Intravenous Infusion Of Ketamine Research Articles

Whole blood transcriptional signatures associated with rapid antidepressant response to ketamine in patients with treatment resistant depression

Ketamine has rapid and sustained antidepressant effects in patients with treatment-resistant depression (TRD). However, the underlying mechanisms of action are not well understood. There is increasing evidence that TRD is associated with a pro-inflammatory state and that ketamine may inhibit inflammatory processes. We thus investigated whole blood transcriptional profiles related to TRD and gene expression changes associated with treatment response to ketamine. Whole blood was collected at baseline (21 healthy controls [HC], 26 patients with TRD) and then again in patients with TRD 24 hours following a single intravenous infusion of ketamine (0.5 mg/kg). We performed RNA-sequencing and analyzed (a) baseline transcriptional profiles between patients with TRD and HC, (b) responders vs. non-responders before ketamine treatment, and (c) gene expression signatures associated with clinical improvement. At baseline, patients with TRD compared to HC showed a gene expression signature indicative of interferon signaling pathway activation. Prior to ketamine administration, the metabotropic glutamate receptor gene GRM2 and the ionotropic glutamate receptor gene GRIN2D were upregulated in responders compared to non-responders. Response to ketamine was associated with a distinct transcriptional signature, however, we did not observe gene expression changes indicative of an anti-inflammatory effect. Future studies are needed to determine the role of the peripheral immune system in the antidepressant effect of ketamine.

Pre-emptive Analgesic Efficacy of Low Dose Ketamine versus Magnesium Sulfate in Patients Undergoing Major Abdominal Surgeries Under General Anaesthesia: A Randomised Clinical Study

Introduction: Pre-emptive analgesia has been proposed to result in better pain management, reduced analgesic consumption, and improved patient satisfaction. Aim: To evaluate pre-emptive analgesic efficacy of intravenous ketamine and intravenous magnesium sulfate in patients undergoing major abdominal surgeries under general anaesthesia by administering it 10 min before the incision. Materials and Methods: This randomised, double-blind, clinical study, was conducted in JLN Medical College, Ajmer, Rajasthan, India, from November 2019 to November 2020. The study included 100 patients, aged 18-60 years of American Society of Anesthesiologists (ASA) physical status I and II were randomly allocated into two groups. Group K (n=50) received intravenous (i.v.) ketamine infusion 0.3 mg/ kg in 100 mL normal saline over 10 minutes. Group M (n=50) received i.v. magnesium sulfate (mgso4) infusion 30 mg/ kg in 100 mL normal saline over 10 minutes. The duration of analgesia, total amount of rescue analgesic consumed in 24 hours, haemodynamics, and side-effects were noted. The quantitative data was presented as mean±standard deviation and were compared by student’s t-test. Results: Duration of analgesia was significantly prolonged in group K (67.96±9.20 min) as compared to group M (30.60±6.44 min) (p-value<0.001). The total dose of rescue analgesic consumption in 24 hours was lesser in group K (1180±388.09) as compared to group M (1280±453.56) (p-value=0.236). Haemodynamics and side-effect profile were comparable in the two groups. Conclusion: In major abdominal surgeries under general anaesthesia, patients getting ketamine have longer duration of analgesia compare to magnesium sulfate, have an improved quality of recovery after surgery and less serious adverse events in the Postanesthesia Care Unit (PACU). Ketamine reduces the need for intraoperative opioids and could suppress the pressure response to endotracheal intubation.

Successful pain control with morphine combined with continuous intravenous infusion of ketamine and amitriptyline for an infant with neuroblastoma

Successful pain control with morphine combined with continuous intravenous infusion of ketamine and amitriptyline for an infant with neuroblastoma

Comparative effectiveness of repeated ketamine infusions in treating anhedonia in bipolar and unipolar depression

ObjectivesAnhedonia is a common, persistent, and disabling phenomenon in patients with major depressive disorder (MDD) and bipolar depression (BD). This study was conducted to investigate the comparative effectiveness of repeated ketamine infusions in treating anhedonia in Chinese individuals suffering from MDD and BD. MethodsNinety-seven individuals suffering from MDD (n = 77) or BD (n = 20) were treated with six intravenous infusions of ketamine (0.5 mg/kg) administered over 40 min. Anhedonia was measured through the Montgomery–Åsberg Depression Rating Scale (MADRS). The antianhedonic response and remission were defined as ≥ 50% and ≥ 75% reduction in MADRS anhedonia subscale score one day after the sixth infusion, respectively. ResultsAnti-anhedonic response and remission rates after the sixth ketamine infusion were 48.5% (95% confidence interval = 38.3%–58.6%) and 30.9% (95% confidence interval = 21.6%–40.3%), respectively. When compared to baseline, a significant reduction in the MADRS anhedonia subscale score was observed at 4 h after the first infusion and was maintained with repeated infusions at any time point (all Ps < 0.05). The anti-anhedonic effect of ketamine did not differ between the MDD and BD groups. ConclusionThis preliminary study found that repeated ketamine infusions appeared to be effective at rapidly ameliorating anhedonia, with similar efficacy in MDD and BD.

Ketamine infusion therapy in treatment-resistant depression

Τhe Food and Drug Administration (FDA) approval of the use of S-ketamine in the form of nasal spray for the treatment of treatment-resistant depression, launched a new category of therapeutic agents in psychiatry. A well-known class of substances, psychedelics, are introduced with a 30-year delay in the treatment of mental disorders. Intravenous ketamine infusion has been studied in the treatment of depression since the 1990s. Here we present the current protocol for the treatment of ketamine infusion in patients with treatment-resistant depression and related clinical information.

Antinociceptive and analgesic effect of continuous intravenous infusion of maropitant, lidocaine and ketamine alone or in combination in cats undergoing ovariohysterectomy

BackgroundMultimodal analgesia consists of the combination of analgesic drugs at low doses to act in different places along the path of pain. Studies with continuous infusion of analgesic drugs in cats are not common. This study aimed to evaluate the analgesic effect of maropitant, lidocaine and ketamine alone or in combination (intravenous bolus + subsequent continuous intravenous infusion) in the management of acute postoperative pain in cats undergoing ovariohysterectomy. Seventy healthy cats undergoing an ovariohysterectomy received a standard anesthetic protocol consisting of acepromazine and morphine, propofol (anesthesia induction), and isoflurane (anesthesia maintenance). The animals were stratified into seven groups (n = 10 in each group): control (CG), maropitant (MG), lidocaine (LG), ketamine (KG), maropitant + lidocaine (LMG), maropitant + ketamine (KMG), and maropitant + lidocaine + ketamine (LKMG). All drugs were injected first as an intravenous bolus and then by continuous intravenous infusion. During surgery, esophageal temperature, respiratory rate, heart rate, oxygen saturation, expired isoflurane concentration, and partial pressure of carbon dioxide at the end of expiration were evaluated at 7 time points. Postoperative pain was evaluated for 6 h after extubation using the visual analogue scale and the UNESP-Botucatu multidimensional composite pain scale for assessing postoperative pain in cats.ResultsAdverse effects related to maropitant, lidocaine and ketamine infusion were not observed. Pain scores were lower in the MG, KG and LG groups when compared to the CG group using both scales. Although pain scores were also lower in all combination groups than CG, more animals in these groups required rescue analgesia compared to MG. This indicates that the postoperative analgesic effect of all drugs, either alone or in combination, confers analgesia, although the combinations did not promote greater analgesia.ConclusionsContinuous intravenous infusion of maropitant, lidocaine, and ketamine alone induces postoperative analgesic effect in cats undergoing ovariohysterectomy, but combinations of these drugs did not increase the analgesic effect. No adverse effect was observed with any drug or their combination.

Identification of an optimal dose of intravenous ketamine for late-life treatment-resistant depression: a Bayesian adaptive randomization trial.

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) seven days after a 40 minute intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and effects on cortical excitation/inhibition (E/I) ratio using resting electroencephalography gamma and alpha power, were also determined. Thirty-three medication-free U.S. military veterans (mean age 62; range: 55 – 72; 10 female) with LL-TRD were randomized double-blind. The trial was terminated when dose superiority was established. All interventions were safe and well-tolerated. Pre-specified decision-rules terminated KET 0.1 (N=4) and KET 0.25 (N=5) for inferiority. Posterior probability was 0.89 that day-seven treatment response was superior for KET 0.5 (N=11; response rate = 70%) compared to MID (N=13; response rate = 46%). Persistent treatment response at day 28 was superior for KET 0.5 (response rate = 82%) compared to MID (response rate = 37%). KET 0.5 had high posterior probability of increased frontal gamma power (posterior probability = 0.99) and decreased posterior alpha power (0.89) during infusion, suggesting an acute increase in E/I ratio. These results suggest that 0.5 mg/kg is an effective initial IV ketamine dose in LL-TRD, although further studies in individuals older than 75 are required.

Ketamine increases activity of a fronto-striatal projection that regulates compulsive behavior in SAPAP3 knockout mice

Obsessive-Compulsive Disorder (OCD), characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions), is associated with dysfunction in fronto-striatal circuits. There are currently no fast-acting pharmacological treatments for OCD. However, recent clinical studies demonstrated that an intravenous infusion of ketamine rapidly reduces OCD symptoms. To probe mechanisms underlying ketamine’s therapeutic effect on OCD-like behaviors, we used the SAPAP3 knockout (KO) mouse model of compulsive grooming. Here we recapitulate the fast-acting therapeutic effect of ketamine on compulsive behavior, and show that ketamine increases activity of dorsomedial prefrontal neurons projecting to the dorsomedial striatum in KO mice. Optogenetically mimicking this increase in fronto-striatal activity reduced compulsive grooming behavior in KO mice. Conversely, inhibiting this circuit in wild-type mice increased grooming. Finally, we demonstrate that ketamine blocks the exacerbation of grooming in KO mice caused by optogenetically inhibiting fronto-striatal activity. These studies demonstrate that ketamine increases activity in a fronto-striatal circuit that causally controls compulsive grooming behavior, suggesting this circuit may be important for ketamine’s therapeutic effects in OCD.

The Effect of Low Dose Ketamine Infusion versus Low Dose Dexmedetomidine Infusion on Stress Responses in Coronary Artery Bypass Graft Surgery

Abstract Background In cardiac surgery, the extent of systemic inflammatory response is closely Mobile associated with patient’s outcome. A systemic inflammatory response syndrome (SIRS) may develop after operations using cardiopulmonary bypass (CPB). Aim of the Work to evaluate the 01006705713 potential effects of intravenous infusion of ketamine versus dexmedetomidine on attenuation f stress responses during coronary artery bypass grafting (CABG) operation. Patients and Email elsayed@hotmail.com Methods This randomized controlled interventional study was conducted on 90 patients who dinaunderwent elective CABG procedure at Ain Shams University Hospital over 24 months from Jan 2018 to Jan 2020. The patients were divided into 3 groups, 30 patients for each group. Group D: received dexmedetomidine infusion, Group K: received ketamine infusion and Group N (control group): received normal saline. Then following measurements recorded at following time interval before induction of anesthesia (T1), after weaning from CPB (T2), 24 h(T3) and 48 h(T4) after completion of the anastomoses. Mean arterial blood pressure records, heart rate &amp; Inflammatory and stress markers including CRP, cortisol, WBC count, glucose and lactate levels. Results Mean arterial pressure among three groups was not statistically significant. Also serum glucose level was not statistically significant between groups. Serum lactate level didn’t show statistically significant difference between groups. From aspects of inflammatory markers, we got good results which were superior for dexmedetomidine followed by ketamine infusion group suggested by statistically significant, suggesting that dexmedetomidine and ketamine may have a role in attenuation inflammatory response during cardiac surgery but have no role in attenuation stress response to surgery. Conclusion Our study that compared Intravenous infusion of ketamine and dexmedetomidine on attenuation of stress responses during coronary artery bypass grafting (CABG) operation suggests that dexmedetomidine was superior to ketamine infusion in attenuation of inflammatory response during cardiac surgery but have no role in attenuation stress response to surgery.

The impact of bolus versus continuous infusion of intravenous ketamine on bispectral index variations and desflurane administration during major surgery: The KETABIS study.

Although ketamine, a NMDA-receptor antagonist, tends to increase the bispectral index (BIS), it remains a widely used analgesic whenever administered in low doses during major surgery. The objective of this study was to compare the impact of intravenous ketamine (given either as a continuous infusion or as a bolus) on BIS and to compare desflurane administration and postoperative outcomes between the groups. Prospective, randomised, parallel-group, open-label study. University hospital, operating room. Fifty patients, scheduled for major abdominal surgery. Patients were randomised into two groups: ketamine by intravenous continuous infusion - group (KI) and ketamine by i.v. bolus - group (KB). In the KI group, ketamine at a rate of 0.25 mg kg-1 h-1 was commenced at skin incision (T0) and maintained at this rate for the duration of surgery. In group KB, a ketamine bolus of 0.25 mg kg-1was administered at T0 and repeated every hour. The difference in BIS between the groups was compared from T0 onwards. The amount of desflurane administered to keep BIS within the usual recommended range (40-60) was compared, as were the doses of phenylephrine and remifentanil. Postoperative pain and recovery outcomes were also assessed. After T0, the BIS increased significantly from baseline in group KB compared with group KI: the rise in BIS was 20 ± 8 vs. 11 ± 6, respectively (P = 0.0001). The between-group mean difference (95% confidence interval (CI), was 9 (5 to 13). In group KB, desflurane administration significantly increased for the first 15 min after T0: 6.3 ± 1.8 vs. 3.8 ± 1.3 ml (P < 0.0001) with a mean intergroup group difference (95% CI) of 2.4 (1.5 to 3.4) ml. There was no difference in desflurane administration when considering the full hour from T0 to T60 min: 16 ± 9 vs. 15 ± 5 ml (P = 0.63) with a mean intergroup difference (95% CI) of 1 (-3 to 5) ml. After surgery, pain scores, opioid consumption, incidence of nausea and vomiting and recovery scores were similar between groups. Compared with a continuous ketamine infusion, a ketamine bolus significantly increased the BIS after T0. In order to keep the BIS below 60, significantly more desflurane was administered from T0 to T15 min in group KB. To prevent such higher desflurane administration and its related atmospheric pollution, our results suggest administering intra-operative intravenous ketamine as an infusion rather than a bolus. Clinicaltrials.gov registration identifier: NCT03781635.

A case of status epilepticus developed after Alpha Lipoic Acid intake

Introduction: Alpha Lipoic Acid (ALA) is an antioxidant used in diabetic neuropathy. It is not prescribed to children. However, rarely, intoxication may occur due to accidental or suicidal intake. Case report: A 16-month-old child presented with confusion after taking 1800 mg of ALA. Convulsions that did not respond to midazolam and levetiracetam started in the emergency room. He was admitted to the intensive care unit and was intubated. Convulsions could be controlled with intravenous Ketamine infusion. He received mechanical ventilation support for five days. Gastrointestinal bleeding developed during follow-up and was treated with pantoprazole. There were laboratory measurements consistent with metabolic acidosis. Central nervous system imaging and cerebrospinal fluid examinations were normal. Electroencephalograms taken under elective conditions were reported as normal for his age. He was discharged on the twelfth day of his hospitalization. Conclusion: Children and adults with suspected ALA intake should be referred to tertiary healthcare facilities as soon as possible. In the first stage, gastric lavage and activated charcoal should be applied. Since there is no specific antidote, it should be prepared to deal with resistant convulsions, metabolic acidosis, and multi-organ failure in addition to general supportive therapy.

Age affects temporal response, but not durability, to serial ketamine infusions for treatment refractory depression.

Ketamine is a novel, rapid-acting antidepressant for treatment refractory depression (TRD); however, clinical durability is poor and treatment response trajectories vary. Little is known about which patient characteristics predict faster or more durable ketamine responses. Ketamine's antidepressant mechanism may involve modulation of glutamatergic signaling and long-term potentiation (LTP); these neuroplasticity pathways are also attenuated with older age. A retrospective analysis examining the impact of patient age on the speed and durability of ketamine's antidepressant effects in 49 veterans receiving serial intravenous ketamine infusions for TRD. The relationship between age and percent change in Beck Depression Inventory (BDI-II) scores was compared across six serial ketamine infusions (twice-weekly for 3weeks) using a linear-mixed model. A significant Age-X-Infusion number interaction (F = 3.01, p = .0274) indicated that the relationship between age and treatment response depended on infusion number. Follow-up tests showed that younger age significantly predicted greater clinical improvement at infusion #4 (t = 3.02, p = .004); this relationship was attenuated at infusion #5 (t = 1.95, p = .057) and was absent at infusion #6. Age was not a significant predictor of treatment durability, defined as percent change in BDI-II 3weeks following infusion #6. These data preliminarily suggest that younger age is associated with a faster response over six serial ketamine infusions; by infusion #6 and subsequent weeks of clinical follow-up, age no longer predicts ketamine's antidepressant activity. Age may mediate the speed but not the durability or total efficacy of ketamine treatment, suggesting that dissociable mechanisms may underlie differing aspects of ketamine's antidepressant activity.

Effects of subanesthetic intravenous ketamine infusion on neuroplasticity-related proteins in male and female Sprague-Dawley rats.

Although ketamine, a multimodal dissociative anesthetic, is frequently used for analgesia and treatment-resistant major depression, molecular mechanisms of ketamine remain unclear. Specifically, differences in the effects of ketamine on neuroplasticity-related proteins in the brains of males and females need further investigation. In the current study, adult male and female Sprague-Dawley rats with an indwelling jugular venous catheter received an intravenous ketamine infusion (0, 10, or 40 mg/kg, 2-h), starting with a 2 mg/kg bolus for ketamine groups. Spontaneous locomotor activity was monitored by infrared photobeams during the infusion. Two hours after the infusion, brain tissue was dissected to obtain the medial prefrontal cortex (mPFC), hippocampus including the CA1, CA3, and dentate gyrus, and amygdala followed by Western blot analyses of a transcription factor (c-Fos), brain-derived neurotrophic factor (BDNF), and phosphorylated extracellular signal-regulated kinase (pERK). The 10 mg/kg ketamine infusion suppressed locomotor activity in male and female rats while the 40 mg/kg infusion stimulated activity only in female rats. In the mPFC, 10 mg/kg ketamine reduced pERK levels in male rats while 40 mg/kg ketamine increased c-Fos levels in male and female rats. Female rats in proestrus/estrus phases showed greater ketamine-induced c-Fos elevation as compared to those in diestrus phase. In the amygdala, 10 and 40 mg/kg ketamine increased c-Fos levels in female, but not male, rats. In the hippocampus, 10 mg/kg ketamine reduced BDNF levels in male, but not female, rats. Taken together, the current data suggest that subanesthetic doses of intravenous ketamine infusions produce differences in neuroplasticity-related proteins in the brains of male and female rats.

Low dose intraoperative ketamine infusion with multilevel paravertebral block for pain after video-assisted thoracic surgery: a randomized-controlled study.

Intraoperative low-dose ketamine infusion has been reported to be an effective adjuvant to opioids for postoperative pain control without major side effects, but it has not been tested in video-assisted thoracic surgery (VATS). The aim of this study was to examine the effect of low-dose intraoperative intravenous ketamine infusion on 24-hour morphine requirement and acute postoperative pain following VATS for lung resection. This study was a single center, randomized, double-blind, placebo-controlled study. Thirty-two patients undergoing elective VATS for lung resection in a university hospital were included. Patients were randomly allocated (1:1 ratio) to receive either intraoperative low-dose ketamine (0.2 mg/kg/h) or normal saline infusion starting from intubation to the beginning of chest closure. All patients received multilevel thoracic paravertebral block (TPVB) and morphine was administered postoperatively via the patient-controlled analgesia pump using the same protocol. Time to first analgesia, postoperative cumulative morphine doses at 10, 30 minutes, and the consecutive 1, 2, 6, 12, 18, and 24 hours were recorded. Pain intensity during rest and deep breathing were also assessed by numeric rating scale (NRS) score at 1- and 24-hour postoperatively. There was no significant difference in median (P25, P75) cumulative 24-hour morphine requirement between the ketamine and the control groups [15 (5.5, 29.5) vs. 22.5 (15.3, 40.8) mg, P=0.090]. Patients in ketamine group had significantly longer median pain free time than the control group (27 vs. 2 minutes, P=0.006). No difference in overall NRS score at rest or during deep breathing at 1- and 24-hour postoperatively was demonstrated (P=0.861). Intraoperative low dose ketamine infusion in addition to TPVB does not reduce postoperative morphine consumption or pain intensity but may prolong pain free time in patients undergoing VATS for lung resection.

Combined Spinal Epidural Anaesthesia Technique with Ketamine Infusion for Emergency Laparotomy of a Known COVID-19 Case at High Altitude of 12000 Feet Above Mean Sea Level

SARS-CoV-2 is a highly infectious virus known to cause severe acute respiratory syndrome in humans known as COVID-19. It is well established that the mode of transmission is through aerosol generation. Since the invasive procedures like endotracheal intubation place the anaesthesiologist and the operating room staff highly exposed to the risk of infection it is prudent to follow regional anaesthesia technique wherever possible. The present case is of a 34-year-old COVID 19 positive male patient who underwent emergency laparotomy in a service hospital of armed forces at 12000 feet above sea level under combined spinal and epidural anaesthesia supplemented with sedation using intravenous infusion of Ketamine. After the attachment of standard ASA monitor and taking in account of baseline readings patient was administered an 18-gauge epidural secured in the T12-L1 level with the catheter was fix at 12 cm on the skin. Sub arachnoid block was administered to the patient using 2.75 ml of 0.5 % Bupivacaine (heavy) and 25 mcg of Fentanyl in L2-L3 space using a 26-gauge spinal needle in sitting position. Once the height of the block was ascertained at T6 level by loss of temperature sensation the surgery commenced. Patient was administered with 3.0 mg of Morphine in epidural space for perioperative analgesia. For allaying intraoperative discomfort patient was sedation infusion of Ketamine of 0.6mg/kg/hr to keep the Ramsay sedation score between 3-4. The intraoperative period was uneventful, and the patient did not require any supplemental analgesia during the surgery. Post operatively the patient was pain free and comfortable with no features of hypopnea, post-operative nausea vomiting and shivering and was shifted to the post-operative care unit in the covid facility of the hospital.

Cognitive Behavioral Therapy to Sustain the Antidepressant Effects of Ketamine in Treatment-Resistant Depression: A Randomized Clinical Trial

Introduction: Ketamine has emerged as a rapid-acting antidepressant. While ongoing treatment can prevent relapse, concerns exist regarding long-term exposure. Objective: We conducted a randomized trial to examine the feasibility and efficacy of cognitive behavioral therapy (CBT) following intravenous ketamine in treatment-resistant depression (TRD). Methods: Subjects with TRD were recruited and treated with 6 intravenous infusions of ketamine over 3 weeks. Subjects who experienced a clinical response (≥50% improvement in depression severity) were then randomized to receiving CBT or treatment as usual (TAU) for an additional 14 weeks, using a sequential treatment model. Results: Of the 42 patients who signed consent, 28 patients achieved a response and were randomized to CBT or TAU. When measured using the Montgomery-Asberg Depression Rating Scale (primary outcome measure), the effect size at the end of the study was moderate (Cohen d = 0.65; 95% CI –0.55 to 1.82), though the group-by-time interaction effect was not significant. There was a significant group-by-time interaction as measured by the Quick Inventory of Depressive Symptomatology (F = 4.58; p = 0.033), favoring a greater sustained improvement in the CBT group. This corresponded to a moderate-to-large effect size of the Cohen d = 0.71 (95% CI –0.30 to 1.70) at the end of the study (14 weeks following the last ketamine infusion). In a subset of patients (N = 20) who underwent cognitive testing using the emotional N-back assessments before and after ketamine, ketamine responders showed improvement in the accuracy of emotional N-back (t[8] = 2.33; p < 0.05) whereas nonresponders did not (t[10] <1; p ns). Conclusions: This proof-of-concept study provides preliminary data indicating that CBT may sustain the antidepressant effects of ketamine in TRD. Further study and optimization of this treatment approach in well-powered clinical trials is recommended.

The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: Results from a randomized double-blind study

This study aimed to assess the effect of a single infusion of intravenous (IV) ketamine on suicidal ideation in patients with treatment-resistant depression (TRD). Patients with TRD were randomized in a double-blind fashion to a single infusion of IV ketamine or IV midazolam placebo. Suicidal ideation was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) suicide item at 3, 5, 7, 14 and 30 days post infusion. Clinically significant suicidal ideation was defined as a MADRS suicide item score ≥2. Forty patients who received IV ketamine and 16 who received IV midazolam had suicide item scores of ≥2 at baseline (IV ketamine group mean 2.90±0.74; IV midazolam group 2.69±0.70). The mean suicide scores of these groups differed significantly from each other on day 30; the IV ketamine group had a lower mean score than controls (2.03±1.59 vs. 3.00±1.41, t-test p = 0.049; Hedges’ g 0.71). Among patients with a suicide score of ≥2 at baseline and <2 at day 3, the two groups did not differ significantly on mean scores changes at days 3, 5, 7, 14 or 30. Recurrence of suicidal ideation was extensive in both treatment groups. A single infusion of IV ketamine may reduce suicidal ideation in TRD out to 30 days post infusion, but early anti-suicidal effects appear to diminish rapidly. This post-hoc analysis was not powered to compare different doses of ketamine. A single infusion of IV ketamine might have a role as an adjunct to standard treatments in patients with TRD and suicidal ideation. Trial registration: NCT01920555.

Enhancing Trauma-Memories Reconsolidation With One-Time Ketamine Infusion

NMDA receptor antagonists were found to have a vital role in extinction and reconsolidation processes. During reconsolidation, memories are activated into a labile state and can be stored in an altered form. This idea might have clinical implications in the treatment of PTSD, with current psychotherapies’ success rate rounding 50%. Here we used a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist; 0.5mg/kg over 40min) to enhance post-retrieval extinction of real traumatic memories.

Effects of perioperative saphenous and sciatic nerve blocks, lumbosacral epidural or morphine–lidocaine–ketamine infusion on postoperative pain and sedation in dogs undergoing tibial plateau leveling osteotomy

ObjectiveTo compare the quality of postoperative analgesia and sedation after preoperative saphenous and sciatic nerve blockade, preoperative lumbosacral epidural injection and perioperative intravenous (IV) morphine, lidocaine and ketamine infusions in dogs undergoing stifle arthroscopy and tibial plateau leveling osteotomy (TPLO) under general anesthesia. Study designProspective, blinded, randomized, clinical comparison study. AnimalsA total of 45 dogs weighing 33.9 (15.9–56.7) kg and aged 5.2 (1.0–12.0) years, mean (range), undergoing elective unilateral TPLO for spontaneous cranial cruciate ligament rupture. MethodsClient-owned dogs were enrolled. Dogs were randomly assigned to one of three groups: group MLK, perioperative IV morphine, lidocaine and ketamine infusion; group EPID, lumbosacral epidural with ropivacaine and morphine; or group SSNB, saphenous and sciatic nerve blockade with ropivacaine. Routine stifle arthroscopy followed by TPLO surgery was performed. Sedation and pain scores were assessed at 0, 2, 4, 8 and 24 hours following extubation. Rescue analgesia was administered as prescribed by Glasgow composite pain score–short form score >5. ResultsSedation scores for MLK were higher than EPID and SSNB. Pain scores for SSNB were lower than those for EPID and MLK. No significant differences were found in anesthesia duration or surgery duration among groups. No dogs required rescue analgesia. Conclusions and clinical relevanceAlthough analgesia was adequate in all groups, the best combination of analgesia without increased sedation was recorded for SSNB.

Subanesthetic ketamine in the ambulatory setting for refractory cancer pain: a 6-year retrospective at a cancer center.

Pain is common in advanced cancer is often refractory to standard treatment. Ketamine has shown promise as an effective adjuvant despite conflicting reports. The aim of this retrospective was to analyze the efficacy of subanesthetic ketamine infusion in the ambulatory setting over an extended follow-up period of 3months for symptoms related to refractory cancer pain. Forty seven patients treated with intravenous ketamine infusion for refractory cancer pain at a tertiary referral cancer center. Patients demonstrated improvement from baseline in worst, mean, currentand least pain immediately after treatment (p<0.05), worst pain 1month after treatment (p=0.003), and current pain (p=0.036) and worst pain (p=0.002) 3months after treatment. Symptoms of quality of life were followed 1month after treatment.