Biomedical subjects
Publications and source records attributed to Elliott Bennett-Guerrero.
The lipopolysaccharides of Gram-negative bacteria have a profound effect on the mammalian immune system and are of great significance in the pathophysiology of many disease processes. Consideration is given in this review to the relationship between structure and function of these lipopolysaccharides.
OBJECTIVE: To investigate potential mechanisms for the differences in thromboelastography variables observed between arterial blood samples and venous blood samples. DESIGN: Prospective cohort study. SETTING: University hospital. PARTICIPANTS: Patients undergoing cardiac surgery (n = 33). INTERVENTIONS: After the withdrawal of 10 mL of discarded blood (>3 deadspace volumes), 3 blood samples were withdrawn simultaneously from the central venous port of the pulmonary artery catheter (CVP), the radial arterial catheter (ART), and the side port of the 9F sheath introducer (SI). MEASUREMENTS AND MAIN RESULTS: Thromboelastography was done simultaneously on each sample. All thromboelastography analyses were performed with 1% celite and heparinase according to the manufacturer's guidelines. A total of 80 ART, SI, and CVP comparisons were obtained. Mean hematocrit values were not different between sampling sites (27 +/- 4 v 27 +/- 4 v 27 +/- 3). Thromboelastography R time values (mean +/- SD) were CVP, 8 +/- 3; ART, 10 +/- 3; and SI, 13 +/- 5 (p = 0.004). Thromboelastography maximal amplitude (MA) values (mean +/- SD) were CVP, 60.4 +/- 11.7; ART, 56.2 +/- 11.4; and SI, 50.5 +/- 13.2 (p = 0.008). Calculated maximal shear stresses were CVP, 48 dyne/cm(2); ART, 36 dyne/cm(2); and SI, 0.3 dyne/cm(2). Blood samples obtained from the CVP (highest shear stress) resulted in faster (shorter R) and stronger (larger MA) coagulation compared with the arterial site (intermediate shear stress) and sheath introducer (lowest shear stress). CONCLUSION: These data show that differences exist in thromboelastography values between arterial and venous blood samples and, more importantly, show that the differences observed are not related to differences in oxygen content. These differences seem to be related to differences in catheter lumen diameter and, presumably, shear forces.
UNLABELLED: Hextend is a new plasma volume expander containing 6% hydroxyethyl starch (HES) in a physiologically balanced medium of electrolytes, glucose, and lactate (weight average, molecular weight 670 kDa, molar substitution 0.75). This open-label study was designed to investigate the pharmacokinetic and pharmacodynamic profiles of Hextend in 21 healthy volunteers. We infused Hextend 10 ml/kg IV over 20 min and determined serum concentrations of HES at selected intervals over a 7-day period. Serum concentration-time curves indicated mixed pharmacokinetic behavior reflecting a two-compartment model in most subjects. The median serum half-life over 7 days was 38.2 h. The balanced formulation of the suspension medium did not seem to affect distribution, metabolism, or excretion of Hextend when compared with similar HES. Pharmacodynamic analysis demonstrated decreases in some plasma components compatible with the infusion of that volume of fluid and the duration of plasma volume expansion. Other plasma components remained unchanged, reflecting the benefit of a balanced electrolyte solution. Hemodilution was observed for 24--48 h after short-term infusion of Hextend. Some hemostatic indices showed moderate changes, and serum amylase demonstrated a temporary increase. Our study suggested that Hextend has pharmacokinetic and pharmacodynamic profiles that are similar to those of other HES. IMPLICATIONS: Hextend is a new plasma volume expander containing 6% hydroxyethyl starch in a physiologically balanced medium. This open-label volunteer study demonstrated that it has pharmacokinetic and pharmacodynamic profiles similar to those of established HES.
UNLABELLED: Low gastric intramucosal pH (pHi) and an increased gastric-arterial PCO2 difference (CO2 gap) are markers of tissue hypoperfusion. Perfluorocarbons (PFCs) have a large oxygen-carrying capacity and release oxygen when encountering low tissue oxygen tension. Nine cardiac surgical patients instrumented for gastric tonometry were enrolled as part of a multicenter, randomized, single-blinded study of a PFC emulsion (perflubron emulsion [Oxygent]). Patients were randomized to receive PFC (n = 4) or placebo (n = 5) after intraoperative autologous blood harvesting by acute normovolemic hemodilution. At baseline there were no intergroup differences in tonometric-, hemodynamic-, or oxygen delivery-derived variables, e.g., Control group (pHi, 7.37 +/- 0.06; CO2 gap, 6.4 +/- 1.3 mm Hg) versus PFC group (pHi, 7.38 +/- 0.06; CO2 gap, 6.7 +/- 1.5 mm Hg). After acute normovolemic hemodilution, pHi was significantly lower (P < 0.01) in the Control group (7.22 +/- 0.25) than in the PFC group (7.44 +/- 0.25), and CO2 gap was significantly higher (P < 0.001) in the Control group (23.4 +/- 5.1 mm Hg) than in the PFC group (1.8 +/- 0.8 mm Hg). These differences in tonometric variables persisted during surgery. The PFC group showed a significantly (P < 0.007) shorter time to first bowel movement postoperatively (2.0 +/- 0.8 vs 5.4 +/- 1.6 days). Time to consumption of solid food was also shorter in the PFC group and almost achieved statistical significance (P = 0.056). IMPLICATIONS: This study suggests that the administration of perflubron emulsion prevents gastrointestinal tract ischemia in cardiac surgical patients and may preserve postoperative gastrointestinal tract function.
UNLABELLED: Outcome after cardiac surgery varies depending on complication type. We therefore sought to determine the association between complication type, mortality, and length of stay in a large series of patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). Multivariate logistic regression was used to test for differences between complication types in mortality and prolonged length of stay (>10 days) while controlling for preoperative and intraoperative risk factors. In 2609 consecutive cardiac surgical patients requiring CPB, the mortality rate was 3.6%; 36.5% had one or more complications, and 15.7% experienced an adverse outcome (death or prolonged length of stay). Multivariate logistic regression demonstrated that complication type was significantly associated with adverse outcome (P < 0.001) independent of Parsonnet score and CPB time (c-index = 0.80). The development of noncardiac complications only (Group NC) and cardiac complications with other organ involvement (Group B) significantly increased mortality and hospital and intensive care unit length of stay (P < 0.001) when compared with cardiac complications only (Group C). The incidences of adverse outcome in Groups C, NC, and B were 15%, 43%, and 67%, respectively; the mortality rates were 3%, 7%, and 20%, respectively. All these intergroup comparisons were significantly different (adjusted P < 0.05). Complications involving organs other than the heart appear to be more deleterious than cardiac complications alone, underscoring the need for strategies to reduce noncardiac complications. IMPLICATIONS: Complications, particularly when they involve organs other than just the heart, increase mortality and prolong the length of hospital stay after heart surgery, independent of a patient's preoperative risk factors and the duration of cardiopulmonary bypass. Strategies aimed at preventing damage to other organs during cardiac surgery need to be improved.
UNLABELLED: Relatively little is known about the influence of intraoperative hemodynamic variables on surgical outcomes. We drew subjects (n = 797) from a study of patients undergoing major noncardiac surgery. The physiological component of the POSSUM (Physiological and Operative Severity Score for the enUmeration of Mortality) operative risk stratification index was determined, and intraoperative measurements of heart rate (HR), mean arterial blood pressure, and systolic arterial blood pressure (SAP) were retrieved from computerized anesthesia records. For every 5-min epoch during the surgery, HR, mean arterial blood pressure, and SAP were each classified as low, normal, or high. Negative surgical outcome (NSO) was defined as a hospital stay of >10 days with a morbid condition or death during the hospital stay. Statistical analyses included Mantel-Haenszel tests and multiple logistic regression. There was no significant association between hemodynamic variables and NSO with short operations. In 388 patients with operations longer than the median time of 220 min, NSO occurred in 15.6%. Controlling for POSSUM score and operation time beyond 220 min, both high HR (odds ratio, 2.704; P = 0.01) and high SAP (odds ratio, 2.095; P = 0.009) were associated with NSO in longer operations. Thus, intraoperative tachycardia and hypertension were associated independently with adverse outcomes after major noncardiac surgery of long duration, over and above the risk imparted by underlying medical conditions. IMPLICATIONS: Intraoperative tachycardia and hypertension were associated with negative postoperative outcomes after major noncardiac surgery of long duration. These results imply that intraoperative tachycardia and hypertension may have independent effects on outcome over and above the risk imparted by underlying medical conditions.
A vaccine that induces humoral immunity to lipopolysaccharide (LPS), while remaining non-pyrogenic should be beneficial, as high levels of antibodies against LPS are associated with a reduced risk of adverse outcome. However, pure LPS or bacteria expressing LPS are generally considered too toxic to be used as vaccines. Recently, a novel, immunogenic complete core lipopolysaccharide vaccine has been described, which has been designed to prevent endotoxin-related inflammatory reactions in surgical and high-risk hospitalized patients. In vivo studies have shown that while administration of the vaccine to rabbits results in no toxicity over 7 days, it does induce significantly enhanced antibody responses towards a broad range of clinically relevant Gram-negative LPSs. Here we show that encapsulation of the four complete core LPS types Escherichia coli K12, Escherichia coli R1, Bacteroides fragilis and Pseudomonas aeruginosa into liposomes greatly reduces the ability of a given amount of LPS to induce TNF-alpha production in vitro from human monocytes. In contrast to previous studies of liposomal LPS, we demonstrate a reduction in activity of approximately 100,000-fold; a reduction approximately 100-1,000-fold more than that previously described. The signalling by the liposomal LPS appears to be entirely dependent on serum factors, though this can be partially restored by soluble CD14 or, to a lesser extent, by lipopolysaccharide binding protein. Time-course experiments reveal that liposomal LPS signalling shows similar kinetics to pure LPS signalling. Therefore, as well as inducing specific antibody responses, liposomal LPS demonstrates characteristics suitable for use as a vaccine to be used in human beings.
Prophylactic optimization of stroke volume during surgery has been thought by some to reduce complications following surgery. Mechanical ventilation has been shown to induce variations in systolic systemic arterial blood pressure. Measuring such variations in systolic pressure (SPV) might serve as an attractive method for guiding fluid therapy intraoperatively. It is unknown if variations in systolic pressure following the rapid intravenous administration of a specific volume of fluid would lead to changes in pressure measurements obtained from a pulmonary artery with sufficient sensitivity to predict or guide the need for expansion of the intravascular volume to optimize stroke volume as an index of cardiac function. The purpose of this study was to determine if such measurements of changes in systolic pressures would be useful in optimizing stroke volume. Nineteen patients undergoing cardiac surgery were enrolled in a prospective cohort study. Following induction of general anesthesia, one or more 250 mL boluses of 6% hetastarch were administered. Stroke volume was calculated from the cardiac output obtained by thermodilution using a pulmonary artery catheter. If the patient s stroke volume increased by less than 10% as a result of a given fluid challenge, the patient was classified as a non-responder. However, if the stroke volume increased by more than 10%, the patient was classified as a responder. The variations in systolic pressure and echocardiographic indices were simultaneously measured before and after the administration of each 250 mL fluid bolus. Pulmonary artery occlusion pressure (PAOP) values were significantly lower in patients who responded to fluid boluses (p=0.0085) than in those who did not. Similarly SPV and SPVdown values (defined as the decrease in systolic pressure with ventilation) were significantly greater in the responders (p<0.05). No significant intergroup differences were observed in SPVup (increase in systolic pressure with ventilation) or echocardiographic-derived left ventricular end diastolic area. A PAOP value less than 10 mm Hg predicted a response (sensitivity 68%, specificity 79%). Although significant intergroup differences in the extent of systolic pressure variations were observed, no appropriate threshold values could be determined that would accurately predict the response to a fluid bolus. There is a relationship between SPV and SPVdown values and intravascular volume status. SPV and echocardiographic-derived values did not predict the response to a fluid bolus as well as values obtained from the pulmonary artery catheter.