Neuromuscular blocker
Cisatracurium (Nimbex)
Also called Nimbex
Indications
- Continuous paralysis during mechanical ventilation in the ICU, the usual infusion choice because its breakdown does not depend on the liver or kidneys
- ARDS with P/F under 150, for synchrony and oxygenation (SCCM 2026 conditional recommendation; ROSE 2019 found no mortality benefit from routine 48-h paralysis)
- Intubation and surgical relaxation in adults and children 1 month and older; not for rapid sequence intubation because onset is slow
- Paralysis in liver or kidney failure and in older adults
Dosing
Cisatracurium drip card and mL/h converterStart: 1–3 mcg/kg/min after a 0.15–0.2 mg/kg bolus
Mechanism of action
Cisatracurium blocks acetylcholine competitively at the postjunctional nicotinic receptor of the motor end plate. Its quaternary nitrogens bind the acetylcholine sites on the α subunits without opening the cation channel, so no end-plate potential forms and the fiber stays relaxed; prejunctional block produces fade on train-of-four. Neostigmine raises acetylcholine in the cleft and reverses the block once recovery has begun, while sugammadex cannot bind it.
Pharmacology
- Neuromuscular: intermediate-acting (ED95 0.05 mg/kg); doubling the dose adds about 25 min of block, and once recovery starts its rate does not depend on dose
- Cardiovascular: no dose-related change in blood pressure or heart rate up to 0.4 mg/kg (8 times ED95), because unlike atracurium it releases little histamine
- Respiratory: apnea; bronchospasm, flushing and rash are rare (0.1–0.4%)
- CNS: none directly; laudanosine is a CNS stimulant that causes seizures in animals, but ICU levels run about a third of those after atracurium (Boyd 1996)
- Other: hypothermia slows its breakdown, so CABG with induced hypothermia needs about half the infusion rate
Pharmacokinetics
| Onset | Maximal block 3.5 min after 0.15 mg/kg and 2.9 min after 0.2 mg/kg; good intubating conditions in 1.5–2 min; about 1 min slower in older adults and kidney failure |
|---|---|
| Duration | Clinically effective block 55 min after 0.15 mg/kg and 65 min after 0.2 mg/kg; recovery after ICU infusions about 50–55 min (range 20–270) |
| Context-sensitive half-time | Essentially context-insensitive: recovery after an infusion of any length matches recovery after a bolus |
| Half-life | 22–29 min; laudanosine about 3 h after surgery and 6.6 h after 24–48 h ICU infusions |
| Distribution | Vss about 0.145 L/kg, kept small by its size and high polarity |
| Protein binding | Not measurable, because it degrades at body pH and temperature during the assay |
| Metabolism | About 80% Hofmann elimination, a non-enzymatic breakdown in plasma and tissue into laudanosine and a monoquaternary acrylate (neither blocks the junction); plasma esterases turn the acrylate into a monoquaternary alcohol |
| Clearance | 4.5–5.7 mL/kg/min with little variation between patients; higher on chronic phenytoin or carbamazepine |
| Elimination | 95% in urine, mostly as conjugated laudanosine metabolites, and 4% in feces; under 10–15% unchanged |
| pH and temperature | Acidosis and hypothermia slow Hofmann elimination and prolong the block; alkalosis and warmth speed it |
| Organ failure | Recovery is unchanged in liver or kidney failure; laudanosine and the alcohol metabolite last longer there and may accumulate with long infusions |
Chemistry
- Benzylisoquinolinium diester: two tetrahydroisoquinolinium heads on a diester chain; a two-carbon bridge links each charged nitrogen to an ester carbonyl, so a base can pull off the hydrogen beside the carbonyl and split off the nitrogen (Hofmann elimination)
- Atracurium is a mixture of 10 stereoisomers; cisatracurium is its single 1R-cis,1′R-cis isomer, about 15% of the mixture and several times as potent, so smaller doses mean less laudanosine and little histamine release
- Permanently charged and very hydrophilic (log P −2.12), so it stays in extracellular fluid; laudanosine, a tertiary amine, enters the brain
- 2 mg/mL (10 mL multidose vials hold 0.9% benzyl alcohol) and 10 mg/mL (20 mL, for ICU infusions), acidified to pH 3.25–3.65 with benzenesulfonic acid because Hofmann breakdown slows in acid and cold
- Refrigerate at 2–8 °C away from light and do not freeze; at room temperature use within 21 days. Do not dilute in lactated Ringer's; incompatible with propofol, ketorolac and alkaline drugs at the Y-site
Adverse effects and cautions
In the one-pagers
- ARDSNeuromuscular blockade and sedation: Paralysis removes dyssynchrony, double-triggering and the large spontaneous efforts that add to transpulmonary pressure (patient self-inflicted lung injury) and lowers oxygen consumption. ACURASYS (Papazian 2010; 340 patients, P/F <150 within 48 h of onset) gave cisatracurium for 48 h: adjusted 90-day hazard ratio for death 0.68 (95% CI 0.48–0.98), crude 90-
- Ventilator Modes and SettingsSevere ARDS: recruitment, proning, paralysis, ECMO: ACURASYS 2010 (n = 340, P/F <150) gave cisatracurium for 48 h and found lower adjusted 90-day mortality (hazard ratio 0.68). ROSE 2019 (n = 1,006, P/F <150 on PEEP ≥8) compared the same regimen with light sedation and stopped for futility: 90-day mortality 42.5% vs 42.8%. ATS 2024 gives a conditional recommendation for neuromuscular blockad
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Sources
- FDA label: Nimbex (2018)
- FDA label: cisatracurium, Hikma (2025)
- Boyd 1996 (ICU laudanosine)
- SCCM ARDS neuromuscular blockade guideline (2026)
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