Online supplementary material

Neurally adjusted ventilatory assist in patients with critical illness-associated polyneuromyopathy

Clinical Trial.gov Identifiers: NCT00614562 and NCT00941044

Daniel Tuchscherer 1, Werner J Z’Graggen 2, 3, Christina Passath 1, Jukka Takala 1, Christer Sinderby 4,5, Lukas Brander 1

Affiliations:

1 Department of Intensive Care Medicine, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

2 Department of Neurosurgery, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

3 Department of Neurology, Inselspital, Bern University Hospital and University of Bern, Bern, Switzerland

4 Interdepartmental Division of Critical Care Medicine, University of Toronto, Department of Critical Care Medicine, St. Michael’s Hospital, Toronto, Canada

5 Keenan Research Center at the Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Canada

Methods

Inclusion criteria: Mechanical ventilation for >48 hours, presence of at least one risk factor known to be associated with CIPM, and clinical suspicion of CIPM indicated by a score <48 in the Medical Research Council (MRC) scale assessed in 12 muscle groups [28]. For exclusion criteria see online supplement.

Exclusion criteria: <18 and >80 years of age, pregnancy, breast-feeding, refusal of enrolment by attending physician, hemodynamic instability, administration of drugs for muscle paralysis, contraindication for insertion or exchange of a nasogastric tube, presence or suspicion of diaphragm injury, severe bleeding disorder, an acute or chronic central or peripheral nervous system disorder, history of cardiac or lung transplantation, any mechanical cardiac assist device except for an intra-aortic balloon pump, a fraction of inspired oxygen (FiO2) >0.8, participation in another interventional clinical trial.

NAVA Methods

NAVA was used as previously described [11,16,22,24,25,29]. Briefly, the EAdi was derived via a modified nasogastric feeding tube (Maquet, Solna, Sweden), processed [11,15,30-32], multiplied by an adjustable proportionality constant (NAVA level), and used to control Paw delivered by the ventilator (Servoi 3.02.01, Maquet, Solna, Sweden). Inspiratory assist was initiated when either the EAdi or the inspiratory flow exceeded an individually set trigger threshold on a first-come first-served basis, and was cycled off at 70% of the peak EAdi for each breath or when an arbitrarily chosen upper Paw limit was reached. During expiration a caregiver-defined positive end-expiratory pressure (PEEP) level was applied.

Data analysis and calculated variables

Breath-by-breath analysis was performed offline using custom-made software (Neurovent Research Inc., Toronto, Canada) as previously described [24]. For inter-individual comparison, EAdi is expressed for each patient as a percentage of the maximum inspiratory EAdi at the lowest NAVA level during the titration (%NAVAzero). Wasted inspiratory efforts during PSV were identified off-line as presence of inspiratory EAdi not followed by delivery of ventilatory assist. Periods of coughing and endotracheal suctioning were excluded from the analyses.

Vt was calculated by integrating flow. Neuro-ventilatory efficiency = Vt/integral of the inspiratory EAdi (Vt/EAdi). Neural respiratory rate (RRneural), minute ventilation (VE), and electrical energy expenditure during inspiration = mean inspiratory EAdi x Tineural x RRneural were calculated.

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Legends to figures in the online supplementary material

Figure E1

Schematic study protocol. During pressure support ventilation (PSV), the assist and positive end-expiratory pressure (PEEP) levels were used as defined by the treating physician. An adequate NAVA level (NAVAal) was identified daily during a NAVA level titration procedure. Throughout the study, the PEEP level was adjusted by the clinical team. Standardized tests of neuro-ventilatory efficiency (NVET) were performed daily. Data were collected during 48 hours on PSV before implementing NAVA, and every 6 hours during NAVAal.

Conventional electrophysiological studies and measurement of the phrenic nerve latency (PNL) and amplitude of compound muscle action potentials (CMAPs) of the diaphragm in response to transcutaneous stimulation of the phrenic nerve were performed before implementation of NAVA (baseline) and after completion of the study.

Figure E2a and b

Individual changes in tidal volume (Vt), diaphragm electrical activity (EAdi), and respiratory rate (RR) (Figure E2a) in the ratio between arterial oxygen tension (PaO2) and the fraction of inspired oxygen (FiO2), as well as the arterial carbon dioxide tension (PaCO2) (Figure E2b) when changing from pressure support ventilation (PSV) to neurally adjusted ventilatory assist (NAVAal) for a maximum of 72 hours. In patients #10 and #15 NAVA was terminated within the first 24 hours due to excessive respiratory drive and myocloni (for details see print version). The data of these patients are not included in the graphs.


Figure E3

Synopsis of all individual titration procedures performed during the study. In order to remove artifacts, we reanalyzed the original data acquired during the titration procedures using filters that calculate the moving average of 7 consecutive values after dropping the highest and lowest value per segment and after removing breaths with Vt <100 ml and those with a respiratory rate >70 breaths per minute. During the study, for each titration a NAVA level early after the transition from an initial steep increase in Paw (1st response) to a less steep increase or plateau in Paw (2nd response) was identified by visual inspection of the Paw and Vt trend graphs and was termed adequate assist level (NAVAal; indicated by the black vertical line in each graph). For details see methods and Figure 3 in the main manuscript. The data of patient #01 could not be re-analyzed due to technical issues during the data recording process.

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Legends to tables in the online supplementary material

Table E1

During all NAVA level titration procedures, tidal volume (Vt) and mean inspiratory airway pressure (Paw) increased before NAVAal (1st response), whereas both parameters remained unchanged (2nd response) between NAVAal and NAVAhigh (i.e. the highest NAVA level used) despite substantial further increases in the NAVA level. At NAVAal during the titrations, the group mean Vt ranged between 6.6 and 7.8 ml/kg predicted body weight (PBW). Increasing the NAVA level had no effect on neural respiratory rate, while electrical energy expenditure decreased, and neuro-ventilatory efficiency (Vt/EAdi) continuously improved. ¶ p0.05 compared to NAVAal.

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