Intraoperative Ketamine Administration Research Articles

Effects of intra-operative administration of subanesthetic s-ketamine on emergence from sevoflurane anesthesia: a randomized double-blind placebo-controlled study

BackgroundKetamine is administered in the perioperative period for its benefits in analgesia, anti-agitation and anti-depression when administered at a small dose. However, it is not clear whether the intra-operative administration of ketamine would affect emergence under sevoflurane anesthesia. To investigate this effect, we designed this trial.MethodsIn this randomized, double-blind, placebo-controlled study, we enrolled 44 female patients aged 18–60 who were scheduled to elective laparoscopic gynecological surgeries. All patients were randomly assigned to saline or s-ketamine group. In s-ketamine group, patients received 0.125 mg/kg s-ketamine 30 min after the start of surgery. In saline group, patients were administered the same volume of saline. Sevoflurane and remifentanil were used to maintain general anesthesia. The primary outcome was emergence time. We also assessed postoperative agitation, cognitive function, and delirium. In addition, we collected and analyzed prefrontal electroencephalogram (EEG) during and after general anesthesia.ResultsThere were no significant differences in emergence time between s-ketamine group and saline group (10.80 ± 3.77 min vs. 10.00 ± 2.78 min, P = 0.457). Neither postoperative agitation (4 [3, 4] vs. 4 [3, 4], P = 0.835) nor cognitive function (25.84 ± 2.69 vs. 25.55 ± 2.19, P = 0.412) differed between groups. No postoperative delirium was observed in either group. Subanesthetic s-ketamine resulted in active EEG with decreased power of slow (-0.35 ± 1.13 dB vs. -1.63 ± 1.03 dB, P = 0.003), delta (-0.22 ± 1.11 dB vs. -1.32 ± 1.09 dB, P = 0.011) and alpha (-0.31 ± 0.71 dB vs. -1.71 ± 1.34 dB, P = 0.0003) waves and increased power of beta-gamma bands (-0.30 ± 0.89 dB vs. 4.20 ± 2.08 dB, P < 0.0001) during sevoflurane anesthesia, as well as an increased alpha peak frequency (-0.16 ± 0.48 Hz vs. 0.31 ± 0.73 Hz, P = 0.026). EEG patterns did not differ during the recovery period after emergence between groups.ConclusionKetamine administered during sevoflurane anesthesia had no apparent influence on emergence time in young and middle-aged female patients undergoing laparoscopic surgery. Subanesthetic s-ketamine induced an active prefrontal EEG pattern during sevoflurane anesthesia but did not raise neurological side effects after surgery.Trial registrationChinese Clinical Trial Registry, ChiCTR2100046479 (date: 16/05/2021).

Impact of Ketamine on Quality of Recovery after Laparoscopic Surgery: A Single-Centre Single-Blinded Trial Using the QoR-15 Questionnaire.

The quality of recovery is a cluster of patient-related outcomes that emphasise not only pain but different physical and emotional dimensions. Traditionally, ketamine is used to improve postoperative analgesia and avoid opioid consumption and opioid-related side effects. The present study sought to evaluate if intraoperative ketamine administration (as a part of multimodal analgesia) influences the quality of recovery after laparoscopic surgery. A prospective two-armed, single-blinded trial. Settings. Tertiary single-centre trial between July 2021 and January 2022. Patients. From the 146 patients initially admitted to the study, 127 patients were enrolled, 60 in the ketamine group (group K) and 67 in the control group (group NK). Intervention. Both groups received a rigid intraoperative anaesthesia protocol; furthermore, in group K, 0.5 mg/kg of the ideal body weight of ketamine was administered. Main Outcome Measures. The primary outcome was to evaluate the effect of ketamine administration on the postoperative quality of recovery using the Portuguese version of the Quality of Recovery-15 (QoR-15) Questionnaire 24 h after surgery. The total score and minimal clinically significant difference (MCID) of the QoR-15 were compared. Other variables were also assessed such as the presence of emergence delirium (ED), the Numeric Rating Scale (NRS) for pain, and the presence of postoperative nausea and vomiting (PONV). A total of 127 patients were allocated to the study groups, 60 in group K and 67 in group NK. Regarding the primary outcome, no differences were found in individual categories (15 items) and in the total score of QoR-15 (p=0.214). Concerning improvement (MCID ≥ 8) or worsening (MCID ≤ 8) in quality of recovery, no difference was found between the groups (24 vs. 32 and 6 vs. 6; p=0.776). Finally, no difference was found in secondary postoperative outcomes including ED (p=0.55), NRS (p=0.401), and PONV (p=0.55). In this study, the administration of ketamine in laparoscopic surgery had no impact on the quality of recovery 24 h after surgery. This trial is registered with NCT03724019.

Association between intraoperative ketamine and the incidence of emergence delirium in laparoscopic surgeries: an observational study

BackgroundEmergence Delirium (ED) is an essential condition in the immediate postoperative period. Systematic review and meta-analysis of randomized controlled trials have concluded that the effect of ketamine on postoperative delirium remains unclear. The present study sought to evaluate if the intraoperative use of ketamine for postoperative analgesia is associated with postoperative ED in laparoscopic surgeries. MethodsA prospective observational study was performed in the PostAnesthetic Care Unit (PACU) to evaluate patients who had undergone laparoscopic surgery under a rigid intraoperative anesthesia protocol from July 2018 to January 2019. Patients submitted to laparoscopic surgery for cholecystectomy, oophorectomy, or salpingectomy with a score ≥1 on the Richmond Assessment Sedation Scale (RASS) or ≥2 on the Nursing Delirium Screening Scale (Nu-DESC) were considered to have ED. t-test, Chi-Square test or Fisher's exact tests were used for comparison. ResultsOne hundred and fifteen patients were studied after laparoscopic surgery. Seventeen patients (14.8%) developed ED, and the incidence of ED in patients who received ketamine was not different from that of other patients (18.3% vs. 10.6%, p = 0.262). Patients with ED had more postoperative pain and morphine requirement at the PACU (p = 0.005 and p = 0.025, respectively). Type of surgery (general surgery, OR = 6.4, 95% CI 1.2‒35.2) and postoperative pain (OR = 3.7, 95% CI 1.2‒11.4) were risk factors for ED. ConclusionIn this study, no association was found between ED and intraoperative administration of ketamine in laparoscopic surgeries. Type of surgery and postoperative pain were risk factors for ED.

Pain Scores and Analgesic Therapy for Complex Spine Surgery in Tertiary Care Center

Background: Complex spine surgery is an extensive operation with severe pain. At Siriraj Hospital, multimodal analgesia has been used, but it is not clear whether this technique provides adequate analgesia for major spine surgery. Objective: To assess the incidence and related factors of severe pain in patients undergoing complex spine surgery. Materials and Methods: A prospective, descriptive, observational study was conducted on adult patients undergoing complex thoracolumbar spine surgery at Siriraj Hospital between September 2016 and November 2018. The authors collected the patient demographic data, surgical data, perioperative pain management, and postoperative pain scores at rest and in movement. The data were analyzed using descriptive statistics, and the related factors to postoperative pain severity were analyzed using logistic regression analyses. Results: The present study enrolled 195 adults with a mean age of 61 years. Most were female (67.7%). The main diagnosis was spinal stenosis (38.5%). The procedures were laminectomies with posterior instrumentation (54.4%) and posterior instrumentation with interbody fusion (40.4%). The incidences of postoperative severe pain, a numeric pain rating scale score of more than 7 at rest/movement, at the PACU and at 4, 8, 12, 16, 20, 24, and 48 hours were 37.4%/47.2%, 33.3%/48.7%, 25.6%/39.0%, 17.4%/34.4%, 13.8%/31.3%, 11.8%/24.6%, 10.3%/24.6%, and 8.7%/15.9%, respectively. The overall incidence of postoperative severe pain was 35.4%. No relationships were established between the patient and the surgical factors. The related factors were intraoperative ketamine administration and severe pain in the recovery room. Conclusion: The incidence of severe pain remained high despite multimodal analgesia. There is room for improvement. Keywords: Complex spine surgery; Postoperative pain; Multimodal analgesia; Pain management

Early reduction in postoperative pain is associated with improved long-term function after shoulder arthroplasty: a retrospective case series.

Mixed modalities are frequently utilized in total shoulder arthroplasty (TSA) to control pain, improve patient satisfaction, reduce narcotics use and facilitate earlier discharge. We investigate the relationship between early postoperative pain control and long-term functional outcomes after shoulder arthroplasty. A retrospective review identified 294 patients (314 shoulders) who underwent anatomic or reverse TSA and received a continuous cervical paravertebral nerve block perioperatively. Opioid and non-opioid analgesics were also available to the patients in an "as needed" capacity to augment perioperative pain control. In addition to demographic and surgical characteristics, the impact on functional outcomes of relative pain (i.e., a patient's subjective pain relative to the entire cohort), pain gradient (i.e., the slope of a patient's subjective pain), and opioid consumption during the first 24h postoperatively were assessed. Shoulder function was assessed using validated outcome measures collected at 2 year follow-up. Outcomes were measured using American Shoulder and Elbow Surgeons questionnaire (ASES), Shoulder Pain and Disability Index (SPADI), SPADI-130, Raw and Normalized Constant Score, SST-12 and UCLA score. Patients younger than 65, females, reverse TSA, revisions, and preoperative opioid users had worse functional outcomes. On univariate analysis, increased pain perioperatively (> 50% percentile relative pain) was associated with decreased function at 2 years when analyzed with all seven outcome scores (P < .001 for all), reaching minimal clinically important difference (MCID) using the Constant Score. On multivariate analysis, increased pain in the first 24h postoperatively (assessed on a continuous scale) was independently associated with worse ASES, SPADI, and SPADI-130 scores. Intraoperative ketamine administration and opioid consumption in the 24h postoperative period did not influence long-term shoulder function. Patients reporting reduced pain after TSA demonstrated improved shoulder function with the Constant score at 2 years postoperatively in both univariate and multivariate analysis. Larger-scale investigation may be warranted to see if this is true for other functional outcome measures. III, treatment study.

187 Ketamine and Spinal Fusion Surgery: Does It Increase or Reduce Postoperative Opioid Consumption? A Systematic Review and Meta-Analysis of Randomized Controlled Trial

INTRODUCTION: Ketamine is a commonly used anesthetic that can also be used for analgesia and sedation. However, none has examined its role in spinal fusion surgery. METHODS: Using the keywords ketamine, spinal fusion surgery, postoperative, and opioid, each reviewer individually carried out a literature search from PubMed, EuroPMC, and Cochrane CENTRAL until May 15, 2021. We only included studies with the adult population, a randomized controlled trial design, English language publications, and reported the key exposure. Additionally, only fully reviewed literature was included. We also excluded non-human literature. The primary endpoint was morphine consumption after 24 and 48 hours of undertaking surgery, whereas secondary endpoints were pain and complications. The pain was analyzed using the visual analogue scale (VAS). We performed a standardized mean difference meta-analysis for postoperative morphine consumption and pain. For complications, we reported the odds ratio as the pooled effect estimate. Each studies quality included was assessed using the Newcastle-Ottawa Scale. RESULTS: We included four notable studies in this study (n = 515). 34.5% male and 65.5% female with the mean age of 45.4 years old. We found that intraoperative ketamine administration were associated with lower postoperative opioid consumption -38.35 mg (95% CI -53.18, -23.52), decreased VAS score -0.83 (95% CI -1.26, -0.39), and lower postoperative complications (OR 0.80, 95% CI 0.60, 1.06). CONCLUSION: Ketamine administration intraoperatively resulted in a considerable reduction in morphine intake, decreased pain, and fewer adverse reactions in spinal fusion surgery patients.

An Analysis of Risk Factors for a Fracture or Luxation in Recovery From General Anesthesia in Horses: A Single Centre Study☆

Catastrophic fractures or luxations (FoL) sustained during recovery from general anesthesia are a significant cause of mortality during equine anesthesia. There is a lack of evidence regarding potential risk factors for a FoL occurring in the immediate anesthetic recovery period. A single center, retrospective, case-matched study was performed to identify risk factors for sustaining a catastrophic FoL during recovery from general anesthesia. Clinical data were obtained for horses which sustained a catastrophic FoL when recovering from general anesthesia from January 2011 to June 2020 in a single center referral population. Multivariable logistical regression analysis was performed to identify risk factors which were significant in horses where a FoL occurred. Statistically significant risk factors in our population of horses of sustaining a FoL in recovery included intraoperative administration of intratracheal salbutamol, intraoperative administration of ketamine and increasing age. Further research in this area, particularly with regards to salbutamol administration, is required.

Ketamine Alleviates Depressive Symptoms in Patients Undergoing Intracranial Tumor Resection: A Randomized Controlled Trial.

Depressive symptoms occur in over 40% of neurosurgical patients during the perioperative period. However, no measure has been suggested to have a rapid effect on depressive surgical patients during increasingly shorter stays in the hospital. This study aimed to determine whether ketamine could improve depressive symptoms rapidly and safely during the hospital stay. This was a randomized, placebo-controlled, and double-blinded trial. Patients with moderate-to-severe depressive symptoms undergoing elective supratentorial brain tumor resection were randomized to intravenously receive either (1) 0.5 mg·kg-1 ketamine for 40 minutes or (2) an identical volume of normal saline. The primary outcome was treatment response on postoperative day 3, defined as a ≥50% reduction from the baseline depressive score. The secondary outcomes included the rate of remission and safety outcomes. The Montgomery-Åsberg Depression Rating Scale was applied by trained psychiatrists to evaluate depressive symptoms. A total of 84 neurosurgical patients were enrolled in the trial. The response rate was increased by the administration of ketamine (41.5% [17/41] vs 16.3% [7/43]; relative risk [RR]: 2.51, 95% confidence interval [CI], 1.18-5.50) relative to the administration of placebo at 3 days. Furthermore, the remission rate at discharge (29.3% [12/41] vs 7.0% [3/43]; RR: 4.20, 95% CI, 1.28-13.80) was also improved by ketamine. No psychotic symptoms or adverse events were reported to be substantially higher in the ketamine group. The trial indicates that the intraoperative administration of ketamine could alleviate moderate-to-severe depressive symptoms in neurosurgical patients without worsening safety.

Intraoperative ketamine may increase risk of post-operative delirium after complex spinal fusion for adult deformity correction.

For complex surgery, intraoperative ketamine administration is readily used to reduce post-operative pain. However, there have been a few studies suggesting that intraoperative ketamine may have deleterious effects and impact post-operative delirium. Therefore, we sought to identify the impact that intraoperative ketamine has on post-operative outcomes after complex spinal surgery involving ≥5 level fusions. The medical records of 138 adult (≥18 years old) spine deformity patients undergoing elective, primary complex spinal fusion (≥5 level) for deformity correction at a major academic institution from 2010 to 2015 were reviewed. We identified 98 (71.0%) who had intraoperative ketamine administration and 40 (29%) who did not (Ketamine-Use: n=98; No-Ketamine: n=40). Patient demographics, comorbidities, intra- and post-operative complication rates were collected for each patient. The primary outcome investigated in this study was the rate of post-operative delirium. A multivariate nominal-logistic regression analysis was used to determine the independent association between intraoperative ketamine and post-operative delirium. Patient demographics and comorbidities were similar between both cohorts, including age, gender, and BMI. The median number of fusion levels operated, length of surgery, estimated blood loss, and proportion of patients requiring blood transfusions were similar between both cohorts. Postoperative complication profile was similar between the cohorts, except for the Ketamine-Use cohort having significantly higher proportion of patients experiencing delirium (Ketamine-Use: 14.3% vs. No-Ketamine: 2.6%, P=0.047). In a multivariate nominal-logistic regression analysis, intraoperative Ketamine-Use was independently associated with post-operative delirium (OR: 9.475, 95% CI: 1.026-87.508, P=0.047). Our study suggests that the intraoperative use of ketamine may increase the risk of post-operative delirium. Further studies are necessary to understand the physiological effect intraoperative ketamine has on patients undergoing complex spinal fusions in order to better overall patient care and reduce healthcare resources.

Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial

BackgroundKetamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. MethodsWe conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg−1 (Lo-K) or 1.0 mg kg−1 (Hi-K)] vs control [saline placebo (P)] in patients ≥60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial. ResultsThere was no significant difference on POD3 in the proportion of patients with symptoms suggestive of depression between the placebo [23/156 (14.7%)] and combined ketamine (Lo-K plus Hi-K) [61/349 (17.5%)] groups [difference = –2.7%; 95% confidence interval (CI), 5.0% to –9.4%; P=0.446]. Of the total cohort, 9.6% (64/670; 95% CI, 7.6–12.0%) had symptoms suggestive of depression before operation, which increased to 16.6% (84/505; 95% CI, 13.6–20.1%) on POD3, and decreased to 11.9% (47/395; 95% CI, 9.1–15.5%) on POD30. Of the patients with depressive symptoms on POD3 and POD30, 51% and 49%, respectively, had no prior history of depression or depressive symptoms. ConclusionsMajor surgery is associated with new-onset symptoms suggestive of depression in patients ≥60 yr old. Intraoperative administration of subanaesthetic ketamine does not appear to prevent or improve depressive symptoms. Clinical trials registrationNCT01690988.

Intraoperative ketamine administration to prevent delirium or postoperative cognitive dysfunction: A systematic review and meta-analysis.

Postoperative cognitive complications are associated with substantial morbidity and mortality. Ketamine has been suggested to have neuroprotective effects in various settings. This systematic review evaluates the effects of intraoperative ketamine administration on postoperative delirium and postoperative cognitive dysfunction (POCD). Medline, Embase and Central were searched to 4 March 2018 without date or language restrictions. We considered randomised controlled trials (RCTs) comparing intraoperative ketamine administration versus no intervention in adults undergoing surgery under general anaesthesia. Primary outcomes were postoperative delirium and POCD. Non-cognitive adverse events, mortality and length of stay were considered as secondary outcomes. Data were independently extracted. The quality of the evidence (GRADE approach) was assessed following recommendations from the Cochrane collaboration. Risk ratios were calculated for binary outcomes, mean differences for continuous outcomes. We planned to explore the effects of age, specific anaesthesia regimen, depth of anaesthesia and intraoperative haemodynamic events through subgroup analyses. Six RCTs were included. The incidence of postoperative delirium did not differ between groups (4 trials, 557 patients, RR 0.83, 95% CI [0.25, 2.80]), but patients receiving ketamine seemed at lower risk of POCD (3 trials, 163 patients, RR 0.34, 95% CI [0.15, 0.73]). However, both analyses presented limitations. Therefore, the quality of the evidence (GRADE) was deemed low (postoperative delirium) and very low (POCD). The effect of ketamine on postoperative delirium remains unclear but its administration may offer some protection towards POCD. Large, well-designed randomised trials are urgently needed to further clarify the efficacy of ketamine on neurocognitive outcomes.

Preventative effect of ketamine on post-surgical hyperalgesia induced at a body part remote from the surgical site.

It is known that pain hypersensitivity can be induced at a body part remote from a surgical site (tertiary hyperalgesia), leading to patient discomfort. Nevertheless, no reported study to date has investigated methods to attenuate such tertiary hyperalgesia. Ketamine is known to modulate hyperalgesia induced by central sensitization. Thus, we investigated whether intraoperative administration of ketamine could decrease post-surgical tertiary hyperalgesia in patients undergoing a laparoscopic hysterectomy. In total 46 patients were studied. Ketamine (1 mg/kg IV and 0.5 mg/kg/h or the same volume of 0.9% saline) was administered during surgery in the ketamine and control groups, respectively. The mechanical pain threshold was measured on the patients' dominant palm before and 24 hours after the surgery to evaluate hyperalgesia. The change in mechanical pain threshold over time (preoperative and postoperative) differed between the groups, with a lower postoperative threshold in the control group (118.6±170.5 vs. 419.2±233; P=0.015). The postoperative visual analogue scale score at rest was lower in the ketamine group (22±16 vs. 13±9; P=0.02). Visual analogue scale scores during deep breathing, consumption of analgesia and antiemetics, and the incidence of dizziness did not differ significantly between the groups (P>0.05). These results suggest that the intraoperative administration of ketamine may decrease post-surgical hyperalgesia developing at a region remote from the surgical site.

Efficacy of Low-dose Ketamine as Sole Analgesic Agent in Maintaining Analgesia and Intraoperative Hemodynamics During Laparoscopic Gynecological Surgeries.

Background:Ketamine, in low doses, is known to possess intense analgesic properties. The available literature shows wide variation regarding the time and dose of administration of ketamine during surgery.Aim:The aim of this study was to evaluate the effect of intraoperative administration of ketamine when used as sole analgesic in low doses, on hemodynamics and postoperative analgesia in patients undergoing laparoscopic gynecological surgery and compared on the basis of duration of surgery.Settings and Design:This prospective, observational study was conducted from July to December 2015, over a period of 6 months in a tertiary care medical college and hospital.Materials and Methods:Seventy patients between 23 and 55 years planned for laparoscopic gynecological surgery were recruited. Ketamine was given in a dose of 0.5 mg/kg preoperatively and then repeated every ½ hourly in a dose of 0.25 mg/kg throughout the surgery. Hemodynamic parameters, time to the first rescue analgesia and complications were recorded for the first 8 h. Statistical evaluation was done and result expressed as percentage. Paired t-test was employed for the comparison of numerical variables within the group.Results:Seventy percent of the patients did not require any postoperative rescue analgesia during the first 8 h after surgery. None of the patients complained of pain immediately after extubation, and 16% of the patients had minor postoperative complications. The intraoperative hemodynamic profile was significantly altered. Duration of surgery and dose of ketamine required did not affect the duration of analgesia.Conclusion:Ketamine in low dose proved to be an efficacious analgesic even in the long duration laparoscopic gynecological surgeries. It stabilizes intraoperative hemodynamics thereby reducing the requirement of other anesthetic and antihypertensive agents.

The intraoperative administration of ketamine to burned U.S. service members does not increase the incidence of post-traumatic stress disorder.

Patients with severe burns typically undergo multiple surgeries, and ketamine is often used as part of the multimodal anesthetic regimen during such surgeries. The anesthetic ketamine is an N-methyl-D-aspartate receptor antagonist that also provides analgesia at subanesthetic doses, but the psychoactive side effects of ketamine have caused concern about its potential psychological effects on a combat-wounded population. Post-traumatic stress disorder (PTSD) affects approximately 30% of burned U.S. service members injured in Operation Iraqi Freedom/Operation Enduring Freedom. A preliminary analysis by our research group reported that patients who received perioperative ketamine had a significantly lower prevalence of PTSD than those injured service members who did not receive ketamine. We have now expanded this research to examine the relationship between ketamine and PTSD development in a much larger population. A retrospective analysis on data from service members being treated for burns at the San Antonio Military Medical Center was conducted. Collected data included drugs received, injury severity score (ISS), total body surface area (TBSA) burned, length of hospital stay (LOS), number of intensive care unit days, number of surgeries, and PTSD Checklist-Military (PCL-M) scores and administration dates. Subjects were grouped based on intraoperative receipt of ketamine, and the groups were compared. The groups were binary for ketamine (yes or no), and dose of ketamine administered was not included in data analyses. Propensity score matching based on ISS and TBSA was performed to control for individual differences in burn severity. Two hundred eighty-nine burned U.S. service members received the PCL-M at least 30 days after injury. Of these subjects, 189 received intraoperative ketamine, and 100 did not. Despite significantly greater injuries, as evidenced by significantly higher TBSA burned and ISS (p < 0.01), patients who received ketamine did not screen positive for PTSD at a different rate than those patients who did not (24% vs. 26.98%, p = 0.582). Patients receiving intraoperative ketamine also underwent a significantly greater number of surgeries, spent more time in the hospital, spent more days in the ICU, and received more morphine equivalent units (p < 0.0001). Propensity score matching based on ISS and TBSA resulted in a total subject number of 130. In the matched samples, subjects who received ketamine still underwent significantly more surgeries and experienced longer hospital stays (p < 0.0001). Again, there was no statistically significant difference in the incidence of a positive screen for PTSD based upon the receipt of ketamine (28% vs. 26.15%, p = 0.843). Ketamine is often used in burn patients to reduce opioid usage and decrease the hemodynamic and respiratory side effects. Although this study does not show a benefit of ketamine on PTSD development that was identified in previous work with a smaller sample number, it does support the conclusion that ketamine does not increase PTSD development in burned service members.

Does Intraoperative Ketamine Attenuate Inflammatory Reactivity Following Surgery? A Systematic Review and Meta-Analysis

Reports regarding the ability of the anesthetic drug ketamine to attenuate the inflammatory response to surgery are conflicting. In this systematic review we examined the effect of perioperative ketamine administration on postoperative inflammation as assessed by concentrations of the biomarker interleukin-6 (IL-6). This study was based on a systematic search in PubMed, Scopus, Web of Knowledge, and the Cochrane Library. English written randomized controlled trials conducted in humans were eligible. To be included in the analysis, outcome had to relate to inflammation or immune modulation. Each study was reviewed independently by 2 assessors. Data were analyzed according to the GRADE's approach and reported in compliance with the PRISMA recommendations. Fourteen studies were eligible for evaluation (684 patients). Surgery was performed under general anesthesia, and ketamine was given before or during the surgery in varied doses Eight studies involved cardiopulmonary bypass operations, 4 were for abdominal surgery, 1 thoracic surgery, and 1 cataract surgery. Three studies were deemed of low quality. Nine studies measured IL-6 concentrations within the first 6 hours postoperatively; but in 3 studies, other potent anti-inflammatory drugs were used as premedication or during the operation; thus 6 studies (n = 331) were included in the meta-analysis. Using postoperative IL-6 concentrations as an outcome, ketamine had an anti-inflammatory effect; the meta-analysis showed a mean preoperative-postoperative IL-6 concentration difference (95% confidence interval) of -71 (-101 to -41) pg/mL. It can be concluded that intraoperative administration of ketamine significantly inhibits the early postoperative IL-6 inflammatory response. Future studies should further examine the anti-inflammatory effect of ketamine during major surgery, determine whether ketamine treatment alters functional outcomes, elucidate the mechanisms of its anti-inflammatory effect, and suggest an appropriate dosing regimen.

Multivariate analysis of factors associated with post-anesthetic times to standing in isoflurane-anesthetized horses: 381 cases

ObjectiveTo identify anesthesia-related variables which may independently predict time to standing in horses anesthetized with ketamine/diazepam/isoflurane. Study designRetrospective case series. AnimalsThree hundred and eighty-one horses. MethodsCase records were searched for the years 2000–2003 and 381 horses older than 12 months which weighed at least 200 kg were identified. Data were extracted from the records, and only horses that were anesthetized with xylazine, ketamine, diazepam and isoflurane were included in the analysis. Multiple linear regression was used to relate time to standing with demographic, intraoperative and anesthetic variables. ResultsMost (326; 86%) horses recovered unassisted and 55 (14%) were assisted in recovery. The model for unassisted recovery had an R2 of 0.228 with colic (p < 0.0001), anesthesia duration (p < 0.02), temperature nadir (p < 0.02) and duration of hypotension (p < 0.0001) being significant predictors of time to standing. The final model for predicting assisted recovery time had an R2 of 0.314 with emergency status (p < 0.0001), warm-blood breed (p < 0.04) and intraoperative administration of ketamine (p < 0.004) being the significant predictor. Conclusions and clinical relevanceVariables which could be impacted by the anesthetist which would result in a faster time to standing include duration of anesthesia, hypothermia and intraoperative hypotension. However, the contribution of anesthesia factors explained <23% of the variability in recovery time, suggesting that other, more important factors contribute to anesthesia recovery time in horses.

Postoperative Ketamine Administration Decreases Morphine Consumption in Major Abdominal Surgery: A Prospective, Randomized, Double-Blind, Controlled Study

Ketamine decreases postoperative morphine consumption, but its optimal dosing and duration of administration remain unclear. In this study, we compared the effects of ketamine administration on morphine consumption limited to the intraoperative period, or continued for 48 h postoperatively. Eighty-one patients scheduled for abdominal surgery were prospectively randomized under double-blind conditions to three groups: (1) PERI group receiving intraoperative and postoperative ketamine for the first 48 h after surgery (2 microg x kg(-1) x min(-1) after a 0.5 mg/kg bolus); (2) INTRA group receiving intraoperative ketamine administration only (2 microg x kg(-1) x min(-1) after a 0.5 mg/kg bolus); and (3) CTRL group receiving placebo. Morphine consumption, visual analog scale scores and side effects (sedation score, nausea-vomiting score, nightmares, psychiatric disorders, or delusions) were recorded for the first 48 h. Cumulative morphine consumption 24 h after surgery was significantly lower in the PERI group (median = 27 mg, interquartile range = [19]) than in the INTRA group (48 mg [41.5]) and CTRL group (50 mg [21]) (P < 0.005). Postoperative visual analog scale scores were significantly lower in the PERI group and INTRA group than in the CTRL group (P < 0.001). A higher rate of nausea was observed in the CTRL group compared with the PERI group (27% vs 4%, P = 0.005). No difference in sedation scores or psychiatric disorders was observed among groups. Low-dose ketamine improved postoperative analgesia with a significant decrease of morphine consumption when its administration was continued for 48 h postoperatively, with a lower incidence of nausea and with no side effects of ketamine.