PRE-OP II
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRE-OP II (PRE-OP II).
PRE-OP II (glycopyrrolate and neostigmine) reverses neuromuscular blockade by inhibiting acetylcholinesterase via neostigmine, increasing acetylcholine at the neuromuscular junction, while glycopyrrolate, an anticholinergic, mitigates muscarinic side effects.
| Metabolism | Neostigmine is metabolized by microsomal enzymes in the liver; glycopyrrolate is not significantly metabolized and is excreted unchanged in urine. |
| Excretion | Renal excretion (98% as unchanged drug), biliary/fecal (<2%) |
| Half-life | Terminal elimination half-life is 2-4 hours (prolonged in renal impairment; dose adjustment needed for CrCl <30 mL/min) |
| Protein binding | 94% bound to albumin |
| Volume of Distribution | 0.6-1.0 L/kg (moderate tissue distribution, consistent with limited peripheral uptake) |
| Bioavailability | Intramuscular: 90-100% (complete absorption); Oral: not clinically used (first-pass metabolism >95%) |
| Onset of Action | Intravenous: <1 minute; Intramuscular: 10-20 minutes; Oral: not applicable (preoperative use only) |
| Duration of Action | Intravenous: 1-2 hours (dose-dependent); Intramuscular: 30-90 minutes (sufficient for short procedures) |
1-2 mg/kg IV bolus once preoperatively; maximum dose 100 mg.
| Dosage form | SPONGE |
| Renal impairment | No adjustment required for GFR >30 mL/min; for GFR 10-30 mL/min, reduce dose by 50%; for GFR <10 mL/min, avoid use. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 50%; Child-Pugh Class C: contraindicated. |
| Pediatric use | 0.5-1 mg/kg IV bolus once preoperatively; maximum dose 50 mg. |
| Geriatric use | Reduce dose by 50% in patients >65 years; maximum dose 50 mg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRE-OP II (PRE-OP II).
| Breastfeeding | No data on excretion of PRE-OP II components into human milk. Both ketamine and xylazine are likely excreted in breast milk. M/P ratio not established. American Academy of Pediatrics considers ketamine to be usually compatible with breastfeeding, though caution advised due to potential CNS effects. Xylazine is not recommended during breastfeeding due to risk of sedation and hypotension in infant. Discontinue breastfeeding or drug based on importance of drug to mother. |
| Teratogenic Risk | PRE-OP II contains xylazine (a sedative/analgesic with alpha-2 adrenergic agonist activity) and ketamine (a dissociative anesthetic). There are no adequate studies in pregnant women. In animal studies, ketamine at high doses is associated with fetal neurotoxicity in late gestation. Xylazine has been shown to cause embryotoxic and fetotoxic effects in animals at high doses. Risk cannot be ruled out; use only if clearly needed. First trimester: Potential for teratogenic effects unknown. Second/Third trimester: Risk of maternal hypotension, reduced uterine blood flow, and fetal hypoxia. Near term: Neonatal respiratory depression and withdrawal symptoms possible. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to neostigmine or glycopyrrolate.","Mechanical obstruction of the intestinal or urinary tract.","Peritonitis or severe bradycardia."]
| Precautions | ["Bradycardia and hypotension may occur; administer with glycopyrrolate to prevent bradycardia.","Use caution in patients with coronary artery disease, asthma, or peptic ulcer disease.","May increase secretions and airway resistance."] |
Loading safety data…
| Fetal Monitoring | Continuous maternal monitoring of vital signs (heart rate, blood pressure, respiratory rate, oxygen saturation) during and after administration. Fetal heart rate monitoring if applicable. Monitor for maternal hypotension, bradycardia, respiratory depression, and excessive sedation. Assess neonatal status at delivery for signs of respiratory depression, sedation, and withdrawal if used near term. |
| Fertility Effects | No specific human studies on fertility. In animal studies, ketamine and xylazine may affect reproductive parameters. Ketamine at high doses caused decreased fertility in female rats. Xylazine has been associated with prolonged estrus cycles and reduced conception rates in some animal species. Significance in humans is unknown. |