Effects of ciprofol for the induction of general anesthesia in patients scheduled for elective surgery compared to propofol: a phase 3, multicenter, randomized, double-blind, comparative study.

OBJECTIVE: Ciprofol is a newly developed intravenous sedative-hypnotic drug. The objective of the study was to prove whether ciprofol was non-inferior to propofol for the successful induction of general anesthesia. The ideal post-induction sedation level was assessed by comparing patients' clinical symptoms and their hemodynamic effects in responding to noxious stimuli, mostly tracheal intubation and bispectral index (BIS) alterations following ciprofol/propofol administration. PATIENTS AND METHODS: In this multi-center, randomized, double-blind phase 3 trial, selective surgery patients were randomly assigned in a 1:1 ratio to either ciprofol 0.4 mg/kg (n = 88) or propofol 2.0 mg/kg (n = 88) groups. The primary endpoint was the percentage of patients with successful anesthesia inductions. Secondary endpoints included the times to successful induction of general anesthesia and loss of the eyelash reflex, changes in BIS, as well as safety indicators. RESULTS: The anesthesia induction success rates for both ciprofol 0.4 mg/kg and propofol 2 mg/kg groups were 100.0%, with a 95% CI lower success limit of -4.18% difference between the two groups, indicating that ciprofol was non-inferior to propofol. For secondary outcomes, the average time to successful anesthesia and loss of the eyelash reflex were 0.91 min and 0.80 min for ciprofol and 0.80 min and 0.71 min for propofol, respectively. The pattern of BIS changes with ciprofol was similar to propofol and stable during the anesthesia maintenance period. Safety was comparable with 88.6% TEAEs in the ciprofol group compared to 95.5% in the propofol group. The incidence of injection pain was significantly lower in the ciprofol group compared to the propofol group (6.8% vs. 20.5%, p < 0.05). In addition, the patients treated with ciprofol had a lesser increase in blood pressure and heart rate, and fewer cases with BIS > 60 within 15 min of intravenous administration, which indicated that ciprofol may provide a better ideal sedation level during the post-induction period under an equivalent dosing regimen to propofol. CONCLUSIONS: Ciprofol for patients undergoing selective surgery is a new option for the induction of general anesthesia.

The minimum effective concentration (MEC90 ) of ropivacaine for ultrasound-guided supraclavicular brachial plexus block.

The aim of this study was to determine the minimum effective concentration of ropivacaine for ultrasound-guided supraclavicular brachial plexus block. Fifty-one patients undergoing arm surgery received double-injection ultrasound-guided supraclavicular block using ropivacaine 40 ml. The concentration of ropivacaine administered to each patient started at 0.225% and then depended on the response of the previous one, based on a biased coin design up-and-down sequential method. In case of failure, the ropivacaine concentration was increased by 0.025% w/v in the next subject. In the case of a successful block, the next patient was randomised to the same concentration or a concentration 0.025% w/v less. Success was defined as complete sensory blockade of the brachial plexus 30 min after the block together with pain-free surgery. The minimum effective ropivacaine concentration in 90% of subjects was 0.257% w/v (95% CI 0.241-0.280%).

GABAergic excitotoxicity injury of the immature hippocampal pyramidal neurons' exposure to isoflurane.

BACKGROUND: Certain anesthetics exhibit neurotoxicity in the brains of immature but not mature animals. γ-Aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the adult brain, is excitatory on immature neurons via its action at the GABAA receptor, depolarizing the membrane potential and inducing a cytosolic Ca2+ increase ([Ca2+]i), because of a reversed transmembrane chloride gradient. Recent experimental data from several rodent studies have demonstrated that exposure to isoflurane during an initial phase causes neuronal excitotoxicity and apoptosis. GABAA receptor-mediated synaptic voltage-dependent calcium channels' (VDCCs) overactivation and Ca2+ influx are involved in these neural changes. METHODS: We monitored [Ca2+]i using Fluo-4 AM fluorescence imaging. Using whole-cell patch clamp techniques, IVDCC (voltage-dependent calcium channel currents) were recorded from primary cultures of rat hippocampal neurons (5-day culture) exposed to isoflurane. To further investigate the neurotoxicity of high cytosolic-free calcium after isoflurane in a dose- and time-dependent manner, the possibility of increased caspase-3 levels was evaluated by Western blot and quantitative real-time polymerase chain reaction. Statistical significance was assessed using the Student t test or 1-way analysis of variance followed by the Tukey post hoc test. RESULTS: Under control conditions, isoflurane enhanced the GABA-induced [Ca2+]i increase in a dose-dependent manner. Dantrolene and nicardipine markedly inhibited this enhancement mediated by isoflurane. Moreover, in Ca2+-free media, pretreatment with isoflurane did not show any influence on the caffeine-induced increase of [Ca2+]i. Similarly, using whole-cell recording, isoflurane increased the peak amplitude of IVDCC in the cultured neurons from rat hippocampus by depolarization pulses. Isoflurane (0.25, 0.5, 0.75, and 1 minimum alveolar concentration [MAC]) potentiated IVDCC peak current amplitude by 109.11%±9.03%, 120.56%±11.46%, 141.33%±13.87%, and 146.78%±15.87%, respectively. To analyze variation in protein levels, the effect of treatments with isoflurane on caspase-3 activity was dose- and time-dependent, reaching a maximal caspase-3 activity after exposure to 1 MAC for 6 hours (P<0.001). However, in the mRNA levels, hippocampal caspase-3 mRNA levels began to be significantly increased in isoflurane-treated developing rat hippocampal neurons after 6 hours of exposure to 0.25 MAC isoflurane (P<0.001). CONCLUSIONS: Isoflurane-mediated enhancement of GABA-triggered [Ca2+]i release results from membrane depolarization with subsequent activation of VDCCs and further Ca2+-induced Ca2+ release from the ryanodine-sensitizing Ca2+ store. An increase in [Ca2+]i, caused by activation of the GABAA receptor and opening of VDCCs, is necessary for isoflurane-induced calcium overload of immature rat hippocampal neurons, which may be involved in the mechanism of an isoflurane-induced neurotoxic effect in the developing rodent brain.

Isoflurane enhances spontaneous Ca(2+) oscillations in developing rat hippocampal neurons in vitro.

BACKGROUND: During the nervous system development, spontaneous synchronized Ca(2+) oscillations are thought to possess integrative properties because their amplitude and frequency can influence the patterning of neuronal connection, neuronal differentiation, axon outgrowth, and long-distance wiring. Accumulating studies have confirmed that some drugs such as volatile anesthetic isoflurane produced histopathologic changes in the central nervous system in juvenile animal models. Because the hippocampus plays an important role in learning and memory, the present work was designed to characterize the Ca(2+) oscillations regulated by volatile anesthetic isoflurane in primary cultures of developing hippocampal neurons (5-day-cultured). METHODS: Primary cultures of rat hippocampal neurons (5-day-cultured) were loaded with the Ca(2+) indicator Fluo-4AM (4 microM) and were studied with a confocal laser microscope. RESULTS: Approximately 22% of 5-day-cultured hippocampal neurons exhibited typical Ca(2+) oscillations. These oscillations were dose-dependently enhanced by isoflurane (EC50 0.5 MAC, minimum alveolar concentration) and this effect could be reverted by bicuculline (50 microM), a specific gamma-aminobutyric acid (GABA(A)) receptor antagonist. CONCLUSION: Unlike its depressant effect on the Ca(2+) oscillations in adult neurons in previous researches, isoflurane dose-dependently enhanced calcium oscillations in developing hippocampal neurons by activating GABA(A) receptors, a major excitatory receptor in synergy with N-methyl-d-aspartate receptors at the early stages of development. It may be involved in the mechanism of an isoflurane-induced neurotoxic effect in the developing rodent brain.

[Patient-controlled analgesia with lornoxicam in patients undergoing gynecological surgery].

OBJECTIVE: To assess the analgesic effect and side effects of PCA with lornoxicam compared with morphine and tramadol. METHODS: 89 patients, scheduled for elective hysterectomy or hysteromyomectomy, were randomly divided into Group L, Group M and Group T. Three drugs administered i.v. via a patient-controlled analgesia for up to 24 h postoperatively. RESULTS: Efficacy was assessed by comparing total pain relief (TOTPAR) and sum of pain intensity difference (SPID) over 24 h. Statistically significant equivalence of lornoxicam, morphine and tramadol was shown by TOTPAR values 15.2 +/- 3.9, 16.4 +/- 3.5 and 15.9 +/- 4.4, by SPID values 10.3 +/- 3.1, 9.0 +/- 2.0 and 9.2 +/- 4.7, respectively (P > 0.05). Lornoxicam caused fewer adverse events than morphine and tramadol (10.0%, 26.7% and 17.2% of patients, respectively). CONCLUSION: The study suggests that lornoxicam provides an alternative to morphine or tramadaol for the treatment of postoperative pain.

[Ondansetron on postoperative nausea and vomiting].

The efficacy and safety of prophylactic intravenous ondansetron on prevention of postoperative nausea and vomiting were investigated in 65 ASA grades I-III patients undergoing elective abdominal surgery and receiving general anesthesia. Patients received ondansetron 4mg i.v. prior to a standardized technique for induction and intubation. Anesthesia was maintained with N2O-O2 and enflurane. The results showed that, by ondansetron 4mg, nausea and emesis could be significantly decreased. The effect lasted around 24h postoperatively without sedation. No one developed vomiting and only 9 patients developed nausea. No changes on laboratory parameters as well as vital signs were observed. No side-effects related to ondansetron were found. In prophylaxis of postoperative nausea and vomiting, ondansetron is effective and safe.

Evaluation of atracurium in myasthenic patients undergoing thymectomy.

Myasthenia gravis is an autoimmune disease involving the acetylcholine receptors at neuromuscular junctions. Perioperative management of patients with myasthenia gravis is complicated by their enhanced sensitivity to nondepolarizing neuromuscular blocking agents and their resistance to depolarizing drugs (1). Prolonged respiratory depression commonly occurs when these agents are used. Atracurium dibesilate is one of a new series of nondepolarizing agents and is promising by virtue of its rapid degradation by 'Hoffmann elimination', leaving products with little or no muscle blocking activity. After encouraging results were obtained with atracurium (2-6), we investigated the neuromuscular blocking effect of different doses of the drug (0.2 mg/kg, 0.5 mg/kg) in sixteen myasthenic patients undergoing thymectomy, with continuous monitoring of neuromuscular function.