocyte HLA-DR
expression was assessed before and after surgery and was found to be related to
the length of hospital stay and the development of complications including
sepsis/SIRS. The inflammatory insult of cardiopulmonary bypass decreased
monocyte HLA-DR expression in all children. Lowest concentrations were seen
within 72 hrs of surgery and were significantly lower in cases that subsequently
required prolonged intensive care support (p <.0001, Mann-Whitney). HLA-DR
expression on <60% of circulating monocytes was associated with a greatly
increased risk of later (minimum 4 days) development of sepsis/SIRS (odds ratio,
12.9; 95% confidence interval, 3.4-47.5). Low HLA-DR was an independent
predictor for the development of sepsis/SIRS after correction for age, bypass
time, complexity of surgery, Paediatric Index of Mortality, and surgeon on
multiple logistic regression analysis. 

CONCLUSIONS: Patients with decreased
HLA-DR in the early postoperative period represent a subpopulation at greatly
increased risk of later sepsis/SIRS. Such patients may benefit from strategies
aimed to reduce this risk.

Heart  2002 May;87(5):461-5 

Transcatheter closure of atrial septal defect preserves right ventricular
function.

Dhillon R, Josen M, Henein M, Redington A.

Department of Paediatric Cardiology, Royal Brompton Hospital, London SW3, UK
Department of Adult Cardiology, Royal Brompton Hospital Department of Paediatric
Cardiology, Great Ormond Street Hospital, London WC1, UK.

Objectives: To determine the effects of atrial septal defects (ASD) and their
closure on systolic and diastolic right and left ventricular function; and by
comparing surgical closure with transcatheter device closure, to establish
differences attributable to cardiopulmonary bypass. Design: Cross sectionally
guided M mode echocardiographic ventricular long axis function was measured
prospectively before and within one week after ASD closure by device in 17
patients and by surgery in 12 patients, and compared with 18 normal subjects.
Results: All indices of right ventricular function were impaired after surgery:
mean total excursion, -1.89 cm (95% confidence interval (CI), -2.18 to -1.59);
peak shortening rate, -9.09 cm/s (-10.82 to -7.35); peak lengthening rate, -9.26
cm/s (-11.09 to -7.43). Total excursion and peak lengthening rate were preserved
after device closure, at -0.12 cm (-0.28 to 0.05) and 0.01 cm/s (-2.29 to 2.31),
respectively. Left ventricular free wall function was unchanged after closure by
either method, while all septal measurements were reduced after closure by
either method (changes ranging from -3.51 to -0.32; 95% CI ranging from -4.90 to
-0.13). Conclusions: Left ventricular free wall function is unaffected by ASD
closure, whereas septal function is impaired, irrespective of the method of
closure. Right ventricular function, both systolic and diastolic, is impaired by
cardiopulmonary bypass but preserved after device closure. These findings
support the transcatheter approach to ASD closure in anatomically suitable
defects.

Ann Vasc Surg  2002 May 2; [epub ahead of print] 

Outcome after Simultaneous Abdominal Aortic Aneurysm Repair and Aortocoronary
Bypass.

El-Sabrout RA, Reul GJ, Cooley DA.

Department of Cardiovascular Surgery, Texas Heart Institute at St. Luke's
Episcopal Hospital, Houston, TX.

Myocardial infarction remains the leading cause of early and late death after
abdominal aortic aneurysm (AAA) repair. Myocardial revascularization is staged
either before or concomitant with AAA resection, but results are far from
uniform. We retrospectively analyzed our experience with patients who underwent
concomitant AAA resection and aortocoronary bypass (ACB) to examine the factors
affecting early morbidity/mortality and early results. Forty-two patients (all
men; mean age, 67.2 years) underwent simultaneous ACB grafting and AAA repair
between 1975 and 1998. All were managed postoperatively in the cardiothoracic
intensive care unit (mean stay, 6.1 days). The mean total hospital stay was 17.2
days. Two died in the early postoperative period (4.8%): 1 of sustained
myocardial failure following a third ACB, and 1 of coagulopathy after
concomitant ACB, aortic valve replacement, and AAA. One patient developed a
nonfatal MI on postoperative day 3. The incidence of wound and bleeding
complications was higher for patients undergoing both ACB and AAA repair than
for patients undergoing AAA resection alone. On follow-up (mean, 10 years;
range, 7 months to 15 years), only 2 of 10 late deaths were due to
cardiovascular causes. We believe that concomitant myocardial revascularization
is warranted in select patients requiring elective or urgent AAA resection in
order to decrease perioperative risk and improve late survival. Cardiac failure
or ischemia during aortic surgery can be prevented by proper perfusion with or
without cardiopulmonary bypass. In patients undergoing simultaneous procedures,
the increased risk is related to the severity of the vascular and coronary
artery disease and not to the combined operations.

Anesthesiology  2002 May;96(5):1115-22 

Utility of whole blood hemostatometry using the clot signature analyzer(r) for
assessment of hemostasis in cardiac surgery.

Faraday N, Guallar E, Sera VA, Bolton ED, Scharpf RB, Cartarius AM, Emery K,
Concord J, Kickler TS.

Departments of Anesthesiology and Critical Care Medicine, Epidemiology, and
Pathology, and the Welch Center for Prevention, Epidemiology, and Clinical
Research, Johns Hopkins Medical Institutions, Baltimore, Maryland.

BACKGROUND: A hemostatic monitor capable of rapid, accurate detection of
clinical coagulopathy within the operating room could improve management of
bleeding after cardiopulmonary bypass (CPB). The Clot Signature Analyzer(R) is a
hemostatometer that measures global hemostasis in whole blood. The authors
hypothesized that point-of-care hemostatometry could detect a clinical
coagulopathic state in cardiac surgical patients. METHODS: Fifty-seven adult
patients scheduled for a variety of elective cardiac surgical procedures were
studied. Anesthesia, CPB, heparin anticoagulation, protamine reversal, and
transfusion for post-CPB bleeding were all managed by standardized protocol.
Clinical coagulopathy was defined by the need for platelet or fresh frozen
plasma transfusion. The Clot Signature Analyzer(R) collagen-induced thrombus
formation (CITF) assay measured platelet-mediated hemostasis in vitro. The
activated clotting time, platelet count, prothrombin time, activated partial
thromboplastin time, and fibrinogen concentration were also measured. RESULTS:
The postprotamine CITF was greater in patients who required hemostatic
transfusion than in those who did not (17.6 +/- 8.0 min vs. 10.5 +/- 5.7 min,
respectively; P < 0.01). Postprotamine CITF values were highly correlated with
platelet and fresh frozen plasma transfusion (Spearman r = 0.50, P < 0.001 and r
= 0.40, P < 0.005, respectively). Receiver operator characteristic curves showed
a highly significant relation between the postprotamine CITF and intraoperative
platelet and fresh frozen plasma transfusion (area under the curve, 0.78-0.81, P
< 0.005) with 60-80% sensitivity, specificity, positive and negative predictive
values at cutoffs of 12-14 min. Logistic regression demonstrated that the CITF
was independently predictive of post-CPB hemostatic transfusion, but standard
hemostatic assays were not. CONCLUSIONS: The Clot Signature Analyzer(R) CITF
detects a clinical coagulopathic state after CPB and is independently predictive
of the need for hemostatic transfusion. Hemostatometry has potential utility for
monitoring hemostasis in cardiac surgery.

Anesthesiology  2002 May;96(5):1095-102 

Recombinant Human Transgenic Antithrombin in Cardiac Surgery: A Dose-finding
Study.

Levy JH, Despotis GJ, Szlam F, Olson P, Meeker D, Weisinger A.

Department of Anesthesiology, Emory University School of Medicine and Division
of Cardiothoracic Anesthesiology and Critical Care, Emory Healthcare, Atlanta,
Georgia.

BACKGROUND: Acquired antithrombin III (AT) deficiency may render heparin less
effective during cardiac surgery and cardiopulmonary bypass (CPB). The authors
examined the pharmacodynamics and optimal dose of recombinant human AT (rh-AT)
needed to maintain normal AT activity during CPB, optimize the anticoagulant
response to heparin, and attenuate excessive activation of the hemostatic system
in patients undergoing coronary artery bypass grafting. METHODS: Thirty-six
patients scheduled to undergo elective primary coronary artery bypass grafting
and who had received heparin for 12 h or more before surgery were enrolled in
the study. Ten cohorts of three patients each received rh-AT in doses of 10, 25,
50, 75, 100, 125, 175, or 200 U/kg, a cohort of six patients received 150 U/kg
of rh-AT, and a control group of six patients received placebo. RESULTS:
Antithrombin III activity exceeded 600 U/dl before CPB at the highest dose (200
U/kg). Doses of 75 U/kg rh-AT normalized AT activity to 100 U/dl during CPB.
Activated clotting times during CPB were significantly (P < 0.0001) greater in
patients who received rh-AT (844 +/- 191 s) compared with placebo patients (531
+/- 180 s). Significant (P = 0.001) inverse relations were observed between
rh-AT dose and both fibrin monomer (r = -0.51) and D-dimer (r = -0.51)
concentrations. No appreciable adverse events were observed with any rh-AT doses
used in the study. CONCLUSIONS: Supplementation of native AT with transgenically
produced protein (rh-AT) in cardiac surgical patients was well tolerated and
resulted in higher activated clotting times during CPB and decreased levels of
fibrin monomer and D-dimer.

Anesth Analg  2002 May;94(5):1072-8, table of contents 

The association of complication type with mortality and prolonged stay after
cardiac surgery with cardiopulmonary bypass.

Welsby IJ, Bennett-Guerrero E, Atwell D, White WD, Newman MF, Smith PK, Mythen
MG.

Department of Anesthesiology, Duke University Medical Center, Durham, North
Carolina 27710, USA. welsb001@duke.edu

Outcome after cardiac surgery varies depending on complication type. We
therefore sought to determine the association between complication type,
mortality, and length of stay in a large series of patients undergoing cardiac
surgery with cardiopulmonary bypass (CPB). Multivariate logistic regression was
used to test for differences between complication types in mortality and
prolonged length of stay (>10 days) while controlling for preoperative and
intraoperative risk factors. In 2609 consecutive cardiac surgical patients
requiring CPB, the mortality rate was 3.6%; 36.5% had one or more complications,
and 15.7% experienced an adverse outcome (death or prolonged length of stay).
Multivariate logistic regression demonstrated that complication type was
significantly associated with adverse outcome (P < 0.001) independent of
Parsonnet score and CPB time (c-index = 0.80). The development of noncardiac
complications only (Group NC) and cardiac complications with other organ
involvement (Group B) significantly increased mortality and hospital and
intensive care unit length of stay (P < 0.001) when compared with cardiac
complications only (Group C). The incidences of adverse outcome in Groups C, NC,
and B were 15%, 43%, and 67%, respectively; the mortality rates were 3%, 7%, and
20%, respectively. All these intergroup comparisons were significantly different
(adjusted P < 0.05). Complications involving organs other than the heart appear
to be more deleterious than cardiac complications alone, underscoring the need
for strategies to reduce noncardiac complications. IMPLICATIONS: Complications,
particularly when they involve organs other than just the heart, increase
mortality and prolong the length of hospital stay after heart surgery,
independent of a patient's preoperative risk factors and the duration of
cardiopulmonary bypass. Strategies aimed at preventing damage to other organs
during cardiac surgery need to be improved.

Kyobu Geka  2002 May;55(5):357-60; discussion 361-3 

[Blood conservation in thoracic aortic surgery with total cardiopulmonary
bypass]

[Article in Japanese]

Suenaga E, Suda H, Katayama Y, Fujita H, Yunoki J, Itoh T.

Department of Thoracic Surgery, Saga Medical School, Saga, Japan.

BACKGROUND: In thoracic aortic surgery, a large number of homologous
transfusions sometimes cause systemic inflammatory response, which may lead to
pulmonary dysfunction, renal dysfunction and brain edema. To predict the need
for homologous blood transfusion in aortic surgery, we use blood transfusion
index (preoperative Ht x body weight) to predict the magnitude of homologous
transfusion. 

PATIENTS AND METHODS: From Dec 1997 to May 2000, 59 consecutive
patients were underwent thoracic aortic graft replacement with total
cardiopulmonary bypass. These patients were divided in 2 groups, who were
underwent graft replacement without blood transfusions, and who needed blood
transfusions. Each group was compared in age, sex, emergency, Ht, CPB time,
blood transfusion index and operative mortality. 

RESULTS: Forty patients (67.7%)
did not required blood transfusion. In elective cases (32 cases), 84.3% were
underwent operation without blood transfusion. There was no significant
difference between 2 groups in terms of age and mean bypass duration. Blood
transfusion index was significantly higher in transfusion group (2,320 +/- 784)
compared with that in not transfusion group (1,445 +/- 706). 

CONCLUSION: Blood
transfusion index was useful preoperative parameter to predict the need for
homologous transfusion.

Anesth Analg  2002 May;94(5):1085-91, table of contents 

Perioperative melatonin secretion in patients undergoing coronary artery bypass
grafting.

Guo X, Kuzumi E, Charman SC, Vuylsteke A.

Anaesthetic Research Unit, Papworth Hospital, Cambridge, UK..

Melatonin, a neurohormone, plays an important role in adjusting the "biological
clock" in humans. We sought to describe perioperative patterns of melatonin
secretion in patients undergoing coronary artery bypass grafting surgery with
cardiopulmonary bypass (CPB). After IRB approval and written informed consent,
12 male patients scheduled for elective coronary artery bypass grafting under
hypothermic CPB were enrolled in the study. During anesthesia, patients' eyes
were carefully covered to prevent light effects. Blood samples were taken at
specific time points during surgery, every 3 h in the immediate postoperative
period, and for 24 h from 6:00 PM of Postoperative Day 2 until 6:00 PM of
Postoperative Day 3. Plasma melatonin and cortisol concentrations were measured
by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. During
surgery, plasma melatonin concentrations were below the minimum sensitivity
concentration, yet small concentrations, without circadian variation, were
detected during the immediate postoperative period. During Postoperative Days 2
and 3, circadian secretion patterns of melatonin were present in 10 patients and
showed an inverse correlation with light intensity (r = 0.480; P < 0.01). Plasma
cortisol concentrations in the immediate postoperative period were significantly
larger than those before the induction of anesthesia (P < 0.01). Only three
patients regained circadian secretion of cortisol. We concluded that melatonin
and cortisol secretion was disrupted during cardiac surgery with CPB and in the
immediate postoperative period. However, circadian rhythms of melatonin were
present in most patients from Postoperative Day 2. Only 30% of the patients
regained circadian rhythm of cortisol secretion. IMPLICATIONS: Melatonin is a
hormone that plays an important role in adjusting the biological clock in humans
and that regulates secretion of various other hormones. We studied melatonin
secretion in patients undergoing cardiac surgery with cardiopulmonary bypass.
Melatonin secretion was disturbed during and immediately after surgery but had
recovered a circadian rhythm 24 h later, raising the question of whether
melatonin should be supplemented before cardiac surgery.