A rapid positive influence of S-ketamine on the anxiety of patients in palliative care: a retrospective pilot study.

BACKGROUND: Patients in palliative care need rapid-acting pharmacological options for psychological distress. N-methyl-D-aspartate antagonist ketamine is known to have a fast onset of anti-depressant and anxiolytic action. Its S-enantiomer S-ketamine (or esketamine) is an analgesic used as a routine treatment for refractory pain as an intravenous infusion (0.25 mg/kg over 45 min). This study investigates whether S-ketamine pain therapy has a positive impact on psychological distress caused by anxiety and depression in palliative care. METHODS: Patient routine data from a palliative care unit of a tertiary care hospital were used in a retrospective analysis after positive ethics approval. Eight patients, who received analgesic S-ketamine treatment, were compared to a control group matched by gender and age. The main analysis was conducted using three-way mixed MANOVA followed by two-way mixed ANOVA. Target variables were the values for anxiety and depression in the state-trait anxiety-depression inventory STADI. The predictor variables were the time of measurement before (T1) and after (T2) S-ketamine application and group membership. RESULTS: Comparison of the S-ketamine group (n = 8; 4 male, 4 female; average age 52 years) with the control group (n = 8; 3 male, 5 female; average age 55 years) revealed a significant multivariate effect on anxiety and depression F(1, 14) = 4.78; p = 0.046; r = 0.50. The univariate comparisons showed a significant reduction of the anxiety scores from T1 to T2 in the S-ketamine group compared to the control group F(1, 14) = 10.14; p = 0.007; r = 0.65. With regard to depression, there was no significant reduction from T1 to T2 in the group comparison F(1, 14) = 1.60; p = 0.23; r = 0.32. No long-lasting effects on pain were found. CONCLUSIONS: Our findings show that psychological distress of patients in palliative care may improve after a single administration of S-ketamine, which mainly alleviates anxiety in those patients. Limitations of this study arise from non-randomization, retrospective analysis and low sample size. Therefore, further prospective and ideally randomized studies are necessary.

A meta-analysis of randomized controlled trials: combination of ketamine and propofol versus ketamine alone for procedural sedation and analgesia in children.

Although ketamine has been used for procedural sedation and analgesia, some researchers have assessed ketamine-propofol as a better alternative because of its reduced adverse events. The goal of this review was to compare adverse events between ketamine-propofol and ketamine for procedural sedation and analgesia in children. We searched the literature from their inception to May 2018 without the restriction of language. We included all randomized controlled trials comparing ketamine-propofol with ketamine for procedural sedation and analgesia in children. The meta-analysis was conducted using the Stata software. A total of six studies involving 693 individuals were included. Pooling of data showed that subjects with ketamine-propofol had similar incidence of respiratory adverse events compared to those with ketamine (RR 1.16, 95% CI 0.68-1.98). However, ketamine-propofol was effective in reducing cardiovascular adverse events compared to ketamine (RR 0.11, 95% CI 0.04-0.31). Ketamine-propofol was also effective in reducing psychomimetic adverse events compared to ketamine (RR 0.39, 95% CI 0.16-0.93). In regard to nausea and vomiting, ketamine-propofol was significantly effective (RR 0.43, 95% CI 0.25-0.74). In addition, we could not demonstrate differences in efficacious sedation between ketamine-propofol and ketamine. Although our study was not able to demonstrate differences in efficacious sedation between ketamine-propofol and ketamine, we confirmed that ketamine-propofol sedation had a lower frequency of adverse events compared to ketamine sedation in children.

The THINK (Treatment of Headache with Intranasal Ketamine) Trial: A Randomized Controlled Trial Comparing Intranasal Ketamine with Intravenous Metoclopramide.

BACKGROUND: Headache is a common chief complaint in the emergency department (ED) setting. OBJECTIVES: To compare analgesia with metoclopramide and diphenhydramine vs. intranasal ketamine among ED patients with primary headache. METHODS: We enrolled a convenience sample of adults with a primary headache in a randomized, single-blind, placebo-controlled trial. We randomized patients to either a control arm (intravenous metoclopramide and diphenhydramine) or intranasal ketamine. The primary outcome was change in pain 0-100 mm visual analog scale (VAS) score measured at study start and 30 min post completion of initial medication administration. Secondary outcomes included side effects, hospital admission, and return to care within 48-72 h. RESULTS: All 53 enrolled subjects completed the study, 26 of whom were allocated to the control arm and 27 to intranasal ketamine. The mean change in pain VAS score at 30 min post intervention was 22.2 mm in the control arm vs. 29.0 in the intranasal ketamine arm (effect size difference 6.8 mm, 95% confidence interval -5.8-19.4). The incidence of reported side effects was 65.4% in the control arm vs. 66.7% in the ketamine arm. Three patients (11.5%) allocated to the control arm required admission for headache pain control vs. 1 patient (3.7%) in the intranasal ketamine arm. Three (11.5%) additional patients in the control arm returned to the ED within 48-72 h for headache pain vs. none in the ketamine arm. CONCLUSIONS: In this small randomized study, intranasal ketamine was not superior to standard therapy among ED patients with primary headache syndromes.

Ketamine Use for Complex Pain in the Palliative Care Population.

Palliative care patients are predisposed to complex pain, including refractory pain, neuropathic pain, opioid-induced hyperalgesia, and opioid-induced neurotoxicity. Palliative care complex pain management can include use of subanesthetic parenteral ketamine. Support for subanesthetic ketamine exists from anecdotal experiences and nonrandomized studies, but there is a lack of statistically significant evidence to support or dismiss its use. Ketamine is sought for illegal, nonmedical purposes, so the lack of evidence coupled with potential for exploitation makes judicious and knowledgeable use critical. Palliative care nurse practitioners, as experts in symptom management, should evaluate and consider all potentially beneficial treatment strategies for complex pain, including novel strategies such as subanesthetic ketamine treatment. Several databases and clinical guideline repositories, along with inspection of germane articles' reference lists, were utilized to collect original research, retrospective studies, literature reviews, and case reports pertinent to the management of palliative care complex pain with parenteral ketamine. In conclusion, the evidence-based clinical decision-making process is engaged to outline a method to weigh the risks versus benefits of subanesthetic ketamine for this population of patients.

Isoflurane is an effective alternative to ketamine/xylazine/acepromazine as an anesthetic agent for the mouse electroretinogram.

The electroretinogram (ERG) is an essential measure of retinal function for studying mouse models of retinal disease. Ketamine, in combination with xylazine and/or acepromazine, is the most commonly used anesthetic agent. Although it works well in most situations, some fragile mouse strains have high mortality rates with this ketamine cocktail. We compared isoflurane with the ketamine cocktail in a longitudinal study of light-adapted and dark-adapted ERGs in C57BL/6J mice. Waveforms were averaged, oscillatory potentials (OPs) were extracted by digital filtration, and key ERG parameters were analyzed. The ERG waveforms were qualitatively similar with both anesthetics, and the male and female ERG parameters did not show significant differences. For light-adapted ERGs, b-wave amplitude and implicit time, and wavelet index were decreased under isoflurane anesthesia, whereas for dark-adapted ERGs, a- and b-wave implicit times were decreased and wavelet index was increased. The dark-adapted b-wave amplitude showed a significant inverse correlation with animal weight and age. Rod phototransduction gain and the Naka-Rushton n and R (max) parameters were the same for both anesthetics, and only the Naka-Rushton log k parameter was significantly elevated for isoflurane anesthesia. We propose that isoflurane is a satisfactory alternative to the ketamine cocktail for anesthesia in the mouse ERG. Precise quantitative comparisons, however, should only employ study designs using isoflurane versus isoflurane, or ketamine versus ketamine. Moreover, in light of the effects of both isoflurane and the ketamine cocktail on blood glucose levels, it would be prudent to control the fasting state of the animals in quantitative ERG studies.

Refractometry for quality control of anesthetic drug mixtures.

Injectable anesthetic drugs used in rodents are often mixed and further diluted to increase the convenience and accuracy of dosing. We evaluated clinical refractometry as a simple and rapid method of quality control and mixing error detection of rodent anesthetic or analgesic mixtures. Dilutions of ketamine, xylazine, acepromazine, and buprenorphine were prepared with reagent-grade water to produce at least 4 concentration levels. The refraction of each concentration then was measured with a clinical refractometer and plotted against the percentage of stock concentration. The resulting graphs were linear and could be used to determine the concentration of single-drug dilutions or to predict the refraction of drug mixtures. We conclude that refractometry can be used to assess the concentration of dilutions of single drugs and can verify the mixing accuracy of drug combinations when the components of the mixture are known and fall within the detection range of the instrument.

Field anesthesia of wild arctic fox (Alopex lagopus) cubs in the Swedish lapland using medetomidine-ketamine-atipamezole.

A safe and effective anesthetic regime for use in arctic fox (Alopex lagopus) cubs was developed. During July 1996, six free-ranging 6-8-wk-old cubs were captured near their den in Vindelfjallen Nature Reserve, Sweden. Medetomidine and ketamine HCI, followed by atipamezole, were selected for the anesthetic trial because of the well-documented safety and efficacy of this drug combination in a broad range of species. The dosage regimen used was 50 microg/kg medetomidine combined with 2.5 mg/kg ketamine followed by reversal with 250 microg/kg atipamezole. Induction was rapid, with a mean induction time of 1 min and 32 sec (range: 58-150 sec). The cubs were anesthetized for a mean time of 18 +/- 5 min (range: 13-25 min). Serially recorded heart rate, respiratory rate, temperature, and pulse oximetry were stable throughout the anesthetic period for all cubs. Anesthetic depth was suitable for safe handling and minor clinical procedures, including venipuncture. Following atipamezole, all cubs were standing within 12 +/- 7 min (range: 5-24 min) and fully recovered at 27 +/- 5 min (range: 19-36 min). This information will be useful for future captive breeding and management programs involving the endangered arctic fox.

Ketamine and its use in the pig. Recommendations of the Consensus meeting on Ketamine Anaesthesia in Pigs, Bergen 1994. Ketamine Consensus Working Group.

Ketamine, when used as a mono-anaesthetic, does not appear to induce surgical anaesthesia in the pig. The addition of other drugs such as opioids, benzodiazepines and alpha 2-adrenergic agonists deepens anaesthesia and enables major surgery to be performed. A decision-tree for the rational use of ketamine for both short and long-term anaesthesia in the pig under three different levels of procedure severity is presented.