Effect of different lung recruitment strategies and airway device on oscillatory mechanics in children under general anaesthesia.

BACKGROUND: Atelectasis has been reported in 68 to 100% of children undergoing general anaesthesia, a phenomenon that persists into the recovery period. Children receiving recruitment manoeuvres have less atelectasis and fewer episodes of oxygen desaturation during emergence. The optimal type of recruitment manoeuvre is unclear and may be influenced by the airway device chosen. OBJECTIVE: We aimed to investigate the different effects on lung mechanics as assessed by the forced oscillation technique (FOT) utilising different recruitment strategies: repeated inflations vs. one sustained inflation and different airway devices, a supraglottic airway device vs. a cuffed tracheal tube. DESIGN: Pragmatic enrolment with randomisation to the recruitment strategy. SETTING: We conducted this single-centre trial between February 2020 and March 2022. PARTICIPANTS: Seventy healthy patients (53 boys) aged between 2 and 16 years undergoing general anaesthesia were included. INTERVENTIONS: Forced oscillations (5 Hz) were superimposed on the ventilator waveform using a customised system connected to the anaesthesia machine. Pressure and flow were measured at the inlet of the airway device and used to compute respiratory system resistance and reactance. Measurements were taken before and after recruitment, and again at the end of surgery. MAIN OUTCOME MEASURES: The primary endpoint measured is the change in respiratory reactance. RESULTS: Statistical analysis (linear model with recruitment strategy and airway device as factors) did not show any significant difference in resistance and reactance between before and after recruitment. Baseline reactance was the strongest predictor for a change in reactance after recruitment: prerecruitment Xrs decreased by mean (standard error) of 0.25 (0.068) cmH 2 O s l -1 per  1 cmH 2 O -1  s l -1 increase in baseline Xrs ( P  < 0.001). After correcting for baseline reactance, the change in reactance after recruitment was significantly lower for sustained inflation compared with repeated inflation by mean (standard error) 0.25 (0.101) cmH 2 O ( P  = 0.0166). CONCLUSION: Although there was no significant difference between airway devices, this study demonstrated more effective recruitment via repeated inflations than sustained inflation in anaesthetised children. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12619001434189.

Jelly snakes to reduce early postoperative vomiting in children after adenotonsillectomy: The randomized controlled snakes trial.

BACKGROUND: Despite the use of dual antiemetic agents, postoperative nausea and vomiting (PONV) occurs in an unacceptably large number of patients post-tonsillectomy. There has been increased interest in alternative and non-pharmacological treatments for PONV e.g., chewing gum. We investigated if chewing a large confectionary jelly snake had prophylactic antiemetic effects postoperatively in young children. METHODS: Prospective, open-label randomised controlled trial of 240 patients, 2-16 years. Patients administered a confectionary jelly snake to chew postoperatively were compared with a control group. The primary outcome was the number of episodes of vomiting within 6 h of the operation on an intention-to-treat basis. SECONDARY OUTCOMES: incidence of nausea, vomiting at 6 and 24 h, rescue antiemetic use, acceptability, delayed discharge. RESULTS: 233 patients were randomised to receive the confectionary snake (snake group, 118) or standard care (control group, 115). The number of vomiting episodes in 6 h was similar between groups on an intention-to-treat basis, with 39 episodes across 22 (19%) patients in the control group and 31 across 19 (16%) patients in the snake group (p = 0.666). From post anaesthetic care unit until 24 h there was no difference in doses of antiemetics or delayed discharge due to PONV. A secondary as per protocol analysis did not change this result. CONCLUSIONS: Chewing of confectionery jelly snakes within one hour of waking following adenotonsillectomy with vapour-maintained anaesthesia and two prophylactic antiemetics did not further reduce the incidence of early vomiting. REGISTRATION: prospective registration at the Australia and New Zealand Clinical Trials Registry (ACTRN12618000637246).

Predicting obstructive sleep apnoea and perioperative respiratory adverse events in children: role of upper airway collapsibility measurements.

BACKGROUND: Obstructive sleep apnoea (OSA) and perioperative respiratory adverse events are significant risks for anaesthesia in children undergoing adenotonsillectomy. Upper airway collapse is a crucial feature of OSA that contributes to respiratory adverse events. A measure of upper airway collapsibility to identify undiagnosed OSA can help guide perioperative management. We investigated the utility of pharyngeal closing pressure (PCLOSE) for predicting OSA and respiratory adverse events. METHODS: Children scheduled for elective adenotonsillectomy underwent in-laboratory polysomnography 2-12 weeks before surgery. PCLOSE measurements were obtained while the child was anaesthetised and breathing spontaneously just before surgery. Logistic regression was used to assess the predictive performance of PCLOSE for detecting OSA and perioperative respiratory adverse events after adjusting for potential covariates. RESULTS: In 52 children (age, mean [standard deviation] 5.7 [1.8] yr; 20 [38%] females), airway collapse during PCLOSE was observed in 42 (81%). Of these, 19 of 42 (45%) patients did not have OSA, 15 (36%) had mild OSA, and eight (19%) had moderate-to-severe OSA. All 10 children with no evidence of airway collapse during the PCLOSE measurements did not have OSA. PCLOSE predicted moderate-to-severe OSA (odds ratio [OR] 1.71; 95% confidence interval [CI]: 1.2-2.8; P=0.011). All children with moderate-to-severe OSA could be identified at a PCLOSE threshold of -4.0 cm H2O (100% sensitivity), and most with no or mild OSA were ruled out (64.7% specificity; receiver operating characteristic/area under the curve=0.857). However, there was no significant association between respiratory adverse events and PCLOSE (OR 1.0; 95% CI: 0.8-1.1; P=0.641). CONCLUSIONS: Measurement of PCLOSE after induction of anaesthesia can reliably identify moderate or severe OSA but not perioperative respiratory adverse events in children before adenotonsillectomy. CLINICAL TRIAL REGISTRATION: ANZCTR ACTRN 12617001503314.

Early life predictors of obstructive sleep apnoea in young adults: Insights from a longitudinal community cohort (Raine study).

OBJECTIVE: Early-life obstructive sleep apnoea (OSA) predictors are unavailable for young adults. This study identifies early-life factors predisposing young adults to OSA. METHODS: This retrospective study included 923 young adults and their mothers from the Western Australian Pregnancy Raine Study Cohort. OSA at 22 years was determined from in-laboratory polysomnography. Logistic regression was used to identify maternal and neonatal factors associated with OSA in young adulthood. RESULTS: OSA was observed in 20.8% (192) participants. Maternal predictors of OSA included gestational diabetes mellitus (odds ratio (OR) 9.54, 95% confidence interval (CI) 1.7, 58.5, P = 0.011), preterm delivery (OR 3.18, 95%CI 1.1,10.5, P = 0.043), preeclampsia (OR 2.95, 95%CI 1.1,8.0, P = 0.034), premature rupture of membranes (OR 2.46, 95%CI 1.2, 5.2, P = 0.015), age ≥35 years (OR 2.28, 95%CI 1.2,4.4, P = 0.011), overweight and obesity (pregnancy BMI≥25 kg/m2) (OR 2.00, 95%CI 1.2,3.2, P = 0.004), pregnancy-induced hypertension (OR 1.89, 95%CI 1.1,3.2, P = 0.019), and Chinese ethnicity (OR 2.36,95%CI 1.01,5.5, P = 0.047). Neonatal predictors included male child (OR 2.10, 95%CI 1.5,3.0, P < 0.0001), presence of meconium-stained liquor during delivery (OR 1.60, 95%CI 1.0,2.5, P = 0.044) and admission to special care nursery (OR 1.51 95%CI 1.0,2.2, P = 0.040). Higher birth lengths reduced OSA odds by 7% for each centimetre (OR 0.93, 95%CI 0.87, 0.99, P = 0.033). CONCLUSIONS: A range of maternal and neonatal factors predict OSA in young adults, including those related to poor maternal metabolic health, high-risk pregnancy and stressful perinatal events. This information could assist in the early identification and management of at-risk individuals and indicates that better maternal health may reduce the likelihood of young adults developing OSA.

A prospective randomised control trial comparing functional with mechanical axis alignment in total knee arthroplasty: study protocol for an investigator initiated trial.

BACKGROUND: A drive to improve functional outcomes for patients undergoing total knee arthroplasty (TKA) has led to alternative alignment being used. Functional alignment (FA) uses intraoperative soft tissue tension to determine the optimal position of the prosthesis within the patient's soft tissue envelope. Angular limits for bone resections are followed to prevent long-term prosthesis failure. This study will use the aid of robotic assistance to plan and implement the final prosthesis position. This method has yet to be compared to the traditional mechanically aligned (MA) knee in a randomised trial. METHODS: A blinded randomised control trial with 100 patients will be undertaken via Perth Hip and Knee Clinic. Fifty patients will undergo a MA TKA and fifty will undergo a FA TKA. Both alignment techniques will be balanced via computer-assisted navigation to assess prosthetic gaps, being achieved via the initial bony resection and further soft tissue releases as required to achieve satisfactory balance. The primary outcome will be the Forgotten Joint Score (FJS) 2 years after surgery, with secondary outcomes being other patient-reported outcome measures, clinical functional assessment, radiographic position and complications. Other data that will be collected will be patient demography (sex, age, level of activity) and medical information (grade of knee injury, any other relevant medical information). The linear statistical model will be fitted to the response (FJS), including all the other variables as covariates. DISCUSSION: Many surgeons are utilising alternative alignment techniques with a goal of achieving better functional outcomes for their patients. Currently, MA TKA remains the gold standard with good outcomes and excellent longevity. There is no published RCTs comparing FA to MA yet and only two registered studies are planned or currently in progress. This study utilises a FA technique which differs from the two studies. This study will help determine if FA TKA has superior functional results for patients. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ANZCTR) http://www.anzctr.org.au : U1111-1257-2291, registered 25th Jan 2021. It is also listed on www.clinicaltrials.gov : NCT04748510.

Prior administration of chocolate improves the palatability of bitter drugs: The Choc-with-Med study.

AIM: The paediatric population has a low adherence and acceptance rate of unpalatable medicines. This study aimed to determine whether eating chocolate immediately prior to drug administration would help to mask the bitter taste of a drug. The difference in taste masking efficacy between white, milk and dark chocolate was a secondary measure outcome. METHODS: A controlled repeated measures crossover taste trial was conducted using a taste panel of 29 young healthy adults who met the criteria to differentiate intensity in bitterness taste. Participants separately tasted solutions of quinine, flucloxacillin and clindamycin using the swill and spit method, singularly and following blinded prior administration of white, milk or dark chocolate. Drug solutions administered without prior chocolate served as controls. Bitterness score for each tasting was recorded using a 5-point scale. RESULTS: Regardless of chocolate type, mean taste scores with prior chocolate for quinine (range 2.00-2.34), clindamycin (3.72-3.83) and flucloxacillin (3.38-3.45) were all lower than mean scores for respective drugs without chocolate (3.24, 4.75 and 4.28, respectively; P < 0.0001 for all comparisons). Dark chocolate was most efficacious for masking the bitter taste of quinine, but the differences in taste masking efficacy between dark, milk and white chocolates were not statistically significant for flucloxacillin and clindamycin. CONCLUSIONS: Prior administration of chocolate results in lower perceived bitterness compared to control tastings of quinine, flucloxacillin and clindamycin solutions; however, there is no clear difference in this effect between the dark, milk and white chocolates used in this study.

Hidden Markov analysis of improved bandwidth mechanosensitive ion channel data.

The gating behaviour of a single ion channel can be described by hidden Markov models (HMMs), forming the basis for statistical analysis of patch clamp data. Extensive improved bandwidth (25 kHz, 50 kHz) data from the mechanosensitive channel of large conductance in Escherichia coli  were analysed using HMMs, and HMMs with a moving average adjustment for filtering. The aim was to determine the number of levels, and mean current, mean dwell time and proportion of time at each level. Parameter estimates for HMMs with a moving average adjustment for low-pass filtering were obtained using an expectation-maximisation algorithm that depends on a generalisation of Baum's forward-backward algorithm. This results in a simpler algorithm than those based on meta-states and a much smaller parameter space; hence, the computational load is substantially reduced. In addition, this algorithm maximises the actual log-likelihood rather than that for a related meta-state process. Comprehensive data analyses and comparisons across all our data sets have consistently shown five subconducting levels in addition to the fully open and closed levels for this channel.

Neutron diffraction structures of water in crystalline hydrates of metal salts.

Neutron diffraction structures of water molecules in crystalline hydrates of metal salts have been collected from the literature up to December 2011. Statistical methods were used to investigate the influence on the water structures of the position and nature of hydrogen bond acceptors and cations coordinated to the water oxygen. For statistical modelling the data were pruned so that only structures with oxygen as hydrogen acceptors, single hydrogen bonds, and no more than two metals or hydrogens coordinated to the water oxygen were included. Multiple linear regression models were fitted with the water OH bond length and bond angle as response variables. Other variables describing the position and nature of the acceptors and ions coordinated to the waters were taken as explanatory variables. These variables were sufficient to give good models for the bond lengths and angles. There were sufficient structures involving coordinated Mg(2+) or Cu(2+) for a separate statistical modelling to be done for these cases.

Hidden Markov analysis of mechanosensitive ion channel gating.

Patch clamp data from the large conductance mechanosensitive channel (MscL) in E. coli was studied with the aim of developing a strategy for statistical analysis based on hidden Markov models (HMMs) and determining the number of conductance levels of the channel, together with mean current, mean dwell time and equilibrium probability of occupancy for each level. The models incorporated state-dependent white noise and moving average adjustment for filtering, with maximum likelihood parameter estimates obtained using an EM (expectation-maximisation) based iteration. Adjustment for filtering was included as it could be expected that the electronic filter used in recording would have a major effect on obviously brief intermediate conductance level sojourns. Preliminary data analysis revealed that the brevity of intermediate level sojourns caused difficulties in assignment of data points to levels as a result of over-estimation of noise variances. When reasonable constraints were placed on these variances using the better determined noise variances for the closed and fully open levels, idealisation anomalies were eliminated. Nevertheless, simulations suggested that mean sojourn times for the intermediate levels were still considerably over-estimated, and that recording bandwidth was a major limitation; improved results were obtained with higher bandwidth data (10 kHz sampled at 25 kHz). The simplest model consistent with these data had four open conductance levels, intermediate levels being approximately 20%, 51% and 74% of fully open. The mean lifetime at the fully open level was about 1 ms; estimates for the three intermediate levels were 54-92 micros, probably still over-estimates.