OxVent: Design and evaluation of a rapidly-manufactured Covid-19 ventilator.

BACKGROUND: The manufacturing of any standard mechanical ventilator cannot rapidly be upscaled to several thousand units per week, largely due to supply chain limitations. The aim of this study was to design, verify and perform a pre-clinical evaluation of a mechanical ventilator based on components not required for standard ventilators, and that met the specifications provided by the Medicines and Healthcare Products Regulatory Agency (MHRA) for rapidly-manufactured ventilator systems (RMVS). METHODS: The design utilises closed-loop negative feedback control, with real-time monitoring and alarms. Using a standard test lung, we determined the difference between delivered and target tidal volume (VT) at respiratory rates between 20 and 29 breaths per minute, and the ventilator's ability to deliver consistent VT during continuous operation for >14 days (RMVS specification). Additionally, four anaesthetised domestic pigs (3 male-1 female) were studied before and after lung injury to provide evidence of the ventilator's functionality, and ability to support spontaneous breathing. FINDINGS: Continuous operation lasted 23 days, when the greatest difference between delivered and target VT was 10% at inspiratory flow rates >825 mL/s. In the pre-clinical evaluation, the VT difference was -1 (-90 to 88) mL [mean (LoA)], and positive end-expiratory pressure (PEEP) difference was -2 (-8 to 4) cmH2O. VT delivery being triggered by pressures below PEEP demonstrated spontaneous ventilation support. INTERPRETATION: The mechanical ventilator presented meets the MHRA therapy standards for RMVS and, being based on largely available components, can be manufactured at scale. FUNDING: Work supported by Wellcome/EPSRC Centre for Medical Engineering,King's Together Fund and Oxford University.

Bedside monitoring of lung volume available for gas exchange.

BACKGROUND: Bedside measurement of lung volume may provide guidance in the personalised setting of respiratory support, especially in patients with the acute respiratory distress syndrome at risk of ventilator-induced lung injury. We propose here a novel operator-independent technique, enabled by a fibre optic oxygen sensor, to quantify the lung volume available for gas exchange. We hypothesised that the continuous measurement of arterial partial pressure of oxygen (PaO2) decline during a breath-holding manoeuvre could be used to estimate lung volume in a single-compartment physiological model of the respiratory system. METHODS: Thirteen pigs with a saline lavage lung injury model and six control pigs were studied under general anaesthesia during mechanical ventilation. Lung volumes were measured by simultaneous PaO2 rate of decline (VPaO2) and whole-lung computed tomography scan (VCT) during apnoea at different positive end-expiratory and end-inspiratory pressures. RESULTS: A total of 146 volume measurements was completed (range 134 to 1869 mL). A linear correlation between VCT and VPaO2 was found both in control (slope = 0.9, R2 = 0.88) and in saline-lavaged pigs (slope = 0.64, R2 = 0.70). The bias from Bland-Altman analysis for the agreement between the VCT and VPaO2 was - 84 mL (limits of agreement ± 301 mL) in control and + 2 mL (LoA ± 406 mL) in saline-lavaged pigs. The concordance for changes in lung volume, quantified with polar plot analysis, was - 4º (LoA ± 19°) in control and - 9° (LoA ± 33°) in saline-lavaged pigs. CONCLUSION: Bedside measurement of PaO2 rate of decline during apnoea is a potential approach for estimation of lung volume changes associated with different levels of airway pressure.

Dexmedetomidine infusion for analgesia and prevention of emergence agitation in children with obstructive sleep apnea syndrome undergoing tonsillectomy and adenoidectomy.

BACKGROUND: Dexmedetomidine, a specific α(2) agonist, has an analgesic-sparing effect and reduces emergence agitation. We compared an intraoperative dexmedetomidine infusion with bolus fentanyl to reduce perioperative opioid use and decrease emergence agitation in children with obstructive sleep apnea syndrome undergoing adenotonsillectomy (T&A). METHODS: One hundred twenty-two patients with obstructive sleep apnea syndrome undergoing T&A, ages 2 to 10 years, completed this prospective, randomized, U.S. Food and Drug Administration-approved study. After mask induction with sevoflurane, group D received IV dexmedetomidine 2 µg · kg(-1) over 10 minutes, followed by 0.7 µg · kg(-1) · h(-1), and group F received IV fentanyl bolus 1 µg · kg(-1). Anesthesia was maintained with sevoflurane, oxygen, and nitrous oxide. Fentanyl 0.5 to 1 µg · kg(-1) was given to subjects in both groups for an increase in heart rate or systolic blood pressure 30% above preincision values that continued for 5 minutes. Observers in the postanesthesia care unit (PACU) were blinded to treatment groups. Pain was evaluated using the objective pain score in the PACU on arrival, at 5 minutes, at 15 minutes, then every 15 minutes for 120 minutes. Emergence agitation was evaluated at the same intervals by 2 scales: the Pediatric Anesthesia Emergence Delirium scale and a 5-point scale described by Cole. Morphine (0.05 to 0.1 mg · kg(-1)) was given for pain (score >4) or severe agitation (score 4 or 5) lasting more than 5 minutes. RESULTS: In group D, 9.8% patients needed intraoperative rescue fentanyl in comparison with 36% in group F (P = 0.001). Mean systolic blood pressure and heart rate were significantly lower in group D (P < 0.05). Minimum alveolar concentration values were significantly different between the 2 groups (P = 0.015). The median objective pain score was 3 for group D and 5 for group F (P = 0.001). In group D, 10 (16.3%) patients required rescue morphine, in comparison with 29 (47.5%) in group F (P = 0.002). The frequency of severe emergence agitation on arrival in the PACU was 18% in group D and 45.9% in group F (P = 0.004); at 5 minutes and at 15 minutes, it was lower in group D (P = 0.028). The duration of agitation on the Cole scale was statistically lower in group D (P = 0.004). In group D, 18% of patients and 40.9% in group F had an episode of Spo(2) below 95% (P = 0.01). CONCLUSIONS: An intraoperative infusion of dexmedetomidine combined with inhalation anesthetics provided satisfactory intraoperative conditions for T&A without adverse hemodynamic effects. Postoperative opioid requirements were significantly reduced, and the incidence and duration of severe emergence agitation was lower with fewer patients having desaturation episodes.

Distraction with a hand-held video game reduces pediatric preoperative anxiety.

BACKGROUND: Video games have received widespread application in health care for distraction and behavior modification therapy. Studies on the effect of cognitive distraction during the preoperative period are lacking. We evaluated the efficacy of an interactive distraction, a hand-held video game (VG) in reducing preoperative anxiety in children. METHODS: In a randomized, prospective study of 112 children aged 4-12 years undergoing outpatient surgery, anxiety was assessed after admission and again at mask induction of anesthesia, using the modified Yale Preoperative Anxiety Scale (mYPAS). Postoperative behavior changes were assessed with the Posthospital Behavior Questionnaire (PHBQ). Patients were randomly assigned to three groups: parent presence (PP), PP+a hand-held VG, and PP+0.5 mg.kg-1 oral midazolam (M) given>20 min prior to entering the operating room. RESULTS: There was a statistically significant increase in anxiety (P<0.01) in groups M and PP at induction of anesthesia compared with baseline, but not in VG group. VG patients demonstrated a decrease in anxiety from baseline (median change in mYPAS -3), the difference compared with PP (+11.8) was significant (P=0.04). The change in anxiety in the M group (+7.3) was not statistically different from other groups. Sixty-three percent of patients in VG group had no change or decrease in anxiety after treatment, compared with 26% in M group and 28% in PP group (P=0.01). There was no difference in anxiety changes between female and male patients. CONCLUSIONS: A hand-held VG can be offered to most children as a low cost, easy to implement, portable, and effective method to reduce anxiety in the preoperative area and during induction of anesthesia. Distraction in a pleasurable and familiar activity provides anxiety relief, probably through cognitive and motor absorption.

Determination of 9-hydroxyellipticine by redox colorimetry.

The chemical reactions involved in the decomposition of 9-hydroxyellipticine (9-OH-E), an anticancer agent, in polar solvents is explained. The reactions, which involve the formation of 9-oxo-ellipticine and the addition of a nucleophilic acid on the C10 site of the heterocyclic system, have been used to measure 9-OH-E quantitatively by colorimetry in solution and by reflection on paper surfaces. A method for the stabilization of 9-OH-E in polar solvents is proposed.

Studies on acetylcholine sensor and its analytical application based on the inhibition of cholinesterase.

Acetylcholine esterase electrodes, based on glass, Pd/PdO and Ir/IrO2 electrodes as pH sensor, using the immobilized acetylcholine esterase in acrylamide-methacrylamide hydrazides prepolymer are reported and compared. New data on the analysis of nicotine, fluoride ion, and some organophosphorus compounds are reported using the present AChE sensor based on the inhibition of the immobilized acetylcholine esterase. Reactivation of immobilized AChE after inhibition with reversible inhibitor, i.e. nicotine and fluoride ion is carried out using a mixture of working buffer and acetylcholine, whereas reactivation after inhibition with irreversible inhibitor, i.e. organophosphorus compounds is carried out using a mixture of acetylcholine and pyridine-2-aldoxime methiodide (PAM). The detection limits for the nicotine and fluoride ion are found to be 10(-5) M whereas for paraoxon, methyl parathion and malathion are found to be 10(-9) M and 10(-10) M.