Reversal of fibrosis in patients with nonalcoholic steatohepatosis after gastric bypass surgery.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) improves the pathophysiology that contributes to obesity-related nonalcoholic steatohepatitis (NASH). Whether obesity-related fibrosis improves is unclear. We hypothesized that RYGB reverses NASH and fibrosis, and indocyanine green (ICG) clearance provides a sensitive measure for detecting asymptomatic fatty liver disease. METHODS: One hundred six obese adults scheduled for RYGB had preoperative liver function assessed using standard tests and ICG clearance and core liver biopsies obtained during RYGB. Once patients lost 60% of their preoperative weight or weight loss plateaued, liver function was reassessed. Repeat liver biopsies were obtained on patients with NASH at the time of RYGB. RESULTS: RYGB improved steatosis, lobular inflammation, hepatocyte ballooning and fibrosis. Serum albumin, AST, and ALT decreased the most in patients with NASH and NASH plus fibrosis. Twenty seven (26%) patients had normal baseline liver histology and 45 (43%) had NASH or NASH plus fibrosis. Nine of 13 patients with substantial fatty liver had normalized histology after weight loss, while severity of disease in the rest had stabilized or was reduced. Mean ICG clearance in patients with normal/mild fatty liver disease and those with histological fatty livers did not differ significantly. CONCLUSIONS: RYGB surgery reverses NASH and liver fibrosis. Underlying mechanisms that facilitate improvement remain unclear.

Postoperative vision loss after spine surgery: a single-institution case-control comparison.

BACKGROUND: Postoperative vision loss (POVL) after spine surgery is a rare but devastating outcome. We present the first case-control study from a single institution for POVL with the diagnoses of ischemic optic neuropathy or central vision loss after complex spine surgery. METHODS: POVL cases following spine surgeries between December 1995 and December 2010 at the Cleveland Clinic were identified retrospectively using administrative codes. Each instance of POVL was matched to 5 case-control patients based on age, gender, body mass index, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and hematocrit. Duration of anesthesia, fluid volumes, and hemodynamic measurements were then compared between POVL cases and control cases using Wilcoxon rank sum test. RESULTS: Six patients developed POVL. These patients had significantly greater blood loss (P=0.002, Wilcoxon test) and a significantly greater volume of red blood cells transfused (P=0.006) than the control patients. No other intraoperative measures differed significantly after Bonferroni correction for multiple outcomes. CONCLUSION: We found that patients with POVL had significantly greater blood loss and significantly more red blood cell transfusions than their matched controls.

Deceased donor hyperglycemia and liver graft dysfunction.

CONTEXT: Hyperglycemia is common in deceased donors, and provokes numerous adverse events in hepatocytic mitochondria. OBJECTIVE: To determine whether hyperglycemia in deceased donors is associated with graft dysfunction after orthotopic liver transplant. METHODS: Charts on 572 liver transplants performed at the Cleveland Clinic between January 2005 and October 2010 were reviewed. The primary measure was time-weighted averages of donors' glucose measurements. Liver graft dysfunction was defined as (1) primary nonfunction as indicated by death or retransplant or (2) liver graft dysfunction as indicated by an aspartate amino transferase level greater than 2000 U/L or prothrombin time greater than 16 seconds during the first postoperative week. The relationship of interest was estimated by using a multivariable logistic regression. RESULTS: The incidence of graft dysfunction was 25%. No significant relationship was found between the range of donor glucose measurements and liver graft dysfunction after donor characteristics were adjusted for (P= .14, Wald test, adjusted odds ratio [95% CI] for liver graft dysfunction corresponding to a relative doubling in time-weighted average for donor glucose of 1.43 [0.89-2.30]). The results thus do not suggest that strict glucose control in donors is likely to improve graft quality.

Prediction of intraoperative transfusion requirements during orthotopic liver transplantation and the influence on postoperative patient survival.

BACKGROUND: Predicting blood product transfusion requirements during orthotopic liver transplantation (OLT) remains difficult. Our primary aim in this study was to determine which patient variables best predict recipient risk for large blood transfusion requirements during OLT. The secondary aim was to determine whether the amount of blood products transfused during OLT impacted patient survival. METHODS: Eight hundred four primary adult OLTs performed during a 9-year period were retrospectively analyzed, and predictive models were developed for blood product usage, usage >20 and usage >30 units of red blood cells (RBCs) plus cell salvage (CS). For survival analysis, potential predictors included all blood products administered during OLT. RESULTS: For analyses of RBC + CS usage, we used several statistical techniques: regression analysis, logistic regression, and classification and regression tree analysis. Several preoperative factors were highly statistically significant predictors of intraoperative blood product usage in each of the analyses, namely lower platelet count and higher Model for End-Stage Liver Disease Score or one or more of its components (creatinine, total bilirubin, international normalized ratio). Despite these highly significant associations, the models were unable to predict reliably that patients might require the largest amount of blood products during OLT. For example, the classification and regression tree analyses were able to predict only 32% and 11% of patients requiring >20 and >30 units of RBC + CS, respectively. Survival analysis demonstrated poorer survival among patients receiving larger amounts of RBC + CS during OLT. CONCLUSION: Prediction of intraoperative blood product requirements based on preoperatively available variables is unreliable; however, there is a strong measurable association between transfusion and postoperative mortality.

Transfusion of older red blood cells is associated with decreased graft survival after orthotopic liver transplantation.

Investigations have demonstrated conflicting results regarding the influence of the red blood cell (RBC) storage duration on outcomes. We evaluated whether graft failure or mortality after orthotopic liver transplantation (OLT) increased when recipients were transfused with older RBCs. This study included 637 patients who underwent OLT between January 2001 and June 2011. Baseline and perioperative data were obtained from our blood bank, the Unified Transplant Center database, and the United Network for Organ Sharing database. Recipients whose transfused RBCs were all stored for ≤ 15 days were grouped in a younger group, and recipients who were transfused with RBCs stored for >15 days were placed in an older group. The relationship between graft survival/mortality and the age of intraoperatively transfused RBCs was studied by Kaplan-Meier estimation with a log-rank test and multivariate Cox proportional hazards regression. Three hundred thirty-four patients and 303 patients were grouped in the younger and the older RBC groups, respectively, on the basis of the ages of intraoperatively transfused RBCs. Kaplan-Meier estimates of graft survival/mortality as a function of the posttransplant time were significantly different: the older group experienced the outcome sooner than the younger group [P = 0.02 (log-rank test)]. After covariate adjustments, the risk of graft failure/mortality was significantly different at any given time after transplantation between patients receiving intraoperative transfusions of older RBC units and patients receiving intraoperative transfusions of younger RBC units (hazard ratio = 1.65, 95% confidence interval = 1.18-2.31). In conclusion, patients who received intraoperative transfusions of RBCs with longer storage times had an increased risk of adverse outcomes.

An evolution in blood management: past, present, and future.

Blood management is a concept that adopts a principle of improving patient outcome by integrating all available techniques to ensure safety, availability, and appropriate allocation of blood products. This constitutes a model of multidisciplinary care where the changes in culture are system directed on the basis of evidence-based medicine. There are about 14% US hospitals where any kind of blood management program exists, although the idea remains the same but the programs vary in their execution, implementation, and ultimately providing the value to patients. In this article, we have described our experience of creating a patient-centric, cost-effective, evidence-based, and multipronged program creation with scalable results. The use of data, education, process improvement, engagement, and accountability of caregivers have resulted in sustained results and helped in creating a comprehensive blood management program.

Pre-transplant MELD and sodium MELD scores are poor predictors of graft failure and mortality after liver transplantation.

BACKGROUND: Incorporating serum sodium concentrations into the model for end-stage liver disease (MELD) score may increase its sensitivity for identifying priority patients for orthotopic liver transplantation (OLT). We, therefore, evaluated and compared the ability of the sodium MELD and MELD scores to predict graft and patient survival after OLT. METHODS: The United Network for Organ Sharing (UNOS) registry includes all US adult OLTs performed between January 2000 and August 2008. For 15,156 patients who met inclusion criteria, MELD score was calculated; for 6,193 patients whose serum sodium concentrations was between 120 and 135 mEq/dl, immediately before OLT, sodium MELD score was calculated. The corresponding hazard ratios (HR) for MELD and sodium MELD on graft and patient survival were assessed using the Cox proportional hazards regression models. The concordance probability estimate (CPE) was used to evaluate predictive ability of each time-to-event model. RESULTS: MELD and sodium MELD scores were both significant predictors in univariable Cox regression models for graft failure [HR (95% CI) for every 10 units increase in the predictor: 1.10 (1.04, 1.17), P = 0.001, and 1.05 (1.00, 1.10), P = 0.03, respectively], and for mortality (1.14 (1.07, 1.21), P < 0.001, and 1.07 (1.02, 1.12), P = 0.01, respectively), with CPE of 0.52-0.53. CONCLUSION: While MELD and sodium MELD were each significantly associated with survival after OLT, their predictive abilities were poor. The sodium MELD score does not improve prediction accuracy over the MELD score. Weak prediction may result from unaccounted variability in recipient and donor status, as well as surgical and postoperative factors.

Predicting immunosuppressant dosing in the early postoperative period with noninvasive indocyanine green elimination following orthotopic liver transplantation.

Twenty adult patients undergoing orthotopic liver transplantation (OLT) were enrolled in this study, with the noninvasive indocyanine green plasma disappearance rate (ICG-PDR) measured both during and after OLT to assess the relationship between ICG-PDR and the ability of patients to achieve therapeutic postoperative tacrolimus immunosuppressant blood levels. Liver function was determined at both 2 and 18 hours post reperfusion with the ICG-PDR k value (1/min). Postoperative standard serum measures of liver function as well as liver biopsies were also collected and analyzed. The median ICG-PDR k value for the study group at 2 hours post reperfusion was 0.20 (0.16, 0.27), whereas at 18 hours post reperfusion, it was 0.22 (0.18, 0.35). The median change in the k value between the two ICG-PDR measurements was 0.05 (-0.02, 0.07) with P = 0.02. There was an interaction between the postoperative day 1 (18 hours post reperfusion) ICG-PDR k value and the linear increase in the tacrolimus blood level, such that the greater the k value was, the more gradual the observed rise was in tacrolimus over time [that is, the longer it took to achieve a therapeutic blood level (>12 ng/mL), P = 0.003]. Of the 16 patients that received tacrolimus, comparable dosing on a per kilogram body weight basis was observed. Also, no significant association between ICG-PDR k values and postoperative liver biopsy results was seen. This study demonstrates that the ICG-PDR measurement is a modality with the potential to assist in achieving adequate blood levels of tacrolimus following OLT.

Association between donor-recipient serum sodium differences and orthotopic liver transplant graft function.

Previous studies have shown that donor hypernatremia and possibly recipient hyponatremia negatively impact graft function after orthotopic liver transplant (OLT). The purpose of this retrospective investigation was to determine whether measured differences in serum sodium values between cadaveric donors and OLT recipients (DeltaNa(+)) influence immediate postoperative allograft function and short-term patient outcomes. Two hundred and fifty patients that underwent OLT from January 2001 to December 2005 were included in this study. The DeltaNa(+) for each donor recipient pair was correlated with standard postoperative liver function tests as well as recipient length of intensive care unit stay (LOICUS), length of hospital stay (LOHS) and recipient survival. The relationship between donor hypernatremia (serum sodium >or= 155 mEq/mL), recipient hyponatremia (serum sodium level

Six sigma methodology can be used to improve adherence for antibiotic prophylaxis in patients undergoing noncardiac surgery.

BACKGROUND: Six Sigma methodology is a data management process that can be used to achieve a goal of near perfection in process performance. An audit of 615 surgeries over 2 mo revealed only 38% of noncardiac patients admitted on the day of surgery at our institution received perioperative antimicrobial prophylaxis within the target interval of < or =60 min before incision. METHODS: Six Sigma methodology was used to improve our process of timing of antimicrobial prophylaxis administration. A multidisciplinary team was assembled which identified seven process inputs by which patients receive antimicrobial prophylaxis. Interventions for improvement included reinforcement of use of preoperative antibiotic order forms, eliminating administration of antibiotics in the preoperative admission area, and sending appropriate antibiotics and IV tubing with the patient to the operating room. We concurrently developed a control plan to sustain this improvement using a recently deployed electronic anesthesia record keeping system using real-time measurement and reporting capabilities of antimicrobial prophylaxis administration. After defining the new process and undertaking a system-wide educational effort, implementation was begun with data collection and analysis occurring over the next 7 mo. RESULTS: For the 8-mo postintervention interval, there was a significant improvement with 86% of 1716 surgical patients receiving their antibiotic prophylaxis within the specified time frame (P < 0.01). The time interval for antibiotic administration before surgical incision also decreased from a preintervention mean of 88 (CI 56-119 min) to 38 min (CI 25-51 min) (P < 0.01). CONCLUSION: We conclude that Six Sigma methods were used to successfully improve our process for timing of perioperative antibiotic prophylaxis before surgical incision. An electronic anesthesia record keeping system is a useful tool to monitor this process improvement.

Anesthetics and anesthesia techniques: impacts on perioperative management and postoperative outcomes.

Inhaled and intravenous anesthetic agents have diverse effects on the nervous, cardiovascular, and respiratory systems. Spinal and epidural anesthetics also produce significant physiologic changes. Some evidence points to improved immediate postoperative outcomes (in terms of cardiovascular outcomes, blood loss, and venous thromboembolism) for certain types of surgical procedures with epidural and spinal techniques relative to general anesthesia. Evidence is just beginning to emerge, however, on the relation between specific anesthetics and anesthetic techniques and long-term clinical outcomes. A proposed relationship between anesthetics, inflammation, and long-term outcomes has attracted increasing research interest but has yet to be well defined.

Dynamic left ventricular outflow tract obstruction in an orthotopic liver transplant recipient.

A 53 year-old man with Laennec's and hepatitis C-related cirrhosis was found to have dynamic left ventricular outflow tract obstruction during routine evaluation for orthotopic liver transplantation. The outflow tract obstruction gradient was quantified as being 155 to 189 mmHg maximally during dobutamine stress echocardiography. The patient subsequently underwent successful orthotopic liver transplantation at our institution. We discuss here the use of intraoperative transesophageal echocardiography to detect early signs of dynamic outflow tract obstruction and provide a rational guide for fluid and hemodynamic management. We conclude that the measured pressure across the left ventricular outflow tract during dobutamine stress testing does not necessarily predict either intraoperative hemodynamic perturbations such as obstruction or outcome in these patients.

A comparison of postoperative pain control in patients after right lobe donor hepatectomy and major hepatic resection for tumor.

After initiating a living donor liver transplant program at our institution, we observed that donor patients experienced significant postoperative pain despite the use of thoracic patient-controlled epidural analgesia (PCEA) infusion catheters. We retrospectively compared patients who underwent right lobe donor hepatectomy (RLDH, n = 15) with patients who had undergone major hepatic resection for tumor (MHRT, n = 15) to elucidate the cause for this observation. All patients had preoperative thoracic epidural catheters placed, and both groups had similar surgical exposure. Demographic information, intraoperative variables, intensity of postoperative pain by visual analog pain score (VAPS), side effects, total number of requested and delivered PCEA doses, and the total amount of bupivacaine (mg) and volume (mL) of PCEA solution administered through 48 h postoperatively were collected and analyzed. The RLDH group had a significantly longer surgical duration than did the MHRT group. The RLDH group patients had higher postoperative pain scores (P = 0.034), and were 2.76 (1.12-6.82, 95% CI) times more likely to have pain than those patients in the MHRT group. There was no significant difference between patient groups for the amount of bupivacaine and volume of PCEA solution administered. These observations may be explained, in part, by the longer duration of surgery in the RLDH group. The possible role of preemptive analgesia via PCEA infusion and better perioperative teaching of PCEA use are discussed; these may lead to improved early postoperative pain control in RLDH patients.

Spontaneous spinal epidural hematoma in a pregnant patient.

Spontaneous spinal epidural hematoma is a rare occurrence during pregnancy with only five cases described in the literature since 1900. Even in the general population, the frequency of spontaneous spinal epidural hematoma is extremely low and the etiology unclear. Several theories exist for the cause of spontaneous spinal epidural hematoma, however, none has gained uniform acceptance. A case of spontaneous spinal epidural hematoma during pregnancy in a 27-year-old, gravida 2, para 1, female at term with 36 hours duration of both paresthesia and progressive weakness of the lower extremities is presented. In addition, all previous known cases are summarized, including outcome. We hypothesize that the cause of spontaneous spinal epidural hematoma is multifactorial, and pregnancy-induced structural changes in arterial walls and hemodynamic changes may play a role. In addition, we postulate that the origin of the bleeding is arterial, rather then venous. Lastly, the symptoms, diagnosis, and management of spontaneous spinal epidural hematoma during pregnancy are discussed.

Quality and resource utilization in managing preoperative evaluation.

The evaluation of patients before surgery is a component of anesthesia practice that must be performed to ensure the safe delivery of anesthesia for every patient. How an anesthesia group performs this evaluation differs from institution to institution as the structure of preoperative clinics in hospitals across the country can be quite variable. However, the major question that anesthesiologists must ask when approaching this area of practice is: "Can a system for preoperative evaluation that uses the expertise of anesthesiologists,surgeons, and internists to deliver high quality, cost conscious, and efficient patient preparation for surgery be developed.

Leukocyte reduction during orthotopic liver transplantation and postoperative outcome: a pilot study.

STUDY OBJECTIVE: To investigate the effect of intraoperative leukocyte reduction of administered blood products on the incidence of acute cellular rejection and postoperative patient outcome. DESIGN: Prospective, nonrandomized, historical control study. SETTING: Academic tertiary medical center. PATIENTS: The study group (Group 1) consisted of 30 consecutive adult patients with end-stage liver disease scheduled to undergo orthotopic liver transplantation (OLT) between 1998 and 2000. The historical control group (Group 2) consisted of 30 adult patients with end-stage liver disease matched to study group patients as closely as possible for age, gender, and etiology of liver disease who underwent OLT between 1995 and 1999. INTERVENTIONS: Group 1 patients had all intraoperative allogeneic and cell salvaged blood products leukocyte reduced before administration. Group 2 patients underwent OLT without leukocyte filtration of any administered blood products. MEASUREMENTS: Demographic data were collected for both patient groups and included age, gender, etiology of liver disease, and both intraoperative and postoperative immunosuppression. Demographic allograft donor data for both patient groups were collected and included age, gender, use of vasopressors during procurement, and cold and warm donor organ ischemic times. Outcome variables measured included incidence of acute cellular rejection, length of intensive care unit (ICU) and length of hospital stay, incidence of both graft loss and retransplantation, and mortality. MAIN RESULTS: The incidence of acute cellular rejection was 40% in Group 1 and 66.7% in Group 2 (p = 0.037). Length of ICU stay was 3.0 (2.0, 5.0) days in Group 1 and 4.0 (3.0, 6.0) days in Group 2 (p = 0.16). Length of hospital stay was 14.0 (11.0, 18.0) days in Group 1 and 18.0 (14.0, 27.0) days in Group 2 (p = 0.035). One allograft was lost in Group 2 because of primary nonfunction requiring retransplantation (p = 0.31), and three postoperative deaths occurred in Group 1 as a result of multisystem organ failure (p = 0.08). CONCLUSIONS: Coincident with leukocyte reduction of all administered blood products during OLT, an improved outcome was observed in Group 1 patients as demonstrated by both a decreased incidence of acute cellular rejection and length of hospital stay.