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1.
Transplant Proc ; 46(10): 3598-602, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25498096

ABSTRACT

BACKGROUND: Ex vivo lung perfusion (EVLP) identifies viability for marginal organs but complicates and lengthens lung transplantation surgery. Preliminary evidence supports equivalency for EVLP-assisted versus traditional (non-EVLP) procedures regarding graft function, postoperative course, mortality, and survival. However, acute kidney injury (AKI), a common serious complication of lung transplantation, has not been assessed. We tested the hypothesis that EVLP-assisted and non-EVLP lung transplantations are associated with different AKI rates. METHODS: Demographic, procedural, and renal data were gathered for 13 EVLP-viable lung transplantations and a non-EVLP group matched 4:1 for single versus double, pulmonary disease, and age. AKI was defined by AKI Network (AKIN) criteria and peak creatinine rise relative to baseline (Δ%Cr) during the 1st 10 postoperative days. Chi-square was performed for AKIN and 2-tailed t test for %ΔCr. RESULTS: Patient and procedural characteristics were similar between the groups. One non-EVLP patient required postoperative dialysis. AKI rates were also similar, as assessed by both AKIN (EVLP 7/13 (54%) vs non-EVLP 32/52 (62%); P = .61) and %ΔCr (EVLP 91 ± 81% vs non-EVLP 72 ± 62%; P = .63). CONCLUSIONS: We did not observe different AKI rates between EVLP-assisted and traditional lung transplant procedures. Although 1 non-EVLP patient required dialysis, AKI rates were otherwise similar. These findings further support EVLP as a strategy to expand the organ pool and reduce concerns for high-renal risk recipients. The small sample size and retrospective design are limitations. However, our sample size is similar to other reports, and it is the first to analyze AKI after EVLP-assisted lung transplantation. Larger multicenter prospective studies are needed.


Subject(s)
Acute Kidney Injury/etiology , Lung Transplantation/methods , Organ Preservation/methods , Perfusion/adverse effects , Acute Kidney Injury/epidemiology , Extracorporeal Circulation/methods , Female , Humans , Incidence , Male , Middle Aged , North Carolina/epidemiology , Retrospective Studies , Risk Assessment , Survival Rate/trends , Tissue and Organ Procurement/methods
2.
Qual Saf Health Care ; 19(5): 405-10, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20702441

ABSTRACT

OBJECTIVE: Recognition of learning curves in medical skill acquisition has enhanced patient safety through improved training techniques. Clinical trials research has not been similarly scrutinised. The VALsartan In Acute myocardial iNfarcTion, a large multinational, pragmatic, randomised, double-blind, multicentre trial, was retrospectively evaluated for evidence of research conduct consistent with a performance "learning curve". DESIGN: Records provided protocol departure (deviations/violations) and documentation query data. For each site, analysis included patient order (eg, first, second), recruitment rate and first enrollment relative to study start date. SETTING: Computerised data from a trial coordinated by an academic research organisation collaborating with 10 academic and 2 commercial research organisations and an industry sponsor. Interventions 931 sites enrolled 14,703 patients. Departures were restricted to the first year. Exclusions included patient's death or loss to follow-up within 12 months and subjects enrolled 80th or higher at a site. Departures were assessed for variance with higher patient rank, more frequent recruitment and later start date. METHODS AND RESULTS: 12,367 patients at 931 sites were analysed. Departures were more common for patients enrolled earlier at a site (p<0.0001). For example, compared with the 30th patient, the first had 47% more departures. Departures were also more common with slower enrollment and site start closer to the trial start date (p<0.0001). Similar patterns existed for queries. CONCLUSIONS: Research performance improved during the VALsartan In Acute myocardial iNfarcTion consistent with a "learning curve". Although effects were not related to a change in outcome (mortality), learning curves in clinical research may have important safety, ethical, research quality and economic implications for trial conduct.


Subject(s)
Clinical Protocols , Guideline Adherence , Learning Curve , Randomized Controlled Trials as Topic , Humans , Multicenter Studies as Topic , Retrospective Studies
3.
Mar Pollut Bull ; 58(10): 1428-36, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19782832

ABSTRACT

Temperature-induced mass coral bleaching causing mortality on a wide geographic scale started when atmospheric CO(2) levels exceeded approximately 320 ppm. When CO(2) levels reached approximately 340 ppm, sporadic but highly destructive mass bleaching occurred in most reefs world-wide, often associated with El Niño events. Recovery was dependent on the vulnerability of individual reef areas and on the reef's previous history and resilience. At today's level of approximately 387 ppm, allowing a lag-time of 10 years for sea temperatures to respond, most reefs world-wide are committed to an irreversible decline. Mass bleaching will in future become annual, departing from the 4 to 7 years return-time of El Niño events. Bleaching will be exacerbated by the effects of degraded water-quality and increased severe weather events. In addition, the progressive onset of ocean acidification will cause reduction of coral growth and retardation of the growth of high magnesium calcite-secreting coralline algae. If CO(2) levels are allowed to reach 450 ppm (due to occur by 2030-2040 at the current rates), reefs will be in rapid and terminal decline world-wide from multiple synergies arising from mass bleaching, ocean acidification, and other environmental impacts. Damage to shallow reef communities will become extensive with consequent reduction of biodiversity followed by extinctions. Reefs will cease to be large-scale nursery grounds for fish and will cease to have most of their current value to humanity. There will be knock-on effects to ecosystems associated with reefs, and to other pelagic and benthic ecosystems. Should CO(2) levels reach 600 ppm reefs will be eroding geological structures with populations of surviving biota restricted to refuges. Domino effects will follow, affecting many other marine ecosystems. This is likely to have been the path of great mass extinctions of the past, adding to the case that anthropogenic CO(2) emissions could trigger the Earth's sixth mass extinction.


Subject(s)
Anthozoa , Carbon Dioxide/analysis , Conservation of Natural Resources/methods , Ecosystem , Extinction, Biological , Global Warming , Temperature , Animals , Atmosphere/chemistry , Seawater/chemistry
4.
Article in English | MEDLINE | ID: mdl-23439283

ABSTRACT

INTRODUCTION: New evidence of potential risks of aprotinin in 2006 generated public concern about a previously approved drug that was routinely used. In response, we assembled a team of experts within the institution to form guidelines for the appropriate use of aprotinin in cardiac surgery. We report the basis for the guidelines, their implementation, follow-up and resulting patterns of change in aprotinin use. METHODS: We proposed a three-tier system for aprotinin use, according to risk of bleeding and transfusion, and evidence of benefit of aprotinin. Specific recommendations were made with regard to discussion with the patient and documentation regarding aprotinin use and options for patients who refuse the drug. Guidelines were disseminated and accessible on all anesthesia workstations. Aprotinin use was compared before and after institution of guidelines in equivalent categories.  RESULTS: Aprotinin was used in 58.5% (469/802) of cases from March 2005 to January 2006. Following institution of guidelines from March 2006 to January 2007, aprotinin was used in 19.7% (151/767) cases representing a 67.8% reduction in usage. In the subset of groups with large reductions in aprotinin use (pre- 82%, n=239; post-guidelines 17%, n=241) there was a significant decrease in acute kidney injury (%?Cr 43.8 vs. 31.7%, p=0.05). CONCLUSIONS: In response to new data and regulatory guidelines, we formulated guidelines based on expert review of data. We reduced aprotinin use, but more importantly, introduced an evidence-based approach to the use of aprotinin, consistent with regulatory guidelines. This model of guideline implementation can be useful in similar scenarios.

5.
Rural Remote Health ; 8(3): 1008, 2008.
Article in English | MEDLINE | ID: mdl-18702572

ABSTRACT

Climate change is likely to have a significant effect on the health of those living in the 70% of Australia that is desert. The direct impacts on health, such as increased temperature, are important. But so too are the secondary impacts that will occur as a result of the impact of climate change on an uncertain and highly variable natural environment and on the interlinking social and economic systems. The consequence of these secondary impacts will appear as changes in the incidence of disease and infections, and on the psychosocial determinants of health. Responding to the impacts of climate change on health in desert Australia will involve the active participation of a variety of interest groups ranging from local to state and federal governments and a range of public and private agencies, including those not traditionally defined as within the health sector. The modes of engagement required for this process need to be innovative, and will differ among regions on different trajectories. To this end, a first classification of these trajectories is proposed.


Subject(s)
Desert Climate , Environmental Health , Greenhouse Effect , Needs Assessment , Australia , Ecosystem , Environmental Health/economics , Forecasting , Health Services, Indigenous , Humans , Medically Underserved Area , Native Hawaiian or Other Pacific Islander , Uncertainty
6.
Qual Saf Health Care ; 15(4): 258-63, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16885250

ABSTRACT

BACKGROUND: We hypothesized that time of day of surgery would influence the incidence of anesthetic adverse events (AEs). METHODS: Clinical observations reported in a quality improvement database were categorized into different AEs that reflected (1) error, (2) harm, and (3) other AEs (error or harm could not be determined) and were analyzed for effects related to start hour of care. RESULTS: As expected, there were differences in the rate of AEs depending on start hour of care. Compared with a reference start hour of 7 am, other AEs were more frequent for cases starting during the 3 pm and 4 pm hours (p < 0.0001). Post hoc inspection of data revealed that the predicted probability increased from a low of 1.0% at 9 am to a high of 4.2% at 4 pm. The two most common event types (pain management and postoperative nausea and vomiting) may be primary determinants of these effects. CONCLUSIONS: Our results indicate that clinical outcomes may be different for patients anesthetized at the end of the work day compared with the beginning of the day. Although this may result from patient related factors, medical care delivery factors such as case load, fatigue, and care transitions may also be influencing the rate of anesthetic AEs for cases that start in the late afternoon.


Subject(s)
Anesthesiology/standards , Medical Audit/methods , Medication Errors/statistics & numerical data , Operating Rooms/standards , Risk Management/methods , Work Schedule Tolerance , Anesthesiology/statistics & numerical data , Appointments and Schedules , Fatigue , Female , Hospitals, University/standards , Humans , Male , Medication Errors/classification , North Carolina , Observation , Operating Rooms/statistics & numerical data , Outcome Assessment, Health Care , Postoperative Nausea and Vomiting/epidemiology , Proportional Hazards Models , Sentinel Surveillance , Time Factors
7.
Circulation ; 114(1 Suppl): I275-81, 2006 Jul 04.
Article in English | MEDLINE | ID: mdl-16820586

ABSTRACT

BACKGROUND: The inflammatory response triggered by cardiac surgery with cardiopulmonary bypass (CPB) is a primary mechanism in the pathogenesis of postoperative myocardial infarction (PMI), a multifactorial disorder with significant inter-patient variability poorly predicted by clinical and procedural factors. We tested the hypothesis that candidate gene polymorphisms in inflammatory pathways contribute to risk of PMI after cardiac surgery. METHODS AND RESULTS: We genotyped 48 polymorphisms from 23 candidate genes in a prospective cohort of 434 patients undergoing elective cardiac surgery with CPB. PMI was defined as creatine kinase-MB isoenzyme level > or = 10x upper limit of normal at 24 hours postoperatively. A 2-step analysis strategy was used: marker selection, followed by model building. To minimize false-positive associations, we adjusted for multiple testing by permutation analysis, Bonferroni correction, and controlling the false discovery rate; 52 patients (12%) experienced PMI. After adjusting for multiple comparisons and clinical risk factors, 3 polymorphisms were found to be independent predictors of PMI (adjusted P<0.05; false discovery rate <10%). These gene variants encode the proinflammatory cytokine interleukin 6 (IL6 -572G>C; odds ratio [OR], 2.47), and 2 adhesion molecules: intercellular adhesion molecule-1 (ICAM1 Lys469Glu; OR, 1.88), and E-selectin (SELE 98G>T; OR, 0.16). The inclusion of genotypic information from these polymorphisms improved prediction models for PMI based on traditional risk factors alone (C-statistic 0.764 versus 0.703). CONCLUSIONS: Functional genetic variants in cytokine and leukocyte-endothelial interaction pathways are independently associated with severity of myonecrosis after cardiac surgery. This may aid in preoperative identification of high-risk cardiac surgical patients and development of novel cardioprotective strategies.


Subject(s)
Cardiac Surgical Procedures , Cardiopulmonary Bypass/adverse effects , Myocardial Infarction/genetics , Polymorphism, Single Nucleotide , Postoperative Complications/epidemiology , Systemic Inflammatory Response Syndrome/genetics , Aged , Alleles , Cohort Studies , E-Selectin/genetics , Elective Surgical Procedures , Female , Genetic Predisposition to Disease , Genotype , Humans , Intercellular Adhesion Molecule-1/genetics , Interleukin-6/genetics , Logistic Models , Male , Middle Aged , Myocardial Infarction/epidemiology , Myocardial Reperfusion Injury/genetics , Prospective Studies , ROC Curve , Risk , Systemic Inflammatory Response Syndrome/etiology
8.
Neuroscience ; 135(2): 507-23, 2005.
Article in English | MEDLINE | ID: mdl-16112482

ABSTRACT

Recent data suggest novel functional roles for cerebellar involvement in a number of neurologic diseases. Function of cerebellar neurons is known to be modulated by norepinephrine and adrenergic receptors. The distribution of adrenergic receptor subtypes has been described in experimental animals, but corroboration of such studies in the human cerebellum, necessary for drug treatment, is still lacking. In the present work we studied cell-specific localizations of alpha1 adrenergic receptor subtype mRNA (alpha 1a, alpha 1b, alpha 1d), and alpha2 adrenergic receptor subtype mRNA (alpha 2a, alpha 2b, alpha 2c) by in situ hybridization on cryostat sections of human cerebellum (cortical layers and dentate nucleus). We observed unique neuron-specific alpha1 adrenergic receptor and alpha2 adrenergic receptor subtype distribution in human cerebellum. The cerebellar cortex expresses mRNA encoding all six alpha adrenergic receptor subtypes, whereas dentate nucleus neurons express all subtype mRNAs, except alpha 2a adrenergic receptor mRNA. All Purkinje cells label strongly for alpha 2a and alpha 2b adrenergic receptor mRNA. Additionally, Purkinje cells of the anterior lobe vermis (lobules I to V) and uvula/tonsil (lobules IX/HIX) express alpha 1a and alpha 2c subtypes, and Purkinje cells in the ansiform lobule (lobule HVII) and uvula/tonsil express alpha 1b and alpha 2c adrenergic receptor subtypes. Basket cells show a strong signal for alpha 1a, moderate signal for alpha 2a and light label for alpha 2b adrenergic receptor mRNA. In stellate cells, besides a strong label of alpha 2a adrenergic receptor mRNA in all and moderate label of alpha 2b message in select stellate cells, the inner stellate cells are also moderately positive for alpha 1b adrenergic receptor mRNA. Granule and Golgi cells express high levels of alpha 2a and alpha 2b adrenergic receptor mRNAs. These data contribute new information regarding specific location of adrenergic receptor subtypes in human cerebellar neurons. We discuss our observations in terms of possible modulatory roles of adrenergic receptor subtypes in cerebellar neurons responding to sensory and autonomic input signals, and review species differences in cerebellar adrenergic receptor expression.


Subject(s)
Cerebellum/pathology , Gene Expression/physiology , Nervous System Diseases/pathology , Neurons/metabolism , Receptors, Adrenergic, alpha/metabolism , Aged , Aged, 80 and over , Cerebellum/drug effects , Emulsions/pharmacology , Gene Expression/drug effects , Gene Expression/genetics , Humans , In Situ Hybridization/methods , Neurons/classification , Postmortem Changes , Protein Subunits/genetics , Protein Subunits/metabolism , RNA, Messenger/metabolism , Receptors, Adrenergic, alpha/classification , Receptors, Adrenergic, alpha/genetics
9.
J Thromb Haemost ; 3(6): 1206-12, 2005 Jun.
Article in English | MEDLINE | ID: mdl-15892865

ABSTRACT

BACKGROUND: Postoperative bleeding remains a common, serious problem for cardiac surgery patients, with striking inter-patient variability poorly explained by clinical, procedural, and biological markers. OBJECTIVE: We tested the hypothesis that genetic polymorphisms of coagulation proteins and platelet glycoproteins are associated with bleeding after cardiac surgery. PATIENTS/METHODS: Seven hundred and eighty patients undergoing aortocoronary surgery with cardiopulmonary bypass were studied. Clinical covariates previously associated with bleeding were recorded and DNA isolated from preoperative blood. Matrix Assisted Laser Desorption/Ionization, Time-Of-Flight (MALDI-TOF) mass spectroscopy or polymerase chain reaction were used for genotype analysis. Multivariable linear regression modeling, including all genetic main effects and two-way gene-gene interactions, related clinical and genetic predictors to bleeding from the thorax and mediastinum. RESULTS: Nineteen candidate polymorphisms were assessed; seven [GPIaIIa-52C>T and 807C>T, GPIb alpha 524C>T, tissue factor-603A>G, prothrombin 20210G>A, tissue factor pathway inhibitor-399C>T, and angiotensin converting enzyme (ACE) deletion/insertion] demonstrate significant association with bleeding (P < 0.01). Adding genetic to clinical predictors results improves the model, doubling overall ability to predict bleeding (P < 0.01). CONCLUSIONS: We identified seven genetic polymorphisms associated with bleeding after cardiac surgery. Genetic factors appear primarily independent of, and explain at least as much variation in bleeding as clinical covariates; combining genetic and clinical factors double our ability to predict bleeding after cardiac surgery. Accounting for genotype may be necessary when stratifying risk of bleeding after cardiac surgery.


Subject(s)
Cardiac Surgical Procedures/adverse effects , Hemorrhage/genetics , Polymorphism, Genetic , Aged , Blood Coagulation Factors/genetics , Cardiopulmonary Bypass , Female , Genotype , Hemorrhage/etiology , Humans , Linear Models , Male , Middle Aged , Molecular Epidemiology , Platelet Membrane Glycoproteins/genetics , Polymerase Chain Reaction , Postoperative Complications/etiology , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
10.
Ann Thorac Surg ; 72(5): 1603-9, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11722052

ABSTRACT

BACKGROUND: Renal dysfunction remains a major complication of cardiac operations. There is concern regarding the possibility of increased renal injury during warm cardiopulmonary bypass (CPB). Therefore, we tested the hypothesis that warm CPB is associated with a greater reduction in creatinine clearance after cardiac surgery than hypothermic CPB. METHODS: We randomly assigned 300 patients who had elective coronary artery bypass grafting to warm (35.5 to 36.5 degrees C) or cold (28 degrees C to 30 degrees C) CPB. Preoperative and peak postoperative serum creatinine values were recorded. Creatinine clearance was estimated using the Cockroft Gault equation. Univariate and multivariable analyses were performed to test the association of CPB temperature and perioperative change in creatinine clearance. RESULTS: Demographic variables were similar between groups. Multivariable analysis did not confirm an association between temperature and change in creatinine clearance (p = 0.87). CONCLUSIONS: We did not confirm an association between warm CPB and increased renal dysfunction after cardiac operations compared with hypothermic CPB.


Subject(s)
Cardiopulmonary Bypass/methods , Creatinine/metabolism , Aged , Female , Humans , Male , Middle Aged , Prospective Studies , Temperature
11.
Anesthesiology ; 94(4): 712, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11379696
12.
Psychosom Med ; 63(2): 300-5, 2001.
Article in English | MEDLINE | ID: mdl-11292279

ABSTRACT

OBJECTIVE: The objective of this study was to evaluate the impact of indices of central nervous system (CNS) serotonin function on cardiovascular reactivity to mental stress. METHODS: Lumbar puncture was performed on 54 healthy volunteers to obtain cerebrospinal fluid (CSF) for determination of 5-hydroxyindoleacetic acid (5HIAA) levels. Genotypes were determined with respect to a functional polymorphism of the serotonin transporter gene promoter region (5HTTLPR). Subjects then underwent mental stress testing. RESULTS: Persons with one or two long (l) 5HTTLPR alleles had CSF levels of the major serotonin metabolite, 5HIAA, that were 50% higher than those of persons with the s/s 5HTTLPR genotype. Persons with one or two l alleles or higher CSF 5HIAA levels also exhibited greater blood pressure and heart rate responses to a mental stress protocol. CONCLUSIONS: These findings suggest the 5HTTLPR polymorphism affects CNS serotonin function, and they are consistent with the general hypothesis that CNS serotonin function is involved in the regulation of potentially health-damaging biobehavioral characteristics. In particular, the l allele could contribute, through its association with increased cardiovascular reactivity to stress, to increased risk of cardiovascular disease.


Subject(s)
Carrier Proteins/genetics , Hemodynamics , Hydroxyindoleacetic Acid/cerebrospinal fluid , Membrane Glycoproteins/genetics , Membrane Transport Proteins , Nerve Tissue Proteins , Serotonin/metabolism , Stress, Psychological/cerebrospinal fluid , Adult , Alleles , Blood Pressure , Female , Genotype , Heart Rate , Humans , Male , Middle Aged , Polymorphism, Genetic , Promoter Regions, Genetic/genetics , Serotonin/genetics , Serotonin Plasma Membrane Transport Proteins , Stress, Psychological/genetics , Stress, Psychological/physiopathology
13.
Anesth Analg ; 92(4): 824-9, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11273909

ABSTRACT

UNLABELLED: Apolipoprotein E (apoE) polymorphisms are heritable determinants of total and low-density lipoprotein cholesterol. The impact of apoE4 genotypes on the severity of atherosclerosis has been debated; however, recent studies have identified a correlation between apoE4 genotype and atherosclerosis. We assessed the impact of apoE4 genotype on age at first coronary artery bypass graft (CABG), hypothesizing that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary revascularization. We assessed individual apoE genotypes and age in 560 patients undergoing primary CABG, by using analysis of variance (ANOVA) and controlling for gender. Because of the small number of patients in individual genotype groups, we compared patients with one or more copies of the apoE4 allele with those having no copies of the allele, again controlling for gender. A comparison of patients with one or more copies of the apoE4 allele with patients without the allele showed an earlier age at first CABG for those with the allele (P: = 0.032). Gene-dose analysis was also significant (P: = 0.012); patients with two copies of the allele presented at 54.2 +/- 6.9 yr. We report that the apoE4 allele is linked to age at first CABG. Identifying at-risk individuals may help prevent atherosclerosis. Further study is needed to define the mechanism of this association, and to define which coronary intervention is appropriate, based on long-term outcome. IMPLICATIONS: A correlation exists between apolipoprotein E (apoE) genotypes and the severity of atherosclerosis. We hypothesized that patients with the apoE4 allele are predisposed to coronary artery disease and present earlier for coronary artery bypass graft (CABG). Individuals with the apoE4 allele presented earlier for CABG, and the apoE4 allele is linked to age at first CABG.


Subject(s)
Apolipoproteins E/genetics , Coronary Artery Bypass , Polymorphism, Genetic/genetics , Age Factors , Aged , Alleles , Arteriosclerosis/genetics , Arteriosclerosis/surgery , Female , Genotype , Humans , Male , Middle Aged , Multivariate Analysis , Stroke Volume/physiology
14.
Anesth Analg ; 91(5): 1080-4, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11049887

ABSTRACT

UNLABELLED: Renal dysfunction is a serious complication after coronary bypass surgery with cardiopulmonary bypass (CABG). Because duration of cardiopulmonary bypass (CPB) is associated with renal outcome, it has been proposed that avoidance of CPB with off-pump coronary bypass (OPCAB) may reduce perioperative renal insult. We therefore tested the hypothesis that OPCAB is associated with less postoperative renal dysfunction compared with CABG surgery. With IRB approval, we gathered data for 690 primary elective coronary bypass patients (OPCAB, 55; CABG, 635). Perioperative change in creatinine clearance (DCrCl) was calculated by using preoperative (CrPre) and peak postoperative (CrPost) serum creatinine values, and the Cockroft-Gault equation (DCrCl = CrPreCl - CrPostCl). Univariate and linear multivariate tests were used in this retrospective analysis; P: < 0.05 was considered significant. Multivariate analysis did not identify OPCAB surgery as an independent predictor of DCrCl. However, previously reported associations of PreCrCl, age, and diabetes with DCrCl were confirmed. Power analysis demonstrated an 80% power to detect a 7.0 mL/min DCrCl difference between study groups. In this retrospective study, we could not confirm that OPCAB significantly reduces perioperative renal dysfunction compared with CABG surgery. Our findings suggest that reduction of renal risk alone should not be an indication for OPCAB over CABG surgery. IMPLICATIONS: Retrospective analysis did not identify any significant difference in perioperative change in creatinine clearance after coronary revascularization with cardiopulmonary bypass compared with off-pump coronary surgery.


Subject(s)
Cardiopulmonary Bypass/adverse effects , Coronary Artery Bypass/adverse effects , Kidney/physiopathology , Biomarkers/blood , Creatinine/blood , Female , Humans , Male , Middle Aged , Multivariate Analysis , Retrospective Studies , Risk Factors
15.
Anesth Analg ; 91(5): 1085-90, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11049888

ABSTRACT

UNLABELLED: Renal dysfunction is a common serious complication after cardiac surgery. Reports of proteinuria and hyperkalemia after cardiac surgery with epsilon-aminocaproic acid (EACA) have therefore raised concerns for renal safety. Since EACA renders these markers unreliable, we used perioperative change in creatinine clearance (DCrCl) to test the hypothesis that EACA is associated with greater reductions in creatinine clearance after heart surgery, particularly for patients with renal disease. We evaluated data from all elective primary coronary bypass patients during EACA introduction at our institution (July 1, 1991-December 31, 1992; 10 g iv bolus pre-cardiopulmonary bypass, then 1 g/h for 5 h). DCrCl was calculated using preoperative (CrPre) and postoperative peak serum creatinine values, using the Cockroft-Gault equation. Patients with CrPre > or = 133 micromol/L were also separately analyzed. Evaluated patients (n = 1502, +/-EACA; 581/905, 16 exclusions) included 233 with CrPre > or = 133 micromol/L (+/-EACA; 98/135). Multivariate analyses confirmed several known risk factors, but no association between DCrCl and EACA in all patients (P: = 0.66), and the subgroup with CrPre > or = 133 micromol/L (P: = 0.42). IMPLICATIONS: In a large population of primary Coronary Artery Bypass Graft including a subset with preoperative renal dysfunction, there were no postoperative reductions in creatinine clearance attributable to epsilon-aminocaproic (EACA) administration. This retrospective study suggests that moderate epsilon-aminocaproic acid dosing during cardiac surgery is safe for the kidney; however, this inference is based on a single marker of renal dysfunction and requires prospective confirmation using a variety of tests of renal function.


Subject(s)
Aminocaproic Acid/adverse effects , Antifibrinolytic Agents/adverse effects , Coronary Artery Bypass , Creatinine/blood , Aged , Cardiopulmonary Bypass , Female , Humans , Kidney/drug effects , Kidney/physiopathology , Male , Middle Aged , Multivariate Analysis , Retrospective Studies
16.
Anesthesiology ; 93(2): 325-31, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10910477

ABSTRACT

BACKGROUND: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery. METHODS: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values. RESULTS: The epsilon4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2). There was no difference in baseline creatinine among allele groups. CONCLUSIONS: Inheritance of the apolipoprotein epsilon4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon3 or epsilon2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.


Subject(s)
Apolipoproteins E/genetics , Coronary Artery Bypass , Creatinine/blood , Postoperative Complications/blood , Renal Insufficiency/genetics , Acute Disease , Alleles , Analysis of Variance , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Genetic , Prospective Studies
17.
Anesthesiology ; 92(4): 968-76, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10754615

ABSTRACT

BACKGROUND: Nonselective alpha2-adrenergic receptor (alpha2AR) agonists (e.g., clonidine) mediate antinociception in part through alpha2ARs in spinal cord dorsal horn; however, use of these agents for analgesia in humans is limited by unwanted sedation and hypotension. The authors previously demonstrated alpha2a approximately alpha2b > > > alpha2c mRNA in human spinal cord dorsal horn cell bodies. However, because 20% of dorsal horn alpha2ARs derive from cell bodies that reside in the associated dorsal root ganglion (DRG), it is important to evaluate alpha2AR expression in this tissue as well. Therefore, the authors evaluated the hypothesis that alpha2b mRNA, alpha2c mRNA, or both are present in human DRG. METHODS: Molecular approaches were used to determine alpha2AR expression in 28 human DRGs because of low overall receptor mRNA expression and small sample size. After creation of synthetic competitor cDNA and establishment of amplification conditions with parallel efficiencies, competitive reverse transcription polymerase chain reaction was performed using RNA isolated from human DRG. RESULTS: Overall expression of alpha2AR mRNA in DRG is low but reproducible at all spinal levels. alpha2b and alpha2cAR subtype mRNAs predominate (alpha2b approximately alpha2c), accounting for more than 95% of the total alpha2AR mRNA in DRG at all human spinal nerve root levels. CONCLUSIONS: Predominance of alpha2b and alpha2cAR mRNA in human DRG is distinct from alpha2AR mRNA expression in cell bodies originating in human spinal cord dorsal horn, where alpha2a and alpha2b predominate with little or absent alpha2c expression. These findings also highlight species heterogeneity in alpha2AR expression in DRG. If confirmed at a protein level, these findings provide an additional step in unraveling mechanisms involved in complex neural pathways such as those for pain.


Subject(s)
Ganglia, Spinal/metabolism , RNA, Messenger/genetics , Receptors, Adrenergic, alpha-2/drug effects , Adult , Aged , Aged, 80 and over , Antisense Elements (Genetics) , Female , Humans , In Vitro Techniques , Male , Middle Aged , RNA, Messenger/biosynthesis , Receptors, Adrenergic, alpha-2/genetics , Reverse Transcriptase Polymerase Chain Reaction , Templates, Genetic
18.
Ann Thorac Surg ; 68(5): 1878-80, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10585088

ABSTRACT

A technique is described for direct aortic arterial cannulation during Port-Access mitral valve or coronary artery bypass grafting. Femoral arterial cannulation is avoided, and endoaortic balloon occlusion is used for cardioplegic arrest. To date, excellent results have been obtained in 45 patients.


Subject(s)
Aorta, Thoracic , Catheters, Indwelling , Coronary Artery Bypass/instrumentation , Heart Valve Prosthesis Implantation/instrumentation , Mitral Valve/surgery , Aorta, Thoracic/surgery , Equipment Design , Humans , Minimally Invasive Surgical Procedures , Punctures/instrumentation
19.
Ann Thorac Surg ; 68(4): 1529-31, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10543561

ABSTRACT

BACKGROUND: Differences in outcome after direct aortic cannulation (AORT) in the chest versus standard femoral arterial cannulation (FEM) have not been defined for minimally invasive cardiac operations utilizing the port-access approach. METHODS: A retrospective study was performed of 165 patients undergoing port-access cardiac mitral valve operation (n = 126) or coronary artery bypass grafting (n = 39). In 113 patients, FEM was used, while in 52 patients, AORT was accomplished through a port in the first intercostal space. RESULTS: AORT eliminated endoaortic balloon clamp migration (0/36 [0%] vs. 17/95 [18%]), and groin wound or femoral arterial complications (0/52 [0%] vs. 11/113 [10%]) without changing procedure times (363+/-55 vs. 355+/-70 minutes). Complications attributable to AORT were injury to the right internal mammary artery and aortic cannulation site bleeding in 1 patient each. CONCLUSIONS: Direct aortic cannulation is technically easy, allows use of an endoaortic clamp, and avoids aorto-iliac arterial disease, the groin incision, and possible femoral arterial injury associated with femoral arterial cannulation. Direct arterial cannulation should expand the pool of patients eligible for port-access operation, and may become the standard for port-access procedures.


Subject(s)
Coronary Artery Bypass/instrumentation , Heart Valve Diseases/surgery , Heart Valve Prosthesis Implantation/instrumentation , Minimally Invasive Surgical Procedures/instrumentation , Mitral Valve/surgery , Adult , Aorta, Thoracic , Catheterization/instrumentation , Equipment Safety , Female , Femoral Artery , Humans , Male , Middle Aged , Punctures/instrumentation , Treatment Outcome
20.
Nephrol Dial Transplant ; 14(5): 1158-62, 1999 May.
Article in English | MEDLINE | ID: mdl-10344355

ABSTRACT

BACKGROUND: Acute renal failure requiring dialysis (ARF-D) occurs in 1.5% of patients following cardiac surgery, and remains a cause of major morbidity and mortality. While some preoperative risk factors have been characterized, the influence of preoperative and intraoperative factors on the occurrence of ARF following cardiac surgery is less well understood. METHODS: Preoperative and intraoperative data on 2843 consecutive adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) from February 1, 1995 to February 1, 1997 were recorded and entered into a computerized database. Two definitions of renal failure were employed: (i) ARF defined as a rise in serum creatinine (Cr) of 1 mg/dl above baseline; and (ii) ARF-D defined as the development of ARF for which some form of dialytic therapy was required. The association between preoperative and intraoperative variables and the development of ARF was assessed by multivariate logistic regression. RESULTS: A total of 2672 of the 2844 patients underwent isolated coronary artery bypass grafting (CABG) surgery, the remaining 172 underwent valve surgery with or without bypass grafting. Of the CABG patients 7.9% developed ARF and 0.7% developed ARF-D. The mortality for patients who developed ARF was 14% (OR 15, P = 0.0001) compared with 1% among those who did not develop ARF. The mortality for CABG patients who developed ARF-D was 28% (OR 20, P = 0.0001) compared with 1.8% among those who did not require dialysis. Variables that were significantly associated with the development of ARF by multivariate analysis included: increased age, elevated preoperative serum Cr, duration of CPB, presence of a carotid artery bruit, presence of diabetes, reduced cardiac ejection fraction and increased body weight. Variables independently associated with ARF-D included serum Cr, duration of CPB, carotid artery bruit and presence of diabetes. The utility of these models for predicting the development of ARF and ARF-D was confirmed by bootstrapping techniques. Because of the small number of patients who underwent valve surgery, none of these variables were significantly associated with the development of ARF or ARF-D in this group of patients. CONCLUSION: The development of ARF or ARF-D is associated with a high mortality following CABG surgery. We have identified perioperative variables, which may be useful in stratifying risk for the development of ARF.


Subject(s)
Acute Kidney Injury/etiology , Cardiac Surgical Procedures/adverse effects , Postoperative Complications/etiology , Adult , Aged , Cohort Studies , Coronary Artery Bypass/adverse effects , Female , Heart Valve Prosthesis Implantation/adverse effects , Humans , Intraoperative Period , Male , Middle Aged , Models, Cardiovascular , Prospective Studies , Risk Factors
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