Is zinc chloride effective in treating sepsis?

Zinc Chloride in Sepsis

Zinc chloride (or zinc supplementation) should not be routinely used to treat sepsis, as current guidelines recommend against zinc supplementation in septic patients and the most recent high-quality evidence shows no mortality benefit or reduction in ICU length of stay. 1, 2

Guideline Recommendations

The most authoritative guidance comes from the 2020 Surviving Sepsis Campaign pediatric guidelines, which explicitly recommend against using zinc supplementation in children with septic shock and other sepsis-associated organ dysfunction (weak recommendation, very low quality of evidence). 1 While this is a pediatric guideline, it represents the most recent international consensus on zinc use in sepsis, and no adult guidelines recommend zinc supplementation for sepsis treatment. 1

Most Recent High-Quality Evidence

The 2024 single-center retrospective study of 247 mechanically ventilated septic patients found that zinc supplementation at any dose (<15 mg, 15-50 mg, or ≥50 mg) did not reduce mortality rates (19%, 21%, and 22% respectively, p=0.36) or ICU length of stay (p=0.06). 2 This study demonstrated that:

• Higher zinc doses increased serum zinc concentrations in the first week but not thereafter 2
• High-dose zinc supplementation may not be effective during acute sepsis 2
• No clinical benefit was observed despite biochemical correction 2

Pathophysiological Context

While zinc plays important immunological roles, the evidence reveals a complex picture:

• Hypozincemia during sepsis represents an innate immune response where the body redistributes zinc from serum into the liver as a defense mechanism against pathogens 3, 4
• This redistribution may be part of "nutritional immunity" to deprive pathogens of zinc 5, 4
• Persistent low serum zinc is associated with recurrent sepsis and worse outcomes, but this may be a marker of disease severity rather than a treatment target 3

Animal Model Data vs. Clinical Reality

Animal studies show zinc deficiency increases sepsis mortality (90% vs. 30% in zinc-replete mice), and zinc repletion provides protection in zinc-deficient models. 6 However, this protective effect in pre-existing deficiency states has not translated to clinical benefit when zinc is administered during acute sepsis in humans. 2

Clinical Algorithm

For patients with sepsis:

1. Do not routinely supplement zinc as a sepsis treatment 1, 2
2. Consider zinc monitoring only in severely malnourished patients or those on prolonged renal replacement therapy 7
3. If zinc deficiency is documented in critically ill patients, supplementation may be considered as part of overall nutritional support, but not as sepsis-specific therapy 8, 7
4. Focus on evidence-based sepsis management: early antibiotics, source control, fluid resuscitation, and vasopressors as needed 1

Important Caveats

• The 2024 study represents the highest quality recent evidence specifically examining zinc supplementation during active sepsis 2
• Low serum zinc during sepsis may be an adaptive response rather than a deficiency requiring correction 5, 4
• Zinc supplementation differs fundamentally from other micronutrients like selenium, which also lacks evidence for routine use in sepsis 1
• Attempting to "correct" hypozincemia during acute sepsis by supplementation may interfere with the body's innate immune strategy 5, 4