A Rabbit Model for the Evaluation of Drugs for Treating the Chronic Phase of Botulism

Antitoxin, the only licensed drug therapy for botulism, neutralizes circulating botulinum neurotoxin (BoNT). However, antitoxin is no longer effective when a critical amount of BoNT has already entered its target nerve cells. The outcome is a chronic phase of botulism that is characterized by prolonged paralysis. In this stage, blocking toxin activity within cells by next-generation intraneuronal anti-botulinum drugs (INABDs) may shorten the chronic phase of the disease and accelerate recovery. However, there is a lack of adequate animal models that simulate the chronic phase of botulism for evaluating the efficacy of INABDs. Herein, we report the development of a rabbit model for the chronic phase of botulism, induced by intoxication with a sublethal dose of BoNT. Spirometry monitoring enabled us to detect deviations from normal respiration and to quantitatively define the time to symptom onset and disease duration. A 0.85 rabbit intramuscular median lethal dose of BoNT/A elicited the most consistent and prolonged disease duration (mean = 11.8 days, relative standard deviation = 27.9%) that still enabled spontaneous recovery. Post-exposure treatment with antitoxin at various time points significantly shortened the disease duration, providing a proof of concept that the new model is adequate for evaluating novel therapeutics for botulism.

Guidelines on analgosedation, monitoring, and recovery time for flexible bronchoscopy: a systematic review

Background Patients undergoing bronchoscopy in spontaneous breathing are prone to hypoxaemia and hypercapnia. Sedation, airway obstruction, and lung diseases impair respiration and gas exchange. The restitution of normal respiration takes place in the recovery room. Nonetheless, there is no evidence on the necessary observation time. We systematically reviewed current guidelines on bronchoscopy regarding sedation, monitoring and recovery. Methods This review was registered at the PROSPERO database (CRD42020197476). MEDLINE and awmf.org were double-searched for official guidelines, recommendation or consensus statements on bronchoscopy from 2010 to 2020. The PICO-process focussed on adults (Patients), bronchoscopy with maintained spontaneous breathing (Interventions), and recommendations regarding the intra- and postprocedural monitoring and sedation (O). The guideline quality was graded. A catalogue of 54 questions was answered. Strength of recommendation and evidence levels were recorded for each recommendation. Results Six guidelines on general bronchoscopy and three expert statements on special bronchoscopic procedures were identified. Four guidelines were evidence-based. Most guidelines recommend sedation to improve the patient’s tolerance. Midazolam combined with an opioid is preferred. The standard monitoring consists of non-invasive blood pressure, and pulse oximetry, furthermore electrocardiogram in cardiac patients. Only one guideline discusses hypercapnia and capnometry, but without consensus. Two guidelines discuss a recovery time of two hours, but a recommendation was not given because of lack of evidence. Conclusion Evidence for most issues is low to moderate. Lung-diseased patients are not represented by current guidelines. Capnometry and recovery time lack evidence. More primary research in these fields is needed so that future guidelines may address these issues, too.

Respiratory physiology

Breathing and normal respiration must be understood by recovery room staff. This chapter explains how patients breathe and what is happening when patterns of respiration alter. Terms that sound complicated, like functional residual capacity, are explained and the way in which breathing is driven from the brain and by chemoreceptors in the lungs is simply described.

Coupling Pressure Sensing with Optical Coherence Tomography to Evaluate the Internal Nasal Valve

Purpose: To evaluate endoscopic long-range optical coherence tomography system combined with a pressure sensor to concurrently measure internal nasal valve cross-sectional area and intraluminal pressure. Methods: A pressure sensor was constructed using an Arduino platform and calibrated using a limiter-controlled vacuum system and industrial absolute pressure gauge. Long-range optical coherence tomography imaging and pressure transduction were performed concurrently in the naris of eight healthy adult subjects during normal respiration and forced inspiration. The internal nasal valve was manually segmented using Mimics software and cross-sectional area was measured. Internal nasal valve cross-sectional area measurements were correlated with pressure recordings. Results: Mean cross-sectional area during forced inspiration was 6.49 mm2. The mean change in pressure between normal respiration and forceful inspiration was 12.27 mmHg. The direct correlation between pressure and cross-sectional area as measured by our proposed system was reproducible among subjects. Conclusions: Our results demonstrate a direct correlation between internal nasal valve cross-sectional area and nasal airflow during inspiration cycles. Endoscopic long-range optical coherence tomography coupled with a pressure sensor serves as a useful tool to quantify the dynamic behavior of the internal nasal valve. Level of Evidence: N/A

Change of Safe Needling Depth at Acupoint GB21 according to Posture and Breathing

Acupoint GB21 (Jianjing) is used for treating back and shoulder pain but is associated with a risk of pneumothorax. We aimed to determine the SND (safe needling depth) at GB21 according to posture and breathing in real time. Ultrasonographic images of GB21 during normal breathing, inspiration, and expiration in a SP (sitting position) were acquired for 52 healthy volunteers. Images were also acquired during normal respiration in the PP (prone position) with arms raised and lowered. The average SND was greater for men than for women (p<0.05). Analysis of variance revealed that the SND was greater for the PP than for the SP (p=0.01 and p<0.05, resp.). Although the SND tended to change according to posture, the average depth tended to deviate widely in some subjects. During breathing, the differences between inspiration and expiration were less than 1 mm in most subjects, but some showed differences more than 4.5 mm. The SND at GB21 was greater in overweight subjects and significantly greater in the PP and during maximal expiration. However, intragroup differences were greater than the intergroup differences. Therefore, it is dangerous to simply apply needling depth on a gender or BMI basis. The practitioner would adjust the SND by examining the individual anatomical structures.

Simulated workplace protection factors for respirators with N95 or higher filters for health care providers in an emergency medical centre: A randomized crossover study

Introduction: Health care providers in emergency medical centres often encounter infected sources during medical procedures; these sources can generate droplets. Wearing respirators could help to protect against infection risk. However, to the best of our knowledge, no previous study has reported the efficacy of N95 or higher respirators for health care providers in emergency medical centres. Methods: A randomized, crossover study of 26 health care providers was conducted to examine the protective performance of respirators. Quantitative fit tests with three types of respirators (cup type, fold type without valve and fold type with valve) were performed using seven exercises. Primary outcomes were the fit factors. Secondary outcomes included the percentage of fit factors above 100 and respirator preference. Results: After excluding one participant, data for 25 participants were analysed. The fit factors and the percentage of fit factors above 100 were higher when participants wore a fold-type respirator (200 fit factors [38.6–200], 100% [0–100]) relative to those for the cup-type respirator (114.0 fit factors [16.0–185.2], 60% [0–100]) and valve-type respirator (84.9 fit factors [14.2–170.8], 23.8 % [0–100]) in normal respiration. There was no clear preference regarding the type of respirator. Conclusion: The type of respirator could influence protective performance for health care providers. Health care providers in emergency medical centres should be aware of and wear the type of respirator that is well-fitted for them in advance.