Dosing Vitamin C in Critically Ill Patients with Attention to Renal Replacement Therapy

Authors: Patrick M. Honore, Herbert D. Spapen, Paul Marik, Willem Boer, Heleen Oudemans-van Straaten

Source: Honore et al. Ann. Intensive Care (2020) 10:23. DOI: 10.1186/s13613-020-0640-6

Abstract

• Objective: Establish agreement on vitamin C dose adjustments in critically ill patients undergoing renal replacement therapy (RRT).
• Key Findings:
  • High-dose vitamin C improves outcomes in sepsis, burns, trauma.
  • RRT patients have similar vitamin C plasma concentrations as non-RRT critically ill patients.
  • Vitamin C is cleared during RRT, but tubular reabsorption is absent.
  • Suggested dose: 1g twice daily for normal plasma levels; more studies needed.
  • No evidence that high doses cause oxalate stones or pro-oxidant effects.

Rationale for Vitamin C Supplementation

• Functions: Antioxidant, anti-inflammatory, immune-enhancer.
• Benefits: Improves hemodynamics, organ failure, survival.
• Deficiency: Common in critical illness due to low intake, high consumption, reduced recycling.

Considerations on Dosing

• Healthy Intake: ~100 mg/day for 60-100 μmol/L plasma levels.
• Critical Illness:
  • IV administration crucial due to impaired gut function.
  • High doses (2–3 g/day) required to restore normal levels.
  • Supranormal levels (100-200 mg/kg/day) need even higher doses.

Pharmacokinetics

• Normal Kidneys: Filtered and partly reabsorbed; linear dose-concentration relationship.
• RRT: Vitamin C removal depends on RRT dose/duration and oxidative stress. Persistent loss due to lack of reabsorption.

Clinical Studies

• Findings: Lower plasma levels in RRT patients; supplementation needed.
• Dosage: Twice 1g daily may maintain normal levels; more data required for precise guidelines.

Recommendations for RRT

• IV Supplementation: Necessary even if full enteral nutrition is provided.
• Dosing: 1g twice daily recommended; higher for oxidative stress conditions.
• Peritoneal Dialysis: CAPD patients benefit from C and E supplementation.

Safety and Side Effects

• Oxalate Stones: High doses may increase risk, especially in men.
• Prooxidant Effects: Theoretical risk at high doses, but not observed in trials.
• Glucose Readings: High ascorbic acid can interfere.
• G6PD Deficiency: Higher doses (>60g) may cause hemolysis; up to 6g/day is safe.

Conclusions

• Vitamin C crucial in managing oxidative stress, inflammation in critically ill.
• Optimal dosing remains undefined; ongoing RCTs aim to provide clarity.
• 1g twice daily dosing appears necessary for normal plasma levels during RRT.
• More pharmacokinetic and doseresponse studies needed.

Abbreviations

• IV: Intravenous
• RRT: Renal replacement therapy
• CRRT: Continuous renal replacement therapy
• CAPD: Continuous ambulatory peritoneal dialysis
• G6PD: Glucose-6-phosphate dehydrogenase

These notes summarize key points from the narrative review on vitamin C dosing in critically ill patients, with an emphasis on those undergoing RRT. The text explores the rationale, dosage considerations, pharmacokinetics, safety, and future research directions.