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1150 1850 1947 1977 2010

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  • Key point: Cholinesterase inhibitors have limitations There are many drawbacks to the use of cholinesterase inhibitors in the reversal of neuromuscular blockade. When compared with Bridion, the most prominent characteristic of cholinesterase inhibitors is that they are relatively slow at reversing neuromuscular blockade. Another important limitation of cholinesterase inhibitors is the fact that these drugs are incapable of reversing deep blockade, as documented by Kopman et al and Bartkowski. 1,2 Their efficacy is also influenced by the maintenance anesthetic used during the procedure, making their effects even more variable. 3 Aside from efficacy, cholinesterase inhibitors are renowned for their side effects if they are not properly managed. These effects are mostly cardiovascular (ie, heart rate, blood pressure) but also include smooth muscle contractions and postoperative nausea and vomiting at higher doses. 4,5 These side effects are due to an abundance of acetylcholine. To mitigate these effects, the use of cholinesterase inhibitors should be accompanied by the administration of anticholinergics. References 1. Kopman AF, Kopman DJ, Ng J, Zank LM. Antagonism of profound cisatracurium and rocuronium block: the role of objective assessment of neuromuscular function. J Clin Anesth. 2005;17:30-35. 2. Bartkowski RR. Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium. Anesth Analg. 1987;66:594-598. 3. Kim KS, Cheong MA, Lee HJ, Lee JM. Tactile assessment for the reversibility of rocuronium-induced neuromuscular blockade during propofol or sevoflurane anaesthesiology. Anesth Analg. 2004;99:1080-1085. 4. Tramer MR, Fuchs-Buder T. Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. A systematic review. Br J Anaesth. 1999;82:379-386. 5. Caldwell JE. Reversal of residual neuromuscular block with neostigmine at one to four hours after a single intubating dose of vecuronium. Anesth Analg. 1995;80:1168-1174.
  • Key point: Neostigmine inadequately reverses deep neuromuscular blockade Twenty patients with American Society of Anesthesiologists classes 1 and 2 status who were to undergo surgical procedures were given anaesthesiology induced with propofol 1.5 to 2.5 mg/kg IV plus fentanyl 2 to 4 µg/kg and maintained on nitrous oxide/desflurane plus narcotic supplementation. Train-of-four (TOF) was monitored via electromyographic response at the adductor pollicis. Neuromuscular blockade was induced with rocuronium 0.6 mg/kg, infused for ≥90 min at 95% twitch depression; reversal was attempted using neostigmine 50 µg/kg administered 2 min after stopping the rocuronium infusion. 1 It was demonstrated that the neostigmine could not satisfactorily antagonize deep neuromuscular blockade. For example, 2 of the 20 patents failed to reach a TOF ratio of 0.7 within 20 minutes of attempted reversal, and only 3 (15%) subjects recovered to a TOF ratio of 0.9 or greater in the same time period. The conclusion was that if the level of block at the neuromuscular junction is great enough, the extent of recovery becomes finite. 1 This tracing is from a pilot study (identical protocol) using vecuronium as the test drug. The infusion lasted 2 hours and 48 minutes. Two minutes after the infusion was stopped at a twitch height equal to 3% of control, neostigmine 50 µg/kg was administered. The TOF ratio did not exceed 0.7 until 27 minutes postreversal. The time interval from a TOF ratio of 0.4 to a value of 0.7 was approximately 17 minutes. Note: This tracing is the printout from the Datex EMG monitor. Solid blue area represents the height of the fourth twitch. The hatched area represents the height of T 1 . 1 Reference 1. Kopman AF, Kopman DJ, Ng J, Zank LM. Antagonism of profound cisatracurium and rocuronium block: the role of objective assessment of neuromuscular function. J Clin Anesth. 2005;17:30-35.
  • Key point: Current reversal agents are associated with several side effects Recovery from neuromuscular blockade is often hastened by the administration of cholinesterase inhibitors such as neostigmine, pyridostigmine, or edrophonium. While effective, cholinesterase inhibitors have limitations. Not only do they increase the amount of acetylcholine at the neuromuscular junction, cholinesterase inhibition increases the availability of acetylcholine at the muscarinic receptors, which may result in bradycardia, hypersalivation, bronchospasm, increased bronchial secretions, urinary frequency, and nausea and vomiting. 1 Furthermore, the use of these agents may not completely avoid the occurrence of residual neuromuscular blockade even after large doses. This was found even after use of intermediate-acting neuromuscular blockers, which are sometimes not monitored because of their decreased incidence of residual neuromuscular blockade. 2 Spontaneous recovery will depend on the inherent pharmacokinetics of the neuromuscular blocking agent administered for the surgical procedure. References 1. Neostigmine Methylsulfate [package insert]. Shirley, NY: American Regent Laboratories, Inc; 2002. 2. Kim KS, Lew SH, Cho HY, Cheong MA. Residual paralysis induced by either vecuronium or rocuronium after reversal with pyridostigmine. Anesth Analg. 2002;95:1656-1660.
  • Key point: Many potential risks associated with residual neuromuscular blockade The above side effects are often due to impaired neuromuscular function in the early postoperative period following general anaesthesiology. 1 As a result, postoperative pulmonary complications may exist, causing a number of dangerous side effects. 2-5 The potential for residual neuromuscular blockade is exacerbated by the fact that it is difficult to clinically recognize, and even minimal neuromuscular blockade may result in upper airway obstruction. 2,6 In the Berg trial, a total of 691 adult patients scheduled to undergo abdominal, gynecologic, or orthopedic surgery under general anaesthesiology were randomized to receive pancuronium, atracurium, or vecuronium. The doses that were used for tracheal intubation in the study included 0.08 to 0.1 mg/kg for pancuronium or vecuronium and 0.4 to 0.5 mg/kg of atracurium. Maintenance doses were 1 to 2 mg for pancuronium or vecuronium and 5 to 10 mg for atracurium. Postoperatively, the response to TOF nerve stimulation was measured via mechanomyography, and through a 6-day follow-up the patients were examined for pulmonary complications. A postoperative pulmonary complication was considered present when pneumonic infiltrates or atelectasis were diagnosed by the radiologist. This study found that 46 (6.7%) patients displayed pneumonic infiltrates and/or atelectasis following pancuronium, vecuronium, or atracurium administration. 3 References 1. Murphy GS. Residual neuromuscular blockade: incidence, assessment, and relevance in the postoperative period. Minerva Anestesiol. 2006;72:97-109. 2. Eikermann M, Blobner M, Groeben H et al. Postoperative upper airway obstruction after recovery of the train of four ratio of the adductor pollicis muscle from neuromuscular blockade. Anesth Analg. 2006;102:937-942. 3. Berg H, Roed J, Viby-Mogensen J et al. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium. Acta Anaesthesiol Scand. 1997;41:1095-1103. 4. Bissinger U, Schimek F, Lenz G. Postoperative residual paralysis and respiratory status: a comparative study of pancuronium and vecuronium. Physiol Res. 2000;49:455-462. 5. Sundman E, Witt H, Olsson R, Ekberg O, Kuylenstierna R, Eriksson LI. The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium. Anesthesiology . 2000;92:977-984. 6. Gatke MR, Viby-Mogensen J, Rosenstock C, Jensen FS, Skovgaard LT. Postoperative muscle paralysis after rocuronium: less residual block when acceleromyography is used. Acta Anaesthesiol Scand. 2002;46:207-213.
  • Wat we als assistant geleerd hebben te doen 1 jaar GSO chirurg eist oudere jaars supervisor is veel beter Wat we effectief deden midazolam at induction Niet doorvertellen Happy chirurg en happy patient Eenmaal vast benoemd, hoge rug Chirurg niet tevreden Lijm om anest te kleven Zeer Lang, zeer sterk werkend spierverslapper, en dan plots afgezet Je moet bij de chirurgen reklame maken, groter buget in operatie, direct akkoord, spijt dat maar in bij begin en dat op het einde
  • Neuromuscular Blockade: Signal transmission via the neuromuscular junction through the transfer of acetylcholine to the nicotinic acetylcholine receptor is blocked by the competitive inhibition of neuromuscular blockers. 1 Conventional Neuromuscular Blockade Reversal: Conventionally, reversal is achieved by inhibiting acetylcholinesterase. This prevents acetylcholine from being metabolized, causing an increase in acetylcholine at the neuromuscular junction giving a competitive advantage to acetylcholine over the neuromuscular blocker. This results in the displacement of the neuromuscular blocker and allows for signal transmission to return. A side effect of this technique is an abundance of acetylcholine that can result in cardiovascular side effects. 1 Reversal With Bridion: The manner in which Bridion functions is by acting as a surrogate receptor for the neuromuscular blocking agent. Because Bridion has such high affinity for rocuronium and vecuronium, these neuromuscular blockers readily dissociate from the nicotinic acetylcholine receptor. This results in a concentration gradient away from the neuromuscular junction, culminating in rapid reversal. Because this has no effect on acetylcholine homeostasis, there are no cardiovascular side effects. 1 Reference 1. Adam JM, Bennett DJ, Bom A et al. Cyclodextrin-derived host molecules as reversal agents for the neuromuscular blocker rocuronium bromide: synthesis and structure-activity relationships. J Med Chem. 2002;45:1806-1816.
  • X-ray crystal structures of Bridion (green) and rocuronium (blue) with filled van der Waals surface, showing that the two structures have many close contacts and are highly compatible with each other. Reference 1. Gijsenbergh F et al. First human exposure of Org 25969, a novel agent to reverse the action of rocuronium bromide. Anesthesiology . 2005;103:695-703.
  • References 1. Data on file. 2. Bridion ® (sugammadex) [Summary of Product Characteristics]. N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands; August 2008.
  • This slide provides an explanation of the various depths of neuromuscular blockade. Reference 1. Fuchs-Buder T, Claudius C, Skovgaard LT et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand. 2007;51:789-808.
  • References 1. Data on file, Schering-Plough Corporation 2. Bridion ® (sugammadex) [Summary of Product Characteristics]. N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands; August 2008.
  • This slide provides an explanation of the various depths of neuromuscular blockade. Reference 1. Fuchs-Buder T, Claudius C, Skovgaard LT et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand. 2007;51:789-808.
  • Key point: Dramatically faster reversal This slide represents a TOF tracing from 2 patients treated with rocuronium 0.6 mg/kg followed by Bridion 2 mg/kg or neostigmine 50 µg/kg combined with glycopyrrolate 10 µg/kg . The solid orange and blue lines represent the height of the muscle twitches, and the grey circles are the value of the TOF ratio. Reference 1. CSR 19.4.301
  • Clinical study 19.4.302 was a randomized, parallel-group, comparative, active controlled, safety-assessor–blinded, phase IIIa, pivotal trial that compared neostigmine with Bridion in the reversal of rocuronium at 1–2 PTCs. Seventy-five subjects were studied: 37 in the Bridion group and 38 in the neostigmine group. One subject in the neostigmine group was treated but did not participate in the ITT analysis. Subjects had to be ASA class 1–4 and the ages ranged from 19 up to and including 85 years. Subjects must have been scheduled for a surgical procedure with general anaesthesiology requiring the use of rocuronium (0.6 mg/kg), which was monitored using TOF via acceleromyography. The subjects were then reversed after the reappearance of 1–2 PTCs with either 4 mg/kg Bridion or 70 µg/kg neostigmine combined with 14 µg/kg glycopyrrolate, based on randomization. Times from the start of administration of Bridion to recovery of the T 4 /T 1 ratio to 0.9 ranged from 1 minute 13 seconds to 16 minutes 5 seconds in the Bridion-treated group, and from 13 minutes 16 seconds to 145 minutes 40 seconds in the neostigmine-treated group. Median recovery times were 2 minutes 42 seconds and 49 minutes in subjects treated with Bridion and neostigmine, respectively. Reference 1. CSR 19.4.302
  • This graphically represents each patient who received the investigative protocol with respect to T 1 to 10% or T 1 to 90% for both treatment groups. 1 The important thing to take away from this slide is the limited variability seen in the rocuronium and Bridion group compared with the succinylcholine group and the time in which this reversal takes place. This reduced variability adds to the dependability of Bridion to produce consistent results that are superior to succinylcholine in terms of reversal time. References CSR 19.4.303
  • Clinical study 19.4.303 was a randomized, parallel-group, comparative, active controlled, safety-assessor–blinded, phase IIIa, trial that compared rocuronium followed by Bridion at 3 minutes with single-dose succinylcholine. One hundred ten subjects were studied: 56 in the rocuronium with Bridion group and 54 in the succinylcholine group. Subjects had to be ASA class 1 or 2 and ages ranged from 18 up to and including 65 years with a body mass index <0.0001). Reference 1. CSR 19.4.303
  • Clinical study 19.4.306 was a multicenter, randomized, parallel dose-finding, safety-assessor–blinded trial to explore the efficacy, safety, and pharmacokinetics of 4 doses of Bridion (0.5 mg/kg, 1 mg/kg, 2 mg/kg, and 4 mg/kg) and placebo in pediatric and adult subjects. Ninety-one subjects were studied: 8 infants (28 days to 23 months), 24 children (2 to 11 years), 31 adolescents (12 to 17 years), and 28 adults (18 to 65 years). Subjects had to be ASA class 1 or 2 and must have been scheduled for a surgical procedure with general anaesthesiology lasting at least 60 minutes. The neuromuscular block was only to require a single dose of rocuronium (0.6 mg/kg), which was monitored using TOF via acceleromyography. This graphically represents the dose response in children and adolescents at TOF 0.9. There is a dramatic difference between placebo and all doses of Bridion, most notably 2 and 4 mg/kg Bridion. Children Times from start of Bridion administration to recovery of T 4 /T 1 ratio to 0.9 • Placebo, n=4: range, 8 min 25 sec to 31 min 47 sec; median, 19 min 2 sec • Bridion 2 mg/kg, n=5: range, 51 sec to 1 min 37 sec; median, 1 min 9 sec • Bridion 4 mg/kg, n=4: range, 36 sec to 4 min 25 sec; median, 38 sec Adolescents Times from start of Bridion administration to recovery of T 4 /T 1 ratio to 0.9 • Placebo, n=6: range, 6 min 50 sec to 41 min 40 sec; median, 23 min 22 sec • Bridion 2 mg/kg, n=6: range, 42 sec to 5 min 14 sec; median, 1 min 8 sec • Bridion 4 mg/kg, n=8: range, 44 sec to 1 min 26 sec; median, 1 min 5 sec Adults Times from start of Bridion administration to recovery of T 4 /T 1 ratio to 0.9 • Placebo, n=6: range, 19 min 37 sec to 43 min 57 sec; median, 28 min 22 sec • Bridion 2 mg/kg, n=5: range, 54 sec to 1 min 34 sec; median, 1 min 13 sec • Bridion 4 mg/kg, n=5: range, 57 sec to 1 min 57 sec; median, 1 min 24 sec Reference 1. CSR 19.4.306
  • Clinical study 19.4.305 was a multicenter, parallel-group, comparative, phase IIIa, trial that compared elderly patients with adult patients in terms of efficacy, safety, and pharmacokinetics. One hundred and fifty subjects were studied: 48 in the adult group, 62 in the 65–74 year group, and 40 in the ≥75 year group. Subjects had to be ASA class 1–3 and ≥18 years of age, scheduled for a surgical procedure in the supine position with general anaesthesiology requiring neuromuscular relaxation with the use of rocuronium, which was monitored using TOF via acceleromyography. Subjects received a single bolus dose of rocuronium 0.6 mg/kg. If further neuromuscular block was required after endotracheal intubation, maintenance dose(s) of rocuronium 0.15 mg/kg may have been administered. Subjects were reversed at reappearance of T 2 with a single bolus dose of Bridion 2 mg/kg. The median times of recovery to T 4 /T 1 ratio to 0.9 for the adult group, age 65-74 year group, and the ≥75 year group were 2.2, 2.6, and 3.6 minutes, respectively. Even though recovery times tend to be slower in the elderly no dose adjustment is necessary. References 1. CSR 19.4.305 2. Bridion ® (sugammadex) [Summary of Product Characteristics]. N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands; August 2008.
  • The safety of Bridion has been described from 2369 exposures in 2054 patients or volunteers who were mostly between 18 and 64 years of age, ASA class 1–2, and predominantly white and not Hispanic or Latino. In these exposures the incidence of AEs was low; however, dysgeusia (metallic, bitter taste) and anesthetic complications (restoration of neuromuscular function) showed a dose response, occurred with a frequency of ≤2%, and was observed twice as often as placebo. 1 Trial 19.4.309 studied patients who were diagnosed with or had a history of cardiac disease (ie, patients with ischemic heart disease, chronic heart failure, or arrhythmia) of New York Heart Association class II to III. The study investigated time to recovery from neuromuscular blockade induced by rocuronium 0.6 mg/kg following administration of 2 or 4 mg/kg Bridion given at the first signs of recovery (reappearance of T 2 ). The trial showed that the median time to recovery of the T 4 /T 1 ratio to 0.9 was 1.7 and 1.3 minutes, respectively, in the 2 and 4 mg/kg Bridion dose groups. It was also found that Bridion can be used safely in cardiac patients. 2 Trial 19.4.308 involved patients who were diagnosed with or had a history of pulmonary complications. The study investigated the time to recovery from neuromuscular blockade induced by rocuronium (0.6 mg/kg) following administration of 2 or 4 mg/kg Bridion given at the first signs of recovery (reappearance of T 2 ). Two patients in the 4 mg/kg group experienced a bronchospasm. The trial showed that for these patients the median time to recovery of the T 4 /T 1 ratio to 0.9 was 2.1 and 1.9 minutes for the 2 mg/kg and 4 mg/kg Bridion dose groups, respectively. It was also found that Bridion can be used safely in patients diagnosed with or having a past history of pulmonary disease. 3 Caution should be taken in patients with severe renal failure (creatinine clearance <30 mL/min) because of the delayed excretion of the Bridion-rocuronium complex. The use of Bridion in this patient population is strongly discouraged. 4 Because Bridion is not metabolized or excreted hepatically, dedicated trials in patients with hepatic dysfunction have not been performed. Therefore, Bridion should be administered very cautiously to this patient population. 4 References 1. Integrated Summary of Safety 2. CSR 19.4.309 3. CSR 19.4.308 4. Bridion ® (sugammadex) [Summary of Product Characteristics]. N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands; August 2008.
  • Throughout the clinical trials, consisting of >2000 patients, no clinically relevant interactions were reported during the clinical development of Bridion. However, through the use of pharmacokinetic and pharmacodynamic simulation models, interactions with toremifene, hormonal contraceptives, high-dose flucloxacillin, and fusidic acid were discovered. 1,2 The toremifene interaction involves a possible displacement of rocuronium or vecuronium due to the high affinity constant and relatively high plasma concentration associated with toremifene. As a result, the recovery to T 4 /T 1 ratio of 0.9 could be delayed in patients who have received toremifene on the same day of surgery. 1,2 The high dose-flucloxacillin (infusion of 500 mg or more) and fusidic acid interactions involve a possible displacement of rocuronium or vecuronium. As a result, the recovery to T 4 /T 1 ratio to 0.9 could be delayed in patients who have received these products in the preoperative phase. The use of these products in the postoperative phase (6 hours) is to be avoided. 1,2 References 1. Integrated Summary of Safety 2. Bridion ® (sugammadex) [Summary of Product Characteristics]. N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands; August 2008.
  • The interaction discovered with hormonal contraceptives found a potential interaction between 4 mg/kg Bridion and a progestogen that could lead to a decrease in exposure (34% of area under the curve). This is similar to the decrease seen when a daily dose of oral contraceptive was missed. For this reason, the administration of a bolus dose of Bridion is considered to be equivalent to 1 missed daily dose of oral contraceptive. 1,2 References 1. Data on file. 2. Bridion ® (sugammadex) [Summary of Product Characteristics]. N.V. Organon, Kloosterstraat 6, 5349 AB Oss, The Netherlands; August 2008.

1150 1850 1947 1977 2010 1150 1850 1947 1977 2010 Presentation Transcript

  • The place of Sugammadex (Bridion ® ) in laparoscopic bariatric surgery
    • Jan Paul Mulier, MD PhD
      • Sint Jan Brugge-Oostende
    1150 1850 1947 1977 2010
  • 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
  • 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.
  • Neostigmine (50 µg/kg) Inadequately Reverses 95% Twitch Depression NEO, neostigmine; ROC, rocuronium; TOF, train-of-four. Kopman AF et al. J Clin Anesth . 2005;17:30-35. NEO administered 10 min 20 min 30 min T 1 = 100% T 1 = 50% Solid area = height of T 4 Hatched area = height of T 1 Vecuronium Protocol Rocuronium Protocol 5 min 10 min 15 min 20 min ROC 0.6 mg/kg n = 20 TOF ratio 0.33 ± 0.13 0.57 ± 0.11 0.70 ± 0.12 0.79 ± 0.12 TOF < 0.9 100% (20) 100% (20) 95% (19) 85% (17)
  • 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.
  • Increased Risk Associated With 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
  • 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?
  • 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.
  • 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?
  • 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
  • E en PV0 determined by ?
    • Mulier Dillemans ESA 2007
    * Sig p<0.05 0.376 Neg 0.001* Neg Muscle relaxation 0.009* Neg 0.191 Neg Prev abd operation 0.049* Neg 0.305 Neg Gravidity 0.536 Neg 0.596 Neg Sex 0.272 Neg 0.054 neg Bmi 0.294 Pos 0.012* Pos Body weigth 0.245 Neg 0.356 Neg Length 0.003* Pos 0.828 Neg Age E sig E P VO sig PV0 factors
  • Patient with no effect of NMB
    • No muscles in abd wall, diaphragm ?
    • Fully relaxed by other factors ?
    • TOF > 90%
    • TOF = ¼
    • TOF 0/4 and PTC < 5
  • 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
  • Pig: High dose desfl sevo
    • Zelfde spier relaxatie effect sevo en desfl
    • data JPMulier 2009
  • Effect of valsalva: breathing against ventilator
    • Valsalva is an active muscle contraction different from breathing to increase the abdominal pressure
    • Happens when patient reacts on Controlled Ventilation
  • BMI effect on abdominal P/V relation
    • J Mulier ISPUB 2009
      • Pressure volume relation is linear
      • PV0 and E define each patient
    • J Mulier IFSO 2007
  • Android versus Gynoid fat distribution has a different Elastance
  • 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
  • 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
  • Two types of android obesity
    • 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.
    Subcutaneus Fat Visceral fat
  • The obese patient is a challenge for anaesthesia if android shape with intra visceral fat.
  • NMB effect on E - PV0
    • E or Compliance unchanged
      • E determined by fascia, size and shape
    • PV0 drops =extra volume at same pressure
  • How to change PV0?
    • Mulier Dillemans 2008
    • NMB
    • Inhalation anesthesia > 2 MAC
    • Table inclination: trendelenburg
    • Smaller tidal volume ventilation
    • Lower peep
  • How to change E : hip flexion
    • Mulier JP, Dillemans B Obes Surg 2009
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Effect of deep muscle relaxation on abdominal PV loop
    • TOF > 90%
    • TOF = ¼ - 0/4
    • TOF 0/4 and PTC < 5
  • 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!)
  • If Yes -> decurarisation needed
    • Only Brideon is able to do so ?
  • Bridion’s Mechanism of Action Is Unlike Traditional Reversal Agents Adam JM et al. J Med Chem . 2002;45:1806-1816. NMBA ACh, acetylcholine; AChE, acetylcholinesterase. ChE, cholinesterase; nAChR, nicotinic acetylcholine receptor; NMBA, neuromuscular blocking agent; NMB, neuromuscular blockade. NMB Choline + acetate AChE ACh nAChR Conventional NMB Reversal Choline + acetate AChE ACh NMBA nAChR ChE inhibitors (eg, neostigmine) Reversal With Bridion Choline + acetate AChE ACh NMBA nAChR Host molecule
  • Encapsulation of Rocuronium By Bridion Cameron KS et al. Org Lett . 2002;4:3403-3406. Gijsenbergh F et al. Anesthesiology . 2005;103:695-703.
  • What happens when Bridion is injected? = Esmeron
  • What happens when Bridion is injected? = Bridion
  • What happens when Bridion is injected? = Bridion - Esmeron complex
  • What happens when Bridion is injected? = Bridion - Esmeron complex
  • What happens when Bridion is injected? = Bridion - Esmeron complex
  • Bridion Pharmacokinetics
    • V ss 11 to 14 L
    • T ½ 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; T ½ , half-life; V ss , volume of distribution at steady state. Data on file. Bridion ® [summary of product characteristics]Organon, Europe; 2008.
  • 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 %
    PTC 0 PTC ≥1 Intense block Deep block Moderate block TOF count 0 TOF count 0 TOF count 1-3 Level of block Response to TOF Response to PTC PTC, posttetanic count; TOF, train-of-four. Fuchs-Buder T et al. Acta Anaesthesiol Scand . 2007;51:789-808. Posttetanic count Twitch response Twitch percentage Superficial block TOF count 4 T1/T4 %
  • 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 T 2 (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.
  • 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.
  • 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?
  • 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
    PTC 0 PTC ≥1 Intense block Deep block Moderate block TOF count 0 TOF count 0 TOF count 1-3 Level of block Response to TOF Response to PTC PTC, posttetanic count; TOF, train-of-four. Fuchs-Buder T et al. Acta Anaesthesiol Scand . 2007;51:789-808. Posttetanic count Twitch response Twitch percentage Superficial block TOF count 4 T1/T4 %
  • More Rapid Recovery With Bridion From T 2 Following Rocuronium Data from Aurora trial. TOF ratio Twitch height TOF, train-of-four. 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 Rocuronium 0.6 mg/kg Bridion 2 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
  • Faster Reversal from Rocuronium at reappearance of 2 Counts CI, confidence interval, NEO, neostigmine. Data from Signal trial. n = 37 NEO 70 µ g/kg 95% CI (35.7–59.5 min) Bridion 4 mg/kg 95% CI (2.3–3.3 min) n = 37
  • Time From T 1 10% to 90% Within Subject T 1 =10% T 1 =90% T 1 =10% T 1 =90% Rocuronium 1.2 mg/kg + Bridion 16 mg/kg Succinylcholine 1.0 mg/kg 0 5 10 15 20 Minutes Data from Spectrum trial. n = 56 n = 54
  • Immediate Reversal of Intense Blockade * P < 0.0001 versus succinylcholine treatment group; results based on intent-to-treat population. SEM, standard error of mean. Data from Spectrum trial. 3 min Bridion administered T 1 to 10% T 1 to 90% * * 1.4 3.2 7.1 10.9 n = 56 n = 54 n = 56 n = 54
  • Rapid Dose-Dependent Reversal From T 2 in Children and Adolescents Following Rocuronium 0.6 mg/kg TOF, train-of-four. *Approved dose in children and adolescents. Data from Libra trial.
  • No Dose Adjustment Required With Increasing Age TOF, train-of-four. *Reversal from T 2 following rocuronium 0.6 mg/kg Data from Diamond trial. Bridion ® [summary of product characteristics]. Organon, Europe; 2008. n = 48 n = 62 n = 40 Age, yr
  • Bridion Has a Demonstrated Safety Profile
    • Bridion has been studied in >2000 clinical trial subjects
    • Safety has been demonstrated in patients with cardiac and pulmonary disease
    • Bridion is not recommended in patients with severe renal failure (CrCl <30 ml/min)
    • Great caution should be taken in patients with severe hepatic disease
      • Dedicated studies in this population have not taken place
    CrCl, creatinine clearance. Data on file. Bridion ® [summary of product characteristics]. Organon, Europe; 2008.
  • Drug-Drug Interactions Affecting the Efficacy of Bridion
    • No clinically relevant drug interactions have been reported with Bridion
    • Pharmacokinetic-pharmacodynamic simulations show that the following displacement interactions are possible:
      • Toremifene
        • The recovery to T 4 /T 1 ratio of 0.9 could be delayed in patients who have received toremifene on the same day of surgery
      • Intravenous administration of high-dose flucloxacillin* and fusidic acid
        • The recovery to T 4 /T 1 ratio of 0.9 could be delayed in patients who receive these products in the preoperative phase
        • Administration of these products in the postoperative phase (6 hours) is to be avoided
    *Infusion of 500 mg or more. Data on file. Bridion ® [summary of product characteristics]. Organon, Europe; 2008.
  • Drug-Drug Interactions Affecting the Efficacy of Other Drugs
    • Pharmacokinetic-pharmacodynamic simulations show that the following capturing interaction is possible:
      • Hormonal contraceptives
        • An interaction between 4 mg/kg Bridion and a progestogen could lead to a decrease in progestogen exposure, 34% of AUC, which is similar to that of a missed dose of oral contraceptive
    AUC, area under the curve. Data on file. Bridion ® [summary of product characteristics]. Organon, Europe; 2008.
  • “ Can not intubate / can not ventilate”
    • How frequently ?
    • Did you ever awakened your patient immediately within the first 30 minutes?
    • Conclusion:
      • It feels safe to have a drug available to bring patient immediately back to spontaneous breathing and to cancel the surgery.
      • Always have it never use it?
  • Rapid sequence / Crush induction
      • Who is at Risk for aspiration?
        • Food or drank recently
        • Obstruction
        • Pregnant
        • Super obese
        • Previous bariatric surgery
    • Long procedure: high dose of NMB
      • No need for bridion or succinylcholine
    • Short procedure: high dose Rocuronium and bridion
      • Esmeron 1,2 mg/kg IBW measure TOF: bridion
  • Very short and superficial blockade
    • Superficial blockade is sufficient for ECT
    • Succinylcholine: 0,5 mg/kg (normal: 2 mg/kg) is sufficient
      • Relative rapid onset, within 2 minutes
      • Spontaneous recovery within 5 minutes possible
    • Rocuronium 0,15 mg/kg (normal: 0,6 mg/kg) slower onset, longer duration
      • Dose of bridion dependent on TOF
      • Neostigmine possible but side effects
  • Tof monitoring
    • TOF measurement is needed
      • To justify use of bridion
      • To lower dose of bridion
  • Immediate effects in morbid obese patients
    • Deep breaths possible
      • Less collaps
    • Aurosal effect
      • Like Amfetamine awakening
      • Sudden muscle fiber stimulation gives aurosal
    • Patient transfers him/her self in bed
      • 50 % of cases instead of only10%
    • Spontaneous movements easier
      • Deep venous trombosis prevention
  • Our Results in lap RNY
    • Adjustable Gastric band Biliary pancreatic div DuodenalSwitch
    • Jejuno ileal bypass
    • Vertical banded gastroplasty Roux & Y Gastric bypass Sleeve Gastrectomy
  • Andere vragen in de anesthesie bij morbide obesitas
    • Pre operatieve voorbereiding
    • Inductie en intubatie
    • Patient positionering
    • Medicatie dosering
    • Extubatie en postoperatief beleid
    • Post op pijn behandeling
    • Enkele items nu belichten
  • Waarom onvoldoende spierrelaxatie geven?
    • Restcurarisatie is zeer beangstigend, slecht ademen post op, lage saturatie, hoge CO2
    • Liever geen neostigmine gebruiken omdat
      • Bradycardie tot totaal AV block
      • Bronchospasme bij asthma patienten
      • Braken en onwel gevoel post op
    • Relaxatie moet voldoende uitgewerkt zijn om te decurariseren met neostigmine
      • TOF minimum één antwoord
  • Continuous deep blockade till end of surgery.
    • 3. Laparoscopy
    • Rapid awakening
    • Keep your surgeon in the OR
    • Quality surgery =
      • short surgical time
      • High volumes
    • Quality anaesthesia =
      • short turn over
      • High volumes
  • Our Results in lap RNY gastric bypass
  • ERAS 1 (early recovery after surgery)
    • Halfway surgery (last 30 min)
      • Large abdomen stop esmeron infusion,
      • Small abd keep esmeron infusion till end of operation.
    • Last stapler
      • Reduce/stop remifentanyl infusion
      • Start pressure support ventilation
        • Hypercapnic PSV increases CO and BP
    • Keep inhalation conc high if small abd till end of pneumoperitoneum.
  • PSV voorkomt tegenademen bij onvoldoende relaxatie
    • 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
  • Hypercapnia / Pressure support J P Mulier, B Dillemans, Use of pressure support ventilation during laparoscopic bariatric surgery is possible and facilitates weaning and extubation. In:Obes Surg 2008; 18:444 J P Mulier, B Dillemans, Hypercapnic lung ventilation reduces airway pressure during laparoscopic surgery. In:Eur J Anesth 2008; 25, S44:78 4 +/- 5 8 +/- 4 Extubation * min 2 +/- 4 4 +/- 4 Breathing * min 5 +/- 8 30 +/- 15 Ephedrine * mg 97 +/- 2 96 +/- 3 O2 sat % 56 +/- 8 38 +/- 6 Et PCO2 * mmHg 26 +/- 3 32 +/- 5 Airw pres * cmH20 7,1 +/- 1,1 11,6 +/- 1,7 Minute vol * L/min hypercapny normocapny Table 3 +/- 2 5 +/- 6 Extubation min 54 +/- 10 44 +/- 6 etPCO2 mmHg 23 +/-2 32 +/- 4 Cisatracurium mg * 1,4 0,6 Number of TOF * PSV PCV Table
  • ERAS 2
    • Leaktest
      • High volume load
      • SAP > 140 mmHg
        • Et CO2 to 60; PSV give extra suf if tachypnoe
        • Ephedrine/phenylephrine bolus
      • dose sufenta till RR < 16
    • Last surgical stich
      • Lower PSV further, keep peep
      • Stop inhalation
      • TOF 4/4 <50% neostigmine
      • TOF < 2/4 bridion dose according to TOF and IBW
        • give bridion after patient is secured on the table
  • PSV pain therapy optimalisation
    • Before after extra suf bolus
  • Hypercapnic pressure support: easier SAP rise J P Mulier (2008) Hypercapnic support ventilation during laparoscopic gastric bypass increases the cardiac output. Anesthesiology 2008 A174 3 * +/- 3 11 +/- 7 Ephedrine mg 7,6 *+/- 1,2 9 +/- 1,3 Min Vol L:min 14,3 * +/- 2,9 6,2 +/- 1,8 CO L/min 53 * +/-6 39 +/- 7 Et P CO2 mmHg 148 +/- 13 143 +/- 25 SAP mmHg Hypercapnic Normocapnic Table
  • Can anesthesiology help to prevent post op bleeding? yes 110/57 145/78 J.P.Mulier, B Dillemans, G Vandrogenbroek, F Akin The effect of systolic arterial pressure on bleeding of the gastric stapling during laparoscopic gastric bypass surgery. Obes Surg 2007; 17: 1051
  • Hypercapnic pressure support ventilation
    • Increases cardiac output
      • Less wound infections
    • Lowers airway pressures
    • Resp freq: morfine if too low stop PSV
    • TV: curarisation corrected by support level
    • Improves saturation per op if low
    • Rapid awakening and spontaneous breathing
      • Non surgical time between OP < 20 min
    • Less pain when awakening
      • Extra doses given during end of surgery
    • Better post op breathing
      • less post ventilation
  • ERAS 3
    • Reversed induction technique ?
      • 50 à 100 mg propofol in bolus
    • Gastric tube suction, oral cavity clean?
    • PSV to Spontaneous, TV > 200 ml
    • Extubation beach chair if possible
      • Diep ademen, benen bewegen
      • Nooit sedativa, benzodiazepines,…
      • Voldoende pijn medicatie perop starten
    • Test: patient moet zich zelf verbedden 3 minuten na extubatie!
    • Turnover time between end surgery - incision next patient < 20 minuten.
  • Conclusion
    • Always have Bridion available.
    • Decide when long and deep relaxation is needed till end.
    • Measure TOF ctu or at end
      • Never believe without control clinical relaxation
    • According to TOF at end operation.
      • (Nothing)
      • (Neostigmine)
      • Bridion
  • Second ESPCOP Scientific meeting Multidisciplinarity Pordenone, Italy 18 sept 2010
    • More info
    • www.publicationslist.com/jan.mulier
    • www.espcop.org