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      Physicochemical stability of ternary admixtures of butorphanol, ketamine, and droperidol in polyolefin bags for patient-controlled analgesia use

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          Delivery of drug admixtures by intravenous patient-controlled analgesia is a common practice for the management of postoperative pain; however, analytical confirmation of the compatibility and stability of butorphanol tartrate, ketamine hydrochloride, and droperidol combined in ternary admixtures is not available.


          Butorphanol tartrate, ketamine hydrochloride, and droperidol have been examined for compatibility and stability when combined with 0.9% sodium chloride injection stored at 4°C and 25°C with light protection for a total of 14 days. Concentrations were 0.067 mg/mL, 1.33 mg/mL, and 0.033 mg/mL for butorphanol tartrate, ketamine hydrochloride, and droperidol, respectively. Drug concentrations were determined using high-performance liquid chromatographic analysis.


          All three drugs were very stable (>97%) at 4°C and 25°C for 14 days. The ternary admixtures were initially clear and colorless throughout the observation period, and the pH value did not change significantly.


          The results confirm that the ternary admixture of butorphanol tartrate 0.067 mg/mL, ketamine hydrochloride 1.33 mg/mL, and droperidol 0.033 mg/mL in 0.9% sodium chloride injection were stable for 14 days when stored in polyolefin bags at 4°C and 25°C and protected from light.

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          Most cited references 42

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          Multimodal therapies for postoperative nausea and vomiting, and pain.

          Postoperative nausea and vomiting (PONV) and pain are two of the major concerns for patients presenting for surgery. The causes of PONV are multifactorial and can largely be categorized as patient risk factors, anaesthetic technique, and surgical procedure. Antiemetics work on several different receptor sites to prevent or treat PONV. This is probably why numerous studies have now demonstrated that using more than one antiemetic is usually more effective and results in fewer side-effects than simply increasing the dose of a single antiemetic. A multimodal approach to PONV should not be limited to drug therapy alone but should involve a holistic approach starting before operation and continuing intraoperatively with risk reduction strategies to which are added prophylactic antiemetics according to the assessed patient risk for PONV. With the increasing understanding of the pathophysiology of acute pain, especially the occurrence of peripheral and central hypersensitization, it is unlikely that a single drug or intervention is sufficiently broad in its action to be adequately effective, especially with moderate or greater pain. Although morphine and its congeners are usually the foundation of pain management regimens, as their dose increases so does the incidence of side-effects. Thus, the approach for the management of acute postoperative pain is to use multiple drugs or modalities (e.g. regional anaesthesia) to maximize pain relief and reduce side-effects.
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            Adding ketamine to morphine for intravenous patient-controlled analgesia for acute postoperative pain: a qualitative review of randomized trials.

            In experimental trials, ketamine has been shown to reduce hyperalgesia, prevent opioid tolerance, and lower morphine consumption. Clinical trials have found contradictory results. We performed a review of randomized, double-blinded clinical trials of ketamine added to opioid in i.v. patient-controlled analgesia (PCA) for postoperative pain in order to clarify this controversy. Our primary aim was to compare the effectiveness and safety of postoperative administered ketamine in addition to opioid for i.v. PCA compared with i.v. PCA with opioid alone. Studies were identified from the Cochrane Library 2003, MEDLINE (1966-2009), and EMBASE (1980-2009) and by hand-searching reference lists from review articles and trials. Eleven studies were identified with a total of 887 patients. Quality and validity assessment was performed on all trials included using the Oxford Quality Scale with an average quality score of 4.5. Pain was assessed using visual analogue scales or verbal rating scales. Six studies showed significant improved postoperative analgesia with the addition of ketamine to opioids. Five studies showed no significant clinical improvement. For thoracic surgery, the addition of ketamine to opioid for i.v. PCA was superior to i.v. PCA opioid alone. The combination allows a significant reduction in pain score, cumulative morphine consumption, and postoperative desaturation. The benefit of adding ketamine to morphine in i.v. PCA for orthopaedic or abdominal surgery remains unclear. Owing to huge heterogeneity of studies and small sample sizes, larger double-blinded randomized studies showing greater degree of homogeneity are required to confirm these findings.
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              Evaluation of physicochemical incompatibilities during parenteral drug administration in a paediatric intensive care unit.

              Patients in paediatric intensive care units (PICU) often receive numerous medications by the parenteral route. Frequently two or more drugs are delivered simultaneously through the same line and the risk of physicochemical incompatibilities is thus important. The objectives of this study were 1) to identify prospectively the combinations of injectable drugs administered in the PICU of our university hospital and 2) to analyze them according to information found in the literature. The data were collected by a pharmacist over a 30-day period and classified in three categories: compatible, incompatible and undocumented. Nineteen patients were included in the study with a median age of 3.2 years. The mean number (+/- SD) of injectable drugs per patient and per day was 6.5 (+/- 2.8), for a total of 26 drugs and 7 solutes. 64 combinations of drugs were observed with 2 (31.3%), 3 (45.3%), 4 (10.9%) or 5 (12.5%) drugs. 81 drug-drug and 94 drug-solute combinations were recorded. Among these, 151 (86.3%) were compatible, 6 (3.4%) incompatible and 18 (10.3%) undocumented. The incompatibilities included furosemide (Lasix), a drug in alkaline solution and Vamina-Glucose, a total parenteral nutrition solution. No clinical consequences resulting from drug incompatibilities were shown in this study. We suggest that in vitro compatibility tests on standard drug combinations, as well as a training program for nurses on drug incompatibility problems would sensitively increase the security of parenteral drug administration.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                24 November 2016
                : 10
                : 3873-3878
                [1 ]Department of Pharmacy, Dongfeng Hospital
                [2 ]Department of Pharmacy
                [3 ]Department of Anesthesiology, Renmin Hospital, Hubei University of Medicine, Hubei, People’s Republic of China
                Author notes
                Correspondence: Xiao-ya Shi, Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, No 16 Daling Road, Shiyan, Hubei, 442008, People’s Republic of China, Email dfyyshixiaoya@ 123456sina.com
                © 2016 Fang 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.

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