Lukas Brander

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.

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.

Physiologic response to changing positive end-expiratory pressure during neurally adjusted ventilatory assist in sedated, critically ill adults.

BACKGROUND Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (Paw) in proportion to neural inspiratory drive as reflected by electrical activity of the diaphragm (EAdi). Changing positive end-expiratory pressure (PEEP) impacts respiratory muscle load and function and, hence, EAdi. We aimed to evaluate how PEEP affects the breathing pattern and neuroventilatory efficiency during NAVA. METHODS In 20 adult patients, adequate assist (NAVAal) was first identified based on Paw and tidal volume (Vt) responses to systematic increases in NAVA level while using preset PEEP (PEEPbl). Thereafter, using NAVAal, PEEP was increased to 20 cm water (H(2)O) (PEEPhigh) and then lowered stepwise to 1 cm H(2)O (PEEP1). EAdi, Paw, and Vt were recorded. RESULTS Median NAVAal was 2.7 (interquartile range, 2.3-3.5) cm H(2)O/muV and was similar to NAVAal identified post hoc by 17 independent physicians (2.5 [2.0-3.4] cm H(2)O/muV; P = NS). Reducing PEEPhigh to PEEP1 increased inspiratory EAdi by 34% (2-67; P = .046) and was associated with an increase in mean Paw above PEEP from 8.5 (6.7-11.4) cm H(2)O to 12.2 (8.8-16.7) cm H(2)O (P = .008), whereas Vt and respiratory rate remained unchanged. The response pattern in Vt/EAdi, indicating changes in neuroventilatory efficiency, differed among patients. Tidal breathing occurred at the lowest EAdi cost in seven patients with PEEP1 or half PEEPbl, in six patients with PEEPbl, and in seven patients with PEEPhigh. CONCLUSIONS During NAVAal, increasing PEEP reduces respiratory drive. Patients adapt their neuroventilatory efficiency such that the individual ventilatory pattern is preserved over a wide range of PEEP levels. Monitoring Vt/EAdi during PEEP changes allows identification of a PEEP level at which tidal breathing occurs at minimal EAdi cost. TRIAL REGISTRATION clinicaltrials.gov; Identifier: NCT00529347.

Physiological response to increasing levels of neurally adjusted ventilatory assist (NAVA).

This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions.

Changes in splanchnic circulation during an alveolar recruitment maneuver in healthy porcine lungs

Recruitment maneuvers (RM) are advocated as a complement to mechanical ventilation during anesthesia and in acute lung injury. However, they produce high intrathoracic pressures and volumes that may compromise hemodynamics. Our aim was to analyze the effect of a RM on hemodynamics in 10 anesthetized pigs. We assessed carotid, pulmonary, femoral, and hepatic arterial pressures, hepatic and portal venous pressures, total splanchnic (celiac trunk + superior mesenteric artery), hepatic, splenic, renal, and carotid arterial flows, and portal venous flow. We recorded hemodynamics, respiratory mechanics and blood gases before and at 8 min after RM (sustained inflation to 40 cm H2O of airway pressure lasting 20 s). Hemodynamics were also measured during RM, and at 1, 3, and 5 min after RM. All flows (P = 0.030) and arterial pressures (P ≤ 0.048) decreased during RM, whereas venous pressures increased (P = 0.030). Flows and pressures returned to 75%–109% of baseline immediately after RM. Total splanchnic, renal and portal flows remained decreased at 8 min after RM (P ≤ 0.042). Oxygenation did not change, and respiratory mechanics improved after the RM. RM produced a marked, though transitory, impairment of blood flow in all studied vessels. Despite prompt partial recovery, total splanchnic circulation remained reduced at 8 min after RM. This residual decrease may present a risk in conditions with markedly compromised circulatory reserves.

Muscle membrane dysfunction in critical illness myopathy assessed by velocity recovery cycles

OBJECTIVE To test the hypothesis that muscle fibers are depolarized in patients with critical illness myopathy by measuring velocity recovery cycles (VRCs) of muscle action potentials. METHODS VRCs were recorded from brachioradialis muscle by direct muscle stimulation in 10 patients in intensive care with evidence of critical illness myopathy (CIM). Two sets of recordings were made, mean 3.9 d apart, and compared with those from 10 age-matched controls. RESULTS Muscle supernormality was reduced in the patients by 50% compared with controls (P<0.002) and relative refractory period was increased by 59% (P<0.01). Supernormality was correlated with plasma potassium levels (R=-0.753, P<0.001), and the slope of this relationship was much steeper than previously reported for non-critically ill patients with renal failure (P<0.01). CONCLUSIONS The abnormal excitability properties indicate that the muscle fibers in CIM were depolarized, and/or that sodium channel inactivation was increased. The heightened sensitivity to potassium is consistent with the hypothesis that an endotoxin reduces sodium channel availability in depolarized muscle fibers. SIGNIFICANCE VRCs provide a practicable means to monitor muscle membrane changes in intensive care and to investigate the pathogenesis of CIM.

Severe transfusion-related acute lung injury.

UNLABELLED A 46-yr-old man developed severe hypoxemia, pulmonary infiltrates, and an acute decrease in his leukocyte count shortly after transfusion of fresh-frozen plasma (FFP) during recovery from cardiac surgery. Cardiogenic pulmonary edema was excluded. Granulocyte-reactive and agglutinating alloantibodies were detected in the serum of the fresh-frozen plasma donor. The cross-match with the patients granulocytes revealed antibodies specific for HLA class I. Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, under-recognized and under-reported complication of transfusion. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and could save lives. IMPLICATIONS Transfusion-related acute lung injury (TRALI) is a potentially life-threatening, probably under-recognized and under-reported complication of transfusing blood products. Conservative transfusion strategies and preclusion of the implicated blood donors with granulocyte-reactive antibodies from future blood donation may prevent TRALI and potentially save lives.

Identification of Adequate Neurally Adjusted Ventilatory Assist (NAVA) During Systematic Increases in the NAVA Level

Neurally adjusted ventilatory assist (NAVA) delivers airway pressure (P_aw) in proportion to the electrical activity of the diaphragm (EAdi) using an adjustable proportionality constant (NAVA level, cm·H₂O/μV). During systematic increases in the NAVA level, feedback-controlled down-regulation of the EAdi results in a characteristic two-phased response in P_aw and tidal volume (Vt). The transition from the 1st to the 2nd response phase allows identification of adequate unloading of the respiratory muscles with NAVA (NAVA_AL). We aimed to develop and validate a mathematical algorithm to identify NAVA_AL. P_aw, Vt, and EAdi were recorded while systematically increasing the NAVA level in 19 adult patients. In a multistep approach, inspiratory P_aw peaks were first identified by dividing the EAdi into inspiratory portions using Gaussian mixture modeling. Two polynomials were then fitted onto the curves of both P_aw peaks and Vt. The beginning of the P_aw and Vt plateaus, and thus NAVA_AL, was identified at the minimum of squared polynomial derivative and polynomial fitting errors. A graphical user interface was developed in the Matlab computing environment. Median NAVA_AL visually estimated by 18 independent physicians was 2.7 (range 0.4 to 5.8) cm·H₂O/μV and identified by our model was 2.6 (range 0.6 to 5.0) cm·H₂O/μV. NAVA_AL identified by our model was below the range of visually estimated NAVA_AL in two instances and was above in one instance. We conclude that our model identifies NAVA_AL in most instances with acceptable accuracy for application in clinical routine and research.

Effects of catecholamines on hepatic and skeletal muscle mitochondrial respiration after prolonged exposure to faecal peritonitis in pigs

Use of norepinephrine to increase blood pressure in septic animals has been associated with increased efficiency of hepatic mitochondrial respiration. The aim of this study was to evaluate whether the same effect could be reproduced in isolated hepatic mitochondria after prolonged in vivo exposure to faecal peritonitis. Eighteen pigs were randomized to 27 h of faecal peritonitis and to a control condition (n = 9 each group). At the end, hepatic mitochondria were isolated and incubated for one hour with either norepinephrine or placebo, with and without pretreatment with the specific receptor antagonists prazosin and yohimbine. Mitochondrial state 3 and state 4 respiration were measured for respiratory chain complexes I and II, and state 3 for complex IV using high-resolution respirometry, and respiratory control ratios were calculated. Additionally, skeletal muscle mitochondrial respiration was evaluated after incubation with norepinephrine and dobutamine with and without the respective antagonists (atenolol, propranolol and phentolamine for dobutamine). Faecal peritonitis was characterized by decreasing blood pressure and stroke volume, and maintained systemic oxygen consumption. Neither faecal peritonitis nor any of the drugs or drug combinations had measurable effects on hepatic or skeletal muscle mitochondrial respiration. Norepinephrine did not improve the efficiency of complex I- and complex II-dependent isolated hepatic mitochondrial respiration [respiratory control ratio (RCR) complex I: 5.6 ± 5.3 (placebo) vs. 5.4 ± 4.6 (norepinephrine) in controls and 2.7 ± 2.1 (placebo) vs. 2.9 ± 1.5 (norepinephrine) in septic animals; RCR complex II: 3.5 ± 2.0 (placebo) vs. 3.5 ± 1.8 (norepinephrine) in controls; 2.3 ± 1.6 (placebo) vs. 2.2 ± 1.1 (norepinephrine) in septic animals]. Prolonged faecal peritonitis did not affect either hepatic or skeletal muscle mitochondrial respiration. Subsequent incubation of isolated mitochondria with norepinephrine and dobutamine did not significantly influence their respiration.