Betulinic acid inhibits high-fat diet-induced obesity and improves energy balance by activating AMPK.

BACKGROUND AND AIM: Metabolic syndromes are prevalent worldwide and result in various complications including obesity, cardiovascular disease and type II diabetes. Betulinic acid (BA) is a naturally occurring triterpenoid that has anti-inflammatory properties. We hypothesized that treatment with BA may result in decreased body weight gain, adiposity and hepatic steatosis in a diet-induced mouse model of obesity. METHODS AND RESULTS: Mice fed a high-fat diet and treated with BA showed less weight gain and tissue adiposity without any change in calorie intake. Gene expression profiling of mouse tissues and cell lines revealed that BA treatment increased expression of lipid oxidative genes and decreased that of lipogenesis-related genes. This modulation was mediated by increased AMP-activated protein kinase (AMPK) phosphorylation, which facilitates energy expenditure, lipid oxidation and thermogenic capacity and exerts protective effects against obesity and nonalcoholic fatty liver disease. Overall, BA markedly inhibited the development of obesity and nonalcoholic fatty liver disease in mice fed a high-fat diet, and AMPK activation in various tissues and enhanced thermogenesis are two possible mechanisms underlying the antiobesity and antisteatogenic effects of BA. CONCLUSIONS: The current findings suggest that treatment with BA is a potential dietary strategy for preventing obesity and nonalcoholic fatty liver disease.

Effect of Institutional Case Volume on In-Hospital Mortality After Deceased Donor Liver Transplantation: A Nationwide Retrospective Cohort Study in Korea.

BACKGROUND: There is still controversy as to whether the case volume affects clinical outcomes after liver transplantation. This nationwide retrospective cohort study aimed to investigate the relationship between institutional case volume and post-transplant outcomes after deceased donor liver transplantation. MATERIAL AND METHODS: The data was extracted from the database of Korean National Healthcare Insurance Service. A total of 2648 adult deceased donor liver transplantations were performed at 54 centers in Korea from January 2007 to December 2016. Centers were divided into high-, medium-, and low-volume centers according to the average annual number of deceased donor liver transplantations as follows: < 10, 10-30, and >30. RESULTS: In-hospital mortality rates in high-, medium-, and low-volume centers were 10.3%, 14.3%, and 17.1%, respectively. Multivariable logistic regression analysis revealed that low-volume centers (adjusted odds ratio 1.953; 95% confidence interval, 1.461-2.611; P < .001) and medium-volume centers (adjusted odds ratio 1.480; 95% confidence interval, 1.098-1.994; P = .010) had a significantly higher in-hospital mortality compared to high-volume centers. Long-term mortality rates were also higher in low-volume centers (P = .007). CONCLUSION: Centers with higher volume showed better in-hospital mortality and long-term survival after deceased donor liver transplantation compared to centers with lower volume.

Utility of the laryngeal handshake method for identifying the cricothyroid membrane.

BACKGROUND: The cricothyroid membrane is the most commonly accessed location for invasive surgical airway. Although the laryngeal handshake method is recommended for identifying the cricothyroid membrane, there is no clinical data regarding the utility of the laryngeal handshake method in cricothyroid membrane identification. The objective of this study was to compare the accuracy of cricothyroid membrane identification between the laryngeal handshake method and simple palpation. METHODS: After anaesthesia induction, the otorhinolaryngology resident and anaesthesia resident identified and marked the needle insertion point for cricothyroidotomy using simple palpation and the laryngeal handshake method, respectively. The cricothyroid membrane was confirmed with ultrasonography. Identification was determined successful if the marked point was placed within the longitudinal area of the cricothyroid membrane and within 5 mm from midline transversely. The accuracy of cricothyroid membrane identification using the laryngeal handshake method and simple palpation was compared. RESULTS: A total of 123 patients were enrolled. The cricothyroid membrane was correctly identified in 87 (70.7%, 95% confidence interval 61.8-78.6%) patients using the laryngeal handshake method compared to 78 (63.4%, 95% confidence interval 54.3-71.9%) patients using simple palpation (P = .188). The time required to identify the cricothyroid membrane was longer when using the laryngeal handshake method (15 [3-48] seconds vs 10.9 [3-55] seconds, P = .003). CONCLUSION: The success rate of identifying the cricothyroid membrane was similar among the anesthesiologists who performed the laryngeal handshake method and also among otorhinolaryngologists who used simple palpation.

Assessment of dynamic variables of fluid responsiveness to predict desufflation-induced hypotension during paediatric laparoscopic surgery.

BACKGROUND: During laparoscopic surgery in paediatric patients, sudden hypotension may occur following peritoneal desufflation due to hypovolaemia or an acute increase in gastrointestinal venous capacitance by the release of intra-abdominal pressure. This study examined whether dynamic variables of fluid responsiveness during pneumoperitoneum can predict the occurrence of hypotension following desufflation. METHODS: A total of 120 paediatric subjects were prospectively enrolled. A predictor was derived from the initial 83 subjects and validated thereafter in 37 high-risk subjects. The pleth variability index, respiratory variation in the pulse oximetry plethysmographic waveform (ΔPOP), systolic pressure variation and pulse pressure variation during pneumoperitoneum were obtained 1 min before desufflation. Predictors of desufflation-induced hypotension were investigated using the multivariable logistic regression analysis. Predictability was assessed using the area under the receiver-operating characteristic curve (AUC). RESULTS: In the derivation cohort, 27% (n=23) of subjects developed hypotension. Only ΔPOP was found to be a predictor, and showed high predictability of desufflation-induced hypotension [AUC 0.87, P<0.0001, 95% confidence interval (CI): 0.78-0.93]. A ΔPOP cut-off point of 38% predicted hypotension with a sensitivity of 83% and a specificity of 90%. In the validation cohort, 43% (n=16) of subjects developed hypotension, and ΔPOP was verified to be highly predictive of the occurrence of hypotension (AUC 0.90, P<0.0001, 95% CI: 0.76-0.98). The sensitivity and specificity of a ΔPOP cut-off point of 38% to predict hypotension was 88% and 90%, respectively. CONCLUSIONS: The ΔPOP during pneumoperitoneum is useful in predicting desufflation-induced hypotension during paediatric laparoscopic surgery. CLINICAL TRIAL REGISTRATION: NCT02536521.

A Comparison of the Effects of Sevoflurane and Desflurane on Corrected QT Interval Prolongation in Patients Undergoing Living Donor Liver Transplantation: A Prospective Observational Study.

BACKGROUND: QT interval prolongation has frequently been observed in patients with advanced liver disease. We investigated the influence of inhalation anesthetics on the corrected QT (QTc) interval prolongation during surgery in patients undergoing living-donor liver transplantation. METHODS: Our study included 43 patients who were assigned to 2 groups: sevoflurane (n = 22) or desflurane anesthesia (n = 21). QTc intervals were measured at perioperative determined time points and calculated using Fridericia's formula. RESULTS: Intraoperative QTc intervals increased during the peri-intubation period versus baseline (P = .003) and were prolonged during the peri-reperfusion period (P < .001). However, there was no significant difference in intraoperative QTc interval changes between patients given sevoflurane or desflurane (P = .59). CONCLUSIONS: In this prospective observational study, there was no significant difference in QTc intervals between sevoflurane and desflurane. QTc intervals increased during intubation and reperfusion relative to preoperative values in patients given either sevoflurane or desflurane.

Nafamostat mesilate attenuates Postreperfusion Syndrome during liver transplantation.

Postreperfusion syndrome (PRS), an acute decrease in blood pressure after reperfusion of the liver graft, occurs frequently during liver transplantation surgery. We supposed that the activation of the kallikrein-kinin system leading to extensive systemic vasodilatation was a possible cause. The effect of pretreatment with nafamostat mesilate (NM), a broad spectrum serine protease inhibitor, on the occurrence of PRS was evaluated. Sixty-two adult liver recipients were randomized to receive an intravenous bolus of either 0.02 mg/kg of NM (NM group, n = 31) or an equal volume of normal saline (control group, n = 31) just before reperfusion of the liver graft. Occurrence of PRS and intraoperative use of vasoactive drugs were compared between the two groups. Postoperative recovery was also compared. PRS was significantly less frequent (48% vs. 81%, p = 0.016) requiring less vasopressors in the NM group compared to the control group. The NM group also showed faster recovery of the mean arterial pressure. Perioperative laboratory values were similar between the two groups. Pretreatment with 0.02 mg/kg of NM immediately before reperfusion decreases the frequency of PRS and vasopressor requirements during the reperfusion period in liver transplantation.

Influence of shoulder position on central venous catheter tip location during infraclavicular subclavian approach.

BACKGROUND: Infraclavicular approach of the subclavian veins is commonly used for central venous access. However, aberrant catheter tip locations are frequently quoted for this approach. It was hypothesized that with the shoulder pulled downwards, the angle between the internal jugular and subclavian veins may increase, directing subclavian catheters into the internal jugular vein. This prospective study assessed the influence of the shoulder position on proper placement of right infraclavicular subclavian catheters. METHODS: Patients who required subclavian central venous catheterization for major neurosurgical and thoracic procedures were randomly divided into two groups: neutral (n=180) vs lowered (n=181) shoulder position. The right shoulder was placed and maintained in the neutral or lowered position during venipuncture and guidewire insertion. Postoperative chest radiographs were obtained to identify the location of catheter tips. RESULTS: There were no differences in gender, age, body weight, and height between the two groups. There were five failures in the neutral position [5/180 (2.8%)] and eight failures in the lowered shoulder position [8/181 (4.0%)] (P=NS). The occurrence of immediate complications such as pneumothorax or arterial puncture was not different. Aberrant placement of the catheter tips was more frequent in the lowered shoulder position [2/173 (1.2%) vs 14/173 (8.1%)] (P<0.01). CONCLUSIONS: The neutral shoulder position minimizes the number of needle passes and the incidence of catheter misplacement during the infraclavicular approach of the right subclavian vein catheterization.

Low central venous pressure with milrinone during living donor hepatectomy.

Maintaining a low central venous pressure (CVP) has been frequently used in liver resections to reduce blood loss. However, decreased preload carries potential risks such as hemodynamic instability. We hypothesized that a low CVP with milrinone would provide a better surgical environment and hemodynamic stability during living donor hepatectomy. Thirty-eight healthy adult liver donors were randomized to receive either milrinone (milrinone group, n = 19) or normal saline (control group, n = 19) infusion during liver resection. The surgical field was assessed using a four-point scale. Intraoperative vital signs, blood loss, the use of vasopressors and diuretics and postoperative laboratory data were compared between groups. The milrinone group showed a superior surgical field (p < 0.001) and less blood loss (142 +/- 129 mL vs. 378 +/- 167 mL, p < 0.001). Vital signs were well maintained in both groups but the milrinone group required smaller amounts of vasopressors and less-frequent diuretics to maintain a low CVP. The milrinone group also showed a more rapid recovery pattern after surgery. Milrinone-induced low CVP improves the surgical field with less blood loss during living donor hepatectomy and also has favorable effects on intraoperative hemodynamics and postoperative recovery.

Comparison of the bedside central venous catheter placement techniques: landmark vs electrocardiogram guidance.

BACKGROUND: Electrocardiogram (ECG)-guided central venous catheter (CVC) placement has been reported to be accurate and successful. It has been shown that the CVC tip can be reliably placed at the level of the carina using a simple formula based on the puncture site, the 'brachiocephalic notch' on the clavicle, and the carina as landmarks. This study was performed to compare the accuracy of CVC tip localization between ECG- and landmark-guided catheterization. METHODS: Patients were randomized either to the ECG (n=121) or to the landmark (n=128) group. All catheterizations were performed via the right internal jugular vein (IJV). In the ECG group, CVCs were placed where P-wave returned to a normal configuration on right atrial ECG. In the landmark group, CVCs were placed at a depth derived by adding the distance between insertion point and the notch on the clavicle and the vertical length between the notch and the carina on a routine chest radiograph. On the postoperative portable chest radiograph, incidences of correct CVC tip position, defined as in the superior vena cava, were checked. RESULTS: CVCs were correctly placed in 96.1% of the landmark group (123/128) and in 95.9% of the ECG group (116/121). The mean CVC tip position relative to the carina was 0.0 [95% confidence interval (CI) -0.28 to 0.19] cm in the landmark group and 0.0 (95% CI -0.19 to 0.28) cm in the ECG group. CONCLUSIONS: During central venous catheterization via the right IJV, landmark guidance was comparable with ECG guidance with regard to CVC tip positioning in the superior vena cava.

Effect of recruitment and body positioning on lung volume and oxygenation in acute lung injury model.

The mechanism of oxygenation improvement after recruitment manoeuvres or prone positioning in acute lung injury or acute respiratory distress syndrome is still unclear. We tried to determine the mechanism responsible for the effects of recruitment manoeuvres or prone positioning on lung aeration using a whole lung computed tomography scan in an oleic acid induced acute lung injury canine model. Twelve adult mongrel dogs were allocated into either the supine group (n=6) or the prone group (n=6). After the establishment of acute lung injury, three recruitment manoeuvres were performed at one-hour intervals. Haemodynamic and ventilatory variables, arterial blood gas analyses and CT scans of the whole lung were obtained 90 minutes after oleic acid injection and five minutes before and after each recruitment manoeuvre. Recruitment manoeuvres in the supine position improved oxygenation (P=0.025) that correlated with increase of the poorly- and well-aerated dorsal (dependent) lung volume (r=0.436, P=0.016). Prone positioning increased oxygenation (P=0.004) that also correlated with increase of the poorly- and well-aerated dorsal (nondependent) lung volume (r=0.787, P<0.001). However, the recruitment manoeuvre in the prone position had no effect on oxygenation despite an increase in ventral (dependent) lung volume. The increase in PaO2 after recruitment manoeuvres in the supine position or after prone positioning is related to the increase of the poorly- and well-aerated dorsal lung.

Remifentanil vs. lignocaine for attenuating the haemodynamic response during rapid sequence induction using propofol: double-blind randomised clinical trial.

This study was conducted to determine whether lignocaine or remifentanil effectively attenuate the response to endotracheal intubation during rapid sequence induction. Forty-eight patients were randomly divided into three groups: Group NS (n = 16) received normal saline 0.1 ml/kg, Group L (n = 16) received lignocaine 1.5 mg/kg, and Group R (n = 16) received remifentanil 1 microg/kg. Anaesthesia was induced with propofol 2 mg/kg after glycopyrrolate 0.2 mg IV. Each study drug was given intravenously over 30 seconds after loss of consciousness. Cricoid pressure was applied until intubation. Succinylcholine 1.0 mg/kg was administered to facilitate tracheal intubation. After intubation, the patient's lungs were ventilated with sevoflurane 1% and nitrous oxide 50% in oxygen. Mean arterial pressure and heart rate were recorded before induction, at loss of consciousness, immediately before laryngoscopy and every minute after intubation for 10 minutes. Mean arterial pressure fell following propofol in all groups. The maximum increase in mean arterial pressure in Group NS and Group L were 46% and 38% respectively above the baseline value one minute after intubation, whereas the mean arterial pressure in Group R increased only back to the baseline value. Heart rate in Group NS and Group L were increased by 27% and 33% above baseline value respectively one minute after intubation, while that in Group R was increased only to the baseline value. The results indicate that remifentanil 1 microg/kg, but not lignocaine 1.5 mg/kg, effectively attenuates the haemodynamic response to endotracheal intubation during rapid sequence induction using propofol.

Bedside prediction of the central venous catheter insertion depth.

BACKGROUND: The carina level has been shown to be near the pericardial reflection and can easily be identified as a landmark on a routine chest radiography. The purpose of this study was to reveal a simple method to predict the adequate central venous catheter (CVC) depth, hereby facilitating safe positioning of the CVC tip. METHODS: Central venous catheterization was performed via the right internal jugular vein (IJV) or the right subclavian vein (SCV). The CVC was placed at a depth derived by adding the length between the needle insertion point and the clavicular notch and the vertical length between the clavicular notch and the carina on the chest radiograph. The distance between the CVC tip and the carina was measured on the postoperative chest radiograph. RESULTS: The tip position of 100 CVCs placed via the right IJV was 0.1 (1.1) cm [mean (SD)] below the carina (95% CI: 0.3 cm below carina-0.2 cm above carina) and the tip position of 153 CVCs placed via the right SCV was 0.0 (1.2) cm [mean (SD)] below the carina (95% CI: 0.2 cm below carina-0.2 cm above carina). There were nine outliers (two in IJV group and seven in SCV group). CONCLUSIONS: When CVCs are inserted to a depth derived by adding the length between the needle insertion point and the clavicular notch and the vertical length between the clavicular notch and the carina, the CVC tip can be reliably placed near the carina level.

The coiling length of thoracic epidural catheters: the influence of epidural approach angle.

BACKGROUND: Thoracic epidural catheters are used for anaesthesia and postoperative analgesia. Usually, epidural catheters are placed without confirmation of their position despite frequent reports of complications as a result of malposition. In this study, we evaluated the threading length of thoracic epidural catheters without coiling and assessed the influence of two different epidural approach angles on the threading length without coiling. METHODS: Eighty-three patients scheduled for thoracotomy were enrolled and randomly allocated into the acute angle group and the obtuse angle group. In both groups, skin insertion was performed at the T8-9 intervertebra level. Epidural access was performed under fluoroscopy using a paramedian approach at the T7-8 level in the acute angle group and at the T6-7 level in the obtuse angle group, and an end-hole 19-gauge epidural catheter was inserted. Coiling length, defined as the length of the catheter within the epidural space when any part of the catheter just begins to head caudally, was measured in both groups. RESULTS: The coiling length was 7.4(4.4) cm (95% CI 6.0-8.7 cm) in the obtuse angle group compared with 4.9(3.3) cm (95% CI 3.8-6.0 cm) in the acute angle group (P = 0.005). CONCLUSIONS: Approaching the thoracic epidural space with an obtuse approach angle provides longer coiling length. We recommend that an obtuse approach angle should be used to maximize the chance of the catheter reaching the intended level with minimum risk of coiling.

Intra- and extra-pericardial lengths of the superior vena cava in vivo: implication for the positioning of central venous catheters.

To reduce the possibility of cardiac tamponade, a rare but lethal complication of central venous catheters, the tip of the central venous catheter should be located above the cephalic limit of the pericardial reflection, not only above the superior vena cava-right atrium junction. This study was performed to measure the superior vena cava lengths above and below the pericardial reflection in cardiac surgical patients. Cardiac surgical patients (n = 61; 27 male), whose age [mean +/- SD (range)] was 47 +/- 15 (15-75) years, were studied. The intrapericardial and extrapericardial lengths, and the length of the medial duplicated part were measured separately. The whole vertical lengths of the superior vena cava on either side were calculated respectively by adding the intra-and extrapericardial and medial duplication lengths. The lateral extrapericardial was 29.1 +/- 6.5 (Mean +/- SD) (9-49) mm (range), and lateral extrapericardial length was 32.6 +/- 6.9 (20-53) mm. The medial extrapericardial length was 23.3 +/- 5.0 (11-39) mm, medical duplicated length was 7.2 +/- 3.3 (4-20) mm, and medial intrapericardial was 28.3 +/- 7.0 (20-52) mm. The averaged superior vena cava length of both sides was 60.3 +/- 9.0 (44.5-90) mm. Almost half of the superior vena cava was found to be within the pericardium and half out. This information may be helpful in deciding how far a central venous catheter should be withdrawn beyond the superior vena cava-right atrial junction during right atrial electrocardiographic guided insertion, and in the prediction of optimal central venous catheter insertion depth.

A new technique to determine the size of double-lumen endobronchial tubes by the two perpendicularly measured bronchial diameters.

The cross-section of the mainstem bronchi is not completely round. For preoperative selection of a double-lumen endobronchial tube size, it may be necessary to measure the mediolateral and the anteroposterior bronchial diameters, which can be measured respectively on chest radiograph and computed tomography. With Internal Review Board approval and patients' informed consent, 105 elective thoracic surgical patients who needed left-sided double-lumen tubes were enrolled. Double-lumen tube size was selected depending on the arithmetic mean of the mediolateral and anteroposterior bronchial diameters. Moreover, the outer diameters of the bronchial tube should be smaller than both mediolateral and anteroposterior diameters. The recommended bronchial diameter for each double-lumen tube size was chosen so that the mean of the two bronchial diameters was 0 to 2.0 mm larger than the upper limit of 95% confidence interval of the averaged outer diameter of the bronchial tube of the selected double-lumen tube. In no case was the predicted double-lumen tube size inappropriate. Generally, anteroposterior bronchial diameters appeared to be different from mediolateral diameters (P=0.001). The double-lumen tube size to be selected based on only one bronchial diameter was different from the one selected based on two perpendicularly measured bronchial diameters in 54.3% of patients (57/105). Preoperative selection of the double-lumen tube size based on the anteroposterior, mediolateral and mean bronchial diameters seems to be useful in that this may obviate the need to change an inappropriately sized double-lumen tube and may be helpful in reducing the related complications.