Correlation between plasma fibrinogen and FIBTEM thromboelastometry during liver transplantation: a comprehensive assessment.

BACKGROUND: Thromboelastometry may reduce red blood cell (RBC) transfusion in liver transplantation (LT). Fibrinogen concentration is a primary determinant of FIBTEM maximum clot firmness (MCF), but several factors could affect the correlation between FIBTEM MCF and fibrinogen values. We aimed to investigate (1) the concordance between fibrinogen level and FIBTEM MCF and (2) the association of fibrinogen level and FIBTEM MCF with RBC transfusion during LT. METHODS: A post hoc analysis of data from a randomized, multicentre, double-blind, saline/fibrinogen trial was used (NCT01539057). A total of 86 adult patients were included. RESULTS: The Lin concordance coefficient (LCC) between FIBTEM MCF and fibrinogen levels with the model formula 1·3679 + 0·05414* FIBTEM MCF was poor overall (LLC [95% CI]: 0·387 [0·340 to 0·432]) and moderate for the preperfusion period (LLC [95% CI]: 0·789 [0·747 to 0·824]), but very poor for the postreperfusion period (LLC [95% CI] 0·170 [0·105 to 0·233]). The model assessed for RBC transfusion for FIBTEM MCF showed an area under the curve of 0·788 [0·745-0·832]. Patients with FIBTEM MCF values <8 mm had a significantly higher likelihood of receiving RBC than patients with higher values. (OR [95% CI]: 2·08 [1·30-3·33], P = 0·002). FIBTEM MCF values over 10 mm do not appear to reduce the likelihood of RBC transfusion. CONCLUSION: FIBTEM MCF is not a good indicator of plasma fibrinogen values after graft reperfusion. FIBTEM MCF >8 mm during the LT procedure is associated with less RBC transfusion. FIBTEM MCF values over 10 mm could lead to unnecessary fibrinogen administration.

Impact of Preemptive Fibrinogen Concentrate on Transfusion Requirements in Liver Transplantation: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial.

We hypothesized that preemptive fibrinogen administration to obtain an initial plasma level of 2.9 g/L would reduce transfusion requirements in liver transplantation. A randomized, multicenter, hemoglobin-stratified, double-blind, fibrinogen-versus-saline-controlled trial was conducted. The primary end point was the percentage of patients requiring red blood cells. We evaluated 51 patients allocated to fibrinogen and 48 allocated to saline; the primary end point was assessed using data for 92 patients because the electronic record forms were offline for three patients in the fibrinogen group and four in the saline group. We injected a median of 3.54 g fibrinogen preemptively in the fibrinogen group. Nine patients in the saline group (20.9%) required fibrinogen at graft reperfusion (compared with one patient [2.1%] in the fibrinogen group; p = 0.005). Blood was transfused to 52.9% (95% confidence interval [CI] 42.5-63.3%) in the fibrinogen group and 42.74% (95% CI 28.3-57.2%) in the saline group (p = 0.217). Relative risk for blood transfusion was 0.80 (95% CI 0.57-1.13). Thrombotic events occurred in one patient (2.1%) and five patients (11.4%) in the fibrinogen and saline groups, respectively. Seven patients (14.6%) in the fibrinogen group and nine (20.3%) in the saline group required reoperation. Preemptive administration of fibrinogen concentrate did not influence transfusion requirements.

Modern hydroxyethyl starch and acute kidney injury after cardiac surgery: a prospective multicentre cohort.

BACKGROUND: Recent trials have shown hydroxyethyl starch (HES) solutions increase the risk of acute kidney injury (AKI) in critically ill patients. It is uncertain whether these adverse effects also affect surgical patients. We sought to determine the renal safety of modern tetrastarch (6% HES 130/0.4) use in cardiac surgical patients. METHODS: In this multicentre prospective cohort study, 1058 consecutive patients who underwent cardiac surgery from 15th September 2012 to 15th December 2012 were recruited in 23 Spanish hospitals. RESULTS: We identified 350 patients (33%) administered 6% HES 130/0.4 intraoperatively and postoperatively, and 377 (36%) experienced postoperative AKI (AKI Network criteria). In-hospital death occurred in 45 (4.2%) patients. Patients in the non-HES group had higher Euroscore and more comorbidities including unstable angina, preoperative cardiogenic shock, preoperative intra-aortic balloon pump use, peripheral arterial disease, and pulmonary hypertension. The non-HES group received more intraoperative vasopressors and had longer cardiopulmonary bypass times. After multivariable risk-adjustment, 6% HES 130/0.4 use was not associated with significantly increased risks of AKI (adjusted odds ratio 1.01, 95% CI 0.71-1.46, P=0.91). These results were confirmed by propensity score-matched pairs analyses. CONCLUSIONS: The intraoperative and postoperative use of modern hydroxyethyl starch 6% HES 130/0.4 was not associated with increased risks of AKI and dialysis after cardiac surgery in our multicentre cohort.

Postoperative analgesia with continuous wound infusion of local anaesthesia vs saline: a double-blind randomized, controlled trial in colorectal surgery.

AIM: The aim of this prospective double-blind randomized clinical trial was to determine whether preperitoneal continuous wound infusion (CWI) of the local anaesthetic ropivacaine after either laparotomy or video-assisted laparoscopy for colorectal surgery would reduce patient consumption of morphine. METHOD: Patients scheduled for colorectal surgery randomly received a 48-h preperitoneal CWI of either 0.38% ropivacaine or 0.9% saline at rates of 5 ml/h after laparotomy or 2 ml/h after laparoscopy. The primary end-point was total morphine consumption in surgery and afterwards through a patient-controlled analgesia device. Results in the laparotomy and laparoscopy subgroups were also compared. RESULTS: Sixty-seven patients were included, 33 in the ropivacaine CWI group and 34 in the saline group. Median [interquartile range (IQR)] morphine consumption was lower in the ropivacaine group [23.5 mg (11.25-42.75)] than in the saline group [52 mg (24.5-64)] (P = 0.010). Morphine consumption was also lower in the laparotomy subgroup receiving ropivacaine [21.5 (15.6-34.7)] than in the saline group [52.5 (22.5-65) ml] (P = 0.041). Consumption was statistically similar in laparoscopy patients on ropivacaine or saline. No side effects were observed. Sixteen patients had a surgical wound infection (23.9%); 11 (16.4%) presented wound infection and five (7.5%) organ space infection. Forty-six catheter cultures were obtained; 10 (21.7%) were positive, assessed to be due to contamination. CONCLUSION: Preperitoneal CWI of ropivacaine is a good, safe addition to a multimodal analgesia regimen for colorectal surgery. CWI can reduce morphine consumption without increasing adverse effects.

Incidence and predictors of major perioperative adverse cardiac and cerebrovascular events in non-cardiac surgery.

BACKGROUND: Major adverse cardiac and cerebrovascular events (MACCE) represent the most common cause of serious perioperative morbidity and mortality. Our aim was to identify risk factors for MACCE in a broad surgical population with intermediate-to-high surgery-specific risk and to build and validate a model to predict the risk of MACCE. METHODS: A prospective, multicentre study of patients undergoing surgical procedures under general or regional anaesthesia in 23 hospitals. The main outcome was the occurrence of at least one perioperative MACCE, defined as any of the following complications from admittance to discharge: cardiac death, cerebrovascular death, non-fatal cardiac arrest, acute myocardial infarction, congestive heart failure, new cardiac arrhythmia, angina, or stroke. The MACCE predictive index was based on ß-coefficients and validated in an external data set. RESULTS: Of 3387 patients recruited, 146 (4.3%) developed at least one MACCE. The regression model identified seven independent risk factors for MACCE: history of coronary artery disease, history of chronic congestive heart failure, chronic kidney disease, history of cerebrovascular disease, preoperative abnormal ECG, intraoperative hypotension, and blood transfusion. The area under the receiver-operating characteristic curve was 75.9% (95% confidence interval, 71.2-80.6%). CONCLUSIONS: The risk score based on seven objective and easily assessed factors can accurately predict MACCE occurrence after non-cardiac surgery in a population at intermediate-to-high surgery-specific risk.

[Anesthesia in the patient with impaired liver function]. / Anestesia en el paciente con alteración de la función hepática.

We review information on impaired liver function, focusing on concepts relevant to anesthesia and postoperative recovery. The effects of impaired function are analyzed by systems of the body, with attention to the complications the patient with liver cirrhosis may develop according to type of surgery. Approaches to correcting coagulation disorders in the cirrhotic patient are particularly controversial because an increase in volume may be a factor in bleeding owing to increased portal venous pressure and imbalances in the factors that favor or inhibit coagulation. Perioperative morbidity and mortality correlate closely to Child-Pugh class and the score derived from the model for end-stage liver disease (MELD). Patients in Child class A are at moderate risk and surgery is therefore not contraindicated. Patients in Child class C or with a MELD score over 20, on the other hand, are at high risk and should not undergo elective surgical procedures. Abdominal surgery is generally considered to put patients with impaired liver function at high risk because it causes changes in hepatic blood flow and increases intraoperative bleeding because of high portal venous pressures.

[Multidisciplinary protocol for computed tomography imaging and angiographic embolization of splenic injury due to trauma: assessment of pre-protocol and post-protocol outcomes]. / Protocolo multidisciplinario basado en la tomografía axial computarizada y la arteriografía-embolización para el tratamiento de lesiones traumáticas esplénicas. Valoración pre y postinstauración del protocolo.

OBJECTIVES: To assess conservative treatment of splenic injury due to trauma, following a protocol for computed tomography (CT) and angiographic embolization. To quantify the predictive value of CT for detecting bleeding and need for embolization. MATERIAL AND METHODS: The care protocol developed by the multidisciplinary team consisted of angiography with embolization of lesions revealed by contrast extravasation under CT as well as embolization of grade III-V injuries observed, or grade I-II injuries causing hemodynamic instability and/or need for blood transfusion. We collected data on demographic variables, injury severity score (ISS), angiographic findings, and injuries revealed by CT. Pre-protocol and post-protocol outcomes were compared. The sensitivity and specificity of CT findings were calculated for all patients who required angiographic embolization. RESULTS: Forty-four and 30 angiographies were performed in the pre- and post-protocol periods, respectively. The mean (SD) ISSs in the two periods were 25 (11) and 26 (12), respectively. A total of 24 (54%) embolizations were performed in the pre-protocol period and 28 (98%) after implementation of the protocol. Two and 7 embolizations involved the spleen in the 2 periods, respectively; abdominal laparotomies numbered 32 and 25, respectively, and 10 (31%) vs 4 (16%) splenectomies were performed. The specificity and sensitivity values for contrast extravasation found on CT and followed by embolization were 77.7% and 79.5%. CONCLUSIONS: The implementation of this multidisciplinary protocol using CT imaging and angiographic embolization led to a decrease in the number of splenectomies. The protocol allows us to take a more conservative treatment approach.

[Perioperative mortality: retrospective cross-sectional study of surgical patients who died between 2004 and 2008 in a tertiary care hospital]. / Mortalidad perioperatoria de los pacientes quirúrgicos: estudio transversal retrospectivo de los pacientes fallecidos en el periodo 2004 a 2008 en un hospital terciario.

OBJECTIVE: Retrospective analysis of all surgical, early postoperative, and 1-week to detect risk factors. MATERIAL AND METHODS: A database was established to record clinical, anesthetic, and surgical variables, grouped as preoperative, intraoperative and postoperative factors, and reflecting comorbidities and postoperative complications. Each patient's cause of death was also recorded. Factors influencing mortality during surgery, at 48 hours, and at 1 week were explored by comparing frequencies to detect correlations. RESULTS: From 2004 to 2008, a total of 809 deaths occurred in the 82412 hospitalized surgical patients. Patients who died during surgery or within 48 hours were younger, had a higher ASA physical status classification, had more cardiovascular risk factors, were less likely to have a diagnosis of cancer, and had spent less time in hospital before the operation. Intraoperative complications, particularly bleeding and cardiac events, were more frequent in patients whose condition was more complex and who died during surgery; that pattern was similar but less marked in patients dying within 48 hours. The patients who died within 48 hours had a higher rate of postoperative hemodynamic complications; the patients who died during the week following surgery had higher rates of septic, neurologic, and respiratory complications. CONCLUSIONS: Emergency surgery stands out as an important predictor of death during or after surgery; other significant risk factors are postoperative complications.

[Ultrasound-guided puncture: applications in a chronic pain clinic]. / La punción guiada con ultrasonidos aplicada a una unidad de dolor crónico.

Ultrasonography provides an excellent tool for the real-time visualization of peripheral nerve structures in regional anesthesia. Techniques are enhanced further when the progress of the needle and diffusion of the anesthetic can be observed. In a chronic pain clinic, ultrasound-guided puncture offers the advantages of accurate images of structures where pain arises: muscles, fascias, tendons, periostea, and joint structures. Visualization also helps the anesthetist to keep the needle away from structures (eg, the esophagus, pleura, vessels or peritoneum) that might lie near the target site. Unlike fluoroscopy, which produces radiation that is potentially dangerous for both patient and health care staff, ultrasound imaging is not harmful. Disadvantages are poor quality images of structures at a certain depth, acoustic shadows from bone structures that block the view of underlying tissues, and poor transport of ultrasound waves by air. Our aim is to describe a series of techniques for ultrasound-guided puncture and the results obtained on applying them weekly for 12 months in a chronic pain clinic.

Switches in 6-phosphofructo-2-kinase isoenzyme expression during rat sperm maturation.

Here we analyzed Pfkfb3 and Pfkfb4 gene expression in rat testis development, isolated testicular cells and spermatozoa. Real time RT-PCR analysis during testis development showed the maximum expression of Pfkfb3 in pre-puber samples and of Pfkfb4 in adult samples. Western blot analysis showed that uPFK-2 protein, a product of Pfkfb3 gene, was present in all the cell types forming the seminiferous epithelium (Sertoli, interstitial and spermatogenic cells). In contrast, tPFK-2, a product of Pfkfb4 gene, was restricted to spermatogenic cells. Confocal analyses by indirect immunofluorescence also corroborated this expression pattern. Immunoblotting studies of isolated spermatozoa demonstrated the presence of uPFK-2 only in immature sperm and once spermatozoa became fully functional this isozyme was replaced by the testicular isozyme tPFK-2. Moreover, immunostaining confirmed that tPFK-2 was localized mainly in the acrosomal region of the sperm head and in the mid-piece of the flagellum, where other spermatogenic cell-specific glycolytic enzymes have been found.

[Mortality in patients with multiple injuries: analysis using the trauma and injury severity score in a referral hospital]. / Análisis de la mortalidad en los pacientes politraumatizados según la metodología TRISS en un hospital traumatológico de referencia.

BACKGROUND AND OBJECTIVES: A growing number of patients with multiple injuries are being treated. Injury severity scales can be used to assess outcomes objectively. This study aimed to assess our hospital's cases on the basis of the Trauma and Injury Severity Score (TRISS) and compare outcomes to those reported in the Major Trauma Outcome Study, as well as to determine preventable mortality and analyze causes of death and associated factors. PATIENTS AND METHODS: Data were extracted from the records of patients admitted with multiple injuries in 2005 and were used to calculate the Revised Trauma Score (RTS), the Injury Severity Score (ISS), and the TRISS or probability of survival. Hospital mortality was also calculated. A TRISS between 25 and 50 was considered to indicate a preventable avoidable death; a TRISS over 50 indicated a preventable death. Logistic regression analysis was used to identify factors associated with mortality. RESULTS: We studied the cases of 198 patients with a mean (SD) age of 43.9 (19) years. Ninety-three percent had suffered blunt trauma. The mean ISS, the prehospital RTS, and the TRISS were 16.9 (11.2), 10.8 (2.5), and 0.95 (0.2), respectively. Twenty-five patients died. Fifteen deaths were classified as preventable or potentially preventable. Factors related to exitus were head injury and age (odds ratios, 4.6 and 4.0, respectively). CONCLUSIONS: The rate of preventable death in our hospital was higher than expected. Mortality was strongly associated with head injury and age. The TRISS model can identify preventable deaths objectively.

PFK-2/FBPase-2: maker and breaker of the essential biofactor fructose-2,6-bisphosphate.

Fructose-2,6-bisphosphate is responsible for mediating glucagon-stimulated gluconeogenesis in the liver. This discovery has led to the realization that this compound plays a significant role in directing carbohydrate fluxes in all eukaryotes. Biophysical studies of the enzyme that both synthesizes and degrades this biofactor have yielded insight into its molecular enzymology. Moreover, the metabolic role of fructose-2,6-bisphosphate has great potential in the treatment of diabetes.

Improvement of associated respiratory problems in morbidly obese patients after open Roux-en-Y gastric bypass.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is present in 44% of patients scheduled for bariatric surgery. Respiratory dysfunction associated with this syndrome is attributable to chronic obstructive pulmonary disease (COPD) and/or obesity hypoventilation syndrome (OHS). We studied the long-term effect of bariatric surgery on weight loss, on the respiratory comorbidities associated with obesity, and on the need for non-invasive positive pressure ventilation. METHODS: We followed a sample of patients with respiratory co-morbidity scheduled for open Capella Roux-en-Y gastric bypass (RYGBP) over 5-years. Patients who were positive for polysomnographic studies and required continous positive airway pressure (CPAP) before surgery were included. All patients were subjected to the same anesthetic and surgical protocols. At 1 year after surgery, polysomnographic studies were performed and arterial blood gases and pulmonary function were tested. RESULTS: Of the 209 patients scheduled for bariatric surgery during the study period, 105 had respiratory co-morbidity. Of these, 30 required CPAP-BiPAP treatment before surgery and were included in our study. Surgery took 128 minutes (range 70 to 210 minutes). Tracheal extubation in the operating theater was possible for 26 patients (86.7%). During the early postoperative period, 7 patients (23.3%) presented respiratory complications. Length of hospitalization was 6.87 days (range 4 to 11 days). At 1 year after RYGBP, patients presented significant weight loss and improvement of hypoxemia (from 73.3 +/- 10.6 to 90.5 +/- 11.5, P = 0.000), hypercarbia (from 44.5 +/- 5.7 to 40.6 +/- 4.9, P = 0.005), and in spirometric (P = 0.004) and polysomnographic results (P = 0.001). CPAP-BiPAP treatment after weight loss was necessary in only 14% of patients (P = 0.001). CONCLUSIONS: Weight loss after RYGBP improved arterial blood gases, respiratory tests and polysomnographic studies. CPAP treatment can be withdrawn in most patients.

PFKFB3 gene silencing decreases glycolysis, induces cell-cycle delay and inhibits anchorage-independent growth in HeLa cells.

The high rate of glycolysis despite the presence of oxygen in tumor cells (Warburg effect) suggests an important role for this process in cell division. The glycolytic rate is dependent on the cellular concentration of fructose 2,6-bisphosphate (Fru-2,6-P2), which, in turn, is controlled by the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2). The ubiquitous PFK-2 isoenzyme (uPFK-2, alternatively named UBI2K5 or ACG) coded by the pfkfb3 gene is induced by different stimuli (serum, progesterone, insulin, hypoxia, etc.) and has the highest kinase/phosphatase activity ratio amongst all PFK-2 isoenzymes discovered to date, which is consistent with its role as a powerful activator of glycolysis. uPFK-2 is expressed in brain, placenta, transformed cells and proliferating cells. In the present work, we analyze the impact of small interfering RNA (siRNA)-induced silencing of uPFK-2 on the inhibition of cell proliferation. HeLa cells treated with uPFK-2 siRNA showed a decrease in uPFK-2 RNA levels measured at 24h. uPFK-2 protein levels were severely depleted at 48-72h when compared with cells treated with an unrelated siRNA, correlating with decreased glycolytic activity, Fru-2,6-P2, lactate and ATP concentrations. These metabolic changes led to reduced viability, cell-cycle delay and an increase in the population of apoptotic cells. Moreover, uPFK-2 suppression inhibited anchorage-independent growth. The results obtained highlight the importance of uPFK-2 on the regulation of glycolysis, on cell viability and proliferation and also on anchorage-independent growth. These data underscore the potential for uPFK-2 as an effective tumor therapeutic target.