Remifentanil in day
Remifentanil in day
surgery
surgery
Claudio Melloni
Servizio di Anestesia e Rianimazione
Ospedale Civi...
Che cosa rende il remifentanil
Che cosa rende il remifentanil
attraente in day surgery?
attraente in day surgery?
Brevi em...
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...
Song et al.Remifentanil infusion facilitates early recovery
for obese outpatients undergoing laparoscopic
cholecystectomy....
Philip et al.Remifentanil Compared with Alfentanil for
Ambulatory Surgery Using Total Intravenous Anesthesia
Anesth Analg ...
Conclusions from Philip_
• Remif more protective and times of
recovery similar between the two drugs…..
• Analgesics reque...
Tempi di ripresa rapidi
Tempi di ripresa rapidi
livelli

Primo

apertura occhi
ripresa respirazione spont.
estubazione
ori...
Bekke AY Turndorf H., Berklay P, Osborn I,Bloo M,
Yarmush J, The Recovery of Cognitive Function After
Remifentanil- Nitrou...
Bekke et al.. The Recovery of Cognitive Function After
Remifentanil- Nitrous Oxide Anesthesia Is Faster than
After an Isof...
Bekke et al The Recovery of Cognitive Function After Remifentanil- Nitrous Oxide Anesthesia Is Faste
than After an Isoflur...
Black ML. Hill JL, Zacny JP. Behavioral and
Physiological Effects of Remifentanil and Alfentanil in
Healthy Volunteers Ane...
Black et al Behavioral and Physiological Effects of
Remifentanil and Alfentanil in Healthy Volunteers
Anesthesiology 80:71...
alf

remi

remi

alf

Black et al Behavioral and Physiological Effects of Remifentanil and Alfentanil
in Healthy Volunteer...
E' necessario
E' necessario
somministrare il
somministrare il
remifentanil in una tecnica
remifentanil in una tecnica
comp...
Interaction between remifentanil and isofluraneIsoflurane
concentration reduction by increasing remifentanil whole blood
c...
Song et al.Remifentanil infusion facilitates early
recovery for obese outpatients undergoing
laparoscopic cholecystectomy....
Conclus from Song et al
• Variable rate infus of remif(0.09
microgr/kg/min) + sevo + N2O :
•
50% sevo %
• Contributed to a...
dimissibilità e
dimissione
la rapidità di ripresa dopo remifentanil si
traduce poi in una dimissione più precoce
rispetto ...
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,Decke...
Davis et al. Randomized, Double-Blinded Study of
Remifentanil Versus Fentanyl for Tonsillectomy and
Adenoidectomy Surgery ...
Davis et al. Randomized, Double-Blinded Study of
Remifentanil Versus Fentanyl for Tonsillectomy and
Adenoidectomy Surgery ...
extubation than subjects in the fent/hal group (P = 0.001). 12% of
the patients anesthetized with remifentanil (10% remi/h...
administration until the patients were eligible for discharge from the
PACU were statistically different among treatment g...
after arrival in PACU. Pairwise comparisons showed that OPDS scores were
statistically higher for remi/hal versus fent/hal...
Davis et al. Randomized, Double-Blinded Study of
Remifentanil Versus Fentanyl for Tonsillectomy and
Adenoidectomy Surgery ...
Davis et al. Randomized, Double-Blinded
Study of Remifentanil Versus Fentanyl for
Tonsillectomy and Adenoidectomy Surgery ...
Davis et al. Randomized, Double-Blinded
Study of Remifentanil Versus Fentanyl for
Tonsillectomy and Adenoidectomy Surgery ...
Davis et al. Randomized, Double-Blinded
Study of Remifentanil Versus Fentanyl for
Tonsillectomy and Adenoidectomy Surgery ...
Discharge of the patient vs home
readiness
Chung

patterns of home readiness

Laparscopy,general surg,orthopedic surg

per...
Pavlin DJ,Rapp SE, Polissar NL,Malmgren JA,
Koerschgen M,Keyes H.Factors Affecting
Discharge Time in Adult Outpatients Ane...
Beers R,Calimlim JR, Uddoh E,Esposito B, Camporesi
EM.A Comparison of the Cost-Effectiveness of
Remifentanil Versus Fentan...
Beers R,Calimlim JR, Uddoh E,Esposito B, Camporesi EM.A Comparison of the Cost-Effectiveness of Remifentanil
rsus Fentanyl...
Il remifentanil è duttile?
Il remifentanil
da sedazione cosciente a analgesia profonda.....
mantenere il respiro spontaneo...
Interazione di remifentanil e sevoflurane 2%in
resp spont per chir minore(LMA)(Madei et
al,Anesthesiology 1997;A7)
90
80
7...
Deduzioni pratiche del lavoro di
Dershwitz: dosaggio del remifentanil
•

a dosaggi > 0,3 µ g/kg/min=1260
µ g/ora/70 kg cio...
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...
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

p...
Babenco H, Conard PF, Gross J. The Pharmacodynamic
Effect of a Remifentanil Bolus on Ventilatory Control .
Anesthesiology ...
Curva di risposta ventilatoria alla CO2 dopo
remifentanil 0.5 microgr/kg

Babenco H, Conard PF, Gross J. The Pharmacodynam...
Ve at PetCO250 following remifentanil 0.5
microgr/kg

Babenco H, Conard PF, Gross J. The Pharmacodynamic Effect of a
Remif...
VT at PetCO250 following remifentanil 0.5
microgr/kg

Babenco H, Conard PF, Gross J. The Pharmacodynamic Effect of a
Remif...
Ve50 and effect site concentration of
remifentanil

Babenco H, Conard PF, Gross J. The Pharmacodynamic Effect of a
Remifen...
Ve50 vs time following remifentanil 0.5
microgr/kg

Babenco H, Conard PF, Gross J. The Pharmacodynamic Effect of a
Remifen...
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 n...
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
...
Pratica
Pratica
boli più infusione continua
sedazione

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

sedazione profonda

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

propofol 6
mg/kg/hr

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

• Chir.laparoscopica ...
Fortier et al.Remifentanil vs alfentanil for
ambulatory surgery using preoperative
naproxen for pain management.Anesthesio...
Fortier risultati:
• Remi

• Alfentanil

•
•
•
•
•
•
•
•

•
•
•
•
•
•
•
•

pacu pain score 3
fentanil in PACU 61%
nausea :...
SK,Hannallah RS,Lynn AM,Kurth CD,Moro M,
Henson LG,Goodman DK,Decker M.
A Randomized, Double-Blinded Study of
Remifentanil...
• The pharmacokinetics of remifentanil make
blood concentrations predictable.
Remifentanil blood concentrations obtained
b...
Ogg, T. W.; Watson, B. J.; Shaikh, S Remifentanil in
combination with propofol for spontaneous
ventilation anaesthesia
Sho...
Peacock, et al Remifentanil in combination
with propofol for spontaneous ventilation
anaesthesia
Short CommunicationBr. J....
Peacock, et al Remifentanil in combination
with propofol for spontaneous ventilation
anaesthesia
Short CommunicationBr. J....
Peacock, et al Remifentanil in combination
with propofol for spontaneous ventilation
anaesthesia
Short CommunicationBr. J....
Charles J., MD‡; Landsman, Ira, MD*; Henson, Lynn
Graham, PharmD½½
A Randomized Multicenter Study of Remifentanil
Compared...
• As the practice of outpatient surgery
advances, the search continues for
anesthetics that provide rapid smooth
induction...
• Part of the reason for not discerning
differences among treatment groups may
have been due to our study design. The dose...
• Of interest is the comparison of remifentanil with the other opioid used
in the study, alfentanil. Although recovery var...
• Alfentanil's pharmacokinetic profile may
also explain its higher incidence of
postoperative hypoxemia. Four of the 19
al...
Rowbotham, D. J.; Peacock, J. E.; Jones, R. M.;
Speedy, H. M.; Sneyd, J. R.; Morris, R. W.;
Nolan, J. P.; Jolliffe, D.; La...
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...
Watson BJ; Shaikh S.
Remifentanil in combination with propofol for
spontaneous ventilation anaesthesia
Short Communication...
• Patient characteristics and surgery
(primarily hernia repair and varicose vein
surgery) were similar in all groups altho...
• The same pattern of response was seen by
Hogue and colleagues in patients
undergoing ventilation; they used a
propofol i...
• Remifentanil can be administered as part of
a TIVA technique with propofol for
spontaneous ventilation anaesthesia. An
i...
CJ,Landsman I,Henso LG, A Randomized Multicenter
Study of Remifentanil Compared with Alfentanil,
Isoflurane, or Propofol i...
Davis et al-.Randomized Multicenter Study of
Remifentanil Compared with Alfentanil,
Isoflurane, or Propofol in Anesthetize...
Davis et al-.Randomized Multicenter Study of
Remifentanil Compared with Alfentanil,
Isoflurane, or Propofol in Anesthetize...
Davis et al-.Randomized Multicenter Study of
Remifentanil Compared with Alfentanil,
Isoflurane, or Propofol in Anesthetize...
Davis et al-.Randomized Multicenter Study of
Remifentanil Compared with Alfentanil,
Isoflurane, or Propofol in Anesthetize...
Rowbotham, D. J.; Peacock, J. E.; Jones, R. M.; Speedy, H.
M.; Sneyd, J. R.; Morris, R. W.; Nolan, J. P.; Jolliffe, D.;
La...
extub

min

60
40
20
0

RS

Rowbotham et al.Comparison of remifentanil in
combination with isoflurane or propofol for
shor...
Rowbotham et al.Comparison of remifentanil in
combination with isoflurane or propofol for shortstay surgical procedures†
B...
Song, D,Whitten CW,Whit PF Use of Remifentanil During
Anesthetic Induction: A Comparison With Fentanyl in the
Ambulatory S...
Song, et al.Use of Remifentanil During Anesthetic
Induction: A Comparison With Fentanyl in the
Ambulatory Setting..Anesth ...
Song, et al.Use of Remifentanil During Anesthetic
Induction: A Comparison With Fentanyl in the
Ambulatory Setting..Anesth ...
•
•
•
•
•
•
•

Song D,Whitten CW,White,PF.Remifentanil
infusion facilitates early recovery for obese
outpatients undergoin...
Song et al.Remifentanil infusion facilitates early
recovery for obese outpatients undergoing
laparoscopic cholecystectomy....
Conclus from Song et al
• Variable rate infus of remif(0.09
microgr/kg/min) + sevo + N2O :
•
50% sevo %
• Contributed to a...
• In praevious laparoscopic cholecistect
studies it has been demonstrated that the
use of sevo as a maintenence drug had a...
Pavlin DJ,Rapp SE, Polissar NL,Malmgren JA,
Koerschgen M,Keyes H.Factors Affecting Discharge
Time in Adult Outpatients Ane...
Pavlin et al..Factors Affecting Discharge Time in Adult
Outpatients Anesth Analg 1998; 87:816–26
• After general anesthesi...
• Animal studies and controlled studies in human
volunteers suggest that there are differences in the
speed of recovery fr...
Intermediate end points vs final
home discharge
• Fisher DM. Surrogate endpoints. Anesthesiology
1994; 81:795-6.
• Fredman...
Philip BK,Scuderi PE,Chung F,Conahan TJ, Maurer
W.Angel JJ, Kallar SK, Skinner EP,Jamerson BD,
Remifentanil Compared with ...
Drugs ratio in Philip et al …
• Induction: bolus dose of propofol 2 mg/kg
followed by a continuous infusion of 150 microg
...
Philip et al.Remifentanil Compared with Alfentanil for
Ambulatory Surgery Using Total Intravenous Anesthesia
Anesth Analg ...
Lang,E, Kapila A,Shlugman D,Hoke JF,Sebel PS,Glass
Reduction of Isoflurane Minimal Alveolar
Concentration by Remifentanil ...
• There was an initial steep decrease in
isoflurane MAC (up to 70%) at relatively
low remifentanil concentrations (2—4
ng/...
• Conclusion: The MAC reduction of
isoflurane by remifentanil is similar to that
produced by other opioids. Although
remif...
Remif in day surg napoli 2001
Remif in day surg napoli 2001
Remif in day surg napoli 2001
Remif in day surg napoli 2001
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Remif in day surg napoli 2001

  1. 1. Remifentanil in day Remifentanil in day surgery surgery Claudio Melloni Servizio di Anestesia e Rianimazione Ospedale Civile di Faenza(RA)
  2. 2. 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........
  3. 3. Context sensitive half time of opioids(influence of P450 ) 3A4 on alfentanil fentanil
  4. 4. 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
  5. 5. 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
  6. 6. 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
  7. 7. Conclusions from Philip_ • Remif more protective and times of recovery similar between the two drugs….. • Analgesics requested earlier following remif…..
  8. 8. Tempi di ripresa rapidi Tempi di ripresa rapidi livelli Primo apertura occhi ripresa respirazione spont. estubazione orientamento Secondo indici di ripresa intellettivi superiori
  9. 9. 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).
  10. 10. 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.
  11. 11. 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
  12. 12. 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.
  13. 13. 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.
  14. 14. alf remi remi alf Black et al Behavioral and Physiological Effects of Remifentanil and Alfentanil in Healthy Volunteers Anesthesiology 80:718-26, 1999
  15. 15. 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!
  16. 16. Interaction between remifentanil and isofluraneIsoflurane concentration reduction by increasing remifentanil whole blood concentration Anesthesiology 85:721-8, 1996
  17. 17. 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
  18. 18. 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 =
  19. 19. dimissibilità e dimissione la rapidità di ripresa dopo remifentanil si traduce poi in una dimissione più precoce rispetto ad altri farmaci comparatori?
  20. 20. 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
  21. 21. 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,
  22. 22. 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. • 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)
  23. 23. 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.
  24. 24. 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). 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.
  25. 25. 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.
  26. 26. 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.
  27. 27. 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.
  28. 28. 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
  29. 29. 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.
  30. 30. 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
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. 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?
  35. 35. 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
  36. 36. 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
  37. 37. ED 50 • 0.052 microgr/kg/min=218 microgr /hr per un adulto di 70 kg
  38. 38. 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
  39. 39. 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
  40. 40. 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
  41. 41. 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
  42. 42. Ve at PetCO250 following 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
  43. 43. VT at PetCO250 following 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
  44. 44. Ve50 and effect site concentration of remifentanil Babenco H, Conard PF, Gross J. The Pharmacodynamic Effect of a Remifentanil Bolus on Ventilatory Control . Anesthesiology 92:393-8, 2000
  45. 45. Ve50 vs time following 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
  46. 46. 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
  47. 47. Practical pharmacokinetics as applied to our daily anesthesia practice Fiset, Pierre.Can J Anesth 1999 / 46 / R122-R126
  48. 48. 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
  49. 49. 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
  50. 50. Infusione rapida Infusione rapida non mai! iniziare in simultanea con propofol propofol 6 mg/kg/hr iniziare dopo midazolam midazolam 2-3 mg ???
  51. 51. Futuro del remifentanil Futuro mercato Remif Competitori +10 1/2 -2
  52. 52. 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
  53. 53. 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
  54. 54. 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
  55. 55. 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
  56. 56. 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 sedazione a 60 min:3 sedazione a 90 min:2 deambulazione a 141 min
  57. 57. SK,Hannallah RS,Lynn AM,Kurth CD,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. 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
  58. 58. • 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>!
  59. 59. 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.
  60. 60. Peacock, et al Remifentanil in combination with propofol for spontaneous ventilation anaesthesia Short CommunicationBr. J. Anaesth. 1998; 80 • 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 compared with 30–40% in the other groups. The majority of patients required additional propofol to maintain anaesthesia and the
  61. 61. Peacock, et al Remifentanil in combination with propofol for spontaneous ventilation anaesthesia Short CommunicationBr. J. Anaesth. 1998; 80 • 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
  62. 62. Peacock, et al Remifentanil in combination with propofol for spontaneous ventilation anaesthesia Short CommunicationBr. J. Anaesth. 1998; 80 • 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
  63. 63. 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
  64. 64. • 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
  65. 65. • 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
  66. 66. • 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.
  67. 67. • 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.
  68. 68. 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
  69. 69. applied to our daily anesthesia practice AUTHOR(S): Fiset, Pierre, MD -
  70. 70. 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.
  71. 71. Watson BJ; Shaikh S. Remifentanil in combination with propofol for spontaneous ventilation anaesthesia Short CommunicationBr. J. Anaesth. 1998; 80 • 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
  72. 72. • 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 compared with 30–40% in the other groups. The majority of patients required additional propofol to maintain anaesthesia and the
  73. 73. • 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
  74. 74. • 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
  75. 75. 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
  76. 76. 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
  77. 77. 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 • 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
  78. 78. Davis et al-.Randomized Multicenter Study of Remifentanil Compared with Alfentanil, Isoflurane, or Propofol in Anesthetized Pediatric Patients Undergoing Elective Strabismus Surgery • 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.
  79. 79. 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 • 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.
  80. 80. 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
  81. 81. 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
  82. 82. Rowbotham et al.Comparison of remifentanil in combination with isoflurane or propofol for shortstay surgical procedures† Br. J. Anaesth. 1998; 80:752-755
  83. 83. 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
  84. 84. Song, et al.Use of Remifentanil During Anesthetic Induction: A Comparison With Fentanyl in the Ambulatory Setting..Anesth Analg 1999; 88:734
  85. 85. Song, et al.Use of Remifentanil During Anesthetic Induction: A Comparison With Fentanyl in the Ambulatory Setting..Anesth Analg 1999; 88:734
  86. 86. • • • • • • • 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
  87. 87. 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
  88. 88. 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 =
  89. 89. • 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)
  90. 90. 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.
  91. 91. 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.
  92. 92. • 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
  93. 93. 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
  94. 94. 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 Anesth Analg 1997; 84:515 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
  95. 95. 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
  96. 96. Philip et al.Remifentanil Compared with Alfentanil for Ambulatory Surgery Using Total Intravenous Anesthesia Anesth Analg 1997; 84:515
  97. 97. 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
  98. 98. • 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.
  99. 99. • 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
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