Relationship of epidural patient-controlled analgesia with postoperative bleeding after unilateral total knee arthroplasty: a propensity score-matching analysis.

Although epidural patient-controlled analgesia (PCA) to control postoperative pain after total knee arthroplasty (TKA), the relationship of epidural PCA with postoperative bleeding remains controversial. Therefore, we aimed to evaluate the effect of epidural and intravenous PCA on postoperative bleeding in patients undergoing unilateral TKA. Total of 2467 patients who underwent TKA were divided to intravenous PCA (n = 2339) or epidural PCA (n = 128) group. After 1:1 propensity score-matching, 212 patients were analyzed to assess the associations between the perioperative blood loss and epidural PCA between the groups. Mean postoperative blood loss was significantly greater in epidural PCA than in intravenous PCA (900.9 ± 369.1 mL vs. 737.8 ± 410.1 mL; P = 0.007). The incidence of red blood cell (RBC) administration (> 3 units) was significantly higher in epidural PCA than in intravenous PCA (30.2% vs. 16.0%; OR 2.5; 95% CI 1.201-5.205; P = 0.014). Epidural PCA may be strongly related to postoperative bleeding and the incidence of RBC transfusion of more than 3 units after unilateral TKA, as compared to intravenous PCA. Therefore, the use of epidural PCA may be carefully considered for postoperative pain management in TKA.

The role of age in determining the effects of lipo-PGE1 infusion on immediate arterial maximal flow velocity in patients with diabetes undergoing free flap surgery for lower extremity reconstruction: A prospective observational study.

BACKGROUND: Diabetes mellitus may have a negative effect on free flap perfusion in patients undergoing reconstructive surgery. Little is known of the effects of lipo-prostaglandin E1 (lipo-PGE1) on flap blood flow in diabetes. This study investigated the effects of lipo-PGE1 on maximal blood flow velocity of the free flap arterial pedicle in patients with diabetes. METHODS: This prospective observational study assessed maximal blood flow velocity in the arterial pedicle before and 30 min after infusion of 0.4 µg/h lipo-PGE1 in 40 patients with diabetes who received a free flap for lower extremity reconstruction. Multivariate logistic regression analysis was performed to determine whether age, hemoglobin A1c concentration, duration of diabetes, and flap type were significantly associated with increased maximal blood flow velocity after lipo-PGE1 infusion or not. RESULTS: The maximal blood flow velocity of the free flap did not differ significantly before and 30 min after lipo-PGE1 infusion. Multivariate logistic regression analysis showed that age <65 years was the only independent factor associated with increased maximal blood flow velocity after lipo-PGE1 infusion (odds ratio = 5.344; p = 0.022). CONCLUSION: Assessments of all patients with diabetes undergoing free flap surgery, when age was not taken into consideration, found that lipo-PGE1 did not significantly increase the maximal blood flow velocity of the free flap arterial pedicle. However, when age was taken into consideration, lipo-PGE1 increased blood flow velocity in patients <65 years old, suggesting that age influences the effect of lipo-PGE1 on the blood flow velocity.

Effect of Prone Positional Apparatus on the Occurrence of Acute Kidney Injury After Spine Surgery.

BACKGROUND AND OBJECTIVE: Increased intra-abdominal pressure with prone positioning for spinal surgery is associated with intraoperative hemodynamic alterations and the potential for postoperative complications. This study investigated the incidence of postoperative acute kidney injury (AKI) in patients undergoing spine surgery on a Jackson spinal table or a Wilson frame. METHODS: A total of 1374 patients who underwent spine surgery were divided into 2 groups: Jackson spinal table (n = 598) and Wilson frame group (n = 776). After 1:1 propensity score matching, a final analysis was performed on 970 patients. The primary endpoint was a comparison of the incidence of AKI in the 2 groups. RESULTS: After propensity score matching analysis, the mean ± standard deviations of spine surgery invasiveness index were 4.7 ± 3.5 and 2.1 ± 1.4 in patients with the Jackson spinal table and the Wilson frame, respectively (P < 0.001). Considering the differences in surgical invasiveness, operative time, estimated blood loss, and administration of packed red blood cells were higher in the Jackson spinal table group than in the Wilson frame group (P < 0.001). However, the incidence of AKI was less with the Jackson spinal table than with the Wilson frame (1.7% vs. 3.7%, 2.25 [0.978-5.175], P = 0.056), not reaching statistical significance. CONCLUSION: This analysis showed that postoperative AKI in patients undergoing spine surgery in the prone position was not different with the Wilson frame than in the Jackson spinal table despite higher surgical severity, longer operative times, and more blood loss in the latter group. In spine surgery, the appropriate selection of prone positioning apparatus can potentially be an important consideration in reducing the risk of AKI.

Lipo-prostaglandin E1 increases immediate arterial maximal flow velocity of free flap in patients undergoing reconstructive surgery.

BACKGROUND: In free flap surgery, the maintenance of proper blood flow after anastomosis of flap pedicle vessels is important. Lipo-prostaglandin E1 (lipo-PGE1) has been empirically administered to prevent blood flow insufficiency in a free flap reconstruction. We tested our hypothesis that lipo-PGE1 administration increases the arterial inflow of free flap. We also evaluated lipo-PGE1-related haemodynamic changes and complications. METHODS: Thirty-seven patients who underwent free flap reconstruction were analysed. Lipo-PGE1 was administered 10 minutes after the vascular anastomosis of the free flap. The maximal blood flow velocity was measured at the free flap pedicle artery before and 30 minutes after lipo-PGE1 administration using duplex ultrasonography. The primary outcome was the difference in the maximal blood flow velocity before and 30 minutes after lipo-PGE1 administration. The arterial blood pressure, heart rate, cardiac output, stroke volume variation, and pulse pressure variation were measured simultaneously. Lipo-PGE1-related complications such as hypotension, bradycardia, hypothermia, facial flushing, diarrhoea, apnoea, and seizure were also investigated. RESULTS: The maximal blood flow velocity was significantly increased at 30 minutes after lipo-PGE1 administration compared to the level before lipo-PGE1 administration (mean (standard deviation): 26.3 (8.7) cm/s vs 22.5 (8.0) cm/s, P = 0.002). The haemodynamic variables were not significantly different before and 30 minutes after lipo-PGE1 administration. No lipo-PGE1-related complications occurred. CONCLUSIONS: Lipo-PGE1 significantly increases the maximal blood flow velocity without complications in patients undergoing free flap reconstruction and may be an effective and safe method of maintaining adequate blood flow in these cases.

Comparison of postoperative pain between laparoscopic and robot-assisted partial nephrectomies for renal tumors: A propensity score matching analysis.

Robot-assisted partial nephrectomy (RAPN) has emerged as an alternative to laparoscopic partial nephrectomy (LPN) for removal of renal tumors. Several advantages of robotic surgery have been reported, but there is no comparative study on postoperative pain between the 2 techniques. Therefore, we compared the postoperative numerical rating scale (NRS) of pain intensity between patients who underwent LPN and those who underwent RAPN.We included 705 patients who underwent either LPN (n = 200) or RAPN (n = 505) for renal tumors between January 2000 and September 2016. After 1:1 propensity score matching, the final analysis included 142 patients each in the LPN and RAPN groups. The primary endpoint was postoperative NRS of pain intensity. The secondary endpoints were opioid requirement, opioid-related complications, and duration of hospital stay.Preoperative and intraoperative values of propensity score matched patients (n = 284) were not significantly different between the LPN and RAPN groups. There was no significant difference in NRS of pain intensity between the 2 groups. Opioid requirement was different between the 2 groups on postoperative day (POD) 0 (12.4 vs 11.3 mg of morphine-equivalent dose), but not from POD 1 to POD 4. The incidence of opioid-related complications and duration of hospital stay were not significantly different between the 2 groups.Postoperative pain was not significantly different between patients who underwent RAPN and those who underwent LPN. This result provides a potentially useful knowledge of postoperative pain characteristics in RAPN and LPN.

Comparison of false-negative/positive results of intraoperative evoked potential monitoring between no and partial neuromuscular blockade in patients receiving propofol/remifentanil-based anesthesia during cerebral aneurysm clipping surgery: A retrospective analysis of 685 patients.

Although the elicited responses of motor evoked potential (MEP) monitoring are very sensitive to suppression by anesthetic agents and muscle relaxants, the use of neuromuscular blockade (NMB) during MEP monitoring is still controversial because of serious safety concerns and diagnostic accuracy. Here, we evaluated the incidence of unacceptable movement and compared false-negative MEP results between no and partial NMB during cerebral aneurysm clipping surgery. We reviewed patient medical records for demographic data, anesthesia regimen, neurophysiology event logs, MEP results, and clinical outcomes. Patients were divided into 2 groups according to the intraoperative use of NMB: no NMB group (n = 276) and partial NMB group (n = 409). We compared the diagnostic accuracy of MEP results to predict postoperative outcomes between both groups. Additionally, we evaluated unwanted patient movement during MEP monitoring in both groups. Of the 685 patients, 622 (90.8%) manifested no intraoperative changes in MEP and no postoperative motor deficits. Twenty patients showed postoperative neurologic deficits despite preserved intraoperative MEP. False-positive MEP results were 3.6% in the no NMB group and 3.9% in the partial NMB group (P = 1.00). False-negative MEP results were 1.1% in the no NMB group and 4.2% in the partial NMB group (P = 0.02). No spontaneous movement or spontaneous respiration was observed in either group. Propofol/remifentanil-based anesthesia without NMB decreases the stimulation intensity of MEPs, which may reduce the false-negative ratio of MEP monitoring during cerebral aneurysm surgery. Our anesthetic protocol enabled reliable intraoperative MEP recording and patient immobilization during cerebral aneurysm clipping surgery.

Comparison of the Efficacy and Safety of a Pharmacokinetic Model-Based Dosing Scheme Versus a Conventional Fentanyl Dosing Regimen For Patient-Controlled Analgesia Immediately Following Robot-Assisted Laparoscopic Prostatectomy: A Randomized Clinical Trial.

Conventional, intravenous, patient-controlled analgesia, which is only administered by demand bolus without basal continuous infusion, is closely associated with inappropriate analgesia. Pharmacokinetic model-based dosing schemes can quantitatively describe the time course of drug effects and achieve optimal drug therapy. We compared the efficacy and safety of a conventional dosing regimen for intravenous patient-controlled analgesia that was administered by demand bolus without basal continuous infusion (group A) versus a pharmacokinetic model-based dosing scheme performed by decreasing the dosage of basal continuous infusion according to the model-based simulation used to achieve a targeted concentration (group B) following robot-assisted laparoscopic prostatectomy.In total, 70 patients were analyzed: 34 patients in group A and 36 patients in group B. The postoperative opioid requirements, pain scores assessed by the visual analog scale, and adverse events (eg, nausea, vomiting, pruritis, respiratory depression, desaturation, sedation, confusion, and urinary retention) were compared on admission to the postanesthesia care unit and at 0.5, 1, 4, 24, and 48 h after surgery between the 2 groups. All patients were kept for close observation in the postanesthesia care unit for 1 h, and then transferred to the general ward.The fentanyl requirements in the postanesthesia care unit for groups A and B were 110.0 ±â€Š46.4 µg and 77.5 ±â€Š35.3 µg, respectively. The pain scores assessed by visual analog scale at 0.5, 1, 4, and 24 h after surgery in group B were significantly lower than in group A (all P < 0.05). There were no differences in the adverse events between the 2 groups.We found that the pharmacokinetic model-based dosing scheme resulted in lower opioid requirements, lower pain scores, and no significant adverse events in the postanesthesia care unit following robot-assisted laparoscopic prostatectomy in comparison with conventional dosing regimen.

Dynamic Arterial Elastance in Predicting Arterial Pressure Increase After Fluid Challenge During Robot-Assisted Laparoscopic Prostatectomy: A Prospective Observational Study.

During robot-assisted laparoscopic prostatectomy, specific physiological conditions such as carbon dioxide insufflation and the steep Trendelenburg position can alter the cardiac workload and cerebral hemodynamics. Inadequate arterial blood pressure is associated with hypoperfusion, organ damage, and poor outcomes. Dynamic arterial elastance (Ea) has been proposed to be a useful index of fluid management in hypotensive patients. We therefore evaluated whether dynamic Ea can predict a mean arterial pressure (MAP) increase ≥ 15% after fluid challenge during pneumoperitoneum and the steep Trendelenburg position.We enrolled 39 patients receiving robot-assisted laparoscopic prostatectomy. Fluid challenge was performed with 500 mL colloids in the presence of preload-dependent conditions and arterial hypotension. Patients were classified as arterial pressure responders or arterial pressure nonresponders according to whether they showed an MAP increase ≥15% after fluid challenge. Dynamic Ea was defined as the ratio between the pulse pressure variation and stroke volume variation. Receiver operating characteristic curve analysis was performed to assess the arterial pressure responsiveness after fluid challenge during robot-assisted laparoscopic prostatectomy.Of the 39 patients, 17 were arterial pressure responders and 22 were arterial pressure nonresponders. The mean dynamic Ea before fluid challenge was significantly higher in arterial pressure responders than in arterial pressure nonresponders (0.79 vs 0.61, P < 0.001). In receiver operating characteristic curve analysis, dynamic Ea showed an area under the curve of 0.810. The optimal cut-off value of dynamic Ea for predicting an MAP increase of ≥ 15% after fluid challenge was 0.74.Dynamic Ea can predict an MAP increase ≥ 15% after fluid challenge during robot-assisted laparoscopic prostatectomy. This result suggests that evaluation of arterial pressure responsiveness using dynamic Ea helps to maintain an adequate arterial blood pressure and to improve perioperative outcomes in preload-dependent patients receiving robot-assisted laparoscopic prostatectomy under pneumoperitoneum and in the steep Trendelenburg position.

Impact of CYP2D6, CYP3A5, CYP2C19, CYP2A6, SLCO1B1, ABCB1, and ABCG2 gene polymorphisms on the pharmacokinetics of simvastatin and simvastatin acid.

OBJECTIVE: The effects of various polymorphisms in cytochrome P450 (CYP) enzyme and transporter genes on the pharmacokinetics (PK) of simvastatin were evaluated in healthy Korean men. METHODS: Plasma concentration data for simvastatin and simvastatin acid were pooled from four phase I studies comprising 133 participants. The polymorphisms CYP2D6*4, CYP2D6*5, CYP2D6*14, CYP2D6*41, CYP3A5*3, CYP2C19*2, CYP2C19*3, CYP2A6*7, and CYP2A6*9; SLCO1B1 rs4149056, rs2306283, and rs4149015; ABCB1 rs1128503, rs2032582, and rs1045642; and ABCG2 rs2231142 were evaluated in each participant. Noncompartmental PK results were compared by genotype. RESULTS: CYP2D6*5 and CYP2D6*14 were found to be associated with a higher area under the curve (AUC) for simvastatin, whereas the AUC of simvastatin acid was significantly increased in patients with the SLCO1B1 rs4149056, ABCG2 rs2231142, and CYP2D6*41 allele variants. Patients with the CYP2D6*41 variant showed a higher peak serum concentration (Cmax) of both simvastatin and simvastatin acid. The SLCO1B1 rs4149056 and rs4149015 polymorphisms were associated with an increased AUC ratio (i.e. ratio of simvastatin acid to simvastatin), whereas the SLCO1B1 rs4149056 and CYP2D6*5 variants were related to a higher Cmax ratio. CONCLUSION: The CYP2D6*5, CYP2D6*14, CYP2D6*41, CYP3A5*3, SLCO1B1 rs4149056 and rs4149015, and ABCG2 rs2231142 genetic polymorphisms are associated with the PK of both simvastatin and simvastatin acid. This could potentially be used as a basis for individualized simvastatin therapy by predicting the clinical outcomes of this treatment.

Correlation between changes in thyromental distance and distance of migration of oral Ring-Adair-Elwyn tubes during neck extension with a shoulder positioner in patients undergoing neck procedures.

OBJECTIVES: To measure the migration of oral Ring-Adair-Elwyn (RAE) preformed tracheal tubes during neck extension compared with the neutral neck position, and to assess the correlation between changes in the thyromental distance (TMD) during changes in neck position and tracheal tube migration. METHODS: This prospective observational study enrolled adult patients undergoing elective neck or thyroid procedures below the mandible. Using fibreoptic bronchoscopy, distances from the RAE tube adapter to the carina and to the tube tip were measured in the neutral position and after neck extension with a 10 cm D-shaped gel shoulder positioner. The change in distance of the RAE tube tip migration was compared with the change in TMD in each patient. RESULTS: This study enrolled 106 patients. During neck extension with a 10-cm shoulder positioner, RAE tubes cranially migrated 2.7 cm from the neutral position, but RAE tube migration was not correlated with the change in external TMD. CONCLUSION: Oral RAE tube migration was not significantly correlated with the change in external TMD. Due to their large variability, changes in TMD were not useful predictors of RAE tube migration.

The pharmacokinetics of letrozole: association with key body mass metrics.

PURPOSE: To characterize the pharmacokinetics (PK) of letrozole by noncompartmental and mixed effect modeling analysis with the exploration of effect of body compositions on the PK. METHODS: The PK data of 52 normal healthy male subjects with intensive PK sampling from two separate studies were included in this analysis. Subjects were given a single oral administration of 2.5 mg letrozole (Femara®), an antiestrogenic aromatase inhibitor used to treat breast cancer. Letrozole concentrations were measured using validated high-performance liquid chromatography with tandem mass spectrometry. PK analysis was performed using NONMEM® 7.2 with first-order conditional estimation with interaction method. The association of body composition (body mass index, soft lean mass, fat free mass, body fat mass), CYP2A6 genotype (*1/*1, *1/*4), and CYP3A5 genotype (*1/*1, *1/*3, *3/*3) with the PK of letrozole were tested. RESULTS: A two-compartment model with mixed first and zero order absorption and first order elimination best described the letrozole concentration-time profile. Body weight and body fat mass were significant covariates for central volume of distribution and peripheral volume of distribution (Vp), respectively. In another model built using more readily available body composition measures, body mass index was also a significant covariate of Vp. However, no significant association was shown between CYP2A6 and CYP3A5 genetic polymorphism and the PK of letrozole in this study. CONCLUSION: Our results indicate that body weight, body fat mass, body mass index are associated with the volume of distribution of letrozole. This study provides an initial step toward the development of individualized letrozole therapy based on body composition.

Pharmacokinetic comparison of 2 formulations of anastrozole (1 mg) in healthy Korean male volunteers: a randomized, single-dose, 2-period, 2-sequence, crossover study.

BACKGROUND: Anastrozole is an aromatase inhibitor used to treat advanced breast cancer in postmenopausal women. A generic 1-mg tablet of anastrozole was recently developed. OBJECTIVE: The study was designed to provide data to submit to Korean regulatory authorities to allow marketing of the test formulation. We evaluated the comparative bioavailability and tolerability of the test and reference formulations in healthy male adult volunteers. METHODS: This single-dose, randomized, double-blind, 2-way crossover trial was conducted in the Clinical Trial Center at the Asan Medical Center (Seoul, Korea). A total of 24 healthy male Korean volunteers were enrolled. Subjects were randomized to receive 1 mg of the test or reference formulation, and pharmacokinetic (PK) parameters were measured. After a 3-week washout period, the other formulation was administered, and PK parameters were measured again. C(max) and AUC(last) were determined from blood samples obtained at 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 216 hours after drug administration. The formulations were considered bioequivalent if the 90% CIs of the geometric mean ratios of test-to-reference formulations for AUC(last) and C(max) were within the bioequivalence limits of 0.8 to 1.25. Nonlinear mixed-effect modeling and Monte Carlo simulations for both formulations were also conducted, and the results were used to characterize and compare the PK properties. Safety profile and tolerability were assessed using measurements of vital signs, clinical chemistry tests, and interviews. RESULTS: All enrolled subjects completed the study. A total of 8 adverse events (AEs) were reported (2 on test formulation, 6 on reference formulation) in 7 of 24 participants. These AEs were headache (n = 1), hordeolum (n = 1), and abnormal laboratory test values (n = 6). Both formulations were well tolerated, and there were no serious AEs. Both formulations were best described by a 2-compartment disposition model with lag phase. The 90% CIs of the geometric mean ratios of test formulation to reference formulation were 0.96 to 1.08 for C(max) and 0.93 to 1.0 for AUC(last). CONCLUSION: The test and reference formulations had similar PK parameters and similar plasma concentration-time profiles. The test formulation of anastrozole met the Korean regulatory criteria (AUC and C(max)) for assuming bioequivalence. ClinicalTrials.gov identifier: NCT01105299.