Ropivacane: A new break through in regional and neuraxial Blockade


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Prof. Mridul M. Panditrao, discusses the merits and demerits of all the three, local anaesthetics, viz; loidocaine, bupivacaine and the new comer, Ropivacaine, their pharmacology, structual differences, comarison, dosing guide and his own experince and a controlled comparative trial

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Ropivacane: A new break through in regional and neuraxial Blockade

  2. 2. Dr. Mridul M. Panditrao Consultant Department of Anesthesiology & Intensive care Rand Memorial Hospital Freeport, Bahamas
  3. 3. Formerly: PROFESSOR & HEAD Department of Anaesthesiology & Critical Care Padmashree Dr. D.Y. Patil Medical College Pimpri, Pune
  4. 4. History: It all started with cocaine  Incas in South Americas chewed coca leaves as a euphoriant, dating back to 3000 B.C. (Erythroxylum coca, Coca Plant)  Numbness of tongue was considered as a temporary side-effect  1860: cocaine isolated coca leaves by Paolo Mantegazza, who tested it on himself.  1860: cocaine formulated into “Dr. Marianis French Tonic”, for which Dr. Mariani received a gold medal from Pope Leo XIII.  1884: cocaine used for topical ophthalmic anesthesia by Carl Koller (at the suggestion of Freud).
  5. 5. 1885 Advertisement !
  6. 6. History: more cocaine 1884: cocaine used for peripheral nerve block (Halstead) 1886: John S. Pemberton invented Coca Cola, combining cocaine with Cola nitida extract (kola nut). 1898: cocaine first for spinal anesthetic (Karl Gustav August Bier)  Personally developed PDPH, which he correctly diagnosed!
  7. 7. Modern local anesthetics 1932: Tetracaine 1943: Lignocaine (Lofgven and Lundquist) 1957: Mepivacaine 1960: Prilocaine 1963: Bupivacaine 1972: Etidocaine discovered  1973: Etidocaine lost 1996: Ropivacaine 1999: Levobupivacaine
  8. 8. Two types of linkages give rise to 2 chemicalclasses of local anesthetics. ESTER LINKAGE (1 EYE!) AMIDE LINKAGE (2 EYES!!) PROCAINE LIGNOCAINE procaine (Novocaine) lignocaine (Xylocaine) tetracaine mepivacaine (Carbocaine) (Pontocaine) bupivacaine (Anavin) benzocaine etidocaine (Duranest) cocaine ropivacaine (Ropin)
  9. 9. Lignocaine (Lignocaine) O N N Amide Linkage
  10. 10. SELECTIVE PHARMACOLOGICAL PROPERTIESOF SOME AMIDE - type LAAs LIGNOCAINE Most widely used LA  Effective by all routes.  Faster onset, more intense, longer lasting, than procaine.  Good alternative for those allergic to ester type  More potent than procaine but about equal toxicity  More sedative than others
  11. 11. Bupivacaine (Anawin) N * N N N * O O S Bupivacaine R Bupivacaine Enantiomer: levobupivacaine, Chirocaine Equipotent, but less cardiotoxic than bupivacaine
  12. 12. SELECTIVE PHARMACOLOGICAL PROPERTIESOF SOME AMIDE - type LAAs Bupivacaine  No topical effect  Slower onset and one of longer duration agents  Unique property of sensory and motor dissociation can provide sensory analgesia with minimal motor block  has been popular drug for analgesia during labor  More cardiotoxic than other LA
  13. 13. Acute Toxicity Main concern is CNS and Cardiac toxicity CNS  Tinnitus, dizziness, lightheadedness are early signs  Anxiety disorientation loss of consciousness seizures respiratory arrest Cardiac  Hypotension  All local anesthetics are negative inotropes  PVC wide QRS Multiform vtach vfib, or  Pattern with bupivacaine  Bradycardia asystole  Pattern with bupivacaine + lignocaine
  14. 14. Acute Toxicity With most drugs like Lignocaine, CNS toxicity precedes cardiac toxicity, providing a warning of impending disaster. With bupivacaine, acute toxicity rapidly progresses to cardiovascular collapse. Pregnancy enhances the risk of cardiac toxicity.
  15. 15. Neurotoxicity Lignocaine  Initially seen with formulation in 10% dextrose  Now seen with all formulations  No longer recommended for spinal anesthesia Bupivacaine appears free of neurotoxicity
  16. 16. Treatment of overdose Airway:  100% oxygen  Intubate if necessary to ventilate CNS:  Break seizure with propofol, thiopental, or midazolam Cardiovascular  Amiodarone has demonstrated efficacy. Use 300 mg  Lidocaine would be a particularly poor choice!  Resuscitation difficult with bupivacaine, more frequently successful in animal studies following ropivacaine and levobupivacaine overdose.
  17. 17. Dosing Guidelines(nerve block)Drug Onset Per Package Insert Local custom Duration Maximum With epinephrineAmides Lidocaine Rapid 4.5 mg/kg 7 mg/kg 900 mg with epi 1-2 h Mepivacaine Medium 6 mg/kg not given 750 mg 2-3 h Etidociaine Rapid 6 mg/kg 8 mg/kg N/A 4-8h Prilocine Medium 8 mg/kg 8 mg/kg N/A 1-2 h Bupivacaine Slow 2.5 mg/kg 3 mg/kg 200 mg 4 - 12 h Ropivacaine Slow 4 mg/kg No effect N/A 4-9h Levobupivacaine Slow 2 mg/kg (!) not given 300 mg 4-8hEsters Procaine Rapid 10 mg/kg 15 mg/kg N/A 15-30 min Chloroprocaine Very rapid 10 mg/kg 15 mg/kg 10 mg/kg 30-60 min Tetracaine Slow 1.5 mg/kg 2.5 mg/kg N/A 3h
  18. 18. What is Ropivacaine Hydrochloride? Ropivacaine is a long-acting, local anesthetic with both anesthetic and analgesic effects. At high doses it produces surgical anesthesia and at lower doses it produces analgesia (sensory block) with limited motor block.. 0.75% is indicated for surgical anesthesia 0.2% is indicated for postoperative pain relief .
  19. 19. Ropivacaine (Ropin) ® N N * O S bupivacaine NOnly available as pure S isomer * NCauses vasoconstrictionLess motor block than bupivacaine OOtherwise, equipotent anesthesia, but lesscardiotoxic
  20. 20. SELECTIVE PHARMACOLOGICAL PROPERTIESOF SOME AMIDE - type LA Ropivacaine  Enantiomer of propivacaine (S stereoisomer)  Structurally very similar to bupivacaine  No topical effectiveness  Clinically ~ equivalent to bupivacaine  Similar sensory versus motor selectivity as bupivacaine with significantly less CV toxicity (allegedly)
  21. 21. PHARMACOLOGY OF ROPIVACAINE  Ropivacaine is less lipid soluble  Less penetration in nerve fibers  Less motor block  Early mobilization  Early recovery
  22. 22. PHARMACOLOGY OF ROPIVACAINEcardio toxicity Less toxic effects to CVS Does not cause arrhythmias Does not cause ECG Changesneurotoxicity Less toxic effects to CNS Ropivacaine will not cause seizures, convulsions Visual and hearing disturbances, paraesthesia rarely
  23. 23. Comparison of LA characteristics Relative Relative onset pKa Local vasodilation Plasma lipid potency duration protein solubility binding lignocaine 4 4 rapid 7.9 moderate +++ 55% bupivacaine 130 16 slow 8.1 long + 90% ropivacaine N/A 12 rapid 8.1 long ± 94% RopivacainePlasma protein binding may be used as an indirect measure of tissue binding tendencies
  24. 24. L A As in Sub- Arachnoid Block ?Name Concen Onset Durati Reco pH Uses Toxicity tration (min.) on mmen (pKa) (%) (min.) ded Max. doseLignocaine 5 1-5 30-90 100 5.0-7.0 No More Neuro With mg (7.9) longer than Cardiac dextrose usedBupivacaine 0.5 1-15 75-200 20 4.0-6.5 Drug of More cardiac With mg (8.1) choice than Neuro dextrose at presentRopivacaine 0.75 ???? ???? ???? N.D. Epi/infi ????? In epi. (8.1) ltration 4mg/k g
  25. 25. Ropivacaine intrathecally ??? To find out the efficacy of 0.75% Ropivacaine isobaric given intrathecally for lower abdominal & lower limb surgeries : A prospective feasibility study
  26. 26. Aims & Objectives : To study the efficacy of 0.75% isobaric ropivacaine in sub-arachnoid block To observe any side- effects of 0.75% isobaric ropivacaine in sub-arachnoid block
  27. 27. MATERIALS & METHODSStringent Inclusion & Exclusion Criteria Age Range of 20 - 75 years Informed Consent ASA I- II Lower Limb/Abdominal & Gynaecological Surgeries Proper Pre-op. evaluation & preparation & I E C Approval
  28. 28. MATERIALS & METHODS NBM overnight All Monitoring Devices Pre-loading with Lactated Ringer – 10 ml/kg (nearly 500ml.) 15 min. prior All aseptic Precautions L2-L3 / L3- L4 space 26 Gz. Quinke’s Spinal needle Sitting or Lateral Position Midline intra-thecal approach
  29. 29. MATERIALS & METHODS 3.0 ml of Ropivacaine 0.75% isobaric after free flow of C S F Supine with 10°-15° Head Down A pillow under the head Pulse/ NIBP/ SpO2 X 5 min. for first 30 min. No interference by surgeons permitted till the desired level is achieved Infusion of R/L continued as per the requirement
  30. 30. MATERIALS & METHODS Assessment of Neuraxial Blockade Sensory Block: Pin-Prick test Observed till T5- T6 level is achieved Then permitted for surgical intervention Motor Block: Bromage Scale Grade Criteria Degree of block I Free movement of legs and feet Nil (0%) Just able to flex knees with free movement of II Partial (33%) feet Unable to flex knees, but with free movement of III Almost complete (66%) feet IV Unable to move legs or feet Complete (100%) Bromage PR. Philadelphia: WB Saunders; 1978: 144
  31. 31. MATERIALS & METHODS Intra-operative Management Continuous Monitoring Intake according to Blood loss/ Urinary output Side effects: N/V, Pain, Shivering, Pruritus, Sedation, Respiratory discomfort, Sensorium etc....,if any Residual neuraxial/ Wearing off of blockade noted Visual Analog Scoring (VAS) VAS More than 7 ….. Rescue Analgesia... Inj. Diclofenac Na 75mg I.M.
  32. 32. MATERIALS & METHODS Readings of Blockade : Observations To Time of Giving Spinal Analgesia T1 Time of Onset of Sensory Blockade T2 Time of Onset of Motor Blockade T3 Time to reach Maximum Sensory level T4 Time to two segment regression of sensory block T5 Time of Wearing off of Sensory Block T6 Time of Wearing off of Motor Block T7 First dose of rescue Analgesia
  33. 33. MATERIALS & METHODS Optimal Surgical Conditions Score (self-devised) Conditions 2 1 0No.1 Intra-operative Muscle relaxation Pronounced Minimal Nil2 Intra-operative Bleeding Minimum Moderate Excessive3 Post-operative Bleeding Minimum Moderate Excessive
  34. 34. Results Total Number of ASA I-II patients (N) = 40 Age Range = 23- 72 yrs. Sex : M = 26, F= 14 Specialty wise distribution: Gen. Surg.= 15, Ortho.=14 , Gyne. = 6, Uro.= 5
  35. 35. ResultsNO. Parameter Range Value Mean ± SD 1 Onset of Sensory block 10-300sec 69.9 ± 69.8 sec 2 Onset of Motor block 10-660sec 165.8 ± 161.7 sec 3 Peak of Sensory block 120-1320 sec 578.2± 298.0 sec 4 2 Segment Regression 60-177min 132.6 ± 36.97 min 5 Wearing off of Sensory block 62-180min 135.8 ± 34.63 min 6 Wearing off of Motor block 45-346min 118.8 ± 46.81 min 7 Time from Spinal to Rescue (1st 110-525min 255.32 ± 88.54 min Dose of Rescue)
  36. 36. Results Onset of Sensory block = 1.5 min. average Onset of Motor block = 3.5 min. average Peak of Sensory block = 10min. average 2 Segment Regression = nearly 2hrs. 30min. Wearing off of Sensory block = nearly 2hrs. 30min. Wearing off of Motor block = nearly 2hrs. st Time from Spinal to Rescue (1 Dose of Rescue) = nearly 4.5 hrs.
  37. 37. Results Intra-operative Vitals Profile & Events Pulse = minimal bradycardia ,< 2 - 5% of baseline NIBP = minimal Fall, < 3.5- 6.8% of baseline SpO2 = 100% , No change, either on room air or on O2 1 - 2 liters /min. No extra Fluid requirement No Pharmacological support required No specific side effects attributable to Spinal/ drug No sedation & comfort level of patients = adequate Optimal Surgical Conditions Score = 5 - 6
  38. 38. Results Post-operative Follow-up No Problems specific to Spinal/ Drug in first 24 hrs, next 72 hrs. or till the patients were discharged! On Follow-ups : No Complaints till now!
  39. 39. Results Encouraged by these observations & results Used In Lower Segment Caesarian sections (LSCS) Specific Modification in Protocol was: 2.0 ml of intra-thecal injection Strict watch was kept on APGAR of the neonate No fall in scores have been observed till now!
  40. 40. Discussion Comparative with other LAAParameter Lignocaine Ropivacaine BupivacaineOnset of Sensory block 1 - 5 min. 0.6 - 5 min. 1 – 15 min.Onset of Motor block 2 - 6 min. 0.6 - 11 min 3 – 20 minPeak of Sensory block 2 – 8 min. 2 - 22 min. 3 – 30 min2 Segment Regression 30 -90 min. 60 - 180 min 75 – 200 min.Wearing off of Sensory block 35 - 105 min. 60 - 180 min 80 - 210 min.Wearing off of Motor block 45 – 120 min. 45 - 346 min 80 – 240 min.Time from Spinal to Rescue 45 – 135 min. 110 - 525 min. 130 – 700 min.(1st Dose of Rescue)
  41. 41. Discussion Ropivacaine as Ropin® is available in 0.75%, 20 & 4 ml. Ropivacaine as Ropin® is available in 0.2%, 20 ml. Has been used for Peripherral Nerve Blocks & Epidurally * Has been used for Labour Analgesia epidurally * Proven to have a very wide safety margin and safety profile**Emanuelsson B.M. Ekblom A. Olofsson C. Reventlid H.: Ropivacaine 7.5 mg/ml for elective Caesarean section. A clinical andpharmacokinetic comparison of 150 mg and 187.5 mg. Acta anaesthesiologica scandinavica 1997, 41, 9, . 1149-1156 ;Kanai.A, Kinoshita S., Suzuki A., Okamoto H., Hoka S Advantage of ropivacaine for postoperative epidural analgesia following legorthopedic surgery [Article in Japanese] . Masui. 2005 Jan;54(1):8-13.Turner, G.; Blake, D.; Buckland, M. Continuous Extradural Infusion of Ropivacaine for Prevention of Postoperative PainAfter,Major Orthopedic surgery :; Survey of Anesthesiology:Regional Anestheisa and Pain Control, 1997, 44, 4, 213-219Emmanuel A, Fabienne B:Patient-Controlled Epidural Analgesia Versus Continuous Epidural Infusion with Ropivacaine forPostoperative Analgesia in Children, Anesth Analg 2003;97:1608–11
  42. 42. Discussion SDERTEaL J E , Article: AstraZenecas Local Anaesthetic Naropin Announced an Additional Approval for a New Route of Administration, Intrathecal (Spinal) use in the European Union (EU). 113834425.html, Jan-Mar 2004 Simpson D, Curran M, Oldfield V, Keating G : Ropivacaine A Review of its Use in Regional Anaesthesia and Acute Pain Management, Drugs 2005; 65 (18): 2675-2717
  43. 43. Conclusion Ropivacaine Intra-thecally : A feasibility study 3.0 ml. appears to be a safe dose Useful in all types of surgical procedures Onset of Sensory Block comparable to that of Lignocaine Onset of Motor Block comparable to that of Bupivacaine Peak of Sensory Block comparable to that of Bupivacaine 2 segment regression & Wearing of Sensory and Motor Block, Intermediate between both the drugs! Motor Recovery appears to be earlier than Sensory recovery Safety Profile appears to be adequate
  44. 44. Conclusion Ropivacaine has All the Advantages of both Lignocaine and Bupivacaine combined Although structurally it is similar to bupivacaine, some of the actions are like Lignocaine Being a Chiral Drug (S-enantiomer) there is definitely no Cardio- vascular toxicity Lesser Motor and Autonomic blocking action Provides Excellent Intra-operative conditions for both Surgeon as well as Anaesthesiologist Appears to be safe for both Mother as well as Newborn
  45. 45. Conclusion Post-operative course- early, intermediate as well as late : appears to be smooth, uneventful and adequate! No neurological, both short term as well as long term problems seem to have happened till now in any of the nearly 80 patients , we have studied (as confirmed by the follow up!) The dose of 3.0 ml used may be slightly on lower side! Peculiarly Motor block wears off earlier than Sensory!
  46. 46. Take Home Message ! We recommend 0.75% isobaric Ropivacaine for intra-thecal use, with all proper precautions & patient selection, in-depth & vigilant intra-operative monitoring and sincere post-operative follow-up, of short as well as long term!