J Thorac Cardiovasc Surg. 2003 Jun;125(6):1426-31.  

Methylene blue: The drug of choice for catecholamine-refractory vasoplegia after
cardiopulmonary bypass?

Leyh RG, Kofidis T, Struber M, Fischer S, Knobloch K, Wachsmann B, Hagl C, Simon
AR, Haverich A.

Division of Thoracic and Cardiovascular Surgery, Hannover Medical School,
Hannover, Germany.

OBJECTIVES: Vasoplegia is a frequent complication after cardiopulmonary bypass
that often requires the application of norepinephrine. In a number of cases,
however, vasoplegia is refractory to norepinephrine. The guanylate cyclase
inhibitor methylene blue could be an attractive treatment alternative in such
cases. This study examines the results of methylene blue therapy for
norepinephrine-refractory vasoplegia after cardiopulmonary bypass. METHODS: A
total of 54 patients with norepinephrine-refractory vasoplegia after
cardiopulmonary bypass were treated with methylene blue (2 mg/kg) administered
intravenously through a period of 20 minutes. The effects on hemodynamics,
norepinephrine dosage, and clinical outcome were evaluated. RESULTS: Three
patients (5.6%) died during the hospital stay. A clinically relevant increase in
systemic vascular resistance and a decrease in norepinephrine dosage were
observed in 51 patients within 1 hour after methylene blue infusion. Four
patients (7.4%) had no response to methylene blue. No adverse effects related to
methylene blue were observed. CONCLUSIONS: A single dose of methylene blue seems
to be a potent approach to norepinephrine-refractory vasoplegia after
cardiopulmonary bypass for most patients, with no obvious side effects.
Guanylate cyclase inhibitors could be a novel class of agents for the treatment
of norepinephrine-refractory vasoplegia after cardiopulmonary bypass. A
controlled clinical trial is now needed to evaluate the role of methylene blue
in this situation.

Eur J Cardiothorac Surg. 2003 Jun;23(6):1007-1016.  

Long-term results after cardiac surgery in patients infected with the human
immunodeficiency virus type-1 (HIV-1).

Mestres CA, Chuquiure JE, Claramonte X, Munoz J, Benito N, Castro MA, Pomar JL,
Miro JM.

Department of Cardiovascular Surgery, Hospital Cli;nico, Institut
d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of
Barcelona, Barcelona, Spain

OBJECTIVES: Assessment of long-term results of immunodeficiency virus type-1
(HIV-1)-infected patients undergoing cardiac surgery. METHODS: Retrospective
analysis of profile and outcomes of 31 HIV-1-infected patients (35 operations,
1985-2002). RESULTS: Twenty-seven males and four females (mean age 34.67) in
three groups: acute infective endocarditis (AIE) 21 (67.74%), coronary (CAD) 5
(16.13%) and non-infective valvular disease (NIVD) 5 (16.13%). HIV factors: drug
addiction (23-74.19%), homosexuality (5-16.12%), heterosexuality (3-9.67%),
hemodialysis (1-3.22%). HIV stage: A (17), B (2), C (2) in AIE; A (2), B (3) in
CAD and A (3), C (2) in NIVD. Mean preoperative CD4 count was 278cells/&mgr;L
(12<200cells/&mgr;L, 38.7%). The most frequent pathogens: S. aureus (52.38%), S.
viridans (23.8%), Candida (19.04%). Native valve involved in 22 cases (78.33%)
and prostheses in 8 (26.67%); 8.57% were operated in 1980-1985, 14.28% in
1986-1990, 22.85% in 1991-1995 and 54.28% in 1996-2002 with 16 elective
(48.17%), 17 urgent (45.71%) and two emergencies (5.71%); mean aortic clamping
and cardiopulmonary bypass time 78.9 and 107.47 min. Hospital mortality was
22.58 and 28.57% in AIE. No CAD patient died. Nine patients (37.5%) died between
2 and 171 months (mean 54.5). Mortality was 50% in AIE. CD4 count increased from
185.33 to 396.55cells/&mgr;L (P=0.43) in nine patients on antiretrovirals.
Fifteen-year actuarial survival is 58.16% overall and 48.01% for AIE.
CONCLUSIONS: There is an increase in HIV-1-infected patients requiring cardiac
surgery, a decrease in AIE, however NIVD and CAD increasingly seen. Cardiac
surgery did not blunt CD4 response induced by antiretrovirals. The late cause of
death were not AIDS-related events.

J Cardiothorac Vasc Anesth. 2003 Jun;17(3):309-13.  

Effect of site of venous protamine administration, previously alleged risk
factors, and preoperative use of aspirin on acute protamine-induced pulmonary
vasoconstriction.

Comunale ME, Maslow A, Robertson LK, Haering JM, Mashikian JS, Lowenstein E.

OBJECTIVE: To determine whether the incidence of protamine-induced pulmonary
vasoconstriction (PIPV) is influenced by central venous versus peripheral venous
infusion of protamine and whether aspirin ingestion within a week of surgery
would decrease the incidence of PIPV. DESIGN: Single-institution, prospective,
observational, randomized trial. SETTING: University teaching hospital.
PARTICIPANTS: One thousand four hundred ninety-seven consecutive patients
undergoing cardiopulmonary bypass procedures. INTERVENTION: Protamine
neutralization of heparin by infusion pump via either central venous or
peripheral venous route.MEASUREMENTS AND MAIN RESULTS: Five previously suspected
risk factors (valve surgery, prior protamine exposure, history of pulmonary
hypertension, fish allergy, and vasectomy), aspirin ingestion within 7 days of
surgery, and demographic information were recorded. PIPV was defined as an
abrupt increase in mean PA pressure of 7 mmHg or more with associated right
ventricular dysfunction as assessed by observation of the right ventricle in the
field and regional wall motion abnormality by transesophageal echocardiogram and
hypotension (systolic blood pressure </= 90 mmHg). Data were collected via
continuous strip chart recording. A total of 10 patients (0.6%) developed PIPV
during protamine infusion. The incidents were similar with respect to the site
of venous administration. Prior exposure to protamine was associated with a
greater incidence of PIPV (odds ratio 6.9; p < 0.01). Other previously suspected
risk factors did not achieve statistical significance. None of the 766 patients
who ingested aspirin experienced PIPV as opposed to 10 of the 731 patients who
did not ingest aspirin (odds ratio 0.08; p < 0.001). CONCLUSIONS: Although the
site of venous protamine administration does not influence incidence of PIPV,
aspirin ingestion within 1 week of surgery may decrease it. These data also
confirmed other studies suggesting that previous protamine administration
predisposes to this protamine reaction.

Anadolu Kardiyol Derg. 2003 Jun;3(2):124-8.  

Effectiveness of intraaortic balloon pumping in patients who were not able to be
weaned from cardiopulmonary bypass after coronary artery bypass surgery and
mortality predictors in the perioperative and early postoperative period.

Tokmakoglu H, Farsak B, Gunaydin S, Kandemir O, Aydin H, Yorgancioglu C, Suzer
K, Zorlutuna Y.

Clinic of Cardiovascular Surgery, Ankara Bayindir Hospital, Ankara, Turkey.

OBJECTIVE: The intraaortic balloon pump (IABP) is usually the first choice of
mechanical device used for perioperative cardiac failure. The aim of this
retrospective study was to determine the effectiveness of intraoperative IABP
use in patients who could not be weaned from cardiopulmonary bypass (CPB) and to
determine the possible perioperative and early postoperative prognostic factors
for mortality. METHODS: Between June 1992-December 2001 a total of 69 patients
who underwent coronary artery bypass grafting and required IABP support in
weaning from CPB due to cardiac pump failure were included into the study. The
mean age was 61.9+/-7.5 years. The effectiveness of IABP and preoperative,
operative and postoperative risk factors for mortality were evaluated
retrospectively. RESULTS: Following the insertion of IABP, 59 (85.5%) patients
could be weaned from CPB whereas 10 patients (14.5%) could not. In the early
postoperative period, 13 (22%) patients died due to cardiac pump failure. The
average in-hospital mortality rate for patients who were treated with an IABP
was found as 33.3% (23 patients). Univariate analysis identified left
ventricular enddiastolic pressure, ventricular performance score, urgent
operation and perioperative myocardial infarction as the risk factors for early
death. The minor and major IABP related complications occurred in only 8
patients. CONCLUSION: Due to the contributory effects, effectiveness and low
complication rate, IABP may be used in patients who cannot be weaned from CPB.

Ann Thorac Surg. 2003 Jun;75(6):1892-7; discussion 1897-8.  

Serial measurement of serum S-100B protein as a marker of cerebral damage after
cardiac surgery.

Ueno T, Iguro Y, Yamamoto H, Sakata R, Kakihana Y, Nakamura K.

Second Department of Surgery, Division of Intensive Care Medicine, Faculty of
Medicine, Kagoshima University, Kagoshima, Japan.
takayuki@m3.kufm.kagoshima-u.ac.jp

BACKGROUND: We used serial measurements of serum S-100B protein to evaluate the
time course of serum S-100B protein concentration after cardiovascular surgery
and to determine the clinical relevance of its concentration and cerebral
damage. METHODS: We assessed neurologic function in 149 patients undergoing
cardiovascular surgery with cardiopulmonary bypass. The patients were classified
into three groups according to their early postoperative outcome: those without
complications (group A), those having unconsciousness or convulsion or both but
no hemiplegia (group B), and those having unconsciousness and hemiplegia either
with or without convulsion (group C). Serum S-100B protein concentrations were
measured with a commercially available immunoluminometric assay, Sangtec 100
LIA, at seven time-points: before cardiopulmonary bypass, at the end of
cardiopulmonary bypass, and at 5, 12, 24, 48, and 72 hours after cardiopulmonary
bypass. RESULTS: At 5 hours after cardiopulmonary bypass, the S-100B values in
groups B and C were significantly higher than the value in group A. Although the
S-100B level decreased in group C during the first 5 hours after cardiopulmonary
bypass, it increased thereafter (12 through 24 hours) and continued at a high
level until the final measurement at 72 hours. At 12 hours after cardiopulmonary
bypass, S-100B was significantly higher in group C than in group B. This late
increase in S-100B was associated with radiologically detected abnormalities and
cerebral damage. CONCLUSIONS: Serial measurement of serum S-100B protein in the
initial 12 hours after cardiopulmonary bypass can be used to predict early
postoperative brain injury.

Kyobu Geka. 2003 Jun;56(6):479-82.  

[Preoperative autologous blood donation with cardiac surgery]

[Article in Japanese]

Yoda M, Nonoyama M, Shimakura T, Morishita A, Takasaki T.

Department of Cardiovascular Surgery, Fukuyama Circulation Hospital, Fukuyama,
Japan.

BACKGROUND: Preoperative autologous blood donation is commonly used to reduce
exposure to homologous blood transfusions among patients undergoing elective
cardiac surgery. The purpose of this study was to ascertain how much volume of
predonated autologous blood need to avoid of homologous blood transfusion in
cardiac procedure. METHODS: One hundred twenty-eight patients underwent
scheduled cardiac procedure between January 1998 and December 1999. Group 1: 400
ml predonated, operation without cardiopulmonary bypass (CPB) [n = 33], group 2:
800 ml predonated, operation without CPB (n = 23), group 3: 800 ml predonated,
operation with CPB (n = 36), group 4: 1,200 ml predonated, operation with CPB (n
= 36). Surgical procedures underwent only off-pump coronary artery bypass
grafting (OPCAB) in groups 1 and 2. In groups 3 and 4 included coronary artery
bypass grafting (CABG), valve replacement, CABG + valve replacement and atrial
septal defect repair. RESULTS: There were no significant differences in mean
body weight, mean preoperative hematocrit values or mean volume of
intraoperative blood loss between groups 1 and 2. There were no significant
differences in mean age, mean body weight, mean preoperative and postoperative
day-7 hematocrit values, mean volume of intraoperative blood loss or mean CPB
time between groups 3 and 4. The mean postoperative day-7 hematocrit value was
significantly lower in group 1 than in group 2. Homologous blood transfusion was
avoided in 63.6% of those with predonation of group 1 versus 100% at group 2 (p
< 0.05), 86.1% at group 3 versus 94.4% at group 4 (p < 0.05). In group 3, all
patients who underwent redo operation or CABG + valve replacement needed
homologous blood transfusion. CONCLUSIONS: Autologous blood transfusion is
effective for reducing the homologous blood requirement. It also seems that
predonation of 800 ml may be sufficient to avoid homologous blood transfusion in
cardiac surgery, however predonation of 1,200 ml is desirable in cases of redo
operation or CABG + valve replacement.

Crit Care Med. 2003 Jun;31(6):1742-5.  

Dexamethasone reduces postoperative troponin levels in children undergoing
cardiopulmonary bypass.

Checchia PA, Backer CL, Bronicki RA, Baden HP, Crawford SE, Green TP, Mavroudis
C.

OBJECTIVEWe previously demonstrated that dexamethasone treatment before
cardiopulmonary bypass in children reduces the postoperative systemic
inflammatory response. The purpose of this study was to test the hypothesis that
dexamethasone administration before cardiopulmonary bypass in children
correlates with a lesser degree of myocardial injury as measured by a decrease
in cardiac troponin I release.DESIGNA prospective, randomized, double-blind
study.SETTINGThe cardiac surgery operating room and intensive care unit of a
pediatric referral hospital.SUBJECTSTwenty-eight patients who underwent
open-heart surgery for congenital heart defects.INTERVENTIONSPatients received
either placebo (group I, n = 13) or dexamethasone, 1 mg/kg iv (group II, n =
15), 1 hr before initiation of cardiopulmonary bypass. Plasma cardiac troponin I
samples were obtained at three time points: immediately before study agent
(sample 1), 10 mins after protamine sulfate administration after cardiopulmonary
bypass (sample 2), and 24 hrs postoperatively (sample 3).MEASUREMENTS AND MAIN
RESULTSMean cardiac troponin I levels (+/-sd) were significantly lower at sample
time 3 in group II (dexamethasone; 33.4 +/- 20.0 ng/mL) vs. group I (control;
86.9 +/- 81.1) (p =.04).CONCLUSIONDexamethasone administration before
cardiopulmonary bypass in children resulted in a significant decrease in cardiac
troponin I levels at 24 hrs postoperatively. We postulate that this may
represent a decrease in myocardial injury, and, thus, a possible
cardioprotective effect produced by dexamethasone.

Expert Opin Pharmacother. 2003 Jun;4(6):919-40.  

Pharmacotherapy of heparin- induced thrombocytopenia.

Dager WE, White RH.

Anticoagulation Service, UC Davis Medical Center, UC Davis School of Medicine,
Sacramento CA, USA. william.dager@ucdmc.ucdavis.edu

Heparin-induced thrombocytopenia (HIT) is a life-and-limb threatening condition
that is associated with the development of antibodies that activate platelets
and the coagulation system in the presence of unfractionated heparin or low
molecular weight heparin. The binding of antibody to heparin-PF-4 complexes can
activate platelets, leading to an acute, often catastropic, thrombotic
diathesis. The most common laboratory finding is the development of
thrombocytopenia 5 or more days after beginning heparin treatment, which occur
in up to 1 - 5% of patients exposed to heparin, depending on type of heparin and
indication for anticoagulation. The onset of thrombocytopenia can be immediate
or delayed for several weeks after the exposure to heparin. Approximately 50 -
60% of patients who develop HIT manifest acute venous or arterial thrombosis and
a significant percentage of these patients die or develop vascular gangrene of a
limb that requires amputation. Given the severe sequelae associated with HIT,
recognition and immediate medical management is essential. Treatment of a
patient with HIT is complex, as there are several different anticoagulants now
available which have been shown to be useful. Optimal management depends on each
patient's individual clinical manifestations, as well as the need for ongoing
anticoagulation therapy. No single agent or treatment approach can be considered
to be 'standard practice' as very few clinical trials have been completed,
compare different treatment options. The use of warfarin alone in a patient with
HIT, must be avoided in order to avoid the possibility of further activating
coagulation, which may hasten the development of venous limb gangrene. There are
several different tests available that detect HIT antibodies and each has
different sensitivity and specificity for HIT. In this review we discuss the
epidemiology and natural history of HIT, risk factors associated with the
development of HIT and the clinical and laboratory tests that aid in the
diagnosis and treatment. Special emphasis is given to addressing the management
of HIT in special populations, particularly patients with renal or liver
disease, acute coronary syndromes, pregnancy, paediatrics and patients who
require cardiopulmonary bypass surgery.

Pediatrics. 2003 Jun;111(6 Pt 1):e671-5.  

Neurodevelopmental outcome of infants supported with extracorporeal membrane
oxygenation after cardiac surgery.

Hamrick SE, Gremmels DB, Keet CA, Leonard CH, Connell JK, Hawgood S, Piecuch RE.

Department of Pediatrics, University of California San Francisco, 521 Parnassus
Ave, C-215, San Francisco, CA 94122-0663, USA. segh@itsa.ucsf.edu

OBJECTIVES: To evaluate the long-term neurodevelopmental outcome of infants who
underwent cardiac surgery and required extracorporeal membrane oxygenation
(ECMO) support, and to examine variables that predict death or disability in
these patients. METHODS: We studied all infants who had congenital heart disease
and were supported postoperatively with ECMO from 1990 to 2001 at our
institution (n = 53). Medical records were reviewed retrospectively to obtain
clinical variables. Neurologic and age-appropriate developmental examinations
occurred at ages 1, 1.5, 2.5, and 4.5 years. Median age at follow-up was 55
months (9-101). Cognitive outcome was defined as suspect when scores were
between 1 and 2 SD below the mean for age and abnormal when scores were >2 SD
below mean for age. Neuromotor outcome was defined as suspect when the patient
manifested clumsiness, tremor, or mild tone and reflex changes without
functional limitations, and abnormal when there were functional limitations.
RESULTS: In-hospital survival was 17 (32%) of 53. Of survivors, 14 (88%) of 16
are living and 1 patient was lost to follow-up. Of the 53 patients, 7 survived
completely intact (13%). Seven (50%) of 14 patients had a normal cognitive
outcome, 3 (21%) had a suspect cognitive outcome, and 4 (29%) were abnormal. Ten
(72%) of 14 patients had a normal neuromotor outcome, 1 (7%) patient had a
suspect neuromotor outcome, and 3 (21%) were abnormal. No survivor with an
aortic cross-clamp time >40 minutes had a normal cognitive outcome. Nonsurvivors
were more likely than survivors to have had cardiac arrest as an indication for
ECMO (31% vs 6%), to have had a longer aortic cross-clamp time (mean 73 minutes
vs 32 minutes), and to have required continuous arteriovenous hemofiltration
(78% vs 35%). The age and weight at cannulation, gender, cardiac diagnosis,
interval from surgery to ECMO, cardiopulmonary bypass time, diagnosis of sepsis
or mediastinitis, and duration of ECMO were not significantly associated with
survival. CONCLUSIONS: Although mortality was 68% in infants who had congenital
heart disease and were treated with ECMO postoperatively, of those who survive
to hospital discharge, 75% have a normal neuromotor outcome and 50% have a
normal cognitive outcome. These high rates of mortality and disability suggest
that increased attention be paid to neuroprotection in these complex disorders.