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Does endothelin antagonist hepatocellular pattern injury

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endothelin receptor antagonists AND liver injury

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endothelin receptor antagonist liver injury hepatocellular pattern bosentan prescribing information

Yes. Bosentan, and historically sitaxsentan, can cause a predominantly hepatocellular drug-induced liver injury pattern, reflected by aminotransferase elevation. It is usually dose-related and reversible after stopping, but rare jaundiced and severe hepatitis cases have occurred.
  • Bosentan: aminotransferase elevations are relatively common. Clinically apparent injury may be hepatocellular or mixed. Monitor liver tests, and do not rechallenge after true clinically apparent DILI.
  • Sitaxsentan: associated with idiosyncratic severe hepatocellular hepatitis and acute liver failure, which led to its withdrawal.
  • Ambrisentan and macitentan: much lower apparent hepatotoxicity risk, though caution is still appropriate in significant hepatic impairment.
Katzung notes endothelin-antagonist hepatotoxicity is generally dose-related and reversible, while sitaxsentan has caused idiosyncratic fatal hepatitis - Katzung's Basic and Clinical Pharmacology, 16th ed. The LiverTox class review similarly identifies bosentan and sitaxsentan as the agents clearly linked to clinically apparent acute liver injury.

Treatment of critical illness neuropathy

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critical illness polyneuropathy AND treatment

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critical illness polyneuropathy management early mobilization glycemic control guideline

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https://pmc.ncbi.nlm.nih.gov/articles/PMC10644573/

Critical illness polyneuropathy (CIP) has no specific curative drug treatment. Management is supportive, focuses on reversing precipitating critical illness, preventing further ICU-acquired weakness, and intensive rehabilitation.
  1. Treat the underlying illness
    • Rapid control of sepsis and multiorgan dysfunction.
    • Correct hypoxia, shock, electrolyte abnormalities, and nutritional deficits.
    • Review and minimize potentially contributory therapies where feasible, such as prolonged deep sedation, immobilization, and unnecessary corticosteroids or neuromuscular blockers.
  2. Early, progressive rehabilitation
    • Begin once physiologically stable: passive range-of-motion, bed mobility, sitting, standing, transfer practice, and walking as tolerated.
    • Involve physiotherapy and occupational therapy early.
    • Use a light-sedation approach and daily spontaneous awakening/breathing trials when appropriate to enable participation. Early mobility is the key intervention with the best practical support for improving functional recovery. A recent ICU-acquired weakness review recommends rehabilitation promptly after diagnosis.
  3. Optimize glucose management
    • Avoid significant hyperglycemia, but do not pursue overly tight glucose targets that increase hypoglycemia risk.
    • In most critically ill adults, use standard ICU glycemic targets, commonly 140-180 mg/dL (7.8-10 mmol/L), individualized to context.
  4. Nutritional support
    • Provide adequate calories and protein using ICU nutrition protocols.
    • Avoid both major underfeeding and indiscriminate early overfeeding. Dietitian input is useful, especially during prolonged ventilation and recovery.
  5. Respiratory and complication care
    • CIP may prolong ventilator weaning. Use lung-protective ventilation when indicated, daily weaning assessment, secretion clearance, and respiratory muscle rehabilitation as appropriate.
    • Prevent pressure injury, contractures, venous thromboembolism, aspiration, and falls.
  6. What is not routinely recommended
    • No proven role for IV immunoglobulin, corticosteroids, plasmapheresis, or other disease-specific pharmacologic therapy for CIP itself.
    • Neuromuscular electrical stimulation can be considered in selected immobilized patients, but evidence remains mixed.
Prognosis: recovery often takes weeks to months and is frequently slower or less complete than in critical illness myopathy, especially after severe axonal neuropathy. Follow-up after discharge should include rehabilitation, functional assessment, and screening for persistent weakness, sensory symptoms, and disability.
Textbook support: Miller's Anesthesia, 10th ed., notes that no pharmacologic treatment is established and supports early ICU physical rehabilitation. A management review likewise supports early mobilization, glucose optimization, and nutrition, while finding insufficient evidence for other interventions.

What is the role of steroid

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critical illness polyneuropathy AND corticosteroids

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critical illness polyneuropathy corticosteroids treatment risk factor evidence

Steroids have no therapeutic role in treating critical illness polyneuropathy (CIP). Do not give corticosteroids to reverse CIP.
They can be necessary for the underlying ICU condition, such as refractory septic shock, ARDS in selected settings, adrenal insufficiency, or an acute asthma/COPD exacerbation. In those cases, use them for that indication, at the lowest effective dose and shortest appropriate duration.
Regarding weakness:
  • High-dose or prolonged steroids can contribute to critical illness myopathy (CIM) or acute steroid myopathy, especially when combined with neuromuscular blocking drugs.
  • This is more relevant to myopathy than the axonal neuropathy of CIP, although CIP and CIM commonly coexist.
  • Evidence is mixed on whether steroids independently cause ICU-acquired weakness. They should not automatically be withheld when clearly indicated, but avoid unnecessary exposure and reassess daily.
If steroid-associated myopathy is suspected, taper or stop steroids when clinically safe, avoid concurrent/prolonged neuromuscular blockade if possible, and emphasize rehabilitation and treatment of sepsis/metabolic abnormalities. Adams and Victor's Principles of Neurology, 12th ed., notes that high-dose corticosteroids, especially with neuromuscular blockers, may cause a myosin-deficient critical illness myopathy. A Cochrane review found no demonstrated benefit of corticosteroids for preventing CIP/CIM.
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