Presentation is loading. Please wait.

Presentation is loading. Please wait.

How to use remifentanil in general anaesthesia

Similar presentations


Presentation on theme: "How to use remifentanil in general anaesthesia"— Presentation transcript:

1 How to use remifentanil in general anaesthesia
ULT/SLK/05/19768/2 August 2005

2 How to use remifentanil in general anaesthesia
Properties of remifentanil Intra-operative control Recovery Reconstitution Dosing protocol for general anaesthesia Hypnotic sparing effects in general anaesthesia Post-operative pain management Summary References Prescribing information

3 Properties of remifentanil
Unique, very short-acting opioid, rapidly cleared by blood and tissue esterases1 Rapid onset of action: t1/2ke0 = 1.3 minutes1 Rapid offset of action: context-sensitive half-time = 3.65 minutes1 Predictable offset of action, independent of duration of infusion1 Pharmacokinetics are unaltered by obesity and renal or hepatic function1,2 Remifentanil is a μ-opioid receptor agonist with unique pharmacokinetic properties giving a rapid onset and offset of effect.1,2 Remifentanil is metabolised by non-specific blood and tissue esterases, offering organ-independent elimination.1 The metabolism of remifentanil results in the formation of an essentially inactive metabolite, remifentanil acid, which is 1/4600th as potent as the parent drug.1,2 t1/2ke0 is a parameter used to characterise the delay between peak blood drug concentration and peak pharmacodynamic effect utilising a theoretical effect compartment. Remifentanil has a rapid onset of action with a t1/2ke0 of 1.3 minutes.1 Context-sensitive half-time is defined as the time required to achieve a 50% decrease in drug concentration after termination of a continuous infusion targeted to maintain a constant concentration (the ‘context’ is the duration of the infusion). Remifentanil has a rapid offset of action with a context-sensitive half-time of 3.65 minutes.1 As remifentanil is metabolised by non-specific blood and tissue esterases it does not accumulate after long-term use resulting in an offset of action independent of duration of infusion.1,3–6 The pharmacokinetics of remifentanil are unaltered by obesity and renal or hepatic impairment.2,7 References Egan TD. Clin Pharmacokinet 1995; 29: 80–94. GlaxoSmithKline. Remifentanil HCl (Ultiva) for injection 1mg, 2mg and 5mg. Summary of Product Characteristics, June 2005. Beers R, Camporesi E. CNS Drugs 2004; 18: 1085–104. Schuttler J, Albrecht S, Breivik H et al. Anaesthesia 1997; 52: 307–17. Patel S, Spencer C. Drugs 1996; 52: 417–27. Bekker A, Berklayd P, Osborn I et al. Anesth Analg 2000; 91: 117–22. Glass P. J Clin Anesthesia 1995; 7: 558–63. Precise intra-operative control and fast, clear-headed recovery1 1. Egan TD. Clin Pharmacokinet 1995; 29: 80–94. 2. GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005.

4 Intra-operative control
Remifentanil is suitable for use in many different types of surgery1–5 Remifentanil’s fast onset and short duration of action enables rapid titration to effect6 Remifentanil offers a unique approach to the management of surgical patients by providing: More effective control of intra-operative responses than alfentanil or fentanyl7,8 More effective at maintaining haemodynamic stability than alfentanil or fentanyl5,9 Control in difficult-to-treat patients with renal or hepatic impairment, with no initial dose adjustment needed10-12 Remifentanil is suitable for use in many different types of surgery, including neurological,1 abdominal and gynaecological,2 cardiac,3 urological,4 ambulatory,5 laparoscopic6 and outpatient/day case7 The fast onset and short duration of action of remifentanil enables rapid titration to the desired clinical effects and precise tailoring of analgesia to the prevailing surgical conditions.8 Remifentanil offers greater control in response to surgical stress than alfentanil or fentanyl9,10 Patients receiving alfentanil (1 μg/kg/min) had more responses and more treated responses to surgical stimulation than patients receiving remifentanil (0.5 μg/kg/min) (p=0.005 and p=0.004 respectively).9 30% of patients on fentanyl (3 μg/kg at induction) responded to tracheal intubation compared to 13% on remifentanil (2 μg/kg followed by 0.4 μg/kg/min) (p<0.01).10 Remifentanil is more effective at maintaining haemodynamic stability than alfentanil or fentanyl7,11 Significantly fewer patients (p<0.05) treated with remifentanil experienced tachycardia and hypertensive episodes compared to those treated with fentanyl.7 Remifentanil more effectively attenuated haemodynamic responses, as demonstrated by blood pressure and heart rate, to anaesthetic and surgical stimuli than alfentanil (p<0.05).11 Remifentanil offers control in difficult-to-treat patients with hepatic impairment12-14 Hepatic dysfunction can alter the metabolism and elimination of fentanyl and alfentanil which are extensively hepatically metabolised12,13 The pharmacokinetics of remifentanil are unchanged in patients with hepatic impairment, so no initial dose adjustment relative to that used in healthy adults is required in these patients.12–14 Patients with severe hepatic impairment may be slightly more sensitive to the respiratory depressant effects of remifentanil. These patients should be closely monitored and the dose of remifentanil should be titrated to the individual patient need.14 Remifentanil offers control in difficult-to-treat patients with renal impairment13–14 Renal dysfunction may alter the rate of clearance of traditional opioids which have active metabolites13 The pharmacokinetics of remifentanil are not significantly changed in patients with renal impairment, so no dose adjustment is required in these patients.13-14 References 1. Sneyd J, Andrews C, Tsubokawa T. Br J Anaesth 2005; 94: 778–83. 2. Demirbilek S, Ganidagli S, Aksoy N et al. J Clin Anesth 2004; 16: 358–63. 3. Howie MB et al. Anesth Analg 2001; 92: 1084–1093. 4. Fish W. Anaesthesiology 1999;54:1002–6. 5. Philip BK, Scuderi PE, Chung F et al. Anesth Analg 1997; 84: 515–21. 6. Chung F, Mulier JP, Scholz J et al. Acta Anaesthesiol Scand 2000; 44: 790–98. 7. Mackey JJ, Parker SD, Nass CM et al. J Clin Anesthesia 2000; 12: 427–32. 8. Egan TD. Clin Pharmacokinet 1995; 29: 80–94. 9. Schuttler J et al. Anaesthesia 1997; 52: 307–317. 10. Sneyd JR, Camu F, Doenicke A et al. Eur J Anaesthesiol 2001; 18: 605–14. 11. Kallar SK et al. Anesthesiol. 1994; 81: A32. 12. Dershwitz M, Hoke J, Rosow F et al. Anesthesiology 1996; 84: 812–20. 13. Dershwitz M, Rosow CE. J Clin Anesthesia 1996; 8: 88S–90S. 14. GlaxoSmithKline. Remifentanil HCl (Ultiva) for injection, 1mg, 2mg and 5mg. Summary of Product Characteristics, June 2005. 1. Sneyd J et al. Br J Anaesth 2005; 94: 778–83. 2. Demirbilek et al. J Clin Anesth 2004; 16: 358–63. 3. Howie MB et al. Anesth Analg 2001; 92: 1084–93. 4. Fish W. Anaesthesiology 1999; 54: 1002–6. 5. Mackey J. et al. J Clin Anesth 2000; 12: 427–32. 6. Egan T. Pharmacokinet 1995; 29: 80–94. 7. Schuttler J et al. Anaesthesia 1997; 52: 307–317. 8. Sneyd J et al. Eur J Anaesthesiol 2001; 18: 605–14. 9. Kallar SK et al Anesthesiol 1994; 81: A32. 10. Dershwitz M et al. Anesthesiology 1996; 84: 812–20. 11. Dershwitz M et al. J Clin Anesthesia 1996; 8: 88S–90S 12. GlaxoSmithKline. Remifentanil HCl (Ultiva) SPC, June 2005.

5 Recovery Remifentanil provides fast, clear-headed recovery1–3
Recovery with remifentanil is more rapid than with fentanyl or alfentanil2,3 Remifentanil facilitates rapid extubation and reduces the need for ICU admission1–5 Remifentanil enables early post-operative neurological assessment1–3 Post-operative pain can be effectively managed6 Remifentanil provides fast, clear-headed recovery Patients on remifentanil responded to verbal commands 6.5 mins earlier (p<0.05), and were extubated 7.5 mins sooner compared with those on alfentanil (p<0.05).1 Elderly patients receiving remifentanil/desflurane anaesthesia were extubated sooner (4.1 minutes) compared with those receiving fentanyl/desflurane (8.2 minutes) (p<0.01).2 Time to extubation was significantly (P< 0.001) shorter for the remifentanil/nitrous oxide group compared with those receiving a isoflurane/nitrous oxide/fentanyl combination (6.8 ± 3.8 vs. 3.2 ± 2.1 minutes).3 Remifentanil reduces the need for ICU admission: The rapid offset of action with remifentanil4 is such that early and predictable extubation is possible after major surgery,2 avoiding the need for prolonged mechanical ventilation and admission to the ICU.5,6 Remifentanil enables earlier post-operative neurological assessment compared with fentanyl or alfentanil.1,2,7,8 It is recommended that for those patients undergoing surgical procedures where post-operative pain is anticipated, analgesics should be administered prior to the discontinuation of remifentanil.9,10 References 1. Kovac AL, Azad SS, Steer P et al. J Clin Anesthesia 1997; 9: 532–41. 2. Wilhelm W, Schlaich N, Harrer J et al. Br J Anaesthesia 2001; 86: 44–49. 3. Bekker A, Berklayd P, Osborn I. Anesth Analg 2000; 91: 117–22. 4. Egan TD. Clin Pharmacokinet 1995; 29: 80–94. 5. Park GR, Evans TN, Hutchins J et al. Eur J Anaesthesiol 2000; 17: 111–19. 6. Eberhart IJ, Eberspaecher M, Wulf H, Geldner G. Eur J Anaesthesiology 2004; 21: 107–14. 7. Cartwright DP, Kvalsvik O, Cassuto J et al. Anesth Analg 1997; 85: 1014–19. 8. Larsen B, Seitz A, Larsen R. Anesth Analg 2000; 90: 168–74. 9. GlaxoSmithKline. Remifentanil HCl (Ultiva) for injection, 1mg, 2mg and 5mg. Summary of Product Characteristics, June 2005. 10. Minkowitz HS, the Multicentre Investigator Group. Can J Anesth 2000; 47: 522–28. 1. Wilhelm W et al. Br J Anaesth 2001; 86: 44–9. 2. Kovac A et al. J Clin Anesth 1997; 9: 532–41. 3. Bekker A et al. Anesth Analg 2000; 91: 117–22. 4. Park G et al. Eur J Anaes 2000; 17: 111–19. 5. Eberhart L et al. Eur J Anaesthesiol 2004; 21: 107–14. 6. Minkowitz H. Can J Anesth 2000; 47: 522–28.

6 See factsheet: Reconstitution Guidelines
Available as lyophilised powder for reconstitution in 1mg, 2mg and 5mg vials To reconstitute add recommended diluent to powder in vial and shake well After reconstitution, further dilute to recommended dilution 50µg/ml is the recommended dilution for adults Target concentration Remifentanil vial size Total volume of recommended diluent required Volume of diluent required for reconstitution Volume of diluent required for dilution 50µg/ml 1mg 20ml 3ml 17ml 2mg 40ml 5ml 35ml 5mg 100ml 10ml 90ml See ‘Reconstitution Guidelines’ factsheet for further information. Excipients are Glycine Ph. Eur and Hydrochloric acid Ph. Eur. As glycine is present in the formulation, remifentanil is contra-indicated for epidural and intrathecal use. Remifentanil is contra-indicated in patients with known hypersensitivity to any component of the preparation and other fentanyl analogues. Storage Store at or below 25ºC. Remifentanil is stable for 24 hours after reconstitution and further dilution to recommended concentrations at room temperature. Remifentanil does not contain an antimicrobial preservative and thus care must be taken to assure the sterility of prepared solutions. Reconstituted product should be used promptly and any unused material discarded. Recommended diluents: Sterilised water for injections 5% dextrose injection 5% dextrose and 0.9% sodium chloride injection 0.9% sodium chloride injection 0.45% sodium chloride injection Remifentanil should only be admixed with recommended infusion solutions. DO NOT: Mix remifentanil with other therapeutic agents prior to administration. Administer remifentanil into the same intravenous line with blood/serum/plasma (non-specific esterases in blood products may hydrolyse remifentanil to its inactive metabolite). Reference GlaxoSmithKline. Remifentanil HCl (Ultiva) for injection, 1mg, 2mg and 5mg. Summary of Product Characteristics, June 2005. 20–25µg/ml is recommended for paediatric patients aged 1 year and over GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005.

7 Dosing protocol for general anaesthesia – induction
See factsheet: Dosing Protocol for General Anaesthesia Dosing protocol for general anaesthesia – induction Remifentanil is indicated as an analgesic agent for use during induction and/or maintenance of general anaesthesia under close supervision1 Induction of anaesthesia in adults:* Remifentanil: continuous infusion 0.5–1µg/kg/min1 Mackey et al used an infusion rate of 0.5µg/kg/min for 2 minutes prior to intubation2 Warner et al used an infusion rate of 0.5–1µg/kg/min for 1 minute prior to intubation3 Isoflurane: starting dose 0.5 MAC1 Propofol: starting dose 100μg/kg/min1 Details of infusion rates required for target dosages according to patient weight are supplied in the corresponding factsheet *When given by bolus injection at induction remifentanil should be administered over not less than 30 seconds1 See ‘Dosing Protocol for General Anaesthesia’ factsheet for further information. Administering remifentanil after a hypnotic agent will reduce the incidence of muscle rigidity. Reference GlaxoSmithKline. Remifentanil HCl (Ultiva) for injection, 1mg, 2mg and 5mg. Summary of Product Characteristics, June 2005. 1. GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005. 2. Mackey J. et al. J Clin Anesth 2000; 12: 427–32. 3. Warner DS. Anesth Analg 1999; 89: S33–39.

8 Dosing protocol for general anaesthesia – maintenance
See factsheet: Dosing Protocol for General Anaesthesia Dosing protocol for general anaesthesia – maintenance Maintenance of anaesthesia in adult ventilated patients: The administration of remifentanil should be individualised based on the patient’s response During anaesthesia, the rate of administration can be titrated: upward in 25–100% increments every 2–5 minutes downward in 25–50% decrements every 2–5 minutes When used with isoflurane: starting rate 0.25µg/kg/min (range 0.05–2µg/kg/min)* When used with propofol: starting rate 0.25µg/kg/min (range 0.05–2µg/kg/min)* See ‘Dosing Protocol for General Anaesthesia’ factsheet for further information. At recommended doses remifentanil significantly reduces the amount of hypnotic agent required to maintain anaesthesia: administration should be altered accordingly as shown in dosing tables to avoid excessive depth of anaesthesia. After endotracheal intubation, the infusion rate of remifentanil should be decreased, according to anaesthetic technique. Care should be taken to avoid inadvertent administration of remifentanil remaining in IV lines and cannulae. In obese patients the dosage of remifentanil should be based on ideal body weight rather than actual body weight. In elderly (> 65 years) patients, the initial starting dose should be half the recommended adult dose. In spontaneous ventilation anaesthesia the recommended starting dose of remifentanil is 0.04g/kg/min with titration to effect, and bolus doses are not recommended. For a quick reference to infusion rates, a remifentanil dosing wheel is available. Please contact your local remifentanil representative for a copy. Reference GlaxoSmithKline. Remifentanil HCl (Ultiva) for injection, 1mg, 2mg and 5mg. Summary of Product Characteristics, June 2005. *For cardiac patients refer to the Summary of Product Characteristics GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005.

9 Dosing protocol for general anaesthesia – summary
See factsheet: Dosing Protocol for General Anaesthesia Dosing protocol for general anaesthesia – summary SCHEMATIC REPRESENTATION ONLY Remifentanil at 0.25μg/kg/min1 Start remifentanil 0.5μg/kg/min1 Start propofol 100μg/kg/min1 Remifentanil: titrate as required1 Increments: 25–100% every 2–5 minutes Decrements: 25–50% every 2–5 minutes Range: 0.05–2.00μg/kg/min Remifentanil Propofol See ‘Dosing Protocol for General Anaesthesia’ factsheet for further information. Morphine Morphine 150–200μg/kg bolus more than 40 minutes before end of surgery2,3 STOP remifentanil and propofol INTUBATION EXTUBATION 1. GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005. 2. Muñoz HR et al. Br J Anaesth 2002; 88: 814–18. 3. Minkowitz H. Can J Anesth 2000; 47: 522–28.

10 Hypnotic sparing effects in general anaesthesia
See factsheet: Hypnotic Sparing Effects in General Anaesthesia Hypnotic sparing effects in general anaesthesia Remifentanil significantly reduces the amount of hypnotic agent required to maintain anaesthesia1 The doses of the following agents used in anaesthesia have been reduced by up to 75% when used concurrently with remifentanil: Isoflurane1 Thiopentone1 Propofol1 Temazepam1 Sevoflurane2 Starting doses of hypnotics are detailed on the corresponding factsheet See ‘Hypnotic Sparing Effects in General Anaesthesia’ factsheet for further information. 1. GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005. 2. Breslin DS et al. Anaesthesia 2001; 56: 114–19.

11 Hypnotic sparing effects in general anaesthesia
See factsheet: Hypnotic Sparing Effects in General Anaesthesia Hypnotic sparing effects in general anaesthesia Combining remifentanil with Isoflurane1 Sevoflurane2 Propofol3 0.05 µg/kg/min remifentanil is associated with a 50% reduction in isoflurane MAC Use of remifentantanil (0.34μg/kg/min) with low concentrations of sevoflurane (0.5 MAC) facilitates early recovery Increasing remifentanil concentrations produces a dose-dependent reduction in propofol requirements It is appropriate to maintain a low concentration of hypnotic agent and titrate remifentanil to produce adequate anaesthesia1-3 See ‘Hypnotic Sparing Effects in General Anaesthesia’ factsheet for further information. MAC = minimal alveolar concentration The recommended starting doses of hypnotics when used with remifentanil for induction of anaesthesia in adults, are outlined in the ‘Hypnotic Sparing Effects in General Anaesthesia’ factsheet. Combining remifentanil with isoflurane:1 A 50% reduction in isoflurane MAC is produced by a remifentanil whole blood concentration of 1.37 ng/ml (0.05 µg/kg/min) A remifentanil infusion rate of 0.15–0.30 µg/kg/min should provide adequate anaesthesia when combined with 0.4–0.5% isoflurane It is appropriate to maintain the isoflurane concentration and titrate the remifentanil concentration to achieve adequate anaesthesia Combining remifentanil with sevoflurane:2 Combining a low concentration of sevoflurane (0.5 MAC) with remifentanil titrated to effect gives the fastest emergence from anaesthesia compared with a high concentration of sevoflurane (1.5 MAC) Combining remifentanil with propofol:3 There is a dose-dependent reduction in propofol requirements with increasing remifentanil concentrations The most rational approach is to ensure a minimum concentration of propofol and titrate remifentanil to provide adequate anaesthesia remifentanil at an infusion rate 0.15–0.30µg/kg/min (4–8ng/ml whole blood concentration) References 1. Lang E et al. Anesthesiology 1996; 85: 721–28. 2. Breslin DS et al. Anaesthesia 2001; 56: 114–19. 3. Milne S et al. Br J Anaesth 2003; 90: 623–29. 1. Lang E et al. Anesthesiology 1996; 85: 721–28. 2. Breslin DS et al. Anaesthesia 2001; 56: 114–19. 3. Milne S et al. Br J Anaesth 2003; 90: 623–29.

12 MAC Reduction of Isoflurane with Remifentanil
See factsheet: Hypnotic Sparing Effects in General Anaesthesia MAC Reduction of Isoflurane with Remifentanil 1.8 Figure showing the reduction in isoflurane concentration to prevent movement at skin incision in 50% of patients by increasing measured remifentanil concentrations. The solid line is a logistic regression line for a patient aged 40 years. 1.6 Patient moved Patient did not move 1.4 1.2 1.0 Isoflurane Concentration (%) 0.8 0.6 See ‘Hypnotic Sparing Effects in General Anaesthesia’ factsheet for further information. Remifentanil significantly reduces the amount of hypnotic agent required to maintain anaesthesia. Therefore, isoflurane and propofol should be administered as recommended to avoid excessive depth of anaesthesia.1 The MAC reduction of isoflurane by remifentanil is similar to that produced by other opioids.2 A 50% isoflurane MAC reduction is produced by 1.37ng/ml remifentanil whole blood concentration compared to plasma concentrations of fentanyl (1.67ng/ml) or sufentanil (0.14ng/ml).2 References 1. GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005 2. Lang E et al., Anesthesiol 1996; 85: 721–28. 0.4 0.2 5 10 15 20 25 30 35 Remifentanil Concentration (ng/ml) Adapted from Lang E et al., Anesthesiol 1996; 85: 721–28.

13 Post-operative pain management
See factsheet: Post-operative Pain Management Post-operative pain management Due to the very rapid offset of action of remifentanil, no residual opioid activity will be present within 5–10 minutes after discontinuation, regardless of duration of infusion Post-operative analgesia, including choice of agent, dose and time of administration must be planned well in advance of remifentanil discontinuation Analgesics should be administered prior to discontinuation of remifentanil Sufficient time must be allowed to reach the maximum effect of the longer-acting analgesic The choice of analgesic should be appropriate for the patient’s surgical procedure and the level of post-operative care See ‘Post-operative Pain Management’ factsheet for further information. Effective analgesia has been established following remifentanil-based anaesthesia using:1 morphine (15mg) fentanyl (150µg) buprenorphine (300µg) piritramide (15mg). Tramadol and ketorolac have also been used successfully.2 References 1. Albrecht S, Fechner J, Geisslinger G et al. Anaesthesia 2000; 55: 315–22. 2. Mastronardi P, Dellacasa P. Minerva Anestesiol 2004; 70: 605–16. GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005.

14 Post-operative pain management
See factsheet: Post-operative Pain Management Post-operative pain management The dosage and timing of administration of the alternative long-acting analgesic agent should be considered to allow therapeutic effects to become established1 Minkowitz et al. achieved adequate post-operative pain management with a 150 or 200μg/kg bolus of morphine sulphate administered 30 minutes before the end of surgery2 Muñoz et al. used 150μg/kg morphine and showed a reduction in the number of patients requiring morphine in the post-anaesthesia care unit, when morphine had been given more than 40 minutes before the end of surgery3 See ‘Post-operative Pain Management’ factsheet for further information The dosage and timing of administration of the alternative long-acting analgesic agent should be considered to allow therapeutic effects to become established.1 Minkowitz demonstrated that morphine sulphate regimens (150 or 200 μg/kg) administered 30 minutes prior to the discontinuation of remifentanil are equally effective transitional analgesic regimens.2 A study of the effect of timing morphine (150 μg/kg IV) administration during remifentanil-based anaesthesia on early recovery from anaesthesia and post-operative pain demonstrated that the administration of morphine more than 40 minutes before the end of surgery has the advantage of reducing, by almost half, the number of patients requiring a second dose in the post-anaesthesia care unit compared with those who received morphine closer to the end of surgery.3 References 1. Lane M et al. Care Crit Ill 2002: 18: 2. Minkowitz HS, the Multicentre Investigator Group. Can J Anesth 2000; 47: 522–28. 3. Muñoz HR et al. Br J Anaesth 2002; 88: 814–18. 1. Lane M et al. Care Crit Ill 2002: 18: 2. Minkowitz H. Can J Anesth 2000; 47: 522–28. 3. Muñoz HR et al. Br J Anaesth 2002; 88: 814–18.

15 Special precautions for use
Due to the very rapid offset of action of remifentanil, post-operative analgesia must be planned well in advance of remifentanil discontinuation Care should be taken to avoid inadvertent administration of remifentanil remaining in IV lines and cannulae Muscle rigidity induced by remifentanil must be treated in the context of the patient's clinical condition with appropriate supporting measures including ventilatory support. Remifentanil should only be used in areas where facilities for monitoring and dealing with respiratory depression are available Hypotension and bradycardia may be managed by reducing the rate of infusion of remifentanil or the dose of concurrent anaesthetics or by using IV fluids, vasopressor or anticholinergic agents as appropriate Due to the very rapid offset of action of remifentanil, patients may emerge rapidly from anaesthesia and no residual opioid activity will be present within 5–10 minutes after the discontinuation of remifentanil. Therefore, analgesics should be administered prior to discontinuation of remifentanil. Sufficient time must be allowed to reach the maximum effect of the longer acting analgesic. Care should be taken to avoid inadvertent administration of remifentanil remaining in IV lines and cannulae. This may be done by administering remifentanil into a fast flowing IV line or via a dedicated IV line which is removed when remifentanil is discontinued. The incidence of muscle rigidity may be reduced by administering remifentanil after a hypnotic agent. Bolus injections should be administered over not less than 30 seconds. Muscle rigidity induced by remifentanil must be treated in the context of the patient's clinical condition with appropriate supporting measures including ventilatory support. Remifentanil should only be used in areas where facilities for monitoring and dealing with respiratory depression are available. Hypotension and bradycardia may be managed by reducing the rate of infusion of remifentanil or the dose of concurrent anaesthetics or by using IV fluids, vasopressor or anticholinergic agents as appropriate. Debilitated, hypovolaemic, and elderly patients may be more sensitive to the cardiovascular effects of remifentanil. Reference GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005 GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005.

16 Summary Rapid and easy titration to effect  titrate remifentanil rather than hypnotic Substantial hypnotic sparing effects The pharmacokinetic profile of remifentanil offers precise intra-operative control of anaesthesia and fast, clear headed recovery The rapid offset of action of remifentanil is independent of dose and duration Post-operative pain is easily managed if planned in advance

17 References Bekker A et al. The recovery of cognitive function after remifentanil-nitrous oxide anesthesia is faster than after an isoflurane-nitrous oxide-fentanyl combination in elderly patients Anesth Analg 2000; 91: 117–22. Breslin DS et al. Sevoflurane--nitrous oxide anaesthesia supplemented with remifentanil: effect on recovery and cognitive function Anaesthesia 2001; 56: 1149. Demirbilek S et al. The effects of remifentanil and alfentanil-based total intravenous anesthesia (TIVA) on the endocrine response to abdominal hysterectomy J Clin Anesth 2004; 16: 358–63. Dershwitz M et al. Pharmacokinetics and pharmacodynamics of remifentanil in volunteer subjects with severe liver disease. Anesthesiology 1996; 84: 812–20. Dershwitz M et al. The pharmacokinetics and pharmacodynamics of remifentanil in volunteers with severe hepatic or renal dysfunction. J Clin Anesthesia 1996; 8: 88S–90S. Eberhart L et al. Fast-track eligibility, costs and quality of recovery after intravenous anaesthesia with propofol-remifentanil versus balanced anaesthesia with isoflurane-alfentanil Eur J Anaesthesiol 2004; 21: 107–14. Egan TD Remifentanil pharmacokinetics and pharmacodynamics. A preliminary appraisal. Clin Pharmacokinet 1995; 29: 80–94. Fish W et al. Comparison of sevoflurane and total intravenous anaesthesia for daycase urological surgery Anaesthesiology 1999; 54: 1002–6. GlaxoSmithKline. Remifentanil HCl (Ultiva) Summary of Product Characteristics, June 2005. Howie MB et al. A randomised double-blinded multicenter comparison of remifentanil versus fentanyl when combined with isoflurane/propofol for early extubation in coronary artery bypass graft surgery. Anesth Analg 2001; 92: Kallar SK et al. A single, blind, comparative study of the safety and efficacy of remifentanil and alfentanil for outpatient anaesthesia. Anesthesiol 1994; 81: A32.

18 References continued Kovac A et al. Remifentanil versus alfentanil in a balanced anesthetic technique for total abdominal hysterectomy J Clin Anesth 1997; 9: 532–41. Lane M et al. The use of remifentanil in the critically ill Care Crit Ill 2002: 18: Lang E et al. Reduction of isoflurane minimal alveolar concentration by remifentanil Anesthesiology 1996; 85: 7218. Mackey J. et al. Effectiveness of remifentanil versus traditional fentanyl-based anesthetic in high-risk outpatient surgery J Clin Anesth 2000; 12: 427–32. Milne S et al. Propofol sparing effect of remifentanil using closed-loop anaesthesia Br J Anaesth 2003; 90: 6239. Minkowitz H. Postoperative pain management in patients undergoing major surgery after remifentanil vs. fentanyl anesthesia. Multicentre Investigator Group. Can J Anesth 2000; 47: 522–8. Muñoz H et al. Effect of timing of morphine administration during remifenanil-based anaesthesia on early recovery from anaesthesia and postoperative pain. Br J Anaesth 2002; 88: Park G et al. Reducing the demand for admission to intensive care after major abdominal surgery by a change in anaesthetic practice and the use of remifentanil Eur J Anaes 2000; 17: 111–9. Schuttler J et al. A comparison of remifentanil and alfentanil in patients undergoing major abdominal surgery. Anaesthesia 1997; 52: 307–317. Sneyd J et al. Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery Br J Anaesth 2005; 94: 778–83. Sneyd J et al. Remifentanil and fentanyl during anaesthesia for major abdominal and gynaecological surgery. An open, comparative study of safety and efficacy Eur J Anaesthesiol 2001; 18: 605–14. Warner DS. Experience with remifentanil in neurosurgical patients Anesth Analg 1999; 89: S33-9. Wilhelm W et al. Recovery and neurological examination after remifentanil-desflurane or fentanyl-desflurane anaesthesia for carotid artery surgery. Br J Anaesth 2001; 86: 44–9.

19 Prescribing information
PRESCRIBING INFORMATION: Ultiva (remifentanil hydrochloride). The following is for guidance only. Refer to Summary of Product Characteristics (SmPC) before prescribing. Ultiva is a very short acting opioid for injection/infusion. Indications: General Anaesthesia. Analgesia/sedation in ICU. Dosage: tailor to individual. Anaesthesia: Adults: Dilute to e.g. 50mcg/ml (2mg in 40 ml). Induction (not sole agent): 1mcg/kg bolus administered over not less than 30 seconds then 0.5 –1 mcg/kg/min. Reduce to 0.25mcg/kg/min (using e.g. propofol or isoflurane). Maintenance: 0.05 – 2 mcg/kg/min with 0.5 – 1mcg/kg bolus or alter infusion rate as needed. Due to rapid metabolism, no residual opioid activity will be present minutes after discontinuation. Where post-operative pain anticipated, analgesics should be administered prior to discontinuation of Ultiva. Spontaneous ventilation: Respiratory depression likely; ventilatory support may be required. Avoid inadvertent administration of Ultiva remaining in IV lines and cannulae. Elderly (over 65 years): initiate half adult dose. Children: see SmPC. Cardiac surgery: See SmPC. Intensive Care: Adults: 0.1 to 0.15mcg/kg/min. Increase by 0.025mcg/kg/min. If inadequate sedation at 0.2mcg/kg/hr add sedative. Elderly (over 65 years): No initial dose reduction required. Children: not recommended. Renal/hepatic impairment: No dosage adjustment necessary. Severe hepatic impairment may be slightly more sensitive to respiratory depressant effects. Contraindications: Epidural and intrathecal use. Known hypersensitivity to any ingredient or other fentanyl analogues. Not for use as sole induction agent. Warnings and Precautions: Administer only in appropriate setting. Interactions: As with other opioids, remifentanil decreases the requirements for inhaled and IV anaesthetics and benzodiazepines. Pregnancy and lactation: No adequate and well-controlled studies. Use only if potential benefit justifies potential risk to the foetus. Caution in nursing mothers. Insufficient evidence to recommend use during labour or Caesarean section. May cause respiratory depression in neonate. Undesirable effects: Acute respiratory depression, bradycardia, hypotension and/or skeletal muscle rigidity all resolve within minutes of discontinuation or decrease in the administration rate. Post-operative shivering, apnoea, hypertension, hypoxia, pruritus, constipation, aches, sedation, nausea and vomiting have also been reported. Very rarely, allergic reactions and bradycardia leading to asystole. As with other opioids remifentanil may produce dependency. Basic NHS Costs: Available as 1mg, 2mg and 5mg vials containing white/off-white powder for reconstitution to provide 1mg/ml remifentanil hydrochloride. 1mg vial x 5, £25.58, 2mg vial x 5, £51.15, 5mg vial x 5, £ Legal category: CD POM. Product Licence numbers: Ultiva 1mg PL19494/0026, Ultiva 2mg PL19494/0027, Ultiva 5mg PL19494/0028. Marketing Authorisation holder: GlaxoSmithKline UK Ltd, 980 Great West Road, Brentford, Middlesex TW8 9GS. Prescribing Information updated: February 2005.


Download ppt "How to use remifentanil in general anaesthesia"

Similar presentations


Ads by Google