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La commande diaphragmatique
Abstract
Le contrôle de la ventilation procède d’une interaction complexe entre des efférences provenant de centres bulbaires et suprapontiques à destination des groupes musculaires ventilatoires et des afférences ventilatoires provenant de mécano- et de chémorécepteurs. La commande ainsi produite est transmise en premier lieu aux muscles dilatateurs des voies aériennes supérieures puis aux muscles thoraciques, dont le diaphragme. Cette distribution de la commande ventilatoire est modifiée face à une contrainte à l’écoulement de l’air.
... Le réglage du débit de balayage de la membrane permet aisément de contrôler le niveau de PaCO 2 et donc le pH. La commande ventilatoire est donc très dépendante des réglages de l'ECMO [36]. L'augmentation du pH permise par l'ECMO permet de diminuer l'activation des chémorécepteurs centraux et périphériqueset donc d'inhiber la commande ventilatoire. ...
Au cours du syndrome de détresse respiratoire aiguë, une stratégie ventilatoire dite « protectrice » nécessite le plus souvent une sédation profonde et une curarisation initiale en raison des risques d’asynchronies majeures et/ou, dans les modes en pression, de volumes courants excessifs liés à l’intensité des efforts inspiratoires. Une approche originale visant à permettre la ventilation spontanée sans s’exposer à ces risques est possible grâce au mode airway pressure release ventilation. Dans ce mode, des cycles contrôlés en pression sont délivrés tout en permettant au patient de réaliser, à tout moment aux deux niveaux de pression, des cycles spontanés sans assistance. Le fonctionnement est par principe parfaitement asynchrone. Ce mode pourrait permettre d’améliorer le recrutement alvéolaire en particulier dans les zones dépendantes, de diminuer le risque de dysfonction diaphragmatique induite par la ventilation mécanique et de réduire la sédation et la durée de ventilation mécanique, et pourrait également avoir des effets hémodynamiques bénéfiques. Cependant, une activité ventilatoire spontanée trop importante pourrait être responsable d’un travail respiratoire excessif et d’un risque accru de lésions induites par la ventilation mécanique.
To determine if, compared with pressure support (PS), neurally adjusted ventilatory assist (NAVA) reduces trigger delay, inspiratory time in excess, and the number of patient-ventilator asynchronies in intubated patients.
Prospective interventional study in spontaneously breathing patients intubated for acute respiratory failure. Three consecutive periods of ventilation were applied: (1) PS1, (2) NAVA, (3) PS2. Airway pressure, flow, and transesophageal diaphragmatic electromyography were continuously recorded.
All results are reported as median (interquartile range, IQR). Twenty-two patients were included, 36.4% (8/22) having obstructive pulmonary disease. NAVA reduced trigger delay (ms): NAVA, 69 (57-85); PS1, 178 (139-245); PS2, 199 (135-256). NAVA improved expiratory synchrony: inspiratory time in excess (ms): NAVA, 126 (111-136); PS1, 204 (117-345); PS2, 220 (127-366). Total asynchrony events were reduced with NAVA (events/min): NAVA, 1.21 (0.54-3.36); PS1, 3.15 (1.18-6.40); PS2, 3.04 (1.22-5.31). The number of patients with asynchrony index (AI) >10% was reduced by 50% with NAVA. In contrast to PS, no ineffective effort or late cycling was observed with NAVA. There was less premature cycling with NAVA (events/min): NAVA, 0.00 (0.00-0.00); PS1, 0.14 (0.00-0.41); PS2, 0.00 (0.00-0.48). More double triggering was seen with NAVA, 0.78 (0.46-2.42); PS1, 0.00 (0.00-0.04); PS2, 0.00 (0.00-0.00).
Compared with standard PS, NAVA can improve patient-ventilator synchrony in intubated spontaneously breathing intensive care patients. Further studies should aim to determine the clinical impact of this improved synchrony.
Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans.
To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena.
Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-κB, and calpains).
TwPtr decreased progressively during MV, with a mean reduction of 32 ± 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 ± 4.8 vs. 4.7 ± 0.6% area), decreased cross-sectional area of muscle fibers (1,904 ± 220 vs. 3,100 ± 329 μm²), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-κB (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm.
Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.
During mechanical ventilation, the respiratory system is under the influence of two pumps, the ventilator pump and the patient's own respiratory muscles. Depending on the mode of mechanical ventilatory support, ventilation may be totally controlled by the ventilator or may be determined by the interaction between patient respiratory effort and ventilator function. In either case, compared to spontaneous breathing, the breathing pattern is altered and this may influence: 1) force-length and force-velocity relationships of respiratory muscles (mechanical feedback); 2) chemical stimuli (chemical feedback); 3) the activity of various receptors located in the respiratory tract, lung and chest wall (reflex feedback); and 4) behavioural response (behavioural feedback). Changes in these feedback systems may modify the function of the ventilator, in a way that is dependent on the mode of mechanical ventilatory support, ventilator settings, mechanics of the respiratory system and the sleep/awake stage. Thus, the response of ventilator to patient effort, and that of patient effort to ventilator-delivered breath are inevitably the two components of control of breathing during mechanical ventilation; the ventilatory output is the final expression of the interaction between these two components. As a result of this interaction, the various aspects of control of breathing of the respiratory system may be masked or modulated by mechanical ventilation, depending on several factors related both to patient and ventilator. This should be taken into consideration in the management of mechanically ventilated patients.
During dynamic hyperinflation, the ventilatory pump is facing increased demand because it must overcome the intrinsic positive end-expiratory pressure (PEEPi) and decreased capacity since it must operate at a dynamically increased end-expiratory lung volume (EELV). The aim of this study was to evaluate the relative pressure contribution by the diaphragm and inspiratory rib cage muscles (RCMs) during dynamic hyperinflation. In six healthy subjects, dynamic hyperinflation was induced by limiting expiratory flow. The global inspiratory muscle pressure (delta Pmus,i) and transdiaphragmatic pressure (delta Pdi) were partitioned into the portion used to overcome PEEPi and the portion used to inflate the respiratory system. The delta Pdi/delta Pmus,i ratio was used to estimate the pressure contribution of RCMs relative to that of the diaphragm. Our results suggest that (1) with increasing severity of dynamic hyperinflation, there is a significant increase in the inspiratory pressure contribution of RCMs relative to that of the diaphragm for inflating the respiratory system; (2) during dynamic hyperinflation, especially at high EELV, the major pressure contribution of the diaphragm is to overcome the PEEPi-imposed inspiratory threshold load, whereas the inspiratory pressure needed for the subsequent task of inflating the respiratory system is largely contributed by RCMs. This arrangement is consistent with the change in mechanical advantages of RCMs and the diaphragm during the development of dynamic hyperinflation.
Respiratory rate (RR) increases as a function of ventilator flow rate (V). We wished to determine whether this is due to a decrease in neural inspiratory time (T In), neural expiratory time (TEn), or both. To accomplish this, we ventilated 15 normal subjects in the assist, volume cycled mode. Ventilator flow rate was varied at random, at four breaths with each step, over the flow range from 0.8 (Vmin) to 2.5 (Vmax) L/s. V T was kept constant. The pressure developed by respiratory muscles (Pmus) was calculated with the equation of motion (Pmus = V. R + V. E - Paw, where R = resistance, V = volume, E = elastance, and Paw = airway pressure). Electromyography of the diaphragm (Edi) was also done in five subjects. TIn and TEn were determined from the Pmus or Edi waveform. TIn decreased progressively as a function of V, from 1.44 +/- 0.34 s at Vmin to 0.62 +/- 0.26 s at Vmax (p < 0.00001). Changes in TEn were inconsistent and not significant. TIn/Ttot decreased significantly (0.30 +/- 0.06 at Vmin to 0.18 +/- 0.09 at Vmax; p < 0. 00001). We conclude that TI is highly sensitive to ventilator flow, and that the RR response to V is primarily related to this T In response. Because an increase in V progressively reduces T In/Ttot, and this variable is an important determinant of inspiratory muscle energetics, we further conclude that inspiratory muscle energy expenditure is quite sensitive to V over the range from 0.8 to 2.5 L/s.
Mechanical ventilation is a life-saving intervention for the management of acute respiratory failure. Its objective is to reduce excessive respiratory effort while improving gas exchange. By applying positive pressure to the airway, the mechanical ventilator assumes to a varying extent the work necessary to breathe, thereby unloading the respiratory muscles. In its most basic form, called controlled mechanical ventilation, a pre-set tidal volume is delivered at a fixed rate, irrespective of the patient's own breathing pattern. If the mechanical and natural respiratory cycles are not matched, however, the patient 'fights' the ventilator, causing discomfort, gas exchange deterioration and cardiovascular impairment1. To avoid discoordination between the patient and the ventilator, it is often necessary to suppress the patient's intrinsic respiratory drive with the use of hyperventilation, sedation or even muscle paralysis, which increase the risk of complications due to excessive ventilation2, 3, drug-related adverse effects4 and muscle disuse atrophy5. Assisted modes of mechanical ventilation, in which the mechanical breath is triggered by the patient's own inspiratory effort, were developed to address this. These modes enable the patient to influence the machine cycling to a varying extent, depending on the specific mode utilized. Although it is believed that assisted modes can reduce side effects and complications associated with controlled mechanical ventilation, coordination between spontaneous breathing and mechanical assistance is not guaranteed. Poor interaction between the patient and the ventilator remains one of the main problems in the management of patients with acute respiratory failure6, 7.
We studied the capacity of four "normal" and six lung transplant subjects to entrain neural respiratory activity to mechanical ventilation. Two transplant subjects were studied during wakefulness and demonstrated entrainment indistinguishable from that of normal awake subjects. We studied four normal subjects and four lung transplant subjects during non-rapid eye movement (NREM) sleep. Normal subjects entrained to mechanical ventilation over a range of ventilator frequencies that were within +/-3-5 breaths of the spontaneous respiratory rate of each subject. After lung transplantation, during which the vagi were cut, subjects did demonstrate entrainment during NREM sleep; however, entrainment only occurred at ventilator frequencies at or above each subject's spontaneous respiratory rate, and entrainment was less effective. We conclude that there is no absolute requirement for vagal feedback to induce entrainment in subjects, which is in striking contrast to anesthetized animals in which vagotomy uniformly abolishes entrainment. On the other hand, vagal feedback clearly enhances the fidelity of entrainment and extends the range of mechanical frequencies over which entrainment can occur.
Recent experiments in vivo and in vitro have advanced our understanding of the sites and mechanisms involved in mammalian respiratory rhythm generation. Here we evaluate and interpret the new evidence for two separate brainstem respiratory oscillators and for the essential role of emergent network properties in rhythm generation. Lesion studies suggest that respiratory cell death might explain morbidity and mortality associated with neurodegenerative disorders and ageing.
Neural drive to inspiratory pump muscles is increased under many pathological conditions. This study determined for the first time how neural drive is distributed to five different human inspiratory pump muscles during tidal breathing. The discharge of single motor units (n = 280) from five healthy subjects in the diaphragm, scalene, second parasternal intercostal, third dorsal external intercostal, and fifth dorsal external intercostal was recorded with needle electrodes. All units increased their discharge during inspiration, but 41 (15%) discharged tonically throughout expiration. Motor unit populations from each muscle differed in the timing of their activation and in the discharge rates of their motor units. Relative to the onset of inspiratory flow, the earliest recruited muscles were the diaphragm and third dorsal external intercostal (mean onset for the population after 26 and 29% of inspiratory time). The fifth dorsal external intercostal muscle was recruited later (43% of inspiratory time; P < 0.05). Compared with the other inspiratory muscles, units in the diaphragm and third dorsal external intercostal had the highest onset (7.7 and 7.1 Hz, respectively) and peak firing frequencies (12.6 and 11.9 Hz, respectively; both P < 0.05). There was a unimodal distribution of recruitment times of motor units in all muscles. Neural drive to human inspiratory pump muscles differs in timing, strength, and distribution, presumably to achieve efficient ventilation.
Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhythm of the patient fails to entrain to machine inflations. Entrainment implies a resetting of the respiratory rhythm such that a fixed temporal relationship exists between the onset of inspiratory activity and the onset of a mechanical breath. We examined the entrainment response to mechanical ventilation of normal humans over a range of machine rates during wakefulness and during isocapnic and hypercapnic NREM sleep. Wakefulness facilitated 1:1 entrainment of the respiratory rhythm to the mechanical ventilator over a wider range of machine frequencies than during NREM sleep (p < 0.001); isocapnic and hypercapnic conditions did not differ (p = 0.95). To evaluate the Hering-Breuer reflexes in the resetting of the respiratory rhythm during sleep, we examined changes in neural inspiratory time (TI) as the relationship between inspiratory efforts and onset of machine inflations changed. As inspiratory efforts extended into the machine inflation cycle, neural TI shortened. We conclude that entrainment responses of normal humans to mechanical ventilation differ depending on state, but mild increases in respiratory drive caused by CO2 stimulation do not affect these entrainment responses. Furthermore, the changes in neural it are consistent with observations in animal studies in which Hering-Breuer reflexes mediated entrainment.
The respiratory command emerges from neuronal networks located in the brainstem. It is then dispatched toward the respiratory muscles. The dilators of the upper airway contract first and the inspiratory muscles of the chest, including the diaphragm, some milliseconds later. Afferent inputs arising from chemo- and mechanoreceptors, related to the physical status of the respiratory system and to the activation of the respiratory muscles, modulate permanently the respiratory command to adapt ventilation to the needs of the body. Many diseases that lead patients to the ICU can modify, directly or indirectly, the respiratory command. Many treatments used in ICU can also alter this command. For example, mechanical ventilation decreases it. Should an inexplicable respiratory trouble or a difficult weaning occur, the control of breathing may be explored. This may help the diagnosis and the treatment. The exploration relies on assessments of spontaneaous ventilation and on its response to stimulations.
Purpose
Patients with acute respiratory distress syndrome (ARDS) requiring extracorporeal membrane oxygenation (ECMO) usually present very low respiratory system compliance (Cstrs) values (i.e., severe restrictive respiratory syndrome patients). As a consequence, they are at high risk of experiencing poor patient–ventilator interaction during assisted breathing. We hypothesized that monitoring of diaphragm electrical activity (EAdi) may enhance asynchrony assessment and that neurally adjusted ventilatory assist (NAVA) may reduce asynchrony, especially in more severely restricted patients.
Methods
We enrolled ten consecutive ARDS patients with very low Cstrs values undergoing ECMO after switching from controlled to pressure support ventilation (PSV). We randomly tested (30 min) while recording EAdi: (1) PSV30 (PSV with an expiratory trigger at 30 % of flow peak value); (2) PSV1 (PSV with expiratory trigger at 1 %); (3) NAVA. During each step, we measured the EAdi-based asynchrony index (AIEAdi) = flow-, pressure- and EAdi-based asynchrony events/EAdi-based respiratory rate × 100.
Results
AIEAdi was high during all ventilation modes, and the most represented asynchrony pattern was specific for this population (i.e., premature cycling). NAVA was associated with significantly decreased, although suboptimal, AIEAdi values in comparison to PSV30 and PSV1 (p
Background:
Diaphragmatic muscle contractions triggered by ventilator insuffl ations constitute a form of patient-ventilator interaction referred to as “entrainment,” which is usually unrecognized in critically ill patients. Our objective was to review tracings, which also included muscular activity, obtained in sedated patients who were mechanically ventilated to describe the entrainment events and their characteristics. The term “reverse triggering” was adopted to describe the ventilator-triggered muscular efforts.
Methods:
Over a 3-month period, recordings containing fl ow, airway pressure, and esophageal pressure or electrical activity of the diaphragm were reviewed. Recordings were obtained from a series of consecutive heavily sedated patients ventilated with an assist-control mode of ventilation for ARDS. The duration of entrainment, the entrainment ratio, and the phase difference elapsing between the commencement of the ventilator and neural breaths were evaluated.
Results:
The tracings of eight consecutive patients with ARDS were reviewed; they all showed different forms of entrainment. Reverse triggering occurred over a portion varying from 12% to 100% of the total recording period. Seven patients had a 1:1 mechanical insuffl ation to diaphragmatic contractions ratio; this coexisted with a 1:2 ratio in one patient and 1:2 and 1:3 ratios in another. One patient exhibited only a 1:2 ratio. The frequency of reverse-triggered breaths had a mean coeffi cient of variability of , 5%, very close to the variability of mechanical breaths.
Conclusions:
To our knowledge, this is the fi rst time that the presence of respiratory entrainment in sedated, critically ill adult patients who are mechanically ventilated has been documented. The “reverse-triggered” breaths illustrate a new form of neuromechanical coupling with potentially important clinical consequences.
Neurally adjusted ventilatory assist (NAVA) is a new mode wherein the assistance is provided in proportion to diaphragm electrical activity (EAdi). We assessed the physiologic response to varying levels of NAVA and pressure support ventilation (PSV).
ICU of a University Hospital.
Fourteen intubated and mechanically ventilated patients. DESIGN AND PROTOCOL: Cross-over, prospective, randomized controlled trial. PSV was set to obtain a VT/kg of 6-8 ml/kg with an active inspiration. NAVA was matched with a dedicated software. The assistance was decreased and increased by 50% with both modes. The six assist levels were randomly applied.
Arterial blood gases (ABGs), tidal volume (VT/kg), peak EAdi, airway pressure (Paw), neural and flow-based timing. Asynchrony was calculated using the asynchrony index (AI).
There was no difference in ABGs regardless of mode and assist level. The differences in breathing pattern, ventilator assistance, and respiratory drive and timing between PSV and NAVA were overall small at the two lower assist levels. At the highest assist level, however, we found greater VT/kg (9.1 +/- 2.2 vs. 7.1 +/- 2 ml/kg, P < 0.001), and lower breathing frequency (12 +/- 6 vs. 18 +/- 8.2, P < 0.001) and peak EAdi (8.6 +/- 10.5 vs. 12.3 +/- 9.0, P < 0.002) in PSV than in NAVA; we found mismatch between neural and flow-based timing in PSV, but not in NAVA. AI exceeded 10% in five (36%) and no (0%) patients with PSV and NAVA, respectively (P < 0.05).
Compared to PSV, NAVA averted the risk of over-assistance, avoided patient-ventilator asynchrony, and improved patient-ventilator interaction.
This study tests the hypothesis that the surface electromyographic (EMG) activity of upper airway dilators would respond to inspiratory loading in a healthy humans model of ventilator trigger asynchrony. EMG activity was measured in levator alae-nasi, genioglossus, parasternal, scalene and diaphragm muscles in eight subjects. They breathed quietly through a face mask and then were connected to a mechanical ventilator. Recordings were performed during nasal breathing against negative pressure triggers (-2.5%, -5% and -10% of maximal inspiratory pressure) and during oro-nasal breathing with a "-10% trigger". Scalene, alae-nasi and genioglossus EMG activity level increased with the "-10% trigger". While no breathing route dependence was found in scalene, the significant increase was only found for nasal breathing in alae-nasi and for oro-nasal breathing in genioglossus. The dyspnea intensity was significantly correlated with the EMG activity level of these three muscles. Surface EMG of airway dilator muscles could be used as a complementary tool to assess inspiratory drive during mechanical ventilation.
To determine the feasibility of daily titration of the neurally adjusted ventilatory assist (NAVA) level in relation to the maximal diaphragmatic electrical activity (EAdi(maxSBT)) measured during a spontaneous breathing trial (SBT) during pressure support ventilation (PSV).
The study included 15 consecutive patients in whom mechanical ventilation weaning was initiated with the NAVA mode. EAdi(maxSBT) was determined daily during an SBT using PSV with 7 cmH2O of inspiratory pressure and no positive end-expiratory pressure (PEEP). If the SBT was unsuccessful, NAVA was used and the level was then adjusted to obtain an EAdi of ~60% of the EAdi(maxSBT). Arterial blood gas analyses were performed 20 min after each change in NAVA level.
Three patients were dropped from the study at day 4 because of worsening of their sickness. The median duration of NAVA ventilation was 4.5 days (IQR 3-6.5). From day 1 to extubation, EAdi(maxSBT) and EAdi increased significantly from 16.6 (9.6) to 21.7 (10.3) μV (P = 0.013) and from 10.0 (5.5) to 15.1 (9.2) μV (P = 0.026), respectively. The pressure delivered significantly decreased from 20 (8) to 10 (5) cmH2O (P = 0.003). Conversely, tidal volume, carbon dioxide tension, and pH values remained unchanged during the same period.
These results suggest that daily titration of NAVA level with an electrical goal of ~60% EAdi(maxSBT) is feasible and well tolerated. The respiratory mechanics improvement and increase in respiratory drive allowed for a daily reduction of the NAVA level while preserving breathing, oxygenation, and alveolar ventilation until extubation.
Patient-ventilator synchrony is a common problem with all patients actively triggering the mechanical ventilator. In many cases synchrony can be improved by vigilant adjustments by the managing clinician. However, in most institutions clinicians are not able to spend the time necessary to ensure synchrony in all patients. Proportional assist ventilation (PAV) and neurally adjusted ventilatory assist (NAVA) were both developed to improve patient-ventilator synchrony by proportionally unloading ventilatory effort and turning control of the ventilatory pattern over to the patient. This paper discusses PAV's and NAVA's theory of operation, general process of application, and the supporting literature.
Neurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation that delivers ventilatory assist in proportion to the electrical activity of the diaphragm. This study aimed to compare the ventilatory and gas exchange effects between NAVA and pressure support ventilation (PSV) during the weaning phase of critically ill patients who required mechanical ventilation subsequent to surgery.
Fifteen patients, the majority of whom underwent abdominal surgery, were enrolled. They were ventilated with PSV and NAVA for 24 h each in a randomized crossover order. The ventilatory parameters and gas exchange effects produced by the two ventilation modes were compared. The variability of the ventilatory parameters was also evaluated by the coefficient of variation (SD to mean ratio).
Two patients failed to shift to NAVA because of postoperative bilateral diaphragmatic paralysis, and one patient interrupted the study because of worsening of his sickness. In the other 12 cases, the 48 h of the study protocol were completed, using both ventilation modes, with no signs of intolerance or complications. The Pao2/Fio2 (mean ± SD) ratio in NAVA was significantly higher than with PSV (264 ± 71 vs. 230 ± 75 mmHg, P < 0.05). Paco2 did not differ significantly between the two modes. The tidal volume (median [interquartile range]) with NAVA was significantly lower than with PSV (7.0 [6.4-8.6] vs. 6.5 [6.3-7.4] ml/kg predicted body weight, P < 0.05).Variability of insufflation airway pressure, tidal volume, and minute ventilation were significantly higher with NAVA than with PSV. Electrical activity of the diaphragm variability was significantly lower with NAVA than with PSV.
Compared with PSV, respiratory parameter variability was greater with NAVA, probably leading in part to the significant improvement in patient oxygenation.
Extracorporeal membrane oxygenation (ECMO) can support oxygenation and carbon dioxide elimination in severe lung failure. Usually it is accompanied by controlled mechanical ventilation. Neurally adjusted ventilatory assist (NAVA) is a new mode of ventilation triggered by the diaphragmatic electrical activity and controlled by the patient's respiratory centre, which may allow a close interaction between ventilation and extracorporeal perfusion. This pilot study intended to measure the physiologic ventilatory response in patients with severe lung failure treated with ECMO and NAVA. We hypothesized that the combination of both methods could automatically provide a protective ventilation with optimized blood gases.
We report a case series of six patients treated with ECMO for severe lung failure. In the recovery phase of the disease, patients were ventilated with NAVA and ventilatory response and gas exchange parameters were measured under different sweep gas flows and temporarily inactivated ECMO.
Tidal volumes on ECMO ranged between 2 and 5 ml/kg predicted body weight and increased up to 8 ml/kg with inactivated ECMO. Peak inspiratory pressure reached 19-29 cmH(2)O with active, and 21-45 cmH(2)O with inactivated ECMO. Ventilatory response to decreased sweep gas flow was rapid, and patients immediately regulated PaCO(2) tightly towards a physiological pH value. Increase in minute ventilation was a result of increased breathing frequency and tidal volumes, and protective ventilation was only abandoned if pH control was not achieved.
With NAVA ventilatory response to decreased ECMO sweep gas flow was rapid, and patients immediately regulated PaCO(2) tightly towards a physiological pH value. Therefore, combination of NAVA and ECMO may permit a closed-loop ventilation with automated protective ventilation.
Neurally adjusted ventilatory assist (NAVA) delivers assist in proportion to the patient's respiratory drive as reflected by the diaphragm electrical activity (EAdi). We examined to what extent NAVA can unload inspiratory muscles, and whether unloading is sustainable when implementing a NAVA level identified as adequate (NAVAal) during a titration procedure.
Fifteen adult, critically ill patients with a Pao(2)/fraction of inspired oxygen (Fio(2)) ratio < 300 mm Hg were studied. NAVAal was identified based on the change from a steep increase to a less steep increase in airway pressure (Paw) and tidal volume (Vt) in response to systematically increasing the NAVA level from low (NAVAlow) to high (NAVAhigh). NAVAal was implemented for 3 h.
At NAVAal, the median esophageal pressure time product (PTPes) and EAdi values were reduced by 47% of NAVAlow (quartiles, 16 to 69% of NAVAlow) and 18% of NAVAlow (quartiles, 15 to 26% of NAVAlow), respectively. At NAVAhigh, PTPes and EAdi values were reduced by 74% of NAVAlow (quartiles, 56 to 86% of NAVAlow) and 36% of NAVAlow (quartiles, 21 to 51% of NAVAlow; p < or = 0.005 for all). Parameters during 3 h on NAVAal were not different from parameters during titration at NAVAal, and were as follows: Vt, 5.9 mL/kg predicted body weight (PBW) [quartiles, 5.4 to 7.2 mL/kg PBW]; respiratory rate (RR), 29 breaths/min (quartiles, 22 to 33 breaths/min); mean inspiratory Paw, 16 cm H(2)O (quartiles, 13 to 20 cm H(2)O); PTPes, 45% of NAVAlow (quartiles, 28 to 57% of NAVAlow); and EAdi, 76% of NAVAlow (quartiles, 63 to 89% of NAVAlow). Pao(2)/Fio(2) ratio, Paco(2), and cardiac performance during NAVAal were unchanged, while Paw and Vt were lower, and RR was higher when compared to conventional ventilation before implementing NAVAal.
Systematically increasing the NAVA level reduces respiratory drive, unloads respiratory muscles, and offers a method to determine an assist level that results in sustained unloading, low Vt, and stable cardiopulmonary function when implemented for 3 h.
We hypothesized that (1) in healthy humans subjected to intermittent positive pressure non-invasive ventilation, changes in the ventilator trigger sensitivity would be associated with increased scalene activity, (2) if properly processed - through inspiratory phase-locked averaging - surface electromyograms (EMG) of the scalenes would reliably detect and quantify this, (3) there would be a correlation between dyspnea and scalene EMG. Surface and intramuscular EMG activity of scalene muscles were measured in 10 subjects. They breathed quietly through a face mask for 10min and then were connected to a mechanical ventilator. Recordings were performed during three 15-min epochs where the subjects breathed against an increasingly negative pressure trigger (-5%, -10% and -15% of maximal inspiratory pressure). With increasing values of the inspiratory trigger, inspiratory efforts, dyspnea and the scalene activity increased significantly. The scalene EMG activity level was correlated with the esophageal pressure time product and with dyspnea intensity. Inspiration-adjusted surface EMG averaging could be useful to detect small increases of the scalene muscles activity during mechanical ventilation.
The respiratory and circulatory activities of patients who underwent carotid body resection (CBR) more than two decades ago were reviewed. No significant ventilatory response to continuous hypoxia was observed. However, in response to stimulation of peripheral chemoreceptors, transient hyperventilation occurred before hypoxemic blood arrived at the central nervous system (single-breath test), which indicated the presence of weak peripheral chemosensitivity. Because of this slight residual peripheral chemosensitivity, which was found shortly after the operation and apparently remained more or less unchanged for greater than 20 years, peripheral chemoreceptor activity, which has been reported in other animal species, does not seem to have returned. Delayed hypoxic hyperventilation reported in dogs and cats with CBR was not observed. Hypoxia significantly depressed the ventilatory response to CO2, but the delayed ventilatory depression with time that has been demonstrated in normal subjects did not occur. In our circulatory studies, hypoxia augmented the heart rate and slightly depressed the stroke volume and total peripheral resistance in the systemic circulation but induced no appreciable changes in arterial blood pressure or cardiac output. We used these results to partition the relative contributions to the overall circulatory response of carotid body stimulation, pulmonary inflation, and other modifying influences. From these calculations, it was inferred that the carotid body reflex plays a dominant role in vascular activities whereas the pulmonary inflation reflex dominates in cardiac activities in humans.
The relation between inspiratory effort and ventilatory return (flow and volume) is usually abnormal in patients who require ventilatory support because of respiratory distress. Although all available support methods provide the patient with greater ventilation than would obtain with the same effort while unsupported, the relation between instantaneous effort and ventilatory consequences is not normalized. We describe an approach with which the ventilator simply amplifies patient instantaneous effort throughout inspiration while leaving the patient with complete control over all aspects of breathing pattern (tidal volume, inspiratory and expiratory durations, and flow patterns). This approach is implemented by monitoring the instantaneous rate (V) and volume (V) of gas flow from ventilator to patient and causing applied pressure (P) to change according to the equation of motion [P = f1(V) + f2(V)], where f1 and f2 are appropriately selected functions for the relation between pressure and volume (elastic assist) and pressure and flow (resistive assist). There are several potential advantages to this approach: (1) greater comfort; (2) reduction of peak airway pressure required to sustain ventilation and, hence, the potential for avoiding intubation; (3) less likelihood of overventilation; (4) preservation and enhancement of patient's own reflex, behavioral, and homeostatic control mechanisms since the ventilator essentially becomes an extension of the patient's own muscles; and (5) improved efficiency of negative pressure ventilation.
The coupling patterns between the rhythm of a mechanical ventilator and the rhythm of spontaneous breathing were studied in enflurane-anesthetized adult human subjects. The spontaneous breathing pattern was altered in response to different frequencies and amplitudes of forced lung inflations. A 1:1 phase locking (the frequency of the mechanical ventilator is matched by the frequency of spontaneous breathing with a fixed phase between the 2 rhythms) was observed in a range of up to +/- 40% of some of the subject's spontaneous breathing frequencies. During 1:1 phase locking, there were marked changes in the expiratory duration as measured from the electromyogram of the diaphragm. The phase relationship between onset of inflation and onset of inspiration depended on the frequency and amplitude of mechanical inflation. At ventilator settings that did not give 1:1 phase locking, other simple phase-locked patterns, such as 1:2 and 2:1, or irregular non-phase-locked patterns were observed. Reflexes arising from lung inflation, which may underlie the entrainment, are discussed in the context of these results.
The effect of inflating a lung on ventilation in the opposite lung was recorded during routine surgical operations under anaesthesia in man. Inflation produced expiration and apnoea followed by diminution in tidal volume. Nerve block of one cervical vagus with 2 % lignocaine showed that the apnoeic response to inflation was mediated by the ipsilateral nerve.The diminution in tidal volume and the expiratory effect were reduced but not abolished by ipsilateral vagal block, and the problems of interpretation of these findings are discussed.
The effects of carbon monoxide inhalation and of consequent carboxyhemoglobinemia (HbCO) on the discharge rates of aortic body and carotid body chemoreceptor afferents were investigated in 18 anesthetized cats. In 10 experiments both aortic and carotid chemoreceptor activities were monitored simultaneously. Carbon monoxide inhalation during normoxia always stimulated aortic chemoreceptors before carotid chemoreceptors, and the steady-state response of aortic chemoreceptors to HbCO was greater than that of most carotid chemoreceptors. Only 2 of the 18 carotid chemoreceptor fibers tested showed a distinct increase in activity in response to moderate increases in HbCO%. Thus, oxyhemoglobin contributed substantially to maintain tissue PO2 of all aortic chemoreceptors and of a few carotid chemoreceptors. Hyperoxia diminished the response of both aortic and carotid chemoreceptors to HbCO, indicating a lowered tissue PO2 as the stimulus source. We hypothesize that the aortic bodies have a much lower perfusion relative to their O2 utilization compared to the carotid bodies. As a consequence, the aortic chemoreceptors are able to act as a sensitive monitor of O2 delivery and to generate a circulatory chemoreflex for O2 homeostasis. carotid chemoreceptors monitor O2 tension and initiate strong reflex effects on the level of ventilation.
Proportional-assist ventilation (PAV) is a form of ventilatory support in which airway pressure increases in proportion to patient effort. Because it effectively reduces the mechanical load to an adjustable extent, PAV permits the study of the pattern of breathing in patients with respiratory disease when unconstrained by abnormal respiratory mechanics. We studied 11 patients with assorted medical problems requiring ventilatory support. The patients were switched to PAV, and the level of support was varied from near-maximal levels to the lowest tolerable level. Each level was maintained for several minutes while ventilation (VE), tidal volume (VT), and respiratory rate (f) were monitored. The breathing pattern observed with the highest assist varied substantially among patients. The ranges (and means) of VE, VT, and f were 5.6-18.7 (12.8) l/min, 203-844 (517) ml, and 18-33 (25) breaths/min, respectively. The correlation between VT and VE at the highest assist was very high (r = 0.91), suggesting that ventilatory demand is the most important determinant of VT variability. There were no systematic changes in breathing pattern as the level of assist was altered; at the highest and lowest levels of support, VE, VT, and f were, respectively, 12.8 +/- 5.4 (SD) vs. 11.6 +/- 4.3 l/min, 517 +/- 217 vs. 459 +/- 175 ml, and 25.0 +/- 4.2 vs. 25.7 +/- 3.9 breaths/min. These results indicate that within each patient, in a given state, there exist unique values for a desired VE, VT, and f that are largely independent of the mechanical load; if assist is increased, patient effort is decreased to maintain the desired ventilatory targets.
Acute hyperinflation causes the inspiratory muscles to operate at shorter than normal lengths. The ability of these muscles, in particular the diaphragm, to lower intrathoracic pressure is therefore reduced. Skeletal muscles, however, adapt to chronic shortening, and animals models of emphysema have shown that with chronic hyperinflation, the diaphragmatic muscle fibres lose sacromeres. As a result, the force-generating ability of these fibres is relatively preserved. In patients with hyperinflation due to chronic obstructive pulmonary disease, the ability of the diaphragm to generate pressure is also better than anticipated on the basis of hyperinflation alone. However, the diaphragm in these patients is also lower in the chest wall than in healthy subjects. Consequently, even though the neural drive to the muscle is greater than normal, its ability to descend during inspiration is impaired. Its rib cage expanding action is also reduced; in patients with severe hyperinflation, contraction of the diaphragm even produces deflation, rather than expansion, of the rib cage. In such patients, therefore, the ability of the diaphragm to increase lung volume is reduced, and hence the act of breathing is more dependent on the rib cage inspiratory muscles.
We tested whether subjects could detect and localize inflation confined to a single lung lobe. A balloon-sealed catheter was placed into a lobar bronchus of unsedated subjects via fiberoptic bronchoscopy. Topical anesthesia (lidocaine) was used to suppress cough and irritation associated with inflation of the sealing balloon. Small (45-60 ml) or large (100-240 ml) stimulus volumes were insufflated via the catheter. In a forced-choice protocol, subjects were readily able to detect large inflations and correctly identify the side on which the stimulus was given, but small inflations were at the threshold of detection and were not correctly localized. Additional lidocaine applied to the bronchus in two subjects did not degrade detection. Circumstantial evidence suggests that the sensation arose in the lung. We conclude that this technique is feasible for the study of pulmonary perception.
We measured pressures and power of diaphragm, rib cage, and abdominal muscles during quiet breathing (QB) and exercise at 0, 30, 50, and 70% maximum workload (Wmax) in five men. By three-dimensional tracking of 86 chest wall markers, we calculated the volumes of lung- and diaphragm-apposed rib cage compartments (Vrc,p and Vrc,a, respectively) and the abdomen (Vab). End-inspiratory lung volume increased with percentage of Wmax as a result of an increase in Vrc,p and Vrc,a. End-expiratory lung volume decreased as a result of a decrease in Vab. DeltaVrc,a/DeltaVab was constant and independent of Wmax. Thus we used DeltaVab/time as an index of diaphragm velocity of shortening. From QB to 70% Wmax, diaphragmatic pressure (Pdi) increased approximately 2-fold, diaphragm velocity of shortening 6.5-fold, and diaphragm workload 13-fold. Abdominal muscle pressure was approximately 0 during QB but was equal to and 180 degrees out of phase with rib cage muscle pressure at all percent Wmax. Rib cage muscle pressure and abdominal muscle pressure were greater than Pdi, but the ratios of these pressures were constant. There was a gradual inspiratory relaxation of abdominal muscles, causing abdominal pressure to fall, which minimized Pdi and decreased the expiratory action of the abdominal muscles on Vrc,a gradually, minimizing rib cage distortions. We conclude that from QB to 0% Wmax there is a switch in respiratory muscle control, with immediate recruitment of rib cage and abdominal muscles. Thereafter, a simple mechanism that increases drive equally to all three muscle groups, with drive to abdominal and rib cage muscles 180 degrees out of phase, allows the diaphragm to contract quasi-isotonically and act as a flow generator, while rib cage and abdominal muscles develop the pressures to displace the rib cage and abdomen, respectively. This acts to equalize the pressures acting on both rib cage compartments, minimizing rib cage distortion.
1. The behaviour of inspiratory motoneurones is poorly understood in humans and even for limb muscles there are few studies of motoneurone behaviour under concentric conditions. The current study assessed the discharge properties of the human phrenic motoneurones during a range of non-isometric voluntary contractions. 2. We recorded activity from 60 motor units in the costal diaphragm of four subjects using an intramuscular electrode while subjects performed a set of voluntary inspiratory contractions. These included a range of inspiratory efforts above and below the usual tidal range: breaths of different sizes (5-40 % vital capacity, VC) at a constant inspiratory flow (5 % VC s-1) and breaths of a constant size (20 % VC) at different inspiratory flows (2.5-20 % VC s-1). 3. For all the voluntary tasks, motor units were recruited throughout inspiration. For the various tasks, half-way through inspiration, 61-87 % of the sampled motor units had been recruited. 4. When the inspiratory task was deliberately altered, most single motor units began their discharge at a particular volume even when the rate of contraction had altered. 5. The initial firing frequency (median, 6.5 Hz) was consistent for tasks with a constant flow regardless of the size of the breath. However, for breaths of a constant size the initial firing frequencies increased as the inspiratory flow increased (range across tasks, 4.8-9.3 Hz). The 'final' firing frequency at the end of inspiration increased significantly above the initial frequency for each task (by 0.8-5.2 Hz) and was higher for those tasks with higher final lung volumes and higher inspiratory flows (range across tasks, 7.8-11.0 Hz). 6. There was no correlation within a task between the time of recruitment and the initial or final firing frequency for each motor unit. However, for each inspiratory task, initial and final firing frequencies were positively correlated. 7. Because the discharge of three to four units could be recorded simultaneously in a range of tasks, a quantitative 'shuffle' index was developed to describe changes in their recruitment order. Recruitment order was invariant in the task with the slowest inspiratory flow, but varied slightly, but significantly, in tasks with higher inspiratory flows. 8. The discharge rates of single motor units were compared for targeted voluntary breaths and non-targeted involuntary breaths which were matched for size. There were no significant differences in the initial or final firing frequencies, but recruitment order was not always the same in the two types of breath.
Lack of synchrony between a patient and the mechanical ventilator occurs when the respiratory rhythm of the patient fails to entrain to machine inflations. Entrainment implies a resetting of the respiratory rhythm such that a fixed temporal relationship exists between the onset of inspiratory activity and the onset of a mechanical breath. We examined the entrainment response to mechanical ventilation of normal humans over a range of machine rates during wakefulness and during isocapnic and hypercapnic NREM sleep. Wakefulness facilitated 1:1 entrainment of the respiratory rhythm to the mechanical ventilator over a wider range of machine frequencies than during NREM sleep (p < 0.001); isocapnic and hypercapnic conditions did not differ (p = 0.95). To evaluate the Hering-Breuer reflexes in the resetting of the respiratory rhythm during sleep, we examined changes in neural inspiratory time (TI) as the relationship between inspiratory efforts and onset of machine inflations changed. As inspiratory efforts extended into the machine inflation cycle, neural TI shortened. We conclude that entrainment responses of normal humans to mechanical ventilation differ depending on state, but mild increases in respiratory drive caused by CO(2) stimulation do not affect these entrainment responses. Furthermore, the changes in neural TI are consistent with observations in animal studies in which Hering-Breuer reflexes mediated entrainment.
The rostro-ventrolateral medulla (RVLM) is a site of chemosensitivity in animals; such site(s) have not been defined in humans. We studied the effect of unilateral focal lesions in the rostrolateral medulla (RLM) of man, on the ventilatory CO(2) sensitivity and during awake and sleep breathing. Nine patients with RLM lesions (RLM group), and six with lesions elsewhere (non-RLM group) were studied. The ventilatory CO(2) sensitivity was lower in the RLM compared with the non-RLM group (mean (S.D.), RLM, 1.4 (0.9), non-RLM 3.0 (0.6) L min(-1) mmHg(-1)). In both groups resting breathing was normal. During sleep all RLM patients had frequent arousals, four had significant sleep disordered breathing (SDB), only one non-RLM patient had SDB. Our findings in humans resemble those in animals with focal RVLM lesions. This review provides evidence that in humans there is an area of chemosensitivity in the RLM. We propose that in humans, dorsal displacement of the RVLM area of chemosensitivity in animals, arises from development of the olive plus the consequences of the evolution of the cerebellum/inferior peduncle.
Peripheral chemoreceptors (carotid and aortic bodies) detect changes in arterial blood oxygen and initiate reflexes that are important for maintaining homeostasis during hypoxemia. This mini-review summarizes the importance of peripheral chemoreceptor reflexes in various physiological and pathophysiological conditions. Carotid bodies are important for eliciting hypoxic ventilatory stimulation in humans and in experimental animals. In the absence of carotid bodies, compensatory upregulation of aortic bodies as well as other chemoreceptors contributes to the hypoxic ventilatory response. Peripheral chemoreceptors are critical for ventilatory acclimatization at high altitude. They also contribute in part to the exercise-induced hyperventilation, especially with submaximal and heavy exercise. During pregnancy, hypoxic ventilatory sensitivity increases, perhaps due to the actions of estrogen and progesterone on chemoreceptors. Augmented peripheral chemoreceptors have been implicated in early stages of recurrent apneas, congestive heart failure, and certain forms of hypertension. It is likely that chemoreceptors tend to maintain oxygen homeostasis and act as a defense mechanism to prevent the progression of the morbidity associated with these diseases. Experimental models of recurrent apneas, congestive heart failure, and hypertension offer excellent opportunities to unravel the cellular mechanisms associated with altered chemoreceptor function.
The human parasternal intercostal muscles are obligatory inspiratory muscles with a diminishing mechanical advantage from cranial to caudal interspaces. This study determined whether inspiratory neural drive to these muscles is graded, and whether this distribution matches regional differences in inspiratory mechanical advantage. To determine the neural drive, intramuscular EMG was recorded from the first to the fifth parasternal intercostals during resting breathing in six subjects. All interspaces showed phasic inspiratory activity but the onset of activity relative to inspiratory flow in the fourth and fifth spaces was delayed compared with that in cranial interspaces. Activity in the first, second and third interspaces commenced, on average, within the first 10% of inspiratory time, and sometimes preceded inspiratory airflow. In contrast, activity in the fourth and fifth interspaces began after an average 33% of inspiratory time. The peak inspiratory discharge frequency of motor units in the first interspace averaged 13.4 +/- 1.0 Hz (mean +/- s.e.m.) and was significantly greater than in all other interspaces, in particular in the fifth space (8.0 +/- 1.0 Hz). Phasic inspiratory activity was sometimes superimposed on tonic activity. In the first interspace, only 3% of units had tonic firing, but this proportion increased to 34% in the fifth space. In five subjects, recordings were also made from the medial and lateral extent of the second parasternal intercostal. Both portions showed phasic inspiratory activity which began within the first 6% of inspiratory time. Motor units from the lateral and medial portions fired at the same peak discharge rate (10.4 +/- 0.7 versus 10.7 +/- 0.6 Hz). These observations indicate that the distribution of neural drive to the parasternal intercostals in humans has a rostrocaudal gradient, but that the drive is uniform along the mediolateral extent of the second interspace. The distribution of inspiratory neural drive to the parasternal intercostals parallels the spatial distribution of inspiratory mechanical advantage, while tonic activity was higher where mechanical advantage was lower.
Faced with mechanical inspiratory loading, awake animals and anaesthetized humans develop alveolar hypoventilation, whereas awake humans do defend ventilation. This points to a suprapontine compensatory mechanism instead of or in addition to the 'traditional' brainstem respiratory regulation. This study assesses the role of the cortical pre-motor representation of inspiratory muscles in this behaviour. Ten healthy subjects (age 19-34 years, three men) were studied during quiet breathing, CO2-stimulated breathing, inspiratory resistive loading, inspiratory threshold loading, and during self-paced voluntary sniffs. Pre-triggered ensemble averaging of Cz EEG epochs starting 2.5 s before the onset of inspiration was used to look for pre-motor activity. Pre-motor potentials were present during voluntary sniffs in all subjects (average latency (+/-s.d.): 1325 +/- 521 ms), but also during inspiratory threshold loading (1427 +/- 537 ms) and during inspiratory resistive loading (1109 +/- 465 ms). Pre-motor potentials were systematically followed by motor potentials during inspiratory loading. Pre-motor potentials were lacking during quiet breathing (except in one case) and during CO2-stimulated breathing (except in two cases). The same pattern was observed during repeated experiments at an interval of several weeks in a subset of three subjects. The behavioural component of inspiratory loading compensation in awake humans could thus depend on higher cortical motor areas. Demonstrating a similar role of the cerebral cortex in the compensation of disease-related inspiratory loads (e.g. asthma attacks) would have important pathophysiological implications: it could for example contribute to explain why sleep is both altered and deleterious in such situations.
Neurally adjusted ventilatory assist (NAVA) is a mode of mechanical ventilation in which the ventilator is controlled by the electrical activity of the diaphragm (EAdi). During maximal inspirations, the pressure delivered can theoretically reach extreme levels that may cause harm to the lungs. The aims of this study were to evaluate whether NAVA could efficiently unload the respiratory muscles during maximal inspiratory efforts, and if a high level of NAVA would suppress EAdi without increasing lung-distending pressures.
In awake healthy subjects (n = 9), NAVA was applied at increasing levels in a stepwise fashion during quiet breathing and maximal inspirations. EAdi and airway pressure (Paw), esophageal pressure (Pes), and gastric pressure, flow, and volume were measured.
During maximal inspirations with a high NAVA level, peak Paw was 37.1 +/- 11.0 cm H(2)O (mean +/- SD). This reduced Pes deflections from - 14.2 +/- 2.7 to 2.3 +/- 2.3 cm H(2)O (p < 0.001) and EAdi to 43 +/- 7% (p < 0.001), compared to maximal inspirations with no assist. At high NAVA levels, inspiratory capacity showed a modest increase of 11 +/- 11% (p = 0.024).
In healthy subjects, NAVA can safely and efficiently unload the respiratory muscles during maximal inspiratory maneuvers, without failing to cycle-off ventilatory assist and without causing excessive lung distention. Despite maximal unloading of the diaphragm at high levels of NAVA, EAdi is still present and able to control the ventilator.
The motor control of the respiratory muscles differs in some ways from that of the limb muscles. Effectively, the respiratory muscles are controlled by at least two descending pathways: from the medulla during normal quiet breathing and from the motor cortex during behavioural or voluntary breathing. Neurophysiological studies of single motor unit activity in human subjects during normal and voluntary breathing indicate that the neural drive is not uniform to all muscles. The distribution of neural drive depends on a principle of neuromechanical matching. Those motoneurones that innervate intercostal muscles with greater mechanical advantage are active earlier in the breath and to a greater extent. Inspiratory drive is also distributed differently across different inspiratory muscles, possibly also according to their mechanical effectiveness in developing airway negative pressure. Genioglossus, a muscle of the upper airway, receives various types of neural drive (inspiratory, expiratory and tonic) distributed differentially across the hypoglossal motoneurone pool. The integration of the different inputs results in the overall activity in the muscle to keep the upper airway patent throughout respiration. Integration of respiratory and non-respiratory postural drive can be demonstrated in respiratory muscles, and respiratory drive can even be observed in limb muscles under certain circumstances. Recordings of motor unit activity from the human diaphragm during voluntary respiratory tasks have shown that depending on the task there can be large changes in recruitment threshold and recruitment order of motor units. This suggests that descending drive across the phrenic motoneurone pool is not necessarily consistent. Understanding the integration and distribution of drive to respiratory muscles in automatic breathing and voluntary tasks may have implications for limb motor control.
The human scalenes are obligatory inspiratory muscles that have a greater mechanical advantage than sternomastoid, an accessory muscle. This study determined scalene and sternomastoid recruitment during voluntary inspiratory tasks, and whether this activity varied with lung volume, when feedback from the lungs and inspiratory muscles would differ. If afferent feedback has a major role in determining the recruitment of the scalenes and sternomastoid, then at each lung volume, activity would be altered. Intramuscular EMG from scalene and sternomastoid muscles, and oesophageal pressure were recorded while subjects (n = 7) performed inspiratory isovolumetric ramps to maximal inspiratory pressure (MIP) and dynamic inspirations from functional residual capacity (FRC) to total lung capacity (TLC). The static inspiratory ramps were repeated at three lung volumes: FRC, FRC + tidal volume, and TLC. To determine the profile of inspiratory activation, i.e. the initial and ongoing recruitment of the muscles, the root mean square of the EMG was measured throughout the tasks. Scalene was recruited early, and EMG increased with pressure, reaching a plateau at 80% MIP. In contrast, sternomastoid activity began later, but then increased with pressure from 20 to 100% MIP. Similar profiles of activation occurred at all three lung volumes (n.s.). The ratio of sternomastoid to scalene EMG was also the same irrespective of the initial lung volume (n.s.). In dynamic inspirations, scalene and sternomastoid activation had similar stereotypical profiles to the static tasks, but scalene EMG was 15-40% greater (P < 0.05). Sternomastoid activation was the same in both tasks (n.s.). These results suggest that in voluntary tasks, scalene and sternomastoid are recruited in the order of their mechanical advantages, and that alterations in feedback related to changes in lung volume failed to alter their activation. Thus, in humans, the mechanism responsible for the differential activation of these two inspiratory muscles has an element that is preset.
Survival requires adequate pulmonary ventilation which, in turn, depends on adequate contraction of muscles acting on the chest wall in the presence of a patent upper airway. Bulbospinal outputs projecting directly and indirectly to 'obligatory' respiratory motoneurone pools generate the required muscle contractions. Recent studies of the phasic inspiratory output of populations of single motor units to five muscles acting on the chest wall (including the diaphragm) reveal that the time of onset, the progressive recruitment, and the amount of motoneuronal drive (expressed as firing frequency) differ among the muscles. Tonic firing with an inspiratory modulation of firing rate is common in low intercostal spaces of the parasternal and external intercostal muscles but rare in the diaphragm. A new time and frequency plot has been developed to depict the behaviour of the motoneurone populations. The magnitude of inspiratory firing of motor unit populations is linearly correlated to the mechanical advantage of the intercostal muscle region at which the motor unit activity is recorded. This represents a 'neuromechanical' principle by which the CNS controls motoneuronal output according to mechanical advantage, presumably in addition to the Henneman's size principle of motoneurone recruitment. Studies of the genioglossus, an obligatory upper airway muscle that helps maintain airway patency, reveal that it receives simultaneous inspiratory, expiratory and tonic drives even during quiet breathing. There is much to be learned about the neural drive to pools of human inspiratory and expiratory muscles, not only during respiratory tasks but also in automatic and volitional tasks, and in diseases that alter the required drive.
Central chemosensitivity and breathing asleep in unilateral medullary lesion patients: comparisons to animal data
- M J Morrell
- P Heywood
- S H Moosavi
- MJ Morrell
Entrainment of respiration in humans by periodic lung inflations. Effect of state and CO2
- P M Simon
- A S Zurob
- W M Wies
- PM Simon