J Cardiothorac Vasc Anesth  2001 Dec;15(6):723-727

Comparison of milrinone versus nitroglycerin, alone and in combination, on
grafted internal mammary artery flow after cardiopulmonary bypass: Effects of
alpha-adrenergic stimulation.

Lobato EB, Janelle GM, Urdaneta F, Martin TD.

Departments of Anesthesiology and Surgery, University of Florida College of
Medicine, Gainesville, FL.

OBJECTIVES: To compare changes in blood flow in a grafted internal mammary
artery (IMA) after cardiopulmonary bypass (CPB) in response to the
administration of milrinone or nitroglycerin and to establish the effects of
alpha-adrenergic stimulation. DESIGN: Randomized study. SETTING: A university
medical center hospital and a Veterans Affairs Medical Center hospital.
PARTICIPANTS: Thirty consenting adults scheduled for elective coronary artery
bypass graft surgery. INTERVENTIONS: Patients were randomized to receive a 2
&mgr;g/kg/min infusion of nitroglycerin (n = 10), a loading dose of 50 &mgr;g/kg
of milrinone (n = 10), or both drugs combined (n = 10) shortly after CPB.
Intravenous phenylephrine was administered to increase mean arterial pressure by
20%. IMA flow was measured with a calibrated laser Doppler flow probe.
Hemodynamic and flow measurements were obtained before and after every
intervention. Measurements and Main Results: Nitroglycerin and milrinone
increased mean IMA flow, but the increase was greater with milrinone. Both drugs
combined were superior to nitroglycerin alone but not to milrinone. The addition
of phenylephrine to nitroglycerin increased IMA flow in 6 of 10 patients. IMA
flow decreased in 4 of 10 patients, however. Phenylephrine significantly
increased IMA blood flow in patients receiving milrinone or in those given both
drugs combined. CONCLUSION: After CPB, milrinone and nitroglycerin vasodilate
the IMA; however, the combination of both drugs was not superior to milrinone
alone. When using alpha-adrenergic stimulation, milrinone proved superior to
nitroglycerin in preserving IMA flow. 

J Cardiothorac Vasc Anesth  2001 Dec;15(6):700-703

Intra-aortic balloon counterpulsation: Outcome in cardiac surgical patients.

Castelli P, Condemi A, Munari M, Savi C, Carro C, Vanelli P.

Anaesthesia and Intensive Care, and Division of Cardiovascular Surgery, "L.
Sacco" Hospital, Milan, Italy.

OBJECTIVE: To identify the major determinants of survival and nonsurvival for
patients in need of intra-aortic balloon pump (IABP) support after cardiac
surgery and to define the role of ventilator-associated pneumonia. DESIGN:
Retrospective study. SETTING: University and general hospital. PARTICIPANTS: A
total of 105 consecutive patients undergoing cardiac surgery requiring IABP
support and prolonged mechanical ventilation for >24 hours. INTERVENTION: All
patients were assigned into 1 of 2 groups: survival (n = 69) and nonsurvival (n
= 36). Measurements and Main Results: Differences between the survival and
nonsurvival groups were tested with the Student's t-test, chi-square test, and
frequency analysis. The overall survival rate was 65.7%. Nonsurvivors (34.3%)
had higher rates of acute myocardial infarction (27.7% v 4.3%; p < 0.002),
Canadian Cardiovascular Society functional class III and IV (44.4% and 13.8%; p
< 0.001), and depressed left ventricular ejection fraction (31.3 +/- 6.4% v 42.4
+/- 7.2%; p < 0.001). The nonsurvival group had longer duration of
cardiopulmonary bypass (165 +/- 74.3 minutes v 135 +/- 36 minutes; p < 0.006)
and aortic occlusion (81.8 +/- 9 minutes v 68.6 +/- 25.7 minutes; p < 0.004). In
the nonsurvival group, 21 patients were not weaned from the IABP, and 15
patients were weaned from the IABP but died from renal failure (26.6%),
multiorgan failure (13.3%), infection, and respiratory failure (66.6%). In the
nonsurvival group, mechanical ventilation time was longer in patients weaned
from the IABP. CONCLUSION: These data suggest that for patients not weaned from
the IABP, the major determinants of death are low cardiac output (33.3%) and
multiorgan failure (47.6%). Patients with a left ventricular ejection fraction
of <30% have a poorer outcome. In patients weaned from the IABP,
ventilator-associated pneumonia (66.6%) was the major cause of death. 

J Cardiothorac Vasc Anesth  2001 Dec;15(6):684-688

Anaphylactic or anaphylactoid reactions in patients undergoing cardiac surgery.

Ford SA, Kam PC, Baldo BA, Fisher MM.

Departments of Anaesthesia and Pain Management and Intensive Care Medicine,
University of Sydney at Royal North Shore Hospital, and Molecular Immunology
Unit, Kolling Institute of Medical Research, St Leonards, Australia.

OBJECTIVE: To examine the clinical features, treatment, and outcome of
anaphylactic and anaphylactoid reactions during cardiac surgery. DESIGN:
Retrospective descriptive study. SETTING: A specialized referral anesthetic
allergy clinic at a university teaching hospital. PARTICIPANTS: Twenty-three
cardiac surgical patients referred after reactions resembling anaphylaxis.
INTERVENTIONS: None. Measurements and Main Results: The database of the
anesthetic allergy clinic was examined, and the data for patients who developed
anaphylactic or anaphylactoid reactions were collated and summarized.
Twenty-three cardiac surgical patients who experienced signs of anaphylactic or
anaphylactoid reactions during anesthesia and surgery from 8 cardiac surgical
centers in a major city were referred to the clinic. Cephalosporin antibiotics
(30%) and gelatin solutions (Hemaccel) (26%) were the most common (56%) causes
of the reactions. Most reactions occurred before the start of cardiopulmonary
bypass. Although metaraminol was the first vasopressor used in 18 of 23
patients, it was not effective in 14 patients. Response to epinephrine was
immediate and effective in 88% of cases. Rapid placement onto cardiopulmonary
bypass facilitated a good outcome and permitted all but one operation to proceed
as planned. No intraoperative or postoperative deaths were recorded. CONCLUSION:
Of the anaphylactic and anaphylactoid reactions, 60% occurred before
cardiopulmonary bypass, and these were caused by antibiotics and gelatin
solution. The results from this limited database showed that cardiac surgery
proceeded without complications after cardiovascular collapse caused by
anaphylactic or anaphylactoid reactions. Rapid institution of cardiopulmonary
bypass may be life-saving and should be considered.

Thorac Cardiovasc Surg  2001 Dec;49(6):349-354

Effect of Cardiopulmonary Bypass on Myocardial Function, Damage and Inflammation
after Cardiac Surgery in Newborns and Children.

Hammer S, Loeff M, Reichenspurner H, Daebritz S, Tiete A, Kozlik-Feldmann R,
Reichart B, Netz H.

Department of Paediatric Cardiology and Intensive Care Medicine.

Postoperative measurement of cardiac troponin I, creatine kinase and
procalcitonin reflects myocardial damage and systemic inflammatory response
after cardiac surgery with cardiopulmonary bypass in children. Pulse-contour
cardiac output technique is a less invasive tool for determining postoperative
cardiac function. OBJECTIVE: The aim of our study was to investigate myocardial
lesions and systemic inflammatory response after cardiac surgery with
cardiopulmonary bypass in children suffering from congenital heart defects.
METHODS: The elevation of cardiac troponin I (cTnI), creatine kinase (CK) and
procalcitonin (PCT) was evaluated in relationship to duration of aortic
cross-clamping, incisional trauma and cardiac bypass temperature in 37
paediatric patients. To assess postoperative cardiac function, the cardiac index
was measured in 7 children using the PiCCO (pulse contour cardiac output)
technique. RESULTS: CTnI and PCT both peaked on the day of surgery and slowly
decreased postoperatively in case of an uncomplicated course. The median values
of both parameters differed significantly from the day of surgery until the
fourth postoperative day in children with an aortic cross-clamping time (CCT)
longer than 80 minutes or after ventriculotomy in comparison to patients with
shorter clamping times or atriotomy only. CK values showed similar results, but
were less significant than cTnI. A relationship between cTnI, CK or PCT and the
body temperature during cardiopulmonary bypass was not found. The cardiac
indices (CI) measured by the PiCCO technique in the first 48 hours after surgery
showed normal values. CONCLUSION: In summary, perioperative measurement of cTnI,
CK and PCT reflects myocardial damage and systemic inflammatory response and
allows an improved peri- and postoperative management. PiCCO technique is an
excellent, less invasive tool to determine postoperative cardiac function.

Chest  2001 Dec;120(6):1776-1782

Increase of Bradykinin in Plasma of Patients Undergoing Cardiopulmonary Bypass :
The Importance of Lung Exclusion.

Cugno M, Nussberger J, Biglioli P, Alamanni F, Coppola R, Agostoni A.

Department of Internal Medicine (Drs. Cugno and Agostoni), IRCCS Maggiore
Hospital.

Study objectives: Hemodynamic complications including hypotensive episodes are
frequently associated with cardiopulmonary bypass (CPB) and can be attributed to
a generalized inflammatory response in which bradykinin may be a mediator. The
purpose of this study was to determine the plasma levels of
bradykinin-(1-9)nonapeptide in patients during CPB and the physiologic
elimination of bradykinin by the lungs. DESIGN: Prospective, observational
study. SETTING: University hospital, cardiac surgery unit. Patients and methods:
Intra-arterial BP was monitored and serial blood samples were obtained from 27
patients undergoing CPB for cardiac surgery. We measured plasma bradykinin and
parameters of coagulation, fibrinolysis, complement, contact system, and the
cytokine tumor necrosis factor (TNF). RESULTS: Mean arterial pressure fell
progressively until the end of CPB (- 18 mm Hg, p = 0.001) but returned to
baseline by the end of surgery. The venous bradykinin level, normal in basal
conditions (median, 1.90 fmol/mL), was increased (p = 0.001) from 15 min after
the beginning of CPB (5.71 fmol/mL) to the end of the operation (7.07 fmol/mL),
with a peak at the end of CPB (9.81 fmol/mL; p = 0.0001); it was normal at
recovery 24 h later (2.81 fmol/mL). Bradykinin plasma levels fell 60% across the
lung when the pulmonary circulation was fully restored while the patients were
still receiving CPB. Activated-factor XII, thrombin-antithrombin complexes,
prothrombin fragment F1 + 2, plasmin-antiplasmin complexes, C(3)a, and TNF
increased significantly after the beginning of the surgical procedure, rising
further during CPB, and remained elevated until the end of surgery, but they all
returned to normal within 24 h. Changes in plasma bradykinin levels were not
correlated with any of the other variables. CONCLUSIONS: During CPB, there is a
progressive increase of plasma bradykinin that is at least partially due to
reduced catabolism as a consequence of shunting the lungs. The increase in
bradykinin may contribute to the fall in BP.

Stroke  2001 Dec 1;32(12):2874-2881

Report of the Substudy Assessing the Impact of Neurocognitive Function on
Quality of Life 5 Years After Cardiac Surgery.

Newman MF, Grocott HP, Mathew JP, White WD, Landolfo K, Reves JG, Laskowitz DT,
Mark DB, Blumenthal JA.

Department of Anesthesiology (M.F.N., H.P.G., J.P.M., W.D.W., J.G.R.),
Department of Surgery (K.L.), Department of Medicine, Division of Neurology
(D.T.L.), Department of Medicine, Division of Cardiology (D.B.M.), and
Department of Psychiatry and Behavioral Sciences (J.A.B.), Duke University
Medical Center, Durham, NC.

Background and Purpose- The importance of perioperative cognitive decline has
long been debated. We recently demonstrated a significant correlation between
perioperative cognitive decline and long-term cognitive dysfunction. Despite
this association, some still question the importance of these changes in
cognitive function to the quality of life of patients and their families. The
purpose of our investigation was to determine the association between cognitive
dysfunction and long-term quality of life after cardiac surgery. METHODS: After
institutional review board approval and patient informed consent, 261 patients
undergoing cardiac surgery with cardiopulmonary bypass were enrolled and
followed for 5 years. Cognitive function was measured with a battery of tests at
baseline, discharge, and 6 weeks and 5 years postoperatively. Quality of life
was assessed with well-validated, standardized assessments at the 5-year end
point. RESULTS: Our results demonstrate significant correlations between
cognitive function and quality of life in patients after cardiac surgery. Lower
5-year overall cognitive function scores were associated with lower general
health and a less productive working status. Multivariable logistic and linear
regression controlling for age, sex, education, and diabetes confirmed this
strong association in the majority of areas of quality of life. CONCLUSIONS:
Five years after cardiac surgery, there is a strong relationship between
neurocognitive functioning and quality of life. This has important social and
financial implications for preoperative evaluation and postoperative care of
patients undergoing cardiac surgery.

Circulation  2001 Dec 11;104(24):2981-2989

Consequences of Brief Ischemia: Stunning, Preconditioning, and Their Clinical
Implications: Part 1.

Kloner RA, Jennings RB.

Heart Institute, Good Samaritan Hospital, Keck School of Medicine, University of
Southern California, Los Angeles (R.A.K.), and the Pathology Department, Duke
University Medical Center, Durham, NC (R.B.J.).

In experimental studies in the dog, total proximal coronary artery occlusions of
up to 15 minutes result in reversible injury, meaning that the myocytes survive
this insult. The 15 minutes of ischemia, however, induce numerous changes in the
myocardium, including certain monuments to the brief episode of ischemia that
may persist for days. One of these monuments is stunned myocardium, which
represents "prolonged postischemic contractile dysfunction of myocardium
salvaged by reperfusion." The mechanism of stunning involves generation of
oxygen radicals as well as alteration in calcium homeostasis and possibly
alteration in contractile protein structure. Stunning has been observed in
several clinical scenarios, including after percutaneous transluminal coronary
angioplasty, unstable angina, stress-induced ischemia, after thrombolysis, and
after cardiopulmonary bypass. Oxygen radical scavengers and calcium channel
blockers have been shown to enhance function of stunned myocardium in
experimental studies, and in a few clinical studies, calcium channel blockers
have been shown to ameliorate stunning. Although brief periods of ischemia can
contribute to prolonged left ventricular dysfunction and even heart failure,
they paradoxically play a cardioprotective role. Episodes of ischemia as short
as 5 minutes, followed by reperfusion, protect the heart from a subsequent
longer coronary artery occlusion by markedly reducing the amount of necrosis
that results from the test episode of ischemia. This phenomenon, called ischemic
preconditioning, has been observed in virtually every species in which it has
been studied and is a powerful cardioprotective effect. The mechanism of
ischemic preconditioning involves both triggers and mediators and involves
complex second messenger pathways that appear to involve such components as
adenosine, adenosine receptors, the epsilon isoform of protein kinase C, the
ATP-dependent potassium channels, as well as others, including a paradoxical
protective role of oxygen radicals. Both an early and a late phase of
preconditioning have been described, and the mechanisms underlying their
induction are under investigation. That preconditioning may occur in humans is
suggested by the observations that repetitive balloon inflations in the coronary
artery are associated with progressively less chest pain, ST-segment elevation,
lactate production, the protective effects of preinfarction angina, the anginal
"warm-up phenomenon," and studies performed on human cardiac biopsies that show
metabolic properties suggesting preconditioning. Development of pharmacological
agents that stimulate second messenger pathways thought to be involved in
preconditioning, but without causing ischemia, could result in novel approaches
to treating ischemia. Hence, on one hand, brief episodes of ischemia can have a
negative effect on the heart: stunning; and on the other hand, they have a
protective effect: preconditioning. The future challenge is how to minimize the
stunning phenomenon and maximize the preconditioning phenomenon in clinical
practice.

J Thorac Cardiovasc Surg  2001 Dec;122(6):1162-6

Expression of chemokine receptors CXCR1 and CXCR2 during cardiopulmonary bypass.

Chishti AD, Dark JH, Kesteven P, Powell H, Snowden C, Shenton BK, Kirby JA,
Baudouin SV.

School of Surgical and Reproductive Sciences, Medical School, University of
Newcastle upon Tyne, Framlington Place, and the Freeman Hospital, University of
Newcastle upon Tyne, High Heaton, Newcastle upon Tyne, United Kingdom.

OBJECTIVE: This study investigated the effects of cardiopulmonary bypass on
neutrophil expression of chemokine receptors, CXCR1 and CXCR2, and the beta(2)
integrin CD11b. METHODS: Ten patients undergoing coronary artery grafting with
cardiopulmonary bypass were studied. Blood samples were collected
preoperatively, before bypass, at termination of bypass, and 12 to 18 hours
postoperatively. In vitro studies were performed on control subjects to
determine changes in the surface expression of CXCR1, CXCR2, and CD11b on
stimulation with interleukin 8. Receptor expression was measured by flow
cytometry. Plasma levels of interleukin 8 from the patients were determined by
enzyme-linked immunoassay. RESULTS: After bypass, CXCR2 expression fell by 66%
(P <.0001) and remained low postoperatively (P <.0001). CXCR1 expression
persisted at preoperative levels. CD11b expression increased significantly after
bypass (P <.0001), returning to prebypass levels postoperatively. In vitro
studies showed a dose-related fall of both CXCR1 (P <.0001) and CXCR2 expression
(P <.0001) and a significant rise in CD11b expression (P <.0001). Plasma
interleukin 8 increased significantly after bypass (P <.0001), remaining
elevated 12 to 18 hours postoperatively (P =.02). Correlations between
interleukin 8 levels and CXCR2 expression (P <.0001) and CD11b expression (P
<.03) were demonstrated. CONCLUSIONS: CXCR2 expression is significantly
down-regulated after bypass; in contrast, CXCR1 expression remains unchanged. In
addition, whereas interleukin 8 is an important determinant of both CXCR1 and
CXCR2 expression in vitro, it only correlates with CXCR2 and CD11b expression in
vivo. This has implications in the search for antagonists against CXC chemokines
and their receptors

Anesth Analg  2001 Dec;93(6):1410-6

Risk factors for ischemic optic neuropathy after cardiopulmonary bypass: a
matched case/control study.

Nuttall GA, Garrity JA, Dearani JA, Abel MD, Schroeder DR, Mullany CJ.

Departments of Anesthesiology, Ophthalmology, and Surgery, Mayo Graduate School
of Medicine, Rochester, Minnesota.

Visual loss (acuity or field) secondary to ischemic optic neuropathy (ION) is a
rare but devastating complication of cardiac surgery involving cardiopulmonary
bypass (CPB). We determined clinical features and risk factors for ION by a
retrospective time-matched, case-control study. ION was identified in 17 (0.06%)
patients out of 27,915 patients who underwent CPB between January 1, 1976, and
December 31, 1994. For each ION patient, two patients who underwent CPB exactly
2 wk before the ION patient were selected as controls. Data were analyzed by
using conditional logistic regression with the 1:2 matched-set feature of 17
cases and 34 controls. Two-tailed P values </=0.05 were considered significant.
From bivariate analysis, smaller minimum postoperative hemoglobin concentration
(odds ratio [OR] = 1.9, P = 0.047) and the presence of atherosclerotic vascular
disease (OR = 7.0, P = 0.026) were found to be independently associated with ION
after CPB, as were smaller minimum postoperative hemoglobin concentration (OR =
2.2, P = 0.027) and preoperative angiogram within 48 h of surgery (OR = 7.2, P =
0.042). In ION patients, 13 (76.5%) of 17 experienced a minimum postoperative
hemoglobin value of <8.5 g/dL, whereas only 14 (41.2%) of 34 control patients
experienced values <8.5 g/dL. IMPLICATIONS: Patients with clinically significant
vascular disease history or preoperative angiogram may be at increased risk for
ischemic optic neuropathy after cardiac surgery, especially if the hemoglobin
remains low in the postoperative period.