Low-dose Ketamine Research Articles

Comparison of Intraoperative Low-Dose Ketodex and Fentanyl Infusion for Postoperative Analgesia In Spine Surgery: A Prospective Randomized Double-Blind Study.

Prospective randomized double-blind study. To assess the analgesic effects of the combination of a low-dose ketamine and dexmedetomidine (ketodex) infusion and compare it with that of fentanyl for postoperative analgesia after spine surgeries. Adequate pain management following spine surgeries is crucial. Approximately 57% of patients experience inadequate pain control in the first 24 hours following elective spine surgery, which is attributable to the extensive soft tissue and muscle damage. The study included 60 patients graded American Society of Anesthesiologists I and II and scheduled for thoracolumbar spine surgery involving >3 vertebral levels. The patients were divided into two groups: group KD (ketodex) and group F (fentanyl). The primary objective was to compare the postoperative analgesic requirements among the groups. The secondary objectives included a comparison of the intraoperative anesthetic requirements, postoperative pain scores, hemodynamic parameters, side effects of the study drugs, and the duration of post-anesthesia care unit stay of both the groups. Ketodex use prolonged the mean time to first rescue analgesia (22.00±2.30 hours vs. 11.69±3.02 hours, p <0.001) and reduced the requirement of rescue analgesics in the first 24 hours postoperatively compared to fentanyl use (70.00±8.16 μg vs. 113.31±36.65 μg, p =0.03). The intraoperative requirement of desflurane was comparable between the groups (p >0.05). The postoperative pain scores were significantly lower in the group KD than in group F at most timepoints (p <0.05). Patients in group KD had a shorter post-anesthesia care unit stay than group F did (p <0.001). Low-dose ketodex could be a safe substitute for fentanyl infusion when employed as an anesthetic adjuvant for patients undergoing thoracolumbar spine surgeries involving >3 vertebral levels to achieve prolonged analgesia without any opioidrelated side effects.

Role of klotho on antidepressant and antisuicidal effects of low-dose ketamine infusion among patients with treatment-resistant depression and suicidal ideation

ObjectivePrevious studies have found an association between klotho, an anti-aging hormone, and major depressive disorder. However, whether low-dose ketamine infusion alters klotho levels among patients with treatment-resistant depression (TRD) remains unknown. MethodsIn total, 48 patients with TRD and strong suicidal ideation were randomly assigned to a single 0.5 mg/kg ketamine or 0.045 mg/kg midazolam regimen and were subjected to a 2-week follow-up. Depressive and suicidal symptoms were assessed before the infusion and during the follow-up. The serum levels of klotho were assessed at baseline and 3 days postinfusion. ResultsA generalized linear model with adjustment of baseline klotho levels showed that, despite the fact that ketamine did not significantly increase levels of klotho, patients in the ketamine group had higher levels of klotho at Day 3 postinfusion than patients in the midazolam group (p = 0.043). However, we found no association between changes in klotho levels and changes in depressive and suicidal symptoms (all p > 0.05). Higher klotho levels at baseline were associated with poorer antidepressant effect of low-dose ketamine during postinfusion follow-up. DiscussionKlotho may play a role in the antidepressant effect of low-dose ketamine. Additional molecular studies are necessary to elucidate the neuromechanisms of TRD, ketamine, and klotho.

Subanaesthetic doses of ketamine reduce but do not eliminate predictive coding responses: implications for mechanisms of sensory disconnection

BackgroundSensory disconnection is a key feature of sleep and anaesthesia. We have proposed that predictive coding offers a framework for understanding the mechanisms of disconnection. Low doses of ketamine that do not induce disconnection should thus diminish predictive coding, but not abolish it. MethodsKetamine was administered to 14 participants up to a blood concentration of 0.3 μg ml−1 Participants were played a series of tones comprising a roving oddball sequence while electroencephalography evoked response potentials were recorded. We fit a Bayesian observer model to the tone sequence, correlating neural activity with the prediction errors generated by the model using linear mixed effects models and cluster-based statistics. ResultsKetamine modulated prediction errors associated with the transition of one tone to the next (transitional probability), but not how often tones changed (environmental volatility), of the system. Transitional probability was reduced when blood concentrations of ketamine were increased to 0.2–0.3 μg ml−1 (96–208 ms, P=0.003); however, correlates of prediction error were still evident in the electroencephalogram (124–168 ms, P=0.003). Prediction errors related to environmental volatility were associated with electroencephalographic activity before ketamine (224–284 ms, P=0.028) and during 0.2–0.3 μg ml−1 ketamine (108–248 ms, P=0.003). At this subanaesthetic dose, ketamine did not exert a dose-dependent modulation of prediction error. ConclusionsSubanaesthetic dosing of ketamine reduced correlates of predictive coding but did not eliminate them. Future studies should evaluate whether states of sensory disconnection, including anaesthetic doses of ketamine, are associated with a complete absence of predictive coding responses. Clinical trial registrationNCT03284307.

Ketamine facilitates appetitive trace conditioning in mice: Further evidence for abnormal stimulus representation in schizophrenia model animals.

Recent studies indicated that positive symptoms of schizophrenia, such as hallucination and delusion, can be modeled using Pavlovian conditioning procedures. Various schizophrenia model animals exhibit abnormally strong associative activations of absent stimuli (i.e., conditioned hallucination) and readily form further associations involving the absent cues (i.e., enhanced mediated conditioning). In the present study using mice, we examined whether the acquisition of appetitive trace conditioning, another Pavlovian task in which animals must form associations between two stimuli that never occur together, is facilitated by injections of ketamine, an N-methyl-D-aspartate-receptor antagonist and a known hallucinogen at low doses in humans and nonhuman animals. Ketamine administration before each conditioning session significantly enhanced the acquisition of 4-s trace conditioning but not delay conditioning. The trace conditioning-specific facilitatory effect of ketamine was replicated in subsequent experiments in which slightly modified procedures were used to enhance the overall levels of conditioned responses. Taken together, the current results demonstrated that low-dose ketamine promotes associative learning between stimuli over a temporal gap, which adds to existing literature illustrating aberrant learning involving absent stimuli in schizophrenia model animals. We discuss potential associative mechanisms through which ketamine promoted trace conditioning with reference to Wagner's (1981) Standard Operating Procedures model. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cellular consequences triggered by ketamine on exposure to human glioblastoma epithelial (LN-229) cells.

Ketamine is generally a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that interrelates with various other receptors, contributing to a wide range of actions. They are mainly approved as a general anesthetic, but a low dose of ketamine is applied for pain management, depression, and as analgesics. However, there is a significant concern regarding the long-term usage as antidepressants and as an abused drug. The study mainly aims to exhibit the possible long-term side effects of ketamine as an antidepressant and in recreational users. The study explores the in vitro cytotoxicity revealed on LN-229 cells in a dose-dependent manner. According to the cell viability assays, there is a dose-dependent response toward ketamine. Morphological and nuclear integrity was changed on exposure and assessed using Giemsa, Rhodamine phalloidin, 4',6-diamidino-2-phenylindole (DAPI), and Acridine orange staining. The apoptotic cell death marked by nuclear condensation, Lactate dehydrogenase leakage, pro-inflammatory cytokine (interleukin [IL]-β) release, and inhibition of cell migration was observed. The study highlights the importance of nonanesthetic usage of ketamine, which can lead to severe adverse side effects on long-term exposure rather than a single exposure as an anesthetic agent.

Low-dose ketamine improves animals' locomotor activity and decreases brain oxidative stress and inflammation in ammonia-induced neurotoxicity.

Ammonium ion (NH4 + ) is the major suspected molecule responsible for neurological complications of hepatic encephalopathy (HE). No specific pharmacological action for NH4 + -induced brain injury exists so far. Excitotoxicity is a well-known phenomenon in the brain of hyperammonemic cases. The hyperactivation of the N-Methyl- d-aspartate (NMDA) receptors by agents such as glutamate, an NH4 + metabolite, could cause excitotoxicity. Excitotoxicity is connected with events such as oxidative stress and neuroinflammation. Hence, utilizing NMDA receptor antagonists could prevent neurological complications of NH4 + neurotoxicity. In the current study, C57BL6/J mice received acetaminophen (APAP; 800 mg/kg, i.p) to induce HE. Hyperammonemic animals were treated with ketamine (0.25, 0.5, and 1 mg/kg, s.c) as an NMDA receptor antagonist. Animals' brain and plasma levels of NH4 + were dramatically high, and animals' locomotor activities were disturbed. Moreover, several markers of oxidative stress were significantly increased in the brain. A significant increase in brain tissue levels of TNF-α, IL-6, and IL-1β was also detected in hyperammonemic animals. It was found that ketamine significantly normalized animals' locomotor activity, improved biomarkers of oxidative stress, and decreased proinflammatory cytokines. The effects of ketamine on oxidative stress biomarkers and inflammation seem to play a key role in its neuroprotective mechanisms in the current study.

Association of Neurofilament Light Chain With the Antidepressant Effects of Low-Dose Ketamine Infusion Among Patients With Treatment-Resistant Depression.

The role of neurofilament light chain (NFL) in treatment-resistant depression (TRD) is unclear. Whether baseline NFL concentrations are associated with the antidepressant effects of low-dose ketamine infusion has not been determined. The NFL concentrations of 71 patients with TRD and 17 healthy controls were assessed. Patients with TRD were randomly administered a single infusion of 0.5mg/kg ketamine, 0.2mg/kg ketamine, or normal saline. Depressive symptoms were assessed prior to infusion and sequentially at postinfusion timepoints (after 240min and 2-7 and 14 days after infusion) using the Hamilton Depression Rating Scale (HDRS). After adjustment for age, sex, and body mass index, patients with TRD were more likely to have higher concentrations of NFL than healthy controls (p < 0.001). A generalized estimating equation model with adjustments for infusion group, age, sex, body mass index, and baseline HDRS scores showed that baseline NFL concentrations were positively associated with subsequent HDRS scores following low-dose ketamine infusion (p = 0.038). Higher concentrations of NFL were observed among patients with TRD compared with healthy controls. Baseline NFL concentrations may predict the antidepressant effects of low-dose ketamine infusion.

Optimum Perioperative Analges ia in Radical Nephrectomy, Multimodel Approach with Nalbuphine and Ketamine

Objective: to find perioperative analgesic effectiveness of low dose Ketamine in radical nephrectomy operations and comparing its anodyne potency with Nalbuphine Hcl (Nalbin). Study Design: Quasi-experimental study. Place and Duration of Study: Armed forces institute of urology from Sep 2016 to June 2019. Methodology: The 60 randomly selected surgical patients for radical nephrectomy were divided into two groups in a random manner. The Anaesthetic technique used in both groups (K and N) was standard along with 10 mg injection Nalbin given to both groups at induction. Group-K (n=30) patients had IV Ketamine bolus 0.3 mg /kg followed by 0.1 mg/kg/h infusion at induction till completion of surgery. Group-N (n=30) received a similar volume of saline in bolus as well as an infusion. The pain score (VAS) at different intervals and total Nalbin consumed in 12 hours were recorded for each group. Patient satisfaction and complications were recorded during this period. Results: The effective intraoperative analgesia was achieved with an infusion of low dose Ketamine which continued till completion of surgery as seen in group K which has reduced Nalbin requirement 8.8± 3.5 mg (Group N 25±5 mg). There was a statistically significant reduction in overall pain scores and Nalbin demand (P≤0.05) in the Ketamine group (p≤0.00, 0.036, 0.286, 0.257, 0.253 respectively). Patient satisfaction was better in the Ketamine group but few patients in this group had delayed recovery. Conclusion: Intraoperative low-dose Ketamine infusion provides good postoperative analgesia while reducing the need for opioid analgesics, which must be con

Effects of low-dose ketamine infusion on vascular endothelial growth factor and matrix metalloproteinase-9 among patients with treatment-resistant depression and suicidal ideation

BackgroundEvidence indicates that vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) influence the pathophysiology of depression. However, whether low-dose ketamine regulates VEGF and MMP-9 levels and whether changes in VEGF and MMP-9 levels are associated with the antidepressant and antisuicidal effects of ketamine remained unclear. MethodsForty-eight patients with treatment-resistant depression and strong suicidal ideation (TRD-SI) were randomly assigned to a single infusion of 0.5-mg/kg ketamine or 0.045-mg/kg midazolam. The Montgomery–Åsberg Depression Rating Scale (MADRS) and Columbia-Suicide Severity Rating Scale–Ideation Severity Subscale (CSSRS-ISS) were used at baseline and subsequently at several postinfusion timepoints. VEGF and MMP-9 serum levels were analyzed at baseline and on day 3 postinfusion. ResultsAfter adjustment for baseline levels, no significant differences in VEGF (p = .912) and MMP-9 (p = .758) levels were identified on day 3 postinfusion between the study groups. Baseline VEGF levels but not MMP-9 levels were negatively associated with MADRS and CSSRS-ISS scores following infusion. DiscussionA single infusion of low-dose ketamine did not alter the VEGF and MMP-9 levels of the patients with TRD-SI. Higher baseline VEGF levels were associated with greater antidepressant and antisuicidal effects of single low-dose ketamine infusion.

Comparison of Intubating Conditions at 60 Seconds with Cisatracurium 4*ED95 Dose and Cisatracurium 2*ED95 Dose Plus Priming Dose and Low Dose Ketamine.

To compare the intubating conditions at 60 seconds between 4*ED95 dose of cisatracurium and 2*ED95 dose of cisatracurium in combination with priming and low dose ketamine. jaw relaxation for laryngoscopy, vocal cord position on laryngoscopy, and coughing or bucking response to intubation. To compare the hemodynamic changes up 10 minutes after intubation in the two groups. In this prospective study, a total of 68 patients were undergoing general anesthesia for surgery with placement of endotracheal tube placement. Patients will be divided into two groups comprising 34 patients each. The patients were allocated one of the two groups by computerized randomization. *Group A received bolus dose of cisatracurium which is 0.2 mg/kg (4*ED95). **Group B received cisatracurium in dose of 0.1 mg/kg (2*ED95) with priming (which is 10% of the bolus dose) and low dose ketamine of about 0.5 mg/kg. It was possible to achieve acceptable laryngoscopy and intubating condition in both the groups within 90 seconds. When grades of laryngoscopy and ease of intubation were compared, 2*ED95 dose along with priming plus low dose ketamine produced superior results than 4*ED95 group. When the mean arterial pressure and pulse rate were compared between the two groups, it was observed that mean arterial pressure and pulse rate were only slightly higher in the 2*ED95 along with priming and ketamine.

Efficacy of intravenous ketamine as premedicant for prevention of intraoperative hypotension after spinal anesthesia in parturients posted for elective cesarean section

Background: Hypotension following spinal anesthesia (SA) in lower segment cesarean section can be deleterious to the parturient and to fetus. Ketamine acts by stimulating the cardiovascular system leading to high blood pressure and increase in heart rate (HR) and cardiac output. Aims and Objectives: This study aimed to assess the efficacy of 15 mg of prophylactic intravenous ketamine in elective cesarean section for prevention of hypotension after SA. Materials and Methods: This double-blinded randomized controlled study was conducted on 98 participating parturients who were American Society of Anesthesiologists term pregnant women. The parturients were randomly divided into two groups (n=49 in each). All the parturients received SA. Ketamine group - Group K received 15 mg of ketamine IV bolus in 3 mL saline and control group - Group C received the same volume of normal saline IV bolus. HR and systolic blood pressure (SBP) were recorded at baseline at 5, 10, 15, and 20 min after the injection and then every 15 min till the end of the operation. Incidences of hypotension were recorded. The total number dose of ephedrine used, APGAR score, and Visual Analog Scale scores were recorded. The Ramsay Sedation Score was also recorded at baseline, then 5, 10, 15, 30, and 45 min after injection, and then at the end of the operation. Results: This study showed a statistically significant increase in the incidence of hypotension and higher use of intravenous ephedrine 6 mg boluses in the control group when compared to the ketamine group. Forty-two parturients in the control group developed hypotension compared to 23 parturients in the ketamine group with P&lt;0.001. The total ephedrine dose was significantly lower among the ketamine group. Sedation was observed for the first 15 min intraoperatively in the ketamine group with P=0.001. There was no statistically significant difference in APGAR score between the two groups. Conclusion: There was significantly higher hemodynamic stability in the ketamine group with regard to SBP, diastolic blood pressure, and HR. Hence, low-dose ketamine, when used as a premedicant, is an effective agent that can be used in preventing post-spinal intraoperative hypotension in parturients undergoing cesarean section delivery.

Sedation Quality of Low – Dose Ketamine Combined with Dexmedetomidine versus Propofol in Phacoemulsification under Local Anesthesia: A Triple-Blinded Randomized Clinical Trial

Purpose: To compare the hemodynamic effects of low-dose ketamine combined with dexmedetomidine versus propofol in phacoemulsification under local anesthesia. Place and Duration of Study: School of Medicine, Isfahan University of Medical Sciences during 2020-2021. Methods: Sixty patients admitted for cataract surgery were included. Those with history of systemic diseases, insufficient pupil dilation, sensitivity to drugs and uncooperative patients were excluded. Participants were randomly allocated to two groups; group which was administered ketamine with dexmedetomidine (Ketodex) and group which was given ketamine with propofol (Ketofel). Effect on blood pressure, pulse and sedation was recorded. Results: Mean age was 65 ± 9.9 years. Sixty-five were females. Ketodex increased the risk of hemodynamic disorders compared to Ketofel (P = 0.04). The risk of nausea and vomiting was higher in the Ketodex group although not significant. The effect of drug course on heart rate, blood pressure and sedation was significant in both groups (P &lt; 0.05). Neither at baseline, nor in the 1st and 5th minutes of surgery, was the mean arterial pressure (MAP) was significantly different between the two groups. From 10th minute of surgery until the end of surgery and from the beginning of recovery until the 30th minute of recovery, the MAP and pulse rate were higher in Ketofol group. Sedation effect during surgery was higher in the Ketodex group compared to the Ketofol group, and the difference was statistically significant at minutes 10, 20 and 30 of surgery. Conclusion: There is higher effect of sedation and fewer side effects of ketamine-dexmedetomidine combination compared to the ketamine-propofol combination.

Ketamine as a pre-emptive analgesia in patients undergoing caesarean delivery under spinal anesthesia

BACKGROUND &amp; OBJECTIVES: Lower segment caesarean section (LSCS) leads to moderate to severe pain in the patient. Pain severity is directly proportional to the functional limitations and depression in the postpartum period, making it essential to provide good pain relief after surgery. Maternal wellbeing and better nursing care of newborn requires good postoperative analgesia with minimal side effects. The main objective of the study was to evaluate the analgesic effect of intravenous low-dose ketamine, when administered pre-emptively, in patients undergoing caesarean delivery under spinal anesthesia.&#x0D; METHODOLOGY: Two groups were made, each with 50 full-term pregnant females with a plan of caesarean section under spinal anesthesia. Group-A received spinal anesthesia with bupivacaine 0.5% along with intravenous placebo of 2cc normal saline, whereas group-B received 0.5mg/kg ketamine intravenously after administration of spinal anesthesia but before the start of surgical incision. Pain intensity was monitored using a visual rating pain scale (VRS), till the need for the first analgesic dose postoperatively.&#x0D; RESULTS: Both groups were comparable in terms of age and weight. Analgesia was markedly prolonged, and postoperative pain scores were significantly less in Group-B (ketamine group) as compared to Group-A; with p-value&lt; 0.001, demonstrating analgesic properties of ketamine when administered pre-emptively as an intravenous dose.&#x0D; CONCLUSION: Our study concluded that pre-emptive analgesic dose of ketamine (administered before surgical incision), leads to prolong analgesia in post-operative period in patients who underwent LSCS under spinal anesthesia.

Ketamine’s rapid antidepressant effects are mediated by Ca2+-permeable AMPA receptors

Ketamine is shown to enhance excitatory synaptic drive in multiple brain areas, which is presumed to underlie its rapid antidepressant effects. Moreover, ketamine’s therapeutic actions are likely mediated by enhancing neuronal Ca2+ signaling. However, ketamine is a noncompetitive NMDA receptor (NMDAR) antagonist that reduces excitatory synaptic transmission and postsynaptic Ca2+ signaling. Thus, it is a puzzling question how ketamine enhances glutamatergic and Ca2+ activity in neurons to induce rapid antidepressant effects while blocking NMDARs in the hippocampus. Here, we find that ketamine treatment in cultured mouse hippocampal neurons significantly reduces Ca2+ and calcineurin activity to elevate AMPA receptor (AMPAR) subunit GluA1 phosphorylation. This phosphorylation ultimately leads to the expression of Ca2+-Permeable, GluA2-lacking, and GluA1-containing AMPARs (CP-AMPARs). The ketamine-induced expression of CP-AMPARs enhances glutamatergic activity and glutamate receptor plasticity in cultured hippocampal neurons. Moreover, when a sub-anesthetic dose of ketamine is given to mice, it increases synaptic GluA1 levels, but not GluA2, and GluA1 phosphorylation in the hippocampus within 1 hr after treatment. These changes are likely mediated by ketamine-induced reduction of calcineurin activity in the hippocampus. Using the open field and tail suspension tests, we demonstrate that a low dose of ketamine rapidly reduces anxiety-like and depression-like behaviors in both male and female mice. However, when in vivo treatment of a CP-AMPAR antagonist abolishes the ketamine’s effects on animals’ behaviors. We thus discover that ketamine at the low dose promotes the expression of CP-AMPARs via reduction of calcineurin activity, which in turn enhances synaptic strength to induce rapid antidepressant actions.

Low-dose ketamine infusions for chronic pain management: Does this qualify as evidence-based practice?

Chronic pain is becoming increasingly prevalent and burdensome both worldwide and in the United Kingdom. Due to the complexity of chronic pain and the therapeutic challenge associated, management is often difficult and requires multidisciplinary care encompassing a combination of pharmacological and non-pharmacological strategies. Conventional analgesic treatments, such as opioids and anticonvulsants, are effective in less than half of chronic pain sufferers and are typically limited to short-term use to prevent complications associated with long-term use such as tolerance and dependence. Consequently, research and clinical interest in alternative management options for chronic pain have increased in recent years, with ketamine being one example under investigation. However, since ketamine has been licensed as an anaesthetic for decades, it has bypassed the traditional scrutinous drug development sequence that is typically seen for therapeutics marketed for pain. As such, data supporting the unlicensed administration of ketamine for chronic pain management is lacking and is being outpaced by the rates of off-label use in pain clinics. Recent limited evidence suggests that ketamine, when given as an intravenous infusion in subanaesthetic doses for refractory pain patients, may provide modest analgesic effects in nearly all aetiologies of chronic pain, with side effects common but typically mild. However, there are concerns over the safety of this practice due to the paucity of robust supportive evidence and the accompanying lack of clinical guidelines or standardised protocols. This review shall summarise the literature examining the use of subanaesthetic-dose ketamine infusions for chronic pain to comment on the current level of evidence, with limitations of existing research and future recommendations discussed.

Baseline cognitive function predicts full remission of suicidal symptoms among patients with treatment-resistant depression and strong suicidal ideation after low-dose ketamine infusion.

Whether pretreatment working memory and response inhibition function are associated with the rapid and sustained antisuicidal effect of low-dose ketamine among patients with treatment-resistant depression (TRD) and strong suicidal ideation is unclear. We enrolled 65 patients with TRD, comprising 33 who received a single infusion of 0.5 mg/kg ketamine and 32 who received a placebo infusion. The participants performed working memory and go/no-go tasks prior to infusion. We assessed suicidal symptoms at baseline and on postinfusion Days 2, 3, 5, and 7. The full remission of suicidal symptoms persisted for 3 days after a single ketamine infusion and the ketamine-related antisuicidal effect persisted for 1 week. Lower cognitive impairment at baseline (indicated by a higher rate of correct responses on a working memory task) was associated with the rapid and sustained antisuicidal effect of low-dose ketamine in patients with TRD and strong suicidal ideation. Patients with TRD and strong suicidal ideation but low cognitive impairment may benefit the most from the antisuicidal effect of low-dose ketamine.

Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice

Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that intraperitoneal injection of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.

Subanesthetic Ketamine Infusion Reducing Symptoms of Depression in a Patient With End-Stage Heart Failure Enrolled in Hospice Care: A Case Report.

Background: The development of major depressive disorder in patients at end of life often goes undiagnosed, as it is difficult to distinguish from preparatory grief and/or hypoactive delirium in this unique patient population. If this preliminary barrier of appropriate diagnosis is overcome, it can be quite difficult to properly select and adjust pharmacological therapy. Many well-established antidepressants take four to five weeks for maximal effectiveness (which may be far too long of a titration period for patients at end of life), have various contraindications to patients' comorbid chronic conditions (particularly patients with cardiovascular disease), or may simply be ineffective. Case: We present a case report of severe treatment-resistant depression in an end-stage heart failure patient enrolled in hospice care. Discussion: We discuss the potential use of a single low-dose intravenous racemic ketamine infusion to reduce end-of-life suffering related to depression, despite the theoretical contraindication of ketamine use in such patients, in part, due to its sympathomimetic secondary effect.

Comparison of four chemical restraint protocols in pacas

Discussions about different anesthetic techniques designed for wild rodents, particularly neotropical species, are scarce in the literature. However, chemical restraint is required for management and medical procedures in these animals, due to their susceptibility to stress and their behavioral characteristics. This research evaluated quality and duration of chemical restraint of pacas (Cuniculus paca) using low doses of ketamine in association with xylazine (Group 1), xylazine and midazolam (Group 2), butorphanol and midazolam (Group 3), and azaperone and midazolam (Group 4). All doses were calculated by interspecific allometric scaling. In Group 1, recovery was disturbed and the moment of incapacity of manipulation occurred early. In Groups 2, 3 and 4, the duration of chemical restraint was higher. The best chemical restraint quality occurred in Group 2 (ketamine, xylazine and midazolam). Midazolam provided an extremely calm recovery, and afforded animals’ manipulation for prolonged time, even and after return of normal ambulation.

Comparison of the effect of a combination of low dose ketamine and dexmedetomidine with a combination of low dose ketamine and midazolam on hemodynamic changes and pain in electroconvulsive therapy.

Background: Currently, electroconvulsive therapy (ECT) is used as an effective treatment method in many psychiatric disorders. The basis of a successful electroshock session is to create a seizure with the precise intensity, quality and duration. In addition to the appropriate method of shock induction, appropriate anesthesia methods should be used to cause such seizures. The present study compared a combination of low-dose ketamine and dexmedetomidine (Ketodex) with a combination of low-dose ketamine and midazolam (Ketomid) on hemodynamic changes in electroshocks applied to patients referred from the psychiatric ward.&#x0D; Methodology: This study was a randomized triple-blind clinical trial performed after obtaining permission from the Medical Ethics Committee of the Isfahan University of Medical Sciences. For this purpose, 70 patients were selected for electroshock therapy and randomly distributed into two groups of 35 people. In the first group, 0.04 mg/kg midazolam was combined with ketamine 0.1 mg/kg and in the second group, 0.5 μg/kg dexmedetomidine with 0.1 mg/kg ketamine. The patients were placed under complete cardiovascular monitoring. Hemodynamic changes of patients were measured and recorded before injection, after injection, after shock, and at 5 and 10 min after the end of seizures.&#x0D; Results: In this study, 70 patients who were candidates for receiving ECT were equally divided into two groups of 35: one group received a mixture of Ketodex and the second group a combination of Ketomid. The two study groups showed no significant difference in terms of systolic pressure (P = 0.883), diastolic (P = 0.443), mean arterial pressure (P = 0.443), oxygen saturation (P = 0.018), and heart rate (P = 0.286). Complications such as headache, muscular pain (P = 0.01), bradycardia, nausea and vomiting were reported in the dexmedetomidine and ketamine groups.&#x0D; Conclusion: Our study showed that although systolic, diastolic and mean arterial blood pressure, heart rate and oxygen saturation were significantly reduced in both study groups, no significant difference was observed between the two groups in terms of hemodynamic changes and neither drug group in our study population was different from the other in terms of these parameters. In addition, neither option was superior to the other. However, due to the fact that complications such as headache, muscular pain, bradycardia, nausea and vomiting were reported in the dexmedetomidine and ketamine groups, the combination of midazolam and ketamine appeared to be a more appropriate combination in patients undergoing electroconvulsive therapy.&#x0D; Key words: Electroshock therapy; Midazolam; Ketamine; Dexmedetomidine; Hemodynamic changes; Headache pain&#x0D; Citation: Nazemroaya B, Manian N. Comparison of the effect of low dose ketamine plus dexmedetomidine vs low dose ketamine plus midazolam on hemodynamic changes and pain in electroconvulsive therapy. Anaesth. pain intensive care 2023;27(3):364−370; DOI: 10.35975/apic.v27i3.1981&#x0D; Received: September 02, 2022; Reviewed: December 03, 2022; Accepted: April 23, 2023