Remif in day surg napoli 2001

Remifentanil in daysurgery

Remifentanil in daysurgeryClaudio MelloniClaudio Melloni

Servizio di Anestesia e RianimazioneServizio di Anestesia e Rianimazione

Ospedale Civile di Faenza(RA)Ospedale Civile di Faenza(RA)

Che cosa rende il remifentanilattraente in day surgery?

Che cosa rende il remifentanilattraente in day surgery?

Brevi emitempicontesto-sensitiviBrevi emitempi

contesto-sensitiviconfrontare!confrontare!

riprese indipendenti dadosaggio e durata

riprese indipendenti dadosaggio e durata

metabolismo organoindipendente.metabolismo organoindipendente.

duttilitàduttilità dalla sedazione leggera allaanalgesia profondadalla sedazione leggera allaanalgesia profonda

rapida dimissione........rapida dimissione........

Context sensitive half time of opioids(influence of P450

3A4 on alfentanil)

fentanil

Tempi di ripresa(da Bekke et al)

0123

45678

910

min

remi fent

fine infu-occhi apertifine infus-estubazfine infus-orientam

Song et al.Remifentanil infusion facilitates early recovery for obese outpatients undergoing laparoscopic

cholecystectomy.AA 2000,90:1111-3.

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awake extub orient

sevoremif

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

Anesth Analg 1997; 84:515

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iot resp trocarresp

skin closresp

lightanesth

suppldoses

remifalfent

* *

*

*

Conclusions from Philip_

• Remif more protective and times of recovery similar between the two drugs…..

• Analgesics requested earlier following remif…..

Tempi di ripresa rapidiTempi di ripresa rapidilivellilivelli

PrimoPrimo

apertura occhiapertura occhi

ripresa respirazione spont.ripresa respirazione spont.

estubazioneorientamentoestubazioneorientamento

SecondoSecondoindici di ripresa intellettivi superioriindici 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. Requirements for postoperative analgesics were similar in the two groups. More patients in the remi group were treated with antiemetics (21 vs 7, P = 0.06). Use of remifentanil-N2O for maintenance did not shorten the overall length of stay in the postanesthesia care unit; a stay is often related to multiple administrative issues, rather than cognitive recovery.

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

Isofl/fent

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.

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

remi

alf

remi

alf

E' necessariosomministrare il

remifentanil in una tecnicacompletamente ev o si può

associare ad inalatori?

E' necessariosomministrare il

remifentanil in una tecnicacompletamente ev o si può

associare ad inalatori?Perbacco se si può!Perbacco se si può!

Interaction between remifentanil and isofluraneIsoflurane concentration reduction by increasing remifentanil whole blood

concentrationAnesthesiology85:721-8, 1996

Song et al.Remifentanil infusion facilitates early recovery for obese outpatients undergoing

laparoscopic cholecystectomy.AA 2000,90:1111-3.

0

2

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8

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1416

18

sevo% opioidintraop

awake extub orient

sevoremif

*

**

*

mg

min

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 edimissione

dimissibilità edimissione

la rapidità di ripresa dopo remifentanil sitraduce poi in una dimissione più precoce

rispetto ad altri farmaci comparatori?

la rapidità di ripresa dopo remifentanil sitraduce 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 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 syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 mg×kg-1×min-1) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children. Implications: This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children.

•

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, midazolam was administered orally (0.5–0.75 mg/kg), with a maximum dose of 15 mg.

• All patients underwent induction of anesthesia with either halothane or sevoflurane, with nitrous oxide and oxygen. After an IV catheter was inserted, atracurium 0.3 to 0.5 mg/kg was administered to facilitate tracheal intubation and prevent chest wall rigidity. Supplemental atracurium was administered as indicated by monitoring the patient's train-of-four ratio. Throughout the operative procedure, ETCO2 was monitored and maintained at 35–45 mm Hg. Before surgical manipulation, ondansetron (100 mg/kg, maximal dose of 4 mg) and dexamethasone (0.25–0.5 mg/kg, maximal dose 8 mg) were administered IV to prevent postoperative nausea and vomiting, and 50 mg/kg of morphine was administered to reduce postoperative pain and discomfort.


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) (sevoflurane 0.8% or halothane 0.3%). Thus, four treatment groups were possible. Syringes of both remifentanil and fentanyl were prepared by the hospital pharmacist. The concentrations of both opioids were 20 mg/mL. Consequently, equal volumes of drug would be administered to the patient for both continuous infusions and bolus injections. The opioid doses were based on clinical practice.

• In all groups, signs of inadequate anesthesia (increases in arterial blood pressure or heart rate more than 20% from baseline or responses such as movement, tearing, or sweating) were treated with an additional bolus dose (1 mg/kg) and an increase in the infusion rate by 50%.

Subjects in the remi/hal group had significantly shorter times to 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.

The distribution of times from the end of the anesthetic 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).


Objective pain discomfort scores were statistically different between the remifentanil and fentanyl groups at arrival in PACU and at 5, 10, 15, and 20 min

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.



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.



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 remi/hal (33%) groups (P = 0.164), this did not reach statistical significance. Most of the inadequate anesthesia responses were hypertension and/or tachycardia. A higher percentage of subjects in the fentanyl groups (45%) were treated for hypertensive responses than subjects in the remifentanil groups (26%). A higher percentage of subjects in the remifentanil groups (15%) were treated for tachycardic responses than subjects in the fentanyl groups (9%). Few subjects were treated for somatic responses (movement, swallowing, grimacing, or eye opening) (1 subject [<1%] in the remifentanil groups and 2 subjects [2%] in the fentanyl groups).



Analg 2000; 90:863–71.

Discharge of the patient vs homereadiness

Discharge of the patient vs homereadiness

ChungChung

patterns of home readinesspatterns of home readiness

persistent symptomspersistent symptoms

recurrence of painrecurrence of pain

PONVPONV

factors that delay dischargefactors that delay discharge

unavailability of escortsunavailability of escorts

Laparscopy,general surg,orthopedic surg

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 study group. However, the incidence of intraoperative adverse events and other postoperative sequelae, recovery times, pain and nausea visual analog scale scores, opioid analgesic dosage requirements in the postanesthetic care unit, and satisfaction survey responses were similar between groups. Perioperative drug costs per patient were $17.72 more in the remifentanil (vs fen-tanyl) group.

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

Il remifentanil è duttile?Il remifentanil è duttile?da sedazione cosciente a analgesia profonda.....da sedazione cosciente a analgesia profonda.....

mantenere il respiro spontaneomantenere il respiro spontaneo

da solo/ con altri farmaci....da solo/ con altri farmaci....

il problema della analgesia postoperatoriail problema della analgesia postoperatoria

che cosa,quando e come per mantenere unaprecoce dimissibilità?che cosa,quando e come per mantenere unaprecoce dimissibilità?

Interazione di remifentanil e sevoflurane 2%in resp spont per chir minore(LMA)(Madei et

al,Anesthesiology 1997;A7)

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risp som depr.resp devHR dev map

0,125+0,025 inf0,25+0,05 inf0,375+0,075inf0,5+0,1inf

Deduzioni pratiche del lavoro di Dershwitz: dosaggio del remifentanil

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

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 g/kg/min da solo o 0.05 g/kg/min con isoflurano 1.1%

• 0.05 g/kg/min+ propof 133 g/kg/min(=133*70*60=558 mg/ora) (Peacock)

• quindi

• 10-12 ml/ora “sicuri”(=200 microgr/hr)

Effetti respiratori del remifentanil

0,0

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min

pkhalftime

50% recovof min vent

elim h.l csht

remifentanilalfent

Da Scott& da Glass

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 remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (keo), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration—response curve (g).

• Results: The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l × min-1 × mmHg-1 [-0.12 to 0.66] 2 min after remifentanil (P < 0.001); within 5 min, it recovered to approximately 0.6 l × min-1 × mmHg-1, and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mmHg (E50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P < 0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of E50 included keo = 0.24 min-1 (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and g = 1.74.

• Conclusions: After administration of 0.5 mg/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.

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


manual opioid infusion schemesmanual opioid infusion schemesfrom many sources...from many sources...

drugdrug plasma targetconcentation(ngml)plasma targetconcentation(ngml)bolus(microgr/kg)bolus(microgr/kg)

infus ion rate(microgr/kg/mininfus ion rate(microgr/kg/min

fentanylfentanyl 11 33 0.0200.020

fentanylfentanyl 44 1010 0.0700.070

alfentanilalfentanil 4040 2020 0.250.25

alfentanilalfentanil 160160 8080 1.001.00

sufentanilsufentanil 0.150.15 0.150.15 0.0030.003

sufentanilsufentanil 0.500.50 0.500.50 0.0100.010

remifentanilremifentanil 66 11 0.020.02

remifentanilremifentanil 12-2012-20 1-21-2 0.4-1.00.4-1.0

Practical pharmacokinetics as applied to our daily anesthesia practice

Fiset, Pierre.Can J Anesth 1999 / 46 / R122-R126

Suggerimenti pratici finaliSuggerimenti pratici finaliinfusione continua con pompa siringainfusione continua con pompa siringa

sedazionesedazioneinizia a 0.02-0.03microgr/kg/min,cioè 50-150microgr/hr....

inizia a 0.02-0.03microgr/kg/min,cioè 50-150microgr/hr....

se ben tolleratose ben tolleratoincrementa del 25% ogni 2-3min,osservando continuamente ilRS(ETCO2,RR)

incrementa del 25% ogni 2-3min,osservando continuamente ilRS(ETCO2,RR)

per anestesiaper anestesiainizia a 0.1 microgr/kg/min,cioè400-500 microgr/hrinizia a 0.1 microgr/kg/min,cioè400-500 microgr/hr

PraticaPraticaboli più infusione continuaboli più infusione continua

sedazionesedazionebolo 0.1 microgr/kg+0.01-0.02 microgr/kg/minbolo 0.1 microgr/kg+0.01-0.02 microgr/kg/min

sedazione profondasedazione profondabolo 0.2 microgr/kg + 0.02microgr/kg/minbolo 0.2 microgr/kg + 0.02microgr/kg/min

anestesiaanestesiabolo 0.5 microgr/kg + 0.10microgr/kg/minbolo 0.5 microgr/kg + 0.10microgr/kg/min

sono dosaggi bassisono dosaggi bassi

Infusione rapidaInfusione rapidanon mai!non mai!

iniziare in simultanea conpropofol

iniziare in simultanea conpropofol

propofol 6mg/kg/hrpropofol 6mg/kg/hr

iniziare dopo midazolaminiziare dopo midazolammidazolam 2-3mgmidazolam 2-3mg

??????

Futuro del remifentanilFuturo del remifentanilmercatomercato

RemifRemif +10 1/2+10 1/2

CompetitoriCompetitori-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 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 remifentanil administration. Using published pharmacokinetic values for remifentanil and the method of collapsing hysteresis loops, the authors estimated the effect-site equilibration rate constant (keo), the effect-site concentration producing 50% respiratory depression (EC50), and the shape parameter of the concentration—response curve (g).

• Results: The slope of the carbon dioxide response decreased from 0.99 [95% confidence limits 0.72 to 1.26] to a nadir of 0.27 l × min-1 × mmHg-1 [-0.12 to 0.66] 2 min after remifentanil (P < 0.001); within 5 min, it recovered to approximately 0.6 l × min-1 × mmHg-1, and within 15 min of injection, slope returned to baseline. The computed ventilation at PET = 50 mmHg (E50) decreased from 12.9 [9.8 to 15.9] to 6.1 l/min [4.8 to 7.4] 2.5 min after remifentanil injection (P < 0.001). This was caused primarily by a decrease in tidal volume rather than in respiratory rate. Estimated pharmacodynamic parameters based on computed mean values of E50 included keo = 0.24 min-1 (T1/2 = 2.9 min), EC50 = 1.12 ng/ml, and g = 1.74.

• Conclusions: After administration of 0.5 mg/kg remifentanil, there was a decrease in slope and downward shift of the carbon dioxide ventilatory response curve. This reached its nadir approximately 2.5 min after injection, consistent with the computed onset half-time of 2.9 min. The onset of respiratory depression appears to be somewhat slower than previously reported for the onset of remifentanil-induced electroencephalographic slowing. Recovery of ventilatory drive after a small dose essentially was complete within 15 min.

Ripresa dopo remifentanil vs alfentanil in chir.ambulatoriale(Philip et al,Anesthesiology

1997;A35)

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min & %

dimissione nausea

rmifalfentanil

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 g/kg/min fino al trocar,poi 75 g/kg/min.

• remifentanil bolo 1 g/kg,poi 0.5 g/kg/min,poi 0.25 g/kg/min;stop alla fine chir.

• alfentanil 20 g/kg bolo,poi 2 g/kg/min poi 1 g/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 g/kg vs alfentanil 20 g/kg

• propof 2 mg/kg+ mivac 0.25 mg/kg

• mantenimento remi 0.5 g/kg/min vs alfentanil 2 g/kg/min + propof 150 g/kg/min,poi riduz al 50% dopo trocar

Fortier risultati:

• Remi• 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

• Alfentanil• pacu pain score 2

• fentanil in PACU 53%

• nausea :16%

• vomito predimissione:9%

• sedazione a 30 min:5



• deambulazione a 141 min

Davis PJ,Finkel JC,Orr RJ,Fazi L,Mulroy JJ,Woelfel 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 syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 mg×kg-1×min-1) was begun. In patients receiving fentanyl, a bolus (2 mg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children. Implications: This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children.

• 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>!

• unlike those of fentanyl and alfentanil, which demonstrate accumulation. (

• 17: Egan TD. Remifentanil pharmacokinetics and pharmacodynamics—a preliminary appraisal. Clinical Pharmacokinetics 1995; 29:80-94.

• 31: Kapila A, Glass PS, Jacobs JR, Muir KT, Hermann DJ, Shiraishi M, Howell S, Smith RL. Measured

context-sensitive half-times of remifentanil and alfentanil. Anesthesiology 1995; 83:968-975)

Peacock, J. E.; Luntley, J. B.; O'Connor, B.; Reilly, C. S.; 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. Respiratory depression after incision increased from 6% with remifentanil 0.025 mg kg-1 min-1 to 73% with 0.1 mg kg-1 min-1. Increases in propofol infusion rate to 7.2–8.4 mg kg-1 h-1 produced adequate maintenance of anaesthesia. Reductions in remifentanil doses to 0.025–0.05 mg kg-1 min-1 resulted in adequate respiration at the end of surgery in 88% of patients. Maintenance infusions of the two drugs for spontaneous ventilation are likely to be in these ranges. However, the ideal loading doses and infusion rates for induction remain to be established.

•

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 final mean propofol infusion rate was 7.2–8.4 mg kg-1 h-1. Respiratory depression after incision increased with higher doses of remifentanil and occurred in 73% of patients receiving remifentanil infusions of 0.1 mg kg-1 min-1. By the end of surgery, 76–100% of all patients had adequate respiration after reductions in remifentanil infusion rates to 0.026–0.053 mg kg-1 min-1 (

• Postoperative questioning revealed no evidence of intraoperative awareness in any patient. The overall incidence of postoperative nausea and vomiting was 7% and 1%, respectively, which was not dose dependent.



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 hypnosis is required in addition to potent doses of opioids to ensure that somatic responses are prevented during anaesthesia. The final propofol infusion rates of 7.2–8.4 mg kg-1 h-1 were higher at the lower remifentanil infusion rates but were lower than the ED95 of 21 mg kg-1 h-1 for propofol and nitrous oxide anaesthesia in patients premedicated with lorazepam.



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 remifentanil greater than 0.125 mg kg-1 min-1 (group 1) was associated with a high incidence of respiratory depression, while inadequate anaesthesia was found for surgical incision with an infusion of propofol 6 mg kg-1 h-1. Further studies are necessary to identify the appropriate combination of loading dose and initial infusion rates of the two drugs and to elucidate the efficacy of such a combination for clinical anaesthesia.

Davis, Peter J., MD*; Lerman, Jerrold, MD†; Suresh, Santhanam, MD‡; McGowan, Francis X., MD*; Coté, Charles J., MD‡; Landsman, Ira, MD*; Henson, Lynn

Graham, PharmD½½A 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 oxygen for maintenance of anesthesia. Induction of anesthesia was by nitrous oxide, oxygen, and halothane or nitrous oxide, oxygen, and propofol. Anesthesia was then maintained with remifentanil 1.0 mg/kg over 30–60 s, followed by a constant infusion of 1.0 mg×kg-1×min-1, alfentanil 100 mg/kg bolus followed by a constant infusion of 2.5 mg×kg-1×min-1, propofol 2.5 mg/kg bolus followed by a constant infusion of 200 mg×kg-1×min-1, or isoflurane 1.0 minimum alveolar anesthetic concentration. The infusions of the anesthetics and the administration of the inhaled gases were adjusted clinically by predetermined protocols. Elapsed time intervals from the end of surgery to the time the patients were tracheally extubated and displayed purposeful movement, as well as the time the patients met the postanesthesia care unit (PACU) and hospital discharge times, were recorded. Heart rate and systolic and diastolic blood pressure were measured at fixed intervals. In addition, cardiovascular side effects (bradycardia, hypotension, and hypertension) as well as vomiting, pruritus, agitation, and postoperative hypoxemia were also noted. There were no significant differences in patient demographics among the treatment groups. There was no difference in the early recovery variables (times to extubation and purposeful movement) or the times to PACU and hospital discharge among groups. There were significant differences in side effects among the groups. Patients who received remifentanil had higher PACU objective pain-discomfort scores than those who received alfentanil and propofol. Patients anesthetized with alfentanil had a greater incidence in the use of naloxone and a greater incidence of postoperative hypoxemia compared with those anesthetized with remifentanil. The incidence of postoperative hypoxemia was the same for remifentanil, propofol, and isoflurane groups. There were no significant differences in the incidence of emesis among the four groups, and all four groups had similar hemodynamic profiles. We conclude that remifentanil appears to be an effective drug for anesthesia. Its hemodynamic and recovery profile appear similar to other comparable drugs. Based on previous pharmacokinetic studies, the 1.0 mg×kg-1×min-1 infusion may be twice the 50% effective dose observed in adults. In this study, the relative “overdose” of remifentanil was well tolerated and did not prolong recovery.

• 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 anesthetic qualities. This multicenter, randomized study was undertaken to compare remifentanil with propofol, alfentanil, and isoflurane in a clinical setting commonly used for pediatric ambulatory surgical patients. We noted that the recovery variables after anesthesia with remifentanil were similar to those of the other anesthetics.

• 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 dose-response 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 surgical responses was 0.52 mg×kg-1×min-1 (95% confidence interval of 0.16–0.88). Our infusion rate was twice the ED50 observed in adults. We initially chose a dose of 1.0 mg×kg-1×min-1 because the pharmacokinetics of opioids in children usually differs from that in adults. Children typically have faster clearance rates and variable volumes of distribution. Thus, a large dose was administered to avoid inadequate anesthesia. Subsequent pharmacokinetic data of remifentanil in children (although preliminary) suggest that the drug's pharmacokinetic profile is, indeed, similar to that observed in adults . Thus, our continuous infusion rate may have been twice the necessary dose. However, even with these apparent relative “overdoses,” remifentanil did not prolong recovery or require naloxone administration.

•

• 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.

• Hospital discharge time is another variable used to assess a drug's duration of action. In both adult and pediatric studies evaluating potent inhaled anesthetics with low solubility, it has been shown that although patients may have faster recovery and shorter PACU times, they do not have earlier hospital discharge times . Why ambulatory patients become alert faster, yet are not discharged from the hospital sooner, is not known. Part of the explanation may be a matter of definition of the criteria for hospital discharge. In this study, intake and retention of oral fluids was a criterion for discharge from the ambulatory surgical unit. Schriner et al. have shown that this criterion unnecessarily prolongs hospital discharge after ambulatory pediatric surgery. We also noted that the need to take oral fluids prolonged discharge time. However, there was still no difference in discharge times among the groups, even when oral fluids were not a part of the hospital discharge criteria (). In adult studies, the times at which patients were “street-ready” were assessed by nurses according to their normal nursing routines, which may have introduced bias (i.e., patients may have been judged street-ready based on how long they had been in the ambulatory unit after surgery rather than by meeting preset discharge criteria). In our study, a blind nurse observer was with all patients from their emergence from anesthesia until their discharge from the hospital. Consequently, they were discharged from their respective units by the same nurse using preset criteria. Yet, even with this “ideal,” careful postoperative nursing evaluation, anesthetics did not appear to influence hospital discharge time.

• In addition to the anesthetics, hospital discharge times can be affected by such factors as pain, agitation, nausea, and vomiting. Although remifentanil is a potent opioid and propofol has been demonstrated to have antiemetic properties, the 24-hour incidence of postoperative vomiting was similar for all the anesthetics. The lack of difference in the incidence of emesis may have been a function of the type of surgery represented in this study, as well as the prophylactic use of ondansetron in all patients. Strabismus surgery is a stimulant for emesis, and ondansetron is an effective antiemetic . Consequently, these factors could have masked differences in the incidence of vomiting secondary to the anesthetics. Although there was no difference in emesis among the groups, nonetheless, 25%–30% of the patients experienced postoperative vomiting. Hospital discharge could have been delayed by the incidence of emesis and by efforts to treat it.

• Remifentanil was also associated with higher objective pain-discomfort scores in the postoperative period. Although patients were treated intraoperatively with rectal acetaminophen, pain relief may have been inadequate. The average duration of anesthesia was 40 minutes, but the mean time to peak analgesic effect after rectal acetaminophen administration has been reported to be 60–180 minutes, and the dose used in this study may have been subtherapeutic . The lower objective pain-discomfort scores in the alfentanil group may be due to alfentanil's longer half-life and residual analgesic effect. The higher incidence of postoperative opioid requirements for the remifentanil (25%), isoflurane (23%), and propofol (30%) groups compared with the alfentanil group (5%) supports the continued analgesic effect of alfentanil and also reinforces that remifentanil has minimum analgesic effects once the infusion is terminated. Since PACU and hospital discharge times are dependent on adequate patient pain control, the lack of postoperative analgesia may be a significant factor in delaying recovery and discharge, even when ultrashort-acting anesthetics are used.

• 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. Goldberg et al. noted in adult patients after an alfentanil-based anesthetic that arterial oxygen desaturation and respiratory drive depression often occurred in the first postoperative hour. These investigators noted that this respiratory depression occurred even when the majority of patients were easily aroused by verbal stimuli. Although the incidence of postoperative hypoxemia differs between the remifentanil- and alfentanil-anesthetized groups, the incidence was similar in the remifentanil, isoflurane, and propofol groups.

• The cardiovascular side effects of remifentanil appear similar to the effects of other opioids in children. However, some of these hemodynamic changes may have been attenuated by the prior administration of atropine. Of interest is the 12% (eight patients) incidence of bradycardia that occurred in the remifentanil-anesthetized patients. All eight episodes of bradycardia occurred at one center, and all were thought to be secondary to the oculocardiac reflex. Whether remifentanil potentiates the oculocardiac reflex or whether this reflex was due to other factors (e.g., surgical pressure on the globe or traction on the conjunctive or extraocular muscles) is unclear. However, the occurrence of bradycardia at only one center during surgical manipulation suggests that the bradycardia may be more a function of the surgical technique than the drug.

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†

Br. J. Anaesth. 1998; 80:752-755• There are few data in the literature that 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 receive a remifentanil loading dose of 1.0 mg kg-1 followed by a continuous infusion of 0.5 mg kg-1 min-1 in combination with isoflurane (end-tidal concentration 0.6%), (Group I, n = 115) or propofol (initial infusion rate 9 mg kg-1 h-1 reduced to 6 mg kg-1 h-1 after 10 min), (Group P, n = 118). The remifentanil infusion rate was reduced by 50%, 5 min after tracheal intubation. Intraoperative stresses were treated with a remifentanil bolus (1 mg kg-1) followed by an increase in the remifentanil infusion rate. At the insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3 min, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4–5 mm Hg).

Practical pharmacokinetics as 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. Each investigator enrolled 10 patients. A standardized protocol for administration of remifentanil was used. Data were analyzed to determine differences between the first three patients and the last three patients enrolled for each anesthesiologist in the study. There were no differences in hemodynamic variables between the first triad and the last triad in either outpatients or inpatients. Requirements for hypnotic drugs and the doses of remifentanil used were also similar between groups. Analgesic medications administered at the end of surgery and in the postanesthesia care unit (PACU) were similar between groups, except that the last triad in the outpatient group received smaller doses of fentanyl compared with the first triad. Times to response to verbal command, tracheal extubation, and operating room discharge did not differ between groups. However, patients in the last triad undergoing outpatient surgery had shorter times to eligibility for PACU discharge, but times to eligibility for discharge home did not differ. The overall incidence of all adverse events (i.e., hypotension, hypertension, muscle rigidity, respiratory depression, apnea, nausea, and vomiting) was less in the last triad as compared with the first triad. When analyzed separately, only the incidence of vomiting (in the outpatient group) was decreased in the last triad as compared with the first triad. This study suggests that there is a learning curve that aids reduction of minor adverse effects associated with the use of analgesic medications administered at the end of surgery in outpatients, which might have reduced the incidence of postoperative vomiting and the duration of PACU stay.

•

Peacock JE.; Luntley JB,O'Connor B, Reilly CS; Ogg TW; 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 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. Respiratory depression after incision increased from 6% with remifentanil 0.025 mg kg-1 min-1 to 73% with 0.1 mg kg-1 min-1. Increases in propofol infusion rate to 7.2–8.4 mg kg-1 h-1 produced adequate maintenance of anaesthesia. Reductions in remifentanil doses to 0.025–0.05 mg kg-1 min-1 resulted in adequate respiration at the end of surgery in 88% of patients. Maintenance infusions of the two drugs for spontaneous ventilation are likely to be in these ranges. However, the ideal loading doses and infusion rates for induction remain to be established.

•

• 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 final mean propofol infusion rate was 7.2–8.4 mg kg-1 h-1. Respiratory depression after incision increased with higher doses of remifentanil and occurred in 73% of patients receiving remifentanil infusions of 0.1 mg kg-1 min-1. By the end of surgery, 76–100% of all patients had adequate respiration after reductions in remifentanil infusion rates to 0.026–0.053 mg kg-1 min-1 (

• Postoperative questioning revealed no evidence of intraoperative awareness in any patient. The overall incidence of postoperative nausea and vomiting was 7% and 1%, respectively, which was not dose dependent.

• 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 hypnosis is required in addition to potent doses of opioids to ensure that somatic responses are prevented during anaesthesia. The final propofol infusion rates of 7.2–8.4 mg kg-1 h-1 were higher at the lower remifentanil infusion rates but were lower than the ED95 of 21 mg kg-1 h-1 for propofol and nitrous oxide anaesthesia in patients premedicated with lorazepam.

• 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 remifentanil greater than 0.125 mg kg-1 min-1 (group 1) was associated with a high incidence of respiratory depression, while inadequate anaesthesia was found for surgical incision with an infusion of propofol 6 mg kg-1 h-1. Further studies are necessary to identify the appropriate combination of loading dose and initial infusion rates of the two drugs and to elucidate the efficacy of such a combination for clinical anaesthesia.

Davis PJ,Lerma J,Suresh S,McGowan FX,Coté 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 oxygen for maintenance of anesthesia. Induction of anesthesia was by nitrous oxide, oxygen, and halothane or nitrous oxide, oxygen, and propofol. Anesthesia was then maintained with remifentanil 1.0 mg/kg over 30–60 s, followed by a constant infusion of 1.0 mg×kg-1×min-1, alfentanil 100 mg/kg bolus followed by a constant infusion of 2.5 mg×kg-1×min-1, propofol 2.5 mg/kg bolus followed by a constant infusion of 200 mg×kg-1×min-1, or isoflurane 1.0 minimum alveolar anesthetic concentration. The infusions of the anesthetics and the administration of the inhaled gases were adjusted clinically by predetermined protocols. Elapsed time intervals from the end of surgery to the time the patients were tracheally extubated and displayed purposeful movement, as well as the time the patients met the postanesthesia care unit (PACU) and hospital discharge times, were recorded. Heart rate and systolic and diastolic blood pressure were measured at fixed intervals. In addition, cardiovascular side effects (bradycardia, hypotension, and hypertension) as well as vomiting, pruritus, agitation, and postoperative hypoxemia were also noted. There were no significant differences in patient demographics among the treatment groups. There was no difference in the early recovery variables (times to extubation and purposeful movement) or the times to PACU and hospital discharge among groups. There were significant differences in side effects among the groups. Patients who received remifentanil had higher PACU objective pain-discomfort scores than those who received alfentanil and propofol. Patients anesthetized with alfentanil had a greater incidence in the use of naloxone and a greater incidence of postoperative hypoxemia compared with those anesthetized with remifentanil. The incidence of postoperative hypoxemia was the same for remifentanil, propofol, and isoflurane groups. There were no significant differences in the incidence of emesis among the four groups, and all four groups had similar hemodynamic profiles. We conclude that remifentanil appears to be an effective drug for anesthesia. Its hemodynamic and recovery profile appear similar to other comparable drugs. Based on previous pharmacokinetic studies, the 1.0 mg×kg-1×min-1 infusion may be twice the 50% effective dose observed in adults. In this study, the relative “overdose” of remifentanil was well tolerated and did not prolong recovery.

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 anesthetic qualities. This multicenter, randomized study was undertaken to compare remifentanil with propofol, alfentanil, and isoflurane in a clinical setting commonly used for pediatric ambulatory surgical patients. We noted that the recovery variables after anesthesia with remifentanil were similar to those of the other anesthetics.



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 dose-response 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 surgical responses was 0.52 mg×kg-1×min-1 (95% confidence interval of 0.16–0.88). Our infusion rate was twice the ED50 observed in adults. We initially chose a dose of 1.0 mg×kg-1×min-1 because the pharmacokinetics of opioids in children usually differs from that in adults. Children typically have faster clearance rates and variable volumes of distribution. Thus, a large dose was administered to avoid inadequate anesthesia. Subsequent pharmacokinetic data of remifentanil in children (although preliminary) suggest that the drug's pharmacokinetic profile is, indeed, similar to that observed in adults . Thus, our continuous infusion rate may have been twice the necessary dose. However, even with these apparent relative “overdoses,” remifentanil did not prolong recovery or require naloxone administration.

•



Anesth Analg 1997; 84:982–9• 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.

• Hospital discharge time is another variable used to assess a drug's duration of action. In both adult and pediatric studies evaluating potent inhaled anesthetics with low solubility, it has been shown that although patients may have faster recovery and shorter PACU times, they do not have earlier hospital discharge times . Why ambulatory patients become alert faster, yet are not discharged from the hospital sooner, is not known. Part of the explanation may be a matter of definition of the criteria for hospital discharge. In this study, intake and retention of oral fluids was a criterion for discharge from the ambulatory surgical unit. Schriner et al. have shown that this criterion unnecessarily prolongs hospital discharge after ambulatory pediatric surgery. We also noted that the need to take oral fluids prolonged discharge time. However, there was still no difference in discharge times among the groups, even when oral fluids were not a part of the hospital discharge criteria (). In adult studies, the times at which patients were “street-ready” were assessed by nurses according to their normal nursing routines, which may have introduced bias (i.e., patients may have been judged street-ready based on how long they had been in the ambulatory unit after surgery rather than by meeting preset discharge criteria). In our study, a blind nurse observer was with all patients from their emergence from anesthesia until their discharge from the hospital. Consequently, they were discharged from their respective units by the same nurse using preset criteria. Yet, even with this “ideal,” careful postoperative nursing evaluation, anesthetics did not appear to influence hospital discharge time.

• In addition to the anesthetics, hospital discharge times can be affected by such factors as pain, agitation, nausea, and vomiting. Although remifentanil is a potent opioid and propofol has been demonstrated to have antiemetic properties, the 24-hour incidence of postoperative vomiting was similar for all the anesthetics. The lack of difference in the incidence of emesis may have been a function of the type of surgery represented in this study, as well as the prophylactic use of ondansetron in all patients. Strabismus surgery is a stimulant for emesis, and ondansetron is an effective antiemetic . Consequently, these factors could have masked differences in the incidence of vomiting secondary to the anesthetics. Although there was no difference in emesis among the groups, nonetheless, 25%–30% of the patients experienced postoperative vomiting. Hospital discharge could have been delayed by the incidence of emesis and by efforts to treat it.

• Remifentanil was also associated with higher objective pain-discomfort scores in the postoperative period. Although patients were treated intraoperatively with rectal acetaminophen, pain relief may have been inadequate. The average duration of anesthesia was 40 minutes, but the mean time to peak analgesic effect after rectal acetaminophen administration has been reported to be 60–180 minutes, and the dose used in this study may have been subtherapeutic . The lower objective pain-discomfort scores in the alfentanil group may be due to alfentanil's longer half-life and residual analgesic effect. The higher incidence of postoperative opioid requirements for the remifentanil (25%), isoflurane (23%), and propofol (30%) groups compared with the alfentanil group (5%) supports the continued analgesic effect of alfentanil and also reinforces that remifentanil has minimum analgesic effects once the infusion is terminated. Since PACU and hospital discharge times are dependent on adequate patient pain control, the lack of postoperative analgesia may be a significant factor in delaying recovery and discharge, even when ultrashort-acting anesthetics are used.



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. Goldberg et al. noted in adult patients after an alfentanil-based anesthetic that arterial oxygen desaturation and respiratory drive depression often occurred in the first postoperative hour. These investigators noted that this respiratory depression occurred even when the majority of patients were easily aroused by verbal stimuli. Although the incidence of postoperative hypoxemia differs between the remifentanil- and alfentanil-anesthetized groups, the incidence was similar in the remifentanil, isoflurane, and propofol groups.

• The cardiovascular side effects of remifentanil appear similar to the effects of other opioids in children. However, some of these hemodynamic changes may have been attenuated by the prior administration of atropine. Of interest is the 12% (eight patients) incidence of bradycardia that occurred in the remifentanil-anesthetized patients. All eight episodes of bradycardia occurred at one center, and all were thought to be secondary to the oculocardiac reflex. Whether remifentanil potentiates the oculocardiac reflex or whether this reflex was due to other factors (e.g., surgical pressure on the globe or traction on the conjunctive or extraocular muscles) is unclear. However, the occurrence of bradycardia at only one center during surgical manipulation suggests that the bradycardia may be more a function of the surgical technique than the drug.

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† Br. J. Anaesth. 1998; 80:752-755• 251 male and female patients

• 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 insertion of the last suture, the remifentanil infusion and concomitant anaesthetic were switched off simultaneously. Times to spontaneous respiration, adequate respiration and tracheal extubation were significantly shorter in group I compared with group P (6.4 min vs 7.6 min, P < 0.01; 7.6 min vs 9.3 min, P < 0.003; 7.8 min vs 9.5 min, P < 0.015). Overall mean systolic blood pressures during surgery were greater in group P compared with group I (P < 0.05) but the absolute differences were clinically insignificant (4–5 mm Hg).

Rowbotham et al.Comparison of remifentanil in combination with isoflurane or propofol for

short-stay surgical procedures† Br. J. Anaesth. 1998; 80:752-755

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Rowbotham et al.Comparison of remifentanil in combination with isoflurane or propofol for short-

stay 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 medication.

• Anesthesia maintained with desflurane 2% +N2O 60%

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

Song et al.Remifentanil infusion facilitates early recovery for obese outpatients undergoing

laparoscopic cholecystectomy.AA 2000,90:1111-3.

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• 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 =

• 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. Postoperative nursing care was the single most important factor after general anesthesia; anesthetic drugs, anesthetic technique, and prevention of pain and emetic symptoms were of selective importance depending on patient gender and type of 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 final discharge times . One of the goals of this study was therefore to identify factors other than anesthetic drugs that influence the speed of recovery and that may account for baseline variability, possibly overwhelming any differences due to type of anesthesia. A second goal was to estimate the importance of these factors in determining discharge time relative to the effects of the anesthetic itself.

• The results of this study indicate that major factors determining discharge time when all types of anesthesia were considered are (in order of importance based on R2unique): the anesthetic technique (general versus local, peripheral nerve block, or spinal-epidural anesthesia), the nurse administering Phase 2 care, the type and duration of surgery, and the time of day that surgery was completed.

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 versus propofol. J Clin Anesth 1993; 5:447-50.

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; 84:515The 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 remifentanil-propofol or alfentanil-propofol regimens. The anesthesia sequence was propofol (2 mg/kg intravenously [IV] followed by 150 mg × kg-1 × min-1), and either remifentanil (1 mg/kg IV followed by 0.5 mg × kg-1 × min-1) or alfentanil (20 mg/kg IV followed by 2 mg × kg-1 × min-1), and vecuronium. After trocar insertion, infusion rates were decreased (propofol to 75 mg × kg-1 × min-1; remifentanil to 0.25 mg × kg-1 × min-1; alfentanil to 1 mg × kg-1 × min-1). Alfentanil and propofol were discontinued at 10 and 5 min, respectively, before the anticipated end of surgery (last surgical suture); remifentanil was discontinued at the end of surgery. Recovery times were calculated from the end of surgery. The median duration of surgery was similar between groups (39 min for remifentanil versus 34 min for alfentanil). A smaller proportion of remifentanil patients than alfentanil patients had any intraoperative responses (53% vs 71%, P = 0.029), had responses to trocar insertion (11% vs 32%, P < 0.001), or required dosage adjustments during maintenance (24% vs 41%, P < 0.05). Early awakening times were similar. Remifentanil patients qualified for Phase 1 discharge later and were given postoperative analgesics sooner than alfentanil patients (P < 0.05). Actual discharge times from the ambulatory center were similar between groups (174 min for remifentanil versus 204 min for alfentanil) (P = 0.06). In conclusion, remifentanil can be used for maintenance of anesthesia in a 1:4 ratio compared with alfentanil, for total IV anesthesia in ambulatory surgery. This dose of remifentanil provides more effective suppression of intraoperative responses and does not result in prolonged awakening.

•

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 facilitate endotracheal

intubation. • After intubation, patients' lungs were ventilated with oxygen or oxygen/air

mixtures. • Five minutes after skin incision/insufflation/trocar insertion (hereafter, called

trocar insertion, due to close proximity of events), infusion rates were decreased: remifentanil to 0.25 microg × kg-1 × min-1, alfentanil to 1 microg × kg-1 × min-1, and propofol to 75 microgr × kg-1 × min-1.

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

Anesth Analg 1997; 84:515

Lang,E, Kapila A,Shlugman D,Hoke JF,Sebel PS,Glass Reduction of Isoflurane Minimal Alveolar Concentration by Remifentanil

Anesthesiology85:721-8, 1996 • Methods: Two centers enrolled a total of 220 patients. Patients were randomized to receive

a target concentration of remifentanil via a computer-assisted 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 concentration. The isoflurane concentration for each subsequent patient was adjusted according to the up/down technique until a minimum of 12 patients were enrolled in each group. Arterial blood samples for remifentanil whole blood concentrations were obtained. The patient was observed for purposeful movement for up to 1 min after skin incision. The minimum alveolar concentration (MAC) of isoflurane (0 ng/ml remifentanil group) and MAC reduction of isoflurane by remifentanil were determined.

• Results: The MAC of isoflurane alone was 1.3%. Remifentanil caused an exponential reduction in the MAC of isoflurane with 1.37 ng/ml remifentanil resulting in a 50% MAC reduction, 4 ng/ml remifentanil a 77% reduction and 32 ng/ml a 91% reduction of isoflurane MAC.

• 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.

• At a remifentanil concentration of 1 ng/ml the MAC of isoflurane was reduced by 30—35%; at 2.0 ng/ml the MAC was reduced by just greater than 50%; and at 4 ng 65—70%. At concentrations greater than 4.0 ng/ml, there is limited further 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 of 1.67 ng/ml or sufentanil of 0.14 ng/ml.

Remif in day surg napoli 2001

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