Choice of muscle relaxant in day surgery

1. I Miorilassanti in day surgeryday anesthesia
Claudio Melloni
Servizio di Anestesia e Rianimazione
Ospedale di Faenza(RA)

2. Caratteristiche del miorilassante
ideale in day surgery-day
anesthesia
• Fast onset & fast offset
• assenza di blocco residuo
– asssenza necessità di antagonizzazione….
• assenza di effetti
collaterali;istaminoliberazione,effetti
cardiovascolari…
• predicibilità durate
• sicurezza
•

3. Problemi dei miorilassanti in day
anesthesia……...
Fast onset
Fast offset
No blocco residuo
No blocco residuo
Profilo
di
sicurezza
Mancanza effetti collaterali
No liberazione di
istamina;
no effetti emodinamici
Evita antagonismo
Evita antagonismo
No metaboliti attivi
No metaboliti attivi
Indipendenza da organi
Valutazione
rischio/beneficio
Facile
Facile conservabilità/utilizz
sicurezza
conservabilità e

4. Valutazione del blocco residuo
• Valutazione della ripresa neuromuscolare:
– prima del risveglio:
• valutazione della forza contrattile in risposta alla
stimolazione:MMG,EMG.accelerometria,qualitative
e quantitative:TOF,DBS,tetano 50,100 HZ…….;
• TV,RR,forza insp ed esp
– dopo il risveglio,volontarietà:
•
•
•
•
•
sollevamento testa> 5 sec
sollevamento braccio
stretta di mano
protrusione lingua
apertura ampia occhi

5. Assiomi della ripresa nm.
• TOF > 0.70 sicuro indice della ripresa
nm……….. Ali HH, Wilson RS, Savarese JJ, Kitz RJ:
The effect of tubocurarine on indirectly elicited train-offour muscle response and respiratory measurements in
humans. Br J Anaesth 47:570-4, 1975
• Brand JB, Cullen DJ, Wilson NE, Ali HH: Spontaneous
recovery from nondepolarizing neuromuscular blockade:
Correlation between clinical and evoked responses. Anesth
Analg 56:55-8, 1977

6. Mutazioni occorse
• Esplosione della chirurgia ambulatoriale
• pressione per la diminuzione della spesa
sanitaria
• aumento delle persone anziane e debilitate
anche in chir amb.
• Disponibilità di nuovi farmaci

7. Kopman AF, Yee PS, Neuman GG: Relationship
of the train-of-four fade ratio to clinical signs and
symptoms of residual paralysis in awake
volunteers. ANESTHESIOLOGY 86:765-71, 1997
• 10 healthy, unpremedicated, and unanesthetized volunteers
underwent baseline testing of neuromuscular function,
followed by administration of a single 5- µg/kg bolus of
mivacurium + continuous infusion at 2 µg×kg-1×min-1.
• Nm function tested using TOF stimulation and was
recorded EMG

8. Kopman 2;
• When the target TOF ratio of 0.65—0.70 was achieved,
the mivacurium infusion was titrated to maintain a stable
TOF ratio of 0.70.
• All volunteers then repeated the tests of neuromuscular
function, and the mivacurium infusion then was titrated to
allow recovery to a TOF ratio of 0.85—0.90.
• Nm function tests repeated, and the mivacurium infusion
was discontinued to allow full recovery.
• All volunteers were observed until they believed they
were back to “normal.”

9. Kopman 3:risultati
• The results are as surprising as they are significant: all
volunteers reported considerable visual disturbances even
when the TOF ratio had recovered to 0.90. Head- and leglift usually were present at a TOF ratio of ³0.60, whereas at
a TOF ratio of <0.75, all volunteers felt uncomfortable,
some reporting persistence of diplopia “for periods in
excess of 1 hour after termination of the mivacurium
infusion.” From a monitoring standpoint, of all clinical
tests of neuromuscular function, the most sensitive (when
compared with the TOF ratio) was the ability of the
volunteers to resist the removal of a wooden tongue blade
from their clenched teeth.

10. Rivalutazione della pratica
clinica
• Età e stato di salute differiscono fra volontari
sani e pazienti!
• La prassi clinica e l’utilizzo dei miorilassanti
variano fra i diversi centri ambulatoriali
• il monitoraggio degli effetti nm non è praticato
in ospedale,figurarsi nei centri ambulatoriali!
• I metodi di monitoraggio usati da Kopman et al
si applico ad una ampia gamma di situazioni
cliniche.
• Esistono pesanti pressioni economiche per la

11. Implicazioni del lavoro di
Kopman:1
• I paz chirurgici sono in genere più anziani e
ammalati dei volontari sani dello studio di
Kopman/( ASA 1, entro il 15% del peso ideale,tra
23—33 anni….)
• gli effetti residui dei miorilassanti è probabile
possano essere + significativi nella pratica
ambulatoriale con pazienti + anziani e debilitati.
• Si potrebbe arguire che i paz.con sedazione
residua siano meno attenti a disturbi visivi e
• debolezza dei muscoli facciali;ma è anche vero

12. Implicazioni del lavoro di
Kopman:2
• mivacurium non è rappresentativo dei
miorilassanti usati in chir amb;il mercato è
dominato dai miorilassanti ad azione intermedia
quali vecuronium, atracurium, rocuronium,
cisatracurium
• se una paralisi residua permane per un’ora dopo
interruzione del mivac,caratterizzato da un RI di
pochi min,che succede dopo la somministrazione
dei mioril a durata intermedia(RI 20-30 min )?

13. Day surgery/ anesthesia e LMA
∀ ↓Miorilassanti, ↓ Anestetici, ↓analgesici
• ↓stimolazione cardiovascolare
riprese più rapide
dimissioni più precoci

14. dati sul ORG9487(Wierda)
25
min
20
15
Succi
ORG9487
ORG9487+neo
10
5
0
t125%
tof20%
T190
tof70%

15. confronto fra succi,ORG9487,mivacurium
250
200
150
succi
ORG9487
Mivac
100
50
0
onset
tof70%

16. tempi di ripresa 25-75%
18
16
14
12
10
8
6
4
2
0
cisatr
vecu
rocu
atrac
miva inf
RI 25-75%

17. Lien CA,Belmont MR,Abalos A,Hass D,Savarese
JJ.The nature of spontaneous recovery from
mivacurium induced neuromuscular block.AA
1999;88:648-53.
• Hypothesis:
– in a given patient recovery from an initial or
intubating dose of mivacurium would indicate
the time course of spontaneous recovery after
discontinuation of an infusion of mivac.

18. 1:Lien CA,Belmont MR,Abalos A,Hass D,Savarese
JJ.The nature of spontaneous recovery from mivacurium
induced neuromuscular block.AA 1999;88:648-53.
•
•
•
•
•
•
•
•
38 paz
27-52 anni
ASA 1 & 2
urology
anest:midaz,fent,prop
iot senza miorilass
mant;N2O/O2,prop inf cont,fent
TOF,meccanomiografia(Grass).

19. 3:Lien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.The
nature of spontaneous recovery from mivacurium induced
neuromuscular block.AA 1999;88:648-53.
• Mivac 0.3 mg/kg in due dosi a distanza di
30 sec.
• Al 25% di T1,mivac inf cont allo scopo di
mantenere 95% di blocco.
• Ripresa spontanea

20. 4:Lien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.The
nature of spontaneous recovery from mivacurium induced
neuromuscular block.AA 1999;88:648-53.
• Mivac infusion rate:7.1 microgr/kg/min +/1.7
• durata infusione:30-241 min.
• tempo richiesto per la ripresa spontanea
dopo interruzione della infusione di mivac
non correlata alla durata della infusione di
mivac.

21. Tempi di ripresa dopo mivacurium,bolo e infus.cont.;dati da
Lien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.The nature of spontaneous
recovery from mivacurium induced neuromuscular block.AA 1999;88:648-53.
25
20
15
min
10
5
0
5-25% dopo bolo
5-25% dopo infus
T1-T3 dopo bolo
bolo-T1
bolo -25% T1
25-75% dopo infus
5-95% dopo infus
fine infus-Tof70%
fine infus-Tof 90%

22. Tempi di ripresa dopo mivacurium,bolo e
infus.cont:correlazioni cliniche ;dati da Lien CA,Belmont MR,Abalos
A,Hass D,Savarese JJ.The nature of spontaneous recovery from mivacurium
induced neuromuscular block.AA 1999;88:648-53.
• Tempo di ripresa del I twitch palpabile
dopo il bolo correlato al tempo dalla fine
della infus alla ripresa del TOF 70%:
• T= 8.8 + 0.3*x :intervallo di confidenza
95% 13.5-15.8

23. Tempi di ripresa dopo mivacurium,bolo e
infus.cont:correlazioni cliniche ;dati da Lien CA,Belmont MR,Abalos
A,Hass D,Savarese JJ.The nature of spontaneous recovery from mivacurium
induced neuromuscular block.AA 1999;88:648-53.
• RI 5-25% dopo il bolo relato al tempo
richiesto dalla fine infusione al tof
70%:T=10.3+ 1.1*x (13.5-15.3 min)
• tempo bolo-5%T1 relato al tof 70 e al tof
90%: T=-0,5 +1*x (16.2-22.3 min)

24. Tempi di ripresa dopo mivacurium,bolo e
infus.cont:conclusioni;dati da Lien CA,Belmont
MR,Abalos A,Hass D,Savarese JJ.The nature of
spontaneous recovery from mivacurium induced
neuromuscular block.AA 1999;88:648-53.
• Per ogni paz,la ripresa nella funzione nm dopo
cessazione dell’ inf.cont di miva è legata alla
ripresa iniziale dopo la dose bolo di 0.3 mg/kg.
• Ogni paziente è l’indicatore della propria ripresa.

25. Kahwaji R,Bevan DR,Bikhazi G,Shanks CA,Fragen RJ,Dyck JB,Angst
MS,Matteo R.Dose ranging stuy in younger adults and elderly patients of ORG
9487,a new rapid onset ,short duration muscle relaxant.Anesth.Analg
1997;84:1011-8.
Studio prospettico,randomizzato,assessor
blind,multicentrico,descrittivo
TPS/fentanyl/N2O e infus cont di propofol
monitoraggio EMG con Datex Relaxograph
dosaggi di ORG 9487;0.5/1/1.5/2/2.5 mg/kg
ripresa spontanea

26. Condizioni di intubazione a 60 sec nei pazienti<65 anni
80
p
a
% z
i
d e
i n
t
i
70
60
50
40
30
eccellente
buona
cattiva
impossibile
20
10
0
placebo 0.5 mg/kg 1 mg/kg 1.5 mg/kg 2 mg/kg 2.5 mg/kg

27. Condizione di intubazione nei pazienti > 65 anni
70
60
50
40
eccellente
buona
cattiva
30
20
10
0
placebo
0.5 1 mg/kg 1.5 2 mg/kg 2,5
mg/kg
mg/kg
mg/kg

28. Dati sull’onset e sulla ripresa di ORG 9487
2,5
mg/kg
2 mg/kg
1.5
mg/kg
1 mg/kg
m
i
n
T1 60 sec
picco
dur 25%
dur T4/T1 70%
0.5
mg/kg
o
placebo
%
100
90
80
70
60
50
40
30
20
10
0

29. Conclusioni su ORG 9487
Condizioni di intubazione buone/eccellenti in 90 sec in quasi
tutti i pazienti con dosi > o = 1.5 mg/kg
durate cliniche< 20 min a <2 mg/kg nei giovani e 1.5 mg/kg
negli anziani
broncospasmo con tachicardia in 2 /148 pazienti
riprese dose dipendenti

30. Selettività di ORG 9487
Vagal/soleus:3(76 per vecu e 8 per rocu)
ganglion/soleus; 24

31. Purdy R,Bevan DR,Donati F,Lichtor,L.Early reversal of
rapacuronium with neostigmine.Anesthesiology
1999;91:51-7.
ASA 1-3
premed con diaz o midaz
anest:fent/propofol + inf cont propofol 50-300 g/min
+N2O
meccanomiografia,ST
rapacuronium 1.5 o 2.5 mg/kg:iot a 60 sec.:tre gruppi in
studio :
no reversal
0.05 mg/kg neostigmina + glicopirrolato 0.01 mg/kg
0.07 mg/kg neostigmina+ glicopirrolato 0.01 mg/kg
dopo o 2 o 5 min

32. Riprese del T1 25%
25
20
15
min
rapa 1.5
rapa 2.5
10
5
0
neo 0
neo 0.05 neo 0.07 neo0.05 a neo 0.07
a 2 min a 2 min 5 min a 5 min

33. Ripresa del T1 75 %dopo rapacuronium
40,0
35,0
30,0
25,0
min 20,0
rapa 1.5
rapa 2.5
15,0
10,0
5,0
0,0
neo 0
neo 0.05 neo 0.07 neo0.05 a neo 0,07
a 2 min a 2 min 5 min a 5 min

34. RI del rapacuronium
16
14
12
10
min 8
rapa 1.5
rapa 2.5
6
4
2
0
neo 0
neo 0.05 neo 0.07 neo0.05 a neo 0,07
a 2 min a 2 min 5 min a 5 min

35. TOF 0.7 dopo rapacuronium
60
50
40
min 30
rapa 1.5
rapa 2.5
20
10
0
neo 0
neo 0.05 neo 0.07 neo0.05 a neo 0,07
a 2 min a 2 min 5 min a 5 min

36. Tof 0.8 dopo rapacuronium
60
50
40
min 30
rapa 1.5
rapa 2.5
20
10
0
neo 0
neo 0.05 neo 0.07 neo0.05 a
a 2 min a 2 min 5 min

37. Quoziente di sicurezza:
ED95 istaminoliberatrice/ED95 blocco nm.
8
7
??
6
5
atrac
mivac
cisatrac
4
3
2
1
0
safety factor

39. Problemi della succinilcolina
 Spasmi muscolari
 rabdomiolisi:crush syndrome,shock ipovolemico,aritmie
cardiache,IRA mioglobinurica….
 ipertermia maligna(miopatie,distrofie muscolari,CCD……)
 mialgie:0.2-89%………:femmine,laparoscopie…..
 Iperkaliemia
 spasmo del massetere,rigidità
 crisi miotoniche
 disturbi cardiovascolari
 anafilassi
 impredicibilità di effetti
 aum.IOP
 aum press intragastrica
 aum ICP

40. Fattori che influenzano le mialgie
da succi
• Tipo di pretrattamento:
• miorilassante non depolarizzante
•
•
•
•
•
•
•
fenitoina
BDZ
clorpromazina
vit E
anlgesico FANs(aspirina,ketorolac….)
analgesico oppioide
grado del blocco pregiunzionale
• intervallo fra non depolarizzante e succi

41. Findlay GP,Spittal MJ. Rocuronium
pretreatment reduces suxamehonium induced
myalgia:comparison with vecuronium.BJA
1996;76:526-29.
• 150 patients
• elective oral surgery
• effectiveness and sequelae of pretreatment with
rocuronium for reducing myalgia after suxamethonium
• Patients allocated randomly to one of three groups:
anaesthesia induced with propofol and fentanyl, and group
V received vecuronium 1 mg, group R rocuronium 6 mg
and group P placebo pretreatment
• Suxamethonium 1.5 mg kg-1 60 s after the pretreatment
agent.
• All patients:ketorolac 10 mg i.v. and morphine 10 mg i.m.
for analgesia.
• incidence of postoperative myalgia compared:

42. Incidenza di mialgie dopo succi 1.5 mg/kg
preceduta da piccola dose di vecu,rocu o
placebo(da Findlay GP,Spittal MJ. Rocuronium pretreatment
reduces suxamehonium induced myalgia:comparison with
vecuronium.BJA 1996;76:526-29.)
100
80
60
vecu 1 mg
rocu 6 mg
placebo
%
40
20
0
day 1
day 4

43. Nimmo S M, McCann N, Broome IJ, Robb HM.
Effectiveness and sequelae of very low dose
suxamethonium for nasal intubation.BJA
1995;74:31-34
•
•
•
•
day–case oral surgery
requiring nasal intubation
Anaesthesia induced with propofol and alfentanil
3 groups: no suxamethonium, suxamethonium
0.25 mg kg-1 or 0.5 mg kg-1.
• All patients received i.v. fentanyl and diclofenac
100 mg rectally for analgesia.

44. Nimmo et al.Effectiveness and sequelae of very
low dose suxamethonium for nasal
intubation.BJA 1995;74:31-34
incidenza di mialgie in chir.orale ambulatoriale
100
80
60
%
succi 0.25 mg/kg
succi 0.5 mg/kg
no succi
40
20
0
day 1
day 5
facilità intub

45. Tang J,Joshi G, White PF.Comparison of
rocuronium and mivacurium to succinylcholine
during outpatient laparoscopic surgery.
Anesth Analg 1996; 82:994–8.
• 100 healthy women undergoing outpatient
laparoscopic surgery
• fentanyl-thiopental induction
• tracheal intubation :
–
–
–
–
succinylcholine 1 mg/kg in Groups I and II
rocuronium 0.6 mg/kg in Group III
mivacurium 0.2 mg/kg in Group IV
If clinically indicated, bolus doses of
rocuronium 5–10 mg (Groups I and III) or

46. Risultati dello studio di Tang et al.
30
25
20
cattiva iot a 90 sec
eritema
mialgie
reversal need
costo
% e $ 15
10
5
0
succi 1
mg/kg +
rocu
succi
+miva
rocu 0,6
mg/kg
mivac
0.2
mg/kg

47. Tempi di azione e di ripresa dello studio di Tang
et al.
250
200
150
95% T1 depress
t1 25%
100
50
0
succi 1
mg/kg +
rocu
succi
+miva
rocu 0,6
mg/kg
mivac
0.2
mg/kg

48. Conclusioni dello studio di Tang
et al.
• Intubating conditions 90 sec dopo
•
•
•
•
•
•
miorilass:succi & rocu + rapidi del mivac
onset time_:succi + breve di rocu + breve di miva
recovery times T1 25% :succi & miva + brevi di
rocu
reversal;succi & miva no;rocu sì
eritema : con mivac!
Postoperative myalgia;succi 16% vs 0 dei
nondepolarizz.
PONV =.

49. Watcha MF, Safavi FZ, McCulloch DA, et al. Effect
of antagonism of mivacurium-induced
neuromuscular block on postoperative emesis in
children. Anesth Analg 1995; 80:713-7.
•
•
•
•
•
•
The routine use of cholinesterase inhibitors to antagonize residual
neuromuscular block may be associated with increased postoperative
emesis.
Rapid spontaneous recovery from mivacurium may obviate the need
for these drugs.
randomized, double-blind, placebo-controlled study
113 healthy children
incidence of postoperative complications after spontaneous recovery
and after the use of neostigmine-glycopyrrolate or edrophoniumatropine.
anesthetic regimen :halothane, nitrous oxide, fentanyl, 2
micrograms/kg mivacurium in an initial dose of 0.2 mg/kg, followed
by an infusion, adjusted to maintain > or = 1 evoked contraction

50. Watcha MF, Safavi FZ, McCulloch DA, et al.
Effect of antagonism of mivacurium-induced
neuromuscular block on postoperative emesis in
children. Anesth Analg 1995; 80:713-7.
Incidenza di PONV nella PACU
60
50
40
% 30
20
10
0
*
*
neostigmine 70
micrograms/kg +
glycopyrrolate 10
micrograms/kg,
edrophonium 1 mg/kg +
atropine 10
micrograms/kg.
saline
PONV antiemetici Vomito
necess
entro 24
ore

51. Ding Y,Fredman B, White PF.Use of mivacurium
during laparoscopic surgery:effect of reversal
drungs on postoperaive recovery.Anesth Analg
1994; 78:450–4
• outpatient laparoscopic tubal ligation
• 60 healthy, nonpregnant women.
• midazolam / fentanyl/tps
• succ 1 mg/kg (Group I) vs mivacurium 0.2 mg/kg (Groups
II and III)
• Anesthesia maintained with isoflurane (0.5%-2% +67%
N2O
• Muscle relaxation maintained in all three groups with
intermittent bolus doses of mivacurium, 2–4 mg, IV.
• In Group III, residual neuromuscular block reversed with
neostigmine 2.5 mg +glycopyrrolate, 0.5 mg,

52. Effetti collat dello studio di Ding et al.
80
*
70
60
*
*
50
*
% 40
succi/miva/no antag
miva/miva/ no antag
miva/miva/antag
30
20
shoulder
pain
neck pain
antiemetici
vomit
0
nausea
10

53. Boeke AJ, de Lange JJ, van Druenen B,
Langemeijer JJM. Effect of antagonizing residual
neuromuscular block by neostigmine and
atropine on postoperative vomiting. Br J Anaesth
1994; 72:654-6.
• 80 patients undergoing outpatient surgery
• allocated randomly to two groups: in group
A residual neuromuscular block was
antagonized with a mixture of neostigmine
1.5 mg and atropine 0.5 mg; in group B
spontaneous recovery was allowed.
• patients assessed after operation in hospital
and 24 h after discharge.

54. Boeke AJ, de Lange JJ, van Druenen B, Langemeijer
JJM. Effect of antagonizing residual neuromuscular block
by neostigmine and atropine on postoperative vomiting.
Br J Anaesth 1994; 72:654-6.
• inguinal hernia repair & stripping of the
major saphenous vein of one leg.
• no premed
• atropine 0.5 mg i.v.
• anaesthesia : tps 5–8 mg/kg + fent 2 µg/kg
• vecu.0.1 mg kg-1.
• 100% oxygen * 3 min
• iot

55. Incid.di PONV nello studio di
Boeke et al.
20
18
16
14
12
num.paz 10
8
6
4
2
0
*
antag
non antag
PONV RR
PONV I
PONV II antiemetici

56. Boeke et al.;risultati e conclusioni.
• We found a significant difference (P < 0.05) in requirements
for antiemetic therapy with a smaller need in the group which
received neostigmine (in group A four of 40 patients received
an antiemetic compared with 12 in group B).
• no significant difference in frequency of nausea or vomiting
between the two groups.
• The incidence of postoperative nausea was 14 in group A and
18 in group B and the number of patients with postoperative
vomiting was 10 in group A and 15 in group B.
• In conclusion, as there was an increase in the number of
patients requiring antiemetics in group B compared with
group A (P < 0.05), the results of this study may suggest an
antiemetic effect of neostigmine.

57. Costi
Diretti:
acquisto
conservazione
indiretti:
trattamento ;
lib istamina
mialgie
bocca secca
PONV…..
prolungamento degenza,:sala op,RR,Pacu...
Ospedalizzazione non prevista

58. Kao YJ, Mian T, McDaniel KE, et al. Neuromuscular
blockade reversal agents induce postoperative nausea and
vomiting [abstract] Anesthesiology 1992;
77(Suppl):A1120.
Minilap per PPTL.Tps/succi/iot/fent/isof/N2O
.Stomaco svuotato.
Atrac 0.15 mg/kg.
35
30
25
% 20
15
10
5
0
no antag
*
PONV
A 0.15 micrG/kg + edroph 1
mg/kg
A 0.15 micrg/kg+neo 0.05
mg/kg
A 0.15 icrg/kg+pirido 0.25
mg/KG

59. Zahl K,Apfelbaum JL.Muscle pain occurs after
outpatient laparoscopy despite the substitution of
vecuronim for succinylcholine.Anesthesioloogy
70;408-11,1989.
• 35 paz sane non gravide per lap diagnostica
• questionario su dolore (VAS) in 11 regioni
corporee;compilato alla sera dell’op. e poi I,II,III giorno
postop.
• no premed
• fent 2 µg/kg,tps 6 m/kg:poi iot dopo succi 1.5 mg/kg( DTC
pretratt.) vs vecu 0.05 mg/kg.
• Posiz litotomica
• mantenim con N2O + tps/fent as required
• ST mantenuto al T1 10% con dosi addiz di vecu o infus di
scc.

60. d
o
l
o
r
e
5
4,5
4
3,5
3
2,5
2
1,5
1
0,5
0
polpaccio
coscia
natiche
addome
dorso
spalle
collo
braccio
gola
mandib
occhi
Zahl K,Apfelbaum JL.
Risultati
succi
vecu

61. Zahl K,Apfelbaum JL.
Risultati

62. Zahl K,Apfelbaum JL.:conclusioni
• Nessuna differenza nelle frequenze e
severità del dolore nelle varie regioni
corporee ai vari tempi

63. Fragen RJ,Shanks CA.Neuromuscular recovery
after laparoscopy.Anesth.Analg.63;51-4.1984.
•
•
•
•
•
•
60 pz sane
laparoscopia:30-60 min.
anest:tps/N2O +fent o isof.
vecu 0.045 mg/kg vs panc 0.07 mg/kg
tof:meccanomiografia e EMG
antag se tof<0.80 alla fine
dell’intervento;edroph 0.5-0.6 mg/kg +
atropa 7-10 µg/kg.eventualmente ripetuti .

64. Risultati monitoraggio nm.(da
Fragen RJ,Shanks CA.Neuromuscular recovery after
laparoscopy.Anesth.Analg.63;51-4.1984.
II dose
antag
antag
necess
ripr
spont
t4/t1 fine
op
20 min
T1%
time to
mx block
vecu
panc
onset
s
e
c
,
m
i
n
,
%
100
90
80
70
60
50
40
30
20
10
0

65. Risultati ripresa nm.(da Fragen RJ,Shanks
CA.Neuromuscular recovery after laparoscopy.Anesth.Analg.63;51-4.1984.
Entro 60 min
errori
Trieger
depr
stretta 30'
depr.forza
diplopia
errori
Trieger
vecu
panc
depr
stretta
p
a
z
.
depr.forza
%
90
80
70
60
50
40
30
20
10
0
Entro 30 min

66. Poler SM,Luchtefeld G,White PF.Comparison of
mivacurium and succinylcholine during
outpatient laparoscopy.Anesthesiology 1989,69:A
523.
•
•
•
•
•
42 paz per laparoscopia
drop+metoclopr
EMG
alf 20 µg /kg+tps 3.5 mg/kg;poi
3 gruppi
– succi 1mg/kg+inf 60 µg/kg/min+alf 1 µg
/kg/min
– mivac 0.15 mg/kg+inf 6 µg /kg/min+alf 1 µg
/kg/min

67. Risultati dello studio di Poler et al.
•
•
•
•
Onset + breve con succi
iot time + lungo con mivac
recovery + rapido con succi
no reversal con succi:75% con miva(infus
cessata 5 min prima della fine operaz)
• no diff in mialgie
• flush cutaneo nel 38% dei paz dopo mivac.

68. Goldberg ME,Larijani GE,Azad SS,Sosis M,Seltzer JL,Ascher
J,Weakly JN. Comparison of trcheal intubating conditions and
neuromuscular blocking profiles after intubating doses of
mivacurium chloride or succinylcholine in surgical
outpatients.Anesth.Analg.1989,69.93-9.
•
•
•
•
30 outpatients
tps/fent/N2O 70%+ fent
MMG, tof
gruppi:
– succi 1 mg/kg
– mivac 0.20 mg/kg
– mivac 0.25 mg/kg
– nm block continuato con inf cont di succi o
mivac.

69. Tempi di ripresa da Goldberg et al( con MIR di
40 µg/kg/min per succi e 6.6 per mivac)
45
40
35
s
30
e m
25
c i
20
n
15
o
10
5
0
%
antag
RI 95
RI 75
Ri 50
RI25
dur 5%
onset(t110%)
succi
mivac 0.20
mivac 0,25

70. Indici di ripresa a 2-3 ED95
35
Da Miller et al.Anesthesiology 1984 ;61:444
30
25
20
Da Goldberg et
al.
mivac
atrac
vecu
15
10
5
0
RI 5-95%
RI25-75%

71. Whalley D,Maurer WG, Knapik AL,Estafanous
FG.Comparison of neuromuscular effects,efficacy and
safety of rocuronium and atracurium in ambulatory
anesthesia.
Can J Anaesth 1998 / 45 / 954-959.
• studio comparativo randomized, assessor-blinded
•
•
•
•
per gli effetti nm,cardiovascolari di dosi
equipotenti di rocu vs atrac
chir laparoscopica ambulat.
41 paz:
– 2 x ED90 rocuronium (0.6 mg×kg-1; n = 20)
– atracurium (0.5 mg×kg-1; n = 21)
anest. propofol/alfentanil/ N2O/O2
MMG,TOF

72. Risultati dello studio di Whalley.
et al.
100
90
80
70
60
50
40
30
20
10
0
min
%
sec
rocu
atrac
min
min
onset
iot<90 sec dur 25%
RI 25-75
Tof 0.70

73. RI da Whalley & Hans(Hans P, Brichant JF,
Franzen A, Faleres X, Lamy M. Comparison of neuromuscular block of
atracurium and rocuronium in adults. Acta Anaesthesiol Belg 1996;
47:53-8. )
18
16
14
12
10
N2O
N2O
enflurano
enflurano
rocu
atrac
8
6
4
2
0
RI Whalley
RI Hans

74. Conclusioni da Whalley et al.
• Rocuronium has minimal side effects,
provides conditions more suitable for rapid
tracheal intubation, and is associated with a
shorter clinical duration than atracurium.
Once begun, the spontaneous recovery
profile of rocuronium is slightly slower than
that of atracurium.

75. Chetty MS, Pollard BL, Wilson A, Healy TEJ.
Rocuronium bromide in dental day case anaesthesia - a
comparison with atracurium and vecuronium. Anaesth
•
•
•
•
•
Intensive Care 1996; 24:37-41.
intubating conditions at 60 seconds, onset times and
reversal characteristics of rocuronium with atracurium and
vecuronium.
Middle age,m & f .
1.75 X ED90 of each agent used to assess their relative
suitability for brief day case dental procedures requiring
intubation
anestesia: propofol, fentanyl, N2O/ isoflurane.
EMG

76. Risultati di Chetty et al.
% paz
80
70
60
%
50
40
min
30
20
min
10
0
rocu
atrac
vecu
successo iot blocco % a
60"
60"
dur25%
Ri con neo

77. Stevens J,Walker SC, Fontenot JP. The clinical
neuromuscular pharmacology of cisatracurium
versus vecuronium during outpatient
anestesia.Anesth Analg 1997; 85:1278–83
• 165 ASA I and II patients
• elective outpatient procedures (primarily
orthopedic, otolaryngologic, gynecologic,
and plastic surgery)
• midaz/alfent/propof→iot →N2O + propofol
• 120 patients received cisatracurium 5, 10,
or 15 µg/kg or normal saline placebo
followed 5 min later by either cisatracurium
100 µg/ /kg or vecuronium 100 µg/ /kg

78. Risultati dello studio di Stevens
et al.
• clinical onset of vecuronium without priming (2.8 ± 0.8
min) (mean ± SD) was significantly (P < 0.05) faster than
the onset of cisatracurium without priming (4.6 ± 1.4 min).
• Cisatracurium 5, 10, or 15 µg/ /kg administered before
cisatracurium 100 µg/ /kg significantly (P < 0.05)
accelerated the time to complete ablation of the evoked
response (3.9 ± 0.9, 2.9 ± 0.8, or 3.0 ± 0.9 min,
respectively) compared with cisatracurium 100 µg/ /kg
without priming.
• The dose of neostigmine required to achieve 50% assisted
recovery of the train-of-four ratio at 5 min was
significantly (P < 0.05) smaller in patients who received
vecuronium (29.1 [17.9–55.3] µg/ /kg) (mean [95%
confidence interval]) compared with those who received

79. dati di farmacodinamica da Stevens et al.
90
80
70
60
50
40
30
20
10
0
cis 100 microgr/kg
ci5 + cis 100
cis 10+ cis 100
cis 15 + cis 100
vec 100
t1 90 sec
t1 95%
depr
T1 zero
T1 10%

80. Tempi per il tof > 0.70 nello
studio di Stevens et al.
12
10
8
cisatrac
vecu
min 6
4
2
0
neo 50 micrgr/kg
neo 30 microgr/kg

81. Conclusioni di Stevens et al.
• Although priming with 10 or 15 µg/kg cisatracurium
resulted in a 35% reduction in clinical onset compared
with cisatracurium 100 µg /kg alone, the clinical onset of
cisatracurium with priming was not significantly different
from the clinical onset of vecuronium 100 µg /kg without
priming.
• both cisatracurium and vecuronium are readily
antagonized to a TOF ratio of 0.7 with neostigmine.
• Patients who received vecuronium, however, recovered to
a TOF ratio >0.7 faster than those who received
cisatracurium.
• Further, our results suggest that a larger dose of
neostigmine is required to rapidly antagonize
cisatracurium than to rapidly antagonize vecuronium.

82. Conclusioni di Stevens et al
• Given its faster clinical onset and greater
sensitivity to antagonism by neostigmine,
we conclude that vecuronium may be more
suitable than cisatracurium for use in
outpatient anesthesia.

83. Criteri di scelta dei miorilassanti
in day surgery-day anesthesia
•
•
•
•
•
•
Conoscenza dei tempi chir e anest;
dosi non >1-1.5 ED 95;
monitoraggio ;
vietati i miorilassanti a durata lunga:
evitare antagonismo se possibile
scelta fra:
– Rapacuronium,rocuronium vecuronium
– mivacurium,atracurium,cisatracurium.

84. Indicazioni di massima per l’uso dei miorilassanti
in day surgery-day anesthesia
• Chirurgia < 30 min: Rapacuronium o
mivacurium,monodose.
• chirurgia 30-60 min:monodose di
rocuronium,vecuronium,atracurium,cisatracurium :
– 2-3 ED di rapacuronium o monodose di mivac + inf
cont
• chirurgia 60-90 min:dose iniziale di
rocuronium,vecuronium,atracurium,cisatracurium con dose
rip possibile opp mivacurium monodose + inf cont.
• chirurgia 90-120 min;tutti i precedenti,sia a dosi rip
che mivac inf cont.
• Chirurgia che si prolunga

85. Future trends
Miraculorium
– fast onset & offset,senza
cumulatività……..
– no metaboliti attivi
– indipendente da organi
– no effetti cardiovascolari
– (selettivo per gruppi muscolari…)