Continuous Infusion Of Ketamine Research Articles

Impact of Continuous Infusion Ketamine Compared to Continuous Infusion Benzodiazepines on Delirium in the Intensive Care Unit.

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods: In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines.

Impact of Prolonged Continuous Ketamine Infusions in Critically Ill Children: A Prospective Cohort Study.

Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24hours) in the pediatric intensive care unit (PICU). We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24hours in mechanically ventilated children. We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p=0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n=4), hypersecretion (n=14), tachycardia (n=6), and nystagmus (n=2). There were no significant changes in hemodynamic variables 24h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p<0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.

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).

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. 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) ≥ 120mg/day. The CIVI of ketamine was increased from .05mg/kg/hour to .5mg/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. 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 186mg/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. 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 intravenous ketamine and fentanyl sedation in duration of mechanical ventilation in intensive care unit

Background and aims: To compare the duration of mechanical ventilation in patients receiving ketamine compared to fentanyl for sedation in mechanically ventilated patients in intensive care unit. Methods: One hundred and six patients requiring mechanical ventilation were randomized to receive continuous intravenous infusion of either ketamine (1 mg/kg bolus followed by 0.4 to 0.8 mg/kg/h) or fentanyl (1mcg/kg bolus followed by 0.3-0.5 mcg/kg/min) with the dose titrated to achieve Richmond Agitation Sedation Scale (RASS) score of 0 to -1 and Behavioral Pain Scale (BPS) score of 3 to 7. The primary outcome was the duration of mechanical ventilation. Secondary outcomes were sedation score, analgesia score and need of vasopressors. Results: The mean duration of ventilation was 2.5±0.6 days and 2.2±1.0 days (p=0.1) in patients receiving ketamine and fentanyl respectively. More patients required vasopressors: 27 (50.9%) vs 9 (17%) in patients receiving fentanyl compared to ketamine (p&lt;0.05). There were no significant changes in hemodynamic variables after the initiation of the study drug in both the groups. Infusion was discontinued for adverse effects in seven (13%) patients in both the groups. Conclusion: When compared with fentanyl, continuous ketamine infusion was tolerated similarly by critically ill adults, with similar duration of mechanical ventilation. Ketamine sedation was associated with decreased requirement for vasopressors.

EFFECTS OF DETOMIDINE AND DEXMEDETOMIDINE ON PHYSIOLOGICAL PARAMETERS AND ANESTHETIC RECOVERY IN TAPIRUS TERRESTRIS ANESTHETIZED WITH KETAMINE, GLYCERYL GUAIACOL ETHER, AND MIDAZOLAM.

The aim of this study was to compare the effects of two anesthetic induction protocols for long procedures carried out in the field in Tapiridae. Sixteen tapirs were divided into two groups (n=8) receiving either detomidine (DET) or dexmedetomidine (DEX) for anesthetic induction. All animals were anesthetized by intramuscular administration of a combination of ketamine (1.5 mg/kg), midazolam (0.2 mg/kg), plus either DET (0.04 mg/kg) or DEX (0.007 mg/kg). Anesthetic maintenance was by continuous infusion of ketamine, midazolam, and glyceryl guaiacol ether at 2 mg/kg per hour, 0.1 mg/kg per hour, and 100 mg/kg per hour, respectively). The animals were kept anesthetized for a total of 50 min to allow physical examination and collection of biological material as part of a research program, and physiological variables (heart rate [HR], respiratory rate, oxyhemoglobin saturation [SpO2], rectal temperature [RT], mean arterial pressure [MAP], blood glucose [GLI], and cortisol) and electrocardiogram were recorded during anesthesia. Anesthetic recovery was monitored by two researchers who were not informed of the induction protocol group. The recorded results were statistically evaluated. In both groups there was an initial increase in MAP, which subsequently decreased; RT gradually decreased during anesthesia; HR and GLI increased throughout the procedure; SpO2 was below normal throughout the procedure. Cortisol levels were significantly higher in the DEX group than in the DET group. Also, the animals in the DEX group had a longer recovery time than those in the DET group. On the basis of the results, we conclude that the combination of alpha-2 agonists and midazolam, ketamine, and glyceryl guaicol ether is an appropriate protocol for the anesthesia of tapirs in the field. However, in moderately extended procedures oxygen supplementation is recommended. Additionally, DEX resulted in fewer cardiovascular effects and longer-lasting sedation than DET.

Ketamine Use in Adult and Pediatric Patients Receiving Extracorporeal Membrane Oxygenation (ECMO): A Systematic Review.

Background: Analgesia and sedation are often critical elements of therapy for patients undergoing extracorporeal membrane oxygenation (ECMO). Aside from potential drug-drug interactions, the PK changes associated with ECMO make appropriate analgosedative selection challenging. Ketamine is less lipophilic and has lower protein binding than alternative agents, and may be less impacted by the PK changes during ECMO. Objective: To systematically identify all instances of ketamine use during ECMO support in the literature to elucidate associated efficacy and safety outcomes and prevalence of use, as well as commonly used dosing strategies and pharmacokinetic data. Methods: Web of Science, Cochrane Library, Scopus, Ovid MEDLINE, PubMed, and OVID Embase were searched through 02/2023 using keywords ketamine and ECMO or extracorporal life support (ECLS). Case reports, case series, and studies were included that had (1) original data, (2) included patients that were on ECMO and continuous infusion ketamine, and (3) reported pertinent ketamine related clinical endpoints or prevalence of use. Results: Of the 307 articles screened, 25 were identified as relevant and 11 met our inclusion criteria. Heterogeneity of patient population, ketamine indication, reported outcomes, and reported safety endpoints were identified in the included articles. Commonly reported information includes indications, pharmacokinetics, dosing, adverse effects and use in pediatrics for ketamine, and suspected opioid sparing effect. Conclusion: Our review has found a lack of consistency in reporting and results in adult and pediatric patients. Increased consistency in reporting and larger studies are required to increase our knowledge of ketamine use in both the adult and pediatric patient population.

Safety and Efficacy of Ketamine Without Intubation in the Management of Refractory Seizures: A Case Series.

Continuous infusion ketamine has demonstrated efficacy in the management of refractory seizures yet does not suppress respiratory drive like other continuous infusion anesthetics (CIAs) used for this indication. The aim of this study is to describe the safety and efficacy of ketamine infusions in patients with refractory seizure without intubation. We analyzed a retrospective cohort of adult patients who were not intubated at the time of initiation of a ketamine infusion for refractory seizures. Seizure onset was determined to be the first clinical seizure or nonconvulsive seizure reported on electroencephalography (EEG) or the start time of EEG for patients with seizures at EEG initiation. Responders were defined as patients with resolution of seizures within 24h of initiation without the need for intubation or an additional CIA. A total of 28 patients were analyzed (median age 62years, 64.3% female, 82.1% African American, 82.1% with structural seizure etiology, and 85.7% focal seizures). Of patients, 78.5% received an initial bolus averaging 0.9mg/kg, and the majority (89.3%) were initiated on an infusion at 10μg/kg/minute; median duration was 39.8h. Maximum infusion rates were 10μg/kg/minute in 16 patients, 20μg/kg/minute in seven patients, and 30μg/kg/minute in five patients. Of patients, 71.4% were assessed to be ketamine responders; six of the eight nonresponders required intubation and an additional CIA. Responders were 80% more likely to have received ketamine 5 or more hours earlier than nonresponders. Hypotension (systolic blood pressure < 90mmHg) occurred in 31.8% of patients receiving only ketamine, which did not correlate with duration or maximum dose of ketamine; hypertension (systolic blood pressure > 180mmHg) occurred in 39.3%. Ketamine represents a safe and effective treatment option for refractory seizures and has potential to reduce morbidity associated with intubation in a carefully selected patient population. Early initiation may increase the likelihood of success.

Efficacy of Continuous Infusion Ketamine for Analgosedation in the Medical Intensive Care Unit: A Propensity-Weighted Analysis.

Few randomized controlled trials have evaluated the use of ketamine vs opiate-based analgosedation. A retrospective cohort analysis of 169 mechanically ventilated patients admitted to the medical intensive care unit (MICU) at an academic medical center was conducted to evaluate efficacy of ketamine vs opiate-based analgosedation by comparing the percentage of time within target sedation range. The primary outcome was percentage of time within target sedation range (RASS -1 to +1) within first 72hours of primary sedation initiation. Secondary outcomes including percentage of time under-sedated, over-sedated, and in coma; use of concomitant analgesic, sedative, and antipsychotic agents; presence of delirium; percentage of CPOT scores at goal; and hemodynamic effects were also evaluated. After weighting, the mean percentage of time at RASS goal for ketamine patients was 43.0% compared to 41.4% for opiate-based sedation patients. Ketamine was not significantly non-inferior to opiate-based sedation for the mean percentage of time at RASS goal (P = .11). The median percentage of CPOT scores at goal was 13.3% higher in the ketamine group (P = .042). Patients in the ketamine group received significantly less additional sedative agents than the patients in the opiate-based sedation group. A similar percent of time at RASS goal was found for the ketamine analgosedation group compared to the opiate-based sedation group, although this did not reach statistical signicance for non-inferiority due to lack of statistical power. This study found a higher percentage of CPOT scores within goal with less additional sedative agents required compared to an opiate-based sedation regimen.

Continuous infusion ketamine for sedation of mechanically ventilated adults in the intensive care unit: A scoping review

Introduction: Mechanical ventilation (MV) is a common and often live-saving intervention on the Intensive Care Unit (ICU). The optimisation of sedation to mechanical ventilation is fundamental, and inappropriate sedation has been associated with worse outcomes. This scoping review has been designed to answer the question ‘ What is known about the use of ketamine as a continuous infusion to provide sedation in mechanically ventilated adults in the intensive care unit, and what are the gaps in the evidence?’ Methods: The protocol was designed using the PRISMA-ScR checklist and the JBI manual for evidence synthesis. Data were extracted and reviewed by a minimum of two reviewers. Results: Searches of electronic databases (PubMed, OVID, Scopus, Web of Science) produced 726 results; 45 citations were identified for further eligibility assessment, an additional five studies were identified through keyword searches, and 12 through searching reference lists. Of these 62 studies, 27 studies were included in the final review: 6 case reports/case series, 11 retrospective cohort/observational studies, 1 prospective cohort study, 9 prospective randomised studies. Conclusion: We found a lack of high-quality well-designed studies investigating the use of continuous ketamine sedation on ICU. The available data suggests this intervention is safe and well tolerated, however this is of very low certainty given the poor quality of evidence.

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.

e24139 Background: The ketamine is used to control refractory cancer pain as adjuvant to opioids. However, usefulness of ketamine has not yet been confirmed due to lack of previous studies. Additionally, most of prior studies were studied in heterogenous patients, and continuous intravenous infusion (CIVI) method was rare. The CIVI method using gradual dose titrations of ketamine is safe. So, it is suitable to terminally ill cancer patients who have available IV access but vulnerable to AEs. This phase II single-arm study investigated efficacy and safety of CIVI of Ketamine in these population. Methods: Cancer patients with expected limited survival time within several months and refractory cancer pain were enrolled. Refractory cancer pain indicates requirements of breakthrough analgesics ≥ 4 times/day or average pain score &gt; personalized pain goal (PPG) in spite of intravenous Morphine Equivalent Daily Dose (MEDD) &gt; 120 mg/day. The CIVI of ketamine was increased from 0.05 mg/kg/hr to 0.5 mg/kg/hr by 0.05 mg/kg/hr every 8hr when average pain score exceeded PPG or breakthrough was needed ≥ 2 times/8hr during 5 days. The primary end-point was overall pain response rate, which indicates complete response (both breakthrough ≤ 3/day and NRS ≤ PPG) plus partial response (breakthrough ≤ 3/day), without unacceptable toxicities. A total of 26 patients are needed to verify assumption of response rate of 40% with width of 0.4 for two-sided 95% CI and assuming 5% drop-out rate. This study was prematurely terminated at enrollment of 21 patients. Results: Among 21 enrolled patients between SEP 2019 and JAN 2023, 20 were analyzed except 1 due to early transfer. Most pain mechanisms were mixed type (n = 15, 75%), while some reported nociceptive pain (n = 3, 15%) or neuropathic pain (n = 2, 10%). The baseline background opioids were MEDD 186 mg/day (range, 124-592), number of breakthrough opioids were 5 (IQR, 5-7). The median PPG were 4 (range, 3-6). After application of ketamine, overall pain response rate was 45% (n = 9), complete pain response was 35% (n = 7) and partial pain response was 10% (n = 2). The other 11 were non-responders (six failed to achieve overall pain response despite of maximal dose or completing 5 days of ketamine, five patients discontinued the treatment due to AEs). AEs included confusion (n = 9, 45%), dizziness (n = 3, 15%), and hypertension (n = 2, 10%). Communication capacities were sustained in 10 patients and decreased in other 10 patients. OS were 21 days (95% CI, 18.1-23.9). Conclusions: Our study showed efficacies and safeties of gradually increasing CIVI of ketamine for terminally ill cancer patients with refractory cancer pain. The CIVI of ketamine can be a useful tool in these patients considering limited treatment options. Further studies comparing usefulness of CIVI of ketamine and usual practice with opioids escalation are needed (NCT03362073). Clinical trial information: NCT03362073 .

Effect of Intraoperative Infusion of Esketamine on Quality of Postoperative Recovery in Patients Undergoing Laparoscopic Bariatric Surgery: A Randomized Controlled Trial.

This study aims to evaluate the efficacy of esketamine on postoperative recovery quality after laparoscopic bariatric surgery. Patients (n = 74) scheduled for laparoscopic bariatric surgery were randomly divided into two groups: the esketamine group (group E: 0.5mg/kg/h infusion, i.e., 0.2mL/kg/h) or the control group (group C: 0.2mL/kg/h normal saline infusion). The infusions were stopped 20min before the end of the procedure. The primary outcome was the Quality of Recovery-40 (QoR-40) score on postoperative day 1 (POD 1). The secondary outcomes included QoR-40 scores on PODs 2 and 7, Numeric Rating Scale (NRS) on PODs 1, 2, and 7, time to extubation, additional postoperative analgesic use, length of hospital stay, and time to first exhaust. Additonally, the safety indices were also recorded, including hemodynamic profile, perioperative anesthesia index (Ai), utilization of vasoactive drugs or urapidil, and side effects. All in all, 70 of the 74 patients completed the study, 35 in each group. The difference of QoR-40 scores on POD 1 was both statistically and clinically significant [difference 7.21, 95% confidence interval (CI) 5.17, 9.25, p < 0.001]. The difference of QoR-40 on POD 2 was statistically significant but clinically insignificant (difference 4.81, 95% CI 2.69, 6.92, p < 0.001). The difference of NRS scores on POD1 was statistically significant (difference -1.23, 95% CI -2.36, -0.10, p= 0.033). Compared with group C, group E had a lower utilization rate of phenylephrine and higher Ai values (p < 0.05). There was no statistical difference between the two groups on other measures. Continuous ketamine infusion seems to be safe and well tolerated in laparoscopic bariatric surgery. It improved the quality of postoperative recovery and reduced pain on POD 1. In spite of the increased Ai value during the surgery, it also provided better hemodynamics with less usage of phenylephrine.

Anaesthesia, analgesia and cardiovascular support in a Kunekune pig undergoing a complicated umbilical hernia repair

AbstractThis report describes the peri‐operative anaesthesia and analgesia management of a 5‐year‐old Kunekune pig undergoing surgical correction of an umbilical hernia. Premedication with azaperone (1 mg/kg), xylazine (0.5 mg/kg), butorphanol (0.2 mg/kg) and ketamine (5 mg/kg) intramuscularly preceded induction of anaesthesia with ketamine (2 mg/kg) intravenously. General anaesthesia was maintained with isoflurane in 100% oxygen. Analgesia was supported intraoperatively by a transversus abominis plane block with lidocaine (1.5 mg/kg), and a ketamine (10 μg/kg/min) infusion intravenously. Crystalloid fluid boluses and atropine intravenously were administered, and mechanical ventilation was stopped to aid correction of hypotension. Post‐operative analgesia was supported with a continuous infusion of ketamine (5 μg/kg/min) intravenously, butorphanol (0.2 mg/kg) intravenously every 6 hours, paracetamol (10 mg/kg) intravenously orally every 8 hours and meloxicam (0.4 mg/kg) intravenously orally every 24 hours. The pig made progressive clinical improvement and was discharged 7 days after the surgery.

Continuous Ketamine Infusion for Treatment of Refractory Headache in the Inpatient Setting (P11-12.008)

<h3>Objective:</h3> The aim of this retrospective case series is to describe our experience using continuous ketamine infusion for treatment of refractory headache in the inpatient setting. We report the efficacy of intravenous (IV) ketamine in a small patient cohort. <h3>Background:</h3> Refractory headaches can be challenging to manage. Ketamine has been proposed for use in intractable headaches. There is limited information available on administering IV ketamine in the inpatient setting for refractory headache, and a protocol has not been established. <h3>Design/Methods:</h3> Four patients ≥ 18 years of age were admitted with refractory headaches and treated with IV ketamine during the study timeframe of January 2020 and December 2021. Demographic and clinical characteristics are reported. <h3>Results:</h3> All four patients were female, with an average age of 48.3+4.9 years (range: 44–53 years). Each experienced headaches despite treatment with an average of 5.8 + 2.5 IV medications. Mean pain score (0–10 scale) prior to ketamine administration was 9.3+1.0 and was significantly lower, 1.8+1.3 post-ketamine (mean difference = 7.5+2.1, p=0.006). All patients achieved target pain (defined as &gt;50% reduction in headache). Ketamine infusion was started at 0.1 mg/kg/hr for three patients and at 0.2 mg/kg/hr for one patient. Average peak rate of ketamine infusion was 0.48+0.17 mg/kg/hr (range 0.3–0.7 mg/kg/hr). Average total time of ketamine infusion administration was 51.9+6.6 hours (range 44.5–60.0 hours). Few transient adverse events were reported, including dysarthria and somnolence, which resolved spontaneously. <h3>Conclusions:</h3> Target pain levels were achieved while on continuous ketamine for all four patients with refractory headache in our case series. It was well tolerated. Larger randomized trials are needed to investigate the safety and efficacy of ketamine infusion for refractory headache in the inpatient setting. <b>Disclosure:</b> Dr. Kim has nothing to disclose. Dr. Park has nothing to disclose. Dr. Shemme has nothing to disclose. Tracy J. Koehler has nothing to disclose. Dr. Phillips has nothing to disclose.

The Effect of Analgesia with Ketamine, Morphine and Paracetamol for Burn Pain in North-Eastern Iran

Background: Pain is a common and challenging problem in burn patients. The severity of pain in these patients often requires multi drug therapy. On the other hand, with increasing the number and dosage of drugs, the complications increase, so finding an instruction that provides acceptable analgesia with minimal complications is necessary.&#x0D; Methods: Based on the dose and half-life, the initial dose for paracetamol was 15 mg/kg every 6 hours, this dose was reduced to 30% after three days of initiation of the treatment to prevent liver toxicity and was discontinued after one week. Morphine started with an initial dose of 0.01 mg/kg/h and for opioid-tolerant patients, the initial dose was 0.02 mg/kg/h. Morphine infusion dose raised by 30 percent every week. The continuous intravenous infusion of ketamine (0.15 mg/kg/hr) with continuous intravenous infusion of morphine was administered by a silicone pump.&#x0D; Results: The mean NRS was significantly reduced in the first visit after the intervention (three hours later) (8.5 ± 1.04 vs.3.9 ± 1.74; p &lt;0.001) and this decrease was observed in NRS in continuous observations (P&gt; 0.001). Pain reduction was independent of history of opioids use.&#x0D; Conclusion: Continuous infusion of ketamine, morphine and paracetamol showed an effective pain management program for burn patients.

Use of Continuous Ketamine Infusion as an Adjunctive Agent in Young Infants With Refractory and Super Refractory Status Epilepticus: A Case Series.

Continuous ketamine infusions have been studied as an adjunctive agent for refractory status epilepticus (RSE) and super refractory status epilepticus (SRSE) in older children and adults. However, minimal information exists on the efficacy, safety, and dosing for continuous ketamine in young infants. We present the clinical course of 3 young infants with RSE and SRSE who received continuous ketamine in conjunction with other antiseizure medications. The condition of these patients was refractory to an average of 6 antiseizure medications before initiation of continuous ketamine infusion. For each patient, a continuous ketamine infusion was initiated at a rate of 1 mg/kg/hr with 1 patient requiring titration to a maximum of 6 mg/kg/hr. In 1 case, the concomitant use of continuous ketamine allowed for a reduction in the benzodiazepine continuous infusion rate. In all cases, ketamine was well tolerated especially in the setting of hemodynamic instability. Ketamine may provide a safe adjunct in the acute setting in severe RSE and SRSE. This is the first case series to document the use of continuous ketamine as a treatment modality in young infants with RSE or SRSE secondary to various underlying etiologies, without adverse events. Further studies are needed to evaluate the long-term safety and efficacy of continuous ketamine in this patient population.

Abstract OT3-20-01: Ketamine Analgesia for Long Lasting Pain Relief after Surgery (KALPAS) Study

Abstract Background: Post-mastectomy pain syndrome (PMPS) affects up to 60% of women undergoing mastectomy. Standard perioperative multimodal analgesia remains only moderately effective in preventing PMPS, and many patients continue to rely on opioids for their chronic pain. In the context of the opioid overdose crisis, alternative interventions are urgently needed. Ketamine targets risks factors for PMPS including acute pain and negative mood, making it an ideal candidate for the prevention of PMPS. Trial Design: This is a multisite, three-arm, double-blind, RCT to test the effectiveness of ketamine in reducing PMPS in women undergoing mastectomy for oncologic indication. Arm 1 consists of continuous perioperative ketamine infusion that begins during surgery and continues for 2 hours in the post-anesthesia care unit (PACU). Arm 2 consists of a single-dose of ketamine in the PACU given over 50-60 minutes. Arm 3 consists of placebo. Standard surgical and postsurgical care remain unchanged across all arms. Eligibility Criteria: Inclusion criteria are: women ≥18 years of age undergoing total mastectomy for oncologic indication +/- lymph node dissection and +/- immediate or delayed reconstruction with no distant metastases. Exclusion criteria include: (1) history of cognitive impairment (2) past ketamine or phencyclidine misuse or abuse, (3) schizophrenia or history of psychosis, (4) history of post-traumatic stress disorder, (5) known sensitivity or allergy to ketamine, (6) liver or renal sufficiency, (7) uncontrolled hypertension, chest pain, cardiac arrhythmia, stroke, head trauma, intracranial mass or hemorrhage, glaucoma, porphyria, uncontrolled thyroid disease, or other contraindication to ketamine, (8) lamotrigine alfentanil, physostigmine, or 4-aminopyridine use, (9) currently pregnant, (10) body mass index greater than 35, (11) non-English or non-Spanish speaker, (12) currently participating in another pain interventional trial, (13) patient has started or undergone hormone therapy for gender transition into male, or (14) patient is scheduled for bilateral (or greater) flap reconstruction. Specific Aims: The primary outcome is pain intensity on the Brief Pain Inventory short form scale at the surgical site three months after mastectomy. Secondary outcomes include pain severity and interference at the surgical site, incidence of PMPS, anxiety, and depression over 12 months after surgery. Tertiary outcomes include neuropathic symptoms, fatigue, sleep, physical function, and opioid use. Statistical Methods: We will test the differences in the primary outcome between 1) the continuous ketamine infusion and the control; and 2) the single-dose ketamine and the control, each at 0.025 significance level (adjusted for multiple comparisons using the Bonferroni correction), based on the two-sample t-tests (allowing unequal variances) if outcome variables are approximately normal, or Wilcoxon’s rank-sum tests otherwise. Accrual: The target accrual for this study is ~750. Recruitment began January 2022. Recruitment is expected to be complete by October 2025. As of July 14, 2022, 43 participants have been enrolled across all sites. If interested in the KALPAS Study, please contact kalpas@nyulangone.org, jing.wang@nyulangone.org, or lisa.doan@nyulangone.org This research is supported by the National Institutes of Health through the NIH HEAL Initiative under UH3CA261067. It is also supported by the NCATS Trial Innovation Network under award numbers U24TR001608 (CCC), U24TR001597 (DCC), U24TR001609 (SSC), U24TR001579 (RIC) Citation Format: Lisa Doan, Raven Perez, Jeana Chun, Randy Cuevas, Pabel Miah, Amber Guth, Karen Hiotis, Freya Schnabel, Michele Curatolo, Robert Edwards, Hyung Park, John Rotrosen, Deborah Axelrod, Jing Wang. Ketamine Analgesia for Long Lasting Pain Relief after Surgery (KALPAS) Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT3-20-01.

Continuous Ketamine Infusion as a Treatment for Refractory Facial Pain.

Complex orofacial pain disorders, such as trigeminal neuralgia (TN) and atypical facial pain (AFP), can be excruciating and debilitating during attacks. Ketamine, an N-methyl-D-aspartate (NMDA) antagonist, is a powerful analgesic that has been used to treat various chronic pain conditions, but its role in treating complex facial pain has only been recently explored. In this retrospective case series, we reviewed the efficacy of continuous ketamine infusion for 12 patients with facial pain refractory to medical treatment. Patients who presented with a diagnosis of TN were more likely to have significant and sustained pain relief after receiving ketamine infusion. By contrast, those who did not respond to the treatment were more likely to have a diagnosis of AFP. The current report suggests a fundamental difference between these two facial pain disorders in their respective underlying pathophysiology and supports the use of continuous ketamine infusion for refractory TN, but not AFP.

Effects of Ketamine Infusion on Oxygenation in Patients with Chronic Obstructive Pulmonary Disease Undergoing Lung Cancer Surgery.

Ketamine changes respiratory mechanics, provides airway relaxation, and alleviates bronchospasm in patients with pulmonary disease. This study investigated the effect of a continuous infusion of ketamine during thoracic surgery on arterial oxygenation (PaO2/FiO2) and the shunt fraction (Qs/Qt) in patients with chronic obstructive pulmonary disease. Thirty patients older than 40 years, diagnosed with chronic obstructive pulmonary disease, and undergoing lobectomy were recruited for this study. Patients were allocated randomly to 1 of 2 groups. At the induction of anaesthesia, group K received intravenous (iv) 1 mg kg-1 ketamine as a bolus and followed by 0.5 mg kg-1 h-1 infusion until the end of the operation. Group S received the same amount of 0.9% saline as a bolus at induction and followed by a 0.5-mL kg-1 h-1 infusion of 0.9% saline until the end of the operation. PaO2 and PaCO2 values, FiO2 levels, PaO2/FiO2 ratio, peak airway pressure (Ppeak), plateau airway pressure (Pplat), dynamic compliance, and shunt fraction (Qs/Qt) were recorded during two-lung ventilation as a baseline and at 30 (one-lung ventilation, OLV-30) and 60 (OLV-60) minutes during one-lung ventilation. PaO2, PaCO2, PaO2/FiO2 values, and Qs/Qt ratio were similar between the 2 groups at OLV-30 minute (P = .36, P = .29, P = .34). However, at OLV-60 minute, PaO2, PaO2/FiO2 values were significantly increased, and Qs/Qt ratios were significantly decreased in group K than in group S (P = .016, P = .011, P = .016). Our data suggest that a continuous infusion of ketamine and desflurane inhalation in patients with chronic obstructive pulmonary disease during one-lung ventilation increase arterial oxygenation (PaO2/FiO2) and decrease shunt fraction.

1116: THE IMPACT OF ADJUNCTIVE KETAMINE ON SEDATION REQUIREMENTS IN VENTILATED PATIENTS WITH COVID-19

Introduction: Patients infected with the SARS-CoV-2 virus (COVID-19) may develop acute respiratory distress syndrome, requiring mechanical ventilation. Reports suggest that these patients may have increased sedation requirements due to intensive mechanical ventilation needs, necessitating the evaluation of additional sedation, with limited guidance available. Due to multiple drug shortages, ketamine became an attractive adjunctive option to meet sedation goals. The primary objective of this study was to compare sedation and analgesic requirements in mechanically ventilated patients with COVID-19 who received continuous ketamine infusions with those who did not. Methods: A multi-center, retrospective cohort study was performed in adult patients with COVID-19 who were mechanically ventilated for at least 24 hours. Groups were allocated based on whether or not adjunctive continuous infusion ketamine was used. The primary outcome was a comparison of the sedation and analgesic agents and the median morphine equivalents (ME) required. Secondary outcomes included intensive care unit (ICU) and hospital length of stay (LOS), duration of mechanical ventilation, and in-hospital mortality. Results: A total of 1,757 patients were screened for inclusion. After exclusions, 40 patients in each group were included for analysis. More patients in the ketamine group received intravenous opiates (100% vs 80%, p < 0.01) and also had higher ME than the non-ketamine group (357 [276–440] vs 222 [141–294] mg ME daily, p < 0.01). There was also a greater LOS in the ketamine group in both the hospital (24 vs 16.5 days, p=0.01) and ICU (18.8 [12.6–27.9] vs 14.9 [7.1–18.7] days, p=0.04). The ketamine group also experienced longer intubation durations (14.5 [9.0–23.5] vs 8.0 [4.0–13.5] days, p=0.01). There were no significant differences in in-hospital mortality or average doses of propofol, midazolam, dexmedetomidine, or vasopressors between groups. Conclusions: Ketamine use was not associated with a decrease in opioid or sedation use in patients with COVID-19 who were mechanically ventilated. Additional studies are needed to assess the role of ketamine and its impact on sedation and analgesia requirements in COVID-19 positive patients.

Ketamine Infusion for Sedation and Analgesia during Mechanical Ventilation in the ICU: A Multicenter Evaluation.

We reviewed the electronic medical record of critically ill adults who received a continuous infusion of ketamine for ≥24 hours during invasive mechanical ventilation in three hospitals over a two-year period. We captured data including ketamine indication, dose, unintended effects, and adjustments to coadministered sedatives or opioids. We analyzed these data to determine the incidence of reported unintended effects of ketamine infusion (primary outcome) and changes in exposure to coadministered sedatives or opioids during ketamine use (secondary outcome). 95 mechanically ventilated adults received a ketamine infusion for a median duration of 75 hours (interquartile range [IQR] 44-115) at a mean ± standard deviation (SD) infusion rate of 1.3 ± 0.5 mg/kg/hour for the first 24 hours. At least one unintended effect attributed to ketamine was documented in 24% of cases, most frequently tachycardia (6%) and sialorrhea (6%). Other sedative or opioid infusions were administered with ketamine in 76% and 92% of cases, respectively. Comparing the total amount of sedative or opioid administered in the 24 hours prior to ketamine infusion with the total amount administered during the first 24 hours on ketamine, there were no significant differences in propofol, midazolam, or dexmedetomidine exposure, but the average fentanyl exposure was higher after ketamine (2740 ± 1812 mcg) than before (1975 ± 1860 mcg) (absolute difference 766 mcg, 95% confidence interval [CI] 442 to 1089 mcg). In this multicenter cohort of critically ill, mechanically ventilated adults, ketamine infusion was primarily used as an adjunct to conventional sedative and opioid infusions, with noticeable but unintended effects potentially related to ketamine in nearly one-quarter of cases.