A systematic review and meta-analysis of ketamine in pediatric status epilepticus.

OBJECTIVE: Status epilepticus (SE) is a common neurological medical emergency in the pediatric population, with 10%-40% of cases progressing to refractory SE (RSE), requiring treatment with anesthetic infusions. We present a systematic review and meta-analysis of the use of ketamine for the treatment of pediatric SE and its potential advantages over other anesthetic infusions. METHODS: This review follows the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Electronic databases, including PubMed, Cochrane Library, Ovid, Embase, and Google Scholar, were searched with the keywords "pediatrics," "status epilepticus," and "ketamine treatment." Randomized trials, prospective and retrospective cohort studies, and case reports were considered for inclusion. RESULTS: Eighteen publications met the initial inclusion criteria. The 18 publications comprise 11 case reports, one nonconclusive clinical trial, two case series, and four retrospective cohorts. After excluding the case reports because of reporting bias, only the six case series and cohorts were included in the final analysis. There were 172 patients in the six included studies. The weighted age was 9.93 (SD = 10.29) years. The weighted maximum dose was 7.44 (SD = 9.39) mg/kg/h. SE cessation was attained in 51% (95% confidence interval = 43-59) of cases with the addition of ketamine. The heterogeneity was I2 = 0%, t2 = 0, χ2 (5) = 3.39 (p = .64). SIGNIFICANCE: Pediatric RSE is difficult to treat, resulting in increased morbidity and mortality. Without strong recommendations and evidence regarding preferred agents, this review provides evidence that ketamine may be considered in managing SE in the pediatric population.

Fixed dose ketamine for prehospital management of hyperactive delirium with severe agitation.

INTRODUCTION: Patients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. METHODS: Emergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. RESULTS: Review of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67-10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. CONCLUSION: The 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors.

Alfentanil versus fentanyl for emergency department rapid sequence induction with ketamine: A-FAKT, a pilot randomized trial.

BACKGROUND: Fentanyl is often administered during rapid sequence induction of anesthesia (RSI) in the emergency department (ED) to ameliorate the hypertensive response that may occur. Due to its more rapid onset, the use of alfentanil may be more consistent with both the onset time of the sedative and the commencement of laryngoscopy. As such, we compared the effect of alfentanil and fentanyl on post-induction hemodynamic changes when administered as part of a standardized induction regimen including ketamine and rocuronium in ED RSI. METHODS: This was a double-blind pilot randomized controlled trial of adult patients requiring RSI in the ED of three urban Australian hospitals. Patients were randomized to receive either alfentanil or fentanyl in addition to ketamine and rocuronium for RSI. Non-invasive blood pressure and heart rate were measured immediately before and at two, four, and six minutes after induction. The primary outcome was the occurrence of at least one post-induction systolic blood pressure outside the pre-specified range of 100-160mmHg (with adjustment for patients with baseline hypertension). Secondary outcomes included hypertension, hypotension, hypoxia, first-pass intubation success, 30-day mortality, and the pattern of hemodynamic changes. RESULTS: A total of 61 patients were included in the final analysis (31 in the alfentanil group and 30 in the fentanyl group). The primary outcome was met in 58% of the alfentanil group and 50% of the fentanyl group (difference 8%, 95% confidence interval: -17% to 33%). The 30-day mortality rate, first-pass success rate, and incidences of hypertension, hypotension, and hypoxia were similar between the groups. There were no significant differences in systolic blood pressure or heart rate between the groups at any of the measured time-points. CONCLUSION: Alfentanil and fentanyl produced comparable post-induction hemodynamic changes when used as adjuncts to ketamine in ED RSI. Future studies could consider comparing different dosages of these opioids.

Intubation Rates following Prehospital Administration of Ketamine for Acute Agitation: A Systematic Review and Meta-Analysis.

BACKGROUND: Ketamine is a fast-acting, dissociative anesthetic with a favorable adverse effect profile that is effective for managing acute agitation as a chemical restraint in the prehospital and emergency department (ED) settings. However, some previously published individual studies have reported high intubation rates when ketamine was administered prehospitally. OBJECTIVE: This systematic review aims to determine the rate and settings in which intubation following prehospital administration of ketamine for agitation is occurring, as well as associated indications and adverse events. METHODS: We searched PubMed, Scopus, Ovid MEDLINE, Embase, CINAHL Plus, PsycINFO, the Cochrane Library, ClinicalTrials.gov, OpenGrey, Open Access Theses and Dissertation, and Google Scholar from the earliest possible date until 13/February/2022. Inclusion criteria required studies to describe agitated patients who received ketamine in the prehospital setting as a first-line drug to control acute agitation. Reference lists of appraised studies were screened for additional relevant articles. Study quality was assessed using the Newcastle-Ottawa quality assessment scale. Synthesis of results was completed via meta-analysis, and the GRADE tool was used for certainty assessment. RESULTS: The search yielded 1466 unique records and abstracts, of which 50 full texts were reviewed, resulting in 18 being included in the analysis. All studies were observational in nature and 15 were from USA. There were 3476 patients in total, and the overall rate of intubation was 16% (95% confidence interval [CI] = 8%-26%). Most intubations occurred in the ED. Within the studies, the prehospital intubation rate ranged from 0% to 7.9% and the ED intubation rate ranged from 0 to 60%. The overall pooled prehospital intubation rate was 1% (95% CI = 0%-2%). The overall pooled ED intubation rate was 19% (95% CI = 11%-30%). The most common indications for intubation were for airway protection and respiratory depression/failure. CONCLUSIONS: There is wide variation in intubation rates between and within studies. The majority of intubations performed following prehospital administration of ketamine for agitation took place in the ED.

Paraphimosis Pain Treatment with Nebulized Ketamine in the Emergency Department.

BACKGROUND: Paraphimosis is an acute urological emergency occurring in uncircumcised males that can lead to strangulation of the glans and painful vascular compromise. Ketamine has been used in the emergency department (ED) as an anesthetic agent for procedural sedation, and when administrated in a sub-dissociative dose (low dose) at 0.1-0.3 mg/kg, ketamine has been utilized in the ED and prehospital settings for pain control as an adjunct and as an alternative to opioid, as well as for preprocedural sedation. This report details the case of a pediatric patient who presented to our Pediatric ED with paraphimosis and had his procedural pain treated with ketamine administrated via a breath-actuated nebulizer (BAN). CASE REPORT: This case report illustrates the potential use of ketamine via BAN to effectively achieve minimal sedation for a procedure in pediatric patients in the ED. The patient was a 15-year-old boy admitted to the Pediatric ED complaining of groin pain due to paraphimosis. The patient was given 0.75 mg/kg of nebulized ketamine via BAN, and 15 min after the medication administration the pain score was reduced from 5 to 1 on the numeric pain rating scale. The patient underwent a successful paraphimosis reduction without additional analgesic or sedative agents 20 min after the administration of nebulized ketamine. The patient was subsequently discharged home after 60 min of monitoring, with a pain score of 0. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: The use of nebulized ketamine via BAN might represent a viable, noninvasive way to provide a mild sedative and be an effective analgesic option for managing a variety of acute painful conditions and procedures in the pediatric ED.

Rapid Agitation Control With Ketamine in the Emergency Department: A Blinded, Randomized Controlled Trial.

STUDY OBJECTIVE: We hypothesized that the use of intramuscular ketamine would result in a clinically relevant shorter time to target sedation. METHODS: We conducted a randomized clinical trial comparing the rapidity of onset, level of sedation, and adverse effect profile of ketamine compared to a combination of midazolam and haloperidol for behavioral control of emergency department patients with severe psychomotor agitation. We included patients with severe psychomotor agitation measured by a Richmond Agitation Score (RASS) ≥+3. Patients in the ketamine group were treated with a 5 mg/kg intramuscular injection. Patients in the midazolam and haloperidol group were treated with a single intramuscular injection of 5 mg midazolam and 5 mg haloperidol. The primary outcome was the time, in minutes, from study medication administration to adequate sedation, defined as RASS ≤-1. Secondary outcomes included the need for rescue medications and serious adverse events. RESULTS: Between June 30, 2018, and March 13, 2020, we screened 308 patients and enrolled 80. The median time to sedation was 14.7 minutes for midazolam and haloperidol versus 5.8 minutes for ketamine (difference 8.8 minutes [95% confidence interval (CI) 3.0 to 14.5]). Adjusted Cox proportional model analysis favored the ketamine arm (hazard ratio 2.43, 95% CI 1.43 to 4.12). Five (12.5%) patients in the ketamine arm and 2 (5.0%) patients in the midazolam and haloperidol arm experienced serious adverse events (difference 7.5% [95% CI -4.8% to 19.8%]). CONCLUSION: In ED patients with severe agitation, intramuscular ketamine provided significantly shorter time to adequate sedation than a combination of intramuscular midazolam and haloperidol.

Ketamine in acute phase of severe traumatic brain injury "an old drug for new uses?"

Maintaining an adequate level of sedation and analgesia plays a key role in the management of traumatic brain injury (TBI). To date, it is unclear which drug or combination of drugs is most effective in achieving these goals. Ketamine is an agent with attractive pharmacological and pharmacokinetics characteristics. Current evidence shows that ketamine does not increase and may instead decrease intracranial pressure, and its safety profile makes it a reliable tool in the prehospital environment. In this point of view, we discuss different aspects of the use of ketamine in the acute phase of TBI, with its potential benefits and pitfalls.

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

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

Safety and Efficacy of the Combination of Propofol and Ketamine for Procedural Sedation/Anesthesia in the Pediatric Population: A Systematic Review and Meta-analysis.

BACKGROUND: Drugs such as propofol and ketamine are used alone or in combination to provide sedation for medical procedures in children. The purpose of this systematic review was to compare the safety and effectiveness of propofol and ketamine to other drug regimens. METHODS: We searched Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Web of Science, and the grey literature (meta-Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar) for randomized controlled studies comparing intravenous propofol and ketamine to any other single or combination drug regimen administered to children undergoing diagnostic or therapeutic procedures. Meta-analyses were performed for primary (hemodynamic and respiratory adverse events) and secondary outcomes using RevMan 5.3. We assessed the risk of bias and the certainty (quality) evidence for all outcomes using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. RESULTS: Twenty-nine studies were included for analysis. Based on low-to-moderate quality evidence, we concluded that the use of propofol and ketamine may result in a slight-to-small reduction in the risk of hypotension, bradycardia, and apnea, and a slight increase in the risk of tachycardia, hypertension, and other respiratory adverse events, such as cough or laryngospasm. The ratio of propofol to ketamine and comparator drug regimen subgroups effects were important for desaturation and some secondary outcomes. CONCLUSIONS: The use of propofol and ketamine had a minimal effect on the incidence of adverse events and other secondary outcomes. Large-scale studies are required to more accurately estimate adverse event rates and the effects of propofol and ketamine on patient-important outcomes.

Description of Adverse Events in a Cohort of Dance Festival Attendees with Stimulant-Induced Severe Agitation Treated with Dissociative-Dose Ketamine.

BACKGROUND: Emergency clinicians often treat severe agitation resulting from intoxicants, psychiatric illness, and other CNS or systemic diseases. Recreational drugs-especially stimulants-are frequently used by attendees of electronic dance music festivals (EDMFs), and festivalgoers may become dangerously agitated and pose an immediate threat to themselves and others. Although benzodiazepines and antipsychotics are classically used to treat severe agitation, these medications are burdened by safety concerns including respiratory depression and cardiac arrhythmias. The effects of ketamine when used to treat severe agitation in an exclusive cohort of patients with psychostimulant drug-induced toxicity (PDIT) has not previously been reported, and existing literature describes a widely variant safety profile when ketamine is used for sedation of the agitated patient. OBJECTIVE: To describe ketamine's adverse event profile when used to treat patients with severe agitation resulting from PDIT. METHODS: This is a retrospective, observational study enrolling consecutive patients who presented for medical attention at a large outdoor EDMF over a period of eight days on two consecutive weekends in the summer of 2017. The EDMF had an estimated attendance of 40,000 per weekend. A medical tent was set up on-site; patients were managed by a team of EMS providers, nurses and emergency physicians. Medications used, adverse events and the need for repeat dosing were abstracted from prehospital care reports. RESULTS: Over the course of eight days, 1081 of 1186 patients who were evaluated in the medical tent had a recorded chief complaint. 274 of these patients (25.3%) had a chief complaint of altered mental status. In patients presenting with AMS, 68 patients (24.8%) had severe agitation that was treated with dissociative-dose (≥4 mg/kg) intramuscular ketamine. The mean initial dose of ketamine was 308 mg. There were four serious adverse events (5.9%): Two patients (2.9%) had copious hypersalivation treated with atropine, one patient (1.5%) had transient apnea requiring assisted ventilation, and one patient (1.5%) was intubated and transported to the hospital. 42 patients (61.8%) required redosing of calming medications. All patients who received ketamine except the single patient who was intubated and transported were observed in the medical tent until resolution of symptoms and discharged back to the festival. CONCLUSION: In this cohort of festival attendees who developed stimulant-induced severe agitation and were treated with dissociative-dose ketamine, serious adverse events occurred in 5.9% of patients including one patient who was intubated.

Impact of young age on outcomes of emergency department procedural sedation.

OBJECTIVES: Relatively little is known about outcomes of procedural sedation in very young children. Our objective was to examine the association between procedural sedation in young children (≤ 2 years) and the incidence of sedation-related adverse events. METHODS: This is a secondary analysis of a prospective cohort study of children 0 to 18 years undergoing parenteral procedural sedation in six Canadian pediatric emergency departments (ED). The primary risk factor was age ≤ 2 years. Secondary risk factors were sex, procedure type, pre-procedure and sedation medications. The outcomes examined were: serious adverse events (SAE), significant interventions, oxygen desaturation and vomiting. RESULTS: Of the 6295 patients included, 946 (15%) were ≤2 years. Children 13-24 months comprised 90% of the young age group. Children ≤ 2 years were sedated most commonly for laceration repair (n = 450; 47.6%), while orthopedic reduction was most common in children > 2 (n = 3983; 74.5%). Ketamine was the most common medication in both groups, but was used more frequently in children ≤ 2 years (80.9% vs 58.9%; p < 0.001). There was no difference in the odds of SAE (OR 0.83, 95% Confidence Interval (CI) 0.4 to 1.9), significant intervention (OR 0.82, 95% CI 0.4 to 1.7) or oxygen desaturation (OR 0.95, 95% CI 0.7 to 1.3) between age groups, however children ≤ 2 years vomited less frequently (OR 0.24, 95% CI 0.1 to 0.6). CONCLUSIONS: Young age, specifically between 13 and 24 months, was not associated with a significant difference in the incidence of adverse events.

Efficacy of ketamine for initial control of acute agitation in the emergency department: A randomized study.

BACKGROUND: Clinicians often encounter agitated patients, and current treatment options include benzodiazepines and antipsychotics. Ketamine rapidly induces dissociation, maintains cardiovascular stability, spontaneous respirations, and airway reflexes. There are no prospective, randomized studies comparing ketamine to other agents in the initial management of acute agitation in the Emergency Department (ED). OBJECTIVE: Determine the efficacy and safety of ketamine compared to parenteral haloperidol plus lorazepam for initial control of acute agitation. METHODS: This study was a prospective, single-institution, randomized, open-label, real world, standard of care pilot study. Adult patients with combative agitation were randomized to ketamine (4 mg/kg IM or 1 mg/kg IV) or haloperidol/lorazepam (haloperidol 5-10 mg IM or IV + lorazepam 1-2 mg IM or IV). The primary outcome was sedation within 5 min, and secondary outcomes included sedation within 15 min, time to sedation, and safety. RESULTS: Ninety three patients were enrolled from January 15, 2018 to October 10, 2018. Significantly more patients who received ketamine compared to haloperidol/lorazepam were sedated within 5 min (22% vs 0%, p = 0.001) and 15 min (66% vs 7%, p < 0.001). The median time to sedation in patients who received ketamine compared to haloperidol/lorazepam was 15 vs 36 min respectively (p < 0.001). Patients who received ketamine experienced a significant, but transient tachycardia (p = 0.01) and hypertension (p = 0.01). CONCLUSION: In patients with combative agitation, ketamine was significantly more effective than haloperidol/lorazepam for initial control of acute agitation, and was not associated with any significant adverse effects.

Comparison of the efficacy of ketamine- propofol versus sodium thiopental-fentanyl in sedation: a randomised clinical trial.

BACKGROUND: Many sedative regimens have been studied with controversial efficiencies. This study tried to assess the desirable and adverse effects of sodium thiopental-fentanyl (TF) with ketamine-propofol (KP) for procedural sedation and analgesia in the emergency department. METHODS: After signing written consent, patients were enrolled in this randomised double-blind trial to receive either KP or TF to reach the desired sedation level. The respiratory and haemodynamic complications, nausea and vomiting, recovery agitation, patient recall and satisfaction, provider satisfaction and recovery time were compared. RESULTS: Of the participants, 47 in the KP group and 49 in the TF group were enrolled. The mean and SD scores were 6.91±1.93 and 8.34±1.25 for patients' satisfaction and 7.55±1.54 and 8.65±1.00 for satisfaction of physicians performing the procedures in TF and KP groups, respectively (p=0.000). Moreover, 39 (79.59%) and 18 (38.29%) of patients declared that they had recalled the procedures in the TF and KP groups, respectively (p=0.000). Transient hypoxia was reported in 2.1% and 8.1% in the KP and TF groups leading to perform 4.2% vs 8.1% airway manoeuvres, respectively, without the need for endotracheal intubation or further admission. CONCLUSIONS: KP and TF combinations were effectively comparable although KP resulted in higher patient and provider satisfaction. This study did not detect a difference regarding adverse respiratory or haemodynamic effects. It is estimated that the TF combination can be potent and efficacious with possible low adverse events in procedural sedation.

Ketamine as an Anesthetic for Patients with Acute Brain Injury: A Systematic Review.

For years, the use of ketamine as an anesthetic to patients suffering from acute brain injury has been debated because of its possible deleterious effects on the cerebral circulation and thus on the cerebral perfusion. Early studies suggested that ketamine could increase the intracranial pressure thus lowering the cerebral perfusion and hence reduce the oxygen supply to the injured brain. However, more recent studies are less conclusive and might even indicate that patients with acute brain injury could benefit from ketamine sedation. This systematic review summarizes the evidence regarding the use of ketamine in patients suffering from traumatic brain injury. Databases were searched for studies using ketamine in acute brain injury. Outcomes of interest were mortality, intracranial pressure, cerebral perfusion pressure, blood pressure, heart rate, spreading depolarizations, and neurological function. In total 11 studies were included. The overall level of evidence concerning the use of ketamine in brain injury is low. Only two studies found a small increase in intracranial pressure, while two small studies found decreased levels of intracranial pressure following ketamine administration. We found no evidence of harm during ketamine use in patients suffering from acute brain injury.

Anaesthetic management for hiatal hernia repair in a child with Bartter's syndrome: A case report.

Bartter syndrome is a rare disorder characterized by reduced sodium chloride transport in the distal nephrons of the kidney. Its clinical features are renal salt wasting, hypokalemic metabolic alkalosis, elevated renin and aldosterone levels with normal or low blood pressure, polyuria, hypercalciuria and malnutrition. The pathophysiologic and biochemical changes in these patients should be kept in mind when considering anaesthetic management. This case report describes our management in a nineteen months old, 3.6 kg weight male child with Bartter's syndrome who underwent elective repair of hiatal hernia and gastrostomy.

Ketamine Sedation of the Pregnant Patient With Acute Suicidal Ideation During Air Medical Transfer.

Aeromedical retrieval of acutely suicidal pregnant patient can be facilitated by novel use of ketamine and it's rapid antidepressant property.

The Use of Ketamine for Air Medical Rapid Sequence Intubation Was Not Associated With a Decrease in Hypotension or Cardiopulmonary Arrest.

OBJECTIVE: Rapid sequence intubation (RSI) is associated with a number of complications that can increase morbidity and mortality. Among RSI agents used to blunt awareness of the procedure and produce amnesia, ketamine is unique in its classification as a dissociative agent rather than a central nervous system depressant. Thus, ketamine should have a lower risk of peri-RSI hypotension because of the minimal sympatholysis compared with other agents. Recent recommendations include the use of ketamine for RSI in hemodynamically unstable patients. The main goal of this analysis was to explore the incidence of hypotension and/or cardiopulmonary arrest in patients receiving ketamine, etomidate, midazolam, and fentanyl during air medical RSI. We hypothesized that ketamine would be associated with a lower risk of hemodynamic complications, particularly after adjusting for covariables reflecting patient acuity. In addition, we anticipated that an increased prevalence of ketamine use would be associated with a decreased incidence of peri-RSI hypotension and/or arrest. METHODS: This was a retrospective, observational study using a large air medical airway database. A waiver of informed consent was granted by our institutional review board. Descriptive statistics were used to present demographic and clinical data. The incidence rates of hypotension and cardiopulmonary arrest were calculated for each sedative/dissociative agent. Multivariable logistic regression was used to calculate the odds ratios of both hypotension and arrest for each of the sedative/dissociative agents. The prevalence of use for each agent and the incidence of hemodynamic complications (hypotension and arrest) were determined over time. RESULTS: A total of 7,466 RSI patients were included in this analysis. The use of ketamine increased over the duration of the study. Ketamine was associated with a higher incidence of both hypotension and arrest compared with other agents, even after adjustment for multiple covariables. The overall incidence of hypotension, desaturation, and cardiopulmonary arrest did not change over the study period. CONCLUSIONS: Although the incidence of hemodynamic complications was higher in patients receiving ketamine, this may reflect a selection bias toward more hemodynamically unstable patients in the ketamine cohort. The incidence of hypotension and arrest did not change over time despite an increase in the prevalence of ketamine use for air medical RSI. These data do not support a safer hemodynamic profile for ketamine.

Starting ketamine for neuroprotection earlier than its current use as an anesthetic/antiepileptic drug late in refractory status epilepticus.

Ketamine is currently being used as an anesthetic/antiepileptic drug in refractory status epilepticus. To validate its use, 2 clinical trials are recruiting patients. However, preclinical studies of its use in chemically induced status epilepticus in rodents have shown that it is remarkably neuroprotective, through N-methyl-d-aspartate-receptor blockade, even when given after the onset of status epilepticus. Human studies have shown that status epilepticus-induced brain damage can be caused by a glutamate analogue and that it occurs in the same brain regions as in the animal studies. We therefore propose that ketamine be started early in the course of human status epilepticus as a neuroprotectant and that it be continued until epileptic discharges are eliminated. Using it as an anesthetic/antiepileptic drug late in the course of refractory status epilepticus only ensures that it is given after widespread brain damage has occurred.

Effects of Anesthetic Ketamine on Anxiety-Like Behaviour in Rats.

There is scarce information regarding the effects of anesthetic doses of the non-competitive N-methyl-D-aspartate receptor antagonist ketamine on anxiety. The current study evaluated the acute effects of intraperitoneally (i.p.) administered anesthetic ketamine (100 mg/kg) i.p. on anxiety in rats. For this purpose, the light/dark and the open field tests were utilized. The effects of anesthetic ketamine on motility were also examined using a motility cage. In the light/dark test, anesthetic ketamine, administered 24 h before testing reduced the number of transitions between the light and dark compartments and the time spent in the light compartment in the rats compared with their control cohorts. In addition, ketamine was found to exert a depressive effect on rats' motility. In the open field test, animals treated with anesthetic ketamine 24 h before testing spent essentially no time in the central area of the apparatus, decreased horizontal ambulatory activity, and preserved to a certain extent their exploratory behaviour compared to their control counterparts. The results suggest that, in spite of its hypokinetic effect, a single anesthetic ketamine administration apparently induces an anxiety-like state, while largely preserving exploratory behaviour in the rat. These effects were time-dependent they since they were extinguished when testing was carried out 48 h after anesthetic ketamine administration.

Subanesthetic ketamine infusions for the management of pediatric pain in non-critical care settings: An observational analysis.

BACKGROUND: Guidelines issued by the American Society of Regional Anesthesia and Pain Medicine suggest that ketamine infusions for acute pain management are advantageous as a primary treatment or as an opioid adjunct. Despite significant data regarding its use in adult patients, there remains a paucity of information related to its quality and side effect profile in pediatrics and how it can be effectively used. We aimed to summarize our practice of utilizing ketamine for pediatric pain management in non-critical care settings. METHODS: Patients aged 0-21 years receiving low-dose ketamine infusions (≤0.3 mg/kg/hour) in inpatient care units over five years were retrospectively analyzed. Demographics, specific quality metrics, and side effects were quantified. RESULTS: About 172 patients received 270 subhypnotic ketamine infusions. The median duration of the infusions was 63.8 hours and 0.2 mg/kg/hour for the highest dose. The primary indication for ketamine was chronic pain exacerbation (83.3%). Despite similar opioid consumption, there was a significant reduction in mean verbal pain scores before (8.9 ± 1.9, P < .001) and after ketamine (6.5 ± 2.7, P < .001) use. Although there were 52 incidences of some side effect (neurologic excitability [10.4%]; over-sedation [7.4%]; rapid response team alerts [1.1%]), none resulted in termination of the infusion or escalations in care. CONCLUSION: Ketamine can effectively be used as part of a multimodal analgesic regimen in pediatric patients in non-critical care settings. Our five-year experience using low-dose ketamine infusions highlights an acceptable side effect profile, with no attributable escalations in care or serious adverse events.