Monitor therapy, Ropivacaine: Propofol may increase the serum concentration of Ropivacaine. Note: If rapid effect is desired, may initiate with a higher infusion rate (eg, 100 to 150 mcg/kg/minute for 3 to 5 minutes) or administer an initial bolus (eg, 0.25 to 0.5 mg/kg) (Rosero 2020; manufacturer's labeling). • It is used to cause sleep during a procedure. Induction of general anesthesia: Children and Adolescents (healthy) 3 to 16 years, ASA-PS 1 or 2: IV: 2.5 to 3.5 mg/kg over 20 to 30 seconds; use a lower dose for ASA-PS 3 or 4. IV: 1.5 to 2 mg/kg once; usual dose range: 1 to 3 mg/kg. If used in a nonintubated and/or nonmechanically ventilated patient, qualified personnel and appropriate equipment for rapid institution of respiratory and/or cardiovascular support must be immediately available. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Note: Continuous infusion may be started if longer sedation is required (see "Mechanically Ventilated Patients in the ICU, Sedation") (Caro 2020; Roberts 2019; Stollings 2014). A holiday from propofol infusion should take place after 5 days of therapy to allow for evaluation and necessary replacement of zinc. • Hypotension: The major cardiovascular effect of propofol is hypotension especially if patient is hypovolemic or if bolus dosing is used. 40 seconds. Note: Use caution when administering high doses (>4 mg/kg/hour [>65 mcg/kg/minute]) for extended periods of time (>48 hours); monitor closely for adverse effects (eg, PRIS) (NCS [Brophy 2012]). Available for Android and iOS devices. Healthy adults, ASA-PS 1 or 2: IV: Usual total dose: 1 to 2.5 mg/kg. Propofol induction dose requirements may be reduced. Diprivan injection should be prepared for single patient use only, just prior to the initiation of each procedure. Soybean fat emulsion is used as a vehicle for propofol. Hypersensitivity to propofol or any component of the formulation; hypersensitivity to eggs, egg products, soybeans, or soy products; when general anesthesia or sedation is contraindicated. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Strong CNS depressants should not be coadministered with blonanserin. Dosage must be individualized based on total body weight and titrated to the desired clinical effect; wait at least 3 to 5 minutes between dosage adjustments to clinically assess drug effects; smaller doses are required when used with opioids; the following are general dosing guidelines (see "Abbreviations, Acronyms, and Symbols" section in front section for explanation of ASA-PS classes). See manufacturer's labeling. Use of propofol in a patient who has been taking rifampin may result in clinically significant hypotension. Metabolism Monitored anesthesia care: Note: For dosing in obese patients, use adjusted body weight for initial weight-based dosing (Schumann 2020). Propofol possesses sedative, anxiolytic, and anticonvulsant properties 46). Propofol, or 2,6-diisopropylphenol (C 12H 18O, MW = 178.271) is a simple molecule and its chemical structure is shown below. Based on the Neurocritical Care Society guidelines for the evaluation and management of status epilepticus, propofol can be used for the treatment of refractory status epilepticus in adults [NSG [Brophy 2012]]. Mechanically ventilated patients in the ICU, sedation: Note: Used as part of a multimodal strategy (eg, combination of sedatives and analgesics) for ICU sedation and preferred over a benzodiazepine due to less risk of prolonged sedation and improved time to extubation; titrate to maintain a light level of sedation (eg, Richmond Agitation Sedation Scale 0 to −2) or clinical effect (eg, ventilator synchrony) (SCCM [Devlin 2018]). If agitated after discontinuation of continuous infusion, then restart at ~50% of the previous maintenance dose (Jakob 2012; Kress 2000; Roberts 2009; SCCM [Barr 2013]; SCCM [Devlin 2018]). Monitor therapy, Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Titrate doses to cessation of electrographic seizures or burst suppression (Legriel 2017; NCS [Brophy 2012]; Rai 2018). • Analgesic supplementation: Propofol lacks analgesic properties; pain management requires specific use of analgesic agents, at effective dosages, propofol must be titrated separately from the analgesic agent. Monitor therapy, Terlipressin: May enhance the bradycardic effect of Bradycardia-Causing Agents. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. Monitor therapy, Bromopride: May enhance the CNS depressant effect of CNS Depressants. • Debilitated patients: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in debilitated patients to reduce the incidence of unwanted cardiorespiratory depressive events. Monitor therapy, Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Smaller doses are generally required in elderly patients and when used with opioids. Consider therapy modification, Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Mechanically ventilated patients in the ICU, sedation: Sedation of intubated, mechanically ventilated adults in the ICU. © 2020 Sedation Certification. Discontinue opioids and paralytic agents prior to weaning. Monitor therapy, Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. No votes so far! Consider therapy modification, Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Consider therapy modification, Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Propofol is not recommended by the manufacturer for obstetrical use, including cesarean section deliveries. Monitor therapy, Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. If, however, higher than necessary infusion levels have been maintained for a long time, propofol redistribution from fat and muscle to the plasma can be significant and slow recovery. • Anaphylaxis/hypersensitivity reactions: May rarely cause hypersensitivity, anaphylaxis, anaphylactoid reactions, angioedema, bronchospasm, and erythema; medications for the treatment of hypersensitivity reactions should be available for immediate use. Because Fresenius Propoven 2% contains double the concentration of propofol (20 mg/mL) compared to the FDA-approved propofol products (10 mg/mL), there is a risk of unintentional overdose. Mechanism of Action. Duration of action: An induction dose of propofol will have a clinical effect for approximately 10 minutes. Management: Patients on lomitapide 5 mg/day may continue that dose. IV: Loading dose: 1 to 2 mg/kg, followed by 0.5 to 2 mg/kg every 3 to 5 minutes until seizures are suppressed; maximum total dose: 10 mg/kg (Legriel 2017; NCS [Brophy 2012]; Rai 2018). Tubing and any unused portions of propofol vials should be discarded after 12 hours. Intravenous anesthetics are a group of fast-acting compounds that are used to induce a state of impaired awareness or complete sedation. • Myoclonus: Perioperative myoclonus (eg, convulsions and opisthotonos) has occurred with administration. Like the newer propofol derivatives, however, its safety in continuous infusion remains to be evaluated. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away: WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Note: The FDA has issued an emergency use authorization (EUA) during the coronavirus disease 2019 (COVID-19) pandemic to permit the emergency use of the unapproved product Fresenius Propoven 2% (propofol 20 mg/mL) emulsion. Long-term infusions can result in some tolerance; taper propofol infusions to prevent withdrawal. Monitor therapy, FentaNYL: Propofol may enhance the CNS depressant effect of FentaNYL. Some research has also suggested that the endocannabinoidsyste… Do not use if there is evidence of separation of phases of emulsion. If combined, limit the dosages and duration of each drug. Consider therapy modification, ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. Propofol has been proposed to have several mechanisms of action, both through potentiation of GABAA receptor activity and therefore acting as a GABAA receptor positive allosteric modulator, thereby slowing the channel-closing time, and at high doses, propofol may be able to activate GABAA receptors in the absence of GABA, behaving as a GABAA receptor agonist as well. An in vivo test in the rats was performed to measure the 50% effective dose (ED50) of the 4 propofol prodrugs. • ECG effects: In most cases, propofol does not significantly affect the QT interval (Staikou 2014). Health care providers should review the Fact Sheet for Health Care Providers for key differences between products: https://www.fda.gov/media/137889/download. However, in cases where general anesthesia is needed for cesarean delivery, propofol has been used as an induction agent (ACOG 209 2019; Devroe 2015). Maximum dose (not well defined and may vary by institution): 200 mcg/kg/minute. Monitor therapy, Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. IV. Monitor patient closely for evidence of CNS depression. desired time of emergence. Patients who develop hypertriglyceridemia (eg, ≥400 mg/dL) are at risk of developing pancreatitis. Propofol decreases the rate of dissociation of the GABA from the receptor, thereby increasing the duration of the GABA-activated opening of the chloride channel with resulting hyperpolarization of cell membranes. Consider therapy modification, DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. • American Society of Anesthesiologists - Physical Status (ASA-PS) 3 or 4 patients: Use a lower induction dose, a slower maintenance rate of administration, and avoid rapidly delivered boluses in ASA-PS 3 or 4 patients to reduce the incidence of unwanted cardiorespiratory depressive events. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Avoid combination, Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. • Pediatric neurotoxicity: In pediatric and neonatal patients <3 years of age and patients in third trimester of pregnancy (ie, times of rapid brain growth and synaptogenesis), the repeated or lengthy exposure to sedatives or anesthetics during surgery/procedures may have detrimental effects on child or fetal brain development and may contribute to various cognitive and behavioral problems. Sedation and regional anesthesia: Combined sedation and regional anesthesia in adults. Consider therapy modification, Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Consider therapy modification, Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Consider therapy modification, Valproate Products: May enhance the therapeutic effect of Propofol. Consider therapy modification. Propofol administration has many important advantages, such as a rapid onset of action—within seconds after administration—and a short duration of action—up to 15 minutes . There is a risk of unintentional overdose and extra precaution should be used to ensure appropriate product selection. Monitor therapy, Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. In a large report of a pediatric sedation program in >4,000 patients (age range: 1 month to 21 years), after an initial bolus of at least 2 mg/kg, an infusion was started at an initial rate of 9 mg/kg/hour (150 mcg/kg/minute) and titrated as required; supplemental doses of 1 to 2 mg/kg were used as needed; however, hypotension occurred in up to 42.5% of patients undergoing MRI and 23.2% of patients undergoing other procedures (Vespasiano 2007). Large volume of distribution; highly lipophilic; Vd: Adults: 2 to 10 L/kg; after a 10-day infusion, Vd approaches 60 L/kg; decreased in the elderly, Hepatic to water-soluble sulfate and glucuronide conjugates (~50%), Urine (~88% as metabolites, 40% as glucuronide metabolite); feces (<2%), Anesthetic: Bolus infusion (dose dependent): 9 to 51 seconds (average: 30 seconds), 3 to 10 minutes depending on the dose, rate and duration of administration; with prolonged use (eg, 10 days ICU sedation), propofol accumulates in tissues and redistributes into plasma when the drug is discontinued, so that the time to awakening (duration of action) is increased; however, if dose is titrated on a daily basis, so that the minimum effective dose is utilized, time to awakening may be within 10 to 15 minutes even after prolonged use, Biphasic: Initial: 40 minutes; Terminal: 4 to 7 hours (after 10-day infusion, may be up to 1 to 3 days). Note: FDA has issued an emergency use authorization (EUA) during the coronavirus disease 2019 (COVID-19) pandemic to permit the emergency use of the unapproved product, Fresenius Propoven 2% (propofol 20 mg/mL) emulsion for ICU sedation in mechanically-ventilated patients >16 years of age. Monitor therapy, Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Monitor therapy, Cannabis: May enhance the CNS depressant effect of CNS Depressants. Talk to your doctor if you have questions. • Injection-site reaction: Transient local pain may occur during IV injection; lidocaine 1% solution may be administered prior to administration or may be added to propofol immediately prior to administration to reduce pain associated with injection (see Administration). Pharmacology: Propofol produces loss of consciousness rapidly within 40 seconds of an intravenous injection. Management: Avoid coadministration of siponimod with drugs that may cause bradycardia. Monitor therapy, Midodrine: May enhance the bradycardic effect of Bradycardia-Causing Agents. Avoid combination, Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Note: Although the manufacturer's labeling lists egg allergy as a contraindication, available studies (mostly retrospective) and an American Academy of Allergy, Asthma, and Immunology statement have suggested that propofol may be used safely in soy- or egg-allergic patients (AAAAI [Lieberman 2015]; AAAAI 2019; Asserhøj 2016; Dziedzic 2016; Murphy 2011). Distribution half-life is about 2 to 5 minutes. • Infection risk: Propofol vials and prefilled syringes have the potential to support the growth of various microorganisms despite product additives intended to suppress microbial growth. Even small boluses (1 2 cc) may cause apnea, especially following a premed. Diprivan: Monitor zinc levels in patients predisposed to deficiency (burns, diarrhea, major sepsis) or after 5 days of treatment. Consider therapy modification, Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Specifically the development of opisthotonus (severe hyperextension and spasticity resulting in arching or bridging position) and/or tonic clonic seizures. To reduce pain associated with injection, use larger veins of forearm or antecubital fossa; lidocaine IV (1 mL of a 1% solution) may also be used prior to administration or it may be added to propofol immediately before administration in a quantity not to exceed 20 mg lidocaine per 200 mg propofol. An alternative sedative agent should be employed if significant hypertriglyceridemia occurs. It has an extremely short duration of action of about 5 to 10 minutes, with complete recovery in as little as 20 to 30 minutes. • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat. Management: Consider alternatives to this combination when possible. Absorption. Monitor therapy, Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Subscribe to Drugs.com newsletters for the latest medication news, new drug approvals, alerts and updates. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. The figure below illustrates the fall of plasma propofol levels following infusions … MOC etomidate is less potent than the etomidate and propofol and given its brief duration of action, maintaining anaesthesia by infusion will require relatively large doses. • Sulfites: Some formulations may contain sulfites. Monitor therapy, Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. 0.5 – 1.0mg/kg infused slowly and titrated to desired effect. The prolonged or repeated administration will accumulate in peripheral tissues and will cause an increased duration of action. Monitor therapy, Siponimod: Bradycardia-Causing Agents may enhance the bradycardic effect of Siponimod. Propofol Dosing Caveats. Maintenance of general anesthesia: Infants ≥2 months, Children, and Adolescents (healthy), ASA-PS 1 or 2: IV infusion: General range: 125 to 300 mcg/kg/minute (7.5 to 18 mg/kg/hour); Initial dose immediately following induction: 200 to 300 mcg/kg/minute; then decrease dose after 30 minutes if clinical signs of light anesthesia are absent; usual infusion rate after initial 30 minutes: 125 to 150 mcg/kg/minute (7.5 to 9 mg/kg/hour); younger pediatric patients may need higher infusion rates than older pediatric patients. 25 – 50mg (0.5 – 1 mg/kg) IV, administered in 10 mg increments over several minutes. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. Continuous IV infusion: Initial: 25 to 75 mcg/kg/minute; titrate to adequate sedation. Propofol use was approved by the food and drug administration (FDA) in November 1989 44). This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Alfentanil use with propofol has precipitated seizure activity in patients without any history of epilepsy. Fresenius Propoven 2% (20 mg/mL) is composed of medium and long-chained triglycerides and is double the concentration of the FDA-approved propofol 1% (10 mg/mL) products (eg, Diprivan). Sleep deprivation reduced the time to loss of righting reflex by 40% for propofol (P < 0.025) and 55% for isoflurane (P < 0.025) and prolonged the time to recovery. Monitor therapy, Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Abrupt discontinuation can result in rapid awakening, anxiety, agitation, and resistance to mechanical ventilation; wean the infusion rate so the patient awakens slowly. Four protons and electrons reduce oxygen to water. Shake well before use. To limit the potential for contamination, strictly adhere to recommendations in product labeling for handling and administering propofol. If blood pressure lowering therapy cannot be held, do not administer amifostine. Cardiac monitor, blood pressure, oxygen saturation (during monitored anesthesia care sedation), arterial blood gas (with prolonged infusions). Continuous IV infusion: Usual dosing range: 50 to 100 mcg/kg/minute; titrate to clinical response. The drug is unrelated to any of the currently used barbiturate, opioid, benzodiazepine, arylcyclohexylamine, or imidazole intravenous anesthetic agents. Short-acting, lipophilic sedative/hypnotic; causes global CNS depression, presumably through agonist actions on GABAa receptors. IV: Administer intermittent bolus or by continuous IV infusion. Pediatric patients may be at greater risk. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Has a rapid onset (about 40 seconds) and a short duration of action. Diprivan: 100 mg/10 mL (10 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL); 1000 mg/100 mL (100 mL) [contains edetate disodium, egg phospholipids (egg lecithin), glycerin, soybean oil], Fresenius Propoven: 2000 mg/100 mL (100 mL) [contains egg phosphatides, soybean oil], Generic: 1000 mg/100 mL (100 mL); 200 mg/20 mL (20 mL); 500 mg/50 mL (50 mL). Monitor therapy, Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Structure: Propofol 5. The mean duration of action of vecuronium injected through the venous line infused with propofol was 32.3 +/- 9.0 (min), while that for vecuronium injected through the venous line without propofol was 32.1 +/- 8.6 (min). Alternate sedative therapy should be considered for patients with escalating doses of vasopressors or inotropes, when cardiac failure occurs during high-dose propofol infusion, when metabolic acidosis is observed, or in whom lengthy and/or high-dose sedation is needed (Corbett 2008; SCCM [Barr 2013]). Monitor therapy, Alfentanil: May enhance the adverse/toxic effect of Propofol. No such dose change is recommended for women. Propofol may increase the serum concentration of Midazolam. ICU sedation: Assess and adjust sedation according to scoring system (Richmond Agitation-Sedation Scale or Sedation-Agitation Scale) (SCCM [Devlin 2018]); assess CNS function daily. However, prolongation of the QT interval, usually within normal limits, has occurred in case reports and small prospective studies and may be dose dependent (Hume-Smith 2008; Kim 2008; McConachie 1989; Saarnivaara 1990; Saarnivaara 1993; Sakabe 2002). Monitor therapy, Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. We comply with the HONcode standard for trustworthy health information -, https://www.fda.gov/media/137889/download. • Increased intracranial pressure: Use with caution in patients with increased intracranial pressure or impaired cerebral circulation; substantial decreases in mean arterial pressure and subsequent decreases in cerebral perfusion pressure may occur; consider continuous infusion or administer as a slow bolus. Management: Monitor closely for evidence of excessive CNS depression. The ACOG recommends that pregnant women should not be denied medically necessary surgery, regardless of trimester. Believing that propofol was "used all the time in ICU," a gastroenterologist asked … Monitor therapy, RifAMPin: May enhance the hypotensive effect of Propofol. Consider therapy modification, Tacrolimus (Systemic): CYP3A4 Inhibitors (Weak) may increase the serum concentration of Tacrolimus (Systemic). Use with caution in patients with preexisting hyperlipidemia as evidenced by increased serum triglyceride levels or serum turbidity. Refer to local/state regulations and institutional policies and procedures regarding administration and monitoring requirements. Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. Monitor therapy, Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Avoid combination, Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Consider therapy modification, Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Serum triglyceride levels should be obtained prior to initiation of therapy and every 3 to 7 days thereafter. Do not use if contamination is suspected. Neurocritical Care Society guidelines for status epilepticus state that use of propofol in young children is contraindicated (NCS [Brophy 2010]): Initial propofol infusion: IV: Loading dose 1 to 2 mg/kg, then initiate continuous IV infusion at 1.2 mg/kg/hour (20 mcg/kg/minute); titrate to desired effect (eg, burst suppression on EEG); usual range: 1.8 to 12 mg/kg/hour (30 to 200 mcg/kg/minute) (NCS [Brophy 2012]). • Opioids: Concomitant use may lead to increased sedative or anesthetic effects of propofol, more pronounced decreases in systolic, diastolic, and mean arterial pressures and cardiac output; lower doses of propofol may be needed. Monitor therapy, Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Debilitated or ASA-PS 3 or 4: IV: Usual total dose: 0.5 to 1.5 mg/kg. Be the first to rate this post. The mechanism of the syndrome has yet to be determined. The onset of the syndrome is rapid, occurring within 4 days of initiation. Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Mechanism of action, structure-activity relationships, and drug delivery Curr Med Chem. Monitor therapy, CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy, Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression).
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