Remifentanil

1. REMIFENTANIL DR GEETANJALI S VERMA DEPT OF ANESTHESIOLOGY & CRITICAL CARE

2. PAIN IASP: unpleasant sensory or emotional experience associated with actual or potential tissue damage or described in terms of such damage. (1979) Types Duration Physiology intensity Tissue involved

3. REMIFENTANIL Methyl 1-(3-methoxy-3-oxopropyl)-4-( N - phenylpropanamido )piperidine-4-carboxylate Marketed by GlaxoSmithKline and Abbott as  Ultiva ) Twice as potent as fentanyl , and 100-200 times as potent as morphine. Blood brain equilibration similar to Alfentanil STRUCTURE: ester linkage

4. PKPD Opioid agonist inhibits ascending pain pathways, which causes alteration in response to pain; produces analgesia (increases pain threshold) respiratory depression, and sedation Pharmacokinetics Half-Life: 3-10 min (rapid recovery) Onset: 1-3 min (IV) Protein Bound: 70% Vd : 100 mL /kg (small Vd ) Clearance: 40 mL /min/kg (rapid) Excretion: Urine

5. Fundamental PK/PD Parameters

6. METABOLISM Hydrolysis by no specific plasma & tissue esterases to inactive metabolite Prinicipal metabolite= remifentanil acid Excreted by kidneys Tissue esterases preserved in hepatic & renal failure – no effect on PK N dealkylation – minor pathway

7. USES Induction of anesthesia 0.5-1 mcg/kg/min IV Maintainence of anesthesia 0.25-0.5 mcg/kg/min IV; may bolus with 0.5-1 mcg/kg q2-5min in response to light anesthesia or transient episodes of intense surgical stress Prevent laryngosc /intubation response Conscious Analgesia 1 mcg/kg IV bolus, followed by 0.05-0.2 mcg/kg/min IV Analgesia – imm post op 0.025-0.2 mcg/kg/min IV

8. ADVERSE EFFECTS >10%: Nausea, Vomiting 1-10%: Respiratory depression Bradycardia (dose dependent) Hypertension / Hypotension (dose dependent) Tachycardia Skeletal muscle rigidity (dose dependent) Postoperative pain Shivering Apnea Hypoxia Respiratory depression

9. STUDIES European Journal of Anaesthesiology: June 2013 - Volume 30 - Issue - p 225–225 Evaluation of analgesic and hypnotic effects of remifentanil by in vivo patch‐clamp recordings: 14AP8‐7 Shiokawa , H.; Yamaura , K.; Karashima , Y.; Hoka , S.; Megumu , Y.; Kumamoto Health Science University CONCLUSION: remifentanil blocks pain transfer to the brain without affecting the condition of consciousness.

10. STUDIES European Journal of Anaesthesiology: June 2013 - Volume 30 - Issue - p 259–259 Park, S. J.; Baek , J.; Choi , E.; Jee , D. Airway Management The inhibitive effect of remifentanil on complications associated with removal of the laryngeal mask airway: 19AP4‐2 The continuous infusion of remifentanil to effect‐site concentration at 1.0ng/ml during emergence can reduce the incidence of airway complications associated with removal of the LMA without any delay in LMA removal time.

11. STUDIES European Journal of Anaesthesiology: June 2012 - Volume 29 - Issue - p 32 Ambulatory Anaesthesia Analgo ‐sedation for colonoscopy: remifentanil vs propofol : 2AP1‐6 Mirabella, L.; Mollica , G.; Di Monte, P.; Spadaro , S.; Caggianelli , G.; Cinnella , G . The study suggests that analgo ‐sedation with low dose of remifentanil is a valid alternative to sedo ‐analgesia with propofol . Indeed, administration of an opioid so fast is just as effective, especially when loss of consciousness of the patient is not required under in environments NORA.

12. BJA 1998; 80:467-69 Effect of remifentanil on hempodynamic responses to orotracheal intubation Conclusion: remifentani attenuated repsonses to laryngoscopy & intubation but pre treatment with vagolytic agent may be reqd to minimise hypotension & bradycardia

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