Elliott Bennett-Guerrero

Structure and function of lipopolysaccharides.

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.

Variation in Use of Blood Transfusion in Coronary Artery Bypass Graft Surgery

CONTEXT Perioperative blood transfusions are costly and have safety concerns. As a result, there have been multiple initiatives to reduce transfusion use. However, the degree to which perioperative transfusion rates vary among hospitals is unknown. OBJECTIVE To assess hospital-level variation in use of allogeneic red blood cell (RBC), fresh-frozen plasma, and platelet transfusions in patients undergoing coronary artery bypass graft (CABG) surgery. DESIGN, SETTING, AND PATIENTS An observational cohort of 102,470 patients undergoing primary isolated CABG surgery with cardiopulmonary bypass during calendar year 2008 at 798 sites in the United States, contributing data to the Society of Thoracic Surgeons Adult Cardiac Surgery Database. MAIN OUTCOME MEASURES Perioperative (intraoperative and postoperative) transfusion of RBCs, fresh-frozen plasma, and platelets. RESULTS At hospitals performing at least 100 on-pump CABG operations (82,446 cases at 408 sites), the rates of blood transfusion ranged from 7.8% to 92.8% for RBCs, 0% to 97.5% for fresh-frozen plasma, and 0.4% to 90.4% for platelets. Multivariable analysis including data from all 798 sites (102,470 cases) revealed that after adjustment for patient-level risk factors, hospital transfusion rates varied by geographic location (P = .007), academic status (P = .03), and hospital volume (P < .001). However, these 3 hospital characteristics combined only explained 11.1% of the variation in hospital risk-adjusted RBC usage. Case mix explained 20.1% of the variation between hospitals in RBC usage. CONCLUSION Wide variability occurred in the rates of transfusion of RBCs and other blood products, independent of case mix, among patients undergoing CABG surgery with cardiopulmonary bypass in US hospitals in an adult cardiac surgical database.

Effects of Red-Cell Storage Duration on Patients Undergoing Cardiac Surgery

BACKGROUND Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

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.

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 ≤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 ≤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.

The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery

Vital healthcare resources are devoted to caring for patients with prolonged hospitalization after routine, moderate-risk surgery. Despite the significant cost,little is known about the overall incidence and pattern of complications in these patients. Four hundred thirty-eight patients undergoing a diverse group of routine, moderate-risk, elective surgical procedures were enrolled into a prospective, blinded, cohort study. Complications were assessed using a postoperative morbidity survey. The main outcome was postoperative complication, defined as either in-hospital death or prolonged postoperative hospitalization (>7 days). The mortality rate was 1.6%. Postoperative complications occurred in 118 patients (27% [95% CI 23-31]). Complications frequently observed in these patients included: gastrointestinal 51% (42-60), pulmonary 25% (17-33), renal 21% (14-28), and infectious 13% (7-19). Most complications were not directly related to the type/site of surgery. indices of tissue trauma (blood loss [P < 0.001], surgical duration [P = 0.001]) and tissue perfusion (arterial base deficit [P = 0.008], gastric pHi [P = 0.02]) were the strongest intraoperative predictors of complications. Despite a low mortality rate, we found that complications after routine, moderate-risk, elective surgery are common and involve multiple organ systems. Our 9-point survey can be used by healthcare providers and payers to characterize postoperative morbidity in their respective settings. Implications: Little is known about the overall incidence and pattern of complications in patients with prolonged hospitalization after routine, elective surgery. We prospectively assessed these complications using a novel postoperative morbidity survey. The postoperative morbidity survey can be used in future clinical outcome trials, as well as in routine hospital-based quality assurance.

Impact of Heart Failure on Patients Undergoing Major Noncardiac Surgery

Background:Changes in the demographics and epidemiology of patients with cardiovascular comorbidities who undergo major noncardiac surgery require an updated assessment of which patients are at greater risk of mortality or readmission. The authors evaluated short-term outcomes among patients with heart failure, coronary artery disease (CAD), or neither who underwent major noncardiac surgery. Methods:Patients were aged 65 and older, had Medicare fee-for-service coverage, and underwent 1 of 13 major noncardiac procedures from 2000 through 2004, excluding patients with end-stage renal disease and patients who did not have at least 1 yr of Medicare fee-for-service eligibility before surgery. Main outcome measures were operative mortality and 30-day all-cause readmission. Results:Of 159,327 procedures, 18% were performed in patients with heart failure and 34% were performed in patients with CAD. Adjusted hazard ratios of mortality and readmission for patients with heart failure, compared with patients with neither heart failure nor CAD, were 1.63 (95% confidence interval, 1.52–1.74) and 1.51 (95% confidence interval, 1.45–1.58), respectively. Adjusted hazard ratios of mortality and readmission for patients with CAD, compared with patients with neither heart failure nor CAD, were 1.08 (95% confidence interval, 1.01–1.16) and 1.16 (95% confidence interval, 1.12–1.20), respectively. These effects were statistically significant. Patients with heart failure were at significantly higher risk for both outcomes compared with patients with CAD. Conclusions:Elderly patients with heart failure who undergo major surgical procedures have substantially higher risks of operative mortality and hospital readmission than other patients, including those with coronary disease, admitted for the same procedures. Improvements in perioperative care are needed for the growing population of patients with heart failure undergoing major noncardiac surgery.

Intraoperative tachycardia and hypertension are independently associated with adverse outcome in noncardiac surgery of long duration.

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 Se- verity 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.

Gentamicin-collagen sponge for infection prophylaxis in colorectal surgery

BACKGROUND Despite the routine use of prophylactic systemic antibiotics, surgical-site infection continues to be associated with significant morbidity and cost after colorectal surgery. The gentamicin-collagen sponge, an implantable topical antibiotic agent, is approved for surgical implantation in 54 countries. Since 1985, more than 1 million patients have been treated with the sponges. METHODS In a phase 3 trial, we randomly assigned 602 patients undergoing open or laparoscopically assisted colorectal surgery at 39 U.S. sites to undergo either the insertion of two gentamicin-collagen sponges above the fascia at the time of surgical closure (the sponge group) or no intervention (the control group). All patients received standard care, including prophylactic systemic antibiotics. The primary end point was surgical-site infection occurring within 60 days after surgery, as adjudicated by a clinical-events classification committee that was unaware of the study-group assignments. RESULTS The incidence of surgical-site infection was higher in the sponge group (90 of 300 patients [30.0%]) than in the control group (63 of 302 patients [20.9%], P=0.01). Superficial surgical-site infection occurred in 20.3% of patients in the sponge group and 13.6% of patients in the control group (P=0.03), and deep surgical-site infection in 8.3% and 6.0% (P=0.26), respectively. Patients in the sponge group were more likely to visit an emergency room or surgeons office owing to a wound-related sign or symptom (19.7%, vs. 11.0% in the control group; P=0.004) and to be rehospitalized for surgical-site infection (7.0% vs. 4.3%, P=0.15). The frequency of adverse events did not differ significantly between the two groups. CONCLUSIONS Our large, multicenter trial shows that the gentamicin-collagen sponge is not effective at preventing surgical-site infection in patients who undergo colorectal surgery; paradoxically, it appears to result in significantly more surgical-site infections. (Funded by Innocoll Technologies; ClinicalTrials.gov number, NCT00600925.)

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 Ringers 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.