Inspiratory Occlusion Research Articles

Respiratory Sensory Gating in Children Measured by the Respiratory‐Related Evoked Potentials

Respiratory neural gating function in the cortices was measured in healthy children using the paired respiratory‐related evoked potential (RREP) measured elicited by inspiratory occlusions. We hypothesized that respiratory sensory gating of healthy children would be normal as represented by a reduced amplitude of the second stimulus (S2) compared by the first stimulus (S1) for the short latency Nf, P1, and N1 peaks. We further hypothesized that the gating peak would be normal as represented by a N1 peak S2/S1 ratio of less than 0.5.Paired 150‐msec inspiratory occlusions with an inter‐stimulus‐interval of 500 milliseconds were given to the subjects. The RREP was recorded with a 40‐channel electroencephalography system. A minimum of 100 paired occlusions were collected for data analysis. The RREP Nf, P1, and N1 peaks were identified in latencies and amplitudes. The S2/S1 ratio was calculated for the amplitudes for each peak.Our preliminary data showed that the averaged latencies for the Nf, P1, and N1 peaks were 40 and 42, 55 and 48, 94 and 81 msec, respectively. The averaged S2/S1 ratio for the RREP Nf, P1, and N1 peak amplitudes were 0.97, 1.13, and 0.64, respectively.The result suggested that young children may have a decreased respiratory gating function represented by increased P1 and N1 peak S2/S1 ratios for the first order neural information processing.Supported by: NSC100–2320‐B‐182–018, CMRPD1A0021, CMRPD1A0022

The effect of anxiety on respiratory sensory gating measured by respiratory-related evoked potentials

Respiratory sensory gating is evidenced by decreased amplitudes of the respiratory-related evoked potentials (RREP) N1 peak for the second (S2) compared to the first occlusion (S1) when two paired occlusions are presented with a 500-millisecond (ms) inter-stimulus-interval during one inspiration. Because anxiety is prevalent in respiratory diseases and associated with altered respiratory perception, we tested whether anxiety can modulate individuals’ respiratory neural gating mechanism.By using high-density EEG, RREPs were measured in a paired inspiratory occlusion paradigm in 11 low and 10 higher anxious individuals with normal lung function.The N1 peak gating S2/S1 ratio and the N1 S2 amplitudes were greater in higher compared to low anxious individuals (p's<0.05). In addition, higher anxiety levels were correlated with greater S2/S1 ratios (r=0.54, p<0.05) and S2 amplitudes (r=−0.49, p<0.05).The results demonstrate that anxiety is associated with reduced respiratory sensory gating which might underlie altered respiratory symptom perception in anxious individuals.

Pulmonary Function and Expiratory Flow Limitation in Acute Cervical Spinal Cord Injury

Alvisi V, Marangoni E, Zannoli S, Uneddu M, Uggento R, Farabegoli L, Ragazzi R, Milic-Emili J, Belloni GP, Alvisi R, Volta CA. Pulmonary function and expiratory flow limitation in acute cervical spinal cord injury. ObjectiveTo identify the nature of the changes of respiratory mechanics in patients with middle cervical spinal cord injury (SCI) and their correlation with posture. DesignClinical trial. SettingAcute SCI unit. ParticipantsPatients with SCI (N=34) at C4-5 level studied within 6 months of injury. InterventionsPatients were assessed by the negative expiratory pressure test, maximal static respiratory pressure test, and standard spirometry. Main Outcome MeasuresThe following respiratory variables were recorded in both the semirecumbent and supine positions: (1) tidal expiratory flow limitation (TEFL); (2) airway resistances; (3) mouth occlusion pressure developed 0.1 seconds after occluded inspiration at functional residual capacity (P0.1); (4) maximal static inspiratory pressure (MIP) and maximal static expiratory pressure (MEP); and (5) spirometric data. ResultsTEFL was detected in 32% of the patients in the supine position and in 9% in the semirecumbent position. Airway resistances and P0.1 were much higher compared with normative values, while MIP and MEP were markedly reduced. The ratio of forced expiratory volume in 1 second to forced vital capacity was less than 70%, while the other spirometric data were reduced up to 30% of predicted values. ConclusionsPatients with middle cervical SCI can develop TEFL. The presence of TEFL, associated with increased airway resistance, could increase the work of breathing in the presence of a reduced capacity of the respiratory muscles to respond to the increased load. The semirecumbent position and the use of continuous positive airway pressure can be helpful to (1) reduce the extent of TEFL and avoid the opening/closure of the small airways; (2) decrease airway resistance; and (3) maintain the expiratory flow as high as possible, which aids in the removal of secretions.

Inspiratory Muscle Strength Training in Infants With Congenital Heart Disease and Prolonged Mechanical Ventilation: A Case Report

Inspiratory muscle strength training (IMST) has been shown to improve maximal pressures and facilitate ventilator weaning in adults with prolonged mechanical ventilation (MV). The purposes of this case report are: (1) to describe the rationale for IMST in infants with MV dependence and (2) to summarize the device modifications used to administer training. Two infants with congenital heart disease underwent corrective surgery and were referred for inspiratory muscle strength evaluation after repeated weaning failures. It was determined that IMST was indicated due to inspiratory muscle weakness and a rapid, shallow breathing pattern. In order to accommodate small tidal volumes of infants, 2 alternative training modes were devised. For infant 1, IMST consisted of 15-second inspiratory occlusions. Infant 2 received 10-breath sets of IMST through a modified positive end-expiratory pressure valve. Four daily IMST sets separated by 3 to 5 minutes of rest were administered 5 to 6 days per week. The infants' IMST tolerance was evaluated by vital signs and daily clinical reviews. Maximal inspiratory pressure (MIP) and rate of pressure development (dP/dt) were the primary outcome measures. Secondary outcome measures included the resting breathing pattern and MV weaning. There were no adverse events associated with IMST. Infants generated training pressures through the adapted devices, with improved MIP, dP/dt, and breathing pattern. Both infants weaned from MV to a high-flow nasal cannula, and neither required subsequent reintubation during their hospitalization. This case report describes pediatric adaptations of an IMST technique used to improve muscle performance and facilitate weaning in adults. Training was well tolerated in 2 infants with postoperative weaning difficulty and inspiratory muscle dysfunction. Further systematic examination will be needed to determine whether IMST provides a significant performance or weaning benefit.

Neuroventilatory efficiency and extubation readiness in critically ill patients

IntroductionBased on the hypothesis that failure of weaning from mechanical ventilation is caused by respiratory demand exceeding the capacity of the respiratory muscles, we evaluated whether extubation failure could be characterized by increased respiratory drive and impaired efficiency to generate inspiratory pressure and ventilation.MethodsAirway pressure, flow, volume, breathing frequency, and diaphragm electrical activity were measured in a heterogeneous group of patients deemed ready for a spontaneous breathing trial. Efficiency to convert neuromuscular activity into inspiratory pressure was calculated as the ratio of negative airway pressure and diaphragm electrical activity during an inspiratory occlusion. Efficiency to convert neuromuscular activity into volume was calculated as the ratio of the tidal volume to diaphragm electrical activity. All variables were obtained during a 30-minute spontaneous breathing trial on continuous positive airway pressure (CPAP) of 5 cm H2O and compared between patients for whom extubation succeeded with those for whom either the spontaneous breathing trial failed or for those who passed, but then the extubation failed.ResultsOf 52 patients enrolled in the study, 35 (67.3%) were successfully extubated, and 17 (32.7%) were not. Patients for whom it failed had higher diaphragm electrical activity (48%; P < 0.001) and a lower efficiency to convert neuromuscular activity into inspiratory pressure and tidal volume (40% (P < 0.001) and 53% (P < 0.001)), respectively. Neuroventilatory efficiency demonstrated the greatest predictability for weaning success.ConclusionsThis study shows that a mixed group of critically ill patients for whom weaning fails have increased neural respiratory drive and impaired ability to convert neuromuscular activity into tidal ventilation, in part because of diaphragm weakness.Trial RegistrationClinicaltrials.gov identifier NCT01065428. ©2012 Liu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The effect of anxiety on respiratory sensory gating measured by the respiratory related evoked potential (RREP)

Respiratory sensory gating is evidenced by decreased amplitude of the respiratory-related evoked potentials (RREP) N1 peak for the second occlusion (S2) when two 200-millisecond (msec) occlusions are presented with a 500-msec interval during inspiration. The N1 peak amplitude ratio of the S2 and first occlusion (S1), S2/S1, is less than 0.5 due to central neural sensory gating. We hypothesized that anxiety can modulate individuals' respiratory neural gating. We tested this hypothesis with the paired inspiratory occlusion protocol in 11 low and 10 high anxious individuals. Individuals were divided into the two groups based on their state anxiety scores obtained by the State-Trait Anxiety Inventory. The results showed a significant difference of the N1 peak gating S2/S1 ratio between the low anxious and high anxious group (0.28 ± 0.13 and 0.42 ± 0.16, respectively, p<0.05). A two-way ANOVA confirmed that this ratio difference was due to significantly lower S2 amplitudes in the low anxious group compared to the high anxious group (−1.31 ± 0.6 μV and −1.83 ± 0.59 μV, respectively). The results demonstrated that the respiratory sensory gating function was decreased in high anxious individuals. This suggests that anxiety was associated with increased neural throughput of redundant respiratory sensory information which might underlie altered respiratory symptom perception in anxious individuals.

The impact of anxiety on the neural processing of respiratory sensations

Previous studies demonstrated that anxiety considerably impacts the reported perceptions of respiratory sensations. A novel feature of the current study is exploring the impact of anxiety on the neural processing of respiratory sensations elicited by short inspiratory occlusions during different affective contexts. Using high-density EEG, respiratory-related evoked potentials (RREP) were recorded in 23 low and 23 matched higher anxious individuals when viewing unpleasant or neutral picture series. Low anxious individuals showed the expected pattern of reduced magnitudes of later RREP components P2 and P3 during the unpleasant compared to the neutral affective context (p<0.05 and p<0.01). In contrast, higher anxious individuals showed greater magnitudes of P2 and P3 during the unpleasant compared to the neutral affective context (p's<0.05). Moreover, higher anxiety levels were correlated with greater magnitudes for P2 (r=0.44, p<0.01) and P3 (r=0.54, p<0.001) during the unpleasant relative to the neutral affective context. Earlier components of the RREP (Nf, P1, N1) were not affected by anxiety. This study demonstrates that anxiety affects the later, higher-order neural processing of respiratory sensations, but not its earlier, first-order sensory processing. These findings might represent a neural mechanism that underlies the increased perception of respiratory sensations in anxious individuals.

Respiratory-related evoked potential measurements using high-density electroencephalography

Objective The respiratory-related evoked potential (RREP) has become an established technique for studying the neural processing of respiratory signals. However, the increasing availability of high-density EEG systems necessitates new criteria for obtaining acceptable RREPs with these systems. Methods The present study examined the minimum criteria for the number of inspiratory occlusions that need to be averaged in order to obtain a signal-to-noise ratio of 2:1 (3 dB) for the RREP components Nf, P1, N1, P2 and P3 with a 129 sensor high-density EEG system in 12 healthy volunteers. RREPs resulting from averaging 8, 16, 32 and 64 inspiratory occlusions were compared. Results Analyses of signal-to-noise ratios demonstrated that a minimum of 32 and 16 inspiratory occlusions should be averaged for Nf and P1, respectively. For N1, P2, and P3, an average of at least 8 inspiratory occlusions is required. However, to account for inter-individual variability, 64 averaged occlusions for Nf, 32 averaged occlusions for P1, and 16 averaged occlusions for N1, P2, and P3 are recommended which more reliably exceed the signal-to-noise threshold. Conclusions These numbers provide the minimum and the recommended criteria for reliable measurements of the RREP for an adequate number of repeated occlusion epochs to be averaged in order to yield a reliable signal-to-noise ratio using a 129 sensor EEG system. Significance The present study provides minimum and recommended criteria for obtaining acceptable RREPs with high-density EEG systems.

Habituation in neural processing and subjective perception of respiratory sensations

Reduced perception of respiratory sensations is associated with negative treatment outcome in asthma. We examined whether habituation in the neural processing of repeatedly experienced respiratory sensations may underlie subjective reports of reduced respiratory perception. Respiratory-related evoked potentials (RREP) elicited by inspiratory occlusions and reports of respiratory perception were compared between early and late experimental periods in healthy subjects. Reports of respiratory perception were reduced during late, compared to early, experimental periods. This was paralleled by reduced magnitudes in RREP components N1, P2, and P3 in late, compared to early, experimental periods. Habituation in the neural processing of respiratory sensations is a potential mechanism that underlies subjective reports of reduced respiratory perception and might represent a risk factor for reduced perception of respiratory sensations in asthma.

The effects of sleeping position on ventilatory responses to carbon dioxide in premature infants

BackgroundThe prone sleeping position, particularly in prematurely born infants, is associated with an increased risk of sudden infant death syndrome. A possible mechanism is an impaired ability to respond to...

Mechanosensory activation of the somatosensory cortex in unanesthetized rats

Respiratory related evoked potentials (RREP) elicited by inspiratory mechanical loads have been demonstrated in humans and lambs. However, it was unknown if an occlusion paradigm can also elicit a RREP in chronically instrumented, awake, spontaneously breathing rats. Rats were instrumented with electrodes on the surface of the cortex and an occluder was sutured around the trachea. After recovery, the tracheal cuff was inflated for 3 to 5 breaths. Occlusions were presented approximately every 30 seconds for approximately 10 to 18 minutes. Occlusion‐elicited evoked potentials (EP) were obtained by computer‐signal averaging the ECoG activity. A short‐latency peak was observed on the averaged occlusion‐elicited evoked potentials in all animals for Day 1 and 2. A long‐latency peak was observed in all animals from Day 3 to 11. The result demonstrated that inspiratory occlusion elicits an evoked potential in the cortex of awake, spontaneously breathing rats. The waveform of the EP changes with chronic occlusion conditioning.

Repeated inspiratory occlusions in anesthetized rats acutely increase blood coagulability as assessed by thromboelastography

Many of the components contributing to coagulability are enhanced by repeated episodes of hypoxia, as occurs in obstructive sleep apnea, but no one has yet measured the global hemostatic properties of blood in an animal model of this disease. Using thromboelastography, a hemostatic assay, we measured hemostasis in six pentobarbital-anesthetized rats before and after 3h of repeated inspiratory occlusions lasting 30s applied every 2 min and compared the results to those in six identically prepared rats before and after 3h of resting breathing. Rats subjected to occlusions displayed faster onset of clotting (p<0.031) and more rapid coagulation (p<0.031). Thus, repeated inspiratory occlusions acutely cause hypercoagulability in rats. Thromboelastography, a simple test of hemostasis, may help evaluate the factors responsible for this increase and, in patients with obstructive sleep apnea, the risk of future cardiovascular disease.

The impact of emotion on respiratory-related evoked potentials

Emotion influences the perception of respiratory sensations, although the specific mechanism underlying this modulation is not yet clear. We examined the impact of viewing pleasant, neutral, and unpleasant affective pictures on the respiratory-related evoked potential (RREP) elicited by a short inspiratory occlusion in healthy volunteers. Reduced P3 amplitude of the RREP was found for respiratory probes presented when viewing pleasant or unpleasant series, when compared to those presented during the neutral series. Earlier RREP components, such as Nf, P1, N1, and P2, showed no modulation by emotion. The results suggest that emotion impacts the perception of respiratory sensations by reducing the attentional resources available for processing afferent respiratory sensory signals.

Neural Processing of Respiratory Sensations when Breathing Becomes More Difficult and Unpleasant

The accurate perception of respiratory sensations is important for the successful management and treatment of respiratory diseases. Previous studies demonstrated that external stimuli such as affective pictures and distracting films can impact the perception and neural processing of respiratory sensations. This study examined the neural processing of respiratory sensations when breathing as an internal stimulus is manipulated and becomes more difficult and unpleasant. Sustained breathing through an inspiratory resistive load was used to increase perceived breathing difficulty in 12 female individuals without respiratory disease. Using high-density EEG, respiratory-related evoked potentials (RREP) to short inspiratory occlusions were recorded at early versus late time points of sustained loaded breathing. Ratings of perceived intensity and unpleasantness of breathing difficulty showed an increase from early to late time points of loaded breathing (p < 0.01 and p < 0.05, respectively). This was paralleled by significant increases in the magnitudes of RREP components N1, P2, and P3 (p < 0.01, p < 0.05, and p < 0.05, respectively). The present results demonstrate increases in the neural processing of respiratory sensations when breathing becomes more difficult and unpleasant. This might reflect a protective neural mechanism allowing effective response behavior when air supply is at risk.

Cortical sources of the respiratory-related evoked potential

The respiratory-related evoked potential (RREP) is increasingly used to study the neural processing of respiratory signals. However, little is known about the cortical origins of early (Nf, P1, N1) and later RREP components (P2, P3). By using high-density EEG, we studied cortical sources of RREP components elicited by short inspiratory occlusions in 18 healthy volunteers (6 female, mean age 20.0+/-1.8 years). Topographical maps for Nf and P1 showed bilateral maximum EEG voltages over the frontal and centro-parietal cortex, respectively. Cortical source analyses (minimum-norm estimates) in addition to topographical maps demonstrated bilateral sensorimotor cortex origins for N1 and P2 which were paralleled by an additional frontal cortex source (p's<0.05). The source of the P3 was located at the parietal cortex (p<0.05). The results support previous findings on the cortical sources of early RREP components Nf, P1 and N1 and demonstrate the cortical sources of later RREP components P2 and P3.

Neurologic Aspects of Sleep Apnea: Is Obstructive Sleep Apnea a Neurologic Disorder?

The upper airway caliber is determined by afferent sensory input to the brainstem respiratory centers and efferent motor neural output to the upper airway structures. Upper airway caliber is altered in obstructive sleep apnea. The mechanosensory receptors of the upper airway are capable of responding to changes in airway pressure, airflow, temperature, and to the upper airway muscle tone itself. Application of topical anesthesia change chronic snorers in apneic patients during sleep and prolong sleep apnea in obstructive sleep apnea (OSA) patients. Respiratory-related evoked potential are significantly reduced in OSA patients during non-rapid eye movement sleep indicating a sleep-related blunted cortical response to inspiratory occlusion. Histologic investigations of palatopharyngeal muscles from OSA patients show evidence of motor neuron lesions and actual damage to the muscles. Currently demonstrated local neurologic impairment and lesions can explain the development of sleep apneas and hypopneas.

Influence of dorsal periaqueductal gray activation on respiratory occlusion reflexes in rats

The dorsal periaqueductal gray (dPAG) is an essential neural component for central integration of defense behavior and associated autonomic regulation. Electrical and chemical stimulation of this region results in a significant decrease of inspiratory (Ti) and expiratory (Te) breathing durations. In the present study it was hypothesized that breath timing changes elicited by dPAG activation would modulate respiratory load compensation volume–timing reflexes. The effect of dPAG activation of breathing pattern was investigated using chemical stimulation with microinjection of the excitatory amino acid D,L-homocysteic acid (DLH) or disinhibition with GABAA (γ-aminobutyric acid) receptor antagonist bicuculline (BIC) in urethane-anesthetized, spontaneously breathing rats. Volume–timing reflexes were studied using inspiratory and expiratory occlusion before and after DLH or BIC dPAG activation. Both BIC and DLH activation of the dPAG significantly increased breathing frequency. Inspiratory occlusion significantly increased Ti before dPAG activation and DLH and BIC potentiated the relative increase in Ti during occlusion. BIC elicited a greater increase in inspiratory occlusion Ti than DLH. Inspiratory occlusion alone also significantly increased diaphragm EMG activity and this response was potentiated with dPAG activation. Expiratory occlusion significantly increased Te and DLH and BIC potentiated the relative increase in Te during expiratory occlusion. These results suggest that dPAG activation modulates the respiratory neural network, resulting in an increased respiratory drive and a decrease in volume–timing reflex sensitivity.

Position and ventilatory response to added dead space in prematurely born infants

Prematurely born infants are at increased risk of sudden infant death syndrome (SIDS) if slept prone. Prematurely born infants would have an impaired response to an added dead space and lower respiratory muscle strength in the prone compared to the supine position. Prospective study. PATIENT-SUBJECT SELECTION: Twenty-five infants, median gestational age of 30 (range 26-32) weeks. The infants were studied supine and prone at a median of 36 weeks postmenstrual age. Breath by breath minute volume was measured at baseline and after a dead space was incorporated into the breathing circuit; the time constant of the response was calculated. The maximum inspiratory occlusion pressure generated (MIOP) and the pressure generated over the first 100 msec (P(0.1)) during airway occlusion were assessed. The median time constant was longer (26 (range 8-106) sec vs. 22 (range 6-92) sec (P = 0.045)) and the median MIOP (P = 0.001) and P(0.1) (P = 0.003) were lower in the prone compared to the supine position. Prematurely born infants have a dampened response to tube breathing and reduced respiratory muscle strength in the prone compared to the supine position, which may contribute to their increased vulnerability to SIDS in the prone position.

Effects of Inspiratory Strength Training on the Detection of Inspiratory Loads

Pressure-threshold loads (DeltaPT) are inspiratory force-related loads, which contrast with resistive loads (DeltaR), are airflow-dependent loads. If detection of respiratory loads is a function of the background load, then pressure-threshold type inspiratory muscle strength training (IMST) would affect the detection of DeltaPT but have less effect on detection of DeltaR. DeltaR and DeltaPT detection and ventilatory responses were measured in healthy volunteers. IMST consisted of 4 sets of 6 breaths per day for 4 weeks, at 75% of maximal inspiratory pressure (MIP). MIP increased and a measure of inspiratory dirve, the mouth pressure generated in the initial 100 msec of an occluded inspiration (P(0.1)), decreased after IMST. IMST significantly increased MIP after 4 weeks of training. IMST did not change DeltaR detection threshold and DeltaR-breathing pattern. IMST decreased DeltaPT detection percent and DeltaPT-breathing pattern. Comparing DeltaR and DeltaPT at the same mouth pressure-generating level, the detection percent was different. We conclude that IMST affects the detection of DeltaPT, but not DeltaR. These results also suggest that mouth pressure is not the primary determinant of the inspiratory load detection. The significance of these results is that inspiratory pressure generating capacity can be increased by our pressure threshold training and this increase in respiratory muscle strength increases the ability of pulmonary patients to compensate for increased respiratory load and modulates the threshold for detection of changes in pulmonary mechanics.

Affective modulation of inspiratory motor drive

The present study aimed to explore inspiratory motor drive as measured by inspiratory occlusion pressure (P100) during affective picture viewing. P100 is the decrease in mouth pressure that develops 100 ms after an inspiratory effort against a closed breathing circuit. The P100 is a measure of the "central respiratory drive." Seventy-eight healthy women viewed four pictures series (160 s) varying in content: neutral, positive, threat, or pain. They also rated each picture series on pleasantness and arousal. An occlusion was applied at the onset of inspiration in 33% of the breaths. The threat and the pain picture series were associated with an increased P100 and were rated as most unpleasant and highest in arousal. We conclude that inspiratory motor drive is affectively modulated and is a measure of the respiratory response to threatful stimuli.