The effect of unilateral chest drainage for transpulmonary pressure during mechanical ventilation.

INTRODUCTION: Chest tube drainage is usually performed through an underwater seal at a level of 10-20 cmH2O. Based on the definition of transpulmonary pressure, continuous chest drainage creates continuous negative pressure, decreasing pleural surface pressure and increasing transpulmonary pressure. We investigated how unilateral chest drainage could affect the tidal volume or driving pressure during mandatory mechanical ventilation. METHODS: This study was an experimental study using a lung-thoracic model and anesthesia ventilator. Tidal volume was set to 300 mL with pressure-controlled ventilation or volume-controlled ventilation. Left tidal volume and right tidal volume were measured independently using respirometers with positive end-expiratory pressure (PEEP) levels of 0, 10, and 20 cmH2O. Simultaneously, left negative pressure of the chest drainage was changed to 0, 10, and 20 cmH2O. RESULTS: In all conditions, a tidal volume of 300 mL was achieved. In both pressure-controlled ventilation and volume-controlled ventilation, the left tidal volume increased with the application of chest drainage at 10 cmH2O when the PEEP level was 0 cmH2O, but left tidal volume decreased with the application of chest drainage at 20 cmH2O. Furthermore, when PEEP was 10 cmH2O, the left tidal volume decreased in proportion to the pressure of thoracic drainage. The right tidal volumes changed inversely with their counterpart left tidal volumes. CONCLUSION: Unilateral chest drainage caused unbalanced ventilation of the left and right lungs regardless of pressure-controlled ventilation or volume-controlled ventilation.

Opening of Intermediate Conductance Ca2+-Activated K+ Channels in C2C12 Skeletal Muscle Cells Increases the Myotube Diameter via the Akt/Mammalian Target of Rapamycin Pathway.

The activation of potassium channels and the ensuing hyperpolarization in skeletal myoblasts are essential for myogenic differentiation. However, the effects of K+ channel opening in myoblasts on skeletal muscle mass are unclear. Our previous study revealed that pharmacological activation of intermediate conductance Ca2+-activated K+ channels (IKCa channels) increases myotube formation. In this study, we investigated the effects of 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DCEBIO), a Ca2+-activated K+ channel opener, on the mass of skeletal muscle. Application of DCEBIO to C2C12 cells during myogenesis increased the diameter of C2C12 myotubes in a concentration-dependent manner. This DCEBIO-induced hypertrophy was abolished by gene silencing of IKCa channels. However, it was resistant to 1 µM but sensitive to 10 µM TRAM-34, a specific IKCa channel blocker. Furthermore, DCEBIO reduced the mitochondrial membrane potential by opening IKCa channels. Therefore, DCEBIO should increase myotube mass by opening of IKCa channels distributed in mitochondria. Pharmacological studies revealed that mitochondrial reactive oxygen species (mitoROS), Akt, and mammalian target of rapamycin (mTOR) are involved in DCEBIO-induced myotube hypertrophy. An additional study demonstrated that DCEBIO-induced muscle hypertrophic effects are only observed when applied in the early stage of myogenic differentiation. In an in vitro myotube inflammatory atrophy experiment, DCEBIO attenuated the reduction of myotube diameter induced by endotoxin. Thus, we concluded that DCEBIO increases muscle mass by activating the IKCa channel/mitoROS/Akt/mTOR pathway. Our study suggests the potential of DCEBIO in the treatment of muscle wasting diseases. SIGNIFICANCE STATEMENT: Our study shows that 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DCEBIO), a small molecule opener of Ca2+-activated K+ channel, increased muscle diameter via the mitochondrial reactive oxygen species/Akt/mammalian target of rapamycin pathway. And DCEBIO overwhelms C2C12 myotube atrophy induced by endotoxin challenge. Our report should inform novel role of K+ channel in muscle development and novel usage of K+ channel opener such as for the treatment of muscle wasting diseases.

Correction to: Evaluation of pharmacokinetic models of intravenous dexmedetomidine in sedated patients under spinal anesthesia.

Inadvertently, the reference [8] was published incorrectly in the original publication of the article. The correct reference [8] is provided below.

Usefulness of oxygen reserve index (ORi™), a new parameter of oxygenation reserve potential, for rapid sequence induction of general anesthesia.

The oxygen reserve index (ORi™) is a new parameter for monitoring oxygen reserve noninvasively. The aim of this study was to examine the usefulness of ORi for rapid sequence induction (RSI). Twenty adult patients who were scheduled for surgical procedures under general anesthesia were enrolled. After attaching a sensor capable of measuring ORi, oxygen (6 L/min) and fentanyl (2 µg/kg) were administered. After 3 min, propofol 2 mg/kg and rocuronium 1 mg/kg were administered without ventilation. Regardless of changes in ORi, tracheal intubation was performed either 2 min after administration of propofol or when percutaneous oxygen saturation (SpO2) reached 98%. Ventilation was then provided with oxygen at 6 L/min, and trends in ORi and SpO2 during RSI were observed. Data from 16 of the 20 patients were analyzed. Before oxygen administration, the median SpO2 was 98% [interquartile range (IQR) 97-98] and ORi was 0.00 in all patients. At 3 min after starting oxygen administration, the median SpO2 was 100% (IQR 100-100) and the median ORi was 0.50 (IQR 0.42-0.57). There was an SpO2 decline of 1% or more from the peak value after propofol administration in 13 patients, and 32.5 s (IQR 18.8-51.3) before the SpO2 decrease, ORi began to decline in 10 of the 13 (77%) patients. The ORi trends enable us to predict oxygenation reduction approximately 30 s before SpO2 starts to decline. By monitoring ORi, the incidence related to hypoxemia during RSI could be reduced.

Effects of indigo carmine intravenous injection on oxygen reserve index (ORi™) measurement.

To retrospectively investigate the effects of indigo carmine intravenous injection on oxygen reserve index (ORi™) in 20 patients who underwent elective gynecologic surgery under general anesthesia. The study subjects were patients who underwent elective gynecologic surgery under general anesthesia between April 2016 and January 2017, and were administered a 5-ml intravenous injection of 0.4% indigo carmine for clinical purposes during surgery with ORi monitoring. Changes in ORi within 20 min after indigo carmine injection were observed. A relevant decrease in ORi was defined as ≥ 10% reduction in ORi from pre-injection level. ORi rapidly decreased after indigo carmine intravenous injection in all patients. In 10 of 19 patients, ORi decreased to 0 after indigo carmine injection. The median lowest value of ORi was 0 (range 0-0.16) and the median time to reach the lowest value of ORi was 2 min (range 1-4 min) after injection. ORi values returned to pre-injection levels within 20 min in 13 of 19 patients, and the median time to return to pre-injection levels was 10 min (range 6-16 min) after injection. During ORi monitoring it is necessary to consider the rapid reduction in ORi after intravenous injection of indigo carmine.

Evaluation of pharmacokinetic models of intravenous dexmedetomidine in sedated patients under spinal anesthesia.

PURPOSE: Little information is available on the predictive ability of previously published pharmacokinetic models of dexmedetomidine in patients under spinal anesthesia. We evaluated nine published pharmacokinetic models that were constructed in different study settings. METHODS: Sixteen patients received dexmedetomidine infusions after spinal anesthesia according to the manufacturer's recommended regimen (6 µg/kg/h over 10 min followed by 0.2-0.7 µg/kg/h) or target-controlled infusion (initial target of 1.5 ng/ml using the Dyck model). Dexmedetomidine concentrations were measured and median performance error (MDPE), median absolute performance error (MDAPE), and wobble were calculated. RESULTS: A total of 84 blood samples were analyzed. The pharmacokinetic model reported by Hannivoort et al. had the greatest ability to predict dexmedetomidine concentrations (MDPE 5.6%, MDAPE 18.1%, and wobble 6.2%). CONCLUSIONS: Hannivoort et al.'s pharmacokinetic model, constructed with a dataset obtained from healthy volunteers, can predict dexmedetomidine concentrations best during continuous infusion under spinal anesthesia.

Population pharmacokinetics of intravenous acetaminophen in Japanese patients undergoing elective surgery.

INTRODUCTION: Intravenous (i.v.) acetaminophen is administered during surgery for postoperative analgesia. However, little information is available on the pharmacokinetics of i.v. acetaminophen in Japanese patients undergoing surgery under general anesthesia. METHODS: The study was approved by the Institutional Review Board and registered at UMIN-CTR (UMIN000013418). Patients scheduled to undergo elective surgery under general anesthesia were enrolled after obtaining written informed consent. During surgery, 1 g of i.v. acetaminophen was administered over 15, 60, or 120 min. Acetaminophen concentrations (15 or 16 samples per case) were measured at time points from 0-480 min after the start of administration (liquid chromatography-mass spectrometry/tandem mass spectrometry; limit of quantitation 0.1 µg/mL). The predictive performance of three published pharmacokinetic models was evaluated. Population pharmacokinetics were also analyzed using a nonlinear mixed-effect model based on the NONMEM program. RESULTS: Data from 12 patients who underwent endoscopic or lower limb procedures were analyzed (male/female = 7/5, median age 55 years, weight 63 kg). Anesthesia was maintained with remifentanil and propofol or sevoflurane. The pharmacokinetic model of i.v. acetaminophen reported by Würthwein et al. worked well. Using 185 datapoints, the pharmacokinetics of i.v. acetaminophen were described by a two-compartment model with weight as a covariate but not age, sex, or creatinine clearance. The median prediction error and median absolute prediction error of the final model were -1 and 10%, respectively. CONCLUSION: A population pharmacokinetic model of i.v. acetaminophen in Japanese patients was constructed, with performance within acceptable ranges.

Effects of indigo carmine intravenous injection on noninvasive and continuous total hemoglobin measurement with using the Revision L sensor.

The effects of intravenous injection of indigo carmine on noninvasive and continuous total hemoglobin (SpHb) measurement were retrospectively evaluated with the Revision L sensor. The subjects were 18 patients who underwent elective gynecologic surgery under general anesthesia. During surgery, 5 mL of 0.4 % indigo carmine was injected intravenously, and changes in SpHb concentrations between before and after the injection were evaluated. The mean age was 52.4 ± 12.8 years. Before injection, the median SpHb level was 10.1 (range, 6.8-13.4) g/dL. The results demonstrated no change in SpHb concentration between before and after indigo carmine injection as detected by the Revision L sensor. SpHb measurements as determined with the Revision L sensor were not affected, even after the intravenous injection of indigo carmine.

THE EFFECT OF OBESITY ON DOSE OF DEXMEDETOMIDINE WHEN ADMINISTERED WITH FENTANYL DURING POSTOPERATIVE MECHANICAL VENTILATION--RETROSPECTIVE.

We carried out a retrospective investigation on the effect of obesity on dexmedetomidine (DEX) requirements when administered with fentanyl (FEN) during mechanical ventilation after major surgeries. After Institutional Review Board approval, 14 obese patients with a body mass index (BMI) ≥ 30 kg/m(2) and the same number of non-obese patients with similar backgrounds to the obese patients were selected from medical records. Doses of DEX in the first 48 h or until the end of sedation or extubation were calculated for comparison. In addition to comparison of dosing between the groups, associations between total body weight (TBW), BMI, and lean body mass (LBM) values and doses of DEX (mcg/h), between BMI and various indices (i.e., amount per TBW per hour and amount per LBM per hour) of DEX doses, and between above indices of DEX and FEN doses were also examined. There were no significant differences in DEX dose indices between the groups. However, DEX requirements (mcg/h) were significantly increased with TBW (kg) (r = 0.51, P = 0.003), BMI (r = 0.49, P = 0.006) and LBM (kg) (r = 0.42, P = 0.02), which might have enhanced the DEX metabolism with physiological changes with obesity. These findings will be beneficial for future clinical pharmacological analysis of DEX.