QT-Interval Prolongation Associated with Supratherapeutic Guanfacine Concentration: A Case Report.

INTRODUCTION: Guanfacine, an alpha-2 adrenergic agonist, is used to treat attention deficit hyperactivity disorder (ADHD). Although cardiovascular effects including hypotension and bradycardia are common adverse effects of guanfacine, the effect of guanfacine on QT intervals remains unclear. The association between the serum concentration of guanfacine and its toxicity has also not been fully investigated. CASE REPORT: This is a case of a 21-year-old woman with ADHD who developed repeated presyncope 1 day before admission. She was taking 3 mg of extended-release guanfacine and 50 mg of sertraline. On admission, she had bradycardia and hypotension. An electrocardiogram (ECG) showed a QT interval of 0.68 s and a QTcF interval of 0.648 s. The QT intervals were manually measured and corrected by the Fridericia formula (QTcF = QT/RR1/3). Although she denied taking an overdose of guanfacine and other drugs, we suspected guanfacine toxicity. The serum guanfacine concentration was 13.0 ng/mL on admission and decreased to 3.2 ng/mL on day 1 and 0.4 ng/mL on day 2. Changes in QTcF intervals and her vital signs correlated with serum guanfacine concentrations. CONCLUSION: Supratherapeutic serum guanfacine concentrations may induce QT prolongation.

Collapse-related traumatic intracranial hemorrhage following out-of-hospital cardiac arrest: A multicenter retrospective cohort study.

Background: Sudden loss of consciousness as a result of cardiac arrest can cause severe traumatic head injury. Collapse-related traumatic intracranial hemorrhage (CRTIH) following out-of-hospital cardiac arrest (OHCA) may be linked to poor neurological outcomes; however, there is a paucity of data on this entity. This study aimed to investigate the frequency, characteristics, and outcomes of CRTIH following OHCA. Methods: Adult patients treated post-OHCA at 5 intensive care units who had head computed tomography (CT) scans were included in the study. CRTIH following OHCA was defined as a traumatic intracranial injury from collapse due to sudden loss of consciousness associated with OHCA. Patients with and without CRTIH were compared. The primary outcome assessed was the frequency of CRTIH following OHCA. Additionally, the clinical features, management, and consequences of CRTIH were analyzed descriptively. Results: CRTIH following OHCA was observed in 8 of 345 enrolled patients (2.3%). CRTIH was more frequent after collapse outside the home, from a standing position, or due to cardiac arrest with a cardiac etiology. Intracranial hematoma expansion on follow up CT was seen in 2 patients; both received anticoagulant therapy, and one required surgical evacuation. Three patients (37.5%) with CRTIH had favorable neurological outcomes 28 days after collapse. Conclusions: Despite its rare occurrence, physicians should pay special attention to CRTIH following OHCA during the post-resuscitation care period. Larger prospective studies are warranted to provide a more explicit picture of this clinical condition.

PCO2 on arrival as a predictive biomarker in patients with out-of-hospital cardiac arrest.

BACKGROUND: Treating patients with out-of-hospital cardiac arrest (OHCA) requires early prediction of outcome, ideally on hospital arrival, as it can inform the clinical decisions involved. This study evaluated whether partial pressure of carbon dioxide (PCO2) on arrival is associated with outcome at one month OHCA patients. METHODS: This was a single-center retrospective study of adult OHCA patients treated between January 2016 and December 2020. Outcomes were defined along the Cerebral Performance Category (CPC) scale. Primary outcome was mortality (CPC 5) at one month. Secondary outcomes were death or unfavorable neurological outcome (CPC 3-5) and unfavorable neurological outcome (CPC 3-4) at one month. Multivariable analysis was adjusted for age, sex, witnessed cardiac arrest, bystander cardiopulmonary resuscitation, initial shockable rhythm, and time from call to emergency medical services to hospital arrival. RESULTS: Out of 977 OHCA patients in the study period, 19 were excluded because they were aged under 18 years, 79 because they underwent extracorporeal cardiopulmonary resuscitation, and 101 due to lack of PCO2 data. This study included 778 patients total; mortality (CPC 5) at one month was observed in 706 (90.7%), death or unfavorable neurological outcome (CPC 3-5) in 743 (95.5%), and unfavorable neurological outcome (CPC 3-4) in 37 (4.8%). In multivariable analysis, high PCO2 levels showed significant association with mortality (CPC 5) at one month (odds ratio [OR] [per 5 mmHg], 1.14; 95% confidence interval [CI], 1.08-1.21), death or unfavorable neurological outcome (CPC 3-5) (OR [per 5 mmHg], 1.29; 95% CI, 1.17-1.42), and unfavorable neurological outcome (CPC 3-4) (OR [per 5 mmHg], 1.21; 95% CI, 1.04-1.41). CONCLUSIONS: High PCO2 on arrival was significantly associated with mortality and unfavorable neurological outcome in OHCA patients.

Unexpectedly Prolonged Serotonin Syndrome and Fatal Complications Following a Massive Overdose of Paroxetine Controlled-Release.

Symptoms caused by a selective serotonin reuptake inhibitor (SSRI) overdose are often mild and can be managed with supportive care and close monitoring, even when complicated by serotonin syndrome. There are limited pharmacokinetic data regarding massive overdoses of paroxetine, and the severity of an SSRI overdose is likely to be underestimated. We describe a fatal case of severe serotonin syndrome and acute respiratory distress syndrome (ARDS) following an overdose of controlled-release paroxetine. A 53-year-old male with depression presented with altered consciousness. He had ingested controlled-release paroxetine along with other medications. On arrival, he had ocular flutter and myoclonus, and blood examinations revealed acute kidney injury and rhabdomyolysis, which suggested serotonin syndrome. Computed tomography (CT) showed pharmacobezoars in the esophagus and stomach. Symptoms of serotonin syndrome and hypotension persisted despite administration of high doses of vasopressors with endotracheal intubation. We performed endoscopic decontamination to remove pharmacobezoars from the stomach. Finally, he developed severe ARDS and died due to respiratory failure on day 23. Sequential serum concentrations of paroxetine were 5.38 µg/mL at admission and 3.21 µg/mL on day 7, both above lethal levels. This case highlights the potential for fatal complications and prolonged toxicity in the case of a massive overdose of controlled-release paroxetine. We should recognize that such an overdose may be life-threatening and should consider aggressive interventions including endoscopic decontamination. A better understanding of the pharmacokinetics of a massive SSRI overdose would be helpful for optimal management.

The impact of vitamin D on the onset and progress of Kawasaki disease.

BACKGROUND: The seasonal epidemic of Kawasaki disease (KD) in winter in Japan suggests that low vitamin D status may affect KD through the immune system. We aimed to evaluate the effect of vitamin D on the onset and clinical course of KD. METHODS: We conducted a case-control study to compare 25-hydroxyvitamin D (25(OH)D) levels in KD patients admitted to our hospital between March 2018 and June 2021, with those in healthy controls from published Japanese data. In patients with KD, we evaluated the association of 25(OH)D levels with intravenous immunoglobulin resistance and coronary artery lesions. RESULTS: We compared 290 controls and 86 age-group-adjusted patients with KD. The 25(OH)D levels in KD patients were lower than those in the controls (median: 17 vs. 29 ng/mL, P < 0.001). In winter, 25(OH)D levels in KD patients were lower than those in summer (median: 13 vs. 19 ng/mL). The adjusted odds ratios for the onset of KD were 4.9 (95% CI: 2.5-9.6) for vitamin D insufficiency (25(OH)D: 12-20 ng/mL) and 29.4 (95% CI: 12.5-78.2) for vitamin D deficiency (25(OH)D < 12 ng/mL). Among 110 KD patients, 25(OH)D levels at diagnosis of KD were not associated with intravenous immunoglobulin resistance or coronary artery lesions. CONCLUSIONS: The 25(OH)D levels in patients with KD were lower than those in the controls, especially in winter. Lower 25(OH)D levels in winter were associated with an increased risk of KD onset. It remains to be elucidated whether the observed association has a causal relationship.

Traumatic Tonsillar Hemorrhage during Hemophilia A Treatment with Emicizumab.

Reports on the treatment of bleeding associated with emicizumab administration are scarce. Herein, we report the case of an eight-year-old boy with moderate hemophilia A with an inhibitor who experienced tonsillar hemorrhage while undergoing emicizumab treatment. He visited our hospital for postprandial bloody vomiting. The activated partial thromboplastin time was 20.8 s; only a small amount of hemorrhage was observed in the retropharyngeal space, and tranexamic acid was administered. He experienced hematemesis on Day 2 of hospitalization, and fiberoptic laryngoscopy confirmed hemorrhage from the posterior tonsil. Varicose vessels were observed at the soft palate, and considering thrombosis, an emergency cauterization was performed instead of bypass therapy. In small children, observing the tonsils is difficult, and the coagulation ability of the patient with hemophilia A is inferior to that of healthy people, even under emicizumab administration. Thus, active hemorrhage assessment and appropriate hemostatic control are necessary.

Association Between Converting Asystole From Initial Shockable ECG Rhythm Before Extracorporeal Cardiopulmonary Resuscitation and Outcome.

BACKGROUND: Initial electrocardiogram (ECG) rhythm is a predictor of outcomes in out-of-hospital cardiac arrest (OHCA) in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). However, ECG rhythm often changes before ECPR, and the consequence of this change remains unclear. This study aimed to assess the relationship between the conversion of ECG rhythm from initial shockable rhythm before ECPR and mortality. PATIENTS AND METHODS: This was a retrospective cohort study of OHCA patients with initial shockable rhythm who underwent ECPR between January 2010 and September 2020. Patients were classified into two groups: asystole (patients whose ECG rhythm converted to asystole at any time before initiating ECPR) and non-asystole (patients whose ECG rhythm did not convert to asystole at any time before initiating ECPR) groups. The primary outcome was in-hospital mortality. RESULTS: A total of 102 patients were included in the study; in-hospital mortality rate was 46.1% (n = 47) and 76 (74.5%) patients had unfavorable neurological outcomes (Cerebral Performance Category: 3-5). There were 33 and 69 patients in the asystole and non-asystole groups, respectively. The mortality rates in the asystole and non-asystole groups were 69.7% and 34.8%, respectively (P = 0.001). On multivariable analysis, the asystole group showed a significant association with mortality (odds ratio, 5.42; 95% confidence interval, 2.11-15.36; P < 0.001). CONCLUSION: Conversion to asystole before ECPR at any time in patients with OHCA is associated with mortality in patients with an initial shockable ECG rhythm.

Severe Anaphylactic Shock Following a Slow Loris Bite in a Patient with Cat Allergy.

The slow loris monkey is one of the few venomous mammals. Its venom repels predators and can cause anaphylactic shock and even death in humans. The venom protein has been evaluated and has high sequence similarity to cat allergen; however, no studies involving subjects with cat allergy and who have been exposed to slow loris venom have been reported. We herein report the first case of severe anaphylactic shock following a slow loris bite in a patient with cat allergy.

Unusual Adverse Event of Tetanus: Rectus Sheath Hematoma.

Tetanus is a nervous system disorder characterized by muscular spasms and autonomic hyperactivity, such as unstable blood pressure. We herein report a case of tetanus in a patient in shock complicated with a rectus sheath hematoma caused by rupture of a pseudo-aneurysm of the inferior epigastric artery. A rectus sheath hematoma might be misdiagnosed as unstable blood pressure associated with autonomic hyperactivity, which is usually observed in patients with tetanus. The possibility of the occurrence of bleeding complications should be considered if a patient with tetanus has severe and persistent blood pressure reduction.

Cytomegalovirus enterocolitis in a patient with dihydropyrimidine dehydrogenase deficiency after capecitabine treatment: A case report.

INTRODUCTION: 5-Fluorouracil (5-FU) is widely used for cancer treatment. The reduced activity of dihydropyrimidine dehydrogenase (DPD), the key enzyme in 5-FU inactivation, increases a patient's risk of developing severe 5-FU related toxicity. However, screening for DPD deficiency is rarely performed before 5-FU administration. PRESENTATION OF CASE: Our patient was a 69-year-old man with rectal cancer (T2N1bM0 stage IIIA) who underwent laparoscopic low anterior resection. He developed severe neutropenia and diarrhea 15 days after the administration of capecitabine for adjuvant chemotherapy, and was admitted to our hospital. Four days after admission, he was transferred to the intensive care unit for sepsis. DPD protein screening revealed DPD deficiency. On day 27, massive melena suddenly appeared. He died of continual bleeding 41 days after admission. Pathological autopsy revealed cytomegalovirus enterocolitis. DISCUSSION: The administration of 5-FU to patients with DPD deficiency is lethal. Genotypic and phenotypic assessments are reliable tests for DPD deficiency. A genetic study can effectively screen for DPD deficiency; however, its use has not been established in the national insurance system. Patients with DPD deficiency tend to develop severe neutropenia, so clinicians should pay attention to opportunistic infections such as cytomegalovirus enterocolitis. CONCLUSION: Screening for DPD deficiency is necessary prior to 5-FU administration.