GI Absorption of Oral Drugs in Critically Ill Patients
Gastrointestinal absorption of oral drugs is significantly impaired in critically ill patients due to multiple pathophysiological derangements, making oral administration unreliable and necessitating consideration of alternative routes or dose adjustments. 1, 2
Primary Mechanisms of Impaired Absorption
Critical illness causes several key alterations that reduce oral drug bioavailability:
Decreased gastric motility and delayed gastric emptying occur due to the underlying illness itself, not from neuromuscular blocking agents, leading to unpredictable drug dispersion and absorption 3, 4
Reduced splanchnic blood flow during shock states and vasopressor use decreases intestinal perfusion, directly impairing drug absorption across the intestinal mucosa 2, 5
Altered gastrointestinal pH from stress, medications (particularly acid suppressants), and critical illness changes drug solubility and dissolution, especially affecting pH-dependent absorption 4, 6
Intestinal edema from fluid resuscitation increases the diffusion distance for drugs to reach systemic circulation, reducing bioavailability 1, 2
Impaired intestinal motility from opioids, sedatives, catecholamines, and metabolic derangements further delays drug transit and absorption 3, 4
Evidence of Altered Absorption
The literature consistently demonstrates absorption problems in the critically ill:
A 2023 systematic review found 43 of 58 studies (74%) reported altered drug absorption in ICU patients, with the majority showing reduced bioavailability 1
Gastrointestinal dysfunction inconsistently affects drug dispersion and absorption, meaning bioavailability may be enhanced or reduced unpredictably depending on the specific drug and patient factors 4
First-pass metabolism is altered, microbiome changes occur, and concurrent medications (vasopressors, acid suppressants) further influence absorption 4, 2
Clinical Implications and Management Strategies
Given these absorption barriers, clinicians must adapt their approach:
Prioritize parenteral routes (IV, IM) for critical medications with narrow therapeutic indices such as anticoagulants, antiepileptics, and antimicrobials during the acute phase 3, 7
Consider alternative routes including transdermal (fentanyl patches for analgesia), sublingual (bypasses first-pass metabolism), rectal suppositories, or intraosseous when IV access is unavailable 3, 7
For antimicrobials specifically, use maximum recommended IV dosages initially to ensure adequate tissue penetration, as inadequate therapy strongly correlates with poor outcomes 3
When oral administration is necessary, use liquid formulations over solid dosage forms to improve dispersion, though be aware these may be hyperosmotic or contain sorbitol causing GI disturbances 4
Hold enteral nutrition 1-2 hours before and after medication administration to minimize drug-nutrient interactions and tube occlusion 4, 1
Monitoring Requirements
Because absorption is unpredictable, enhanced monitoring is essential:
Therapeutic drug monitoring for medications with measurable levels (vancomycin, aminoglycosides, antiepileptics, immunosuppressants) 7, 1
Clinical efficacy assessment rather than assuming standard dosing achieves therapeutic effect 7, 4
Watch for signs of malabsorption including treatment failure, subtherapeutic levels, or paradoxically, toxicity if absorption suddenly improves 1, 2
Special Considerations
Renal replacement therapy adds another layer of complexity, causing loss of water-soluble drugs and requiring dose adjustments beyond absorption concerns 3
The hyperdynamic phase of resuscitation may paradoxically increase hepatic and renal clearance, opposing the decreased absorption and creating competing pharmacokinetic effects 2
Enteral nutrition itself does not impair absorption as severely as parenteral nutrition causes hyperglycemia, and the incretin effect from enteral feeding may provide metabolic benefits 3
Common Pitfalls to Avoid
Do not assume standard oral dosing will be effective in critically ill patients—this puts patients at risk for treatment failure 1
Do not attribute gastric dysfunction to neuromuscular blockade—the underlying illness causes GI dysmotility, not the paralytic agents 3
Avoid delayed-release or enteric-coated formulations as the altered GI transit and pH make their absorption even more unpredictable 3
Do not use actual body weight for obese critically ill patients when calculating drug doses; use adjusted body weight methods 3