[Analysis of the application effect and safety of transnasal humidified rapid insufflation ventilatory exchange technique in hysteroscopic diagnostic and therapeutic surgery].

Objective: To investigate the effect and safety of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) technique in hysteroscopic diagnostic and therapeutic surgery. Methods: This study was a randomized controlled trial. A total of 100 female patients undergoing hysteroscopy surgery at Beijing Tongren Hospital from September to December 2023 were selected and randomly divided into two groups by the random number table method: the THRIVE group and the mask oxygen group, with 50 patients in each group. Patients in both groups were given total intravenous anesthesia with propofol combined with remifentanil and preserved spontaneous respiration. The THRIVE group was given oxygen by the THRIVE device with an oxygen flow rate of 50 L/min, while the mask oxygen group was given oxygen by the mask with an oxygen flow rate of 5 L/min; the oxygen concentration of both groups was set at 100%. The general condition of the patients, vital signs during the operation, the amount of anesthesia drugs used and the operation time were recorded. The primary observation index was the incidence of hypoxic events in the two groups; the secondary observation indexes were the incidence and time of intraoperative apnea as well as the corresponding oxygenation interventions and the incidence of non-hypoxic adverse events. Results: The age of the THRIVE group was (42±14) years, and the age of the mask oxygen group was (43±15) years. The duration of surgery in the THRIVE group was (15.9±3.4) min, which was statistically lower than that of the mask oxygen group (16.3±4.5) min (P=0.041), and there were no differences observed in the duration of awakening time and anesthesia time (both P>0.05). There was no significant difference in the dosage of propofol, remifentanil, and intraoperative vasoactive drugs between the two groups (all P>0.05). The SpO2 of the patients in the THRIVE group at the end of the operation was (99.7±1.1) %, which was higher than that of the mask-oxygen group (99.1±1.1) % (P<0.05). There was no difference in SpO2 of the two groups at the other time points (all P>0.05). There were no differences in HR and MAP of two group patients at each time point (all P>0.05). The incidence of hypoxic events in the THRIVE group was 12.0% (6/50), which was lower than that of 28.0% (14/50) in the mask oxygen group (P=0.045). The difference in the incidence and duration of apnea between the two groups was not statistically significant (all P>0.05). There were no cases of temporary need for laryngeal mask or tracheal intubation during surgery in both groups. There was no statistically significant difference in the incidence of intraoperative body movement, dizziness, nausea and vomiting between the two groups (all P>0.05), and no cardiac, cerebral, renal or other important organ insufficiency occurred in the two weeks after surgery. Conclusion: THRIVE technology can provide effective oxygenation for patients undergoing hysteroscopic diagnosis and treatment, maintain patients' circulatory stability, and improve the safety and efficiency of surgery.

Value of integrated pulmonary index monitoring for the detection of adverse respiratory events in patients undergoing sedation for gastrointestinal system endoscopy.

Objectives: To determine if the integrated pulmonary index detects changes in ventilation status early in patients undergoing gastrointestinal endoscopy under sedation, and to determine the risk factors affecting hypoxia. METHODS: The retrospective study was conducted at the endoscopy unit of a tertiary university hospital in Turkey and comprised data between October 2018 and December 2019 related to patients of either gender aged >18 years who were assessed as American Society of Anaesthesiologists grade I-III and underwent elective lower and upper gastrointestinal endoscopy. Monitoring was done with capnography in addition to standard procedures. Data was analysed using SPSS 23. RESULTS: Of the 154 patients, 94(%) were females and 60(%) were males. The overall mean age was 50.88±11.8 years (range: 20-70 years). Mean time under anaesthesia was 23.58±4.91 minutes and mean endoscopy time was 21.73±5.06 minutes. During the procedure, hypoxia was observed in 42(27.3%) patients, severe hypoxia in 23(14.9%) and apnoea in 70(45.5%). Mean time between apnoea and hypoxia was 12.59±7.99 seconds, between apnoea and serious hypoxia 21.07±17.64 seconds, between integrated pulmonary index score 1 and hypoxia 12.91±8.17 sec, between integrated pulmonary index score 1 and serious hypoxia 21.59±14.13 seconds, between integrated pulmonary index score <7 and hypoxia 19.63±8.89 seconds, between integrated pulmonary index score <7 and serious hypoxia 28.39±12.66 seconds, between end-tidal carbon dioxide and hypoxia 12.95±8.33 seconds, and between end-tidal carbon dioxide and serious hypoxia 21.29±7.55 seconds. With integrated pulmonary index score 1, sensitivity value for predicting hypoxia and severe hypoxia was 88.1% and 95.7%, respectively, and specificity was 67% and 60.3%, respectively. With integrated pulmonary index score <7, the corresponding values were 100%, 100%, 42% and 64.1%, respectively. CONCLUSIONS: Capnographic monitoring, especially the follow-up integrated pulmonary index score, was found to be valuable and reliable in terms of finding both time and accuracy of the risk factor in the diagnosis of respiratory events.

Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients

Introduction Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. Methods Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. Results Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells’ membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. Conclusion Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients. (AU)

Relación entre la apnea obstructiva del sueño y la diabetes mellitus tipo 2 / Relationship between obstructive sleep apnea and type 2 diabetes mellitus

Introducción: La asociación entre la apnea obstructiva del sueño (AOS) y el metabolismo de la glucosa sigue siendo controvertida. Este estudio investiga la relación entre la AOS y la diabetes mellitus tipo 2 (DM) y prediabetes (preDM) incidentes, así como el efecto del tratamiento con presión positiva continua en la vía aérea (CPAP) a largo plazo. Métodos: Estudio de seguimiento en cohorte retrospectiva clínica de pacientes con AOS y controles seleccionados de manera aleatoria. Los datos sobre DM incidente y preDM, así como de la CPAP se obtuvieron de los registros hospitalarios. La relación entre AOS basal y la DM incidente se examinó con modelos de regresión de Cox. Resultados: De un total de 356 pacientes, 169 con AOS y 187 controles fueron seguidos por una mediana de 98 meses; 47 enfermos (13,2%) desarrollaron DM y 43 (12,1%) preDM. La incidencia acumulada a los cinco años de DM fue de 10,7% (6,5-13,9%). De los sujetos con preDM en la muestra basal, 87% evolucionaron a DM incidente. Se demuestra que el índice de masa corporal (IMC), la hipoxia nocturna y el índice de apnea hipopnea (IAH) son factores de riesgo para el desarrollo de DM, y que la CPAP los disminuye. Conclusiones: Los pacientes con AOS tienen mayor probabilidad de desarrollar DM. Los factores de riesgo implicados son el IMC, la hipoxia nocturna y el IAH. El uso regular de CPAP a largo plazo se asoció con una disminución de estos. (AU)

Introduction: The association between obstructive sleep apnea (OSA) and glucose metabolism remains controversial. This study investigates the relationship between OSA and incident type 2 diabetes (DM) and prediabetes (preDM), as well as the effect of long-term CPAP (continuous positive airway pressure) treatment. Methods: Follow-up study in a retrospective clinical cohort of patients with OSA and randomly selected controls. Data on incident DM and preDM as well as CPAP were obtained from hospital records. The relationship between baseline OSA and incident DM was examined using COX regression models. Results: Three hundred and fifty-six patients, 169 with OSA and 187 controls were followed for a median of 98 months; 47 patients (13.2%) developed DM and 43 (12.1%) developed preDM. The 5-year cumulative incidence of DM was 10.7% (6.5–13.9%). 87% of subjects with preDM in the baseline sample progressed to incident DM. It is shown that body mass index (BMI), nocturnal hypoxia and apnea hypopnea index (AHI) are risk factors for the development of DM and that CPAP reduces this risk. Conclusions: Patients with OSA have a higher risk of developing DM. The risk factors involved are BMI, nocturnal hypoxia and AHI. Regular long-term CPAP use was associated with a decreased risk. (AU)

Relation between resting spleen volume and apnea-induced increases in hemoglobin mass.

Introduction: Indigenous populations renowned for apneic diving have comparatively large spleen volumes. It has been proposed that a larger spleen translates to heightened apnea-induced splenic contraction and elevations in circulating hemoglobin mass (Hbmass), which, in theory, improves O2 carrying and/or CO2/pH buffering capacities. However, the relation between resting spleen volume and apnea- induced increases in Hbmass is unknown. Therefore, we tested the hypothesis that resting spleen volume is positively related to apnea-induced increases in total Hbmass. Methods: Fourteen healthy adults (six women; 29 ± 5 years) completed a two-minute carbon monoxide rebreathe procedure to measure pre-apneas Hbmass and blood volume. Spleen length, width, and thickness were measured pre-and post-five maximal apneas via ultrasound. Spleen volume was calculated via the Pilström equation (test-retest CV:2 ± 2%). Hemoglobin concentration ([Hb]; g/dl) and hematocrit (%) were measured pre- and post-apneas via capillary blood samples. Post-apneas Hbmass was estimated as post-apnea [Hb] x pre-apnea blood volume. Data are presented as mean ± SD. Results: Spleen volume decreased from pre- (247 ± 95 mL) to post- (200 ± 82 mL, p<0.01) apneas. [Hb] (14.6 ± 1.2 vs. 14.9 ± 1.2 g/dL, p<0.01), hematocrit (44 ± 3 vs. 45 ± 3%, p=0.04), and Hbmass (1025 ± 322 vs. 1046 ± 339 g, p=0.03) increased from pre- to post-apneas. Pre-apneas spleen volume was unrelated to post-apneas increases in Hbmass (r=-0.02, p=0.47). O2 (+28 ± 31 mL, p<0.01) and CO2 (+31 ± 35 mL, p<0.01) carrying capacities increased post-apneas. Conclusion: Larger spleen volume is not associated with a greater rise in apneas-induced increases in Hbmass in non-apnea-trained healthy adults.

Physical and Physiological Predictors Determining the Maximal Static Apnea Diving Time of Male Freedivers.

This study aimed to investigate what factors determine freedivers' maximal static apnea dive time. We correlated some physical/physiological factors with male freedivers' maximum apnea diving duration. Thirty-six experienced male freedivers participated in this study. The divers participated in two days of the experiments. On the first day, apnea diving time, blood oxygen saturation (SpO2), heart rate (HR), blood pressure (BP), stress index, and blood parameters were measured before, during, and after the apnea diving in the pool. On the second day, body composition, lung capacity, resting and maximal oxygen consumption (VO2max), and the Wingate anaerobic power were measured in the laboratory. The data were analyzed with Pearson's Correlation using the SPSS 22 program. The correlation coefficient (R) of determination was set at 0.4, and the level of significance was set at p <0.05. There were positive correlations of diving experience, maximum SpO2, and lung capacity with the maximum apnea time R>0.4, P<0.05). There were negative correlations of BMI, body fat percentage, body fat mass, minimum SpO2, stress index, and total cholesterol with the maximum apnea diving time (R>-0.4, P<0.05). No correlations of age, height, weight, fat-free mass, skeletal muscle mass, HR, BP, blood glucose, beta- hydroxybutyrate, lactate, and hemoglobin levels with the maximum apnea diving time were observed (R<0.4, P>0.05). It is concluded that more experience in freediving, reduced body fat, extended SpO2 range, and increased lung capacity are the performance predictors and beneficial for freedivers to improve their maximum apnea diving performance.

Apnea during moderate to deep sedation using continuous infusion of remimazolam compared to propofol and dexmedetomidine: A retrospective observational study.

Remimazolam's rapid onset and offset make it an innovative sedative for use during regional anesthesia. However, its respiratory safety profile is not well understood. We compared the continuous infusion of remimazolam with commonly used sedatives, propofol and dexmedetomidine, after regional anesthesia. In this retrospective study, the incidence of apnea (>10 seconds) was assessed in patients who underwent orthopedic surgery under regional anesthesia and received moderate to deep sedation using continuous infusion of remimazolam (group R: 0.1 mg/kg in 2 minutes followed by 0.5 mg/kg/hr). The incidence was compared with that of propofol (group P: 2-3 µg/mL target-controlled infusion) and dexmedetomidine (group D: 1 µg/kg in 10 minutes followed by 0.4-1 µg/kg/hr). Propensity score weighted multivariable logistic regression model was utilized to determine the effects of the sedative agents on the incidence of apnea. A total of 634 (191, 278, and 165 in group R, P, and D) cases were included in the final analysis. The incidence of apnea was 63.9%, 67.3%, and 48.5% in group R, P, and D, respectively. The adjusted odds ratios for apnea were 2.33 (95% CI, 1.50 to 3.61) and 2.50 (95% CI, 1.63 to 3.85) in group R and P, compared to group D. The incidence of apnea in patients receiving moderate to deep sedation using continuous infusion of remimazolam with dosage suggested in the current study was over 60%. Therefore, careful titration and respiratory monitoring is warranted.

Association of Caffeine Daily Dose With Respiratory Outcomes in Preterm Neonates: A Retrospective Cohort Study.

Apnea and poor respiratory drive increase the risk of extubation failure (EF) and prolonged invasive mechanical ventilation (IMV) in preterm neonates (pre-nates) with respiratory distress. Caffeine citrate (CC) is often prescribed for pre-nates in doses of 5-10 mg/kg in 24 h. This study aimed to evaluate the most effective dosage regimen (5 mg/kg/day vs >5-10 mg/kg/day) to prevent apnea and EF with minimal caffeine-associated potential side effects (CC-APSEs) in pre-nates. This one-year retrospective cohort study included all the eligible neonates admitted to NICU and received CC-therapy till 28 days of life (DOL) or discharge. Based on CC-daily dose formed LD-caffeine-group (5 mg/kg/day) and HD-caffeine-group (>5-10 mg/kg/day). Antenatal, prenatal, and postnatal characteristics, CC-regimen, comorbidities, and CC-APSEs were compared between the groups. Predictors of apnea and EF were analyzed through logistic regression. There were 181 and 72 neonates in the LD and HD-caffeine-groups respectively. In HD-caffeine-group daily CC-dose was 7 to 7.5 mg/kg/day in 93% of neonates and >7.5 to 10 mg/kg/day in only 7%. Significantly fewer neonates experienced apnea and EF in the HD-caffeine-group till 28DOL or discharge. This difference was even greater in the subgroup of ≤28 weeks GA (15.6% vs 40.0%; P < .01). In HD-caffeine-group the incidence of severe/moderate-BPD was significantly lower and the frequency of CC-APSEs was higher. Multivariate analysis showed that; the smaller the GA higher the risk of apnea (AOR = 0.510, 95% CI 0.483-0.999) and EF (AOR = 0.787, 95% CI 0.411-0.997). The HD-caffeine was inversely associated with developing apnea (AOR = 0.244, 95% CI 0.053-0.291) and EF (AOR = 0.103, 95% CI 0.098-2.976). IMV-duration before extubation (AOR = 2.229, 95% CI 1.672-2.498) and severe/moderate-BPD (AOR = 2.410, 95%CI 1.104-2.952) had a high risk of EF. Initiating early HD-caffeine may prevent apnea and extubation failure in preterm neonates. Optimization of caffeine initiation time and dosages can be a safe and feasible approach to decrease the burden of neonatal respiratory morbidities.

Pulmonary strain and end-expiratory lung volume during apnea test: a comparative analysis using electrical impedance tomography.

The apnea test, employed for brain death assessment, aims to demonstrate the absence of respiratory drive due to hypercapnia. The tracheal oxygen insufflation apnea test mode (I-AT) involves disconnecting the patient from invasive mechanical ventilation (iMV) for approximately 8 minutes while maintaining oxygenation. This test supports the diagnosis of brain death based on a specified increase in PaCO2. Common complications include hypoxemia and hemodynamic instability, and lung collapse-induced reduction in end-expiratory lung volume (EELV). In our case series utilizing electrical impedance tomography (EIT), we observed that continuous positive airway pressure during the apnea test (CPAP-AT) effectively mitigated lung collapse. This resulted in improved pulmonary strain compared to the disconnection of iMV. These findings suggest the potential benefits of routine CPAP-AT, particularly for potential lung donors, emphasizing the relevance of our study in providing quantitative insights into EELV loss and its association with pulmonary strain and potential lung injury.

La prueba de apnea es una técnica diagnóstica ampliamente utilizada para la evaluación de la muerte cerebral, con el objetivo de demostrar la ausencia de impulso respiratorio debido a la hipercapnia. La variante de la prueba de apnea con insuflación de oxígeno traqueal (I-AT) implica desconectar al paciente de la ventilación mecánica invasiva (iVM) durante aproximadamente 8 minutos, manteniendo la oxigenación mediante un catéter de insuflación. Esta prueba respalda el diagnóstico de muerte cerebral cuando se determina un aumento de la PaCO 2 superior a 20 mmHg en comparación con el valor inicial o un nivel de PaCO 2 superior a 60 mmHg al final de la prueba. En nuestra serie de casos, la implementación de la tomografía de impedancia eléctrica (EIT) reveló que la prueba de apnea con presión positiva continua (CPAPAT) mitiga eficazmente el colapso pulmonar. Este enfoque resulta en una mejora en la tensión pulmonar en comparación con la desconexión de iMV, demostrando su relevancia en el contexto de potenciales donantes de pulmones.

Effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange compared with standard facemask oxygenation for pre- and apneic oxygenation during anesthesia induction: A meta-analysis based on randomized controlled trials.

PURPOSE: To further identify the effectiveness of trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) for pre- and apneic oxygenation during the anesthesia induction by comparison to facemask ventilation (FMV) based on current available evidence. METHODS: Medline, EMBASE, Web of Science, Cochrane Library and CNKI databases were searched from inception to December 22, 2023 for available randomized controlled trials (RCTs). Primary outcomes were PaO2 and PaCO2 after intubation and safe apnoea time. Secondary outcomes included the O2 desaturation, end expiratory carbon dioxide (EtCO2) and complications. The effect measures for continuous and categorical outcomes were separately the mean difference (MD) and relative risk (RR) with 95% confidence interval. RESULTS: Twelve RCTs with 403 patients in the THRIVE group and 401 patients in th FMV group were included. Pooled results demonstrated that the PaO2 after intubation was significantly higher (MD = 82.90mmHg, 95% CI: 12.25~153.54mmHg, P = 0.02) and safe apnoea time (MD = 103.81s, 95% CI: 42.07~165.56s, P = 0.001) was longer in the THRIVE group. Besides, the incidence rate of O2 desaturation (RR = 0.28, 95% CI: 0.12-0.66, P = 0.004) and gastric insufflation (RR = 0.26, 95% CI: 0.13-0.49, P<0.001) was significantly lower in the THRIVE group. CONCLUSION: Based on current evidence, THRIVE manifested better effectiveness representing as improved oxygenation, prolonged safe apnoea time and decreased risk of complications compared to standard FMV in surgical patients. Therefore, THRIVE could be served as a novel and valuable oxygenation technology for patients during anesthesia induction.

Apneic response to fentanyl in adult rats: Role of laryngeal afferents.

Intravenous (systemic) bolus injection of fentanyl (FNT) reportedly induces an immediate vagal-mediated apnea; however, the precise origin of vagal afferents responsible for this apnea remains unknown. We tested whether intralaryngeal (local) application of FNT would also trigger an apnea and whether the apneic response to both local and systemic administration of FNT was laryngeal afferent-mediated. Cardiorespiratory responses to FNT were recorded in anesthetized male adult rats with and without bilateral sectioning of the superior laryngeal nerve (SLNx) or peri-SLN capsaicin treatment (SLNcap) to block local C-fiber signal conduction. Opioid mu-receptor (MOR)-immunoreactivity was detected in laryngeal C- and myelinated neurons. We found that local and systemic administration of FNT elicited an immediate apnea. SLNx, rather than SLNcap, abolished the apneic response to local FNT application though MORs were abundantly expressed in both laryngeal C- and myelinated neurons. Importantly, SLNx failed to affect the apneic response to systemic FNT administration. These results lead to the conclusion that laryngeal afferents' MORs are responsible for the apneic response to local, but not systemic, administration of FNT.

Parametric analysis of an integrated cardio-respiratory model in preterm newborns during apnea.

The analysis of the complex interactions involved in the acute physiological response to apnea-bradycardia events in preterm newborns remains a challenging task. This paper presents a novel integrated model of cardio-respiratory interactions, adapted to preterm newborns. A sensitivity analysis, based Morris' screening method, was applied to study the effects of physiological parameters on heart rate and desaturation, during the simulation of a 15-seconds apnea-bradycardia episode. The most sensitive parameters are associated with fundamental, integrative physiological mechanisms involving: (i) respiratory mechanics (intermediate airways and lung compliance), (ii) fraction of inspired oxygen, (iii) metabolic rates (oxygen consumption rate), (iv) heart rate regulation and (v) chemoreflex (gain). Results highlight the relevant influence of physiological variables, involved in preterm apnea-bradycardia events.

Brainstem depolarization-induced lethal apnea associated with gain-of-function SCN1AL263V is prevented by sodium channel blockade.

Apneic events are frightening but largely benign events that often occur in infants. Here, we report apparent life-threatening apneic events in an infant with the homozygous SCN1AL263V missense mutation, which causes familial hemiplegic migraine type 3 in heterozygous family members, in the absence of epilepsy. Observations consistent with the events in the infant were made in an Scn1aL263V knock-in mouse model, in which apnea was preceded by a large brainstem DC-shift, indicative of profound brainstem depolarization. The L263V mutation caused gain of NaV1.1 function effects in transfected HEK293 cells. Sodium channel blockade mitigated the gain-of-function characteristics, rescued lethal apnea in Scn1aL263V mice, and decreased the frequency of severe apneic events in the patient. Hence, this study shows that SCN1AL263V can cause life-threatening apneic events, which in a mouse model were caused by profound brainstem depolarization. In addition to being potentially relevant to sudden infant death syndrome pathophysiology, these data indicate that sodium channel blockers may be considered therapeutic for apneic events in patients with these and other gain-of-function SCN1A mutations.

Stimulatory effect of methylglyoxal on capsaicin-sensitive lung vagal afferents in rats: role of TRPA1.

Methylglyoxal (MG), a reactive metabolic byproduct of glycolysis, is a causative of painful diabetic neuropathy. Patients with diabetes are associated with more frequent severe asthma exacerbation. Stimulation of capsaicin-sensitive lung vagal (CSLV) afferents may contribute to the pathogenesis of hyperreactive airway diseases such as asthma. However, the possibility of the stimulatory effect of MG on CSLV afferents and the underlying mechanisms remain unknown. Our results showed that intravenous injection of MG (25 mg/kg, MG25) in anesthetized, spontaneously breathing rats elicited pulmonary chemoreflexes characterized by apnea, bradycardia, and hypotension. The MG-induced apneic response was reproducible and dose dependent. MG25 no longer evoked these reflex responses after perineural capsaicin treatment of both cervical vagi to block C-fibers' conduction, suggesting that the reflexes were mediated through the stimulation of CSLV afferents. Pretreatment with HC030031 [an antagonist of transient receptor potential ankyrin subtype 1 protein (TRPA1)] or AP18 (another TRPA1 antagonist), but not their vehicle, markedly attenuated the apneic response induced by MG25. Consistently, electrophysiological results showed that pretreatment with HC030031 largely attenuated the intense discharge in CSLV afferents induced by injection of MG25 in open-chest and artificially ventilated rats. In isolated CSLV neurons, the perfusion of MG evoked an abrupt and pronounced increase in calcium transients in a concentration-dependent manner. This stimulatory effect on CSLV neurons was also abolished by HC030031 treatment but not by its vehicle. In conclusion, these results suggest that MG exerts a stimulatory effect on CSLV afferents, inducing pulmonary chemoreflexes, and such stimulation is mediated through the TRPA1 activation.NEW & NOTEWORTHY Methylglyoxal (MG) is implicated in the development of painful diabetic neuropathy. A retrospective cohort study revealed an increased incidence of asthma exacerbations in patients with diabetes. This study demonstrated that elevated circulating MG levels stimulate capsaicin-sensitive lung vagal afferents via activation of TRPA1, which in turn triggers respiratory reflexes. These findings provide new information for understanding the pathogenic mechanism of diabetes-associated hyperreactive airway diseases and potential therapy.

Thoracic impedance pneumography in propofol-sedated patients undergoing percutaneous endoscopic gastrostomy (PEG) placement in gastrointestinal endoscopy: A prospective, randomized trial.

STUDY OBJECTIVE: To assess the efficacy of an ECG-based method called thoracic impedance pneumography to reduce hypoxic events in endoscopy. DESIGN: This was a single center, 1:1 randomized controlled trial. SETTING: The trial was conducted during the placement of percutaneous endoscopic gastrostomy (PEG). PATIENTS: 173 patients who underwent PEG placement were enrolled in the present trial. Indication was oncological in most patients (89%). 58% of patients were ASA class II and 42% of patients ASA class III. INTERVENTIONS: Patients were randomized in the standard monitoring group (SM) with pulse oximetry and automatic blood pressure measurement or in the intervention group with additional thoracic impedance pneumography (TIM). Sedation was performed with propofol by gastroenterologists or trained nurses. MEASUREMENTS: Hypoxic episodes defined as SpO2 < 90% for >15 s were the primary endpoint. Secondary endpoints were minimal SpO2, apnea >10s/>30s and incurred costs. MAIN RESULTS: Additional use of thoracic impedance pneumography reduced hypoxic episodes (TIM: 31% vs SM: 49%; p = 0.016; OR 0.47; NNT 5.6) and elevated minimal SpO2 per procedure (TIM: 90.0% ± 8.9; SM: 84.0% ± 17.6; p = 0.007) significantly. Apnea events >10s and > 30s were significantly more often detected in TIM (43%; 7%) compared to SM (1%; 0%; p < 0.001; p = 0.014) resulting in a time advantage of 17 s before the occurrence of hypoxic events. As a result, adjustments of oxygen flow were significantly more often necessary in SM than in TIM (p = 0.034) and assisted ventilation was less often needed in TIM (2%) compared with SM (9%; p = 0.053). Calculated costs for the additional use of thoracic impedance pneumography were 0.13$ (0.12 €/0.11 £) per procedure. CONCLUSIONS: Additional thoracic impedance pneumography reduced the quantity and extent of hypoxic events with less need of assisted ventilation. Supplemental costs per procedure were negligible. KEY WORDS: thoracic impedance pneumography, capnography, sedation, monitoring, gastrointestinal endoscopy, percutaneous endoscopic gastrostomy.

Apnea behavior in early- and late-stage mouse models of Parkinson's disease: Cineradiographic analysis of spontaneous breathing, acute stress, and swallowing.

This study aimed to evaluate the timing and frequency of spontaneous apneas during breathing and swallowing by using cineradiography on mouse models of early/initial or late/advanced Parkinson's disease (PD). C57BL/6 J mice received either 6-OHDA or vehicle injections into their right striatum, followed by respiratory movement recordings during spontaneous breathing and swallowing, and a stress challenge, two weeks later. Experimental group animals showed a significantly lower respiratory rate (158.66 ± 32.88 breaths/minute in late PD, 173.16 ± 25.19 in early PD versus 185.27 ± 25.36 in controls; p<0.001) and a significantly higher frequency of apneas (median 1 apnea/minute in both groups versus 0 in controls; p<0.001). Other changes included reduced food intake and the absence of swallow apneas in experimental mice. 6-OHDA-induced nigrostriatal degeneration in mice disrupted respiratory control, swallowing, stress responsiveness, and feeding behaviors, potentially hindering airway protection and elevating the risk of aspiration.

Effects of hyperventilation on repeated breath-holding while in a fasting state: do risks outweigh the benefits?

Breath-holding preceded by either an overnight fast or hyperventilation has been shown to potentiate the risk of a hypoxic blackout. However, no study has explored the combined effects of fasting and hyperventilation on apneic performance and associated physiological responses. Nine nondivers (8 males) attended the laboratory on two separate occasions (≥48 h apart), both after a 12-h overnight fast. During each visit, a hyperoxic rebreathing trial was performed followed by three repeated maximal static apneas preceded by either normal breathing (NORM) or a 30-s hyperventilation (HYPER). Splenic volume, hematology, cardiovascular, and respiratory variables were monitored. There were no interprotocol differences at rest or during hyperoxic rebreathing for any variable (P ≥ 0.09). On nine occasions (8 in HYPER), the subjects reached our safety threshold (oxygen saturation 65%) and were asked to abort their apneas, with the preponderance of these incidents (6 of 9) occurring during the third repetition. Across the sequential attempts, longer apneas were recorded in HYPER [median(range), 220(123-324) s vs. 185(78-296) s, P ≤ 0.001], with involuntary breathing movements occurring later [134(65-234) s vs. 97(42-200) s, P ≤ 0.001] and end-apneic partial end-tidal pressures of oxygen (PETO2) being lower (P ≤ 0.02). During the final repetition, partial end-tidal pressure of carbon dioxide [(PETCO2), 6.53 ± 0.46 kPa vs. 6.01 ± 0.45 kPa, P = 0.005] was lower in HYPER. Over the serial attempts, preapneic tidal volume was gradually elevated [from apnea 1 to 3, by 0.26 ± 0.24 L (HYPER) and 0.28 ± 0.30 L (NORM), P ≤ 0.025], with a correlation noted with preapneic PETCO2 (r = -0.57, P < 0.001) and PETO2 (r = 0.76, P < 0.001), respectively. In a fasted state, preapnea hyperventilation compared with normal breathing leads to longer apneas but may increase the susceptibility to a hypoxic blackout.NEW & NOTEWORTHY This study shows that breath-holds (apneas) preceded by a 12-h overnight fast coupled with a 30-s hyperventilation as opposed to normal breathing may increase the likelihood of a hypoxic blackout through delaying the excitation of hypercapnic ventilatory sensory chemoreflexes. Evidently, this risk is exacerbated over a series of repeated maximal attempts, possibly due to a shift in preapneic gas tensions facilitated by an unintentional increase in tidal volume breathing.

Respiratory activity during seizures induced by pentylenetetrazole.

This study investigated the respiratory activity in adult Wistar rats across different behavioral seizure severity induced by pentylenetetrazole (PTZ). Animals underwent surgery for electrodes implantation, allowing simultaneous EEG and diaphragm EMG (DIAEMG) recordings and the respiratory frequency and DIAEMG amplitude were measured. Seizures were acutely induced through PTZ injection and classified based on a pre-established score, with absence-like seizures (spike wave discharge (SWD) events on EEG) representing the lowest score. The respiratory activity was grouped into the different seizure severities. During absence-like and myoclonic jerk seizures, the breathing frequency decreased significantly (∼50% decrease) compared to pre- and post-ictal periods. Pronounced changes occurred with more severe seizures (clonic and tonic) with periods of apnea, especially during tonic seizures. Apnea duration was significantly higher in tonic compared to clonic seizures. Notably, during PTZ-induced tonic seizures the apnea events were marked by tonic DIAEMG contraction (tonic-phase apnea). In the majority of animals (5 out of 7) this was a fatal event in which the seizure-induced respiratory arrest preceded the asystole. In conclusion, we provide an assessment of the respiratory activity in the PTZ-induced acute seizures and showed that breathing dysfunction is more pronounced in seizures with higher severity.

Stress biomarker changes following a series of repeated static and dynamic apneas in non-divers.

PURPOSE: This study examined the magnitude of physiological strain imposed by repeated maximal static and dynamic apneas through assessing a panel of stress-related biomarkers. METHODS: Eleven healthy men performed on three separate occasions (≥72-h apart): a series of five repeated maximal (i) static (STA) or (ii) dynamic apneas (DYN) or (iii) a static eupneic protocol (CTL). Venous blood samples were drawn at 30, 90, and 180-min after each protocol to determine ischaemia modified albumin (IMA), neuron-specific enolase (NSE), myoglobin, and high sensitivity cardiac troponin T (hscTnT) concentrations. RESULTS: IMA was elevated after the apnoeic interventions (STA,+86%;DYN,+332%,p ≤ 0.047) but not CTL (p = 0.385). Myoglobin was higher than baseline (23.6 ± 3.9 ng/mL) 30-min post DYN (+70%,38.8 ± 13.3 ng/mL,p = 0.030). A greater myoglobin release was recorded in DYN compared with STA and CTL (p ≤ 0.035). No changes were observed in NSE (p = 0.207) or hscTnT (p = 0.274). CONCLUSIONS: Five repeated maximal DYN led to a greater muscle injury compared with STA but neither elicited myocardial injury or neuronal-parenchymal damage.

First Real-Life Data on the Diving Response in Healthy Children.

Swimming and diving are popular recreational activities, representing an effective option in maintaining and improving cardiovascular fitness in healthy people. To date, only little is known about the cardiovascular adaption to submersion in children. This study was conducted to improve an understanding thereof. We used a stepwise apnea protocol with apnea at rest, apnea with facial immersion, and at last apnea during whole body submersion. Continuous measurement of heart rate, oxygen saturation, and peripheral resistance index was done. Physiologic data and analysis of influencing factors on heart rate, oxygen saturation, and peripheral vascular tone response are reported. The current study presents the first data of physiologic diving response in children. Data showed that facial or whole body submersion leads to a major drop in heart rate, and increase of peripheral resistance, while the oxygen saturation seems to be unaffected by static apnea in most children, with apnea times of up to 75 s without change in oxygen saturation.