The arousal effect of An-Gong-Niu-Huang-Wan on alcoholic-induced coma rats: A research based on EEG.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute alcohol intoxication is one of the leading causes of coma. A well-regarded Chinese herbal formula, known as An-Gong-Niu-Huang-Wan (AGNHW), has garnered recognition for its efficacy in treating various brain disorders associated with impaired consciousness, including acute alcohol-induced coma. Despite its clinical effectiveness, the scientific community lacks comprehensive research on the mechanistic aspects of AGNHW's impact on the electroencephalogram (EEG) patterns observed during alcohol-induced coma. Gaining a deeper understanding of AGNHW's mechanism of action in relation to EEG characteristics would hold immense importance, serving as a solid foundation for further advancing its clinical therapeutic application. AIM OF THE STUDY: The study sought to investigate the impact of AGNHW on EEG activity and sleep EEG patterns in rats with alcoholic-induced coma. MATERIALS AND METHODS: A rat model of alcohol-induced coma was used to examine the effects of AGNHW on EEG patterns. Male Sprague-Dawley rats were intraperitoneally injected with 32% ethanol to induce a coma, followed by treatment with AGNHW. Wireless electrodes were implanted in the cortex of the rats to obtain EEG signals. Our analysis focused on evaluating alterations in the Rat Coma Scale (RCS), as well as assessing changes in the frequency and distribution of EEG patterns, sleep rhythms, and body temperature subsequent to AGNHW treatment. RESULTS: The study found a significant increase in the δ-band power ratio, as well as a decrease in RCS scores and ß-band power ratio after modeling. AGNHW treatment significantly reduced the δ-band power ratio and increased the ß-band power ratio compared to naloxone, suggesting its superior arousal effects. The results also revealed a decrease in the time proportion of WAKE and REM EEG patterns after modeling, accompanied by a significant increase in the time proportion of NREM EEG patterns. Both naloxone and AGNHW effectively counteracted the disordered sleep EEG patterns. Additionally, AGNHW was more effective than naloxone in improving hypothermia caused by acute alcohol poisoning in rats. CONCLUSION: Our study provides evidence for the arousal effects of AGNHW in alcohol-induced coma rats. It also suggests a potential role for AGNHW in regulating post-comatose sleep rhythm disorders.

Clinical characteristics of acute lacosamide poisoning: Pavia Poison Control Centre experience.

AIMS: Lacosamide is a third-generation antiepileptic drug used as adjunctive therapy for partial seizures. Since its approval in 2008 very few cases of lacosamide overdose have been described in literature. The aim of our study was to evaluate clinical characteristics of acute lacosamide poisoning. METHODS: A retrospective observational study was performed including all cases of acute lacosamide poisoning referred to Pavia Poison Control Centre from January 2012 to December 2021. For each patient age, sex, ingested dose, coingestants, clinical manifestations, treatment and outcome were collected. RESULTS: A total of 31 subjects (median age 39 years, [interquartile range: 26.5-46.5]; females 22/31) were included. The median lacosamide ingested dose was 1500 mg [650-2800]. In 35.5% of cases lacosamide was the single ingested substance, while in 64.5% coingestants were also present. Coingestants varied from a minimum of 1 to a maximum of 3, with the more common being benzodiazepines and valproic acid. Clinical manifestations were present in 87% patients the most common were: vomiting (29%); seizures (29%), coma (25.8%), drowsiness (25.8%), confusion (12.9%), agitation (12.9%), tachycardia (12.9%), tremors (9.7%), bradycardia (9.7%), headache (6.5%) and hypertension (3.2%). The median lacosamide ingested dose was significantly higher in patients that experienced coma compared to patient who did not (2800 vs. 800 mg; P = .0082). Orotracheal intubation was necessary in 32.3% of patients. All patients fully recovered. CONCLUSION: Lacosamide acute overdose may lead to a severe clinical picture. Dentral nervous system symptoms predominated, particularly seizures and coma occurred in a high percentage of cases.

Neurological evolution of severe baclofen intoxication: from brain death mimic to recovered brain function.

Patients with brain death have by definition irreversible and complete loss of brainstem reflexes. Before a definite diagnosis of brain death can be confirmed, all potential confounders must be thoroughly excluded. Baclofen intoxication is a rare cause of brain death mimic characterised by transient deep coma and absence of brainstem reflexes and might be mistaken with brain death. We report the case of a female patient in her 70s who ingested baclofen with suicidal intent and was admitted with a deep coma and loss of all brainstem reflexes and a spontaneous burst-suppression pattern in the electroencephalography which resolved over 10 hours. After a state mimicking brain death for 6 hours, the patient experienced complete recovery. Severe baclofen intoxication can mimic brain death clinically and is associated with temporary pathological electroencephalographic findings. Awareness of this toxidrome is crucial, as appropriate management can lead to full recovery.

Poisoning by abnormally high blood phenobarbital concentration treated with extracorporeal therapy.

Phenobarbital poisoning, which may cause circulatory collapse as well as respiratory arrest in severe cases, has one of the highest mortality rates among acute drug poisonings. A 58-year-old man arrived at the emergency room in a deep coma (Glasgow Coma Scale E1V1M1) after taking an unknown dose of phenobarbital which had been prescribed for his cat's seizures. Venous blood gas analysis revealed hypercapnia (PvCO2: 113.0 mmHg) and a blood phenobarbital concentration of 197.3 µg/mL. Shortly after his arrival, respiratory arrest and circulatory collapse occurred. Mechanical ventilation after intubation, intravenous noradrenaline infusion, and multiple-dose activated charcoal through a nasogastric tube was started. Six hours after arrival, blood phenobarbital concentration was abnormally elevated to 356.8 µg/mL with circulatory collapse requiring an increased dose of intravenous noradrenaline infusion (up to 0.13 µg/kg/min). Continuous renal replacement therapy including high flow continuous hemodialysis was performed until hospital day 5, during which blood phenobarbital concentration decreased to 96.2 µg/mL on hospital day 4, resulting in a sufficient resumption of spontaneous breathing and full improvement of circulatory collapse. A search of the literature revealed that the peak phenobarbital concentration in the present case exceeded those of fatal cases, as well as those of survivors of acute phenobarbital poisoning. However, the patient was successfully treated with continuous renal replacement therapy. Among modalities of extracorporeal treatment, continuous renal replacement therapy could be considered if a patient's circulation is unstable.

An 81-Year-Old Man Presenting with Asthenia and Anorexia After an Alcohol-Induced Hypoglycemic Coma and a Diagnosis of Central Adrenal Insufficiency: A Case Report.

BACKGROUND Alcohol abuse inhibits the ability of the liver to release glucose into the bloodstream, primarily by inhibiting gluconeogenesis, so chronic alcohol abusers exhibit hypoglycemia after drinking alcohol without eating; this is called alcohol-induced hypoglycemia. Central adrenal insufficiency (AI) is characterized by cortisol deficiency due to a lack of adrenocorticotropic hormone. It is challenging to diagnose central AI, as it usually presents with nonspecific symptoms, such as asthenia, anorexia, and a tendency toward hypoglycemia. Here, we report a rare case of central AI that presented with AI symptoms shortly after an alcohol-induced hypoglycemic coma. CASE REPORT An 81-year-old Japanese man who had been a moderate drinker for >40 years developed a hypoglycemic coma after consuming a large amount of sake (alcohol, 80 g) without eating. After the hypoglycemia was treated with a glucose infusion, he rapidly recovered consciousness. After stopping alcohol consumption and following a balanced diet, he had normal plasma glucose levels. However, 1 week later, he developed asthenia and anorexia. The endocrinological investigation results indicated central AI. He was started on oral hydrocortisone (15 mg/day), which relieved his AI symptoms. CONCLUSIONS Cases of central AI associated with alcohol-induced hypoglycemic attacks have been reported. Our patient developed AI symptoms following an alcohol-induced hypoglycemic attack. His alcohol-induced hypoglycemic attack likely occurred in combination with a developing cortisol deficiency. This case highlights the importance of considering central AI in chronic alcohol abusers presenting with nonspecific symptoms, including asthenia and anorexia, especially when patients have previously experienced alcohol-induced hypoglycemic attacks.

Piperacillin-Tazobactam Versus Anti-Pseudomonal Cephalosporins and Renal and Neurologic Outcomes in Critically Ill Adults: A Secondary Analysis of the SMART Trial.

Background: Prior studies suggest associations between receipt of piperacillin-tazobactam and development of acute kidney injury and receipt of anti-pseudomonal cephalosporins and neurotoxicity. We compared clinically-relevant renal and neurologic outcomes in critically ill patients who received piperacillin-tazobactam versus anti-pseudomonal cephalosporins. Methods: We conducted a secondary analysis of data from the Isotonic Solutions and Major Adverse Renal Events Trial examining patients who received piperacillin-tazobactam or an anti-pseudomonal cephalosporin within 24 h of intensive care unit admission. We performed multivariable analysis using a proportional odds model to examine the association between the first antibiotic received and the outcomes of Major Adverse Kidney Events within 30 days (MAKE30) and days alive and free of delirium and coma to day 28. Results: 3199 were included in the study; 2375 (74%) receiving piperacillin-tazobactam and 824 (26%) receiving anti-pseudomonal cephalosporin. After adjustment for prespecified confounders, initial receipt of piperacillin-tazobactam, compared to anti-pseudomonal cephalosporins, was not associated with higher incidence of MAKE30 (adjusted odds ratio, 1.03; 95% CI, 0.83-1.27; P = .80) but was associated with a greater number of days alive and free of delirium and coma (adjusted odds ratio, 1.18; 95% CI, 1.00-1.38; P = .04). In a sensitivity analysis adjusting for baseline receipt of medications which may impact neuro function, this finding was not significant. Conclusion: Among critically ill adults, receipt of piperacillin-tazobactam was not associated with an increased incidence of death, renal replacement therapy, or persistent renal dysfunction or a greater number of days alive and free of delirium and coma. Randomized trials are needed to inform the choice of antibiotics for empiric treatment infection in critically ill adults.

Liquid levothyroxine in the treatment of myxoedema coma.

Not required for Clinical Vignette.

Brimonidine eye drops reveal diminished sympathetic pupillary tone in comatose patients with brain injury.

BACKGROUND: There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly, the sympathetic control of pupil size is thought to be lost in states of unconsciousness. We therefore hypothesized that administration of brimonidine (an alpha-2-adrenergic agonist) eye drops into one eye should produce a pharmacologic Horner's syndrome if the clinically unresponsive patient is conscious, but not if the patient is unconscious. Here, in a first step to explore this hypothesis, we investigated the potential of brimonidine eye drops to distinguish preserved sympathetic pupillary function in awake volunteers from impairment of sympathetic tone in patients in a coma. METHODS: We enrolled comatose patients admitted for acute brain injury to one of the intensive care units (ICU) of a tertiary referral center, in whom EEG and/or neuroimaging for all practical purposes had ruled out residual consciousness. Exclusion criteria were deep sedation, medications with known drug interactions with brimonidine, and a history of eye disease. Age- and sex-matched healthy and awake volunteers served as controls. We measured pupils of both eyes, under scotopic conditions, at baseline and five times 5-120 min after administering brimonidine into the right eye, using automated pupillometry. Primary outcomes were miosis and anisocoria at the individual and group levels. RESULTS: We included 15 comatose ICU patients (seven women, mean age 59 ± 13.8 years) and 15 controls (seven women, mean age 55 ± 16.3 years). At 30 min, miosis and anisocoria were seen in all 15 controls (mean difference between the brimonidine-treated pupil and the control pupil: - 1.31 mm, 95% CI [- 1.51; - 1.11], p < 0.001), but in none (p < 0.001) of the 15 ICU patients (mean difference: 0.09 mm, 95% CI [- 0.12;0.30], p > 0.99). This effect was unchanged after 120 min and remained robust in sensitivity analyses correcting for baseline pupil size, age, and room illuminance. CONCLUSION: In this proof-of-principle study, brimonidine eye drops produced anisocoria in awake volunteers but not in comatose patients with brain injury. This suggests that automated pupillometry after administration of brimonidine can distinguish between the extremes of the spectrum of consciousness (i.e., fully conscious vs. deeply comatose). A larger study testing the "intermediate zone" of disorders of consciousness in the ICU seems warranted.

Experience in the treatment of chlorfenapyr poisoning.

In China, the extensive use of the pesticide chlorfenapyr has led to an increase in chlorfenapyr poisoning. However, there are limited reports on chlorfenapyr poisoning, and most of them are fatal cases. This study retrospectively analyzed four patients admitted to the emergency room after chlorfenapyr intake and detected different concentrations of chlorfenapyr in their plasma. Among them, one patient died and three patients survived. Case 1 suffered respiratory and circulatory failure with a deep coma shortly after oral administration of 100 mL of a the chlorfenapyr-containing mixture and died 30 min after admission. Case 2 experienced transient nausea and vomiting after oral administration of chlorfenapyr (50 mL). The patient had normal laboratory results and was discharged with no further treatment. Case 3 developed nausea and vomiting and a light coma after taking 30 mL of chlorfenapyr orally. He underwent blood perfusion and plasma exchange in the intensive care unit (ICU) and was discharged with recovery. A two-week follow-up visit, however, revealed hyperhidrosis. Case 4 (advanced age with severe underlying disease) developed a light coma after oral intake of 30 mL of chlorfenapyr. Subsequently, pulmonary infection and gastrointestinal bleeding were developed. The patient experienced blood perfusion and mechanical ventilation in the ICU and finally survived after treatment. The present study provides the basic information, plasma concentration of toxins, onset of poisoning and treatment process of the four patients mentioned above, providing novel insights into the clinical diagnosis and treatment of chlorfenapyr poisoning.

[Shock and Coma after Ingestion of Morels]. / Morchelvergiftung mit Schock und Koma.

Shock and Coma after Ingestion of Morels Abstract. We present the case report of a previously healthy, 42-year-old woman who suffered from a hypovolemic shock, hypoglycemic coma, NSTEMI and temporary dependency on dialysis following the ingestion of morels. Alas there is little public knowledge about the toxicity of morels and the importance of their appropriate preparation so that intoxications can be prevented.

[Antidepressant overdose resulting in coma and hypothermia]. / Coma en hypothermie door een antidepressivum.

BACKGROUND: Cognitive disorders lead to an increased risk of misuse of medication, resulting in possible auto-intoxication. CASE DESCRIPTION: We describe the case of a 68-year-old patient, with hypothermia and a coma, with accidental tricyclic antidepressant (TCA) intoxication. What is remarkable about this case is that there were no cardiac or hemodynamic abnormalities, which is to be expected with both hypothermia and TCA-intoxication. CONCLUSION: Intoxication should be considered in patients with hypothermia and a decreased level of consciousness, in addition to primarily neurological or metabolic causes. A good (hetero)anamnesis with attention to pre-existent cognitive functioning is important. Early screening for intoxication in patients with cognitive disorders with a coma and hypothermia is advisable, even in the absence of a typical toxidrome.

Hemodialysis as emergency treatment of a severe baclofen intoxication in a 3 kg dog.

OBJECTIVE: To describe the clinical efficacy and drug removal kinetics of hemodialysis (HD) as emergency treatment in a small size dog with severe baclofen intoxication. CASE DESCRIPTION: A 2-year-old dog was presented in stupor to the emergency service a few hours after ingestion of up to 25 mg of baclofen. Medical stabilisation was attempted but was unsuccessful in improving the neurological condition and the patient rapidly progressed to coma. A 4-h session of HD was performed in emergency with near complete resolution of neurological signs and only mild disorientation by the end of the treatment. No adverse side effects occurred during HD. Baclofen concentration was measured serially during the session. Drug extraction ratio, clearance and mass removal by the dialyser were calculated. Dialytic elimination rate constant (Kd ) was seven times higher than the intrinsic elimination rate constant (Kintr ) and the half-life (t½) during HD was nearly nine times shorter than the endogenous one. NEW OR UNIQUE INFORMATION PROVIDED: This is the first case report providing pharmacokinetic data associated with HD treatment of severe baclofen intoxication in a dog.

Coma, Severe Hypotension, and Pinpoint Pupils After Olanzapine Intoxication in the Intensive Care Unit with Symptom Reversal After Administration of Flumazenil.

BACKGROUND Olanzapine is an antipsychotic drug and is used in critical care to treat delirium. There is no known antidote to olanzapine intoxication. Overdosing olanzapine can cause, tremor, bradykinesia, hypotension somnolence, coma, and miosis. CASE REPORT We present the case of a previously healthy 69-year-old man who after routine mitral valve surgery developed pneumonia and severe sepsis requiring several weeks on a ventilator in the Intensive Care Unit. He developed delirium and paranoia and was prescribed olanzapine. After 4 doses, he became hypotensive and nonresponsive and developed pinpoint pupils. The symptoms were reversed minutes after administration of flumazenil. The clinical picture in this case corresponds well with an olanzapine intoxication. No other drugs, such as benzodiazepines or opioids, had been administered that could explain the reaction. Olanzapine intoxication is known to present with hypotension, coma, and miosis. The doses given were normal starting doses for olanzapine in the outpatient setting but much higher than recommended doses in the intensive care setting. CONCLUSIONS This case illustrates a risk for severe adverse effects, even within normal prescription range, when olanzapine is used in the intensive care setting. Finally, it is intriguing that the symptoms were reversed after administration of flumazenil, a selective competitive antagonist of the GABA receptor. Olanzapine mainly effects dopamine, serotonin, a1-adrenergic, histamine, and muscarinic receptors, but a low affinity to GABA and benzodiazepine sites can perhaps explain the observed effect.

[Nasal glucagon (Baqsimi®), new treatment for hypoglycaemic coma]. / Le médicament du mois. Le glucagon nasal (Baqsimi®), nouveau traitement du coma hypoglycémique.

Patients with insulin-treated type 1 diabetes (T1D) are exposed to hypoglycaemia, which may be serious. Serious cognitive impairment (including coma and seizure) that requires the help of a third party is a medical emergency. Besides the intravenous injection of glucose by a health care provider, its treatment consists of the subcutaneous or intramuscular injection of glucagon which may be performed by a family member. However, such an injection is not easy and puts off some people, which retards the initiation of a potentially life-saving therapy. The intranasal administration of 3 mg glucagon has been shown as efficacious as the subcutaneous or intramuscular injection of 1 mg glucagon in controlled studies carried out in both adult and youth patients with T1D. Stimulation and real-life studies among caregivers, patients and acquaintances showed a preference for nasal glucagon because of its easy and quick use. The launch of nasal glucagon (Baqsimi®) offers new perspectives for the ambulatory emergency management of severe hypoglycaemia and hypoglycaemic coma with a special obvious advantage in children.

La personne avec un diabète de type 1 (DT1) traité par insuline est exposée à un risque d'hypoglycémie, parfois grave. L'hypoglycémie sévère qui désigne tout trouble cognitif grave (y compris coma, convulsion) nécessitant l'intervention d'un tiers est une urgence médicale. Outre l'injection de glucose par voie intraveineuse, réservée à un personnel de santé, le traitement consiste en l'injection de glucagon par voie sous-cutanée ou intramusculaire qui peut être réalisée par un membre de l'entourage. Cependant, cette injection n'est pas aisée et rebute certaines personnes, ce qui retarde la mise en route d'un traitement potentiellement salvateur. L'administration nasale de glucagon 3 mg s'est avérée aussi performante que l'injection sous-cutanée ou intramusculaire de 1 mg dans des études contrôlées réalisées chez des patients DT1 adultes ou enfants/adolescents. Des études de simulation et de vraie vie réalisées auprès de soignants, de patients et de connaissances ont montré une préférence pour la forme nasale en raison de sa facilité et rapidité d'utilisation. La commercialisation du glucagon nasal (Baqsimi®) offre de nouvelles perspectives pour le traitement d'urgence ambulatoire de l'hypoglycémie sévère et du coma, avec un avantage particulièrement évident chez les enfants.