Novel uses of ketamine in the emergency department.

INTRODUCTION: Ketamine is gaining renewed interest among healthcare providers in the emergency department (ED) setting due to its novel clinical applications. AREAS COVERED: This article provides a comprehensive discussion of ketamine's pharmacological properties, safety profile, and an overview of current evidence for ketamine in the management of ED patients with acute agitation, pain, depression/suicide ideation. EXPERT OPINION: Ketamine is an effective adjunct to opioids, providing greater pain relief than morphine alone. Ketamine (0.1-0.3 mg/kg IV) alone can provide analgesia similar to that of morphine in patients with acute visceral and musculoskeletal pain, as well as for chronic painful conditions (cancer, vaso-occlusive pain crisis associated with sickle cell disease, and in patients with high opioid tolerance and/or opioid dependency). Available literature shows that ketamine (1-2 mg/kg IV or 4-5 mg/kg IM) is a safe, rapid (<5 minutes) and effective tranquilization agent for ED patients with acute agitation. Finally, there is growing evidence that suggests ketamine may have potential utility in the management of patients with self-harm ideation or acute depressive episodes. Intravenous infusion of ketamine (0.5 mg/kg over 40 mins) has been shown to produce an antidepressant effect and decrease in suicidal ideation within 4 hours with effects lasting up to one week.

Rapid tranquilization of the agitated patient in the emergency department: A systematic review and network meta-analysis.

BACKGROUND: Safe and effective tranquilization of the acutely agitated patient is challenging, and head-to-head comparisons of medications are limited. We aimed to identify the most optimal agent(s) for rapid tranquilization of the severely agitated patient in the emergency department (ED). METHODS: The protocol for systematic review was registered (PROSPERO; CRD42020212534). We searched MEDLINE, Embase, PsycINFO, and Cochrane Database/CENTRAL from inception to June 2, 2021. We limited studies to randomized controlled trials that enrolled adult ED patients with severe agitation and compared drugs for rapid tranquilization. Predetermined outcomes were: 1) Adequate sedation within 30 min (effectiveness), 2) Immediate, serious adverse event - cardiac arrest, ventricular tachydysrhythmia, endotracheal intubation, laryngospasm, hypoxemia, hypotension (safety), and 3) Time to adequate sedation (effect onset). We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2 tool. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effects model and vague prior distribution to calculate odds ratios with 95% credible intervals for dichotomous outcomes and frequentist NMA to calculate mean differences with 95% confidence intervals for continuous outcomes. We assessed confidence in results using CINeMA. We used surface under the cumulative ranking (SUCRA) curves to rank agent(s) for each outcome. RESULTS: Eleven studies provided data for effectiveness (1142 patients) and safety (1147 patients). Data was insufficient for effect onset. The NMA found that ketamine (SUCRA = 93.0%) is most likely to have superior effectiveness; droperidol-midazolam (SUCRA = 78.8%) is most likely to be safest. There are concerns with study quality and imprecision. Quality of the point estimates varied for effectiveness but mostly rated "very low" for safety. CONCLUSIONS: Available evidence suggests that ketamine and droperidol have intermediate effectiveness for rapid tranquilization of the severely agitated patient in the ED. There is insufficient evidence to definitively determine which agent(s) may be safest or fastest-acting. Further, direct-comparison study of ketamine and droperidol is recommended.

Kinematic Patterns in Horses Sedated With Low Doses of Detomidine: An Accelerometric Evaluation.

Alpha-2-adrenergic drugs, such as detomidine, are commonly used to sedate lame horses during examination. However, the use of these drugs should be minimized, as they have numerous side-effects, like ataxia. Therefore, we wanted to test the effects, on the locomotor pattern, of low doses of detomidine (0.003 mg/kg). Six horses were sedated with 0.003 mg/kg of detomidine and compared with the same horses administered a saline solution. Using a triaxial accelerometer, data of kinetic, coordination and energetic locomotor parameters and the degree of sedation were collected. The effects were monitored for 60 minutes after treatment administration. No effects on coordination parameters were observed, but some kinetic and energetic parameters were significantly altered after detomidine administration compared to the saline group. These results show that administering low doses of detomidine to lame horses can be a useful sedative solution, ensuring a safe examination with lower side-effects.

Sedative effects of acepromazine in combination with nalbuphine or butorphanol, intramuscularly or intravenously, in healthy cats: a randomized, blinded clinical trial.

OBJECTIVES: The aim of this study was to compare the sedative effects in cats administered acepromazine-nalbuphine and acepromazine-butorphanol, intramuscularly (IM) and intravenously (IV), and the occurrence of adverse cardiorespiratory effects. METHODS: Forty-six cats were randomly divided into four groups and administered acepromazine (0.05 mg/kg) combined with nalbuphine (0.5 mg/kg) or butorphanol (0.4 mg/kg), IV (ACP-NALIV and ACP-BUTIV groups, respectively) or IM (ACP-NALIM and ACP-BUTIM groups, respectively). Sedation scores, ease of intravenous catheter placement (simple descriptive scale [SDS] scores), physiologic variables, venous blood gases and the propofol dose required for anesthetic induction were recorded. RESULTS: Mild sedation was observed in all groups approximately 30 mins after treatment administration (timepoint T1, prior to propofol administration). Sedation scores at T1 increased above baseline in all groups (P <0.05), but no significant difference was observed among groups. Dynamic interactive visual analogue scale sedation scores (range 0-100 mm) recorded at T1 were (median [interquartile range]): ACP-NALIM, 12 (10-12); ACP-NALIV, 11 (6-16); ACP-BUTIM, 11 (7-14); and ACP-BUTIV, 12 (7-19). Overall, SDS scores did not change from baseline at T1 and there was no significant difference among groups. The propofol dose did not differ among groups. Blood gases remained within the reference intervals for cats. Significant decreases from baseline were detected for all groups in systolic arterial pressure (SAP). Mean ± SD values at T1 were (mmHg): ACP-NALIM, 108 ± 13; ACP-NALIV, 102 ± 10; ACP-BUTIM, 97 ± 13; and ACP-BUTIV, 98 ± 21. Arterial hypotension (SAP <90 mmHg) was recorded at T1 in 0/11, 1/13, 4/11 and 5/11 cats in groups ACP-NALIM, ACP-NALIV, ACP-BUTIM and ACP-BUTIV, respectively, and was further exacerbated after the induction of anesthesia with propofol. CONCLUSIONS AND RELEVANCE: In healthy cats administered acepromazine-nalbuphine and acepromazine-butorphanol, IM and IV, the degree of sedation was mild regardless of the protocol and the route of administration. The main adverse effect observed was a reduction in arterial blood pressure.

Safety and efficacy of pharmacologic agents used for rapid tranquilization of emergency department patients with acute agitation or excited delirium.

Introduction: Management of patients with acute agitation or aggressive behavior can pose a significant challenge to health-care providers in emergency departments. Areas covered: This article provides a comprehensive review of the pharmacologic properties, efficacy, and safety profiles of select intramuscular (IM) sedative agents (i.e., antipsychotics, benzodiazepines, and ketamine) for rapid tranquilization. Expert opinion: Using antipsychotics and benzodiazepines - whether a single agent or combined - will have similar efficacy in producing sedation. But there are differences in the time to sedation depending on which agent is used. Based upon the available studies, droperidol (5-10 mg IM) and midazolam (5-10 mg IM) have the fastest onset of sedation when either is used as a single agent. When combination therapy is used, using midazolam with an antipsychotic agent, instead of lorazepam, may result in faster sedative effect. QT prolongation and torsades de pointes are uncommon adverse drug effects of antipsychotic administration. Ketamine is often reserved as a second-line agent when antipsychotics and benzodiazepines fail to produce the desired tranquilization. However, ketamine (5 mg/kg IM) is more frequently associated with airway compromise requiring endotracheal intubation. A low-dose of ketamine (2 mg/kg IM) may reduce the risk of airway compromise while providing adequate sedation.

Efeitos cardiovasculares da medetomidina e cetamina em Puma concolor e tempo de recuperação após aplicação de ioimbina ou atipamezole / [Cardiovascular effects of medetomidine and cetamine in Puma concolor and recovery time after application of ioimbin or atipamezole]

O objetivo deste estudo foi avaliar as alterações cardiorrespiratórias causadas pela medetomidina associada à cetamina, e o tempo de recuperação após aplicação intramuscular de atipamezole ou ioimbina em Puma concolor. Para isso, foi realizada a aplicação de medetomidina (100µg/kg) associada à cetamina (5mg/kg) em 11 onças-pardas, sendo os parâmetros cardiorrespiratórios registrados a cada 15 minutos, durante 90 minutos de avaliação. Em seguida, a anestesia foi revertida com aplicação intramuscular de ioimbina (0,4mg/kg; n=5) ou atipamezole (0,25mg/kg; n=6), sendo analisado o tempo até a recuperação. Dos parâmetros cardiorrespiratórios avaliados, houve diferença apenas na frequência respiratória (entre os momentos 60 e 90 minutos), estando esta, todavia, dentro do intervalo de referência para a espécie. Além disso, verificou-se tempo para decúbito esternal significativamente menor nos animais do grupo atipamezole (18±7 minutos), quando comparado ao grupo ioimbina (36±17 minutos), entretanto o tempo de recuperação completa foi estatisticamente igual entre os dois reversores analisados. Assim, a associação anestésica promoveu anestesia eficiente, segura e de rápida indução em onças-pardas, permitindo a imobilização dos animais durante os 90 minutos de avaliação, sem a ocorrência de complicações. Ao se comparar a reversão anestésica com atipamezole e ioimbina, observou-se equivalência dos fármacos no tempo de recuperação completa dos animais.(AU)

The aim of this study was to evaluate the cardiorespiratory changes caused by ketamine-associated medetomidine, and the recovery time after intramuscular application of atipamezole or yohimbine in Puma concolor. For this, the application of medetomidine (100µg/kg) associated with ketamine (5mg/kg) was performed in eleven brown ounces, and the cardiorespiratory parameters were recorded every 15 minutes during 90 minutes of evaluation. Afterwards, anesthesia was reversed with intramuscular application of yohimbine (0.4mg/kg; n=5) or atipamezole (0.25mg/kg; n=6), and time to recovery was analyzed. Of the cardiorespiratory parameters evaluated, there was a difference only in respiratory rate (between 60 and 90 minutes), however, within the reference range for the species. In addition, there was a significantly shorter time for sternal decubitus in the animals of the atipamezole group (18±7 minutes) when compared to the yohimbine group (36±17 minutes), however the complete recovery time was statistically equal between the two reversers analyzed. Thus, the anesthetic association promoted efficient, safe and fast induction anesthesia in puma, allowing the animals to be immobilized during the 90 minutes of evaluation without complications. Comparing anesthetic reversal with atipamezole and yohimbine, drug equivalence was observed in the complete recovery time of the animals.(AU)

Hemodynamic, respiratory and sedative effects of progressively increasing doses of acepromazine in conscious dogs.

OBJECTIVE: To evaluate the effects of progressively increasing doses of acepromazine on cardiopulmonary variables and sedation in conscious dogs. STUDY DESIGN: Prospective, experimental study. ANIMALS: A group of six healthy, adult, mixed-breed dogs weighing 16.5 ± 5.0 kg (mean ± standard deviation). METHODS: Dogs were instrumented with thermodilution and arterial catheters for evaluation of hemodynamics and arterial blood gases. On a single occasion, acepromazine was administered intravenously to each dog at 10, 15, 25 and 50 µg kg-1 at 20 minute intervals, resulting in cumulative acepromazine doses of 10 µg kg-1 (ACP10), 25 µg kg-1 (ACP25), 50 µg kg-1 (ACP50) and 100 µg kg-1 (ACP100). Hemodynamic data and sedation scores were recorded before (baseline) and 20 minutes after each acepromazine dose. RESULTS: Compared with baseline, all acepromazine doses significantly decreased stroke index (SI), mean arterial pressure (MAP) and arterial oxygen content (CaO2) with maximum decreases of 16%, 17% and 21%, respectively. Cardiac index (CI) decreased by up to 19% but not significantly. Decreases of 26-38% were recorded for oxygen delivery index (DO2I), with significant differences for ACP50 and ACP100. Systemic vascular resistance index (SVRI) and heart rate did not change significantly. No significant difference was found among acepromazine doses for hemodynamic data. After ACP10, mild sedation was observed in five/six dogs and moderate sedation in one/six dogs, whereas after ACP25, ACP50 and ACP100, moderate sedation was observed in five/six or six/six dogs. CONCLUSIONS AND CLINICAL RELEVANCE: In conscious dogs, acepromazine decreased MAP, SI, CaO2 and DO2I, but no significant dose effect was detected. SVRI was not significantly changed, suggesting that the reduction in MAP resulted from decreased CI. The ACP25, ACP50 and ACP100 doses resulted in moderate sedation in most dogs; ACP10 resulted in only mild sedation.

Tranquilizer effect on the Lyapunov exponents of lame horses.

Tranquilization of horses with acepromazine has been used to suppress erratic head movements and increase the accuracy of a lameness examination. Some equine clinicians believe that tranquilization with acepromazine will make lameness more evident by causing the horse to focus on adjusting its gait to avoid limb pain rather than its surroundings. The aim of this study was to investigate the effect of acepromazine on the Lyapunov exponents of lame horses. Ten lame horses were trotted in a straight line for a minimum of 25 strides. Kinematic data created by head movement were analyzed. Nonlinear analysis methods were applied to lame horse locomotion. The effect of acepromazine on the largest Lyapunov exponents of the lame horses were investigated. There was no statistically significant effect of acepromazine on the maximum value of Lyapunov exponents. The nonlinear dynamic methods can be used to analyze the gait in horses. Local stability of horse gait remains unchanged after the administration of acepromazine.

[Pathophysiology of aggressive behavior: evaluation and management of pathological aggression].

This work aims to define the aggression in all its forms, with notes on management and rapid tranquilization. The pathological aggression is described as a non-homogeneous phenomenon, it is variable in according to social, psychological and biological agents. The distinction of violence between affective aggression and predatory aggression can be functional to the prediction of outcome of any treatment. In general, a pattern of predatory violence tend to match with patients unresponsive and not compliant to treatment, a low probability to predict future violence and, therefore, a difficulty in managing risk. The affective aggressor, however, shows increased probability of treatment response, with more predictability of violent actions in reaction to situations perceived as threatening and, therefore, greater management of future violence risk. Those who act affective violence tend to show a wide range of emotional and cognitive problems, while those who act with predatory patterns show greater inclination to aggression and antisocial behavior. Aggression that occurs in psychiatry mostly appears to be affective, therefore susceptible to modulation through treatments.

Issues in the management of acute agitation: how much current guidelines consider safety?

Agitated behavior constitutes up to 10% of emergency psychiatric interventions. Pharmacological tranquilization is often used as a valid treatment for agitation but a strong evidence base does not underpin it. Available literature shows different recommendations, supported by research data, theoretical considerations, or clinical experience. Rapid tranquilization (RT) is mainly based on parenteral drug treatment and the few existing guidelines on this topic, when suggesting the use of first generation antipsychotics and benzodiazepines, include drugs with questionable tolerability profile such as chlorpromazine, haloperidol, midazolam, and lorazepam. In order to systematically evaluate safety concerns related to the adoption of such guidelines, we reviewed them independently from principal diagnosis while examining tolerability data for suggested treatments. There is a growing evidence about safety profile of second generation antipsychotics for RT but further controlled studies providing definitive data in this area are urgently needed.