Christer Sinderby

Neural control of mechanical ventilation in respiratory failure

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 impairment 1 . 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 ventilation 2‐3 , drug-related adverse effects

Patient-ventilator interaction during pressure support ventilation and neurally adjusted ventilatory assist.

Objective: To compare the effect of pressure support ventilation and neurally adjusted ventilatory assist on breathing pattern, patient-ventilator synchrony, diaphragm unloading, and gas exchange. Increasing the level of pressure support ventilation can increase tidal volume, reduce respiratory rate, and lead to delayed ventilator triggering and cycling. Neurally adjusted ventilatory assist uses diaphragm electrical activity to control the timing and pressure of assist delivery and is expected to enhance patient-ventilator synchrony. Design: Prospective, comparative, crossover study. Setting: Adult critical care unit in a tertiary university hospital. Patients: Fourteen nonsedated mechanically ventilated patients (n = 12 with chronic obstructive pulmonary disease). Interventions: Patients were ventilated for 10-min periods, using two pressure support ventilation levels (lowest tolerable and +7 cm H2O higher) and two neurally adjusted ventilatory assist levels (same peak pressures and external positive end-expiratory pressure as with pressure support ventilation), delivered in a randomized order. Measurements and Main Results: Diaphragm electrical activity, respiratory pressures, air flow, volume, neural and ventilator respiratory rates, and arterial blood gases were measured. Peak pressures were 17 ± 6 cm H2O and 24 ± 6 cm H2O and 19 ± 5 cm H2O and 24 ± 6 cm H2O with high and low pressure support ventilation and neurally adjusted ventilatory assist, respectively. The breathing pattern was comparable with pressure support ventilation and neurally adjusted ventilatory assist during low assist; during higher assist, larger tidal volumes (p = .003) and lower breathing frequencies (p = .008) were observed with pressure support ventilation. Increasing the assist increased cycling delays only with pressure support ventilation (p = .003). Compared with pressure support ventilation, neurally adjusted ventilatory assist reduced delays of ventilator triggering (p < .001 for low and high assist) and cycling (high assist: p = .004; low assist: p = .04), and abolished wasted inspiratory efforts observed with pressure support ventilation in six subjects. The diaphragm electrical activity and pressure-time product for ventilator triggering were lower with neurally adjusted ventilatory assist (p = .005 and p = .02, respectively; analysis of variance). Arterial blood gases were similar with both modes. Conclusions: Neurally adjusted ventilatory assist can improve patient-ventilator synchrony by reducing the triggering and cycling delays, especially at higher levels of assist, at the same time preserving breathing and maintaining blood gases.

Patient-ventilator interaction during neurally adjusted ventilatory assist in low birth weight infants.

Neurally adjusted ventilatory assist (NAVA), a mode of mechanical ventilation controlled by diaphragmatic electrical activity (EAdi), may improve patient-ventilator interaction. We examined patient-ventilator interaction by comparing EAdi to ventilator pressure during conventional ventilation (CV) and NAVA delivered invasively and non-invasively. Seven intubated infants [birth weight 936 g (range, 676–1266 g); gestational age 26 wk (range, 25–29)] were studied before and after extubation, initially during CV and then NAVA. NAVA-intubated and NAVA-extubated demonstrated similar delays between onset of EAdi and onset of ventilator pressure of 74 ± 17 and 72 ± 23 ms (p = 0.698), respectively. During CV, the mean trigger delays were not different from NAVA, however 13 ± 8.5% of ventilator breaths were triggered on average 59 ± 27 ms before onset of EAdi. There was no difference in off-cycling delays between NAVA-intubated and extubated (32 ± 34 versus 28 ± 11 ms). CV cycled-off before NAVA (120 ± 66 ms prior, p < 0.001). During NAVA, EAdi and ventilator pressure were correlated [mean determination coefficient (NAVA-intubated 0.8 ± 0.06 and NAVA-extubated 0.73 ± 0.22)]. Pressure delivery during conventional ventilation was not correlated to EAdi. Neural expiratory time was longer (p = 0.044), and respiratory rate was lower (p = 0.004) during NAVA. We conclude that in low birth weight infants, NAVA can improve patient-ventilator interaction, even in the presence of large leaks.

Titration and Implementation of Neurally Adjusted Ventilatory Assist in Critically Ill Patients

BACKGROUND Neurally adjusted ventilatory assist (NAVA) delivers assist in proportion to the patients 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Inspiratory Muscle Unloading by Neurally Adjusted Ventilatory Assist During Maximal Inspiratory Efforts in Healthy Subjects

BACKGROUND 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. METHOD 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. RESULTS 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). CONCLUSION 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.

Improved synchrony and respiratory unloading by neurally adjusted ventilatory assist (NAVA) in lung-injured rabbits

With increasing pressure support ventilation (PSV), a form of pneumatically triggered ventilation, there can be an increase in wasted inspiratory efforts (neural inspiratory efforts that fail to trigger the ventilator). With neurally adjusted ventilatory assist (NAVA), a mode of ventilation controlled by the electrical activity of the diaphragm (EAdi), synchrony should be maintained at high levels of assist. The aim of this study was to evaluate the response to increasing levels of PSV and NAVA on synchrony and diaphragm unloading in lung-injured rabbits. Animals were ventilated on PSV or NAVA in random order, each at three levels. We measured neural and ventilator respiratory rates, EAdi, transdiaphragmatic pressure (Pdi), and tidal volume (Vt). At low PSV, 95% of neural efforts were triggered, compared with high PSV, where only 66% of the neural efforts were triggered. During NAVA, all neural efforts were triggered, regardless of level. Increasing NAVA levels reduced EAdi and Pdi-time products by 48% (p < 0.05) and 66% (p < 0.05). In contrast, increasing PSV did not reduce the diaphragm electrical activity-time product and increased the transdiaphragmatic pressure-time product (p < 0.05) due to the increased wasted efforts. We conclude that synchrony with the ventilator is an important determinant for diaphragm unloading.

Influence of neurally adjusted ventilatory assist and positive end-expiratory pressure on breathing pattern in rabbits with acute lung injury.

Objective:To evaluate the influence of neurally adjusted ventilatory assist (NAVA) and positive end-expiratory pressure (PEEP) on the control of breathing in rabbits with acute lung injury. Design:Prospective animal study. Setting:Experimental laboratory in a university hospital. Subjects:Male White New Zealand rabbits (n = 18). Intervention:Spontaneously breathing rabbits with hydrochloric acid-induced lung injury were ventilated with NAVA and underwent changes in NAVA gain and PEEP (six nonvagotomized and five vagotomized). Seven other nonvagotomized rabbits underwent 4 hrs of ventilation with hourly titration of PEEP, Fio2, and NAVA gain. Measurements and Main Results:We studied diaphragm electrical activity, respiratory pressures, and breathing pattern. After lung injury, 0 cm H2O of PEEP resulted in high tonic and no discernible phasic diaphragm electrical activity in the nonvagotomized rabbits; stepwise increases in PEEP (up to 11.7 ± 2.6 cm H2O) reduced tonic but increased phasic diaphragm electrical activity. Increasing the NAVA gain reduced phasic diaphragm electrical activity to almost half and abolished esophageal pressure swings. Tidal volume remained at 4–5 mL/kg, and respiratory rate did not change. In the vagotomized group, lung injury did not induce tonic activity, and phasic activity and tidal volume were several times higher than in the nonvagotomized rabbits. Four hours of breathing with NAVA restored breathing pattern and neural and mechanical breathing efforts to pre-lung injury levels. Conclusions:Acute lung injury can cause a vagally mediated atypical diaphragm activation pattern in spontaneously breathing rabbits. Modulation of PEEP facilitates development of phasic diaphragm electrical activity, whereupon implementation of NAVA can efficiently maintain unloading of the respiratory muscles without delivering excessive tidal volume in rabbits with intact vagal function.

Prolonged neural expiratory time induced by mechanical ventilation in infants.

Mechanical ventilation may interfere with the spontaneous breathing pattern in infants because they have strong reflexes that play a large role in the control of breathing. This study aimed to answer the following questions: does a ventilator-assisted breath 1) reduce neural inspiratory time, 2) reduce the amplitude of the diaphragm electrical activity, and 3) prolong neural expiration, within the delivered breath? In 14 infants recovering from acute respiratory failure (mean age and weight were 2.3 ± 1.3 mo and 3.95 ± 0.82 kg, respectively), we measured 1) the electrical activity of the diaphragm with a multiple-array esophageal electrode, and 2) airway opening pressure, while patients breathed on synchronized intermittent mandatory ventilation (mean rate, 11.2 ± 6.5 breaths/min). We compared neural inspiratory and expiratory times for the mandatory breaths and for the spontaneous breaths immediately preceding and following the mandatory breath. Although neural inspiratory time was not different between mandatory and spontaneous breaths, neural expiratory time was significantly increased (p < 0.001) for the mandatory breaths (953 ± 449 ms) compared with the premandatory and postmandatory spontaneous breaths (607 ± 268 ms and 560 ± 227 ms, respectively). Delivery of the mandatory breath resulted in a reduction in neural respiratory frequency by 28.6 ± 6.4% from the spontaneous premandatory frequency. The magnitude of inspiratory electrical activity of the diaphragm was similar for all three breath conditions. For the mandatory breaths, ventilatory assist persisted for 507 ± 169 ms after the end of neural inspiratory time. Infant–ventilator asynchrony (both inspiratory and expiratory asynchrony) was present in every mandatory breath and constituted 53.4 ± 26.2% of the total breath duration.

The Calcium Sensitizer Levosimendan Improves Human Diaphragm Function

RATIONALE Acquired diaphragm muscle weakness is a key feature in several chronic conditions, including chronic obstructive pulmonary disease, congestive heart failure, and difficult weaning from mechanical ventilation. No drugs are available to improve respiratory muscle function in these patients. Recently, we have shown that the calcium sensitizer levosimendan enhances the force-generating capacity of isolated diaphragm fibers. OBJECTIVES To investigate the effects of the calcium sensitizer levosimendan on in vivo human diaphragm function. METHODS In a double-blind, randomized, crossover design, 30 healthy subjects performed two identical inspiratory loading tasks. After the first loading task, subjects received levosimendan (40 μg/kg bolus followed by 0.1/0.2 μg/kg/min continuous infusion) or placebo. Transdiaphragmatic pressure, diaphragm electrical activity, and their relationship (neuromechanical efficiency) were measured during loading. Magnetic phrenic nerve stimulation was performed before the first loading task and after bolus administration to assess twitch contractility. Center frequency of diaphragm electrical activity was evaluated to study the effects of levosimendan on muscle fiber conduction velocity. MEASUREMENTS AND MAIN RESULTS The placebo group showed a 9% (P=0.01) loss of twitch contractility after loaded breathing, whereas no loss in contractility was observed in the levosimendan group. Neuro-mechanical efficiency of the diaphragm during loading improved by 21% (P<0.05) in the levosimendan group. Baseline center frequency of diaphragm electrical activity was reduced after levosimendan administration (P<0.05). CONCLUSIONS The calcium sensitizer levosimendan improves neuromechanical efficiency and contractile function of the human diaphragm. Our findings suggest a new therapeutic approach to improve respiratory muscle function in patients with respiratory failure.

Proportional Assist Ventilation and Neurally Adjusted Ventilatory Assist : Better Approaches to Patient Ventilator Synchrony?

Understanding the regulation of breathing in the critical care patient is multifaceted, especially in ventilator-dependent patients who must interact with artificial respiration. Mechanical ventilation originally consisted of simple, manually-driven pump devices, but it has developed into advanced positive pressure ventilators for continuous support of patients in respiratory failure. This evolution has resulted in mechanical ventilators that deliver assist intermittently, attempting to mimic natural breathing. Recently, modes of mechanical ventilation that synchronize not only the timing, but also the level of assist to the patients own effort, have been introduced. This article describes the concepts related to proportional assist ventilation and neurally adjusted ventilatory assist, and how they relate to conventional modes in terms of patient-ventilator synchrony.