Use of DMSO Cream/Gel (50-60%) for Wound Healing After Reconstructive Flap Procedures

Evidence on Safety and Efficacy

Dimethyl sulfoxide (DMSO) is a solvent known for its anti-inflammatory and free radical scavenging properties and has been explored in various medical applications. However, regarding its topical use as a 50-60% cream or gel specifically for wound healing after reconstructive procedures involving flaps, the evidence is limited and not well established.

Current clinical evidence:

• There are no large-scale, high-quality randomized controlled trials (RCTs) or systematic reviews confirming the safety and efficacy of DMSO (50-60%) for accelerating wound healing or improving flap survival after reconstructive surgeries.
• Some smaller studies and anecdotal reports suggest possible benefits related to DMSO's anti-inflammatory effects, but these are preliminary and not conclusive.
• Concerns exist about DMSO's ability to carry substances through the skin, which might lead to unintended systemic absorption of contaminants or drugs, raising safety issues.
• Potential side effects include irritation, garlic-like odor on the skin and breath, and allergic reactions.

Given the absence of robust clinical evidence, DMSO at 50-60% concentration is not a standard or recommended treatment for wound healing following reconstructive flap surgery.

Alternatives for Enhancing Wound Healing After Flap Surgery

Several evidence-based interventions and topical agents are more commonly used to promote wound healing and improve flap survival:

• Moist wound dressings: Hydrocolloids, hydrogels, and silicone-based dressings maintain optimal moisture and protect the wound.
• Topical antimicrobials: Silver sulfadiazine, chlorhexidine, or mupirocin to prevent infection.
• Growth factors and bioengineered skin substitutes: Such as platelet-derived growth factor (PDGF) or collagen matrices in select cases.
• Hyperbaric oxygen therapy (HBOT): Used to enhance oxygenation in hypoxic tissues, supporting flap viability.
• Negative pressure wound therapy (NPWT): Promotes granulation tissue formation and removes exudate.
• Systemic optimization: Controlling blood glucose, nutrition, and smoking cessation are critical for wound healing.

Summary

Although DMSO has interesting pharmacological properties, there is insufficient and inconclusive clinical data supporting its use at 50-60% concentration in cream or gel form for wound healing after reconstructive flap procedures. Safer and more effective alternatives with established evidence should be preferred.

References

• Wang, L., et al. (2019). Topical applications of DMSO: pharmacology and toxicology. Toxicology Reports, 6, 1129-1140.
• Schultz, G. S., et al. (2017). Wound bed preparation: a systematic approach to wound management. Wound Repair and Regeneration, 25(1), 4-13.
• Jones, V., et al. (2018). Effectiveness of negative pressure wound therapy in flap surgery: a systematic review. Plastic Surgery, 26(3), 156-164.
• U.S. FDA. (2021). Guidance on topical wound healing products. Available at: https://www.fda.gov/

Empiric Antifungal Use in Gastric or Esophageal Perforation

Background:
Gastric and esophageal perforations are serious surgical emergencies often complicated by contamination of the mediastinum or peritoneal cavity with microorganisms, including bacteria and fungi. Candida species are commonly found in the gastrointestinal tract and can cause invasive infection, particularly in the context of perforation and subsequent contamination.

Current Evidence

• Incidence of Fungal Infection: Studies demonstrate that Candida species can be isolated from peritoneal or mediastinal cultures in patients with gastrointestinal perforations. In some cases, invasive candidiasis has been associated with worse outcomes.
• Clinical Guidelines: Most clinical guidelines do not provide firm recommendations for routine empiric antifungal therapy solely based on gastric or esophageal perforation. However, empiric antifungal therapy is often considered in high-risk patients, such as those who are immunocompromised, critically ill, or with recurrent upper GI perforations.
• Risk Factors Suggesting Benefit: - Presence of Candida in surveillance cultures or prior colonization
  - Hemodynamic instability or septic shock
  - Prolonged hospitalization or prior broad-spectrum antibiotic use
  - Evidence of fungal infection on histopathology or intraoperative specimens
• Clinical Studies: Evidence is mostly from retrospective cohort studies and case series rather than randomized controlled trials. Some studies indicate that empiric antifungal therapy may reduce fungal-related morbidity and mortality in selected high-risk populations.

Summary

There is limited direct evidence supporting routine empiric antifungal therapy for all patients with gastric or esophageal perforation. Empiric antifungal treatment may be justified in high-risk patients exhibiting signs of fungal infection or with known risk factors for invasive candidiasis. Clinical judgment and local epidemiology should guide the decision to initiate antifungal therapy.

References

• Eggimann P, Garbino J, Pittet D. Epidemiology of Candida species infections in critically ill non-immunosuppressed patients. Lancet Infect Dis. 2003 Nov;3(11):685-702.
• Clancy CJ, Nguyen MH. Diagnosis and treatment of invasive candidiasis. Infect Dis Clin North Am. 2015 Jun;29(2):247-65.
• European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines for the diagnosis and management of Candida diseases 2012.
• Freifeld AG, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011 Feb 1;52(4):e56-93.

Direct Oral Anticoagulants (DOACs) for Acute VTE in Patients on Xtandi (Enzalutamide)

Background: Xtandi (enzalutamide) is an androgen receptor inhibitor commonly used in prostate cancer treatment. It is a strong inducer of CYP3A4 and P-glycoprotein (P-gp), which may reduce plasma concentrations of some Direct Oral Anticoagulants (DOACs) that are substrates of these pathways. This interaction can potentially decrease the effectiveness of certain DOACs when used concurrently with Xtandi.

Considerations

• Enzalutamide induction: May significantly reduce levels of DOACs metabolized by CYP3A4 and/or transported by P-gp.
• Reduced DOAC levels: Could lead to subtherapeutic anticoagulation and increased risk of thromboembolism.

DOAC Options and Safety

Summary and Recommendations

• Due to the potent induction of CYP3A4 and P-gp by enzalutamide, all DOACs may have reduced plasma concentrations and efficacy when used concomitantly.
• No DOAC has been definitively proven safe and fully effective with enzalutamide.
• Consider alternative anticoagulation strategies such as low molecular weight heparin (LMWH) or vitamin K antagonists (VKAs), which are not metabolized by CYP3A4 or P-gp.
• If DOAC use is necessary, close clinical monitoring and possibly anti-Xa level monitoring (where available) is recommended.
• Consultation with a hematologist or clinical pharmacist is advised.

References

• FDA prescribing information for Xtandi (enzalutamide)
• Clinical pharmacology data on DOAC interactions
• Guidelines on anticoagulation in cancer-associated thrombosis

Long-Acting Corticosteroids for Epidural Administration

Commonly Used Long-Acting Corticosteroids Administered Epidurally

• Methylprednisolone acetate (e.g., Depo-Medrol)
• Triamcinolone acetonide
• Betamethasone acetate
• Dexamethasone phosphate (less commonly used but sometimes preferred due to safety profile)

Safety Regarding Formulations Containing Preservatives

Epidural corticosteroid injections ideally should be preservative-free. Formulations containing preservatives or particulate matter pose risks including:

• Neurotoxicity: Preservatives and particulate steroids have been linked to potential neurotoxic effects when injected into the epidural or intrathecal space.
• Embolic events: Particulate corticosteroids may cause vascular occlusion if inadvertently injected intravascularly.
• Inflammation and arachnoiditis: Preservatives can provoke inflammatory reactions leading to complications.

Summary

Long-acting corticosteroids like methylprednisolone acetate and triamcinolone acetonide are commonly administered epidurally. However, it is recommended to use preservative-free formulations to minimize the risk of neurotoxicity and other complications.

Early Lipid Administration in the NICU

Summary

Early administration of intravenous lipids in neonates, particularly in the neonatal intensive care unit (NICU), has been studied to evaluate its benefits on growth, metabolic stability, and clinical outcomes. Evidence suggests that early lipid initiation (within the first 24 hours of life) in preterm and very low birth weight (VLBW) infants supports improved energy provision and may contribute to better growth without increasing adverse effects.

Evidence and Patient Populations

• Preterm Infants <1500g (VLBW): Multiple randomized controlled trials and guidelines recommend starting lipids early, often within the first 24 hours, to prevent essential fatty acid deficiency, support neurodevelopment, and promote positive nitrogen balance.
• Extremely Low Birth Weight (ELBW) Infants (<1000g): Early lipid administration is generally considered beneficial to provide adequate calories and essential fatty acids critical for growth and brain development.
• Critically Ill Neonates: Early lipids may help maintain energy supply during catabolic stress states and reduce reliance on glucose-based calories alone, thus potentially preventing hyperglycemia.
• Term Infants: Less data is available, and lipid initiation is usually tied to clinical status and nutrition plans rather than early universal administration.

Optimal Timing

The consensus from neonatal nutritional guidelines (e.g., American Society for Parenteral and Enteral Nutrition [ASPEN], European Society for Paediatric Gastroenterology Hepatology and Nutrition [ESPGHAN]) is to initiate intravenous lipid emulsions within the first 24 hours of life in preterm and VLBW infants, often starting at 1–2 g/kg/day and advancing to 3 g/kg/day as tolerated.

Early initiation helps prevent essential fatty acid deficiency and supports early growth, compared to delayed lipid administration (after 48 hours). However, lipid dosing should be individualized based on clinical status, tolerance, and metabolic monitoring.

Supporting References

• Demerath TW et al. Early versus delayed initiation of intravenous lipid emulsions in preterm infants: a systematic review and meta-analysis. Clin Nutr. 2020;39(7):2112-2120.
• Koletzko B, Poindexter B, Uauy R. Nutritional care of preterm infants: scientific basis and practical guidelines. World Rev Nutr Diet. 2014;110:1-4.
• American Society for Parenteral and Enteral Nutrition (ASPEN) Neonatal Parenteral Nutrition Guidelines. JPEN J Parenter Enteral Nutr. 2017;41(1):159-176.

Summary

In conclusion, early lipid administration within the first 24 hours of life is beneficial in preterm, VLBW, and critically ill neonates in the NICU by providing essential fatty acids, supporting growth, and improving metabolic outcomes. Initiation and advancement should be carefully monitored and individualized.