I Miorilassanti in day surgery-day anesthesia

Claudio Melloni

Servizio di Anestesia e Rianimazione

Ospedale di Faenza(RA)

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

• indipendenza da organi….(ma Asa dei paz,ambulat...)

Problemi dei miorilassanti in day anesthesia……...

Fast onset

Fast offset

No blocco residuoEvita antagonismo

No metaboliti attivi

Mancanza effetti collaterali

Profilodi

sicurezza

Facile conservabilità e

Valutazione rischio/beneficio

No blocco residuo

No metaboliti attivi

No liberazione di istamina;no effetti emodinamici

Evita antagonismo

Facile conservabilità/utilizzo

Indipendenza da organi sicurezza

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

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-of-four 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

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

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- g/kg bolus of mivacurium + continuous infusion at 2 g×kg-1×min-1.

• Nm function tested using TOF stimulation and was recorded EMG

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.”

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 leg-lift 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.

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 diminuzione della spesa sanitaria.

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 che dal punto di vista della sicurezza i paz postop siano esposti a rischio maggiore di aumento della morbilità,poichè la debolezza residua nm può essere aggravata da residui dell’anestesia.

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 )?

Day surgery/ anesthesia e LMA

Miorilassanti, Anestetici, analgesici

• stimolazione cardiovascolare

riprese più rapidedimissioni più precoci

dati sul ORG9487(Wierda)

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Lien CA,Belmont MR,Abalos A,Hass D,SavareseJJ.The nature of spontaneous recovery from

mivacurium induced neuromuscular block.AA1999;88:648-53.

• Hypothesis:– in a given patient recovery from an initial or

intubating dose of mivacurium would indicatethe time course of spontaneous recovery afterdiscontinuation of an infusion of mivac.

1:Lien CA,Belmont MR,Abalos A,Hass D,SavareseJJ.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).

3:Lien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.Thenature of spontaneous recovery from mivacurium induced

neuromuscular block.AA 1999;88:648-53.

• Mivac 0.3 mg/kg in due dosi a distanza di30 sec.

• Al 25% di T1,mivac inf cont allo scopo dimantenere 95% di blocco.

• Ripresa spontanea

4:Lien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.Thenature 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 spontaneadopo interruzione della infusione di mivacnon correlata alla durata della infusione dimivac.

Tempi di ripresa dopo mivacurium,bolo e infus.cont.;dati daLien CA,Belmont MR,Abalos A,Hass D,Savarese JJ.The nature of spontaneousrecovery from mivacurium induced neuromuscular block.AA 1999;88:648-53.

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5-25%dopo bolo5-25% dopo infusT1-T3 dopo bolobolo-T1bolo -25%T125-75% dopo infus5-95% dopo infusfine infus-Tof70%fine infus-Tof 90%

Tempi di ripresa dopo mivacurium,bolo einfus.cont:correlazioni cliniche ;dati da Lien CA,Belmont MR,Abalos

A,Hass D,Savarese JJ.The nature of spontaneous recovery from mivacuriuminduced neuromuscular block.AA 1999;88:648-53.

• Tempo di ripresa del I twitch palpabiledopo il bolo correlato al tempo dalla finedella infus alla ripresa del TOF 70%:

• T= 8.8 + 0.3*x :intervallo di confidenza95% 13.5-15.8

Tempi di ripresa dopo mivacurium,bolo einfus.cont:correlazioni cliniche ;dati da Lien CA,Belmont MR,Abalos

A,Hass D,Savarese JJ.The nature of spontaneous recovery from mivacuriuminduced neuromuscular block.AA 1999;88:648-53.

• RI 5-25% dopo il bolo relato al temporichiesto dalla fine infusione al tof70%:T=10.3+ 1.1*x (13.5-15.3 min)

• tempo bolo-5%T1 relato al tof 70 e al tof90%: T=-0,5 +1*x (16.2-22.3 min)

Tempi di ripresa dopo mivacurium,bolo einfus.cont:conclusioni;dati da Lien CA,BelmontMR,Abalos A,Hass D,Savarese JJ.The nature ofspontaneous recovery from mivacurium induced

neuromuscular block.AA 1999;88:648-53.

• Per ogni paz,la ripresa nella funzione nm dopocessazione dell’ inf.cont di miva è legata allaripresa iniziale dopo la dose bolo di 0.3 mg/kg.

• Ogni paziente è l’indicatore della propria ripresa.

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,descrittivoTPS/fentanyl/N2O e infus cont di propofolmonitoraggio EMG con Datex Relaxographdosaggi di ORG 9487;0.5/1/1.5/2/2.5 mg/kgripresa spontanea

Condizioni di intubazione a 60 sec nei pazienti<65 anni

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placebo 0.5 mg/kg 1 mg/kg 1.5 mg/kg 2 mg/kg 2.5 mg/kg

eccellentebuonacattivaimpossibile

Condizione di intubazione nei pazienti > 65 anni

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Dati sull’onset e sulla ripresa di ORG 9487

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Conclusioni su ORG 9487

Condizioni di intubazione buone/eccellenti in 90 sec in quasi tutti i pazienti con dosi > o = 1.5 mg/kgdurate cliniche< 20 min a <2 mg/kg nei giovani e 1.5 mg/kg negli anzianibroncospasmo con tachicardia in 2 /148 pazientiriprese dose dipendenti

Selettività di ORG 9487

Vagal/soleus:3(76 per vecu e 8 per rocu)ganglion/soleus; 24

Purdy R,Bevan DR,Donati F,Lichtor,L.Early reversal of rapacuronium with neostigmine.Anesthesiology 1999;91:51-7.

ASA 1-3premed con diaz o midazanest:fent/propofol + inf cont propofol 50-300 g/min +N2Omeccanomiografia,STrapacuronium 1.5 o 2.5 mg/kg:iot a 60 sec.:tre gruppi in studio :

no reversal0.05 mg/kg neostigmina + glicopirrolato 0.01 mg/kg0.07 mg/kg neostigmina+ glicopirrolato 0.01 mg/kgdopo o 2 o 5 min

Riprese del T1 25%

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Quoziente di sicurezza:ED95 istaminoliberatrice/ED95 blocco nm.

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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

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

• velocità di azione del non depolarizzante

• dose della succi

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:

– Intubating conditions were not affected adversely by any pretreatment regimen.

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.)

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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.

Nimmo et al.Effectiveness and sequelae of very low dose suxamethonium for nasal

intubation.BJA 1995;74:31-34

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incidenza di mialgie in chir.orale ambulatoriale

succi 0.25 mg/kgsucci 0.5 mg/kgno succi

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 mivacurium 2–4 mg (Groups II and IV) were

administered during the maintenance period– Anesthesia maintained with desflurane and nitrous oxide 60% in oxygen.– At the end of the surgery, residual neuromuscular block was reversed with edrophonium 0.5 mg/kg and atropine 10 mg/kg, – The neuromuscular function was assessed using electromyography with a train-of-four mode of stimulation every 10 s at the

wrist.– Intubating conditions 90 s after succinylcholine and rocuronium were significantly better than after mivacurium. The onset time

(from the end of injection until 95% suppression of the first twitch [T1]) for succinylcholine (63 ± 21 s and 62 ± 17 s in Groups I and II, respectively) were significantly shorter than for rocuronium (158 ± 76 s) or mivacurium (210 ± 93 s). Moreover, the onset times for rocuronium were significantly shorter than mivacurium. The recovery times (of T1 to 25% of the control value) were significantly shorter with succinylcholine and mivacurium than rocuronium. Significantly fewer patients needed reversal of residual neuromuscular blockade after mivacurium compared to rocuronium. One patient in Group I and six patients in Group IV displayed erythema on the upper body. Postoperative myalgia were experienced by 16% of the patients in Groups I and II compared to none in Groups III and IV. There was no difference in the incidence of postoperative nausea and vomiting among the four groups. In conclusion, rocuronium appears to be an acceptable alternative to succinylcholine for tracheal intubation. However, rocuronium's longer duration of 45action increases the need for reversal drugs.

Risultati dello studio di Tang et al.

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Tempi di azione e di ripresa dello studio di Tang et al.

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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 =.

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 edrophonium-atropine. • 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 response to a supramaximum train-of-four stimulus.

• At the end of the procedure, patients received by random assignment one of three drug combinations: 1) neostigmine 70 micrograms/kg + glycopyrrolate 10 micrograms/kg, i.v., 2) edrophonium 1 mg/kg + atropine 10 micrograms/kg, i.v., and 3) saline.

• trachea extubated when evoked responses to peripheral nerve stimulation and clinical signs of adequate neuromuscular recovery were present.

• Postoperative pain was treated with morphine and emesis with metoclopramide.

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.

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PONV antiemeticinecess

Vomitoentro 24

ore

Incidenza di PONV nella PACU

neostigmine 70micrograms/kg +glycopyrrolate 10micrograms/kg, edrophonium 1 mg/kg +atropine 10micrograms/kg.

saline

**

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,

Effetti collat dello studio di Ding et al.

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*

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.

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 g/kg

• vecu.0.1 mg kg-1.

• 100% oxygen * 3 min

• iot

• IPPV 66% N2O/ haloth. 0.5%

Incid.di PONV nello studio di Boeke et al.

02468

101214161820

num.paz

PONV RR PONV I PONV II antiemetici

antagnon antag

*

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.

Costi Diretti:

acquisto conservazione

indiretti: trattamento ;

lib istaminamialgiebocca seccaPONV…..

prolungamento degenza,:sala op,RR,Pacu...Ospedalizzazione non prevista aumento del discomfort,ansietà,stress…

Kao YJ, Mian T, McDaniel KE, et al. Neuromuscular blockade reversal agents induce postoperative nausea and

vomiting [abstract] Anesthesiology 1992; 77(Suppl):A1120.

05

101520253035

%

PONV

Minilap per PPTL.Tps/succi/iot/fent/isof/N2O.Stomaco svuotato.Atrac 0.15 mg/kg.

no antag

A 0.15 micrG/kg + edroph 1mg/kg

A 0.15 micrg/kg+neo 0.05mg/kg

A 0.15 icrg/kg+pirido 0.25mg/KG

*

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 g/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.• Vecu antagonizzato con edroph/glicopir.

Zahl K,Apfelbaum JL.Risultati

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Zahl K,Apfelbaum JL.Risultati

Zahl K,Apfelbaum JL.:conclusioni

• Nessuna differenza nelle frequenze e severità del dolore nelle varie regioni corporee ai vari tempi

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 g/kg.eventualmente ripetuti .

Risultati monitoraggio nm.(da Fragen RJ,Shanks CA.Neuromuscular recovery after

laparoscopy.Anesth.Analg.63;51-4.1984.

0102030405060708090

100sec,

min,

%

onse

t

tim

e to

mx

bloc

k

20 m

inT

1%

t4/t

1 fi

neop ri

prsp

ont

anta

gne

cess

II d

ose

anta

g

vecupanc

Risultati ripresa nm.(da Fragen RJ,Shanks

CA.Neuromuscular recovery after laparoscopy.Anesth.Analg.63;51-4.1984.

010

2030

40

5060

70

8090

% paz.

d

epr.

forz

a

dep

rst

rett

a

erro

riT

rieg

er

dip

lop

ia

d

epr.

forz

a

dep

rst

rett

a 30

'

erro

riT

rieg

er

vecupanc

Entro 30 min Entro 60 min

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 g /kg+tps 3.5 mg/kg;poi

• 3 gruppi– succi 1mg/kg+inf 60 g/kg/min+alf 1 g /kg/min – mivac 0.15 mg/kg+inf 6 g /kg/min+alf 1 g /kg/min – mivac 0.15 mg/kg+inf 6 g /kg/min+ enfl 1%

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.

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.

Tempi di ripresa da Goldberg et al( con MIR di 40 g/kg/min per succi e 6.6 per mivac)

05

1015202530354045

sec o

min

onse

t(t1

10%

)

dur

5%

RI2

5

Ri 5

0

RI

75

RI

95

anta

g

succimivac 0.20mivac 0,25

%

Indici di ripresa a 2-3 ED95

0

5

10

15

20

25

30

35

RI 5-95% RI25-75%

mivacatracvecu

Da Goldberg et al.

Da Miller et al.Anesthesiology 1984 ;61:444

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• confronto fra condiz iot,cardiovasc,eventi avversi

Risultati dello studio di Whalley. et al.

0

10

20

30

40

50

60

70

80

90

100

onset iot<90 sec dur 25% RI 25-75 Tof 0.70

rocuatracsec

min

min

min%

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. )

0

2

4

6

8

10

12

14

16

18

RI Whalley RI Hans

rocuatrac

N2ON2O

enfluranoenflurano

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.

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

Risultati di Chetty et al.

0

10

20

30

40

50

60

70

80

successo iot60"

blocco % a60"

dur25% Ri con neo

rocuatracvecu

% paz

%

min

min

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/propofiot N2O + propofol• 120 patients received cisatracurium 5, 10, or 15 g/kg or normal saline

placebo followed 5 min later by either cisatracurium 100 g/ /kg or vecuronium 100 g/ /kg (always after placebo).

• MMG• When the evoked response spontaneously recovered to 10% of control

height, neostigmine 5, 10, 30, or 50 g/ /kg or placebo was administered, and recovery of neuromuscular function was recorded for the next 15 min.

•

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 g/ /kg administered before cisatracurium 100 g/ /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 g/ /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] g/ /kg) (mean [95% confidence interval]) compared with those who received cisatracurium (53.7

[31.6–131.5] g /kg).

dati di farmacodinamica da Stevens et al.

0

10

20

30

40

50

60

7080

90

t1 90 sec t1 95%depr

T1 zero T1 10%

cis 100 microgr/kgci5 + cis 100cis 10+ cis 100cis 15 + cis 100vec 100

Tempi per il tof > 0.70 nello studio di Stevens et al.

0

2

4

6

8

10

12

min

neo 50 micrgr/kg neo 30 microgr/kg

cisatracvecu

Conclusioni di Stevens et al.

• Although priming with 10 or 15 g/kg cisatracurium resulted in a 35% reduction in clinical onset compared with cisatracurium 100 g /kg alone, the clinical onset of cisatracurium with priming was not significantly different from the clinical onset of vecuronium 100 g /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.

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.

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.

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 inaspettatamente;dose inziale di qualsiasi + miva inf cont o dosi rip.

Future trends

– fast onset & offset,senza cumulatività……..

– no metaboliti attivi– indipendente da organi– no effetti cardiovascolari– (selettivo per gruppi muscolari…)

Miraculorium