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Dalle miscele di Piante, per preparare il curaro, un composto catramoso e

appiccicoso si intingono le frecce per cacciare animali , fino ad arrivare alla


Sintesi Chimica

Strychnos (fam. Loganiaceae)

Chondodendron tomentosum
(fam. Menispermaceae).

D- tubocurarina (Intracostin)

Mr. B. Townsend, Jan 23rd 1942


Twenty-five patients during
cyclopropane anesthesia.
Small doses of Intocostrin.

Artificial respiration not


necessary.

We believe the investigation should


continue.

Questi farmaci agiscono a livello della placca neuromuscolare, andando a


competere con il mediatore naturale fisiologico lAcetilcolina.
Il target recettoriale rappresentato dal recettore pentamerico nicotinico
post- sinaptico un recettore di tipo ionico formato da 5 sub unit: 2 alfa, 1
beta , 1 delta, 1 epslon o gamma se trattasi di individui prematuri o neonati

Rationale of NMBAs
Adjuvant for tracheal intubation

Adjuvant for mechanical ventilation


Adjuvant for surgery

NO THERAPEUTIC ACTION PER SE

NMB-Induced Relaxation Eased


Intubation1

NMB-induced relaxation
Improved visualization of vocal
cords
Limited resistance to the
laryngoscope
Decreased frequency of vocal
cord inflammation, laryngeal
hematomas, and postoperative
hoarseness

a Patients

received either NMB or saline. Three minutes after the


injection of the study drug, tracheal intubation was performed by
an anesthesiologist who was blinded to the group assignment.
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1. Mencke T et al. Anesthesiology. 2003;98(5):10491056.

Intubating conditions without NMB (top)


and with NMB (bottom). a
6

THE IDEAL RELAXANT


Non-depolarizing

Rapid onset
Rapid recovery
Dose-dependent duration

No side-effects
Elimination independent of organ function
No active or toxic metabolites
Reversible

Tappe sintesi NMBA

1942
1949
1951
1960
1964
1980
1980
1992
1994
1995

INTOCOSTRIN
d-TUBOCURARINA
SUCCINILCOLINA
PANCURONIO
ALCURONIO
ATRACURIO
VECURONIO
MIVACURIO
ROCURONIO
CISATRACURIO

Muscle Relaxants
Definition
Muscle relaxants are agents that interfere with ACh action
Depending on their effects they are classified in
AGONISTS (depolarizing)
ANTAGONISTS or COMPETITIVES (non depolarizing)

D-Tubocurarine
Succinylcholine

1951

1942

Aminosteroids
Pancuronium

Vecuronium

1967

Rocuronium

1980

1990

Benzylisoquinolines
Atracurium - Cis.Atracurium

1980

1995

Mivacurium

1988

Classificazione dei Miorilassanti


MECCANISMO DAZIONE
Depolarizzanti non competitivi
Non depolarizzanti o competitivi

STRUTTURA CHIMICA
Composti dellammonio quaternario (succinilcolina)
Aminosteroidi ( pancuronio, vecuronio, mivacurio,
rocuronio, rapacuronio)
Derivati benzilisochinolinici ( atracurio, cis-atracurio)

DURATA DAZIONE
Breve, media , lunga

Muscle Relaxants
Dose-Effect
Ed 95: effective dose (mg/kg) to block 95% of receptors

Onset Time: time lapse from NMBA administration to maximum


effect
Clinical Duration of Action: time lapse from administration to
recovery of 25%
Recovery index: time lapse from 25% to 75% recovery

Muscle Relaxants Potency


ED95 in mg/Kg
Vecuronium

0,05

Cis Atracurium

0,05

Pancuronium

0,06

Mivacurium

0,08

Succinylcholine

0,15 - 0,3

Atracurium

0,25

Rocuronium

0,3

DURATION OF ACTION OF NEUROMUSCULAR


BLOCKING AGENTS
Ultra-Short:

Succinylcholine chloride

Short:

Mivacurium chloride

Intermediate: Rocuronium bromide, Vecuronium


bromide, Atracurium besylate
Long:

Pancuronium bromide, curare,


metocurine, Pipecuronium bromide,
Doxacurium chloride

Classification of Neuromuscular
Blockers by Duration of Action (Minutes)
UltraShort

Short

Intermediate

Long

Clinical duration
(injection to T25)

6-8

12 - 20

30 - 45

>60

Recovery time
(injection to T95)

<15

25 - 30

50 - 70

90 -180

Recovery index
(T25 to T75)

2-3

10 -15

>30

Examples

succinylcholine 1

mivacurium

Cis-atracurium

Assumes bolus dose = 2x ED95

doxacurium

NMBAs

Summary

Time to
Intubation
(min)
Clinical
Duration
(min)

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Roc

Vec

Panc

Atra

1.5-2

1.5-2.5 1.5-2

30-40

20-30

86-100 15-40

Cis

Miv

1.5-2.5 0.5-1

55

20-25

Sux

+8

16

Economic Evaluation of
Anesthesia
The Cost of Intubation
Succinylcholine

100 mg

$1

Atracurium

100 mg

$ 33.50

Mivacurium

20 mg

$ 20.90

Pancuronium

5 mg

$ 6.80

Vecuronium

10 mg

$ 16.0

Rocuronium

50 mg

$ 12.75

Cisatracurium

20 mg

$ 19.95

Muscle Relaxants
Depolarizing
Succinylcholine is rapidly hydrolized by plasma cholinesterase (not by
acetylcholinesterase)

Multiple Actions:
1) Depolarizes muscular membrane
2) Inactivates Na+ channels (perijunctionale)
3) Inhibits normal cycle of Na+ channels (remaining membrane)

Succinylcholine
Side Effects (1)
Myalgia (72% Can J Anesth 2000 (47) 5:
427-432)
Fasciculations (about 30-50%)
Malignant Hypothermia
Hyperpotassimia
Increased IOP and ICP
Vagal effects

Succinylcholine
Side Effects (2)
Anaphylaxis
Prolonged block
Masseter spasm
Neuromuscular diseases
Cardiac Arrest
Wide range of Contradictions

CONTRAINDICATIONS OF SUCCINYLCHOLINE

Burns
Sepsis
Severe trauma
Acidosis
Muscular diseases (muscular dystrophy)
Upper neuron lesions and peripheral denervation
Hyper/hypokaliemia
Eye trauma
Prolonged immobility
Atypical cholinesterase

Rosenberg and Gronert


Anesthesiology 1992; 77:1054

Reported four cases of hyperkalaemic cardiac


arrest secondary to SCh-induced muscle
damage in children
Estimated that the US incidence of this
complication could be as high as six cases per
year

...Succinylcholine controversy
Burroughs Wellcome applied to the FDA for a
change in the package insert to limit the use
of SCh in children
After receiving evidence from the profession,
FDA recommended that use of SCh in children
be reserved for emergency intubation or
instances where immediate securing of the
airway is necessary.

Succinylcholine
Because succinylcholine is more hazardous
than any other relaxants, the risk involved in its
use must be counterbalanced by a benefit to
the patient(Feldman, 1996)
In spite of all its disavantages, it has unique
properties: it produces a rapid, profound,
short-lived relaxation (Lee, Baillieres Clinical
Anaesthesiology, 1994)

Neuromuscular Blockers:
Chemical Structure & Key Characteristics
Aminosteroids
Vagolytic
Partially block cardiac muscarinic receptors involved in
heart rate slowing, resulting in increased heart rate:
rapacuronium > pancuronium > rocuronium >
vecuronium
Generally do not promote histamine release
Exception: rapacuronium
Organ-dependent elimination
Kidneys and liver

Savage DS, et al. Br J Anaesth. 1980;52 Suppl 1:3S


Durant NN, et al. J Pharm Pharmacol. 1979:31(12):831
Marshall IG, et al. Br J Anaesth. 1980;52 Suppl 1:11S

Neuromuscular Blockers:
Chemical Structure & Key Characteristics
Benzylisoquinolines
Absence of vagolytic effect
these drugs do not block cardiac-vagal (muscarinic)
receptors
Histamine release
dTc > atracurium > mivacurium > cisatracurium
can cause rare bronchospasm, decreased blood
pressure, increase of heart rate
Generally organ-independent elimination1
esp: atracurium, cisatracurium, mivacurium
Noncumulative2
1Stenlake
2Ali

JB, et al. Br J Anaesth. 1983;55;3S


HH, et al. Br J Anaesth. 1983;55:107S

Sensibilit muscolare ai miorilassanti


1.MUSCOLI ESTRINSECI
LARINGE: massetere

5. DIAFRAMMA

4. ADDUTTORE POLLICE
3. ORBICULARIS OCULI

2.MUSCOLI
INTRINSECI
LARINGE: corde
vocali

INTERMEDIATE
ACTING

Rocuronium and cis-atracurium


Recently introduced neuromuscular blocking
agents

Both represent an evolution within their families


(aminosteroids and benzylisoquinolines)

Rocuronium
Structurally similar to vecuronium
Introduced in clinical practice in 1994
First non-depolarizing to compete with
succinylcholine for rapid sequence intubation
(rapid onset)

Rocuronium

Rapid Onset

Intermediate duration
Reversible
Stable hemodynamics
No histamine release
No active metabolites

Metabolism is organ dependent

Rocuronium
Pharmacokinetics
Plasma elimination by hepatic uptake and
elimination
No active metabolites
Reduced volume of distribution (Vd) compared
to vecuronium

ROCURONIUM BROMIDE:
CARDIOVASCULAR PROFILE
Favorable cardiovascular profile
Histamine release unlikely

Minimal vagolytic activity

Effects of Rocuronium on Heart Rate


600 mcg/kg
900 mcg/kg
1200 mcg/kg

Heart Rate (beats/min)

100
90

80
70
60
50
40

3.0
0.0 1.0 2.0
4.05.0
Time (minutes)

Levy et al. Anesth Analg 1994;78,318-321.

6.0

Mean Arterial Pressure (mmHg)

Effects of Rocuronium on Mean Arterial


Pressure
600 mcg/kg
900 mcg/kg
1200 mcg/kg

100
90
80

70
60
50
0.0 1.0 2.0 3.0 4.0 5.0 6.0
Time (minutes)

Levy et al. Anesth Analg 1994;78,318-321.

Plasma Histamine (ng/ml)

Effects of Rocuronium on Histamine Release


3.0
2.5

600 mcg/kg
900 mcg/kg
1200 mcg/kg

2.0
1.5
1.0
0.5
0.0
0.0

1.0 2.0 3.0 4.0


Time (minutes)

Levy et al. Anesth Analg 1994;78,318-321.

5.0

GUIDA AL DOSAGGIO ROCURONIO


Dose
durata clinica(media)
Onset time(entro)
0,3 mg/kg
15 min
100 sec
0,45 mg/kg
20-25 min
90 sec
0,6 mg/kg
30 min
60 sec
0,9 mg/kg
55 min

1,2 mg/kg
1h e 15 min

1-2-3 Boli di mantenimento 0,1 mg/kg 0,2 mg/kg


durano dai 10 min ai 20 min
2 Infusione continua range da 0,3-0,6 mg/kg/ ora dopo bolo start a
0,6 mg/kg
1 Monografia di prodotto, Cap.3,pp10-23
2 H.J.Sparr, K.S. Khuenl-Brady et al. EJA 1994, 11(suppl. 9),63-65
3 E.P. McCoy, R.K. Mirakhur et al., Anaesthesia,1994, Volume 49, pp 940-945

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Cis-atracurium
One of the 10 stereoisomers of
atracurium
No histamine release

Pharmacokinetics similar to atracurium


Plasma clearance negatively influenced
by renal failure

ED95 0.05 mg/kg (3 times more potent


than atracurium)

Cis-atracurium
Pharmacokinetics
Metabolized by Hofmann reaction
Metabolites: laudanosine
More potent so less molecules thus less
laudanosine

Cis-atracurium
Pharmacodynamics
Histamine release starting from 5 x
ED95
Clinically relevant from 8 x ED95
No cumulative effects

Stable cardiovascular profile similar


to vecuronium

Cis-Atracurium

Slow Onset

Intermediate duration
Reversal is possible
Stable cardiovascular
No histamine release
Non active metabolites (less laudanosine)

Metabolized via Hofmann (influenced by RF)

Neuromuscular Monitoring

Neuromuscular Monitoring
WHY ?
When to intubate
When to extubate

When to administer more NMBA


When to administer the anticholinesterase

Control the level of blockade


Corrections for appropriate level during infusion
Evaluate pharmacodynamic parameters
Costs

When to use it
Should be used whenever utilizing NMBAs
Particulary indicated:
LONG SURGICAL PROCEDURES
.

PATIENTS IN
DISEASES)

WHICH

BLOCKADE

WHEN REVERSAL IS AVOIDED

DRUG INTERCATIONS

CONTINUOS INFUSION IN ICU

MAY

BE

PROLONGED

(NEUROM.

Quando e perch il monitoraggio


neuromuscolare
Stabilire il momento esatto per intubare
Stabilire lintensit e la profondit del blocco
neuromuscolare (ricorda per sapere se il
diaframma fermo, devo sapere il valore della
PTC , non mi basta sapere che il TOF=0).
Migliorare le condizioni del campo operatorio
( es. in laparoscopia)
Valutare il recupero del blocco
neuromuscolare a fine intervento
Guidare lutilizzo del miorilassante nelle
patologie neuromuscolari ( es: Miastenia)
Valutare il momento migliore per usare gli
agenti dinversione del blocco ( a maggior
ragione se utilizzo Neostigmina devo fare il
monitoraggio neuromuscolare perch va
somministrata nel recupero dal 25% al 75%)
Evitare la PORC (Post-operative residual curarization)

Muscle Relaxants
Dose-Effect
100

50
Recovery Index

Onset Time

0
Time

Profilo tipico della farmacodinamica dei


bloccanti neuromuscolari

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Somministrazione
miscela (neostigm+
atropina)

47

Neuromuscular Monitoring
in clinical practice

Extubation

Intubation

NMBA bolus

NMBA bolus

Anticohlinesterase

Neuromuscular Monitoring

Mechanomyography

Neuromuscular Monitoring

Electromyography

Neuromuscular Monitoring

Acceleromyography

Neuromuscular Monitoring
Principle of Acceleromyography
Newtons Law of Acceleration

F (force) = M (mass) X A (acceleration)


(K)
Thus what you measure is Acceleration

Neuromuscular Monitoring
In clincal practice
Acceleromyographic
transducer

Stimulation
electrodes

Tape transducer to the tip of the thumb

Neuromuscular Monitoring

Electrodes position

Neuromuscular Monitoring

position of stimulating electrodes

TOF Guard (acceleromyography)

Electrodes Cable
Acceleration transducer cable

TRAIN OF FOUR STIMULATION (TOF)

Assessing Postoperative Neuromuscular


Function
Train-of-Four (TOF) Fade Ratio

Ali HH, et al. Br J Anaesth. 1975;47:570

Definizione dei Livelli di Blocco/Paralisi


durante la chirurgia

Assessing Postoperative Neuromuscular


Function
ASSESSING TOF FADE RATIO
Patients are often returned to the PACU with residual
paralysis 1
The TOF ratio of 0.70 may be inadequate for discharge of
an ambulatory patient1
TOF ratios 0.40 are difficult to
assess clinically2
1Viby-Mogensen

J, et al. Anesthesiology. 1979;50:539


2Kopman AF, et al. Anesthesiology. 1994;81:1394

Conseguenze cliniche
della curarizzazione residua
recupero post operatorio prolungato
alterazione della funzione respiratoria
alterazione dei riflessi protettivi delle vie aeree

sintomi derivanti dalla debolezza muscolare


riduzione della risposta ventilatoria ipossica
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Complicazioni derivate da una estubazione


precoce
Aumentato rischio di ipossemia,
Ostruzione delle vie aeree superiori,

TOF <0.9:

Eventi critici respiratori in PACU,


Necessit di ventilazione meccanica

Coordinamento e capacit di contrazione faringea ridotta

TOF <0.8:

Disfunzione della deglutizione


Aumentato rischio di aspirazione
Riduzione della capacit muscolare delle vie aeree
superiori

TOF <0.7:

Riduzione della capacit ventilatorie e ipossemia,


Miastenia grave
Rischio di polmonite postoperatoria

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TOF 0,7

TOF 0,9

The undesirable effects of neuromuscular blocking drugs


Claudius C. et al. Anaestesia 2009

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Assessing Postoperative Neuromuscular


Function
THE ORIGIN OF THE GOLD STANDARD
TOF
Ratio

Vital
Capacity

Inspiratory
Force

Peak Exp.
Flow Rate

100

100

100

60%

91

70

95

70%*

97

82

92

80%

100

88

94

90%

100

91

95

100%

100

97

99

Control
=100

* Historically regarded as the Gold Standard

Clinical Tests Are Not a Substitute for


Objective Monitoring
Tongue depressor
test

0,52

Hand grip, 5 s

0,51

Head lift, 5 s

0,51

General weakness

0,51

Leg lift, 5 s

0,5

Smile, swallow
or speak

0,47

0,2

0,4

0,6

0,8

Positive Predictive Value for Identifying TOF <90%


Cammu G, et al. Anesth Analg. 2006;102:426-429.

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AVOIDANCE OF LONG ACTING MUSCLE


RELAXANTS
USE OF NEUROMUSCULAR MONITORING
REVERSAL OF TOF COUNT OF 2 -3
EARLY ADMINISTRATION OF REVERSAL AGENTS

SUGAMMADEX?!

Spesso per inattivare lazione del BNM a fine intervento


si ricorre agli ANTICOLINESTERASICI

NEOSTIGMINA

EDROFONIO

PIRIDOSTIGMINA

Molecole in grado di revertire un blocco neuromuscolare bloccando le colinesterasi e rendendo


disponible piu acetilcolina ma con tempi ed effetti collaterali spesso non trascurabili ..
Vanno dosati opportunamente e somministrati con una certa cautela rispettando anche un buon
MN.Dato che l acetilcolina va ad agire anche sul recettore muscarinico inducendo effetti collaterali.
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Non-depolarizing Neuromuscular Blocking Agents (NMBAs)


Are Competitive Antagonists
Normal acetylcholine action

NMBA-induced blockade of
acetylcholine receptor

Neostigmine increases acetylcholine


levels to displace the NMBA

Nerve

Nerve

Nerve

Muscle

Muscle

Muscle

Acetylcholine receptor

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Acetylcholine

Transmission

Non-depolarizing NMBA

75

Reversal Agent Pharmacology


Drug

Recommended
Dose (mg/kg)

Onset
of
Action
(min)

Duration
of Action
(min)

Site of
Action

neostigmine

0.01 to 0.05

7-11

60-90

postjunction

edrophonium

0.15 to 1.0

1-2

10-30

prejunction

pyridostigmine

0.02 to 0.5

Up to 16

60-120

postjunction

43. Bevan et al, Anesthesiology 1992;77:785-805


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Neuromuscular Block Management

Limitations of Current Reversal agents (Cholinesterase Inhibitors)

Relatively slow in reversing neuromuscular blockade


Limited ability to reverse deep blockade
Efficacy influenced by maintenance anesthetics
Well-known side effect profile
Require concomitant administration of anticholinergics

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Bartkowski RR. Anesth Analg. 1987;66:594-598.


Kim KS, et al. Anesth Analg. 2004;99:1080-1085.
77
Kopman AF, et al. J Clin Anesth. 2005;17:30-35.

Effetti collaterali associati con i comuni agenti reversal


(anticolinesterasici)
Gli anticolinesterasici da soli possono determinare

Bradicardia 1
Ipersalivazione2
Broncospasmo3
Aumento delle secrezioni bronchiali4
Aumenta la frequenza urinaria
Nausea e vomito

La cosomministrazione con un agente antimuscarinico

Tachicardia
Secchezza fauci
Midriasi
Ritenzione urinaria
1 2 3 4 Van den brock et al. Eur Jour Anaesthesiol Suppl 1994;9:128-32

ChE, cholinesterase.
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*Atropine use causes dose-dependent adverse effects.

Neostigmine Methylsulfate Injection [package insert]; 2002.


Atropine Sulfate Injection, USP [package insert]; 2003.
78
Glycopyrrolate Injection, USP [package insert]; 2006.

Tentativi di neutralizzare il curaro in modo diverso


f descritto in Russia da Petroff nel 1924 usando il
rosso congo per neutralizzare il curaro grezzo nei
cani. Suggerendo un mecanismo di
incapsulamento del curaro nelle micelle formate
dal rosso congo. Journal of Pharmacology and Experimental
Therapeutics 1948; 95: 28-44

C.J. Kensler nel 1948 studia in dettaglio


linterazione tra rosso congo e tubarine osservando
che il meccanismo dazione non era legato ad un
antagonismo ma alla formazione di un composto
inattivo.
Negli anni seguenti altri autori si occuparono del
fenomeno.

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CONTINUA
Per neutralizzare il curaro in modo
diverso ci si concentrati su alcune
sostanze che hanno alcune propriet
interessanti, gli AA. anglosassoni
hanno coniato il termine
HOST_GUEST (Ospite Ospitante)
come descritto nel 1961 da Linssen .
Curariform Drugs. The action of the different types and their
combinations on the neuromuscolar trasmission. PhD Thesis,
Nijmegen, The Netherlands: Radboud University 1961: 104-13

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Cyclodextrins

Six units MW 973

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Seven units MW 1135

Eight units MW 1297

82

Incapsulamento del rocuronio


da parte di Sugammadex

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Cameron KS et al. Org Lett. 2002;4:3403-3406.


83
Gijsenbergh F et al. Anesthesiology. 2005;103:695-703.

Sugammadex the first SRBA

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Discovery of a New Concept

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Abstracts from 7th International Neuromuscular Meeting, Belfast, June 2001.

Pharmacotherapy. 2007 Aug;27(8):1181-8

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SIGNAL

Phase III study

n = 74 pts

USA multicenter, randomized, active control, safety assessor-blinded trial


rocuronium 0.6 mg/kg + 0.15 mg/kg redoses
sugammadex 4 mg/kg (n=37)
neostigmine
1st

aim:

70 mcg/kg (n=37)

time

from

1 or 2 PTCs

sugammadex

or

neostigmineglycopyrrolate

administration to return of the train-of-four ratio to 0.9.


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Median Time to Recovery (min)

Faster Reversal From 1 to 2 Posttetanic Counts


Bridion vs Neostigmine Following
withWith
Sugammadex
Rocuronium 0.6 mg/kg
60

Recovery of TOF Ratio to 0.9


49

50
40
30
20
10
2.7
0

Bridion 4 mg/kg
Sugammadex
n = 37
95% CI (2.33.3 min)
CI, confidence interval; NEO, neostigmine; TOF, train-of-four.

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NEO 70 g/kg
n = 37
95% CI (35.759.5 min)
Data from Signal trial.
Jones RK et al. Anesthesiology. 2008;109:816-824.

90

Faster Reversal With Sugammadex vs


Neostigmine From T2
Recovery of TOF Ratio to 0.9
Rocuronium 0.6 mg/kg

Vecuronium 0.1 mg/kg


20

17,6

18
16
14
12
10
8
6
4
1,4

0
Sugammadex 2 mg/kg
n = 48
95% CI (1.2-1.5 min)

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Median Time to Recovery (min)

Median Time to Recovery (min)

20

18,9

18
16
14
12
10
8
6
4

2,13

2
0

NEO 50 g/kg
n = 48
95% CI (12.7-26.4 min)

CI, confidence interval, NEO, neostigmine; TOF, train-of-four.

Sugammadex 2 mg/kg
n = 48
95% CI (1.9-3.0 min)

NEO 50 g/kg
n = 45
95% CI (12.2-25.5 min)

91

Data from Aurora trial.

Highly sensitive to NMBAs


(nondepolarizing)

Prolonged duration

High risk of PORC and mechanical


ventilationrelated morbidity and mortality
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Sugammadex in Myasthenia Gravis

Spontaneous recovery (PTC 1) 36 min, 30 s

Reversal after sugammadex PTC 1 to TOF 0.9 73 s


No signs of residual NMB of recurarization
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de Boer, et al. Rev Esp Anesthesiol Reanim. 2010;57:115-118.

93

CONCLUSIONS
RESIDUAL NEUROMUSCULAR BLOCKADE (RNB) IS FREQUENTLY
OBSERVED DURING THE EARLY RECOVERY PERIOD FROM
GENERAL ANESTHESIA
SMALL DEGREES OF RESIDUAL PARESIS CAN PRODUCE A VARIETY
OF ADVERSE PHYSIOLOGIC EFFECTS

RNB CAN IMPAIR CLINICAL RECOVERY AND MAY BE BE


ASSOCIATED WITH INCREASED MORBIDITY
THE RISK OF RESIDUAL PARALYSIS CAN BE REDUCED BUT NOT
ELIMINATED BY CAREFUL INTRAOPERATIVE DOSING,
MONITORING AND REVERSAL
SUGAMMADEX IS A FUTURE PROSPECTTIVE FOR THE
ELIMINATION OF RNB IN POST OPERATIVE PERIOD

CHRURGIA LAPAROSCOPICA

I vantaggi della laparoscopia


L'intervento di laparoscopia caratterizzato da una notevole riduzione del
trauma chirurgico.
Un intervento chirurgico effettuato in laparoscopia comporta un dolore
post-operatorio inferiore rispetto ad un intervento chirurgico tradizionale.
La non apertura dell'addome si traduce in un minor trauma per gli organi
addominali
Negli interventi in laparoscopia le perdite ematiche risultano decisamente
minori
Con la laparoscopia risulta ridotto il rischio di infezione delle ferite
La ripresa globale post-operatoria decisamente migliore per gli
interventi in laparoscopia.

Laparoscopia: quali indicazioni?


chirurgia del fegato
chirurgia della colecisti e della via biliare
chirurgia del pancreas
chirurgia delle ghiandole surrenali
chirurgia dell'esofago
chirurgia di stomaco e duodeno
chirurgia della milza
chirurgia dell'intestino tenue
chirurgia dell'appendice
chirurgia del colon
chirurgia del retto
chirurgia della parete addominale
chirurgia dell'apparato urinario
chirurgia dell'apparato riproduttivo femminile
chirurgia dell'obesit grave (chirurgia bariatrica)
chirurgia d'urgenza.

Pathophysiological effects
CO2 pneumoperitoneum (Safran and Orlando AJS 1994)

Hypertension, tachycardia leading to increased myocardial oxygen demand

Increased noradrenaline levels leads to increased SVR (and decreased Q)

Hypercarbia and acidosis

Decrease in urine output and increased plasma renin activity (PRA)


due to increased intra-abdominal pressure (IAP) and the local compression of renal
vessels

Intra-abdominal distension leads to a decrease in pulmonary dynamic compliance .

Low compliance, together with an increased minute volume of ventilation, is


accompanied by high peak airway pressures .

head-up positioning and fluid deficit accounts for many of the adverse
effects in haemodynamics during laparoscopic cholecystectomy (Hirvonen et
al 2000).

Chirurgia Robotica

The physiologic perturbations during


robotic surgery are similar for both
laparoscopic and thoracoscopic
procedures
M.E.J. ANESTH 19 (5) 2008

Decreased Level of Insufflation Pressure With NMB-Induced Relaxation1

NMB-induced relaxation
maintained the
integrity of
pneumoperitoneum
without increased CO2
insufflation pressure

Visual field during a laparoscopic procedure


approaching recovery from NMB (top) and
deep NMB (bottom).

NMB=neuromuscular blockade; CO2=carbon dioxide.


1. Chui PT et al. Anaesth Intensive Care. 1993;21(2):163171.

112

Clinical Example of a Laparoscopy


in a Patient With BMI of 46

More Workspace with NMBAs


at Similar Insufflation Pressure
3 litre workspace without NMBAs
IAP 15 mmHg

4 litre workspace with NMBAs


IAP 14 mmHg

NMBAs=neuromuscular blocking agents; IAP=intra-arterial pressure.

113

Improved Access and Visualization


in Laparoscopic Surgery With NMB

NMB facilitated
introduction of
instruments into the
cavity and extraction
of tissue.1
NMB created a more
open surgical field for
greater mobility.1,2

NMB improved visualization of the abdominal cavity


during laparoscopic surgery

NMB=neuromuscular blockade.
1. Ogunnaike BO et al. Anesth Analg. 2002;95(6):17931805. 2. Welliver M et al. Drug Des Devel Ther. 2008;2:4959.

114

BLOCCO PROFONDO/DEEP BLOCK

Si definisce blocco profondo /deep block:


I seguenti valori al monitoraggio neuromuscolare

TOF=0 PTC=1-2

Perch deep block in laparoscopia?

Condizioni stabili in corso di procedura

Riduzione dei tempi chirurgici

Riduzione della pressione di insufflazione


- meno dolore
- meno problemi ventilatori
- meno problemi emodinamici

Riduzione delle complicanze chirurgiche


- maggiore workspace
- evita erniazioni parete

Dubois PE, Donnez O et al : Abstract Societ Francaise Anesthesie Reanimation, 09 2012. Societ Belge dAnesthesie
Reanimation 09 2012

CONCLUSIONS
LAPAROSCOPY IS A GROWING SURGICAL TECHNIQUE

LOW ABDOMINAL PRESSURE REDUCES THE INCIDENCE OF


PNEUMOPERITONEUM SIDE EFFECTS
LOW ABDOMINAL PRESSURE REDUCES THE INTENSITY OF
POSTOPRATIVE PAIN
DEEP NEUROMUSCULAR BLOCKADE OPTIMIZES SURGICAL SPACE
AND REDUCES POSTOPRATIVE PAIN DURING LOW PRESSURE
LAPAROSCOPY

WITH THE INTRODUCTION OF SUGAMMADEX RAPID REVERSAL


OF A DEEP NEUROMUSCULAR BLOCKADE IS FEASIBLE
MORE STUDIES AND LARGER PATIENT GROUPS ARE NEEDED