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      The Effect Of The Use Of Pre-Emptive Oral Pregabalin On The Postoperative Spinal Analgesia In Patients Presented For Orthopedic Surgeries: Randomized Controlled Trial

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          Abstract

          Background

          Preoperative oral pregabalin could improve postoperative analgesia and prevent chronic pain development. The aim of this study is to evaluate the effect of oral pregabalin on the duration and quality of postoperative analgesia in spinal anesthesia.

          Methods

          Sixty adult patients presented for internal fixation of femoral fracture under spinal anesthesia were included in the study. They were randomly distributed to a placebo group and a pregabalin group receiving 150 mg pregabalin capsules 1 hr before surgery. The onset, duration, and regression of sensory and motor block were recorded. Rescue analgesia consumption, postoperative pain score, and quality of sleep were also assessed.

          Results

          Oral pregabalin significantly prolonged the time to two-segment regression of sensory block, reaching 86.67±17.88 mins, the time required to regression of spinal block to L2, reaching 155.33± 34.71 mins, and the duration of motor block, reaching 138 ± 23.5 mins, with no effect on the onset of sensory or motor block ( P = 0.60 and 0.62). It significantly decreased the VAS score 4 hrs, 6 hrs, and 12 hrs postoperatively, prolonged the duration of postoperative analgesia, reaching 392.00±47.23 mins, and decreased morphine consumption to 7.67±3.65 mg. It also improved the quality of sleep in the first night after surgery.

          Conclusion

          Preemptive oral pregabalin prolonged the time to the first request for postoperative analgesics and improved sleep in the first night after surgery.

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          Most cited references 17

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          Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety.

          Gabapentin and pregabalin have antiallodynic and antihyperalgesic properties useful for treating neuropathic pain. These properties may also be beneficial in acute postoperative pain. In this study we evaluated randomized, controlled trials examining the analgesic efficacy, adverse effects, and clinical value of gabapentinoids in postoperative pain. A systematic search of Medline, PubMed, and Cochrane Central Register of Controlled Trials (CENTRAL) databases yielded 22 randomized, controlled trials on perioperative administration of gabapentinoids for postoperative pain relief. Pain relief was better in the gabapentin groups compared with the control groups. The opioid-sparing effect during the first 24 h after a single dose of gabapentin 300-1200 mg, administered 1-2 h preoperatively, ranged from 20% to 62%. The combined effect of a single dose of gabapentin was a reduction of opioid consumption equivalent to 30 +/- 4 mg of morphine (mean +/- 95% CI) during the first 24 h after surgery. Metaregression analysis suggested that the gabapentin-induced reduction in the 24-h opioid consumption was not significantly dependent on the gabapentin dose. Gabapentin reduced opioid-related adverse effects, such as nausea, vomiting, and urinary retention (number-needed-to-treat 25, 6, and 7, respectively). The most common adverse effects of the gabapentinoids were sedation and dizziness (number-needed-to-harm 35 and 12, respectively). Gabapentinoids effectively reduce postoperative pain, opioid consumption, and opioid-related adverse effects after surgery. Conclusions about the optimal dose and duration of the treatment cannot be made because of the heterogeneity of the trials. Studies are needed to determine the long-term benefits, if any, of perioperative gabapentinoids.
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            Pregabalin pharmacology and its relevance to clinical practice.

            Pregabalin is a potent ligand for the alpha-2-delta subunit of voltage-gated calcium channels in the central nervous system that exhibits potent anticonvulsant, analgesic, and anxiolytic activity in a range of animal models. In addition, pregabalin has been shown to be a highly effective adjunctive therapy for partial seizures in clinical trials. Potent binding to the alpha-2-delta site reduces depolarization-induced calcium influx with a consequential modulation in excitatory neurotransmitter release. Pregabalin has no demonstrated effects on GABAergic mechanisms. Pregabalin demonstrates highly predictable and linear pharmacokinetics, a profile that makes it easy to use in clinical practice. Absorption is extensive, rapid, and proportional to dose. Time to maximal plasma concentration is approximately 1 h and steady state is achieved within 24-48 h. These characteristics reflect the observed onset of efficacy as early as day two in clinical trials. High bioavailability, a mean elimination half life (t(1/2)) of 6.3 h, and dose-proportional maximal plasma concentrations and total exposures predict a dose-response relationship in clinical practice and allow an effective starting dose of 150 mg/day in clinical practice without need for titration. Administration with food has no clinically relevant effect on the amount of pregabalin absorbed, providing for a dosing regimen uncomplicated by meals. Pregabalin does not bind to plasma proteins and is excreted virtually unchanged (<2% metabolism) by the kidneys. It is not subject to hepatic metabolism and does not induce or inhibit liver enzymes such as the cytochrome P450 system. Therefore, pregabalin is unlikely to cause, or be subject to, pharmacokinetic drug-drug interactions--an expectation that has been confirmed in clinical pharmacokinetic studies. However, dose adjustment may be necessary in patients with renal insufficiency. Thus, the pharmacological and pharmacokinetic profiles of pregabalin provide a predictable basis for its use in clinical practice.
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              Intravenous dexmedetomidine, but not midazolam, prolongs bupivacaine spinal anesthesia.

              Midazolam has only sedative properties. However, dexmedetomidine has both analgesic and sedative properties that may prolong the duration of sensory and motor block obtained with spinal anesthesia. This study was designed to compare intravenous dexmedetomidine with midazolam and placebo on spinal block duration, analgesia, and sedation in patients undergoing transurethral resection of the prostate. In this double-blind randomized placebo-controlled trial, 75 American Society of Anesthesiologists' I and II patients received dexmedetomidine 0.5 microg . kg(-1), midazolam 0.05 mg . kg(-1), or saline intravenously before spinal anesthesia with bupivacaine 0.5% 15 mg (n = 25 per group). The maximum upper level of sensory block and sensory and motor regression times were recorded. Postoperative analgesic requirements and sedation were also recorded. Sensory block was higher with dexmedetomidine (T 4.6 +/- 0.6) than with midazolam (T 6.4 +/- 0.9; P < 0.001) or saline (T 6.4 +/- 0.8; P < 0.001). Time for sensory regression of two dermatomes was 145 +/- 26 min in the dexmedetomidine group, longer (P < 0.001) than in the midazolam (106 +/- 39 min) or the saline (97 +/- 27 min) groups. Duration of motor block was similar in all groups. Dexmedetomidine also increased the time to first request for postoperative analgesia (P < 0.01 compared with midazolam and saline) and decreased analgesic requirements (P < 0.05). The maximum Ramsay sedation score was greater in the dexmedetomidine and midazolam groups than in the saline group (P < 0.001). Intravenous dexmedetomidine, but not midazolam, prolonged spinal bupivacaine sensory blockade. It also provided sedation and additional analgesia.
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                Author and article information

                Journal
                J Pain Res
                J Pain Res
                JPR
                jpainres
                Journal of Pain Research
                Dove
                1178-7090
                30 September 2019
                2019
                : 12
                : 2807-2814
                Affiliations
                [1 ]Department of Anesthesiology and Surgical Intensive Care, Faculty of Medicine, Tanta University , Tanta 31527, Egypt
                Author notes
                Correspondence: Amany F Omara Department of Anesthesiology and Surgical Intensive Care, Faculty of Medicine, Tanta University , Tanta, EgyptTel +20401008372249 Email amanyfaheem2011@yahoo.com
                Article
                216184
                10.2147/JPR.S216184
                6777433
                © 2019 Omara et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                Page count
                Figures: 2, Tables: 4, References: 23, Pages: 8
                Categories
                Original Research

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