RESUMO
BACKGROUND AND OBJECTIVES: Intrathecal epinephrine has been examined by clinical studies, but its effects on analgesia/anesthesia outcomes as well as on undesirable adverse effects is not clearly defined. The objective of this study was to examine the effects of intrathecal epinephrine on intrathecal anesthesia/analgesia. METHODS: We performed a meta-analysis, using a random-effects model. Effects of intrathecal epinephrine dose were evaluated by pooling studies into 3 dosage groups: low (1-100 µg), intermediate (101-200 µg), and high (≥200 µg). Metaregression analyses were also performed to examine the presence of a linear association between intrathecal epinephrine dose and effect size on evaluated outcomes. RESULTS: Twenty-four randomized clinical trials with 1,271 subjects were included. The mean (95% confidence interval [CI]) combined effects favored intrathecal epinephrine over placebo for duration of analgesia, 27.0 mins (20.8-33.3 mins); sensory, 35.0 mins (22.8-47.3 mins); and motor block, 32.2 mins (26.2-38.2 mins). The incidence of hypotension and postoperative nausea and vomiting (PONV) was greater for the low dose (1-100 µg) intrathecal epinephrine group compared with placebo (odds ratios [95% CI], 3.0 [1.5-5.9] and 2.7 [1.5-4.8], respectively). A greater incidence of hypotension and PONV was not detected for the intermediate-dose group (101-200 µg): odds ratios (95% CI) of 0.9 (0.5-1.7) and 1.6 (0.6-4.6), respectively. CONCLUSIONS: Intrathecal epinephrine has dose-dependent clinical and adverse effects. Doses of 100 µg or less prolonged sensory and motor block duration but were associated with greater incidence of hypotension or PONV. Intrathecal epinephrine doses greater than 100 µg prolonged sensory and motor block and were not associated with greater incidence of hypotension and PONV.
Assuntos
Analgesia , Anestesia , Epinefrina/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Analgésicos Opioides/administração & dosagem , Relação Dose-Resposta a Droga , Epinefrina/efeitos adversos , Humanos , Hipotensão/epidemiologia , Injeções Espinhais , Náusea e Vômito Pós-Operatórios/epidemiologia , Fatores de TempoRESUMO
Inhibitor of apoptosis (IAP) proteins are involved in the suppression of apoptosis, signal transduction, cell cycle control and gene regulation. Here we describe the cloning and characterization of viral IAP-associated factor (VIAF), a highly conserved, ubiquitously expressed phosphoprotein with limited homology to members of the phosducin family that associates with baculovirus Op-IAP. VIAF bound Op-IAP both in vitro and in intact cells, with each protein displaying a predominantly cytoplasmic localization. VIAF lacks a consensus IAP binding motif, and overexpression of VIAF failed to prevent Op-IAP from protecting human cells from a variety of apoptotic stimuli, suggesting that VIAF does not function as an IAP antagonist. VIAF was unable to directly inhibit caspase activation in vitro and a reduction of VIAF protein levels by RNA interference led to a decrease in Bax-mediated caspase activation, suggesting that VIAF functions to co-regulate the apoptotic cascade. Finally, VIAF is a substrate for ubiquitination mediated by Op-IAP. Thus, VIAF is a novel IAP-interacting factor that functions in caspase activation during apoptosis.