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The place of Sugammadex (Bridion ® ) in laparoscopic bariatric surgery

The place of Sugammadex (Bridion ® ) in laparoscopic bariatric surgery. 1150 1850 1947 1977 2010 . Jan Paul Mulier, MD PhD Sint Jan Brugge-Oostende. Overview. Current state of reversal

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The place of Sugammadex (Bridion ® ) in laparoscopic bariatric surgery

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  1. The place of Sugammadex (Bridion®) in laparoscopic bariatric surgery 1150 1850 1947 1977 2010 Jan Paul Mulier, MD PhD Sint Jan Brugge-Oostende 4 03 2010 J P Mulier

  2. Overview • Current state of reversal • Limitations / Potential risks with residual blockade • Techniques to reduce need for reversal • Reversal with bridion® (Sugammadex) • Mechanism of action / Pharmacokinetics, pharmacodynamics • Efficacy / Safety - Practical dosage • Indications for bridion ® (Sugammadex) • “Can not intubate / can not ventilate” • Rapid sequence induction for short procedures • Continuous deep blockade till end of surgery • Sudden / not predicted / need for awakening • Need for an amfetamine like arousal effect • Practical use in bariatric laparoscopy • Anaesthesia induction • Anaesthesia maintenance • Anaesthesia awakening ERAS technique of Bruges 4 03 2010 J P Mulier

  3. Limitations of Cholinesterase Inhibitors Relatively slow in reversing neuromuscular blockade Insufficient or impossible to reverse deep blockade Require concomitant administration of anticholinergics Well-known side effect profile Bartkowski RR. Anesth Analg. 1987;66:594-598. Kim KS et al. Anesth Analg. 2004;99:1080-1085. Kopman AF et al. J Clin Anesth. 2005;17:30-35. 4 03 2010 J P Mulier

  4. Neostigmine (50 µg/kg) Inadequately Reverses 95% Twitch Depression Vecuronium Protocol T1 = 100% Hatched area = height of T1 T1 = 50% Solid area = height of T4 NEO administered 10 min 20 min 30 min Rocuronium Protocol NEO, neostigmine; ROC, rocuronium; TOF, train-of-four. Kopman AF et al. J Clin Anesth. 2005;17:30-35. 4 03 2010 J P Mulier

  5. Side Effects Associated With Current Reversal Agents ChE inhibitors in the reversal can cause Bradycardia / Hypersalivation Bronchospasm / Increased bronchial secretions Urinary frequency / Nausea and vomiting Coadministration of antimuscarinic agents Tachycardia Dryness of mouth and nose Mydriasis / Urinary retention Neostigmine Methylsulfate Injection [package insert]; 2002. Atropine Sulfate Injection, USP [package insert]; 2003. Glycopyrrolate Injection, USP [package insert]; 2006. ChE, cholinesterase. *Atropine use causes dose-dependent adverse effects. 4 03 2010 J P Mulier

  6. Increased Risk AssociatedWith Residual Blockade Increased risk of postoperative pulmonary complications coughing, expectoration, pain when breathing, increased risk of aspiration; Hypoxemia, hypercapnia, the need for reintubation, non invasive ventilation delay in meeting PACU discharge criteria and achieving actual discharge Berg H et al. Acta Anaesthesiol Scand. 1997;41:1095-1103. Bissinger U et al. Physiol Res. 2000;49:455-462. Eikermann M et al. Anesth Analg. 2006;102:937-942. Murphy GS. Minerva Anestesiol. 2006;72:97-109. PACU, post anaesthesiology care unit 4 03 2010 J P Mulier

  7. What was our answer before Bridion? • Waiting for reversal before awakening, extubation and transfer to PACU • Turnover time increased or ventilation in PACU • Incomplete reversal at extubation • If patient can breath it is oke? • If patient can lift head it is oke? • Ad midazolam so patients are not aware? • Earlier decurarisation (spont or neostigmine) • Is every surgeon happy? • Extra dose neostigmine • has only little effect but could even worsen decurarisation. • Inject water instead of NMB • To make your surgeon happy? • Be a transdisciplinary team • do you really know what surgeons think? 4 03 2010 J P Mulier

  8. My technique (before Bridion) to reduce the need for reversal in laparoscopy Measure Abdominal Compliance • Measure abdominal compliance and give less relaxants if Compliance is large. • Or use 2 MAC deep inhalation anaesthesia at end surgery. • Use pressure support ventilation to prevent patient from breathing against ventilator. 4 03 2010 J P Mulier

  9. Are NMB needed ? • Gynecologic laparoscopy without curare is possible. • Chassard D. Ann Fr Anesth Reanim. 1996;15(7):1013-7 • Only when compliance is very high? • Or when surgeons do not complain? 4 03 2010 J P Mulier

  10. APVR description • Measure pressure volume relation • Angle is compliance or elastance E • Section with Y axis is PV0: pressure at zero vol P = 3,30 V + 8,40 mmHg Squared R = 0,96 E : 3,3 mmHg/L PV0 : 8,4 mmHg 4 03 2010 J P Mulier

  11. E en PV0 determined by ? • Mulier Dillemans ESA 2007 4 03 2010 J P Mulier

  12. No muscles in abd wall, diaphragm ? Fully relaxed by other factors ? Patient with no effect of NMB • TOF > 90% • TOF = ¼ • TOF 0/4 and PTC < 5 4 03 2010 J P Mulier

  13. Why NMB sometimes have no effect on APVR? • Muscle total relaxed before giving NMB. • Deep anesthesia? • Volatile anesthetics? • Muscle very thin or non existent • Muscle fascia parallel 4 03 2010 J P Mulier

  14. Zelfde spier relaxatie effect sevo en desfl data JPMulier 2009 Pig: High dose desfl sevo 4 03 2010 J P Mulier

  15. Valsalva is an active muscle contraction different from breathing to increase the abdominal pressure Happens when patient reacts on Controlled Ventilation Effect of valsalva: breathing against ventilator 4 03 2010 J P Mulier

  16. J Mulier ISPUB 2009 Pressure volume relation is linear PV0 and E define each patient J Mulier IFSO 2007 BMI effect on abdominal P/V relation 4 03 2010 J P Mulier

  17. Android versus Gynoid fat distribution has a different Elastance 4 03 2010 J P Mulier

  18. Waist to Hip ratio (WHR) • Man normal WHR: 0,9 • Woman normal WHR: 0,7 • Android fat distribution • WHR > 0,8 • Gynoid fat distribution • WHR < 0,8 4 03 2010 J P Mulier

  19. Remember:Patient type with a high mortality risk • Elderly male diabetes patient with hypertension and being super obese, no weigth loss. • Buchwald 2007 • Central abdominal fat, not stopped smoking, alcoholic • General risk • Asthma and coronary artery disease • Cardio pulmonary risks 4 03 2010 J P Mulier

  20. Two types of android obesity Subcutaneus FatVisceral fat Intra visceral adiposity Extra visceral adiposity Subcutaneus fat is scant and Subcutaneus fat is thick and intra abdominal fat is thick and intra abdominal fat is scant. 4 03 2010 J P Mulier

  21. The obese patient is a challenge for anaesthesia if android shape with intra visceral fat. 4 03 2010 J P Mulier

  22. NMB effect on E - PV0 • E or Compliance unchanged • E determined by fascia, size and shape • PV0 drops =extra volume at same pressure 4 03 2010 J P Mulier

  23. How to change PV0? Mulier Dillemans 2008 • NMB • Inhalation anesthesia > 2 MAC • Table inclination: trendelenburg • Smaller tidal volume ventilation • Lower peep 4 03 2010 J P Mulier

  24. How to change E : hip flexion • Mulier JP, Dillemans B Obes Surg 2009 4 03 2010 J P Mulier

  25. Begin – End of first laparoscopy • Abdominal compliance changes during pneumoperitoneum • Inflation volume rises more than 1 liter! • No NMB needed at end of operation ? One Hour Laparoscopy at 15 mmHg Elongates the Abdominal Wall Mulier IFSO 2009 4 03 2010 J P Mulier

  26. Laparoscopy without muscle relaxants ? • Laparoscopy is possible without muscle relaxants or at reduced dose if • adominal compliance > 0,5 L/mmHg • IAV > 4 L at 15 mmHg at start laparoscopy • Gravidity > 3 • Previous multiple laparoscopies/laparotomies • > 10 kg weight reduction • No man with android fat distribution and • Sufficient deep sleep • As patient should not breath against ventilator. • Pressure support ventilation • Easier to prevent breathing against ventilator 4 03 2010 J P Mulier

  27. Are NMB needed in laparoscopy? • No if abdominal compliance is large • Yes as inflation pressure can be lower • Yes to prevent breathing agains ventilator • After one hour laparoscopy compliance is rosen 4 03 2010 J P Mulier

  28. PSV • PSV is not a valsalva effect: IAV is not changing. • PSV is possible during deep muscle relaxation. PROFOUND MUSCLE RELAXATION DOES NOT DISTURB PRESSURE SUPPORT VENTILATION. Mulier J, Blacoe D PGA 2009 4 03 2010 J P Mulier

  29. Is deep relaxation needed and possible? • Time between end pneumoperitoneum and end operation is very short: in 5 min from TOF 0/4 -¼ till 90% is not possible with neostigmine. • Sugammadex • TOF 0/4 till end pneumoperitoneum • Very deep NMB PTC < 5 is possible till the end 4 03 2010 J P Mulier

  30. Effect deep muscle relaxation on IAP with constant IAV • Gradual pressure drop until flat line • Max effect at TOF 0/4 • At PTC 0 no extra pressure drop TOF 4/4 TOF ¼ PTC 10 PTC 5 PTC 0 4 03 2010 J P Mulier

  31. Effect of deep muscle relaxation on abdominal PV loop • TOF > 90% • TOF = ¼ - 0/4 • TOF 0/4 and PTC < 5 4 03 2010 J P Mulier

  32. Conclusion: NMB needed • Yes • Larger surgical workvolume for lower pressures • At low pressures less structural damage and less post op pain? • Sometimes no sufficient workspace and angry surgeons: try to do everything. • No • Abd Compliance sometimes large enough • Work at higher intra abd pressure? • 2 MAC inhalation has same effect? • Effect of position and of time? Meten is weten (Measuring is knowing!) 4 03 2010 J P Mulier

  33. If Yes -> decurarisation needed • Only Brideon is able to do so ? 4 03 2010 J P Mulier

  34. Bridion’s Mechanism of Action Is Unlike Traditional Reversal Agents NMB Conventional NMB Reversal AChE AChE Choline+acetate Choline+acetate NMBA ACh ACh ChE inhibitors(eg, neostigmine) nAChR nAChR Reversal With Bridion AChE Choline+acetate NMBA ACh Hostmolecule nAChR NMBA ACh, acetylcholine; AChE, acetylcholinesterase.ChE, cholinesterase; nAChR, nicotinic acetylcholine receptor;NMBA, neuromuscular blocking agent; NMB, neuromuscular blockade. Adam JM et al. J Med Chem. 2002;45:1806-1816. 4 03 2010 J P Mulier

  35. Encapsulation of Rocuronium By Bridion Cameron KS et al. Org Lett. 2002;4:3403-3406. Gijsenbergh F et al. Anesthesiology. 2005;103:695-703. 4 03 2010 J P Mulier

  36. What happens when Bridion is injected? = Esmeron 4 03 2010 J P Mulier

  37. = Bridion What happens when Bridion is injected? 4 03 2010 J P Mulier

  38. What happens when Bridion is injected? = Bridion - Esmeron complex 4 03 2010 J P Mulier

  39. What happens when Bridion is injected? = Bridion - Esmeron complex 4 03 2010 J P Mulier

  40. What happens when Bridion is injected? = Bridion - Esmeron complex 4 03 2010 J P Mulier

  41. Bridion Pharmacokinetics Vss 11 to 14 L T½ elimination 1.8 hours Cl estimated to be ~88 mL/min Major route of elimination: renal 96% of the dose excreted in urine, of which at least 95% could be attributed to unchanged Bridion Cl, clearance; T½, half-life; Vss, volume of distribution at steady state. Data on file.Bridion® [summary of product characteristics]Organon, Europe; 2008. 4 03 2010 J P Mulier

  42. Various Depths of Blockade Intense block: no response to either TOF or PTC stimulation Deep block: response to PTC but not to TOF stimulation Moderate block: reappearance of response to TOF stimulation Superficial block: reappearance of T4 T4/T1 ratio > 1% No block: T4/T1 ratio > 90 % Posttetaniccount Twitchresponse Twitchpercentage Level of block Intense block Deep block Moderate block Superficial block TOF count 4 Response to TOF TOF count 0 TOF count 0 TOF count 1-3 T1/T4 % Response to PTC PTC ≥1 PTC 0 PTC, posttetanic count; TOF, train-of-four. Fuchs-Buder T et al. Acta Anaesthesiol Scand. 2007;51:789-808. 4 03 2010 J P Mulier

  43. Increased Flexibility in the Time of Reversal Immediate Reversal* Within 3 min following administration of rocuronium, 16 mg/kg Routine Reversal 4 mg/kg if recovery has reached 1–2 PTC (deep blockade) 2 mg/kg if spontaneous recovery has reached the reappearance of T2 (moderate blockade) Bridion allows full relaxation until the end of surgical procedures *Only recommended with rocuronium-induced blockade.PTC, posttetanic count. Data on file.Bridion® [summary of product characteristics]. Organon, Europe; 2008. 4 03 2010 J P Mulier

  44. Recommended dosage • 16 mg/kg intense block • 4 mg/kg deep block • 2 mg/kg all other blocks • Maximum safety: • overloading t1/2 longer than roc • Fastest reversal • Never recurarisation • Individual variation covered • Less? • No studies yet • Re-occurrence of relaxation • TBW or IBW ? • No studies yet but as rocuronium is dosed according to IBW and has the same water solubility ??? • Combination with neostigmine is possible but you get the side effects back. 4 03 2010 J P Mulier

  45. Practical bridion use Vial 2 ml, 100 mg/ml 200 mg per vial • 2 mg/kg in a 70 kg person: • 140 mg one vial • 2 mg/kg in a 200 kg person: • 400 mg or two vials or IBW 140 mg? Is the patient, willing to pay for it? • Yes if • previous history of rest curarisation • you explain that procedure • is otherwise not safe • might take longer • Is not possible • You prevent post op complications? 4 03 2010 J P Mulier

  46. Measure Depth of Blockade Intense block: 16 mg/kg Deep block: 4 mg/kg Moderate block: 2 mg/kg + Neostigmine? Superficial block: 1 mg/kg + Neostigmine? No block: 0 mg/kg Posttetaniccount Twitchresponse Twitchpercentage Level of block Intense block Deep block Moderate block Superficial block TOF count 4 Response to TOF TOF count 0 TOF count 0 TOF count 1-3 T1/T4 % Response to PTC PTC ≥1 PTC 0 PTC, posttetanic count; TOF, train-of-four. Fuchs-Buder T et al. Acta Anaesthesiol Scand. 2007;51:789-808. 4 03 2010 J P Mulier

  47. More Rapid Recovery With Bridion From T2 Following Rocuronium (%) Bridion 2 mg/kg Rocuronium 0.6 mg/kg 100 50 10:21:06 10:32:38 10:44:08 10:55:38 11:07:08 11:18:53 11:30:38 11:42:08 11:53:53 12:04:39 12:13:56 (%) Rocuronium 0.6 mg/kg Neostigmine 50 µg/kg 100 50 7:49:34 7:59:34 8:09:34 8:19:34 8:29:49 8:39:49 8:50:03 9:00:19 9:10:19 9:20:34 9:30:49 9:41:04 TOF ratioTwitch height TOF, train-of-four. Data from Aurora trial. 4 03 2010 J P Mulier

  48. Faster Reversal from Rocuronium at reappearance of 2 Counts Bridion 4 mg/kg NEO 70 µg/kg n = 37 n = 37 95% CI (2.3–3.3 min) 95% CI (35.7–59.5 min) CI, confidence interval, NEO, neostigmine. Data from Signal trial. 4 03 2010 J P Mulier

  49. Time From T1 10% to 90% Within Subject 20 n = 56 n = 54 15 Minutes 10 5 0 T1=10% T1=90% T1=10% T1=90% Rocuronium 1.2 mg/kg +Bridion 16 mg/kg Succinylcholine 1.0 mg/kg Data from Spectrum trial. 4 03 2010 J P Mulier

  50. Immediate Reversal of Intense Blockade 10.9 * 7.1 3.2 * 1.4 3 min Bridion administered n = 56 n = 54 n = 56 n = 54 T1 to 90% T1 to 10% *P < 0.0001 versus succinylcholine treatment group; results based on intent-to-treat population.SEM, standard error of mean. Data from Spectrum trial. 4 03 2010 J P Mulier

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