Comparison of the time to extubation after use of remifentanil or sufentanil in combination with propofol as anesthesia in adults undergoing nonemergency intracranial surgery: a prospective, randomized, double-blind trial.

BACKGROUND: Anesthetics with a short context-sensitive half-time (ie, the time required for the effect-site concentration of an IV drug to decrease by 50% at steady state), such as the opioids remifentanil and sufentanil, are suitable for anesthesia when early neurologic assessment is desired to detect postoperative complications. OBJECTIVE: This study compared the efficacy and safety profile of remifentanil and sufentanil in combination with propofol for anesthesia in adult patients undergoing nonemergency intracranial surgery. METHODS: This was a prospective, randomized, double-blind study in adults aged 18 to 75 years who were scheduled to undergo a supratentorial neurosurgical procedure with a maximum anticipated duration of 480 minutes. Eligible patients had no incapacitating severe systemic disease (American Society of Anesthesiologists physical status class 1-3), and only those in whom immediate postoperative extubation was planned were included. Anesthesia was induced with propofol and either remifentanil 1 microg/kg or sufentanil 0.25 microg/kg. Propofol was continued using a target-controlled infusion (TCI) system. Maintenance infusion rates for remifentanil and sufentanil were 0.25 and 0.0025 microg.kg-1.min-1, respectively. The opioid and propofol infusions were adjusted based on hemodynamic parameters (mean arterial blood pressure, heart rate). The primary end point was the time to extubation. Secondary end points were hemodynamic stability (defined as the number of anesthetic adjustments required to maintain intraoperative hemodynamic parameters within 20% of preinduction values), postoperative IV morphine requirement, postoperative nausea/vomiting (PONV), and intraoperative anesthetic costs. RESULTS: Sixty adults (29 remifentanil, 31 sufentanil) were included in the study. The 2 groups were similar with respect to sex, weight, indication for surgery, and duration of anesthesia. The sufentanil group was significantly older than the remifentanil group (55.3 vs 45.7 years, respectively; P=0.001). The median extubation time was similar in the remifentanil and sufentanil groups (10 minutes [interquartile range, 5-19 minutes] and 16 minutes [interquartile range, 10-30 minutes], respectively). Remifentanil was associated with the need for significantly fewer adjustments to maintain hemodynamic stability compared with sufentanil (0.8 vs 2.1; P=0.037), greater use of postoperative morphine (44.8% vs 22.6% of patients, P=0.01; mean IV morphine dose per patient: 4 vs 1.3 mg, P=0.016), and higher intraoperative opioid costs per patient euro vs euro P<0.001). The incidence of PONV did not differ significantly between groups. The total cost of intraoperative anesthetics per patient was similar in the 2 groups euro and euro as was the cost of propofol euro vs euro CONCLUSION: In these adults undergoing nonemergency intracranial surgery, there was no significant difference in extubation time between those receiving remifentanil and sufentanil infusions adjusted based on hemodynamic parameters in combination with propofol administered by TCI.

Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia.

The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway has been shown to be frequently activated in blast cells from patients with acute myeloid leukemia (AML) and to contribute to survival and proliferation of these cells. Of the 8 distinct mammalian isoforms of PI3K, it is the class I PI3Ks (p110alpha, p110beta, p110gamma, and p110delta) that are responsible for Akt activation. It is not known which PI3K isoform is critical in AML. Here we show that the p110delta isoform of PI3K is consistently expressed at a high level in blast cells from AML, in contrast to the other class I isoforms, the expression of which was very variable among patients. IC87114, a p110delta-selective inhibitor, suppressed both constitutive and Flt-3-stimulated Akt activation in blasts to the same extent as Ly294002, an inhibitor of all PI3K isoforms. Moreover, IC87114 inhibited AML cell proliferation without affecting the proliferation of normal hematopoietic progenitor cells. These observations identify p110delta as a potential therapeutic target in AML.