Anesthesiology 2001 May;94(5):745-53; discussion 5A

Tissue injury and the inflammatory response to pediatric cardiac surgery with
cardiopulmonary bypass: a descriptive study.

Chew MS, Brandslund I, Brix-Christensen V, Ravn HB, Hjortdal VE, Pedersen J,
Hjortdal K, Hansen OK, Tonnesen E.

Department of Anesthesia & Intensive Care, Aarhus University Hospital, Denmark.
mchew@iekf.au.dk

BACKGROUND: There are few detailed descriptions of the inflammatory response to
cardiac surgery with cardiopulmonary bypass (CPB) in children beyond 24 h
postoperatively. This is especially true for the antiinflammatory cytokines and
the extent of tissue injury. The aim of the current study was to describe the
inflammatory and injury responses in uncomplicated pediatric cardiac surgery
with CPB, where methylprednisolone and modified ultrafiltration (MUF) were used.
METHODS: Blood samples were collected up to 48 h postoperatively. Cytokines
(tumor necrosis factor-alpha and interleukin-6, -1beta, -10, and -1ra),
complement (C3d and C4d) and coagulation system (prothrombin activation
fragments 1 and 2 and antithrombin III) activation, neutrophil elastase, and the
resulting tissue injury (creatine kinase, lactate dehydrogenase, alanine
transaminase, amylase, and gamma-glutamyl transferase) were measured. RESULTS:
The proinflammatory cytokine release varied widely, in contrast to a clear-cut
antiinflammatory response. Cytokine concentrations did not decrease immediately
after MUF, and no rebound increases later in the postoperative period were
observed. The coagulation system, but not complement, was activated. There was a
late release of C-reactive protein. Tissue injury could be quantified
biochemically without evidence of hepatic or pancreatic dysfunction. CONCLUSION:
In this group of uncomplicated subjects, the antiinflammatory cytokine and
tissue injury responses were well defined, in contrast to a variable
proinflammatory cytokine release. This was accompanied by activation of the
coagulation system but not of complement. Concentrations of inflammatory
mediators did not decrease immediately after MUF, and there was no evidence for
rebound release later in the postoperative period.

Ann Thorac Surg 2001 May;71(5):1524-9

Prophylactic use of pentoxifylline on inflammation in elderly cardiac surgery
patients.

Boldt J, Brosch C, Lehmann A, Haisch G, Lang J, Isgro F.

Department of Anesthesiology and Intensive Care Medicine, Klinikum der Stadt
Ludwigshafen, Germany. boldtj@gmx.net

BACKGROUND: Inflammation plays a pivotal role in the pathogenesis of organ
injury after cardiopulmonary bypass (CPB). Elderly patients appear to be
especially prone to develop general inflammation. Use of pentoxifylline (PTX)
before surgery may be a promising approach to minimize the negative effects of
CPB in these patients. METHODS: In a prospective, randomized study, patients
more than 80 years old undergoing aortocoronary artery bypass grafting received
either PTX (n = 15) after induction of anesthesia (initial bolus of 300 mg
followed by a continuous infusion of 1.5 mg.kg(-1).h(-1) during the next 2 days)
or saline as placebo (control group; n = 15). Polymorphonuclear neutrophil (PMN)
elastase, C-reactive protein (CRP), and interleukins (IL-6, IL-8, IL-10) were
measured from arterial blood samples before surgery (T0), at the end of surgery
(T1), 5 hours after surgery (T2), and at the morning of the first (T3) and
second (T4) postoperative day. RESULTS: Postoperatively, PTX-treated patients
less often needed catecholamines and were extubated earlier than the control
patients (p < 0.05). On the intensive care unit, cardiac index inceased more in
the PTX-treated (from 1.95 +/- 0.3 to 3.26 +/- 0.4 L.min(-1).m(-2)) than in the
control patients (from 1.89 +/- 0.2 to 2.78 +/- 0.3 L.min(-1).m(-2)). Increase
in CRP and PMN-elastase was significantly higher in the untreated control than
in the PTX patients. After CPB, IL-6, IL-8, and IL-10 increased in both groups
showing a significantly higher increase in the untreated control patients (IL-8
control: from 11.3 +/- 2.6 to 154.4 +/- 57 pg/mL [T1]); IL-8 PTX: from 10.9 +/-
2.7 to 71.8 +/- 23 pg/mL [T1]). CONCLUSIONS: In elderly cardiac surgery
patients, use of PTX before surgery and continued after CPB resulted in less
inflammatory response than in an untreated control group. The value of
attenuating the inflammatory process by PTX on outcome in this patient
population needs to be evaluated in further controlled studies.

Ann Thorac Surg 2001 May;71(5):1428-32

Risk factors for post-cardiopulmonary bypass vasoplegia in patients with
preserved left ventricular function.

Mekontso-Dessap A, Houel R, Soustelle C, Kirsch M, Thebert D, Loisance DY.

Service de Chirurgie Thoracique et Cardiovasculaire, CNRS UPRES-A 7053, Centre
Hospitalo-Universitaire Henri Mondor, Creteil, France.

BACKGROUND: Although vasodilatory shock (VS) is one of the main complications of
cardiopulmonary bypass (CPB), its pathophysiologic basis remains unclear. The
aim of this study was to identify predisposing factors for the development of VS
after CPB independent of ventricular function. METHODS: Thirty-six patients
undergoing coronary artery bypass grafting who developed VS were compared with
72 control patients without post-CPB cardiogenic or vasoplegic shock, in a 2:1
case control study. Patients and controls underwent the same anesthetic protocol
and were matched by age, sex, operation date, and left ventricle ejection
fraction. RESULTS: Preoperative and intraoperative patient characteristics were
not significantly different between the two groups. Preoperative use of
angiotensin-converting enzyme inhibitors and intravenous heparin were
independent predictors for post-CPB VS by multivariate analysis (relative risk
of 2.26 and 2.78, respectively). Intensive care unit stay and hospital stay were
significantly longer in VS cases than controls, without any difference in early
postoperative mortality. CONCLUSIONS: The only independent risk factors for
postoperative VS identified were preoperative use of angiotensin-converting
enzyme inhibitors and intravenous heparin. These risk factors were independent
of age, gender, anesthetic protocol, and left ventricle ejection fraction.

Clin Endocrinol (Oxf) 2001 May;54(5):689-92

Cardiac phaeochromocytoma presenting with severe hypertension and chest pain.

Sawka AM, Young WF, Schaff HV.

Division of Endocrinology, Metabolism and Nutrition, Internal Medicine, Division
of Hypertension and Internal Medicine, Division of Cardiovascular Surgery, Mayo
Clinic, Mayo Foundation, Rochester, MN, USA.

Cardiac phaeochromocytoma is a rare cause of endocrine hypertension. We report a
case of a 25-year-old woman, who presented with severe hypertension and
intermittent chest pain. The patient denied typical phaeochromocytoma spells of
palpitation, headache, and diaphoresis. The 24-hr urinary excretion of
norepinephrine was increased sevenfold above the upper limit of normal; however,
the excretion of total metanephrines, epinephrine, and dopamine were normal.
Computed tomography (CT) scan of the abdomen was normal. An 131I-labelled
metaiodobenzylguanidine (MIBG) scan was falsely negative while the patient was
taking labetalol. The cardiac phaeochromocytoma was localized with
indium-111-pentetreotide scintigraphy and chest magnetic resonance imaging scan.
Repeat 123I-MIBG scintigraphy was positive after discontinuing labetalol. The
cardiac phaeochromocytoma was located in the right atrial groove, adjacent to
the tricuspid valve, and contained multiple feeder arteries from the right
coronary artery. After treatment with volume expansion, alpha-methyl-p-tyrosine,
and alpha- and beta-adrenergic blockade, surgical resection was performed. While
under cardiopulmonary bypass, coronary bypass grafting and tricuspid
annuloplasty were performed to facilitate the complete surgical resection of the
4.5-cm tumour. The surgical course was uncomplicated, with complete cure of
hypertension and normalization of catecholamine excretion. Post-operative
cardiac function, as measured by echocardiogram, was normal. Although cardiac
phaeochromocytoma may be highly vascular, invasive and difficult to resect, it
can be cured.

Circulation 2001 May 1;103(17):2133-7

Sex differences in neurological outcomes and mortality after cardiac surgery : a
society of thoracic surgery national database report.

Hogue CW Jr, Barzilai B, Pieper KS, Coombs LP, DeLong ER, Kouchoukos NT,
Davila-Roman VG.

Department of Anesthesiology (C.W.H., V.G.D.-R.) and the Cardiovascular
Division, Department of Medicine (B.B., V.G.D.-R.), Washington University School
of Medicine, St Louis, Mo.

Background-The purpose of this study was to evaluate whether women undergoing
cardiac surgery are more likely to suffer neurological complications than men
and whether these complications could explain, at least in part, their higher
perioperative mortality. Methods and Results-The Society of Thoracic Surgery
National Cardiac Surgery Database was examined for the years 1996 and 1997 to
determine the frequency of new neurological events (stroke, transient ischemic
attack, or coma) occurring after cardiac surgery. We reviewed clinical
information on 416 347 patients (32% women) for whom complete neurological
outcome data were available. New neurological events after surgery were higher
for women than for men (3.8% versus 2.4%, P=0.001). For the whole group, the
30-day mortality was higher for women than for men (5.7% versus 3.5%, P=0.001),
and among those patients who suffered a perioperative neurological event,
mortality was also significantly higher for women than men (32% versus 28%,
P=0.001). After adjustment for other risk factors (eg, age, history of
hypertension and/or diabetes, duration of cardiopulmonary bypass, and other
comorbid conditions) by multivariable logistic regression, female sex was
independently associated with significantly higher risk of suffering new
neurological events after cardiac surgery (OR 1.21, 95% CI 1.14 to 1.28,
P=0.001). Conclusions-Women undergoing cardiac surgery are more likely than men
to suffer new perioperative neurological events, and they have higher 30-day
mortality when these complications occur. The higher incidence of perioperative
neurological complications in women cannot be explained by currently known risk
factors.

Paediatr Anaesth 2001 May;11(3):303-8

Soluble P-selectin and the postoperative course following cardiopulmonary bypass
in children.

Lotan D, Prince T, Dagan O, Keller N, Ben-Abraham R, Weinbroum A, Gaby A,
Augarten A, Smolinski A, Barzilay Z, Paret G.

Department of Pediatric Intensive Care, The Chaim Sheba Medical Center,
Tel-Hashomer, Israel Department of Anaesthesiology and Critical Care Medicine,
Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel-Aviv
University, Tel-Aviv, Israel.

BACKGROUND: Cytokine-inducible leucocyte-endothelial adhesion molecules were
shown to affect the postoperative inflammatory response following
cardiopulmonary bypass (CPB). Soluble P-selectin (sP-selectin) is one of these
molecules. We investigated the correlation between plasma sP-selectin levels and
the intra- and postoperative course in children undergoing CPB. METHODS: Serial
blood samples of 13 patients were collected preoperatively upon initiation of
CPB and seven times postoperatively. Plasma was recovered immediately and frozen
at - 70 degrees C until use. Circulating soluble selectin molecules were
measured with a sandwich enzyme-linked immunoabsorbent assay technique. RESULTS:
The significant post-CPB changes in sP-selectins plasma levels were associated
with patient characteristics, operative variables and postoperative course.
sP-selectin levels correlated significantly with surgery time, aortic
cross-clamping time and inotropic support, as well as with the postoperative
Pediatric Risk of Mortality score, hypotension and tachycardia. CONCLUSIONS: A
relation between CPB-induced mediators and both early and late clinical effects
is suggested. The up-regulation and expression of sP-selectin indicate
neutrophil activation as a possible mechanism for the increase, and inhibiting
it may reduce the inflammatory response associated with CPB.

Jpn J Thorac Cardiovasc Surg 2001 Apr;49(4):216-9

Kinetics of pro-inflammatory cytokines release in cardiac surgery with
cardiopulmonary bypass.

Hirai S, Sueda T, Orihashi K, Watari M, Okada K.

Department of Thoracic Surgery, Hiroshima Prefecture Hospital, 1-5-54
Ujinakanda, Minami-ku, Hiroshima 734-8530, Japan.

OBJECTIVE: Cytokine induction can occur routinely in cardiac surgery with
cardiopulmonary bypass. We have studied the relationships between the kinetics
of pro-inflammatory cytokine release and the postoperative organ function.
METHODS: Ten adult patients (6 men and 4 women) undergoing elective cardiac
surgery with cardiopulmonary bypass, at Hiroshima University Hospital were
studied. Patients with acute infection, insulin-dependent diabetes, acute or
chronic respiratory failure, renal or hepatic failure, acute cardiogenic shock,
and emergency patients were not included. The age of the patient ranged from 44
to 78 years (mean 69 +/- 2.0 years). The type of surgical intervention performed
was coronary artery bypass grafting in four patients, mitral valve plasty or
replacement with modified maze procedure in another five patients, and both
procedures in the other one patient. Plasma cytokine levels until 48 hours after
aortic declamping were measured in blood samples. The Respiratory Index and the
serum levels of choline esterase and creatinine were also measured. The plasma
levels of the pro-inflammatory cytokines (interleukin-6 and interleukin-8) were
measured. RESULTS: The highest interleukin-6 levels were significantly
correlated with hepatic dysfunction (r = -0.80, p = 0.006) and with renal
dysfunction (r = 0.78, p = 0.009). The highest interleukin-8 levels were
significantly correlated with respiratory dysfunction (r = 0.86, p = 0.001).
CONCLUSION: The highest proinflammatory cytokines levels at 1 hour after aortic
declamping were related to damage to postoperative organ functions, involving
the lung, kidney and liver.

J Am Coll Cardiol 2001 May;37(6):1700-6

The effect of short-term prophylactic methylprednisolone on the incidence and
severity of postpericardiotomy syndrome in children undergoing cardiac surgery
with cardiopulmonary bypass.

Mott AR, Fraser CD Jr, Kusnoor AV, Giesecke NM, Reul GJ Jr, Drescher KL, Watrin
CH, Smith EO, Feltes TF.

Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
AMott@bcm.tmc.edu

OBJECTIVE: The aim of this study was to determine the effect of prophylactic
immune suppression on the incidence and severity ofpostpericardiotomy syndrome
(PPS) in children after cardiac surgery with cardiopulmonary bypass (CPB).
BACKGROUND: Prophylactic suppression of the inflammatory response has an unknown
effect on the incidence and severity of PPS in children undergoing surgery with
CPB. METHODS: This randomized double-blind placebo controlled trial included two
study groups. Group A received pre-CPB intravenous methylprednisolone (1 mg/kg)
plus four additional intravenous doses over 24 h, and Group B received
intravenous saline placebo at identical intervals. Data included patient
demographics, cardiac diagnosis/operation, CPB time, incidence and severity of
PPS. Noncomplicated PPS--temperature >100.5 degrees F, pericardial friction rub,
patient irritability, small pericardial +/- pleural effusion. Complicated
PPS--noncomplicated PPS plus hospital readmission +/- pericardiocentesis or
thoracentesis. RESULTS: We randomized 266 children: 20 exclusions (6
perioperative deaths, 14 reasons unrelated to treatment) leaving Group A (n =
126) and Group B (n = 120). There were no significant group differences in
gender, cardiac diagnosis or CPB time. Group mean age differed (p = 0.05) and
was treated as a covariate with no substantive outcome effect. In total, 39/246
children (16%) developed PPS (noncomplicated: n = 30, complicated: n = 9). There
was no inter-group difference in overall PPS incidence (p = 0.73). However,
Group A had a marginally significant increase in complicated PPS (p = 0.05).
CONCLUSIONS: Intravenous methylprednisolone at a standard anti-inflammatory dose
administered pre-CPB and early post-CPB neither prevents nor attenuates PPS in
children. Short-term pre-CPB and post-CPB methylprednisolone treatment may
complicate PPS.

Eur J Cardiothorac Surg 2001 May;19(5):678-83

Reliable long-term non-pulsatile circulatory support without anticoagulation.

Saito S, Westaby S, Piggott D, Katsumata T, Dudnikov S, Robson D, Catarino P,
Nojiri C.

Oxford Heart Centre, John Radcliffe Hospital, Headley Way, Headington, OX3 9DU,
Oxford, UK

Objective: The Terumo implantable left ventricular assist system (T-ILVAS)
consists of a titanium centrifugal pump with a unique magnetically suspended
impeller producing continuous (non-pulsatile) flow up to 10 l/min. The interior
surface is heparin-coated and there is no purge system. We implanted the device
into six sheep to ascertain in-vivo haemodynamic function, mechanical
reliability and biocompatibility. Methods: The T-ILVAS was implanted via left
thoracotomy without cardiopulmonary bypass. The inflow cannula was placed in the
left ventricular apex and a Dacron outflow graft anastomosed to the descending
aorta. All animals recovered well. No anticoagulation (heparin or warfarin) was
given after the surgery. Suspension position, motor current, impeller speed and
pump flow were continuously monitored and stored by on-line computer. Serial
blood samples were collected to determine haematological and biochemical indices
of renal function, liver function and haemolysis. All animals were electively
euthanized between 3 and 7 months postoperatively. The explanted pumps were
examined for mechanical reliability and thrombus formation. Major organs were
examined macroscopically and histologically for thromboembolism. Results: All
animals appeared completely normal for up to 210 days. At speeds between 1500
and 2000 rev./min the device pumped up to 8 l/min capturing all mitral flow.
There were no major complications (pump failure, thromboembolism, haemorrhage,
or driveline infection). Indices of haemolysis, liver and renal function
remained within normal limits. All pumps were mechanically sound and free from
thrombus. One embolus was found in a sectioned kidney. Conclusion: The T-ILVAS
successfully supported the systemic circulation without anticoagulation for up
to 210 days. Mechanical reliability and biocompatibility were demonstrated.
Organ function remained within normal limits during continuous non-pulsatile
flow.