Original Research Management of mechanical ventilation and weaning in critically ill patients with neuromuscular disorders Pinar Kucukdemirci Kaya * , Remzi Iscimen Bursa Uludag University Faculty of Medicine, Department of Anesthesiology and Reanimation, Bursa, Turkey A R T I C L E I N F O Keywords: Mechanical ventilation Neuromuscular disorders Neuromuscular respiratory failure Biphasic positive airway pressure ventilation (BIPAP) Weaning from mechanical ventilation A B S T R A C T Purpose: Myasthenia-gravis and Guillain-Barre-syndrome are two of the most common causes of acute and reversible neuromuscular-respiratory-failure(ARNRF), both may worsen respiratory-failure and need for invasive-mechanical-ventilation(IMV) for long-periods due to muscle-weakness. However, approitive IMV-mode for ARNRF patients that better gas-exchange and weaning in ARNRF remain unclear. Materials and methods: Critically-ill-patiens with IMV due to ARNRF, who could meet the weaning-criterias (after intubation for more than 7-days; difficult-weaning), between 2013, and 2023 were included in the study. IMV- settings, simultaneous arterial-blood-gas (ABG) analyses, and prognosis were recorded for each patient on relevant days. Results: Sixty-critically-ill-patients with ARNRF who defined as difficult-weaning were included in the study. When different IMV-modes were used in the same patient, simultaneous ABG results were compared for each ventilation-mode. It was determined that the partial-pressure-of-oxygen/fraction of inspired-oxygen-ratios were significantly higher and partial-carbon-dioxide-levels were significantly lower when critically-ill-patients were ventilated with the biphasic-positive-airway-pressure-ventilation(BIPAP) (95 % CI: [0.641–1.41]; p < .001; 95 % CI: [-1.05-.351]; p < .001, respectively). Length-of-time-until-weaning was significantly shorter in BIPAP-mode for each patient in the study group(95 % CI: [0.717–0.188]; p < .001). Moreover, weaning-success was statis tically higher in patients with ARNRF were ventilated with BIPAP one-week-before spontenous-breathing-trial (95 % CI [1.026–21.65]; p = .046) than with all other IMV-modes. Conclusion: According to our findings, when BIPAP was selected as the IMV-settings, gas exchange was improved, and weaning-success was higher in critically-ill-patients with ARNRF. 1. Introduction Patients with neuromuscular disorders are at high risk for respiratory failure [1]. However, extubation of critically ill patients with diseases involving muscles, nerves, and neuromuscular junctions poses a great challenge for intensivists. Myasthenia gravis (MG) and Guillain-Barre syndrome (GBS) are two of the most common acute and reversible causes of neuromuscular respiratory failure (ARNRF) seen in the intensive care unit (ICU) [1,2]. The incidence of ARNRF in adult patients with GBS ranges from 6 % to 33 % and 32 % in adult patients with MG [1, 3–5]. The current approach is to use non invasive ventilation (NIV) for ARNRF with mild bulbar involvement [6]. Bilevel positive airway pressure (BPAP) is most common mode used as NIV for NRF [6]. BPAP requires inspiratory and expiratory PAP. Thus, the bigger difference of Abbreviations: MG, Myasthenia gravis; GBS, Guillain-Barre syndrome; ARNRF, Acute and reversible neuromuscular respiratory failure; ABG, Arterial blood gas; BIPAP, biphasic-positive-airway-pressure-ventilation; ICU, Intensive care unit; BPAP, Bilevel positive airway pressure; NIV, non invasive ventilation; IMV, invasive mechanical ventilation; VAP, Ventilator-associated pneumonia; PEEP, Positive end-expiratory pressures; KDIGO, Kidney Disease Improving Global Outcomes; APACHE, Acute Physiology and Chronic Health Evaluation; SOFA, Sequential Organ Failure Assessment; EGRIS, Erasmus Guillain-Barre Syndrome Respiratory Insufficiency Score; ARS, Advanced respiratory support; HFNOT, High-flow nasal oxygen nasal threapy; CPAP, Continuous positive airway pressure; PCV-VG, Pressure control ventilation/volume guaranteed; SIMV-PC, Synchronized-intermittent-mandatoryventilation/pressure-control ventilation; SIMV-VC, Synchronized- intermittent-mandatoryventilation/volume-control ventilation; FiO2, Fraction of inspired-oxygen; PO2, Partial-pressure-of-oxygen; PCO2, Partial-pressure-of-car bon-dioxide; P/F, The partial-pressure-of-oxygen/fraction of inspired-oxygen ratio; WBC, White blood cell count; PCT, Procalcitonin; CRP, C-reactive protein; IVIg, Intravenous immunoglobin; PE, Plasma exchange; APRV, Airway pressure release ventilation; ARDS, Acute respiratory distress syndrome. * Corresponding author. E-mail address: pinark.kaya@yahoo.com (P. Kucukdemirci Kaya). Contents lists available at ScienceDirect Respiratory Medicine journal homepage: www.elsevier.com/locate/rmed https://doi.org/10.1016/j.rmed.2025.107951 Received 13 May 2024; Received in revised form 2 January 2025; Accepted 13 January 2025 Respiratory Medicine 237 (2025) 107951 Available online 16 January 2025 0954-6111/© 2025 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ). https://orcid.org/0000-0002-8428-8245 https://orcid.org/0000-0002-8428-8245 https://orcid.org/0000-0001-8111-5958 https://orcid.org/0000-0001-8111-5958 mailto:pinark.kaya@yahoo.com www.sciencedirect.com/science/journal/09546111 https://www.elsevier.com/locate/rmed https://doi.org/10.1016/j.rmed.2025.107951 https://doi.org/10.1016/j.rmed.2025.107951 http://crossmark.crossref.org/dialog/?doi=10.1016/j.rmed.2025.107951&domain=pdf http://creativecommons.org/licenses/by/4.0/ pressure support cause large tidal volumes and better compliance of patients with respiratory muscle weakness [7]. Observational studies suggest that NIV may decrease the need for invasive mechanical venti lation (IMV), shorten ICU length of stay, and improve mortality [6]. However, both MG and GBS may worsen respiratory failure and the need for IMV for long periods due to muscle weakness [1,8]. Moreover, prolonged IMV causes respiratory muscle and diaphragm weakness [9, 10]. Weaning failure was reported at rates as high as 40 % in patients with MG and 80 % with GBS [2,11]. Despite all these poor odds, data on the optimal timing of weaning, describing outcome of patients under going tracheostomy, and IMV mode approaches with ARNRF patients are limited. While NRF patients with acute reversible etiologies, such as GB or MG have a high likehood of being liberated from IMV [6]. Pro longation of ICU stay may increase the morbidity and mortality of pa tients by increasing complications. There are several complications associated with IMV, including barotrauma, ventilator-associated pneumonia (VAP) [12], and decreased cardiac output. In ICU reducing the amount of time that patients are exposed to IMV is important way to avoid complications [9,10]. Therefore, it is vital to determine an effec tive ventilation approach in patients with IMV due to ARNRF; for reduce respiratory muscles weakness and to discontinue ventilatory support as soon as possible. The present study aimed to investigate an appropriate IMV mode that can provide effective gas exchange without increasing respiratory muscle weakness to ensure weaning from MV while awating improve ment from specific therapies for ARNRF and to identifying patients who may have difficult weaning, to estimate the prognosis in patients with ARNRF such as GB and MG. 2. Material and methods 2.1. Study design and patient selection Data were collected in Bursa Uludag University tertiary care ICU from patients who met the inclusion criteria between January 1st, 2013, and January 1st, 2023. Inclusion criteria were determined as patients with acute onset of respiratory muscle weakness such as GB and myas thenic crisis [6], relapsing or acute-on-chronic neuromuscular disease as MG who can meet the weaning criteria and defined as difficult or pro longed weaning (requiring up to three attempts or intubation for more than 7-days) [13]. Critically ill patiens with ARNRF who could not meet the weaning criterias or who can meet the weaning criterias before one week of IMV, diagnosed critical-illness-related-muscle-weakness, acute spinal cord or phrenic nerve trauma or infarction, epidural abscess, acute poisoning, medications, metabolic disturbances, tetanus or other infections, multiple sclerosis, progressive, irreversible and chronic neuromuscular diseases such as amyotrophic lateral sclerosis were excluded. Moreover, patients with MG who had other causes of respi ratory failure, such as exacerbation of chronic obstructive pulmonary disease, were excluded from the analysis. The decision to perform an IMV mode trial was based on the clinical assessment of the treating intensivist. IMV mode change was seen in the presence of hypoxemia (PO2 ≤ 60 mm Hg) or worsening hypercapnia (PCO2 ≧ 50 mm Hg), air hunger and inadequate gas exchange manifested by poor tolerance or tachypnea and inadequate tidal volume. 2.2. Weaning criterias The following protocols were considered for inclusion: 1. BIPAP ventilation, with gradual reduction of inspratuar pressure, support pressure and the difference between Phigh and Plow drops to 10 cmH2O. 2. SIMV, with gradual reduction of mandatary respiratory rate (<5) and support pressure. All critically ill patients with ARNRF with difficult weaning or pro longed weaning(requiring up to three attempts or intubation for more than 7-days) [13] underwent spontaneous breathing trials (SBT) with the use of CPAP (CPAP level of maximum 6 cm of water and maximum 10 cm of water pressure support (PS)) before weaning. Among them patients, who have a swallowing reflex; weaning was applied when rapid shallow breathing index (RSBI) was <105 as a result of 2-h SBT and ABG values, P/F and diaphragm motion values were within appropriate limits (P/F > 200, diaphragm motion with ultrasound; women> 9 mm, .men>10 mm). The weaning process; patients, who tolerated such a SBT with the use of CPAP were successfully extubated. Weaning failure (resumption of invasive ventilatory support or death within 48 h after weaning, discharged from ICU with tracheostomy and IMV support) and weaning success [ defined as ability to maintain spontaneous breathing without the need for reintubation and IMV for 48 h after weaning [13] were recorded. 2.3. Data collection Demographic data (age and sex) of the patients, their comorbidities [diagnosis of acute renal failure was made according to the Kidney Disease Improving Global Outcomes (KDIGO) guidelines [14], Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Sequential Organ Failure Assessment (SOFA) scores, indications for ICU admission, and neuromuscular disorder type (GBS or MG) were recor ded.Weakness symptoms onset time, respiratory failure causes, alveolar arterial gradient, predisposing factors, whether VAP [diagnosis of VAP was made according to the Infectious Diseases Society of America (IDSA) and the American Thorasic Society (ATS) guidelines [12] occurs during mechanical ventilation treatments, lenght of stay in the ICU, the Eras mus Guillain-Barre Syndrome Respiratory Insufficiency Score (EGRIS), GBS types for patients with GBS, and the presence of thymoma in pa tients, modified osserman classification and whether thymectomy was performed for patients with MG at admission to the ICU were recorded. 2.4. Mechanical ventilation approaches and arterial blood gas analyses of patients with NRF Advanced respiratory support (ARS) [high-flow nasal oxygen nasal threapy (HFNOT), continuous positive airway pressure (CPAP), and the combination of HFNOT and CPAP and IMV were delivered either by GE Engstrom Carestation or Drager Evita V800 ventilators. Pressure- controlled modes that allow spontaneous ventilation modes, [synchro nized intermittent mandatory ventilation/pressure control (SIMV-PC), synchronized intermittent mandatory ventilation/volume control (SIMV-VC), and biphasic positive airway pressure plus spontaneous breathing (BIPAP: BiLevel, Bi-Vent, BiPhasic, DuoPAP – BIPAP will be the preferred abbreviation for this review)], ventilation parameters [fraction of inspired-oxygen (FiO2), driving pressure, tidal volume, positive end-expiratory pressure (PEEP), respiratory rate], arterial blood gas (ABG) analyses (pH, partial-pressure-of-oxygen; PO2, Partial- pressure-of-carbon-dioxide; PCO2), and the partial-pressure-of- oxygen/fraction of inspired-oxygen (P/F) ratios were recorded for each patient immediately before beginning MV, the period immediately after starting MV, and the 1st, 3rd, 5th, 7th, 10th, 15th, and 28th days (if it is not included in these days, one week before weaning). Ventilation approaches and simultaneous 8.00 a.m. ABG measurements of the pa tients on the specified days in the first 28th days after ICU admission were included in the study. Ventilation modes were recorded daily until weaning, death or discharge. Also, whether patients had diaphragm paralysis, atelectasis during ventilator therapy and physical therapy and rehabilitation; nutrition status were recorded. 2.5. Laboratory findings The highest level of white blood cell count (WBC), procalcitonin P. Kucukdemirci Kaya and R. Iscimen Respiratory Medicine 237 (2025) 107951 2 (PCT), C-reactive protein (CRP), and albumin levels were recorded. 2.6. Medical treatments and complications in ARNRF Intravenous immunoglobin (IVIg), plasma exchange (PE), IMV and ICU-related complications (VAP, alveolar hemorrhage, pneumothorax and pressure injuries), the presence of dysautonomia (clinically repeti tive labile blood pressure values and cardiac arrhythmias were evalu ated as dysautonomia), and whether the patients needed vasopressor or esmelol (during the ICU stay) were recorded. 2.7. Prognosis and mortality Discharge to ward or home, 28-day mortality and 90-day mortality) were recorded. 2.8. Primary outcome The primary outcome was determine an effective IMV mode (for the effects of mechanical ventilation mode; P/F ratios, CO2 removal and atelectasis of the same patients on the relevant day were compared. 2.9. Secondary outcomes We assessed the following secondary outcomes: 1. Weaning success and hospitalization of critically ill patients with IMV due to ARNRF. 2. Effects of medical treatments and complications on outcome 3. 28-day mortality and affecting factors after ARNRF 2.10. Statistical analyses Continuous variables are expressed as the mean (standard deviation) or median (interquartile range) and n (%), depending ± on the normality of the distribution for continuous variables; the Kolmogor ov–Smirnov test was used to test the normality of the distribution for continuous variables. An average value for each ventilator mode and simultaneous blood gas results was determined for each patient and compared using the paired-sample t-test(to compare two measurements such asP/F, PaCO2, tidal volume, PEEP were taken from same patient with different ventilation modes). Bivariate logistic regression models were used to examine the relationships between clinical variables (medical treatments in ARNRF, comorbidities, atelectasis, 28-day mor tality and affecting factors after NRF). Also, a logistic regression analysis was conducted to determine the effects of different IMV mode settings which is used before SBT (last week), on the likelihood of weaning (the logistic model employed a binomial distribution with a logit link func tion). Data analysis was performed using the SPSS statistical software (SPSS 28.0: SPSS, Chicago, IL, USA), and p-values of < .05 were considered statistically significant. Using Kaplan-Meier curves and the long-rank test to time to weaning. List-based delete was used for missing data. 2.11. Ethics approval This retrospective cohort study ‘‘Management of Mechanical Venti lation in Critically Ill Patients with Neuromuscular Disorders: A Retro spective Study’’ was approved on January/18/2023 by the ethics committee of Bursa Uludag Medical Faculty (IRB00004769, decision number: 2023-1/37). No study-related interventions were performed on human subjects in accordance with the Helsinki Declaration of 1975; our study was conducted retrospectively, and approval was obtained from all patients/patient relatives during admission to the ICU for their clinical status, laboratory, and radiologic examination results to be used for scientific publications without specifying the descriptive characteristics (name, surname, ID number) of the patients. The need for informed consent was, therefore, waived by the ethics committee. 3. Results 3.1. Patient population and characteristics Between January 1st, 2013, and January 1st, 2023, 105 patients were treated with ARNRF in the ICU. Among these, acute or acute on chronic reversible causes of NRF; 33 patients with GBS and 27 patients with MG who defined as difficult weaning or prolonged mechanical ventilation [13] were included in this retrospective study (See Fig. 1). These ARNRF patients were 58 ± 17 years old and thirty-one were male. APACHEII scores on admission to ICU were 17 ± 9 and patients un derwent MV for NRF on 1559 days. Patient demographic characteristics, hospitalization, scoring systems, and laboratory findings in patients with IMV due to ARNRF are shown in Table 1. 3.2. Primary outcomes 3.2.1. The effects of mechanical ventilation on oxygenation, carbon dioxide removal, and atelectasis To compare the two most commonly used IMV modes, SIMV-PC and BIPAP, 40 patients were identified in whom both modes were used on 305 different ventilator days. An average value for each ventilator mode and simultaneous blood gas results were determined for each patient and compared using the paired-sample t-test. It was observed that the P/ F ratios measured when the patients were ventilated with the BIPAP mode were significantly higher than the P/F ratios measured with the SIMV-PC mode (95 % CI: [0.641–1.41]; p < .001). There was a signifi cant difference between CO2 removal in the two ventilation modes. Moreover, arterial PaCO2 levels were significantly lower in the BIPAP ventilation group (95 % CI: [− 1.05-.351]; p < .001) (See Table 2). We found no significant differences between the BIPAP ventilation group and the SIMV-PC ventilation group according to atelectasis on the chest radiograph (It was accepted that unilateral elevation of the diaphragm indicates the presence of atelectasis, ultrasonography was used to determine whether the opacity represents fluid or collapsed lung) taken the week before extubation. However, when atelectasis was examined during intensive care treatment, it was seen to be significantly higher in patients with GBS (p = .024). 3.3. Secondary outcomes 3.3.1. Weaning success and hospitalization of patients who had NRF A logistic regression analysis was conducted to determine the effects of different SBT settings on the likehood of weaning success. The anal ysis indicated that the model was a significant predictor of weaning outcomes, χ2 (3) = 8.96, p = .030, suggesting that changes in IMV mode settings before SBT significantly predicted the odds of weaning. BIPAP setting resulted in an estimated effect of 1.55, SE = 0.778, with an odds ratio of 4,7 (95 % CI [1.026–21.65]), which was statistically significant (p = .046), indicating as the IMV setting to BIPAP before SBT increases the probability of weaning compared to SIMV-PC and SIMV-VC. Also, patients with GB with lower EGRIS scores increases the probability of weaning (OR = 0.02, p = .036). The length of the time until weaning (Kaplan-Meier analysis of time to extubation; see Fig. 2).) was signifi cantly shorter in the BIPAP ventilation group (95 % CI: [13.7–26.4]; p < .001). When patients with GB were compared according to phenotypes and patients with MG were compared with classes no difference was found (p > .0,05 for all). We found no significant differences in weaning success and length of stay in the ICU according to age, sex, comorbid ities, WBC counts, CRP, PCT nutrition, physiotherapy, medical treat ments (IVIg, PE), and VIP (p > .05 for all). Also, there were no significant differences between GBS and MG according to weaning success and length of stay in the ICU (p > .05 for all). P. Kucukdemirci Kaya and R. Iscimen Respiratory Medicine 237 (2025) 107951 3 3.3.2. Medical treatments in NRF For neuromuscular diseases, 14 out of 60 patients received IVIg, six received PE, and 30 received both IVIg and PE. None of these treatments could be shown to have a statistically significant effect on ICU length of stay or weaning success. However, IVIg treatment was preferred in pa tients with MG (p = .036). Esmolol and vasopressors were used for dysautonomia, which was significantly more common in patients with GBS (p = .028 and p = .024, respectively). 3.3.3. 28-day mortality and affecting factors after NRF A higher alveolar-arterial (A-a) gradient during admission to the ICU was associated with an increased risk of 28-day mortality (OR = 1.1, 95 % CI: [1.0–1.1]; p = .02). It was identified that the presence of renal failure during hospitalization in the ICU significantly increased mor tality (OR = 26.5, 95 % CI: [2.4–290]; p = .01). However, age, sex, diabetes mellitus, sepsis, congestive heart failure or coronary artery disease, dysautonomia, length of stay in the ICU, and time since the onset of symptoms, were not associated with increased risk for 28-day mortality (p > .3 for all). 4. Discussion Mechanical ventilation, which is often needed in ARNRF, is a sup portive treatment for improving oxygenation, unloading the respiratory muscles, and gaining time until the patient’s condition improves [15]. However, MV is a precision treatment for every patient and cannot be used in the same way in respiratory failures with different pathophysi ologies. Numerous reviews have been published involving the man agement of MV in various diseases with different pathophysiologies [16–18]. BPAP is the recommended mode for NIV for ARNRF patients [6]. Rabinstein et al. found that BPAP could prevent intubation in 70 % of trials, but failed improve pCO2 levels and suggested that BPAP could be tried first in patients with acute respiratory failure from MG crisis while awaiting improvement from specific therapies [7]. However, which IMV mode is more appropriate for patients with ARNRF? have not been well described. In our clinical experience, it is even more difficult to manage the ventilation and weaning processes of critically ill patients with diseases involving muscles, nerves, and neuromuscular junctions. As a result of our investigation, it was found that patients had better P/F ratios, lower pCO2 levels and higher weaning success rates when they were ventilated with the BIPAP mode. The reason why pCO2 levels with BPAP did not decrease in the study conducted by Rabinstein et al. [7] may be the air leaks that occurred while applying NIV and the non-compliance of the patients. In particular, these data aim to help provide the most appropriate support with effective gas exchange without increasing respiratory muscle weakness to the patient during IMV. BIPAP is a mode of MV designed to allow patients to breathe spon taneously while receiving two levels of CPAP [19]. In this ventilation mode, spontaneous breathing can occur at any stage of the ventilation cycle. BIPAP mode is similar to the airway pressure release ventilation (APRV) mode, but there are no restrictions on the timing of the pressure release. Thus, in BIPAP, spontaneous breathing efforts may be present during the longer release phase. APRV and BIPAP modes have been used frequently in patients with acute respiratory distress syndrome (ARDS) [20]. Yoshida et al. reported that mild spontaneous breathing effort may be beneficial to improve gas exchange and to recruit the collapsed lung when compared with controlled breathing with muscle relaxants [21]. Fig. 1. Flowchart Abrevetions:CIPs; critically ill patients, ICU; intensive care unit, NRF; neuromuscular respiratory failure, GBS Guillain-Barre syndrome, MG; myasthenia gravis, DW; difficult weaning, ABG; arterial blood gas, IMV; invasive mechanical ventilation. P. Kucukdemirci Kaya and R. Iscimen Respiratory Medicine 237 (2025) 107951 4 Moreover, in a recent study, it was shown that atelectasis in dependent lung areas was reduced, that were spontaneously breathing with the BIPAP mode [22]. In the current study, patients were ventilated with BIPAP plus spontaneous breathing, thus the ventilator allowed sponta neous breathing and supported every triggered breath without two pressure levels that had been set. Ventilation with two levels of pressure and supporting spontaneous breathing in patients with ARNRF may decreases respiratory drive, which in turn reduces inspiratory muscle workload and reduces double triggering, a patient-ventilator asyn chrony. Combined with an increase in pressure support, decreasing respiratory drive contributes to the reduction of dyspnea in patients receiving IMV. We suggest that the reason for the better oxygenation and lower pCO2 levels with the BIPAP mode in the present study was due to improved gas exchange, which allowed the patients to breathe spontaneously with bi-level pressure. Moreover, reducing patient-ventilator asynchrony, which is common in patients with ARNRF, also contributes to the improvement in gas exchange. The weaning process from invasive ventilation represents a corner stone in the prognosis of critically ill patients [23]. Therefore, it is very important to initiate it at the right time. Prolonged MV has been asso ciated with higher mortality rates in NRF [11]. Weaning failure was reported at rates as high as 40 % in patients with MG and 80 % with GBS [11]. These high rates may be due to an imbalance between respiratory muscle capacity and respiratory load. However, how to manage the weaning process and anticipate weaning failure remains unclear. In the literature published on NRF to date, intubation rates and predisposing factors have been reported [24–26]. The EGRIS score is used to calculate the probability that a patient requires MV within 1 week of assessment, and higher scores are associated with respiratory failure [24]. Similar to respiratory failure, we found that weaning failure was higher in patients with GBS with high EGRIS scores at ICU admission. The recent sys tematic review reported that; It does not allow to conclude the superi ority of any particular weaning protocol for patients with NRF or to determine the impact of different types of protocols on other outcomes such as duration of mechanical ventilation and weaning [13]. To the best of our knowledge, in such studies conducted so far, weaning has been evaluated and the patient’s IMV mode approaches have not been examined until the weaning process. In our study, it was observed that in patients who underwent BIPAP, the weaning process was started earlier and weaning success rate was higher. This was associated with earlier initiation of spontaneous breathing trials due to earlier P/F ratios and pCO2 levels reaching the desired level. Furthermore, “air hunger’’ is very common in patients with NRF, which occurs in particular when the inspiratory flow rate is insufficient or when tidal volumes are decreased under MV while the pCO2 level is held constant. Based on our clinical experience, we think that it is easier for patients with IMV due to ARNRF to switch from the BIPAP mode to the CPAP mode in relation to the factors described above. The American Academy of Neurology suggests immunosuppressive therapy for patients with GBS and MG in emergency care [1]. This immunosuppressive therapy includes IVIg, PE, or both. No superiority has been demonstrated for these treatments or their combinations over each other [1–3]. Similarly, we found no significant associations be tween these treatments according to the length of stay in the ICU or weaning success. Autonomic dysfunction associated with GBS often re quires close attention in the ICU [27]. Our analyses indicated that esmolol and noradrenaline were effectively used in the treatment of patients with GBS with dysautonomia to regulate blood pressure and heart rates. Willison et al. identified dysautonomia as one of the causes that increased mortality [3]. In our study, no effect was found on the 28 and 90-day mortality of patients with GBS with or without dysautonomia. The incidence of mortality in adult patients with GBS ranges from 2 % to 12 %, and 5 %–19 % in adult patients with MG [1–3]. Poor prog nosis and mortality were associated with respiratory failure requiring Table 1 Differences in demographic characteristics, hospitalization, scoring systems, and laboratory findings in patients with NRF. Variables GBS (n:33) MG (n:27) P Age 57 ± 17 58 ± 18 .92 Sex (male:n:31) 17 14 .98 Scoring systems APACHEII 18 ± 9 15 ± 8 .49 SOFA (mean ± SD) 3 ± 1.1 3 ± 1 .175 NRF causes Infection (n) 27 13 ​ Vaccine (n) 1 0 ​ Surgery (n) 5 9 ​ Unknown(n) 0 5 ​ Weakness symptoms onset time (days) 34 ± 11 26 ± 7 .07 ICU stay 36 ± 11.8 24 ± 6.5 .009 Hospital stay 33 ± 11 28 ± 7.4 .23 IMV on admission to ICU(n) 22 23 .971 ARS on admission to ICU(n) CPAP 3 0 ​ HFNOT 2 4 ​ HFNOT + CPAP 6 0 ​ VAP (n) 17 7 .044 Weaning success in two weeks (n) 13 14 .49 Tracheostomy 19 11 .2 Tracheostomy length of stay (mean ± SD) 33 ± 11 27 ± 7 .18 Decanulation in ICU (n) 6 3 .5 Physical therapy and rehabilitation (n) 18 15 .80 Nutrition (70 % in1 st week) n 27 23 .50 Laboratory Findings WBC 103 per microliter (mean ± SD) 15 ± 8 10 ± 5 .13 CRP mg/dL (mean ± SD) 33 ± 10 26 ± 7 .11 D-Dimer ng/mL (mean ± SD) 220 ± 212 280 ± 223 .06 IVIg (n) 18 26 .036 PE (n) 8 1 .60 Vasopressor 19 5 .002 Esmolol 8 1 .027 Dysautonomia (n) 16 1 <.001 28-day mortality (n) 7 3 .33 90-day mortality (n) 9 5 .43 Phenotypical variants of GBS AIDP 8 (24.2 %) ​ ​ AMAN 21 (63.6 %) ​ ​ AMSAN 4 (12.1 %) ​ ​ Modified osserman classification Class I ​ 2 (7.4 %) ​ Class II ​ 10 (37 %) ​ Class III ​ 13 (48.2 %) ​ Class IV ​ 2 (7.4 %) ​ Abrevetions: NRF; neuromuscular respiratory failure, GBS Guillain-Barre syn drome, MG; myasthenia gravis, APACHE II; Acute Physiology and Chronic Health Evaluation scores, SOFA; Sequential Organ Failure Assessment, SD; standart deviation, ICU; intensive care unit, ARS; Advanced respiratory support IMV; invasive mechanical ventilation, CPAP; continuous positive airway pres sure, HFNOT; high-flow nasal oxygen therapy,VAP; ventilator-associated pneumonia, AIDP; acute inflammatory demyelinating polyradiculoneuropathy, AMAN; acute motor axonal neuropathy, AMSAN; acute motor-sensory axonal neuropathy. Table 2 Values of each patient’s in different controlled modes that allow spontaneous ventilation. Variable SIMV-PC (n:40) BIPAP (n:40) P Tidal volume ml (mean ± SD) 502 ± 89 612 ± 72 < .001 PEEP cm of water (mean ± SD) 7 ± 1.5 5.8 ± .89 < .001 P/F (mean ± SD) 225 ± 77 296 ± 60 < .001 PCO2 mm Hg (mean ± SD) 43.8 ± 6.5 38.8 ± 4.6 < .001 Days before initial SBT (mean ± SD) 8.3 ± 15.6 6.9 ± 15.7 < .001 Abrevetions:SIMV-PC; synchronized intermittent mandatory ventilation/pres sure control, BIPAP; biphasic positive airway pressure plus spontaneous breathing, SD; standart deviation, P/F; partial-pressure-of-oxygen/fraction of inspired-oxyge, SBT; spontaneous breathing trials. P. Kucukdemirci Kaya and R. Iscimen Respiratory Medicine 237 (2025) 107951 5 prolonged MV, dysautonomia, higher preintubation CO2, pulmonary complications, and sepsis in different studies [28–32]. In the present study, a higher A-a gradient and the presence of renal failure during admission to the ICU were associated with an increased risk for 28-day mortality. However, age, sex, diabetes mellitus, sepsis, congestive heart failure or coronary artery disease, dysautonomia, length of stay in the ICU, and time since symptom onset were not associated with an increased risk for 28-day mortality. The current study has some limitations. Having included critically ill patients with ARNRF admitted to a single referral university tertiary ICU limited the generalizability of our findings. The fact that not all patients with ARNRF were included in the study and reviewing patients’ data only on selected days due to the retrospective nature of the study may have affected the results. Although the gas exchanges caused by IMV modes are made by looking at the gas exchanges of the same patient on different days in order to minimize in-vivo changes, this may not be the only effect of the IMV mode, as other reasons such as pneumonia and aspiration may cause differences between days even in the same patient. Future studies to guide MV approaches or weaning strategies should include advanced lung monitoring methods. However, this is the first study ever performed on appropriate IMV mode for gas exchange and weaning in critically ill patients with IMV due to ARNRF. 5. Conclusions We found that gas exchange was improved, the transition to the weaning process was shortened and weaning failure was reduced when patients with ARNRF were ventilated with the BIPAP mode before SBT when compared with the SIMV-PC mode. The impact of providing appropriate IMV approaches or identifying patients who may have difficult weaning or can not wean requires further evaluation, but these findings might be crucial to predict ICU outcomes to ensure that appropriate support can be provided during ICU treatment. CRediT authorship contribution statement Pinar Kucukdemirci Kaya: Writing – review & editing, Writing – original draft, Visualization, Validation, Supervision, Software, Re sources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Remzi Iscimen: Writing – review & editing, Supervision, Resources, Project administration, Methodology, Formal analysis. Fig. 2. Kaplan-Meier Analysis of Time to Extubation. Abrevations: BIPAP; biphasic positive airway pressure plus spontaneous breathing. P. Kucukdemirci Kaya and R. Iscimen Respiratory Medicine 237 (2025) 107951 6 Data availability statement The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Funding None. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article. Acknowledgements We thank Burcu Kaya Kızılöz, for consultancy in data analysis. References [1] T.B. Birch, Neuromuscular disorders in the intensive care unit, Am. Academy Neurol. 27 (2021) 1344–1364, https://doi.org/10.1212/ CON.0000000000001004. [2] P. Shang, Mingqin Zu, M. Baker, J. Feng, C. Zhou, H.L. Zhang, Mechanical ventilation in Guillain-Barre syndrome, Expet Rev. Clin. Immunol. 16 (2020) 1053–1064, https://doi.org/10.1080/1744666X.2021.1840355. [3] H.J. Willison, B.C. 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Iscimen Respiratory Medicine 237 (2025) 107951 7 https://doi.org/10.1212/CON.0000000000001004 https://doi.org/10.1212/CON.0000000000001004 https://doi.org/10.1080/1744666X.2021.1840355 https://doi.org/10.1016/S0140-6736(16)00339-1 https://doi.org/10.1001/archneur.58.6.893 https://doi.org/10.1212/WNL.0000000000008688 https://www.uptodate.com/contents/respiratory-muscle-weakness-due-to-neuromuscular-disorder:management?search https://www.uptodate.com/contents/respiratory-muscle-weakness-due-to-neuromuscular-disorder:management?search https://doi.org/10.1212/01.wnl.0000033797.79530.16 https://doi.org/10.1212/01.wnl.0000033797.79530.16 https://doi.org/10.1002/mus.26689 https://doi.org/10.1183/09031936.00010206 https://doi.org/10.1183/09031936.00010206 https://doi.org/10.1186/s40248-018-0118-7 https://doi.org/10.1186/s40248-018-0118-7 https://doi.org/10.1007/s12028-008-9139-y https://doi.org/10.1136/bmjopen-2020-047449 https://doi.org/10.1136/bmjopen-2020-047449 https://kdigo.org/guidelines/acute-kidney-injury/ https://kdigo.org/guidelines/acute-kidney-injury/ https://doi.org/10.1097/MCC.0000000000000270 https://doi.org/10.1007/s00134-020-06291-0 https://doi.org/10.1186/s13054-021-03686-3 https://doi.org/10.1113/EP089400 https://doi.org/10.1113/EP089400 https://doi.org/10.1097/TA.0b013e31803c562f https://doi.org/10.1164/ajrccm.164.1.2001078 https://doi.org/10.1164/ajrccm.164.1.2001078 https://doi.org/10.1186/s40560-015-0083-6 https://doi.org/10.1186/s12890-023-02730-y https://doi.org/10.1097/MCC.0000000000000941 https://doi.org/10.1186/s13613-020-00742-z https://doi.org/10.1186/s13613-020-00742-z https://doi.org/10.1007/s12028-016-0311-5 https://doi.org/10.1007/s12028-016-0311-5 https://doi.org/10.1212/WNL.0000000000002790 https://doi.org/10.1212/WNL.0000000000002790 https://doi.org/10.1007/s12028-019-00781-w https://doi.org/10.1007/s12028-019-00781-w https://doi.org/10.1016/S0140-6736(16)00339-1 https://doi.org/10.1212/wnl.54.12.2311 https://doi.org/10.1002/mus.24175 https://doi.org/10.1097/01.ccx.0000168530.30702.3e https://doi.org/10.1097/01.ccx.0000168530.30702.3e https://doi.org/10.1212/WNL.0b013e3182904fcc https://doi.org/10.1212/WNL.0b013e3182904fcc Management of mechanical ventilation and weaning in critically ill patients with neuromuscular disorders 1 Introduction 2 Material and methods 2.1 Study design and patient selection 2.2 Weaning criterias 2.3 Data collection 2.4 Mechanical ventilation approaches and arterial blood gas analyses of patients with NRF 2.5 Laboratory findings 2.6 Medical treatments and complications in ARNRF 2.7 Prognosis and mortality 2.8 Primary outcome 2.9 Secondary outcomes 2.10 Statistical analyses 2.11 Ethics approval 3 Results 3.1 Patient population and characteristics 3.2 Primary outcomes 3.2.1 The effects of mechanical ventilation on oxygenation, carbon dioxide removal, and atelectasis 3.3 Secondary outcomes 3.3.1 Weaning success and hospitalization of patients who had NRF 3.3.2 Medical treatments in NRF 3.3.3 28-day mortality and affecting factors after NRF 4 Discussion 5 Conclusions CRediT authorship contribution statement Data availability statement Funding Declaration of competing interest Acknowledgements References