The UMSS is a simple, valid and reliable tool that facilitates rapid and frequent assessment and documentation of depth of sedation in children.

Pruritus (itch sensation) is a significant clinical problem. The aim of this study was to elucidate the roles of opioid receptor types and the site of action in opioid-induced itch in monkeys. Observers who were blinded to the conditions counted scratching after administration of various drugs. Intravenous (i.v.) administration of opioid receptor (MOR) agonists (fentanyl, alfentanil, remifentanil, and morphine) evoked scratching in a doseand time-dependent manner. However, the opioid agonist

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Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide for the NOP receptors. Depending on the doses, intrathecal administration of N/OFQ has dual actions (ie, hyperalgesia and antinociception) in rodents. However, the pharmacological profile of intrathecal N/OFQ is not fully known in primates. The aim of this study was to investigate behavioral effects of intrathecal N/OFQ over a wide dose range and to compare its effects with ligands known to produce hyperalgesia or antinociception in monkeys. Intrathecal N/OFQ from 1 fmol to 1 nmol did not produce any hyperalgesic or scratching responses. In contrast, intrathecal substance P 100 nmol produced hyperalgesia, and intrathecal DAMGO 10 nmol produced antinociception. At the dose range between 10 nmol and 1 µmol, intrathecal N/OFQ dose-dependently produced thermal antinociception against a noxious stimulus in 2 intensities. More importantly, N/OFQ in combined with intrathecal morphine dose-dependently potentiated morphine-induced antinociception without inhibiting morphineinduced itch/scratching. Taken together, this study is the first to provide a unique functional profile of intrathecal N/OFQ over a wide dose range in primates. Intrathecal N/OFQ produces thermal antinociception without anti-morphine actions or scratching responses, indicating that N/OFQ or NOP receptor agonists represent a promising target as spinal analgesics.Perspective: Intrathecal administration of N/OFQ only produced thermal antinociception, not hyperalgesia, in monkeys. In addition, intrathecal N/OFQ does not have anti-morphine actions or itch/scratching responses. This study strongly supports the therapeutic potential of N/OFQ or NOP receptor agonists as spinal analgesics for clinical trials. KeywordsSpinal cord; analgesia; NOP receptors; substance P; thermal hyperalgesia Spinal administration of µ-opioid receptor agonists is an important method for pain management, and it is widely used for obstetric analgesia. 8,10 However, itch/pruritus is the most common side effect derived from spinal opioids, and it reduces the value of pain relief afforded by spinal opioids. 8 Therefore, the aim of this study was to extensively investigate and directly compare the behavioral effects of intrathecally administered N/OFQ over a wide dose range in monkeys.As noted, rodent studies have shown that intrathecal DAMGO and substance P produced antinociceptive and pronociceptive effects, respectively. 29,30,41 By using both behavioral end points (ie, antinociception/hyperalgesia and scratching responses), effects of intrathecal DAMGO and substance P were compared with those of intrathecal N/OFQ. Antinociceptive effects of intrathecal N/OFQ were further studied against a noxious stimulus in 2 intensities. In addition, the potential interaction between intrathecal N/OFQ and morphine was determined to explore whether N/OFQ modulated intrathecal morphine-induced antinociception and scratching responses. Materials and Methods SubjectsEighteen adult intact male and female rhesus monkeys (Macacamulatta) with...

Pruritus (itch sensation) is the most common side effect associated with spinal administration of morphine given to humans for analgesia. A variety of agents have been proposed as antipruritics with poorly understood mechanisms and they are effective with variable success. kappa-Opioid agonists possess several actions that are opposite to micro -opioid agonists. We proposed to investigate the role of kappa-opioid receptors (KORs) in morphine-induced scratching and antinociception in monkeys. Scratching responses were counted by observers blinded to treatment. Antinociception was measured by a warm water (50 degrees C) tail-withdrawal assay. Pretreatment with low doses of trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide (U-50488H) (0.032-0.18 mg/kg s.c.), a selective KOR agonist, dose dependently suppressed the s.c. morphine dose-effect curve for scratching and potentiated s.c. morphine-induced antinociception. In addition, s.c. U-50488H attenuated i.t. morphine (10 and 32 micro g)-induced scratching while maintaining or enhancing i.t. morphine-induced antinociception. The combination of s.c. or i.t. morphine with low doses of U-50488H did not cause sedation. More importantly, pretreatment with 3.2 mg/kg nor-binaltorphimine, a selective KOR antagonist, blocked the effects of s.c. U-50488H on both s.c. and i.t. morphine-induced scratching. These results indicate that activation of KOR attenuates morphine-induced scratching without interfering with antinociception in monkeys. This mechanism-based finding provides functional evidence in support of the clinical potential of KOR agonists as antipruritics in the presence of MOR agonist-induced pruritus.

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The 8 anesthesia-related and seven anesthesia-contributing maternal deaths in Michigan between 1985 and 2003 illustrate three key points. First, all anesthesia-related deaths from airway obstruction or hypoventilation took place during emergence and recovery, not during the induction of general anesthesia. Second, system errors played a role in the majority of cases. Of concern, lapses in postoperative monitoring and inadequate supervision by an anesthesiologist seemed to contribute to more than half of the deaths. Finally, this report confirms previous work that obesity and African-American race are important risk factors for anesthesia-related maternal mortality.

Butorphanol is effective in attenuating systemic or spinal morphine-induced itch without reducing morphine analgesia. This study provides functional evidence that both partial MOR and KOR agonist actions contribute to the effectiveness of butorphanol as an antipruritic in primates.