Neuromuscular Respiratory Failure

VERSION: 1.0 CREATED: January 27, 2026 STATUS: Approved

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DIAGNOSIS: Neuromuscular Respiratory Failure

ICD-10: G70.00 (Myasthenia gravis without exacerbation), G70.01 (Myasthenia gravis with exacerbation), G61.0 (Guillain-Barré syndrome), J96.00 (Acute respiratory failure, unspecified hypoxia/hypercapnia), G71.0 (Muscular dystrophy), G12.21 (Amyotrophic lateral sclerosis)

CPT CODES: 82803 (Arterial blood gas (ABG)), 85025 (CBC with differential), 80053 (CMP (BMP + LFTs)), 83735 (Magnesium), 84100 (Phosphorus), 82330 (Calcium (ionized)), 86235 (Acetylcholine receptor (AChR) antibodies), 84443 (TSH), 84145 (Procalcitonin), 86255 (Anti-ganglioside antibodies (GM1, GD1a, GD1b, GQ1b)), 95937 (Repetitive nerve stimulation (RNS)), 95872 (Single-fiber EMG (SFEMG)), 95907-95913 (Nerve conduction studies), 71260 (CT chest (with contrast)), 71046 (Chest X-ray), 94010 (Bedside spirometry (FVC)), 94799 (Negative inspiratory force (NIF/MIP)), 93000 (ECG (12-lead)), 93306 (Echocardiogram), 78816 (PET/CT), 62270 (LP), 96365 (IVIG (Intravenous Immunoglobulin)), 36514 (Plasma exchange (PLEX))

SYNONYMS: Neuromuscular respiratory failure, NMRF, respiratory failure from weakness, GBS respiratory failure, myasthenic respiratory failure, NIF less than 20, FVC less than 20, impending respiratory failure, neuromuscular ventilatory failure, ventilatory failure, diaphragmatic weakness

SCOPE: Emergency evaluation and management of respiratory failure from neuromuscular disorders in adults. Covers recognition of impending respiratory failure, monitoring parameters (FVC, NIF), indications for intubation, non-invasive ventilation (NIV) considerations, disease-specific treatments (myasthenia gravis crisis, GBS, ALS, muscular dystrophy, other myopathies), and weaning considerations. Excludes central causes of respiratory failure (brainstem stroke, sedative overdose) and primary pulmonary causes (pneumonia, ARDS, COPD exacerbation).

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PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

═══════════════════════════════════════════════════════════════ SECTION A: ACTION ITEMS ═══════════════════════════════════════════════════════════════

1. LABORATORY WORKUP

1A. Essential/Core Labs

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Arterial blood gas (ABG) (CPT 82803)	STAT	STAT	-	STAT	CRITICAL: Assess ventilation (PaCO2) and oxygenation (PaO2); hypercapnia (PaCO2 >45) indicates hypoventilation; respiratory acidosis = severe; PaO2/FiO2 ratio	Normal: pH 7.35-7.45, PaCO2 35-45, PaO2 >80; Hypercapnia with respiratory acidosis = impending/current respiratory failure — consider intubation
CBC with differential (CPT 85025)	STAT	STAT	ROUTINE	STAT	Infection (pneumonia as trigger or complication); baseline; anemia (reduces O2 carrying capacity)	Normal; leukocytosis → infection; anemia → correct
CMP (BMP + LFTs) (CPT 80053)	STAT	STAT	ROUTINE	STAT	Electrolytes (K, Mg, Ca, Phos — all affect muscle function); renal function; glucose	Normal; hypokalemia, hypophosphatemia, hypomagnesemia, hypocalcemia can all worsen neuromuscular weakness
Magnesium (CPT 83735)	STAT	STAT	ROUTINE	STAT	Hypomagnesemia worsens neuromuscular junction transmission and muscle weakness	>2.0 mg/dL; replete if low
Phosphorus (CPT 84100)	STAT	STAT	ROUTINE	STAT	Hypophosphatemia causes profound muscle weakness including respiratory muscles	>2.5 mg/dL; replete if low (can cause respiratory failure at <1.0)
Calcium (ionized) (CPT 82330)	STAT	STAT	ROUTINE	STAT	Hypocalcemia increases neuromuscular excitability; hypercalcemia causes weakness	Normal ionized Ca
Acetylcholine receptor (AChR) antibodies (CPT 86235)	-	URGENT	ROUTINE	URGENT	MG workup: positive in 85% of generalized MG; 50% of ocular MG; confirms diagnosis	Positive = MG; negative does NOT exclude (check MuSK, LRP4)
Anti-MuSK antibodies (CPT 86235)	-	URGENT	ROUTINE	URGENT	If AChR negative but MG suspected clinically; MuSK-positive MG has distinct features (bulbar predominant, may not respond well to cholinesterase inhibitors)	Positive = MuSK MG
Anti-LRP4 antibodies	-	ROUTINE	ROUTINE	-	If both AChR and MuSK negative ("seronegative MG"); less commonly available	Positive = LRP4 MG (rare)
Creatine kinase (CK)	STAT	STAT	ROUTINE	STAT	Elevated in myopathies, muscular dystrophies; may be normal in MG, GBS, ALS	Normal in MG, GBS; elevated in myopathies, rhabdomyolysis; very high (>10,000) in inflammatory myopathies, dystrophies
TSH (CPT 84443)	-	ROUTINE	ROUTINE	-	Thyroid dysfunction: hyperthyroidism worsens MG; hypothyroidism causes myopathy	Normal
Procalcitonin (CPT 84145) / CRP (CPT 86140)	STAT	STAT	-	STAT	Infection as trigger (pneumonia, UTI can precipitate MG crisis); distinguish infection from disease exacerbation	Normal; elevated → infection workup
Urine drug screen	STAT	-	-	STAT	Drugs affecting neuromuscular function; intoxication as mimicker	Negative

1B. Extended Workup (Second-line)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Pyridostigmine level (if available)	-	ROUTINE	-	ROUTINE	Rarely available; assess for cholinergic crisis (too much pyridostigmine vs. myasthenic crisis)	Therapeutic range varies; clinical assessment more reliable
Anti-ganglioside antibodies (GM1, GD1a, GD1b, GQ1b) (CPT 86255)	-	URGENT	ROUTINE	URGENT	GBS workup; GQ1b positive in Miller Fisher syndrome	Positive supports GBS diagnosis; negative does NOT exclude
CSF analysis	-	URGENT	ROUTINE	-	GBS: albuminocytologic dissociation (elevated protein, normal cells — may not be present in first week); exclude infection	GBS: protein elevated (>45 mg/dL), WBC <10 (usually <5); may be normal early
Repetitive nerve stimulation (RNS) (CPT 95937)	-	URGENT	ROUTINE	-	MG diagnosis: decremental response at 3 Hz stimulation (>10% decrement) in proximal muscles	>10% decrement = neuromuscular junction defect (MG); no decrement does NOT exclude MG
Single-fiber EMG (SFEMG) (CPT 95872)	-	-	ROUTINE	-	Most sensitive test for MG (92-98%); increased jitter and blocking	Increased jitter = neuromuscular transmission defect
Nerve conduction studies (CPT 95907-95913) / EMG (CPT 95886)	-	URGENT	ROUTINE	URGENT	GBS: demyelinating pattern (prolonged F-waves, conduction block, temporal dispersion) or axonal (reduced amplitudes); ALS: widespread denervation; myopathy: myopathic units	GBS: demyelinating or axonal; ALS: diffuse denervation; myopathy: small, polyphasic MUPs
CT chest (with contrast) (CPT 71260)	-	URGENT	ROUTINE	-	Thymoma screening in MG: 10-15% of MG patients have thymoma; all MG patients need chest imaging	Thymoma (anterior mediastinal mass); thymic hyperplasia; normal thymus
Anti-striational (anti-titin, anti-RyR) antibodies	-	ROUTINE	ROUTINE	-	Associated with thymoma in MG; may indicate need for more aggressive thymoma search	Positive in older MG patients and thymoma-associated MG
Paraneoplastic antibody panel (CPT 86255)	-	ROUTINE	ROUTINE	-	Paraneoplastic neuromuscular syndromes (LEMS with anti-VGCC and small cell lung cancer); myositis with malignancy	Anti-VGCC (LEMS); anti-Hu, anti-CV2 (paraneoplastic)
Anti-VGCC antibodies	-	URGENT	ROUTINE	-	Lambert-Eaton myasthenic syndrome (LEMS); associated with SCLC in 50-60%	Positive = LEMS (check for underlying malignancy)

1C. Rare/Specialized (Refractory or Atypical)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
Muscle biopsy	-	-	EXT	-	Inflammatory myopathy (dermatomyositis, polymyositis); muscular dystrophy; congenital myopathy	Inflammatory infiltrate; dystrophic changes; structural abnormalities
Genetic testing (muscular dystrophy panel)	-	-	EXT	-	Suspected hereditary myopathy/dystrophy; known family history; young patient with progressive weakness	Specific mutations (dystrophin, FSHD, myotonic dystrophy, etc.)
Myositis-specific antibodies (Jo-1, Mi-2, SRP, MDA5, etc.)	-	ROUTINE	ROUTINE	-	Inflammatory myopathy workup	Specific antibodies guide diagnosis and prognosis
Edrophonium (Tensilon) test	-	EXT	EXT	-	Rarely done now (replaced by serologic testing and SFEMG); bedside MG test; risk of cholinergic crisis; atropine must be at bedside	Transient improvement = positive (MG); false positives/negatives occur
Ice pack test	-	URGENT	ROUTINE	URGENT	Bedside test for ocular MG; apply ice pack to closed eyelid for 2 min; improvement in ptosis suggests MG	Improvement = positive; negative does NOT exclude
Spirometry with flow-volume loop	-	URGENT	ROUTINE	URGENT	Upper airway obstruction pattern (variable extrathoracic obstruction in vocal cord weakness); restrictive pattern in neuromuscular disease	Restrictive pattern; flattened inspiratory loop suggests extrathoracic obstruction
Polysomnography	-	-	ROUTINE	-	Sleep-disordered breathing in neuromuscular disease; nocturnal hypoventilation; assess need for nocturnal NIV	Hypoventilation; desaturations; REM-related hypopneas
Pulmonary function tests (full)	-	-	ROUTINE	-	Baseline and monitoring in chronic neuromuscular disease; FVC, MIP, MEP, SNIP	FVC; supine vs. upright FVC (>20% drop suggests diaphragm weakness)

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Essential/First-line

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Chest X-ray (CPT 71046)	STAT	STAT	-	STAT	Immediate; assess for aspiration, pneumonia (trigger for crisis), atelectasis, elevated hemidiaphragm	Aspiration pneumonia; atelectasis (from weak cough); elevated hemidiaphragm (diaphragm weakness); anterior mediastinal mass (thymoma)	None
Bedside spirometry (FVC) (CPT 94010)	STAT	STAT	ROUTINE	STAT	CRITICAL: q4-6h in unstable patients; q1-2h if rapidly declining; most important monitoring parameter	FVC >20 mL/kg = adequate; FVC <15-20 mL/kg = consider intubation; FVC declining >30% from baseline = concerning	Patient cooperation required; cannot perform if intubated (use ventilator parameters)
Negative inspiratory force (NIF/MIP) (CPT 94799)	STAT	STAT	ROUTINE	STAT	CRITICAL: Assess inspiratory muscle strength; complement to FVC; easier for fatigued patients	NIF < -30 cm H2O = adequate; NIF > -20 to -25 cm H2O (less negative) = weak, consider intubation	Patient cooperation
Maximum expiratory pressure (MEP)	-	URGENT	ROUTINE	STAT	Assess cough strength; correlates with ability to clear secretions	MEP <40 cm H2O = weak cough; aspiration risk
ABG (arterial blood gas) (CPT 82803)	STAT	STAT	-	STAT	Assess ventilation and oxygenation; hypercapnia is late sign	PaCO2 >45 = hypoventilation; rising PaCO2 is ominous; PaO2 <60 = hypoxemia
ECG (12-lead) (CPT 93000)	STAT	STAT	-	STAT	Arrhythmia from autonomic dysfunction (GBS); cardiac involvement in muscular dystrophies; baseline for IVIG/PLEX	Arrhythmia; conduction abnormalities; cardiomyopathy (DMD, LGMD)

2B. Extended

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
CT chest with contrast (CPT 71260)	-	URGENT	ROUTINE	-	Within 24-48h for MG; thymoma screening; all newly diagnosed generalized MG	Thymoma (anterior mediastinal mass); thymic hyperplasia	Contrast allergy; renal impairment
MRI chest (non-contrast)	-	-	ROUTINE	-	If CT contraindicated or additional characterization needed	Thymoma; thymic abnormality	MRI-incompatible implants
Echocardiogram (CPT 93306)	-	URGENT	ROUTINE	URGENT	Cardiomyopathy screening in muscular dystrophies (DMD, BMD, LGMD2I, myotonic dystrophy); autonomic dysfunction in GBS; baseline before IVIG	Cardiomyopathy; reduced EF; conduction abnormalities (perform ECG first)	None
Diaphragm ultrasound	-	URGENT	ROUTINE	URGENT	Assess diaphragm excursion and thickness; non-invasive diaphragm function assessment; bedside	Reduced diaphragm excursion (<1.5 cm during tidal breathing, <4 cm during deep breath); paradoxical motion = diaphragm paralysis	Operator-dependent; obesity may limit views
CT angiography (pulmonary)	-	URGENT	-	URGENT	If pulmonary embolism suspected (immobile patients at high VTE risk)	PE	Contrast allergy; renal impairment
PET/CT (CPT 78816)	-	-	ROUTINE	-	If LEMS diagnosed to search for underlying malignancy (SCLC in 50-60%)	Lung mass; lymphadenopathy; occult malignancy	Uncontrolled diabetes

2C. Rare/Advanced

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Phrenic nerve conduction study	-	-	ROUTINE	-	Assess phrenic nerve function; bilateral phrenic neuropathy as cause of respiratory failure	Absent or reduced phrenic CMAP = phrenic neuropathy; prolonged latency	Pacemaker (relative)
Fluoroscopic sniff test	-	-	ROUTINE	-	Diaphragm function; "sniff test" — paradoxical upward diaphragm motion with sniff = paralysis	Paradoxical motion = diaphragm paralysis	Radiation exposure; pregnancy
Transdiaphragmatic pressure (Pdi)	-	-	EXT	-	Gold standard for diaphragm strength; requires esophageal and gastric balloon catheters; specialized centers	Reduced Pdi = diaphragm weakness	Invasive; specialized equipment
Polysomnography with capnography	-	-	ROUTINE	-	Nocturnal hypoventilation assessment; sleep-disordered breathing; guide NIV	Nocturnal hypoventilation (elevated PtcCO2); desaturations; REM-related events	Sleep lab availability

Lumbar Puncture

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
LP (CPT 62270) with CSF analysis	-	URGENT	ROUTINE	-	GBS diagnosis (albuminocytologic dissociation); may be normal in first week; NOT typically needed for MG diagnosis	GBS: elevated protein (often >100 mg/dL after first week), normal WBC (<10, usually <5); cytoalbuminous dissociation	Coagulopathy; skin infection at LP site; elevated ICP

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3. TREATMENT PROTOCOLS

3A. Acute/Emergent Treatment

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Airway assessment and monitoring	-	-	20 mL/kg :: - :: - :: "20/30/40 Rule": FVC <20 mL/kg, NIF > -30 cm H2O (less negative), MEP <40 cm H2O = HIGH RISK for respiratory failure; monitor q2-4h (or more frequently if declining); INTUBATION THRESHOLD: FVC <15-20 mL/kg, NIF > -20 to -25 cm H2O, rising PaCO2, or clinical distress	-	NMD respiratory failure is often predictable by serial FVC/NIF; intubate BEFORE crisis (controlled intubation is safer); ABG abnormalities are LATE signs	STAT	STAT	-	STAT
Elective intubation (if criteria met)	-	-	15-20 mL/kg :: - :: - :: Indications: FVC <15-20 mL/kg (or <1 L); NIF > -20 to -25 cm H2O; PaCO2 rising or >50; clinical respiratory distress; inability to clear secretions; aspiration; fatigue; RSI considerations: AVOID succinylcholine in myopathies/muscular dystrophy (hyperkalemia), MG (resistance); use rocuronium (may need reduced dose in MG); can use sugammadex for reversal	-	Elective intubation is safer than emergent; neuromuscular patients are difficult to bag-mask ventilate; have difficult airway equipment ready; avoid neuromuscular blockers post-intubation if possible	STAT	STAT	-	STAT
Non-invasive ventilation (NIV)	-	-	N/A :: - :: continuous :: ROLE IS LIMITED IN ACUTE NMD RESPIRATORY FAILURE; may be considered as bridge in: stable patients with nocturnal hypoventilation, mild hypercapnia without distress, secretion clearance ability preserved, no aspiration risk, patient can protect airway; AVOID NIV if: Bulbar dysfunction (aspiration risk), unable to clear secretions, severe hypercapnia (PaCO2 >60), acidosis, rapid decline, altered mental status	-	NIV (BiPAP) has lower threshold for failure in neuromuscular disease than COPD/CHF; bulbar weakness increases aspiration risk; low threshold for intubation; useful for chronic nocturnal hypoventilation	STAT	STAT	ROUTINE	STAT
Supplemental oxygen	-	-	96% :: - :: - :: Use CAUTIOUSLY: Oxygen can mask hypoventilation (hypercapnia develops before desaturation); may eliminate hypoxic drive (though less relevant in NMD than COPD); titrate to SpO2 92-96%; If hypoxemic + hypercapnic: This indicates severe failure — intubate, do NOT rely on oxygen alone	-	Hypoxemia is a late finding in pure neuromuscular hypoventilation; if hypoxemic, consider aspiration, atelectasis, or imminent failure	STAT	STAT	-	STAT
Secretion management	-	-	N/A :: - :: PRN :: Weak cough = poor secretion clearance; Techniques: Assisted cough (abdominal thrust during cough); mechanical insufflation-exsufflation (CoughAssist) — pressures +40/-40 cm H2O; aggressive pulmonary toilet; chest physiotherapy; suction PRN; If unable to clear secretions: Intubate	-	Aspiration pneumonia is leading cause of death in chronic NMD; weak cough (MEP <40) = high risk; mechanical cough assist is underutilized and highly effective	STAT	STAT	-	STAT
Stop/avoid precipitating medications	IV	-	N/A :: IV :: N/A :: MG crisis precipitants (AVOID): Aminoglycosides (gentamicin, tobramycin), fluoroquinolones (ciprofloxacin, levofloxacin — less risky but still caution), macrolides (azithromycin, erythromycin), beta-blockers, magnesium (IV), neuromuscular blockers, D-penicillamine, interferon-alpha, checkpoint inhibitors (nivolumab, pembrolizumab); Full list in Appendix	-	Many medications can worsen neuromuscular transmission; careful medication review essential; see comprehensive list in appendix	STAT	STAT	ROUTINE	STAT
DVT prophylaxis	SC	-	40 mg :: SC :: daily :: SCDs immediately; pharmacologic prophylaxis (enoxaparin 40 mg SQ daily) once stable; immobile patients at very high VTE risk	-	High VTE risk in paralyzed/weak patients; balance with IVIG timing (hold anticoagulation during IVIG infusion in some protocols)	STAT	STAT	-	STAT
Aspiration precautions	-	-	N/A :: - :: once :: HOB elevated 30-45°; NPO if significant bulbar weakness; speech-language pathology evaluation; modified diet or enteral feeding if prolonged weakness	-	Aspiration pneumonia is major complication; bulbar weakness (dysphagia, weak cough, voice changes) = high risk	STAT	STAT	ROUTINE	STAT

3B. Disease-Specific Treatment

MYASTHENIA GRAVIS CRISIS

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
IVIG (Intravenous Immunoglobulin) (CPT 96365)	IV	-	2 g/kg :: - :: daily x 5 days :: First-line for MG crisis (with PLEX): 2 g/kg total divided over 2-5 days (400 mg/kg/day x 5 days OR 1 g/kg/day x 2 days); Onset: 2-5 days; Duration: 3-6 weeks; Pre-treatment: Check IgA (IgA deficiency = anaphylaxis risk); renal function; volume status	-	Efficacy equivalent to PLEX (RCTs); easier logistics than PLEX; side effects: headache (aseptic meningitis), renal failure (sucrose-containing products), thrombosis, hemolysis; slower onset than PLEX	-	STAT	-	STAT
Plasma exchange (PLEX) (CPT 36514)	-	-	N/A :: - :: once :: First-line for MG crisis (with IVIG): 5-7 exchanges over 10-14 days (1-1.5 plasma volumes per exchange; typically 3-4 L); Onset: Faster than IVIG (improvement may begin after 2-3 exchanges); requires large-bore central venous access; Caution: Hypotension, citrate toxicity (hypocalcemia), infection	-	May work faster than IVIG; useful if rapid response needed; RCT showed PLEX and IVIG equivalent in MG exacerbation; PLEX preferred if IVIG contraindicated (IgA deficiency, renal failure)	-	STAT	-	STAT
HOLD pyridostigmine (cholinesterase inhibitors)	-	-	N/A :: - :: per protocol :: In intubated MG crisis patients: STOP pyridostigmine while intubated; excessive secretions worsen pulmonary toilet; cannot distinguish myasthenic from cholinergic crisis if on pyridostigmine; Resume cautiously when extubation nearing	-	Pyridostigmine increases secretions; in intubated patient, secretions worsen; hold until preparing for extubation; some restart at lower dose (30 mg q6h) and titrate	STAT	STAT	-	STAT
Corticosteroids (delayed initiation)	IV	-	10-20 mg :: IV :: daily :: CAUTION: Steroids can cause TRANSIENT WORSENING in MG (up to 50% of patients); In crisis: Start AFTER IVIG/PLEX initiated and patient stabilizing (days 3-5 or later); do NOT start steroids as initial therapy in crisis; Protocol: Prednisone 10-20 mg daily, increase by 10 mg every 3-5 days to 1 mg/kg/day (max 60-80 mg); OR IV methylprednisolone 1g daily x 3-5 days then oral	-	Steroids are maintenance therapy but can worsen MG acutely ("steroid dip"); always start with IVIG or PLEX first in crisis; steroid-sparing agents (azathioprine, mycophenolate) for long-term	-	URGENT	ROUTINE	URGENT
Treat precipitant	-	-	N/A :: - :: per protocol :: Infection: Most common trigger; treat aggressively but AVOID contraindicated antibiotics (see list); Medication-induced: Stop offending drug; Surgery/anesthesia: Stress can trigger crisis; Tapering immunosuppression: Restart or increase	-	30-40% of MG crises have identifiable trigger; treating trigger may hasten recovery	STAT	STAT	-	STAT

GUILLAIN-BARRÉ SYNDROME (GBS)

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
IVIG (CPT 96365)	-	-	2 g/kg :: - :: daily x 5 days :: First-line for GBS: 2 g/kg total over 5 days (400 mg/kg/day x 5 days); start within 2-4 weeks of symptom onset for best efficacy; Efficacy: Equivalent to PLEX; faster recovery; fewer complications; Onset: Days to 1-2 weeks	-	RCTs show IVIG = PLEX; IVIG preferred due to availability and easier administration; start as soon as diagnosis confirmed (or highly likely); do NOT delay for CSF/EMG confirmation	-	STAT	-	STAT
Plasma exchange (PLEX) (CPT 36514)	-	-	200-250 mL/kg :: - :: - :: Alternative to IVIG: 5 exchanges over 1-2 weeks (200-250 mL/kg total); start within 2-4 weeks of onset; Consider PLEX if: IVIG contraindicated; IVIG failure; severe/refractory	-	PLEX and IVIG equivalent; do NOT combine (no added benefit, more complications); PLEX if renal failure (IVIG risk)	-	STAT	-	STAT
Corticosteroids — NOT effective in GBS	-	-	N/A :: - :: per protocol :: Do NOT use steroids for GBS; no benefit; may cause harm	-	Multiple RCTs: steroids do NOT improve GBS outcomes; may delay recovery	-	-	-	-
Autonomic monitoring	-	-	70% :: - :: - :: GBS has significant autonomic dysfunction (up to 70%): Cardiac monitoring (arrhythmias, heart block); BP monitoring (labile — hypertension and hypotension); ileus; urinary retention; treat arrhythmias; short-acting antihypertensives (avoid long-acting due to swings); pacing if bradycardia	-	Autonomic death is second leading cause of GBS mortality after respiratory failure; close cardiac monitoring; avoid medications that worsen autonomic dysfunction	-	STAT	-	STAT
Pain management	PO	-	300 mg :: PO :: TID :: Pain in GBS is common (60-90%) and often severe; neuropathic pain; back pain; radicular pain; Treatment: Gabapentin 300 mg TID → titrate; pregabalin; opioids PRN; AVOID NSAIDs if renal concerns	-	Pain can be as debilitating as weakness; multimodal approach; gabapentinoids first-line	-	STAT	ROUTINE	STAT

ALS / MOTOR NEURON DISEASE

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Goals of care discussion	-	-	N/A :: - :: once :: CRITICAL: ALS is progressive and fatal; respiratory failure is end-stage; discuss intubation, tracheostomy, long-term mechanical ventilation BEFORE crisis; many ALS patients choose comfort care / no intubation; Advance directive should be documented	-	Intubation in ALS often leads to chronic ventilator dependence (cannot wean); tracheostomy and home ventilation is option for some but significantly impacts QoL; respect patient autonomy	-	URGENT	ROUTINE	URGENT
Non-invasive ventilation (NIV)	-	-	50% :: - :: - :: Standard of care for ALS respiratory insufficiency: Start NIV when FVC <50% predicted or symptoms of nocturnal hypoventilation; prolongs survival (median 7-11 months) and improves QoL; Settings: BiPAP S/T mode; IPAP 10-20, EPAP 4-6; titrate to comfort; initially nocturnal → extended daytime use as disease progresses	-	Cochrane review: NIV improves survival and QoL in ALS (especially with limb-onset); bulbar patients benefit less but still benefit; no evidence for invasive ventilation superiority over NIV with experienced teams	-	URGENT	ROUTINE	URGENT
Mechanical insufflation-exsufflation (CoughAssist)	-	-	270 L/min :: - :: daily :: All ALS patients with weak cough (PCF <270 L/min or MEP <60); reduces respiratory infections; can be used with NIV; Settings: +40/-40 cm H2O; 4-5 cycles; several times daily	-	Improves secretion clearance; reduces pneumonia; can prolong NIV effectiveness; underutilized	-	URGENT	ROUTINE	URGENT
Riluzole	PO	-	50 mg :: PO :: BID :: 50 mg PO BID; modestly prolongs survival (~2-3 months); neuroprotective; continue unless intolerant	-	Only FDA-approved disease-modifying drug for ALS with survival benefit (though modest); continue through respiratory failure unless goals of care dictate otherwise	-	ROUTINE	ROUTINE	-
Edaravone (Radicava)	IV	-	N/A :: IV :: continuous :: IV infusion or oral formulation; may slow functional decline; expensive; used in early ALS	-	Recent approval; modest benefit in selected patients; often continued if started	-	-	ROUTINE	-
Symptomatic treatment	-	-	N/A :: - :: per protocol :: Sialorrhea (glycopyrrolate, atropine drops, botulinum toxin to salivary glands); thick secretions (guaifenesin, N-acetylcysteine, hydration); pseudobulbar affect (dextromethorphan/quinidine); spasticity (baclofen, tizanidine); pain; depression	-	Palliative symptom management is cornerstone of ALS care; multidisciplinary team essential	-	ROUTINE	ROUTINE	STAT
Comfort-focused care / Palliative care	IV	-	2-5 mg :: IV :: PRN :: If patient declines intubation or chronic mechanical ventilation; opioids for dyspnea (morphine 2-5 mg IV/SQ q2-4h PRN — does NOT hasten death and relieves suffering); anxiolytics (lorazepam); comfort measures; hospice referral	-	Dyspnea is the most distressing symptom at end of life; opioids are safe and effective; do not withhold for fear of "hastening death"	-	URGENT	ROUTINE	URGENT

MUSCULAR DYSTROPHY / MYOPATHY

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Treat underlying cause (if treatable)	-	-	1 mg/kg :: - :: - :: Inflammatory myopathy: Corticosteroids (prednisone 1 mg/kg/day) + steroid-sparing agent (methotrexate, azathioprine, IVIG for dermatomyositis); Hypothyroid myopathy: Thyroid replacement; Drug-induced myopathy (statins): Stop drug; Metabolic myopathy: Specific treatment (enzyme replacement for Pompe disease)	-	Many myopathies are treatable; identify and treat cause; inflammatory myopathies are steroid-responsive	-	STAT	ROUTINE	STAT
Nocturnal NIV	-	-	50% :: - :: - :: Chronic respiratory insufficiency in muscular dystrophy (DMD, BMD, LGMD, myotonic dystrophy); start when FVC <50%, symptoms, or nocturnal hypoventilation on PSG; prolongs survival in DMD	-	NIV is standard of care for chronic respiratory failure in MD; delays tracheostomy; improves survival and QoL	-	URGENT	ROUTINE	URGENT
CoughAssist / Secretion management	-	-	N/A :: - :: per protocol :: Same as ALS; weak cough universal in advanced MD; prevents pneumonia	-	Critical for preventing respiratory infections	-	URGENT	ROUTINE	URGENT
Cardiac monitoring (DMD, BMD, LGMD2I, myotonic DM)	-	-	N/A :: - :: per protocol :: Cardiomyopathy is common and can cause death; annual echocardiogram; ACE inhibitors / beta-blockers for cardiomyopathy; antiarrhythmics / pacemaker / ICD as indicated	-	Cardiac disease is leading cause of death in some muscular dystrophies; proactive cardiac management essential	-	STAT	ROUTINE	STAT
Avoid succinylcholine	-	-	N/A :: - :: N/A :: Absolute contraindication in muscular dystrophy and most myopathies: Hyperkalemic cardiac arrest; use rocuronium (with sugammadex available for reversal)	-	Succinylcholine causes massive K+ release from dystrophic muscle; fatal hyperkalemia	STAT	STAT	-	STAT

3C. Ventilator Management and Weaning

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Initial ventilator settings	-	-	6-8 mL/kg :: - :: - :: Mode: Volume-controlled (AC/VC) or Pressure-support (PS) during weaning; Tidal volume: 6-8 mL/kg IBW (lung-protective); Rate: 12-16 to achieve adequate minute ventilation; PEEP: 5 (higher if atelectasis or hypoxemia); FiO2: Titrate to SpO2 92-96%; I:E ratio: 1:2 or 1:3; avoid breath-stacking	-	NMD patients generally have healthy lungs; lung-protective ventilation still applies; goal is to support ventilation while disease-specific treatment works	-	STAT	-	STAT
Weaning from mechanical ventilation	-	-	15 mL/kg :: - :: - :: NMD weaning is often prolonged: Disease-specific treatment must take effect (MG: IVIG/PLEX effect in 3-7 days; GBS: weeks); Weaning trial criteria: FVC >15 mL/kg; NIF < -25 cm H2O; adequate cough; secretions manageable; underlying disease improving; SBT (spontaneous breathing trial): T-piece or low PS (5-8 cm H2O) x 30-120 min; assess for fatigue, tachypnea, hypercapnia	-	Premature extubation leads to re-intubation; NMD patients may need longer ventilation than other ICU patients; patience; daily SBT when criteria met	-	ROUTINE	-	STAT
Extubation criteria	-	-	15-20 mL/kg :: - :: - :: Pass SBT; FVC >15-20 mL/kg AND improving trajectory; NIF < -25 to -30 cm H2O; effective cough (able to clear secretions); alert and cooperative; bulbar function adequate (can swallow); no heavy sedation; consider cuff leak test	-	Higher threshold for extubation in NMD than general ICU patients; failed extubation is dangerous	-	-	-	STAT
Tracheostomy (if prolonged ventilation anticipated)	-	-	N/A :: - :: once :: Consider if: Unable to wean after 2-3 weeks of optimal disease-specific treatment; ALS with decision for long-term ventilation; severe GBS; Timing: No firm consensus; typically discuss at 10-14 days if no progress; earlier in conditions with known prolonged course	-	Tracheostomy allows for weaning, reduces sedation needs, allows speech (with speaking valve), but has complications and care burden; goals of care discussion essential	-	ROUTINE	-	ROUTINE
Post-extubation monitoring	-	-	N/A :: - :: per protocol :: Close monitoring for 24-48h; serial FVC/NIF; watch for fatigue, stridor; have reintubation equipment ready; consider prophylactic NIV post-extubation in borderline cases	-	Re-intubation rates higher in NMD; close monitoring; low threshold for NIV support post-extubation	-	-	-	STAT

3D. Medications to AVOID in Neuromuscular Disease

Medication Class	Examples	Risk	Safer Alternative
Aminoglycosides	Gentamicin, tobramycin, amikacin, streptomycin	Neuromuscular blockade; worsen MG, GBS	Beta-lactams, fluoroquinolones (with caution)
Fluoroquinolones	Ciprofloxacin, levofloxacin, moxifloxacin	Associated with MG exacerbation; FDA warning	Beta-lactams (cephalosporins, penicillins)
Macrolides	Azithromycin, erythromycin, clarithromycin	May worsen MG	Beta-lactams
Beta-blockers	Propranolol, metoprolol, etc.	Worsen MG; use with caution	Cardioselective (metoprolol) if essential
Magnesium (IV high-dose)	MgSO4	Blocks neuromuscular transmission	Avoid unless life-threatening (e.g., eclampsia, torsades)
Neuromuscular blockers	Succinylcholine, rocuronium, vecuronium	Succinylcholine: hyperkalemia in myopathies; all NMBs: prolonged weakness in MG	Avoid if possible; if needed: rocuronium (reduced dose in MG) + sugammadex
Calcium channel blockers	Verapamil, diltiazem (less with dihydropyridines)	May worsen neuromuscular transmission	Dihydropyridines (amlodipine) if needed
Botulinum toxin	Botox, Dysport	Can worsen MG	Avoid in MG
D-Penicillamine	Cuprimine	Can induce MG (autoimmune)	Alternative for Wilson disease
Checkpoint inhibitors	Nivolumab, pembrolizumab, ipilimumab	Can trigger or worsen MG, myositis, GBS-like syndromes	Oncology risk-benefit discussion
Statins	Atorvastatin, simvastatin, etc.	Can cause myopathy; worsen pre-existing myopathy	Discontinue if causing myopathy
Corticosteroids (acutely in MG)	Prednisone, methylprednisolone	Can cause transient worsening of MG ("steroid dip")	Start AFTER IVIG/PLEX in MG crisis

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4. OTHER RECOMMENDATIONS

4A. Essential

Recommendation	ED	HOSP	OPD	ICU	Details
Neurology consultation — EMERGENT	STAT	STAT	ROUTINE	STAT	All patients with suspected neuromuscular respiratory failure; confirm diagnosis; guide disease-specific treatment (IVIG, PLEX, steroids)
Pulmonology / Critical Care consultation	STAT	STAT	-	STAT	Respiratory failure management; ventilator management; weaning protocols; NIV expertise
Serial FVC and NIF monitoring	STAT	STAT	-	STAT	Most important monitoring parameter; q4-6h initially; q1-2h if declining; trends are more important than absolute values; decline >30% is concerning
ICU admission	-	STAT	-	STAT	All patients with impending or established respiratory failure; FVC <25 mL/kg; declining trajectory; need for close monitoring
Speech-language pathology	-	URGENT	ROUTINE	URGENT	Dysphagia evaluation; aspiration risk assessment; safe diet recommendations; NPO if severe bulbar weakness
Medication review	STAT	STAT	ROUTINE	STAT	Review ALL medications for neuromuscular-impairing drugs; stop or substitute offending agents; see comprehensive list above
Goals of care discussion	-	URGENT	ROUTINE	URGENT	Especially important in ALS and progressive muscular dystrophies; discuss intubation, tracheostomy, long-term ventilation preferences EARLY
DVT prophylaxis	STAT	STAT	-	STAT	SCDs; pharmacologic prophylaxis (enoxaparin); immobile patients at very high risk

4B. Extended

Recommendation	ED	HOSP	OPD	ICU	Details
Respiratory therapy	-	STAT	ROUTINE	STAT	CoughAssist; chest physiotherapy; secretion management; NIV setup and titration
Physical therapy	-	URGENT	ROUTINE	URGENT	Early mobilization when stable; prevent contractures; maintain function; ROM exercises
Occupational therapy	-	ROUTINE	ROUTINE	ROUTINE	ADL assessment; adaptive equipment; hand function preservation
Nutrition / Dietitian	-	ROUTINE	ROUTINE	ROUTINE	Caloric needs (often increased in NMD); dysphagia diet; enteral feeding if prolonged weakness; avoid overfeeding (increases CO2 production)
Social work	-	ROUTINE	ROUTINE	ROUTINE	Family support; discharge planning; long-term care needs; financial resources
Palliative care	-	ROUTINE	ROUTINE	ROUTINE	Symptom management; goals of care facilitation; especially important in ALS and progressive disorders
Cardiology	-	ROUTINE	ROUTINE	ROUTINE	If cardiomyopathy (DMD, LGMD, myotonic dystrophy); autonomic dysfunction (GBS)
Psychiatry / Psychology	-	ROUTINE	ROUTINE	-	Depression, anxiety common; ICU delirium; adjustment to chronic illness; ALS psychological support

4C. Atypical/Refractory

Recommendation	ED	HOSP	OPD	ICU	Details
Repeat IVIG or PLEX	-	URGENT	ROUTINE	URGENT	If inadequate response to first course (MG, GBS); may need 2nd course of IVIG or PLEX; combination (IVIG + PLEX) not recommended (IVIG washed out by PLEX)
Rituximab (MG)	-	-	ROUTINE	-	Refractory MG; anti-CD20; especially useful in MuSK MG; onset weeks to months
Eculizumab (MG)	-	-	ROUTINE	-	Complement inhibitor; FDA-approved for refractory generalized AChR-positive MG; reduces exacerbations
Thymectomy (MG)	-	-	ROUTINE	-	Elective; for AChR-positive MG (benefit even without thymoma per MGTX trial); not in crisis; schedule when stable
Tracheostomy and long-term ventilation	-	ROUTINE	ROUTINE	ROUTINE	If unable to wean after 2-4 weeks; ALS patients who choose long-term ventilation; chronic NMD with respiratory failure
Home mechanical ventilation	-	-	ROUTINE	-	Transition from hospital/trach to home ventilation; requires extensive training; home nursing; sleep medicine / pulmonology follow-up
Diaphragm pacing	-	-	EXT	-	For high cervical spinal cord injury; some ALS patients; investigational in many settings

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═══════════════════════════════════════════════════════════════ SECTION B: SUPPORTING INFORMATION ═══════════════════════════════════════════════════════════════

5. DIFFERENTIAL DIAGNOSIS

Causes of Neuromuscular Respiratory Failure

Category	Etiologies	Key Distinguishing Features
Neuromuscular junction	Myasthenia gravis; Lambert-Eaton myasthenic syndrome (LEMS); botulism; organophosphate poisoning	MG: fatigable weakness, ptosis, diplopia, AChR Ab; LEMS: proximal weakness, autonomic symptoms, improves with repetition, anti-VGCC; Botulism: descending paralysis, dilated pupils, recent exposure; OP poisoning: miosis, salivation, bradycardia, cholinergic crisis
Peripheral nerve	Guillain-Barré syndrome; critical illness polyneuropathy (CIP); phrenic nerve injury (cardiac surgery); Charcot-Marie-Tooth (rare)	GBS: ascending weakness, areflexia, post-infectious, elevated CSF protein; CIP: ICU patient, sepsis, prolonged weakness; Phrenic injury: post-cardiac surgery, unilateral diaphragm paralysis
Anterior horn cell	ALS (amyotrophic lateral sclerosis); spinal muscular atrophy; poliomyelitis (rare)	ALS: UMN + LMN signs, progressive, fasciculations, no sensory involvement; SMA: childhood onset, proximal weakness
Muscle	Muscular dystrophies (DMD, BMD, LGMD, myotonic, FSHD); inflammatory myopathies (dermatomyositis, polymyositis, inclusion body myositis); critical illness myopathy; metabolic myopathies	DMD: young males, elevated CK, cardiac involvement; Myotonic: myotonia, cataracts, cardiac; Inflammatory: elevated CK, rash (DM), proximal weakness; CIM: ICU patient, prolonged steroids/NMB, flaccid weakness
Respiratory muscle specific	Bilateral diaphragm paralysis; diaphragmatic fatigue; isolated phrenic neuropathy	Orthopnea; paradoxical breathing; supine FVC drop >20%; fluoroscopy: paradoxical motion

Myasthenic Crisis vs. Cholinergic Crisis

Feature	Myasthenic Crisis	Cholinergic Crisis
Cause	Worsening MG; undertreated; triggered by infection, medication, stress	Excessive cholinesterase inhibitor (pyridostigmine overdose)
Symptoms	Weakness, respiratory failure, ptosis, diplopia, dysphagia	Weakness PLUS: salivation, lacrimation, urination, defecation, GI upset, emesis (SLUDGE); miosis; bradycardia; fasciculations; bronchospasm
Pupils	Normal	Miotic (constricted)
Secretions	May be increased (from weak swallow)	Profusely increased
Response to edrophonium	Improves	Worsens
Treatment	IVIG/PLEX; hold pyridostigmine; supportive	Stop pyridostigmine; atropine for muscarinic symptoms; supportive
Clinical clue	Usually distinguishable clinically; cholinergic crisis is rare and usually obvious	Excessive secretions + diarrhea + small pupils + bradycardia

Red Flags for Imminent Respiratory Failure

Red Flag	Action
FVC <20 mL/kg or declining >30% from baseline	Prepare for intubation; ICU transfer; increase monitoring frequency
NIF > -30 cm H2O (less negative)	Prepare for intubation
Rising PaCO2 (especially with respiratory acidosis)	Intubate — this is a LATE sign
Use of accessory muscles; tripoding	Impending failure
Tachypnea >30 with shallow breathing	Compensating; fatigue imminent
Paradoxical breathing (abdomen moves IN with inspiration)	Diaphragm fatigue/paralysis; intubate
Inability to count to 20 in one breath	Simple bedside test; very weak if cannot count to 10
Weak cough; inability to clear secretions	Aspiration risk; may need intubation for airway protection
Orthopnea (cannot lie flat)	Diaphragm weakness; FVC drops supine
Altered mental status	Hypercapnia; severe — intubate immediately

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6. MONITORING PARAMETERS

Acute Phase Monitoring (ICU)

Parameter	Frequency	Target	Action if Abnormal
FVC (forced vital capacity)	q4-6h initially; q1-2h if declining	>20 mL/kg safe; <15-20 mL/kg = intubation threshold	Declining trend or <15-20: prepare for intubation
NIF (negative inspiratory force)	q4-6h initially	< -30 cm H2O safe; > -20 to -25 = intubation threshold	Worsening (less negative): prepare for intubation
ABG	q6-8h or PRN; with any clinical change	PaCO2 35-45; pH 7.35-7.45	Rising PaCO2 or acidosis: intubate
SpO2	Continuous	>92%	Desaturation: assess for aspiration, atelectasis, failure; supplement O2 cautiously
Respiratory rate	Continuous	12-20	Tachypnea >30 with shallow breathing suggests fatigue
Neurologic exam (strength, bulbar function)	q4-8h	Stable or improving	Worsening weakness: reassess treatment; anticipate respiratory decline
Autonomic function (GBS)	Continuous (telemetry); q4h BP checks	Stable HR 60-100; BP 90-140 systolic	Arrhythmia: treat; wide BP swings: short-acting agents; bradycardia: atropine/pacing
Secretion assessment	q2-4h	Manageable; patient can cough	Excessive secretions + weak cough: aggressive pulmonary toilet; consider intubation

Weaning Phase Monitoring

Parameter	Frequency	Target	Action if Abnormal
Daily SBT (spontaneous breathing trial)	Daily when criteria met	Pass SBT without distress	Fail: resume full support; reassess next day
FVC (pre-extubation)	Daily; before extubation	>15-20 mL/kg AND improving	Do not extubate if still declining
NIF (pre-extubation)	Daily	< -25 to -30 cm H2O	Weak NIF: high re-intubation risk
Cough strength / PCF	Daily	PCF >160 L/min for successful extubation; MEP >40	Weak cough: high aspiration risk; continue CoughAssist; delay extubation
Bulbar function	Daily	Able to swallow saliva; protect airway	Severe bulbar weakness: aspiration risk; consider tracheostomy

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7. DISPOSITION CRITERIA

Admission Criteria

Level of Care	Criteria
ICU	FVC <25 mL/kg or declining; NIF > -40 cm H2O; any respiratory distress; autonomic instability (GBS); need for frequent monitoring (q1-4h); NIV initiation for acute failure; intubation anticipated or performed
Step-down / Intermediate	Stable but requires monitoring q4-6h; improving trajectory; stable on NIV; post-extubation observation
General floor	Stable respiratory function; FVC >30 mL/kg and stable; for diagnostic workup of mild exacerbation; initiation of immunotherapy without respiratory compromise

Discharge Criteria

Criterion	Details
Respiratory stability	FVC >25-30 mL/kg and stable/improving; off supplemental O2 or at baseline; able to clear secretions
Off mechanical ventilation (or stable on chronic NIV)	Extubated and stable x 24-48h; or established on home NIV with stable settings
Disease-specific treatment initiated and tolerated	IVIG/PLEX completed; oral immunosuppression started (MG); able to continue treatment outpatient
Adequate nutrition	Tolerating oral diet or enteral feeding established; swallowing safe per SLP
Functional mobility	PT/OT clearance; able to perform ADLs or adequate support
Follow-up arranged	Neurology (1-2 weeks); pulmonology (if chronic respiratory issues); PCP; cardiology (if applicable)
Education	Disease education; medication instructions; when to return to ED (worsening weakness, dyspnea, dysphagia); MedicAlert bracelet for MG; medication list (avoid contraindicated drugs)
Equipment	CoughAssist, suction machine, NIV (if prescribed); home nursing if tracheostomy/ventilator

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8. EVIDENCE & REFERENCES

Key Guidelines

Guideline	Source	Year	Key Recommendation
Myasthenia Gravis Treatment Guidelines	AAN / MGFA	2016/2021	IVIG and PLEX are equivalent for MG exacerbation; thymectomy benefits AChR+ MG; corticosteroid caution (steroid dip); rituximab and eculizumab for refractory
Guillain-Barré Syndrome Guidelines	AAN	2012	IVIG or PLEX within 4 weeks of onset; equivalent efficacy; do NOT combine; steroids NOT effective
ALS Practice Parameters	AAN	2009/Updates	NIV prolongs survival; CoughAssist; multidisciplinary care; riluzole modestly prolongs survival
Respiratory Management in NMD	ATS	2004/Updates	NIV for chronic respiratory failure; FVC <50% threshold; CoughAssist; monitoring parameters

Landmark Studies

Study	Finding	Impact
Plasma Exchange/Sandoglobulin GBS Trial (1997)	IVIG = PLEX for GBS; combination not better	Either IVIG or PLEX; no combination
MG Thymectomy Trial (MGTX, 2016)	Thymectomy + prednisone > prednisone alone for AChR+ MG (even without thymoma); improved outcomes at 3 years	Thymectomy recommended for generalized AChR+ MG
Radunovic et al. NIV in ALS (2017 Cochrane)	NIV prolongs survival in ALS (7-11 months) and improves QoL	NIV is standard of care for ALS respiratory insufficiency
Lawn et al. Respiratory Failure in GBS (2001)	FVC <20 mL/kg or NIF > -30 cm H2O predicted need for intubation; "20/30/40 rule"	Established monitoring thresholds for MG crisis
REGAIN Trial (Eculizumab in MG, 2017)	Eculizumab reduced exacerbations in refractory generalized MG	FDA approval of eculizumab for refractory AChR+ MG

The "20/30/40" Rule

Parameter	Threshold	Interpretation
FVC	<20 mL/kg	Impending respiratory failure; consider intubation
NIF (MIP)	> -30 cm H2O (less negative)	Weak inspiratory muscles; impending failure
MEP	<40 cm H2O	Weak cough; unable to clear secretions; aspiration risk

Clinical Pearl: These values suggest impending failure and need for intubation. Do NOT wait for PaCO2 elevation — this is a LATE sign. Trend is more important than absolute values.

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APPENDICES

Appendix A: Medications to AVOID in Myasthenia Gravis (Comprehensive)

ABSOLUTE CONTRAINDICATION / HIGH RISK: - Aminoglycosides (gentamicin, tobramycin, amikacin, streptomycin, neomycin) - Botulinum toxin (Botox) - D-Penicillamine (can induce MG) - Magnesium (IV high-dose) - Neuromuscular blocking agents (use reduced dose if essential; avoid succinylcholine) - Telithromycin (Ketek) - Quinine / Quinidine - Procainamide

USE WITH CAUTION / MODERATE RISK: - Fluoroquinolones (ciprofloxacin, levofloxacin, moxifloxacin) — FDA warning - Macrolides (azithromycin, erythromycin, clarithromycin) - Beta-blockers (especially non-selective; propranolol > metoprolol) - Calcium channel blockers (verapamil, diltiazem) - Lithium - Phenytoin - Chloroquine / Hydroxychloroquine - Interferon-alpha - Checkpoint inhibitors (nivolumab, pembrolizumab, ipilimumab) — can trigger or worsen MG - Statins (rare exacerbation) - Iodinated contrast (rare) - Corticosteroids (transient worsening — "steroid dip")

GENERALLY SAFE: - Beta-lactams (penicillins, cephalosporins, carbapenems) - Vancomycin - TMP-SMX - Metronidazole - Doxycycline (though tetracycline class has theoretical risk — doxycycline generally safe) - Acetaminophen - NSAIDs - Opioids - Dihydropyridine calcium channel blockers (amlodipine) - ACE inhibitors - Most anticonvulsants (levetiracetam, valproate)

Appendix B: RSI Considerations in Neuromuscular Disease

Agent	Consideration
Succinylcholine	AVOID in myopathies/muscular dystrophies — causes massive hyperkalemia and cardiac arrest; AVOID in denervated patients (ALS, GBS) — hyperkalemia; MG patients: Relative resistance — may need higher dose (but risk of prolonged effect) → generally avoid
Rocuronium	Preferred NMB in NMD; MG patients: Increased sensitivity — use 50% of usual dose (0.3-0.5 mg/kg instead of 0.6-1.2 mg/kg); have sugammadex available for reversal
Sugammadex	Reverses rocuronium; useful for failed intubation or when rapid reversal needed; standard dose 2-4 mg/kg; immediate reversal 16 mg/kg
Etomidate	Safe; no effect on neuromuscular transmission
Propofol	Safe; no NM effects
Ketamine	Safe from NM perspective; avoid in intracranial pathology
Fentanyl	Safe; useful for blunting response
Lidocaine	Safe; may reduce airway reactivity

Appendix C: Pulmonary Function Thresholds in Neuromuscular Disease

Parameter	Normal	Abnormal	Critical / Intubation Threshold
FVC	>80% predicted; >40-50 mL/kg	<50% predicted; <25-30 mL/kg	<15-20 mL/kg
Supine FVC	<10% drop from sitting	10-20% drop	>25% drop (diaphragm weakness)
NIF (MIP)	< -80 cm H2O (more negative)	> -60 cm H2O	> -20 to -30 cm H2O
MEP	>80 cm H2O	<60 cm H2O	<40 cm H2O (weak cough)
Peak cough flow (PCF)	>360 L/min	<270 L/min	<160 L/min (inadequate secretion clearance)
PaCO2	35-45 mmHg	>45 mmHg (hypoventilation)	Rising PaCO2; >50-55 mmHg
SpO2	>95% on room air	<92% on room air	Declining despite O2 (assess for aspiration, PE)

Appendix D: Neuromuscular Respiratory Failure Decision Algorithm

SUSPECTED NEUROMUSCULAR RESPIRATORY FAILURE
                │
    IMMEDIATE ASSESSMENT:
    • ABG (PaCO2, pH)
    • Bedside FVC and NIF
    • Secretion assessment / cough strength
    • Bulbar function (swallow, voice)
    • Vital signs, SpO2
                │
    RESPIRATORY STATUS?
         │
    ┌────┴────────┬───────────────┐
    │             │               │
  STABLE      BORDERLINE       FAILING
(FVC >25,    (FVC 15-25,     (FVC <15-20,
NIF < -40)   NIF -25 to -40) NIF > -20-25,
    │             │            rising PaCO2)
    │             │               │
Floor admission  ICU admission  INTUBATE
Serial q6h      Serial q2-4h   (RSI considerations)
monitoring       monitoring        │
    │             │               │
    │             │         ICU management
    │             │         Disease-specific Rx
    │             │               │
    └─────────────┴───────────────┘
                │
    DISEASE-SPECIFIC TREATMENT:
    • MG crisis → IVIG or PLEX; HOLD pyridostigmine
    • GBS → IVIG or PLEX (NOT both)
    • ALS → NIV; goals of care; palliative
    • Inflammatory myopathy → Corticosteroids + IVIG
    • Critical illness polyneuromyopathy → Supportive; treat sepsis
                │
    WEANING (when disease improving):
    • Daily SBT when FVC >15, NIF <-25
    • Extubate when: FVC >15-20 AND improving, effective cough, bulbar function intact
    • Monitor closely post-extubation

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This template represents the initial build phase (Skill 1) and requires validation through the checker pipeline (Skills 2-6) before clinical deployment.