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![Page 1: Recovery from NMBA : problems and solutions Wirat Wasinwong Anesthesia department Faculty of Medicine Prince of Songkla University.](https://reader035.fdocuments.in/reader035/viewer/2022062718/56649e7d5503460f94b7f38c/html5/thumbnails/1.jpg)
Recovery from NMBA : problems and solutionsRecovery from NMBA : problems and solutions
Wirat WasinwongWirat WasinwongAnesthesia department
Faculty of MedicinePrince of Songkla University
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Muscle relaxant
• 1912 : curare
• 1970s : pancuronium
• 1980s : vecuronium, cisatracurium, mivacurium, rocuronium
• rapacuronium
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Ideal muscle relaxant
• Onset
• Duration
• Metabolite/accumulation
• Safety
• Reversibility
• Cost
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Rocuronium
• Dose 0.6-0.9 mg/kg
• Onset 60-90 sec.
• Duration 20-40 min.
• Minimal cardiovascular effect
• Hepatorenal excretion
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Dam and Goldman “ Today, the most common cause
of postoperative respiratory inadequacy is the use and misuse of muscle relaxant drugs”
Anesthesiology 1961; 22:699-707
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Postoperative residual curarization (PORC)
• 1979– Residual postoperative weakness– Incomplete recovery– Ventilatory complications
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Anesthesiology 1997; 86:765-71
• Kopman, Yee and Neuman
“ normal vital muscle function, including normal pharyngeal function, requires the TOF ratio at the adductor pollicis to recover to > 0.9 ”
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relationship between receptor occupancy and neuromuscular monitoring
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0
25
50
75
100
125
concentration
rece
pto
r o
ccu
pat
ion
(%
) no neuromuscular block block
A.H. Bom , Dept. Pharmacology, Organon Newhouse, Scotland, UK
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Minimal residual paralysis
• Impair pharyngeal muscle function
• Reduce lower esophageal sphincter tone
• Increase risk – Aspiration– Upper airway obstruction– Impair hypoxic ventilatory response
Eriksson LI, et al. Anesthesiology 1997;87: 1035-43. Eikerman M, et al. Anesthesiology 2003; 98: 1333-7.Eriksson LI, et al. Anesthesiology 1993;78: 693-9.
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Incidence of residual blockStudy year n TOF NDMR PORC
reverse
Cammu G 2002 30 <O.7 cisatracurium 40 % Y
rocuronium 47Gatke MR 2002 120 <0.8 roc with TOF 3 without TOF 16.7Hayes AH 2001 150 <0.8 vecuronium 64 atracurium 52 rocuronium 47Baillaed C 2000 568 <O.7 vecuronium 42
NBerg H 1997 691 <0.7 pancuronium 26 atr, vec
5.3Shorten GD 1992 panc with TOF 15 wthout TOF 47
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Debeane B,et al. Anesthesiology,2003;98(5):1042-8
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Naguib M, et al. Br J Anaesth 2007;98(3):302-16.
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Murphy GS,et al. Anesth Analg 2004,98:193-200
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Berg H,et al. Acta Anaesthesiol Scand 1997;41:1095
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Pancuronium in cardiac surgery
• Increase duration of weaning and tracheal extubation
• Significant muscle weakness after tracheal extubation
Murphy GS, et al. Anesth Analg 2002;95:1534-9 Murphy GS, et al. Anesth Analg 2003;96:1301-7
Thomas R, et al. Anaesthsia 2003;58:265-70
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How to avoid PORC
• Avoid long acting NMBA
• Avoid unnecessary deep block
• Antagonize block at the end
• Do not initiate reversal before– Spontaneous muscle activity presents– 3 or 4 response of TOF
• Use reliable clinical evaluation
• Objective neuromuscular monitoring
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• Objective neuromuscular monitoring is evidence based practice
Ericksson LI. Anesthesiology
2003;98:1037-9.
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Neuromuscular blockade reversal
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Disadvantages of anticholinesterases
• Inability to antagonize profound block• Relatively slow onset of action to peak1
–neostigmine (7–11 min)–pyridostigmine (15–20 min)
• Muscarinic effects–bradycardia and hypotension–bronchoconstriction and excessive
secretions–nausea and vomiting
1. Bevan DR et al. Anesthesiology. 1992; 77:785–805
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Sugammadex
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top / bottom view side view
-cyclodextrin
6 glucose units
-cyclodextrin
7 glucose units
-cyclodextrin
8 glucose units
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Hydrophilic exterior : polar hydroxyl group
O
S
OH
OH
O S
OH
OH
O
OS
OH O
O
S
OHOH OO
S
OH
OH
O
OS
OH
OH
O
OS
OH
OH
O
O
S
OHOHO
O
OH
CO2Na
CO2Na
NaO2C
NaO2C
NaO2C
NaO2C
CO2Na
CO2Na
Hydrophobic cavity
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Carboxyethyl group
Quaternary nitrogen
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Sugammadex• Water-soluble complex formation
1:1 ratio with steroidal muscle relaxants
• rocuronium > vecuronium >> pancuronium
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Sugammadex• No effects on acetylcholinesterase or any
other receptors (nicotinic, muscarinic)
• Acid-base change: no effects on sugammadex efficacy
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Pharmacokinetics
• Elimination half-life ≈100 min
• Clearance 120 mL/min– similar to normal glomerular filtration rate
• Volume of distribution 18 L– > blood volume, but substantially
< the volume of the extracellular space
• 59–80% of administered dose excreted in the urine over 24 h
Gijsenbergh F et al. Anesthesiology. 2005; 103:695–703
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Sugammadex increases renal excretion of rocuronium• 14% of an administered rocuronium dose
is excreted in the urine within 0–24 h
• With concomitant administration of sugammadex (8.0 mg/kg at 3 min) renal excretion of rocuronium within 0–24 h increased to 39–68%
Gijsenbergh F et al. Anesthesiology. 2005; 103:695–703
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Sugammadex
• Drugs that potentiate effects of neuromuscular blocking agents (Mg2+, aminoglycosides) may need higher sugammadex dose
• Other steroids– Cortisone, atropine, verapamil– 120-700 time < rocuronium– Clinical insignificant
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Clinical studies
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Reversal of Rocuronium-induced Neuromuscular Block by the Selective Relaxant Binding Agent Sugammadex : A Dose-finding and Safety StudySorgenfrei IF. Anesthesiology 2006 10466; :7 74–
• Randomized, placebo-controlled, assessor-blinded trial
• 27 male patients.
• 0.6 mg/kg rocuronium
• Sugammadex 0.5, 1, 2, 3 ,4 mg/kg at T2 of TOF
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Reversal of Rocuronium-induced (1.2 mg/kg) ProfoundNeuromuscular Block by SugammadexA Multicenter, Dose-finding and Safety Study
de Boer, HD, et al. Anesthesiology 2007 107239; : –44
• phase II, multicenter,assessor-blinded, placebo-controlled, parallel study.
• 43 patients
• 5-min reversal after rocuronium
• Adverse effects : diarrhea, light anesthesia
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Early Reversal of Profound Rocuronium-inducedNeuromuscular Blockade by Sugammadex in aRandomized Multicenter StudyEfficacy, Safety, and Pharmacokinetics
Sparr HJ , et al. Anesthesiology 2007 106935 4; : –3
• 98 male adult patients
• Reversal at 3,5 and 15 min
• After rocuronium 0.6 mg/kg.
• Adverse effect: sucking, moving, glimace, cough
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Anesth Analg 2007;104(3):569-74
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Sugammadex• 3 times more rapid than edrophonium
• 10 times more rapid than neostigmine
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Side effects • Hypotension• Cough• Vomitting• Dry mouth• Abnormal smell• Sensation of a changed temperature
• Abnormal level of N-acetyl glucosaminidase in urine
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Safety
• Biologically inactive• Not bind to plasma proteins • Sugammadex well tolerated in studies to date
Gijsenbergh F et al. Anesthesiology. 2005; 103:695–703
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Limitation • succinylcholine, benzylisoquinolinium
– Ineffective– After reversing with sugammadex
: difficult ,unpredictable dose of rocuronium, vecuronium to re-establish block
: more intense block benzylisoquinolinium
: decrease dose
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Limitation • Cost
• Sugammadex-rocuronium complex in renal disease : unclear
• Reverse profound block with inadequate dose : incomplete recovery
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Approval of Sugammadex 11-Mar-08 07:05 pm • Schering-Plough announces the FDA Advisory
Committee unanimously recommends U.S. approval of sugammadex, the first and only selective relaxant binding agent (19.82 +0.17) -Update-
Co announced that the U.S. Food and Drug Administration (FDA) Advisory Committee on Anesthetics and Life Support has recommended sugammadex for approval. After reviewing data on the safety
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Gantacurium• Lack of accumulation• Dose 2.5-3 x ED95
– Maximum block onset within 90 sec.
• 25-75% recovery index = 3 min.– 7 min. for mivacurium– 9 min. for rapacuronium– 14 min. for cisatracurium
• Clinical duration < 10 min.• Complete recovery to TOF>0.9 within 15 min.
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Thank youThank you