Synthesis of Some Novel 2,6-Disubstituted Pyridazin-3(2H)-one Derivatives as Analgesic, Anti-Inflammatory, and Non-Ulcerogenic Agents.

Some novel 2,6-disubstituted pyridazine-3(2H)-one derivatives were synthesized and evaluated for in vitro cyclooxygenase-2 (COX-2) inhibitory efficacy. Compounds 2-{[3-(2-methylphenoxy)-6-oxopyridazin-1(6H)-yl]methyl}-1H-isoindole-1,3(2H)-dione (5a), 2-propyl-6-(o-tolyloxy)pyridazin-3(2H)-one (6a), and 2-benzyl-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazin-3(2H)-one (16a) showed the most potent COX-2 inhibitory activity with IC50 values of 0.19, 0.11, and 0.24 µM, respectively. The synthesized compounds with the highest COX-2 selectivity indices were evaluated for their anti-inflammatory, analgesic, and ulcerogenic activities. Compounds 6a and 16a demonstrated the most potent and consistent anti-inflammatory activity over the synthesized compounds, which was significantly higher than that of celecoxib in the carrageenin rat paw edema model and with milder ulcer scoring than that of indomethacin in the ulcerogenicity screening.

Enhancement of ropivacaine caudal analgesia using dexamethasone or magnesium in children undergoing inguinal hernia repair.

BACKGROUND: Caudal analgesia is the most commonly used technique providing intra- and postoperative analgesia for various pediatric infraumbilical surgical procedures but with the disadvantage of short duration of action after single injection. Caudal dexamethasone and magnesium could offer significant analgesic benefits. We compared the analgesic effects and side-effects of dexamethasone or magnesium added to caudal ropivacaine in pediatric patients undergoing inguinal hernia repair. MATERIALS AND METHODS: A total of 105 (1-6 years) were randomly assigned into three groups in a double-blinded manner. After a standardized sevoflurane in oxygen anesthesia, each patient received a single caudal dose of ropivacaine 0.15% 1.5 mL/kg combined with either magnesium 50 mg in normal saline 1 mL (group RM), dexamethasone 0.1 mg/kg in normal saline 1 mL (group RD), or corresponding volume of normal saline (group R) according to group assignment. Postoperative analgesia, use of analgesics, and side-effects were assessed during the first 24 h. RESULTS: Addition of magnesium or dexamethasone to caudal ropivacaine significantly prolonged analgesia duration 8 (5-11) h and 12 (8-16) h, respectively compared with 4 (3-5) h with the use of ropivacaine alone. The incidence of postoperative rescue analgesia was significantly higher in group R compared with groups RM and RD. The time to 1(st) analgesic dose was significantly longer in groups RM and RD (500 ± 190 and 730 ± 260 min) respectively compared with group R (260 ± 65 min). Group R patients achieved significantly higher Children's Hospital of Eastern Ontario Pain Scale and Faces Legs Activity Cry Consolability scores (4(th) hourly) compared with groups RM and RD patients (8(th) and 12(th) hourly, respectively). CONCLUSION: The addition of dexamethasone or magnesium to caudal ropivacaine significantly prolonged the duration of postoperative analgesia in children undergoing inguinal hernia repair. Also the time to 1(st) analgesic dose was longer and the need for rescue postoperative analgesic was reduced and without increase in incidence of side effects.

Effect of bispectral index monitoring on desflurane consumption and recovery time in morbidly obese patients undergoing laparoscopic sleeve gastrectomy.

BACKGROUND: Morbid obesity magnifies the importance of the fat-blood solubility coefficient of the anesthetic in its relation to emergence and recovery. Using bispectral index (BIS) monitoring for the titration of the administration of inhaled anesthetics such as desflurane may permit a less consumption and more rapid recovery from desflurane anesthesia in morbidly obese patients, which enables earlier maintenance of a patent airway, better protection against aspiration, and better oxygenation. OBJECTIVE: The aim of this study was to investigate the effect of BIS monitoring on postoperative extubation and recovery times, and intraoperative desflurane consumption in morbidly obese patients undergoing laparoscopic sleeve gastrectomy under general anesthesia using desflurane for maintenance. PATIENTS AND METHODS: Forty morbidly obese patients were randomly enrolled in this study and divided into two groups of 20 patients each: Non-BIS group and BIS group. End-tidal desflurane concentration, mean blood pressure, and heart rate were regularly recorded. Recovery times (eye opening to verbal commands, time to extubation, and orientation to time, place, and person) and the time to achieve a modified Aldrete score of ≥ 9 were recorded by blinded study anesthesia nurse. Desflurane consumption was calculated in milliliters through gas usage option of Datex-Ohmeda S/5 anesthesia machine. RESULTS: The mean end-tidal concentrations of desflurane were significantly decreased in the BIS group compared to the non-BIS group (P < 0.05). The mean desflurane consumption and cost were significantly lower in the BIS group (124.8 ± 5.1 ml/patient) compared to the non-BIS group (150.6 ± 6.5 ml/patient) (P < 0.05). Recovery times were significantly shorter in the BIS group versus non-BIS group (P < 0.05). CONCLUSION: The use of BIS monitoring was effective in reducing intraoperative desflurane requirement (cost) and in shortening early recovery times after laparoscopic sleeve gastrectomy in morbidly obese patients without compromising the hemodynamic stability, adequacy of anesthesia, or patient outcome.

Orotracheal intubation of morbidly obese patients, comparison of GlideScope(®) video laryngoscope and the LMA CTrach™ with direct laryngoscopy.

BACKGROUND: Morbidly obese patients are at increased risk of difficult mask ventilation and intubation as well as increased risk of hypoxemia during tracheal intubation. Recently, new video-assisted intubation devices have been developed. The GlideScope(®) videolaryngoscope and LMA CTrach™ (CT) allows continuous video-endoscopy of the tracheal intubation procedure. OBJECTIVE: this study is to determine whether the GlideScope(®) videolaryngoscope (GVL) and the LMA CTrach™ (CT) provide the best airway management, measured primarily in intubation difficulty scale (IDS) scores, time and numbers of intubation attempts, and improvement in the intubation success rate of morbidly obese patients when compared with the direct Macintosh laryngoscope (DL). MATERIALS AND METHODS: After Ethics' Committee approval, 90 morbidly obese patients (BMI > 35 kg/m(2)) scheduled for general, gynecological, and bariatric surgery were included in this prospective study. Patients were randomly assigned in three groups: tracheal intubation using direct laryngoscopy (DL), GlideScope(®) videolaryngoscope (GVL) or the LMA CTrach™ (CT). Characteristics and consequences of airway management were evaluated. The primary outcome was the intubation difficulty scale score (IDS), Secondary outcomes were theintubation time, overall success rate, number of attempts, Cormack-Lehane grade, subjective difficulty of intubation, desaturation and upper airway morbidity. RESULTS: Difficulty in facemask ventilation was similar in the three groups. IDS scores were significantly lower with GVL and CT than with DL. The mean TTI was 14 s faster in patients intubated with the GVL (86 s, IQR: 68-115) compared with DL (100 s, IQR; 80-150), and was 34 s faster when compared with CT (120 s, IQR; 95-180). The success rate of tracheal intubation was lower with the DL (80%) compared with the GVL (100%) or the CT (100%). Six cases of failed intubation occurred in group DL, four patients from the six patients were intubated successfully with GVL, and two patients were intubated with the CT. Both the GVL and the CTimproved the Cormack and Lehane view obtained at laryngoscopy, compared with the DL. Significantly high percent of patients in DL (43%) and CT (27%) required optimization maneuvers (external laryngeal pressure) compared with GVL (0%). In the CT group, 30% of the patients required laryngeal mask manipulation (for view optimization) compared with (0%) in GVL and CT groups. CONCLUSION: The GlideScope(®) videolaryngoscope and the LMA CTrach™ reduced the difficulty, improved laryngoscopic views and overall success rate of tracheal Intubationto a similar extent compared with the Macintosh laryngoscope in morbidly obese patients. The GVL improved intubation time for tracheal intubation compared with the CT and DL but no patient became hypoxic with CT because of prolonged intubation time.