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Biomedical subjects

W D White

Publications and source records attributed to W D White.

At least 19 recordsLinked to original sources
PubMed2006

Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.

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.

Aged↗
PubMed2006

A randomized, prospective double-blind comparison of the efficacy of generic propofol (sulphite additive) with diprivan.

BACKGROUND AND OBJECTIVE: We compared the dose requirement and side effect profile of total intravenous anaesthesia using Diprivan to generic propofol at a specific anaesthetic target level utilizing the bispectral index monitor to determine efficacy differences between the two products. METHODS: Sixty women undergoing abdominal hysterectomy were induced with propofol 2 mg kg-1 and maintained with infusion (20-200 microg kg-1 min-1) adjusted to maintain a bispectral index of 50-65. Plasma propofol concentration was measured at 1 and 2 h post induction in 25 patients. RESULTS: Mean (SD) drug doses adjusted for weight and time were similar in the Diprivan and generic propofol groups: 90 (30) microg kg-1 min-1 vs. 90 (20) microg kg-1 min-1 respectively. Mean (SD) plasma propofol levels at 1 and 2 h were also similar (3.0 (1.0) microg mL-1 vs. 3.6 (1.4) microg mL-1, P = 0.2 and 3.0 (1.9) microg mL-1 vs. 3.4 (1.6) microg mL-1, P = 0.58). CONCLUSIONS: Diprivan and generic propofol have similar efficacy at a specified, bispectral index-defined, depth of anaesthesia.

Adult↗
PubMed2005

The desaturation response time of finger pulse oximeters during mild hypothermia.

Pulse oximeters may delay displaying the correct oxygen saturation during the onset of hypoxia. We investigated the desaturation response times of pulse oximeter sensors (forehead, ear and finger) during vasoconstriction due to mild hypothermia and vasodilation caused by glyceryl trinitrate. Ten healthy male volunteers were given three hypoxic challenges of 3 min duration under differing experimental conditions. Mild hypothermia increased the mean response time of finger oximeters from 130 to 215 s. Glyceryl trinitrate partly offset this effect by reducing the response time from 215 to 187 s. In contrast, the response times of the forehead and ear oximeters were unaffected by mild hypothermia, but the difference between head and finger oximeters was highly significant (p < 0.0001). The results suggest that the head oximeters provide a better monitoring site for pulse oximeters during mild hypothermia.

Adult↗
PubMed2001

Report of the substudy assessing the impact of neurocognitive function on quality of life 5 years after cardiac surgery.

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.

Age Distribution↗
PubMed2001

Temperature during coronary artery bypass surgery affects quality of life.

BACKGROUND: The objective of this study was to examine the effects of temperature on a variety of indices of psychologic adjustment and quality of life. METHODS: A total of 209 patients randomly received normothermic (warm) or hypothermic (cold) conditions during coronary artery bypass surgery (CABS), and a number of physical, social, and psychologic measures were assessed before as well as 6 weeks and 6 months after CABS. RESULTS: Repeated measures analyses of covariance revealed significant temperature group main effects for anxiety (p = 0.008) and depression (p = 0.039), with the normothermic group obtaining lower anxiety and depression levels than the hypothermic group at both 6 weeks and 6 months after surgery. Additionally, among patients who entered the study with higher depression levels, those in the hypothermic group tended to have higher depression scores at follow-up compared with patients in the normothermic condition (p = 0.012). No temperature group differences were observed on other quality of life indices. CONCLUSIONS: The results of the present study indicate that hypothermic conditions during CABS are associated with higher levels of emotional distress after CABS than normothermic conditions, particularly for patients with greater stress to begin with.

Aged↗
PubMed2001

Bispectral analysis during cardiopulmonary bypass: the effect of hypothermia on the hypnotic state.

STUDY OBJECTIVE: To evaluate the hypothesis that the bispectral index (BIS) is not affected by the hypothermia that is associated with cardiopulmonary bypass (CPB). DESIGN: Prospective, observational study. SETTING: Cardiac surgical operating suite of a university medical center. PATIENTS: 100 patients undergoing cardiac surgery requiring CPB. INTERVENTIONS: A constant effect site concentration of 2.2 ng/mL for fentanyl and 60 ng/mL for midazolam was maintained throughout surgery using a computer-assisted continuous infusion technique. MEASUREMENTS: The BIS value, percent isoflurane administered, predicted brain concentrations of midazolam and fentanyl, and nasopharyngeal temperature were recorded before CPB, at 15 minutes after the onset of CPB, at placement of the aortic cross-clamp, at start of rewarming, on separation from CPB, and 15 minutes after the end of CPB. Data were analyzed using a repeated-measures mixed-effects method, taking into account temperature, age, and predicted level of each anesthetic. MAIN RESULTS: A significant overall association between temperature and BIS was observed independent of patient age, predicted brain midazolam or fentanyl concentration, percent isoflurane administered, and surgical time point (p < 0.001). The BIS is estimated to decrease by 1.12 units for each degree Celsius decrease in body temperature. CONCLUSIONS: Hypothermia decreases the BIS by 1.12 units per degree Celsius decline in temperature.

Adjuvants, Anesthesia↗
PubMed2001

Apolipoprotein E polymorphisms and age at first coronary artery bypass graft.

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.

Age Factors↗
PubMed2001

Prospective randomized trial of normothermic versus hypothermic cardiopulmonary bypass on cognitive function after coronary artery bypass graft surgery.

BACKGROUND: Despite significant advances in cardiopulmonary bypass (CPB) technology, surgical techniques, and anesthetic management, central nervous system complications occur in a large percentage of patients undergoing surgery requiring CPB. Many centers are switching to normothermic CPB because of shorter CPB and operating room times and improved myocardial protection. The authors hypothesized that, compared with normothermia, hypothermic CPB would result in superior neurologic and neurocognitive function after coronary artery bypass graft surgery. METHODS: Three hundred patients undergoing elective coronary artery bypass graft surgery were prospectively enrolled and randomly assigned to either normothermic (35.5-36.5 degrees C) or hypothermic (28-30 degrees C) CPB. A battery of neurocognitive tests was performed preoperatively and at 6 weeks after surgery. Four distinct cognitive domains were identified and standardized using factor analysis and were then compared on a continuous scale. RESULTS: Two hundred twenty-seven patients participated in 6-week follow-up testing. There were no differences in neurologic or neurocognitive outcomes between normothermic and hypothermic groups in multivariable models, adjusting for covariable effects of baseline cognitive function, age, and years of education, as well as interaction of these with temperature treatment. CONCLUSIONS: Hypothermic CPB does not provide additional central nervous system protection in adult cardiac surgical patients who were maintained at either 30 or 35 degrees C during CPB.

Anesthetics, Intravenous↗
PubMed2001

Effect of apolipoprotein E genotype on cerebral autoregulation during cardiopulmonary bypass.

BACKGROUND AND PURPOSE: The presence of the apolipoprotein E epsilon4 (apoE4) allele has been associated with cognitive decline after cardiac surgery. We compared autoregulation of cerebral blood flow (CBF), cerebral metabolic rate for oxygen (CMRO(2)), and arterial-venous oxygen content difference [C(A-V)O(2)], during cardiopulmonary bypass (CPB) in patients with and without the apoE4 allele to help define the mechanism of association with cognitive decline. METHODS: One hundred fifty-four patients underwent coronary artery bypass grafting with CPB, nonpulsatile flow, and alpha-stat management. CBF was measured by using (133)Xe washout methods. C(A-V)O(2), CMRO(2), and oxygen delivery were calculated. Pressure-flow autoregulation was tested by using 2 CBF measurements at stable hypothermia: the first at stable mean arterial pressure (MAP) and the second 15 minutes later, when MAP had increased or decreased >/=20%. Metabolism-flow autoregulation was tested by varying the temperature and measuring the coupling of CBF and CMRO(2). RESULTS: In patients with (n=41) or without (n=113) the apoE4 allele, there were no differences in CBF, CMRO(2), C(A-V)O(2), pressure-flow and metabolism-flow autoregulation corrected for age, gender, non-insulin-dependent diabetes, hemoglobin, CPB time, and temperature. CONCLUSIONS: We conclude that apoE genotype does not affect global CBF and oxygen delivery/extraction during CPB, which suggests that other mechanisms are responsible for the apoE isoform-related neurocognitive dysfunction seen in patients undergoing CPB.

Apolipoproteins E↗
PubMed2000

Beta(2)-adrenergic and several other G protein-coupled receptors in human atrial membranes activate both G(s) and G(i).

Cardiac G protein-coupled receptors that couple to Galpha(s) and stimulate cAMP formation (eg, beta-adrenergic, histamine, serotonin, and glucagon receptors) play a key role in cardiac inotropy. Recent studies in rodent cardiac myocytes and transfected cells have revealed that one of these receptors, the beta(2)-adrenergic receptor (AR), also couples to the inhibitory G protein Galpha(i) (activation of which inhibits cAMP formation). If beta(2)ARs could be shown to couple to Galpha(i) in the human heart, it would have important ramifications, because levels of Galpha(i) increase with age and in failing human heart. Therefore, we investigated whether beta(2)ARs in the human heart activate Galpha(i). By photoaffinity labeling human atrial membranes with [(32)P]azidoanilido-GTP, followed by immunoprecipitation with antibodies specific for Galpha(i), we found that Galpha(i) is activated by stimulation of beta(2)ARs but not of beta(1)ARs. In addition, we found that other Galpha(s)-coupled receptors also couple to Galpha(i), including histamine, serotonin, and glucagon. When coupling of these receptors to Galpha(i) is disrupted by pertussis toxin, their ability to stimulate adenylyl cyclase is enhanced. These data provide the first evidence that beta(2)AR and many other Galpha(s)-coupled receptors in human atrium also couple to Galpha(i) and that abolishing the coupling of these receptors to Galpha(i) increases the receptor-mediated adenylyl cyclase activity.

Adenylate Cyclase Toxin↗
PubMed2000

How much labor is in a labor epidural? Manpower cost and reimbursement for an obstetric analgesia service in a teaching institution.

BACKGROUND: Some anesthesiologists avoid provision of obstetric analgesia services (OAS) because of low reimbursement rates for the work involved. This study defines the manpower costs of operating an OAS in a tertiary referral center and examines reimbursement for this cost. METHODS: The time spent providing OAS in a total of 55 parturients was studied prospectively using a modification of classic time and motion studies. RESULTS: Mean duration of OAS in our population was 412 +/- 313 min. Mean bedside anesthesia staff time was 90 +/- 40 min, and mean number of visits to each patient's bedside was 6.3 +/- 2.0 visits. Assuming staffing on demand for service (intermittent staffing), a minimum of 2.5 full-time equivalent (FTE) attending anesthesiologists was required to meet demand. With intermittent staffing, labor cost was $325 per patient. Actual practice at Duke University Medical Center is around-the-clock (dedicated) staffing, which requires 4.4 FTEs at a cost of $728 per patient. Neither average indemnity reimbursement ($299) nor Medicaid reimbursement ($204) covered the cost per OAS patient. Breaking even is possible under indemnity reimbursement because operating room reimbursement subsidizes OAS costs. Breaking even cannot occur with Medicaid reimbursement under any circumstances. CONCLUSIONS: Obstetric analgesia services requires a minimum of 2.5 FTE attending anesthesiologists at Duke University Medical Center. With the current payer mix, positive-margin operating room activities associated with the obstetric service are not sufficient to compensate for the losses incurred by an OAS. Around-the-clock dedicated obstetric staffing (4.4 FTEs) cannot operate profitably under any reasonable circumstances at our institution.

Adult↗
PubMed2000

Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients.

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.

Acute Disease↗
PubMed1999

Mortality and need for reoperation in patients with mild-to-moderate asymptomatic aortic valve disease undergoing coronary artery bypass graft alone.

BACKGROUND: Patients presenting for coronary artery bypass graft (CABG) surgery may have concurrent asymptomatic aortic stenosis (AS) or aortic insufficiency (AI). This retrospective study was performed to evaluate outcomes in patients with aortic valve disease undergoing CABG with or without aortic valve replacement (AVR). METHODS: Study groups included 414 patients undergoing combined AVR and CABG (AVR-CABG group) and 62 patients with asymptomatic mild-to-moderate AS, AI, or both undergoing CABG but not AVR (CABG group). End points included 30-day mortality rate, time to cardiac mortality, time to all-cause mortality, and time to aortic valve reoperation. Reoperation refers to surgery for replacement of the native aortic valve in the CABG group or replacement of the prosthetic aortic valve in the AVR-CABG group. Important patient characteristics affecting outcomes were determined by using Cox proportional-hazard analysis. These variables were then included in multivariable analyses by using logistic regression analysis and Cox proportional-hazard modeling to compare outcomes between each patient group. RESULTS: No difference was seen in any of the mortality end points between the CABG group and the AVR-CABG group after controlling for significant differences between the groups. However, the need for reoperation for AVR was significantly higher for the CABG group than the AVR-CABG group. For patients followed for up to 6 years, the estimated need for aortic valve reoperation was 24.3% in the CABG group versus 3% in the AVR-CABG group. CONCLUSION: On the basis of these results, patients with asymptomatic AS or AI should be considered for AVR at the time of CABG.

Aged↗
PubMed1999

Epsilon-aminocaproic acid administration and stroke following coronary artery bypass graft surgery.

BACKGROUND: Epsilon-aminocaproic acid is routinely used to reduce bleeding during cardiac surgery. Anecdotal reports of thrombotic complications have led to speculation regarding this drug's safety. We investigated the association between epsilon-aminocaproic acid administration and postoperative stroke. METHODS: Six thousand two hundred ninety-eight patients undergoing isolated coronary artery bypass graft surgery between 1989 and 1995 were studied. Data was obtained from the Duke Cardiovascular Database as well as from an automated intraoperative anesthesia record keeper. Patients identified as having postoperative stroke were reviewed and confirmed by a board certified neurologist blinded to epsilon-aminocaproic acid administration. RESULTS: Postoperative stroke occurred in 97 patients (1.5%). Three thousand one hundred thirty-five (49.8%) patients received epsilon-aminocaproic acid. Increased age was associated with a higher incidence of postoperative stroke (p = 0.0001). In contrast, there was no significant difference (p = 0.7370) in the incidence of stroke between use of epsilon-aminocaproic acid (1.3%) and nonuse (1.7%). Multivariable logistic regression found no significant effect of epsilon-aminocaproic acid use on stroke after accounting for age, date of surgery, and history of diabetes. CONCLUSIONS: This series suggests that epsilon-aminocaproic acid administration does not increase the risk of postoperative stroke.

Adult↗
PubMed1999

Cognitive decline after major noncardiac operations: a preliminary prospective study.

BACKGROUND: Cardiac operations frequently are complicated by postoperative cognitive decline. Less common and less studied is postoperative cognitive decline after noncardiac surgery, so we determined its incidence, severity, and possible predictors. METHODS: Twenty-nine patients who had thoracic and vascular procedures were studied. A neurocognitive test battery was administered preoperatively and 6 to 12 weeks postoperatively. A change score (preoperative minus postoperative) was calculated for each measure in each individual. Cognitive deficit (a measure of incidence) was defined as a 20% decrement in 20% or more of the completed tests. The average scores of all tests and the average decline (a measure of severity) were determined. RESULTS: The incidence of cognitive deficit was 44.8%. Overall the severity of the decline was an average of 15% decline. In the 44.8% of patients who had cognitive deficit, the severity was 24.7%. Multivariable predictors of cognitive decline were age (for incidence and severity) and years of education (for severity). CONCLUSIONS: Cognitive decline after noncardiac operations is a frequent complication of surgical procedures. The severity could preclude successful return to a preoperative lifestyle.

Adult↗
PubMed1999

Acute renal failure following cardiac surgery.

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.

Acute Kidney Injury↗