Remif in day surg napoli 2001

Remifentanil in day
Remifentanil in day
surgery
surgery
Claudio Melloni
Servizio di Anestesia e Rianimazione
Ospedale Civile di Faenza(RA)

Che cosa rende il remifentanil
Che cosa rende il remifentanil
attraente in day surgery?
attraente in day surgery?
Brevi emitempi
contesto-sensitivi
riprese indipendenti da
dosaggio e durata
duttilità

confrontare!

metabolismo organo
indipendente.

dalla sedazione leggera alla
analgesia profonda

rapida dimissione........

Context sensitive half time of opioids(influence of P450

)

3A4 on alfentanil

fentanil

Tempi di ripresa(da Bekke et al)
10
9
8
7
6
min 5
4
3
2
1
0

fine infu-occhi aperti
fine infus-estubaz
fine infus-orientam

remi

fent

Song et al.Remifentanil infusion facilitates early recovery
for obese outpatients undergoing laparoscopic
cholecystectomy.AA 2000,90:1111-3.
18
16
14
12
min

10

sevo
remif

8
6
4
2
0

awake

extub

orient

Philip et al.Remifentanil Compared with Alfentanil for
Ambulatory Surgery Using Total Intravenous Anesthesia
Anesth Analg 1997; 84:515

*

80
70
60
50
% 40
30

*

*

*

rem
alf

20
10
0

iot resp

trocar
resp

skin clos
resp

light
anesth

suppl
doses

Conclusions from Philip_
• Remif more protective and times of
recovery similar between the two drugs…..
• Analgesics requested earlier following
remif…..

Tempi di ripresa rapidi
Tempi di ripresa rapidi
livelli

Primo

apertura occhi
ripresa respirazione spont.
estubazione
orientamento

Secondo indici di ripresa intellettivi superiori

Bekke AY Turndorf H., Berklay P, Osborn I,Bloo M,
Yarmush J, The Recovery of Cognitive Function After
Remifentanil- Nitrous Oxide Anesthesia Is Faster than
After an Isoflurane-Nitrous Oxide-Fentanyl
Combination in Elderly Patients Anesth Analg 2000;
91:117–22
• Remif .-nitrous oxide (N2O) vs isoflurane-N2O-fentanyl
• elderly patients undergoing spinal surgery.
• 60 patients (>65 yr old) randomly assigned to one of two
groups for maintenance of anesthesia.
• induction with 3.6 ± 1.2 mg/kg IV thiopental and
endotracheal intubation facilitated with 1.4 ± 0.5 mg/kg
succinylcholine
• patients maintained with either 0.5%–1.5% isoflurane, 70%
N2O, and up to 7 microg/kg fentanyl (iso/fent group) or 48
± 11 microg/kg remifentanil and 70% N2O (remi group).

Bekke et al.. The Recovery of Cognitive Function After
Remifentanil- Nitrous Oxide Anesthesia Is Faster than
After an Isoflurane-Nitrous Oxide-Fentanyl
Combination in Elderly Patients Anesth Analg 2000;
91:117–22
• A mini-mental status examination was used to assess
cognitive ability preoperatively, at 15, 30, and 60 min after
arrival at the postanesthesia care unit and again 12–24 h
postoperatively. The time from the conclusion of anesthesia
to spontaneous respiration was similar in both groups.
Times to eye opening (4.8 ± 2.6 vs 2.3 ± 1.1 min),
extubation (6.8 ± 3.8 vs 3.2 ± 2.1 min), and verbalization
(9.9 ± 6.2 vs 3.9 ± 2.6 min) were significantly shorter for
the remi group (P < 0.05). Postoperative mini-mental status
examination scores were significantly lower in the iso/fent
group at 15 (16.3 ± 5.8 vs 23.7 ± 3.3), 30 (20.2 ± 5.2 vs
26.3 ± 2.7), and 60 min (23.5 ± 4.4 vs 27.5 ± 2.0) (P <
0.001); however, the scores equalized after 12 h.

Bekke et al The Recovery of Cognitive Function After Remifentanil- Nitrous Oxide Anesthesia Is Faste
than After an Isoflurane-Nitrous Oxide-Fentanyl Combination in Elderly Patients Anesth Analg 2000;

Isofl/fen

Remif/N2O

Black ML. Hill JL, Zacny JP. Behavioral and
Physiological Effects of Remifentanil and Alfentanil in
Healthy Volunteers Anesthesiology 80:718-26, 1999
• Background: The subjective and psychomotor effects of remifentanil
have not been evaluated. Accordingly, the authors used mood
inventories and psychomotor tests to characterize the effects of
remifentanil in healthy, non—drug-abusing volunteers. Alfentanil was
used as a comparator drug.
•
Methods: Ten healthy volunteers were enrolled in a randomized,
double-blinded, placebo-controlled, crossover trial in which they
received an infusion of saline, remifentanil, or alfentanil for 120 min.
The age- and weight-adjusted infusions (determined with
STANPUMP, a computer modeling software package) were given to
achieve three predicted constant plasma levels for 40 min each of
remifentanil (0.75, 1.5, and 3 ng/ml) and alfentanil (16, 32, and 64
ng/ml). Mood forms and psychomotor tests were completed, and
miosis was assessed, during and after the infusions. In addition,
analgesia was tested at each dose level using a cold-pressor test.

Black et al Behavioral and Physiological Effects of
Remifentanil and Alfentanil in Healthy Volunteers
Anesthesiology 80:718-26, 1999
• Results: Remifentanil had prototypic m-like opioid subjective effects,
impaired psychomotor performance, and produced analgesia.
Alfentanil at the dose range tested had more mild effects on these
measures, and the analgesia data indicated that a 40:1 potency ratio,
rather than the 20:1 ratio we used, may exist between remifentanil and
alfentanil. A psychomotor test administered 60 min after the
remifentanil infusion was discontinued showed that the volunteers
were still impaired, although they reported feeling no drug effects.
•
Conclusions: The notion that the pharmacodynamic effects of
remifentanil are extremely short-lived after the drug is no longer
administered must be questioned given our findings that psychomotor
effects were still apparent 1 h after the infusion was discontinued.

alf

remi

remi

alf

Black et al Behavioral and Physiological Effects of Remifentanil and Alfentanil
in Healthy Volunteers Anesthesiology 80:718-26, 1999

E' necessario
E' necessario
somministrare il
somministrare il
remifentanil in una tecnica
remifentanil in una tecnica
completamente ev o si può
completamente ev o si può
associare ad inalatori?
associare ad inalatori?
Perbacco se si può!

Interaction between remifentanil and isofluraneIsoflurane
concentration reduction by increasing remifentanil whole blood
concentration
Anesthesiology
85:721-8, 1996

Song et al.Remifentanil infusion facilitates early
recovery for obese outpatients undergoing
laparoscopic cholecystectomy.AA 2000,90:1111-3.

*
18
16
14
12
10
8
6
4
2
0

*

*
min

sevo
remif

*
mg

sevo%

opioid
intraop

awake

extub

orient

Conclus from Song et al
• Variable rate infus of remif(0.09
microgr/kg/min) + sevo + N2O :
•
50% sevo %
• Contributed to a more rapid emergence
• Postop side effects not increased(PONV=)
• PACU stay and discharge times =

dimissibilità e
dimissione
la rapidità di ripresa dopo remifentanil si
traduce poi in una dimissione più precoce
rispetto ad altri farmaci comparatori?

Davis PJ,Finkel J,Orr RJ,Fazi L, Mulroy JJ, Woelfel
SK,Hannallah RS,Lynn AM, Kurth C D,Moro M,
Henson LG, Goodman DK,Decker M. A Randomized,
Double-Blinded Study of Remifentanil Versus
Fentanyl for Tonsillectomy and Adenoidectomy
Surgery in Pediatric Ambulatory Surgical Patients
Anesth Analg 2000; 90:863–71.

• We compared, in a double-blinded manner, the
anesthetic maintenance and recovery properties of
remifentanil with a clinically comparable fentanylbased anesthetic technique in pediatric ambulatory
surgical patients. Anesthesia was induced with
either halothane or sevoflurane and nitrous oxide
and oxygen. Patients were randomized (computer
generated) to receive either remifentanil or fentanyl

Davis et al. Randomized, Double-Blinded Study of
Remifentanil Versus Fentanyl for Tonsillectomy and
Adenoidectomy Surgery in Pediatric Ambulatory
Surgical Patients Anesth Analg 2000; 90:863–71.

• Patients were randomized to receive either
remifentanil or fentanyl and randomized to
receive halothane or sevoflurane in one of
four possibilities.
•
All children were premedicated with
midazolam. For children less than 20 kg,
midazolam was administered either
intranasally (0.2–0.3 mg/kg) or orally (0.5–
0.75 mg/kg). For children larger than 20 kg,


• After the trachea was intubated, patients
received either a placebo bolus dose and a
continuous infusion (0.25 mg×kg-1×min-1)
of remifentanil, or the patients received a
bolus dose of fentanyl (2 mg/kg) and a
placebo continuous infusion. The nitrous
oxide and oxygen were administered with
the potent inhaled anesthetic used for
induction at 0.3% minimum alveolar
anesthetic concentration (MAC)

extubation than subjects in the fent/hal group (P = 0.001). 12% of
the patients anesthetized with remifentanil (10% remi/hal, 13%
remi/sevo) required stimulation at 10 min after the cessation of the
anesthesia compared with 31% of patients in the fentanyl group
(34% fent/hal, 28% fent/sevo) (P = 0.003).

Davis et al. Randomized, Double-Blinded Study of Remifentanil Versus Fentanyl for Tonsillectomy and
Adenoidectomy Surgery in Pediatric Ambulatory Surgical Patients Anesth Analg 2000; 90:863–71.

administration until the patients were eligible for discharge from the
PACU were statistically different among treatment groups (P =
0.013) Specifically, as shown in , subjects in the remi/hal group had
statistically significantly shorter recovery times than subjects in the
fent/hal group (P = 0.001).


after arrival in PACU. Pairwise comparisons showed that OPDS scores were
statistically higher for remi/hal versus fent/hal groups at PACU arrival (P <
0.001), +5 min (P < 0.001), +10 min (P < 0.001), +15 min (P = 0.008), and +20 min
(P = 0.001). Pairwise comparisons showed that OPDS scores were significantly
higher for remi/sevo versus fent/sevo groups at 5 min after PACU arrival (P =
0.031) and at 10 min after PACU arrival (P = 0.035). Median OPDS scores were
zero for all treatment groups at 60 min after PACU arrival.


Davis et al. Randomized, Double-Blinded
Study of Remifentanil Versus Fentanyl for
Tonsillectomy and Adenoidectomy Surgery in
Pediatric Ambulatory Surgical Patients Anesth
Analg 2000; 90:863–71.

Davis et al. Randomized, Double-Blinded
Study of Remifentanil Versus Fentanyl for
Tonsillectomy and Adenoidectomy Surgery in
Pediatric Ambulatory Surgical Patients Anesth
Analg 2000; 90:863–71.

• There was no statistically significant
difference (P = 0.212) among treatment
groups in the proportion of subjects who
received medication to treat inadequate
and/or excessive anesthesia responses.
Although a higher percentage of subjects in
the fent/sevo (54%) and fent/hal (42%)
groups received medication to treat
inadequate anesthesia responses than
subjects in the remi/sevo (38%) and

Discharge of the patient vs home
readiness
Chung

patterns of home readiness

Laparscopy,general surg,orthopedic surg

persistent symptoms

factors that delay discharge

recurrence of pain
PONV

unavailability of escorts

Pavlin DJ,Rapp SE, Polissar NL,Malmgren JA,
Koerschgen M,Keyes H.Factors Affecting
Discharge Time in Adult Outpatients Anesth
Analg 1998; 87:816–26

•
•
•
•
•

Le cause più comuni dei ritardi nella dimissione:
anesthetic technique:GA
Phase 2 nurse
pain,drowsiness,ponv
lack of escort

Beers R,Calimlim JR, Uddoh E,Esposito B, Camporesi
EM.A Comparison of the Cost-Effectiveness of
Remifentanil Versus Fentanyl as an Adjuvant to
General Anesthesia for Outpatient Gynecologic
Surgery Anesth Analg 2000; 91:1420
• The unique pharmacokinetic properties of remifentanil make it a potentially useful
adjuvant during general anesthesia for ambulatory surgery. Fentanyl, inexpensive
and easy to administer, is the most common opioid used for this purpose. As an
adjuvant to general anesthesia for outpatient gynecologic surgery, we questioned if
remifentanil was cost-effective as an alternative to fentanyl. Thirty-four patients
undergoing gynecologic laparoscopy or hysteroscopy were prospectively and
randomly assigned to a standard practice (n = 18) or a study (n = 16) group.
Standard practice patients received fentanyl(3 microg/kg) before induction; study
patients received remifentanil by continuous infusion (0.5 microg×kg×min-1 at
induction, then 0.2 microg×kg×min-1). Sevoflurane was titrated to a Bispectral
index value of 40–55.

• Fentanyl administered to studty pts for analgesia before
awakening! the We investigated recovery profiles, patient and health care
professional satisfaction, and drug costs . The incidence of rescue antiemetic
treatment (2 of 16 vs 8 of 18; P = 0.013) and the nausea visual analog scale scores
during second stage recovery (0.2 vs 0.6; P = 0.044) were more frequent in the

Beers R,Calimlim JR, Uddoh E,Esposito B, Camporesi EM.A Comparison of the Cost-Effectiveness of Remifentanil
rsus Fentanyl as an Adjuvant to General Anesthesia for Outpatient Gynecologic Surgery Anesth Analg 2000; 91:14

Il remifentanil è duttile?
Il remifentanil
da sedazione cosciente a analgesia profonda.....
mantenere il respiro spontaneo
da solo/ con altri farmaci....

il problema della analgesia postoperatoria
che cosa,quando e come per mantenere una
precoce dimissibilità?

Interazione di remifentanil e sevoflurane 2%in
resp spont per chir minore(LMA)(Madei et
al,Anesthesiology 1997;A7)
90
80
70
60
%

0,125+0,025 inf
0,25+0,05 inf
0,375+0,075inf
0,5+0,1inf

50
40
30
20
10
0

risp som

depr.resp

devHR

dev map

Deduzioni pratiche del lavoro di
Dershwitz: dosaggio del remifentanil
•

a dosaggi > 0,3 µ g/kg/min=1260
µ g/ora/70 kg cioè 63 ml/ora delle
diluizione a 20 µ g/ml,solo il 14%
dei pazienti rispondono alle
manipolazioni chirurgiche
;comunque 0.1 µ g/kg/min
adeguati ⇒ 420 µ g/h/70kg=21

ED 50

• 0.052 microgr/kg/min=218
microgr /hr per un adulto
di 70 kg

Effetti respiratori del
remifentanil:RS mantenuto se:
• <0.1 µg/kg/min da solo o 0.05
µg/kg/min con isoflurano 1.1%
• 0.05 µg/kg/min+ propof 133
µg/kg/min(=133*70*60=558 mg/ora)
(Peacock)
•
quindi

• 10-12 ml/ora “sicuri”(=200

Effetti respiratori del remifentanil
120,0

Da Scott& da Glass

100,0
80,0
min 60,0

remifentanil
alfent

40,0
20,0
0,0

pkhalf
time

50% recov
of min vent

elim h.l

csht

Babenco H, Conard PF, Gross J. The Pharmacodynamic
Effect of a Remifentanil Bolus on Ventilatory Control .
Anesthesiology 92:393-8, 2000
•

Methods: In eight healthy volunteers, the authors
determined the time course of the ventilatory response to
carbon dioxide using the dual isohypercapnic technique.
Subjects breathed via mask from a to-and-fro circuit with
variable carbon dioxide absorption, allowing the authors to
maintain end-tidal pressure of carbon dioxide (PETCO2) at
approximately 46 or 56 mmHg (alternate subjects). After 6
min of equilibration, subjects received 0.5 mg/kg
remifentanil over 5 s, and minute ventilation (E) was
recorded during the next 20 min. Two hours later, the study
was repeated using the other carbon dioxide tension (56 or
46 mmHg). The E data were used to construct two-point
carbon dioxide response curves at 30-s intervals after

Curva di risposta ventilatoria alla CO2 dopo
remifentanil 0.5 microgr/kg

Babenco H, Conard PF, Gross J. The Pharmacodynamic Effect of a
Remifentanil Bolus on Ventilatory Control . Anesthesiology 92:393-8, 2000

Ve at PetCO250 following remifentanil 0.5
microgr/kg


VT at PetCO250 following remifentanil 0.5
microgr/kg


Ve50 and effect site concentration of
remifentanil


Ve50 vs time following remifentanil 0.5
microgr/kg


m anu al op ioid infu sion s ch em es
fro m m an y sou rc es ...
so u
d rug

pla s m a targ et
in fus io n ra te
co n ce ntation (ng m b olu s (m ic ro g r/k g) icro gr/kg /m in
l)
(m

fen tan yl

1

3

0 .0 20

fen tan yl

4

10

0 .0 70

alfe n ta n il

40

20

0.25

alfe n ta n il

1 60

80

1.00

su fe n ta n il

0.15

0.15

0 .0 03

su fe n ta n il

0.50

0.50

0 .0 10

6

1

0.02

1 -2

0 .4-1 .0

re m ife n ta n il
re m ife n ta n il

12 -20

Practical pharmacokinetics as applied to our
daily anesthesia practice
Fiset, Pierre.Can J Anesth 1999 / 46 / R122-R126

Suggerimenti pratici finali
Suggerimenti pratici finali
infusione continua con pompa siringa

sedazione

se ben tollerato

per anestesia

inizia a 0.02-0.03
microgr/kg/min,cioè 50-150
microgr/hr....
incrementa del 25% ogni 2-3
min,osservando continuamente il
RS(ETCO2,RR)
inizia a 0.1 microgr/kg/min,cioè
400-500 microgr/hr

Pratica
Pratica
boli più infusione continua
sedazione

bolo 0.1 microgr/kg+
0.01-0.02 microgr/kg/min

sedazione profonda

bolo 0.2 microgr/kg + 0.02
microgr/kg/min

anestesia

bolo 0.5 microgr/kg + 0.10
microgr/kg/min

sono dosaggi bassi

Infusione rapida
Infusione rapida
non mai!
iniziare in simultanea con
propofol

propofol 6
mg/kg/hr

iniziare dopo midazolam

midazolam 2-3
mg

???

Futuro del remifentanil
Futuro
mercato

Remif

Competitori

+10 1/2

-2

Babenco HD,Conard PF,Gross JB.The
Pharmacodynamic Effect of a Remifentanil Bolus on
Ventilatory Control. Anesthesiology 92:393-8, 2000

• Background: In doses typically
administered during conscious sedation,
remifentanil may be associated with
ventilatory depression. However, the time
course of ventilatory depression after an
initial dose of remifentanil has not been
determined previously.
•
Methods: In eight healthy volunteers, the
authors determined the time course of the

Ripresa dopo remifentanil vs alfentanil in
chir.ambulatoriale(Philip et al,Anesthesiology
1997;A35)
250
200
150
rmif
alfentanil

min & %
100
50
0

dimissione

nausea

Ripresa dopo remifentanil vs alfentanil in
chir.ambulatoriale(Philip et al,Anesthesiology
1997;A35)

• Chir.laparoscopica ambulatoriale > 30 min.
• propofol 2 mg/kg+ inf cont 150 µg/kg/min
fino al trocar,poi 75 µg/kg/min.
• remifentanil bolo 1 µg/kg,poi 0.5
µg/kg/min,poi 0.25 µg/kg/min;stop alla fine
chir.
• alfentanil 20 µg/kg bolo,poi 2 µg/kg/min
poi 1 µg/kg/min.;stop 10 min prima fine op.
• vecuronium per miorisoluzione

Fortier et al.Remifentanil vs alfentanil for
ambulatory surgery using preoperative
naproxen for pain management.Anesthesiology
•
•
•
•
•
•

1997;87:A15.

Multicentrico
chir laparoscopica o artroscopica
naproxen p.o preoperatorio
remifentanil 1 µg/kg vs alfentanil 20 µg/kg
propof 2 mg/kg+ mivac 0.25 mg/kg
mantenimento remi 0.5 µg/kg/min vs
alfentanil 2 µg/kg/min + propof 150
µg/kg/min,poi riduz al 50% dopo trocar

Fortier risultati:
• Remi

• Alfentanil

•
•
•
•
•
•
•
•

•
•
•
•
•
•
•
•

pacu pain score 3
fentanil in PACU 61%
nausea :3%†
vomito predimissione:0
sedazione a 30 min:3 †
sedazione a 30 min:2†
sedazione a 90 min:1†
deambulazione a 129 min

pacu pain score 2
fentanil in PACU 53%
nausea :16%
vomito predimissione:9%
sedazione a 30 min:5
deambulazione a 141 min

SK,Hannallah RS,Lynn AM,Kurth CD,Moro M,
Henson LG,Goodman DK,Decker M.
A Randomized, Double-Blinded Study of
• Surgical Patients Anesth Analg 2000; 90:863.
We compared, in a double-blinded manner,

the anesthetic maintenance and recovery
properties of remifentanil with a clinically
comparable fentanyl-based anesthetic
technique in pediatric ambulatory surgical
patients. Anesthesia was induced with
either halothane or sevoflurane and nitrous
oxide and oxygen. Patients were
randomized (computer generated) to receive
either remifentanil or fentanyl in a blinded

• The pharmacokinetics of remifentanil make
blood concentrations predictable.
Remifentanil blood concentrations obtained
by infusions of 1.0–2.0 mg kg-1 min-1 were
related linearly to the rate of infusion and
unrelated to the duration of infusion,
( References
•

14: Duthie DJR, Stevens JJWM, Doyle AR, Baddoo HHK, Gupta SK,
Muir KT, Kirkham AJT. Remifentanil and pulmonary extraction
during and after cardiac anesthesia. Anesthesia and Analgesia 1997;
84:740-744. <ldn>!

Ogg, T. W.; Watson, B. J.; Shaikh, S Remifentanil in
combination with propofol for spontaneous
ventilation anaesthesia
Short CommunicationBr. J. Anaesth. 1998; 80

• We have investigated the effect of four doses of
remifentanil on the incidence of respiratory
depression and somatic response at incision.
Remifentanil was administered as a loading dose of
0.125, 0.25, 0.375 or 0.5 mg kg-1 and at a
maintenance infusion rate of 0.025, 0.05, 0.075 or
0.1 mg kg-1 min-1, respectively, with an infusion of
propofol 6 mg kg-1 h-1. Responses occurred in 88%
of patients with remifentanil 0.025 mg kg-1 min-1
compared with 30–40% in the other groups.

Peacock, et al Remifentanil in combination
with propofol for spontaneous ventilation
anaesthesia

• Patient characteristics and surgery
(primarily hernia repair and varicose vein
surgery) were similar in all groups although
there were more males in groups 1 and 2 ().
At skin incision somatic responses occurred
in 88% of patients at an infusion rate of
remifentanil of 0.025 mg kg-1 min-1
The majority of patients required additional
propofol to maintain anaesthesia and the

anaesthesia

• The same pattern of response was seen by
Hogue and colleagues in patients
undergoing ventilation; they used a
propofol infusion rate of 4.5 mg kg-1 h-1
with higher remifentanil infusion rates of
0.5 and 1.0 mg kg-1 min-1, which were
reduced by 50% after tracheal intubation.
They found that 19% and 23% of patients
required propofol rescue medication for
light anaesthesia, confirming that adequate

anaesthesia

• Remifentanil can be administered as part of
a TIVA technique with propofol for
spontaneous ventilation anaesthesia. An
infusion of 0.05 mg kg-1 min-1 or less was
associated with adequate ventilation in the
majority of patients, and in combination
with a propofol infusion of 7.2–8.4 mg kg-1
h-1 provided clinically acceptable
maintenance of anaesthesia. Induction of
anaesthesia after a loading dose of

Charles J., MD‡; Landsman, Ira, MD*; Henson, Lynn
Graham, PharmD½½
A Randomized Multicenter Study of Remifentanil
Compared with Alfentanil, Isoflurane, or Propofol in
Anesthetized Pediatric Patients Undergoing Elective
• Remifentanil hydrochloride is 1997; 84:982–9
Strabismus Surgery Anesth Analg a new,

ultrashort-acting opioid metabolized by
nonspecific plasma and tissue esterases. We
conducted this multicenter study to examine
the hemodynamic response and recovery
profile of premedicated children undergoing
strabismus repair who were randomly
assigned to receive one of four treatment
drugs (remifentanil, alfentanil, isoflurane,
or propofol) along with nitrous oxide and

• As the practice of outpatient surgery
advances, the search continues for
anesthetics that provide rapid smooth
induction, intraoperative analgesia,
amnesia, rapid emergence, a short
postoperative recovery period, and
minimum side effects. New, potent, inhaled
anesthetics with low blood-gas solubility
coefficients and IV anesthetics of ultrashort
duration could provide these optimum

• Part of the reason for not discerning
differences among treatment groups may
have been due to our study design. The dose
of remifentanil used for the continuous
infusion (1 mg×kg-1×min-1) may have
been larger than necessary. No doseresponse study had been performed before
this study was initiated. Dershwitz et al.
noted in adults that the 50% effective dose
(ED50) for remifentanil to abolish all

• Of interest is the comparison of remifentanil with the other opioid used
in the study, alfentanil. Although recovery variables were similar with
both drugs, nonetheless, 21% of the patients anesthetized with alfentanil
required naloxone for tracheal extubation and emergence. Had these
patients not been administered naloxone, their recovery times would
have been markedly longer.
• The study design may also have affected our tracheal extubation
times. In an effort not to have anesthetic practices influence extubation
times and knowing that the responsible anesthesiologist was not blinded
to the anesthetic, no physical stimulation of the patient was allowed for
the first 10 min after discontinuation of the anesthetic. Consequently,
during these first 10 min, patients spontaneously recovered from
anesthesia. Had stimulation been allowed (i.e., oral suctioning, jaw
thrust), it is conceivable that some patients could have been extubated
earlier.

• Alfentanil's pharmacokinetic profile may
also explain its higher incidence of
postoperative hypoxemia. Four of the 19
alfentanil-anesthetized patients had clinical
evidence of respiratory depression in the
postoperative period. These four patients
were not the individuals who received
naloxone. Recurrent respiratory depression
after apparent recovery from alfentanil
anesthesia has been previously reported.

Rowbotham, D. J.; Peacock, J. E.; Jones, R. M.;
Speedy, H. M.; Sneyd, J. R.; Morris, R. W.;
Nolan, J. P.; Jolliffe, D.; Lang, G.
Comparison of remifentanil in combination with
isoflurane or propofol for short-stay surgical
procedures†
• There Br. J. Anaesth. 1998;literature that
are few data in the 80:752-755

describe the use of remifentanil when
administered as a component of an
inhalation or total i.v. anaesthetic (TIVA)
technique. We studied 251 male and female
patients, aged 18–75 years, ASA I-II,
undergoing inguinal hernia repair,
arthroscopic knee surgery or varicose vein
surgery of at least 30 min duration without
premedication. Patients were randomized to

applied to our daily anesthesia
practice
AUTHOR(S): Fiset, Pierre, MD
-

Joshi GP,Jamerson BD, Roizen MF,Fleisher L,Twersky
RS,Warner DS,Colopy M.Is There a Learning Curve
Associated with the Use of Remifentanil?
Anesth Analg 2000; 91:1049–55
• AUTHOR(S): †
•
• *This study prospectively determined whether
there was a learning curve with the use of
remifentanil, as indicated by decreased
hemodynamic variability, improved recovery
profile, and decreased incidence of opioid-related
adverse events with increasing experience.
Patients undergoing diverse surgical procedures
(outpatient [n = 1340] and inpatient [n = 560])
were enrolled by investigators (n = 190) who had
no previous experience with remifentanil use.

Watson BJ; Shaikh S.
Remifentanil in combination with propofol for
spontaneous ventilation anaesthesia

• ABSTRACT: Summary
• We have investigated the effect of four
doses of remifentanil on the incidence of
respiratory depression and somatic response
at incision. Remifentanil was administered
as a loading dose of 0.125, 0.25, 0.375 or
0.5 mg kg-1 and at a maintenance infusion
rate of 0.025, 0.05, 0.075 or 0.1 mg kg-1
min-1, respectively, with an infusion of

• Patient characteristics and surgery
(primarily hernia repair and varicose vein
surgery) were similar in all groups although
there were more males in groups 1 and 2 ().
At skin incision somatic responses occurred
in 88% of patients at an infusion rate of
remifentanil of 0.025 mg kg-1 min-1
The majority of patients required additional
propofol to maintain anaesthesia and the

• The same pattern of response was seen by
Hogue and colleagues in patients
undergoing ventilation; they used a
propofol infusion rate of 4.5 mg kg-1 h-1
with higher remifentanil infusion rates of
0.5 and 1.0 mg kg-1 min-1, which were
reduced by 50% after tracheal intubation.
They found that 19% and 23% of patients
required propofol rescue medication for
light anaesthesia, confirming that adequate

• Remifentanil can be administered as part of
a TIVA technique with propofol for
spontaneous ventilation anaesthesia. An
infusion of 0.05 mg kg-1 min-1 or less was
associated with adequate ventilation in the
majority of patients, and in combination
with a propofol infusion of 7.2–8.4 mg kg-1
h-1 provided clinically acceptable
maintenance of anaesthesia. Induction of
anaesthesia after a loading dose of

CJ,Landsman I,Henso LG, A Randomized Multicenter
Study of Remifentanil Compared with Alfentanil,
Isoflurane, or Propofol in Anesthetized Pediatric Patients
Undergoing Elective Strabismus Surgery Anesth Analg
1997; 84:982–9

• Remifentanil hydrochloride is a new,
ultrashort-acting opioid metabolized by
nonspecific plasma and tissue esterases. We
conducted this multicenter study to examine
the hemodynamic response and recovery
profile of premedicated children undergoing
strabismus repair who were randomly
assigned to receive one of four treatment
drugs (remifentanil, alfentanil, isoflurane,
or propofol) along with nitrous oxide and

Davis et al-.Randomized Multicenter Study of
Remifentanil Compared with Alfentanil,
Isoflurane, or Propofol in Anesthetized Pediatric
Patients Undergoing Elective Strabismus Surgery
Anesth Analg 1997; 84:982–9

• As the practice of outpatient surgery
advances, the search continues for
anesthetics that provide rapid smooth
induction, intraoperative analgesia,
amnesia, rapid emergence, a short
postoperative recovery period, and
minimum side effects. New, potent, inhaled
anesthetics with low blood-gas solubility
coefficients and IV anesthetics of ultrashort
duration could provide these optimum


• Part of the reason for not discerning
differences among treatment groups may
have been due to our study design. The dose
of remifentanil used for the continuous
infusion (1 mg×kg-1×min-1) may have
been larger than necessary. No doseresponse study had been performed before
this study was initiated. Dershwitz et al.
noted in adults that the 50% effective dose
(ED50) for remifentanil to abolish all

• Of interest isAnesth Analg 1997; 84:982–9 opioid used
the comparison of remifentanil with the other
in the study, alfentanil. Although recovery variables were similar with
both drugs, nonetheless, 21% of the patients anesthetized with alfentanil
required naloxone for tracheal extubation and emergence. Had these
patients not been administered naloxone, their recovery times would
have been markedly longer.
• The study design may also have affected our tracheal extubation
times. In an effort not to have anesthetic practices influence extubation
times and knowing that the responsible anesthesiologist was not blinded
to the anesthetic, no physical stimulation of the patient was allowed for
the first 10 min after discontinuation of the anesthetic. Consequently,
during these first 10 min, patients spontaneously recovered from
anesthesia. Had stimulation been allowed (i.e., oral suctioning, jaw
thrust), it is conceivable that some patients could have been extubated
earlier.


• Alfentanil's pharmacokinetic profile may
also explain its higher incidence of
postoperative hypoxemia. Four of the 19
alfentanil-anesthetized patients had clinical
evidence of respiratory depression in the
postoperative period. These four patients
were not the individuals who received
naloxone. Recurrent respiratory depression
after apparent recovery from alfentanil
anesthesia has been previously reported.

Rowbotham, D. J.; Peacock, J. E.; Jones, R. M.; Speedy, H.
M.; Sneyd, J. R.; Morris, R. W.; Nolan, J. P.; Jolliffe, D.;
Lang, G.
Comparison of remifentanil in combination with
isoflurane or propofol for short-stay surgical procedures†
• 251 male and female patients
Br. J. Anaesth. 1998; 80:752-755
•
•
•
•

18–75 years
ASA I-II
undergoing inguinal hernia repair, arthroscopic knee surgery or varicose vein
surgery of at least 30 min duration without premedication.
Groups:I:REMI/isof
– remifentanil loading dose of 1.0 microg/kg followed by a continuous infusion of
0.5 microgr/kg/min in combination with isoflurane (end-tidal concentration
0.6%)
– II REMI/PROP propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg
kg-1 h-1 after 10 min)
– The remifentanil infusion rate was reduced by 50%, 5 min after tracheal
intubation. Intraoperative stresses were treated with a remifentanil bolus (1
microgr/kg) followed by an increase in the remifentanil infusion rate. At the

extub

min

60
40
20
0

RS

Rowbotham et al.Comparison of remifentanil in
combination with isoflurane or propofol for
short-stay surgical procedures†
Br. J. Anaesth. 1998; 80:752-755

Remi/
isofl
0.6
remi/
propo
f

Rowbotham et al.Comparison of remifentanil in
combination with isoflurane or propofol for shortstay surgical procedures†
Br. J. Anaesth. 1998; 80:752-755

Song, D,Whitten CW,Whit PF Use of Remifentanil During
Anesthetic Induction: A Comparison With Fentanyl in the
Ambulatory Setting..Anesth Analg 1999; 88:734
• 75 outpatients for gynecologic laparoscopy or
inguinal herniorrhaphy
• midazolam 2 mg IV
• bolus of fentanyl 1 mg/kg IV (Group I) or a bolus
dose of remifentanil 0.5 mg/kg (Group II) or 1
mg/kg (Group III
• Propofol 2 mg/kg IV and SC 1 mg/kg IV were
administered 1 min after the bolus dose of the
study medication.
• Laryngoscopy and endotracheal intubation
performed 3 min after injection of the study

Song, et al.Use of Remifentanil During Anesthetic
Induction: A Comparison With Fentanyl in the
Ambulatory Setting..Anesth Analg 1999; 88:734

•
•
•
•
•
•
•

Song D,Whitten CW,White,PF.Remifentanil
infusion facilitates early recovery for obese
outpatients undergoing laparoscopic
cholecystectomy.AA 2000,90:1111-3.
30 obese outpts for lap cholcystect.
Premed midaz 2 mg
Fent/prop/rocu iot
Sevo 0.8% +N2O 65%
2 groups:sevo variable conc 0.4-4% vs remif
variable rate 0.05-2 microgr/kg/min
Fent as rescue
At the end of surg. bupi 0.25% at portals,ketor 30
mg i.v+30 mg i.m.+drop 0.625

• In praevious laparoscopic cholecistect
studies it has been demonstrated that the
use of sevo as a maintenence drug had a
more favourable recovery profile when
compared with desfl for emetic symptoms
(ref 7) and provided a more rapid
emergence than propofol(ref 8)

Pavlin DJ,Rapp SE, Polissar NL,Malmgren JA,
Koerschgen M,Keyes H.Factors Affecting Discharge
Time in Adult Outpatients Anesth Analg 1998; 87:816–
26
• Discharge time (total recovery time) is one determinant of the overall
cost of outpatient surgery. We performed this study to determine what
factors affect discharge time. Details regarding patients, anesthesia,
surgery, and recovery were recorded prospectively for 1088 adult
patients undergoing ambulatory surgery over an 8-mo period. The
contribution of factors to variability in the discharge time was
assessed by using multivariate linear regression analysis. In the last 4
mo of the study, nurses indicated the causes of discharge delays ³50
min in Phase 1 or ³70 min in Phase 2 recovery. When all

anesthetic techniques were included, anesthetic

technique was the most important determinant
of discharge time (R2 = 0.10–0.15; P = 0.001),
followed by the Phase 2 nurse.

Pavlin et al..Factors Affecting Discharge Time in Adult
Outpatients Anesth Analg 1998; 87:816–26
• After general anesthesia, the Phase 2 nurse was the most
important factor (R2 = 0.13; P = 0.01–0.001). In women, the
choice of general anesthetic drugs was significant (R2 = 0.04; P =
0.002). The three most common medical causes of delay
were pain, drowsiness, and nausea/vomiting. System factors
were the foremost cause of Phase 2 delays (41%), with lack of

immediate availability of an escort accounting for 53%

of system-related delays. We conclude that efforts to shorten
discharge time would best be directed at improving nursing
efficiency; ensuring availability of an escort for the patient; and
preventing postoperative pain, drowsiness, and emetic symptoms. The
selection of anesthetic technique and anesthetic drug seems to be of
selective importance in determining discharge time depending on
patient gender and type of surgery. Implications: The relative
importance of anesthetic and nonanesthetic factors were evaluated as
determinants of discharge time after ambulatory surgery.

• Animal studies and controlled studies in human
volunteers suggest that there are differences in the
speed of recovery from various anesthetics . This
may be expected to translate into differences in
discharge time. However, such differences are not
necessarily transferable to the general surgical
patient population of a busy operating room. In
fact, many studies have identified differences in
intermediate end points of recovery (i.e.,
emergence, time to take oral fluids or ambulate,
recovery of cognitive function) but have found no
difference in discharge time or failed to report

Intermediate end points vs final
home discharge
• Fisher DM. Surrogate endpoints. Anesthesiology
1994; 81:795-6.
• Fredman BD, Nathanson MH, Smith J, et al.
Sevoflurane for outpatient anesthesia: a
comparison with propofol. Anesth Analg 1995;
81:823-8.
• Ghouri AF, Bodner M, White PF. Recovery
profile after desflurane-nitrous oxide versus
isoflurane-nitrous oxide in outpatients.
Anesthesiology 1991; 74:419-24.
• Ding Y, Fredman B, White PF. Recovery
following outpatient anesthesia: use of enflurane

Philip BK,Scuderi PE,Chung F,Conahan TJ, Maurer
W.Angel JJ, Kallar SK, Skinner EP,Jamerson BD,
Remifentanil Compared with Alfentanil for Ambulatory
Surgery Using Total Intravenous Anesthesia
The purpose of this study was to test the hypothesis that using
a 1:4 ratio of remifentanil to alfentanil, a remifentanil
infusion would provide better suppression of intraoperative
responses and comparable recovery profiles after
ambulatory laparoscopic surgery than an alfentanil infusion,
as part of total intravenous anesthesia. Two hundred ASA
physical status I, II, or III adult patients participated in this
multicenter, double-blind, parallel group study. Patients
were randomly assigned 2:1 to either the remifentanilpropofol or alfentanil-propofol regimens. The anesthesia
sequence was propofol (2 mg/kg intravenously [IV]
followed by 150 mg × kg-1 × min-1), and either

Drugs ratio in Philip et al …
• Induction: bolus dose of propofol 2 mg/kg
followed by a continuous infusion of 150 microg
× kg-1 × min-1.
• Opioid.:bolus syringe (either remifentanil 1
microg/kg or alfentanil 20 microg/kg)
• followed by maintenance Syringe 1 (either
remifentanil 0.5 microg × kg-1 × min-1 or
alfentanil 2 microg × kg-1 × min-1).
• Loss of consciousness was assessed with lack of
response to verbal command.
• Musclerrelax:vecuronium (up to 0.1 mg/kg) to

Philip et al.Remifentanil Compared with Alfentanil for
Ambulatory Surgery Using Total Intravenous Anesthesia

Lang,E, Kapila A,Shlugman D,Hoke JF,Sebel PS,Glass
Reduction of Isoflurane Minimal Alveolar
Concentration by Remifentanil Anesthesiology
85:721-8, 1996

• Methods: Two centers enrolled a total of 220
patients. Patients were randomized to receive a
target concentration of remifentanil via a computerassisted continuous infusion device of either 0.0,
0.5, 1.0, 1.5, 2.0, 4.0, 8.0, 16.0, and 32.0 ng/ml
initiated before the administration of isoflurane.
Patients were also stratified by age groups 18—30,
31—55, and 56—65 yr. After induction of
anesthesia with isoflurane the initial patient in each
dose group was assigned an age-adjusted isoflurane

• There was an initial steep decrease in
isoflurane MAC (up to 70%) at relatively
low remifentanil concentrations (2—4
ng/ml), and this was followed by a much
flatter reduction in the MAC of isoflurane
with 32 ng/ml, resulting in only a 90%
isoflurane MAC reduction. A remifentanil
whole blood concentration of 1.37 ng/ml
resulted in a 50% reduction in the MAC of
isoflurane.

• Conclusion: The MAC reduction of
isoflurane by remifentanil is similar to that
produced by other opioids. Although
remifentanil was given at extremely high
concentrations in the absence of isoflurane,
it did not provide adequate anesthesia. A
50% isoflurane MAC reduction is produced
by 1.37 ng/ml remifentanil whole blood
concentration compared to previously
published plasma concentrations of fentanyl

Remif in day surg napoli 2001

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