Esmeron and Clinical Experience
Esmeron and Clinical Experience
Esmeron and Clinical Experience
Esmeron ®
Clinical experiences
Esmeron®
Clinical Experiences
• Chemistry & pharmacology
• Pharmacokinetics
• Pharmacodynamics
• Special patient groups
• Special procedures
• Safety profile
• Summary
Esmeron®
Clinical Experiences
• Chemistry & pharmacology
• Pharmacokinetics
• Pharmacodynamics
• Special patient groups
• Special procedures
• Safety profile
• Summary
Esmeron®
Chemistry & pharmacology
OAc
+
O N
C D
N CH2
a B
CH
HO H -
Br CH2
Chemistry & pharmacology
Affinity for receptor in the NMJ
ACh-like fragment
on the D-ring OAc
+
O N
C D
N CH2
a B
CH
HO H -
Br CH2
Rocuronium
Chemistry & pharmacology
Low potency
Absence ACh-like fragment on A-ring
Replacement methyl
OAc
by allyl group
O N+
C D
N CH2
a B
CH
HO H -
Br CH2
Rocuronium
Chemistry & pharmacology
Stable solution
Replacement acetate
by hydroxy group OAc
O N+
C D
N CH2
a B
CH
HO H -
Br CH2
Rocuronium
Esmeron®
Clinical Experiences
• Chemistry & pharmacology
• Pharmacokinetics
• Pharmacodynamics
• Special patient groups
• Special procedures
• Safety profile
• Summary
Esmeron®
Pharmacokinetics (1)
• Highly ionized, low lipid solubility
• Small central volume of distribution (VDc) high
initial blood concentration
• Creates gradient between blood & tissues fast
onset
• Volume of distribution at steady state (VDss)= ~
200mg/kg
• Plasma clearance (Clp) = 3.7 mg/kg/min
Esmeron®
Pharmacokinetics (2)
• Elimination
– hepatobiliary 50%
– renally 50%
• No accumulation during maintenance
infusions lasting up to 140 hours
Esmeron®
Clinical Experiences
• Chemistry & pharmacology
• Pharmacokinetics
• Pharmacodynamics
• Special patient groups
• Special procedures
• Safety profile
• Summary
Esmeron®
Pharmacodynamics
• Rapid onset of action
• Intermediate duration of action
• Dose-response relationship
• Rapid recovery
(in 14 min from T1 25% to T1 75%)
• Reversal
(on T1 25% in 5 min from T1 25% to T1 75%)
Pharmacodynamics
Routine intubating dose
• Esmeron 0.6 mg/kg ( 2x ED 95 )
gives good to clinically acceptable
intubating conditions within 60 sec
• Mean onset time ( until maximum block)
60 - 120 sec
• Clinical duration 30 - 40 min
Pharmacodynamics
Routine infusion dose
7
6
5
4
3
2
1
0
0 50 100 200 300 400 500 600 700 800
Effective dose for 90% block (mcg/kg)
Onset of
neuromuscular block
at the larynx and
adductor pollicis
muscles after 0.5
mg/kg rocuronium
bromide
Pharmacodynamics
Dose-response relationship
Esmeron onset duration
(mg/kg) (min) (min)
0.3 2 15
0.45 1.5 25
0.6 1 30-40
0.9 0.75 50-55
Esmeron®
Clinical Experiences
• Chemistry & pharmacology
• Pharmacokinetics
• Pharmacodynamics
• Special patient groups
• Special procedures
• Safety profile
• Summary
Special patients groups
Elderly
total body water
higher peak plasma concentration
lower drug clearance due to:
liver blood flow, volume and metabolic capacity
renal blood flow/ clearance and creatinine
Children:
• higher plasma clearance
shorter duration of block
Special patient groups
Influence of age - overview
Varialbe Units Infnts Children Normal Elderly
Adults
Onset Sec 50 - 60 50 - 60 60 - 120 60 -120
Time
Clinical min 42 21- 29 30 - 40 42
Duration
Revover min 27 9 - 13 14 22
y Rate
Vdss: apparent volume of distribution at steady state; Cl: plasma clearance; T½-
beta: terminal elimination half-life; MRT: mean residence time
10000
healthy cirrhotic
10
0 60 120 180 240 300 360 420 480
Time (min)
Adapted from Van Miert et al. Br J Clin Pharm 1997;44:139-44
Special patient groups
Liver disease (3)
• Hepatic failure: reduced clearance
• Cirrhosis: recovery time from NM block
T1 25% 54 min (cirrh.) vs 42 min (control)
TOF 70% 115 (cirrh.) vs 76 min (control)
MRT Min NR NR 97 58
Vdss: apparent volume of distribution at steady state; Cl: plasma clearance; t½-
beta: terminal elimination half-life; MRT: mean residence time
From: Reeves et al.1999 Crit.Care Med 27suppl, Circeo et al. South Med.J 2001;94:36,
Sparr et al. Br.J.Anaesth 1997;78:267
Esmeron®
Clinical Experiences
• Chemistry & pharmacology
• Pharmacokinetics
• Pharmacodynamics
• Special patient groups
• Special procedures
• Safety profile
• Summary
Clinical experiences
Special procedures
• Rapid Sequence Induction (RSI)
• Day care
• Neurosurgery
• Ocular surgery
• Cardiac surgery
• Cesarean section
• Surgery under hypothermic conditions
Special procedures
RSI (1)
100%
Comparison of 90%
80%
intubating
70%
conditions with
60% Fair
suxamethonium 50% Good
1.0 mg/kg and 40% Excellent
rocuronium 30%
0.6mg/kg and 20%
1.0mg/kg 10%
0%
Sux Roc Roc
1mg/kg 1.0mg/kg
0.6mg/kg
Adapted from: McCourt et al 1998Anaesthesia 53:867-87)
Special procedures
RSI (2)
From: Mazurek etal. Anesth Analg 1998;87:1259-62; Laurin et al. Acad EMerg MEd 2000;7:1362-
9
Special procedures
Day case anesthesia
• Short clinical duration and rapid recovery
are important
• 0.3 - 0.45 mg/kg Esmeron:
– Intubation within 90 seconds
– Duration of action = 14 - 22 min.
From: Chetty et al. Anaesth Intensive Care 1996;24:37-41; Pollard et al. Eur J Anaesth
1995;12:81-3; Prien et al. Eur J Anaesth 1995;12:85-90
Special procedures
Ocular and neurosurgery
Ocular surgery
• Esmeron has no effect on Intra-Ocular
Pressure (IOP)
Neurosurgery
• Esmeron has no effect on Intra-Cranial
Pressure (ICP)
From: Robertson et al. Eur J Anaesth 1994;11:116-21; Schramm et al. Br J Anaesth
1996;76:607-11
Special procedures
Cardiac surgery
From: McCoy et al. Can J Anaesth 1993;40:703-8 and Levy et al. Anesth Analg 1994;78:318-
21
Safety profile
Histamine release
30 0.6 mg/kg
0.9 mg/kg
2.5
Plasma Histamine (ng/ml)
1.2 mg/kg
2.0
1.5
Minimal histamine release
even at higher doses
1.0
0.5
0
0 1.0 2.0 3.0 4.0 5.0
Time (min)