Residual neuromuscular blockade

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SAFETY IN THE MANAGEMENT OF NEUROMUSCULAR BLOCKADE SIMÃO ESTEVES SERVIÇO DE ANESTESIOLOGIA CHP - PORTO

DISCLOSURE MSD

CONSULTANT

L ECTURES ABOUT

NMB MONITORING AND SUGAMMADEX PROMOTED BY

MSD

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OVERVIEW • Use of neuromuscular blockers • Safety in the management of neuromuscular blockade • Side effects of neuromuscular blockers • Residual neuromuscular blockade • Contribution of sugammadex for the safety of neuromuscular blockade management

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CLASSIC INDICATIONS • Facilitate intubation

• Facilitate ventilation • Facilitate surgery

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FACILITATE INTUBATION

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FACILITATE SURGERY

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WHERE ARE THE DIFFERENCES…

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FACILITATE SURGERY

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ADVANTAGES OF NMB OPTIMIZATION • Assurance of immobility • Neurosurgery, microsurgery (ENT), ophthalmology

1-3

• Less abdominal muscle tone • Better conditions for laparoscopic surgery→ GI surgery, gynecology 2,4,5,6

• Lower abdominal pressure→ NMB may limit insufflation pressure 7

• Lower incidence of some complications

3,4,7,8

• Cough, higher abdominal and intrathecal pressures, upper airway lesions

1. Lemmens HJM et al. BMC Anesthesiol. 2010;10:15; 2. Meretoja OA. Paediatr Anaesth. 2010;20:591-604; 3. Rossiter JD et al. Eye (Lond). 2006;20:55-58; 4. Welliver M et al. Drug Des Devel Ther. 2008;2:49-59; 5. Ogunnaike BO et al. Anesth Analg. 2002;95:1793-1805; 6. Chassard D et al. Ann Fr Anesth Réanim. 1996;15:1013-1017. 7. Chui PT et al. Anaesth Intensive Care. 1993;21:163-171; 8. Mencke T et al. Anesthesiology. 2003;98:1049-1056

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SAFETY IN THE MANAGEMENT OF NEUROMUSCULAR BLOCKADE •

Side effects of neuromuscular blockers • Autonomic effects • Cardiovascular • Dysrhythmias, tachycardia, hypotension • Respiratory • Bronchospasm • Histamine release

• Hypotension, cutaneous rash • Alergic reactions • Anaphylaxis

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ANAPHYLAXIS

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Quaternary ammonia ions seems to be related

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Cross reactivity between different muscle relaxants and other daily life products

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Rocuronium and sux are the drugs most related with anaphylaxis and anesthesia in Françe1

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Rocuronium and atracurium were considered as drugs with moderate risk of anaphylaxis compared with sux (high risk) and vecuronium (low risk) 2

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The higher incidence of anaphylaxis with rocuronium may only reflect it’s large use 2,3

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Although relatively rare anaphylaxis related with rocuronium may be serious even fatal

1. Mertes PM, Laxenaire MC, Alla F: Anaphylactic and anaphylactoid reactions occurring during anesthesia in France in 1999-2000. Anesthesiology 2003; 99:536-545; 2. Rose M, Fisher M: Rocuronium: High risk for anaphylaxis?. Br J Anaesth 2001; 86:678-682; 3. Watkins J: Incidence of UK reactions involving rocuronium may simply reflect market use. Br J Anaesth 2001; 87:522

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Side effects of neuromuscular blockers antagonists • Neostigmine • Bradycardia, hypersalivation, bronchospasm, increased bronchial secretions, urinary frequency, nausea and vomiting • Atropine • Tachycardia, dryness of mouth and nose, mydriasis, urinary retention, delirium • Sugammadex • Allergy and anaphylaxis

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ANAPHYLAXIS AND SUGAMMADEX •

Some cases described (< 10) mainly in Japan

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Several grades of severity (mild allergic reaction to anaphylactic shock)

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Cause-effect relationship only in some cases

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Possible causes – sugammadex as an antigen, sugammadex-rocuronium complex as an antigen, sugammadex structural changes mediated by light exposures an antigen

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Residual neuromuscular blockade – presence of signals and symptoms of muscle weakness following the use of neuromuscular blockers

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The diagnosis implies the use of quantitative monitors and a TOF R < 0.9 (although there are some studies that states that a TOF R =1.0 should be obtained when using the TOF Watch monitor)

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Residual neuromuscular blockade may have harmful consequences for patients suffering this complication

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(Anesth Analg 2010;111:120–8)

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RECOVERY FROM NMB All patients (n = 526) 1.0 0.9

TOF Ratio

0.8 0.7 0.6

0.5 0.4 0.3 0.2 0.1 0.0 0

50

100

150

200

250

300

350

400

Time (min)

Debaene B et al. Anesthesiology. 2003;98:1042-1048

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(Anesth Analg 2010;111:120–8)

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ROLE OF SUGAMMADEX • Sugammadex may increase safety in the management of neuromuscular blockade: • Allowing a rapid and complete reversal of neuromuscular blockade, independent of the depth of blockade • Allowing an optimized use of neuromuscular blockade – deeper blockade until the end of surgery • Allowing the use of neuromuscular blockers in clinical situations where they were previously contra-indicated or pose difficulties in management - myopathies, myasthenia gravis

• Contributing as an adjunct therapy in anaphylactic reactions associated to amino steroid muscle relaxants • Contributing to a reduction in the incidence of residual neuromuscular blockade

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RAPID REVERSAL Reversão mais rápida com Sugamadex vs. Neostigmina (após reaparecimento de T2) Recuperação da razão TOF para 0,9 Rocurónio 0,6 mg/kg

Vecurónio 0,1 mg/kg

Sugamadex 2 mg/kg

NEO 50 µg/kg

Sugamadex 2 mg/kg

n = 48

n = 48

n = 48

95% IC (1,2-1,5 min)

95% IC (12,7-26,4min)

95% IC (1,9-3,0 min)

NEO 50 µg/kg n = 45 95% IC (12,2-25,5 min)

Dados do ensaio Aurora.

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RAPID REVERSAL INDEPENDENT OF DEPTH

Reversão mais rápida com Sugamadex vs. Neostigmina (após Rocurónio 0,6 mg/kg e a partir de 1-2 CPTs)

Reversão mais rápida com Sugamadex vs. Neostigmina (após Rocurónio 0,6 mg/kg e a partir de 1-2 CPTs) Os doentes tratados com Sugamadex atingiram mais cedo uma razão T4/T1 de 0,9

75 doentes ASA classe 1-4 Idade: 19-85 Anos

Sugamadex 4 mg/kg

n = 37

95% IC (2,3-3,3 min)

95% IC (35,7-59,5 min)

80 60

Sugamadex4 mg/kg

40

NEO 70 µg/kg

20 0

NEO 70 µg/kg

n = 37

Doentes que atingiram uma razão T4 /T1 de 0,9 (%)

100

0

20

40

60

80

100

120

140

160

Tempo (min) Dados do ensaio Signal.

Dados do ensaio Signal.

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USE IN SPECIAL CIRCUMSTANCES

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ANAPHYLAXIS TREATMENT (ROCURONIUM)

Br. J. Anaesth. (2011) 107 (2): 275-276.

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RESIDUAL BLOCKADE AND SUGAMMADEX What contribution ?

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CLOSING REMARKS • Contributions for neuromuscular blockade management safety: • Being aware of clinical importance of residual neuromuscular blockade

• Use of intermediate neuromuscular blockers • Systematic utilization of neuromuscular monitoring (quantitative if possible) • Regular use of neuromuscular reversal • Use of sugammadex when considered clinically indicated