Poisoning Overview & Toxidromes — SAQ

Stem

A 24-year-old man is brought to the emergency department unconscious, 30 minutes after being found by his flatmate next to empty blister packs on his bedside table. On arrival his GCS is 7 (E1 V2 M4), respirations 8 per minute and shallow, oxygen saturation 88% on room air, heart rate 48, blood pressure 84/50, pupils 2 mm and reactive, temperature 35.4 degrees C. He has needle-track marks but no other external signs. An ECG shows a sinus bradycardia with a QRS of 100 ms. Capillary glucose is 3.2 mmol/L. The flatmate reports a history of heroin use, depression treated with an unknown antidepressant, and chronic heavy alcohol intake.

Questions

a) Outline your immediate resuscitation in the first 5 minutes (ABCDE), naming each empirical treatment with drug, dose and route where an established dose exists. (3 marks)

b) Which toxidromes are competing as the dominant diagnosis, and which single finding best differentiates opioid overdose from each of the others? (2 marks)

c) Describe the specific naloxone regimen (drug, dose, route, target) and the rationale for an infusion rather than a single bolus. State two complications of naloxone. (2 marks)

d) The flatmate is unsure what tablets were taken. List the FOUR core bedside/blood investigations for this overdose of unknown composition, and state the bedside test you perform FIRST and why. (2 marks)

e) Name TWO classic management pitfalls in this scenario and how each is avoided. (1 mark)

Model answers

a) Resuscitation (ABCDE):

• Airway. He is in ventilatory failure with an unprotected airway. Open the airway and support ventilation now; ventilations alone may be all that is needed to prevent deterioration to cardiac arrest. Intubate on standard indications — failure to protect the airway, failure to oxygenate or ventilate, or haemodynamic collapse — not at an automatic GCS threshold. Do not wait for naloxone: opioid antagonists can require several minutes and repeated doses, so standard resuscitation is started immediately and continued until he is breathing normally. ^[10][1]
• Breathing. Support oxygenation and ventilation — give oxygen and assist ventilation with a bag-valve-mask while preparing for intubation. Ventilation is the intervention that prevents deterioration while the antagonist takes effect. ^[10]
• Circulation. Secure IV access and give an IV fluid bolus for the blood pressure of 84/50, adding vasopressors on standard indications if perfusion remains inadequate. Volume repletion improves haemodynamics and optimises elimination of some drugs. ^[1]
• Disability. Glucose 3.2 mmol/L — treat now. Adults are hypoglycaemic below 4.0 mmol/L, hypoglycaemia must be considered in every patient with altered consciousness, glucose is the brain's essential metabolic fuel, and IV glucose is the first-line strategy when oral glucose cannot be swallowed. ^[8] As an attributed pre-hospital example, Queensland Ambulance Service gives glucose 10% as 15 g (150 mL) IV initially, repeated as 10 g (100 mL) boluses every 5 minutes until the level is 4.0 mmol/L or above. ^[9] Give thiamine alongside the dextrose: the product label indicates thiamine injection where rapid restoration is necessary — as in Wernicke's encephalopathy — and when giving IV dextrose to individuals with marginal thiamine status, to avoid precipitating heart failure. The label's named regimens cover beriberi, so no empiric milligram dose for coma is stated from this source. ^[12] Then naloxone 0.04 mg IV with titration (see c). ^[2] Keep continuous cardiac monitoring until past the anticipated peak effect of the ingestion and until recovery. ^[1]
• Exposure. Complete the detailed assessment: undress, examine for injuries and further clues to the ingestion, and ask the flatmate to bring every medicine container so the risk assessment can establish what was taken, how much, how long ago, by whom and when. Involve a clinical toxicologist or poison control centre early — recommended in most cases. ^[1]

b) Competing toxidromes and the discriminating finding:

• The dominant toxidrome is opioid. The diagnostic combination in acute opioid intoxication is CNS depression, ventilatory depression under 10 breaths per minute, and miosis — his coma, respiratory rate of 8 and 2 mm pupils. The needle tracks make an opioid component likely, but the agent is unconfirmed. ^[2]
• Do not assume a single agent. Most opioid deaths involve additional substances that contribute to respiratory depression, and non-opioid sedatives commonly contribute and are typically not reversed by opioid antagonists. Benzodiazepines and ethanol were the commonest self-reported co-ingestants in the low-dose naloxone case series. ^[10][2]
• Against a sedative-hypnotic component: benzodiazepine overdose causes CNS depression and respiratory compromise through loss of protective airway reflexes, and a partial response to naloxone does not clear it — ventilatory support continues regardless. ^[10]
• Against a tricyclic antidepressant: the antidepressant history keeps TCA in play, and his QRS sits exactly at the 0.10-second threshold. In the prospective study of acute TCA overdose, a maximal limb-lead QRS of 0.10 second or longer defined the group with 34% seizures and 14% ventricular arrhythmias; ventricular arrhythmias occurred only at 0.16 second or longer, and serum drug levels were not predictive. That evidence comes from patients already poisoned by TCAs, so a QRS of 100 ms in this unknown ingestion neither confirms nor excludes TCA co-ingestion — continue cardiac monitoring. ^[6][1]
• The single most discriminating finding is pinpoint pupils with ventilatory depression. Miosis is the bedside sign that marks the opioid component, and a ventilatory response to titrated naloxone confirms it, because non-opioid sedatives are not reversed by opioid antagonists. Toxidromes help identify a poison when clinical information is lacking, but they do not replace the risk assessment. ^[2][10][1]

c) Naloxone regimen, infusion and complications:

• Regimen here (monitored, likely opioid-dependent adult): naloxone 0.04 mg IV, repeated every 2–3 minutes, titrated to adequate ventilation, not full consciousness — the aim of treatment is restoration of respiration rather than awakening. In the ED case series the median naloxone dose was 0.08 mg (range 0.04–0.12 mg). Limits: 15 patients, retrospective, predominantly methadone — this is monitored IV titration in opioid-dependent adults, not intramuscular dosing and not every overdose. ^[2][3]
• Emergency, community or life-threatening dosing differs: AHA 2025 gives adults 0.2–2 mg IV/IO/IM or 2–4 mg intranasal, repeated every 2–3 minutes as needed, titrated to reversal of respiratory depression and restoration of protective airway reflexes. The pharmacokinetic review describes titration to response after initial doses of 0.4–2 mg, balancing restoration of respiration against precipitated withdrawal. ^[10][3]
• Why an infusion rather than a single bolus: naloxone is cleared rapidly — half-life 60–120 minutes, with 1 mg IV acting about 2 hours — shorter than long-acting or slowly dissociating opioids, so respiratory depression can return as it wears off. Recurrent toxicity is the return of overdose symptoms after naloxone; it occurred in 72% of patients treated with titrated low-dose IV naloxone in one study, and a 31% overdose recurrence rate is reported in hospitalised patients. Infusion is for severe intoxications, large doses, and long-acting or slowly dissociating opioids; repeat boluses are the alternative. ^[3][10]
• Infusion regimen: AHA 2025 maintenance is two thirds of the waking dose per hour. The pharmacokinetic review separately describes an older, simulation-derived nomogram — half the effective bolus each hour plus a second half-dose 15 minutes after starting — a different calculation that must not be interchanged with the AHA regimen. ^[10][3]
• Two complications: (1) precipitated acute opioid withdrawal — nausea, vomiting and agitation occurred after as little as 0.08 mg in dependent patients, and precipitated withdrawal can be life-threatening, with acute respiratory distress, seizure and cardiac dysrhythmia described; (2) recurrent respiratory depression as the antagonist wears off before the opioid. Major complications are rare and dose-related. ^[2][3][10]

d) FOUR core investigations and the first test:

1. Bedside capillary glucose — FIRST. Hypoglycaemia must be considered in every patient with altered consciousness, glucose is the brain's essential metabolic fuel, and adults are hypoglycaemic below 4.0 mmol/L. It is already measured here (3.2 mmol/L) and treated in (a). ^[8]
2. 12-lead ECG — essential to the toxicological risk assessment; in acute TCA overdose the maximal limb-lead QRS predicts seizures and ventricular arrhythmias, and serum drug levels do not. ^[1][6]
3. Venous blood gas with routine chemistry including kidney function — part of the essential core of toxicological investigations. ^[1]
4. Drug assays — here paracetamol and salicylate concentrations. A salicylate concentration above 7.2 mmol/L (100 mg/dL) warrants extracorporeal treatment regardless of symptoms (EXTRIP 1D). ^[33]

The bedside test performed FIRST is capillary glucose: hypoglycaemia must be considered in every altered-consciousness patient, IV glucose acts rapidly, and the value is already abnormal here. ^[8][9]

e) Classic pitfalls and how each is avoided:

1. Empirical flumazenil for the unknown antidepressant with possible benzodiazepine. In the meta-analysis of randomised trials flumazenil caused more adverse events than placebo (risk ratio 2.85) and more serious adverse events (risk ratio 3.81), the commonest serious events being supraventricular arrhythmia and convulsions, and it should not be used routinely. In mixed overdose it may not fully reverse respiratory depression while increasing seizure and arrhythmia risk, and the risks likely exceed the benefit in undifferentiated coma. Avoided by reserving flumazenil for reliably low-risk settings, such as iatrogenic overdose during procedural sedation once chronic benzodiazepine dependence and dangerous co-ingestion are excluded. ^[5][10]
2. Delaying IV dextrose to give thiamine first. A literature review found no evidence above the level of case reports and concluded that a delay in giving glucose to hypoglycaemic patients cannot be recommended, with prompt thiamine alongside or after the return to normoglycaemia. A national 10-year Veterans Affairs study identified no Wernicke encephalopathy among 120 dextrose-first encounters — retrospective observational data, so absence of cases is not proof of zero risk. Treat the 3.2 mmol/L now and give thiamine concurrently; the label's indications for thiamine injection include use with IV dextrose when thiamine status is marginal, without an empiric-coma milligram dose. ^[7][4][12]

Other acceptable pitfalls: withholding ventilatory support while waiting for naloxone (support airway and breathing first) ^[10]; giving activated charcoal through an unprotected airway — strong guidance advises against charcoal when airway protective reflexes are absent without intubation, and intubation should not be performed solely to give charcoal unless clinically significant toxicity is anticipated ^[11]; and assuming a single agent, since most opioid deaths involve additional substances ^[10].

References13ShowHide

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12. [12]HF Acquisition Co LLC, DBA HealthFirst THIAMINE HYDROCHLORIDE INJECTION, SOLUTION injection, solution DailyMed; updated May 2026, 2026.Source
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