Reversal of Neuromuscular Blockade by Sugammadex after Continuous Infusion of Rocuronium in Patients Randomized to Sevoflurane or Propofol Maintenance Anesthesia - PowerPoint PPT Presentation

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Reversal of Neuromuscular Blockade by Sugammadex after Continuous Infusion of Rocuronium in Patients Randomized to Sevoflurane or Propofol Maintenance Anesthesia

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Title: Reversal of Neuromuscular Blockade by Sugammadex after Continuous Infusion of Rocuronium in Patients Randomized to Sevoflurane or Propofol Maintenance Anesthesia


1
Reversal of Neuromuscular Blockade by
Sugammadex after Continuous Infusion of
Rocuronium in Patients Randomized to Sevoflurane
or Propofol Maintenance Anesthesia
????????????Sugammadex????????????????
  • Christopher Rex, M.D., Stefanie Wagner, M.D.,
  • Anesthesiology, Jul 2009,111305.

2
Background
Nondepolarizing neuromuscular blockade (NMB).
REVERSAL agents
Partially effective against
Residual NMB
Profound NMB.
Acetylcholinesterase inhibitors neostigmine and
edrophonium.
Especially in the presence of volatile
anesthetics sevo.
Adverse effects cholinergic cardiovascular and
gastrointestinal events.
3
Background
Modified gamma cyclodextrin specifically designed
for steroidal neuromuscular blocking agent (NMBA)
rocuronium.
Sugammadex
acts by encapsulating unbound rocuronium
molecules and reducing their concentration at the
neuromuscular junction (NMJ).
rapidly and safely reverses rocuronium- and
vecuronium-induced NMB.
also effective in reversal of profound NMB.
4
Su-gamma-dex
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????
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Background
Previous studies
single /repeat bolus doses
Vs.
Stable drug concentrations Constant degree of
paralysis
continuous infusion
However, continuous infusion of Roc significantly
increase the recovery time compared with single
bolus doses. Jellish, the median recovery index
(time for T1 recover from 25-75) A single bolus
dose 17 min Continuous infusion24 min Some
patients 70min Prolonged infusion - require a
reversal agent.
10
Background
NMBAs--- more potentiated with sevoflurane than
propofol. AchE-I RECOVERY DELAYED!
Sugammadex under maintenance anesthesia with
sevoflurane and propofol have recently been
investigated, but only after administration at
reappearance of the second twitch of the TOF
after a single bolus dose of rocuronium.
(representing a time of partial spontaneous
recovery of neuromuscular function.????????)
Residual NMB
11
Background
Rapid reversal of sugammadex
Redistribution of rocuronium
explained
Continuous infusion Redistribute is decreased as
a result of distribution compartment saturation.
Whether volatile anesthetics do influence the
clinical effect and safety of sugammadex when
used for reversal from NMB induced by continuous
infusion of rocuronium?
12
Objective
  • Primary objective show equivalence in recovery
    from NMB after a single dose of sugammadex (4
    mg/kg) administered at T1 310 of baseline after
    continuous infusion of rocuronium in patients
    receiving propofol or sevoflurane.
  • Secondary objective investigate safety and to
    compare plasma rocuronium concentrations between
    groups before sugammadex administration.

Profound NMB.
13
Materials and Methods
  • Study Design and Patient Selection
  • phase III, safety assessor-blinded trial
  • Dec 2006-Mar 2007
  • 4 surgical centers in Germany (Reutlingen, Kiel,
    Berlin,and Marburg).
  • 52 pts.
  • 20-65yrs.
  • gt2-5h surgery in GA, required NMB.

14
Materials and Methods
  • Exclusion criteria were
  • neuromuscular disorder
  • an anatomical malformation that predicted
    difficult intubation
  • history of malignant hyperthermia
  • significant renal dysfunction
  • allergy to medications used during GA
  • concurrent use of medications known to interfere
    with NMBAs (e.g., antibiotics, anticonvulsants,
    magnesium salts)
  • and women who were pregnant, breastfeeding, or of
    childbearing potential and not using an adequate
    method of contraception.

15
Materials and Methods
  • Group Assignment
  • Patients were randomized to either propofol or
    sevoflurane ( a central randomization list
    system).
  • Induction IV opioid propofol
  • Maintainence IV opioid sevoflurane (target 1.5
    vol end tidal) or propofol.

16
Materials and Methods
  • Study Procedures

0.6 mg/kg Rocuronium
Tracheal intubation
Continuous infusion of 7 ug kg-1 min-1
Zero response to TOF a PTC of lt 10 responses gt
90 min.
END infusion
4 mg/kg Sugammadex at a target NMB of T1 of 310.
ONLY ONE DOSE Sugammadex ONLY ROC CI !
17
Materials and Methods
  • Neuromuscular function was monitored by
    acceleromyography at the adductor pollicis muscle
    using the TOF-Watch SX.
  • Repetitive TOF sti was applied at the ulnar
    nerve every 15 s until the end of anesthesia.

18
Zero response to TOF a PTC of lt 10 responses
19
TOF?????
???? ????()
T4?? 75
T3?? 80
T2?? 90
T1?? 100
20
Materials and Methods
  • Safety
  • Adverse events (AEs) and serious AEs.
  • BP HR bf Roc---bf Sug---2,5,10,30min aft Sug,
    and Po-visit (gt10h aft Sug).
  • RR SpO2, RR( aft TOF0.9 1h)
  • Clinical evidence of NMB.
  • ECG QT interval.
  • Venous blood samples (10 ml per sample)
    biochemistry and hematology variables

21
Materials and Methods
  • Plasma Concentration Analysis
  • Two venous blood samples (2 ml per sample)
  • (one before administration of rocuronium and one
    within 2 min before administration of sugammadex).

22
Results
Patients
One patient in the propofol group discontinued
from the study before anesthesia was started and
before sugammadex was administered because of
pretreatment AEs. (severe vomiting and nausea)
23
Results
Dose/ concentration Sevo(sug-TOF0.9) (vol) Sevo(sug-TOF0.9) (vol) Pro (ug/kg/h)
0.5-3.0 17 1.6(mean) 0.5-10.2
(n26) 1 stop bf sug 9.5min (n25)
Target-1.5 8 0.5-2.7
Core body temperature ( nose or bladder)
maintained gt35C except for one subject who was
not covered due to surgery. Mean peripheral
temperature (skin of the hand) was 35C and was
maintained at gt32C in 48 / 52 patients 4
patients, 31.4-31.8C, but no abnormalities in
the time to recovery .
24
Results
Clinical Effect
lt2.5min
25
Results
Clinical Effect Plasma Concentrations
Roc (ug/kg.h) 0.43 0.46 7
T1() 3-10 5.9 6.7
Ps roc (ng/ml) 680 959 33 (plt0.05)
26
Results
Safety
  • 46 patients had 1 AE (92 sevo VS 88 in pro).
  • Most frequent AEs procedural pain, constipation,
    and nausea.
  • No serious AEs , no deaths. No patients
    discontinued .
  • 1 Pts procedural hypotension in the sevo .
  • 2 min after sugammadex, BP 102/65 - 73/47 mmHg ,
    lasted 3 min. By 5 min postdose, recovered to
    96/62 mmHg. No markedly abnormal HR.

27
Results
Safety
  • No differences in laboratory parameters, vital
    signs, or respiratory rate.
  • No reports of residual or reoccurrence of NMB
    based on neuromuscular monitoring.

28
Discussion
  • This study showed that a single dose of
    sugammadex (4mg/kg) administered at T1 310
    after continuous infusion of rocuronium was
    equally effective for the reversal of NMB,
    regardless of whether sevoflurane (1.3min) or
    propofol(1.2min).
  • Vanacker et al., mean time to recovery of the TOF
    ratio to 0.9 was 1.8 min after 2.0 mg/kg
    sugammadex at reappearance of the second twitch .
  • The mode of roc (redistribution from the NMJ is
    likely to be reduced with continuous infusion
    when the peripheral compartment has become
    saturated) led us to select 4 mg/kg sugammadex.

29
Discussion
  • The recovery times reported in our study are
    faster than has been previously reported for the
    reversal of NMB with anticholinesterases.
  • 7.5min--50ug/kg neostigmine
  • 9.3 min --1.0 mg/kg edrophonium
  • (at 10 of T1).

30
Conclusion
  • In conclusion, a single dose of sugammadex after
    continuous infusion of rocuronium is equally
    effective for NMB reversal and well tolerated
    during maintenance anesthesia with sevoflurane or
    propofol.

31
Thank you!
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