Minimizing Lung Injury During Laparoscopy in Head-Down Tilt: A Physiological Cohort Study.

BACKGROUND: Increased intra-abdominal pressure during laparoscopy induces atelectasis. Positive end-expiratory pressure (PEEP) can alleviate atelectasis but may cause hyperinflation. Cyclic opening of collapsed alveoli and hyperinflation can lead to ventilator-induced lung injury and postoperative pulmonary complications. We aimed to study the effect of PEEP on atelectasis, lung stress, and hyperinflation during laparoscopy in the head-down (Trendelenburg) position. METHODS: An open-label, repeated-measures, interventional, physiological cohort trial was designed. All participants were recruited from a single tertiary Belgian university hospital. Twenty-three nonobese patients scheduled for laparoscopy in the Trendelenburg position were recruited.We applied a decremental PEEP protocol: 15 (high), 10 and 5 (low) cm H 2 O. Atelectasis was studied with the lung ultrasound score, the end-expiratory transpulmonary pressure, the arterial oxygen partial pressure to fraction of inspired oxygen concentration (P ao2 /Fi o2 ) ratio, and the dynamic respiratory system compliance. Global hyperinflation was evaluated by dead space volume, and regional ventilation was evaluated by lung ultrasound. Lung stress was estimated using the transpulmonary driving pressure and dynamic compliance. Data are reported as medians (25th-75th percentile). RESULTS: At 15, 10, and 5 cm H 2 O PEEP, the respective measurements were: lung ultrasound scores (%) 11 (0-22), 27 (11-39), and 53 (42-61) ( P < .001); end-expiratory transpulmonary pressures (cm H 2 O) 0.9 (-0.6 to 1.7), -0.3 (-2.0 to 0.7), and -1.9 (-4.6 to -0.9) ( P < .001); P ao2 /Fi o2 ratios (mm Hg) 471 (435-538), 458 (410-537), and 431 (358-492) ( P < .001); dynamic respiratory system compliances (mL/cm H 2 O) 32 (26-36), 30 (25-34), and 27 (22-30) ( P < .001); driving pressures (cm H 2 O) 8.2 (7.5-9.5), 9.3 (8.5-11.1), and 11.0 (10.3-12.2) ( P < .001); and alveolar dead space ventilation fractions (%) 10 (9-12), 10 (9-12), and 9 (8-12) ( P = .23). The lung ultrasound score was similar between apical and basal lung regions at each PEEP level ( P = .76, .37, and .76, respectively). CONCLUSIONS: Higher PEEP levels during laparoscopy in the head-down position facilitate lung-protective ventilation. Atelectasis and lung stress are reduced in the absence of global alveolar hyperinflation.

The Relationship Between Esophageal Pressure and Diaphragm Thickening Fraction in Spontaneously Breathing Sedated Children: A Feasibility Study.

OBJECTIVES: Diaphragm ultrasound is a novel alternative to esophageal pressure measurements in the evaluation of diaphragm function and activity, but data about its reliability in a pediatric setting are lacking. We aimed to compare the esophageal pressure swing (∆P es , gold standard) with the diaphragmatic thickening fraction (DTF) as a measure of inspiratory effort in sedated children. Additionally, we studied the effect of positive end-expiratory pressure (PEEP) on the end-expiratory thickness of the diaphragm (DT ee ). DESIGN: Prospective open-label non-randomized interventional physiological cohort study. SETTING: Operating room in tertiary academic hospital. PATIENTS: Children 28 days to 13 years old scheduled for elective surgery with general anesthesia, spontaneously breathing through a laryngeal mask airway, were eligible for inclusion. Exclusion criteria were disorders or previous surgery of the diaphragm, anticipated difficult airway or acute cardiopulmonary disease. All measurements were performed prior to surgery. INTERVENTIONS: Patients were subjected to different levels of respiratory load, PEEP and anesthetic depth in a total of seven respiratory conditions. MEASUREMENTS AND MAIN RESULTS: The esophageal pressure and diaphragm thickening fraction were simultaneously recorded for five breaths at each respiratory condition. The relation between ∆P es and DTF was studied in a mixed model. We analyzed 407 breaths in 13 patients. Both DTF ( p = 0.03) and ∆Pes ( p = 0.002) could detect respiratory activity, and ∆P es and DTF were associated across respiratory conditions ( p < 0.001; R2 = 31%). With increasing inspiratory load, ∆P es increased significantly, while DTF did not ( p = 0.08). Additionally, DT ee did not differ significantly between 10, 5, and 0 cm H 2 O PEEP ( p = 0.08). CONCLUSIONS: In spontaneously breathing sedated children and across different respiratory conditions, DTF could differentiate minimal or no inspiratory effort from substantial inspiratory effort and was associated with ∆P es . Increased efforts resulted in higher ∆P es but not larger DTF.

Sugammadex for reversal of neuromuscular blockade in pediatric patients: Results from a phase IV randomized study.

BACKGROUND: Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants. AIM: To assess sugammadex for reversal of neuromuscular blockade in pediatric participants. METHODS: This was a randomized, phase IV, active comparator-controlled, double-blind study. Participants aged 2 to <17 years, under moderate or deep neuromuscular blockade, were administered sugammadex (2 or 4 mg/kg) or neostigmine (50 µg/kg; for moderate neuromuscular blockade only). Predefined adverse events of clinical interest, including clinically relevant bradycardia, hypersensitivity, and anaphylaxis, were monitored. The primary efficacy endpoint was time to recovery to a train-of-four ratio of ≥0.9 in participants receiving sugammadex 2 mg/kg versus neostigmine for reversal of moderate neuromuscular blockade, analyzed by analysis of variance adjusted for neuromuscular blocking agent and age. RESULTS: Of 288 randomized participants, 272 completed the study and 276 were included in the analyses. Clinically relevant bradycardia was experienced by 2.0%, 1.6%, and 5.9% of participants in the sugammadex 2 mg/kg, sugammadex 4 mg/kg, and neostigmine groups, respectively. No hypersensitivity or anaphylaxis events were observed. Recovery to a train-of-four ratio of ≥0.9 with sugammadex 2 mg/kg was faster than neostigmine (1.6 min, 95% CI 1.3 to 2.0 vs. 7.5 min, 95% CI 5.6 to 10.0; p < .0001) and was comparable to sugammadex 4 mg/kg (2.0 min, 95% CI 1.8 to 2.3). CONCLUSIONS: Pediatric participants recovered from rocuronium- or vecuronium-induced moderate neuromuscular blockade significantly faster with sugammadex 2 mg/kg than with neostigmine. Time to reversal of deep neuromuscular blockade with sugammadex 4 mg/kg was consistent with that of moderate neuromuscular blockade reversal. No meaningful differences in clinically relevant bradycardia, hypersensitivity, or anaphylaxis were seen with sugammadex vs neostigmine. These results support the use of sugammadex for reversal of moderate and deep rocuronium- and vecuronium-induced neuromuscular blockade in patients aged 2 to <17 years. CLINICAL TRIAL REGISTRATION: NCT03351608/EudraCT 2017-000692-92.

Neuromuscular-blocking agents for tracheal intubation in pediatric patients (0-12 years): A systematic review and meta-analysis.

BACKGROUND: The benefit of using neuromuscular-blocking agents to facilitate tracheal intubation in pediatric patients remains unclear due to variations in design, treatments, and results among trials. By combining the available evidence, we aimed to establish whether scientific findings are consistent and can be generalized across various populations, settings, and treatments. METHODS: A systematic search for randomized controlled trials, related to the use of neuromuscular-blocking agents for tracheal intubation in American Society of Anesthesiologists class I-II participants (0-12 years), was performed. We considered all randomized controlled trials that studied whether intubation conditions and hemodynamics obtained by using neuromuscular-blocking agents were equivalent to those that were achieved without neuromuscular-blocking agents. We combined the outcomes in Review Manager 5.3 (RevMan, The Cochrane Collaboration) by pairwise random-effects meta-analysis using a risk ratio (RR) for intubation conditions and mean difference for hemodynamic values (mean [95% Confidence Intervals]). Heterogeneity among trials was explored using sensitivity analyses. RESULTS: We identified 22 eligible randomized controlled trials with 1651 participants. Overall, the use of a neuromuscular-blocking agent was associated with a clinically important increase in the likelihood of both excellent (RR = 1.41 [1.19-1.68], I2  = 76%) and acceptable (RR = 1.13 [1.07-1.19], I2  = 68%) intubating conditions. There is strong evidence that both unacceptable intubation conditions (RR = 0.35 [0.22-0.46], I2  = 23%) and failed first intubation attempts (RR = 0.25 [0.14-0.42], I2  = 0%) were less likely to occur when a neuromuscular-blocking agent was used compared with when it was not. Higher systolic or mean arterial pressures (mean difference = 13.3 [9.1-17.5] mm Hg, I2  = 69%) and heart rates (mean difference = 15.9 [11.0-20.8] beats/min, I2  = 75%) as well as a lower incidence of arrhythmias were observed when tracheal intubation was facilitated by neuromuscular-blocking agents. CONCLUSION: The use of a neuromuscular-blocking agent during light-to-moderate depth of anesthesia can improve the quality as well as the success rate of tracheal intubation and is associated with better hemodynamic stability during induction of anesthesia.

Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial.

BACKGROUND: The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission. METHODS: This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath. RESULTS: For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3-9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group. CONCLUSIONS: In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013-001926-25 on October 10, 2013.

Electromyographic activity of the diaphragm during neostigmine or sugammadex-enhanced recovery after neuromuscular blockade with rocuronium: a randomised controlled study in healthy volunteers.

BACKGROUND: The use of neuromuscular blocking agents has been associated with severe postoperative respiratory morbidity. Complications can be attributed to inadequate reversal, and reversal agents may themselves have adverse effects. OBJECTIVE: To compare the electromyographic activity of the diaphragm (EMGdi) during recovery from neuromuscular blockade using neostigmine and sugammadex. The hypothesis was that there would be better neuromuscular coupling of the diaphragm when sugammadex was used. DESIGN: A randomised, controlled, parallel-group, single-centre, double-blinded study. SETTING: District general hospital in Belgium. PARTICIPANTS: Twelve healthy male volunteers. INTERVENTIONS: Individuals were anaesthetised with propofol and remifentanil. After rocuronium 0.6 mg kg, a transoesophageal electromyography (EMG) recorder was inserted. For reversal of neuromuscular blockade, volunteers received sugammadex 2 mg kg (n = 6) or neostigmine 70 µg kg (n = 6). MAIN OUTCOME MEASURES: EMGdi, airway pressure and flow were continuously measured during weaning from the ventilator until tracheal extubation. Arterial blood gas samples were obtained for PaO2 and PaCO2 analysis at the first spontaneous breathing attempt and after tracheal extubation. RESULTS: During weaning, 560 breaths were retained for analysis. The median (95% CI) peak EMGdi was 1.1 (0.9 to 1.5) µV in the neostigmine group and 1.6 (1.3 to 1.9) µV in the sugammadex group (P < 0.001). Individuals in the neostigmine group had 125 of 228 (55%) breaths with associated EMGdi at least 1 µV vs. 220 of 332 (66%) breaths in the sugammadex group (P = 0.008). The median (95% CI) tidal volume was 287 (256 to 335) ml after neostigmine and 359 (313 to 398) ml after sugammadex (P = 0.013). The median (95% CI) PaO2 immediately after extubation was 30.5 (22.8 to 37.1) kPa after sugammadex vs. 20.7 (12.9 to 27.5) kPa after neostigmine (P = 0.03). CONCLUSION: EMGdi, tidal volume and PaO2 following tracheal extubation were increased after sugammadex compared with neostigmine, reflecting diaphragm-driven inspiration after sugammadex administration. Sugammadex may free more diaphragmatic acetylcholine receptors than neostigmine, which has an indirect effect. TRIAL REGISTRATION: EudraCT ref: 2013-002078-30.

Paediatric perioperative hypersensitivity: the performance of the current consensus formula and the effect of uneventful anaesthesia on serum tryptase.

Background: Paired sampling of acute (aST) and basal (bST) serum tryptase has been recommended when investigating patients with a suspected perioperative hypersensitivity (POH) reaction. In the current consensus formula, an aST value exceeding (1.2×bST+2) confirms mast cell activation. The current consensus formula has been validated in adults but not in children. Methods: We prospectively included 96 children who underwent uneventful anaesthesia and sampled serum tryptase at baseline and 60-90 min after induction. Tryptase changes were then compared with those in 94 children with suspected POH who were retrospectively included from four reference centres in Belgium, France, and Denmark. Results: We observed a median decrease in serum tryptase during uneventful anaesthesia of 0.41 µg L-1 (-15.9%; P<0.001). The current consensus formula identified mast cell activation in 31.9% of paediatric POH patients. After generating receiver operating characteristic curves through 100 repeated five-fold cross-validation, aST>bST+0.71 was identified as the optimal cut-off point to identify mast cell activation. This new paediatric formula has higher sensitivity than the current consensus formula (53.2% vs 31.9%, P<0.001) with a specificity of 96.9%. Analysis in the subpopulation where a culprit was identified and in grade 3-4 reactions similarly yielded higher sensitivity for the new paediatric formula when compared with the current consensus formula (85.3% vs 61.8%; P=0.008 and 78.0% vs 48.8%; P<0.001, respectively). Internally cross-validated sensitivity and specificity were 53.3% and 93.3%, respectively. Conclusions: This is the first study suggesting the need for an adjusted formula in children to identify perioperative mast cell activation as tryptase is significantly lowered during uneventful anaesthesia. We propose a new formula (aST>bST+0.71) which performs significantly better than the current consensus formula in our multicentric paediatric population.

A Multi-Country Survey on the Availability of Intraoperative Use of Echocardiography for Noncardiac Surgery.

BACKGROUND: This survey aimed to explore the availability and accessibility of echocardiography during noncardiac surgery worldwide. METHODS: An internet-based 45-item survey was sent, followed by reminders from August 30, 2021, to August 20, 2022. RESULTS: 1189 responses were received from 62 countries. Nearly seventy-one percent of respondents had intraoperatively used transesophageal or transthoracic echocardiography (TEE and TTE, respectively) for monitoring or examination. The unavailability of echocardiography machines (30.3%), lack of trained personnel (30.2%), and absence of clinical indications (22.6%) were the top 3 reasons for not using intraoperative echocardiography in noncardiac surgery. About 61.5% of participants had access to at least one echocardiography machine. About 41% had access to at least 1 TEE probe, and 62.2% had access to at least 1 TTE probe. Seventy-four percent of centers had a procedure to request intraoperative echocardiography if needed for noncardiac cases. Intraoperative echocardiography service was immediately available in 58% of centers. CONCLUSIONS: Echocardiography machines and skilled echocardiographers are still unavailable at many centers worldwide. National societies should aim to train a critical mass of certified TEE/TTE anesthesiologists and provide all anesthesiologists access to perioperative TEE/TTE machines in anesthesiology departments, considering the increasing number of older and sicker surgical patients scheduled for noncardiac surgery.

Sleep endoscopy with simulation bite for prediction of oral appliance treatment outcome.

The aim of this study was to assess the value of drug-induced sleep endoscopy (DISE) using a custom-made simulation bite in maximal comfortable protrusion (MCP) of the mandible, in the prediction of treatment outcome for obstructive sleep apnea (OSA) with a mandibular advancement device (MAD). Two hundred patients (74% male; age 46 ± 9 years; apnea-hypopnea index [AHI] 19 ± 13 h(-1) sleep; body mass index [BMI] 27 ± 4 kg m(-2) ) with sleep-disordered breathing underwent DISE with a simulation bite in MCP. One hundred and thirty-five patients with an established diagnosis of OSA commenced MAD treatment. The associations between the findings during DISE with simulation bite and treatment outcome were evaluated. Treatment response was defined as a reduction in AHI following MAD treatment of ≥ 50% compared to baseline. Overall MAD treatment response in the studied population was 69%. The results of this study demonstrated a statistically significant association between a positive effect of the simulation bite on the upper airway patency during DISE and treatment response with MAD (P < 0.01). The results of this study suggest that the use of a simulation bite in maximal comfortable protrusion (MCP) of the mandible, as used during DISE in patients with OSA, tends to be effective in predicting treatment response of MAD treatment.

The Tritube: Facilitating Upper Airway Surgery With an Ultrathin Cuffed Airway Device.

The Tritube is a narrow-bore cuffed tracheal tube (outer diameter 4.4 mm and inner diameter ~2.4 mm) that permits effective alveolar gas exchange using flow-controlled ventilation. Constant gas flow delivers physiological minute volumes, within preset pressure limits, and applies suction to the airway during expiration. The technique has attracted interest for laryngotracheal microsurgery as it provides superior surgical exposure and avoids many of the complications associated with high-frequency jet ventilation. Cuff inflation protects the lower airway and produces a motionless operating field. We describe the structure of the device, discuss its benefits, and suggest how it should be used clinically.

Evaluating the Predictive Value of a Short Preoperative Holistic Risk Factor Screening Questionnaire in Preventing Persistent Pain in Elective Adult Surgery: Study Protocol for a Prospective Observational Pragmatic Trial [PERISCOPE].

Background: The global incidence of persistent pain after surgery is approximately 10%, with considerable clinical and socioeconomic impacts. Despite identifying many risk factors in its development and the challenging management of the often neuropathic pain complaints, preoperative recognition of high-risk patients in various surgical populations using a standardized risk factor assessment questionnaire is lacking. This study evaluates the predictive value of a short holistic risk factor screening questionnaire as a first step in preventing and treating persistent pain in adults undergoing elective surgery. Methods: This prospective observational pragmatic trial will include 560 adults undergoing elective surgery. The primary endpoint is the evaluation of the predictive value of the screening questionnaire, including the optimal cut-off determination in terms of sensitivity and specificity for inclusion in a perioperative high-vigilance program. Secondary endpoints are postoperative pain (intensity and characterization using the NRS and DN4), postoperative analgesic usage, and well-being using the EQ-5D-5 L. To assess the performance of the designed screening questionnaire in the identification of psychosocial pain aspects, HADs, and STAI-trait are being surveyed. Additionally, the multidimensional pain inventory (MPI, part 1) is being used to assess the impact of pain on daily life in patients. Discussion: This pragmatic clinical trial will evaluate a short preoperative screening questionnaire to predict persistent postoperative pain after elective surgery in adults. Suppose high-risk patients could be identified earlier using this short preoperative holistic screening questionnaire. In that case, it might contribute to a more widespread implementation of standardized preoperative assessment and awareness for preventing persistent postoperative pain. Trial Registration: Local ethics committee: B3002022000112. ClinicalTrials.gov identifier: NCT05526976. Registered on: 02 September 2022. Start of recruitment: 22 December 2022. Trial Status: This paper is based on protocol version 4.0. The first patient was assigned to the research project on the 22 of December 2022. We anticipate including the last patient in October 2023 and plan to finalize the study by January 2024.

A quarter of a century fundamental and translational research in perioperative hypersensitivity and anaphylaxis at the Antwerp university hospital, a Belgian Centre of Excellence of the World Allergy Organization.

Perioperative hypersensitivity constitutes an important health issue, with potential dramatic consequences of diagnostic mistakes. However, safe and correct diagnosis is not always straightforward, mainly because of the application of incorrect nomenclature, absence of easy accessible in-vitro/ex-vivo tests and uncertainties associated with the non-irritating skin test concentrations. In this editorial we summarize the time line, seminal findings, and major realizations of 25 years of research on the mechanisms, diagnosis, and management of perioperative hypersensitivity.

Pupillary reflex dilation and pain index evaluation during general anesthesia using sufentanil: a double-blind randomized controlled trial.

Aim: In a single-center, double-blind, randomized controlled trial, we evaluated whether pupillometry-controlled use of sufentanil is better than free-choice administration of sufentanil by anesthesiologists. Patients & methods: 61 patients undergoing daycare gynecological or abdominal surgery were enrolled. A pupillometry pain index score chart was introduced for administration guidance of sufentanil. Results: The first objective, patient well-being, did not show a significant difference with painkiller usage and health state index at day 1 postoperatively. Second, we experienced difficulty in interpretation of the pupillometry score. Third, opioid usage was higher in the intervention group (20.1 vs 14.8 mcg; p = 0.017). Conclusion: The use of pupillometry and pain index chart for bolus sufentanil with our protocol showed an unwanted higher sufentanil usage without a significant difference in patient wellbeing. (Ethics Committee EC17/28/319 of the University Hospital of Antwerp. Registration at clinicaltrials.gov NCT03248908).

Communication with patients under general anesthesia is impossible. A potential solution is to measure pain. One of seven commercially available options is to use a pupillometer. Automated painful stimuli are given and the dilation of the pupil is measured. We hoped to use this method to better control the dose of the opioid sufentanil. During daycare gynecological and abdominal procedures, we had a 25% higher sufentanil usage in the intervention group. We experienced difficulties in reaching the right pain score in both groups. The well-being of the patients, namely pain and painkiller usage at day 1 after surgery, did not show any significant difference. With our protocol, there is no benefit to controlling the dose of sufentanil by pupillometer measurement.

Worsening COVID-19 Disease Course After Surgical Trauma: A Case Series.

Introduction: Current guidelines from the American Society of Anesthesiologists recommend postponing elective surgery on COVID-19-positive patients for a minimum of four to twelve weeks. However, literature focusing on the outcomes of COVID-19-positive patients undergoing surgery is scarce. In this case series, the outcome of asymptomatic COVID-19 patients undergoing acute or semi-urgent surgery was evaluated. Case Presentation: A case series of four patients between 32 and 82 years old with a confirmed SARS-CoV-2 infection undergoing acute or semi-urgent surgery was presented here. All four patients were asymptomatic for COVID-19, developing severe respiratory failure following endo CABG, caesarian section, a thyroidectomy, or abdominal surgery. ICU admission, together with invasive ventilation, was necessary for all patients. Two patients required venovenous extracorporeal membrane oxygenation treatment. A mortality of 50% was observed. Conclusions: In conclusion, the present case series suggests that elective surgery in asymptomatic SARS-CoV-2 infected patients might elicit an exacerbated COVID-19 disease course. This study endorses the current international guidelines recommending postponing elective surgery for SARS-CoV-2-positive patients for seven weeks, depending on the severity of the surgery and perioperative morbidities, to minimize postoperative mortality.

Effect of Oral Allylnitrile Administration on Cochlear Functioning in Mice Following Comparison of Different Anesthetics for Hearing Assessment.

Background: Allylnitrile is a compound found in cruciferous vegetables and has the same lethality and toxic effects as the other nitriles. In 2013, a viable allylnitrile ototoxicity mouse model was established. The toxicity of allylnitrile was limited through inhibition of CYP2E1 with trans-1,2-dichloroethylene (TDCE). The allylnitrile intoxication model has been extensively tested in the 129S1 mouse strain for vestibular function, which showed significant HC loss in the vestibular organ accompanied by severe behavioral abnormalities. However, the effect of allylnitrile on auditory function remains to be evaluated. Commonly used anesthetics to conduct hearing measurements are isoflurane and ketamine/xylazine anesthesia but the effect of these anesthetics on hearing assessment is still unknown. In this study we will evaluate the otovestibular effects of oral allylnitrile administration in mice. In addition, we will compare the influence of isoflurane and ketamine/xylazine anesthesia on hearing thresholds. Methods and Materials: Fourteen Coch+/- CBACa mice were randomly allocated into an allylnitrile (n = 8) and a control group (n = 6). Baseline measurements were done with isoflurane and 1 week later under ketamine/xylazine anesthesia. After baseline audiovestibular measurements, mice were co-administered with a single dose of allylnitrile and, to reduce systemic toxicity, three intraperitoneal injections of TDCE were given. Hearing loss was evaluated by recordings of auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). Specific behavioral test batteries for vestibular function were used to assess alterations in vestibular function. Results: Hearing thresholds were significantly elevated when using isoflurane anesthesia compared to ketamine/xylazine anesthesia for all frequencies of the ABR and the mid-to-high frequencies in DPOAE. Allylnitrile-treated mice lacked detectable ABR thresholds at each frequency tested, while DPOAE thresholds were significantly elevated in the low-frequency region of the cochlea and completely lacking in the mid-to high frequency region. Vestibular function was not affected by allylnitrile administration. Conclusion: Isoflurane anesthesia has a negative confounding effect on the measurement of hearing thresholds in mice. A single oral dose of allylnitrile induced hearing loss but did not significantly alter vestibular function in mice. This is the first study to show that administration of allylnitrile can cause a complete loss of hearing function in mice.

A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia.

BACKGROUND: Sugammadex is the first of a new class of selective muscle relaxant binding drugs developed for the rapid and complete reversal of neuromuscular blockade induced by rocuronium and vecuronium. Many studies have demonstrated a dose-response relationship with sugammadex for reversal of neuromuscular blockade in patients induced and maintained under propofol anesthesia. However, sevoflurane anesthesia, unlike propofol, can prolong the effect of neuromuscular blocking drugs (NMBDs) such as rocuronium and vecuronium. METHODS: We designed this randomized, open-label, dose-response trial to explore the dose-response relationship of sugammadex for the reversal of deep neuromuscular blockade induced by rocuronium or vecuronium under propofol-induced and sevoflurane-maintained anesthesia. As a secondary objective, the safety variables of sugammadex were evaluated. After anesthesia induction with propofol, 102 patients aged > or = 20 and < 65 yr were randomized to receive a single bolus dose of rocuronium 0.9 mg/kg (n = 50) or vecuronium 0.1 mg/kg (n = 52), followed by maintenance doses (rocuronium 0.1-0.2 mg/kg or vecuronium 0.02-0.03 mg/kg) as needed. Neuromuscular blockade was monitored using acceleromyography. After the last dose of NMBD, at 1-2 posttetanic counts, a single bolus dose of sugammadex 0.5, 1.0, 2.0, 4.0, or 8.0 mg/kg was administered. The primary efficacy variable was time from start of sugammadex administration to recovery of the T(4)/T(1) ratio to 0.9. RESULTS: The per-protocol population consisted of 48 patients in the rocuronium group and 47 in the vecuronium group. A dose-response effect was demonstrated for decreased mean time to recovery of the T(4)/T(1) ratio to 0.9 with increasing sugammadex dose in both NMBD groups (per-protocol population): rocuronium group, 79.8 (SD 33.0) min (sugammadex 0.5 mg/kg) to 1.7 (0.7) min (4.0 mg/kg) and 1.1 (0.3) min (8.0 mg/kg subgroup); vecuronium group, 68.4 (31.9) min (0.5 mg/kg) to 3.3 (3.5) min (4.0 mg/kg), and 1.7 (0.8) min (8.0 mg/kg subgroup). Neuromuscular monitoring showed recurrent neuromuscular blockade in 5 patients, all in the rocuronium group (2 given sugammadex 0.5 mg/kg and 3 given 1.0 mg/kg), but there were no clinical events attributable to recurrent or residual neuromuscular blockade. CONCLUSION: Sugammadex at doses of > or = 4 mg/kg provides rapid reversal of deep rocuronium- and vecuronium-induced neuromuscular blockade under sevoflurane maintenance anesthesia.

Prevalence of obstructive sleep apnea in children with laryngomalacia and value of polysomnography in treatment decisions.

OBJECTIVES: Children with laryngomalacia may present with obstructive sleep apnea (OSA). The role of polysomnography (PSG) in treatment decision making for laryngomalacia is not well defined. We aimed to investigate the prevalence of OSA in children with laryngomalacia and the role of PSG in treatment decision. METHODS: Retrospective medical record review of children with laryngomalacia, confirmed by direct laryngoscopy, during a period of 3 years. Demographic data, presenting symptoms, severity classification, comorbidities and pre- and postoperative PSG data were retrieved and analyzed. Data are expressed as a median (25th - 75th percentile). RESULTS: Forty-six patients were with diagnosed laryngomalacia between March 2016 and April 2019. A complete data set was available for 44 patients, 24 males and 20 females. The median age at the time of PSG was 12 weeks (6.3-29.8). Thirty-four children (77.4%) were diagnosed with concomitant OSA. A diagnosis of OSA changed the severity classification and treatment decision in 24 cases (54.5%). Twenty-three patients underwent supraglottoplasty, five patients were treated with continuous positive airway pressure (CPAP) and nine patients had both treatments. Seven patients received conservative treatment. The obstructive apnea/hypopnea index decreased from 8.9 events/hour (4.4-12.1) to 2.4 events/hour (1.5-4.4) after supraglottoplasty (p = 0.009). CONCLUSIONS: A diagnosis of OSA was established in 77.4% of patients with larygomalacia The presence of OSA may increase the severity of symptoms in laryngomalacia, leading to a transition from watchful-waiting to active intervention with CPAP therapy or supraglottoplasty. Supraglottoplasty is a safe and effective surgical procedure for laryngomalacia. When performed in the setting of laryngomalacia with concomitant OSA, it also significantly improves OSA symptomatology.

Real-time Monitoring of Cerebral Blood Flow and Cerebral Oxygenation During Rapid Ventricular Pacing in Neurovascular Surgery: A Pilot Study.

BACKGROUND: Rapid ventricular pacing (RVP) can be used to produce short periods of flow arrest during dissection or rupture of a cerebral aneurysm but carries the risk of inducing cerebral ischemia. This study evaluates the intraoperative effect of RVP on local cerebral blood flow (CBF) and cerebral oxygenation during neurovascular surgery. MATERIALS AND METHODS: Five patients undergoing elective cerebrovascular surgery were included in a single-center prospective study. RVP was applied in pacing periods of 40 seconds with 30% and 100% FiO2. Regional cerebral oxygenation was monitored using a Foresight near-infrared spectroscopy sensor. A Clark-type electrode and a thermal diffusion microprobe located in the white matter were used to monitor brain tissue pO2 and CBF, respectively. RESULTS: CBF response to RVP closely followed the blood pressure pattern and resulted in a low-flow state. Unlike CBF, brain tissue pO2 and regional cerebral oxygenation showed a delayed response to RVP, decreasing beyond the pacing period and slowly recovering after RVP cessation. We found a correlation between brain tissue pO2 and regional cerebral oxygenation. Increasing the inspired oxygen concentration had a positive impact on absolute regional cerebral oxygenation and brain tissue pO2 values, but the pattern resulting from applying RVP remained unaltered. CONCLUSIONS: RVP reduces CBF and cerebral oxygenation. Brain tissue pO2 and regional cerebral oxygenation are correlated but unlike CBF respond to RVP in a delayed manner. Further research is required to evaluate the impact of longer RVP bursts on brain oxygenation.