Effect of low-dose ketamine on post-operative serum IL-6 production among elective surgical patients: a randomized clinical trial.
ABSTRACT: BACKGROUND:Surgery and Anesthesia cause an excessive pro-inflammatory response. Mulago Hospital is faced with staff shortage making post-operative pain management difficult.Interleukin-6 (IL-6) drives inflammatory pain, endothelial cell dysfunction and fibrogenesis. Ketamine is cheap and, readily available. We hypothesized that its attenuation of serum IL-6 was a surrogate for clinical benefit. MATERIALS AND METHODS:Institutional Review Board's approval was sought and RCT was registered at clinical trials.gov (identifier number: NCT01339065). Consenting patients were randomized to receive pre-incision intravenous ketamine - 0.5mg/kg or 0.9% saline placebo in weighted dosing. Blood samples were collected and laboratory analyzed at baseline, post-operatively in PACU, 24 and 48 hours respectively. RESULTS:We recruited 39 patients of whom 18 were randomized to the ketamine arm and 21 in the placebo arm with follow up at 24 and 48 hours. Serum IL-6 and IL-1? levels were analyzed using ELIZA assay of pre-coated micro wells. Ketamine suppressed serum IL-6 at PACU with reduced increase at 24 hours. There was no reaction in 98% of IL-1? assayed. CONCLUSION:Low-dose ketamine attenuated early serum IL-6 levels due to surgical response with reduced 24 hour increase, but the difference was not statistically significant and we recommend more studies.
Project description:Aim. A double-blind, randomized, placebo-controlled trial was designed to evaluate the efficacy of continuous intraoperative infusion of S(+)-ketamine under intravenous anesthesia with target-controlled infusion of remifentanil and propofol for postoperative pain control. Methods. Forty-eight patients undergoing laparoscopic cholecystectomy were assigned to receive continuous S(+)-ketamine infusion at a rate of 0.3?mg·kg(-1)·h(-1) (n = 24, intervention group) or an equivalent volume of saline at the same rate (n = 24, placebo group). The same target-controlled intravenous anesthesia was induced in both groups. Pain was assessed using a 0 to 10 verbal numeric rating scale during the first 12 postoperative hours. Pain scores and morphine consumption were recorded in the postanesthesia care unit (PACU) and at 4 and 12 hours after surgery. Results. Pain scores were lower in the intervention group at all time points. Morphine consumption did not differ significantly between groups during PACU stay, but it was significantly lower in the intervention group at each time point after PACU discharge (P = 0.0061). At 12 hours after surgery, cumulative morphine consumption was also lower in the intervention group (5.200 ± 2.707) than in the placebo group (7.525 ± 1.872). Conclusions. Continuous S(+)-ketamine infusion during laparoscopic cholecystectomy under target-controlled intravenous anesthesia provided better postoperative pain control than placebo, reducing morphine requirement. Trial Registration. This trial is registered with ClinicalTrials.gov NCT02421913.
Project description:Management of acute postoperative pain is challenging, particularly in patients with preexisting narcotic dependency. Ketamine has been used at subanesthetic doses as a N-methyl D-aspartate (NMDA) receptor antagonist to block the processing of nociceptive input in chronic pain syndromes. This prospective randomized study was designed to assess the use of ketamine as an adjunct to acute pain management in narcotic tolerant patients after spinal fusions. Twenty-six patients for 1-2 level posterior lumbar fusions with segmental instrumentation were randomly assigned to receive ketamine or act as a control. Patients in the ketamine group received 0.2 mg/kg on induction of general anesthesia and then 2 mcg kg(-1) hour(-1) for the next 24 hours. Patients were extubated in the operating room and within 15 minutes of arriving in the Post Anesthesia Care Unit (PACU) were started on intravenous patient-controlled analgesia (PCA) hydromorphone without a basal infusion. Patients were assessed for pain (numerical rating scale [NRS]), narcotic use, level of sedation, delirium, and physical therapy milestones until discharge. The ketamine group had significantly less pain during their first postoperative hour in the PACU (NRS 4.8 vs 8.7) and continued to have less pain during the first postoperative day at rest (3.6 vs 5.5) and with physical therapy (5.6 vs 8.0). Three patients in the control group failed PCA pain management and were converted to intravenous ketamine infusions when their pain scores improved. Patients in the ketamine group required less hydromorphone than the control group, but the differences were not significant. Subanesthetic doses of ketamine reduced postoperative pain in narcotic tolerant patients undergoing posterior spine fusions.
Project description:Hypoglycemia is a major cause of morbidity and mortality among preterm infants and its management remains a challenge in resource limited settings. Use of dextrose infusion by the recommended infusion pumps is not feasible in our environment due to their high costs and yet the current use of mini dextrose boluses with syringes as adapted at Mulago national referral and tertiary teaching hospital has unknown efficacy in prevention of hypoglycemia.We determined the efficacy of dextrose infusions by burettes versus two hourly dextrose boluses in prevention of hypoglycemia among preterms admitted in the first 72 hours at Special Care Unit, Mulago Hospital.One hundred and forty preterms aged 0 to 24 hours of life were randomized to receive 10% IV dextrose either as mini boluses or by infusion using burettes in an open label clinical trial. Blood glucose was measured at 0, two hourly for next 6 hours, 6 hourly for next 12 hours and thereafter 12 hourly until end of 72 hours following admission. Primary end point was incidence of hypoglycemia (random blood sugar (RBS) < 2.6 mmol/l) which was expressed as relative risk (RR). Efficacy of the dextrose infusion was computed using 1-RR.From February 2012 to April 2012, 68 preterms in the bolus arm and 72 in the infusion arm were studied. Hypoglycemia was detected in 34% (48/140). The incidence of hypoglycemia in the bolus arm was 59% (40/68) compared to 11% (8/72) in the infusion arm (RR; 0.19, 95% CI; 0.09-0.37). Efficacy (1-RR) of infusion by burettes versus boluses in prevention of hypoglycemia among preterms was 0.81 (95% CI; 0.63-0.90).Continuous 10% dextrose infusion by burettes reduced the incidence of hypoglycemia by 81% in the first 72 hours of admission compared to two hourly 10% mini dextrose boluses among preterms admitted at Special Care Unit, Mulago Hospital. (ClinicalTrials.gov Identifier: NCT01688674).
Project description:Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS).The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively.Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
Project description:Introduction:An opioid-sparing anesthetic involves a multi-modal technique with non-opioid medications targeting different analgesic pathways. Such techniques may decrease adverse effects related to opioids. These techniques may be considered in patients at higher risk for opioid-related adverse effects including obstructive sleep apnea or sleep disordered breathing. Methods:A prospective, pilot study was performed in 10 patients (3-8 years of age), presenting for adenoidectomy. The perioperative regimen included oral dextromethorphan (1 mg/kg) and acetaminophen (15 mg/kg) plus single boluses of intraoperative dexmedetomidine (0.5 ?g/kg) and ketamine (0.5 mg/kg). Pain scores were assessed in the post anesthesia care unit (PACU) using the FLACC (Face, Legs, Activity, Cry, Consolability) scale. Patients with a pain score >4 received fentanyl as needed. PACU time, pain scores, and parent satisfaction were recorded. Postoperatively, patients were instructed to use oral acetaminophen or ibuprofen every 6 hours as needed for pain. Results:The study cohort included 10 patients, 3-8 years of age. All patients had opioid-free anesthetic care. PACU time ranged from 24 to 102 minutes (median: 56 minutes). FLACC pain scores were 0 for all PACU assessments. Nine patients were discharged home and 1 patient had a planned overnight admission. Following hospital discharge, the pain scores were satisfactory during the 72-hour study period and 90% of the patients' guardians were satisfied or highly satisfied with their child's pain control. Conclusion:This opioid-sparing approach provided safe and effective pain control as well as parental satisfaction following adenoidectomy in children. Additional prospective studies are needed to determine whether this regimen is effective in a larger cohort of patients with and for other otolaryngology procedures.
Project description:A prospective, double-blind, randomized controlled trial to compare the effect of preoperative midazolam or ketamine on the incidence of emergence agitation (EA) following sevoflurane anaesthesia in children.Paediatric patients (2-6 years old) undergoing ophthalmic surgery were allocated to receive premedication with either 0.1?mg/kg midazolam or 1?mg/kg ketamine. Incidence of EA and postoperative pain scores were recorded at 10-min intervals in the postanaesthetic care unit (PACU). The use of EA rescue medications (fentanyl or midazolam) was recorded.The incidence of EA was significantly lower in the ketamine group (n?=?33) than the midazolam group (n?=?34) at 10 and 20?min after transfer to PACU. There was no significant difference in overall incidence of EA. The frequency of midazolam use as rescue medication was significantly lower in the katamine group than in the midazolam group.Premedication with ketamine is more effective than midazolam in preventing EA during the early emergence period after sevoflurane anaesthesia in children.
Project description:High-risk, noncardiac surgery represents only 12.5% of surgical procedures, but 83.3% of deaths. The postanaesthetic care unit (PACU) addresses the need for an improved level of care for these patients by providing postoperative high-dependency or intensive care (Level 2 or 3). The PACU aims to improve the structure of care provision for high-risk surgical patients. By maintaining 24-hour cover at the same staffing level, the risk of poorer 'out-of- hours' care is reduced. In a PACU, whose remit is solely postoperative care, evidence-based protocols can be established to standardize the care given. The aim is to provide 24 hours of postoperative optimized care, thus targeting the period when these patients are most vulnerable, to reduce the risk of complications developing and identify complications promptly, should they occur. The PACU is set up to facilitate certain processes to aid optimized care in the postoperative period. These include invasive and noninvasive ventilation, goal-directed haemodynamic management, invasive monitoring and optimal pain management. Identification of high-risk patients who might benefit from PACU care is not always straightforward. However, tools are available to aid the clinician, supplementing clinical assessment and basic investigations. These include clinical prediction rules and cardiopulmonary exercise testing. Both the setting up and the running of a PACU clearly have cost implications. However, the reduction in postoperative morbidity, and thus patients' length of stay, should, overall, reduce costs. The benefits of a PACU should therefore be seen in terms of improved surgical outcomes, reducing postoperative morbidity and mortality, and cost savings.
Project description:Paediatric cardiac surgery with cardiopulmonary bypass (CPB) is associated with a marked inflammatory response and triggers release of inflammatory cytokines. The aim of this study was to study the effect of ketamine on the inflammatory response during correction of congenital cyanotic heart diseases.Sixty-six patients with congenital cyanotic heart diseases scheduled for cardiac surgery were randomised into three groups. Group A patients did not receive ketamine (control group), Group B patients received 2 mg/kg ketamine intravenous (IV) and Group C patients received ketamine 2 mg/kg IV and an IV infusion of ketamine (50 μg/kg/min). Interleukin (IL) levels for IL-6, IL-8, IL-10, C-reactive protein (CRP) and tumour necrosis factor-α (TNF-α) levels were examined in the three groups at four timings: pre-operative (baseline), intraoperative (after weaning off the CPB) and post-operative (6 and 24 h after weaning off CPB). Paired sample t-test and ANOVA test were used for statistical analysis and P < 0.05 was considered statistically significant.Within each group, the intra- and post-operative serum levels of IL-6, IL-8, IL-10 and CRP were significantly elevated from the baseline, however, TNF-α was not significantly elevated. There were no statistically significant differences in the IL, CRP or TNF-α levels between the three groups.Paediatric cardiac surgery for congenital cyanotic heart disease is a triggering factor for the inflammatory response, yet we could not detect any beneficial effect of ketamine on that response whether given either as an IV induction dose or continued as an IV infusion.
Project description:<h4>Background and objectives</h4>The goal of this meta-analysis study was to perform a systematic review of the literature on the effects of ketamine on postoperative pain following tonsillectomy and adverse effects in children.<h4>Subjects and methods</h4>Two authors independently searched three databases (MEDLINE, SCOPUS, Cochrane) from their inception of article collection to February 2014. Studies that compared preoperative ketamine administration (ketamine groups) with no treatment (control group) or opioid administration (opioid group) where the outcomes of interest were postoperative pain intensity, rescue analgesic consumption, or adverse effects (sedation, nausea and vomiting, bad dream, worsening sleep pattern, and hallucination) 0-24 hours after leaving the operation room were included in the analysis.<h4>Results</h4>The pain score reported by the physician during first 4 hours and need for analgesics during 24 hours postoperatively was significantly decreased in the ketamine group versus control group and was similar with the opioid group. In addition, there was no significant difference between ketamine and control groups for adverse effects during 24 hours postoperatively. In the subgroup analyses (systemic and local administration) regarding pain related measurements, peritonsillar infiltration of ketamine was more effective in reducing the postoperative pain severity and need for analgesics.<h4>Conclusion</h4>Preoperative administration of ketamine systemically or locally could provide pain relief without side-effects in children undergoing tonsillectomy. However, considering the insufficient evaluation of efficacy of ketamine according to the administration methods and high heterogeneity in some parameters, further clinical trials with robust research methodology should be conducted to confirm the results of this study.
Project description:STUDY DESIGN:A meta-analysis of randomized controlled trials (RCTs). OBJECTIVE:The aim of this study was to evaluate the effectiveness of perioperative supplemental ketamine to reduce postoperative opioid analgesic consumption following spine surgery. SUMMARY OF BACKGROUND DATA:Although low-dose supplemental ketamine has been known to reduce pain after surgery, there is conflicting evidence regarding whether ketamine can be effective to reduce opioid consumption following spine surgery. METHODS:Comprehensive search of PubMed, the Cochrane Central Register of Controlled Trials for prospective RCTs, Web of Science, and Scopus. Patients who received supplemental ketamine were compared with the control group in terms of postoperative morphine equivalent consumption, pain scores, and adverse events. Mean differences (MDs) and 95% confidence intervals (CIs) were used to describe continuous outcomes. Odds ratios (ORs) and 95% CIs were applied to dichotomous outcomes. RESULTS:A total of 14 RCTs comprising 649 patients were selected for inclusion into the meta-analysis. Patients who were administered adjunctive ketamine exhibited less cumulative morphine equivalent consumption at 4, 8, 12, and 24?hours following spine surgery (all Ps?<?0.05). The ketamine group also reported lower postoperative pain scores at 6, 12, and 24?hours (all Ps?<?0.05). None of the adverse events studied attained statistical significance (all Ps?>?0.05). CONCLUSION:Supplemental perioperative ketamine reduces postoperative opioid consumption up to 24?hours following spine surgery. LEVEL OF EVIDENCE:1.