Low-dose Ketamine Infusion Research Articles

Effect of low dose ketamine on perioperative analgesia in patients undergoing open abdominal hysterectomy - A double-blind, randomized, placebo-controlled trial

Background: Low-dose ketamine can provide effective perioperative analgesia while reducing its side effects. This study aims to estimate the effect of a low dose of ketamine administered preemptively and during the surgery on postoperative opioid requirement and the incidence of side effects of ketamine. Methods: This prospective, double-blind, randomized control trial enrolled 60 adult women (>18 years) scheduled for open abdominal hysterectomy. All patients received general anesthesia using a standard protocol. Patients were randomized to receive 0.2 mg/kg of ketamine as bolus before induction of anesthesia, followed by an infusion of 0.002 mg/kg/min for the duration of surgery (Group K) or an equivalent volume of 0.9% saline (Group C). The primary outcome was to compare the morphine requirement over the 24 h postoperatively between the two groups. The secondary outcomes were to compare the intraoperative morphine requirement, and the incidence of side effects of ketamine. Results: The intraoperative morphine requirement was significantly less (P = 0.006) in those who received ketamine (6.5 ± 1.5 mg) compared to the placebo (7.67 ± 1.7 mg). The 24-hour morphine requirement was less in the Group K (7.87 ± 4.7 mg) compared to Group C (9.2 ± 4.5 mg), but was not statistically significant. The incidence of hallucination and nystagmus was significantly higher in the ketamine group, but it lasted Conclusion: The preemptive and the intraoperative infusion of low-dose ketamine decreases the morphine requirement intraoperatively but not during the postoperative period.

Treatment response to low-dose ketamine infusion for treatment-resistant depression: A gene-based genome-wide association study

BackgroundsEvidence suggested the crucial roles of brain-derived neurotrophic factor (BDNF) and glutamate system functioning in the antidepressant mechanisms of low-dose ketamine infusion in treatment-resistant depression (TRD). Methods65 patients with TRD were genotyped for 684,616 single nucleotide polymorphisms (SNPs). Twelve ketamine-related genes were selected for the gene-based genome-wide association study on the antidepressant effect of ketamine infusion and the resulting serum ketamine and norketamine levels. ResultsSpecific SNPs and whole genes involved in BDNF–TrkB signaling (i.e., rs2049048 in BDNF and rs10217777 in NTRK2) and the glutamatergic and GABAergic systems (i.e., rs16966731 in GRIN2A) were associated with the rapid (within 240 min) and persistent (up to 2 weeks) antidepressant effect of low-dose ketamine infusion and with serum ketamine and norketamine levels. DiscussionOur findings confirmed the predictive roles of BDNF–TrkB signaling and glutamatergic and GABAergic systems in the underlying mechanisms of low-dose ketamine infusion for TRD treatment.

Low-Dose Ketamine Infusion Versus Morphine Infusion During Abdominoplasty to Change the Postoperative Pain Profile.

BackgroundWith the increased number of abdominoplasty all over the world, and the need to manage postoperative pain, it is a must to find proper and effective drugs to decrease opioid consumption in the postoperative period.ObjectivesIn this double-blind randomized controlled clinical trial, we assumed that low-dose ketamine infusion will reduce the postoperative pain profile than the conventional method of morphine.MethodsThe scheduled patients for abdominoplasty under general anesthesia were recruited in two groups: group (K) with low-dose ketamine infusion intra-operatively (80 patients) and group (M) with morphine infusion intra-operatively (80 patients). Both groups were monitored intraoperatively and postoperatively for rescue doses of fentanyl, visual analogue scale (VAS), and side effects.ResultsThere were no statistical differences between both groups regarding the fentanyl rescue doses intra- and postoperative with no remarkable side effects.ConclusionsLow-dose ketamine has a useful analgesic effect in abdominoplasty similar to morphine without remarkable side effects, such as sedation or hallucinations.

701: Adjunct Low-Dose Ketamine Infusion in Critically Ill Patients at a Saudi Hospital (ATTAINMENT Trial)

INTRODUCTION: A noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care (SOC) in critically ill patients on mechanical ventilation (MV) for ≥ 24 h METHODS: This trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult intensive care unit (ICU) patients (> 14 years old) on MV at King Faisal Specialist Hospital and Research Center, Saudi Arabia, and will enroll 80 patients Patients was randomized post-intubation into two groups: the intervention group received an adjunct lowdose ketamine infusion plus SOC administered over a period of 48 h at a fixed infusion rate of 2 μg/kg/min (0 12 mg/kg/h) in day 1 followed by 1 μg/kg/min (0 06 mg/kg/h) in day 2 The control group received SOC (propofol and/or fentanyl and/or midazolam) according to our sedation and analgesia protocol as clinically appropriate The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first RESULTS: As of 25 July 2020, a total of 65 patients had been enrolled We expect to complete the recruitment by 31 December 2020 Recruitment rate has been slowed down due to COVID-19 pandemic An Interim analysis was conducted and showed 45% were in medical ICU, 35 % in surgical ICU, and 20 % in transplant/oncology ICU, range SOFA 2-18, and APACHE II 7-39 About 70 % of the patients was extubated within 28 days post-randomization to ketamine compared to 50 % randomized to SOC The percentage of the patient at goal RASS in 48 hours is 61 11 % in ketamine vs 57 89 % in SOC No significant difference between the 2 arms in 28 days mortality CONCLUSIONS: The findings of this pilot trial will justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial The trial is registered at ClinicalTrials gov: NCT04075006, Saudi Food and Drug Authority: SCTR #19063002, and Current controlled trials: ISRCTN14730035

Perioperative Intravenous Low-Dose Ketamine Infusion to Minimize Pain for Septorhinoplasty: A Prospective, Randomized, Double-Blind Study.

Studies investigating the effects of intravenous (IV) ketamine in pain management after septorhinoplasty is limited. This study aims to evaluate the efficacy of low-dose IV infusion of ketamine on pain scores. This randomized, prospective, double-blind study was conducted with 48 patients who underwent septorhinoplasty. Intravenous ketamine bolus (0.5 mg/kg) was administered to the ketamine group (group K, n = 24) at anesthesia induction, and ketamine infusion was continued (0.25 mg/kg/h) during the surgery. In the control group (group C, n = 24), the same protocol was administered using saline instead of ketamine. Furthermore, 50-mg dexketoprofen trometamol was administered to both groups 30 minutes before the end of the surgery. Then it was repeated at the 12th and 24th hours postoperatively. Pain scores were evaluated with the visual analogue scale. Consumptions intraoperative of opioid and sevoflurane, rescue opioid requirement, patient satisfaction, and side effects were recorded. Pain scores were significantly lower in group K at all postoperative periods (P < .05). There was no significant difference between the groups in terms of intraoperative sevoflurane and remifentanil consumptions (P > .05). Rescue opioid analgesic requirements were significantly lower in group K than group C (0/24 vs 6/24, respectively; P = .022). Side effects were similar between the groups (P > .05). We recommend the administration of low-dose ketamine infusion during septorhinoplasty surgery because it reduces the requirement for rescue opioid analgesia and postoperative pain scores.

Using classification and regression tree modelling to investigate treatment response to a single low-dose ketamine infusion: Post hoc pooled analyses of randomized placebo-controlled and open-label trials

Background: Evidence suggests that clinical markers, such as comorbid anxiety, body weight, and others can assist in predicting response to low-dose ketamine infusion in treatment resistant depression patients. However, whether a composite of clinical markers may improve the predicted probability of response is uncertain. Methods: The current study investigated the results of our previous randomized placebo-controlled and open-label trials in which 73 patients with treatment-resistant depression (TRD) received a single ketamine infusion of 0.5 mg/kg. Clinical characteristics at baseline, including depression severity, duration of the current episode, obesity, comorbidity of anxiety disorder, and current suicide risk, were assessed as potential predictors in a classification and regression tree model for treatment response to ketamine infusion. Results: The predicted probability of a composite of age at disease onset, depression severity, duration of current episode, and obesity/overweight was significantly greater (area under curve = .736, p = .001) than that of any one marker (all p > .05). The most powerful predictors of treatment response to ketamine infusion were younger age at disease onset and obesity/overweight. The strongest predictors of treatment nonresponse were longer duration of the current episode and greater depression severity at baseline. Discussion: Depression severity, duration of the current episode, obesity, and age at disease onset may predict treatment response versus nonresponse to low-dose ketamine infusion. However, whether our predicted probability for a single infusion may be applied to repeated infusions would require further investigation. Clinical trial registration: UMIN Clinical Trials Registry (UMIN000023581 and UMIN000016985).

Happiness During Low-Dose Ketamine Infusion Predicts Treatment Response: Reexploring the Adjunctive Ketamine Study of Taiwanese Patients With Treatment-Resistant Depression.

Studies have reported that ketamine potentially increases subjective happiness in healthy volunteers. However, whether ketamine-induced happiness can predict the treatment response of ketamine infusion among patients with treatment-resistant depression (TRD) remains unknown. Between 2012 and 2015, 71 adult patients with TRD (based on DSM-IV-TR criteria) were enrolled and randomly assigned to receive a 40-minute ketamine (0.5 mg/kg or 0.2 mg/kg) or normal saline placebo infusion. Depressive symptoms were measured using the 17-item Hamilton Depression Rating Scale. Measurements were conducted prior to infusion, at 40 and 240 minutes postinfusion, and, sequentially, on days 2 to 7 and 14 postinfusion. The visual analog scale for happiness (VASH) was used to assess happiness during infusion. The positive symptoms subscale of the Brief Psychiatric Rating Scale (BPRS-P) was used to measure the potential psychotomimetic effects of ketamine. For both the 2-factor (ketamine vs placebo) and 3-factor (ketamine 0.5 mg/kg vs 0.2 mg/kg vs placebo) models, a generalized estimating equation model indicated that infusion response type (happiness vs nonhappiness) significantly (P = .008 vs P = .002) predicted the trajectory of depressive symptoms after infusion. Changes in VASH and BPRS-P measures were not associated with each other. Subjective happiness during ketamine infusion predicted the antidepressant effect of both 0.5 mg/kg and 0.2 mg/kg ketamine infusion over time. Happiness during ketamine infusion, which was not related to the psychotomimetic effect of ketamine, may be associated with the reduction of depressive symptoms during the follow-up. UMIN Clinical Trials Registry registration number: UMIN000016985.

A Combination of Inhaled Nitrous Oxide and Low-Dose Ketamine Infusion for Labor Analgesia

(J Clin Anesth. 2019;57:64–65) While ketamine is useful in a labor analgesia setting, it is typically used infrequently due to its association with lower Apgar scores, uterine hypertonus, and maternal psychological reactions. Inhaled nitrous oxide (iNO) is another analgesia option, although it provides maternal anxiolytic effects but limited labor analgesia. Not much research has been done on using the combination of a low-dose ketamine infusion (&lt;0.5 mg/kg/h intravenous) and iNO for labor analgesia. These authors outlined 2 cases that apply this analgesic regimen.

Functional Dysconnectivity of Frontal Cortex to Striatum Predicts Ketamine Infusion Response in Treatment-Resistant Depression.

BackgroundFrontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown.MethodsIn total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls.ResultsCompared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion.ConclusionReduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.

Pilot randomized active-placebo-controlled trial of low-dose ketamine for the treatment of multiple sclerosis–related fatigue

Background: Fatigue is the most common symptom of MS and has no effective pharmacotherapy. Objective: To determine the tolerability, safety, and efficacy of low-dose ketamine infusion for MS-related fatigue. Methods: In this double-blind, randomized, active-placebo-controlled trial, 18 subjects with multiple sclerosis (MS) and reported fatigue received a single intravenous infusion of ketamine (0.5 mg/kg) or midazolam (0.05 mg/kg). The primary outcome was change in Daily Fatigue Severity (DFS) for 7 days following the infusion. Secondary outcomes included Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS) measured up to day 28 post-infusion. We analyzed changes in all outcomes using mixed-effect models. Results: In total, 18 participants were enrolled; 67% participants received ketamine. Side effects of ketamine were transient. No change in the DFS was observed after 7 days (−0.10 point; 95% confidence interval (CI): −0.32, 0.12; p = 0.40). We observed a trend in reduced FSS scores at 1 week (−5.2 points; 95% CI: −10.4, 0.14; p = 0.06) and a clinically and statistically significant reduction in MFIS score at day 28 (−13.5 point; 95% CI: −25.0, −1.98; p = 0.04). Conclusions: Ketamine infusions were safe and well-tolerated. While no change in DFS after 7 days was observed, secondary analyses suggest a benefit of ketamine infusion for reduction of longer term fatigue severity in people with MS.

Efficacy of low-dose ketamine infusion in anxious vs nonanxious depression: revisiting the Adjunctive Ketamine Study of Taiwanese Patients with Treatment-Resistant Depression.

The antidepressant effect of low-dose ketamine infusion on Taiwanese patients with anxious vs nonanxious treatment-resistant depression (ANX-TRD vs NANX-TRD) has remained unknown. In total, 71 patients with TRD were randomized to three groups. Each group had participants who received saline infusions mixed with 0 (a normal saline infusion), 0.2, and 0.5 mg/kg of ketamine. Participants were followed up for 2 weeks. Anxious depression was defined as major depressive disorder with a total score of 7 or more on the 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor. Generalized estimating equation models were used to investigate the effects of treatment (ketamine vs placebo) and depression type (ANX-TRD vs NANX-TRD) in the reduction of depressive symptoms during the follow-up period. Patients with ANX-TRD were less likely to respond to a single low-dose ketamine infusion than those with NANX-TRD. Among patients with NANX-TRD, low-dose ketamine infusion was significantly superior to placebo for reducing depressive symptoms. However, among patients with ANX-TRD, ketamine was not superior to placebo; nonetheless, approximately 30% of the patients responded to ketamine infusion compared to 13% who responded to the placebo. Low-dose ketamine infusion was effective for Taiwanese patients with NANX-TRD but not so effective for those with ANX-TRD. A higher level of anxiety severity accompanying depression was related to greater depression severity. This may confound and reduce the antidepressant effect of ketamine infusion.

Adjunct low-dose ketamine infusion vs standard of care in mechanically ventilated critically ill patients at a Tertiary Saudi Hospital (ATTAINMENT Trial): study protocol for a randomized, prospective, pilot, feasibility trial

BackgroundA noticeable interest in ketamine infusion for sedation management has developed among critical care physicians for critically ill patients. The 2018 Pain, Agitation/sedation, Delirium, Immobility, and Sleep disruption guideline suggested low-dose ketamine infusion as an adjunct to opioid therapy to reduce opioid requirements in post-surgical patients in the intensive care unit (ICU). This was, however, rated as conditional due to the very low quality of evidence. Ketamine has favorable characteristics, making it an especially viable alternative for patients with respiratory and hemodynamic instability. The Analgo-sedative adjuncT keTAmine Infusion iN Mechanically vENTilated ICU patients (ATTAINMENT) trial aims to assess the effect and safety of adjunct low-dose continuous infusion of ketamine as an analgo-sedative compared to standard of care in critically ill patients on mechanical ventilation (MV) for ≥ 24 h.Methods/designThis trial is a prospective, randomized, active controlled, open-label, pilot, feasibility study of adult ICU patients (> 14 years old) on MV. The study will take place in the adult ICUs in the King Faisal Specialist Hospital and Research Center (KFSH&RC), Riyadh, Saudi Arabia, and will enroll 80 patients. Patients will be randomized post-intubation into two groups: the intervention group will receive an adjunct low-dose continuous infusion of ketamine plus standard of care. Ketamine will be administered over a period of 48 h at a fixed infusion rate of 2 μg/kg/min (0.12 mg/kg/h) in the first 24 h followed by 1 μg/kg/min (0.06 mg/kg/h) in the second 24 h. The control group will receive standard of care in the ICU (propofol and/or fentanyl and/or midazolam) according to the KFSH&RC sedation and analgesia protocol as clinically appropriate. The primary outcome is MV duration until ICU discharge, death, extubation, or 28 days post-randomization, whichever comes first.DiscussionThe first patient was enrolled on 1 September 2019. As of 10 October 2019, a total of 16 patients had been enrolled. We expect to complete the recruitment by 31 December 2020. The findings of this pilot trial will likely justify further investigation for the role of adjunct low-dose ketamine infusion as an analgo-sedative agent in a larger, multicenter, randomized controlled trial.Trial registrationClinicalTrials.gov: NCT04075006. Registered on 30 August 2019. Current controlled trials: ISRCTN14730035. Registered on 3 February 2020.

Low Dose Ketamine Infusion for the Treatment of Resistant Depression

Low Dose Ketamine Infusion for the Treatment of Resistant Depression

Effects of Intraoperative Low-Dose Ketamine on Persistent Postsurgical Pain after Breast Cancer Surgery: A Prospective, Randomized, Controlled, Double-Blind Study

Compared to acute postsurgical pain, studies regarding the role of ketamine in persistent postsurgical pain (PPSP) are limited. The aim of this clinical trial was to test if intraoperative low-dose ketamine without postoperative infusion would reduce PPSP development after breast cancer surgery. We used a randomized, double-blinded, placebo study design. This study was conducted at Pusan National University Hospital, Republic of Korea, between December 2013 and August 2016. A total of 184 patients scheduled for breast cancer surgery were randomly assigned to either the control or ketamine group. Before skin incision, a bolus (0.5 mg/kg of ketamine or placebo), followed by a continuous infusion (0.12 mg/kg/h of ketamine or placebo), was administered until the end of the surgery. The patients were interviewed via telephone 1, 3, and 6 months after surgery. The first question was whether the patient had surgery-related pain. If answered affirmatively, questions from the Numeric Rating Scale for pain at rest (NRSr) and for coughing (NRSd) were also asked. Our primary outcome was the incidence of PPSP at 3 months after surgery. For PPSP analysis, 168 patients were included. The number of patients who experienced pain was significantly lower in the ketamine group at 3 months (86.9% in the control group vs 69.0% in the ketamine group, P = .005) postoperatively. However, the NRSr and NRSd did not differ between the groups throughout the follow-up. There were no postoperative low-dose ketamine infusion groups to compare due to hospital regulations. Dosage of ketamine was too low to reduce the severity of PPSP. And by using propofol and remifentanil for anesthesia, different results can be deduced with volatile anesthetics. Data from written questionnaires would have been more specific than telephone interviews for long-term assessment. Though intraoperative low-dose ketamine without postoperative infusion significantly reduced the incidence of PPSP up to 3 months after breast cancer surgery, it failed to reduce clinically significant PPSP and improve patients' quality of life. Analgesia, breast cancer, chronic pain, ketamine, mastectomy, morphine, pain, postoperative, propofol.

Low Dose Ketamine Infusion for Comorbid Posttraumatic Stress Disorder and Chronic Pain: A Randomized Double-Blind Clinical Trial

Objective To date, treatment options (i.e. psychotherapy, antidepressant medications) for patients with posttraumatic stress disorder (PTSD), are relatively few, and considering their limited efficacy, novel therapies have gained interest among researchers and treatment providers alike. Among patients with chronic pain (CP) about one third experience comorbid PTSD, which further complicates their already challenging pharmacological regimens. Low dose ketamine infusion has shown promise in PTSD, and in treatment of CP, however they have not been studied in comorbid population and under rigorous control conditions. Methods We compared the effects of a single dose of either ketamine (0.5 mg/kg) or ketorolac (15 mg) over a 40-minute of IV infusion in CP patients with and without PTSD, in double blind, randomized study. Measures were collected before, during, one day and seven days after the infusion. A planned sample size of 40 patients randomly assigned to treatment order was estimated to provide 80% power to detect a hypothesized treatment difference after the infusion. Main Outcome and Measures: The primary outcome measures were change in PTSD symptom severity assessed with the Impact of Event Scale–Revised (IES-R) and Visual Analogue Scale (VAS) for pain administered by a study clinician 24 hours post infusion. Secondary outcome measures included Impact of Event Scale–Revised (IES-R), VAS and Brief Pain Inventory (Short Form) for pain 1 week after the infusion. Results Both treatments offered comparable improvement of PTSD and CP symptoms that persisted for 7 days after the infusion. Patients with comorbid PTSD and CP experienced less dissociative side effects compared to the CP group. Surprisingly, ketorolac infusion resulted in dissociative symptoms in CP patients only. Conclusions This first prospective study comparing effects of subanesthetic ketamine versus ketorolac infusions for comorbid PTSD and CP, suggests that both ketamine and ketorolac might offer meaningful and durable response for both PTSD and CP symptoms.

Comparative study of retrobulbar block versus ketamine infusion during eye enucleation/evisceration (randomized controlled trial)

Background:The aim of this study is to compare the safety and efficacy of retrobulbar block versus intraoperative ketamine infusion in eye enucleation or evisceration under general anesthesia.Materials and Methods:Forty-five patients belonging to American Society of Anesthesiologists Physical Status I and II undergoing eye enucleation or evisceration were randomly allocated to three equal groups (15 patients each). General anesthesia was used as the standardized technique in all patients. Group R received a single retrobulbar injection, Group K received intravenous ketamine infusion, and Group C received normal saline with the same rate of ketamine infusion. Intraoperative heart rate and mean arterial pressure, recovery time, postoperative pain score, time to first rescue analgesic, number of patients who required rescue analgesia, and any adverse events were reported.Results:Postoperative pain Visual Analog Scale was significantly lower in R and K groups in comparison to the C group and was significantly higher in K than R group at 3, 6, 12, and 24 h. In addition, the time to first rescue analgesic was significantly longer in R group (429 ± 54 min) than that in K group (272 ± 34 min), but compared to both groups, it was longer in C group (52 ± 7 min). In K group, the recovery time was longer with higher sedation score in comparison to the other two groups.Conclusions:Single retrobulbar injection and low-dose ketamine infusion are safe and effective when used as adjuvants to general anesthesia, but retrobulbar block provides better control of postoperative pain with prolonged time to first rescue analgesic and reduced analgesic consumption.

Prophylactic low dose ketamine infusion for prevention of shivering during spinal anesthesia: A randomized double blind clinical trial.

Background and Aims:Regional anesthesia is known to produce perioperative hypothermia and shivering. We aimed to evaluate if prophylactic low dose ketamine bolus followed by infusion would prevent intraoperative and postoperative shivering under spinal anesthesia.Material and Methods:Sixty patients belonging to American Society of Anaesthesiologists (ASA) 1 and 2 undergoing abdominal and lower limb surgery were randomized to receive either 0.2 mg/kg iv of ketamine bolus followed by infusion 0.1 mg/kg/hr (Group K) or5 ml of saline followed by 0.1 ml/kg/hr solution (Group S) as an infusion throughout the period of surgery. The incidence of shivering was the primary outcome of the study with degree of sedation and the hemodynamic profile between the two groups being the secondary outcomes. Hemodynamics (Heart rate, Mean Blood Pressure and temperature), Grade of shivering and grade of sedation were assessed intraoperatively and for grade of shivering and sedation two hours postoperatively. Repeated measures Analysis of Variance (ANOVA) was used to compare the hemodynamic variables and Chisquare test/Fisher's exact test to compare the grades of shivering and sedation between the two groups.Results:Intraoperative shivering was seen in eighteen patients in saline group (58.06%) and only with four patients (13.79%) with ketamine group (P < 0.001). Post operative shivering was also significantly less in ketamine group compared to saline (P = 0.01). Also, patients who received ketamine had significant sedation in the intraoperative period (P < 0.001).Conclusion:Prophylactic low dose ketamine administered as a small bolus followed by an infusion was effective in preventing both intraoperative and postoperative shivering.

The Effect of Low Dose Ketamine Infusion on Postoperative Acute and chronic Pain after Thoracotomy

Objective: The aim of this study was to investigate the effects of a perioperatively administered low dose of ketamine on postoperative acute, chronic pain following thoracotomy. Methods: Forty patients with ASA I–III and aged between 18 and 65 years were included in the study. Patients were randomly divided into two groups. Group I (n=20) was administered a ketamine 0.5 mg.kg-1 bolus followed by a 2 mcg.kg-1.dk-1 infusion for 24 hours before the incision. Group II (n=20) was given normal saline at the same dose and duration. Postoperative analgesia was achieved through patient-controlled morphine administration. Postoperative resting and moving Visual Analogue Scale values, total morphine consumption, preoperative and postoperative values of FVC, FEV1 and FEF25-75 from pulmonary function tests were recorded. Patients were evaluated in terms ofchronicpain in the surgical incision area at 1 and 3 months after the operation. Nausea, vomiting, agitation, delirium, hallucination and sedation scores were recorded. Results: No statistical difference was found between groups in terms of demographic characteristics and operational features. Visual analogue scale values at rest and on movement were significantly lower in Group I. Total morphine consumption was also significantly lower in Group I. There was no difference between the groups in terms of pulmonary function tests. There was no difference between groups in terms of the incidence of chronic pain and development during the first month after the operation, while the incidence of chronic pain in the third month was significantly lower in Group I.No significant difference was observed between groups in terms of sedation scores. The incidence of side effects such as nausea, vomiting, agitation, delirium and hallucinations was similar in both groups. Conclusion: Low-dose ketamine infusion is an efficient method in postoperative acute and chronic pain management after thoracotomy, it reduces analgesic consumption.

Perioperative intravenous low-dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo-controlled study.

Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low-dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, 6 and 12months after major lower back surgery. In this single-centre randomized trial, 80 patients received intravenous ketamine 0.25mg/kg preoperatively, followed by 0.25mgkg-1 hr-1 intraoperatively, and 0.1mgkg-1 hr-1 from 1hr before the end of surgery until the end of recovery room stay; 80 controls received placebo. Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8mg (IQR 67.4-106.7) and the median plasma level was 97ng/ml (IQR 77.9-128.0). At 6months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI -10.7 to 21.1; p=.607). At 12months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI -6.7 to 23.6; p=.319). In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low-dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at 6 or 12months postoperatively. We were unable to show any analgesic benefit of a short-term perioperative ketamine infusion as an adjuvant to multimodal analgesia in patients with a high prevalence of neuropathic lower back pain undergoing major back surgery. Based on these data, the widespread opinion that ketamine is universally analgesic across different pain conditions must be challenged. Abstract presentation at the annual congress of the Swiss Society of Anaesthesiology, 2016, Basel, Switzerland. Registered by Dr Christoph Czarnetzki as principal investigator on February 20, 2008 at clinicaltrials.gov (NCT00618423).

A Bolus Dose of Ketamine Reduces the Amplitude of the Transcranial Electrical Motor-evoked Potential: A Randomized, Double-blinded, Placebo-controlled Study.

A low-dose bolus or infusion of ketamine does not affect transcranial electrical motor-evoked potential (MEP) amplitude, but a dose ≥1 mg/kg may reduce MEP amplitude. We conducted a randomized, double-blinded, placebo-controlled study to evaluate the effect of ketamine (1 mg/kg) on transcranial electrical MEP. Twenty female patients (aged 12 to 18 y) with adolescent idiopathic scoliosis scheduled to undergo posterior spinal fusion were randomly allocated to receive ketamine or saline. General anesthesia was induced and maintained with continuous infusions of propofol and remifentanil. MEP was elicited by supramaximal transcranial electrical stimulation. MEP recordings were obtained at baseline and then at 2, 4, 6, 8, and 10 minutes after administration of ketamine (1 mg/kg) or saline (0.1 ml/kg). The primary endpoint was the minimum relative MEP amplitude (peak-to-peak amplitude, % of baseline value) recorded from the left tibialis anterior muscle. The baseline amplitude recorded before test drug administration was defined as 100%. Medians (interquartile range) minimum MEP amplitudes in the left tibialis anterior muscle in the ketamine and saline groups were 26% (9% to 34%) and 87% (55% to 103%) of the baseline value, respectively (P<0.001). MEP amplitudes in other muscles were significantly reduced by ketamine. The suppressive effect of ketamine lasted for at least 10 minutes in each muscle. A 1-mg/kg bolus dose of ketamine can reduce MEP amplitude. Anesthesiologists should consider the dosage and timing of intravenous ketamine administration during MEP monitoring.