We assessed the effects of neurokinin (tachykinin) depletion by capsaicin (CAP) treatment on airway inflammation induced by repeated ovalbumin (OA) aerosol exposures (twice a week for 4 wk) in guinea pigs. The animals were then anesthetized, tracheostomized, mechanically ventilated and challenged with ovalbumin aerosol. Maximal values of respiratory system resistance and elastance after antigen challenge were significantly lower in capsaicin-treated guinea pigs than in intact animals (p < 0.001). Morphometric analysis of noncartilaginous airways revealed less intense bronchoconstriction (p < 0.001) and peribronchiolar edema (p < 0.001) in capsaicin-treated guinea pigs. Chronic antigen exposure resulted in a significant increase in lymphocytes and eosinophils both in bronchoalveolar lavage (BAL) fluid and airway wall. Immunohistochemistry with monoclonal antibodies revealed that most of the lymphocytes present in airway wall were CD4+ T cells. Capsaicin treatment resulted in values of CD4+ T cells in airway wall significantly lower than non-capsaicin-treated guinea pigs (p < 0.005). This difference was not observed in eosinophil recruitment. Our results suggest that neurokinin release by sensory nerve terminals results in an amplification of the pulmonary inflammatory changes induced by chronic antigen exposure. In addition, neurokinins play a role in T-cell recruitment induced by chronic allergen exposure.

Consent to participate: Written informed consent was obtained from all subjects or their legally authorised representatives. Consent for publication: Not applicableAvailability of data and material: De-identified data collected during the trial will be made available upon reasonable request to researchers who provide a methodologically sound proposal, after approval by the study authors, and with a signed data access agreement. Questions about data are handled by the corresponding author.

Background: Neuromuscular blocking agents (NMBAs) with a non-depolarising mechanism of action carry the risk of postoperative residual paralysis and are associated with postoperative pulmonary complications (POPC). Owing to the shorter duration of action, the depolarising NMBA succinylcholine may be associated with less postoperative residual paralysis, and hence fewer POPC. We tested the association of succinylcholine administration during anaesthesia and POPC. Methods: In a retrospective cohort study of registry data from two large US academic medical centres, 244 850 adult noncardiac surgical patients undergoing general anaesthesia were included. The primary outcome was POPC, defined as post-extubation haemoglobin oxygen de-saturation to <90%, or re-intubation requiring intensive care unit admission within 7 days after surgery. The association between succinylcholine and POPC and its dose-dependency were tested in a hierarchical fashion using a multivariable logistic regression model. Results: A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [OR Adj ]¼1.11; 95% confidence interval [CI], 1.06e1.16; P<0.001; adjusted risk¼5.18%; 95% CI, 5.06e5.30 without and 5.69%; 95% CI, 5.53e5.85 with succinylcholine), with a dose-dependent relationship (OR Adj ¼1.08; 95% CI, 1.05e1.11 per mg kg À1 ; P<0.001). In patients receiving non-depolarising NMBAs, succinylcholine further increased the risk of POPC (ORAdj¼1.08; 95% CI, 1.03e1.14; P¼0.001). The association between succinylcholine and POPC was modified (P¼0.03 for interaction) by the duration of surgery with higher odds of POPC in patients undergoing surgeries of <2 vs !2 h (OR Adj ¼1.24; 95% CI, 1.15e1.33 and 1.05; 95% CI, 1.00e1.10, respectively). Conclusions: In contrast to our prediction, succinylcholine administration was associated with an increased risk of POPC. This association was dose-dependent and magnified in surgeries of shorter duration.

We studied the effects of selective depletion of neurokinins in sensory nerve fibers by capsaicin treatment on the airway and pulmonary tissue responses to methacholine. Dose-response curves to aerosolized methacholine were performed on anesthetized and mechanically ventilated Wistar rats. Capsaicin (50 mg/kg sc) was administered to 2-day-old rats, and the animals were studied after 12 wk. The response to each dose of methacholine was determined by measuring changes in airway resistance (R(aw)), dynamic pulmonary elastance (Edyn), and pulmonary tissue resistance (Rtis). We calculated sensitivity (Kx) as the concentration of methacholine required for a one-half maximal response and reactivity as the relationship between the maximum response and Kx. Capsaicin treatment resulted in significantly greater values of Kx and lower values of reactivity for R(aw), Edyn, and Rtis compared with control rats. Morphometric analysis of airways showed similar values of the area occupied by smooth muscle but a significantly lower (P < 0.02) area of airway epithelium in capsaicin-treated rats. Our results suggest that methacholine requires capsaicin-sensitive nerves for part of its airway and lung tissue effects.

BACKGROUND: Residual neuromuscular blockade is associated with an increased incidence of postoperative respiratory complications. The REsidual neuromuscular block Prediction Score (REPS) identifies patients at high risk for residual neuromuscular blockade after surgery. METHODS: A total of 101,510 adults undergoing noncardiac surgery under general anesthesia from October 2005 to December 2018 at a tertiary care center in Massachusetts were analyzed for the primary outcome of postoperative respiratory complications (invasive mechanical ventilation requirement within 7 postoperative days or immediate postextubation desaturation [oxygen saturation {Spo 2} <90%] within 10 minutes). The primary objective was to assess the association between the REPS and respiratory complications. The secondary objective was to compare REPS and train-of-four (TOF) ratio <0.90 on the strength of their association with respiratory complications. RESULTS: A high REPS (≥4) was associated with an increase in odds of respiratory complications (adjusted odds ratio [OR], 1.13 [95% confidence interval {CI}, 1.06-1.21]; P < .001). In 6224 cases with available TOF ratio measurements, a low TOF ratio (<0.9) was associated with respiratory complications (adjusted OR, 1.43 [95% CI, 1.11-1.85]; P = .006), whereas a high REPS was not (adjusted OR, 0.96 [95% CI, 0.74-1.23]; P = .73) (P = .018 for comparison between ORs). CONCLUSIONS: The REPS may be implemented as a screening tool to encourage clinicians to use quantitative neuromuscular monitoring in patients at risk of residual neuromuscular blockade. A positive REPS should be followed by a quantitative assessment of the TOF ratio.

BackgroundThis study evaluated the association between neuromuscular blocking agent dose and post‐operative respiratory complications in infants and children.MethodsData from 6507 general anaesthetics provided to children aged 0‐10 years undergoing surgery were analysed to examine the effects of neuromuscular blocking agent dose on post‐operative respiratory complications (primary endpoint) and secondary endpoints. Confounder‐adjusted analyses addressed age, surgical duration, and comorbidity burden.ResultsIn confounder‐adjusted analyses, high doses of neuromuscular blocking agents were associated with higher risk of post‐operative respiratory complications (OR 2.27; 95% CI 1.12‐4.59; P = .022). The effect was modified by age (P‐for‐interaction = .016) towards a more substantial risk in infants ≤1 year (OR 3.84; 95% CI 1.35‐10.94; P = .012), by duration of surgery (P‐for‐interaction = .006) towards a higher difference in odds for surgeries <90 minutes (OR 4.25; 95% CI 1.19‐15.18; P = .026), and by ASA physical status (P‐for‐interaction = .015) with a greater effect among patients with higher operative risk (ASA >1: OR 3.17; 95% CI 1.43‐7.04; P = .005). Neostigmine reversal did not modify the association between neuromuscular blocking agents and post‐operative respiratory complications (P‐for‐interaction = .38). Instrumental variable analysis confirmed that high doses of neuromuscular blocking agents were associated with post‐operative respiratory complications (probit coefficient 0.25; 95% CI 0.04‐0.46; P = .022), demonstrating robust results regarding concerns of unobserved confounding.ConclusionsHigh dose of neuromuscular blocking agents is associated with post‐operative respiratory complications. We have identified subcohorts of paediatric patients who are particularly vulnerable to the respiratory side‐effects of neuromuscular blocking agents: infants, paediatric patients undergoing surgeries of short duration, and those with a high ASA risk score.

CPT Code Procedure Description Cystourethroscopy for treatment of the female urethral syndrome with any or all of the following: urethral meatotomy, urethral dilation, internal urethrotomy, lysis of urethrovaginal septal fibrosis, lateral incisions of the bladder neck, and fulguration of polyp(s) of urethra, bladder neck, and/or trigone Cystourethroscopy, with injection(s) for chemodenervation of the bladder Cystourethroscopy; with ureteral meatotomy, unilateral or bilateral Cystourethroscopy; with resection or fulguration of orthotopic ureterocele(s), unilateral or bilateral Cystourethroscopy; with resection or fulguration of ectopic ureterocele(s), unilateral or bilateral Cystourethroscopy; with incision or resection of orifice of bladder diverticulum, single or multiple Cystourethroscopy, with removal of foreign body, calculus, or ureteral stent from urethra or bladder (separate procedure); simple Cystourethroscopy, with removal of foreign body, calculus, or ureteral stent from urethra or bladder (separate procedure); complicated litholapaxy: crushing or fragmentation of calculus by any means in bladder and removal of fragments; simple or small (less than 2.5 cm) Litholapaxy: crushing or fragmentation of calculus by any means in bladder and removal of fragments; complicated or large (over 2.5 cm) Cystourethroscopy (including ureteral catheterization); with removal of ureteral calculus Cystourethroscopy (including ureteral catheterization); with fragmentation of ureteral calculus (eg, ultrasonic or electro-hydraulic technique) Cystourethroscopy (including ureteral catheterization); with subureteric injection of implant material Cystourethroscopy (including ureteral catheterization); with manipulation, without removal of ureteral calculus Cystourethroscopy, with insertion of indwelling ureteral stent (eg, gibbons or double-j type) Cystourethroscopy with insertion of ureteral guide wire through kidney to establish a percutaneous nephrostomy, retrograde Cystourethroscopy; with treatment of ureteral stricture (eg, balloon dilation, laser, electrocautery, and incision) Cystourethroscopy; with treatment of ureteropelvic junction stricture (eg, balloon dilation, laser, electrocautery, and incision) Cystourethroscopy; with treatment of intra-renal stricture (eg, balloon dilation, laser, electrocautery, and incision) Cystourethroscopy with ureteroscopy; with treatment of ureteral stricture (eg, balloon dilation, laser, electrocautery, and incision) Cystourethroscopy with ureteroscopy; with treatment of ureteropelvic junction stricture (eg, balloon dilation, laser, electrocautery, and incision) Cystourethroscopy with ureteroscopy; with treatment of intra-renal stricture (eg, balloon dilation, laser, electrocautery, and incision) Acute ICD-9 codes within Diagnosis CCS 149: Biliary tract disease 5740 Calculus of gallbladder with acute cholecystitis Calculus of gallbladder with acute cholecystitis without mention of obstruction Calculus of gallbladder with acute cholecystitis with obstruction 5743 Calculus of bile duct with...

IntroductionInsomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients.Methods and analysisIn this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 120 patients, aged 60 years or older, undergoing elective cardiac surgery with planned postoperative admission to the ICU. Participants will be randomised to receive oral suvorexant (20 mg) or placebo one time a day starting the night after extubation. The primary outcome will be wakefulness after persistent sleep onset. The secondary outcome will be total sleep time. Exploratory outcomes will include time to sleep onset, incidence of postoperative in-hospital delirium, number of delirium-free days and subjective sleep quality.Ethics and disseminationEthics approval was obtained through the ‘Committee on Clinical Investigations’ at Beth Israel Deaconess Medical Center (protocol number 2019P000759). The findings will be published in peer-reviewed journals.Trial registration numberThis trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).