Anesthesia Management via an Automated Control System for Propofol, Remifentanil, and Rocuronium Compared to Management by Anesthesiologists: An Investigator-Initiated Study.

BACKGROUND: We previously developed an automated total intravenous anesthesia control system that uses new closed-loop system algorithms to administer propofol, remifentanil, and rocuronium based on the bispectral index and train-of-four data. We recently improved this automated control system by adding a safety mechanism and using a modified monitoring device. METHODS: Patients scheduled for elective surgery were randomly assigned to closed-loop feedback control (automatic group) or the manual administration of propofol, remifentanil, and rocuronium (manual group). The proportion of time during which the proper management of three-agent anesthesia was maintained during surgery was determined as the primary endpoint. RESULTS: The proportion of time during which the three components of sedation, analgesia, and muscle relaxation were adequately controlled was 87.21 ± 12.79% in the automatic group, which was non-inferior to the proportion of 65.19 ± 20.16% in the manual group (p < 0.001). Adverse events during the operative or postoperative observation periods were significantly less frequent in the automatic group (54 patients, 90.0%) than in the manual group (60 patients, 100.0%; p = 0.027). CONCLUSION: Our three-agent automated control system, which features an improved muscle relaxation monitor and safety mechanism added to the basic control algorithms, maintained sedation, analgesia, and muscle relaxation appropriately in a manner non-inferior to anesthesiologists without compromising safety.

A case of glossopharyngeal neuralgia successfully treated with levetiracetam.

BACKGROUND: Glossopharyngeal neuralgia is a condition that causes severe pain in the throat during swallowing. Although carbamazepine is a viable option for treating glossopharyngeal neuralgia, there are minimal data regarding the effect of alternative agents to treat it. We report on glossopharyngeal neuralgia, which is successfully controlled by levetiracetam. PRESENTATION: A woman in her 70s checked into our hospital with a chief complaint of neck pain lasting 5 years. She had a history of carbamazepine-induced interstitial pneumonia. As a result, we prescribed oral levetiracetam 1000 mg daily in addition to mirogabalin, which was previously prescribed. This effectively reduced the numerical rating scale from 9 to 1 with no adverse effects. Finally, she underwent microvascular decompression, and her symptoms were resolved. CONCLUSION: Levetiracetam may be an option for patients with glossopharyngeal neuralgia who cannot receive carbamazepine. However, levetiracetam is for off-label use according to the Japanese medical system.

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™.

[Intestinal Occlusion Clip Device].

In laparoscopic sigmoidectomy and rectal resection, intestinal tract irrigation is performed after temporary intestinal occlusion to prevent the dissemination of cancer cells in the intestine and to ensure a clean anastomosis. At this time, a temporary intestinal occlusion clip is used, but it may be difficult to place it at a predetermined position. Therefore, we made a small hole at the tip of the clip, made a loop with a thread that passed through it, grasped it, and manipulated the clip, such that it was relatively easy to place the clip in the proper position.

Comparison of Single and Dual Monitoring during Carotid Endarterectomy.

We compared the rate of selective shunt and pattern of monitoring change between single and dual monitoring in patients undergoing carotid endarterectomy (CEA). A total of 121 patients underwent 128 consecutive CEA procedures. Excluding five procedures using internal shunts in a premeditated manner, we classified patients according to the monitoring: Group A (n = 72), patients with single somatosensory evoked potential (SSEP) monitoring; and Group B (n = 51), patients with dual SSEP and motor evoked potential (MEP). Among the 123 CEAs, an internal shunt was inserted in 12 procedures (9.8%) due to significant changes in monitoring (Group A 5.6%, Group B 15.7%, p = 0.07). The rate of shunt use was significantly higher in patients with the absence of contralateral proximal anterior cerebral artery (A1) on magnetic resonance angiography (MRA) than in patients with other types of MRA (p <0.001). Significant monitor changes were seen in 16 (12.5%) in both groups. In four of nine patients in Group B, SSEP and MEP changes were synchronized, and in the remaining five patients, a time lag was evident between SSEP and MEP changes. In conclusion, the rate of internal shunt use tended to be more frequent in patients with dual monitoring than in patients with single SSEP monitoring, but the difference was not significant. Contralateral A1 absence may predict the need for a shunt and care should be taken to monitor changes throughout the entire CEA procedure. Use of dual monitoring can capture ischemic changes due to the complementary relationship, and may reduce the rate of false-negative monitor changes during CEA.

Development of a novel analgesic for neuropathic pain targeting brain-derived neurotrophic factor.

Effective treatment of neuropathic pain is challenging as its underlying mechanism remains largely unknown. Recently, the participation of brain-derived neurotrophic factor (BDNF) in neuropathic pain has been attracting increased attention. BDNF binds to a member of the tyrosine kinase receptor family, the TrkB receptor, that is specific for BDNF and is the transmembrane receptor on the posterior horn of spinal cord. In the present study, we purified two proteins that included the BDNF-binding domain of TrkB (eTrkB) and eTrkB coupled with a liposomal outer surface (liposomal eTrkB) in order to inhibit the BDNF-TrkB pathway in neuropathic pain. Results of the pull-down assay showed that eTrkB was bound to BDNF. We investigated the neuropathic pain suppression effect of this purified protein by its intrathecal administration in a rat neuropathic pain model. Mechanical and thermal hyperalgesia induced by L5 lumbar nerve ligation was markedly suppressed by treatment with eTrkB protein. Furthermore, we showed a prolonged algetic inhibition by liposomal eTrkB protein treatment. In conclusion, this study suggests that eTrkB, which sequesters endogenous BDNF and inhibits the BDNF-TrkB pathway, may prove to be a novel analgesic to treat neuropathic pain.

[A Case of Metachronous Multiple Liver Metastases of AFP and PIVKA-â ¡ Producing Gastric Cancer, Responding to Transcatheter Arterial Chemoembolization].

We report a case of a 75-year-old man with a-fetoprotein(AFP)-producing gastric cancer accompanied by multiple large liver metastases. The patient underwent a total gastrectomy for gastric cancer(p-T3N3H0P0M0, fStage ⅢB). The patient then underwent chemotherapy(TS-1 80m g/day)following the radical operation. However, 5 months after the radical operation, he presented with multiple large liver tumors, which were subsequently biopsied. Based on immunohistochemical examination, the liver tumors were negative for AFP protein, but were similar to hepatoid adenocarcinoma, and no fibrosis was observed in the background liver. Therefore, we diagnosed the tumors as liver metastases of AFP producing gastric cancer and metachronous liver metastasis. The patient underwent transcatheter arterial chemoembolization(TACE). TACE decreased the AFP and PIVKA-Ⅱ levels and reduced the multiple huge liver metastases. Due to the increase in AFP and the multiple liver metastases, despite intensive hepatic infusion chemotherapy, he died 5 months after admission.

Ultrasonographic Diagnosis for Dysfunction of the Diaphragm After Iatrogenic Tension Pneumoperitoneum by a Gastrointestinal Endoscopic Procedure: A Case Report.

There are various causes of dysfunction of the diaphragm. We present a case of diaphragm dysfunction caused by an excessive pneumoperitoneum in a 65-year-old woman. Her abdomen became distended during endoscopic investigation and circulatory failure occurred. A computed tomography scan revealed excessive pneumoperitoneum. Urgent laparotomy was performed to repair gastric perforation. Tracheal extubation was successfully performed in the intensive care unit. After extubation, a paradoxical breathing pattern appeared in addition to tachypnea. A diagnosis of dysfunction of the bilateral diaphragm was made by ultrasonography. Although nasal high-flow cannula therapy was required for several days, she was discharged from our hospital 2 weeks after surgery without any further complications. We should keep in mind that diaphragm dysfunction after excessive abdominal extension can be a cause of respiratory failure.

Preoperative continuation of aspirin administration in patients undergoing major abdominal malignancy surgery.

PURPOSE: In contrast to that in a nonoperative setting, it has been shown that perioperative administration of aspirin did not decrease the rate of death or myocardial infarction but increased major bleeding risk. Since these conflicting results might be due to concurrent use of anticoagulants and a lower thrombotic risk of patients, this cohort study was carried out for patients at a high thrombotic risk without concurrent use of anticoagulants. METHODS: Medical records for patients who underwent major abdominal malignancy surgery and who were on a preoperative antiplatelet regimen were reviewed. The patients were divided into two groups according to perioperative antiplatelet management: administration of all preoperative antiplatelet agent-suspended (no aspirin) group and only aspirin administration-continued (aspirin) group. The incidence of symptomatic thromboembolic events, frequency of exogenous blood transfusion within 30 days after surgery and the amount of intraoperative bleeding were compared between the two groups. RESULTS: After propensity score matching, 105 patients of each group were matched. The incidence of perioperative thromboembolic events in the no-aspirin group was significantly higher than that in the aspirin group [7/105 (6.7%) vs 0/105 (0%), 95% CI 1.44-∞, P = 0.016]. In contrast, neither the frequency of exogenous transfusion [21.0% vs 11.4%, 95% CI 0.88-4.38 P = 0.110] nor the amount of intraoperative bleeding [median (interquartile range), ml: 230 (70-500) vs 208 (50-500), P = 0.325] was different between the two groups. CONCLUSION: Although the sample size is relatively small, our findings suggest that continuation of aspirin administration is likely to reduce the thrombotic risk but unlikely to increase the bleeding risk of patients who undergo major abdominal surgery for malignancy.

Current Ventilator and Oxygen Management during General Anesthesia: A Multicenter, Cross-sectional Observational Study.

BACKGROUND: Intraoperative oxygen management is poorly understood. It was hypothesized that potentially preventable hyperoxemia and substantial oxygen exposure would be common during general anesthesia. METHODS: A multicenter, cross-sectional study was conducted to describe current ventilator management, particularly oxygen management, during general anesthesia in Japan. All adult patients (16 yr old or older) who received general anesthesia over 5 consecutive days in 2015 at 43 participating hospitals were identified. Ventilator settings and vital signs were collected 1 h after the induction of general anesthesia. We determined the prevalence of potentially preventable hyperoxemia (oxygen saturation measured by pulse oximetry of more than 98%, despite fractional inspired oxygen tension of more than 0.21) and the risk factors for potentially substantial oxygen exposure (fractional inspired oxygen tension of more than 0.5, despite oxygen saturation measured by pulse oximetry of more than 92%). RESULTS: A total of 1,786 patients were found eligible, and 1,498 completed the study. Fractional inspired oxygen tension was between 0.31 and 0.6 in 1,385 patients (92%), whereas it was less than or equal to 0.3 in very few patients (1%). Most patients (83%) were exposed to potentially preventable hyperoxemia, and 32% had potentially substantial oxygen exposure. In multivariable analysis, old age, emergency surgery, and one-lung ventilation were independently associated with increased potentially substantial oxygen exposure, whereas use of volume control ventilation and high positive end-expiratory pressure levels were associated with decreased potentially substantial oxygen exposure. One-lung ventilation was particularly a strong risk factor for potentially substantial oxygen exposure (adjusted odds ratio, 13.35; 95% CI, 7.24 to 24.60). CONCLUSIONS: Potentially preventable hyperoxemia and substantial oxygen exposure are common during general anesthesia, especially during one-lung ventilation. Future research should explore the safety and feasibility of a more conservative approach for intraoperative oxygen therapy.

[A Case of Melena Caused by Peritoneal Dissemination, Treated with Interventional Radiology].

We reported a case of melena caused by perineal dissemination and treated with radiologic intervention. The patient was a 67-year-old woman, who underwent a partial duodenectomy for duodenal(4th portion)cancer in 2013. The pathological examination revealed that the tumor was tub2>por2 adenocarcinoma, SE, n+(10/20), M0. The patient received 2 courses of cisplatin(CDDP)plus S-1 and 8 courses of S-1 monotherapy. About 2 years postoperatively, the patient was hospitalized due to unauthorized bleeding. Metrorrhagia was diagnosed as intrapelvic dissemination based on abdominal computed tomography in April 2016. The patient underwent sigmoid colostomy because she developed bowel obstruction. Postoperatively, the patient received 6 courses of capecitabine plus oxaliplatin(CapeOX)plus bevacizumab. Three months later, a reduction in the recurrent lesion was observed. However, after 6 months, the patient was again hospitalized due to melena. Her condition improved after receivinga blood transfusion and infusinga hemostat. In order to control the hemorrhage, radiation therapy of 50 Gy/25 fractions to the intrapelvic dissemination was conducted. Bleedingcould not be controlled by conservative treatment with blood transfusion. Therefore, radiologic intervention was performed for melena caused by peritoneal dissemination. Neither rebleedingnor symptoms of possible ischemic complications were observed after the intervention until she died 3 months later.

[A Case of Angiosarcoma of the Breast Following Breast-Conserving Surgery with Radiotherapy for Breast Cancer].

We report a case of angiosarcoma of the breast following breast-conserving surgerywith radiotherapyfor breast cancer. The patient was 82-year-old woman, developed induration and eruption in the bilateral breast more than 8 years after the initial operation for breast cancer. The induration was diagnosed as angiosarcoma based on skin-biopsyand vacuum-assisted biopsy. The patient received simple mastectomy, and has been become recurrent condition about one month after simple mastectomy. We operated partial excision for recurrence tumor. She is still alive after rearly 1 year of past operation. There are no established therapies for angiosarcoma of the breast following breast-conserving surgerywith radiotherapyfor breast cancer. Although radiotherapy-induced sarcoma is rare, earlydetection of the tumor in the irradiation area is important, as radiotherapyis often performed for the breast cancer patients. This interesting case of angiosarcoma of the breast after breast-conserving surgeryfor breast cancer is reported.

Localized Hepatic Tuberculosis with Imaging Changes Caused by the Progression of Tuberculosis.

Localized hepatic tuberculosis (LHTB) is difficult to diagnose preoperatively, and most cases of LHTB are diagnosed based on pathological findings. A relationship between imaging features and the pathological stage of hepatic tuberculosis (TB) has recently been reported, which could aid in the diagnosis of hepatic TB. We herein present a case study of a patient with LHTB diagnosed postoperatively who demonstrated imaging changes due to the progression of TB. An awareness of the presence of LHTB might have permitted a preoperative diagnosis. This is the first report of an LHTB patient who exhibited imaging changes during the course of the disease.

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.

The incidence of pulmonary embolism and deep vein thrombosis and their predictive risk factors after lower extremity arthroplasty: a retrospective analysis based on diagnosis using multidetector CT.

PURPOSE: The true incidence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE) events, and the predictive risk factors are not well-defined in patients who undergo major lower extremity arthroplasty such as total hip arthroplasty (THA) or total or partial knee arthroplasty (TPKA). Using multidetector computed tomography (MDCT), pulmonary angiography (CTA), and MDCT venography (CTV), we investigated the prevalence of VTE and its predictive risk factors in patients for whom the guideline recommends prophylaxis. METHODS: The electronic records of patients who underwent elective THA or TPKA at our institution from April 2010 through July 2013 were surveyed. We examined a total of 1,163 patient records for 986 patients who had undergone MDCT seven days after THA or TPKA. RESULTS: No PE-related deaths occurred in this study, though arterial embolization was needed for major bleeding in two cases. CTA-CTV revealed VTE in 51 (4.4 %) patients, PE in 20 (1.7 %), and DVT in 43 (3.3 %). Five of 51 patients had symptoms suggestive of DVT. In the logistic regression model, the type of surgery (TPKA > THA), patient age, and body mass index (BMI) were identified as predictive risk factors for VTE. CONCLUSIONS: This observational study showed that the overall incidence of VTE after THA and TPKA is 4.4 % in patients receiving recommended antithrombotic prophylaxis. TPKA is associated with a higher incidence of VTE than of THA, and greater BMI and older patient age are also independent risk factors.

Changes in the incidence, case fatality rate, and characteristics of symptomatic perioperative pulmonary thromboembolism in Japan: Results of the 2002-2011 Japanese Society of Anesthesiologists Perioperative Pulmonary Thromboembolism (JSA-PTE) Study.

PURPOSE: This study aimed to examine the incidence, case fatality rate, and characteristics of perioperative symptomatic pulmonary thromboembolism (PS-PTE) throughout Japan. METHODS: From 2002 to 2011, confidential questionnaires were mailed annually to all Japanese Society of Anesthesiologists-certified training hospitals for data collection to determine the incidence and case fatality rate of PS-PTE patients. Data from 10,537 institutions in which a total of 11,786,489 surgeries had been performed were analyzed using the Mann-Whitney and Chi-square tests. RESULTS: In total, 3,667 PS-PTE cases were identified. The average incidence of PS-PTE was 3.1 (2.2-4.8) per 10,000 surgeries, and the average case fatality rate was 17.9% (12.9-28.8%). The incidence of PS-PTE began to significantly decrease in 2004 compared with that of 2002 (0.0036 vs. 0.0044%: p < 0.01). The case fatality rate temporarily increased toward 2005 (17.9 to 28.8%); however, it gradually decreased since 2008 (15.7%) and was the lowest (12.9%) in 2011. Regarding the trends in prophylaxis, the rate of mechanical prophylaxis increased significantly in 2003 compared with that of 2002 (59.5 vs. 35.0%: p < 0.01), and almost plateaued (73.1-83.1%) after 2004. Furthermore, the rate of pharmacological prophylaxis started increasing in 2008 (17.6%) and reached around 30% after 2009 (28.8-30.2%). CONCLUSIONS: The results of our 10-year survey study show that the incidence of PS-PTE decreased significantly since 2004, and the case fatality rate seemed to show a downward trend since 2008. Major changes in the distribution of prophylaxis in PS-PTE patients were observed.

[Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients].

BACKGROUND: Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. METHODS: We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. RESULTS: For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. CONCLUSIONS: The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.

[A case of portal vein stenting for portal vein stenosis due to pancreatic cancer recurrence after pancreatoduodenectomy].

We report a case of portal vein stenosis due to pancreatic cancer recurrence that was successfully treated with intravenous stent implantation. The patient was a 70-year-old man who had undergone a subtotal stomach-preserving pancreatoduodenectomy with the modified Child method for pancreatic cancer. He was readmitted due to melena, dorsal pain, and severe ascites 8 months after the operation. Computed tomography (CT) findings revealed that pancreatic cancer recurrence had narrowed the portal vein. Neither gastrointestinal nor colon endoscopy could locate the source of gastrointestinal bleeding. Bleeding from the varices increased, and a hepatopetal collateral was considered to be the cause. We therefore placed an intravenous stent at the site of portal vein stenosis, by the transileocolic portal vein. After the stent placement, no further gastrointestinal hemorrhagic episodes occurred.

[Incidence and characteristics of perioperative pulmonary thromboembolism in Japan from 2009 through 2011 -the results of perioperative pulmonary thromboembolism research by the Japanese society of anesthesiologists (JSA-PTE research) --].

BACKGROUND: This study was designed to investigate the annual incidence and characteristics of perioperative pulmonary thromboembolism (PTE) in Japan from 2009 through 2011, and to compare the current trend with that observed in our previous studies conducted since 2002. METHODS: In the 3-year study period, a questionnaire was annually mailed to all institutions certified as training hospitals for anesthesiologists by the Japanese Society of Anesthesiologists (JSA). The survey included the parameters of age, sex, type of surgery, and the risk factors in patients who were operated upon. RESULTS: The questionnaire was sent out to total of 3,556 institutions and obtained answers from 2,511 institutions (70.6%) in the 3-year study period. Total 4,432,538 surgeries were conducted and 1,300 cases (0.03%) of perioperative PTE were registered. The incidence of PTE in all the 3 years was significantly lower than that observed in 2002-2003 (P<0.01). In addition, the mortality in 2011 was also significantly lower than that in 2002-2003 (P<0.05). The incidence of PTE in females (0.04%) was twice of the incidence of males (0.02%). The types of surgery with higher incidence of perioperative PTE were "thoracotomy with laparotomy" (0.08%),"hip joint, limbs" (0.07%) and"craniotomy" (0.06%). Compared with the middle age group (19-65 year-old), the incidence of PTE was twice in the elderly's (66-85 year-old) and in the super-elderly (over 86 year-old) it was thrice. In this survey, most approved risk factors were obesity (44%), malignancy (35%) and long term bed-rest (26%), and the ratio of long term bed-rest was decreasing compared with 2008. In the PTE cases, the ratio of the patients who received anticoagulant drugs (29-30%) or IVC filters placement (4-5%) increased compared with the results of JSA-PTE research in 2008 (P<0.01). CONCLUSIONS: The incidence and mortality of perioperative PTE decreased;although the factor of decrease in an incidence was considered to be the result of preventive method, as in the decrease in the mortality, the survey should be continued.

[Anticholinesterases; peripheral and central effects].

Anticholinesterase, such as neostigmine, was used to be a standard drug at the end of surgery for reversal of nondepolarizing neuromuscular block. Neostigmine decreases the metabolism of acetylcholine (ACh) at the neuromuscular junction and allows its concentration to increase and overcome the effect of the muscle relaxant. But this approach is ineffective against profound block. Rapid reversal from deep block is not possible and giving a reversal agent early will not speed up the recovery time. Anticholinesterases have actions both at the nicotinic and the muscarinic receptors, and even when accompanied by an antimuscarinic agent, they produce undesirable autonomic responses. Some anticholinesterase, like donepezil, exhibits high specificity for centrally active acetylcholinesterase and raise ACh levels in the brain. The deficiency in cholinergic neurotransmission in Alzheimer's disease (AD) has led to the development of cholinesterase inhibitors as the first-line treatment for symptoms of this disease. In addition to donepezil, two other cholinesterase inhibitors have recently been approved for the treatment of AD patients. The drugs have slightly different pharmacological properties, but they all work by inhibiting the breakdown of acetylcholine, an important neurotransmitter associated with memory, by blocking the enzyme acetylcholinesterase. Donepezil can also reverse opioid-induced respiratory depression.