Critical Care Disorders of the Peripheral Nervous System

(Source: Harrison's Principles of Internal Medicine, 22nd Ed., 2025)

Overview

Critical illness involving PNS disorders arises in two main contexts:

Primary neurologic diseases that require critical care interventions (intubation, mechanical ventilation):
- Acute polyneuropathies - Guillain-Barre syndrome (GBS)
- Neuromuscular junction disorders - myasthenia gravis, botulism
- Primary muscle disorders - polymyositis
Secondary PNS manifestations of systemic critical illness (often multisystem organ failure), collectively termed ICU-acquired weakness (ICUAW)

General Principles: Respiratory Evaluation in PNS Disorders

Regardless of cause, the following must be assessed:

Parameter	Critical Threshold for Intubation
Maximal Inspiratory Force (MIF)	Falls below -25 cmH2O
Vital Capacity (VC)	< 1 L
Bulbar muscle strength	Severe palatal weakness = risk of airway obstruction/aspiration

Key principles:

Arterial blood gases and pulse oximetry are used for monitoring, but intubation should be based on clinical assessment - do NOT wait for O2 saturation drop or CO2 retention
Non-invasive mechanical ventilation may be tried initially in myasthenia gravis but is insufficient in severe bulbar weakness or ventilatory failure with hypercarbia

1. Neuropathy - Critical Illness Polyneuropathy (CIP)

Context: Prolonged critical illness (weeks), sepsis, multisystem organ failure; clinically suspected when patient fails to wean from the ventilator despite improving sepsis.

Clinical features:

Diffuse weakness
Decreased reflexes
Distal sensory loss

Investigations:

Electrophysiology: diffuse, symmetric, distal axonal sensorimotor neuropathy
Pathology: axonal degeneration

Pathophysiology: Exact mechanism unclear; circulating factors (cytokines) associated with sepsis/SIRS are implicated.

Epidemiology: Up to 70% of patients with sepsis syndrome have some degree of neuropathy; far fewer develop severe respiratory muscle weakness.

Management:

Aggressive glycemic control with insulin infusions - reduces risk of CIP
Otherwise supportive; treat underlying illness
Spontaneous recovery is usual but may take weeks to months, requiring prolonged ventilatory support

2. Disorders of Neuromuscular Transmission

A. Botulism

Food-borne: ingesting botulinum toxin from improperly stored food
Wound botulism: anaerobic abscess from Clostridium botulinum (e.g., injection drug use)
Infant botulism: gut-derived Clostridium infection (especially from honey ingestion)
Early signs: diplopia and dysphagia (food-borne form)
Treatment: Mostly supportive; antitoxin early in the course may limit duration of neuromuscular blockade
Notify public health officers urgently to prevent further exposure

B. Myasthenia Gravis (Undiagnosed or Known)

May present as unexplained weakness in ICU patients
Non-invasive ventilation may be trialed but often insufficient with severe bulbar weakness

C. Drug-Induced Neuromuscular Blockade (Most Common NMJ Cause in ICU)

Aminoglycosides, beta-blockers impair NMJ transmission
Nondepolarizing NMBAs (nd-NMBAs): pancuronium, vecuronium, rocuronium, cisatracurium
- Used to facilitate mechanical ventilation
- Prolonged use causes persistent blockade hours to days after discontinuation

Risk factors for prolonged nd-NMBA action:

Female sex
Metabolic acidosis
Renal failure

Key point: Prolonged neuromuscular blockade causes NO permanent PNS damage - full strength restored after drug discontinuation (may take days).

Prevention: Use lowest effective dose; monitor with a peripheral nerve stimulator

3. Critical Illness Myopathy (CIM)

Critically ill patients (especially with sepsis) frequently develop muscle weakness/wasting despite adequate nutrition.

Types:

Type	Mechanism	CK	EMG	Biopsy
Cachectic myopathy	Elevated cortisol/catecholamines/SIRS factors	Normal	Normal	Type II fiber atrophy
Acute necrotizing ICU myopathy	Profound sepsis	Elevated (+ myoglobinuria)	Abnormal (eventually)	Panfascicular necrosis + inflammation
Thick-filament myopathy	Glucocorticoids + nd-NMBA (classic: severe asthmatic)	Variable	Abnormal	Loss of thick (myosin) filaments

Thick-Filament Myopathy (Most Important ICU Myopathy)

Classic scenario: Asthmatic patient requiring high-dose glucocorticoids + nd-NMBAs for ventilation
Can also occur with high-dose glucocorticoids or sepsis alone
Clinically recognized when patient fails to wean despite resolution of the primary pulmonary problem
This is true muscle damage (not just NMJ blockade) - recovery takes weeks to months
Tracheotomy with prolonged ventilatory support may be needed
Prognosis: Generally good if patient survives the critical illness; myopathy invariably improves; some residual weakness possible
Prevention: Avoid nd-NMBAs when possible; use peripheral nerve stimulator to minimize overuse

Acute Rhabdomyolysis

Can occur from alcohol ingestion or compartment syndromes

Summary Comparison Table

Condition	Key Setting	Primary Feature	Recovery
Critical illness polyneuropathy	Sepsis, MOF, prolonged ICU	Axonal neuropathy, failure to wean	Weeks-months
Botulism	Tainted food/wound/infants	Diplopia, dysphagia, descending paralysis	Supportive; antitoxin if early
Prolonged nd-NMBA blockade	ICU drugs (aminoglycosides, NMBAs)	Weakness post-discontinuation	Days; no permanent damage
Cachectic myopathy	Sepsis/SIRS	Type II fiber atrophy, normal CK/EMG	Variable
Thick-filament myopathy	Steroids + nd-NMBAs	Myosin loss, failure to wean	Weeks-months; good prognosis
Acute necrotizing myopathy	Profound sepsis	Rapid weakness, elevated CK	Variable

Harrison's Principles of Internal Medicine, 22nd Ed. (2025), pp. 2394-2395

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