Ketamine Treatment Options

Ketamine is an IV anesthetic with non-opioid analgesic properties that has been shown to reduce pain while also decreasing intraoperative and postoperative opioid requirements when used in subanesthetic doses after a variety of surgical procedures.1 It is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, and by this mechanism ketamine is believed to block the development of central sensitization and wind-up phenomenon,2,3 which may be helpful in preventing acute and chronic pain after repetitive insults. In a systematic review of ketamine as an adjuvant to opioid analgesia, low-dose ketamine was found to be a useful addition to standard postoperative pain management practice with opioids in 54% of studies.1 The studies that did not show a significant effect were in patient populations with low opioid requirements. Therefore, it has been suggested that future clinical trials be focused on patient populations with significant post-operative pain, such as spine surgery and major orthopedic surgery not amenable to regional analgesia, and postoperative pain in patients on chronic preoperative opioid therapy.1 There are few studies examining outcomes after ketamine in the perioperative period after spine surgery. Loftus et al randomized patients with a history of chronic preoperative opioid use (i.e., daily opiate use for at least 6 weeks) to intraoperative ketamine versus placebo and found a 30% reduction in morphine consumption at 48 hours and an approximately 25% reduction in visual analog scale (VAS) pain score in the post anesthesia care unit and at 6 weeks.4 Although this study provided evidence that there may be reduction in long-term postoperative pain, additional studies are needed to provide evidence that this effect is sustained beyond the 6-week period. We are interested in examining ketamine more closely in spine surgery because this patient population experiences significant postoperative pain that may be difficult to control due to preoperative opioid use (i.e., opioid tolerance). The investigators chose to study ACDF patients specifically because it is a common spine procedure throughout the United States and the patients have significant opioid requirements postoperatively. In a study examining the effects of the low dose ketamine for postoperative IV PCA fentanyl after cervical and lumbar surgery, patients in the placebo group (and thus only receiving fentanyl PCA) reported mean VAS scores of 4-5 with movement while receiving opioids.5 Further, while previous studies have shown an opioid-sparing effect of ketamine as measured by opioid consumption and a decrease in pain as measured by VAS scores, no study to our knowledge has examined quality of recovery after intraoperative ketamine infusion. The Quality of recovery (QoR-40) score was developed by Myles et al to assess quality of recovery after anesthesia based on forty questions in five dimensions,6 and this score has been shown to be a reliable and valid outcome for patients undergoing both spine and cranial surgery.7 QoR-40 is also of interest because it should be able to provide a global assessment of the possible benefit or harm of using ketamine in patients by simultaneously characterizing the detrimental side effects as well as the positive benefits of ketamine when used as an infusion at subanesthetic levels (studies thus far have shown that there are minimal side effects such as hallucinations).1,4 Significance: Previous studies have shown an opioid-sparing effect of ketamine, however further research is warranted in patients whose pain may be difficult to control and whether this effect is sustained. ACDF patients experience significant pain post-operatively, and ketamine may improve their quality of recovery due to its opioid-sparing effects and prevention of chronic pain. Further, patient centered outcomes as measured by the QoR-40 have not been reported in the literature when ketamine, or other opioid sparing anesthetics, have been administered. This study will not only determine if the "moderate" dose of ketamine is beneficial or detrimental to the recovery of patients but also whether it can improve long term patient function, presumably by decreasing central pain sensitization. In addition, this study will set the stage for further RCT's examining other analgesic strategies in cervical spine surgery patients (i.e., intraoperative lidocaine infusions, volatile anesthetic vs. propofol as the primary hypnotic, COX-2 inhibitors, pregabalin, etc.). The overall goal would be to develop a multi-faceted regimen that decreases the postoperative inpatient opioid requirements of these patients and may facilitate long term recovery. The research questions:Does ketamine improve the quality of recovery at 24 hours after anterior cervical discectomy and fusion (ACDF)? The hypothesis: the investigators hypothesize that ketamine will improve the quality of recovery after ACDF surgery Read Less

Background: The poor prognosis and public health burden of PTSD necessitates the development of more effective and broader treatment approaches. In the etiopathogenesis of PTSD, trauma memories become ingrained into key brain areas through conditioned learning and are triggered by various situations of daily life. The brain glutamate system plays a key role in the process of trauma learning and trauma memories via long-term potentiation. Ketamine administration modulates the glutamate system and has been used in the treatment of depression and PTSD. Previous studies demonstrate that a single low dose of ketamine rapidly improves symptoms of refractory PTSD and treatment resistant depression. Unfortunately the observed response is short-lived (4-7 days, maximum up to 2 weeks) and multiple doses often produce unacceptable side effects. TIMBER (Trauma Interventions using Mindfulness Based Extinction and Reconsolidation for trauma memory) psychotherapy, is a manualized and translational mindfulness based cognitive behavioral therapy specifically designed to target trauma memories and their expressions in PTSD patients. The placebo controlled pilot study examined the efficacy of a protocol combining a single infusion of low dose ketamine (0.5mg/kg) and TIMBER psychotherapy in subjects suffering from chronic PTSD. The objective of this pilot study was to optimize and individualize treatment of chronic PTSD using a rapid, effective, trauma specific, user friendly and inexpensive approach that uses cutting edge psychopharmacological combined with novel psychotherapeutic approaches. Methodology: The randomized, double blind, placebo-controlled pilot study used a crossover design. Ten subjects with refractory PTSD were assigned to one of two arms: one arm (n=5) received combined ketamine infusion and TIMBER therapy (TIMBER-K arm) and the second (n=5) received combined placebo (normal saline) infusion and TIMBER therapy (TIMBER-P arm). All 10 subjects received a short version of TIMBER therapy after 10 minutes of onset of the infusion in which reactivation of trauma memories was initiated in a controlled manner using standardized scales and scripted narrative of the index trauma. This was followed by a standardized mindfulness based cognitive therapy module to quickly de-escalate the arousal symptoms followed by induction of detached observation and reappraisal of the trauma experience. After completion of the 40-min infusion, all subjects were trained on the full version of TIMBER therapy using methods of mindfulness based graded exposure therapy and a twice-daily schedule of home practice was initiated. The investigators are currently in a process of recruiting fifty more subjects to examine the effects in a larger sample. Read Less

The purpose of this study is to test whether ketamine and D-cycloserine can be safely and effectively used for the treatment of depression. The investigators hypothesize that ketamine will serve as a rapid acting and safe antidepressant in patients with bipolar depression, and furthermore, that D-cycloserine will serve as an effective therapy following ketamine treatment. Read Less

To evaluate the safety and effectiveness of Wafermine administered with and without an opioid medication for acute pain following bunionectomy surgery. Read Less

Dosing of medications is based on the plasma level achieved with a given dose and how long the medicine remains in the body. This study is called pharmacokinetics-that is, what the body does to the medication. Ketamine is an intravenous medication used for anesthesia and sedation in children. However the pharmacokinetics of Ketamine has not been systematically studied. We propose to study the pharmacokinetics of ketamine in different age groups of children ranging from infants to teenagers. Read Less

This study investigates the common features of electrophysiological measures in schizophrenia and effects of NMDA antagonist ketamine in healthy volunteers. Read Less

Depression is common in patients with cancer. Current medications for depression, while effective, take several weeks to take effect. Ketamine has emerged as a drug with promise for cancer patients. In two reported cases, a single dose of ketamine induced rapid and moderately sustained symptom reduction in depression and anxiety with no adverse side effects. Benefit was seen in as little as 1 hour and sustained up to 30 days. This study is a randomized, double-blind, placebo-controlled investigation testing whether a single dose of ketamine improves depression and anxiety relative to placebo in patients with cancer. Read Less

The primary objectives of the study are to evaluate the efficacy of subdissociative dose intravenous ketamine compared with intravenous morphine in relieving acute pain in the ED. Secondary objectives will include the rate of adverse effects and need for rescue analgesia. The hypothesis is that intravenous administration of subdissociative dose ketamine at 0.3 mg/kg is superior to intravenous morphine at 0.1mg/kg in treating moderate and severe acute pain in patients presenting to the ED. Read Less

Ketamine, an FDA approved anesthetic agent, is becoming the sedative/analgesic of choice for emergency sedation in children because it causes deep sedation with minimal respiratory depression in comparison to other available agents. However, emergence reactions are an important adverse effect of ketamine, characterized by transient changes in cognitive function, dissociation and mild schizophrenia-like symptoms. These cognitive and behavioral effects are dose-dependently induced by ketamine and other antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor. NMDA receptor hypofunction can disinhibit excitatory (cholinergic/glutamatergic) projections in key areas of the brain, and this has been proposed to explain key features of schizophrenia. Several treatments that block excessive excitatory transmitter release have also been shown to prevent cognitive and behavioral effects of ketamine-induced NMDA receptor hypofunction in humans. Alpha-2 adrenergic agonists, which can presynaptically inhibit acetylcholine release, can prevent mild ketamine-induced behavioral and cognitive symptoms in healthy human adults. However, this prevention strategy has not been evaluated in children. Children currently receive clinically-indicated treatment with the NMDA antagonist, ketamine, and this age group is an important target for pharmacological strategies aimed at the prevention of schizophrenia. This application proposes a double-blind, placebo-controlled, randomized trial to test the safety and effectiveness of dexmedetomidine, an FDA approved alpha-2 adrenergic agonist, in preventing ketamine-induced mental symptoms in children. Planned primary analyses will evaluate effects of the hypothesized prevention treatment on clinical and cognitive variables using analysis of variance (ANOVA). The proposed experiments are relevant to future prevention trials for individuals at risk for schizophrenia, and to preventing adverse effects of NMDA antagonist anesthetic agents (ketamine, nitrous oxide). Read Less

The purpose of this study is to: 1. Establish whether ketamine can decrease opioid consumption and modulate the onset of opioid tolerance and prevent opioid-induced hyperalgesia in pediatric subjects, ages 10 years to 18 years, undergoing posterior spinal fusion and instrumentation. Read Less

Burn-related pain is severe and often difficult to manage. Healthcare workers struggle with keeping burn patients comfortable, especially when these patients undergo dressing changes of their burn wounds of their skin since these procedures often cause severe pain. Patients with burn wounds frequently require high doses of opioids (narcotics) and calming (anxiolytic) agents to the extent that clinicians must weigh the risks associated with these doses against achieving adequate analgesia and comfort. The biggest risk is over-sedation to cause breathing troubles. Inadequate pain control during these procedures heightens pain perception, anxiety, and fear surrounding the experience and may lead to patients experiencing additional psychological disorders like depression, acute stress disorder (ASD), and post-traumatic stress disorder (PTSD). Therefore, therapeutic options for better management of pain and anxiety during these procedures need to be identified. This study will address whether the addition of ketamine during dressing changes improves patients' pain control and comfort and whether this leads to favorable psychological outcomes. The study is designed to compare ketamine with placebo when they are added to usual care (opioids and anxiolytics) during dressing changes. The main outcomes of the study will be the amount of opioid and anxiolytic agents each group receives during their procedure; the presence of pain-related anxiety shortly after the procedures; blood markers of stress during the procedures; and the presence of depression, anxiety and stress disorders prior to discharge. This study will assess whether the early administration of ketamine reduces pain and anxiety to prevent the need for high doses of opioids and anxiolytics. A total of 30 patients will be enrolled. Read Less

RATIONALE: Topical cream containing amitriptyline and ketamine may help relieve pain, numbness, tingling, and other symptoms of peripheral neuropathy. It is not yet known whether topical amitriptyline and ketamine cream is more effective than a placebo in treating peripheral neuropathy caused by chemotherapy. PURPOSE: This randomized phase III trial is studying the side effects and how well topical amitriptyline and ketamine cream work compared with a placebo in treating peripheral neuropathy caused by chemotherapy in patients with cancer. Read Less