PubMed Health⌕ Search

Biomedical subjects

Mark Stafford-Smith

Publications and source records attributed to Mark Stafford-Smith.

At least 19 recordsLinked to original sources
PubMed2007

Heart and kidneys: sharing more than just blood.

PURPOSE OF REVIEW: To describe the relationship of renal disease and metabolic syndrome with cardiovascular disease and explore the role of toxic solutes retained due to renal impairment as mediators of cardiovascular risk. RECENT FINDINGS: Metabolic syndrome and chronic kidney disease are related. Chronic kidney disease is partly caused by, but also mediates, some of the adverse effects of metabolic syndrome. Uremic toxins with potent effects have been identified. Examples include the nitric oxide synthase inhibitor asymmetric dimethyl arginine - this substance accumulates as renal function declines and has a strong relationship with cardiovascular events and mortality in a variety of populations. The effect of asymmetric dimethyl arginine in causing arterial stiffness, a phenomenon which has been linked with risk of vascular disease, offers a mechanistic explanation for the importance of this substance. SUMMARY: A pathophysiology that links renal impairment with cardiovascular risk has long been suspected and is being elucidated through the effects of uremic toxins.

Coronary Circulation↗
PubMed2006

Invited commentary.

Explore the source record for details and available documents.

Acute Kidney Injury↗
PubMed2006

Efficacy of single-dose, multilevel paravertebral nerve blockade for analgesia after thoracoscopic procedures.

BACKGROUND: Although video-assisted thoracoscopic surgery for pulmonary resection is increasingly chosen over thoracotomy, the optimal analgesia regimen for thoracoscopy is unknown. The purpose of this trial was to compare the efficacy of analgesia from preoperative bupivacaine paravertebral nerve blockade with that from placebo injections. METHODS: Eighty adult patients undergoing unilateral thoracoscopic procedures were enrolled in a prospective, double-blinded, randomized clinical trial of preoperative, multilevel, single-dose paravertebral nerve blockade. Patients received six paravertebral injections with 5 ml of either 0.5% bupivacaine with 0.0005% epinephrine (treated, n = 40) or preservative-free saline (control, n = 40). Cumulative weight-adjusted intraoperative fentanyl and postoperative patient-controlled morphine usage, visual analog pain scores, and spirometry were used to compare efficacy of analgesia between groups. RESULTS: The treated group received significantly less intraoperative fentanyl compared with the control group (P = 0.003) and had a 31% smaller cumulative patient-controlled morphine dose (P = 0.03) in the 6 h after block placement. Within 6 h, treated patients also reported lower maximum pain scores (P = 0.02) and demonstrated less pain score variability (P = 0.01). No statistically significant difference in cumulative morphine usage existed at 12 or 18 h after block placement. No significant difference in spirometry, cortisol levels, or cytokine production was found between treatments. CONCLUSIONS: Single-dose paravertebral nerve blockade with bupivacaine is effective in reducing pain after thoracoscopic surgery, but only during the first 6 h after nerve blockade. Because of the limited duration of effect with currently available local anesthetic agents, the current data suggest that, at present, this technique is not indicated in the setting of thoracoscopic surgery.

Adult↗
PubMed2006

The genetic determinants of renal impairment following cardiac surgery.

Cardiac surgery is frequently performed, and acute renal dysfunction is a common adverse event following this procedure. Cardiac surgery-related renal injury independently predicts longer hospital stays and greater rates of morbidity and mortality. Although much work has been completed toward better understanding of this phenomenon, the state of knowledge concerning surgery-related renal injury remains limited. Currently, there is no effective paradigm to identify patients who are at risk for this condition; the specific mechanisms of renal injury during surgery are incompletely understood; and few therapies exist to prevent or treat this phenomenon. To better understand this common clinical problem, recent research has focused on the importance of genetic variability within the physiological and patho-physiological systems that underlie renal dysfunction following cardiac surgery. Emphasizing the importance of using genetics to elucidate molecular mechanisms of this disease, this article reviews the current literature on genetic polymorphisms and post cardiac surgery-related renal dysfunction.

Acute Disease↗
PubMed2006

Symmetry aortic connector devices and acute renal injury: a comparison of renal dysfunction after three different aortocoronary bypass surgery techniques.

Although the pathogenesis of acute renal injury after cardiac surgery is multifactorial, atherosclerosis of the ascending aorta and embolic burden are strong independent predictors. Use of the Symmetry aortic connector device (ACD) for proximal anastomosis of coronary grafts may reduce ascending aortic atheroembolism. Therefore, we tested the hypothesis that off-pump coronary artery bypass (OPCAB) surgery performed using an ACD is associated with less postoperative renal dysfunction compared with conventional OPCAB or on-pump coronary artery bypass graft (CABG) surgery. Three-thousand-three-hundred consecutive patients undergoing non-emergent aortocoronary bypass surgery were retrospectively divided into three groups by surgical procedure; Group A: OPCAB with ACD (n = 124), Group B: standard OPCAB (n = 313), Group C: on-pump CABG (n = 2863). Postoperative peak fractional change in creatinine compared with baseline was used as a measure of renal outcome. Multivariable analysis did not identify ACD use as an independent predictor of postoperative peak fractional change in creatinine (P = 0.71), although the relationships of several known renal risk factors with postoperative peak fractional change in creatinine were confirmed. We could not find evidence that OPCAB surgery using ACDs reduces acute renal injury compared with standard OPCAB or CABG surgery.

Acute Kidney Injury↗
PubMed2006

The association between duration of storage of transfused red blood cells and morbidity and mortality after reoperative cardiac surgery.

Red blood cells (RBCs) undergo numerous changes during storage; however, the clinical relevance of these storage "lesions" is unclear. We hypothesized that the duration of storage of transfused RBCs is associated with mortality after repeat sternotomy for cardiac surgery, because these patients are at high risk for both RBC transfusion and adverse outcome. We retrospectively analyzed 434 patients who underwent repeat median sternotomy for coronary artery bypass graft or valve surgery and who received allogeneic RBCs. Three-hundred-twenty-one (74%) patients met the criteria for eligibility. After adjusting for the effects of confounders and the total number of RBC transfusions, the duration of storage of the oldest RBC unit transfused was found to be associated with both in-hospital mortality (Cox proportional hazard ratio (HR) = 1.151; P < 0.0001) and out-of-hospital mortality (HR = 1.116; P < 0.0001). The mean duration of storage of transfused RBCs was also an independent predictor of in-hospital mortality (HR = 1.036; P < 0.0001). Independent associations between the duration of storage of transfused RBCs and acute renal dysfunction and intensive care unit and hospital length of stay were also observed. The duration of storage of RBCs is associated with adverse outcome after repeat sternotomy for cardiac surgery. The clinical significance of this finding should be investigated in a large, randomized, blinded clinical trial.

Acute Kidney Injury↗
PubMed2005

The use of high-fidelity human patient simulation as an evaluative tool in the development of clinical research protocols and procedures.

Errors in clinical research can be costly, in terms of patient safety, data integrity, and data collection. Data inaccuracy in early subjects of a clinical study may be associated with problems in the design of the protocol, procedures, and data collection tools. High-fidelity patient simulation centers provide an ideal environment to apply human-centered design to clinical trial development. A draft of a complex clinical protocol was designed, evaluated and modified using a high-fidelity human patient simulator in the Duke University Human Simulation and Patient Safety Center. The process included walk-throughs, detailed modifications of the protocol and development of procedural aids. Training of monitors and coordinators provided an opportunity for observation of performance that was used to identify further improvements to the protocol. Evaluative steps were used to design the research protocol and procedures. Iterative modifications were made to the protocol and data collection tools. The success in use of human simulation in the preparation of a complex clinical drug trial suggests the benefits of human patient simulation extend beyond training and medical equipment evaluation. Human patient simulation can provide a context for informal expert evaluation of clinical protocol design and for formal "rehearsal" to evaluate the efficacy of procedures and support tools.

Clinical Competence↗
PubMed2005

Changing systems for measuring activated clotting times: impact on the clinical practice of heparin anticoagulation during cardiac surgery.

BACKGROUND: The activated clotting time (ACT) is a standard monitor for heparin anticoagulation during cardiopulmonary bypass (CPB). This study determines the effect of upgrading our ACT system on our clinical practice with regards to the conduct and safety of heparin anticoagulation during cardiopulmonary bypass. METHODS: We compared the intraoperative heparin doses required for all adult cardiac surgery patients (n=1240) and postoperative bleeding for a subset of primary aortocoronary bypass (CABG) surgery procedures (n=285) from cohorts before and after the change in ACT systems. RESULTS: The heparin dose needed to exceed our target ACT of 480 sec for the duration of CPB was higher (45000 vs. 40000 units; p<0.0001), and the mean ACT during CPB was lower (557 vs. 618 sec; p<0.05) using the new ACT system. Furthermore, this coincided with decreased postoperative bleeding in the CABG subset (median value of 417 vs. 575 ml over 12 h; p<0.0005). CONCLUSIONS: We demonstrated that the introduction of the Actalyke ACT system significantly altered our clinical practice by increasing the heparin dose required to exceed our target ACT during CPB. Prospective study to determine the effect of Actalyke ACT system monitoring on hemostasis after cardiac surgery is merited.

Adult↗
PubMed2005

Invited commentary.

Explore the source record for details and available documents.

Coronary Artery Bypass↗
PubMed2005

Association of genetic polymorphisms with risk of renal injury after coronary bypass graft surgery.

BACKGROUND: Post-cardiac surgery renal dysfunction is a common, serious, multifactorial disorder, with interpatient variability predicted poorly by preoperative clinical, procedural, and biological markers. Therefore, we tested the hypothesis that selected gene variants are associated with acute renal injury, reflected by a serum creatinine level increase after cardiac surgery. METHODS: One thousand six hundred seventy-one patients undergoing aortocoronary surgery were studied. Clinical covariates were recorded. DNA was isolated from preoperative blood; mass spectrometry was used for genotype analysis. A model was developed relating clinical and genetic factors to postoperative acute renal injury. RESULTS: A race effect was found; therefore, Caucasians and African Americans were analyzed separately. Overall, clinical factors alone account poorly for postoperative renal injury, although more so in African Americans than Caucasians. When 12 candidate polymorphisms were assessed, 2 alleles (interleukin 6 -572C and angiotensinogen 842C) showed a strong association with renal injury in Caucasians (P < 0.0001; >50% decrease in renal filtration when they present together). Using less stringent criteria for significance (0.01 > P > 0.001), 4 additional polymorphisms are identified (apolipoproteinE 448C [4], angiotensin receptor1 1166C, and endothelial nitric oxide synthase [eNOS] 894T in Caucasians; eNOS 894T and angiotensin-converting enzyme deletion and insertion in African Americans). Adding genetic to clinical factors resulted in the best model, with overall ability to explain renal injury increasing approximately 4-fold in Caucasians and doubling in African Americans (P < 0.0005). CONCLUSION: In this study, we identify genetic polymorphisms that collectively provide 2- to 4-fold improvement over preoperative clinical factors alone in explaining post-cardiac surgery renal dysfunction. From a mechanistic perspective, most identified genetic variants are associated with increased renal inflammatory and/or vasoconstrictor responses.

Acute Kidney Injury↗
PubMed2005

Preoperative statin therapy does not reduce cognitive dysfunction after cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to determine if patients receiving statin therapy before coronary artery bypass grafting surgery would have less cognitive dysfunction after cardiopulmonary bypass as a consequence of a diminished inflammatory response. DESIGN: Retrospective observational study of patients undergoing coronary artery bypass grafting surgery. SETTING: Referral center for cardiothoracic surgery at a university hospital. PARTICIPANTS: Four hundred forty patients undergoing coronary artery bypass grafting surgery with cardiopulmonary bypass. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Thirty-five percent of patients received statins in the preoperative period. Multivariable analysis revealed no effect of preoperative statin therapy on cognitive function (p = 0.67). Post hoc analysis revealed that statin therapy at hospital discharge was associated with less improvement in cognitive performance at 6 weeks after surgery (p = 0.011). No significant differences were found between statin therapy groups in either range or maximum value of any of the cytokines (p > 0.05). CONCLUSIONS: Preoperative statin therapy did not decrease the inflammatory response to cardiopulmonary bypass or the cognitive dysfunction commonly seen after cardiac surgery.

C-Reactive Protein↗
PubMed2005

Hemodynamic changes after protamine administration: association with mortality after coronary artery bypass surgery.

BACKGROUND: Protamine sulfate is standard therapy to reverse heparin anticoagulation. Hemodynamic responses to protamine are common, ranging from minor perturbations to cardiovascular collapse. Although severe fatal reactions occur, the relation of less extreme responses with postoperative mortality is unknown. Therefore, the authors tested the hypothesis that hemodynamic "protamine reactions" (systemic hypotension and pulmonary hypertension) are associated with mortality after cardiac surgery. METHODS: In a university hospital setting, the authors studied 6,921 coronary bypass patients using automated anesthesia record-keeping data and quality assurance databases. Degree/duration integrals of systemic hypotension (< 100 mmHg) and pulmonary hypertension (> 30 mmHg) for the 30-min after protamine administration were assessed for linear associations with mortality using multiple logistic regression models adjusting for risk factors. RESULTS: Overall mortality was 2%; greater hemodynamic responses were associated with increased mortality by odds ratios of 1.28 (systemic hypotension: 95% confidence interval, 1.14-1.43; P < 0.001) and 1.27 (pulmonary hypertension: 95% confidence interval, 1.06-1.48; P < 0.001) per 150-mmHg . min increment. Proximity of the response to protamine administration strengthened the relation, which persisted after exclusion of major hemodynamic disturbances. Tests for linearity confirmed an association even at the lowest range of values for both pressure effects. CONCLUSIONS: Hemodynamic perturbations after protamine administration are independently related to in-hospital mortality after primary coronary artery bypass surgery; the relation is present even in the lowest observed range of values for both systemic hypotension and pulmonary hypertension. Although randomized trials are necessary to address causality, this evidence suggests that strategies that avoid or attenuate these reactions may improve patient care.

Aged↗
PubMed2005

Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass.

BACKGROUND: Hemodynamic protamine reactions with heparin reversal during cardiac surgery are common and associated with adverse outcomes. As an alternative to protamine, the authors examined heparinase I reversal of heparin after aortocoronary bypass graft surgery. METHODS: In a randomized, double-blind, double-dummy trial, 167 on- and off-pump aortocoronary bypass graft surgery patients received either heparinase I (maximum 35 microg/kg) or protamine (maximum 650 mg) for heparin reversal, monitored by activated clotting time values and clinical assessment. Hemodynamic parameters were recorded electronically; safety evaluation was to 30 days postoperatively. Noninferiority was predefined as 400 ml or less median 12-h chest tube drainage from intensive care unit arrival for heparinase I patients, after risk adjustment. Hemodynamic instability was defined as systemic hypotension (> or = 30 mmHg decrease) and/or pulmonary hypertension (> or = 40 mmHg with an increase > or = 10 mmHg) within 30 min of heparin reversal initiation. RESULTS: Patient enrollment was terminated on advisement of the Data Safety Monitoring Board. Although heparinase I was noninferior for 12-h chest tube drainage, protamine had a superior safety profile. Overall, heparinase I subjects had longer hospital stays (P = 0.04), were more likely to experience a serious adverse event (P = 0.01), and were less likely to avoid transfusion (P = 0.006). A composite morbidity score was not different (P = 0.24), and similar rates of hemodynamic instability were observed between groups. Findings were consistent in analyses stratified by on- and off-pump surgery. CONCLUSIONS: Heparinase I reverses heparin anticoagulation after aortocoronary bypass graft surgery but is not equivalent to protamine because of its inferior safety profile.

Adolescent↗
PubMed2005

Evidence-based renal protection in cardiac surgery.

Acute renal dysfunction is a common serious complication of cardiac surgery. Although a diversity of mechanisms exist by which the kidney can be damaged during cardiac surgery, atheroembolism, ischemia-reperfusion, and inflammation are believed to be primary contributors to perioperative renal insult. In addition, the high metabolic demands of active tubular reabsorption and the oxygen diffusion shunt characteristic of renal circulation make the kidney particularly vulnerable to ischemic injury. Remote effects of acute renal injury likely contribute to the strong association of this condition with other major postoperative morbidities and mortality and justify the search for renoprotective agents, even when dialysis is never required. Nonpharmacologic preventive strategies include procedure planning that is based on risk stratification, avoidance of nephrotoxins, and meticulous perioperative clinical care, including optimizing intravascular volume and attention to modifiable risk factors such as minimizing hemodilution. Although numerous pharmacologic interventions to prevent or treat acute renal injury have shown promise in animal models, randomized placebo-controlled clinical trials that have looked at measures of significant adverse outcomes such as death and dialysis have not confirmed a benefit.

Cardiac Surgical Procedures↗