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.

PD-1 inhibitor-associated type 1 diabetes: A case report and systematic review.

Objective: This study aimed to summarize the clinical characteristics of programmed death receptor 1 (PD-1) inhibitor-associated type 1 diabetes so as to improve the ability of clinicians to correctly diagnose and treat it. Methods: We reported a case of a 70-year-old woman with gastric cancer who developed hyperosmolar hyperglycemic coma during camrelizumab (a PD-1 inhibitor) treatment and was diagnosed with PD-1 inhibitor-associated type 1 diabetes. We conducted a systematic review of 74 case reports of type 1 diabetes associated with PD-1 inhibitor therapy published before June 2022. Results: The patient developed type 1 diabetes with hyperosmolar hyperglycemic coma after receiving camrelizumab chemotherapy for 6 months (9 cycles). We searched 69 English articles comprising 75 patients, all of whom had been treated with a PD-1 inhibitor (nivolumab or pembrolizumab) and progressed to diabetes after an average of 6.11 (1-28) cycles. Nivolumab combined with ipilimumab (a cytotoxic T lymphocyte-associated protein 4 inhibitor) had the shortest onset (4.47 cycles on average). A total of 76% (57/75) of patients developed diabetic ketoacidosis (DKA) at onset, and 50.67% (38/75) of patients had C-peptide <0.1 ng/mL. Most of the patients were tested for insulin autoantibodies, with a positive rate of 33.33% (23/69); of these, 86.96% (20/23) were tested for glutamate decarboxylase antibody and 46.67% (35/75) were tested for human leukocyte antigen (HLA). HLA-DR4 was the most common type. Conclusions: The progression of type 1 diabetes induced by PD-1 inhibitors is relatively rapid. Islet failure often occurs when detected, seriously endangering patients' lives. Patients treated with PD-1 inhibitors should closely monitor their plasma glucose level during treatment to detect, diagnose, and treat diabetes on time.

Case Report: A Patient With Neuroleptic Malignant Syndrome, Water Intoxication and Hyponatremia Associated With Severe Cerebral Edema and Coma.

Background: Water intoxication is typically caused by primary or psychogenic polydipsia that potentially may lead to fatal disturbance in brain functions. Neuroleptic malignant syndrome (NMS) is a serious complication induced by administration of antipsychotics and other psychotropic drugs. The combination of inappropriate secretion of antidiuretic hormone (SIDAH), NMS and rhabdomyolysis have been rarely reported. Our patient also developed severe water intoxication. Case presentation: Herein we report a comatose case of NMS complicated with water intoxication, syndrome of SIADH and rhabdomyolysis. This patient had severe cerebral edema and hyponatremia that were improved rapidly by the correction of hyponatremia within a couple of days. Conclusions: Malignant neuroleptic syndrome water intoxication, SIADH and rhabdomyolysis can occur simultaneously. Comatose conditions induced by cerebral edema and hyponatremia can be successfully treated by meticulous fluid management and the correction of hyponatremia.

Pentobarbital Coma Use in a Pregnant Patient With Refractory Intracranial Hypertension: A Case Report.

OBJECTIVE: Intracranial hypertension is a life-threatening condition that requires emergent diagnosis and management. Although pentobarbital coma for refractory intracranial hypertension has been studied in the general population, this study is the first reported case of pentobarbital coma use in a pregnant patient. METHODS: We performed a retrospective chart review of a pregnant patient with refractory intracranial hypertension and reviewed the current literature on the role of pentobarbital coma. RESULTS: We present the case of a 35-year-old woman at 26 weeks of gestation who developed refractory intracranial hypertension secondary to rupture of a dural arteriovenous fistula. The patient was taken to surgery for decompressive hemicraniectomy, clot evacuation, and dural arteriovenous fistula resection. Subsequently, the patient was treated with pentobarbital coma for 5 days and achieved adequate control of her intracranial pressures. The patient and fetus were closely monitored by the obstetrics team with no apparent harm to fetal well-being during her hospital stay. The patient underwent planned cesarean delivery at term, and both the mother and newborn were discharged in stable condition with no known pentobarbital-related complications. CONCLUSIONS: Thus, we present the first case report demonstrating that pentobarbital coma may be a safe and efficacious option for treating pregnant patients with life-threatening refractory intracranial hypertension. We also provide dosing information for pentobarbital administration. Additional studies and reports involving pregnant patients are needed to better understand the impact of pentobarbital on both the mother and fetus. Furthermore, long-term follow-up of both the mother and newborn is critical to identifying any delayed sequelae of neonatal exposure to pentobarbital.

[How does one die from SARS-CoV-2 infection? Analysis of the death process in patients admitted to an acute hospital]. / ¿Cómo se fallece por infección por SARS-CoV-2?: Análisis del proceso de muerte en pacientes ingresados en un hospital de agudos.

INTRODUCTION: The SARS-CoV-2 pandemic has generated a mortality rate 10times higher than normal influenza according to the World Health Organization (WHO), yet they do not mention palliative care in their action guidelines on maintaining essential health services during this crisis. The aim of this study was to analyse the death process of patients who died from SARS-CoV-2 at the Hospital Costa del Sol. MATERIAL AND METHODS: Descriptive cross-sectional study of the period in which all patients who died of SARS-CoV-2 from February to April 2020 were analysed. Sociodemographic characteristics, sample characterization and a set of variables related to the death process were collected in the death event. RESULTS: A total of 16 deaths were recorded out of a total of 103 admissions positive for SARS-CoV-2. Limitation of therapeutic effort was decided in 68.8% of the patients, and admission to the intensive care unit was refused in 56.3%. Support devices had not been removed in any of the cases on the day of death, 43.8% had palliative sedation, and 18.8% were in induced coma. CONCLUSIONS: Quality standards were maintained in the death process in patients who died from SARS-CoV-2, although there were aspects that could be improved. Palliative care is an essential component of the response to SARS-CoV-2 that must be incorporated into all health care settings.

[Acute severe oral poisoning with 1,4-butandiol and ethanol with the development of coma]. / Ostroe tyazheloe peroral'noe otravlenie 1,4-butandiolom i etanolom s razvitiem komatoznogo sostoyaniya.

A case of acute oral poisoning by 1.4-butanediol, complicated by the development of severe hypoxia in a 34-year-old patient actively engaged in bodybuilding, is presented. The psychoactive substance was used by the patient to increase sexual activity and physical stamina. The duration of systematic daily intake was 4 months. The toxicogenic stage of acute poisoning was caused by a single dose of 50 ml of undiluted 13% 1.4-butanediol together with ethanol, manifested by convulsive syndrome, depression of consciousness to the level of coma II, acute respiratory failure with aspiration syndrome, respiratory acidosis (pH 7.22; partial pressure carbon dioxide 61.2 mm Hg), lactic acidosis up to 7 mmol / L, hyperammonemia up to 240 µmol / L, cerebral edema (decrease in white matter density to 21.6 ± 1.7 HU units), loss of vascular tone resistance (pareso arterioles) and a significant increase in cerebral blood flow rate to 115 ± 20.1 ml / 100 g per minute, increasing the volume of extracellular fluid (+ 130% of the proper volumes). Intensive therapy was complex, including infusion and detoxification therapy, correction of acid-base disorders, hypoxic disorders by using a substrate antihypoxant (Cytoflavin) in a daily dosage of 0.57 ml / kg body weight daily, for 9 days. The article discusses the toxicokinetics and toxicodynamics of 1.4-butanediol, radiation diagnostics and the clinical picture of acute poisoning, the features of its course, and pathogenetic approaches to therapy.

Rectosigmoid ischemia and cerebral coma following gadolinium-induced anaphylaxis: A new manifestation of Kounis syndrome presented as devastating complication.

Gadolinium-based contrast mediums are the most commonly used agents in magnetic resonance imaging for both angiography, and brain tumor enhancement due to their association with the degradation of the blood-brain barrier. When oxidation is removed from gadolinium medium and gadolinium salts, a silvery-white metal anions remain that are able to induce allergic reactions and anaphylaxis. Whereas such reactions are not common, other reactions including nephrogenic systemic fibrosis and acute kidney injury due to primary excretion of gadolinium from the kidneys and various cardiac arrhythmias including QTc electrocardiographic prolongation are occasionally encountered 1,2. Despite that gadolinium-based contrast mediums are characterized as benign agents, in some occasions they can lead to life threatening conditions and Kounis syndrome 2-5. The concurrence of acute coronary syndromes such as coronary spasm, acute myocardial infarction, and stent thrombosis, with conditions associated with mast-cell and platelet activation involving other interrelated and interacting inflammatory cells, such as macrophages and Tlymphocytes in the setting of allergic or hypersensitivity and anaphylactic or anaphylactoid insults constitute the Kounis syndrome 6. This syndrome is caused by inflammatory mediators such as histamine, neutral proteases, arachidonic acid products, platelet-activating factor, and a variety of cytokines and chemokines released during the degranulation process of these inflammatory cells. Platelets bearing specific fragment crystallizable region receptors are also involved in the activation cascade 7. All these inflammatory cells participate in an inflammatory cycle and activate each other via multidirectional signals.

Deep coma in a child treated with propranolol for infantile hemangioma.

BACKGROUND: Propranolol hydrochloride is the first-line agent recommended for the treatment of infantile hemangiomas (IH). Serious adverse effects of propranolol therapy for hemangiomas are infrequent. CASE PRESENTATION: We report a case presented in deep hypoglycemic coma during his treatment with propranolol for IH. Through our case report and the review of the literature, we aimed to underline the importance of recognizing adverse effects during propranolol therapy. Although propranolol has a long history of safe and effective use in infants and children, pediatricians should be aware that life-threatening adverse effects can happen during propranolol therapy for IH. CONCLUSION: Early identification of these adverse effects can be of great importance for patient management and prognosis. It must certainly be noted that not just early identification among doctors, but education for parents is crucial.

Effects of Xingnaojing Injection on Adenosinergic Transmission and Orexin Signaling in Lateral Hypothalamus of Ethanol-Induced Coma Rats.

Acute alcohol exposure induces unconscious condition such as coma whose main physical manifestation is the loss of righting reflex (LORR). Xingnaojing Injection (XNJI), which came from Chinese classic formula An Gong Niu Huang Pill, is widely used for consciousness disorders in China, such as coma. Although XNJI efficiently shortened the duration of LORR induced by acute ethanol, it remains unknown how XNJI acts on ethanol-induced coma (EIC). We performed experiments to examine the effects of XNJI on orexin and adenosine (AD) signaling in the lateral hypothalamic area (LHA) in EIC rats. Results showed that XNJI reduced the duration of LORR, which implied that XNJI promotes recovery form coma. Microdialysis data indicated that acute ethanol significantly increased AD release in the LHA but had no effect on orexin A levels. The qPCR results displayed a significant reduction in the Orexin-1 receptors (OX1R) expression with a concomitant increase in the A1 receptor (A1R) and equilibrative nucleoside transporter type 1 (ENT1) expression in EIC rats. In contrast, XNJI reduced the extracellular AD levels but orexin A levels remained unaffected. XNJI also counteracted the downregulation of the OX1R expression and upregulation of A1R and ENT1 expression caused by EIC. As for ADK expression, XNJI but not ethanol, displayed an upregulation in the LHA in EIC rats. Based on these results, we suggest that XNJI promotes arousal by inhibiting adenosine neurotransmission via reducing AD level and the expression of A1R and ENT1.

Early prediction of neurological outcome after barbiturate coma therapy in patients undergoing brain tumor surgery.

After a difficult brain tumor surgery, refractory intracranial hypertension (RICH) may occur due to residual tumor or post-operative complications such as hemorrhage, infarction, and aggravated brain edema. We investigated which predictors are associated with prognosis when using barbiturate coma therapy (BCT) as a second-tier therapy to control RICH after brain tumor surgery. The study included adult patients who underwent BCT after brain tumor surgery between January 2010 and December 2016. The primary outcome was neurological status upon hospital discharge, which was assessed using the Glasgow Outcome Scale (GOS). In the study period, 4,296 patients underwent brain tumor surgery in total. Of these patients, BCT was performed in 73 patients (1.7%). Among these 73 patients, 56 (76.7%) survived to discharge and 25 (34.2%) showed favorable neurological outcomes (GOS scores of 4 and 5). Invasive monitoring of intracranial pressure (ICP) was performed in 60 (82.2%) patients, and revealed that the maximal ICP within 6 h after BCT was significantly lower in patients with favorable neurological outcome as well as in survivors (p = 0.008 and p = 0.028, respectively). Uncontrolled RICH (ICP ≥ 22 mm Hg within 6 h of BCT) was an important predictor of mortality after BCT (adjusted hazard ratio 12.91, 95% confidence interval [CI] 2.788-59.749), and in particular, ICP ≥ 15 mm Hg within 6 h of BCT was associated with poor neurological outcome (adjusted odds ratio 9.36, 95% CI 1.664-52.614). Therefore, early-controlled ICP after BCT was associated with clinical prognosis. There were no significant differences in the complications associated with BCT between the two neurological outcome groups. No BCT-induced death was observed. The active and timely control of RICH may be beneficial for clinical outcomes in patients with RICH after brain tumor surgery.

[Sustained upgaze in a patient who ingested high doses of bupropion. Report of one case]. / Supraversión de la mirada en intoxicación mortal por bupropión.

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

Psychogenic coma after dental surgery under general anaesthesia.

Delayed awakening after general anaesthesia due to psychogenic coma is a phenomenon that rarely presents to the oral and maxillofacial surgeon. A case of psychogenic coma following general anaesthesia for dental extractions is presented here. It is recommended that patients at risk of conversion disorder should be counselled about the risks of psychogenic coma. Early diagnosis of this condition could lead to better patient management.

Myxedema Coma Following the Administration of Gonadotropin-releasing Hormone Agonist Complicated by Acute Pancreatitis.

Gonadotropin-releasing hormone (GnRH) agonists have been used for the treatment of various diseases. Although autoimmune thyroid disease has been reported as a rare complication of these agents, the symptoms are almost always transient and non-life-threatening. We herein report a rare case of an 83-year-old man receiving GnRH agonist treatment for prostate cancer who developed myxedema coma complicated by acute pancreatitis. This is the first report of myxedema coma potentially associated with a GnRH agonist. The follow-up of the thyroid function is necessary for patients undergoing treatment with GnRH agonists, especially those known to have or to be susceptible to autoimmune thyroid disease.

Supraversión de la mirada en intoxicación mortal por bupropión / Sustained upgaze in a patient who ingested high doses of bupropion: report of one case

Upgaze or sustained elevation of the eyes, is an alteration of ocular motility initially described in hypoxic coma. We report a 65-year-old woman admitted with hypotension and alteration of sensorium due to the ingestion of 9.5 g of Bupropion. She presented two seizures of short duration, without epileptic activity on the EEG. She had a persistent asynchronous myoclonus in extremities, tachycardia and prolonged Q-t. She suffered a cardiac arrest caused by asystole, which recovered quickly in five minutes. At that moment, upgaze appeared, associated with a persistent ocular opening, which persisted for days, but finally disappeared, without remission of coma. A magnetic resonance imaging done at the eighth day, showed hyperintensity of the oval center and corpus callosum which disappeared in a new imaging study done 30 days later, where images of hypoxia in the basal nuclei and cortex appeared. The patient died forty seven days after admission. Up-gaze is an ominous oculomotor alteration linked to an important but incomplete damage in the cerebral cortex, a condition that perverts some sequences of the ocular opening, reversing the Bell phenomenon and producing eyelid retraction.

Hyperammonemic coma after craniotomy: Hepatic encephalopathy from upper gastrointestinal hemorrhage or valproate side effect?: Case report and literature review.

RATIONALE: Postoperative coma is not uncommon in patients after craniotomy. It generally presents as mental state changes and is usually caused by intracranial hematoma, brain edema, or swelling. Hyperammonemia can also result in postoperative coma; however, it is rarely recognized as a potential cause in coma patients. Hyperammonemic coma is determined through a complicated differential diagnosis, and although it can also be induced as a side effect of valproate (VPA), this cause is frequently unrecognized or confused with upper gastrointestinal hemorrhage (UGH)-induced hepatic encephalopathy. We herein present a case of valproate-induced hyperammonemic encephalopathy (VHE) to illustrate the rarity of such cases and emphasize the importance of correct diagnosis and proper treatment. PATIENT CONCERNS AND DIAGNOSES: A 61-year-old woman with meningioma was admitted into our hospital. Radical resection of the tumor was performed, and the patient recovered well as expected. After administration of valproate for 7 days, the patient was suddenly found in a deep coma, and her mental state deteriorated rapidly. The diagnoses of hepatic encephalopathy was confirmed. However, whether it origins from upper gastrointestinal hemorrhage or valproate side effect is uncertain. INTERVENTIONS AND OUTCOMES: The patient's condition fluctuated without improvement during the subsequent 3 days under the treatment of reducing ammonia. With the discontinuation of valproate treatment, the patient regained complete consciousness within 48 hours, and her blood ammonia decreased to the normal range within 4 days. LESSONS SUBSECTIONS: VHE is a rare but serious complication in patients after craniotomy and is diagnosed by mental state changes and elevated blood ammonia. Thus, the regular perioperative administration of VPA, which is frequently neglected as a cause of VHE, should be emphasized. In addition, excluding UGH prior to providing a diagnosis and immediately discontinuing VPA administration are recommended.