Intravenous Ketamine for Cancer Pain: A Single-Center Retrospective Analysis Comparing Fixed-Rate Versus Weight-Based Dosing.

Although weak evidence exists to support subanesthetic ketamine for cancer pain treatment, successful use may be hindered in the absence of standardized dosing guidance. We aimed to compare the success rates of intravenous ketamine fixed-rate versus weight-based dosing strategies for cancer pain treatment, and to assess patient characteristics that correlate with treatment success. We conducted a single-center retrospective review including non-critically ill adults with cancer pain who received subanesthetic ketamine for at least 24-h. All patients received fixed-rate ketamine; weight-based doses were retrospectively determined using total body weight. Treatment was considered successful if after reaching the maximum prescribed ketamine dose the patient had a 30% reduction in: baseline pain score, as-needed opioid use, or total morphine equivalent daily dose over a standardized 24-h. Of 105 included patients, 51 (48.6%) successfully responded to ketamine. Responders had lower fixed-rate ketamine doses compared to non-responders (median[IQR] 15 mg/hr[10-15] vs. 15 mg/hr[15-20], p = 0.043), but no difference in retrospectively calculated weight-based doses (0.201 ± 0.09 mg/kg/hr vs. 0.209 ± 0.08 mg/kg/hr, p = 0.59). Responders had higher daily opioid requirements at baseline compared to non-responders (p = 0.04). Though underpowered, our findings suggest that weight-based ketamine dosing may not convey additional benefit over fixed-rate dosing.

Comparison of intranasal dexmedetomidine and ketamine for paediatric premedication: A randomized study.

INTRODUCTION AND OBJECTIVES: Paediatric patients are given premedication in order to decrease preoperative anxiety, allow smooth induction, and prevent postoperative psychological insult and behavioural changes. A child friendly method of administration is desirable. We compared intranasal administration of dexmedetomidine and ketamine in the operating room environment, to evaluate the Faces, Legs, Activity, Cry and Consolability (FLACC) score at the time of establishing intravenous access for induction of general anaesthesia. METHODS: This prospective, double-blind, randomized controlled trial was conducted at a tertiary care center. One hundred patients, 2-10 years of age, ASA physical status 1 & 2, scheduled for general anaesthesia were enrolled. Patient's presedation behaviour was assessed by the modified Yale Preoperative Anxiety Scale Short Form (mYPAS-SF). Patients in Group D received Dexmedetomidine 1 mcg/kg intranasally, and patients in Group K received Ketamine 5 mg/kg intranasally. After 45 min, patients were transferred to the operating table where intravenous cannulation was carried out and the response to needle insertion was assessed by FLACC scale. Vital signs, including the pulse-oximetry, heart rate and respiratory rate were monitored. Side effects such as nausea, vomiting, and agitation were also recorded. RESULTS: A significantly higher FLACC score was seen in Group D as compared to Group K (p = 0.001). The mean heart rate between two groups was found to be significantly (p = 0.001) lower in Group D compared to Group K. However, the proportion of adverse events was 8% in patients who received ketamine. CONCLUSIONS: Intranasal ketamine in a dose of 5 mg/kg is clinically more effective as premedication in children aged 2-10 years in comparison with intranasal dexmedetomidine in a dose of 1 mcg/kg.

Dexmedetomidine-ketamine combination versus fentanyl-midazolam for patient sedation during flexible bronchoscopy: a prospective, single-blind, randomized controlled trial.

BACKGROUND: Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB. METHODS: Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction. RESULTS: The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033). CONCLUSION: DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.

Methadone in combination with magnesium, ketamine, lidocaine, and dexmedetomidine improves postoperative outcomes after coronary artery bypass grafting: an observational multicentre study.

BACKGROUND: An optimal pharmacological strategy for fast-track cardiac anesthesia (FTCA) is unclear. This study evaluated the effectiveness and safety of an FTCA program using methadone and non-opioid adjuvant infusions (magnesium, ketamine, lidocaine, and dexmedetomidine) in patients undergoing coronary artery bypass grafting. METHODS: This retrospective, multicenter observational study was conducted across private and public teaching sectors. We studied patients managed by a fast-track protocol or via usual care according to clinician preference. The primary outcome was the total mechanical ventilation time in hours adjusted for hospital, body mass index, category of surgical urgency, cardiopulmonary bypass time and EuroSCORE II. Secondary outcomes included successful extubation within four postoperative hours, postoperative pain scores, postoperative opioid requirements, and the development of postoperative complications. RESULTS: We included 87 patients in the fast-track group and 88 patients in the usual care group. Fast-track patients had a 35% reduction in total ventilation hours compared with usual care patients (p = 0.007). Thirty-five (40.2%) fast-track patients were extubated within four hours compared to 10 (11.4%) usual-care patients (odds ratio: 5.2 [95% CI: 2.39-11.08; p < 0.001]). Over 24 h, fast-track patients had less severe pain (p < 0.001) and required less intravenous morphine equivalent (22.00 mg [15.75:32.50] vs. 38.75 mg [20.50:81.75]; p < 0.001). There were no significant differences observed in postoperative complications or length of hospital stay between the groups. CONCLUSION: Implementing an FTCA protocol using methadone, dexmedetomidine, magnesium, ketamine, lignocaine, and remifentanil together with protocolized weaning from a mechanical ventilation protocol is associated with significantly reduced time to tracheal extubation, improved postoperative analgesia, and reduced opioid use without any adverse safety events. A prospective randomized trial is warranted to further investigate the combined effects of these medications in reducing complications and length of stay in FTCA. TRIALS REGISTRATION: The study protocol was registered in the Australian New Zealand Clinical Trials Registry ( https://www.anzctr.org.au/ACTRN12623000060640.aspx , retrospectively registered on 17/01/2023).

Ketamine Induced Acute Systolic Heart Failure.

Background: Studies have shown major cardiovascular effects associated with ketamine use disorder including dose-dependent negative inotropic effects. Preoperative ketamine use has been linked to ketamine-induced stress cardiomyopathy. Case presentation: A 28-year-old female with a history of recurrent cystitis and ketamine use disorder (twice weekly for 14 years) presented with bilateral lower extremity oedema and shortness of breath for 3 months. She was tachycardic with a troponin level of 0.07 ng/ml and a B-type natriuretic peptide (BNP) level of 2511 pg/ml. Electrocardiogram showed normal sinus rhythm and transthoracic echocardiography (TTE) showed left ventricular ejection fraction (EF) of 15%, dilated left ventricle, and severe tricuspid and mitral regurgitation. Computed tomography (CT) scan of the chest and abdomen showed bilateral pleural effusions with congestive hepatopathy and ascites. The patient was started on intravenous furosemide, metoprolol, and sacubitril/valsartan. Rheumatological workup including complement levels, and antinuclear anti-double-stranded DNA was negative. A repeat TTE 2 weeks later revealed an EF of 25% and moderate tricuspid regurgitation. Four months later, the EF was 54% with normal left ventricular cavity size. Conclusion: Although ketamine use disorder is increasing, data on long-term side effects is minimal. Screening for ketamine use disorders should be considered in patients presenting with acute systolic heart failure. Long-term studies are needed to evaluate the benefits of adding ketamine screening to standard urine toxicology. LEARNING POINTS: Ketamine use disorder can lead to severe cardiovascular complications, including acute systolic heart failure, likely due to its direct negative inotropic effects and dose-dependent impact on cardiac function.Clinicians should consider screening for ketamine use disorder in young adults presenting with acute systolic heart failure, especially when other common aetiologies have been ruled out.Early recognition and prompt treatment of ketamine-induced heart failure with diuretics and guideline-directed medical therapy can lead to significant improvement in cardiac function, but long-term management should also focus on ensuring cessation of ketamine use disorder.

Adjuvant Analgesics in Acute Pain - Evaluation of Efficacy.

PURPOSE OF THE REVIEW: Acute postoperative pain impacts a significant number of patients and is associated with various complications, such as a higher occurrence of chronic postsurgical pain as well as increased morbidity and mortality. RECENT FINDINGS: Opioids are often used to manage severe pain, but they come with serious adverse effects, such as sedation, respiratory depression, postoperative nausea and vomiting, and impaired bowel function. Therefore, most enhanced recovery after surgery protocols promote multimodal analgesia, which includes adjuvant analgesics, to provide optimal pain control. In this article, we aim to offer a comprehensive review of the contemporary literature on adjuvant analgesics in the management of acute pain, especially in the perioperative setting. Adjuvant analgesics have proven efficacy in treating postoperative pain and reducing need for opioids. While ketamine is an established option for opioid-dependent patients, magnesium and α2-agonists have, in addition to their analgetic effect, the potential to attenuate hemodynamic responses, which make them especially useful in painful laparoscopic procedures. Furthermore, α2-agonists and dexamethasone can extend the analgesic effect of regional anesthesia techniques. However, findings for lidocaine remain inconclusive.

Total intravenous anesthesia with Ketofol in rabbits: a comparison of the effects of constant rate infusion of midazolam, fentanyl or dexmedetomidine.

BACKGROUND: When inhalant anesthetic equipment is not available or during upper airway surgery, intravenous infusion of one or more drugs are commonly used to induce and/or maintain general anesthesia. Total intravenous anesthesia (TIVA) does not require endotracheal intubation, which may be more difficult to achieve in rabbits. A range of different injectable drug combinations have been used as continuous infusion rate in animals. Recently, a combination of ketamine and propofol (ketofol) has been used for TIVA in both human patients and animals. The purpose of this prospective, blinded, randomized, crossover study was to evaluate anesthetic and cardiopulmonary effects of ketofol total intravenous anesthesia (TIVA) in combination with constant rate infusion (CRI) of midazolam, fentanyl or dexmedetomidine in eight New Zealand White rabbits. Following IV induction with ketofol and endotracheal intubation, anesthesia was maintained with ketofol infusion in combination with CRIs of midazolam (loading dose [LD]: 0.3 mg/kg; CRI: 0.3 mg/kg/hr; KPM), fentanyl (LD: 6 µg/kg; CRI: 6 µg/kg/hr; KPF) or dexmedetomidine (LD: 3 µg/kg; CRI: 3 µg/kg/hr; KPD). Rabbits in the control treatment (KPS) were administered the same volume of saline for LD and CRI. Ketofol infusion rate (initially 0.6 mg kg- 1 minute- 1 [0.3 mg kg- 1 minute- 1 of each drug]) was adjusted to suppress the pedal withdrawal reflex. Ketofol dose and physiologic variables were recorded every 5 min. RESULTS: Ketofol induction doses were 14.9 ± 1.8 (KPM), 15.0 ± 1.9 (KPF), 15.5 ± 2.4 (KPD) and 14.7 ± 3.4 (KPS) mg kg- 1 and did not differ among treatments (p > 0.05). Ketofol infusion rate decreased significantly in rabbits in treatments KPM and KPD as compared with saline. Ketofol maintenance dose in rabbits in treatments KPM (1.0 ± 0.1 mg/kg/min) and KPD (1.0 ± 0.1 mg/kg/min) was significantly lower as compared to KPS (1.3 ± 0.1 mg/kg/min) treatment (p < 0.05). Ketofol maintenance dose did not differ significantly between treatments KPF (1.1 ± 0.3 mg/kg/min) and KPS (1.3 ± 0.1 mg/kg/min). Cardiovascular variables remained at clinically acceptable values but ketofol infusion in combination with fentanyl CRI was associated with severe respiratory depression. CONCLUSIONS: At the studied doses, CRIs of midazolam and dexmedetomidine, but not fentanyl, produced ketofol-sparing effect in rabbits. Mechanical ventilation should be considered during ketofol anesthesia, particularly when fentanyl CRI is used.

The impact of ketamine on pain-related outcomes after thoracotomy: a systematic review with meta-analysis of randomized controlled trials.

Objective: This meta-analysis aims to examine how effective ketamine is in the management of acute and preventing chronic post-thoracotomy pain by synthesizing the available research. Method: A systematic literature search was conducted across PubMed, Scopus, and Cochrane Library till May 2023. Randomized Controlled Trials (RCT) examining the influence of ketamine on post-thoracotomy pain in adults were included. The intervention group included ketamine plus morphine, while the control group included morphine only. The outcome measures were opioid intake and pain scores at rest and on moving/coughing. Evidence quality was evaluated using the Cochrane Risk of Bias and GRADE assessment. Results: Nine articles comprising 556 patients were selected for meta-analysis. The intervention group had a significant decrease in pain at rest (Std. Mean Difference (SMD = -0.60 with 95% CI [-0.83, -0.37]) and on movement/cough (SMD = -0.73 [-1.27, -0.18]) in the first postoperative days. Also, the ketamine group had lower opioid consumption (mg) in comparison with controls (SMD = -2.75 [-4.14, -1.36], p-value = 0.0001) in postoperative days 1-3. There was no data to assess the long-term effect of ketamine on chronic pain. Conclusion: This meta-analysis shows that ketamine use can lower acute pain levels and morphine use after thoracotomy. In the future, larger RCTs using standardized methods and assessing both short-term and long-term analgesic effects of ketamine are necessary to deepen the understanding of the issue.

The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery.

BACKGROUND: Postoperative delirium (POD) and cognitive dysfunction (POCD) are common complications following thoracic surgery, particularly in patients aged 65 years and above. These complications can significantly affect recovery and increase healthcare costs. This study investigates the effects of low-dose S-ketamine on reducing POD and POCD in this patient demographic. METHODS: In this retrospective cohort study, medical records of patients aged ≥ 65 years who underwent elective thoracic surgery from January 2019 to August 2023 were reviewed. Patients were categorized into S-ketamine and Control groups based on intraoperative S-ketamine exposure. POD was assessed using the Confusion Assessment Method (CAM), while cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) at baseline, 1 week, 1 month, and 6 months post-surgery. Intraoperative and postoperative parameters, including hemodynamic stability, blood loss, pain scores, and ICU stay length, were also recorded. RESULTS: The study comprised 140 participants, with 70 in each group. The S-ketamine group demonstrated a significantly lower incidence of POD at 7 days post-surgery (12.0% vs. 26.7%, P < 0.001), and reduced POCD at 1 month (18.7% vs. 36.0%, P < 0.05) and 6 months (10.7% vs. 21.3%, P < 0.05). The Ketamine group had a significantly higher median MoCA score compared to the Control group both at 1 month (P = 0.021) and 6 months (P = 0.007). Adverse events, such as infection, bleeding, and respiratory failure, showed no significant differences between the groups, suggesting a safe profile for S-ketamine. CONCLUSION: Administering low-dose S-ketamine during thoracic surgery in patients aged 65 years and above significantly reduces the incidence of POD and POCD, highlighting its neuroprotective potential. These findings advocate for the inclusion of S-ketamine in anesthetic protocols to improve postoperative outcomes and reduce healthcare costs in this patient population.

Opioid-Free Anesthesia in Bariatric Surgery: Is It the One and Only? A Comprehensive Review of the Current Literature.

Opioid-free anesthesia (OFA) is a heterogeneous group of general anesthesia techniques in which the intraoperative use of opioids is eliminated. This strategy aims to decrease the risk of complications and improve the patient's safety and comfort. Such potential advantages are particularly beneficial for selected groups of patients, among them obese patients undergoing laparoscopic bariatric surgery. Opioids have been traditionally used as an element of balanced anesthesia, and replacing them requires using a combination of coanalgesics and various types of local and regional anesthesia, which also have their side effects, limitations, and potential disadvantages. Moreover, despite the growing amount of evidence, the empirical data on the superiority of OFA compared to standard anesthesia with multimodal analgesia are contradictory, and potential benefits in many studies are being questioned. Additionally, little is known about the long-term sequelae of such a strategy. Considering the above-mentioned issues, this study aims to present the potential benefits, risks, and difficulties of implementing OFA in bariatric surgery, considering the current state of knowledge and literature.

The Effect of Different Propofol-Ketamine Combinations on Emergence Delirium in Children Undergoing Adenoidectomy and Tonsillectomy Surgery.

PURPOSE: Emergence delirium (ED) after sevoflurane anesthesia remains a serious issue in children. We aimed to compare different ratios of propofol-ketamine combinations to determine a better option for preventing ED. DESIGN: A prospective, randomized clinical trial. METHODS: In this study, 112 children aged between 3 and 12 years who underwent adenoidectomy and tonsillectomy were recruited. Propofol 1 mg kg-1 + ketamine 1 mg kg-1 (1:1 ratio), propofol 1.5 mg kg-1 + ketamine 0.75 mg kg-1 (2:1 ratio), propofol 2 mg kg-1 + ketamine 0.66 mg kg-1 (3:1 ratio), and propofol 3 mg kg-1 were applied at induction of anesthesia for Groups I, II, III, and IV, respectively. Fentanyl 1 mcg kg-1 and rocuronium 0.6 mg kg-1 were applied at induction, and anesthesia was maintained with sevoflurane and O2/N2O mixture for all participants. Intravenous morphine 0.1 mg kg-1 was applied for postoperative analgesia in the last 10 minutes of surgery. ED was defined as a Watcha score of ≥3. Demographics, hemodynamics, extubation time, Watcha scores, the Face, Legs, Activity, Cry, and Consolability scores, length of stay in the postanesthesia care unit (PACU), rescue analgesic requirement, and postoperative complications were recorded. FINDINGS: ED was significantly higher at 10 and 20 minutes in Group IV. Eighteen children experienced ED in PACU, (3, 2, 2, and 11 children in Groups I, II, III, and IV, respectively). Face, Legs, Activity, Cry, and Consolability scores were significantly different at all times. Rescue analgesics were required by 3 children (10.7%) in Group I, 2 (7.1%) in Group II, 2 (7.1%) in Group III, and 10 (35.7%) in Group IV (P = .012). The PACU stay was 21.9 ± 6.4 in Group I, 18.7 ± 6.3 in Group II, 16.7 ± 5.8 in Group III, and 17.4 ± 5.8 in Group IV. Nystagmus was observed in three children in Group I. CONCLUSIONS: To addition of ketamine to propofol during the induction of sevoflurane anesthesia can reduce the ED and analgesic requirements in children. A propofol-to-ketamine ratio of 3:1 provided better postoperative recovery with less pain and ED, without prolonging the PACU length of stay.

Effect of Low-dose Ketamine Infusion on Opioid Consumption in Children Undergoing Open Cardiac Surgery: A Randomized Controlled Double-Blind Study.

OBJECTIVE: This study was designed to evaluate the effect of low-dose ketamine infusion on the perioperative consumption of opioids in pediatric open cardiac surgery. DESIGN: A randomized, controlled, double-blinded single-center study was conducted. SETTING: The study took place in a tertiary care children's hospital. PARTICIPANTS: Patients of both sexes aged 2-12 years who underwent cardiac surgery were included. INTERVENTIONS: Patients in the ketamine group received a bolus of 0.3 mg/kg of ketamine before skin incision followed by continuous intraoperative infusion of 0.25 mg/kg/h and postoperative infusion of 0.1 mg/kg/h for 24 h. Patients in the control groups received volumes of normal saline either bolus or continuous infusion like that of the ketamine group. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the total dose of fentanyl consumed over the first 24 hours postoperatively. Secondary outcomes were intraoperative fentanyl consumption, time to extubation, modified objective pain score, and incidence of vomiting, pruritus, diplopia, or hallucinations. A total of 80 patients were recruited but the final analysis was done on 35 patients in the ketamine group and 34 in the control group. Fentanyl consumption during surgery and in the first 24 hours postoperatively was significantly lower in the ketamine than the control group. Patients in both the ketamine and control groups had similar times to extubation. Modified objective pain scores were significantly lower in the ketamine group than the control group. None of the patients in either group had diplopia or hallucinations. CONCLUSIONS: Low-dose ketamine infusion in children undergoing open cardiac surgery reduced intra- and postoperative opioid consumption and postoperative pain scores. Moreover, ketamine did not cause diplopia or hallucinations.

A Phase II Study About Efficacy and Safety of the Continuous IntraVenous Infusion of Ketamine as Adjuvant to Opioids in Terminally Ill Cancer Patients With Refractory Cancer Pain (CIVIK Trial).

BACKGROUND: Ketamine has been used to control refractory cancer pain as an adjuvant to opioids. We conducted a prospective phase II study to investigate the efficacy and safety of 5-day continuous intravenous infusion (CIVI) of Ketamine in terminally ill cancer patients with refractory cancer pain. METHODS: Hospitalized terminally ill cancer patients with refractory cancer pain were enrolled. Refractory cancer pain was indicated by requirements for 4 or more rescue opioids or pain intensity using numerical rating scale > personalized pain goal (PPG) despite of intravenous morphine equivalent daily dose (IV MEDD) ≥ 120 mg/day. The CIVI of ketamine was increased from .05 mg/kg/hour to .5 mg/kg/hour by .05 every 8 hours if pain intensity exceeded PPG or if number of rescue opioids ≥2 during prior 8 hours was required. The primary end-point was overall pain response rate, which indicates complete response (both rescue opioid ≤3/day and pain intensity ≤ PPG) plus partial response (rescue opioid ≤3/day), without unacceptable toxicities. RESULTS: Among 21 eligible patients enrolled between September 2019 and January 2023, 20 were analyzed. Most pain mechanisms were mixed type (n = 15, 75%), with neuropathic component (n = 17, 85%). The baseline background opioids were IV MEDD 186 mg/24hour (range, 124-592), number of rescue opioids was 6 (IQR, 5-9), and median PPG was 4 (IQR, 3-4). The overall pain response rate was 50% (n = 10) including 40% (n = 8) for complete pain response and 10% (n = 2) for partial pain response. CONCLUSION: This study showed efficacy of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. CIVI of ketamine could be a useful tool in these patients considering the limited treatment options. (NCT03362073, Initial Release: November 15, 2017).

Comparison of Dexmedetomidine and Ketamine in Serratus Anterior Plane Block for Postoperative Pain Control in Thoracotomy Patients: A Randomized Clinical Trial.

Background: Postoperative pain control after thoracotomy is very important, and if not controlled, it can cause severe complications. Objectives: This study aimed to compare dexmedetomidine and ketamine in serratus anterior plane block (SAPB) in pain control after thoracotomy. Methods: This randomized clinical trial was conducted on 74 patients aged 18 to 60 years old with American Society of Anesthesiologists (ASA) class I or II who were referred to Imam Khomeini hospital in Ahvaz, Iran, for thoracotomy and randomly divided into two groups. After surgery, the SAPB with ultrasound-guided was performed. In the ropivacaine-ketamine (RK) group, ketamine 0.5 mg/kg and 0.4 cc/kg ropivacaine solution 0.25% and in the ropivacaine-dexmedetomidine (RD) group, in addition to 0.4 cc/kg ropivacaine 0.25%, dexmedetomidine 0.5 µg/kg was added. Verbal Numeric Scale (VNS), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiratory rate (RR), heart rate (HR), and mean arterial blood pressure (MAP) were recorded. Results: There was no significant difference in both groups in terms of demographic information (P < 0.05). The average VNS was lower in the ketamine group than in the dexmedetomidine group; however, there was a significant difference only at 1, 12, and 24 hours after surgery (P < 0.05). There was no statistically significant difference between the two groups in terms of SBP and DBP, HR, and MAP. There was a significant difference in the RR in the two groups at 12 and 24 hours after the operation (P < 0.05). Conclusions: Dexmedetomidine and ketamine, which were used as supplements to ropivacaine for SAPB in patients undergoing elective thoracotomy, reduced the pain intensity after thoracotomy; nevertheless, the intensity of pain reduction was more and more effective in the group receiving ketamine.

Substance specific EEG patterns in mice undergoing slow anesthesia induction.

The exact mechanisms and the neural circuits involved in anesthesia induced unconsciousness are still not fully understood. To elucidate them valid animal models are necessary. Since the most commonly used species in neuroscience are mice, we established a murine model for commonly used anesthetics/sedatives and evaluated the epidural electroencephalographic (EEG) patterns during slow anesthesia induction and emergence. Forty-four mice underwent surgery in which we inserted a central venous catheter and implanted nine intracranial electrodes above the prefrontal, motor, sensory, and visual cortex. After at least one week of recovery, mice were anesthetized either by inhalational sevoflurane or intravenous propofol, ketamine, or dexmedetomidine. We evaluated the loss and return of righting reflex (LORR/RORR) and recorded the electrocorticogram. For spectral analysis we focused on the prefrontal and visual cortex. In addition to analyzing the power spectral density at specific time points we evaluated the changes in the spectral power distribution longitudinally. The median time to LORR after start anesthesia ranged from 1080 [1st quartile: 960; 3rd quartile: 1080]s under sevoflurane anesthesia to 1541 [1455; 1890]s with ketamine. Around LORR sevoflurane as well as propofol induced a decrease in the theta/alpha band and an increase in the beta/gamma band. Dexmedetomidine infusion resulted in a shift towards lower frequencies with an increase in the delta range. Ketamine induced stronger activity in the higher frequencies. Our results showed substance-specific changes in EEG patterns during slow anesthesia induction. These patterns were partially identical to previous observations in humans, but also included significant differences, especially in the low frequencies. Our study emphasizes strengths and limitations of murine models in neuroscience and provides an important basis for future studies investigating complex neurophysiological mechanisms.

Ketamine-induced prevention of SD-associated late infarct progression in experimental ischemia.

Spreading depolarizations (SDs) occur frequently in patients with malignant hemispheric stroke. In animal-based experiments, SDs have been shown to cause secondary neuronal damage and infarct expansion during the initial period of infarct progression. In contrast, the influence of SDs during the delayed period is not well characterized yet. Here, we analyzed the impact of SDs in the delayed phase after cerebral ischemia and the potential protective effect of ketamine. Focal ischemia was induced by distal occlusion of the left middle cerebral artery in C57BL6/J mice. 24 h after occlusion, SDs were measured using electrocorticography and laser-speckle imaging in three different study groups: control group without SD induction, SD induction with potassium chloride, and SD induction with potassium chloride and ketamine administration. Infarct progression was evaluated by sequential MRI scans. 24 h after occlusion, we observed spontaneous SDs with a rate of 0.33 SDs/hour which increased during potassium chloride application (3.37 SDs/hour). The analysis of the neurovascular coupling revealed prolonged hypoemic and hyperemic responses in this group. Stroke volume increased even 24 h after stroke onset in the SD-group. Ketamine treatment caused a lesser pronounced hypoemic response and prevented infarct growth in the delayed phase after experimental ischemia. Induction of SDs with potassium chloride was significantly associated with stroke progression even 24 h after stroke onset. Therefore, SD might be a significant contributor to delayed stroke progression. Ketamine might be a possible drug to prevent SD-induced delayed stroke progression.

Mechanisms and Preventative Strategies for Persistent Pain following Knee and Hip Joint Replacement Surgery: A Narrative Review.

Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention.

Enhancing ketamine anesthesia with midazolam and fentanyl for children's ear surgery: a prospective randomized study.

Background: Myringotomy with tympanostomy tube insertion (MTI) is a superficial surgical procedure used to prevent hearing loss in children with serous otitis media. Intravenous anesthesia, often ketamine, is preferred for this procedure because of its ability to induce sedation without compromising airway reflexes. However, ketamine alone may be insufficient and potentially lead to spontaneous movement during surgery. This study evaluated the effectiveness of midazolam and fentanyl as adjuvants to ketamine in reducing spontaneous movement during MTI and enhancing the quality of recovery. Methods: This study involved two groups of 30 patients each: one group received intravenous ketamine (1.5 mg/kg) with an equal volume of normal saline (K group), while the other received a combination of midazolam, fentanyl, and ketamine (0.05 mg/kg, 1 µg/kg, and 1.5 mg/kg, respectively; MFK group). We assessed side effects, intraoperative patient movement, surgeon satisfaction, and emergence agitation scores. Results: The MFK group exhibited significantly lower scores for patient movement (p<0.01) and emergence agitation (p<0.01) and markedly higher surgeon satisfaction scores (p<0.01) than the K group. Conclusion: Administering a midazolam-fentanyl-ketamine combination effectively reduced spontaneous movement during surgery and emergence agitation during recovery without prolonging discharge times in children undergoing MTI.

British Association of Urological Surgeons Consensus statements on the management of ketamine uropathy.

OBJECTIVES: To provide guidance in the form of consensus statement in the management of ketamine uropathy. METHODS: A literature review of ketamine uropathy was performed. The consensus method was of a modified nominal group technique and has been use in the previous British Association of Urological Surgeons (BAUS) consensus documents and was led by the Female, Neurological and Urodynamic Urology Section of the BAUS. RESULTS: A number of consensus statements detailing the assessment and management of urological complications relate to the recreational use of ketamine (ketamine uropathy) in both elective and emergency urology settings. CONCLUSION: Comprehensive management pathway for ketamine-related urinary tract dysfunction and uropathy has been detailed.

Ketamine administration causes cognitive impairment by destroying the circulation function of the glymphatic system.

BACKGROUND: Ketamine, as a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was originally used in general anesthesia. Epidemiological data show that ketamine has become one of the most commonly abused drugs in China. Ketamine administration might cause cognitive impairment; however, its molecular mechanism remains unclear. The glymphatic system is a lymphoid system that plays a key role in metabolic waste removal and cognitive regulation in the central nervous system. METHODS: Focusing on the glymphatic system, this study evaluated the behavioral performance and circulatory function of the glymphatic system by building a short-term ketamine administration model in mice, and detected the expression levels of the 5-HT2c receptor, ΔFosb, Pten, Akt, and Aqp4 in the hippocampus. Primary astrocytes were cultured to verify the regulatory relationships among related indexes using a 5-HT2c receptor antagonist, a 5-HT2c receptor short interfering RNA (siRNA), and a ΔFosb siRNA. RESULTS: Ketamine administration induced ΔFosb accumulation by increasing 5-HT2c receptor expression in mouse hippocampal astrocytes and primary astrocytes. ΔFosb acted as a transcription factor to recognize the AATGATTAAT bases in the 5' regulatory region of the Aqp4 gene (-1096 bp to -1087 bp), which inhibited Aqp4 expression, thus causing the circulatory dysfunction of the glymphatic system, leading to cognitive impairment. CONCLUSIONS: Although this regulatory mechanism does not involve the Pten/Akt pathway, this study revealed a new mechanism of ketamine-induced cognitive impairment in non-neuronal systems, and provided a theoretical basis for the safety of clinical treatment and the effectiveness of withdrawal.