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      Efficacy of ondansetron for the prevention of propofol injection pain: a meta-analysis

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          This review was performed to investigate the effect of ondansetron on the prevention of propofol injection pain.


          PubMed, Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched for randomized controlled trials (RCTs) of ondansetron in preventing the pain on injection of propofol. Then, RevMan 5.2 was adopted to conduct a meta-analysis on propofol injection pain.


          Ten RCTs, totaling 782 patients, were included in this analysis. The meta-analysis showed that: 1) compared with the control group, the ondansetron group was related to a decreasing incidence of propofol injection pain, and it was statistically significant (risk ratio [RR] = 0.41, 95% confidence interval [CI, 0.34, 0.49], P < 0.00001); 2) compared with the incidence of propofol injection pain in the lidocaine group, there was no difference and no statistical significance (RR = 1.28, 95% CI [0.85, 1.93], P = 0.25); 3) no statistically significant differences were found between the ondansetron and magnesium sulfate groups in the incidence of propofol injection pain (RR = 1.20, 95% CI [0.87, 1.66], P = 0.27); and 4) the incidence of ondansetron group igniting moderate pain (RR = 0.37, 95% CI [0.26, 0.52], P < 0.00001) and severe pain (RR = 0.27, 95% CI [0.17, 0.43] P < 0.00001) was less likely to occur during the injection of propofol compared with the control group, but there was no difference between the ondansetron and control groups in the incidence of mild propofol injection pain (RR = 0.83, 95% CI [0.63, 1.10], P = 0.20).


          Ondansetron can effectively prevent propofol injection pain, and the effect is similar to that of magnesium sulfate and lidocaine.

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          Most cited references 16

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          Propofol: the challenges of formulation.

          Propofol is a potent lipophilic anesthetic that was initially formulated in Cremophor El for human use. Because of the occurrence of Cremophor EL anaphylaxis and improvements in the quality of lipid emulsions, it was ultimately brought to market as 1% propofol formulated in 10% soybean oil emulsion. Emulsions represent complex formulation compositions whose suitability for intravenous administration is dependent on a number of factors. Despite the success of propofol emulsions, drawbacks to such formulations include inherent emulsion instability, injection pain, a need for antimicrobial agents to prevent sepsis, and a concern of hyperlipidemia-related side effects. Efforts to overcome such drawbacks have involved the development of propofol emulsions with altered propofol and lipid contents, the addition of different excipients to emulsions for antimicrobial activity, and study of nonemulsion formulations including propofol-cyclodextrin and propofol-polymeric micelle formulations. In addition, a number of propofol prodrugs have been made and evaluated.
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            Ondansetron pretreatment to alleviate pain on propofol injection: a randomized, controlled, double-blinded study.

            We used a randomized, controlled, double-blinded design to study the effect of ondansetron (OND) pretreatment on the pain produced by the IV injection of propofol. Eighty patients were randomly assigned to one of two groups: Group I received 2 mL of IV 0.9% saline pretreatment, and Group II received OND (4 mg in 2 mg/mL solution) pretreatment in the dorsum of the hand, followed by propofol 1 min later. Pain was reduced significantly in the OND group (P<0.05). Approximately one third of the patients in each group had myoclonic movements or skin rashes in the limb that received propofol. We conclude that the OND pretreatment may be used to reduce the incidence of pain on injection of propofol and to prevent postoperative nausea and vomiting. In a double-blinded, controlled study, IV ondansetron (4 mg) pretreatment was used to alleviate pain on injection of propofol. Ondansetron was successful in relieving pain without any adverse effect in a significant number of patients.
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              Pain on injection with microemulsion propofol.

              To evaluate the incidence and severity of injection pain caused by microemulsion propofol and lipid emulsion propofol in relation to plasma bradykinin generation and aqueous free propofol concentrations. Injection pain was evaluated in 147 patients. Aqueous free propofol concentrations in each formulation, and in formulation mixtures containing agents that reduce propofol-induced pain, were measured by high-performance liquid chromatography. Plasma bradykinin concentrations in both formulations and in their components mixed with blood sampled from six volunteers were measured by radioimmunoassays. Injection pain caused by 8% polyethylene glycol 660 hydroxystearate (PEG660 HS) was evaluated in another 10 volunteers. The incidence of injection pain [visual analogue scale (VAS) >30 mm] caused by microemulsion and lipid emulsion propofol was 69.7 and 42.3% (P < 0.001), respectively. The median VAS scores for microemulsion and lipid emulsion propofol were 59 and 24 mm, respectively (95% confidence interval for the difference 12.5, 40.0). The aqueous free propofol concentration of microemulsion propofol was seven times higher than that of lipid emulsion propofol. Agents that reduce injection pain did not affect aqueous free propofol concentrations. Microemulsion propofol and 8% PEG660 HS enhanced plasma bradykinin generation, whereas lipid emulsion propofol and lipid solvent did not. PEG660 HS did not cause injection pain. Higher aqueous free propofol concentrations of microemulsion propofol produce more frequent and severe pain. The plasma kallikrein-kinin system may not be involved, and the agents that reduce injection pain may not act by decreasing aqueous free propofol concentrations.

                Author and article information

                J Pain Res
                J Pain Res
                Journal of Pain Research
                Journal of Pain Research
                Dove Medical Press
                21 February 2017
                : 10
                : 445-450
                [1 ]Department of Anesthesiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning
                [2 ]Zhaoqing Medical College, Zhaoqing, People’s Republic of China
                Author notes
                Correspondence: Bing Huang, Department of Anesthesiology, Affiliated Tumor Hospital of Guangxi Medical University, 71 River Road, Nanning, Guangxi 532100, People’s Republic of China, Fax +86 771 533 0700, Email Huangbing187@ 123456126.com

                These authors contributed equally to this work

                © 2017 Pei 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.

                Original Research

                Anesthesiology & Pain management

                meta-analysis, propofol injection pain, ondansetron


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