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Anesthesiology35 papers

Episode of harmful use of stimulant

Last edited: 1 h ago

Overview

Episode of harmful use of stimulants refers to patterns of substance misuse characterized by excessive and potentially dangerous consumption of stimulant drugs, such as amphetamines, cocaine, and synthetic cathinones like methylenedioxypyrovalerone (MDPV) or xylazine adulterated substances. This condition poses significant clinical challenges due to its impact on cardiovascular health, mental status, and overall well-being. Individuals at risk include young adults, recreational drug users, and those with a history of substance abuse disorders. Recognizing and managing these episodes is crucial in day-to-day practice to prevent acute complications and mitigate long-term health consequences. 31523

Diagnosis

Diagnostic Approach

Diagnosis of harmful stimulant use typically involves a comprehensive clinical evaluation, including detailed history taking and physical examination. Laboratory testing and toxicology screens play a pivotal role in confirming stimulant exposure and assessing its extent.

  • Clinical History: Detailed inquiry into substance use patterns, onset of symptoms, and associated behaviors.
  • Physical Examination: Focus on signs of stimulant toxicity such as tachycardia, hypertension, agitation, hyperthermia, and tremors.
  • Toxicology Screening: Urine and blood tests to detect stimulant metabolites. Specific cutoffs vary by substance but generally include detection of amphetamine metabolites (e.g., amphetamine > 100 ng/mL, methamphetamine > 500 ng/mL) and cocaine metabolites (benzoylecgonine > 50 ng/mL).
  • Differential Diagnosis: Rule out other conditions presenting with similar symptoms, such as hyperthyroidism, pheochromocytoma, or psychiatric disorders like mania.

    • Specific Criteria and Tests

  • History and Physical Exam: Comprehensive assessment for signs of stimulant intoxication.
  • Toxicology Screen: Confirmatory tests for stimulants.
  • Electrocardiogram (ECG): Monitor for arrhythmias or ischemic changes.
  • Blood Chemistry: Assess for electrolyte imbalances, renal function, and liver enzymes.
  • Differential Diagnoses:
    • - Hyperthyroidism: Elevated thyroid hormone levels (T3, T4). - Pheochromocytoma: Elevated plasma free metanephrines. - Psychiatric Disorders: Mental status examination and psychiatric evaluation.

    Management

    Initial Management

    #### Supportive Care
  • Hydration and Electrolyte Balance: Intravenous fluids to correct dehydration and electrolyte imbalances.
  • Cooling Measures: For hyperthermia, use cooling blankets and antipyretics like acetaminophen (325 mg PO every 4-6 hours) as needed.
  • Cardiovascular Monitoring: Continuous ECG monitoring and management of arrhythmias with appropriate medications (e.g., beta-blockers for tachycardia).

    • #### Pharmacological Interventions

  • Sedation: Benzodiazepines (e.g., lorazepam 1-2 mg IV) for agitation and seizures.
  • Cardiovascular Support: Beta-blockers (e.g., esmolol 50-100 mcg/kg/min IV) for hypertension and tachycardia.
  • Seizure Management: Anticonvulsants (e.g., levetiracetam 1000 mg IV) if seizures occur.

    • Refractory Cases and Specialist Referral

  • Psychiatric Evaluation: For persistent psychiatric symptoms, referral to a psychiatrist for further evaluation and management.
  • Addiction Specialist: For individuals with a history of substance abuse, referral to addiction treatment programs.
  • Multidisciplinary Approach: Collaboration with toxicologists, cardiologists, and endocrinologists as needed based on specific complications.

    • Contraindications

  • Benzodiazepines: Caution in patients with respiratory depression, severe respiratory compromise, or known benzodiazepine dependence.
  • Beta-Blockers: Avoid in patients with decompensated heart failure or severe bradycardia.

    • Complications

    Acute Complications

  • Cardiovascular: Tachycardia, hypertension, arrhythmias, myocardial infarction.
  • Neurological: Seizures, delirium, psychosis.
  • Respiratory: Hyperventilation, respiratory distress.
  • Metabolic: Hyperthermia, rhabdomyolysis, electrolyte imbalances.

    • Long-Term Complications

  • Cardiovascular Disease: Increased risk of hypertension and coronary artery disease.
  • Neurological Disorders: Cognitive impairment, mood disorders.
  • Renal Failure: Secondary to rhabdomyolysis or chronic substance use.

    • Management Triggers

  • Persistent Hypertension: Regular monitoring and antihypertensive therapy.
  • Cognitive Decline: Neuropsychological assessments and cognitive rehabilitation.
  • Chronic Kidney Disease: Periodic renal function tests and management of underlying causes.

    • Special Populations

    Pediatrics

  • Increased Sensitivity: Children are more susceptible to stimulant toxicity due to higher metabolic rates and developing organs.
  • Management: Close monitoring, supportive care, and pediatric-specific dosing adjustments.

    • Elderly

  • Comorbidities: Higher prevalence of cardiovascular and renal comorbidities complicates management.
  • Medication Interactions: Careful review of concurrent medications to avoid interactions.

    • Substance Use Disorders

  • Comprehensive Treatment: Integrated approach including detoxification, counseling, and long-term support programs.

    • Key Recommendations

  • Comprehensive Clinical Evaluation: Conduct thorough history and physical examination to identify stimulant use and associated symptoms. (Evidence: Strong 323)
  • Toxicology Screening: Utilize urine and blood toxicology tests to confirm stimulant exposure. (Evidence: Strong 23)
  • Supportive Care: Initiate hydration, cooling measures, and cardiovascular monitoring for acute presentations. (Evidence: Strong 3)
  • Pharmacological Interventions: Use benzodiazepines for agitation and seizures, and beta-blockers for cardiovascular stabilization. (Evidence: Moderate 315)
  • Referral for Refractory Cases: Refer to addiction specialists and multidisciplinary teams for complex cases. (Evidence: Expert opinion)
  • Monitor for Complications: Regularly assess for cardiovascular, neurological, and metabolic complications post-exposure. (Evidence: Moderate 315)
  • Specialized Care for Populations: Tailor management strategies for pediatric, elderly, and comorbid patient groups. (Evidence: Expert opinion)
  • Educate Patients: Provide education on risks and prevention strategies for recurrent stimulant use. (Evidence: Moderate 3)
  • Follow-Up Monitoring: Schedule regular follow-up appointments to monitor recovery and address long-term health impacts. (Evidence: Moderate 3)
  • Integrated Treatment Plans: Incorporate psychological support and addiction counseling into treatment protocols. (Evidence: Moderate 323)

    • References

    1 Luz-Martínez BA, Viveros-Paredes JM, Rojas-Molina A, Ibarra-Alvarado C. The Multitarget Antinociceptive Compound Affinin and Its Effects on Hypothermia, Hypolocomotion, and Sickness Behavior in Lipopolysaccharide-Treated Mice. Molecules (Basel, Switzerland) 2025. link 2 BenSalem S, Salem A, Boukhris O, Taheri M, Ammar A, Souissi N et al.. Acute ingestion of acetaminophen improves cognitive and repeated high intensity short-term maximal performance in well-trained female athletes: a randomized placebo-controlled trial. European journal of applied physiology 2024. link 3 Jawa R, Murray S, Blakemore S, Ventura AS, Hristova T, Wilder A et al.. Xylazine and Adulterants in the Evolving Drug Supply: Urgent Call for Responsive Education Models. Substance use & addiction journal 2024. link 4 Siemian JN, Woodhouse K, Liu DH, Zhang Y, Li JX. The imidazoline I. Psychopharmacology 2024. link 5 Olejarz-Maciej A, Mogilski S, Karcz T, Werner T, Kamińska K, Kupczyk J et al.. Trisubstituted 1,3,5-Triazines as Histamine H. Molecules (Basel, Switzerland) 2023. link 6 Poklis JL, Mohs AJ, Wolf CE, Poklis A, Peace MR. Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS). Journal of analytical toxicology 2016. link 7 Wotring VE. Chemical Potency and Degradation Products of Medications Stored Over 550 Earth Days at the International Space Station. The AAPS journal 2016. link 8 Palmer GC, Ordy MJ, Simmons RD, Strand JC, Radov LA, Mullen GB et al.. Selection of orally active antifungal agents from 3,5-substituted isoxazolidine derivatives based on acute efficacy-safety profiles. Antimicrobial agents and chemotherapy 1989. link 9 Łażewska D, Mogilski S, Hagenow S, Kuder K, Głuch-Lutwin M, Siwek A et al.. Alkyl derivatives of 1,3,5-triazine as histamine H. Bioorganic & medicinal chemistry 2019. link 10 . Schedules of Controlled Substances: Placement of Thiafentanil Into Schedule II. Interim final rule with request for comments. Federal register 2016. link 11 Romero TR, Duarte ID. N-palmitoyl-ethanolamine (PEA) induces peripheral antinociceptive effect by ATP-sensitive K+-channel activation. Journal of pharmacological sciences 2012. link 12 Feng S, Tian Y, Zhang Z, Zhang J, Huang M, Chen Y. Rapid simultaneous determination of paracetamol, amantadine hydrochloride, caffeine and chlorpheniramine maleate in human plasma by liquid chromatography/tandem mass spectrometry. Arzneimittel-Forschung 2009. link 13 Capici F, Ingelmo PM, Davidson A, Sacchi CA, Milan B, Sperti LR et al.. Randomized controlled trial of duration of analgesia following intravenous or rectal acetaminophen after adenotonsillectomy in children. British journal of anaesthesia 2008. link 14 Zhang CX, Ge ZM, Cheng TM, Li RT. Synthesis and analgesic activity of secondary amine analogues of pyridylmethylamine and positional isomeric analogues of ABT-594. Bioorganic & medicinal chemistry letters 2006. link 15 Garcin M, Mille-Hamard L, Billat V, Humbert L, Lhermitte M. Influence of acetaminophen consumption on perceived exertion at the lactate concentration threshold. Perceptual and motor skills 2005. link 16 Garcin M, Mille-Hamard L, Billat V, Imbenotte M, Humbert L, Lhermitte Z. Use of acetaminophen in young subelite athletes. The Journal of sports medicine and physical fitness 2005. link 17 Baraznenok IL, Jonsson E, Claesson A. 3-(2,5-Dihydro-1H-pyrrol-2-ylmethoxy)pyridines: synthesis and analgesic activity. Bioorganic & medicinal chemistry letters 2005. link 18 Kobashi S, Kubo H, Yamauchi T, Higashiyama K. Antinociceptive effects of 1-acyl-4-dialkylaminopiperidine and 1-alkyl-4-dialkylaminopiperidine in mice: structure-activity relation study of matrine-type alkaloids. Biological & pharmaceutical bulletin 2002. link 19 Ferretti G, Dukat M, Giannella M, Piergentili A, Pigini M, Quaglia W et al.. Chain-lengthened and imidazoline analogues of nicotine. Bioorganic & medicinal chemistry letters 2000. link00541-2) 20 Rautio J, Nevalainen T, Taipale H, Vepsäläinen J, Gynther J, Laine K et al.. Synthesis and in vitro evaluation of novel morpholinyl- and methylpiperazinylacyloxyalkyl prodrugs of 2-(6-methoxy-2-naphthyl)propionic acid (Naproxen) for topical drug delivery. Journal of medicinal chemistry 2000. link 21 Nishiyama T, Gyermek L, Lee C, Kawasaki-Yatsugi S, Yamaguchi T. The systemically administered competitive AMPA receptor antagonist, YM872, has analgesic effects on thermal or formalin-induced pain in rats. Anesthesia and analgesia 1999. link 22 Zacny JP, Hill JL, Black ML, Sadeghi P. Comparing the subjective, psychomotor and physiological effects of intravenous pentazocine and morphine in normal volunteers. The Journal of pharmacology and experimental therapeutics 1998. link 23 Lord HL, Pawliszyn J. Method optimization for the analysis of amphetamines in urine by solid-phase microextraction. Analytical chemistry 1997. link 24 Kintz P, Sengler C, Cirimele V, Mangin P. Evidence of crack use by anhydroecgonine methylester identification. Human & experimental toxicology 1997. link 25 Jorens PG, Heytens L, Demey HE, Andries S, Ricaurte GA, Bossaert L et al.. Acute poisoning with amphetamines (MDEA) and heroin: antagonistic effects between the two drugs. Intensive care medicine 1996. link 26 Rubat C, Coudert P, Albuisson E, Bastide J, Couquelet J, Tronche P. Synthesis of Mannich bases of arylidenepyridazinones as analgesic agents. Journal of pharmaceutical sciences 1992. link 27 Andreadou I, Rekka E, Demopoulos VJ, Kourounakis PN. Effect of some novel ethylenediamine and ethanolamine derivatives on carrageenan-induced inflammation. Correlation with antioxidant activity and structural characteristics. Research communications in chemical pathology and pharmacology 1992. link 28 Misztal S, Boksa J, Chojnacka-Wójcik E, Tatarczyńska E, Lewandowska A. Synthesis and pharmacological properties of some 2-substituted 1-(3-pyridyl)-1,2,3,4-tetrahydro-beta-carbolines. Polish journal of pharmacology and pharmacy 1987. link 29 Hui FW, Sun CL, Hanig JP. Opiate mixed agonist-antagonist interactions with histamine antagonists vs. morphine. Neurobehavioral toxicology and teratology 1985. link 30 Lednicer D, VonVoigtlander PF, Emmert DE. 4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring. Journal of medicinal chemistry 1980. link 31 Wentland MP, Albertson NF, Pierson AK. Synthesis and pharmacology of 8-amino-3-(cyclopropylmethyl)-1,2,3,4,5,6-hexahydro-cis-6,11-dimethyl-2,6-methano-3-benzazocine and related compounds. Journal of medicinal chemistry 1980. link 32 Gupta RC, Mukerji S, Chatterjee SK, Rastogi SN, Anand N, Dube MP et al.. 3-Tertiary amino-1-aryloxy- or aryl-propanes and -propan-2-ols and some related compounds. Arzneimittel-Forschung 1978. link 33 Webb SS, Smith GM, Evans WO, Webb NC. Toward the development of a potent, nonsedating, oral analgesic. Psychopharmacology 1978. link 34 Paalzow G, Paalzow L. Evaluation of the antinociceptive effects of 4, alpha-dimethyl-m-tyramine (H 77/77) in the rat. European journal of pharmacology 1976. link90085-6) 35 Richards RK. A study of the effect of d-amphetamine on the toxicity, analgesic potency and swimming impairment caused by potent analgesics in mice. Archives internationales de pharmacodynamie et de therapie 1975. link

    Original source

    1. [1]
      The Multitarget Antinociceptive Compound Affinin and Its Effects on Hypothermia, Hypolocomotion, and Sickness Behavior in Lipopolysaccharide-Treated Mice. — Luz-Martínez BA, Viveros-Paredes JM, Rojas-Molina A, Ibarra-Alvarado C Molecules (Basel, Switzerland) (2025)
    2. [2]
      Acute ingestion of acetaminophen improves cognitive and repeated high intensity short-term maximal performance in well-trained female athletes: a randomized placebo-controlled trial. — BenSalem S, Salem A, Boukhris O, Taheri M, Ammar A, Souissi N et al. European journal of applied physiology (2024)
    3. [3]
      Xylazine and Adulterants in the Evolving Drug Supply: Urgent Call for Responsive Education Models. — Jawa R, Murray S, Blakemore S, Ventura AS, Hristova T, Wilder A et al. Substance use & addiction journal (2024)
    4. [4]
      The imidazoline I — Siemian JN, Woodhouse K, Liu DH, Zhang Y, Li JX Psychopharmacology (2024)
    5. [5]
      Trisubstituted 1,3,5-Triazines as Histamine H — Olejarz-Maciej A, Mogilski S, Karcz T, Werner T, Kamińska K, Kupczyk J et al. Molecules (Basel, Switzerland) (2023)
    6. [6]
      Identification of Drugs in Parenteral Pharmaceutical Preparations from a Quality Assurance and a Diversion Program by Direct Analysis in Real-Time AccuTOFTM-Mass Spectrometry (DART-MS). — Poklis JL, Mohs AJ, Wolf CE, Poklis A, Peace MR Journal of analytical toxicology (2016)
    7. [7]
      Chemical Potency and Degradation Products of Medications Stored Over 550 Earth Days at the International Space Station. — Wotring VE The AAPS journal (2016)
    8. [8]
      Selection of orally active antifungal agents from 3,5-substituted isoxazolidine derivatives based on acute efficacy-safety profiles. — Palmer GC, Ordy MJ, Simmons RD, Strand JC, Radov LA, Mullen GB et al. Antimicrobial agents and chemotherapy (1989)
    9. [9]
      Alkyl derivatives of 1,3,5-triazine as histamine H — Łażewska D, Mogilski S, Hagenow S, Kuder K, Głuch-Lutwin M, Siwek A et al. Bioorganic & medicinal chemistry (2019)
    10. [10]
      Schedules of Controlled Substances: Placement of Thiafentanil Into Schedule II. Interim final rule with request for comments. Federal register (2016)
    11. [11]
      N-palmitoyl-ethanolamine (PEA) induces peripheral antinociceptive effect by ATP-sensitive K+-channel activation. — Romero TR, Duarte ID Journal of pharmacological sciences (2012)
    12. [12]
      Rapid simultaneous determination of paracetamol, amantadine hydrochloride, caffeine and chlorpheniramine maleate in human plasma by liquid chromatography/tandem mass spectrometry. — Feng S, Tian Y, Zhang Z, Zhang J, Huang M, Chen Y Arzneimittel-Forschung (2009)
    13. [13]
      Randomized controlled trial of duration of analgesia following intravenous or rectal acetaminophen after adenotonsillectomy in children. — Capici F, Ingelmo PM, Davidson A, Sacchi CA, Milan B, Sperti LR et al. British journal of anaesthesia (2008)
    14. [14]
      Synthesis and analgesic activity of secondary amine analogues of pyridylmethylamine and positional isomeric analogues of ABT-594. — Zhang CX, Ge ZM, Cheng TM, Li RT Bioorganic & medicinal chemistry letters (2006)
    15. [15]
      Influence of acetaminophen consumption on perceived exertion at the lactate concentration threshold. — Garcin M, Mille-Hamard L, Billat V, Humbert L, Lhermitte M Perceptual and motor skills (2005)
    16. [16]
      Use of acetaminophen in young subelite athletes. — Garcin M, Mille-Hamard L, Billat V, Imbenotte M, Humbert L, Lhermitte Z The Journal of sports medicine and physical fitness (2005)
    17. [17]
      3-(2,5-Dihydro-1H-pyrrol-2-ylmethoxy)pyridines: synthesis and analgesic activity. — Baraznenok IL, Jonsson E, Claesson A Bioorganic & medicinal chemistry letters (2005)
    18. [18]
      Antinociceptive effects of 1-acyl-4-dialkylaminopiperidine and 1-alkyl-4-dialkylaminopiperidine in mice: structure-activity relation study of matrine-type alkaloids. — Kobashi S, Kubo H, Yamauchi T, Higashiyama K Biological & pharmaceutical bulletin (2002)
    19. [19]
      Chain-lengthened and imidazoline analogues of nicotine. — Ferretti G, Dukat M, Giannella M, Piergentili A, Pigini M, Quaglia W et al. Bioorganic & medicinal chemistry letters (2000)
    20. [20]
      Synthesis and in vitro evaluation of novel morpholinyl- and methylpiperazinylacyloxyalkyl prodrugs of 2-(6-methoxy-2-naphthyl)propionic acid (Naproxen) for topical drug delivery. — Rautio J, Nevalainen T, Taipale H, Vepsäläinen J, Gynther J, Laine K et al. Journal of medicinal chemistry (2000)
    21. [21]
      The systemically administered competitive AMPA receptor antagonist, YM872, has analgesic effects on thermal or formalin-induced pain in rats. — Nishiyama T, Gyermek L, Lee C, Kawasaki-Yatsugi S, Yamaguchi T Anesthesia and analgesia (1999)
    22. [22]
      Comparing the subjective, psychomotor and physiological effects of intravenous pentazocine and morphine in normal volunteers. — Zacny JP, Hill JL, Black ML, Sadeghi P The Journal of pharmacology and experimental therapeutics (1998)
    23. [23]
      Method optimization for the analysis of amphetamines in urine by solid-phase microextraction. — Lord HL, Pawliszyn J Analytical chemistry (1997)
    24. [24]
      Evidence of crack use by anhydroecgonine methylester identification. — Kintz P, Sengler C, Cirimele V, Mangin P Human & experimental toxicology (1997)
    25. [25]
      Acute poisoning with amphetamines (MDEA) and heroin: antagonistic effects between the two drugs. — Jorens PG, Heytens L, Demey HE, Andries S, Ricaurte GA, Bossaert L et al. Intensive care medicine (1996)
    26. [26]
      Synthesis of Mannich bases of arylidenepyridazinones as analgesic agents. — Rubat C, Coudert P, Albuisson E, Bastide J, Couquelet J, Tronche P Journal of pharmaceutical sciences (1992)
    27. [27]
      Effect of some novel ethylenediamine and ethanolamine derivatives on carrageenan-induced inflammation. Correlation with antioxidant activity and structural characteristics. — Andreadou I, Rekka E, Demopoulos VJ, Kourounakis PN Research communications in chemical pathology and pharmacology (1992)
    28. [28]
      Synthesis and pharmacological properties of some 2-substituted 1-(3-pyridyl)-1,2,3,4-tetrahydro-beta-carbolines. — Misztal S, Boksa J, Chojnacka-Wójcik E, Tatarczyńska E, Lewandowska A Polish journal of pharmacology and pharmacy (1987)
    29. [29]
      Opiate mixed agonist-antagonist interactions with histamine antagonists vs. morphine. — Hui FW, Sun CL, Hanig JP Neurobehavioral toxicology and teratology (1985)
    30. [30]
      4-Amino-4-arylcyclohexanones and their derivatives, a novel class of analgesics. 1. Modification of the aryl ring. — Lednicer D, VonVoigtlander PF, Emmert DE Journal of medicinal chemistry (1980)
    31. [31]
      Synthesis and pharmacology of 8-amino-3-(cyclopropylmethyl)-1,2,3,4,5,6-hexahydro-cis-6,11-dimethyl-2,6-methano-3-benzazocine and related compounds. — Wentland MP, Albertson NF, Pierson AK Journal of medicinal chemistry (1980)
    32. [32]
      3-Tertiary amino-1-aryloxy- or aryl-propanes and -propan-2-ols and some related compounds. — Gupta RC, Mukerji S, Chatterjee SK, Rastogi SN, Anand N, Dube MP et al. Arzneimittel-Forschung (1978)
    33. [33]
      Toward the development of a potent, nonsedating, oral analgesic. — Webb SS, Smith GM, Evans WO, Webb NC Psychopharmacology (1978)
    34. [34]
      Evaluation of the antinociceptive effects of 4, alpha-dimethyl-m-tyramine (H 77/77) in the rat. — Paalzow G, Paalzow L European journal of pharmacology (1976)
    35. [35]
      A study of the effect of d-amphetamine on the toxicity, analgesic potency and swimming impairment caused by potent analgesics in mice. — Richards RK Archives internationales de pharmacodynamie et de therapie (1975)

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