01Approach to the Critical Patient/attcp40

Immediate stabilization priorities

›Airway and breathing threats

›Respiratory depression from desomorphine (opioid effect)

›GCS < 8 or inability to protect airway — immediate airway intervention

›Naloxone 0.4–2 mg IV/IM/IN; repeat every 2–3 minutes up to 10 mg

›Desomorphine half-life ~2–3 hours; re-sedation risk after naloxone

›Wound botulism respiratory compromise

›Descending flaccid paralysis with bulbar onset

›Early intubation for progressive dysphagia or dysarthria

›ICU-level ventilatory monitoring

›Septic pulmonary emboli from endocarditis or NSTI

›SpO2 < 92% triggers supplemental oxygen escalation

›HFNC for hypoxemic respiratory failure not requiring intubation

›Circulatory and sepsis priorities

›Septic shock criteria

›MAP < 65 mmHg despite 30 ml/kg IV crystalloid resuscitation

›Lactate >= 2 mmol/l

›Norepinephrine 0.01–0.3 mcg/kg/min via central access

›Broad-spectrum antibiotics within 1 hour of sepsis recognition

›Class I recommendation; each hour delay worsens mortality

›Blood cultures x2 before antibiotics if no delay

›Necrotizing soft tissue infection (NSTI) — surgical emergency

›Pain out of proportion to exam with systemic toxicity

›Immediate surgical consultation for operative debridement

›Do not wait for imaging if clinical suspicion is high

Key decision points

›Differentiate NSTI from severe cellulitis

›NSTI features: crepitus, hemorrhagic bullae, woody induration, rapid progression

02History/hx45

Substance use history

›Krokodil use pattern

›Duration, frequency, and quantity of use

›Route: IV injection versus skin-popping (subcutaneous); skin-popping 5x higher SSTI risk

›Injection sites used: arms, groin, neck, legs

›Communal drug preparation and needle sharing (major infection amplifier)

›Cost motivation: ~$6–8/dose vs. heroin (primary driver of switch)

›Last dose and withdrawal timeline

›Desomorphine half-life ~2–3 hours; withdrawal onset very rapid

›Clinical Opiate Withdrawal Scale (COWS) baseline assessment

›Prior opioid use disorder history

›Previous methadone or buprenorphine treatment

›Naltrexone history (opioid-free duration required)

›Prior overdoses and naloxone use

Skin and wound history

›Lesion timeline

›Onset and progression: color change to ulceration to necrosis

›Green/black discoloration at injection sites (characteristic presentation)

›Prior abscesses, surgical debridements, or amputations

›Alarm features in wound history

›Rapidly progressive gangrene extending beyond injection site

›Pain out of proportion to visible wound severity

›Crepitus or gas sensation under skin

Systemic symptom history

›Infectious systemic symptoms

›Fever, chills, rigors

›Weight loss and constitutional decline

›Bone pain (osteomyelitis), jaw pain (osteonecrosis of jaw)

03Physical Exam/exam43

Vital signs assessment

›Sepsis and withdrawal hemodynamics

›Temperature: fever > 38.3 C (sepsis) versus diaphoresis (withdrawal)

›Heart rate: tachycardia in both sepsis and opioid withdrawal

›Blood pressure: hypotension (sepsis/distributive shock) versus hypertension (withdrawal)

›Respiratory rate >= 22/min (sepsis criterion)

›SpO2 on room air

Skin and wound exam

›Lesion characterization

›Green/black discoloration, scaly desquamating skin at injection sites

›Ulcer depth: superficial vs. subcutaneous tissue vs. exposed bone or tendon

›Necrotic base versus clean granulation tissue

›Surrounding erythema, induration, warmth, fluctuance

›NSTI alarm signs

›Crepitus on palpation (gas-forming organisms)

›Hemorrhagic bullae

›Woody induration with tissue firmness

›Violaceous skin discoloration beyond wound margins

›Vascular exam

›Peripheral pulses: venous sclerosis from repeated injection

›Thrombophlebitis: cord-like, tender veins

›Track marks, scarring from prior injection sites

Cardiac and respiratory exam

›Endocarditis evaluation

›Murmur: tricuspid regurgitation murmur of right-sided endocarditis

›Janeway lesions: painless hemorrhagic macules on palms/soles

›Splinter hemorrhages under nails

›Osler nodes: painful nodules on finger pads

04Differential Diagnosis/ddx42

Life-threatening mimics and complications

›Necrotizing soft tissue infection (NSTI)

›ICD-10: M72.6

›Crepitus, rapid spread, systemic toxicity, pain out of proportion

›Polymicrobial (Group A Streptococcus, Staphylococcus, anaerobes, gram-negatives)

›Distinguishing: gas on imaging, LRINEC > 6 (poorly sensitive in IDU), surgical finding

›Infective endocarditis

›ICD-10: I33.0

›Right-sided (tricuspid) most common in IDU

›Septic pulmonary emboli, embolic pneumonia, right heart failure

›Wound botulism

›ICD-10: A05.1

›Clostridium botulinum in devitalized tissue

›Descending paralysis, bulbar onset, afebrile early course

›Sepsis with multiorgan dysfunction

›ICD-10: A41.9

›From SSTI, endocarditis, osteomyelitis, or pneumonia

Skin and soft tissue differential

›Xylazine-associated wound necrosis

›ICD-10: T36.5 (analogue)

›Increasingly common US adulterant in fentanyl supply

›Similar necrotic ulcers; xylazine not reversed by naloxone

›Distinguishing: urine drug screen positive for xylazine (if available); history

›Levamisole-induced vasculopathy

›Cocaine adulterant causing retiform purpura and neutropenia

›Distinct reticular skin pattern; anti-neutrophil antibodies

›Calciphylaxis

›Painful necrotic lesions in ESRD patients

05Laboratory Tests/lt40

Infection and sepsis workup

›Complete blood count with differential

›Leukocytosis (bacterial infection/sepsis)

›Leukopenia (overwhelming sepsis, levamisole-associated neutropenia)

›Anemia of chronic disease or blood loss

›Comprehensive metabolic panel

›Creatinine and BUN: nephrotoxicity from heavy metals (lead, phosphorus), rhabdomyolysis

›AST/ALT: hepatotoxicity from solvent contaminants, viral hepatitis

›Bilirubin, albumin: hepatic synthetic function

›Electrolytes: hyponatremia (SIADH in infection), hypokalaemia (withdrawal)

›Lactate

›Lactate >= 2 mmol/l: sepsis criterion and mortality predictor

›Lactate >= 4 mmol/l: septic shock regardless of blood pressure

›Inflammatory markers

›C-reactive protein (CRP): infection severity; markedly elevated in NSTI

›Erythrocyte sedimentation rate (ESR): osteomyelitis monitoring

›Blood cultures

›Two sets from separate sites before antibiotics

›Aerobic and anaerobic bottles; incubation minimum 5 days for fastidious organisms

Toxicology and organ-specific labs

›Urine drug screen

›Standard opiate immunoassays cross-react with desomorphine at 2.5–77% (variable)

›Morphine-directed ELISA has better cross-reactivity than codeine-based assays

›Confirmatory GC-MS or LC-MS/MS required for definitive desomorphine detection

›Screen for xylazine, benzodiazepines, stimulants (polysubstance use common)

›Creatine kinase

›Rhabdomyolysis screening from prolonged immobility or infection

›CK > 5000 U/L: aggressive IV hydration target urine output > 200 ml/h

06Diagnostic Tests/dt52

Scoring Systems

›LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis)

›Components: CRP > 150 mg/l (4 pts), WBC > 25 x10^9/l (2 pts), Hgb < 110 g/l (2 pts), Na < 135 mmol/l (2 pts), creatinine > 141 mmol/l (2 pts), glucose > 10 mmol/l (1 pt)

›Score >= 6: moderate risk for NSTI; score >= 8: high risk

›PITFALL: LRINEC performs poorly in IDU patients — MacLeod 2023 cohort showed poor discrimination

›Clinical judgment supersedes LRINEC in IDU populations

›Clinical Opiate Withdrawal Scale (COWS)

›11-item observer-rated scale; score 0–48

›Score 5–12: mild withdrawal; 13–24: moderate; 25–36: moderately severe; > 36: severe

›Used to guide buprenorphine initiation timing (COWS >= 8–12 before first dose)

›Duke Criteria for Infective Endocarditis

›Major criteria: positive blood cultures, echocardiographic evidence of endocarditis

›Minor criteria: IDU, fever, vascular phenomena, immunologic phenomena, serology

›Definite IE: 2 major, 1 major + 3 minor, or 5 minor criteria

MRI

›MRI of affected extremity

›Gold standard for osteomyelitis: sensitivity 90%, specificity 82%

›T1-weighted: low signal replaces normal marrow fat in osteomyelitis

›T2/STIR: high signal edema in bone and soft tissue infection

›Gadolinium-enhanced: distinguishes abscess from phlegmon; rim-enhancing abscess requires drainage

›Delineates deep tissue involvement and surgical planning for NSTI

›MRI jaw/mandible

›Evaluates extent of osteonecrosis of jaw

›T1 low signal and T2 high signal in necrotic bone

›Differentiates viable from avascular bone for surgical planning

›MRI spine

›Vertebral osteomyelitis and epidural abscess in bacteremic IDU

›Gadolinium required for epidural abscess detection (neurosurgical emergency)

07Disposition/dispo34

Admission indications

›Mandatory admission criteria

›Sepsis or septic shock (hemodynamic instability, lactate > 2 mmol/l)

›Suspected or confirmed NSTI (surgical emergency — direct to OR)

›Extensive gangrene or necrosis requiring serial surgical debridements

›Infective endocarditis (confirmed or suspected with bacteremia)

›Osteomyelitis or septic arthritis requiring IV antibiotics

›Wound botulism (ICU-level airway monitoring and antitoxin administration)

›Multiorgan dysfunction: acute kidney injury, hepatic failure, DIC

›Severe opioid withdrawal with autonomic instability or inability to tolerate oral medications

Level of care determination

›ICU indications

›Septic shock requiring vasopressors

›Respiratory failure requiring mechanical ventilation

›Wound botulism with progressive weakness

›Severe electrolyte abnormalities or multiorgan failure

›Step-down/monitored bed indications

›Moderate-to-severe SSTI with systemic signs requiring IV antibiotics

›Moderate opioid withdrawal requiring parenteral adjuncts

›Endocarditis without hemodynamic compromise

›Observation indication

›Moderate soft tissue infection with uncertain trajectory: serial exams every 4–6 hours

Discharge criteria and planning

›Discharge eligibility criteria

›Simple abscess post-incision and drainage with reliable follow-up arranged

›Stable wound amenable to outpatient wound care

›Tolerating oral medications including buprenorphine

›OUD treatment plan in place (buprenorphine prescription or methadone clinic referral)

08Treatment/t88

Surgical and wound management

›NSTI operative management

›Immediate surgical debridement — do not delay for imaging if clinical diagnosis clear

›Class I recommendation: operative debridement within 12–24 hours improves survival

›Each hour delay in OR increases mortality

›Wide margin debridement of all necrotic tissue to healthy bleeding margins

›Re-exploration at 24–48 hours planned for second-look debridement

›Continue debridements until no further necrosis progression

›Amputation may be required for extensive extremity involvement

›Abscess management

›Incision and drainage with wound cultures (aerobic and anaerobic)

›Local anesthesia with lidocaine 1%; epinephrine avoided in compromised tissue

›Wound packing with non-adherent gauze; daily dressing changes

›Negative-pressure wound therapy (NPWT) for large soft tissue defects

›Promotes granulation and reduces wound contraction

›Applied after surgical debridement with clean wound bed

›Wound care essentials

›Serial wound reassessment every 4–6 hours in admitted patients

›Tetanus prophylaxis: Td or Tdap if not immunized within 5 years

›Tetanus immunoglobulin (TIG) 250 units IM if unvaccinated with contaminated wound

Antibiotic therapy

›Empiric antibiotic selection for NSTI or severe SSTI

›Vancomycin IV for MRSA coverage

›Loading dose 25–30 mg/kg IV then 15–20 mg/kg IV every 8–12 hours

›Target AUC/MIC 400–600 mg·h/l (pharmacy-guided dosing)

›Alternative: daptomycin 6–10 mg/kg IV daily for bacteremia/endocarditis

›Piperacillin-tazobactam 4.5 g IV every 6 hours (gram-negative and anaerobic coverage)

›Alternative: meropenem 1 g IV every 8 hours for resistant organisms or severe sepsis

›Clindamycin 600–900 mg IV every 8 hours for toxin suppression in streptococcal NSTI

›Inhibits ribosomal protein synthesis; reduces streptococcal exotoxin production

›Added to beta-lactam in confirmed or suspected GAS necrotizing infection

›Endocarditis antibiotic regimen

›MSSA endocarditis: oxacillin 2 g IV every 4 hours or cefazolin 2 g IV every 8 hours

›MRSA endocarditis: vancomycin as above; daptomycin 8–10 mg/kg IV daily alternative

›Duration: right-sided MRSA endocarditis minimum 6 weeks

›If penicillin allergy: daptomycin preferred over vancomycin for bacteremia

›Osteomyelitis antibiotic regimen

›Empiric IV antibiotics pending culture; narrow on sensitivities

›Staphylococcal osteomyelitis: oxacillin 2 g IV every 4 hours (MSSA) or vancomycin (MRSA)

›Duration: 4–6 weeks total; transition to oral after clinical improvement with sensitive organism

Opioid use disorder and withdrawal management

›Buprenorphine initiation (preferred first-line OUD treatment)

›Initiate when COWS >= 8–12 (moderate withdrawal symptoms)

›Desomorphine short half-life means COWS >= 8 achievable within hours of last use

›Sublingual buprenorphine/naloxone 2/0.5 mg; reassess COWS at 1–2 hours

›Titrate to 8–16 mg/0.5–4 mg on day 1; target 16–24 mg/day for maintenance

›Do NOT delay buprenorphine initiation pending cessation of acute medical illness

›Hospitalization is a critical treatment engagement window (ASAM recommendation)

›Low-dose buprenorphine induction (Bernese method) for patients with ongoing fentanyl/desomorphine use

›Buprenorphine 0.5 mg SL daily, increasing by 1–2 mg/day over 3–7 days

›Avoids precipitated withdrawal; does not require full withdrawal state

›Methadone alternative for OUD

›Indicated if buprenorphine intolerant or patient preference

›Initiation in hospital: 20–30 mg oral day 1; increase 5–10 mg/day under supervision

›QTc monitoring: baseline ECG; target QTc < 500 ms

›Must be enrolled in opioid treatment program (OTP) for outpatient continuation

›Withdrawal symptom management (adjuncts)

›Clonidine 0.1–0.3 mg orally every 6–8 hours for autonomic symptoms

›Contraindicated if SBP < 90 mmHg or significant bradycardia

›Lofexidine 0.54 mg orally four times daily (alpha-2 agonist; FDA-approved for withdrawal)

›Ondansetron 4 mg IV/orally every 6 hours for nausea

›Loperamide 4 mg orally then 2 mg after each loose stool (max 16 mg/day) for diarrhea

›Ibuprofen 400–600 mg orally every 6 hours for myalgias (if renal function adequate)

›Diazepam 5–10 mg orally every 6–8 hours for anxiety and insomnia (short-term)

›Naltrexone: avoid initiation until opioid-free 7–10 days

›Precipitates severe withdrawal if residual opioids present

Management of specific complications

›Wound botulism management

›Heptavalent botulinum antitoxin (HBAT): contact CDC/public health immediately for release

›Administer as soon as possible; antitoxin does not reverse established paralysis

›HBAT 1 vial IV single dose; monitor for anaphylaxis (horse serum-derived)

›ICU admission for airway monitoring and ventilatory support

›Wound debridement to remove toxin-producing source

›Penicillin G 3–4 million units IV every 4 hours or metronidazole 500 mg IV every 8 hours

›Jaw osteonecrosis management

›Oral maxillofacial surgery (OMFS) referral

›Conservative: antibiotics, chlorhexidine mouth rinses, debridement of exposed bone

›Surgical: sequestrectomy or jaw resection for extensive necrosis

›Amoxicillin-clavulanate 875/125 mg orally twice daily for oral flora coverage

›Clindamycin 300 mg orally four times daily if penicillin allergic

›Infectious disease co-management

›HIV-positive: antiretroviral therapy initiation after stabilization

›Bictegravir/emtricitabine/tenofovir alafenamide once daily preferred (high barrier to resistance)

›HCV-positive: direct-acting antivirals after acute illness resolution

›Sofosbuvir/velpatasvir once daily for 12 weeks (pangenotypic)

›Vaccinations: HAV, HBV (if non-immune), tetanus, influenza, pneumococcal

Nutritional support

›Nutritional rehabilitation

›Severe malnutrition is universal in chronic krokodil use

›High-protein diet 1.5–2 g/kg/day for wound healing

›Caloric target 25–30 kcal/kg/day; enteral preferred over parenteral

›Micronutrient supplementation: vitamin C 500 mg daily, zinc sulfate 220 mg daily

›B-vitamin complex (thiamine 100 mg daily) and iron for anemia

09Special Populations/sp47

Pregnancy

›Maternal risks in pregnancy

›Krokodil contaminants (heavy metals, solvents) are teratogenic — no safe exposure level

›Fetal exposure to iodine, phosphorus, organic solvents during organogenesis

›Risk of intrauterine growth restriction, preterm birth, fetal demise

›Maternal sepsis carries highest fetal mortality risk — aggressive early treatment mandatory

›OUD treatment in pregnancy

›Methadone or buprenorphine are both first-line and safe in pregnancy

›ACOG and ASAM: medication for OUD (MOUD) reduces maternal and neonatal mortality

›Buprenorphine associated with lower neonatal opioid withdrawal syndrome (NOWS) severity vs. methadone

›Methadone requires OTP enrollment; dose adjustments needed as pregnancy progresses (increased volume of distribution)

›Naltrexone: avoid in pregnancy (precipitates fetal withdrawal; inadequate safety data)

›Clonidine: use with caution; may cause neonatal hypotension and bradycardia

›Antibiotic considerations in pregnancy

›Vancomycin: FDA category B; preferred for MRSA in pregnancy

›Clindamycin: acceptable for skin flora coverage

›Avoid ciprofloxacin and doxycycline (fluoroquinolones and tetracyclines contraindicated)

›Piperacillin-tazobactam: acceptable in pregnancy

›Neonatal opioid withdrawal syndrome (NOWS) planning

›Coordinate with neonatology for NICU-level monitoring post-delivery

›Finnegan Neonatal Abstinence Scoring (FNAS) protocol for newborn monitoring

›Rooming-in and breastfeeding encouraged if no active HIV and on stable MOUD

Geriatric

›Altered presentation in older adults

›Krokodil use less common in elderly but complications may be more severe

›Atypical sepsis presentation: confusion and falls without fever

›Baseline cognitive impairment may mask COWS assessment

›Comorbid peripheral vascular disease worsens tissue healing

10Background/b54

Epidemiology

›Global distribution and emergence

›Originated in Russia and Ukraine; estimated 100,000+ users in Russia by 2011

›Spread to Eastern Europe (Poland, Georgia, Kazakhstan) and Central Asia

›Sporadic cases reported in Western Europe and North America (US cases from 2013)

›International Drug Policy (Grund 2013): krokodil driven by heroin unavailability and cost disparity

›Mortality and morbidity

›Average survival estimated at 1–3 years after initiation of krokodil use (Alves 2020)

›Amputation rates high — limb loss reported in majority of long-term users

›HIV prevalence: Ukrainian krokodil injectors inject 85% more frequently than HIV-naive users (Booth 2016)

›HCV seroprevalence approaches 90% in long-term IDU populations

›ICD-10 coding

›F11.20: Opioid use disorder, moderate, uncomplicated (desomorphine)

›L97.909: Non-pressure chronic ulcer of unspecified part of lower leg

›M86.9: Unspecified osteomyelitis

›T40.2X1A: Poisoning by other opioids, accidental (initial encounter)

Pathophysiology

›Active compound: desomorphine

›Semi-synthetic opioid derived from codeine via reductive amination

›Potency approximately 10x morphine; rapid onset with very short half-life 2–3 hours

›High frequency of dosing required (up to 8–10 times daily) drives rapid physical dependence

›Mu-opioid receptor full agonist with high receptor affinity

›Metabolized by hepatic CYP3A4 and CYP2D6; glucuronidation to active metabolites

›Tissue destruction from contaminants

›Red phosphorus: bone toxicity, mitochondrial dysfunction, hepatotoxicity

›Analogous to "phossy jaw" in historical match factory workers

›Avascular necrosis of jaw bone through local tissue penetration and systemic absorption

›Iodine: local caustic injury, thyroid dysfunction (excess iodine), antiseptic failure at sites

›Wolff-Chaikoff effect: iodine excess transiently suppresses thyroid hormone synthesis

›Organic solvents (lighter fluid, paint thinner): lipid membrane dissolution, protein denaturation

›Cutaneous and subcutaneous tissue destruction at injection site

›Hepatorenal toxicity from systemic absorption

›Heavy metals (lead from batteries): peripheral neuropathy, nephropathy, bone marrow suppression

›Tissue necrosis and infection cascade

›Devitalized tissue from contaminant injury provides anaerobic niche for gas-forming organisms

›Polymicrobial infection: Staphylococcus, Streptococcus, Clostridium, gram-negative enteric organisms

›Vascular damage from repeated injection causes local ischemia and thrombophlebitis

›Impaired immune function from malnutrition, HIV, and opioid immunosuppression amplifies infection risk

Therapeutic Considerations

›Harm reduction framework

›Needle and syringe exchange programs reduce HIV and HCV transmission (ACEP Level B)

›Naloxone distribution: patients and contacts should receive naloxone training and supply

›Naloxone 4 mg intranasal (Narcan) or 2 mg/0.4 ml prefilled autoinjector

›Safe injection site referral where legally available

›Evidence base for OUD pharmacotherapy

›Buprenorphine: Class I recommendation for OUD treatment (ASAM, SAMHSA guidelines)

›Reduces overdose mortality by 50–70% (Blanco & Volkow, Lancet 2019)

›Hospital-initiated buprenorphine improves treatment retention at 30 days vs. referral alone

›Methadone: Class I recommendation; reduces illicit opioid use and criminal activity

›Requires enrollment in federally licensed OTP for outpatient dispensing in US

›Naltrexone: effective for motivated opioid-free patients; monthly extended-release injection preferred

›Vivitrol 380 mg IM monthly; requires 7–10 opioid-free days to avoid precipitated withdrawal

›Antibiotic stewardship considerations

›Culture-directed therapy on sensitivity results to narrow empiric broad-spectrum coverage

›Clindamycin added specifically for toxin suppression in GAS necrotizing infection (Class IIa)

›Minimum antibiotic duration for osteomyelitis: 4–6 weeks; endocarditis: 6 weeks

›Oral step-down antibiotic therapy acceptable in osteomyelitis after 1 week IV if sensitive organism and good GI absorption (OVIVA trial, NEJM 2019)

11Patient Discharge Instructions/pdi31

copy discharge instructions

›Wound care instructions

›Keep all wounds clean and dry; change dressings as instructed by your wound care nurse

›Do not pick at or probe wounds — this increases infection risk

›Watch for signs of worsening infection at wound sites

›Return to ER immediately for: increasing redness, swelling, warmth, or pain at wound

›Return immediately for: new skin color changes (green, black, purple) spreading from wound

›Return immediately for: foul-smelling drainage or pus from wound

›Opioid use disorder treatment instructions

›Take buprenorphine/naloxone exactly as prescribed — do not miss doses

›Buprenorphine is a medication that treats opioid use disorder and prevents withdrawal

›Your prescription: buprenorphine/naloxone (Suboxone) dose as prescribed, placed under your tongue to dissolve

›Do not use krokodil or other street opioids while taking buprenorphine — serious harm can result

›Contact your addiction medicine follow-up clinic within 1 week of discharge

›Infection warning signs — return immediately for

›Fever (temperature > 38 C) or chills

›New shortness of breath or chest pain

›Jaw pain, jaw swelling, or exposed bone in your mouth

›Double vision, difficulty swallowing, or slurred speech (nerve problem — call 911)

›Feeling confused or unusually drowsy

›Inability to eat or drink due to nausea and vomiting

›Safe use and harm reduction

›Krokodil causes severe, permanent tissue damage and organ failure — there is no safe dose

›Average survival with continued krokodil use is estimated at 1–3 years

›If you cannot stop, please use sterile needles every time — never share needles, cookers, or water

›Naloxone (Narcan) has been given to you — keep it with you and teach someone how to use it

›Local needle exchange and harm reduction program contact: connect with your social worker before discharge

›Follow-up appointments

12References/r32

Guidelines and key sources

›Alves EA et al. DARK Classics in Chemical Neuroscience: Krokodil. ACS Chemical Neuroscience. 2020. PMID: 32877160

›Comprehensive review of desomorphine chemistry, pharmacology, and tissue toxicity mechanisms

›Alves EA et al. The Harmful Chemistry Behind Krokodil (Desomorphine) Synthesis and Mechanisms of Toxicity. Forensic Science International. 2015. PMID: 25710781

›Street synthesis analysis and contaminant identification

›Grund JP, Latypov A, Harris M. Breaking Worse: The Emergence of Krokodil and Excessive Injuries Among People Who Inject Drugs in Eurasia. International Journal on Drug Policy. 2013. PMID: 23726898

›Epidemiologic emergence, geographic spread, and harm profile

›Booth RE et al. Krokodile Injectors in Ukraine: Fueling the HIV Epidemic? AIDS and Behavior. 2016. PMID: 26033290

›HIV risk amplification in krokodil-injecting populations

›McDermott J et al. Necrotizing Soft Tissue Infections: A Review. JAMA Surgery. 2024

›Comprehensive NSTI management including diagnosis, surgical approach, and antibiotic selection

›Hua C et al. Necrotising Soft-Tissue Infections. Lancet Infectious Diseases. 2023. PMID: 36252579

›Evidence-based NSTI pathogenesis and treatment

›MacLeod CS et al. Predicting Necrotising Soft Tissue Infections in People Who Inject Drugs. International Journal of Surgery. 2023. PMID: 37042577

›LRINEC poor performance in IDU; novel predictive nomogram

›Rich KM, Solomon DA. Medical Complications of Injection Drug Use — Part I. NEJM Evidence. 2023

›Systematic review of SSTI, endocarditis, and other IDU complications

›Harris MTH et al. Medications for Opioid Use Disorder, Opioid Withdrawal, and Opioid Overdose. JAMA. 2026

›Current pharmacotherapy evidence for OUD including buprenorphine and methadone

›Weimer MB et al. ASAM Clinical Considerations: Buprenorphine Treatment of OUD for High-Potency Synthetic Opioids. Journal of Addiction Medicine. 2023

›Low-dose buprenorphine induction (Bernese method) and COWS-guided initiation

›Hatten BW et al. Clinical Policy: Critical Issues Related to Opioids in Adult Patients Presenting to the Emergency Department. Annals of Emergency Medicine. 2020

›ACEP clinical policy on opioid use disorder management in the ED

›Blanco C, Volkow ND. Management of Opioid Use Disorder in the USA: Present Status and Future Directions. Lancet. 2019. PMID: 30878228

›Evidence base for buprenorphine and methadone mortality reduction (50–70%)

›Winborn J, Kerrigan S. Desomorphine Screening Using Commercial Enzyme-Linked Immunosorbent Assays. Journal of Analytical Toxicology. 2017. PMID: 28369523

›Cross-reactivity data for UDS detection of desomorphine (2.5–77%)

›Marks LR et al. Infectious Complications of Injection Drug Use. Medical Clinics of North America. 2022. PMID: 34823730

Evidence & Review

Evidence & Review