Update on the Diagnosis and Management of Acute Colonic Pseudo-obstruction (ACPO).

PURPOSE OF REVIEW: Acute Colonic Pseudo-obstruction (ACPO) is a cause of large intestinal dilation and obstruction without any physical transition point. It remains difficult to diagnose and treat. We review the recent updates on diagnosis and management of ACPO. RECENT FINDINGS: Recent guidelines have posited that conservative management can be tried in most cases of ACPO, but that early decompression and surgery should be considered. Use of neostigmine is still a viable option but there is also promising data on pyridostigmine as well as prucalopride. Resolution of ACPO should be followed by daily use of polyethylene glycol (PEG) to help prevent recurrence. ACPO warrants early and accurate diagnosis with exclusion of alternate causes of large bowel dilation. Conservative management can be attempted for 48-72 h in those with cecal diameters < 12 cm and without signs of peritonitis and perforation. Early escalation of management should be attempted with neostigmine followed by endoscopy and/or surgery as needed, given that longer periods of dilation are associated with worse outcomes. There is promising new evidence for use of pyridostigmine and prucalopride, but further trials are needed prior to incorporating them into regular use. Finally, studies are lacking regarding prevention of ACPO after initial resolution.

Measuring Caenorhabditis elegans Sensitivity to the Acetylcholine Receptor Agonist Levamisole.

At the neuromuscular junction (NMJ), the binding of the excitatory neurotransmitter acetylcholine (ACh) to postsynaptic receptors leads to muscle contraction. As in vertebrate skeletal muscle, cholinergic signaling in the body wall muscles of the model organism Caenorhabditis elegans is required for locomotion. Exposure to levamisole, a pharmacological agonist of one class of ACh receptors on the body wall muscles, causes time-dependent paralysis of wild-type animals. Altered sensitivity to levamisole suggests defects in signaling at the NMJ or muscle function. Here, a protocol for a liquid levamisole assay performed on C. elegans grown in 24-well plates is presented. Vigorous swimming of the animals in liquid allows for the assessment and quantitation of levamisole-induced paralysis in hundreds of worms over a one-hour time period without requiring physical manipulation. This procedure can be used with both wild-type and mutants that have altered sensitivity to levamisole to demonstrate the functional consequences of altered signaling at the NMJ.

The effectiveness of parasympathomimetics for treating underactive bladder: A systematic review and meta-analysis.

AIMS: Biological rationale suggests that parasympathomimetics (cholinergic receptor stimulating agents) could be beneficial for patients with underactive bladder. However, no systematic review with meta-analysis addressing potential benefits or adverse effects exists. The aim of this review was to assess the effectiveness, both benefits and harms, of using parasympathomimetics for the treatment of underactive bladder. METHODS: The protocol was registered in PROSPERO, and searches undertaken in PubMed, Embase, and CENTRAL, including randomized and non-randomized controlled trials of patients with underactive bladder, comparing parasympathomimetic to placebo, no treatment, or other pharmaceuticals. Risk ratios, odds ratios, and mean differences were calculated. RESULTS: Twelve trials with 3024 participants were included. There was a significant difference between parasympathomimetics and comparators (favoring parasympathomimetics) in the number of patients with urinary retention (risk ratio 0.55, 95% confidence interval [CI] 0.3-0.98, p = 0.04, low quality of evidence). There was no difference in mean postvoid volume overall (MD -41.4 ml, 95% CI -92.0 to 9.1, p = 0.11, low quality of evidence). There was a significant difference at up to 1 week post-intervention, favoring parasympathomimetics (MD -77.5 ml, 95% CI -90.9 to -64.1, p < 0.001, low quality of evidence), but no difference at 1 month post-intervention. There was no difference in adverse events (odds ratio 1.19, 95% CI 0.62-2.28, p = 0.6, moderate quality of evidence). CONCLUSIONS: The evidence supporting the use of parasympathomimetics is of low quality, with relatively short follow-up durations. Overall, it is not possible to draw clear evidence-based conclusions from the current literature, presenting the use of parasympathomimetics for treating underactive bladder as a key area that requires future well-controlled clinical trials.

Comparing the Effect of Neostigmine and Metoclopramide on Gastric Residual Volume of Mechanically Ventilated Patients in Intensive Care Unit: A Double-Blind Randomized Clinical Trial.

INTRODUCTION: The gastric residual volume (GRV) monitoring in patients with mechanical ventilation (MV) is a common and important challenge. The purpose of this study was to compare the effect of neostigmine and metoclopramide on GRV among MV patients in the intensive care unit (ICU). METHODS: In a double-blind randomized clinical trial, a total of 200 mechanically ventilated ICU patients with GRV > 120 ml (6 hours after the last gavage) were randomly assigned into two groups (A and B) with 100 patients in each group. Patients in groups A and B received intravenous infusion of neostigmine at a dose of 2.5 mg/100 ml normal saline and metoclopramide at a dose of 10 mg/100 ml normal saline, within 30 minutes, respectively. GRV was evaluated 5 times for each patient, once before the intervention and 4 times (at 3, 6, 9, and 12 hours) after the intervention. In addition, demographic characteristics including age and gender, as well as severity illness based on the sequential organ failure assessment score (SOFA), were initially recorded for all patients. RESULTS: After adjusting of demographic and clinical characteristics (age, gender, and SOFA score), the generalized estimating equation (GEE) model revealed that neostigmine treatment increased odds of GRV improvement compared to the metoclopramide group (OR = 2.45, 95% CI: 1.60-3.76, P < 0.001). However, there is a statistically significant time trend (within-subject differences or time effect) regardless of treatment groups (P < 0.001). CONCLUSION: According to the results, although neostigmine treatment significantly improved GRV in more patients in less time, within 12 hours of treatment, all patients in both groups had complete recovery. Considering that there was no significant difference between the two groups in terms of side effects, it seems that both drugs are effective in improving the GRV of ICU patients.

Comparison of neuromuscular blockade recovery co-administered with neostigmine and different doses of calcium gluconate: a randomized control trial.

BACKGROUND: Calcium increases the probability of transmitter release at the neuromuscular junction. It is not known whether there is a dose-dependent relationship between the dosage of calcium gluconate and the probability of transmitter release for non-depolarizing neuromuscular blockade (NMB) recovery by acetylcholinesterase inhibitors (AchEIs). This study compared the neuromuscular recovery time and the incidence of postoperative residual curarization (PORC) according to the dosage of calcium gluconate co-administered with neostigmine in three patient groups. METHODS: Patients were randomly allocated to a control group, a 5 mg/kg calcium gluconate group (calcium 5 group), or a 10 mg/kg calcium gluconate group (calcium 10 group). In patients with a TOF ratio (TOFr) between 0.2-0.7, 0.04 mg/kg of neostigmine was administered and both 0.2 mg of glycopyrrolate and 0.4 mg of atropine per 1 mg of neostigmine were administered. And additional 5 or 10 mg/kg of calcium gluconate were administrated to the calcium 5 and 10 groups. The primary endpoint was neuromuscular recovery time (the time between reversal and TOFr≥0.9). The secondary endpoints were the incidence of PORC at 5, 10, and 20 min after reversal administration and the train-of-four ratio (TOFr) at each time point. RESULTS: The neuromuscular recovery time was 5.3 min in the control group, 3.9 min in the calcium 5 group, and 4.1 min in the calcium 10 group, respectively (P = 0.004). The incidence of PORC at 5 min after neostigmine administration was 12 in the control group, 4 in the calcium 5 group, and 4 in the calcium 10 group, respectively, with statistical significance (P = 0.014). CONCLUSIONS: The co-administration of calcium gluconate with neostigmine safely promoted early NMB recovery, and the neuromuscular recovery time of the calcium 10 group tended to be more evenly distributed than that of the calcium 5 group. TRIAL REGISTRATION: https://cris.nih.go.kr/cris/index.jsp(KCT0004182 ). Date of registration: August 122,019.

Postoperative interventions for preventing bladder dysfunction after radical hysterectomy in women with early-stage cervical cancer.

BACKGROUND: Bladder dysfunction is a common complication following radical hysterectomy, caused by the damage to pelvic autonomic nerves that innervate the muscles of the bladder, urethral sphincter, and pelvic floor fasciae. Bladder dysfunction increases the rates of urinary tract infection, hospital visits or admission, and patient dissatisfaction. In addition, bladder dysfunction can also negatively impact patient quality of life (QoL). Several postoperative interventions have been proposed to prevent bladder dysfunction following radical hysterectomy. To our knowledge, there has been no systematic review evaluating the effectiveness and safety of these interventions for preventing bladder dysfunction following radical hysterectomy in women with cervical cancer. OBJECTIVES: To evaluate the effectiveness and safety of postoperative interventions for preventing bladder dysfunction following radical hysterectomy in women with early-stage cervical cancer (stage IA2 to IIA2). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 4) in the Cochrane Library, MEDLINE via Ovid (1946 to April week 2, 2020), and Embase via Ovid (1980 to 2020, week 16). We also checked registers of clinical trials, grey literature, conference reports, and citation lists of included studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) evaluating the effectiveness and safety of any type of postoperative interventions for preventing bladder dysfunction following a radical hysterectomy in women with stage IA2 to IIA2 cervical cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently selected potentially relevant RCTs, extracted data, assessed risk of bias, compared results, and made judgments on the quality and certainty of the evidence. We resolved any disagreements through discussion or consultation with a third review author. Outcomes of interest consisted of spontaneous voiding recovery one week after the operation, quality of life (QoL), adverse events, post-void residual urine volume one month after the operation, urinary tract infection over the one month following the operation, and subjective urinary symptoms. MAIN RESULTS: We identified 1464 records as a result of the search (excluding duplicates). Of the 20 records that potentially met the review criteria, we included five reports of four studies. Most of the studies had unclear risks of selection and reporting biases. Of the four studies, one compared bethanechol versus placebo and three studies compared suprapubic catheterisation with intermittent self-catheterisation. We identified two ongoing studies. Bethanechol versus placebo The study reported no information on the rate of spontaneous voiding recovery at one week following the operation, QoL, adverse events, urinary tract infection in the first month after surgery, and subjective urinary symptoms for this comparison. The volume of post-void residual urine, assessed at one month after surgery, among women receiving bethanechol was lower than those in the placebo group (mean difference (MD) -37.4 mL, 95% confidence interval (CI) -60.35 to -14.45; one study, 39 participants; very-low certainty evidence). Suprapubic catheterisation versus intermittent self-catheterisation The studies reported no information on the rate of spontaneous voiding recovery at one week and post-void residual urine volume at one month following the operation for this comparison. There was no difference in risks of acute complication (risk ratio (RR) 0.77, 95% CI 0.24 to 2.49; one study, 71 participants; very low certainty evidence) and urinary tract infections during the first month after surgery (RR 0.77, 95% CI 0.53 to 1.13; two studies, 95 participants; very- low certainty evidence) between participants who underwent suprapubic catheterisation and those who underwent intermittent self-catheterisation. Available data were insufficient to calculate the relative measures of the effect of interventions on QoL and subjective urinary symptoms. AUTHORS' CONCLUSIONS: None of the included studies reported rate of spontaneous voiding recovery one week after surgery, time to a post-void residual volume of urine of 50 mL or less, or post-void residual urine volume at 6 and 12 months after surgery, all of which are important outcomes for assessing postoperative bladder dysfunction. Limited evidence suggested that bethanechol may minimise the risk of bladder dysfunction after radical hysterectomy by lowering post-void residual urine volume. The certainty of this evidence, however, was very low. The effectiveness of different types of postoperative urinary catheterisation (suprapubic and intermittent self-catheterisation) remain unproven.

Progressive cardiorespiratory dysfunction in Kv1.1 knockout mice may provide temporal biomarkers of pending sudden unexpected death in epilepsy (SUDEP): The contribution of orexin.

OBJECTIVE: Immediately preceding sudden unexpected death in epilepsy (SUDEP), patients experienced a final generalized tonic-clonic seizure (GTCS), rapid ventilation, apnea, bradycardia, terminal apnea, and asystole. Whether a progressive pathophysiology develops and increases risk of SUDEP remains unknown. Here, we determined (a) heart rate, respiratory rate, and blood oxygen saturation (SaO2 ) in low-risk and high-risk knockout (KO) mice; and (b) whether blocking receptors for orexin, a cardiorespiratory neuromodulator, influences cardiorespiratory function mice or longevity in high-risk KO mice. METHODS: Heart rate and SaO2 were determined noninvasively with ECGenie and pulse oximetry. Respiration was determined with noninvasive airway mechanics technology. The role of orexin was determined within subject following acute treatment with a dual orexin receptor antagonist (DORA, 100 mg/kg). The number of orexin neurons in the lateral hypothalamus was determined with immunohistochemistry. RESULTS: Intermittent bradycardia was more prevalent in high-risk KO mice, an effect that may be the result of increased parasympathetic drive. High-risk KO mice had more orexin neurons in the lateral hypothalamus. Blocking of orexin receptors differentially influenced heart rate in KO, but not wild-type (WT) mice. When DORA administration increased heart rate, it also decreased heart rate variability, breathing frequency, and/or hypopnea-apnea. Blocking orexin receptors prevented the methacholine (MCh)-induced increase in breathing frequency in KO mice and reduced MCh-induced seizures, via a direct or indirect mechanism. DORA improved oxygen saturation in KO mice with intermittent hypoxia. Daily administration of DORA to high-risk KO mice increased longevity. SIGNIFICANCE: High-risk KO mice have a unique cardiorespiratory phenotype that is characterized by progressive changes in five interdependent endpoints. Blocking of orexin receptors attenuates some of these endpoints and increases longevity, supporting the notion that windows of opportunity for intervention exist in this preclinical SUDEP model.

Comparison of the Effects of Neostigmine and Sugammadex on Colonic Anastomotic Strength in Rats.

BACKGROUND: After colorectal surgery, anastomotic leakage is a major cause of mortality and morbidity. There are many factors affecting anastomotic leakage. It is known that agents such as neostigmine that is used to reverse neuromuscular blockade have certain effects on anastomosis. In our study, in which we planned to test this hypothesis, we aimed to compare the possible effects of different doses of sugammadex and neostigmine on colon anastomosis strength in a colonic resection anastomosis model in rats. MATERIALS AND METHODS: Forty adult Wistar albino male rats were divided into five groups as control (group C), Sugammadex 16 mg/kg (group SL), sugammadex 96 mg/kg (group SH), neostigmine 0.3 µmol/kg (group NL), and neostigmine 1.5 µmol/kg (group NH). The transverse colons of all rats were resected, and colonic anastomosis was performed. Appropriate drug doses according to the groups were given on the postoperative seventh day, and tissue hydroxyproline (TH) level and anastomotic bursting pressure were measured. RESULTS: Anastomotic bursting pressure values were statistically significantly different between the groups (P = 0.001). The bursting pressure in group SH was significantly higher compared with group C, group NL, and group NH. The hydroxyproline values were statistically significantly different between the groups (P = 0.015). According to the post hoc test results, the difference was between group SH and group C (P = 0.007). There were no significant differences between the other groups (P > 0.05). There was no significant difference in terms of intra-abdominal adhesion rates between the groups. CONCLUSIONS: In our study, we found that low and high doses of neostigmine had no variable effect on anastomosis, but high dose of sugammadex (96 mg/kg) had an increasing effect on intestinal anastomosis strength.

Evaluation of Neuromuscular Blockade Reversal on Postoperative Mechanical Ventilation Time in a Cardiovascular Surgery Population.

OBJECTIVE: To report on postoperative outcomes related to the administration of neostigmine for reversal of nondepolarizing neuromuscular blocking agents in cardiovascular surgery patients, with a specific focus on the duration of postoperative mechanical ventilation as the primary endpoint. DESIGN: A retrospective cohort study design was followed to achieve the study objectives. SETTING: This was a single-center, chart review study conducted at a large academic medical center of adult patients post-cardiovascular surgery. PARTICIPANTS: Patients were included if they had received a bolus dose of perioperative nondepolarizing neuromuscular blocking agent and underwent one of the targeted cardiovascular surgeries. INTERVENTIONS: Final analysis comprised of 175 patients, 95 of whom received neostigmine and 80 who did not receive neostigmine. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was the duration of postoperative mechanical ventilation. When controlling for all covariates, neostigmine use was associated with a 0.34-hour reduction (∼20.4 min) in duration of mechanical ventilation (parameter estimate: 0.66, 95% confidence interval 0.49-0.89; p = 0.0071). More patients who received neostigmine met the early extubation benchmark of less than 6 hours (55 v 34 patients; p = 0.04). Finally, neostigmine use was not found to be associated with increased risk of respiratory complications or postoperative nausea and/or vomiting. CONCLUSIONS: The use of neostigmine was found to have a protective effect on the duration of postoperative mechanical ventilation without increasing the risk of adverse complications.

The effect of astragaloside IV on JAK2-STAT6 signalling pathway in mouse model of ovalbumin-induced asthma.

Asthma is a chronic inflammatory lung disease of the airway; the incidence and prevalence of asthma remain high worldwide. Astragaloside IV (AS-IV) is the main active constituent of Astragalus membranaceus. Accumulating evidence suggests that AS-IV possesses anti-inflammatory and anti-asthmatic ability, but the potential molecular mechanism is required to further clarify. In this study, the anti-asthmatic effects of AS-IV on mice with ovalbumin (OVA)-induced allergic inflammation were analysed. We analysed airway hyperresponsiveness (AHR), numbers of inflammatory cells, inflammation situation in lung tissue and cytokines level in bronchoalveolar lavage fluid (BALF) between OVA-induced mice with and without AS-IV treatment. Moreover, we explored the possible signalling pathway behind the anti-asthmatic effects. Our results revealed that AS-IV treatment ameliorates airway inflammation and AHR in an OVA-induced asthma model. Besides, AS-IV treatment inhibits the interleukin (IL)-4, -5 and -13 production, and further study indicated that AS-IV treatment downregulates the expression level of p-JAK2/p-STAT6 proteins. Taken together, the present study suggested that the inhibitory effects of AS-IV on asthma therapy are at least partially involved in inhibiting the JAK2/STAT6 signalling pathway.

A randomized-controlled, double-blind study to evaluate the efficacy of caudal midazolam, ketamine and neostigmine as adjuvants to bupivacaine on postoperative analgesic in children undergoing lower abdominal surgery.

• Background: Caudal epidural is the most commonly used technique for the management of postoperative pain in children. The aim of the present study was to assess and compare the efficacy of caudal bupivacaine as a postoperative analgesic alone or combined with midazolam, ketamine, and neostigmine in pediatric patients undergoing lower abdominal surgery. METHODS: Eighty pediatric patients categorized under the American Society of Anesthesiologists Physical Status I and II Classification System, who have been scheduled to undergo lower abdominal surgery were randomly designated into four groups to receive caudal block with either 1 ml/kg of 0.25% caudal bupivacaine for group B, 1 ml/kg of 0.25% caudal bupivacaine mixed with 2 µg/kg neostigmine for group BN, 1 ml/kg of 0.25% caudal bupivacaine mixed with 0.5 mg/kg ketamine for group BK or 1 ml/kg of 0.25% caudal bupivacaine mixed with 50 mcg/kg midazolam for group BM. Postoperative analgesia was examined by a blinded anesthetist utilizing a Revised Faces Pain Scale.Consumption of the total amount of rescue analgesic each 24 h, postoperative time to requirement of the first dose and any adverse effects were noted. RESULTS: The four groups were comparable as regards age, sex, weight, duration of surgery, heart rate, blood pressure and the time from induction of anesthesia to response to voice. The Revised Faces Pain Scale was 2.6±1.5 in group BN, 3.1±1.8 in group BM, 4.4±2.4 in group BK, and 5.6±1.3 in group B (p=0.005). Postoperative duration of analgesia was 433±68 min, 769±118 min, 1097±126 min and 1254±176 min in groups B, BK, BM and BN respectively (P=0.001). The dose of rescue analgesic within 24 h in group B was significantly higher than those of the other three groups (P<0.05). CONCLUSION: Addition of either neostigmine, midazolam, or ketamine to caudal bupivacaine extended analgesia time and decreased rescue analgesic compared to bupivacaine alone in children who underwent lower abdominal surgery.

New classes of glaucoma medical treatment

Glaucoma is a progressive degenerative disease of the optic nerve head, characterized by a specific pattern of axonal loss and visual field deterioration. This review aims at introducing the different novel pharmacologic agents for its treatment, as well as their mechanisms. Most glaucoma patients require lifelong care and individualized treatment. Intraocular pressure (IOP), which is regulated by aqueous humor production, outflow via the trabecular meshwork (parasympathomimetics only) and uveoscleral outflow pathways, is currently the only treatable target for glaucoma treatment. Conventional glaucoma medications are categorized as β blockers, α agonists, carbonic anhydrase inhibitors, parasympathomimetics, and prostaglandin analogues. The development of basic research-derived novel classes of pharmacologic agents features novel action mechanisms, which are different from those of conventional medications. New classes of recently approved or clinical trial-tested medications include Rho-kinase inhibitors, nitric oxide donors, adenosine agonists, and prostaglandin analogs targeting E-type prostanoid receptors, etc. Their integration and future development will facilitate the expansion and customization of therapeutic options.

Association between normal tension glaucoma and the risk of Alzheimer's disease: a nationwide population-based cohort study in Taiwan.

OBJECTIVES: To investigate a possible association between normal tension glaucoma (NTG) and an increased risk of developing Alzheimer's disease (AD). DESIGN: Retrospective cohort study. SETTING: NTG group and the comparison group were retrieved from the whole population of the Taiwan National Health Insurance Research Database from 1 January 2001 to 31 December 2013. PARTICIPANTS: A total of 15 317 subjects with NTG were enrolled in the NTG group, and 61 268 age-matched and gender-matched subjects without glaucoma were enrolled in the comparison group. PRIMARY AND SECONDARY OUTCOME MEASURES: Kaplan-Meier curves were generated to compare the cumulative hazard of AD between the two groups. A multivariable Cox regression analysis was used to estimate the adjusted hazard ratios (HRs) of AD, adjusted for diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke. Furthermore, risk factors for developing AD among the NTG group were investigated. RESULTS: The mean age of the cohort was 62.1±12.5 years. Patients with NTG had significantly higher proportions of diabetes, hypertension, hyperlipidaemia, coronary artery disease and stroke than the comparisons. Patients with NTG had a significantly higher cumulative hazard for AD than the comparisons (p<0.0001). In the multivariable Cox regression after adjustment for confounders, the NTG group had a significantly higher risk of AD (adjusted HR 1.52; 95% CI 1.41 to 1.63). Moreover, in the NTG group, when we compared the effects of different types of glaucoma eye drops, none of the eye drops used were significant risk factors or protective factors for AD. CONCLUSIONS: People with NTG are at a significantly greater risk of developing AD compared with individuals without glaucoma. Among patients with NTG, none of the glaucoma eye drops used significantly changed the risk of subsequent AD.

Possible role of hydrogen sulfide as an endogenous relaxation factor in the rat bladder and prostate.

AIMS: To clarify the roles of hydrogen sulfide (H2 S), an endogenous gasotransmitter, in the rat bladder and prostate, we investigated the distribution of enzymes related to H2 S biosynthesis (cystathionine ß-synthase [CBS], cystathionine γ-lyase [CSE], 3-mercaptopyruvate sulfurtransferase [MPST], cysteine aminotransferase [CAT], and D-amino acid oxidase [DAO]) and the content of H2 S. We also investigated the effects of H2 S donors (NaHS and GYY4137) on the contractility of both tissues and on micturition. METHODS: The distribution of these enzymes was investigated by real-time PCR, Western blot, and immunohistochemistry. Tissue H2 S content was measured by the methylene blue method. The effects of NaHS (1 × 10-9 to 3 × 10-4 M) were evaluated on carbachol (10-5 M)-induced pre-contracted bladder strips, and on noradrenaline (10-5 M)-induced pre-contracted prostate strips, which were pretreated with propranolol (10-6 M). In addition, in urethane-anesthetized male Wistar rats, the effects of intravesically instilled GYY4137 (10-8 , 10-7 , and 10-6 M) on micturition were evaluated by cystometry. RESULTS: MPST and CAT were detected in the bladder and prostate, CBS was only detected in the prostate, while CSE and DAO were not detected in both tissues. Immunoreactivity of these enzymes was mainly detected in the urothelium and smooth muscle layer of the bladder and in the prostate glandular epithelium. H2 S was detected in both tissues. NaHS dose-dependently induced relaxation of pre-contracted bladder and prostate strips. Intravesically instilled GYY4137 significantly prolonged intercontraction intervals. CONCLUSIONS: It is possible that H2 S can function as an endogenous relaxation factor in the rat bladder and prostate.

Management of rocuronium neuromuscular block using a protocol for qualitative monitoring and reversal with neostigmine.

BACKGROUND: Neuromuscular block using subjective monitoring and neostigmine reversal is commonly associated with postoperative residual neuromuscular block. We tested whether a protocol for the management of neuromuscular block that specified appropriate dosing and optimal neostigmine reversal was associated with a reduction in postoperative residual neuromuscular block. METHODS: Rocuronium administration was guided by surgical requirements and based on the ideal body weight, with dose reductions for female sex and age >55 yr. Neostigmine was administered in adjusted doses after a train-of-four count of four was confirmed at the thumb. The protocol ensured a minimum of 10 min between neostigmine administration and tracheal extubation. We measured the postoperative residual neuromuscular block in patients undergoing abdominal surgery before and after introduction of the protocol. Pre-specified primary and secondary endpoints were incidence of postoperative residual neuromuscular block and severe postoperative residual neuromuscular block at the time of tracheal extubation, defined as normalised train-of-four ratios <0.9 and <0.7, respectively. RESULTS: The incidence of postoperative residual neuromuscular block at tracheal extubation was 14/40 (35%) for patients managed according to the protocol compared with 22/38 (58%) for patients in the control group, odds ratio of 0.39, and 95% confidence interval of 0.14-1.07; P=0.068. The incidence of severe postoperative residual neuromuscular block at tracheal extubation showed a highly significant difference, odds ratio=0.06, and confidence interval of 0.00-0.43; P=0.001. CONCLUSIONS: The incidence of severe postoperative residual neuromuscular block was significantly reduced after the protocol was introduced. Given the limitations inherent in this before-and-after study, further research is needed to confirm these results. CLINICAL TRIAL REGISTRATION: NCT02660398.

Postoperative complications with neuromuscular blocking drugs and/or reversal agents in obstructive sleep apnea patients: a systematic review.

BACKGROUND: Neuromuscular blocking drugs (NMBD) are administered intra-operatively to facilitate intubation and to achieve muscle relaxation for surgical procedures. Incomplete reversal of NMBD can lead to adverse events in the postoperative period. Patients with obstructive sleep apnea (OSA) may be at higher risk of complications related to the use of NMBD. The objectives of this systematic review were to determine whether: 1) OSA patients are at higher risk of postoperative complications from the use of NMBD than non-OSA patients, and 2) the choice of NMBD reversal agent affects the risk of postoperative complications in OSA patients. METHODS: A literature search of multiple databases was conducted up to April 2017. The inclusion criteria were: (1) adult surgical patients (≥18 years old) with OSA diagnosed by polysomnography, or history, or suspected by screening questionnaire; (2) patients who were given NMBD and/or NMBD reversal agents intraoperatively; (3) reports on postoperative adverse events, particularly respiratory events were available; (4) published studies were in English; and (5) RCTs or observational cohort studies. The quality of evidence was determined by the Oxford Center for Evidence Based Medicine levels of evidence. RESULTS: Out of 4123 studies, five studies (2 RCTs and 3 observational studies) including 1126 patients were deemed eligible. These studies were heterogeneous precluding a meta-analysis of the results. Two of three studies (1 RCT, 2 observational studies) reported that OSA patients given NMBD may be at higher risk of developing postoperative pulmonary complications (PPCs) like hypoxemia, residual neuromuscular blockade or respiratory failure compared to non-OSA patients. Two studies (1 RCT, 1 observational study) reported that OSA patients who were reversed with sugammadex vs. neostigmine had less PPCs and chest radiographic changes, but the quality of the included studies was Oxford level of evidence: low to moderate. CONCLUSIONS: OSA patients who receive intraoperative NMBD may be at higher risk for postoperative hypoxemia, respiratory failure and residual neuromuscular blockade compared to non-OSA patients. There is some, albeit very limited evidence that NMBD reversal with sugammadex may be associated with less PPCs than neostigmine in patients with OSA. More high-quality studies are needed.

Are There Pharmacotherapeutic Options for Underactive Bladder?

Currently, underactive bladder, the symptom-based correlate of the urodynamic diagnosis of detrusor underactivity, has no effective drug treatments. Use of sympathomimetics, targeting cholinergic receptors, is not supported by current evidence. Several potential targets are the subject of ongoing investigation.

Sudden-onset unilateral ptosis induced by pituitary Macroadenoma, with false-positive jolly and neostigmine tests.

The development of ptosis as a consequence of pituitary tumor is an exceptionally rare occurrence. Here, we describe the case of sudden-onset unilateral ptosis induced by pituitary macroadenoma. The condition was characterized by false-positive Jolly and neostigmine tests. These findings mimic oculomotor nerve palsy and make the correct diagnostics rather challenging. The case points to the fact that patients with acquired ptosis need detailed neuroophthalmological examination.