Thiopental (Thiopentone sodium)

# 1) Receptor-level action → clinical effects

**Primary:** **GABA-A positive allosteric modulator (PAM)**

* ↑ *duration* of Cl⁻ channel opening when GABA is bound; at higher concentrations can directly gate the channel → **neuronal hyperpolarisation** → hypnosis, anticonvulsant effects, ↓CMRO₂/CBF/ICP. ([DrugBank][1])

**Other receptor effects (lesser):**

* ↓ Excitatory transmission (AMPA/kainate) → adds to CNS depression (analgesia is *not* provided).

* Brainstem/reticular activating system depression → hypnosis.

**Clinical effects from the above:**

* **CNS:** rapid hypnosis; strong **neuroprotection** (↓CMRO₂, ↓CBF, ↓ICP). Anticonvulsant at anaesthetic doses.

* **CVS:** venodilation + myocardial depression → **hypotension** (worse if hypovolaemic/poor EF).

* **Resp:** dose-dependent **apnoea** / respiratory depression.

* **Airway:** cough, sneeze, laryngospasm can occur (avoid as sole agent for per-oral endoscopy). 

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# 2) Vial strength, preparation & basic PK (+ disadvantages)

**Supply / prep**

* Vials commonly **500 mg powder**; reconstitute to **2.5%** (500 mg in 20 mL) or **5%** (500 mg in 10 mL). Alkaline solution. Use soon after reconstitution per local policy. 

* **Never intra-arterial**; alkaline solutions cause intense vasospasm and tissue injury if extravasated/IA. 

**PK (what matters at the bedside)**

* **Onset ~30 s**, duration **5–10 min** (redistribution). Highly lipid-soluble; **high protein binding**; hepatic metabolism; elimination t½ hours → **accumulation** with repeats/infusion.

* **Disadvantages (from effects):** hypotension/apnoea; no analgesia; airway reactivity; accumulation → prolonged sedation; **porphyria precipitation** (class contraindication). 

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# 3) Practical dosing

## Induction (adult)

* Typical **3–4 mg/kg IV** (often in 2–4 small fractions and titrated). Reduce to **1–3 mg/kg** in frail/poor EF/hypovolaemia. ([OpenAnesthesia][2])

* For neuro cases needing blunting of ICP surges: similar dosing but titrate slowly with vasopressor ready.

## Neuro/ICU use (selected centres; protocol-driven)

* **Refractory intracranial hypertension or status epilepticus (barbiturate coma)**: load (e.g., 2–5 mg/kg) then **infuse ~3–5 mg/kg/h**, titrating to **EEG burst-suppression**; some protocols permit higher rates in short bursts. Expect hypotension and need for vasopressors; continuous EEG is essential. *Follow your unit’s protocol.* ([lhsc.on.ca][3])

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# 4) Special populations — dosing cautions

## Pregnancy

* Crosses placenta → neonatal depression possible; historically used, but **prefer alternatives** unless benefit outweighs risk (keep dose low if used). **Appears in breast milk** → consider temporary suspension just around induction if repeated doses are anticipated. 

## Lactation

* Small transfer; after a **single induction dose** breastfeeding is generally considered acceptable once the mother is awake and alert (local policies vary). 

## Hepatic impairment

* Hepatic metabolism → **reduce dose**; avoid prolonged/large repeat dosing due to accumulation. 

## Renal impairment

* Use **caution** in severe disease; titrate to effect; recovery may be prolonged. 

## Obesity (clinically useful even if not requested)

* Highly lipophilic (large Vd) → induction to **LBW/AdjBW**, then titrate carefully; avoid frequent top-ups to limit hangover. (General barbiturate pharmacokinetics support this approach.)

## Paediatrics

* Typical induction: **5–6 mg/kg** (higher in infants due to ↑Vd/clearance). Neonates more sensitive to respiratory depression; titrate slowly. ([OpenAnesthesia][2])

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# 5) Drug interactions (high-yield)

* **Synergistic CNS depression** with opioids/benzodiazepines/volatiles → **lower thiopental dose**; greater apnoea risk. 

* **Antihypertensives/vasodilators/ACE-Is/ARBs/β-blockers** → **enhanced hypotension** with induction. 

* **Sulfonamides / probenecid / metoclopramide / droperidol** can **potentiate** thiopental effects → reduce dose. 

* **Alcohol & other sedatives**: additive post-op sedation. 

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# 6) Significant complications (what to recognise + what to do)

* **Porphyria precipitation** (class effect) → **contraindicated** in acute porphyrias; choose a non-porphyrogenic agent. 

* **Accidental intra-arterial injection** → severe **arterial spasm** and burning pain; **leave needle in situ**, give **intra-arterial antispasmodic** (e.g., papaverine or local anaesthetic), consider **anticoagulation**, urgent vascular surgery consult; expect risk of ischaemia/necrosis. 

* **Extravasation** → local necrosis; cold compresses; follow local injury protocol. 

* **Prolonged sedation/airway events** after repeated doses.

* **During infusions for ICP control:** reported **severe/refractory hypokalaemia** with **rebound hyperkalaemia** on cessation → **close K⁺ monitoring** and controlled wean. 

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## Pocket viva line

*Thiopental is a barbiturate **GABA-A PAM** (prolongs Cl⁻ channel open time) causing rapid hypnosis and strong neuroprotection (↓CMRO₂/CBF/ICP) but with **hypotension**, **apnoea**, no analgesia, **porphyria risk**, and **accumulation** with repeated dosing; induction 3–4 mg/kg IV, and protocol-based ICU infusions for refractory ICP require EEG guidance and vasopressor support.* ([DrugBank][1])

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If you’re happy with this structure, tomorrow we can do **Ketamine** in the exact same template (including **Special Populations & Interactions**). Want me to also draft a **one-page printable card** for thiopental (with contraindication checklist and IA-injection rescue steps) for your pocket or ICU wall?

[1]: https://go.drugbank.com/drugs/DB00599?utm_source=chatgpt.com "Thiopental: Uses, Interactions, Mechanism of Action"

[2]: https://www.openanesthesia.org/keywords/thiopental/?utm_source=chatgpt.com "Thiopental - OpenAnesthesia"

[3]: https://www.lhsc.on.ca/critical-care-trauma-centre/thiopental-sodium-pentothal?utm_source=chatgpt.com "THIOPENTAL SODIUM (Pentothal)"