Intensive Care Med. 2005 Jan 28; 

Identifying infants at risk of marked thyroid suppression post-cardiopulmonary bypass.

Plumpton K, Haas NA.

Pediatric Intensive Care Unit, Queensland Center for Congenital Heart Disease,
Prince Charles Hospital, Rode Road, Chermside, 4032, Brisbane, QLD, Australia,
Nikolaus_Haas@ health.qld.gov.au.

OBJECTIVE: The clinical benefit of tri-iodothyrinone (T(3)) replacement
following congenital heart surgery with cardiopulmonary bypass (CPB) is not
clear in unselected cohorts of children. Infants with more marked thyroid
hormone suppression or prolonged post-CPB recovery may benefit from T(3)
replacement. This study aimed to identify infants at risk of more marked
suppression by examining the relationship between organ support parameters
during CPB and post-operative thyroid hormone levels.

DESIGN AND SETTING: Prospective observational study in a tertary referral centre for congenital
heart surgery.

PATIENTS: 36 infants less than 12 months of age were recruited following CPB.

MEASUREMENTS AND RESULTS: Thyroid hormone levels were measured on
admission to the intensive care unit and on post-operative days 1 and 2.
Increasing CPB time was associated with decreasing admission free T(3) and
thyroid-stimulating hormone. Younger, smaller infants had lower admission levels
of free T(3) on univariant analysis. Infants who continued to require
ventilation 48 h after admission to the ICU had a mean free T(3) level on
post-operative day 2 that was 0.9 pmol/l lower than in those who had been
extubated.

CONCLUSIONS: Prospective studies of T(3) replacement in selected young
infants (less than 3 months) with long CPB time (greater than 120 min) during
congenital heart surgery are warranted.

Acta Anaesthesiol Scand. 2005 Jan;49(1):35-40. 

Thermogenic effect of amino acids not demonstrated in heart surgery with
cardiopulmonary bypass.

Sellden E, Rimeika D, Settergren G.

Department of Surgical Sciences, Karolinska Institute, Divisions of Anaesthesia
and Intensive Care, Karolinska University Hospital, Solna, Stockholm, Sweden.

Background: In abdominal surgery and in healthy volunteers, amino acids
increased thermogenesis. In this double-blind study we investigated if a similar
effect would ensue in heart surgery and accelerate the rewarming process
postoperatively. 

Methods: Thirty-four patients undergoing coronary artery bypass
grafting or aortic valve replacement were randomized into two groups, and
received either 500 ml of amino acids or Ringer's solution intravenously during
4 h. The infusion was started approximately 30 min before the end of a
cardiopulmonary bypass (CPB), performed at a temperature of 34 degrees C with
rewarming to 36-37 degrees C. The lowest pulmonary artery (PA) temperature after
the CPB and the time interval until the temperature reached 37 degrees C were
recorded. Oxygen uptake was calculated from cardiac output (thermodilution) and
the pulmonary av-difference of oxygen after induction of anaesthesia, at the end
of surgery, and 1 and 2 h after the CPB. 

Results: Demographic data, medication including beta-blockers, CPB data and case mix were similar. The lowest
temperature after the CPB was 35.9 +/- 0.1 degrees C in the amino acid group and
35.6 +/- 0.2 degrees C in the control group, and the increase per hour was 0.6
+/- 0.1 degrees C and 0.6 +/- 0.0 degrees C, respectively, with no differences
between the groups. During the infusion, oxygen uptake was higher in the amino
acid group, 115 +/- 4 ml m(-2), than in the controls, 102 +/- 3 ml m(-2) (P <
0.05). No adverse effects of the infusions were noted. 

Conclusion: The lack of a thermal effect of the amino acids in the heart surgery was most probably due to
the temperature gradients between the different body compartments, and also may
have been due to the use of beta-blockers.

J Card Surg. 2005 Jan-Feb;20(1):60-4. 

Surgery for chronic total occlusion of the left main coronary artery- myocardial
preservation.

Ipek G, Omeroglu SN, Ardal H, Mansuroglu D, Kayalar N, Sismanoglu M, Guler M,
Daglar B, Yakut C.

Department of Cardiovascular Surgery, Kosuyolu Heart and Research Hospital,
Istanbul, Turkey.

Abstract We report seven patients with chronic total occlusion of the left main
coronary artery that were operated in our institution and discuss the myocardial
preservation options in these patients. In addition to total occlusion of the
left main coronary artery, three patients also had severe lesions of right
coronary artery. Prior myocardial infarction history and significantly depressed
left ventricle functions were detected in all three patients with right coronary
artery lesions. Five patients were operated on cardiopulmonary bypass while two
patients were operated off pump. All patients received alternating
antegrade/retrograde cardioplegia for myocardial preservation. In patients with
simultaneous right coronary artery disease we first established the origin of
the collaterals to the left coronary system. For patients with collaterals
arising from the right coronary artery segment distal to the right coronary
artery lesion, the antegrade component was administered through the saphenous
vein graft bypassed to a distal part of right coronary artery segment. Thus we
have achieved a more effective distribution of the antegrade cardioplegia. In
off-pump-operated patients the left coronary system was revascularized before
the right coronary system. Postoperative low cardiac output syndrome occurred in
only one patient who was operated off pump. There was no operative and early
mortality. Mean follow-up was 32 +/- 21.42 (range, 4 to 60) months. Alternating
antegrade/retrograde cardioplegia was used with acceptable results in patients
with total occlusion of the left main coronary artery. In patients with
simultaneous RCA lesion we recommend regulation of the antegrade component based
on the origin of collaterals that supplies the left coronary system. In
off-pump-operated patients we suggest avoiding of clamping of right coronary
artery at the beginning of the operation while it still supplies all the
coronary circulation. 

J Card Surg. 2005 Jan-Feb;20(1):52-7. 

Risk factors for stroke following coronary artery bypass operations.

Ali Ozatik M, Kamil Gol M, Fansa I, Uncu H, Alp Kucuker S, Kucukaksu S, Bayazit
M, Sener E, Tasdemir O.

Turkiye Yuksek Ihtisas Egitim ve Arastirma Hospital, Cardiovascular Surgery
Clinic, Ankara, Turkey.

Background: Although the overall complication rates have been decreased
significantly in recent years, stroke rates still remain high in patients
undergoing coronary bypass operations. This study is designed to evaluate the
risk factors for stroke in patients who had undergone coronary artery bypass
surgery in an 8-year period in our clinic. 

Methods: Between 1995 and 2003, 8547 coronary artery operations under cardiopulmonary bypass were performed.
Retrospective analysis of the patient files revealed that 75 (0.9%) patients had
stroke in the early postoperative period. 

Results: Mean age of these patients was 62.3 +/- 9.5 years, and 54 (72%) were males. Stroke rate was 1.2% between
1995 and 1998 and this was significantly higher from the stroke rate (0.7%) of
the period 1998 to 2003 (p = 0.03). Major technical differences between these
two periods were the routine application of preoperative carotid arteries
Doppler evaluation and intraoperative epiaortic echocardiography after 1998.
Higher age (p = 0.000), female sex (p = 0.005), smoking (p = 0.03), presence of
diabetes mellitus (p = 0.01), hypertension (p = 0.008), and left main coronary
artery disease (p = 0.001), carotid surgery (p = 0.000), and peripheral vascular
disease (p = 0.049) were identified as important risk factors in univariate
analysis for stroke development. Higher age (p = 0.000; OR = 21.38), left main
coronary artery disease (p = 0.007; OR = 7.26), peripheral vascular disease (p =
0.050; OR = 3.08), and operation date before 1998 (p = 0.012; OR = 6.33) were
identified as important risk factors in logistic regression analysis. According
to intraoperative epiaortic ultrasonography, operative strategy was changed in
9% of patients. Thirty-seven (49.3%) of the stroke patients died. Female sex (p
= 0.023; OR = 5.18) and preoperative hypertension (p = 0.045; OR = 4.03) were
observed as significant risk factors for mortality after stroke. 

Conclusion: Development of stroke is one of the major reasons of mortality after coronary
artery bypass operations. It is essential to take all the measures to prevent
this complication, especially in patients with known risk factors. Evaluation of
carotid arteries prior to operation and application of routine intraoperative
epiaortic echocardiography may in part eliminate stroke.

Br J Surg. 2005 Jan 25; 

Gastrointestinal complications after cardiac surgery.

Andersson B, Nilsson J, Brandt J, Hoglund P, Andersson R.

Department of Surgery, Lund University Hospital, Lund, Sweden.

BACKGROUND:: Gastrointestinal complications after cardiac surgery are often
difficult to diagnose, and are associated with high morbidity and mortality
rates. The aim of this study was to determine risk factors for these
complications. 

METHOD:: Between 1996 and 2001 data were collected prospectively
from 6119 patients who underwent 6186 cardiac surgical procedures. Data from
patients who experienced major gastrointestinal complications were analysed
retrospectively by univariate and multivariate analysis. 

RESULTS:: Fifty major gastrointestinal complications were identified in 47 patients (incidence 0.8 per
cent). Thirteen of these patients died within 30 days. The most common
complication was upper gastrointestinal bleeding (16 patients). Intestinal
ischaemia was the most lethal complication (eight of ten patients died).
Abdominal surgical operations were performed in 12 patients. Multivariate
analysis identified nine variables that independently predicted major
gastrointestinal complications: age over 80 years, active smoker, need for
preoperative inotropic support, New York Heart Association class III-IV,
cardiopulmonary bypass time more than 150 min, postoperative atrial
fibrillation, postoperative heart failure, reoperation for bleeding and
postoperative vascular complications. 

CONCLUSION:: Nine risk factors for the development of major gastrointestinal complications after cardiac surgery were
identified. Gastrointestinal complications were often lethal but did not
independently predict death within 30 days. 

Thromb Res. 2005;115(4):327-40. 

The kinetics of plasmin inhibition by aprotinin in vivo.

Kang HM, Kalnoski MH, Frederick M, Chandler WL.

Department of Laboratory Medicine, Box 357110, University of Washington,
Seattle, WA 98195-7110, USA.

INTRODUCTION: The purpose of this study was to estimate, in patients undergoing
cardiopulmonary bypass (CPB), the in vivo rates of tissue plasminogen activator
(tPA) and plasminogen activator inhibitor 1 (PAI-1) secretion, plasmin
generation, fibrin degradation, and plasmin inhibition by aprotinin versus
antiplasmin. 

MATERIALS AND METHODS: Estimates of in vivo rates were based on
measured levels of tPA, PAI-1, antiplasmin, plasmin-antiplasmin complex (PAP),
total aprotinin, plasmin-aprotinin complex and D-dimer, combined with a computer
model of each patient's vascular system that continuously accounted for
secretion, clearance, hemodilution, blood loss and transfusion. Plasmin
regulation was studied in nine control patients undergoing CPB without aprotinin
versus six patients treated with aprotinin. 

RESULTS: In controls, plasmin-antiplasmin levels rose from a baseline of 3.0+/-0.9 to a peak of
8.1+/-2.7 nmol/L after CPB due to an average 44-fold rise in the plasmin
generation rate. This rise in plasmin generation during CPB lead to increased
fibrin degradation causing D-dimer levels to increase from a baseline of
1.2+/-0.6 to a peak of 9.7+/-4.4 nmol/L due to an average 74-fold rise in the
D-dimer generation rate. During CPB in the aprotinin group, plasmin-antiplasmin
levels dropped, plasmin-aprotinin complex levels rose, while D-dimer levels
remained unchanged from baseline. Compared to controls, the aprotinin group
showed similar rates of plasmin generation during CPB, but an 11-fold faster
plasmin inhibition rate and a 10-fold lower D-dimer generation rate.

CONCLUSIONS: The rise in plasmin generation and fibrin degradation that occurs
during standard CPB is suppressed by the addition of aprotinin, which returns
the patient to near baseline fibrin degradation rates during CPB.

Epilepsia. 2005 Jan;46(1):84-90. 

Electrographic neonatal seizures after infant heart surgery.

Clancy RR, Sharif U, Ichord R, Spray TL, Nicolson S, Tabbutt S, Wernovsky G,
Gaynor JW.

Division of Neurology, The Children;s Hospital of Philadelphia, Philadelphia,
Pennsylvania, U.S.A.

Summary: Purpose: Neonatal seizures are relatively common and an important early
sign of acute encephalopathy in those who survive infant heart surgery. The
contemporary occurrence of seizures in this setting is not fully known, and
their electrographic characteristics are incompletely described. This study
describes the characteristics of electrographic neonatal seizures (ENSs) in
contemporary infants with congenital heart disease (CHD) surgically repaired by
using cardiopulmonary bypass, with or without deep hypothermic circulatory
arrest. Methods: Consecutive infants undergoing heart surgery were monitored by
video-EEG for 48 h postoperatively to establish the time of first seizure, total
number of ENSs, site(s) of ENS(s) origin and other characteristics. Results:
ENSs occurred in 21 (11.5%) of 183 infants. None had clinically visible
seizures. The mean time to the first ENS was 21 h (range, 10-36 h). The total
number of ENSs among the entire cohort was 1,429. Mean total number of ENSs per
patient over a 48-h period was 72 (range, 1-217). Phenobarbital administration
was associated with a >/=50% reduction in seizure counts in five (41.7%) of 12
subjects. Conclusions: ENSs were relatively common in a large, contemporary
cohort of infants after infant heart surgery. A wide variation was noted in
seizure burden, but many experienced numerous seizures. Electrographic neonatal
seizures are a candidate outcome end point in future neuroprotection trials in
this patient population.

Bioconjug Chem. 2005 Jan-Feb;16(1):147-55. 

PEG-Modified Protamine with Improved Pharmacological/Pharmaceutical Properties
as a Potential Protamine Substitute: Synthesis and in Vitro Evaluation.

Chang LC, Lee HF, Chung MJ, Yang VC.

School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC,
Industrial Science & Technology Network Inc., York, Pennsylvania 17404, and
College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109.

Cardiopulmonary bypass (CPB) procedures are frequently associated with massive
inflammatory responses, resulting in a high rate of morbidity and mortality in
routine cardiac operations. One recognized attribute of these deleterious
responses is the synergic effect of heparin and protamine, which elicit the
activation of the complement system in vivo. To circumvent such toxic effects
following protamine reversal of heparin anticoagulation in the CPB procedures,
we proposed that poly(ethylene glycol) (PEG)-modified protamine could retain the
heparin-neutralization ability and yet diminish the induced complement
activation by the formed heparin-protamine complexes (HPC), thereby providing
highly improved pharmacological properties. PEGylation of protamine was carried
out by utilizing N-hydroxysuccinimidyl (NHS) conjugation chemistry. Size
exclusion chromatography (SEC), reverse-phase high performance liquid
chromatography (RP-HPLC), and matrix-assisted laser desorption mass spectrometry
(MALDI-MS) were used to assess the conjugation stiochiometry, the purity of the
conjugates, and the site of PEG modification, respectively. The
heparin-neutralizing activity was determined by using heparin affinity
chromatography and various biological assays including the plasma-activated
partial thromboplastin time (aPTT), anti-Xa, and anti-IIa methods. The potency
in inducing complement activation was examined in vitro using the CH(50)
hemolytic assay. The PEG-modified protamine was successfully synthesized with a
PEG/protamine stiochiometry of 1:1. Only one conjugation site for PEG that was
located at the N-terminal end of protamine was obtained. In the biological
evaluations, the PEG-modified protamine displayed a full retention of the
heparin-neutralizing ability of protamine and a significantly reduced activity
in complement activation following its complexation with heparin. Results from
studies of the particle size and zeta potential indicated that the PEG-modified
protamine formed substantially smaller aggregates with heparin, rendering them
less effective in triggering the size-dependent complement responses. As with
protamine, PEG-modified protamine exhibited an enhanced aqueous solubility,
therefore attaining significantly improved pharmaceutical properties. These
preliminary results suggested that the PEG-modified protamine conjugate might
serve as a potential protamine substitute with improved therapeutic and
pharmaceutical properties in heparin reversal.

Paediatr Anaesth. 2005 Jan;15(1):41-6. 

Which may be effective to reduce blood loss after cardiac operations in cyanotic
children: tranexamic acid, aprotinin or a combination?

Bulutcu FS, Ozbek U, Polat B, Yalcin Y, Karaci AR, Bayindir O.

Department of Anaesthesiology and Reanimation Kadir Has University, Florence
Nightingale Hospital, Istanbul, Turkey.

Summary Background: Children with cyanotic heart disease undergoing cardiac
surgery in which cardiopulmonary bypass is used are at increased risk of
postoperative bleeding. In this study, the authors investigated the possibility
of reducing postoperative blood loss by using aprotinin and tranexamic acid
alone or a combination of these two agents. Methods: In a prospective,
randomized, blind study, 100 children undergoing cardiac surgery were
investigated. In group 1 (n = 25) patients acted as the control and did not
receive either study drugs. In group 2 (n = 25) patients received aprotinin
(30.000 KIU.kg(-1) after induction of anesthesia, 30.000 KIU.kg(-1) in the pump
prime and 30.000 KIU.kg(-1) after weaning from bypass). In group 3 (n = 25)
patients received tranexamic acid (100 mg.kg(-1) after induction of anesthesia,
100 mg.kg(-1) in the pump prime and 100 mg.kg(-1) after weaning from bypass). In
group 4 (n = 25) patients received a combination of the two agents in the same
manner. Total blood loss and transfusion requirements during the period from
protamine administration until 24 h after admission to the intensive care unit
were recorded. In addition, hemoglobin, platelet counts and coagulation studies
were recorded. Results: Postoperative blood loss was significantly higher in the
control group (group 1) compared with children in other groups who were treated
with aprotinin, tranexamic acid or a combination of the two agents (groups 2, 3
and 4) during the first 24 h after admission to cardiac intensive care unit (40
+/- 18 ml.kg(-1).24 h(-1), aprotinin; 35 +/- 16 ml.kg(-1).24 h(-1), tranexamic
acid; 34 +/- 19 ml.kg(-1).24 h(-1), combination; 35 +/- 15 ml.kg(-1).24 h(-1)).
The total transfusion requirements were also significantly less in the all
treatment groups. Time taken for sternal closure was longer in the control group
(68 +/- 11 min) compared with treatment groups 2, 3 and 4, respectively (40 +/-
18, 42 +/- 11, 42 +/- 13 min, P < 0.05). The coagulation parameters were not
found to be significantly different between the three groups. Conclusions: Our
results suggested that both agents were effective to reduce postoperative blood
loss and transfusion requirements in patients with cyanotic congenital heart
disease. However, the combination of aprotinin and tranexamic acid did not seem
more effective than either of the two drugs alone.

Ann Thorac Surg. 2005 Jan;79(1):104-7. 

Determining the utility of temporary pacing wires after coronary artery bypass
surgery.

Bethea BT, Salazar JD, Grega MA, Doty JR, Fitton TP, Alejo DE, Borowicz LM Jr,
Gott VL, Sussman MS, Baumgartner WA.

Division of Cardiac Surgery, The Johns Hopkins Medical Institution, Baltimore,
Maryland, USA.

BACKGROUND: Temporary epicardial pacing wires are used routinely after coronary
artery bypass graft (CABG) surgery and can cause rare, catastrophic
complications. This study's purpose was to identify patient characteristics
predicting the need for pacing after CABG surgery with the potential to limit
their utilization. 

METHODS: This prospective observational study involved 290
consecutive patients undergoing CABG at our institution from August 2000 to
January 2001. Sixty-eight patients were excluded for the following reasons:
off-pump CABG, preoperative pacemaker, no pacing wire placement, or incomplete
follow-up. Among the remaining 222 patients, the incidence of pacing during the
postoperative period was recorded. Univariate and independent multivariate
predictors for postoperative pacing were determined using medical records, the
Johns Hopkins Hospital cardiac surgery database and the Society of Thoracic
Surgery database. 

RESULTS: In the postoperative period, 19 of 222 patients
(8.6%) required pacing. Univariate analysis identified age, cardiomegaly,
preoperative antiarrhythmic therapy, diabetes mellitus, preoperative arrhythmia,
inotropic agents leaving the operating room, and pacing initialized at the
separation from cardiopulmonary bypass as predictors of the need for
postoperative pacing. Only diabetes mellitus, preoperative arrhythmia, and
pacing utilized to separate from bypass were found to be significant on
multivariate analysis. Using this model, if we exclude the patients with any of
these three risk factors, only 2.6% of them would have required pacing.

CONCLUSIONS: Few patients require temporary epicardial pacing after routine
CABG. This study identified specific predictors for postoperative pacing
requirements and provides criteria for the selective use of epicardial pacing
wires after CABG.