A Review of the Pharmacokinetics and Pharmacodynamics of Remifentanil

P Pu ur rp po os se e: : Controlling the cerebral and systemic hemodynamic responses to laryngoscopy and tracheal intubation may play a role in determining clinical outcome in pediatric neurosurgical patients. This study compared the effects of remifentanil and fentanyl on cerebral blood flow velocity (CBFV) and hemodynamic profile during laryngoscopy and tracheal intubation in children under sevoflurane anesthesia.M Me et th ho od ds s: : Sixty healthy children aged two to six years undergoing dental surgery under general anesthesia were enrolled. Each child was randomly assigned to receive a remifentanil or fentanyl infusion, at a rate of 0.75, 1.0, or 1.5 µg·kg -1 ·min -1 after induction of anesthesia with 2% sevoflurane. Middle cerebral artery blood flow velocity was measured by transcranial Doppler (TCD) sonography. Once a baseline set of hemodynamic variables and TCD measurements were recorded, the opioid infusion was started. Measurements were taken at two-minute intervals, starting four minutes prior to laryngoscopy until four minutes following naso-tracheal intubation.R Re es su ul lt ts s: : Remifentanil caused a more significant decrease in mean arterial pressure and CBFV prior to tracheal intubation than did fentanyl (P < 0.001). During laryngoscopy and for two minutes following tracheal intubation, CBFV increased in all remifentanil groups (P < 0.05), whereas it remained stable in all fentanyl groups. C Co on nc cl lu us si io on n: : This study suggests that fentanyl was more effective than remifentanil at preventing increases in CBFV during and immediately following laryngoscopy and tracheal intubation in children undergoing sevoflurane anesthesia. Fentanyl also seemed to provide a more stable hemodynamic profile prior to laryngoscopy and tracheal intubation when compared to remifentanil. ARYNGOSCOPY and tracheal intubation may cause significant cerebral and systemic hemodynamic responses, including tachycardia, hypertension and increased intracranial pressure. [1][2][3] Controlling these responses on induction of anesthesia may be an important factor in improving outcome in pediatric neurosurgical patients. Remifentanil is a µ-opioid receptor agonist, rapidly metabolized by nonspecific esterases throughout the blood and tissues. The elimination half-life of remifentanil is less than ten minutes, compared to 219 min for fentanyl. 4-6 It does not accumulate after prolonged continuous infusion and the blood brain equilibration time is rapid. 5,7 Its use is characterized by rapid and complete offset of opioid effects within minutes of infusion discontinuation. 4 These distinctive pharmacokinetic and pharmacodynamic characteristics make remifentanil a potentially attractive opioid for use in pediatric anesthesia. Comparative data assessing cerebral blood flow velocity (CBFV) on induction and tracheal intubation with remifentanil and fentanyl has not been documented in the pediatric population. ObjectifThe aim of this study was to compare the effects of remifentanil and fentanyl on CBFV and hemodynamic...

Section: Objectifmentioning

confidence: 88%

Fentanyl is more effective than remifentanil at preventing increases in cerebral blood flow velocity during intubation in children

Abdallah

Karsli

Bissonnette

2002

“…A constant-rate infusion of remifentanil achieves steady plasma levels in about ten minutes 18 and the half-time for equilibration between plasma and its effect compartment is about 1-1.5 min. 2 Therefore a stable level of sedation and analgesia is achieved in a few minutes following any infusion rate adjustment; on this basis, in this study we chose to perform the measures 25 min following each infusion rate adjustment. A further advantage of remifentanil is represented by its constant and short context-sensitive plasma half-time, which allows a prompt recovery after stopping the infusion to evaluate the neurological state of the patient.…”

Section: Discussionmentioning

confidence: 99%

“…Pressure support level was adjusted to obtain a tidal volume (TV) between 8 and 10 mL·kg -1 of ideal body weight and a respiratory rate lower than 30 breaths·min -1 ; positive end-expiratory pressure and FIO 2 were adjusted in order to obtain PaO 2 values higher than 90 mmHg. No patient was under the effect of opioids, benzodiazepines, propofol, or other medications that could reasonably affect the study.…”

Section: Me Et Th Ho Od Ds S Patientsmentioning

confidence: 99%

“…NALGESIA and sedation with opioids are used widely to obtain quietness and cooperation from critically ill patients as most diagnostic and therapeutic procedures performed in intensive care units (ICUs) are painful or cause psychologic distress. In this context remifentanil, a µ-agonist opioid characterized by a short blood-brain equilibration time and a rapid metabolism by non specific esterases, could be particularly useful because adjustments of the infusion rate quickly achieve correspondent and stable new plasma levels and because the short and constant context-sensitive plasma half-time allows the patient fast arousability [1][2][3] Only few authors have investigated the safety and feasibility of remifentanil infusion for sedation in ICUs. [4][5][6] A high incidence of undesirable effects, like respiratory depression, nausea and emesis, has been pointed out by a multicenter study focused on postoperative analgesia with remifentanil.…”

mentioning

confidence: 99%

See 1 more Smart Citation

A low-dose remifentanil infusion is well tolerated for sedation in mechanically ventilated, critically-ill patients

Cavaliere

Antonelli

Arcangeli

et al. 2002

P Pu ur rp po os se e: : To study the analgesic and sedative effects of remifentanil in critically-ill patients.M Me et th ho od ds s: : Remifentanil infusion was started at 0.02 µg·kg -1 ·min -1 in ten mechanically ventilated critically-ill patients, and the infusion rate was increased to 0.05, 0.10, 0.15, 0.20, and 0.25 µg·kg -1 ·min -1 every 30 min. Basally and 25 min after each increase we measured: the Ramsey sedation score (RSS) and the respiratory response subscore of comfort scale (CSRR); the bispectral index (BIS) before and after lightly touching tracheal mucosa; heart rate and systemic arterial pressure; respiratory variables; plasma epinephrine and norepinephrine levels.R Re es su ul lt ts s: : Infusion rates up to 0.05 µg·kg -1 ·min -1 were effective against agitation and achieved a good degree of adaption to the respirator in all patients (RSS 2 or more and CSRR 3 or less); BIS decreased significantly; respiratory and circulatory variables were unaffected; mean plasma epinephrine levels decreased. At infusion rates higher than 0.05 µg·kg -1 ·min -1 RSS but not BIS decreased further and patient arousability caused by noxious stimuli was not prevented; respiratory drive suppression occurred at the infusion rates higher than 0.05 µg·kg -1 ·min -1 in four patients; bradycardia and arterial hypotension was observed in three patients; plasma epinephrine levels decreased significantly, while norepinephrine was unaffected; severe itching was experienced by one patient.C Co on nc cl lu us si io on ns s: : Low doses of remifentanil (up to 0.05 µg·kg -1 ·min -1 ) can be useful in critically-ill patients in order to achieve calm and sedation. Higher doses can inhibit respiratory drive and require controlled mechanical ventilation. Objectif

“…13 This decrease was due to use of a carefully standardized anesthetic induction sequence and consideration of the unique pharmacokinetic and pharmacodynamic attributes of propofol and remifentanil such that LMA insertion occurred at the time when effect-site concentration peaked for both agents. 17,18 In fact, insertion of the LMA constitutes a less noxious stimulus compared with laryngoscopy. Billard et al observed a significant increase in systolic blood pressure ([ 40%) during laryngoscopy and tracheal intubation after induction of anesthesia with propofol 2.5 mgÁkg -1 given alone, 19 whereas Hickey et al 20 reported minor cardiovascular response to insertion of LMA after the same dose of propofol.…”

Section: Discussionmentioning

confidence: 99%

Dose optimale de rémifentanil pour l’insertion d’un masque laryngé lors de la co-administration d’une dose standard unique de propofol

Bouvet

Da-Col

Rimmelé

et al. 2010

Purpose This dose-response study aimed to determine the optimal dose of remifentanil combined with propofol 2.5 mgÁkg -1 iv in order to achieve excellent conditions for laryngeal mask airway (LMA TM ) insertion in 95% of adult female patients. Methods Sixty-eight adult premedicated female patients, American Society of Anesthesiologists (ASA) physical status I and II requiring anesthesia for ambulatory surgery, were randomly allocated to one of four remifentanil dose groups (0.25, 0.5, 1, or 2 lgÁkg -1 ). Induction of anesthesia was achieved with one of the four blinded doses of remifentanil infused over 60 sec and simultaneously co-administered with propofol 2.5 mgÁkg -1 iv infused over 45 sec. Insertion of the LMA was attempted 150 sec after the beginning of the induction sequence. Insertion conditions were assessed using a six-category score according to resistance to mouth opening and insertion, swallowing, coughing and gagging, movement, and laryngospasm. A probit analysis was performed to calculate the effective dose for insertion of the LMA in 95% of patients (efficient dose [ED] 95 ). The changes in heart rate (HR) and mean arterial blood pressure (MAP) in response to LMA insertion were recorded and compared as secondary outcome variables. Results The ED 95 of remifentanil was 1.32 (95% confidence interval [CI] 0.99-2.46) lgÁkg -1 . Changes in heart rate and mean arterial pressure were modest and similar over time across groups, with maximum decreases in heart rate and mean arterial pressure \ 30% each during induction of anesthesia. Conclusions The required dose of remifentanil is 1.32 (95% CI 0.99-2.46) lgÁkg -1 to achieve excellent LMA insertion conditions in 95% of patients when co-administered with propofol 2.5 mgÁkg -1 in healthy premedicated female patients undergoing elective ambulatory surgery. RésuméObjectif L'objectif de cette e´tude de dose-re´ponse e´tait de de´terminer la dose optimale de re´mifentanil lors de l'administration conjointe de propofol 2,5 mgÁkg -1 iv afin d'obtenir des conditions excellentes pour l'insertion d'un masque larynge´(LMAÒ) chez 95 % de patientes adultes. Méthode Soixante-huit patientes adultes ASA I et II pre´me´dique´es et ne´cessitant une anesthe´sie pour une chirurgie ambulatoire ont e´te´randomise´es en quatre groupes selon la dose de re´mifentanil (0,25, 0,5, 1 ou 2 lgÁkg -1 ). L'induction de l'anesthe´sie a e´te´re´alise´e avec l'une des quatre doses de re´mifentanil en aveugle perfuse´e sur 60 secondes, administre´e simultane´ment a`du propofol 2,5 mgÁkg -1 iv perfuse´sur 45 secondes. L'insertion du Support was provided solely by institutional sources.