Design of a flow modulation device to facilitate individualized ventilation in a shared ventilator setup.

This study aims to resolve the unmet need for ventilator surge capacity by developing a prototype device that can alter patient-specific flow in a shared ventilator setup. The device is designed to deliver a predictable tidal volume (VT), requiring minimal additional monitoring and workload. The prototyped device was tested in an in vitro bench setup for its performance against the intended use and design criteria. The ventilation parameters: VT and airway pressures, and ventilation profiles: pressure, flow and volume were measured for different ventilator and device settings for a healthy and ARDS simulated lung pathology. We obtained VTs with a linear correlation with valve openings from 10 to 100% across set inspiratory pressures (IPs) of 20 to 30 cmH2O. Airway pressure varied with valve opening and lung elastance but did not exceed set IPs. Performance was consistent in both healthy and ARDS-simulated lung conditions. The ventilation profile diverged from traditional pressure-controlled profiles. We present the design a flow modulator to titrate VTs in a shared ventilator setup. Application of the flow modulator resulted in a characteristic flow profile that differs from pressure- or volume controlled ventilation. The development of the flow modulator enables further validation of the Individualized Shared Ventilation (ISV) technology with individualization of delivered VTs and the development of a clinical protocol facilitating its clinical use during a ventilator surge capacity problem.

Combined ultrasound of m. quadriceps and diaphragm to determine the occurrence of sarcopenia and prolonged ventilation in a COVID-19 ICU cohort: The COVID-SARCUS trial.

OBJECTIVE: The aim of this study was to determine the development of sarcopenia in a COVID-19 intensive care unit population by sequential quadriceps and diaphragm ultrasound and its relationship with hospital outcomes. METHODS: We assessed muscle thickness, cross-sectional area, fascicle length, pennation angle, and echo intensity within 48 h after intubation, at days 5 and 10 and at discharge from the intensive care unit in 30 critically ill patients with confirmed COVID-19. RESULTS: A different evolution of muscle thickness of the diaphragm and m. rectus femoris was observed; the changes between the two muscles were not correlated (Pearson's χ2 3.91, P = 0.419). The difference in muscle thickness was linked to the outcome for both m. rectus femoris and diaphragm, with the best survival seen in the group with stable muscle thickness. The greatest loss of muscle thickness occurred between days 5 and 10. The echo intensity was higher in the patients with increased muscle thickness, who also had a worse prognosis. There was a correlation between cross-sectional area on day 5 and handgrip strength (r = 0.290, P = 0.010). Only 31% of patients were able to return to their preadmission residence without any additional rehabilitation. CONCLUSIONS: Muscle atrophy and decline in muscle strength appear in the earliest stages after admission to the intensive care unit and are related to functional outcome.

Risk Factors Associated with Severe RSV Infection in Infants: What Is the Role of Viral Co-Infections?

The respiratory syncytial virus (RSV) represents the leading cause of viral lower respiratory tract infections (LRTI) in children worldwide and is associated with significant morbidity and mortality rates. The clinical picture of an RSV infection differs substantially between patients, and the role of viral co-infections is poorly investigated. During two consecutive winter seasons from October 2018 until February 2020, we prospectively included children up to 2 years old presenting with an acute LRTI, both ambulatory and hospitalized. We collected clinical data and tested nasopharyngeal secretions for a panel of 16 different respiratory viruses with multiplex RT-qPCR. Disease severity was assessed with traditional clinical parameters and scoring systems. A total of 120 patients were included, of which 91.7% were RSV positive; 42.5% of RSV-positive patients had a co-infection with at least one other respiratory virus. We found that patients suffering from a single RSV infection had higher pediatric intensive care unit (PICU) admission rates (OR = 5.9, 95% CI = 1.53 to 22.74), longer duration of hospitalization (IRR = 1.25, 95% CI = 1.03 to 1.52), and a higher Bronchiolitis Risk of Admission Score (BRAS) (IRR = 1.31, 95% CI = 1.02 to 1.70) compared to patients with RSV co-infections. No significant difference was found in saturation on admission, O2 need, or ReSViNET-score. In our cohort, patients with a single RSV infection had increased disease severity compared to patients with RSV co-infections. This suggests that the presence of viral co-infections might influence the course of RSV bronchiolitis, but heterogeneity and small sample size in our study prevents us from drawing strong conclusions. IMPORTANCE RSV is worldwide the leading cause of serious airway infections. Up to 90% of children will be infected by the age of 2. RSV symptoms are mostly mild and typically mimic a common cold in older children and adolescents, but younger children can develop severe lower respiratory tract disease, and currently it is unclear why certain children develop severe disease while others do not. In this study, we found that children with a single RSV infection had a higher disease severity compared to patients with viral co-infections, suggesting that the presence of a viral co-infection could influence the course of an RSV bronchiolitis. As preventive and therapeutic options for RSV-associated disease are currently limited, this finding could potentially guide physicians to decide which patients might benefit from current or future treatment options early in the course of disease, and therefore, warrants further investigation.

The Relationship Between Esophageal Pressure and Diaphragm Thickening Fraction in Spontaneously Breathing Sedated Children: A Feasibility Study.

OBJECTIVES: Diaphragm ultrasound is a novel alternative to esophageal pressure measurements in the evaluation of diaphragm function and activity, but data about its reliability in a pediatric setting are lacking. We aimed to compare the esophageal pressure swing (∆P es , gold standard) with the diaphragmatic thickening fraction (DTF) as a measure of inspiratory effort in sedated children. Additionally, we studied the effect of positive end-expiratory pressure (PEEP) on the end-expiratory thickness of the diaphragm (DT ee ). DESIGN: Prospective open-label non-randomized interventional physiological cohort study. SETTING: Operating room in tertiary academic hospital. PATIENTS: Children 28 days to 13 years old scheduled for elective surgery with general anesthesia, spontaneously breathing through a laryngeal mask airway, were eligible for inclusion. Exclusion criteria were disorders or previous surgery of the diaphragm, anticipated difficult airway or acute cardiopulmonary disease. All measurements were performed prior to surgery. INTERVENTIONS: Patients were subjected to different levels of respiratory load, PEEP and anesthetic depth in a total of seven respiratory conditions. MEASUREMENTS AND MAIN RESULTS: The esophageal pressure and diaphragm thickening fraction were simultaneously recorded for five breaths at each respiratory condition. The relation between ∆P es and DTF was studied in a mixed model. We analyzed 407 breaths in 13 patients. Both DTF ( p = 0.03) and ∆Pes ( p = 0.002) could detect respiratory activity, and ∆P es and DTF were associated across respiratory conditions ( p < 0.001; R2 = 31%). With increasing inspiratory load, ∆P es increased significantly, while DTF did not ( p = 0.08). Additionally, DT ee did not differ significantly between 10, 5, and 0 cm H 2 O PEEP ( p = 0.08). CONCLUSIONS: In spontaneously breathing sedated children and across different respiratory conditions, DTF could differentiate minimal or no inspiratory effort from substantial inspiratory effort and was associated with ∆P es . Increased efforts resulted in higher ∆P es but not larger DTF.

Minimizing Lung Injury During Laparoscopy in Head-Down Tilt: A Physiological Cohort Study.

BACKGROUND: Increased intra-abdominal pressure during laparoscopy induces atelectasis. Positive end-expiratory pressure (PEEP) can alleviate atelectasis but may cause hyperinflation. Cyclic opening of collapsed alveoli and hyperinflation can lead to ventilator-induced lung injury and postoperative pulmonary complications. We aimed to study the effect of PEEP on atelectasis, lung stress, and hyperinflation during laparoscopy in the head-down (Trendelenburg) position. METHODS: An open-label, repeated-measures, interventional, physiological cohort trial was designed. All participants were recruited from a single tertiary Belgian university hospital. Twenty-three nonobese patients scheduled for laparoscopy in the Trendelenburg position were recruited.We applied a decremental PEEP protocol: 15 (high), 10 and 5 (low) cm H 2 O. Atelectasis was studied with the lung ultrasound score, the end-expiratory transpulmonary pressure, the arterial oxygen partial pressure to fraction of inspired oxygen concentration (P ao2 /Fi o2 ) ratio, and the dynamic respiratory system compliance. Global hyperinflation was evaluated by dead space volume, and regional ventilation was evaluated by lung ultrasound. Lung stress was estimated using the transpulmonary driving pressure and dynamic compliance. Data are reported as medians (25th-75th percentile). RESULTS: At 15, 10, and 5 cm H 2 O PEEP, the respective measurements were: lung ultrasound scores (%) 11 (0-22), 27 (11-39), and 53 (42-61) ( P < .001); end-expiratory transpulmonary pressures (cm H 2 O) 0.9 (-0.6 to 1.7), -0.3 (-2.0 to 0.7), and -1.9 (-4.6 to -0.9) ( P < .001); P ao2 /Fi o2 ratios (mm Hg) 471 (435-538), 458 (410-537), and 431 (358-492) ( P < .001); dynamic respiratory system compliances (mL/cm H 2 O) 32 (26-36), 30 (25-34), and 27 (22-30) ( P < .001); driving pressures (cm H 2 O) 8.2 (7.5-9.5), 9.3 (8.5-11.1), and 11.0 (10.3-12.2) ( P < .001); and alveolar dead space ventilation fractions (%) 10 (9-12), 10 (9-12), and 9 (8-12) ( P = .23). The lung ultrasound score was similar between apical and basal lung regions at each PEEP level ( P = .76, .37, and .76, respectively). CONCLUSIONS: Higher PEEP levels during laparoscopy in the head-down position facilitate lung-protective ventilation. Atelectasis and lung stress are reduced in the absence of global alveolar hyperinflation.

Flow-controlled ventilation in moderate acute respiratory distress syndrome due to COVID-19: an open-label repeated-measures controlled trial.

BACKGROUND: Flow-controlled ventilation (FCV), a novel mode of mechanical ventilation characterised by constant flow during active expiration, may result in more efficient alveolar gas exchange, better lung recruitment and might be useful in limiting ventilator-induced lung injury. However, data regarding FCV in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome (ARDS) are scarce. OBJECTIVES: We hypothesised that the use of FCV is feasible and would improve oxygenation in moderate COVID-19 ARDS compared to conventional ventilation. DESIGN: Open-label repeated-measures controlled trial. SETTING: From February to April 2021, patients with moderate COVID-19 ARDS were recruited in a tertiary referral intensive care unit. PATIENTS: Patients with moderate ARDS (PaO2/FIO2 ratio 100-200 mmHg, SpO2 88-94% and PaO2 60-80 mmHg) were considered eligible. Exclusion criteria were: extremes of age (< 18 years, > 80 years), obesity (body mass index > 40 kg/m2), prone positioning at the time of intervention, mechanical ventilation for more than 10 days and extracorporeal membrane oxygenation. Eleven patients were recruited. INTERVENTION: Participants were ventilated in FCV mode for 30 min, and subsequently in volume-control mode (VCV) for 30 min. MAIN OUTCOME MEASURES: Feasibility of FCV to maintain oxygenation was assessed by the PaO2/FiO2 ratio (mmHg) as a primary outcome parameter. Secondary outcomes included ventilator parameters, PaCO2 and haemodynamic data. All adverse events were recorded. RESULTS: FCV was feasible in all patients and no adverse events were observed. There was no difference in the PaO2/FIO2 ratio after 30 min of ventilation in FCV mode (169 mmHg) compared to 30 min of ventilation in VCV mode subsequently (168 mmHg, 95% CI of pseudo-medians (- 10.5, 3.6), p = 0.56). The tidal volumes (p < 0.01) and minute ventilation were lower during FCV (p = 0.01) while PaCO2 was similar at the end of the 30-min ventilation periods (p = 0.31). Mean arterial pressure during FCV was comparable to baseline. CONCLUSIONS: Thirty minutes of FCV in patients with moderate COVID-19 ARDS receiving neuromuscular blocking agents resulted in similar oxygenation, compared to VCV. FCV was feasible and did not result in adverse events. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04894214.

Reoperation for bleeding after cardiac surgery.

BACKGROUND: Postoperative cardio-surgical haemostatic management is centre-specific and experience-based, which leads to a variability in patient care. This study aimed to identify which postoperative haemostatic interventions may reduce the need for reoperation after cardiac surgery in adults. METHODS: A retrospective case-control study in a tertiary centre. Adult, elective, primary cardiac surgical patients were selected (n = 2098); cases (n = 42) were patients who underwent reoperation within 72 h after the initial surgery. Interventions administered to control surgical bleeding were compared for the need to re-operate using multiple logistic regression. RESULTS: Rate of cardiac surgical reoperation was 2% in the study population. Three variables were found to be associated with cardiac reoperation: preoperative administration of fresh frozen plasma (OR 5.45, CI 2.34-12.35), cumulative volume of chest tube drainage and cumulative count of packed red blood cells transfusion on ICU (OR 1.98, CI 1.56-2.51). CONCLUSION: No significant difference among specific types of postoperative haemostatic interventions was found between patients who needed reoperation and those who did not. Perioperative transfusion of fresh frozen plasma, postoperative transfusion of packed cells and cumulative volume of chest tube drainage were associated with reoperation after cardiac surgery. These variables could help predict the need for reoperation.

The Challenges of Crizotinib Treatment in a Child With Anaplastic Large Cell Lymphoma.

Survival in cases involving childhood malignancy is reaching nearly 80% in high-income countries, yet cancer remains one of the leading disease-related causes of death in children. In adult oncology the role of targeted therapies is established, but information regarding the use of these therapies in children is limited, largely because targeted therapies were developed in the context of adult pathologies. The few pediatric reports regarding crizotinib, an anaplastic lymphoma kinase (ALK) inhibitor, seem promising. This case of an 8-year-old male with an ALK-positive anaplastic large cell lymphoma highlights the challenges of treating children with crizotinib. Our experience with crizotinib was more challenging than described in the limited pediatric reports. Not only was the tumor response poorer than described in the reports, but a substantial amount of side-effects and practical difficulties, such as the method of administration and dosing, made management challenging. Many challenges for the use of targeted therapy in pediatric care currently persist. The limited research in pediatric populations leaves uncertainty regarding efficacy and short- and long-term side effects as well as practical difficulties. Despite a clear underlying biological rationale for certain targeted therapies, their contribution toward improving the outcome of childhood cancer remains largely unclear.

Respiratory support in the absence of abdominal muscles: A case study of ventilatory management in prune belly syndrome.

Prune belly syndrome (PBS) results in a total lack of abdominal musculature. Abdominal muscles have an important function during inspiration and expiration. This puts the patient at risk for respiratory complications since they have a very limited ability to cough up secretions. Patients in an intensive care unit (ICU) with PBS who receive mechanical ventilation are at even greater risk for respiratory complications. We review the function of the abdominal muscles in breathing and delineate why they are important in the ICU. We include an illustrative case of a long-term ventilated patient with PBS and offer respiratory management options.

Individualized mechanical ventilation in a shared ventilator setting: limits, safety and technical details.

The COVID-19 pandemic has resulted in an increased need for ventilators. The potential to ventilate more than one patient with a single ventilator, a so-called split ventilator setup, provides an emergency solution. Our hypothesis is that ventilation can be individualized by adding a flow restrictor to limit tidal volumes, add PEEP, titrate FiO2 and monitor ventilation. This way we could enhance optimization of patient safety and clinical applicability. We performed bench testing to test our hypothesis and identify limitations. We performed a bench testing in two test lungs: (1) determine lung compliance (2) determine volume, plateau pressure and PEEP, (3) illustrate individualization of airway pressures and tidal volume with a flow restrictor, (4a) illustrate that PEEP can be applied and individualized (4b) create and measure intrinsic PEEP (4c and d) determine PEEP as a function of flow restriction, (5) individualization of FiO2. The lung compliance varied between 13 and 27 mL/cmH2O. Set ventilator settings could be applied and measured. Extrinsic PEEP can be applied except for settings with a large expiratory time. Volume and pressure regulation is possible between 70 and 39% flow restrictor valve closure. Flow restriction in the tested circuit had no effect on the other circuit or on intrinsic PEEP. FiO2 could be modulated individually between 0.21 and 0.8 by gradually adjusting the additional flow, and minimal affecting FiO2 in the other circuit. Tidal volumes, PEEP and FiO2 can be individualized and monitored in a bench testing of a split ventilator. In vivo research is needed to further explore the clinical limitations and outcomes, making implementation possible as a last resort ventilation strategy.

A physiology-based mathematical model for the selection of appropriate ventilator controls for lung and diaphragm protection.

Mechanical ventilation is used to sustain respiratory function in patients with acute respiratory failure. To aid clinicians in consistently selecting lung- and diaphragm-protective ventilation settings, a physiology-based decision support system is needed. To form the foundation of such a system, a comprehensive physiological model which captures the dynamics of ventilation has been developed. The Lung and Diaphragm Protective Ventilation (LDPV) model centers around respiratory drive and incorporates respiratory system mechanics, ventilator mechanics, and blood acid-base balance. The model uses patient-specific parameters as inputs and outputs predictions of a patient's transpulmonary and esophageal driving pressures (outputs most clinically relevant to lung and diaphragm safety), as well as their blood pH, under various ventilator and sedation conditions. Model simulations and global optimization techniques were used to evaluate and characterize the model. The LDPV model is demonstrated to describe a CO2 respiratory response that is comparable to what is found in literature. Sensitivity analysis of the model indicate that the ventilator and sedation settings incorporated in the model have a significant impact on the target output parameters. Finally, the model is seen to be able to provide robust predictions of esophageal pressure, transpulmonary pressure and blood pH for patient parameters with realistic variability. The LDPV model is a robust physiological model which produces outputs which directly target and reflect the risk of ventilator-induced lung and diaphragm injury. Ventilation and sedation parameters are seen to modulate the model outputs in accordance with what is currently known in literature.

Lung- and Diaphragm-Protective Ventilation.

Mechanical ventilation can cause acute diaphragm atrophy and injury, and this is associated with poor clinical outcomes. Although the importance and impact of lung-protective ventilation is widely appreciated and well established, the concept of diaphragm-protective ventilation has recently emerged as a potential complementary therapeutic strategy. This Perspective, developed from discussions at a meeting of international experts convened by PLUG (the Pleural Pressure Working Group) of the European Society of Intensive Care Medicine, outlines a conceptual framework for an integrated lung- and diaphragm-protective approach to mechanical ventilation on the basis of growing evidence about mechanisms of injury. We propose targets for diaphragm protection based on respiratory effort and patient-ventilator synchrony. The potential for conflict between diaphragm protection and lung protection under certain conditions is discussed; we emphasize that when conflicts arise, lung protection must be prioritized over diaphragm protection. Monitoring respiratory effort is essential to concomitantly protect both the diaphragm and the lung during mechanical ventilation. To implement lung- and diaphragm-protective ventilation, new approaches to monitoring, to setting the ventilator, and to titrating sedation will be required. Adjunctive interventions, including extracorporeal life support techniques, phrenic nerve stimulation, and clinical decision-support systems, may also play an important role in selected patients in the future. Evaluating the clinical impact of this new paradigm will be challenging, owing to the complexity of the intervention. The concept of lung- and diaphragm-protective ventilation presents a new opportunity to potentially improve clinical outcomes for critically ill patients.

Assessing Diaphragmatic Function.

The diaphragm is vulnerable to injury during mechanical ventilation, and diaphragm dysfunction is both a marker of severity of illness and a predictor of poor patient outcome in the ICU. A combination of factors can result in diaphragm weakness. Both insufficient and excessive diaphragmatic contractile effort can cause atrophy or injury, and recent evidence suggests that targeting an appropriate amount of diaphragm activity during mechanical ventilation has the potential to mitigate diaphragm dysfunction. Several monitoring tools can be used to assess diaphragm activity and function during mechanical ventilation, including pressure-derived parameters, electromyography, and ultrasound. This review details these techniques and presents the rationale for a diaphragm-protective ventilation strategy.

Functional respiratory imaging of the airways in the acute respiratory distress syndrome.

BACKGROUND: Alveolar flooding and airway obstruction are present in the acute respiratory distress syndrome. The impact of positive end-expiratory pressure on regional airway aeration has not been described. AIM: To assess bronchial and lung recruitment and distension during an incremental positive end-expiratory pressure trial in patients with acute respiratory distress syndrome. METHODS: Six patients underwent lung and airway imaging at four positive end-expiratory pressure levels in a cohort trial. Images were post-processed by means of Functional Respiratory Imaging. This technique offers 3-dimensional visualisation and quantification of patients' airway and lung geometry on a regional level. RESULTS: With increasing positive end-expiratory pressure from 0 to 20 cmH2O, the median bronchial recruitment was 151% and the median bronchial distension 43%. Non-aerated lower lobes bronchi had more bronchial volume increase at high positive end-expiratory pressure than partially aerated upper lobes bronchi. Lung recruitment tended to be higher in patients with non-focal acute respiratory distress syndrome. In two patients, bronchial volume increase at high positive end-expiratory pressure largely exceeded bronchial volume increase observed in matched healthy control subjects at total lung capacity, suggesting severe bronchial over-distension. CONCLUSIONS: In early acute respiratory distress syndrome, Functional Respiratory Imaging gives an innovative insight into the relationship between positive end-expiratory pressure-induced bronchial distension and recruitment, positive end-expiratory pressure-induced lung recruitment and hyperinflation and lung morphology.

Real-time Monitoring of Cerebral Blood Flow and Cerebral Oxygenation During Rapid Ventricular Pacing in Neurovascular Surgery: A Pilot Study.

BACKGROUND: Rapid ventricular pacing (RVP) can be used to produce short periods of flow arrest during dissection or rupture of a cerebral aneurysm but carries the risk of inducing cerebral ischemia. This study evaluates the intraoperative effect of RVP on local cerebral blood flow (CBF) and cerebral oxygenation during neurovascular surgery. MATERIALS AND METHODS: Five patients undergoing elective cerebrovascular surgery were included in a single-center prospective study. RVP was applied in pacing periods of 40 seconds with 30% and 100% FiO2. Regional cerebral oxygenation was monitored using a Foresight near-infrared spectroscopy sensor. A Clark-type electrode and a thermal diffusion microprobe located in the white matter were used to monitor brain tissue pO2 and CBF, respectively. RESULTS: CBF response to RVP closely followed the blood pressure pattern and resulted in a low-flow state. Unlike CBF, brain tissue pO2 and regional cerebral oxygenation showed a delayed response to RVP, decreasing beyond the pacing period and slowly recovering after RVP cessation. We found a correlation between brain tissue pO2 and regional cerebral oxygenation. Increasing the inspired oxygen concentration had a positive impact on absolute regional cerebral oxygenation and brain tissue pO2 values, but the pattern resulting from applying RVP remained unaltered. CONCLUSIONS: RVP reduces CBF and cerebral oxygenation. Brain tissue pO2 and regional cerebral oxygenation are correlated but unlike CBF respond to RVP in a delayed manner. Further research is required to evaluate the impact of longer RVP bursts on brain oxygenation.

Diaphragm protection: what should we target?

PURPOSE OF REVIEW: Diaphragm weakness can impact survival and increases comorbidities in ventilated patients. Mechanical ventilation is linked to diaphragm dysfunction through several mechanisms of injury, referred to as myotrauma. By monitoring diaphragm activity and titrating ventilator settings, the critical care clinician can have a direct impact on diaphragm injury. RECENT FINDINGS: Both the absence of diaphragm activity and excessive inspiratory effort can result in diaphragm muscle weakness, and recent evidence demonstrates that a moderate level of diaphragm activity during mechanical ventilation improves ICU outcome. This supports the hypothesis that by avoiding ventilator overassistance and underassistance, the clinician can implement a diaphragm-protective ventilation strategy. Furthermore, eccentric diaphragm contractions and end-expiratory shortening could impact diaphragm strength as well. This review describes these potential targets for diaphragm protective ventilation. SUMMARY: A ventilator strategy that results in appropriate levels of diaphragm activity has the potential to be diaphragm-protective and improve clinical outcome. Monitoring respiratory effort during mechanical ventilation is becoming increasingly important.

Respiratory muscle activity after spontaneous, neostigmine- or sugammadex-enhanced recovery of neuromuscular blockade: a double blind prospective randomized controlled trial.

BACKGROUND: The use of neostigmine after neuromuscular blockade (NMB) has been associated with postoperative respiratory complications. In previous studies, we found lower diaphragmatic activity after neostigmine reversal of NMB, compared to sugammadex. It is still unclear whether the adequate use of neostigmine guarantees normal respiratory muscle function after NMB. In this study, we wanted to assess the effect of commonly used degrees of NMB and their possible reversal strategies on respiratory muscle activity after the return of normal neuromuscular transmission. METHODS: This is a randomized, controlled, parallel-group, single-centre, double-blind study in patients scheduled for intracranial surgery at a tertiary academic hospital in Belgium. All participants received target controlled propofol/remifentanil anesthesia and were randomized into one of five groups, receiving either a shallow NMB with no reversal (shallow/saline), a shallow NMB with sugammadex reversal (shallow/sugammadex), a moderate NMB with neostigmine reversal (moderate/neostigmine), a moderate NMB with sugammadex reversal (moderate/sugammadex), or a deep NMB with sugammadex reversal (deep/sugammadex). Primary and secondary outcome parameters were diaphragm and intercostal electromyographic (EMG) activity at the moment of resumed spontaneous breathing activity, defined as a maximal interval of 10 min after the first spontaneous breath. RESULTS: For the five groups, a total of 55 patients could be included in the final analysis. Median time of spontaneous breathing analyzed was 5 min (IQR 3-9.5 min). Both the moderate/sugammadex and the moderate/neostigmine groups had lower levels of diaphragm EMG compared to the shallow/sugammadex group. The moderate/neostigmine group had lower levels of intercostal EMG activity compared to the shallow/saline group. CONCLUSIONS: In this study, the depth of neuromuscular blockade and type of reversal strategy impacts respiratory muscle activity at the moment of resumed spontaneous breathing and recovery of neuromuscular blockade. Both groups that received moderate NMB had lower levels of diaphragm EMG, compared to the shallow NMB group with sugammadex reversal. Compared to the shallow NMB group with no reversal, the moderate NMB with neostigmine reversal group had lower intercostal EMG activity. TRIAL REGISTRATION: Clinicaltrials.gov NCT01962298 on October 9, 2013 and EudraCT 2013-001926-25 on October 10, 2013.