Comparison of Outcomes between a Basket Catheter and a Balloon Catheter for Endoscopic Common Bile Duct Stone Removal.

INTRODUCTION: Evidence for the outcomes of endoscopic retrograde cholangiopancreatography (ERCP) between a basket catheter and a balloon catheter for endoscopic common bile duct stone (CBDS) removal is lacking. This study aimed to compare ERCP outcomes using a basket catheter and a balloon catheter for endoscopic CBDS removal. METHODS: This multicenter retrospective study included 904 consecutive patients with native papilla who underwent endoscopic stone removal for CBDS ≤10 mm using a basket catheter and/or a balloon catheter at three institutions in Japan. ERCP outcomes between the basket and balloon groups were compared using inverse probability of treatment weighting (IPTW) method. RESULTS: ERCP-related adverse events occurred in 6.5% (29/449) and 7.7% (35/455) of patients in the basket and balloon groups, respectively (IPTW-adjusted p = 0.52). The incidences of post-ERCP pancreatitis, cholangitis, and perforation were similar in the basket and balloon groups (3.8% vs. 2.9%, 1.3% vs. 0.9%, and 0.7% vs. 0.7%, respectively). However, bleeding incidences were significantly higher in the balloon group than in the basket group (3.3% vs. 0.7%, IPTW-adjusted p = 0.012). Successful complete stone removal at one ERCP session using a single catheter was achieved in 17.8% (80/449) in the basket group and in 81.3% (370/455) in the balloon group (IPTW-adjusted p < 0.001). DISCUSSION: A balloon catheter is more likely to complete stone extraction for CBDS ≤10 mm with a single catheter at one endoscopic stone removal session. However, the risk for post-ERCP bleeding is higher in the balloon group than in the basket group.

Low Detection Rates of Bile Duct Stones During Endoscopic Treatment for Highly Suspected Bile Duct Stones with No Imaging Evidence of Stones.

BACKGROUND: The revised American Society for Gastrointestinal Endoscopy (ASGE) guideline 2019 provides the high-risk criteria for suspected common bile duct stones (CBDSs). AIMS: To evaluate CBDS detection rates during endoscopic retrograde cholangiopancreatography (ERCP) in high-risk patients with suspected CBDSs based on the ASGE guideline 2019. METHODS: This multicenter retrospective study included 1100 consecutive patients who underwent ERCP for suspected CBDSs with any high-risk criteria based on the revised ASGE guideline 2019: Criterion 1, CBDSs on imaging; Criterion 2, clinical ascending cholangitis; and Criterion 3, total bilirubin exceeding 4 mg/dL and dilated common bile duct on imaging. We compared CBDS detection rates during ERCP based on individual and combined high-risk criteria. RESULTS: The CBDS detection rates of patients who met any of the criteria, only Criterion 1, and Criteria 2 or 3 were 86.0% (946/1100), 93.4% (113/121), and 50.0% (106/212), respectively. In patients who met Criteria 1 and 2, 1 and 3, 2 and 3, and all criteria, CBDSs were confirmed during ERCP in 95.1% (490/515), 96.2% (25/26), 55.3% (26/47), and 98.4% (186/189), respectively. The CBDS detection rate during ERCP of patients with at least Criterion 1 significantly exceeded that of patients without at least Criterion 1 [95.7% (814/851) vs. 51.0% (132/259), respectively, P < 0.001]. CONCLUSIONS: Patients with CBDS visualization on imaging have very high CBDS detection rates during ERCP. However, performing ERCP on patients with only clinical predictors, such as cholangitis and dilated CBD with total bilirubin exceeding 4 mg/dL, often results in unnecessary ERCP.

Unnecessary endoscopic retrograde cholangiopancreatography associated with the spontaneous passage of common bile duct stones into the duodenum: a multicenter retrospective study.

BACKGROUND: Unnecessary endoscopic retrograde cholangiopancreatography (ERCP) after spontaneous passage of common bile duct stones (CBDSs) should be avoided. This study aimed to examine the cumulative diagnosis rate and the predictive factors of spontaneous CBDS passage during the interval between the imaging diagnosis and ERCP. METHODS: This multicenter retrospective study included 1260 consecutive patients with native papilla diagnosed with CBDSs using imaging modalities. Predictive factors and cumulative diagnosis rate of spontaneously passed CBDSs during the interval between imaging diagnosis and ERCP were analyzed. RESULTS: The overall cumulative diagnosis rate of spontaneous CBDS passage was 6.2% (78/1260) during a mean interval of 5.0 days. In the multivariate analysis, CBDS sized < 6 mm on diagnostic imaging, solitary CBDS on diagnostic imaging, intervals between the imaging diagnosis and ERCP, and nondilated common bile duct (< 10 mm) were the significant factors associated with spontaneous CBDS passage. Specifically, the cumulative diagnosis rate of spontaneous passage was significantly higher in patients with solitary and CBDSs sized < 6 mm than in those with other CBDSs (14.4% [54/376] vs. 2.7% [24/884], P < 0.001). In both the asymptomatic and symptomatic groups, the cumulative diagnosis rate of the spontaneous passage of CBDSs was significantly higher in patients with solitary and CBDSs sized < 6 mm on diagnostic imaging than in those with multiple and/or CBDSs sized ≥ 6 mm on diagnostic imaging during a mean interval of 20.5 and 2.4 days, respectively (asymptomatic group: 22.4% [15/67] vs. 3.5% [4/113], P < 0.001, symptomatic group: 12.6% [39/309] vs. 2.6% [20/771], P < 0.001). CONCLUSIONS: Solitary and CBDSs sized < 6 mm on diagnostic imaging can often lead unnecessary ERCP due to spontaneous passage. Preliminary endoscopic ultrasonography immediately before ERCP is recommended, especially in patients with solitary and small CBDSs on diagnostic imaging.

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.

The impact of electrosurgical devices on electromyography-based neuromuscular monitoring during abdominal laparotomy: a case series.

The present study aimed to evaluate the effect of electrosurgical devices on neuromuscular monitoring using an electromyography (EMG)-based neuromuscular monitor during abdominal laparotomy. Seventeen women (aged 32-64 years) undergoing gynecological laparotomy under total intravenous general anesthesia were enrolled in the study. A TetraGraph™ was placed to stimulate the ulnar nerve and to monitor the abductor digiti minimi muscle. After device calibration, train-of-four (TOF) measurements were repeated at intervals of 20 s. Rocuronium 0.6 to 0.9 mg/kg was administered for induction, and additional doses of 0.1 to 0.2 mg/kg were administered to maintain TOF counts ≤ 2 during the surgery. The primary outcome of the study was the ratio of measurement failure. The secondary outcomes of the study were the total number of measurements, the number of measurement failures, and the most extended consecutive number of measurement failures. The data are expressed as median (range). Of the 3091 (1480-8134) measurements, the number of measurement failures was 94 (60-200), resulting in a failure ratio of 3.5% (1.4-6.5%). The most extended consecutive number of measurement failures was 8 (4-13). All attending anesthesiologists were able to maintain and reverse neuromuscular blocks under EMG guidance. This prospective observational study demonstrated that the use of EMG-based neuromuscular monitoring does not seem to be heavily affected by electrical interference during lower abdominal laparotomic surgery. Trial registration This trial was registered in the University Hospital Medical Information Network under registration number UMIN000048138 (registration date; June 23, 2022).

A Comparison Between the Adductor Pollicis Muscle Using TOF-Watch SX and the Abductor Digiti Minimi Muscle Using TetraGraph in Rocuronium-Induced Neuromuscular Block: A Prospective Observational Study.

BACKGROUND: The commonly used acceleromyography (AMG)-based neuromuscular monitor TOF-Watch SX is no longer manufactured. Recently, a new portable electromyography (EMG)-based neuromuscular monitor TetraGraph was introduced in clinical anesthesia. The aim of the study was to compare the responses obtained simultaneously from the abductor digiti minimi (ADM) muscle with TetraGraph and the adductor pollicis (AP) muscle with TOF-Watch SX during rocuronium-induced neuromuscular block. METHODS: Patients undergoing orthopedic surgery with general anesthesia were enrolled in this prospective, observational study. During total intravenous general anesthesia, train-of-four (TOF) responses following 0.9-mg·kg -1 rocuronium administration were monitored at the AP muscle with TOF-Watch SX and the ADM muscle with TetraGraph on the opposite arms. Sugammadex 2 mg·kg -1 was administered when both devices showed TOF counts (TOFCs) = 2. The primary outcome was time from rocuronium administration to first appearance of posttetanic count (PTC) response (first PTC). The secondary outcomes were baseline TOF ratios (TOFRs), onset time, time to first reappearance of TOFC = 1 (time to TOFC1), time to first reappearance of TOFC = 2 (time to TOFC2), and time from sugammadex administration to TOFR ≥0.9 with TetraGraph or to normalized TOFR ≥0.9 with TOF-Watch SX (recovery time). We used paired t test and Wilcoxon signed-rank test to analyze parametric and nonparametric data, respectively. P <.05 defined statistical significance. RESULTS: A total of 20 patients were analyzed. The baseline TOFRs were significantly higher with TOF-Watch SX than with TetraGraph (105 [96-110] vs 100 [98-101]; P = .0002). The time to first PTC (minutes) (31.7 ± 9.6 vs 41.1 ± 12.3; P < .001), time to TOFC1 (minutes) (48.0 ± 12.7 vs 58.8 ± 19.2; P < .001), time to TOFC2 (minutes) (56.2 ± 15.7 vs 74.2 ± 23.7; P < .001), and recovery time (seconds) (61.5 [32-148] vs 75.5 [94-102]); P = .043) were significantly faster with TOF-Watch SX than with TetraGraph. There were no significant differences in onset time. CONCLUSIONS: TOF-Watch SX overestimated recovery from rocuronium-induced neuromuscular block compared with TetraGraph.

A comparison between the adductor pollicis muscle and the abductor digiti minimi muscle using electromyography AF-201P in rocuronium-induced neuromuscular block: a prospective comparative study.

BACKGROUND: The AF-201P, a new electromyography (EMG)-based neuromuscular monitor has been developed recently. The aim of this clinical study was to compare two ulnar nerve innervated muscles: the adductor pollicis (AP) muscle and the abductor digiti minimi (ADM) muscle during the recovery from rocuronium-induced neuromuscular block by using EMG AF-201P. METHODS: Twenty patients undergoing surgery with general anesthesia were enrolled in the study. During total intravenous general anesthesia, train-of-four (TOF) and post-tetanic counts (PTC) responses following 0.9 mg/kg rocuronium administration were concurrently monitored at the AP and the ADM muscles with EMG AF-201P on the opposite arms. At the end of the surgery, sugammadex 2 mg/kg was administered when TOF counts of 2 (TOFC2) was observed at both muscles. The primary outcome of the study was time from administration of rocuronium to first appearance of PTC response (first PTC). The secondary outcomes of the study were time from administration of rocuronium to TOF count of 1 (TOFC1), time from first PTC to TOFC1 (PTC-TOF time), time to TOFC2, and time from administration of sugammadex to TOF ratio ≥ 0.9. Agreement between the two muscles was assessed using the Bland-Altman analysis. Data are expressed as mean ± standard deviation. RESULTS: Nineteen patients were included in the analysis. Time to first PTC was significantly faster at the ADM muscle than the AP muscle (24.4 ± 11.4 min vs 32.4 ± 13.1 min, p = 0.006). PTC-TOF time was significantly longer with the ADM muscle than the AP muscle (19.4 ± 7.3 min vs 12.4 ± 10.6 min, p = 0.019). There were no significant differences in time to TOFC2 and sugammadex-facilitated recovery between the two muscles. Bland-Altman analyses showed acceptable ranges of bias and limits of agreement of the two muscles. CONCLUSIONS: The ADM muscle showed a good agreement with the AP muscle during rocuronium-induced neuromuscular block but faster recovery of PTC response when using EMG. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000044904 ). Registered 19 July 2021 -Retrospectively registered, https://center6.umin.ac.jp/cgi-bin/ctr_e/ctr_view.cgi?recptno=R000051290 .

Plasma rocuronium concentration in cell salvage blood following cardiac surgery: a case series.

PURPOSE: The aim of the study was to evaluate the plasma rocuronium concentration in autologous blood transfusion obtained from the cell salvage (CS) system following cardiac surgery with cardiopulmonary bypass (CPB). METHODS: This prospective observational study was conducted in a university teaching hospital from July to November 2020. Patients undergoing general anesthesia for cardiac surgery with CPB were enrolled in the study. After separation from CPB, residual blood remaining in the extracorporeal system was collected as the control sample. The second sample (CS blood) was collected from the autologous blood transfusion obtained after completion of the CS system with Cell Saver® Elite®. Hematocrit values of both samples were also examined. RESULTS: Ten subjects (aged 57-86 years) were enrolled in this study. Plasma rocuronium concentrations (ng/ml) were significantly lower in the CS blood (94.0 ± 77.5) compared to the control (2950 ± 812.2) (p = 0.002). Hematocrit values (%) were significantly higher in the CS blood (75.2 ± 11.3) compared to the control (40.2 ± 10.2) (p = 0.002). CONCLUSION: Autologous blood transfusion obtained from CS system following cardiac surgery with CPB, only retained a small amount of plasma rocuronium concentration, therefore, the risk of autologous blood transfusion contributing to clinically relevant residual neuromuscular blockade postoperatively should be considered to be low. TRIAL REGISTRATION: This trial was registered in the University Hospital Medical Information Network under registration number UMIN000040877 (registration date; June 24, 2020).

Extravascular leakage of induction doses of rocuronium: four cases in which both depth of neuromuscular block and plasma concentration of rocuronium were assessed.

The duration of action of extravasated rocuronium varies depending on the patient's comorbidities. In patients who receive high doses of non-depolarizing neuromuscular blocking agents subcutaneously, anesthesiologists should be aware of unexpected prolongation of the progress and recovery of neuromuscular block. In such cases, the depth and recovery of neuromuscular block should be objectively monitored to avoid residual neuromuscular block and recurarization.

Comparison of a new EMG module, AF-201P, with acceleromyography using the post-tetanic counts during rocuronium-induced deep neuromuscular block: a prospective, multicenter study.

Recent advances in neuromuscular monitors have facilitated the development of a new electromyographic module, AF-201P™. The purpose of this study was to investigate the relationship between post-tetanic counts (PTCs) assessed using the AF-201P™ and the acceleromyographic TOF Watch SX™ during rocuronium-induced deep neuromuscular block. Forty adult patients consented to participate in this study. The integrated AF-201P™ stimulating and sensing electrode was placed over the ulnar nerve on the distal volar forearm and the belly of the abductor digiti minimi muscle of one arm. The TOF Watch SX™ was applied with the provided hand adaptor on the opposite arm, to observe twitch responses of the adductor pollicis muscle. After stabilization of train-of-four (TOF) responses, rocuronium 0.9 mg kg-1 was administered intravenously. Then, PTCs were observed every 3 min using both monitors. Whenever the TOF count was detected with the TOF Watch SX™, rocuronium 0.2 mg kg-1 was administered, and successive PTC measurements were continued. A total of 1732 paired PTC data points were obtained and analyzed. Regression analysis showed no significant difference in PTCs between the two monitors (PTCs measured by the TOF Watch SX™ = 0.78·PTCs measured by AF-201P™ + 0.21, R = 0.56). Bland-Altman analysis also showed acceptable ranges of bias [95% CI] and limits of agreement (0.3 [0.2 to 0.5] and - 4.6 to 5.3) for the PTCs. The new EMG module, AF-201P™, showed reliable PTCs during deep neuromuscular block, as well as the TOF Watch SX™.

Comparison of intrathecal morphine with continuous patient-controlled epidural anesthesia versus intrathecal morphine alone for post-cesarean section analgesia: a randomized controlled trial.

BACKGROUND: Several neuraxial techniques have demonstrated effective post-cesarean section analgesia. According to previous reports, it is likely that patient-controlled epidural analgesia (PCEA) without opioids is inferior to intrathecal morphine (IM) alone for post-cesarean section analgesia. However, little is known whether adding PCEA to IM is effective or not. The aim of this study was to compare post-cesarean section analgesia between IM with PCEA and IM alone. METHODS: Fifty patients undergoing elective cesarean section were enrolled in this prospective randomized study. Patients were randomized to one of two groups: IM group and IM + PCEA group. All patients received spinal anesthesia with 12 mg of 0.5% hyperbaric bupivacaine, 10 µg of fentanyl, and 150 µg of morphine. Patients in IM + PCEA group received epidural catheterization through Th11-12 or Th12-L1 before spinal anesthesia and PCEA (basal 0.167% levobupivacaine infusion rate of 6 mL/h, bolus dose of 3 mL in lockout interval of 30 min) was commenced at the end of surgery. A numerical rating scale (NRS) at rest and on movement at 4,8,12,24,48 h after the intrathecal administration of morphine were recorded. In addition, we recorded the incidence of delayed ambulation and the number of patients who requested rescue analgesics. We examined NRS using Bonferroni's multiple comparison test following repeated measures analysis of variance; p < 0.05 was considered as statistically significant. RESULTS: Twenty-three patients in each group were finally analyzed. Mean NRS at rest was significantly higher in IM group than in IM + PCEA group at 4 (2.7 vs 0.6), 8 (2.2 vs 0.6), and 12 h (2.5 vs 0.7), and NRS during mobilization was significantly higher in IM group than in IM + PCEA group at 4 (4.9 vs 1.5), 8 (4.8 vs 1.9), 12 (4.9 vs 2), and 24 h (5.7 vs 3.5). The number of patients who required rescue analgesics during the first 24 h was significantly higher in IM group compared to IM + PCEA group. No significant difference was observed between the groups in incidence of delayed ambulation. CONCLUSIONS: The combined use of PCEA with IM provided better post-cesarean section analgesia compared to IM alone. TRIAL REGISTRATION: UMIN-CTR (Registration No. UMIN000032475). Registered 6 May 2018 - Retrospectively registered.

Use of intraoperative neuromuscular monitor reduces the reversal dose of sugammadex: a single-center retrospective study.

PURPOSE: We compared the reversal doses of sugammadex in surgical cases in which intraoperative neuromuscular monitor were used, to cases in which intraoperative neuromuscular monitoring was not used, retrospectively. METHODS: Data were collected by reviewing the electronic medical records of patients who received rocuronium and sugammadex during general anesthesia at Asahikawa Medical University Hospital between May 1, 2017 and April 30, 2018. The primary outcome was the reversal dose of sugammadex per patient actual body weight (mg/kg) between the group in which intraoperative neuromuscular monitoring was used (NM+ group) and the group in which intraoperative neuromuscular monitoring was not used (NM- group). RESULTS: A total of 3496 patients were evaluated, with 2544 patients (73%) included in NM+ group and 952 patients (27%) in NM- group. The reversal doses of sugammadex per actual body weight were significantly higher in NM- group compared to NM+ group. In the NM+ group, 521 patients (20%) received < 2 mg/kg sugammadex, 1377 patients (54%) received 2 ~ 2.5 mg/kg sugammadex, and 646 patients (25%) received > 2.5 mg/kg sugammadex. In contrast, 128 patients (13%) received < 2 mg/kg sugammadex, 362 patients (38%) received 2 ~ 2.5 mg/kg sugammadex and 462 patients (49%) received > 2.5 mg/kg sugammadex in NM- group. CONCLUSION: This single-center retrospective study demonstrated that the use of intraoperative neuromuscular monitor reduced the reversal dose of sugammadex.

Morphologic Evaluation of the Mitral Annulus During Displacement of the Heart in Off-Pump Coronary Artery Bypass Surgery.

OBJECTIVE: To evaluate the morphologic changes of the mitral annulus using 3-dimensional transesophageal echocardiography during heart displacement to expose the anastomosis site in off-pump coronary artery bypass surgery (OPCAB). DESIGN: Prospective case series. SETTING: Single center, university hospital. PARTICIPANTS: The study comprised 34 consecutive patients who underwent OPCAB of the left circumflex artery (LCX) and the right coronary artery (RCA). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mitral annulus parameters were measured using the Mitral Valve Quantification program after sternotomy (physiologic position) and during displacement of the heart to expose the LCX (LCX position) and the RCA (RCA position). The height of the mitral annulus was significantly lower in the LCX (5.76 ± 0.90 mm) and RCA (5.92 ± 0.97 mm) positions than in the physiologic position (6.96 ± 0.99 mm; both p < 0.0001). The percent change in the height of the mitral annulus was significantly greater in the mitral regurgitation group than in the mitral regurgitation nondeterioration group when in the LCX (-16.3% ± 6.0% v -11.9% ± 3.3%, p = 0.0203) and RCA (-16.9% ± 6.3% v -12.1% ± 3.8%, p = 0.0207) positions. The anteroposterior and intercommissural diameters, annulus perimeter, and surface area of the mitral annulus did not differ significantly among all heart positions. CONCLUSIONS: The mitral annulus flattened and lost its saddle shape without expanding while in the LCX and RCA positions. The greater percent change in the height of the mitral annulus may aggravate mitral regurgitation.

Preparing for the unexpected: special considerations and complications after sugammadex administration.

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal.

We report the use of rocuronium to re-establish neuromuscular block after reversal with sugammadex. The aim of this study was to investigate the relationship between the dose of rocuronium needed to re-establish neuromuscular block and the time interval between sugammadex administration and re-administration of rocuronium. Patients who required re-establishment of neuromuscular block within 12 h after the reversal of rocuronium-induced neuromuscular block with sugammadex were included. After inducing general anesthesia and placing the neuromuscular monitor, the protocol to re-establish neuromuscular block was as follows. An initial rocuronium dose of 0.6 mg/kg was followed by additional 0.3 mg/kg doses every 2 min until train-of-four responses were abolished. A total of 11 patients were enrolled in this study. Intervals between sugammadex and second rocuronium were 12-465 min. Total dose of rocuronium needed to re-establish neuromuscular block was 0.6-1.2 mg/kg. 0.6 mg/kg rocuronium re-established neuromuscular block in all patients who received initial sugammadex more than 3 h previously. However, when the interval between sugammadex and second rocuronium was less than 2 h, more than 0.6 mg/kg rocuronium was necessary to re-establish neuromuscular block.

Cannabinoid receptor type 1 antagonist, AM251, attenuates mechanical allodynia and thermal hyperalgesia after burn injury.

BACKGROUND: Burn injury causes nociceptive behaviors, and inflammation-related pathologic pain can lead to glial cell activation. This study tested the hypothesis that burn injury activates glial cells, and cannabinoid receptor 1 (CB1R) antagonist, AM251, will decrease burn pain. METHODS: Anesthetized rats received 0.75-cm third-degree burn on dorsal hind paw. Vehicle or AM251 30 µg intrathecally (older rats, n=6 per group) or, either vehicle, 0.1 or 1.0 mg/kg intraperitoneally (younger rats, n=6 per group), started immediate postburn, was administered for 7 days. Mechanical allodynia and thermal hyperalgesia were tested on ventral paw for 14 days. Microglial and astroglial activity was assessed by immunocytochemistry. RESULTS: Allodynia, observed on burn side from day 1 to 14, was significantly (P<0.05) attenuated by intrathecal and intraperitoneal AM251 (1 mg/kg) starting from 3 to 14 days. Hyperalgesia, observed from day 3 to 12, was completely (P<0.05) reversed by intrathecal and intraperitoneal AM251 (1 mg/kg). AM251 0.1 mg/kg had no effect. Microglial activity (n=3 per time point) increased (P<0.05) 18.5±7.5 and 12.3±1.6 (mean±SD) fold at 7 and 14 days, respectively. Astroglial activity (n=4 per time point) increased 2.9±0.3 fold at day 7 only. Glial activities were unaltered by AM251. CONCLUSIONS: AM251 inhibited nociceptive behaviors after burn even beyond 7-day period of administration. Although many studies have documented the utility of CB1R agonists, this study indicates that endogenous cannabinoids may have an unexpected pronociceptive effect during development of burn pain, explaining why CB1R antagonist, AM251, improves nociceptive behaviors. The decreased nociception with AM251 without altering glial activity indicates that AM251 acts further downstream of activated glial cells.

A temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in a pediatric patient.

We report a temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in our dose-finding study in pediatric patients. A 19-month-old female infant (9.6 kg, 80 cm) was scheduled for elective cheiloplasty surgery. Anesthesia was induced with nitrous oxide 50% and sevoflurane 5% and maintained with air, oxygen, sevoflurane 3%, and fentanyl (total, 3 µg/kg). Neuromuscular monitoring was performed at the adductor pollicis muscle after induction of anesthesia but before the administration of rocuronium. Total dose of rocuronium during the surgery was 0.9 mg/kg. Neuromuscular block was reversed with 0.5 mg/kg sugammadex when one response was observed with post-tetanic count stimulation. Twitch responses after sugammadex administration showed a temporary decrease after its initial recovery. Maximum decreases in twitch responses were observed 17 min after initial dose of sugammadex. Twitch responses recovered to their control values after additional doses of 3.5 mg/kg sugammadex (4 mg/kg in total). Time from sugammadex administration to maximum decreases in twitch responses is earlier than has been reported in adults (20-70 min). It is demonstrated that following neuromuscular block reversal with insufficient dose of sugammadex, there is a possibility of the recurrence of residual paralysis within less than 20 min in pediatric patients.

Laryngospasm Treated With Intramuscular Rocuronium in a Pediatric Patient Without Intravenous Access: A Case Report.

We present a case in which intramuscular rocuronium was used successfully to treat laryngospasm in a pediatric patient. An 11-month-old infant weighing 9.7 kg was scheduled for an elective laparoscopic inguinal hernia repair surgery. Anesthesia was induced with oxygen, nitrous oxide, and sevoflurane. After loss of consciousness, mask ventilation became impossible, and laryngospasm was suspected. Intravenous access was attempted without success; as there was no immediate access to succinylcholine, rocuronium 10 mg (1.0 mg/kg) was injected intramuscularly into the vastus lateralis muscle. We were able to mask-ventilate the patient within one minute of intramuscular rocuronium, followed by successful endotracheal intubation with a video laryngoscope. The duration of hypoxia (saturation of peripheral oxygen (SpO2) < 90%) was approximately two minutes, and the patient's lowest oxygen saturation during induction was 76%. At the end of the surgery, the patient was uneventfully extubated. We conclude that intramuscular rocuronium may provide an alternative treatment for laryngospasm in pediatric patients with no intravenous access and no availability of succinylcholine.

Disulfide Bonds of Thyroid Peroxidase Are Critical Elements for Subcellular Localization, Proteasome-Dependent Degradation, and Enzyme Activity.

Background: Congenital hypothyroidism (CH) is caused by mutations in cysteine residues, including Cys655 and Cys825 that form disulfide bonds in thyroid peroxidase (TPO). It is highly likely that these disulfide bonds could play an important role in TPO activity. However, to date, no study has comprehensively analyzed cysteine mutations that form disulfide bonds in TPO. In this study, we induced mutations in cysteine residues involved in disulfide bonds formation and analyzed their effect on subcellular localization, degradation, and enzyme activities to evaluate the importance of disulfide bonds in TPO activity. Methods: Vector plasmid TPO mutants, C655F and C825R, known to occur in CH, were transfected into HEK293 cells. TPO activity and protein expression levels were measured by the Amplex red assay and Western blotting. The same procedure was performed in the presence of MG132 proteasome inhibitor. Subcellular localization was determined using immunocytochemistry and flow cytometry. The locations of all disulfide bonds within TPO were predicted using in silico analysis. All TPO mutations associated with disulfide bonds were induced. TPO activity and protein expression levels were also measured in all TPO mutants associated with disulfide bonds using the Amplex red assay and Western blotting. Results: C655F and C825R showed significantly decreased activity and protein expression compared with the wild type (WT) (p < 0.05). In the presence of the MG132 proteasome inhibitor, the protein expression level of TPO increased to a level comparable with that of the WT without increases in its activity. The degree of subcellular distribution of TPO to the cell surface in the mutants was lower compared with the WT TPO. Twenty-four cysteine residues were involved in the formation of 12 disulfide bonds in TPO. All TPO mutants harboring an amino acid substitution in each cysteine showed significantly reduced TPO activity and protein expression levels. Furthermore, the differences in TPO activity depended on the position of the disulfide bond. Conclusions: All 12 disulfide bonds play an important role in the activity of TPO. Furthermore, the mutations lead to misfolding, degradation, and membrane insertion.

Monitoring of neuromuscular blockade in one muscle group alone may not reflect recovery of total muscle function in patients with ocular myasthenia gravis.

PURPOSE: We report on two patients with ocular myasthenia gravis who received rocuronium, followed later by sugammadex to reverse neuromuscular blockade. Recovery was monitored simultaneously at the adductor pollicis muscle (APM) and the corrugator supercilii muscle (CSM). CLINICAL FEATURES: Two patients with ocular myasthenia gravis (case 1: 74 yr-old female, 54 kg; case 2: 71 yr-old male, 72 kg) were scheduled for surgery under general anesthesia. Neuromuscular blockade was induced with rocuronium 0.3 mg·kg(-1) after placing two separate monitors at the APM and the CSM, respectively. Additional doses of rocuronium 0.1-0.2 mg·kg(-1) were given to maintain neuromuscular blockade at fewer than two twitches at the APM during surgery. Train-of-four response at the CSM did not show recovery of the twitch after its initial disappearance. At the end of surgery, sugammadex was administered. Twitch height at the APM recovered to the control value in 12 min (case 1) and 13 min (case 2) after sugammadex administration; however, twitch height at the CSM took 26 min (case 1) and 14 min (case 2) to recover to the control value. CONCLUSION: After rocuronium-induced paralysis in both patients with ocular myasthenia, spontaneous recovery and sugammadex-assisted recovery were slower at the CSM than at the APM. In patients without the disorder, CSM recovery is faster than APM recovery. Thus, in ocular myasthenia gravis, neuromuscular recovery at the APM may not reflect recovery of all muscles.