Cerebrovascular and blood pressure responses during voluntary apneas are larger than rebreathing.

Both voluntary rebreathing (RB) of expired air and voluntary apneas (VA) elicit changes in arterial carbon dioxide and oxygen (CO2 and O2) chemostimuli. These chemostimuli elicit synergistic increases in cerebral blood flow (CBF) and sympathetic nervous system activation, with the latter increasing systemic blood pressure. The extent that simultaneous and inverse changes in arterial CO2 and O2 and associated increases in blood pressure affect the CBF responses during RB versus VAs are unclear. We instrumented 21 healthy participants with a finometer (beat-by-beat mean arterial blood pressure; MAP), transcranial Doppler ultrasound (middle and posterior cerebral artery velocity; MCAv, PCAv) and a mouthpiece with sample line attached to a dual gas analyzer to assess pressure of end-tidal (PET)CO2 and PETO2. Participants performed two protocols: RB and a maximal end-inspiratory VA. A second-by-second stimulus index (SI) was calculated as PETCO2/PETO2 during RB. For VA, where PETCO2 and PETO2 could not be measured throughout, SI values were calculated using interpolated end-tidal gas values before and at the end of the apneas. MAP reactivity (MAPR) was calculated as the slope of the MAP/SI, and cerebrovascular reactivity (CVR) was calculated as the slope of MCAv or PCAv/SI. We found that compared to RB, VA elicited ~ fourfold increases in MAPR slope (P < 0.001), translating to larger anterior and posterior CVR (P ≤ 0.01). However, cerebrovascular conductance (MCAv or PCAv/MAP) was unchanged between interventions (P ≥ 0.2). MAP responses during VAs are larger than those during RB across similar chemostimuli, and differential CVR may be driven by increases in perfusion pressure.

Duration at high altitude influences the onset of arrhythmogenesis during apnea.

PURPOSE: Autonomic control of the heart is balanced by sympathetic and parasympathetic inputs. Excitation of both sympathetic and parasympathetic systems occurs concurrently during certain perturbations such as hypoxia, which stimulate carotid chemoreflex to drive ventilation. It is well established that the chemoreflex becomes sensitized throughout hypoxic exposure; however, whether progressive sensitization alters cardiac autonomic activity remains unknown. We sought to determine the duration of hypoxic exposure at high altitude necessary to unmask cardiac arrhythmias during instances of voluntary apnea. METHODS: Measurements of steady-state chemoreflex drive (SS-CD), continuous electrocardiogram (ECG) and SpO2 (pulse oximetry) were collected in 22 participants on 1 day at low altitude (1045 m) and over eight consecutive days at high-altitude (3800 m). SS-CD was quantified as ventilation (L/min) over stimulus index (PETCO2/SpO2). RESULTS: Bradycardia during apnea was greater at high altitude compared to low altitude for all days (p < 0.001). Cardiac arrhythmias occurred during apnea each day but became most prevalent (> 50%) following Day 5 at high altitude. Changes in saturation during apnea and apnea duration did not affect the magnitude of bradycardia during apnea (ANCOVA; saturation, p = 0.15 and apnea duration, p = 0.988). Interestingly, the magnitude of bradycardia was correlated with the incidence of arrhythmia per day (r = 0.8; p = 0.004). CONCLUSION: Our findings suggest that persistent hypoxia gradually increases vagal tone with time, indicated by augmented bradycardia during apnea and progressively increased the incidence of arrhythmia at high altitude.

The impact of 6 months of exercise-based cardiac rehabilitation on sympathetic neural recruitment during apneic stress.

The current study evaluated the hypothesis that 6 mo of exercise-based cardiac rehabilitation (CR) would improve sympathetic neural recruitment in patients with ischemic heart disease (IHD). Microneurography was used to evaluate action potential (AP) discharge patterns within bursts of muscle sympathetic nerve activity (MSNA), in 11 patients with IHD (1 female; 61 ± 9 yr) pre (pre-CR) and post (post-CR) 6 mo of aerobic and resistance training-based CR. Measures were made at baseline and during maximal voluntary end-inspiratory (EI-APN) and end-expiratory apneas (EE-APN). Data were analyzed during 1 min of baseline and the second half of apneas. At baseline, overall sympathetic activity was less post-CR (all P < 0.01). During EI-APN, AP recruitment was not observed pre-CR (all P > 0.05), but increases in both within-burst AP firing frequency (Δpre-CR: 2 ± 3 AP spikes/burst vs. Δpost-CR: 4 ± 3 AP spikes/burst; P = 0.02) and AP cluster recruitment (Δpre-CR: -1 ± 2 vs. Δpost-CR: 2 ± 2; P < 0.01) were observed in post-CR tests. In contrast, during EE-APN, AP firing frequency was not different post-CR compared with pre-CR tests (Δpre-CR: 269 ± 202 spikes/min vs. Δpost-CR: 232 ± 225 spikes/min; P = 0.54), and CR did not modify the recruitment of new AP clusters (Δpre-CR: -1 ± 3 vs. Δpost-CR: 0 ± 1; P = 0.39), or within-burst firing frequency (Δpre-CR: 3 ± 3 AP spikes/burst vs. Δpost-CR: 2 ± 2 AP spikes/burst; P = 0.21). These data indicate that CR improves some of the sympathetic nervous system dysregulation associated with cardiovascular disease, primarily via a reduction in resting sympathetic activation. However, the benefits of CR on sympathetic neural recruitment may depend upon the magnitude of initial impairment.

Five repeated maximal efforts of apneas increase the time to exhaustion in subsequent high-intensity exercise.

Ten subjects were tested on a cycle ergometer to exhaustion with intensity corresponding to 150 % of their peak power output (TF150) under three conditions [C: base line measurement; PRE: after five repeated breath hold maneuvers (BH); and POST: after 5BH, preceded by two weeks of BH training]. Respiratory and blood measurements were carried out. Upon cessation of 5BH, subjects compared to C condition started TF150 with reduced arterialized blood pH (C:7.428±0.023, PRE:7.419±0.016, POST:7.398±0.021) and elevated bicarbonate concentration (mmol/l), ventilation (l/min) and oxygen uptake (ml/min) (C:28.4±1.5, PRE:29.9±1.2, POST:30.0±1.8; C:10.4±2.5, PRE:13.3±3.3, POST:15.6±5.6; C:333.0±113.8, PRE:550.1±131.1, POST:585.1±192.8, respectively). After TF150, subjects had significantly reduced pH and elevated ventilation, and oxygen uptake in PRE and POST, in comparison to the C condition. TF150 (sec) significantly improved after 5BH without being further affected by BH training (C:44.8±8.1, PRE:49.2±4.8, POST:49.3±8.2). Priming breath holds prior to middle-distance racing may improve performance.

Time to desaturation in preterm infants undergoing endotracheal intubation.

BACKGROUND: Neonatal endotracheal intubation is often associated with physiological instability. The Neonatal Resuscitation Program recommends a time-based limit (30 s) for intubation attempts in the delivery room, but there are limited physiological data to support recommendations in the neonatal intensive care unit (NICU). We aimed to determine the time to desaturation after ceasing spontaneous or assisted breathing in preterm infants undergoing elective endotracheal intubation in the NICU. METHODS: Observational study at The Royal Women's Hospital, Melbourne. A secondary analysis was performed of video recordings of neonates ≤32 weeks' postmenstrual age undergoing elective intubation. Infants received premedication including atropine, a sedative and muscle relaxant. Apnoeic oxygenation time (AOT) was defined as the time from the last positive pressure or spontaneous breath until desaturation (SpO2 <90%). RESULTS: Seventy-eight infants were included. The median (IQR) gestational age at birth was 27 (26-29) weeks and birth weight 946 (773-1216) g. All but five neonates desaturated to SpO2 <90% (73/78, 94%). The median (IQR) AOT was 22 (14-32) s. The median (IQR) time from ceasing positive pressure ventilation to desaturation <80% was 35 (24-44) s and to desaturation <60% was 56 (42-68) s. No episodes of bradycardia were seen. CONCLUSIONS: This is the first study to report AOT in preterm infants. During intubation of preterm infants in the NICU, desaturation occurs quickly after cessation of positive pressure ventilation. These data are important for the development of clinical guidelines for neonatal intubation. TRIAL REGISTRATION NUMBER: ACTRN12614000709640.

Physiology, pathophysiology and (mal)adaptations to chronic apnoeic training: a state-of-the-art review.

Breath-hold diving is an activity that humans have engaged in since antiquity to forage for resources, provide sustenance and to support military campaigns. In modern times, breath-hold diving continues to gain popularity and recognition as both a competitive and recreational sport. The continued progression of world records is somewhat remarkable, particularly given the extreme hypoxaemic and hypercapnic conditions, and hydrostatic pressures these athletes endure. However, there is abundant literature to suggest a large inter-individual variation in the apnoeic capabilities that is thus far not fully understood. In this review, we explore developments in apnoea physiology and delineate the traits and mechanisms that potentially underpin this variation. In addition, we sought to highlight the physiological (mal)adaptations associated with consistent breath-hold training. Breath-hold divers (BHDs) are evidenced to exhibit a more pronounced diving-response than non-divers, while elite BHDs (EBHDs) also display beneficial adaptations in both blood and skeletal muscle. Importantly, these physiological characteristics are documented to be primarily influenced by training-induced stimuli. BHDs are exposed to unique physiological and environmental stressors, and as such possess an ability to withstand acute cerebrovascular and neuronal strains. Whether these characteristics are also a result of training-induced adaptations or genetic predisposition is less certain. Although the long-term effects of regular breath-hold diving activity are yet to be holistically established, preliminary evidence has posed considerations for cognitive, neurological, renal and bone health in BHDs. These areas should be explored further in longitudinal studies to more confidently ascertain the long-term health implications of extreme breath-holding activity.

Short-term hypoxia does not promote arrhythmia during voluntary apnea.

The presence of bradycardic arrhythmias during volitional apnea at altitude may be caused by chemoreflex activation/sensitization. We investigated whether bradyarrhythmic episodes became prevalent in apnea following short-term hypoxia exposure. Electrocardiograms (ECG; lead II) were collected from 22 low-altitude residents (F = 12; age=25 ± 5 years) at 671 m. Participants were exposed to normobaric hypoxia (SpO2 ~79 ± 3%) over a 5-h period. ECG rhythms were assessed during both free-breathing and maximal volitional end-expiratory and end-inspiratory apnea at baseline during normoxia and hypoxia exposure (20 min [AHX]; 5 h [HX5]). Free-breathing HR became elevated at AHX (78 ± 10 bpm; p < 0.0001) and HX5 (80 ± 12 bpm; p < 0.0001) compared to normoxia (68 ± 10 bpm), whereas apnea caused significant bradycardia at AHX (nadir end-expiratory -17 ± 14 bpm; p < 0.001) and HX5 (nadir end-expiratory -19 ± 15 bpm; p < 0.001), but not during normoxia (nadir end-expiratory -4 ± 13 bpm), with no difference in bradycardia responses between apneas at AHX and HX5. Conduction abnormalities were noted in five participants during normoxia (Premature Ventricular Contraction, Sinus Pause, Junctional Rhythm, Atrial Foci), which remained unchanged during apnea at AHX and HX5 (Premature Ventricular Contraction, Premature Atrial Contraction, Sinus Pause). End-inspiratory apneas were overall longer across conditions (normoxia p < 0.05; AHX p < 0.01; HX5 p < 0.001), with comparable HR responses to end-expiratory and fewer occurrences of arrhythmia. While short-term hypoxia is sufficient to elicit bradycardia during apnea, the occurrence of arrhythmias in response to apnea was not affected. These findings indicate that previously observed bradyarrhythmic events in untrained individuals at altitude only become prevalent following chronic hypoxia specificlly.

Prior oxygenation, but not chemoreflex responsiveness, determines breath-hold duration during voluntary apnea.

Central and peripheral respiratory chemoreceptors are stimulated during voluntary breath holding due to chemostimuli (i.e., hypoxia and hypercapnia) accumulating at the metabolic rate. We hypothesized that voluntary breath-hold duration (BHD) would be (a) positively related to the initial pressure of inspired oxygen prior to breath holding, and (b) negatively correlated with respiratory chemoreflex responsiveness. In 16 healthy participants, voluntary breath holds were performed under three conditions: hyperoxia (following five normal tidal breaths of 100% O2 ), normoxia (breathing room air), and hypoxia (following ~30-min of 13.5%-14% inspired O2 ). In addition, the hypoxic ventilatory response (HVR) was tested and steady-state chemoreflex drive (SS-CD) was calculated in room air and during steady-state hypoxia. We found that (a) voluntary BHD was positively related to initial oxygen status in a dose-dependent fashion, (b) the HVR was not correlated with BHD in any oxygen condition, and (c) SS-CD magnitude was not correlated with BHD in normoxia or hypoxia. Although chemoreceptors are likely stimulated during breath holding, they appear to contribute less to BHD compared to other factors such as volitional drive or lung volume.

Splenic responses to a series of repeated maximal static and dynamic apnoeas with whole-body immersion in water.

NEW FINDINGS: What is the central question of this study? Splenic contractions occur in response to apnoea-induced hypoxia with and without face immersion in water. However, the splenic responses to a series of static or dynamic apnoeas with whole-body water immersion in non-divers and elite breath-hold divers are unknown. What is the main finding and its importance? Static and dynamic apnoeas were equally effective in stimulating splenic contractions across non-divers and elite breath-hold divers. These findings demonstrate that the magnitude of the splenic response is largely dictated by the degree of the hypoxemic stress encountered during voluntary apnoeic epochs. ABSTRACT: Splenic contractions occur in response to apnoea-induced hypoxia with and without facial water immersion. However, the splenic responses to a series of static (STA) or dynamic (DYN) apnoeas with whole-body water immersion in non-divers (NDs) and elite breath-hold divers (EBHDs) are unknown. EBHD (n = 8), ND (n = 10) and control participants (n = 8) were recruited. EBHD and ND performed a series of five maximal DYN or STA on separate occasions. Control performed a static eupnoeic (STE) protocol to control against any effects of water immersion and diurnal variation on splenic volume and haematology. Heart rate (HR) and peripheral oxygen saturation (SpO2 ) were monitored for 30 s after each apnoea. Pre- and post-apnoeic splenic volumes were quantified ultrasonically, and blood samples were drawn for haematology. For EBHD and ND end-apnoeic HR was higher (P < 0.001) and SpO2 was lower in DYN (P = 0.024) versus STA. EBHD attained lower end-apnoeic SpO2 during DYN and STA than NDs (P < 0.001). Splenic contractions occurred following DYN (EBHD, -47 ± 6%; ND, -37 ± 4%; P < 0.001) and STA (EBHD, -26 ± 4%; ND, -26 ± 8%; P < 0.01). DYN-associated splenic contractions were greater than STA in EBHD only (P = 0.042). Haemoglobin concentrations were higher following DYN only (EBHD, +5 ± 8g/L  , +4 ± 2%; ND, +8 ± 3 g/L , +4.9 ± 3%; P = 0.019). Haematocrit remained unchanged after each protocol. There were no between group differences in post-apnoeic splenic volume or haematology. In both groups, splenic contractions occurred in response to STA and DYN when combined with whole-body immersion. DYN apnoeas, were effective at increasing haemoglobin concentrations but not STA apnoeas. Thus, the magnitude of the splenic response relates to the hypoxemic stress encountered during apnoeic epochs.

The use of apnea test and brain death determination in patients on extracorporeal membrane oxygenation: A systematic review.

OBJECTIVE: To review practices of brain death (BD) determination in patients on extracorporeal membrane oxygenation (ECMO). METHODS: A systematic search was applied to PubMed and 6 electronic databases from inception to May 22, 2019. Studies reporting methods of BD assessment in adult patients (>18 years old) while on ECMO were included, after which data regarding BD assessment were extracted. RESULTS: Twenty-two studies (n = 177 patients) met the inclusion criteria. Eighty-eight patients (50%) in 19 studies underwent the apnea test (AT); most commonly through decreasing the ECMO sweep flow in 14 studies (n = 42, 48%), followed by providing CO2 through the ventilator in 2 studies (n = 6, 7%), and providing CO2 through the ECMO oxygenator in 1 study (n = 1, 1%). The details of the AT were not reported in 2 studies (n = 39, 44%). In 19 patients (22%), the AT was nonconfirmatory due to hemodynamic instability, hypoxia, insufficient CO2 rise, or unreliability of the AT. A total of 157 ancillary tests were performed, including electroencephalogram (62%), computed tomography angiography (22%), transcranial Doppler ultrasound (6%), cerebral blood flow nuclear study (5%), cerebral angiography (4%), and other (1%). Forty-seven patients (53% of patients with AT) with confirmatory AT still underwent additional ancillary for BD confirmation. Only 21 patients (12% of all patients) were declared brain-dead using confirmatory ATs alone without ancillary testing. CONCLUSIONS: Performing AT for patients with ECMO was associated with high failure rate and hemodynamic complications. Our study highlights the variability in practice in regard to the AT and supports the use of ancillary tests to determine BD in patients on ECMO.

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea.

NEW FINDINGS: What is the central question of this study? What is the relative contribution of a putative tonic splenic contraction to the haematological acclimatization process during high altitude ascent in native lowlanders? What is the main finding and its importance? Spleen volume decreased by -14.3% (-15.2 ml) per 1000 m ascent, with an attenuated apnoea-induced [Hb] increase, attesting to a tonic splenic contraction during high altitude ascent. The [Hb]-enhancing function of splenic contraction may contribute to restoring oxygen content early in the acclimatization process at high altitude. ABSTRACT: Voluntary apnoea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in haemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation ( SpO2 ), which may cause tonic splenic contraction, which may contribute to haematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, SpO2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0) to 3440 m (day 3), 4240 m (day 7) and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnoea-induced responses in HR, SpO2 and splenic volume were measured before and after two separate voluntary maximal apnoeas (A1-A2) at 1400, 3440 and 4240 m. Resting spleen volume decreased -14.3% (-15.2 ml) per 1000 m with ascent, from 140 ± 41 ml (1400 m) to 108 ± 28 ml (3440 m; P > 0.99), 94 ± 22 ml (4240 m; P = 0.009) and 84 ± 28 ml (5160 m; P = 0.029), with concomitant increases in [Hb] from 125 ± 18.3 g l-1 (1400 m) to 128 ± 10.4 g l-1 (3440 m), 138.8 ± 12.7 g l-1 (4240 m) and 157.5 ± 8 g l-1 (5160 m; P = 0.021). Apnoea-induced splenic contraction was 50 ± 15 ml (1400 m), 44 ± 17 ml (3440 m; P > 0.99) and 26 ± 8 ml (4240 m; P = 0.002), but was not consistently associated with increases in [Hb]. The apnoea-induced bradycardia was more pronounced at 3440 m (A1: P = 0.04; A2: P = 0.094) and at 4240 m (A1: P = 0.037 A2: P = 0.006) compared to values at 1400 m. We conclude that hypoxia-induced splenic contraction at rest (a) may contribute to restoring arterial oxygen content through its [Hb]-enhancing contractile function and (b) eliminates further apnoea-induced [Hb] increases in hypoxia. We suggest that tonic splenic contraction may contribute to haematological acclimatization early in HA ascent in humans.

Neonatal apneic phenotype in a murine congenital central hypoventilation syndrome model is induced through non-cell autonomous developmental mechanisms.

Congenital central hypoventilation syndrome (CCHS) represents a rare genetic disorder usually caused by mutations in the homeodomain transcription factor PHOX2B. Some CCHS patients suffer mainly from deficiencies in CO2 and/or O2 respiratory chemoreflex, whereas other patients present with full apnea shortly after birth. Our goal was to identify the neuropathological mechanisms of apneic presentations in CCHS. In the developing murine neuroepithelium, Phox2b is expressed in three discrete progenitor domains across the dorsal-ventral axis, with different domains responsible for producing unique autonomic or visceral motor neurons. Restricting the expression of mutant Phox2b to the ventral visceral motor neuron domain induces marked newborn apnea together with a significant loss of visceral motor neurons, RTN ablation, and preBötzinger complex dysfunction. This finding suggests that the observed apnea develops through non-cell autonomous developmental mechanisms. Mutant Phox2b expression in dorsal rhombencephalic neurons did not generate significant respiratory dysfunction, but did result in subtle metabolic thermoregulatory deficiencies. We confirm the expression of a novel murine Phox2b splice variant which shares exons 1 and 2 with the more widely studied Phox2b splice variant, but which differs in exon 3 where most CCHS mutations occur. We also show that mutant Phox2b expression in the visceral motor neuron progenitor domain increases cell proliferation at the expense of visceral motor neuron development. We propose that visceral motor neurons may function as organizers of brainstem respiratory neuron development, and that disruptions in their development result in secondary/non-cell autonomous maldevelopment of key brainstem respiratory neurons.

Tolerance to Opioid-Induced Respiratory Depression in Chronic High-Dose Opioid Users: A Model-Based Comparison With Opioid-Naïve Individuals.

Chronic opioid consumption is associated with addiction, physical dependence, and tolerance. Tolerance results in dose escalation to maintain the desired opioid effect. Intake of high-dose or potent opioids may cause life-threatening respiratory depression, an effect that may be reduced by tolerance. We performed a pharmacokinetic-pharmacodynamic analysis of the respiratory effects of fentanyl in chronic opioid users and opioid-naïve subjects to quantify tolerance to respiratory depression. Fourteen opioid-naïve individuals and eight chronic opioid users received escalating doses of intravenous fentanyl (opioid-naïve subjects: 75-350 µg/70 kg; chronic users: 250-700 µg/70 kg). Isohypercapnic ventilation was measured and the fentanyl plasma concentration-ventilation data were analyzed using nonlinear mixed-effects modeling. Apneic events occurred in opioid-naïve subjects after a cumulative fentanyl dose (per 70 kg) of 225 (n = 3) and 475 µg (n = 6), and in 7 chronic opioid users after a cumulative dose of 600 (n = 2), 1,100 (n = 2), and 1,800 µg (n = 3). The time course of fentanyl's respiratory depressant effect was characterized using a biophase equilibration model in combination with an inhibitory maximum effect (Emax ) model. Differences in tolerance between populations were successfully modeled. The effect-site concentration causing 50% ventilatory depression, was 0.42 ± 0.07 ng/mL in opioid-naïve subjects and 1.82 ± 0.39 ng/mL in chronic opioid users, indicative of a 4.3-fold sensitivity difference. Despite higher tolerance to fentanyl-induced respiratory depression, apnea still occurred in the opioid-tolerant population indicative of the potential danger of high-dose opioids in causing life-threatening respiratory depression in all individuals, opioid-naïve and opioid-tolerant.

Physiological responses to facemask application in newborns immediately after birth.

OBJECTIVE: Application of a face mask may induce apnoea and bradycardia, possibly via the trigeminocardiac reflex (TCR). We aimed to describe rates of apnoea and bradycardia in term and late-preterm infants following facemask application during neonatal stabilisation and compare the effects of first facemask application with subsequent applications. DESIGN: Subgroup analysis of a prospective, randomised trial comparing two face masks. SETTING: Single-centre study in the delivery room PATIENTS: Infants>34 weeks gestational age at birth METHODS: Resuscitations were video recorded. Airway flow and pressure were measured using a flow sensor. The effect of first and subsequent facemask applications on spontaneously breathing infants were noted. When available, flow waveforms as well as heart rate (HR) were assessed 20 s before and 30 s after each facemask application. RESULTS: In total, 128 facemask applications were evaluated. In eleven percent of facemask applications infants stopped breathing. The first application was associated with a higher rate of apnoea than subsequent applications (29% vs 8%, OR (95% CI)=4.76 (1.41-16.67), p=0.012). On aggregate, there was no change in median HR over time. In the interventions associated with apnoea, HR dropped by 38bpm [median (IQR) at time of facemask application: 134bpm (134-150) vs 96bpm (94-102) 20 s after application; p=0.25] and recovered within 30 s. CONCLUSIONS: Facemask applications in term and late-preterm infants during neonatal stabilisation are associated with apnoea and this effect is more pronounced after the first compared with subsequent applications. Healthcare providers should be aware of the TCR and vigilant when applying a face mask to newborn infants. TRIAL REGISTRATION NUMBER: ACTRN12616000768493.

Evaluating the ventilatory effect of transnasal humidified rapid insufflation ventilatory exchange in apnoeic small children with two different oxygen flow rates: a randomised controlled trial.

Transnasal humidified rapid insufflation ventilatory exchange prolongs safe apnoeic oxygenation time in children. In adults, transnasal humidified rapid insufflation ventilatory exchange is reported to have a ventilatory effect with PaCO2 levels increasing less rapidly than without it. This ventilatory effect has yet to be reproduced in children. In this non-inferiority study, we tested the hypothesis that children weighing 10-15 kg exhibit no difference in carbon dioxide clearance when comparing two different high-flow nasal therapy flow rates during a 10-min apnoea period. Following standardised induction of anaesthesia including neuromuscular blockade, patients were randomly allocated to high-flow nasal therapy of 100% oxygen at 2 or 4 l.kg-1 .min-1 . Airway patency was ensured by continuous jaw thrust. The study intervention was terminated for safety reasons when SpO2 values dropped < 95%, or transcutaneous carbon dioxide levels rose > 9.3 kPa, or near-infrared spectroscopy values dropped > 20% from their baseline values, or after an apnoeic period of 10 min. Fifteen patients were included in each group. In the 2 l.kg-1 .min-1 group, mean (SD) transcutaneous carbon dioxide increase was 0.46 (0.11) kPa.min-1 , while in the 4 l.kg-1 .min-1 group it was 0.46 (0.12) kPa.min-1 . The upper limit of a one-sided 95%CI for the difference between groups was 0.07 kPa.min-1 , lower than the predefined non-inferiority margin of 0.147 kPa.min-1 (p = 0.001). The lower flow rate of 2 l.kg-1 .min-1 was non-inferior to 4 l.kg-1 .min-1 relative to the transcutaneous carbon dioxide increase. In conclusion, an additional ventilatory effect of either 2 or 4 l.kg-1 .min-1 high-flow nasal therapy in apnoeic children weighing 10-15 kg appears to be absent.

Limitations of surface EMG estimate of parasternal intercostal to infer neural respiratory drive.

BACKGROUND: Recently, surface EMG of parasternal intercostal muscle has been incorporated in the "ERS Statement of Respiratory Muscle Testing" as a clinical technique to monitor the neural respiratory drive (NRD). However, the anatomy of the parasternal muscle risks confounding EMG "crosstalk" activity from neighboring muscles. OBJECTIVES: To determine if surface "parasternal" EMG: 1) reliably estimates parasternal intercostal EMG activity, 2) is a valid surrogate expressing neural respiratory drive (NRD). METHODS: Fine wire electrodes were implanted into parasternal intercostal muscle in 20 severe COPD patients along with a pair of surface EMG electrodes at the same intercostal level. We recorded both direct fine wire parasternal EMG (EMGPARA) and surface estimated "parasternal" EMG (SurfEMGpara) simultaneously during resting breathing, volitional inspiratory maneuvers, apnoea with extraneous movement of upper extremity, and hypercapnic ventilation. RESULTS: Surface estimated "parasternal" EMG showed spurious "pseudobreathing" activity without any airflow while real parasternal EMG was silent, during apnoea with body extremity movement. Surface estimated "parasternal" EMG did not faithfully represent real measured parasternal EMG. Surface estimated "parasternal" EMG was significantly less active than directly measured parasternal EMG during all conditions including baseline, inspiratory capacity and hypercapnic ventilation. Bland-Altman analysis showed consistent bias between direct parasternal EMG recording and surface estimated EMG during stimulated breathing. CONCLUSION: Surface "parasternal" EMG does not consistently or reliably express EMG activity of parasternal intercostal as recorded directly by implanted fine wires. A chest wall surface estimate of parasternal intercostal EMG may not faithfully express NRD and is of limited utility as a biomarker in clinical applications.

Baroreflex responses during dry resting and exercise apnoeas in air and pure oxygen.

PURPOSE: We analysed the characteristics of arterial baroreflexes during the first phase of apnoea (φ1). METHODS: 12 divers performed rest and exercise (30 W) apnoeas (air and oxygen). We measured beat-by-beat R-to-R interval (RRi) and mean arterial pressure (MAP). Mean RRi and MAP values defined the operating point (OP) before (PRE-ss) and in the second phase (φ2) of apnoea. Baroreflex sensitivity (BRS, ms·mmHg-1) was calculated with the sequence method. RESULTS: In PRE-ss, BRS was (median [IQR]): at rest, 20.3 [10.0-28.6] in air and 18.8 [13.8-25.2] in O2; at exercise 9.2[8.4-13.2] in air and 10.1[8.4-13.6] in O2. In φ1, during MAP decrease, BRS was lower than in PRE-ss at rest (6.6 [5.3-11.4] in air and 7.7 [4.9-14.3] in O2, p < 0.05). At exercise, BRS in φ1 was 6.4 [3.9-13.1] in air and 6.7 [4.1-9.5] in O2. After attainment of minimum MAP (MAPmin), baroreflex resetting started. After attainment of minimum RRi, baroreflex sequences reappeared. In φ2, BRS at rest was 12.1 [9.6-16.2] in air, 12.9 [9.2-15.8] in O2. At exercise (no φ2 in air), it was 7.9 [5.4-10.7] in O2. In φ2, OP acts at higher MAP values. CONCLUSION: In apnoea φ1, there is a sudden correction of MAP fall via baroreflex. The lower BRS in the earliest φ1 suggests a possible parasympathetic mechanism underpinning this reduction. After MAPmin, baroreflex resets, displacing its OP at higher MAP level; thus, resetting may not be due to central command. After resetting, restoration of BRS suggests re-establishment of vagal drive.

Utility of oxygen insufflation through working channel during fiberoptic intubation in apneic patients: a prospective randomized controlled study.

BACKGROUND: Airway management is a part of routine anesthetic procedures; however, serious complications, including hypoxia and death, are known to occur in cases of difficult airways. Therefore, alternative techniques such as fiberoptic bronchoscope-assisted intubation (FOB intubation) should be considered, although this method requires more time and offers a limited visual field than does intubation with a direct laryngoscope. Oxygen insufflation through the working channel during FOB intubation could minimize the risk of desaturation and improve the visual field. Therefore, the aim of this prospective randomized controlled study was to evaluate the utility and safety of oxygen insufflation through the working channel during FOB intubation in apneic patients. METHODS: Thirty-six patients were randomly allocated to an N group (no oxygen insufflation) or an O group (oxygen insufflation). After preoxygenation, FOB intubation was performed with (O group) or without (N group) oxygen insufflation in apneic patients. The primary outcome was the velocity of decrease in the partial pressure of oxygen (PaO2) during FOB intubation (VPaO2, mmHg/sec) defined as the difference of PaO2 before and after intubation divided by the time to intubation. The secondary outcomes included the success rate for FOB intubation, time to intubation, visual field during FOB intubation, findings of arterial blood gas analysis, and occurrence of FOB intubation-related complications. RESULTS: We found that VPaO2 was significantly greater in the N group than in the O group (1.0 ± 0.4 vs. 0.4 ± 0.4; p < 0.001), while the visual field was similar between groups. There were no significant intergroup differences in the secondary outcomes. CONCLUSIONS: These findings suggest that oxygen insufflation through the working channel during FOB intubation aids in extending the apneic window during the procedure. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02625194 , registered at December 9, 2015.

Frequent epileptic apnoea in a patient with Pitt-Hopkins syndrome.

Pitt-Hopkins syndrome is a rare genetic disease, characterised by severe intellectual disability, distinctive dysmorphic features, epilepsy and distinctive breathing abnormalities during wakefulness. Here, we describe the case of a 22-year-old woman with Pitt-Hopkins syndrome who presented with intractable generalised tonic seizures from the age of 11 years, which increased in frequency with age and onset of menstruation despite usage of some anticonvulsant drugs. From the age of 16 years, polysomnography and video-EEG led to the detection of frequent epileptic apnoea during sleep. Although the frequency of generalised tonic seizure clusters was reduced by treatment with phenobarbital and potassium bromide, epileptic apnoea persisted. Furthermore, frequent epileptic apnoea observed in our patient was regarded as a factor for aspiration and deterioration of respiratory function. This study indicates that patients with Pitt-Hopkins syndrome require close monitoring for epileptic apnoea. Moreover, long-term EEG and respiratory monitoring are necessary to distinguish epileptic apnoea from other respiratory disorders in patients with Pitt-Hopkins syndrome.

Influence of sympathetic activation on myocardial contractility measured with ballistocardiography and seismocardiography during sustained end-expiratory apnea.

Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. BCG and SCG kinetic energies (KE) and their temporal integrals (iK) during a single heartbeat are computed in linear and rotational dimensions. Our aim was to test the hypothesis that iK from BCG and SCG are related to sympathetic activation during maximal voluntary end-expiratory apnea. Multiunit muscle sympathetic nerve traffic [burst frequency (BF), total muscular sympathetic nerve activity (tMSNA)] was measured by microneurography during normal breathing and apnea (n = 28, healthy men). iK of BCG and SCG were simultaneously recorded in the linear and rotational dimension, along with oxygen saturation ([Formula: see text]) and systolic blood pressure (SBP). The mean duration of apneas was 25.4 ± 9.4 s. SBP, BF, and tMSNA increased during the apnea compared with baseline (P = 0.01, P = 0.002,and P = 0.001, respectively), whereas [Formula: see text] decreased (P = 0.02). At the end of the apnea compared with normal breathing, changes in iK computed from BCG were related to changes of tMSNA and BF only in the linear dimension (r = 0.85, P < 0.0001; and r = 0.72, P = 0.002, respectively), whereas changes in linear iK of SCG were related only to changes of tMSNA (r = 0.62, P = 0.01). We conclude that maximal end expiratory apnea increases cardiac kinetic energy computed from BCG and SCG, along with sympathetic activity. The novelty of the present investigation is that linear iK of BCG is directly and more strongly related to the rise in sympathetic activity than the SCG, mainly at the end of a sustained apnea, likely because the BCG is more affected by the sympathetic and hemodynamic effects of breathing cessation. BCG and SCG may prove useful to assess sympathetic nerve changes in patients with sleep disturbances.NEW & NOTEWORTHY Ballistocardiography (BCG) and seismocardiography (SCG) assess vibrations produced by cardiac contraction and blood flow, respectively, through micro-accelerometers and micro-gyroscopes. Kinetic energies (KE) and their temporal integrals (iK) during a single heartbeat are computed from the BCG and SCG waveforms in a linear and a rotational dimension. When compared with normal breathing, during an end-expiratory voluntary apnea, iK increased and was positively related to sympathetic nerve traffic rise assessed by microneurography. Further studies are needed to determine whether BCG and SCG can probe sympathetic nerve changes in patients with sleep disturbances.