01Approach to the Critical Patient/attcp61

Immediate stabilization

›Airway and breathing threats

›Severely obtunded or comatose — secure airway with RSI

›Coma suggests massive overdose or dangerous co-ingestant

›Pre-oxygenate with BVM if SpO2 declining

›Respiratory depression

›SpO2 < 92% on room air

›Naloxone 0.4–2 mg IV if opioid co-ingestion suspected

›Aspiration risk

›Lateral decubitus positioning in vomiting patient

›NPO status for altered mental status

›Circulation threats

›Severe hypertension

›SBP > 180 mmHg sustained

›Benzodiazepines first-line for sympathomimetic hypertension

›Tachyarrhythmia

›HR > 130 bpm persistent

›ECG immediately for wide complex or irregular rhythm

›Cardiac arrest

›Rare but documented in poison center data

›Standard ACLS with attention to reversible toxicologic causes

Monitoring and targets

›Monitoring bundle

›Continuous cardiac monitoring

›QTc monitoring especially if antipsychotics given

›Watch for wide complex tachycardia suggesting non-LSD substance

›Continuous pulse oximetry

›SpO2 target 94–98%

02History/hx58

Substance and exposure details

›Agent identification

›Route of administration

›Oral (blotter paper/tab or liquid) most common

›Insufflation of powder (rare, higher concentration risk)

›Estimated dose

›Typical recreational dose 75–150 micrograms

›Onset 1–2 hours oral; peak effect 2–3 hours; duration 6–12 hours

›Intentional vs. accidental exposure

›Recreational use vs. unknown substance sold as LSD

›NBOMe compounds commonly sold as LSD — significantly higher toxicity

›Time of ingestion

›Determines expected duration of effect at time of presentation

›Co-ingestions

›Substance co-ingestion rate approximately 34–41% of cases

›Alcohol, cannabis, MDMA, stimulants most common

›Serotonergic agents increase serotonin syndrome risk

›Current medications

›SSRIs, SNRIs, MAOIs, lithium, tramadol — serotonin syndrome risk

›Monoamine oxidase inhibitors contraindicated with LSD

Symptom profile

›Psychological symptoms

›Hallucinations

›Visual predominant — colors, geometric patterns, visual distortions

›Auditory hallucinations less prominent than in psychosis

›Affective symptoms

›Euphoria, dysphoria, anxiety, panic, paranoia

›Ego dissolution in high-dose exposures

03Physical Exam/exam49

Vital signs

›Vital sign pattern in pure LSD

›Heart rate

›Mild-moderate tachycardia in approximately 38.6% of cases

›Peak HR rarely exceeds 130 bpm in pure LSD

›Blood pressure

›Mild hypertension typical

›SBP typically does not exceed 180 mmHg in pure LSD toxicity

›Temperature

›Mild hyperthermia (> 38°C) in up to 34% at 200 microgram doses

›Core temp > 40°C — life-threatening emergency

›Respiratory rate

›Typically normal unless co-ingestant depressant

›Tachypnea with agitation or hyperthermia

Neurological exam

›Pupillary exam

›Mydriasis — hallmark finding of LSD intoxication

›Bilateral, symmetric

›Distinguishes from miosis of opioid toxidrome

›Nystagmus — if present, suggests PCP, ketamine, or NBOMe

›Reflexes and tone

›Hyperreflexia in sympathomimetic state

›Clonus — if present, raises serotonin syndrome concern

›Muscle rigidity or fasciculations in severe toxicity

›Mental status

›Generally preserved orientation in mild-moderate cases

›Patient knows where they are but perceptions are distorted

›Agitation, confusion, combativeness in severe cases

04Differential Diagnosis/ddx43

Toxicologic differentials

›NBOMe and substituted phenethylamine toxicity

›ICD-10 T40.99 — Other psychodysleptics

›Severe sympathomimetic toxicity, seizures, cardiac arrest

›Bitter taste on blotter is distinguishing clue

›Far higher fatality risk than true LSD

›Sympathomimetic toxidrome

›Amphetamines, cocaine, synthetic cathinones

›More prominent hypertension, tachycardia, hyperthermia

›Agitation with diaphoresis and moist skin

›ICD-10 T43.6 — Psychostimulant poisoning

›Anticholinergic toxidrome

›Dry skin, dry mucous membranes, urinary retention, absent bowel sounds

›True visual hallucinations with clouded sensorium

›LSD preserves sensorium with perceptual distortions

›ICD-10 T44.3 — Poisoning by other parasympatholytics

›Serotonin syndrome

›Clonus and hyperreflexia as distinguishing features

›ICD-10 G21.0 association when drug-induced

›Particularly if on concurrent serotonergic medications

›Boyer and Shannon criteria; Hunter Serotonin Toxicity Criteria

›PCP and ketamine intoxication

›Nystagmus (horizontal, vertical, or rotatory) — distinguishing feature

›Dissociation, violence, analgesia

›ICD-10 T41.29 — Other general anaesthetic poisoning

Psychiatric and medical differentials

›Acute psychosis or first-episode schizophrenia

›ICD-10 F29 — Unspecified nonorganic psychosis

05Laboratory Tests/lt42

Point-of-care and emergency labs

›Immediate bedside tests

›Point-of-care glucose

›Mandatory in all altered mental status presentations

›Hypoglycemia excluded before attributing symptoms to LSD

›Pulse oximetry

›Continuous monitoring from arrival

›Electrolytes and renal function

›Basic metabolic panel

›Sodium — hyponatremia if MDMA co-ingestion or water intoxication

›Potassium — elevated in rhabdomyolysis (hyperkalemia risk)

›Creatinine — elevation seen in severe toxicity with organ involvement

›Bicarbonate — decreased in metabolic acidosis from prolonged agitation

Rhabdomyolysis and metabolic markers

›Creatine kinase (CK)

›Indication: agitation, hyperthermia, prolonged physical restraint, seizure

›Screen for rhabdomyolysis in all moderate-severe cases

›CK > 1000 U/L initiates aggressive IV fluid resuscitation

›Serial CK measurements to track trend

›Repeat every 6–8 hours if elevated

›Lactate

›Metabolic acidosis marker from prolonged muscular agitation

›Lactate >= 2 mmol/l signals significant hypoperfusion

›Serial measurement guides resuscitation response

›Urinalysis

›Myoglobinuria — tea-colored or red-brown urine with rhabdomyolysis

›Urine dipstick positive for blood without red cells on microscopy

›Target urine output 1–2 mL/kg/hour during IV fluid resuscitation

06Diagnostic Tests/dt61

Scoring Systems

›Hunter Serotonin Toxicity Criteria

›Serotonin syndrome diagnosis — requires one of:

›Spontaneous clonus

›Inducible clonus with agitation or diaphoresis

›Ocular clonus with agitation or diaphoresis

›Tremor with hyperreflexia

›Hypertonia with temperature > 38°C and ocular or inducible clonus

›Sensitivity 84%, specificity 97% vs. Sternbach criteria

›CIWA-Ar (Clinical Institute Withdrawal Assessment)

›If alcohol co-ingestion or withdrawal mimicking presentation

›Score >= 8 warrants pharmacologic treatment

›Distinguish withdrawal from LSD toxicity

›Richmond Agitation-Sedation Scale (RASS)

›Titration guide for sedation in agitated patients

›Target RASS -1 to 0 for cooperative sedation

›RASS -2 to -3 acceptable for severe agitation management

›Poison Center Severity Score

›Moderate effects approximately 62% of LSD poison center cases

›Severe effects in small subset with co-ingestants or massive dose

›Minor effects most common in isolated low-dose exposures

MRI

›Brain MRI for LSD toxicity

›Not routinely indicated in uncomplicated LSD intoxication

›No characteristic MRI findings expected from LSD alone

›Delayed after acute stabilization if persistent neurologic deficits

›Indications for urgent MRI/MRA

›Focal neurologic deficit not explained by toxidrome

07Disposition/dispo38

Discharge criteria

›Safe for discharge from ED

›Clinical resolution criteria

›Resolution of agitation and perceptual disturbances

›Stable vital signs — HR, BP, temperature normalized

›Normal mental status returned

›Able to care for self or supervised by responsible adult

›Safety screening mandatory before discharge

›No active suicidal ideation or intent

›No homicidal ideation

›Safe social environment confirmed

›Most patients can be treated and released from ED

›Per-event risk of seeking emergency care approximately 0.2%

›Moderate effects most common (~62% of poison center cases)

Observation indications

›Extended ED observation

›Repeated sedation requirement during ED stay

›Typically observe until 2 hours after last dose required

›Persistent agitation with mild vital sign abnormalities

›Drug effects typically resolve within 12–24 hours

›Unable to confirm co-ingestant cleared

›Persistent perceptual disturbances beyond expected drug duration

Admission indications

›General ward admission

›Persistent psychosis beyond drug expected duration

›Psychiatry co-management required

›Rhabdomyolysis with CK elevation requiring IV fluid therapy

›Persistent suicidal ideation requiring psychiatric hold

08Treatment/t85

Environmental and non-pharmacologic

›Calm low-stimulation environment

›First-line intervention for mild-moderate LSD toxicity

›Quiet room with dim lighting

›Calm, reassuring "talk-down" approach

›May obviate need for pharmacologic sedation in mild cases

›Patient orientation maneuvers

›Repeatedly orient to time, place, and temporary nature of symptoms

›Reduce fear response to perceptual distortions

›Decontamination — not routinely indicated

›Activated charcoal not recommended

›Doses involved are micrograms — minimal charcoal benefit

›Rapid GI absorption eliminates decontamination window

›Gastric lavage not indicated for standard LSD overdose

Benzodiazepines (first-line pharmacotherapy)

›Mild anxiety and panic ("bad trip")

›Lorazepam

›1–2 mg PO or IV

›Onset IV: 1–5 minutes; PO: 15–30 minutes

›Repeat dosing every 15–30 minutes as needed

›Diazepam

›5–10 mg IV for rapid anxiolysis

›Long duration useful for prolonged drug effect

›Moderate to severe agitation

›Midazolam IM — fastest onset for intramuscular route

›2–5 mg IM as initial dose

›Onset 5–10 minutes IM

›Repeat 2.5–5 mg every 5–10 minutes as needed

›Lorazepam IV

›2–4 mg IV for severe agitation

›May require repeated dosing every 5–15 minutes

›Benzodiazepines are first-line for toxin-associated seizures

›Lorazepam 4 mg IV for seizure

›Diazepam 10 mg IV as alternative

Antipsychotics (second-line, refractory agitation)

›Olanzapine IM

›5–10 mg IM for refractory agitation

›Avoid with respiratory compromise

›Do not combine with IM benzodiazepine — respiratory depression risk

›QTc check before administration

›Obtain ECG prior to antipsychotic dosing

›Haloperidol IM

›5 mg IM as alternative to olanzapine

›Risk of extrapyramidal side effects

›May lower seizure threshold

›Avoid if suspected serotonin syndrome — impairs heat dissipation

Hyperthermia management

›Core temperature > 40°C — emergency cooling protocol

›Aggressive external cooling

›Ice water immersion preferred method

›Cold IV crystalloid for internal cooling

›Target core temperature < 39°C rapidly

›Antipyretics NOT effective

›Hyperthermia from muscular activity, not hypothalamic set-point elevation

›Acetaminophen and ibuprofen will not reduce LSD-associated hyperthermia

›Neuromuscular paralysis for refractory hyperthermia

›Nondepolarizing neuromuscular blocking agent

›Rocuronium 1.2 mg/kg IV for intubated patient

›Avoid succinylcholine — hyperkalemia risk from rhabdomyolysis

›Intubation if paralysis required

›Requires full ventilatory support

Serotonin syndrome treatment

›Cyproheptadine (5-HT2A antagonist)

›Initial dose: 12 mg PO

›Available only in oral formulation — give via NG tube if necessary

›Maintenance: 2 mg every 2 hours as needed

›Scheduled maintenance: 8 mg every 6 hours

›Discontinue all serotonergic agents immediately

›SSRIs, SNRIs, MAOIs, lithium, tramadol

›Severe serotonin syndrome

›Intubation and neuromuscular paralysis

›Continuous benzodiazepine infusion for muscle rigidity

›Nondepolarizing paralysis for hyperthermia refractory to other measures

Rhabdomyolysis treatment

›IV fluid resuscitation

›Normal saline or lactated Ringer's solution

›Initiate at 500–1000 mL/hour in severe rhabdomyolysis

›Target urine output 1–2 mL/kg/hour

›Titrate to clinical response and fluid balance

›Monitor electrolytes closely

›Hyperkalemia risk with severe rhabdomyolysis

›Hypocalcemia may occur during muscle injury phase

›Urinary alkalinization — controversial, not routinely recommended

›Sodium bicarbonate may reduce myoglobin tubular toxicity

›Limited evidence for routine use

›Consider in severe cases with very high CK

Ketamine (last resort)

›Ketamine IM for excitatory agitation refractory to all other agents

›2–5 mg/kg IM for procedural or emergency sedation

›Higher risk of intubation compared to benzodiazepines

›Reserve for immediate physical danger to patient or staff

›Prepare for possible airway management after administration

09Special Populations/sp55

Pregnancy

›Physiologic considerations in pregnancy

›LSD safety profile in pregnancy

›No controlled human studies; animal data suggest chromosomal concerns historically debated

›Vasoconstriction risk — potential for placental insufficiency at high doses

›Maternal hyperthermia is teratogenic — aggressive cooling priority

›Obstetric consultation for second and third trimester presentations

›Fetal heart rate monitoring

›Uterine contractions from sympathomimetic stimulation

›Drug treatment in pregnancy

›Benzodiazepines

›Lorazepam acceptable for acute maternal safety

›Risk-benefit favors maternal stabilization

›Neonatal respiratory depression risk if used near delivery

›Antipsychotics in pregnancy

›Avoid haloperidol in first trimester if possible

›Olanzapine — limited data; use only for refractory agitation

›Cyproheptadine — limited pregnancy safety data

›Use only if serotonin syndrome life-threatening

Geriatric

›Physiologic changes affecting presentation

›Reduced drug metabolism and clearance

›Prolonged duration of action expected

›Lower doses produce greater effect

›Higher risk of medical co-morbidities masquerading as toxicity

›Stroke, delirium, metabolic derangement must be excluded

›Polypharmacy interaction risk

›Serotonergic medications more prevalent

10Background/b81

Epidemiology

›Prevalence and incidence

›United States lifetime LSD use

›SAMHSA data: approximately 10% of US adults report lifetime LSD use

›Use increasing per JAMA Psychiatry 2024 data (Walsh et al.)

›Association with major depression subpopulation — increased rates

›Poison center case data

›Leonard et al. 2018: 2000–2016 National Poison Center data

›Simon et al. 2024: US Poison Centers 2012–2022 report (Annals EM)

›Approximately 62% moderate effects; serious outcomes uncommon

›Demographics of ED presentations

›Age: 13–29 years account for approximately 89% of LSD cases

›Sex: male approximately 74% of poison center LSD cases

›Co-ingestion in 34–41% of cases — worsens outcomes

›Per-event risk of seeking emergency medical treatment approximately 0.2%

›Adverse events

›Kopra et al. 2022 (Journal of Psychopharmacology): adverse experience emergency treatment study

›Psychological distress most common reason for ED presentation

›Approximately 11% reported persistent issues beyond 4 weeks

›Hinkle et al. 2024 (JAMA Psychiatry): meta-analysis of adverse events in classic psychedelics

›Serious adverse events uncommon in controlled studies

Pathophysiology

›Mechanism of action

›Primary receptor: 5-HT2A partial agonism

›Visual cortex and prefrontal cortex activation

›Produces hallucinations, perceptual distortions, altered consciousness

›Additional receptor binding

›5-HT1A, 5-HT2C, 5-HT2B agonism

›Dopamine D2 receptor binding

›Multiple receptor interactions explain diverse clinical effects

›ICD-10: T40.8 — Poisoning by lysergide (LSD)

›SNOMED CT: LSD intoxication disorder

›Pharmacokinetics

›Oral bioavailability approximately 71%

›Onset 1–2 hours; peak 2–3 hours; duration 6–12 hours

›Half-life approximately 3–5 hours

›Metabolism: hepatic — extensive first-pass metabolism

›Main metabolite: 2-oxo-3-hydroxy-LSD (inactive)

›Only approximately 1% excreted unchanged in urine

›Dose-dependent effects documented at 25, 50, 100, 200 micrograms

›Holze et al. 2021 (Neuropsychopharmacology): controlled dose-escalation study

›Schmid et al. 2015 (Biological Psychiatry): acute effects in healthy subjects

›Sympathomimetic and serotonergic toxidrome mechanism

›Sympathomimetic effects via 5-HT2A and noradrenergic activation

›Tachycardia, hypertension, hyperthermia, mydriasis

›Serotonin excess risk with co-administration of serotonergic agents

›SSRIs, SNRIs, MAOIs amplify serotonergic tone

›Complications pathophysiology

›Hyperthermia mechanism

›Muscular hyperactivity — not hypothalamic thermoregulatory failure

›Explains why antipyretics are ineffective

›Cascade: agitation → hyperthermia → rhabdomyolysis → AKI → MOF

›Hallucinogen Persisting Perception Disorder (HPPD)

›Persistent visual disturbances after acute drug clearance

›Pathophysiology incompletely understood — cortical hyperexcitability proposed

›Müller et al. 2022: flashback phenomena after LSD in controlled settings

Therapeutic Considerations

›No specific antidote for LSD exists

›Management is entirely supportive

›Benzodiazepines cornerstone of acute pharmacotherapy

›No role for physostigmine or naloxone specifically for LSD

›5-HT2A antagonists as targeted therapy

›Ketanserin — effectively blocks LSD effects in controlled studies

›Not widely clinically available

›Not recommended for routine ED use

›Cyproheptadine — indicated specifically for serotonin syndrome component

›Oral only formulation limits use in uncooperative patients

›Evidence basis for current management

›AHA 2023 Focused Update — cardiac arrest from toxicity (Lavonas et al.)

›Standard ACLS algorithms apply

›Supportive care emphasized

›AHA 2025 Guidelines Part 10 — Special circumstances of resuscitation (Cao et al.)

›ACEP 2017 Clinical Policy on Psychiatric Patients in ED (Nazarian et al.)

›Chemical sedation preferred over physical restraints alone — Level B

›Kim et al. 2021 (Expert Opinion on Drug Safety): pharmacologic agents for rapid tranquilization

›Avoid list — critical safety points

›Physical restraints without chemical sedation

›Associated with death from positional asphyxia and rhabdomyolysis

›Succinylcholine for intubation if rhabdomyolysis present

›Hyperkalemia from depolarizing blockade in injured muscle

›Antipyretics for LSD-associated hyperthermia

›Ineffective — mechanism is muscular, not hypothalamic

›MAOIs + LSD combination

›Increased serotonin syndrome risk

11Patient Discharge Instructions/pdi32

copy discharge instructions

›What happened to you

›You were seen in the emergency department for effects from LSD (lysergic acid diethylamide)

›LSD is a hallucinogen that affects how you see, hear, and feel things

›Effects typically last 6–12 hours but may take up to 24 hours to fully resolve

›Your tests and assessment showed that you are safe to go home

›You were given medication to help with anxiety and agitation during your visit

›What to expect at home

›Mild residual effects

›Some fatigue, mild mood changes, or mild visual disturbances may persist for up to 24 hours

›This is expected and should gradually improve

›HPPD (Hallucinogen Persisting Perception Disorder)

›Some people experience visual disturbances (halos, trailing images, visual snow) days to weeks after use

›Most cases resolve on their own within one year

›See a doctor if visual disturbances are persistent or distressing

›Return to the emergency department immediately for

›Severe anxiety, panic, or psychotic symptoms returning after leaving

›Suicidal thoughts or urges to harm yourself or others

›Visual disturbances that persist or worsen after drug effects should have resolved

›Fever, dark-colored urine, or severe muscle pain

›These symptoms may indicate a serious muscle breakdown condition

›Chest pain, palpitations, or difficulty breathing

›Seizure (shaking or loss of consciousness)

›Safety information

›Do not drive or operate machinery for at least 24 hours

›Do not use alcohol or other drugs, especially in the next 24–48 hours

›Stay with a trusted person who can monitor you

›Lock away all medications and substances in your home environment

12References/r44

Guidelines and key sources

›Simon MW, Olsen HA, Hoyte CO, et al. Clinical Effects of Psychedelic Substances Reported to United States Poison Centers: 2012 to 2022. Annals of Emergency Medicine. 2024

›PMID 39093248

›US Poison Center data 2012–2022; epidemiology and clinical outcomes

›Leonard JB, Anderson B, Klein-Schwartz W. Does Getting High Hurt? Characterization of Cases of LSD and Psilocybin-Containing Mushroom Exposures to National Poison Centers Between 2000 and 2016. Journal of Psychopharmacology. 2018

›PMID 30182795

›National Poison Center 2000–2016 LSD and psilocybin case series

›Kopra EI, Ferris JA, Rucker JJ, et al. Adverse Experiences Resulting in Emergency Medical Treatment Seeking Following the Use of LSD. Journal of Psychopharmacology. 2022

›PMID 35672900

›Adverse events leading to emergency care after LSD use

›Hinkle JT, Graziosi M, Nayak SM, Yaden DB. Adverse Events in Studies of Classic Psychedelics: A Systematic Review and Meta-Analysis. JAMA Psychiatry. 2024

›Systematic review of adverse events in controlled psychedelic studies

›Holze F, Vizeli P, Ley L, et al. Acute Dose-Dependent Effects of LSD in a Double-Blind Placebo-Controlled Study in Healthy Subjects. Neuropsychopharmacology. 2021

›PMID 33059356

›Controlled human dose-response study; pharmacodynamics

›Dolder PC, Schmid Y, Steuer AE, et al. Pharmacokinetics and Pharmacodynamics of LSD in Healthy Subjects. Clinical Pharmacokinetics. 2017

›PMID 28197931

›Pharmacokinetics: half-life, duration, dose-response relationship

›Holze F, Erne L, Duthaler U, Liechti ME. Pharmacokinetics, Pharmacodynamics and Urinary Recovery of Oral LSD in Healthy Participants. British Journal of Clinical Pharmacology. 2024

›PMID 37596682

›Urinary metabolite and pharmacokinetic characterization

›Lavonas EJ, et al. 2023 AHA Focused Update: Management of Patients With Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning. Circulation. 2023

›AHA toxicology-specific ACLS guideline update

›Cao D, Arens AM, Chow SL, et al. Part 10: Adult and Pediatric Special Circumstances of Resuscitation: 2025 AHA Guidelines. Circulation. 2025

›2025 AHA guidance on toxicologic cardiac arrest and resuscitation

›Nazarian DJ, Broder JS, Thiessen MEW, et al. ACEP Clinical Policy: Critical Issues in the Diagnosis and Management of the Adult Psychiatric Patient in the ED. Annals of Emergency Medicine. 2017

›ACEP evidence-based policy for agitation management; chemical sedation over restraints

›Boyer EW, Shannon M. The Serotonin Syndrome. New England Journal of Medicine. 2005

Evidence & Review

Evidence & Review