Hemodynamic and mortality effects of continuous ketamine infusion in critically ill pediatric patients. A retrospective cohort in a tertiary pediatric intensive care unit (PICU) from 2015 to 2017.

Background: There is a compelling evidence from animal models that early exposure to clinically relevant general anesthetics (GAs) interferes with brain development, resulting in long-lasting cognitive impairments. Human studies have been inconclusive and are challenging due to numerous confounding factors. Here, we employed primary human neural cells to analyze ketamine neurotoxic effects focusing on the role of glial cells and their activation state. We also explored the roles of astrocyte-derived extracellular vesicles (EVs) and different components of the brain-derived neurotrophic factor (BDNF) pathway.Methods: Ketamine effects on cell death were analyzed using live/dead assay, caspase 3 activity and PARP-1 cleavage. Astrocytic and microglial cell differentiation was determined using RT-PCR, ELISA and phagocytosis assay. The impact of the neuron-glial cell interactions in the neurotoxic effects of ketamine was analyzed using transwell cultures. In addition, the role of isolated and secreted EVs in this cross-talk were studied. The expression and function of different components of the BDNF pathway were analyzed using ELISA, RT-PCR and gene silencing.Results: Ketamine induced neuronal and oligodendrocytic cell apoptosis and promoted pro-inflammatory astrocyte (A1) and microglia (M1) phenotypes. Astrocytes and microglia enhanced the neurotoxic effects of ketamine on neuronal cells, whereas neurons increased oligodendrocyte cell death. Ketamine modulated different components in the BDNF pathway: decreasing BDNF secretion in neurons and astrocytes while increasing the expression of p75 in neurons and that of BDNF-AS and pro-BDNF secretion in both neurons and astrocytes. We demonstrated an important role of EVs secreted by ketamine-treated astrocytes in neuronal cell death and a role for EV-associated BDNF-AS in this effect.Conclusions: Ketamine exerted a neurotoxic effect on neural cells by impacting both neuronal and non-neuronal cells. The BDNF pathway and astrocyte-derived EVs represent important mediators of ketamine effects. These results contribute to a better understanding of ketamine neurotoxic effects in humans and to the development of potential approaches to decrease its neurodevelopmental impact.

ObjectiveA simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and without airway management. However, there are important pitfalls to be avoided by special precautions and monitoring, as shown subsequently.Study designObservational study.AnimalsTwenty-four anaesthetic procedures for bile duct ligation, sham operation or carotid artery dilatation in 20 male Sprague-Dawley rats, preoperatively weighing between 440 and 550 g.MethodsIntolerable high mortality rates occurred in the first 7 postoperative days while establishing a new experimental model in rats using ketamine-xylazine anaesthesia. Rats were spontaneously breathing ambient air during the first 12 surgeries without airway management. An observed high mortality rate in these animals led to a change in the trial protocol: the insufflation of 2 litres of oxygen per minute via nose cone during the following 12 rat surgeries. Retrospective comparison of the outcome (without oxygen vs. with oxygen insufflation) was conducted.ResultsThe perioperative mortality rate could be significantly reduced from 58% (7/12) to 17% (2/12) (p = 0.036) by oxygen insufflation via nose cone. Significantly different levels of intraoperative oxygen saturation (SpO2; 89 ± 4% [without oxygen] vs. 97 ± 0.5% [with oxygen], p < 0.0001), but no significant differences in heart rate (HR; 267 ± 7 beats minute–1 [bpm] [without oxygen] vs. 266 ± 6 bpm [with oxygen], p = 0.955) were observed.Conclusions and clinical relevanceIn summary, rats under ketamine-xylazine anaesthesia are susceptible to hypoxia. This may lead to increased delayed mortality related to hypoxia induced lung failure. Apparently, this is an underestimated problem. We highly recommend using additional oxygen insufflation in spontaneously breathing rats under ketamine-xylazine anaesthesia with basic monitoring such as measurement of oxygen saturation.

Hemorrhage is a leading cause of preventable battlefield and civilian trauma deaths. Ketamine, fentanyl, and morphine are recommended analgesics for use in the prehospital (i.e., field) setting to reduce pain. However, it is unknown whether any of these analgesics reduce hemorrhagic tolerance in humans. We tested the hypothesis that fentanyl (75 µg) and morphine (5 mg), but not ketamine (20 mg), would reduce tolerance to simulated hemorrhage in conscious humans. Each of the three analgesics was evaluated independently among different cohorts of healthy adults in a randomized, crossover (within drug/placebo comparison), placebo-controlled fashion using doses derived from the Tactical Combat Casualty Care Guidelines for Medical Personnel. One minute after an intravenous infusion of the analgesic or placebo (saline), we employed a pre-syncopal limited progressive lower-body negative pressure (LBNP) protocol to determine hemorrhagic tolerance. Hemorrhagic tolerance was quantified as a cumulative stress index (CSI), which is the sum of products of the LBNP and the duration (e.g., [40 mmHg x 3 min] + [50 mmHg x 3 min] …). Compared with ketamine (p = 0.002 post hoc result) and fentanyl (p = 0.02 post hoc result), morphine reduced the CSI (ketamine (n = 30): 99 [73–139], fentanyl (n = 28): 95 [68–130], morphine (n = 30): 62 [35–85]; values expressed as a % of the respective placebo trial’s CSI; median [IQR]; Kruskal-Wallis test p = 0.002). Morphine-induced reductions in tolerance to central hypovolemia were not well explained by a prediction model including biological sex, body mass, and age (R2=0.05, p = 0.74). These experimental data demonstrate that morphine reduces tolerance to simulated hemorrhage while fentanyl and ketamine do not affect tolerance. Thus, these laboratory-based data, captured via simulated hemorrhage, suggest that morphine should not be used for a hemorrhaging individual in the prehospital setting.

In Germany, the illegal drugs with the highest street value were cocaine and heroin, with the former costing around **** euros per gram or consumption unit, and the latter **** euros in 2023. Ecstasy had the lowest price at *** euros per gram. Illegal drugs There is debate worldwide about whether drugs should be legal or not. Some experts say that legalizing drugs will help those who are addicted as they will not be forced to buy drugs on the black market where they are often mixed with other substances, making them extremely dangerous and often even lethal. However, others feel that keeping certain drugs illegal dissuades people from trying them. Different nations also have different approaches when it comes to which drugs are made legal and which are not. In Germany, drugs such as cocaine, heroin, crystal meth, ecstasy, and cannabis are all illegal. The German government is going through the process of legalizing cannabis. However, this is proving to be a long and complex undertaking. Illegal drug use in Germany Illegal drug use and abuse are prevalent all over the world, and Germany is no different. In 2023, there were over ***** drug-related deaths in Germany. The most common cause of death related to drugs was damage caused by long-term drug use. Other causes included mixes of various drugs causing an overdose. The average age of people who had drug-related deaths in Germany was ** years old, which is almost half the average life expectancy in Germany. This is not surprising, considering the physical toll that prolonged drug use can take on the body, and the risks of accidentally taking drugs that are contaminated or even laced with other even stronger substances when buying on the black market.

Objective Ketamine, as a sedative, has been administered during mechanical ventilation in critically ill patients; however, its impact on survival outcomes in this patient population remains uncertain. Methods This retrospective cohort study extracted data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, version 3.0. Patients were categorized into the ketamine group and the control group based on whether ketamine was administered during mechanical ventilation. Propensity score matching was performed to adjust for demographic variables and coexisting conditions. The primary outcome was 28-day mortality. Secondary outcomes included 14-day and 90-day mortality rates, as well as hospital and ICU lengths of stay. Results The study included a total of 8569 patients, with 330 in the ketamine group and 8239 in the control group. After propensity score matching, significant differences in mechanical ventilation duration and the proportion of patients with acute respiratory distress syndrome remained between groups. No significant differences were observed in 28-day and 90-day mortality rates between the groups. Subgroup analysis indicated that ketamine was associated with lower 14-day mortality rates among younger patients, those with acute respiratory distress syndrome, and norepinephrine users. Ketamine administration was also found to correlate with increased lengths of stay in both the hospital and ICU. Conclusions Ketamine was more frequently selected for patients requiring prolonged mechanical ventilation. The administration of ketamine was associated with reduced 14-day but not with 28-day or 90-day mortality rates.

Overview of the number of rats and the number of interventions included in the two study groups.

Rabbits have a high anesthesia-related mortality rate because of their small size, high metabolic rate and challenging airway management. This study aimed to investigate different combinations of intramuscularly administered anesthetics in New Zealand White rabbits, focusing on their effects on anesthetic depth, physiological parameters, and electroencephalogram (EEG) recordings. Defined doses ketamine (K), esketamine (SK), medetomidine (M), dexmedetomidine (D), midazolam (Mi), and butorphanol (B) were investigated and compared in five different combinations: KM (25/0.25 mg/kg), SKM (17/0.25 mg/kg), SKD (17/0.15 mg/kg), MMiB (0.25/1/0.2 mg/kg), and DMiB (0.15/1/0.2 mg/kg). For 60 minutes, the anesthetic depth was assessed using an anesthesia score, and physiological parameters, including heart rate (HR), respiratory rate (RR), oxygen saturation and blood pressure were recorded. The study also assessed the latencies to loss and recovery of reflexes after targeted antagonization, and EEGs were measured. The rabbits were not intubated and were supplied with oxygenated air via nasal probes. All anesthetic combinations achieved anesthesia with surgical tolerance, with significant intergroup differences in HR, RR, blood pressure and EEG power spectra. The KM group demonstrated the most stable anesthesia and rapid recovery, while SKD and SKM groups showed prolonged recovery times. Oxygen saturation remained consistently high across all groups, obviating the need for intubation. All rabbits recovered fully after anesthesia. In conclusion, intramuscular administered anesthetic combinations can provide effective anesthesia with surgical tolerance for short procedures in rabbits. Monitoring circulatory parameters during and after anesthesia and adequate pain management pre-, inter-, and postoperatively are essential. Considering these criteria, the KM group presented the best results compared with the other groups.