Apnea management during WATCHMAN device deployment with apneic oxygenation: A case report of three cases.

WATCHMAN is a percutaneous left atrial appendage closure device that is implanted in patients who are unsuitable for anticoagulation therapy for atrial fibrillation. During WATCHMAN implantation, inducing apnea in the patient is preferable to allow stable deployment. We present three cases in which apneic oxygenation was employed to maintain oxygenation during apnea, and oxygen reserve index (ORiTM) was measured to evaluate its safety and efficacy. Oxygen was administered continuously via the endotracheal tube during apnea. During all four apneic events in three patients (mean duration of 356 seconds), the ORi values maintained above 0.24, which is generally considered the threshold of partial pressure of arterial oxygen (PaO2) > 100 mmHg. Transcutaneous oxygen saturation and PaO2 remained above 99% and 300 mmHg, respectively. There were no respiratory or circulatory complications during or after the surgery.

Rebounds of sevoflurane concentration during simulated trigger-free pediatric and adult anesthesia.

BACKGROUND: In trigger-free anesthesia a volatile anesthetic concentration of 5 parts per million (ppm) should not be exceeded. According to European Malignant Hyperthermia Group (EMHG) guideline, this may be achieved by removing the vapor, changing the anesthetic breathing circuit and renewing the soda lime canister followed by flushing with O2 or air for a workstation specific time. Reduction of the fresh gas flow (FGF) or stand-by modes are known to cause rebound effects. In this study, simulated trigger-free pediatric and adult ventilation was carried out on test lungs including ventilation maneuvers commonly used in clinical practice. The goal of this study was to evaluate whether rebounds of sevoflurane develop during trigger-free anesthesia. METHODS: A Dräger® Primus® was contaminated with decreasing concentrations of sevoflurane for 120 min. Then, the machine was prepared for trigger-free anesthesia according to EMHG guideline by changing recommended parts and flushing the breathing circuits using 10 or 18 l⋅min- 1 FGF. The machine was neither switched off after preparation nor was FGF reduced. Simulated trigger-free ventilation was performed with volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) including various ventilation maneuvers like pressure support ventilation (PSV), apnea, decreased lung compliance (DLC), recruitment maneuvers, prolonged expiration and manual ventilation (MV). A high-resolution ion mobility spectrometer with gas chromatographic pre-separation was used to measure sevoflurane in the ventilation gas mixture in a 20 s interval. RESULTS: Immediately after start of simulated anesthesia, there was an initial peak of 11-18 ppm sevoflurane in all experiments. The concentration dropped below 5 ppm after 2-3 min during adult and 4-18 min during pediatric ventilation. Other rebounds of sevoflurane > 5 ppm occurred after apnea, DLC and PSV. MV resulted in a decrease of sevoflurane < 5 ppm within 1 min. CONCLUSION: This study shows that after guideline-compliant preparation for trigger-free ventilation anesthetic machines may develop rebounds of sevoflurane > 5 ppm during typical maneuvers used in clinical practice. The changes in rate and direction of internal gas flow during different ventilation modes and maneuvers are possible explanations. Therefore, manufacturers should provide machine-specific washout protocols or emphasize the use of active charcoal filters (ACF) for trigger-free anesthesia.

The effect of capnography on the incidence of hypoxia during sedation for EGD and colonoscopy in mildly obese patients: a randomized, controlled study.

BACKGROUND: By continually monitoring end-tidal carbon dioxide concentrations, capnography can detect abnormal ventilation or apnoea early. This randomized, controlled study explored the effect of early intervention with capnography on the incidence of hypoxia in mildly obese patients undergoing sedation for esophagogastroduodenoscopy (EGD) and colonoscopy. METHODS: This is a single-center, randomized, single-blind, parallel-assignment, controlled trial. Mildly obese patients (28 kg/m2 ≤ BMI < 40 kg/m2) undergoing sedation for EGD and colonoscopy were randomly assigned to either the standard or capnography group. Standard cardiopulmonary monitoring equipment was used in both groups, and additional capnography was performed in the capnography group. In the event of inadequate alveolar ventilation during sedation, five interventions were administered in sequence (a-e) : a: increasing oxygen flow (5 L/min); b: a chin lift or jaw thrust maneuver; c: placement of the nasopharyngeal airway and chin lift; d: mask positive-pressure ventilation, and e: ventilator-assisted ventilation with tube insertion. The primary outcome was the incidence of hypoxia (SpO2 < 90%, ≥ 10 s) in each group. The secondary outcomes included the incidence of severe hypoxia (SpO2 ≤ 85%), subclinical respiratory depression (90% ≤ SpO2 < 95%), interventions, minimum SpO2 during operation, patient satisfaction, endoscopist satisfaction, and other adverse events of anesthesia sedation. RESULTS: 228 patients were included (capnography group = 112; standard group = 113; three patients were excluded) in this study. The incidence of hypoxia was significantly lower in the capnography group than in the standard group (13.4% vs. 30.1%, P = 0.002). Subclinical respiratory depression in the capnography group was higher than that of the standard group (30.4% vs. 17.7%, P = 0.026). There was only a 5.4% incidence of severe hypoxia in the capnography group compared with 14.2% in the standard group (P = 0.026). During sedation, 96 and 34 individuals in the capnography and standard groups, respectively, underwent the intervention. There was a statistically significant difference (P < 0.0001) in the number of the last intraoperative intervention between the two groups ( a:47 vs. 1, b:46 vs. 26, c:2 vs. 5, d:1 vs. 2, e:0 vs. 0 ). No significant differences were found between the two groups in terms of minimum SpO2 during operation, patient satisfaction, or endoscopist satisfaction rating. There was no statistically significant difference in adverse events of anesthesia sedation between the two groups. CONCLUSION: Capnography during sedation for EGD and colonoscopy allows for the detection of apnea and altered breathing patterns in mildly obese patients before SpO2 is reduced. Effective intervention measures are given to patients within this time frame, which reduces the incidence of hypoxia and severe hypoxia in patients. TRIAL REGISTRATION: Ethical approval was granted by the Medical Ethics Committee (Chairperson Professor Tian Hui) of Qilu Hospital, Shandong University ((Ke) Lun Audit 2021 (186)) on 15/07/2021. The study was registered ( https://www.chictr.org.cn ) on 23/10/2021(ChiCTR2100052234). Designed and reported using CONSORT statements.

Análisis de causas atribuidas a "BRUE" entre los años 2017 a 2020 / Analysis of etiologies attributed to "BRUE" between the years 2017 to 2020

El término BRUE describe un evento en un lactante menor, repentino, breve, ya resuelto y sólo aplica cuando no existe una explicación para este episodio. Es escasa la literatura nacional e internacional sobre el estudio etiológico en BRUE. Objetivos: Caracterizar lactantes con episodio de BRUE y hacer un análisis etiológico. Métodos: Estudio retrospectivo, descriptivo lactantes hospitalizados por BRUE. Resultados: Se encontraron 50 lactantes con BRUE, la mayoría de ellos presentó un solo evento y ninguno requirió reanimación cardiopulmonar. Las características principales de los eventos fueron apnea, cianosis y tono disminuido. Las etiologías encontradas, más habituales, fueron reflujo gastro-esofágico, infección respiratoria, mala técnica alimentaria y crisis epilépticas. La evaluación clínica fue el principal elemento diagnóstico. Discusión: Nuestro análisis etiológico concuerda con la literatura nacional e internacional. La anamnesis y examen físico son la principal herramienta diagnóstica. Es fundamental contar con guías, adaptadas a la realidad nacional y local, que dirijan el estudio de lactantes con BRUE.

BRUE is an event occurring in an infant when the observer reports a sudden, brief, and now-resolved episode. BRUE is a diagnosis of exclusion and is used only when there is no explanation for the event after conducting an appropriate history and physical examination. There is little literature on the etiological study in BRUE. Objectives: To characterize infants with a BRUE episode and to carry out an etiological analysis. Methods: A retrospective study including infants who have experienced a BRUE between the years 2017 to 2020. Results: 50 infants with BRUE, most of them presented a single event and none required cardiopulmonary resuscitation. The main characteristics of the events were apnea, cyanosis and decreased tone. The most common etiologies found were gastroesophageal reflux, respiratory infection, poor feeding technique, and seizures. History and physical examination are the fundamental diagnostic tools. Discussion: Our etiological analysis agrees with the national and international literature. The clinical evaluation was the main diagnostic tool. It is essential to create local guidelines for the evaluation investigation and management of infants with BRUE.

Efficacy of capnographic and bispectral index monitoring on trans-oral therapeutic endoscopy: A prospective observational study.

BACKGROUND AND AIM: Oral therapeutic and invasive endoscopy requires deep sedation to reduce patient distress due to prolonged examination and procedures. The usefulness of capnography and bispectral index (BIS) monitoring in the early hypoxia detection in oral therapeutic and invasive endoscopy has yet to be evaluated. This study aimed to investigate the clinical impact of capnography and BIS monitoring on hypoxic events during oral therapeutic and invasive endoscopic procedures. METHODS: This is a prospective observational study. Trans-oral non-intubated therapeutic and/or invasive endoscopic procedures were performed with conventional monitoring (pulse oximetry, pulse, and blood pressure) as well as additional monitoring (BIS and end-tidal CO2 concentration). Hypoxia is defined as oxygen saturation of <90% that lasts >15 s. The clinical impact of capnography and BIS monitoring on hypoxic events during oral therapeutic and invasive endoscopic procedures were investigated with the risk factors for hypoxia in each patient. RESULTS: Patients with hypoxia had significantly more apneas detected using capnography than other patients. The multivariate analysis revealed the detected apnea by capnography as an independent risk factor for hypoxia (odds ratio: 3.48[95% confidence interval: 1.24-9.78], P = 0.02). The BIS was not significantly different as a risk factor for hypoxia; however, per-event analysis revealed significantly decreased BIS values over time in 3 min before hypoxic events. CONCLUSIONS: Apnea detected by capnography was an independent predictor of hypoxia. The BIS value was not associated with hypoxia events; however, it showed a significant downward trend before hypoxia events.

Apnoeic oxygenation with high-flow oxygen for tracheal resection and reconstruction surgery.

BACKGROUND: Tracheal resection and reconstruction are the most effective treatments for tracheal stenosis, but the difficulties are surgery and maintaining ventilation performed on the patient's same airway. High-flow oxygen has begun to be applied to prolong the apnoea time in the tracheal anastomosis period for tracheal resection and reconstruction. This study aims to evaluate the effectiveness of apneic conditions with high-flow oxygen as the sole method of gas exchange during anastomosis construction. METHODS: A prospective study was performed on 16 patients with tracheal stenosis, with ages ranging from 19 to 70, who underwent tracheal resection and reconstruction from April 2019 to August 2020 in 108 Military Central Hospital. During the anastomosis phase using high flow oxygen of 35-40 l.min-1 delivered across the open tracheal with an endotracheal tube (ETT) at the glottis in apnoeic conditions. RESULTS: The mean (SD) apnoea time was 20.91 (2.53) mins. Mean (SD) time anastomosis was 22.9 (2.41) mins. The saturation of oxygen was stable during all procedures at 98-100%. Arterial blood gas analysis showed mean (SD) was hypercapnia and acidosis acute respiratory after 10 mins of apnoea and 20 mins apnoea respectively. However, after 15 mins of ventilation, the parameters are ultimately returned to normal. All 16 patients were extubated early and safely at the end of the operation. There were no complications, such as bleeding, hemothorax, pneumothorax, or barotrauma. CONCLUSION: High-flow oxygen across the open tracheal under apnoeic conditions can provide a satisfactory gas exchange to allow tubeless anesthesia for tracheal resection and reconstruction.

Relationship between Occurrence and Progression of Lung Cancer and Nocturnal Intermittent Hypoxia, Apnea and Daytime Sleepiness.

The possible relationship between lung cancer and nocturnal intermittent hypoxia, apnea and daytime sleepiness, especially the possible relationship between the occurrence and progression of lung cancer and obstructive sleep apnea syndrome (OSAS) was explored. Forty-five cases of primary lung cancer suitable for surgical resection at the Third Affiliated Hospital of Kunming Medical University between January 2017 and December 2017 were recruited (lung cancer group), and there were 45 patients in the control group who had no significant differences in age, sex and other general data from lung cancer group. The analyzed covariates included general situation, snore score, the Epworth Sleeping Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), apnea and hypopneas index (AHI), oxygen desaturation index 4 (ODI4), lowest arterial oxygen saturation [LSpO2 (%)], oxygen below 90% of the time [T90% (min)], the percentage of the total recorded time spend below 90% oxygen saturation (TS90%), to explore the possible relationship between lung cancer and above indicators. The participants were followed up for one year. The results showed that: (1) There was significant difference in body mass index (BMI), ESS, AHI, T90% (min), TS90%, ODI4, snore score and LSpO2 (%) between lung cancer group and control group (P<0.05). There was no statistically significant difference in age, gender, PSQI score, incidence of concurrent hypertension, diabetes and coronary heart disease (CHD), and smoking history between the two groups (P>0.05); (2) Patients in the lung cancer group were divided into OSAS subgroup and non-OSAS subgroup according to the international standard for the diagnosis of OSAS. There was significant difference in BMI, age, staging, incidence of concurrent hypertension and concurrent CHD, snore score, ESS score, T90% (min), TS90%, ODI4 and LSpO2 (%) between OSAS subgroup and non-OSAS subgroup (P<0.05). There was no statistically significant difference in gender, PSQI score, incidence of concurrent diabetes, smoking history and lung cancer type between the two groups (P>0.05); (3) AHI was strongly negatively correlated with the LSpO2 (%) and positively with ESS, staging, snoring score, T90% (min), TS90%, ODI4 and BMI (P<0.05); (4) There were 3 deaths, 5 cases of recurrence, and 4 cases of metastasis in OSAS subgroup; and there was 1 death, 4 cases of recurrence and 2 cases of metastasis in non-OSAS subgroup during the follow-up period of one year, respectively. There was no significant difference in mortality, recurrence rate and metastasis rate between the two subgroups, and the total rate of deterioration in OSAS subgroup was significantly increased compared to the non-OSAS subgroup (P<0.05). It was concluded that the patients with lung cancer are prone to nocturnal hypoxemia, apnea, snoring and daytime sleepiness compared to control group. The incidence of OSAS in patients with lung cancer was higher, and the difference in the hypoxemia-related indicators was statistically significant. The mortality, recurrence rate, and metastasis rate increases in lung cancer patients with OSAS during the one-year follow-up period, suggesting that OSAS may be a contributing factor to the occurrence and progression of lung cancer.

Proposed safe apnea test using positive end-expiratory pressure valve and short-term blood gas analysis: Observational study.

The apnea test is an essential examination for the determination of brain death; however, hypotension, hypoxemia, and other complications during the apnea test can affect the stability of brain-dead patients, as well as organ function for recipients. Therefore, it is necessary to establish standard guidelines for apnea testing.The modified apnea test (MAT) comprises delivery of 100% oxygen through the endotracheal tube connected to manual resuscitator (Ambu bag) with the positive end-expiratory pressure (PEEP) valve after disconnection of the mechanical ventilator for maintenance of PEEP. Forty-nine instances of the conventional apnea test (CAT) were performed in 25 brain-dead patients; 77 instances of the MAT were performed in 39 brain-dead patients.The mean duration of the apnea test was 3.5 ±â€Š1.4 minutes in the CAT group and 3.0 ±â€Š1.2 minutes in the MAT group. There were no significant changes in PaCO2, PaO2, or pH between the CAT and MAT groups (P = .341, .593, and .503, respectively). In overweight patients (body mass index ≥ 23 kg/m), MAT prevented dramatic reductions in PaO2 and SaO2 (P < .05 for both). In the patients who had hypoxic brain injury due to hanging, differences in PaO2 and SaO2 in the MAT group were significantly smaller than in the CAT group (P < .05).Although MAT, which was invented to maintain PEEP, was not efficient for all brain-dead patients, it could be helpful in selected patient groups, such as overweight patients or those who had hypoxic injury due to hanging. And clinicians should consider short-term apnea test to avoid unnecessarily prolonged hypoxemia.

Pseudocholinesterase Deficiency: What the Proceduralist Needs to Know.

Pseudocholinesterase deficiency is a rare genetic as well as an acquired disorder that affects the body's ability to metabolize choline esters such as succinylcholine and mivacurium. It can be inherited as an autosomal recessive trait, occurring in approximately 1 in 3,200 to 1 in 5,000 people. In most cases of pseudocholinesterase deficiency, no signs or symptoms of the condition exist. It is first suspected after a prolonged recovery from paralysis following general anesthesia in which succinylcholine or mivacurium are administered. We emphasize the importance of obtaining a detailed history prior to any endoscopic intervention or surgery requiring monitored anesthesia care or general anesthesia. In addition, a family history of anesthesia complications may help identify patients at risk. This article examines a case of a patient who underwent a successful endoscopic pneumatic dilation under general anesthesia for the treatment of achalasia, but was subsequently admitted to the intensive care unit, requiring mechanical ventilator support, for 18 hours. The patient made a complete recovery and was discharged home with no further complications. This case stimulated a review of this entity and we provide recommendations relevant to all proceduralist and anesthesia staff, as well as all personnel involved in procedures.

High versus standard dose caffeine for apnoea: a systematic review.

BACKGROUND: Placebo-controlled trials have shown that caffeine is highly effective in treating apnoea of prematurity and reduces the risk of bronchopulmonary dysplasia (BPD) and neurodevelopmental impairment (NDI). OBJECTIVE: To identify, appraise and summarise studies investigating the modulating effect of different caffeine dosages. METHODS: A systematic review identified all randomised controlled trials (RCTs) comparing a high versus a standard caffeine treatment regimen in infants with a gestational age <32 weeks, by searching the main electronic databases and abstracts of the Pediatric Academic Societies. Studies comparing caffeine to placebo or theophylline only were excluded. Primary outcomes were BPD and mortality at 36 weeks postmenstrual age. Secondary key-outcome was neurodevelopmental outcome at 12 and 24 months corrected age. Meta-analysis was performed using RevMan 5.3. RESULTS: Six RCTs including 620 infants were identified. Meta-analysis showed a significant decrease in BPD, the combined outcome BPD or mortality, and failure to extubate in infants allocated to a higher caffeine dose. No differences were found in mortality alone and NDI. The quality of the outcome measures were deemed low to very low according to the Grading of Recommendations Assessment, Development and Evaluation guidelines. CONCLUSIONS: Although this review suggests that administering a higher dose of caffeine might enhance its beneficial effect on death or BPD, firm recommendations on the optimal caffeine dose cannot be given due to the low level of evidence. A large RCT is urgently needed to confirm or refute these findings and determine the optimal dose of caffeine.

Short term general anesthesia for retro-bulbar block in ophthalmic surgery generates no significant hypercapnia.

To assess the impact of short time hypnosis for retro-bulbar anesthesia on ventilation in patients undergoing ophthalmic surgery of the anterior eye chamber. In all patients, a combined continuous transcutaneous carbon dioxide tension (PtcCO2) and partial oxygen saturation (SpO2) measurement was applied in addition to routine monitoring. To enable unconscious application of retro-bulbar anesthesia, intravenous thiopental was given in one to multiple bolus doses. Transient breathing support included chin lift, Esmarch maneuver and manual hand-bag ventilation via face mask. Main endpoints were apnea time, recovery time according to the Richmond Agitation Sedation Scale, as well as SpO2 and PtcCO2 readings at predefined time points. Fifty-two patients with a mean age of 68 ± 13 years were included. Average thiopental dose was 2.7 ± 0.6 mg/kg. In seven (13.5%) patients repeated doses of thiopental were necessary to a total of 3.3 ± 1.1 mg/kg. Except one patient, no severe, significant or clinical relevant hypercapnia or desaturation periods were observed, and the occurring elevation of PtcCO2 values did not correlate with the application of repeated doses of thiopental or the need for the Esmarch maneuver. Higher PtcCO2 values were associated with the presence of hypertension and smoking. Apnea (p < 0.001) and recovery (p = 0.003) time were significantly prolonged in the patients needing the Esmarch maneuver. Short term anesthesia with thiopental in ophthalmic surgery is associated with a mild but not clinically relevant hypercapnia.

Long-term neurodevelopment outcome of caffeine versus aminophylline therapy for apnea of prematurity.

OBJECTIVE: Methylxanthines are the most commonly prescribed drug in neonatal setups. However, Clinicians show indecision in choosing the right agent for Apnea of Prematurity in most of the developing countries. Present study aimed to compare rate of mortality and survival with normal neurodevelopment outcome at 18 to 24 months of corrected age, between Caffeine- and Aminophylline-treated infants for apnea of prematurity. METHODS: 240 infants were randomly allocated to caffeine and aminophylline for apnea of prematurity during February 2012 to January 2015. Long-term neurodevelopmental assessment was done only from children who had attained corrected age of 18 to 24 months during April 2014 to February 2016. Cognitive, language and motor deficits were assessed by Bayley Scale of infant and toddler development (BSID - III). Postnatal characteristics such as hearing and visual impairments during NICU stay were noted and same were followed up. RESULTS: Infants allocated to caffeine group showed 83% less risk of getting cognitive impairment (RR 0.16; CI 95% range 0.02 to 1.36), 50% less risk of developing motor deficits (RR 0.50; CI 95% range 0.12 to 1.95) and 24% less risk of developing language problems (RR 0.76; CI 95% range 0.36 to 1.58). However in all the neurodevelopment domains the difference between groups was not statistically significant. Risk of mortality in caffeine group was 9% less over aminophylline group which was statistically non-significant (RR - 0.92; CI 95% range - 0.45 to 1.84; p = 0.81). Physical growth parameters were found to be similar in both the groups. Risk of developing visual abnormality and hearing impairments was also statistically non-significant between the groups. CONCLUSION: Caffeine and aminophylline showed similar effects in reducing the rate of mortality and improving the survival without neurodevelopment delays; though the clinical significance of caffeine over aminophylline cannot be undermined.

Academic Performance, Motor Function, and Behavior 11 Years After Neonatal Caffeine Citrate Therapy for Apnea of Prematurity: An 11-Year Follow-up of the CAP Randomized Clinical Trial.

Importance: Caffeine citrate therapy for apnea of prematurity reduces the rates of bronchopulmonary dysplasia, severe retinopathy, and neurodevelopmental disability at 18 months and may improve motor function at 5 years. Objective: To evaluate whether neonatal caffeine therapy is associated with improved functional outcomes 11 years later. Design, Setting, and Participants: A follow-up study was conducted at 14 academic hospitals in Canada, Australia, and the United Kingdom from May 7, 2011, to May 27, 2016, of English- or French-speaking children who had been enrolled in the randomized, placebo-controlled Caffeine for Apnea of Prematurity trial between October 11, 1999, and October 22, 2004. A total of 1202 children with birth weights of 500 to 1250 g were eligible for this study; 920 (76.5%) had adequate data for the main outcome. Interventions: Caffeine citrate or placebo until drug therapy for apnea of prematurity was no longer needed. Main Outcomes and Measures: Functional impairment was a composite of poor academic performance (defined as at least 1 standard score greater than 2 SD below the mean on the Wide Range Achievement Test-4), motor impairment (defined as a percentile rank of ≤5 on the Movement Assessment Battery for Children-Second Edition), and behavior problems (defined as a Total Problem T score ≥2 SD above the mean on the Child Behavior Checklist). Results: Among the 920 children (444 females and 476 males; median age, 11.4 years [interquartile range, 11.1-11.8 years]), the combined rates of functional impairment were not significantly different between the 457 children assigned to receive caffeine compared with the 463 children assigned to receive placebo (145 [31.7%] vs 174 [37.6%]; adjusted odds ratio, 0.78; 95% CI, 0.59-1.02; P = .07). With all available data, including those from up to 24 Swedish trial participants, the rates of poor academic performance on 1 or more of 4 subtests (66 of 458 [14.4%] vs 61 of 462 [13.2%]; adjusted odds ratio, 1.11; 95% CI, 0.77-1.61; P = .58) and behavior problems (52 of 476 [10.9%] vs 40 of 481 [8.3%]; adjusted odds ratio, 1.32; 95% CI, 0.85-2.07; P = .22) were broadly similar between the group that received caffeine and the group that received placebo. However, caffeine therapy was associated with a reduced risk of motor impairment compared with placebo (90 of 457 [19.7%] vs 130 of 473 [27.5%]; adjusted odds ratio, 0.66; 95% CI, 0.48-0.90; P = .009). Conclusions and Relevance: Caffeine therapy for apnea of prematurity did not significantly reduce the combined rate of academic, motor, and behavioral impairments but was associated with a reduced risk of motor impairment in 11-year-old children with very low birth weight. At the doses used in this trial, neonatal caffeine therapy is effective and safe into middle school age. Trial Registration: clinicaltrials.gov Identifier: NCT00182312; isrctn.org Identifier: ISRCTN44364365.

Nasal high-flow oxygen delivery in children with abnormal airways.

BACKGROUND: Transnasal Humidified Rapid-Insufflation Ventilatory Exchange has been shown to safely prolong the safe apnea time in well children post induction of anesthesia and is rapidly becoming a new standard for apneic oxygenation in adults. The same oxygenation technique is described as nasal high flow and can be used in infants and children at risk of apnea during anesthesia. AIM: We investigated the use of nasal high flow oxygen delivery during anesthesia in children with abnormal airways requiring tubeless airway assessment or surgery. METHODS: Data and outcomes of pediatric patients receiving nasal high flow for upper airway procedures were analyzed. Four categories were defined: (i) tubeless airway surgery, (ii) flexible bronchoscopy, (iii) expected difficult airway, and (iv) comorbidity related risk of apnea. Anesthesia was induced intravenously or with sevoflurane (4-8%) and then converted to total intravenous anesthesia aiming for spontaneous ventilation. Age appropriate nasal high flow cannulae were secured with 100% oxygen delivery at weight-related flow rates. Topicalization of the airway was achieved with lignocaine. Complication rates of desaturation requiring interruption of procedure for rescue oxygenation were recorded. RESULTS: Twenty children were analyzed with age range of 5 days to 11 years, ASA 1-4, and weight range 3-57 kg. Fifteen were induced with sevoflurane and 100% oxygen, five received total intravenous anesthesia only. All children received Optiflow™ nasal high flow and intravenous anesthesia during their procedure. Average SpO2 recorded was 96% with lowest SpO2 77%. One required rescue oxygenation. Median length of procedure was 32 min, (range 3-61). Most common indication was tubeless airway surgery but seven children had more than one indication. CONCLUSION: Nasal high flow can be used in spontaneously breathing children with abnormal airways for maintenance of oxygenation during anesthesia for tubeless airway procedures.

Hemoglobin Vesicles prolong the time to circulatory collapse in rats during apnea.

BACKGROUND: Hemoglobin vesicles (HbV) are hemoglobin-based oxygen carriers manufactured by liposome encapsulation of hemoglobin molecules. We hypothesised that the infusion of oxygenated HbV could prolong the time to circulatory collapse during apnea in rats. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into four groups (Air, Oxy, NS and HbV). The rats were anaesthetized with isoflurane and the trachea was intubated using 14-gauge intravenous catheters. Rats in the Air group were mechanically ventilated with 1.5% isoflurane in room air, and those in other groups received 1.5% isoflurane in 100% oxygen. Mechanical ventilation was withdrawn 1 min after the administration of rocuronium bromide to induce apnea. After 30 s, 6 mL saline and HbV boluses were infused at a rate of 0.1 mL/s in the NS and HbV groups, respectively. Circulatory collapse was defined as a pulse pressure < 20 mmHg and the time to reach this point (PP20) was compared between the groups. The results were analysed via a one-way analysis of variance and post-hoc Holm-Sidak test. RESULTS: PP20 times were 30.4 ± 4.2 s, 67.5 ± 9.7 s, 95 ± 17.3 s and 135 ± 38.2 s for the Air (ventilated in room air with no fluid bolus), Oxy (ventilated with 100% oxygen with no fluid bolus), NS (ventilated with 100% oxygen with a normal saline bolus), and HbV (ventilated in 100% oxygen with an HbV bolus) groups, respectively, and differed significantly between the four groups (P = 0.0001). The PP20 times in the HbV group were significantly greater than in the Air (P = 0.0001), Oxy (P = 0.007) and NS (P = 0.04) groups. CONCLUSION: Infusion of oxygenated HbV prolongs the time to circulatory collapse during apnea in rats.

Impaired Presynaptic High-Affinity Choline Transporter Causes a Congenital Myasthenic Syndrome with Episodic Apnea.

The neuromuscular junction (NMJ) is one of the best-studied cholinergic synapses. Inherited defects of peripheral neurotransmission result in congenital myasthenic syndromes (CMSs), a clinically and genetically heterogeneous group of rare diseases with fluctuating fatigable muscle weakness as the clinical hallmark. Whole-exome sequencing and Sanger sequencing in six unrelated families identified compound heterozygous and homozygous mutations in SLC5A7 encoding the presynaptic sodium-dependent high-affinity choline transporter 1 (CHT), which is known to be mutated in one dominant form of distal motor neuronopathy (DHMN7A). We identified 11 recessive mutations in SLC5A7 that were associated with a spectrum of severe muscle weakness ranging from a lethal antenatal form of arthrogryposis and severe hypotonia to a neonatal form of CMS with episodic apnea and a favorable prognosis when well managed at the clinical level. As expected given the critical role of CHT for multisystemic cholinergic neurotransmission, autonomic dysfunctions were reported in the antenatal form and cognitive impairment was noticed in half of the persons with the neonatal form. The missense mutations induced a near complete loss of function of CHT activity in cell models. At the human NMJ, a delay in synaptic maturation and an altered maintenance were observed in the antenatal and neonatal forms, respectively. Increased synaptic expression of butyrylcholinesterase was also observed, exposing the dysfunction of cholinergic metabolism when CHT is deficient in vivo. This work broadens the clinical spectrum of human diseases resulting from reduced CHT activity and highlights the complexity of cholinergic metabolism at the synapse.

Clinical associations of immature breathing in preterm infants: part 1-central apnea.

BACKGROUND: Apnea of prematurity (AOP) is nearly universal among very preterm infants, but neither the apnea burden nor its clinical associations have been systematically studied in a large consecutive cohort. METHODS: We analyzed continuous bedside monitor chest impedance and electrocardiographic waveforms and oxygen saturation data collected on all neonatal intensive care unit (NICU) patients <35 wk gestation from 2009 to 2014 (n = 1,211; >50 infant-years of data). Apneas, with bradycardia and desaturation (ABDs), defined as central apnea ≥10 s associated with both bradycardia <100 bpm and oxygen desaturation <80%, were identified using a validated automated algorithm. RESULTS: Number and duration of apnea events decreased with increasing gestational age (GA) and postmenstrual age (PMA). ABDs were more frequent in infants <31 wk GA at birth but were not more frequent in those with severe retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), or severe intraventricular hemorrhage (IVH) after accounting for GA. In the day before diagnosis of late-onset septicemia and necrotizing enterocolitis, ABD events were increased in some infants. Many infants continued to experience short ABD events in the week prior to discharge home. CONCLUSION: Frequency of apnea events is a function of GA and PMA in infants born preterm, and increased apnea is associated with acute but not with chronic pathologic conditions.

Intermittent but not sustained hypoxia activates orexin-containing neurons in mice.

Hypothalamic orexin-containing neurons are activated by CO2 and contribute to hypercapnic ventilatory activation. However, their role in oxygen-related regulation of breathing is not well defined. In this study, we examined whether an experimental model mimicking apnea-induced repetitive hypoxemia (intermittent hypoxia [IH]) activates orexin-containing neurons. Mice were exposed to IH (5×5min at 10% O2), intermittent hyperoxia (IO; 5×5min at 50% O2), sustained hypoxia (SH; 25min at 10% O2), or sham stimulation. Their brains were examined using double immunohistochemical staining for orexin and c-Fos. The results indicated that IH (25.8±3.0%), but not SH (9.0±1.5%) activated orexin-containing neurons when compared to IO (5.5±0.6%) and sham stimulation (5.9±1.4%). These results correlate with those of our previous work showing that IH-induced respiratory long-term facilitation is dependent on orexin-containing neurons. Taken together, orexin contributes to repetitive hypoxia-induced respiratory activation and the hypoxic activation of orexin-containing neurons is pattern dependent.

The nuclear progesterone receptor reduces post-sigh apneas during sleep and increases the ventilatory response to hypercapnia in adult female mice.

We tested the hypothesis that the nuclear progesterone receptor (nPR) is involved in respiratory control and mediates the respiratory stimulant effect of progesterone. Adult female mice carrying a mutation in the nPR gene (PRKO mice) and wild-type controls (WT) were implanted with an osmotic pump delivering vehicle or progesterone (4 mg/kg/day). The mice were instrumented with EEG and neck EMG electrodes connected to a telemetry transmitter. The animals were placed in a whole body plethysmograph 7 days after surgery to record ventilation, metabolic rate, EEG and neck EMGs for 4 consecutive hours. The animals were exposed to hypercapnia (5% CO2), hypoxia (12% O2) and hypoxic-hypercapnia (5% CO2+12% O2-5 min each) to assess chemoreflex responses. EEG and EMG signals were used to characterize vigilance states (e.g., wake, non-REM, and REM sleep). PRKO mice exhibited similar levels of minute ventilation during non-REM and REM sleep, and higher frequencies of sighs and post-sigh apneas during non-REM sleep compared to WT. Progesterone treatment increased minute ventilation and metabolic rate in WT and PRKO mice during non-REM sleep. In WT mice, but not in PRKO mice, the ventilation under hypercapnia and hypoxic hypercapnia was enhanced after progesterone treatment. We conclude that the nPR reduces apnea frequency during non-REM sleep and enhances chemoreflex responses to hypercapnia after progesterone treatment. These results also suggest that mechanisms other than nPR activation increase metabolic rate in response to progesterone treatment in adult female mice.