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Biomedical subjects

Elliott Bennett-Guerrero

Publications and source records attributed to Elliott Bennett-Guerrero.

At least 19 recordsLinked to original sources

Calcium supplementation of saline-based colloids does not produce equivalent coagulation profiles to similarly balanced salt preparations.

OBJECTIVES: The primary objective of this study was to test the hypothesis that calcium alone does not account for the observed coagulation differences between saline-based and balanced electrolyte IV fluid preparations. DESIGN: Controlled, nonblinded, in vitro observational study. SETTING: University-based anesthesia research laboratory. PARTICIPANTS: Ten healthy volunteers. INTERVENTIONS: The volunteers donated fresh blood for in vitro 40% and 60% dilution with 6 intravenous fluid preparations (lactated Ringer's solution, human albumin solution, and 4 hydroxyethyl starch preparations). All saline-based fluids were supplemented with calcium chloride to obtain ionized concentrations >or=1.0 mmol/L. MEASUREMENTS AND MAIN RESULTS: After dilution of the fresh blood with the study fluids, samples were analyzed by using the Thrombelastograph. Three colloid preparations produced minimal coagulation derangement, even at 60% dilution (human albumin solution, tetrastarch in saline, and pentastarch in balanced electrolyte solution), whereas pentastarch in saline and hetastarch in balanced electrolyte produced a mildly hypocoagulable state at 60% dilution. CONCLUSIONS: The different coagulation profiles between the 2 pentastarch preparations, as well as similar profiles of pentastarch in saline and hetastarch in balanced electrolyte solution, suggest that calcium is not solely responsible for previously observed effects.

Albumins↗

A randomized, double-blind, placebo-controlled study assessing the anti-inflammatory effects of ketamine in cardiac surgical patients.

OBJECTIVE: To determine whether ketamine administration affects markers of inflammation in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate differences between 2 low-dose ketamine regimens. DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: Single-center university hospital. PARTICIPANTS: Patients undergoing cardiac surgery with CPB. INTERVENTION: Patients (n = 50) were randomized to 1 of 3 groups: ketamine, 0.25 mg/kg (n = 15); ketamine, 0.5 mg/kg (n = 18);or placebo (n = 17) in a double-blind manner at the time of induction of general anesthesia. MEASUREMENTS AND MAIN RESULTS: Serum C-reactive protein (CRP) and interleukin (IL)-6, IL-8, and IL-10 were measured at baseline, on intensive care unit (ICU) arrival, and on the first postoperative day (POD 1). Both ketamine doses decreased the serum IL-6 response at ICU arrival and POD 1 compared with placebo (p < 0.05). CRP was lower in the 0.5-mg/kg group than placebo on POD 1 (p = 0.003). IL-10 was lower in the ketamine groups (p = 0.01) at POD 1 compared with placebo; IL-8 levels were not affected by ketamine. Mean arterial pressure and systemic vascular resistance were higher at the end of surgery, arrival in the ICU, and POD 1 in the ketamine groups (p < 0.05). CONCLUSION: Low-dose ketamine (0.5 mg/kg) attenuates increases in CRP, IL-6, and IL-10 while decreasing vasodilatation after CPB.

Aged↗

The kaolin-activated Thrombelastograph predicts bleeding after cardiac surgery.

OBJECTIVE: The objective of this study was to determine the relationship of the kaolin-activated Thrombelastograph (TEG) with postoperative bleeding and laboratory tests of coagulation in the setting of cardiac surgery with the routine use of -aminocaproic acid. DESIGN: Prospective observational study. SETTING: An adult heart center at a tertiary referral, university hospital. PARTICIPANTS: Thirty adult cardiac surgical patients. INTERVENTIONS: The kaolin-activated TEG, platelet counts, prothrombin times, activated partial thromboplastin times, and fibrinogen levels were measured before induction of anesthesia, during cardiopulmonary bypass, and on arrival in the intensive care unit. Mediastinal and thoracostomy drainage were measured every hour for 4 hours after arrival in the intensive care unit. MEASUREMENTS AND MAIN RESULTS: Correlation and multivariate linear regression modeling were used to describe relationships among coagulation tests, TEG parameters, and early postoperative bleeding. The TEG maximum amplitude (MA) parameter correlated well with postoperative bleeding (r = -0.6, p = 0.0018), more so than platelet count (r = -0.45, p = 0.02), fibrinogen level (r = -0.40, p = 0.06), or prothrombin time (r = 0.43, p = 0.02). The receiver operating characteristic curve c-index describing MA as a predictor for postoperative bleeding is 0.78. Abnormalities in all the laboratory test results were associated with an abnormal MA. CONCLUSIONS: In conclusion, the kaolin-activated TEG is associated with early coagulopathic bleeding. It may reflect the severity of a global coagulopathy affecting both platelets and coagulation factors and be a guide to incremental prohemostatic therapy in this setting.

Aged↗

Effects of decreased preoperative endotoxin core antibody levels on long-term mortality after coronary artery bypass graft surgery.

HYPOTHESIS: Decreased preoperative levels of antiendotoxin core antibody (EndoCAb) in patients undergoing cardiac surgery with cardiopulmonary bypass are associated with increased long-term mortality. DESIGN: Observational study. SETTING: Academic medical center. PATIENTS: A total of 474 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. INTERVENTIONS: Preoperative serum IgM EndoCAb levels were determined, and established preoperative risk factors were assessed. Patients were assigned a risk score using a validated method. MAIN OUTCOME MEASURES: The primary end point was mortality. Statistical analysis used the Cox proportional hazards regression model with log EndoCAb as the predictor of interest and Parsonnet additive risk score as a covariate. Kaplan-Meier survival curves were generated to visually compare groups with high vs low EndoCAb levels. RESULTS: Forty-six deaths occurred in 5 years. Annual follow-up rates during the 5 years were 100%, 94%, 93%, 98%, and 98% for the 1-, 2-, 3-, 4-, and 5-year periods, respectively. Parsonnet additive risk score (hazard ratio, 1.07; 95% confidence interval [CI], 1.04-1.11; P < .001) and log EndoCAb (hazard ratio, 0.73; 95% CI, 0.53-0.99; P = .04) were independent predictors of long-term mortality in the final model. Kaplan-Meier analysis revealed that the preoperative EndoCAb level was significantly associated with mortality up to 5 years (P = .01 by log-rank test). CONCLUSION: Lower preoperative serum EndoCAb level is a significant predictor of long-term mortality independent of other known risk factors.

Biomarkers↗

A head-to-head comparison of the in vitro coagulation effects of saline-based and balanced electrolyte crystalloid and colloid intravenous fluids.

Both fluid composition (e.g., type of hydroxyethyl starch) and formulation (e.g., saline or balanced salt carrier solution) may alter whole blood coagulation. We therefore enrolled 10 healthy volunteers to test ex vivo, thrombelastograph-based blood coagulation differences of eight crystalloid and colloid solutions at 20%, 40%, and 60% dilutions. Saline and lactated Ringer's solution produced a hypercoagulable state at 20%-40% dilutions. Saline, hetastarch in saline, pentastarch in saline, tetrastarch in saline, and human albumin solutions all produced a hypocoagulable state at 60% dilution. Hetastarch in saline also produced a hypocoagulable state at 40% dilution. The larger molecular weight starches produced more intense coagulation abnormalities than the medium molecular weight compounds formulated similarly (i.e., suspended in saline or balanced salt solution). The balanced salt solutions caused fewer coagulation abnormalities, especially pentastarch in balanced salt solution. This balanced salt pentastarch preparation produced the least derangement of coagulation of the colloid solutions at all dilutions, causing hypercoagulability at the lower dilutions and minimal coagulation derangement at 60% dilution. These data support the theory that smaller molecular weight hydroxyethyl starches and colloids suspended in balanced salt solutions preserve coagulation better than large molecular weight starches and saline-based colloids, as judged by thrombelastography.

Analysis of Variance↗

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↗

Preoperative anti-PF4/heparin antibody level predicts adverse outcome after cardiac surgery.

OBJECTIVE: Preexisting serum antibodies to heparin/platelet factor 4 complexes may predispose adult cardiac surgical patients to increased perioperative morbidity and mortality. We sought to determine the association between preoperative serum antibodies directed against platelet factor 4/heparin complexes and major complications (in-hospital death or length of stay >10 days) in adult cardiac surgical patients. METHODS: In a prospective observational study of 466 patients undergoing elective coronary artery bypass grafting, valvular heart surgery, or both, preoperative serum was assayed for anti-platelet factor 4/heparin antibody by using a commercially available enzyme-linked immunosorbent assay (Asserachrom HPIA). Known preoperative risk factors were assessed, and patients were assigned a risk score by using the validated method of Parsonnet and colleagues. RESULTS: Major complications (death or postoperative hospitalization >10 days) occurred in 108 patients (23%). Overall, 59 (13%) patients had a positive preoperative anti-platelet factor 4/heparin antibody screen (upper limit of normal is 0.5 optical density units). A positive assay result independently predicted an increased risk of major complications (P = .0284; odds ratio, 1.98; 95% confidence interval, 1.06-3.62) over and above the effect of the Parsonnet risk score (P < .001; odds ratio, 1.07; 95% confidence interval, 1.05-1.10). The level of preoperative anti-platelet factor 4/heparin antibody was also significantly associated with major complications (P = .036; odds ratio, 1.31; 95% confidence interval, 1.02-1.68) independently of the Parsonnet risk score. No association (P > .75) existed between the Parsonnet risk score and preoperative anti-platelet factor 4/heparin antibody level. CONCLUSIONS: Serum antibodies directed against platelet factor 4/heparin complexes are prevalent in the adult patient population undergoing cardiac surgery. The presence of these antibodies before surgery is an independent predictor for death or prolonged hospitalization after adult cardiac surgery.

Aged↗

National survey regarding the management of an intraoperatively diagnosed patent foramen ovale during coronary artery bypass graft surgery.

OBJECTIVE: With the increased use of intraoperative transesophageal echocardiography (TEE), patent foramen ovale (PFO) has become a common finding during routine coronary artery bypass graft (CABG) surgery. This survey was designed to study potential differences in the management of intraoperatively diagnosed PFO. DESIGN: A written survey. SETTING: US university and community hospitals. PARTICIPANTS: The authors randomly selected 50% of US cardiac surgeons listed in the Cardiothoracic Surgery Network Database (n = 734). INTERVENTIONS: A written survey was mailed to the participants. The survey questions included respondents' use of TEE during CABG surgery, examination for a PFO with TEE, and management of intraoperatively diagnosed PFO in the CABG surgery. MEASUREMENTS AND MAIN RESULTS: Overall, 64% of individuals (468/734) responded to the survey request. TEE is available in the primary institution of 98.6% of respondents and used to search for a PFO in approximately one third of all CABG surgeries. During planned on-pump CABG surgery, 27.9% of respondents always close an intraoperatively diagnosed PFO, whereas 10.2% of respondents never close an intraoperatively diagnosed PFO. During planned off-pump CABG surgery, 27.6% of surgeons never change their plan, and 11% of respondents always convert the procedure to on-pump CABG to close the PFO. The majority of respondents decide whether to close a PFO based on the size of the PFO, the right atrial pressure, and a history of possible paradoxical embolism. CONCLUSIONS: In the United States, TEE is used extensively during CABG surgery. There is significant variability in how intraoperatively diagnosed PFO is managed during CABG surgery.

Blood Pressure↗

Low-dose endotoxin elicits variability in the inflammatory response in healthy volunteers.

Endotoxin has been implicated as a cause of sepsis, inflammation and organ dysfunction after surgery. Patients differ in their response to endotoxin, and this may account for differences in outcome. The traditional human model of endotoxin challenge (2-4 ng/kg) is not associated with significant inter-individual variability in systemic inflammation and may not be suitable for studying variability in the inflammatory response. We examined whether low-dose regimens of endotoxin cause significant variability in inflammation. Volunteers (n = 30) were randomised in a double-blinded ('double-dummy') study to one of 6 dosing regimens: saline (placebo) or Escherichia coli O:113 endotoxin as a 4 ng/kg bolus (positive control), 0.25 ng/kg (bolus), 0.25 ng/kg (30 min infusion), 0.75 ng/kg (bolus) or 0.75 ng/kg (30 min infusion). Temperature, white cell count, platelet count, C-reactive protein and cytokine changes from baseline were measured. In contrast to subjects receiving placebo, those randomised to 4 ng/kg endotoxin exhibited significant systemic inflammation during the 10-h observation period. The four low-dose regimens elicited variability in most markers of inflammation. We conclude that low-dose endotoxin elicits inter-individual variability in inflammation and could be used to test factors that may affect the human response to endotoxin.

Adolescent↗

The relationship between a pentagastrin-stimulated gastric luminal acid production test (Gastrotest) and enteral feeding-related gastrointestinal complications in critically ill patients.

Gastrointestinal feeding-related complications (GICs) are common in critically ill patients. Unfortunately, patients at risk for GICs cannot be easily identified. Therefore, we performed a prospective study of 20 critically ill patients to determine the association between a pentagastrin-stimulated gastric acid production test and GICs. Before feeding, the change in the pH of gastric juice was measured in response to a subcutaneous injection of pentagastrin (Gastrotest). We recorded GICs and the feeding volume ratio during each patient's intensive care unit (ICU) stay. Nineteen patients' data were analyzed and 9 patients (47%) developed > or =1 GIC, including large gastric residuals, 26%; abdominal distension, 26%; and vomiting, 21%. Patients with GICs had a longer length of ICU stay (mean 21.3, range 5-45 versus 10.1, range 3-32; P < 0.05). The 9 patients (47%) who were Gastrotest responders before starting enteral feeding exhibited a significantly larger volume ratio (P = 0.01) and fewer GICs (1 [11%] versus 8 [80%]; P < 0.05). Abdominal distension was seen in only nonresponders. The positive and negative predictive values for this test's ability to predict GICs were 80% and 88.9%, respectively. Responding to a pentagastrin-stimulated gastric luminal acid production test is associated with the administration of larger volumes of enteral feed and fewer GICs.

Adult↗

A randomized, double-blind comparison of lactated Ringer's solution and 0.9% NaCl during renal transplantation.

Normal saline (NS; 0.9% NaCl) is administered during kidney transplantation to avoid the risk of hyperkalemia associated with potassium-containing fluids. Recent evidence suggests that NS may be associated with adverse effects that are not seen with balanced-salt fluids, e.g., lactated Ringer's solution (LR). We hypothesized that NS is detrimental to renal function in kidney transplant recipients. Adults undergoing kidney transplantation were enrolled in a prospective, randomized, double-blind clinical trial of NS versus LR for intraoperative IV fluid therapy. The primary outcome measure was creatinine concentration on postoperative Day 3. The study was terminated for safety reasons after interim analysis of data from 51 patients. Forty-eight patients underwent living donor kidney transplants, and three patients underwent cadaveric donor transplants. Twenty-six patients received NS, and 25 patients received LR. There was no difference between groups in the primary outcome measure. Five (19%) patients in the NS group versus zero (0%) patients in the LR group had potassium concentrations >6 mEq/L and were treated for hyperkalemia (P = 0.05). Eight (31%) patients in the NS group versus zero (0%) patients in the LR group were treated for metabolic acidosis (P = 0.004). NS did not adversely affect renal function. LR was associated with less hyperkalemia and acidosis compared with NS. LR may be a safe choice for IV fluid therapy in patients undergoing kidney transplantation.

Acidosis↗

Thromboelastography maximum amplitude predicts postoperative thrombotic complications including myocardial infarction.

Postoperative thrombotic complications increase hospital length of stay and health care costs. Given the potential for thrombotic complications to result from hypercoagulable states, we sought to determine whether postoperative blood analysis using thromboelastography could predict the occurrence of thrombotic complications, including myocardial infarction (MI). We prospectively enrolled 240 patients undergoing a wide variety of surgical procedures. A cardiac risk score was assigned to each patient using the established revised Goldman risk index. Thromboelastography was performed immediately after surgery and maximum amplitude (MA), representing clot strength, was determined. Postoperative thrombotic complications requiring confirmation by a diagnostic test were assessed by a blinded observer. Ten patients (4.2%) suffered a total of 12 postoperative thrombotic complications. The incidence of thrombotic complications with increased MA (8 of 95 = 8.4%) was significantly (P = 0.0157) more frequent than that of patients with MA < or =68 (2 of 145 = 1.4%). Furthermore, the percentage suffering postoperative MI in the increased MA group (6 of 95 = 6.3%) was significantly larger than that in the MA < or =68 group (0 of 145 = 0%) (P = 0.0035). In a multivariate analysis, increased MA (P = 0.013; odds ratio, 1.16; 95% confidence interval, 1.03-1.20) and Goldman risk score (P = 0.046; odds ratio, 2.39; 95% confidence interval, 1.02-5.61) both independently predicted postoperative MI. A postoperative hypercoagulable state as determined by thromboelastography is associated with postoperative thrombotic complications, including MI, in a diverse group of surgical patients.

Adult↗

Gastric hypercarbia and adverse outcome after cardiac surgery.

OBJECTIVE: It has been postulated that splanchnic ischemia, as manifested by gastric hypercarbia, helps to trigger excessive systemic inflammation, which has been linked to the development of adverse postoperative outcome. This study examined whether gastric PCO(2) values are associated with adverse outcome in cardiac surgical patients. DESIGN AND SETTING: Prospective cohort study in a tertiary-care hospital. PATIENTS: 43 patients undergoing elective cardiac surgery. INTERVENTIONS: Simultaneous measurements of gastric PCO(2) (using automated air tonometry) and arterial PCO(2) were obtained at the beginning and end of surgery. The difference (gap) between regional PCO(2) and arterial PCO(2) (corrected for temperature) was calculated. Adverse outcome was defined as in-hospital death or prolonged (>10 days) postoperative hospitalization. MEASUREMENTS AND RESULTS: Fourteen patients fulfilled the predefined definition for adverse outcome. Postoperative ICU stay and postoperative hospital length of stay were significantly longer in these patients. At the end of surgery gastric minus arterial PCO(2) gap was significantly larger in patients with adverse outcome. Global hemodynamic and perfusion related variables were not associated with adverse outcome (cardiac index, mean arterial pressure, mixed venous oxygen saturation, arterial lactate, arterial base excess). CONCLUSIONS: Gastric minus arterial PCO(2) gap after surgery is larger in patients with adverse postoperative outcome, which supports the theory that gastrointestinal reduced perfusion is relevant to the pathogenesis of postoperative morbidity.

Aged↗

Stroke after cardiac surgery: a retrospective analysis of the effect of aprotinin dosing regimens.

BACKGROUND: Half-dose aprotinin (HDA) appears to be equivalent to full-dose aprotinin (FDA) in its ability to prevent bleeding. However, data regarding the potential effect of aprotinin use and dosage on other outcomes such as the occurrence of perioperative stroke are limited. It has been postulated that the higher level of kallikrein inhibition obtained with FDA dosing may be required for end-organ protection. Therefore, we performed a retrospective study in cardiac surgery patients at high risk for developing stroke to determine the relative effects of FDA and HDA regimens on the incidence of postoperative stroke. METHODS: Records of 1,524 patients undergoing cardiac surgery over a 15-month period were reviewed. Patients at high risk for stroke were selected if they met all of the following predefined criteria: age greater than 70 years, history of hypertension, history of diabetes mellitus, history of stroke or transient ischemic attack, and presence of aortic atheroma. A validated preoperative stroke risk index was calculated for each patient. Postoperative stroke required confirmation by computed tomography or magnetic resonance imaging. Patients were divided into three groups according to whether they were administered no aprotinin, HAD, or FDA. RESULTS: A total of 149 patients fulfilled the criteria for being at high risk for stroke. Stroke risk index was very similar (p = 0.56) in the three groups: those who received no aprotinin and served as a control group (124 +/- 15, n = 56), those who were given HDA (123 +/- 12, n = 67), and those who received FDA (122 +/- 11 n = 26). Preoperative and intraoperative characteristics were also similar between the three study groups. Overall, the incidence of stroke was 16% (24/149). The incidence of stroke differed (p < 0.05) among the three groups: no aprotinin 16% (9/56), HDA 22% (15/67), and FDA 0% (0/26). CONCLUSIONS: In this retrospective study of cardiac surgery patients at high risk for postoperative stroke, the administration of FDA but not HDA was associated with a lower incidence of stroke.

Aged↗

Abnormal gastric tonometric variables and vasoconstrictor use after left ventricular assist device insertion.

BACKGROUND: Abnormal gastric tonometric variables, a surrogate for splanchnic ischemia, occur in approximately 50% of patients at the end of routine cardiac operations and are associated with postoperative morbidity. We sought to determine whether gastric tonometric variables deteriorate after left ventricular assist device insertion and to explore the association between abnormal gastric tonometric variables and vasoconstrictor use. METHODS: Nineteen patients who had insertion of a left ventricular assist device were enrolled in a prospective, observational study. Automated air tonometry was used to determine the difference between gastric and arterial partial pressure of carbon dioxide (CO2 gap) at five time points perioperatively. RESULTS: Compared with baseline, systemic blood flow was significantly increased at the end of operation (1.9 +/- 0.6 versus 2.9 +/- 0.7 L x min(-1) x m(-2), p < 0.0001). Tonometric variables, which were normal at baseline, became abnormal in 90% of patients (baseline CO2 gap 4 +/- 2 mm Hg versus end of operation CO2 gap 24 +/- 15 mm Hg, p < 0.0001). Elevated CO2 gaps correlated with larger doses of norepinephrine (r = 0.69, p = 0.001) and vasopressin (r = 0.88, p < 0.0001). Abnormal gastric tonometric variables at the end of operation correlated with postoperative intensive care unit length of stay (r = 0.70, p = 0.0009) and multiple organ dysfunction score (r = 0.64, p = 0.0033). CONCLUSIONS: Despite a significant increase in systemic blood flow after left ventricular assist device implantation, abnormal gastric tonometric variables developed and were associated with larger vasoconstrictor dose. These data provide evidence that gastric ischemia can develop independently of changes in systemic blood flow and support the potential role of vasoconstrictors as a cause of splanchnic ischemia.

Acid-Base Equilibrium↗