Disease relevance of SUFENTANIL

• The group that received deep anesthesia had a decreased incidence of sepsis (P = 0.03), metabolic acidosis (P less than 0.01), and disseminated intravascular coagulation (P = 0.03) and fewer postoperative deaths (none of 30 given sufentanil vs. 4 of 15 given halothane plus morphine, (P less than 0.01) [1].
• The incidence of intraoperative ischemia was similar in patients who received isoflurane or sufentanil anesthesia (20 [32%] of 62 patients vs. 37 [30%] of 124 patients, p = 0.87) [2].
• Midazolam causes more nasal irritation during instillation, and sufentanil causes more postoperative nausea and vomiting [3].
• Antagonistic effects of naloxone and naloxonazine on sufentanil-induced antinociception and respiratory depression in rats [4].
• These results suggest that preinjury i.v. sufentanil is not more beneficial for postoperative pain control than the postinjury administration [5].

Psychiatry related information on SUFENTANIL

• Morphine 4 mg.kg-1.h-1, alfentanil 0.45 mg.kg-1.h-1, and sufentanil 0.0085 mg.kg-1.h-1 caused approximately similar increases in the pain threshold [6].
• Bupivacaine, 0.0625%, with 0.33 microg/ml sufentanil was infused throughout labor at 13.5-15 ml/h. Analgesia balance, proprioception, motor block, and patient ability to stand and walk were evaluated at various intervals [7].
• These concentrations of morphine and sufentanil yielded a comparable near maximal hot-plate response latency on day 1 of the infusion [8].
• Pretreatment with sufentanil (1 microgram/kg, i.p.) induced an elevation in apomorphine-induced stereotyped behaviour, but attenuated locomotor activity [9].
• A further aim was to study whether elderly patients developed withdrawal symptoms after discontinuing prolonged sufentanil administration [10].

High impact information on SUFENTANIL

• Halothane-morphine compared with high-dose sufentanil for anesthesia and postoperative analgesia in neonatal cardiac surgery [1].
• Similarly, [D-Ala2, D-Leu5]enkephalin and sufentanil selectively protected binding sites for 3H-labeled [D-Ala2, D-Leu5]enkephalin and [3H]dihydromorphine, respectively [11].
• In contrast, patients who received 72 h of PCV had lower CRS, PaO2, CI, DO2, and Q VA/Q T values (p < 0.05) and required higher doses of sufentanil (p < 0.05), midazolam (p < 0.05), noradrenalin (p < 0.05), and dobutamine (p < 0.05) [12].
• Relationship between the pharmacokinetics and the analgesic and respiratory pharmacodynamics of epidural sufentanil [13].
• Enrichment was obtained by treatment of membranes with the alkylating agent beta-chlornaltrexamine in the presence of appropriate protecting ligands, sufentanil for mu sites, [D-Ala2, D-Leu5] enkephalin for delta sites, and dynorphin A for kappa sites [14].

Chemical compound and disease context of SUFENTANIL

• Fentanyl and sufentanil increase intracranial pressure in head trauma patients [15].
• Muscular spasm in the lower limbs of laboring patients after intrathecal administration of epinephrine and sufentanil [16].
• CONCLUSIONS: The present study shows that the increase in sufentanil or ketamine plasma concentrations using a target-controlled infusion is not associated with adverse effects on cerebral hemodynamics in patients with severe brain injury [17].
• Echocardiographic results: The incidence of precordial echocardiographic ischemia during anesthetic induction was 13% (5/39) in the desflurane group versus 0% (0/29) in the sufentanil group (P = 0.1) [18].
• Isoflurane (0.93 minimum alveolar concentration [MAC]), sevoflurane (1.03 MAC), or sufentanil (1.2 nM) was added 15 min before ischemia and throughout reperfusion, either alone or in combination with HOE 642 (5 microM) [19].

Biological context of SUFENTANIL

• We previously demonstrated that chronic treatment of rats with the mu-opioid receptor agonist sufentanil induced pharmacological tolerance associated with mu-opioid receptor desensitization and down-regulation [20].
• Chronic s.c. infusion of sufentanil (2 microg/h) for 7 days, which has been shown to induce tolerance to the opioid antinociceptive effect, produced an up-regulation of DHP binding sites [21].
• The area under the concentration-time curve (AUC) from zero to 1h, 2h, 3h, tracheal extubation and infinity, the absorption and distribution half-lives, maximum plasma and CSF concentrations, time to the peak concentration of sufentanil, and the fraction of sufentanil that reached the central circulation after epidural administration were assessed [22].
• We developed another pain model, postpartum resection of the fallopian tubes for sterilisation, in which each patient serves as her own control when one side is infiltrated with the active drug (in this study sufentanil 5 mg) and the contralateral side with normal saline [23].
• Thus, although inactivation of the inhibitory signal transduction pathway (via pertussis toxin) is sufficient to unmask excitatory sufentanil effects in opiate naive preparations, this mechanism cannot explain the reversal of sufentanil inhibition to facilitation that is observed in tolerant/dependent tissue [24].

Anatomical context of SUFENTANIL

• The initial transfer of sufentanil from the epidural space to the systemic circulation appeared to be very rapid [22].
• A mu-selective opiate receptor agonist, sufentanil, can either increase or decrease the stimulated formation of cyclic AMP (cAMP) in the myenteric plexus [25].
• Under these conditions, a greater increase in the number of DHP binding sites was observed in the spinal cord, central grey matter, dorsal raphe nucleus, and somatosensory neocortex, when compared to the sufentanil group [21].
• Acute treatments with high doses of sufentanil and morphine (mu-agonists), SNC-80 (delta-agonist), and U50488H (kappa-agonist) induced significant decreases (30-60%) in FADD immunodensity in the cerebral cortex, through specific opioid receptor mechanisms (effects antagonized by naloxone, naltrindole, or nor-binaltorphimine) [26].
• Comparative efficacy of patient-controlled administration of morphine, hydromorphone, or sufentanil for the treatment of oral mucositis pain following bone marrow transplantation [27].

Associations of SUFENTANIL with other chemical compounds

• For the remaining 41 patients, target concentrations associated with adequate analgesia were achieved for both sufentanil and fentanyl [28].
• Alfentanil and sufentanil need further investigations to define their pharmacokinetic-pharmacodynamic properties in neonates [29].
• Administration of the calcium channel blocker nimodipine during chronic treatment with sufentanil prevented mu-opioid receptor down-regulation, induced down-stream supersensitization, and produced supersensitivity to the opioid effects [20].
• The ontogeny of mu- and kappa-receptor function was determined by assessing the PRL response to the mu-agonist sufentanil (SUF) and the kappa-agonist U50488 in 5-, 10-, 15-, 20-, and 60-day-old rats [30].
• Addition of cholesteryl hemisuccinate (CHS) to cell membranes increased membrane microviscosity and reduced the inhibitory effect of sodium and guanine nucleotides on the affinity of the full agonists sufentanil and [D-Ala2,N-MePhe4,Gly-ol5]enkephalin (DAMGO) for the mu-opioid receptor [31].

Gene context of SUFENTANIL

• Sufentanil (1-30 microg/kg, 30-120 min) induced dose- and time-dependent increases in MEK1/2 phosphorylation in the cerebral cortex and corpus striatum (30-177%) through a naloxone-sensitive mechanism [32].
• Identification of human liver cytochrome P-450 3A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation [33].
• Acute and chronic treatment with sufentanil induced analgesic tolerance, associated with up-regulation of GRK2, GRK6, and beta-arrestin 2 [20].
• Little is known about the involvement of CYP enzymes in the oxidative metabolism of fentanyl and sufentanil [34].
• Thus the addition of somatostatin increased the suppression of the hormonal response to cardiac surgery by sufentanil [35].

Analytical, diagnostic and therapeutic context of SUFENTANIL

• To establish the relationships between epidural sufentanil analgesia and respiratory effects and to determine the pharmacokinetics of the drug, 22 adult patients undergoing thoracotomy were put into a randomized, double-blind study and received either 30, 50, or 75 micrograms per dose in 20 ml normal saline solution [13].
• Comparison of intranasal midazolam and sufentanil premedication in pediatric outpatients [3].
• Absence of spontaneous breathing (PCV Group) was induced with sufentanil and midazolam (RSS of 5) and neuromuscular blockade [12].
• CONCLUSION: Both intranasal midazolam and sufentanil provide rapid, safe, and effective sedation in small children before anesthesia for ambulatory surgery [3].
• After 30 min from the end of anaesthesia onwards, 26 out of 30 patients observed significant pain relief on the side of the sufentanil infiltration, which in 11 patients lasted until the end of the observation period 24 h postoperatively; no difference was observed in the control group [23].

References