REMIFENTANILDR GEETANJALI S VERMA

DEPT OF ANESTHESIOLOGY & CRITICAL CARE

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

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

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

Fundamental PK/PD Parameters

Fentanyl Alfentanil Sufentanil Remifentanil Morphine Methadone Meperidine HydromorphoneVolumes (l)

V1 12.7 2.2 17.8 4.9 17.8 7.7 18.1 11.5V2 50 7 47 9 87 12 61 115V3 295 15 476 5 199 184 166 968

Clearances (l/min)Cl1 0.62 0.20 1.16 2.44 1.26 0.13 0.76 1.33Cl2 4.82 1.43 4.84 1.75 2.27 2.19 5.44 3.45Cl3 2.27 0.25 1.29 0.06 0.33 0.38 1.79 0.92

Exponents (min-1)a 0.67 1.03 0.48 0.96 0.23 0.50 0.51 0.51b 0.037 0.052 0.030 0.103 0.010 0.025 0.031 0.012g 0.0015 0.0062 0.0012 0.0116 0.0013 0.0005 0.0026 0.0005

Half Lives (min)t 1/2 a 1.03 0.67 1.43 0.73 2.98 1.38 1.37 1.35t 1/2 b 19 13 23 7 68 28 22 59t 1/2 g 475 111 562 60 548 1377 271 1261

Blood Brain Equilibrationke0 (min-1) 0.147 0.770 0.112 0.525 0.005 0.110 0.067 0.015

t 1/2 ke0 (min) 4.7 0.9 6.2 1.3 139 6.3 10.3 46Tpeak (min) 3.7 1.4 5.8 1.6 93.8 11.3 8.5 19.6VD Peak Effect (l) 76.9 6.0 94.9 17.0 590.2 30.9 143.3 383.3

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

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 op0.025-0.2 mcg/kg/min IV

ADVERSE EFFECTS >10%: Nausea, Vomiting 1-10%:Respiratory depressionBradycardia (dose dependent)Hypertension / Hypotension (dose dependent)TachycardiaSkeletal muscle rigidity (dose dependent)Postoperative painShiveringApneaHypoxiaRespiratory depression

STUDIES European Journal of Anaesthesiology:June 2013 - Volume 30 - Issue - p 225–225Evaluation 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.

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.

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.

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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