[A Case of Esophageal Cancer with Consciousness Disorder Due to Hyperammonemia during FP Treatment].

Hyperammonemia induced by 5-fluorouracil(5-FU)is known as a rare adverse event, but there are few reports of hyperammonemia occurring during FP(5-FU plus CDDP)treatment for esophageal cancer. We report a case of esophageal cancer with consciousness disorder due to hyperammonemia during FP treatment with an examination of some of the relevant literature. The patient was a man of approximately 70 years of age who was received FP treatment. He showed consciousness disorder on day 4. A blood test showed hyperammonemia(427µg/dL), which was considered to be the cause of his consciousness disorder. He was treated with branched chain amino acid infusion, lactulose and kanamycin and made a full recovery. An operation for esophageal cancer was performed after 3 months and he is currently followed up without recurrence. Hyperammonemia should be considered as a differential diagnosis of consciousness disorder during chemotherapy including 5-FU.

[A case of meningoencephalitis associated with pembrolizumab treated for squamous cell lung cancer].

A 61-year-old man with squamous cell lung cancer was admitted to our hospital because of consciousness disturbance after treated with pembrolizumab. Cerebrospinal fluid examination revealed increased protein level (209.2 mg/dl) and lymphocytic pleocytosis(79/µl). He was diagnosed as a meningoencephalitis probably caused by an immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs), and was successfully treated with 1,000 mg methylprednisolone intravenously for 3 days twice and the consequent oral 1 mg/kg prednisolone. As ICIs, which activate the immune systems, are becoming important choices of the treatments against malignancies, we should keep the possibility of irAE in mind and, when needed, start the treatment as soon as possible.

Cellular stress and AMPK links metformin and diverse compounds with accelerated emergence from anesthesia and potential recovery from disorders of consciousness.

The neural correlates of consciousness and the mechanisms by which general anesthesia (GA) modulate such correlates to induce loss of consciousness (LOC) has been described as one of the biggest mysteries of modern medicine. Several cellular targets and neural circuits have been identified that play a critical role in LOC induced by GA, including the GABAA receptor and ascending arousal nuclei located in the basal forebrain, hypothalamus, and brain stem. General anesthetics (GAs) including propofol and inhalational agents induce LOC in part by potentiating chloride influx through the GABAA receptor, leading to neural inhibition and LOC. Interestingly, nearly all GAs used clinically may also induce paradoxical excitation, a phenomenon in which GAs promote neuronal excitation at low doses before inducing unconsciousness. Additionally, emergence from GA, a passive process that occurs after anesthetic removal, is associated with lower anesthetic concentrations in the brain compared to doses associated with induction of GA. AMPK, an evolutionarily conserved kinase activated by cellular stress (e.g. increases in calcium [Ca2+] and/or reactive oxygen species [ROS], etc.) increases lifespan and healthspan in several model organisms. AMPK is located throughout the mammalian brain, including in neurons of the thalamus, hypothalamus, and striatum as well as in pyramidal neurons in the hippocampus and cortex. Increases in ROS and Ca2+ play critical roles in neuronal excitation and glutamate, the primary excitatory neurotransmitter in the human brain, activates AMPK in cortical neurons. Nearly every neurotransmitter released from ascending arousal circuits that promote wakefulness, arousal, and consciousness activates AMPK, including acetylcholine, histamine, orexin-A, dopamine, and norepinephrine. Several GAs that are commonly used to induce LOC in human patients also activate AMPK (e.g. propofol, sevoflurane, isoflurane, dexmedetomidine, ketamine, midazolam). Various compounds that accelerate emergence from anesthesia, thus mitigating problematic effects associated with delayed emergence such as delirium, also activate AMPK (e.g. nicotine, caffeine, forskolin, carbachol). GAs and neurotransmitters also act as preconditioning agents and the GABAA receptor inhibitor bicuculline, which reverses propofol anesthesia, also activates AMPK in cortical neurons. We propose the novel hypothesis that cellular stress-induced AMPK activation links wakefulness, arousal, and consciousness with paradoxical excitation and accelerated emergence from anesthesia. Because AMPK activators including metformin and nicotine promote proliferation and differentiation of neural stem cells located in the subventricular zone and the dentate gyrus, AMPK activation may also enhance brain repair and promote potential recovery from disorders of consciousness (i.e. minimally conscious state, vegetative state, coma).

[A Case of Consciousness Disorder Induced by the Syndrome of Inappropriate Antidiuretic Hormone Secretion Following Cisplatin and 5-Fluorouracil Chemotherapy in a Patient with Tongue Cancer].

We herein report a case of a consciousness disorder that was induced by the syndrome of inappropriate antidiuretic hormone secretion following cisplatin (CDDP) and 5 -fluorouracil (5-FU) chemotherapy in a patient with tongue cancer. A 72- year-old woman complained of tongue pain and was admitted to our hospital for neoadjuvant chemotherapy, under a diagnosis of tongue squamous cell carcinoma (T4aN2bM0). She was treated with CDDP and 5-FU. On the second day after administration, she complained of nausea and anorexia, and on the third day, she showed impaired consciousness. Laboratory studies revealed that the patient had a serum sodium concentration 112mEq/L, and no dehydration was noted. The patient was diagnosed with SIADH, using the appropriate diagnostic criteria based on serum and urine hypoosmolality. We subsequently discontinued chemotherapy and initiated fluid restriction and sodium supplements. Two days after this treatment, her consciousness level improved, and on the fifth day of treatment, laboratory studies revealed a serum sodium level of 134mEq/ L.

Epidemiología de las intoxicaciones agudas por drogas de abuso en las urgencias de un hospital del Centro de España basada en datos de análisis toxicológico de orina / Epidemiology of acute poisonings for drugs of abuse in the emergency room of a hospital from the Center of Spain based on analysis data toxicological urine

Introducción: las intoxicaciones agudas son motivo de consulta cada vez más frecuente en los Servicios de Urgencia hospitalarios (SUH) debido a la mayor disponibilidad y acceso a productos químicos tóxicos. Se observan diferentes patrones en cada área sanitaria según el tipo de población, geografía y perfil epidemiológico de consumo. Material y métodos: el objetivo de nuestro estudio es realizar un perfil epidemiológico y describir el manejo del paciente que acude por clínica compatible con intoxicación aguda por drogas de abuso (IA) basado en la determinación de tóxicos en orina para seis sustancias (cannabis, opiáceos, cocaína, anfetaminas, benzodiazepinas y éxtasis) solicitados en el período de estudio 2010-2012. Resultados: se solicitaron 2755 peticiones, de las cuales fueron positivas 1429, y se estudiaron al azar 661 historias clínicas. El perfil de paciente intoxicado de nuestra área es el de varón de entre 30 y 40 años, consumidor preferentemente de cannabis y cocaína; las benzodiazepinas son el tóxico más frecuente en las mujeres, con clínica mayoritariamente neurológica, sin diferencias en cuanto a la franja horaria o el mes del año en que recibió el alta desde el propio SUH en casi el 60% de los casos. Discusión: las IA en los SUH representan casi el 1% de las consultas y tienen una escasa mortalidad. En algunos casos, el médico de urgencias comienza el tratamiento antes de conocer el resultado toxicológico, lo que nos hace plantearnos la utilidad real y el coste-efectividad de estas determinaciones en todos los pacientes con alteración del nivel de conciencia. (AU)

Introduction: acute intoxications are a rising and common query demand on the emergency rooms because of the easy access and disponibility to toxic substances, where we can observe different patterns attending to type of population, geography and epidemiologic consume profile. Material and methods: our objective is to analyze the epidemiology and patient handling coming to the Emergency Room (ER) with compatible symptoms of street drugs abuse, based on the determination of cannabis, cocaine, amphetamine, benzodiazepine, opiates and ectasy urine levels in the period 2010-2012. Results: the ER requested 2755 determinations being positive 1429 and randomly examined 661 clinical histories. The profile of intoxicated patient was male, 30 to 40 years old, preferently cannabis and cocaine consumer (benzodiazepine in women), mostly with neurological symptoms when arrive, without differences between months or day time and, almost 60% of them, discharged directly from the ER. Conclusions: acute intoxications barely represent 1% of ER demands and produce poor or scarce mortality. Sometimes, doctors in charge start with therapeutic measures before knowing the results of toxicology, what leads us to ask about actual usefulness and cost-efficiency of the toxicology assay to every patient with low conscious level. (AU)

How common is subsequent central nervous system toxicity in asymptomatic patients with haematologic malignancy and supratherapeutic voriconazole serum levels?

OBJECTIVES: We sought to determine the frequency at which patients with elevated voriconazole (VRC) levels but no clinically evident central nervous system (CNS) toxicity subsequently develop CNS toxicity. METHODS: We retrospectively reviewed the records of adult patients with haematolologic malignancy who had a VRC serum level >5.5 µg/mL at MD Anderson Cancer Center (January 2010 to December 2015). Patients with any documented CNS toxicity at the time the VRC level was obtained or patients whose VRC was discontinued as a response to high VRC level were excluded. Neurologic status was assessed using standard grading scales. Demographic and clinical characteristics, including potentially interacting medications, were correlated with the development of toxicity. RESULTS: We identified 320 such patients (mean age, 57 ± 15 years; 202 male (63%)). Subsequent CNS toxicity was documented in only 16 patients (5%). The most common CNS toxicities were visual disturbances (9/16, 56%), depressed consciousness (5/16, 31%) and cognitive disturbance (4/16, 19%). Patients with CNS toxicity tended to be older than those without (64 ± 8 vs 57 ± 15 y, p 0.08). The use of one or more neurotoxic drugs was common in patients with subsequent CNS toxicity (14/16, 88%). Reduction of VRC dose associated with the high VRC level did not correlate with less subsequent CNS toxicity. CONCLUSIONS: Development of subsequent CNS toxicity is uncommon in haematolologic malignancy patients with elevated VRC levels who had no evidence of toxicity at the time the level was obtained. Automatic reduction of VRC dose out of concern for impending CNS toxicity might not be warranted.

[Consciousness Impairment and Left Hemiparesis due to Contrast Medium in the Coil Embolization of Unruptured Large Right Middle Cerebral Artery Aneurysm: A Case Report].

Neurological deficits following coil embolization of anterior circulation aneurysms due to the toxicity of contrast medium are rare. Here, we describe a patient with mild consciousness impairment and left hemiparesis following coil embolization of a large right middle cerebral artery aneurysm without evidence of ischemia or hemorrhage, who recovered completely with conservative treatment. The patient's clinical course and radiological findings led us to conclude that the neurological deficits were due to the toxic effect of contrast medium used during the coil embolization.

[Prolonged Disturbance of Consciousness following Preoperative Glycerin Enema in an Elderly Patient].

A 94-year-old female patient with femoral neck fracture received 60 ml glycerin enema prior to surgery, according to the preoperative preparation protocol. She was found unconscious and unresponsive 60 minutes after the treatment. Vital signs were checked and ECG monitoring was started. The results were unremarkable and similar to those recorded at the time of admission. A neurologist was consulted, and a thorough evaluation was performed. None of physical and neurological examination, laboratory testing and urgent intracranial imaging revealed significant abnormalities or lesion responsible for the depressed consciousness. Vasovagal reflex triggered by enema and the consequent hypotension was thought to be the most likely cause of transient cerebral hypoperfusion resulting in loss of consciousness. The patient remained unresponsive for the next 2 hours, and came to open her eyes with tapping stimuli. She took another hour to fully regain consciousness without any residual neurologic deficit. Her surgery was cancelled. Vasovagal reflex is known to be one of the potential complications associated with enema. Our experience suggests that the necessity of glycerin enema for preoperative bowel preparation in elderly patients should be cautiously determined and it should be given, if necessary, under adequate vigilance.

Posterior reversible encephalopathy syndrome with thalamic involvement during vasopressor treatment of vertebrobasilar vasospasm after subarachnoid hemorrhage.

Hemodynamic augmentation is the primary medical intervention employed to reverse neurological deficits associated with vasospasm and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage. Failure to improve despite induced hypertension (IH) may raise concern for persistent hypoperfusion and prompt even more aggressive blood pressure augmentation. However, posterior reversible encephalopathy syndrome (PRES) is a hyperperfusion syndrome reported as a rare complication of IH that may confound this picture. We report a case of PRES with prominent thalamic involvement and impaired level of consciousness secondary to blood pressure augmentation for the treatment of symptomatic vertebrobasilar vasospasm. Recognition of this syndrome in distinction to worsening ischemia is particularly critical, as normalization of blood pressure should lead to rapid clinical improvement.

[Detection of adverse events in hospitalized adult patients by using the Global Trigger Tool method]. / Detección de eventos adversos en pacientes adultos hospitalizados mediante el método Global TriggerTool.

OBJECTIVES: To identify and characterize adverse events (AE) in an Internal Medicine Department of a district hospital using an extension of the Global Trigger Tool (GTT), analyzing the diagnostic validity of the tool. METHODS: An observational, analytical, descriptive and retrospective study was conducted on 2013 clinical charts from an Internal Medicine Department in order to detect EA through the identification of 'triggers' (an event often related to an AE). The 'triggers' and AE were located by systematic review of clinical documentation. The AE were characterized after they were identified. RESULTS: A total of 149 AE were detected in 291 clinical charts during 2013, of which 75.3% were detected directly by the tool, while the rest were not associated with a trigger. The percentage of charts that had at least one AE was 35.4%. The most frequent AE found was pressure ulcer (12%), followed by delirium, constipation, nosocomial respiratory infection and altered level of consciousness by drugs. Almost half (47.6%) of the AE were related to drug use, and 32.2% of all AE were considered preventable. The tool demonstrated a sensitivity of 91.3% (95%CI: 88.9-93.2) and a specificity of 32.5% (95%CI: 29.9-35.1). It had a positive predictive value of 42.5% (95%CI: 40.1-45.1) and a negative predictive value of 87.1% (95%CI: 83.8-89.9). CONCLUSIONS: The tool used in this study is valid, useful and reproducible for the detection of AE. It also serves to determine rates of injury and to observe their progression over time. A high frequency of both AE and preventable events were observed in this study.

Adverse drug event nonrecognition in emergency departments: an exploratory study on factors related to patients and drugs.

BACKGROUND: Many adverse drug events (ADEs) are not identified by emergency physicians. Research has been done to study risk factors for ADEs and help emergency physicians diagnose ADEs. However, no research has specifically examined the causes underlying a lack of attribution of ADEs to medications in emergency department (ED) patients. OBJECTIVE: We conducted an exploratory study in a medical ED to search for the factors associated with ADE nonrecognition that are related to ED patients and ADEs. METHODS: We conducted an observational study in the medical ED of a French tertiary care hospital between January and December 2009. The study focused on all ADEs, whether or not they were related to the patient's chief complaint. ADEs were identified by an expert physician and pharmacist based on National Electronic Injury Surveillance System criteria. An ADE was considered "attributed" if any evidence of ADE suspicion, ADE diagnosis, or ADE management was documented on ED charts. Factors associated with ADE nonrecognition were identified using multiple logistic regression analysis. RESULTS: Of the 465 included patients, 90 experienced an ADE at ED visit (19.4%; 95% confidence interval [CI] 15.9%-23.2%). Emergency physicians correctly recognized 36 of these cases (40.0%; 95% CI 29.8%-50.9%). On multivariate analysis, ADE nonrecognition was significantly associated with the following variables: nonrelation between the ADE and the patient's chief complaint; daily prescription of four drugs or more; and hospitalization ADE severity category. CONCLUSIONS: Our results emphasize the importance of searching for ADEs in patients with daily polypharmacy or whose chief complaint does not seem to be drug related.

[Accidental levomethadone intoxication in a palliative patient]. / Akzidentielle Levomethadonintoxikation bei einer Palliativpatientin.

Levomethadone is a strong opioid which is used rarely in the treatment of special pain syndromes in Germany. A main field for the usage of Levomethadone, which has be applied as a oral fluid, is the opioid replacement therapy of heroin-addicts. Due to the long plasma half life and its high inter-individual variability, the application implies a risk of cumulation leading to an overdosage. It is not recommended to use a fixed equianalgesic formula for the dosage conversion from other opioids. The conversion starts with a low start dose, an individual titration follows. In this case-report, the difficulty of cumulation, inaccurate drug dispensary and the characteristic of dosage calculation of levomethadone is discussed.

Alcaloides e o chá de ayahuasca: uma correlação dos "estados alterados da consciência" induzido por alucinógenos / Alkaloids and ayahuasca tea: a correlation of hallucinogen-induced "altered states of consciousness"

Dentre as inúmeras plantas alucinógenas utilizadas por populações indígenas da bacia amazônica, talvez nenhuma delas seja mais interessante ou complexa em termos botânicos, químicos ou etnográficos, como a bebida alucinógena conhecida como ayahuasca, hoasca, medicina, vegetal ou daime. Ayahuasca é bebida psicotrópica da América do Sul de destacado uso no xamanismo de muitas tribos indígenas da Amazônia, obtida pela fervura da casca do cipó de Banisteriopis caapi com a mistura de folhas de Psycotria, principalmente P. viridis. No Brasil, ocupa posição de destaque na etnomedicina. A natureza química dos compostos ativos, bem como, a maneira de utilização faz com que essa bebida ocupe posição de destaque nos atuais estudos da neurofarmacologia, neurofisiologia e psiquiatria. Alucinógenos e substâncias relacionadas constituem poderosa base experimental para investigar a correlação biológica dos estados alterados de consciência. O estudo de alucinógenos em humanos é de suma importância porque as substâncias com essas propriedades afetam certas funções cerebrais que tipicamente caracterizam a mente humana, incluindo a cognição, volição, ego e auto-percepção. As várias manifestações dos "desequilíbrios do ego" são especialmente características psicodélicas proeminentes, que acabam naturalmente criando psicoses. Sumarizamos nessa revisão alguns aspectos importantes no estudo do chá de ayahuasca em humanos, as indicações e contra-indicações para fins terapêuticos e religiosos.

Among the numerous hallucinogenic plants utilized by indigenous populations of the Amazon Basin, perhaps none is as interesting or complex in terms of botany, chemistry or ethnography as the hallucinogenic beverage known as ayahuasca, hoasca, medicine, vegetable or daime. Ayahuasca is a South American psychotropic beverage that is prominent in the shamanism of many indigenous Amazonian tribes and is obtained by boiling the bark of the liana Banisteriopsis caapi together with the mixture of leaves of Psychotria, principally P. viridis. In Brazil, it occupies a central position in ethnomedicine. The chemical nature of its active constituents and the manner of its use makes it relevant to contemporary studies in neuropharmacology, neurophysiology, and psychiatry. Hallucinogens and related substances constitute a powerful experimental basis to investigate the biological correlation of altered states of consciousness. The study of hallucinogens in humans is important because these substances affect a number of brain functions that typically characterize the human mind, including cognition, volition, ego, and self-consciousness. The several manifestations of "ego disorders" are especially prominent psychedelic features that naturally lead to psychoses. In the present review, we summarize some of the important aspects in the study of ayahuasca tea in humans, its indications and contraindications for therapeutic and religious purposes.

Seizures as a cause of altered mental status.

The differential diagnosis and empiric management of altered mental status and seizures often overlap. Altered mental status may accompany seizures or simply be the manifestation of a postictal state. This article provides an overview of the numerous causes of altered mental status and seizures: metabolic, toxic, malignant, infectious, and endocrine causes. The article focuses on those agents that should prompt the emergency physician to initiate unique therapy to abate the seizure and correct the underlying cause.

Psychiatric considerations in patients with decreased levels of consciousness.

When patients present to the emergency department with changes in behavior and levels of consciousness, psychiatric causes often move to the top of the list of diagnostic considerations. It is important to thoroughly assess such patients for medical causes. Although it is not common for primary psychiatric conditions to present with altered levels of consciousness, severe cases may present in this fashion. Altered mental states may also be caused by adverse reactions to psychiatric medications. In this article, the authors review some of the psychiatric causes of decreased levels of consciousness, as well as certain adverse drug reactions to psychotropic medications.

[A case of hyperammonemia with encephalopathy related to FOLFIRI chemotherapy for advanced colon cancer].

A 50-year-old man undergoing operations for sigmoid colon cancer, small intestine invasion, and liver metastasis was given adjuvant chemotherapy postoperatively. During the course, lung, brain and bone metastasis were found, FOLFIRI therapy was started. Fifth FOLFIRI therapy was performed, but on the night of the next day, he was transported on an emergency basis to our hospital because of a coma. Laboratory examination revealed hyperammonemia, so aminoleban was started for its treatment. After 3 days in the hospital, consciousness and serum ammonia were improved. Cases of hyperammonemia caused by 5-FU have been reported in the literature, and this case was diagnosed with the same. Hyperammonemia should be taken into account as a differential diagnosis in the disturbance of consciousness in chemotherapy.

[Marked hyponatremia with consciousness disturbance probably caused by linezolid in a patient with acute myeloid leukemia].

We report the case of a 75-year-old man with acute myeloid leukemia who developed hyponatremia after linezolid administration. Because induction therapy did not achieve complete remission for this man, we initiated re-induction therapy with enocitabin and daunomycin. Seven days after chemotherapy, the patient experienced a catheter-related blood stream infection (CRBSI) due to methicilin resistant staphylococcus aureus (MRSA). When treatment with albekacin and fosfomycin was in effective, linezolid was administrated intravenously and he became afebrile. On day 8 after linezolid administration, however, he reported general fatigue and slight consciousness disturbance. His serum sodium concentration was 119 mEq/L and his urinary sodium excretion rose to 143 mEq/day, although intravenous sodium intake was 98 mEq/day. Because of the sufficiency of urine volume and weight loss, we surmise that inappropriate ADH secretion (SIADH) syndrome was unlikely. We diagnosed renal salt wasting syndrome (RSWS) based on calculation of the amount of sodium intake and the amount of sodium excreted from the kidneys. After linezolid was discontinued and aggressive treatment with sodium supplement begun, his consciousness cleared as his low serum sodium level rose. This is, to the best of our knowledge, the first case reported on the development of RSWS after linezolid treatment. Although the process remains unclear, our case suggests that linezolid may induce RSWS after intensive chemotherapy.

Acute transient encephalopathy following paclitaxel treatment in an adolescent with a recurrent suprasellar germinoma.

Paclitaxel is an antineoplastic agent that is used in the treatment of a variety of solid tumors. Dose-limiting side effects of myelosuppression and peripheral neuropathy are well known. Paclitaxel has minimal penetration of the blood-brain barrier and central nervous system side effects are rare. However, transient encephalopathy following paclitaxel infusion has been described in adults but not in children. We present the case of a 14-year-old female with a recurrent suprasellar germinoma who developed an acute encephalopathy 4-6 hr following paclitaxel infusion.