Remimazolam-remifentanil general anaesthesia without muscle relaxants for percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis: A retrospective analysis

INTRODUCTION

Amyotrophic lateral sclerosis (ALS) patients with bulbar dysfunction require percutaneous endoscopic gastrostomy (PEG) for nutritional support, but anaesthesia poses significant risks due to respiratory impairment and aspiration.[1] Current protocols vary between propofol-based sedation[2] and general anaesthesia with tracheal intubation.[3] Remimazolam, a novel ultra-short-acting benzodiazepine with rapid plasma esterase metabolism (hepatic/renal-independent) and flumazenil reversibility,[4] aligns with ALS pathophysiology.

This study introduces a neuromuscular blockade (NMBA) free) protocol combining remimazolam and remifentanil. The primary objective was to evaluate this protocol’s efficacy in preventing respiratory complications (reintubation and prolonged ventilation more than 24 hours) and 30-day mortality. Secondary objectives included quantifying emergence time, intensive care unit (ICU) utilisation rates, and time to pulmonary rehabilitation initiation. We hypothesise that compared to conventional anaesthesia, this protocol will significantly reduce respiratory adverse events and accelerate postoperative functional recovery.

METHODS

After approval from the local institutional review board (vide approval number YCCPHMEC/2025-138-01, dated 9 April 2025), the records of 21 ALS patients who underwent PEG from March 2021 to December 2024 were retrospectively reviewed. Informed consent was waived in view of the retrospective nature of the study. The study was carried out by the principles of the Declaration of Helsinki (2013) and Good Clinical Practice guidelines.

The extracted data encompassed demographics (age, gender, body mass index, and serum albumin levels), comorbidities (hypertension, diabetes mellitus, and depression), ALS-specific parameters [time from symptom onset to PEG placement, preoperative non-invasive ventilation (NIV) use, ALS Functional Rating Scale-Revised score, and Water Swallow Test classification], and perioperative variables [anaesthetic protocol details including anaesthesia duration (min), procedure duration (min), awakening time (min), extubation time (min), length of hospital stay (days), postoperative respiratory failure (%), postoperative sore throat (%), compliance with early pulmonary rehabilitation (%), and 30-day mortality (%)]. The data were extracted from electronic medical record systems and standardised forms, and were then stored.

Patients were positioned in Fowler’s position with standard monitoring [electrocardiogram (ECG), saturation of peripheral oxygen (SpO₂), automated non-invasive blood pressure (NIBP), and bispectral index (BIS)]. Gradual intravenous induction included remimazolam (0.3 mg/kg), remifentanil (2–3 μg/kg), and lignocaine (1.5 mg/kg). Following confirmation of unconsciousness (loss of eyelash reflex and spontaneous breathing), airway management utilised a video laryngoscope to visualise the epiglottis and glottis. A laryngeal anaesthesia tube was positioned at the glottis (Henan Tuoren Best Medical Device Co., Ltd in Xinxiang City, Henan Province), followed by 2 mL of 2% lignocaine spray, followed by tracheal intubation. The ventilation parameters were adjusted to maintain end-tidal carbon dioxide (CO₂) between 35 and 45 mmHg. Anaesthesia maintenance involved continuous intravenous infusions of remimazolam (0.3 mg/kg/h) and remifentanil (0.1–0.2 μg/kg/min). Haemodynamic instability (heart rate <50 bpm or >20% blood pressure drop) was managed with atropine (0.5 mg) or ephedrine/phenylephrine intravenous boluses. The intravenous infusion rates of remifentanil and remimazolam were adjusted based on BP, heart rate (HR), and BIS values to maintain BP and HR within ±20% of baseline and BIS between 40 and 60.

After endoscopic placement, surgeons administered 10 mL of 0.5% ropivacaine for local infiltration anaesthesia at the puncture site under endoscopic guidance. Maintenance agents were discontinued post-endoscopic withdrawal, and flumazenil [0.5 mg intravenous] reversed residual sedation. Extubation criteria required spontaneous breathing and recovery of consciousness (Steward score ≥4). Patients were transferred to the anaesthesia recovery unit and later discharged to the neurological care unit for postoperative monitoring.

Data were analysed using Statistical Package for the Social Sciences (SPSS) statistics software version 25.0 [International Business Machines Corporation (IBM Corp.), Armonk, NY, USA]. Descriptive statistics (Mean [standard deviation], frequencies) were used for data analysis.

RESULTS

This study evaluated 21 high-risk ALS patients with advanced bulbar dysfunction. The cohort demonstrated severe disease progression, characterised by marked respiratory compromise (85.7% with vital capacity <60% predicted), prevalent non-invasive ventilation dependence (71.4%), and profound dysphagia (52.4% at Water Swallow Test stages IV-V), confirming the population’s vulnerability [Table 1]. All procedures were completed without interruption. Notable rapid recovery was observed, with patients achieving tracheal extubation within minutes of flumazenil reversal and brief post-anaesthesia care unit stays. Crucially, no instances of postoperative respiratory failure, reintubation, or 30-day mortality occurred despite the cohort’s high-risk profile. Transient hypotension requiring vasopressor support affected a minority of cases (14.3%), whilst minor complications were limited to self-resolving sore throat (9.5%). The protocol facilitated timely discharge readiness with high compliance (90.5%) in early pulmonary rehabilitation initiation. Critically, no cases required reintubation, developed respiratory failure, or resulted in 30-day mortality, confirming the protocol’s safety profile in advanced ALS, with no episodes of intraoperative arrhythmia, hypoxaemia, or major complications [Table 2].

Table 1.

Baseline patient characteristics

Variable	Study Population (n=21)
Age (years)	54.9 (9.8) (50.49, 59.41)
Gender: Male/Female	12 (57.1)/9 (42.9)
BMI (kg/m2)	20.7 (3.8) (19.03, 22.46)
Serum albumin (g/L)	40.5 (3.4) (38.90, 42.03)
Comorbidities
Hypertension	6 (28.6)
Diabetes mellitus	4 (19.0)
Depression	2 (9.5)
None	9 (42.9)
Time from ALS onset to PEG (years)	2.6 (1.1) (2.11, 3.09)
Preoperative NIV use	15 (71.4)
ALSFRS-R score	25.5 (7.4) (22.13, 28.91)
Vital capacity <60% of predicted	18 (85.7)
Mean overnight oxygenation <93%	12 (57.1)
WST classification-Stage I/II/III/IV/V	1 (4.8)/4 (19.0)/5 (23.8)/8 (38.1)/3 (14.3)

Data expressed as mean (standard deviation) (95% confidence interval) or n (%). BMI=body mass index; ALS=amyotrophic lateral sclerosis; PEG=percutaneous endoscopic gastrostomy; NIV=non-invasive ventilation; ALSFRS-R=Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised; WST=water swallow test

Table 2.

Perioperative outcomes in ALS patients: PEG with remimazolam-remifentanil

Variable	Study Population (n=21)
Time from PEG request to procedure (days)	4.3 (2.1) (3.36, 5.30)
Anaesthesia duration (min)	40.4 (4.8) (38.18, 42.58)
Surgical duration (min)	29.8 (4.2) (27.88, 31.74)
Awakening time (min)	2.4 (0.9) (2.03, 2.82)
Extubation time (min)	4.8 (1.2) (4.28, 5.34)
Hypotension incidencea	3 (14.3)
Duration of PACU stay (min)	26.7 (4.0) (24.85, 28.48)
Time to discharge (days)	4.1 (0.7) (3.78, 4.41)
Postoperative respiratory failure	0 (0)
Compliance with early pulmonary rehabilitation	19 (90.5)
postoperative sore throat	2 (9.5)
30-day mortality	0 (0)

Data expressed as mean (standard deviation) (95% confidence interval) or n (%). ^aDefined as MAP <65 mmHg lasting >5 min requiring vasopressors. ALS=amyotrophic lateral sclerosis; PEG=percutaneous endoscopic gastrostomy; PACU=post-anaesthesia care unit

DISCUSSION

By eliminating NMBAs while achieving stable sedation through synergistic pharmacokinetics, our study protocol safeguards respiratory function, reduces ICU reliance, and enables early pulmonary rehabilitation in advanced ALS.

PEG improves nutrition and quality of life in ALS with bulbar dysfunction;[5] however, anaesthesia management remains contentious due to aspiration-respiratory failure trade-offs. Propofol sedation risks inadequate depth (increasing aspiration)[6] or excessive respiratory depression requiring ICU admission.[6]

Remifentanil’s ultra-short half-life (<10 min)[7] minimises respiratory depression in vital capacity-compromised patients, while remimazolam’s organ-independent metabolism[8] circumvents propofol-induced instability. Nishihara et al.[9] reported the successful use of remazolam combined with remifentanil in tracheotomy in ALS patients. Similarly, Morimoto et al.[10] achieved precise sedation by low-dose remazolam combined with BIS monitoring in anaesthesia for patients with myotonic dystrophy and avoided postoperative complications by using flumazenil for rapid reversal. Transient hypotension requiring phenylephrine occurred in 14.3% of cases, consistent with remifentanil’s vasodilatory effects,[11] but no patients needed extended support—a critical advantage given ALS-associated autonomic dysfunction.

Avoiding neuromuscular blocking agents in ALS patients carries significant clinical value. First, depolarising agents such as succinylcholine entail life-threatening hyperkalaemia risks in denervating diseases, which supports the avoidance of this pharmacological class.[12] Second, even non-depolarising neuromuscular blockers may pose risks. Residual weakness after rocuronium administration, despite reversal with sugammadex, has been observed in patients with an undiagnosed neuromuscular disease, necessitating prolonged postoperative ventilation.[13] Furthermore, ALS-related alterations in acetylcholine receptor sensitivity may predispose patients to exaggerated or prolonged responses to muscle relaxants. These risks are effectively mitigated through regional anaesthesia or total intravenous anaesthesia without NMBA, with supporting clinical evidence.[14] Collectively, these findings emphasise that minimising or eliminating NMBA in ALS patients reduces perioperative complications, mitigates respiratory risks, and aligns with the principle of tailoring anaesthesia to preserve neuromuscular integrity in this fragile population.

CONCLUSION

We advocate for the inclusion of remimazolam-remifentanil protocols in standardised anaesthesia guidelines for high-risk amyotrophic lateral sclerosis patients undergoing percutaneous endoscopic gastrostomy.

Presentation at conferences/CMEs and abstract publication

Nil.

Study data availability

De-identified data may be requested with reasonable justification from the authors (email to the corresponding author) and shall be shared after approval as per the authors’ institution’s policy.

Disclosure of use of artificial intelligence (AI)-assistive or generative tools

The authors confirm that no AI tools or language models (LLMs) were used in the writing or editing of the manuscript, and no images were manipulated using AI.

Declaration of use of permitted tools

Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised score and Steward score are freely available and not copyrighted.

Authors contributions

XY was involved in conceptualisation, design, definition of intellectual content, literature search, conduct of cases, data acquisition, and manuscript preparation. WZ was involved in literature search, conduct of cases, data acquisition, and data analysis. CXC was involved in design, literature search, data analysis, editing, review, and approval. XBC was involved in conceptualisation, design, definition of intellectual content, manuscript preparation, editing, review, and approval.

Conflicts of interest

There are no conflicts of interest.

Supplementary material

Nil.

Funding Statement

Nil.