3. Italian survey 2010
(Minerva Anestesiol. 2012 Jul;78(7):767-73.Neuromuscular block in Italy: a survey of current management.
Della Rocca G, Iannuccelli F, Pompei L, Pietropaoli P, Reale C, Di Marco P
Acta Anaesthesiol Scand. 2010 Mar;54(3):307-12. doi: 10.1111/j.1399-6576.2009.02131.x. Epub 2009 Oct 15.
Knowledge of residual curarization: an Italian survey.
Di Marco P, Della Rocca G, Iannuccelli F, Pompei L, Reale C, Pietropaoli P.
Only 35% of italian anesthesiologists use
TOF.........
73% of italian anesthesiologists rely on clinical signs for return of
muscular power
24% know that before extubation at least a TOF 0f 0.90 is
needed
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5. What is adequate neuromuscular
recovery?
Ability
to breathe
normally;TV,paO2,SaO2,etCO2,PEF,FEV....
maintain a patent upper airway,
preserve protective airway reflexes,
swallow,
cough,
smile,
Talk.
Arm and leg movements........
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6. TOF(R)
introduced in the early 1970s by Ali et al.
Four supramaximal stimuli are delivered every 0.5 second (2 Hz)
muscle response to the fourth stimulus is compared with that of the first
stimulus.
Fade of force of muscle contraction in response to repetitive nerve
stimulation provides the basis for evaluation; the degree of fade is
proportional to the intensity of the neuromuscular block.
Advantages:
» does not require a control,prerelaxant twitch height
» less pain on stimulation over tetanic stimulation
» lack of posttetanic facilitation
» Threshold??????
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10. TOFR thresholds(in the definition of residual
neuromuscular block)
,
1970 –1977
a mean TOF ratio of 0.74 represented―acceptable recovery” from d-tubocurarine blockade.
Patients with this level of recovery were able to open eyes widely, cough, protrude the tongue,
sustain head lift for 5 seconds, develop a forced vital capacity of at least 15 to 20 mL/kg, and sustain
tetanic stimulation without fade for 5 seconds.
changes in measured respiratory variables, including tidal volume, vital capacity, inspiratory
force, and peak expiratory flow rate, were ―negligible‖ until TOF ratios decreased To 0.6.
At a TOF ratio of 0.7, all patients were able to sustain eye opening, hand grasp, and tongue
protrusion, whereas 9 of 10 were able to maintain a 5-second head lift
Ali HH, Kitz RJ. Evaluation of recovery from nondepolarizing neuromuscular block, using a digital neuromuscular transmission analyzer: preliminary report.
Anesth Analg 1973;52:740–5.
AliHH,Wilson RS, Savarese JJ, Kitz RJ. The effect of tubocurarineon indirectly elicited train-offour muscle response and respiratory measurements
in humans. Br J Anaesth 1975;47:570–4
Brand JB, Cullen DJ, Wilson NE, Ali HH. Spontaneous recovery from nondepolarizing neuromuscular blockade: correlation between clinical and evoked
responses. Anesth Analg 1977;56:55–8.
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12. Train of four ratio>0.7, <=0.9
1997-2000
TOFR 0.9 to ensure optimal patient safety.
pharyngeal dysfunction and an increased risk for aspiration occur at TOF ratios 0.9.
Impaired inspiratory flow and partial upper airway obstruction have been observed
frequently at TOF ratios of 0.8.
subtle levels of neuromuscular blockade may produce distressing symptoms in awake
patients, which may persist even at TOF ratios 0.9.
These recent data suggest that the new ―gold standard‖ for the minimal acceptable level
of neuromuscular recovery is an EMG or MMG TOF ratio of 0.9 (or perhaps 1.0 when
AMG is used
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15. PO RE NMB ??
POSTOPERATIVE RESIDUAL
NEUROMUSCULAR BLOCKADE OR
WEAKNESS
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16. Dichiarazione di assenza di
conflitto di interessi
non ho alcun interesse finanziario o attività
commerciale né sono supportato dalla azienda
produttrice del Sugammadex(Bridion).
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17. PORC % nella metanalisi di Naguib
Br J Anaesth. 2007 Mar;98(3):302-16.Neuromuscular monitoring and postoperative residual curarisation: a
meta-analysis.Naguib M, Kopman AF, Ensor JE.
panc
Dtc
Galla
panc
panc
Atrac 0
galla
vari
Atrac 0
panc
Panc
vecu
Panc
vecu
panc
Tof<70
Tof <90
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18. PORC % nella metanalisi di Naguib ;parte II
100
90
80
70
60
50
40
tof <0.70
tof < 0.90
30
20
10
0
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19. Residual Paralysis at the Time of Tracheal Extubation
Glenn S. Murphy, Joseph W. Szokol, Jesse H. Marymont, Mark Franklin,
Michael J. Avram, Jeffery S. Vender.(Anesth Analg 2005;100:1840–5)
120 pts
Nm block maintained at TOF 1-2
12% only with
tof>0.9
Midazolam,1–2 mg.; propofol 1.5–
2.5 mg/kg , fentanyl ,sevoflurane
0.5%–3.5% in an air/oxygen
mixture.
neuromuscular
blockade was reversed with
neostigmine 50 microg/kg
and glycopyrrolate 10 micro g/kg
adequacy of neuromuscular reversal using
standard clinical criteria :(5-s head lift or
hand grip, eye opening on command,
negative inspiratory force more than 20 cm
H2 O, or vital capacity breath 15 cc/kg) and
peripheral
nerve stimulation (no evidence of fade with
TOF
or tetanic stimulation [50 Hz]). A 5-s head lift
(or hand
grip) and the observation of an absence of
fade with
peripheral nerve stimulation were the
minimal requirements
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20. Residual Paralysis at the Time of Tracheal Extubation
Glenn S. Murphy, Joseph W. Szokol, Jesse H. Marymont, Mark Franklin,
Michael J. Avram, Jeffery S. Vender.(Anesth Analg 2005;100:1840–5)
The use of a peripheral nerve stimulator in the OR
may reduce, but does not eliminate, the problem of
postoperative paresis.
Detection of incomplete reversal of neuromuscular
blockade is difficult with standard TOF or tetanic
stimulation. Experienced observers are unable to
detect fade when the TOF ratio is 0.4 Viby-Mogensen J, Jensen
NH, Englbaek J, et al. Tactile and visual evaluation of the response to train-of-four nerve stimulation.
Anesthesiology 1985;63:440 –3.).
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21. Residual Neuromuscular Block: Lessons Unlearned.
Part I: Definitions, Incidence, and Adverse Physiologic
Effects of Residual Neuromuscular Block
Glenn S. Murphy, Sorin J. Brull,
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Anesth Analg 2010;111:120–8
22. What are the factors that alter the incidence of postoperative
residual paralysis?
The great variability is due to different methods:
use of T4/T1 ratio of 0.7, 0.8 or 0.9 as PORP criterion
use of different NMB of short, intermediate and long-term duration
use of single or repeated doses, or continuous infusion of NMB
assessment method of the residual NMB
with or without reversal of neuromuscular blockade at the end of anesthesia with
anticholinesterase drugs
with dose and interval between the anticholinesterase drugs and degree assessment
of neuromuscular blockade
Age
presence of kidney, cardiac or neuromuscular dysfunction
drug use that can alter the pharmacodynamics and/or pharmacokinetics of NMB
(calcium channel blockers, magnesium, lithium, antibiotics, local anesthetics, inhaled
anesthetics, opioids, benzodiazepines
electrolyte abnormalities, metabolic or respiratory acidosis and hypothermia.
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24. Kopman et al.Relationship of the train of four fade
ratio to clinical signes and symptoms of residual
paralysis in awake volunteers.Anesthesioloogy,1997;86:765-71.
Volontari sani
infusione di mivacurium
monitoraggio Datex 221 NMT
valutazione;
stretta di mano
sollev,testa & gamba per 5 sec.
Ritenzione di abbassalingua
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25. Osservazioni cliniche sulla relazione fra tof e correlati di
forza:
disturbi visivi sempre con tof di
0.90(diplopia,diff.seguire oggetti in moto,ecc)
forza dei masseteri ridotta sempre
sollev.testa e gamba sempre possibile > 0.60
stretta di mano variabile,ma 83% del basale a tof
0.90
per tof < 0.75 tutti disturbati
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26. Conclusioni delle correlazioni fra segni clinici di forza
muscolare e tof
Capacità di ritenzione
dell’abbassalingua è un test più
sensibile del sollevamento del capo
tof <1 ancora residuano disturbi visivi e
senso generalizzato di fatica
tof = 1 (o altri monitoraggi) per
dimissione in chirurgia ambulatoriale??
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27. 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 trainof-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
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28. 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
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29. 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
applicano ad una ampia gamma di situazioni cliniche.
Esistono pesanti pressioni economiche per la
diminuzione della spesa sanitaria.
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30. 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.
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31. 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 )?
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33. Conclusioni
Esiste evidenza sperimentale e
clinica che i nmb nondepolarizzanti
interferiscano con il controllo della
ventilazione in condizioni di
ipossia,verosimilmente attraverso
una depressione reversibile della
attività chemorecettoriale dei corpi
carotidei
implicazioneclinica
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36. Eriksson LI,Sundman E,Olsson R,NilssonL,Witt H,Ekberg O,Kuylenswtierna R.
Functional Assessment of the Pharynx at Rest and during Swallowing in Partially
Paralyzed Humans: Simultaneous Videomanometry and Mechanomyography of
Awake Human Volunteers,Anesthesiology 1997;67:1035-43.
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38. Eriksson LI,Sundman E,Olsson R,NilssonL,Witt H,Ekberg O,Kuylenswtierna R.
Functional Assessment of the Pharynx at Rest and during Swallowing in
Partially Paralyzed Humans: Simultaneous Videomanometry and
Mechanomyography of Awake Human Volunteers,Anesthesiology
1997;67:1035-43.
Vecuronium induced partial paralysis(tof o.600.80) cause pharyngeal disfunction:
upper esophageal sphincter tone
Pharynx muscle coordination
Bolus transit time
–6/14 volunteers aspirated at tof<0.90
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40. The Incidence and Mechanisms of pharyngeal and Upper Esophageal Dysfunction in
Partially Paralyzed humans.Eva Sundrnan,H anne Witt, Rolf Olsson, Olle Ekberg, S
Richard Kuylenstierna, Lars I. Eriksson.Anesthesiology 2000;92:977-84
20 healthy volunteers studied awake during liquid-contrast bolus swallowing.
The incidence of pharyngeal dysfunction was studied by fluoroscopy.+
Simultaneous manometry
After control recordings, an iv infusion of atracurium was administered to obtain
TOF 0.60, 0.70, and 0.80, followed by recovery to a > 0.90.
The incidence of pharyngeal dysfunction increased to 28%, 17%, and 20% at TOF
0.60, 0.70, and 0.80, respectively.
Pharyngeal dysfunction occurred in 74/ 444 swallows, the majority (80%) resulting
in laryngeal penetration.
The initiation of the swallowing reflex was impaired during partial paralysis
The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70
. A marked reduction in the upper esophageal sphincter resting tone was found, as
well as a reduced contraction force in the pharyngeal constrictor muscles. The
bolus transit time did not change significantly.
.
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41. Time interval between passage of bolus from the anterior
faucial arches and hyoid bone
ms
42. Time interval between start of contraction of pharyngeal constrictor and start of
relaxation of upper esophageal sphincter
ms
45. The Incidence and Mechanisms of pharyngeal and Upper
Esophageal Dysfunction in Partially Paralyzed humans
Partial neuromuscular paralysis caused by atracurium
is associated with a four- to fivefold increase in the
incidence of misdirected swallowing. The mechanism
behind the pharyngeal dysfunction is
1) a delayed initiation of the swallowing reflex,
2)impaired pharyngeal muscle function,
3)impaired coordination.
The majority of misdirected swallows resulted in
penetration of bolus to the larynx
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47. Predictive value of mechanomyography and accelerometry for
pulmonary function in partially paralyzed volunteers.
Eikermann M, Groeben H, Hüsing J, Peters J.
:
In awake partially paralyzed volunteers
spirometrically assessed pulmonary function every 5 min until recovery.
Rocuronium (0.01 mg kg(-1) + 2-10 microg kg(-1) min(-1)) was administered to maintain
train-of-four (TOF)-ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period
of more than 5 min.
The TOF-ratio associated with 'acceptable' pulmonary recovery [forced vital capacity
(FVC) and forced inspiratory volume in 1 s (FIV1) of > or =90% of baseline] was
calculated using a linear regression model. During 5-min periods of repetitive nerve
stimulation we compared the squared residuals of the FVC and FIV1 estimates from
TOFACM vs. TOFMMG, and compared variance of values derived from ACM and MMG
using Wilcoxon's test.
RESULTS:
TOF ACM(0.56 (0.22-0.71) [mean (95%CI) and 0.6 MMG
(0.28-0.74)], respectively, predict 'acceptable' (90%) recovery
of FVC while FIV1 remains impaired until TOF-ratios of
0.91 (0.82-1.07) and 0.95 (0.82-1.18), respectively.
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48. Anesthesiology. 2012 Dec;117(6):1234-44..
Residual neuromuscular blockade affects postoperative pulmonary function.
Kumar GV, Nair AP, Murthy HS, Jalaja KR, Ramachandra K, Parameshwara G.
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49. Heier T,. Caldwell,JE. Feiner JR, Liu, L, Ward, T, B,. Wright PMC.
Relationship between Normalized Adductor PollicisTrain-of-four Ratio and Manifestations of Residual
Neuromuscular Block A Study Using Acceleromyography during Near Steady–stateConcentrations of Mivacurium
Anesthesiology 2010 : 113 ;2010.825-832 .
12 healthy volunteers
3 steady–state levels of neuromuscular block were achieved with mivacurium infusions. TOF ratio of 0.85– 0.95
(block level 1), TOF ratio of 0.65– 0.75 (block level 2), and TOF ratio of 0.45– 0.55 (block level 3).
TOF ratio was measured acceleromyographically at the adductor pollicis using a preload.
Lung volume measurements and a series of clinical tests were made at each stable block and reconciled to the
normalized TOF measures.
Results: None experienced airway obstruction or arterial oxygen desaturation, even at normalized TOF ratio less
than 0.4. Functional residual capacity remained unchanged whereas vital capacity decreased linearly with
decreasing TOF ratio.
The ability to protrude the tongue was preserved at all times. The ability to clench the teeth was lost in one
volunteer at normalized TOF ratio of 0.84 but retained in four at normalized TOF ratio less than 0.4. Four volunteers
lost the ability both to raise the head more than 5 s and to swallow, with the most sensitive individual demonstrating
these effects at normalized TOF ratio of 0.60. At mean normalized TOF ratio of 0.42, the mean handgrip strength
was approximately 20% of baseline value.
Conclusion: Lung vital capacity decreased linearly with decreasing TOF ratio. Responses to clinical tests of muscle
function varied to a large extent among individuals at comparable TOF ratios. None of the volunteers had significant
clinical effects of neuromuscular block at normalized acceleromyographic TOF ratio greater than 0.90.
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50. The relationship between normalized acceleromyography adductor pollicis train-of-four
(AMG AP TOF) ratio and vital capacity of the lungs and between normalized AMG AP TOF
ratio and handgrip strength in 12 volunteers during stable mivacurium blocks.Both vital
capacity and handgrip strength decreased significantly with decreasing AMG AP TOF
ratio.Heier T,. Caldwell,JE. Feiner JR, Liu, L, Ward, T, B,. Wright PMC. Relationship between Normalized Adductor PollicisTrain-of-four Ratio and Manifestations of Residual
Neuromuscular Block A Study Using Acceleromyography during Near Steady–stateConcentrations of Mivacurium Anesthesiology 2010 : 113 ;2010.825-83
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51. Number of individuals who lost muscle functions
TOF ratio of 0.85– 0.95 (block level 1), TOF ratio of 0.65– 0.75
(block level 2), and TOF ratio of 0.45– 0.55 (block
TOFR 0.85-0.95
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level 3).
TOFR 0.65-0.75
TOFR ratio of
52. Accelerometry of adductor pollicis muscle predicts recovery of
respiratory function from neuromuscular blockade.
Eikermann M, Groeben H, Hüsing J, Peters J.
Source
Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Germany. matthais.eikermann@uni-essen.de
Abstract
BACKGROUND:
Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry
predicts effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and
pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers.
METHODS:
Rocuronium (0.01 mg/kg + 2-10 microg x kg-1 x min-1) was administered to maintain train-of-four (TOF) ratios (assessed every 15
s) of approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions
during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was
defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with
"acceptable" pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of > or =90% of baseline) was
calculated using a linear regression model.
RESULTS:
At peak blockade (TOF ratio 0.5 +/- 0.16), forced inspiratory flow was impaired (53 +/- 19%) to a greater degree than forced
expiratory flow (75 +/- 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 +/- 0.6. Upper
airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In
contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56
(95% confidence interval, 0.22-0.71) predicts "acceptable" recovery of forced vital capacity, whereas forced inspiratory volume in 1
s was impaired until a TOF ratio of 0.95 (0.82-1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of
forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in
93%, 73%, and 88% of measurements (calculated negative predictive values), respectively.
CONCLUSION:
Impaired inspiratory flow and upper airway obstruction frequently occur during minimal neuromuscular blockade (TOF ratio 0.8),
and extubation may put the patient at risk. Although a TOF ratio of unity predicts a high probability of adequate recovery from
neuromuscular blockade, respiratory function can still be impaired.
Comment in
Residual neuromuscular blockade: importance of upper airway integrity. [Anesthesiology. 2004
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53. Anesthesiology. 2003 Jun;98(6):1333-7.
Accelerometry of adductor pollicis muscle predicts recovery of
respiratory function from neuromuscular blockade.
Eikermann M, Groeben H, Hüsing J, Peters J.
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54. Muscle function and tofr in 12 partially paralyzed volunteers
Anesthesiology.
2003 Jun;98(6):1333-7.
Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade.
Eikermann M, Groeben H, Hüsing J, Peters J.
12
Num
10
8
tof 0.5
tof 0.8
tof 1
6
4
2
0
inability to sustain
head lift >5 sec
iability to seal
mouthpiece
inability to swallow fade of contraction
normally
visible
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upper airway
obstruction
55. Eikermann M, Vogt FM, Herbstreit F, Vahid-Dastgerdi M,Zenge MO,
Ochterbeck C, de Greiff A, Peters J. The predisposition to inspiratory upper
airway collapse during partialneuromuscular blockade. Am J Respir Crit
Care Med 2007;175:9–15
Partial neuromuscular blockade (train-of-four [TOF] ratio: 0.5 and 0.8) was
associated with the following:
(1) a decrease of inspiratory retropalatal and retroglossal upper airway volume
to 66 ( 22) and 82 (12)% of baseline, whichwas significantly more intense in
the retropalatal area;
(2) an attenuation of the normal increase in anteroposterior upper airway
diameter during forced inspiration to 74 (18)% of baseline;
(3) a decrease in genioglossus activity during maximum voluntary tongue
protrusion to 39 (19)% (TOF, 0.5) and 73 (29)% (TOF, 0.8) of Baseline
(4) no effects on upper airway size during expiration, lung volume, and
respiratory timing.
Conclusions: Thus, impaired neuromuscular transmission, even to a degree
insufficient to evoke respiratory symptoms, markedly impairs upper airway
dimensions and function. This may be explained by an impairment of the
balance between upper airway dilating forces and negative intraluminal
pressure generated during inspiration by respiratory ―pump‖ muscles.
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57. End-inspiratory and end-expiratory upper airway volume before neuromuscular blockade
(baseline) at a steady-state train-of-four (TOF) ratio of 0.5 and 0.8, after recovery of the TOF
ratio to 1.0, and15 min later (same TOF ratio)
.Before neuromuscular
blockade and with
recovery from
neuromuscular blockade,
end-inspiratory volume
was significantly
greater than endexpiratory volume. Endinspiratory volume
decreased
significantly during
partial neuromuscular
blockade, and was even
lower
than end-expiratory
upper airway volume at
a TOF ratio of 0.5.
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58. Upper airway volume at end inspiration (quiet breathing) before neuromuscular
blockade, at a steady-state TOF ratio of 0.5 and 0.8, after recovery of the TOF ratio to
1.0, and 15 min later. Upperpanel: retroglossal area; lower panel: retropalatal area. 15
min.
During partial
neuromuscular blockade,
upper airway volume
decreased significantly
both in the retroglossal
and retropalatal part of
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the upper airway, but
was no longer significantly
different from baseline
values with recovery
of the TOF ratio to 1.0.
However, 4 of 10 volunteers
still showed a
marked impairment of
retropalatal airway volume
despite recovery of
the TOF ratio to unity,
which disappeared within
15 min.
59. Changes in upper airway volume at end inspiration (quiet breathing) from baseline during steady-state
neuromuscular blockade.The percentage decrease of retroglossal and retropalatal upper airway volume. At a
TOF ratio of 0.5, upper airway volume decrease was
significantly greater in the retropalatal area compared with the retroglossal
area.
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60. Minimum cross-sectional area at end inspiration of the retroglossal
and retropalatal part of the upper airway. Measurements during
quiet breathing before neuromuscular blockade (baseline) at a steadystate
TOF ratio of 0.5 and 0.8, after recovery of the TOF ratio to 1.0,
and 15 min later.
During neuromuscular
blockade, airway
crosssectional
area decreased
significantly in both
regions of the upper airway
and recovered to baseline
values with a TOF ratio of
unity. The smallest
cross-sectional area of the
retropalatal area was
significantly less than
the smallest cross-sectional
area of the retroglossal area
of the upper
airway.
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63. Impaired upper airway integrity by residual neuromuscular blockade:
increased airway collapsibility and blunted genioglossus muscle activity in
response to negative pharyngeal pressure.
Herbstreit F, Peters J, Eikermann M. Anesthesiology. 2009 Jun;110(6):125360
Epiglottic and nasal mask pressures, genioglossus electromyogram, respiratory timing, and
changes in lung volume were measured in awake healthy volunteers (n 15) before, during
(TOF 0.5 and 0.8 [steady state]), and after recovery of TOF to unity from rocuronium-induced
partial neuromuscular blockade.
Passive upper airway closing pressure (negative pressure drops, random order, range 2 to –
30 cm H2O) and pressure threshold for flow limitation were determined.
Results: Upper airway closing pressure increased (was less negative) significantly from
baseline by 54 (4.4)% ,37 (4.2)%, and 16 ( 4.1) % at TOF ratios of 0.5, 0.8, and
1.0.,respectively (P < 0.01 vs. baseline for any level).
Phasic genioglossus activity almost quadrupled in response to negative (–20
cm H2O) pharyngeal pressure at baseline, and this increase was significantly impaired by
57 ( 44)% and 32 (6)% at TOF ratios of 0.5 and 0.8, respectively (P < 0.01 vs. baseline).
End-expiratory lung volume, respiratory rate, and tidal volume did not change.
Conclusion: Minimal neuromuscular blockade markedly increases upper airway closing
pressure, partly by impairing the genioglossus muscle compensatory response. Increased
airway collapsibility despite unaffected values for resting ventilation may predispose patients
to postoperative respiratory complications, particularly during airway challenges.
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64. atmospheric pressure.Inspiratory time was longer during impaired neuromuscular transmission, but no flow limitation was
observed at this maskpressure. (B) Same volunteer during a negative pressure challenge (–20 cm H2O). Before partial
neuromuscular blockade, phasicgenioglossus activity is markedly increased compared to breathing near atmospheric
pressure, but no flow limitation is observed,despite such negative pharyngeal pressure. During partial neuromuscular
blockade, phasic genioglossus activity is markedlyincreased compared with breathing at atmospheric pressure. However, the
magnitude of the compensatory increase in genioglossus
activity to negative pharyngeal pressure is impaired and flow limitation is observed. EMG electromyogram.
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65. Upper airway closing pressure (black bars) significantl increased during partial neuromuscular blockade and
was still abnormal, even with recovery of the TOF ratio to
unity. With neuromuscular transmission intact at baseline, evidenceof flow limitation (gray bars) was first
observed at anaverage pressure of –12 cm H2O. With partial neuromuscular blockade at a TOF ratio of 0.5 and
0.8, flow limitation occurred at significantly less negative values of mask pressure, i.e.,airway
integrity is impaired
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66. .Genioglossus activity increases markedly and significantly as negative
pressure is applied. However, the magnitude of this effect
is significantly attenuated with partial neuromuscular blockade
Napoli SIA 2013
67. Herbstreit F, Peters J, Eikermann M. Anesthesiology. 2009;110(6):1253-60
Minimal neuromuscular blockade (TOF ratio 0.5–1)
markedly increased upper airway collapsibility and
impaired the genioglossus response to negative
pharyngeal pressure challenges.
Thus, our data suggest that minimal neuromuscular blockade
evokes increased upper airway collapsibility by blunting upper
airway dilator compensatory responses to negative pharyngeal
pressure.
Imaging studies during complete or partialEikermann M, Vogt FM, Herbstreit F, VahidDastgerdi M, Zenge MO, Ochterbeck C, de Greiff A, Peters J: The predisposition to inspiratory upper airway collapse during partial neuromuscular
blockade. Am J Respir Crit Care
neuromuscular blockade and in patients with
obstructive sleep apnea suggest that the soft palate plays an
important role in mediating airway narrowing during airway
muscle paralysis and sleep.
Med 2007; 175:9–15
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68. Eur J Anaesthesiol. 201128(12):842-8.
The influence of residual neuromuscular block on the incidence of critical
respiratory events. A randomised, prospective, placebo-controlled trial.
Sauer M, Stahn A, Soltesz S, Noeldge-Schomburg G, Mencke T.
Department of Anaesthesiology and Intensive Care Medicine, University of Rostock, Rostock, Germany.
incidence of critical respiratory events, such as hypoxaemia, in patients with minimal
residual neuromuscular blockade and compared these data with those from patients
with full recovery of blockade.
Randomised, prospective, placebo-controlled trial.
132 adult patients, 18-80ASA I-III ,orthopaedic surgery ,GA with rocuronium
randomised to one of two groups: neostigmine group (neostigmine 20 μg kg-1) or
placebo group (saline).
In the patients in the neostigmine group, the tracheal tube was removed at a
train-of-four (TOF) ratio of 1.0; in the patients in the placebo group, the trachea
was extubated at a TOF ratio less than 1.0, but without fade in TOF and
double-burst stimulation (DBS).
Neuromuscular monitoring was assessed simultaneously with qualitative TOF/DBS
monitoring, and with quantitative calibrated acceleromyography.
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Critical respiratory events, such as hypoxaemia, were assessed in the postanaesthesia care unit.
69. The influence of residual neuromuscular block on the incidence of
critical respiratory events. A randomised, prospective, placebocontrolled trial
45 pts (39.5%) became hypoxaemic (SaO2 < 93%);
there was a significant difference between the groups (29
patients in the placebo group versus 16 in the neostigmine
group; P = 0.021).
In the neostigmine group, all patients were extubated at a TOF ratio of 1.0. In
the placebo group, the median TOF ratio was 0.7 (range: 0.46-0.9; P < 0.001).
The median time for spontaneous recovery in the placebo group was 16 min
(range 3-49 min). Neostigmine 20 μg kg was effective in antagonising
rocuronium-induced blockade without fade in TOF and DBS.
In this randomised, prospective, placebo-controlled trial, minimal
residual block was associated with hypoxaemia in the postNapoli SIA
anaesthesia care unit. Neostigmine 2013 μg kg was effective in
20
antagonising rocuronium-induced (minimal) blockade
70. Bissinger U,Schimek,F,Lenz,G.Postoperative residual paralys and
respiratory status:a comparative study of pancuronium and
vecuronium.Physiol Rev. 2000:49;455-462.
83 patients,balanced or inhalation
maintenance
Panc for op>2hrs,vecu for op>1 hr
PORP defined as tofr<70,hypoxemia as
SaO‖ > 5% lower than basal or postop
SaO2<93%,hypercapnia as paCO2>46
mmHg.
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71. Bissinger U,Schimek,F,Lenz,G.Postoperative residual paralys and
respiratory status:a comparative study of pancuronium and
vecuronium.Physiol Rev. 2000:49;455-462.
panc
vecu
PORP
20%
7%
hypoxemia
60%
10%
hypercapnia
30%
8%
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75. Viby Mogensen et al,AAS 1997
•
•
•
•
693 paz.randomizzati,cieco
chir elettiva
monitoraggio periop con Myotest e Tof
confronto fra 1-5-2 ED95 di
atrac,vecu,panc.
• Antagonismo se necessario;
• estubaz a tof eguale, tattile e resp adeguata.
79. Popc secondo il tipo di
chirurgia
16
14
12
10
addom
ortop
ginecol
% 8
6
4
2
0
popc
80. Fattori di rischio per POPC
nello studio AAS1997
Tipo
di chirurgia;freq * 2-10(addominale)
età:ogni 10 anni * 1.68
durata di anestesia(> o < 200 min)*3.3
panc e tof<0.70:*5
81. What is the validity and correlation between the different PORP
diagnostic tests ?
Clinical tests have shown the following values of sensitivity,
specificity, positive and negative predictive values19(D):
Capacity to keep the head up for 5 seconds: 0.19; 0.88; 0.51; 0.64;
• Capacity to hold up the arm or the leg for 5 seconds: 0.25; 0.84; 0.50; 0.64;
• Protrusion or capacity to remove the tongue: 0.22; 0.88; 0.52; 0.64;
• Maintenance of hand grip strength: 0.18; 0.89; 0.51; 0.63.
None of the available clinical trials showed a positive correlation with the T4/T1 >
0.9, or ruled out the possibility of PORP7,8,19(B)21(C).
82. Br J Anaesth. 2010 Sep;105(3):304-9. Postoperative residual curarization from
intermediate-acting neuromuscular blocking agents delays recovery room
discharge.
Butterly A, Bittner EA, George E, Sandberg WS, Eikermann M, Schmidt U.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA.
Postoperative residual curarization (PORC) [train-of-four ratio (T4/T1) <0.9] is associated with increased
morbidity and may delay postoperative recovery room (PACU) discharge. We tested the hypothesis that
postoperative T4/T1 <0.9 increases PACU length of stay.
At admission to the PACU, neuromuscular transmission was assessed by acceleromyography (stimulation
current: 30 mA) in 246 consecutive patients. The potential consequences of PORC-induced increases in
PACU length of stay on PACU throughput were estimated by application of a validated queuing model
taking into account the rate of PACU admissions and mean length of stay in the joint system of the PACU
plus patients recovering in operation theatre waiting for PACU beds.
PACU length of stay was significantly longer in patients with T4/T1 <0.9 (323 min), compared with patients
with adequate recovery of neuromuscular transmission (243 min). Age (P=0.021) and diagnosis of T4/T1
<0.9 (P=0.027), but not the type of neuromuscular blocking agent, were independently associated with
PACU length of stay. The incidence of T4/T1 <0.9 was higher in patients receiving vecuronium. Delayed
discharge significantly increases the chances of patients having to wait to enter the PACU. The presence
of PORC is estimated to be associated with significant delays in recovery room admission.
CONCLUSIONS:
PORC is associated with a delayed PACU discharge. The magnitude of the effect is clinically significant. In
our system, PORC increases the chances of patients having to wait to enter the PACU.
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85. DO WE ALWAYS NEED TO
REVERSE NMB?
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86. Anesthesiology. 2005 Feb;102(2):257-68.Impact of anesthesia management
characteristics on severe morbidity and mortality.
Arbous MS, Meursing AE, van Kleef JW, de Lange JJ, Spoormans HH, Touw P,
Werner FM, Grobbee DE.
A case-control study was performed of all patients undergoing anesthesia (1995-1997):
869,483 patients; 807 cases and 883 controls were analyzed
ONLY coma or death reported during or within 24 h of undergoing anesthesia..
.The incidence of 24-h postoperative death was 8.8 ( 8.2-9.5) per 10,000 anesthetics.
The incidence of coma was 0.5 (0.3-0.6).
Anesthesia management factors that associated with a decreased risk :
equipment check with protocol and checklist,
documentation of the equipment check ,
a directly available anesthesiologist,
no change of anesthesiologist during anesthesia,
presence of a full-time working anesthetic nurse
two persons present at emergence,
reversal of anesthesia (for muscle relaxants and the combination of muscle
relaxants and opiates;
postoperative pain medication as opposed to no pain medication, particularly
Napoli SIA 2013
if administered epid or i.m. as opposed toi.v..
87. Neostigmine/glycopyrrolate administered after recovery from neuromuscular block
increases upper airway collapsibility by decreasing genioglossus muscle activity in
response to negative pharyngeal pressure.
Herbstreit F, Zigrahn D, Ochterbeck C, Peters J, Eikermann M.
Anesthesiology. 2010 ;113(6):1280-8.
10 healthy male volunteers
epiglottic and nasal mask pressures, genioglossus electromyogram, air flow, respiratory
timing, and changes in lung volume before, during (TOF ratio: 0.5), and after recovery of the
TOF ratio to unity, and after administration of neostigmine 0.03 mg/kg IV (with glycopyrrolate
0.0075 mg/kg).
Upper airway critical closing pressure (Pcrit) was calculated from flow-limited breaths during
random pharyngeal negative pressure challenges.
Pcrit increased significantly after administration of neostigmine/glycopyrrolate compared with
both TOF recovery (mean SD, by 27 21%; P 0.02) and baseline (by 38 17%; P 0.002). In
parallel, phasic genioglossus activity evoked by negative pharyngeal pressure decreased (by
37 29%, P 0.005) compared with recovery, almost to a level observed at a TOF ratio of 0.5.
Lung volume, respiratory timing, tidal volume, and minute ventilation remained unchanged after
neostigmine/glycopyrrolate injection.
Conclusion: Neostigmine/glycopyrrolate, when administered after recovery from
neuromuscular block, increases upper airway collapsibility and impairs genioglossus muscle
activation in response to negative pharyngeal pressure. Reversal with acetylcholinesterase
inhibitors may be undesirable 2013the absence of neuromuscular blockade.
in
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88. Representative recording of main variables from an awake healthy volunteer before partial neuromuscular
blockade
(baseline), during impaired neuromuscular transmission with a target train-of-four (TOF) ratio of 0.5, after
spontaneous recoveryof the TOF ratio to unity, and during measurements initiated 2 min after injection of
neostigmine (0.03 mg/kg) and glycopyrrolate(0.0075 mg/kg).
A) Mask pressure at 2 cm H2O. Phasic (respiratory)
genioglossus activity is very low while breathing near
atmospheric pressure. During impaired neuromuscular
transmission, no flow limitation is observed at this mask
pressure.
(B) Same volunteer during a negative pressure challenge
(20 cm H2O). Before partial neuromuscular blockade,
phasic
genioglossus activity is markedly increased compared
with breathing near atmospheric pressure. During partial
neuromuscular
blockade, phasic genioglossus activity is markedly
increased compared with breathing at atmospheric
pressure. However, the
magnitude of the compensatory increase in genioglossus
activity in response to negative pharyngeal pressure is
impaired, and
flow limitation is observed. After spontaneous recovery of
the TOF ratio to unity, the compensatory phasic
genioglossus activity
is restored. Injection of neostigmine/glycopyrrolate
attenuates the increase in genioglossus activity, and the
changes observed
attain similar values as those seen with partial
neuromuscular blockade with a TOF ratio of 0.5.
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89. Upper airway closing pressure significantly increased during partial neuromuscular blockade and was
still abnormal even with recovery of the TOF ratio to unity (i.e.,before injection of neostigmine/glycopyrrolate)
(P 0.01 vs.baseline). However, upper airway closing pressure significantly
increased after injection of neostigmine/glycopyrrolate.
Upper airway critical closing pressure (Pcrit) in awake healthy volunteers at baseline before
neuromuscular blockade, with impaired neuromuscular transmission and a target train-offour (TOF) ratio of 0.5, after spontaneous recovery of the TOF ratio to unity, and after injection
of neostigmine/glycopyrrolate
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90. The genioglossus activity is presente as a percentage of maximal activity (observed when the volunteer pressed his tongue with
maximum strength against his teeth with the mouth closed). Genioglossus activity evoked in response to negative pressure
challenges isimpaired with neuromuscular blockade. The compensatorygenioglossus response to a pressure drop is restored
after return of the TOF ratio to unity. After administration ofneostigmine/glycopyrrolate, genioglossus activity in response to
negative airway pressure is markedly and significantly decreased.
Genioglossus muscle activity as a function of negative mask pressure with neuromuscular blockade at a target
TOFratio of 0.5 (open squares), after spontaneous recovery of the TOF ratio to unity (solid squares), and after
injection of neostigmine/glycopyrrolate
Napoli SIA 2013
91. Neostigmine/glycopyrrolate administered after recovery from neuromuscular block increases upper airway
collapsibility by decreasing genioglossus muscle activity in response to negative pharyngeal pressure.
Herbstreit F, Zigrahn D, Ochterbeck C, Peters J, Eikermann M.
Anesthesiology. 2010 ;113(6):1280-8.
Administration of neostigmine/glycopyrrolate, when
administered after spontaneous recovery of
neuromuscular function, in a dose similar to that
recommended, and in routine clinical use, led to a
significant increase in Pcrit and thus increased
airway collapsibility in healthy volunteers. The
increase in airway collapsibility was of a magnitude
comparable with neuromuscular blockade with a TOF
ratio of 0.5.
Furthermore, the normal compensatory activation of the genioglossus muscle in
response to airway negative pressure challenges was blunted after administration of
neostigmine/ glycopyrrolate (i.e. , neostigmine/glycopyrrolate evoked a significant
impairment of upper airway dilator muscle function).
Accordingly, whereas previous studies demonstrated airway compromise with residual
neuromuscular blockade and thus a probable clinical need for reversal agents,
theresults of this study reveal increased airway collapsibility as a result of
Napoli SIA 2013
neostigmine/glycopyrrolate, if given after recovery from neuromuscular transmission
94. TOF vs time after neostigmine 40 gr/kg (from T1
25%);control(fent/N2O),isoflurane stopped,isoflurane continued
(1.25%)Baurain MJ, d'Hollander AA,Melot C, Dernovoi BS,Barvais L.Effects of residual concentrations
of isoflurane on the reversal of vecuronium induced neuromuscular blockade.Anesthesiology 1991:71:474)
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95. Valori del tetanic fade (stimolazione a 50 Hz sn,100 Hz dx)dopo 15
min dalla somministrazione di neostigmina 40 microgr/kg Baurain
MJ, d'Hollander AA,Melot C, Dernovoi BS,Barvais L.Effects of residual concentrations of isoflurane on the reversal of
vecuronium induced neuromuscular blockade.Anesthesiology 1991:71:474- )
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98. Mean first twitch height vs time after administration of various doses of
neostigmine and edrophonium starting from T 1 10% following atracurium
and vecuronium Smith, CE, Donati F., Bevan DR.Dose-Response Relationships for Edrophonium and Neostigmine as
Antagonists of Atracurium and Vecuronium neuromuscular Blockade.Anesthesiology 1989;71: 37-43.
Inspired enflurane concentration maintained at 0.5-1%
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99. Dose response relationship of first twitch and TOF assisted recovery 5 and 10
min. following administration of the antagonist as a function of the dose of
neostigmine and edrophonium following atracurium and vecuronium. Smith, CE,
Donati F., Bevan DR.Dose-Response Relationships for Edrophonium and Neostigmine as Antagonists of Atracurium and Vecuronium
Neuromuscular Blockade.Anesthesiology 1989;71: 37-43.
???
?
Inspired enflurane concentration maintained at 0.5-1%
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100. Effect on Tof of 2 doses of neostigmine and edrophonium
following atracurium and vecuronium Smith, CE, Donati F., Bevan DR.Dose-Respons
Relationships for Edrophonium and Neostigmine as Antagonists of Atracurium and Vecuronium Neuromuscular
Blockade.Anesthesiology 1989;71: 37-43.
80
70
Inspired enflurane concentration maintained at 0.5-1%
Tof si ferma a 0.7!!!
60
50
atrac at 5'
atrac at 10'
vecu at 5'
vecu at 10'
40
30
20
10
0
neo 0.02
mg/kg
neo 0.04
mg/kg
Napoli SIA 2013
edroph
0.5 mg/kg
edroph 1
mg/kg
101. Conclusione 1
La dose giusta di neostigmina
è…………
Meditate gente meditate………………
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102. Insomma,l’antagonismo dipende
da:
Profondità di blocco al momento della
somministrazione dell’antagonista
Presenza o meno di potenzianti nmb.
Tipo di antagonista somministrato
Tipo di miorilassante somministrato
Dose dell’antagonista somministrato
end point scelto;T1/Tc,Tof,ecc.
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103. Conclusione 2
E’ meglio somministrare gli antidoti quando la
ripresa nm è iniziata
È meglio cessare la somministrazione degli
alogenati ( e monitorizzare la % et)…….
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104. Anesthesiology. 2002 Jan;96(1):45-50.
Efficacy of tactile-guided reversal
from cisatracurium-induced
neuromuscular block.
Kirkegaard H, Heier T, Caldwell JE.
Source
Department of Anesthesia and
Perioperative Care, University of
California, San Francisco, USA.
Napoli SIA 2013
105. Kirkegaard H,Heier T,Caldwell JE Efficacy of tactile guided
reversal from cisatracurium induced neuromuscular
block.Anesthesiology 2002;96:45-50
Anest with fent/prop/N2O
cisatrac 0.15 mg/kg
neostigmine 0.07 mg/kg administered at
reappearance of I,II,III,IV of TOF;tactile
vs Meccanomyography contralateral.
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106. Time from neostigmine
administration to TOFR 0.70
25.00
20.00
low
10.00
5.00
0.00
I twitch
II twitch
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III twitch
IV twitch
max
min
15.00
mediana
107. Time from neostigmine administration
to TOFR 0.80
80
70
60
low
50
max
40
min
30
mediana
20
10
0
I twitch
II twitch
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III twitch
IV twitch
108. Time from neostigmine administration
to TOFR 0.90
80
70
60
low
50
max
40
min
30
mediana
20
10
0
I twitch
II twitch
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III twitch
IV twitch
109. MMG magnitude of the first TOF twitch(T1) measured at the
reappearance of each of the 4 tactile TOF responses.
80
70
T1 %
60
low
max
min
mediana
50
40
30
20
10
0
I twitch
II twitch
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III twitch
IV twitch
110. Kirkegaard H,Heier T,Caldwell JE Efficacy of tactile guided
reversal from cisatracurium induced neuromuscular
block.Anesthesiology 2002;96:45-50
This
study shows that achieving a TOFR
of 0.90 in <10 min following neostigmine
reversal is not a realistic goal;therefore
counting the number of tactile responses to tof stimulation
cannot be used as a guide for neostigmine admninistration if
the end point of reversal is a TOFR of 0.90 or higher within
10 min;but
is a good predictor of TOFR
0.70.
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111. Time to tof 0.9 after neostigmine 0.07 mg/kg + glycopirrolate
when tactile tof is 1,2,3,4(groups) Kyo S. Kim, MD, PhD, Mi A. Cheong, MD, PhD, Hee J. Lee, MD,
and Jae M. Lee,.Tactile Assessment for the Reversibility of RocuroniumInduced Neuromuscular Blockade During Propofol or
Sevoflurane Anesthesia. Anesth Analg 2004;99:1080 –5)
rocuronium 0.6 mg/kg and maintained with rocuronium
0.1 mg/kg given every time the height of first twitch
(T1) in TOF recovered to approximately 15% of Tc
obtained before induction of neuromuscular blockade.
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114. Effetti fisiologici della presenza di
Ach
Bradicardia
Salivazione
Iperperistalsi
Secrezioni bronchiali
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115. Pericoli degli AntiAchE: arresto cardiaco
Bjerke, Richard J., MD; Mangione, Michael P.Asystole after
intravenous neostigmine in a heart transplant
recipinet.Can.Anaesth.J. 2001;48:305-07.
Purpose: To describe a heart transplant recipient who developed
asystole after administration of neostigmine which suggests that surgical
dennervation of the heart may not permanently prevent significant
responses to anticholinesterases.
Clinical features: A 67-yr-old man, 11 yr post heart transplant underwent
left upper lung lobectomy. He developed asystole after intravenous
administration of 4 mg neostigmine with 0.8 mg glycopyrrolate for
reversal of the muscle relaxant. He had no history of rate or rhythm
abnormalities either prior to or subsequent to the event.
Conclusion: When administering anticholinesterase medications to heart
transplant patients, despite surgical dennervation, one must be
prepared for a possible profound cardiac response.
Napoli SIA 2013
116. Pericoli degli ACHE:FA con rapida
risposta ventricolare…..
Kadoya, TSA, Aoyama K, Takenaka I.Development of rapid atrial
fibrillation with wide QRS complex after neostigmine in a patient
with intermittent WPW stndrome.BJA 1999;83:815-818
1Department of Anaesthesia, Nippon Steel Yawata Memorial Hospital, 1-1-1 Harunomachi,
Yahatahigashi-ku,
ABSTRACT: We report the case of a 67-yr-old man with intermittent Wolff-Parkinson-White
(WPW) syndrome in whom neostigmine produced life-threatening tachyarrhythmias. The
patient was scheduled for microsurgery for a laryngeal tumour. When he arrived in the
operating room, the electrocardiogram showed normal sinus rhythm with a rate of 82 beat
min-1 and a narrow QRS complex which remained normal throughout the operative period.
On emergence from anaesthesia, the sinus rhythm (87 beat min-1) changed to atrial
fibrillation with a rate of 80–120 beat min-1 and a normal QRS complex. We did not treat the
atrial fibrillation because the patient was haemodynamically stable. Neostigmine 1 mg without
atropine was then administered to antagonize residual neuromuscular block produced by
vecuronium. Two minutes later, the narrow QRS complexes changed to a wide QRS complex
tachycardia with a rate of 110–180 beat min-1, which was diagnosed as rapid atrial
fibrillation. As the patient was hypotensive, two synchronized DC cardioversions of 100 J and
200 J were given, which restored sinus rhythm. No electrophysiological studies of
anticholinesterase drugs have been performed in patients with WPW syndrome. We discuss
the use of these drugs in this condition.
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117. Pericoli degli antiAchE:broncocostrizione
Shibata O,Tsuda A,Makita T, Iwanaga S,Hara T,Shibata S,Sumikawa K.
Contractile and phosphadytilinositol responses of rat trachea to
anticholinesterase drugs.Can.Anaesth.J.1998;45:1190-95
Purpose: Some anticholinesterases (anti-ChE) such as neostigmine and pyridostigmine but not edrophonium, stimulate phosphaticlylinositol
(PI) response.
Although a direct relationship was suggested between the increase in PI response and airway smooth muscle contraction,
there are no data regarding the effects of anti-ChE drugs on airway smooth muscle. Thus, we examined the contractile
properties and PI responses produced by anti-ChE drugs.
Methods: Contractile response. Rat tracheal ring was suspended between two stainless hooks in Krebs-Henseleit (K-H)
solution. (1) Carbachol (CCh), anti-ChE drugs (neostigmine, pyridostigmine, edrophonium) or DMPP (a selective ganglionic
nicotinic agonist) were added to induce active contraction. (2) The effects of 4-diphenylacetoxy-N-methyl-piperidine
methobromide (4-DAMP), an M3 muscarinic receptor antagonist, on neostigmine- or pyridostigmine-induced contraction of
rat tracheal ring were examined. (3) Tetrodotoxin (TTX) was tested on the anti-ChE drugs-induced responses. PI response.
The tracheal slices were incubated in K-H solution containing LiCl and 3[H]myo-inositol in the presence of neostigmine or
pyridostigmine with or without 4-DAMP, an M3 muscarinic receptor antagonist. 3[H]inositol monophosphate (IP1) formed
was counted with a liquid scintillation counter.
Results: Carbachol (0.1 mM), neostigmine. (1 mM), pyridostigmine (10 mM) but not edrophonium or DMPP, caused tracheal
ring contraction. 4-DAMP, but not tetrodotoxin, inhibited neostigmine and pyridostigmine-induced contraction. Neostigmineor pyridostigmine-induced IP1 accumulation was inhibited by 4-DAMP.
Conclusions: The data suggest that anti-ChE drugs activate the M3 receptors at the tracheal effector site.
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119. Effetti contrattili di antiACHE,carbacolo e dimetilfenilpiperazinio sugli anelli
tracheali di ratto.
Shibata O,Tsuda A,Makita T, Iwanaga S,Hara T,Shibata S,Sumikawa K. Contractile and phosphadytilinositol
responses of rat trachea to anticholinesterase drugs.Can.Anaesth.J.1998;45:1190-95
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121. Tramèr, M. R. Fuchs-Buder, T..Omitting antagonism of nm
block:effect on PONV and risk of residual paralysis.A systematic
review.BJA 1999;82:379-386
A systematic search (MEDLINE, EMBASE, Biological Abstracts, Cochrane library,
reference lists and hand searching; no language restriction, up to March 1998) was
performed for relevant randomized controlled trials. In eight studies (1134 patients),
antagonism with neostigmine or edrophonium was compared with spontaneous
recovery after general anaesthesia with pancuronium, vecuronium, mivacurium or
tubocurarine. On combining neostigmine data, there was no evidence of an antiemetic
effect when it was omitted. However, the highest incidence of emesis with neostigmine
1.5 mg was lower than the lowest incidence of emesis with 2.5 mg. These data
suggested a clinically relevant emetogenic effect with the higher
dose of neostigmine in the immediate postoperative period but not
thereafter.
Numbers-needed-to-treat to prevent emesis by omitting neostigmine compared with
using it were consistently negative with 1.5 mg, and consistently positive (3–6) with 2.5
mg. There was a lack of evidence for edrophonium. In two studies, three patients with
spontaneous recovery after mivacurium or vecuronium needed rescue
anticholinesterase drugs because of clinically relevant muscle weakness (numberneeded-to-harm, 30). Omitting neostigmine may have a clinically
relevant antiemetic effect when high doses are used. Omitting
antagonism, however, introduces a non-negligent risk of residual
paralysis even with short-acting neuromuscular blocking agents.
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122. 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
neostigmine 70
micrograms/kg +
glycopyrrolate 10
micrograms/kg,
edrophonium 1 mg/kg +
atropine 10
micrograms/kg.
50
40
*
% 30
*
20
saline
10
0
PONV
antiemetici
necess
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Vomito entro
24 ore
123. 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,
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124. Effetti collat dello studio di Ding et al.
80
70
*
*
succi/miva/no antag
60
miva/miva/ no antag
*
50
miva/miva/antag
*
% 40
30
20
10
0
nausea
vomit
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antiemetici
neck pain
shoulder pain
126. Comportamento suggerito per l’antagonismo dei miorilassanti a
lunga e media durata di azione secondo le risposte al Tof
TOF
esaurimento
farmaco
dose
Twitch visibili
nessuno
1-2
Posponi antagonismo finchè almeno 1 o 2 contrazioni
visibili!!
++++
neostigmina
0.07 mg/kg
3-4
+++
neostigmina
0.04 mg/kg
4
++
edrofonio
0.5 mg/kg
4
+/-
edrofonio
0.25
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127. Time from administration of neostigmine or placebo/spontaneous recovery to
recovery of the TOF ratio 0.7, 0.8 or 0.9 in non-sugammadex studies
60
50
40
rocu 0,6+neo
rocu0,6 spont
30
rocu 0,9+neo
rocu 0,9 spont
20
10
0
tof 0,9 Adamus
tof0,9 Barrio
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tof 0,9 Adamus
tof 0,9 Bevan
tof 0,8 Della Rocca
128. Benefici attesi con
Sugammadex
Aumentata sicurezza per I pazienti
Aumentata sicurezza in anestesia e
chirurgia
Ridotta incidenza(eliminazione) del blocco
nm residuo
Aumentata efficienza
» Benefici economici per accelerazione della
ripresa,turnover + rapido?
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130. Clinical signs
Clinical signs
correlation with residual force
patient cooperation!
tongue
tongue
depres s or
depres s or
c lenching
c lenching
head llift
head ift
> 5 s ec
> 5 s ec
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arm or leg
arm or leg
li ft> 5 sec
li ft> 5 sec
s us tai ned
s us tai ned
hand gri p
hand gri p
s trenght
s trenght
131. clinical sig ns
reliable vs not rel iabl e
reliable vs not rel iabl e
TVn or ma ll
TVn or ma
N eg Pres s < 2 5 mmH g
N eg Pres s < 2 5 mmH g
N eg p res s < 5 0 mmH g
N eg p res s < 5 0 mmH g
c ou gh
c ou gh
e ye op en in g
e ye op en in g
to ng u e p ro tru sion
to ng u e p ro tru sion
unrel iable
unrel iable
unrel iable
unrel iable
reliable
reliable
unrel iable
unrel iable
unrel iable
unrel iable
unrel iable
unrel iable
b efo re p atien t c oo pe ra tio n ri....
b efo re p atien t c oo pe ra tio n ri....
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132. Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of
residual curarization using double burst stimulation: A
comparison with train-of-four. Anesthesiology 1989; 70:578-81
- Double burst stimulation (DBS.
The stimulus consists of two short bursts of 50 Hz tetanic stimulation,
separated by 750 ms
:
52 healthy patients undergoing surgery were studied.
For both stimulation patterns the frequencies of manually detectable
AB
fade in the response to stimulation were determined and compared at
various electromechanically measured TOF ratios.
A total of 369 fade evaluations for DBS and TOF were performed.
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133. Probability of being within defined TOFR intervals when
different clinical fade evaluations are given (Drenck NE, Ueda N,
Olsen NV, et al. Manual evaluation of residual curarization using double burst
stimulation: A comparison with train-of-four. Anesthesiology 1989; 70:578-81)
60
50
40
tof<0.4
tof 0.41-0.50
tof 051-0.60
tof 0.61-0.70
tof >0.70
% 30
20
10
0
no tof fade
no tof,no dbs fade fade in dbs,not tof
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134. Dbs 3-3
Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of residual curarization using
double burst stimulation: A comparison with train-of-four. Anesthesiology 1989; 70:57881)
Fade frequencies with DBS more frequent than with
TOF
Absence of fade with tof implies a 52% probability
than tof>0.60
absence of fade with dbs implies a tof >0.60 in
91% of cases
only tOFR<0.40 can be assessedd manually
therefore,evaluation of DBS is relevant only when
there is no fade to tof
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135. Conclusions:
Drenck NE, Ueda N, Olsen NV, et al. Manual evaluation of residual curarization using
double burst stimulation: A comparison with train-of-four. Anesthesiology 1989; 70:57881)
absence
of fade to DBS normally
excludes severe residual nm
blockade(tofr<0.60) BUT DOES
NOT NECESSARILY INDICATE
ADEQUATE CLINICAL
RECOVERY.
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136. Meccanomiographic vs tactile
Meccanomiographic vs tactile
evaluation
evaluation
Drenck et al.Anesthesiology 79;578:1989.
qualitative tof
evaluation
48% chances of
evaluating a real fade
qualitative DBS
evaluation
9% chances of non
discerning a real fade
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137. Viby-Mogensen J, Jensen NH, Engbæk J, Ørding H, Skovgaard LT,
Chæmmer-Jørgensen B. Tactile and visual evaluation of response to
train-of-four nerve stimulation. Anesthesiology 1985; 63:440-3.
Diaz/tps/N2O 66%/haloth 0.75-1.5%
IOT with SCC ,then panc
simult MMG in one arm & visual/tactile evaluation
in the opposite.
Experienced and (inexperienced)
anesthesiologists
6 different TOFR from every patient
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138. Viby-Mogensen et al Tactile and visual evaluation of
response to train-of-four nerve stimulation. Anesthesiology
1985; 63:440-3.
100
90
80
70
fade
60
observed 50
%
40
30
20
10
0
true tofr <0.30
true tof 0.31-0.40
true tof 0.41-0.50
true tof 0.51-0.60
true tof 0.61-0.70
true tof>0.70
inexp.observers
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exp.observers
139. Threshold fade by 3 very experienced observers (VibyMogensen et al. Tactile and visual evaluation of response to train-of-four nerve
stimulation. Anesthesiology 1985; 63:440-3)
0,7
0,6
0,5
0,4
onset
offset
0,3
0,2
0,1
0
visual
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manual
140. Threshold fade by 3 very experienced observers (Viby-
TOFR
Mogensen et al. Tactile and visual evaluation of response to train-of-four nerve
stimulation. Anesthesiology 1985; 63:440-3.)
1
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
max
min
mean
visual onset
visual recovery
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manual onset
manual recovery
141. Which
is the TOFR level that can be reliably
detected visually by observing tetanic fade
of the AP in response to 100-Hz, 5-s tetanus
in anesthetized patients.?
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143. FINAL QUESTION 1:
Does qualitative neuromuscular
monitoring reduce the risk of residual
block?
–NO
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144. 100 Hz visual assessment seems to be highly sensitive in evaluating residual paralysis, as
the absence of RF100 Hz visual fading at the AP is compatible with a TOF ratio >0.85
Baurain et al.Visual Evaluation of Residual Curarization in Anesthetized Patients
Using One Hundred-Hertz, Five-Second Tetanic Stimulation at the Adductor
Pollicis Muscle .Anesth Analg 1998; 87:185–9
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145. Residual block in patients
monitored with AMG
Mortensen Gatke
TOF watch 5.3
No monit 50
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17
Murphy
34.5
30
146. Final question 2:Does quantitative neuromuscular
monitoring reduce the risk of residual block?
It reduces but does not eliminate
residual block
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147. But.....
Despite high quality studies demonstrating
a beneficial effect of quantitative monitoring
on the incidence of PORC , few clinicians
routinely use this type of monitoring.
22.7% USA (Naguib et al , Anesth Analg 2010;1111:110-9)
35% Italy (Della Rocca et al,Minerva Anestesiol. 2012 Jul;78(7):767
73.
Neuromuscular block in Italy: a survey of current management.
Della Rocca G, Iannuccelli F, Pompei L, Pietropaoli P, Reale C, Di Marco
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P
148. Conclusions
Until neuromuscular block during surgery
is not routinely monitored with obiective
means(MMG,AMG...) residual paralyss
would continue and contribute to
postoperative complications!
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