Nebulized and intraperitoneal ketamine have equivalent antidepressant-like effect in the forced swim and tail suspension tests in mice.

Major depressive disorder (MDD) is a debilitating illness that affects millions of people worldwide. Currently available antidepressants often take weeks to months to reach their full effect, which leads to an increased risk of suicidal behavior in patients with MMD. Intranasally, esketamine has emerged as an alternative to current antidepressants because of its rapid onset and long-lasting effects in patients with MDD. Animal models are useful for the initial pharmacological screening and for a better understanding of the mechanisms underlying the effects of new drugs with potential against MDD. There is a lack of data on alternative routes of drug administration, either oral or injectable, that can be used in preclinical studies. This study aimed to test whether ketamine has antidepressant-like effects in mice when administered via nebulization using a low-cost apparatus. When mice whose depressive-like behavior was induced by corticosterone were treated with nebulized ketamine at concentrations of 1.3, 2.6, and 5.2 mg/mL, immobility was reduced by 38.6 %, 62.0 %, and 61.1 %, respectively, in the forced swimming test (FST) and 43.6 %, 42.1 %, and 57.9 %, respectively, in the tail suspension test (TST). When depression-like behavior was induced by dexamethasone, nebulization with ketamine reduced immobility by 79.7 %, 49.2 %, and 44.4 % in the FST and 80.9 %, 71.4 %, and 80.4 %, respectively, in the TST. When depression-like behavior was induced by the association between dexamethasone and unpredictable chronic mild stress (UCMS) exposure, immobility was reduced by 26.1 %, 55.3 %, and 19.1 % in FST. Mice treated with nebulized ketamine did not show significant changes in the distance covered or in the time spent moving in the open field test. The efficacy of intraperitoneal and nebulized ketamine is equivalent, which shows that nebulization can be an alternative inexpensive route of drug administration for behavioral studies in rodents.

[Preemptive nebulized ketamine for pain control after tonsillectomy in children: randomized controlled trial]. / Uso preventivo de cetamina nebulizada para controle da dor após amigdalectomia em crianças: estudo randômico e controlado.

OBJECTIVES: The administration of ketamine as nebulized inhalation is relatively new and studies on nebulized ketamine are scarce. We aimed to investigate the analgesic efficacy of nebulized ketamine (1 and 2mg.kg-1) administered 30min before general anesthesia in children undergoing elective tonsillectomy in comparison with intravenous ketamine (0.5mg.kg-1) and saline placebo. METHODS: One hundred children aged (7-12) years were randomly allocated in four groups (n=25) receive; Saline Placebo (Group C), Intravenous Ketamine 0.5mg.kg-1 (Group K-IV), Nebulized Ketamine 1mg.kg-1 (Group K-N1) or 2mg.kg-1 (Group K-N2). The primary endpoint was the total consumption of rescue analgesics in the first 24h postoperative. RESULTS: The mean time to first request for rescue analgesics was prolonged in K-N1 (400.9±60.5min, 95% CI 375.9-425.87) and K-N2 (455.5±44.6min, 95% CI 437.1-473.9) groups compared with Group K-IV (318.5±86.1min, 95% CI 282.9-354.1) and Group C (68.3±21.9min, 95% CI 59.5-77.1; p<0.001), with a significant difference between K-N1 and K-N2 Groups (p<0.001). The total consumption of IV paracetamol in the first 24h postoperative was reduced in Group K-IV (672.6±272.8mg, 95% CI 559.9-785.2), Group K-N1 (715.6±103.2mg, 95% CI 590.4-840.8) and Group K-N2 (696.6±133.3mg, 95% CI 558.8-834.4) compared with Control Group (1153.8±312.4mg, 95% CI 1024.8-1282.8; p<0.001). With no difference between intravenous and Nebulized Ketamine Groups (p=0.312). Patients in intravenous and Nebulized Ketamine Groups showed lower postoperative VRS scores compared with Group C (p<0.001), no differences between K-IV, K-N1 or K-N2 group and without significant adverse effects. CONCLUSION: Preemptive nebulized ketamine was effective for post-tonsillectomy pain relief. It can be considered as an effective alternative route to IV ketamine.

Preemptive nebulized ketamine for pain control after tonsillectomy in children: randomized controlled trial / Uso preventivo de cetamina nebulizada para controle da dor após amigdalectomia em crianças: estudo randômico e controlado

Abstract Objectives The administration of ketamine as nebulized inhalation is relatively new and studies on nebulized ketamine are scarce. We aimed to investigate the analgesic efficacy of nebulized ketamine (1 and 2 mg.kg-1) administered 30 min before general anesthesia in children undergoing elective tonsillectomy in comparison with intravenous ketamine (0.5 mg.kg-1) and saline placebo. Methods One hundred children aged (7-12) years were randomly allocated in four groups (n = 25) receive; Saline Placebo (Group C), Intravenous Ketamine 0.5 mg.kg-1 (Group K-IV), Nebulized Ketamine 1 mg.kg-1 (Group K-N1) or 2 mg.kg-1 (Group K-N2). The primary endpoint was the total consumption of rescue analgesics in the first 24 h postoperative. Results The mean time to first request for rescue analgesics was prolonged in K-N1 (400.9 ± 60.5 min, 95% CI 375.9-425.87) and K-N2 (455.5 ± 44.6 min, 95% CI 437.1-473.9) groups compared with Group K-IV (318.5 ± 86.1 min, 95% CI 282.9-354.1) and Group C (68.3 ± 21.9 min, 95% CI 59.5-77.1; p < 0.001), with a significant difference between K-N1 and K-N2 Groups (p < 0.001). The total consumption of IV paracetamol in the first 24 h postoperative was reduced in Group K-IV (672.6 ± 272.8 mg, 95% CI 559.9-785.2), Group K-N1 (715.6 ± 103.2 mg, 95% CI 590.4-840.8) and Group K-N2 (696.6 ± 133.3 mg, 95% CI 558.8-834.4) compared with Control Group (1153.8 ± 312.4 mg, 95% CI 1024.8-1282.8; p < 0.001). With no difference between intravenous and Nebulized Ketamine Groups (p = 0.312). Patients in intravenous and Nebulized Ketamine Groups showed lower postoperative VRS scores compared with Group C (p < 0.001), no differences between K-IV, K-N1 or K-N2 group and without significant adverse effects. Conclusion Preemptive nebulized ketamine was effective for post-tonsillectomy pain relief. It can be considered as an effective alternative route to IV ketamine.

Resumo Objetivos A administração de cetamina por via inalatória através de nebulizador é relativamente nova e os estudos sobre este assunto são escassos. Nosso objetivo foi investigar a eficácia analgésica da cetamina nebulizada (1 e 2 mg.kg-1) administrada 30 minutos antes da anestesia geral em crianças submetidas à amigdalectomia eletiva, em comparação com cetamina intravenosa (0,5 mg.kg-1) e placebo (soro fisiológico). Métodos Cem crianças entre 7-12 anos foram randomicamente alocadas em quatro grupos (n = 25) e receberam: soro fisiológico para controle (Grupo C); 0,5 mg.kg-1 de cetamina intravenosa (Grupo C-IV); 1 mg.kg-1 de cetamina nebulizada (Grupo C-N1); 2 mg.kg-1 de cetamina nebulizada (Grupo C-N2). O desfecho primário foi o consumo total de analgésicos de resgate nas primeiras 24 horas de pós-operatório. Resultados O tempo médio para a primeira solicitação de analgésicos de resgate foi prolongado nos grupos C-N1 (400,9 ± 60,5 min, IC 95% 375,9-425,87) e C-N2 (455,5 ± 44,6 min, IC 95% 437,1-473,9) em comparação com o Grupo C-IV (318,5 ± 86,1 min, IC 95% 282,9-354,1) e o Grupo C (68,3 ± 21,9 min, IC 95% 59,5-77,1; p < 0,001), com uma diferença significativa entre os grupos C-N1 e C-N2 (p < 0,001). O consumo total de paracetamol IV nas primeiras 24 horas de pós-operatório foi reduzido no Grupo C-IV (672,6 ± 272,8 mg, IC 95% 559,9-785,2), Grupo C-N1 (715,6 ± 103,2 mg, IC 95% 590,4-840,8) e Grupo C-N2 (696,6 ± 133,3 mg, IC 95% 558,8-834,4) em comparação com o Grupo C (1153,8 ± 312,4 mg, IC 95% 1024,8-1282,8; p < 0,001). Não houve diferença entre os grupos de cetamina intravenosa e nebulizada (p = 0,312). Os pacientes dos grupos de cetamina intravenosa e nebulizada apresentaram escores VRS pós-operatórios menores, em comparação com o Grupo C (p < 0,001), sem diferenças entre os grupos C-IV, C-N1 ou C-N2 e sem efeitos adversos significativos. Conclusão A administração preventiva de cetamina nebulizada foi eficaz no alívio da dor pós-amigdalectomia. Cetamina nebulizada pode ser considerada como uma via alternativa eficaz à cetamina IV.