Methylene blue: a controversial diagnostic acid and medication?

A narrative review of the literature was conducted to determine if the administration of methylene blue (MB) in humans has potential risks. Studies were identified from MEDLINE, Web of Science, Scopus, and Cochrane. MB is a diagnostic substance used during some diagnostic procedures and also a part of the treatment of several diseases including methemoglobinemia, vasoplegic syndrome, fosfamide-induced encephalopathy, and cyanide intoxication, and the detection of leaks or position of parathyroid corpuscles during surgery. Although the use of MB is historically justified, and it ought to be safe, because it originated as a diagnostic material, the basic toxicological characteristics of this substance are unknown. Despite reports of severe adverse effects of MB, which could significantly exceed any possible benefits evaluated for the given indication. Therefore, the clinical use of MB currently represents a controversial problem given the heterogeneity of available data and the lack of preclinical data. This is in conflict with standards of safe use of such substances in human medicinal practice. The toxic effects of the application of MB are dose-dependent and include serious symptoms such as hemolysis, methemoglobinemia, nausea and vomitus, chest pain, dyspnoea, and hypertension. Some countries regard MB as harmful because of the resulting skin irritation and triggering of an adverse inflammatory response. MB induced serotoninergic toxicity clinically manifests as neuromuscular hyperactivity. This review aims to summarize the current understanding concerning the indications for MB administration and define the potential adverse effects of MB.

Case Presentation Competition, 5 Back to Basics

Serotonin syndrome associated with clozapine withdrawal and concurrent selective serotonin reuptake inhibitor (SSRI) use has previously been reported. A 56-year-old female with schizophrenia was admitted for pyrexia, rigidity, and altered mental state after her second dose of clozapine restart. She had discontinued her long-term clozapine 2 weeks prior. She developed ventilatory failure, reduced consciousness, eye deviation, and worsening rigidity, requiring ICU support. Examination showed a right upper motor neurone syndrome with absent ankle reflexes. She had raised inflammatory markers and creatine kinase. Serum neuropathy, encephalitis screen, and COVID PCR were negative. Respiratory investigations were unfruitful. MRI head and spine did not show brain or cord signal change to correlate to signs. Lumbar puncture showed a quiet CSF, negative culture, viral PCR, and encephalitis antibodies. EEG showed bihemispheric background slowing. Despite clinical improvement, repeat examination showed persistent signs. She was diagnosed with serotonin syndrome after developing a bilateral tremor. Treatment with cyproheptadine correlated with an improvement in her signs, cognitive state, and EEG. Serotonin syndrome can present with reversible neuromuscular signs. With clozapine withdrawal, it can require a prolonged time course of recovery in contrast with classical serotonin syndrome. Cyprohepta- dine can cause agranulocytosis and this delays clozapine restart.

Risk of serotonin syndrome in critically ill COVID-19 patients receiving linezolid and opioids concomitantly: A retrospective cohort study

Introduction: Linezolid is an oxazolidinone antibiotic characterized by a reversible, non-selective monoamine oxidase inhibitory (MAOI) effect. Combining linezolid with MAOIs may increase serotonin syndrome (SS) risk. Secondary to its high lung tissue penetration, linezolid is recommended in patients with suspected or confirmed resistant gram-positive bacterial pneumonia, especially if vancomycin cannot be used. Opioids are required for sedation and analgesia in patients with respiratory failure requiring invasive mechanical ventilation. However, it remains unclear whether co-administration of linezolid with opioids should be avoided due to the risk of Serotonin syndrome. Research Question or Hypothesis: Whether combing linezolid with opioids will increase the incidence of SS in coronavirus disease 2019 (COVID-19) critically ill patients. Study Design: Retrospective observational study. Methods: All adult patients admitted to the intensive care units with COVID-19 pneumonia who received linezolid between March 2020 and September 2020 were included in the study. The primary outcome is the prevalence of SS defined by Hunter's criteria. SS was confirmed if the patient had spontaneous clonus;inducible clonus plus agitation or diaphoresis;ocular clonus plus agitation or diaphoresis;tremor plus hyperreflexia;or hypertonia plus fever plus ocular clonus or inducible clonus. Descriptive statistical analysis was done using SPSS version25. Results: We included 106 patients, most of the patients were males (91.5%). Approximately half of the patients had hypertension and diabetes (51.9%, and 44.3%, respectively). More than half of the cohort (56.6%) received a concomitant opioid agent. Morphine and fentanyl were the most commonly prescribed opioids (37.7% and 34%, respectively). Among patients who received opioids, only one incident of SS (1.6%) manifested as spontaneous clonus. However, this patient developed spontaneous clonus post cardiac arrest, which made the association with the linezolid-opioids combination doubtful. Conclusion: In this study, the incidence of SS was low in COVID-19 patients who received concomitant linezolid and opioids. However, larger prospective studies are required to confirm this finding.

Acute psychosis and serotonin syndrome in the setting of "Triple-C" overdose: a case report.

BACKGROUND: Over-the-counter medication overdose is a difficult diagnostic challenge for many physicians as common drug screening assays cannot detect these substances. We present a case of acute psychosis, serotonin syndrome, and anticholinergic overdose-like properties in the setting of Coricidin HBP Cough & Cold tablets, known by their street name Triple-C. This is the first case report we are aware of involving a patient presenting with these symptoms and requiring critical-care-level support. CASE PRESENTATION: A 31-year-old African American female with a past medical history of anxiety, childhood asthma, previous methamphetamine abuse, and coronavirus disease 2019 infection in August 2020 was brought to the emergency department by the local police department with altered mental status. Initial blood work, including extended drug screens, were unremarkable for a definitive diagnosis. This patient required critical-care-level support and high sedation because of her symptoms. Collateral history revealed the patient regularly consumed Triple-C daily for the 6 weeks prior to admission. A trial off sedation was attempted after 24 hours with no complications. The patient admitted to regular Triple-C consumption and auditory hallucinations since adolescence. She was discharged safely after 48 hours back into the community. She was lost to follow-up with psychiatry and internal medicine; however, she was evaluated in the emergency room 1 month later with a similar psychiatric presentation. CONCLUSION: Overdose of Triple-C should be kept in the differential diagnosis of patients presenting with a triad of psychosis, serotonin syndrome, and anticholinergic overdose, in the setting of unknown substance ingestion.

New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations.

Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic neuronal uptake of serotonin and norepinephrine and prolong the effects of the monoamines in the synaptic cleft within the central nervous system, leading to increased postsynaptic receptor activation and neuronal activities. Serotonin-norepinephrine reuptake inhibitors can have multiple clinical indications, including as the first-line agents for the management of depression and anxiety, and as analgesics in the treatment of chronic pain. The effects of reuptake inhibition of norepinephrine and serotonin are often dose-dependent and agent-dependent. There are five FDA-approved serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, levomilnacipran, milnacipran and sibutramine) currently being marketed in the United States. As the COVID-19 pandemic significantly increased the incidence and prevalence of anxiety and depression across the country, there are significantly increased prescriptions of these medications perioperatively. Thus, anesthesiologists are more likely than ever to have patients administered with these agents and scheduled for elective or emergency surgical procedures. A thorough understanding of these commonly prescribed serotonin-norepinephrine reuptake inhibitors and their interactions with commonly utilized anesthetic agents is paramount. There are two potentially increased risks related to the continuation of SNRIs through the perioperative period: intraoperative bleeding and serotonin syndrome. SNRIs have some off-label uses, more new indications, and ever-increasing new applications in perioperative practice. This article aims to review the commonly prescribed serotonin-norepinephrine reuptake inhibitors and the current clinical evidence regarding their considerations in perioperative anesthesia and analgesia.

Unprovoked serotonin syndrome-like presentation of SARS-CoV-2 infection: A small case series.

Clinicians and researchers have reported an array of neurological abnormalities in coronavirus disease 2019 (COVID-19), and while serotonin excess has been observed we are unaware of reports of central nervous system serotonin toxicity in COVID-19. We present two cases that resemble serotonin syndrome in COVID-19, but without identifiable inciting medications. A 54-year-old with multiple sclerosis and diabetes mellitus presented with altered mental status. His altered sensorium was attributed to diabetic ketoacidosis, but his condition quickly deteriorated with fever to 105 degrees Fahrenheit, rigidity in all extremities, inducible clonus, and hyperreflexia. He was intubated and was treated for possible meningitis and seizure. Neurologic workup was negative for acute pathology. Despite acetaminophen, his core temperature remained elevated to 105 degrees Fahrenheit. He was treated with external cooling and cyproheptadine and within 48 h, his fever, rigidity, hyperreflexia, and clonus resolved. He was extubated and discharged home on day 14. A 72-year-old with hyperlipidemia was admitted with tremors, 4 days after testing positive for COVID-19. His symptoms rapidly worsened, and he was transferred to the Intensive Care Unit on day 3 in extremis, febrile to 104.4 degrees Fahrenheit, heart rate of 180 beats per minute, and apparent whole body myoclonus. He was intubated and developed fever refractory to acetaminophen requiring external cooling. Extensive neurologic workup was negative. He received cyproheptadine and slowly improved. He was extubated and discharged to rehab on day 11. These cases represent a unique presentation in COVID-19 that must be considered and requires a high index of suspicion.

Abnormal movements in hospitalized COVID-19 patients: A case series.

BACKGROUND: Abnormal movements in Covid-19 patients have been reported with varying degree of frequency, prompting neurologic consultation and additional diagnostic evaluation. We sought to evaluate the frequency and etiology of abnormal movements among hospitalized Covid-19 patients undergoing neurologic consultation. METHODS: We retrospectively analyzed the first 50 consecutive patients with confirmed Covid-19 hospitalized at our tertiary medical care center who underwent acute inpatient neurology consultation from March 2020 through May 2020. Indication for neurologic consultation and diagnostic studies performed were identified by electronic medical record review. RESULTS: Of the 50 initial consultation requests, 11 (22.0%) patients were evaluated for abnormal movements (nine male and two female). Myoclonus was diagnosed in 6/11 (54.5%) patients. Additionally, two patients were diagnosed with seizures (confirmed on EEG in one), while two additional patients were diagnosed with tremor (physiologic and probable functional). A single case of serotonin syndrome was also identified. CONCLUSION: Abnormal movements observed in hospitalized Covid-19 patients can have a wide range of etiologies and were a frequent initial indication for neurologic consultation. Myoclonus was the most frequent type of abnormal movement observed. Early clinical recognition and directed diagnostic work-up is essential for accurate diagnoses in these patients.