Ketamine Solution Research Articles

Dual-responsive in situ gelling polymer matrix for tunable ketamine general anesthesia in experimental animals

Animal experimentation is a critical part of the drug development process and pharmaceutical research. General anesthesia is one of the most common procedures. Careful administration and dosing of anesthetics ensure animal safety and study success. However, repeated injections are needed to maintain anesthesia, leading to adverse effects. Ketamine, a dissociative anesthetic, is commonly used for inducing anesthesia in animals and suffers from a short half-life requiring repeated dosing. Herein, we report a novel system for controlled anesthesia post-intraperitoneal administration. A polymer solution called “premix” was developed using two stimuli-responsive polymers, Pluronic (PF) and Carbopol (CP). As the premix was mixed with ketamine solution and injected, it underwent in situ gelation, hence controlling ketamine release and anesthesia. The PF and CP concentrations were optimized for the gelation temperature and viscosity upon mixing with the ketamine solution. The optimal premix/ketamine formulation (1.5:1) was liquid at room temperature and gel at physiological conditions with favorable mucoadhesion and rheology. Premix retarded the release of ketamine, translating to tunable anesthesia in vivo. Anesthesia duration and recovery were tunable per ketamine dose with minimal side effects. Therefore, we propose the implementation of PF/CP premix as a vehicle for general anesthesia in animals for optimal duration and effect.

Ketamine Induced Bladder Fibrosis Through MTDH/P38 MAPK/EMT Pathway.

Purpose: Ketamine is an anesthetic in clinical, but it has also been used as an abusing drug due to its low price and hallucinogenic effects. It is proved that ketamine abusing would cause multiple system damage including the urinary system, which is called ketamine-induced cystitis (KIC). Bladder fibrosis is late stage in KIC and threaten abusers’ life. This study aimed to investigate the molecular mechanism of ketamine-induced bladder fibrosis. Methods: Female Sprague Dawley (SD) rats were randomly divided into 3 groups. 2 groups were treated with tail vein injection of ketamine (25 mg/kg/day, 50 mg/kg/day ketamine hydrochloride solution, respectively) for 12 weeks, whereas the control group was treated with normal saline solution. In each group, rat bladders were extracted and samples were examined for pathological and morphological alterations via hematoxylin and eosin (HE) staining, Masson’s trichrome staining and immunohistochemistry (IHC). SV-HUC-1 cells were treated with different concentrations of ketamine solution (0, 0.1, 0.5, 1 mmol/L). Rat bladder and SV-HUC-1 cells were extracted protein and RNA for Western blot and RT-PCR detection. Metadherin (MTDH) siRNAs and overexpression plasmids were used to knock down and overexpress the relative genes. P38 mitogen-activated protein kinase (MAPK) inhibitor was utilized to inhibit the MAPK pathway. Results: Rats in the ketamine group exhibited fibrosis compared to rats of the control group and fibrosis were also markedly upregulated in SV-HUC-1 cells after treated with ketamine, which were ketamine concentration-dependent. After treating with ketamine in SV-HUC-1 cells, there was an increase expression of MTDH, epithelial-mesenchymal transition (EMT) markers, P38 MAPK. MTDH knockdown would suppresses P38 MAPK/EMT pathway to inhibit fibrosis, however, MTDH overexpression could promote the pathway in SV-HUC-1 cells. Conclusion: In rats and SV-HUC-1 cells ketamine-treated models, MTDH can regulate EMT through the P38 MAPK pathway to regulate the process of bladder fibrosis.

This Month in Anesthesiology

This Month in Anesthesiology

Stability of 10-mg/mL and 50-mg/mL ketamine oral solutions.

Ketamine is an anesthetic agent commonly used for the induction of anesthesia. Ketamine is also given to control pain, for treatment of posttraumatic stress disorder, and to induce bronchodilation in refractory asthma. Moreover, ketamine therapy is gaining ground as an intervention for patients with treatment-resistant depression and individuals who have depression with serious suicidal ideation. Recently, the drug has been used to disrupt maladaptive reward memories in individuals with harmful alcohol consumption behaviors. The stability of 10-mg/mL and 50-mg/mL ketamine solutions stored at ambient and refrigeration temperatures was assessed over 90 days. Three batches of 10-mg/mL and 50-mg/mL ketamine solutions were stored for 90 days under two temperature conditions (2°C-8°C and 22°C-25°C) in amber plastic bottles. Chemical stability was assessed using a stability-indicating high-performance liquid chromatography assay. At each study time, visual inspection and pH assessments of ketamine concentration and pH were conducted. For all solutions tested at each condition, the ketamine concentration remaining was at least 98% of the initial concentration over 90 days of storage. Throughout the study period, solution pH remained stable and the color and odor of the suspensions remained unchanged. Extemporaneously compounded 10-mg/mL and 50-mg/mL oral solutions of ketamine prepared in a flavored suspending excipient and stored in amber polypropylene plastic bottles were stable for at least 90 days at both ambient and refrigeration temperatures.

Indices Changes of Central Hemodynamics at Carry Out Anesthesia with Keeping Independent Breathing at Children

Introduction: The aim of study was to research hemodynamic shifts in conditions of carry out combinedanesthesia on the base of isoflurane with preservation of spontaneous breathing at small surgical operationsin children.Materials and Method: The research was carried out at 44 sick children at the age from 3 to 14 years withinguinal and inguinal hernias (41,7 %), hydrocele was (19,4 %) section of abscesses and suppurations were(38,9%). The duration of anesthesia benefit at 58,3 % patients was from 30 to 40 minutes, at 40,66 % it wasabout 60 minutes.Results: The clinical monitoring was performed with study AP, HR and oxygen. For objective evaluationof cardiovascular functional condition, the echocardiography way was use. The first group patients wereintroduced intravenously the ketamine solution in doze 3 mgr/kg of body weight, propofole in dose 2 mgr/kg of body weight and izoflurane up to 3 ob % in 30-40 minutes after premedication. The second grouppatients were introduced intravenously the ketamine solution in dose 4-5 mgr/body weight and sibazone indose 0,4 mgr/kg.Conclusion: Complex clinical study and taken results of hemodynamic parameters showed the efficiency ofcarried out anesthesia with safety of independent breathing at small surgical operations at children.

Accuracy of the Securetec DrugWipe 6s Ketamine device in detecting acute and residual salivary ketamine following a stepwise intravenous treatment protocol

To evaluate the sensitivity of the Securetec DrugWipe 6 S Ketamine device in detecting salivary ketamine, we administered three fixed, increasing sub-anaesthetic doses of intravenous ketamine solution to 20 participants using an open-label, within subjects’ protocol. Results indicated, at a cut-off level of 5 ng/mL for ketamine in oral fluid, the Securetec DrugWipe 6 S Ketamine device indicated a uniformly positive result for the presence of ketamine during the acute dosing phase where corresponding mean whole blood ketamine concentrations were 0.38 mg/L (dose 1), 0.48 mg/L (dose 2) and 0.82 mg/L (dose 3), respectively. At 2-hours post treatment, the positive detection rate was 85% where corresponding mean whole blood concentrations of ketamine were 0.21 mg/L. Device detection rate reduced to 40% at 4-hours post-treatment.

Effects of ketamine on orientation selectivity and variability of neuronal responses in primary visual cortex

The plasticity of the adult brain is one of the most highly evolving areas of recent neuroscience research. It has been acknowledged that the visual cortex in adulthood can adapt and restructure the neuronal connections in response to a sensory experience or to an imposed input such as in adaptation or ocular deprivation protocols. In order to understand the basic cellular mechanisms of plasticity in the primary visual cortex (V1), we examined the effects of ketamine, a non-competitive, glutamatergic NMDAR (N-methyl-D-aspartate receptor) antagonist, on the orientation of cortical cells by measuring their response variability and the Gaussian tuning curves in adult anesthetised mouse and cat. Neurons were recorded extracellularly using glass electrodes. The ketamine was applied locally by placing a custom-cut filter paper (1x1mm) soaked in ketamine solution (10 mg/ml) on the cortical surface next the site of the recording tip, in both species. Our results show that the local and acute exposure of ketamine on V1 changes the preferred orientation of the visual neurons established during the critical period of development. Furthermore, ketamine also leads to a decrease in the orientation selectivity (measured by orientation selectivity index, OSI) and the variability of neuronal evoked responses (measured by Fano factor), but does not affect spontaneous activity. These results suggest that ketamine induces plasticity in V1 neurons that might be operated by a different pathway than that of NMDARs.

Clinical case of postoperative anesthesia of a patient by using subanesthetic dose of ketamine in severe abdominal pathology

Pain is an inevitable consequence of surgical interventions in children, resulting in great stress and discomfort not only for patients but also for their parents. The intensity of the pain depends not only on the level of injury after the operation, but also on the localization and the nature of the procedure. Management of pain in children is best done through a multimodal approach: opioids, auxiliary drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs) and acetaminophen, anti-neuroleptics such as gabapentin, and regional anesthetic methods. Postoperative anesthesia in abdominal surgery at present is a topical problem in anesthetic practice. In this clinical case, we would like to demonstrate the experience of applying post-operative anesthesia using subnormal dosages of ketamine. The patient was given anesthesia with prolonged infusion of a ketamine solution in a submorbid dose of 0.2 mg/kg/h IV. An assessment of the quality of anesthesia by assessing the level of stress markers, such as blood glucose, cortisol levels, and the assessment of the pain level on the NIPS scale was performed. Conclusion: The use of a ketamine solution in a dose of 0.2 mg/kg/h has a positive effect on treating postoperative pain in patients after severe abdominal surgical interventions. Applying a ketamine solution in a dose of 0.2 mg/kg/h reduces tolerance of the patient to opioid analgesics and the development of hyperalgesia and allodynia.

Prehospital Analgesia With Intranasal Ketamine (PAIN-K): A Randomized Double-Blind Trial in Adults

We compare intranasal ketamine with intranasal placebo in providing pain reduction at 30 minutes when added to usual paramedic care with nitrous oxide. This was a randomized double-blind study of out-of-hospital patients with acute pain who reported a verbal numeric rating scale (VNRS) pain score greater than or equal to 5. Exclusion criteria were younger than 18 years, known ketamine intolerance, nontraumatic chest pain, altered mental status, pregnancy, and nasal occlusion. Patients received usual paramedic care and were randomized to receive either intranasal ketamine or intranasal saline solution at 0.75 mg/kg. The primary outcome was the proportion of patients with VNRS score reduction greater than or equal to 2 at 30 minutes. Secondary outcomes were pain reduction at 15 minutes, patient-reported comfort, satisfaction scores, nitrous oxide consumption, and incidence of adverse events. One hundred twenty subjects were enrolled. Seventy-six percent of intranasal ketamine patients versus 41% of placebo patients reported a greater than or equal to 2-point VNRS reduction at 30 minutes (difference 35%; 95% confidence interval 17% to 51%). Median VNRS reduction at 15 minutes was 2.0 and 1.0 and at 30 minutes was 3.0 and 1.0 for ketamine and placebo, respectively. Improved comfort at 15 and 30 minutes was reported for 75% versus 57% and 61% versus 46% of ketamine and placebo patients, respectively. Sixty-two percent of patients (95% confidence interval 49% to 73%) versus 20% (95% confidence interval 12% to 32%) reported adverse events with ketamine and placebo, respectively. Adverse events were minor, with no patients requiring physical or medical intervention. Added to nitrous oxide, intranasal ketamine provides clinically significant pain reduction and improved comfort compared with intranasal placebo, with more minor adverse events.

The acute and residual effects of escalating, analgesic-range doses of ketamine on driving performance: A simulator study

Ketamine hydrochloride elicits potent psychotomimetic and neurobehavioural effects which make it incompatible with driving; however, the direct effect on driving performance is yet to be assessed. Using an open label, within-subjects protocol, 15 males and 5 females (mean age = 30.8 years) were administered three fixed, stepwise increasing sub-anaesthetic doses of intravenous (IV) ketamine solution [(i) 8 mg/h IV infusion plus 30 mg bolus, (ii) 12 mg/h IV infusion and (iii) 20 mg/h infusion]. Whole blood ketamine and norketamine concentrations were determined at each treatment step and at 2 h post-infusion. Driving performance was assessed at baseline, at each treatment step and at 2 h post-treatment using a validated computerised driving simulator. Standard Deviation of Lateral Position (SDLP) and Steering Variability (SV) were assessed. Linear Fixed Effect Modelling indicated a main effect for time (dose) for SDLP (F[4,72] = 33.22, p < 0.0001) and SV (F[4,72] = 4.65, p < 0.002). Post-hoc analyses revealed significant differences from baseline at each treatment step for SDLP (all p < 0.001), and for 12 mg/h treatment step for SV (p = 0.049). Post-treatment driving performance returned to baseline levels. Weak positive linear associations were observed between SDLP and whole blood ketamine concentrations (R2 = 0.11, β = 29.96, p = 0.001) and norketamine (R2 = 0.09, β = 28.87, p = 0.003). These findings suggest that even under highly controlled conditions, ketamine intoxication significantly alters simulated driving performance. At the highest dose, ketamine produced changes to SDLP considered incompatible with safe driving, highlighting how ketamine consumption may translate to an increased risk of road trauma.

Naked-eye quantitative assay on paper device for date rape drug sensing via smart phone APP

The present work aimed for the development of a low-cost, naked eye assay indicating the presence of date-rape drug (DRD) in the alcoholic beverages. A microfluidic paper-based analytical device (μPAD) was used as the platform to prepare this sensor. Bromocresol green (BCG; 0.04% and 5%) was used as the indicator for the colorimetric assay of DRD,.i.e., ketamine. The developed paper based strip was coated with BCG and further ketamine solution. The complexation between dye and drug lead to the change in color of the strip. The color also varied upon change in the concentration of ketamine (0.1 M, 0.01 M, 0.001 M) in the solution which forms the basis of the detection. The color change of BCG at 0.04% was not much detectable, therefore, 5% BCG concentration was chosen for development of the colorimetric sensor. The device was linked with a smart phone app which depicts the change in color and displays whether the beverage is safe or unsafe for drinking. In addition, the app sends message to selected number, if the person is in danger.

Experts Remain Enthusiastic About NMDA-Targeting Antidepressants

Experts Remain Enthusiastic About NMDA-Targeting Antidepressants

The effect of using pre-operative ketamine injection on post-tonsillectomy pain intensity in children

Introduction: Tonsillectomy in children is associated with some major complications originating from intense post-tonsillectomy pain which can distress patients, cause swallowing difficulties and discomfort, and also lead to aspiration. Thus, this study aimed to investigate the effect of using pre-operative ketamine injection on post-tonsillectomy pain intensity in children.&#x0D; Methods: This double-blind clinical trial was carried out on 60 patients undergoing elective tonsillectomy. To this end, all the patients were anaesthetized by the same method. In the first group, 2 cc of ketamine (0.5mg/kg) solution was topically injected into the soft tissue of tonsillar fossa (peritonsillar space); in the second group, a similar administration was performed but with normal saline. For all the patients, incision was made 5 minutes after injection with the Blast Dissection Snare method. Moreover, the patients’ pain intensity and analgesics consumption were measured 30 minutes, and 1, 2, 4, and 6 hours after surgery. Finally, the collected data were analyzed using the SPSS software.&#x0D; Results: The present study was conducted on 60 patients, 37 males and 23 females, with the mean age of 9.3±3.4 years. In this respect, repeated measures analysis of variance of patients’ pain scores collected in five post-operative stages showed that pain intensity in both groups was at the highest level immediately after operation; it gradually decreased during measurement stages. However, at each measurement, the pain intensity experienced in the ketamine-treated group was significantly lower than that for the placebo group.&#x0D; Conclusion: It was concluded that pre-incision topical injection of ketamine can serve as an effective method to control post-tonsillectomy throat pain.

Illicit drug ketamine induces adverse effects from behavioral alterations and oxidative stress to p53-regulated apoptosis in medaka fish under environmentally relevant exposures.

With increasing problems of drug abuse worldwide, aquatic ecosystems are contaminated by human pharmaceuticals from the discharge of hospital or municipal effluent. However, ecotoxicity data and related toxic mechanism for neuroactive controlled or illicit drugs are still lacking, so assessing the associated hazardous risk is difficult. This study aims to investigate the behavioral changes, oxidative stress, gene expression and neurotoxic or apoptosis effect(s) in larvae of medaka fish (Oryzias latipes) with environmentally relevant exposures of ketamine (KET) solutions for 1-14 days. KET exposure at an environmentally relevant concentration (0.004μM) to 40μM conferred specific patterns in larval swimming behavior during 24h. At 14 days, such exposure induced dose- and/or time-dependent alteration on reactive oxygen species induction, the activity of antioxidants catalase and superoxide dismutase, glutathione S-transferase and malondialdehyde contents in fish bodies. KET-induced oxidative stress disrupted the expression of acetylcholinesterase and p53-regulated apoptosis pathways and increased caspase expression in medaka larvae. The toxic responses of medaka larvae, in terms of chemical effects, were qualitatively analogous to those of zebrafish and mammals. Our results implicate a toxicological impact of waterborne KET on fish development and human health, for potential ecological risks of directly releasing neuroactive drugs-containing wastewater into the aquatic environment.

277 Intranasal Ketamine for Peripheral Venous Access: A Randomized Double Blind and Placebo-Controlled Study

Effectiveness of intranasal ketamine as an analgesic and sedative for pediatrIc procedures in pediatric intensive care unit (PICU) has been reported previously. Few studies avaluated IN ketamine comparing with placebo as sedative agent. Verify the efficacy of intranasal ketamine as sedative agent for venous access. Randomized, double blind, placebo-controlled study conducted at PICU from November 2015 to August 2016. Children needing venous access were randomized to receive intranasal ketamine (4mg/Kg) or normal saline solution. Groups were compared regarding the time for venous access, facility for performing the procedure, adverse events, disturbances in vital signs and perception of the accompanying adult. 39 children (21 Ketamine; 18 Placebo) were included without differences regarding to age, sex, weight, reason for hospitalization and professional experience. The median age was similar (19.8 x 15.8 months), as well as the median weight (10.0 x 11.3Kg). Ketamine reduced the length for venous access (23.0 x 67.5 seconds; p=0.01), and facilitated the procedure (p=0.00009). Ketamine induced sleepiness 15 minutes after its administration (p=0.003) and reduced the number of people for the child’s restraint (p=0.025). No difference was verified between groups regarding adverse effects or vital signs disturbances. Side effects were observed in 29% of the children in the Ketamine group and 17% in the Placebo group, irritability being the most common for both. The accompanying adult reported that 81% of children in ketamine group were calm and quiet (p=0.0003). Intranasal ketamine reduces the time for venous puncture, facilitates the procedure to the nurse, and provides a calm environment.

Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: Effects on postoperative pain and recovery profiles: A consort compliant article.

Background:Robotic or endoscopic thyroidectomy using bilateral axillo-breast approach (BABA) is frequently performed for excellent cosmesis. However, postoperative pain is remained as concerns due to the extent tissue dissection and tension during the operation. Ketamine is a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist that reduces acute postoperative pain. We evaluated the effects of intraoperative ketamine infusion on postoperative pain control and recovery profiles following BABA robotic or endoscopic thyroidectomy.Methods:Fifty-eight adult patients scheduled for BABA robotic or endoscopic thyroidectomy were randomized into a control group (n = 29) and ketamine group (n = 29). Following induction of anesthesia, patients in each group were infused with the same volume of saline or ketamine solution (1 mg/kg bolus, 60 μg/kg/h continuous infusion). Total intravenous anesthesia with propofol and remifentanil was used to induce and maintain anesthesia. Pain scores (101-point numerical rating scale, 0 = no pain, 100 = the worst imaginable pain), the consumption of rescue analgesics, and other postoperative adverse effects were assessed at 1, 6, 24, and 48 hours postoperatively.Results:Patients in the ketamine group reported lower pain scores than those in the control group at 6 hours (30 [30] vs 50 [30]; P = 0.017), 24 hours (20 [10] vs 30 [20]; P < 0.001), and 48 hours (10 [10] vs 20 [15]; P < 0.001) in neck area. No statistically significant differences were found between the 2 groups in terms of the requirements for rescue analgesics or the occurrence of adverse events.Conclusion:Intravenous ketamine infusion during anesthesia resulted in lower postoperative pain scores following BABA robotic or endoscopic thyroidectomy, with no increase in adverse events.

The Effects of Ketamine on Cognitive Function in Elderly Patients Undergoing Ophthalmic Surgery

Acute postoperative cognitive dysfunction is characterized by neurocognitive dysfunction and confusion. In this study, we compared the cognitive status of a geriatric population undergoing ophthalmic surgery, as assessed by the Short Portable Mental Status Questionnaire (SPMSQ) before and after ketamine administration. Eighty patients were enrolled and randomly assigned in a double-blind study to receive either ketamine (0.3 mg/kg dose) or physiologic solution (control group). Sixty-five (control, n = 32; ketamine, n = 33) patients completed the trial. Cognitive performance was assessed with an abbreviated version of the SPMSQ. Measurements of analgesia, sedation, intraocular pressure, and hemodynamic variables were recorded. With respect to cognitive performance, the baseline evaluation was similar for the control and ketamine groups. Postoperative evaluation showed an improvement only in the ketamine group. No increase in intraocular pressure or a secondary nystagmus was observed. The average dose of midazolam was higher in the control group, but the difference was not clinically significant. After surgery, analgesic behavior was better in the ketamine group than in the control group. There were no differences between groups in the sedation scale or in hemodynamic variables. The administration of 0.3 mg/kg ketamine during ophthalmic surgery in geriatric patients changed their cognitive status as assessed by the SPMSQ, decreased the required dose of anesthetics, and produced no increase in intraocular pressure or in hemodynamic variables. However, because the evaluation only analyzed the immediate effects of the administered drug, further research will be required to examine the impact of ketamine on the postoperative cognitive performance of geriatric patients before the drug can be formally recommended for this purpose.

Ketamine in prevention of pain during propofol injection

Background: Propofol has the disadvantage of causing pain or discomfort on injection. The aim of the study was to assess the efficacy of ketamine pretreatment to alleviate the propofol injection pain. Methods: One hundred ASA I and II adults, scheduled for various elective surgical procedures under Genral anaesthesia were included in the study. The patients were randomly divided into two groups to receive 2ml of pretreatment ketamine solution (0.2mg.kg1) or 0.9% saline intravenously. The venous drainage was occluded manually at mid arm. One fourth of the total calculated induction dose of propofol was administered over a period of 5 seconds. The patients were asked about the pain on injection. The verbal response and the behavioral signs, such as facial grimacing, arm withdrawal or tears were noted. A score of 0-3 which corresponds to no, mild, moderate and severe pain was recorded. Results: Pain was reduced significantly in the ketamine group (p<0.001) with no significant side-effects. Conclusions: We concluded that pretreatment with intravenous 0.2 mg kg-1 ketamine was effective in relieving propofol injection pain.

The effect of addition of ketamine to lidocaine on postoperative pain in rhinoplasties.

The objective of this study was to examine the effect of addition of subanesthetic doses of ketamine to an epinephrine-lidocaine solution on postoperative pain, analgesic use, and patient comfort during rhinoplasties. Ninety patients were randomly divided into three groups: Group L, lidocaine with epinephrine; Group K, lidocaine with epinephrine plus ketamine; and Group S (control group), physiological saline solution with epinephrine. The local anesthetic solution was injected as preincisionally with intranasal submucosal infiltration following induction of general anesthesia. We evaluated visual pain score, analgesic demand, Wilson sedation score, and antiemetic demand at 5, 15, and 30 min and 1, 2, 4, 6, 8, 16, and 24 h after the operation. The patient satisfaction score was checked 24 h after the operation. Visual pain score was significantly reduced in Group K in comparison with the other groups and this group did not need any rescue analgesics (P < 0.05). The postoperative patient satisfaction scores were highest in Group K compared with the other groups (P < 0.05). Addition of ketamine solution to lidocaine for infiltration block during rhinoplasty was successful in decreasing pain during postoperative periods and reducing analgesic consumption during the first 24 h after the operation.

Long-Term Stability of Tramadol and Ketamine Solutions for Patient-Controlled Analgesia Delivery

BackgroundSubanesthetic doses of ketamine as an adjuvant to tramadol in patient-controlled analgesia (PCA) for postoperative pain have been shown to improve the quality of analgesia. However, there are no such commercially available drug mixtures, and the stability of the combination has rarely been assessed.Material/MethodsAdmixtures were assessed for periods of up to 14 days at 4°C and 25°C. Three different mixtures of tramadol and ketamine (tramadol 5.0 mg/mL + ketamine 0.5 mg/mL, tramadol 5.0 mg/mL + ketamine 1.0 mg/mL, and tramadol 5.0 mg/mL + ketamine 2.0 mg/mL) were prepared in polyolefin bags by combining these 2 drugs with 0.9% sodium chloride (normal saline [NS]). The chemical stability of the admixtures was evaluated by a validated high-performance liquid chromatography (HPLC) method and by measurement of pH values. Solution appearance and color were assessed by observing the samples against black and white backgrounds. Solutions were considered stable if they maintained 90% of the initial concentration of each drug.ResultsThe percentages of initial concentration of tramadol and ketamine in the various solutions remained above 98% when stored at 4°C or 25°C over the testing period. No changes in color or turbidity were observed in any of the prepared solutions. Throughout this period, pH values remained stable.ConclusionsThe results indicate that the drug mixtures of tramadol with ketamine in NS for PCA delivery systems were stable for 14 days when stored in polyolefin bags at 4°C or 25°C.