Delirious Behavior Research Articles

Coadministration of Voriconazole and Rifabutin Can Increase the Risk of Adverse Drug Reactions in Patients with Multiple Infections.

Coinfection of tuberculosis or nontuberculous mycobacteria and Aspergillus presents a challenge in medication selection because of the pharmacokinetic interactions between rifampin and voriconazole. Some researchers have suggested the use of rifabutin as an alternative to rifampin because of its lower hepatic cytochrome P450 enzyme induction potency despite its contraindication to drug labels. This study presents clinical cases of voriconazole and rifabutin coadministration and their potential risks. This retrospective study was conducted using clinical data from patients who met the following criteria: (1) admitted to Seoul National University Hospital between July 2014 and August 2023 and (2) concurrently administered rifabutin and voriconazole for more than 5 days. Among the 6 patients analyzed, 4 experienced adverse drug reactions (ADRs). Three patients experienced visual and auditory hallucinations, lower extremity numbness, or delirious behavior. Two patients had prolonged the time from the start of the Q wave to the end of the T wave intervals, and 1 had elevated aspartate aminotransferase and alanine aminotransferase levels. In addition, 2 patients experienced severe nausea, poor oral intake, and weight loss. Despite receiving 1.81-fold the recommended voriconazole dosage, a therapeutic concentration (1.0-5.5 mg/L) was not achieved because of cytochrome P450 induction by rifabutin. However, during septic shock, the voriconazole concentration increased by 13.7- to 36-fold. Concurrent use of rifabutin and voriconazole was associated with ADRs, including the time from the start of the Q wave to the end of the T wave prolongation, hallucinations, and severe nausea. Moreover, initially, there was a significant decrease in voriconazole concentrations; however, these concentrations substantially increased during septic shock. Therefore, it is essential to monitor drug concentrations and ADRs during concurrent use of voriconazole and rifabutin.

Perioperative Delirium/Agitation Associated With the Use of Anesthetics and/or Adjunct Agents: A Study of Patient Behaviors, Injuries, and Interventions to Mitigate Risk

Anesthetics and adjunct agents have a long history of being associated with patients engaging in delirious or agitated behavior in a perioperative setting. Prior to this study, few have explored the topic with a focus on safety for both the patient and staff. We explored the Pennsylvania Patient Safety Reporting System (PA-PSRS) database for event reports to identify bouts of delirium/ agitation associated with anesthetics and/or adjunct agents that occurred during the pre-, intra-, or postoperative period. We identified 97 event reports from 63 healthcare facilities over a two-year period. Patients’ ages ranged from 1 to 91 years and 66% of the patients were reported as male. Also, 8% of the delirium/agitation occurred preoperatively, 8% intraoperatively, and 84% postoperatively. Across all three operative periods, 62% of the reports described dangerous/nonviolent behavior and 26% described dangerous/violent behavior. Additionally, 40% of the event reports described one or more patient injuries (e.g., cardiopulmonary arrest, asphyxiation, hematoma, prolapse/dehiscence, progressive ischemia) and 36% of the patients required additional healthcare services or monitoring (e.g., intra- or interfacility transfer, additional surgical procedure). Finally, 54% of the event reports described patient behavior that created an immediate and high risk of staff harm. Overall, the current study provides novel insight into how delirium/agitation has varying safety implications depending on the operative period. We encourage readers to review Table 5, which proposes a four-phase intervention package to prevent, treat, and de-escalate bouts of delirium/agitation.

Reversible splenial lesions during febrile illness with or without white matter lesions

ObjectiveReversible splenium lesions during febrile illness (RESLEF) are found in a spectrum. There are two types of corpus callosum (CC) lesions: CC-only type, with limited lesions and the CC (+) type, with extensive white-matter lesions. This retrospective study aimed to describe the differences in clinical findings between CC-only and CC (+) lesions and the association between onset age and clinico-radiological features in RESLEF. MethodsFifty-two episodes of CC-only or CC (+) lesions accompanied by neurological symptoms, e.g., seizures, delirious behavior (DB), and disturbance of consciousness (DC), from January 2008 to October 2019 were included. We analyzed the etiology (pathogen), clinical course, laboratory data, magnetic resonance imaging and electroencephalography findings, therapy, and prognosis. ResultsThe rate of DC in the CC (+) was significantly higher than that in the CC-only group (5/6 [83%] vs 7/46 [15%]; p = 0.0016). The median number of seizures in the CC (+) was also significantly higher than that in the CC-only group (4 [0–7] vs 0 [0–7]; p = 0.034). Further, in RESLEF, the median onset age (months) in the seizure was significantly lower than that in the no-seizure group (39 [12–74] vs 83 [28–174]; p = 0.0007). The median onset age (months) in the DB was significantly higher than that in the no-DB group (74.5 [26–174] vs 28 [12–139]; p = 0.003). ConclusionsIn RESLEF, CC (+) is a more severe neurological symptom than CC-only. Furthermore, the onset age is related to the type of neurological symptoms that appear.

Restraint use in the acute-care hospital setting: A cross-sectional multi-centre study

BackgroundRestraints are likely to negatively affect patients’ health and therefore a reduction in their usage is recommended for all health-care settings. To date, research on restrictive practices has concentrated on mental health and long-term care settings. In the acute-care hospital setting few studies have been published and these studies mainly focus on physical/mechanical restraints in specific subpopulations and/or on intensive care units. However, to ensure restraints are used as little as possible in the acute-care hospital setting, it seems important to investigate more comprehensively the use of restraints, to include all types of restraints irrespective of ward type or subpopulations and to identify factors associated with restraint use. ObjectiveThe aim of this study was to investigate restraint use regardless of ward type in the acute-care hospital setting, including restraint type, reasons for restraint use, process indicators when using restraints and restraint use-associated patient characteristics. MethodsUsing a cross-sectional multi-centre design, data were collected by means of an annual international prevalence measurement in acute-care hospitals in Switzerland and Austria. All hospitalised patients aged 18+ who gave informed consent were included. Data were collected at three measurement points between 2016 and 2018. Descriptive and multivariate logistic regression analyses were performed. ResultsA total of 29,477 patients hospitalised in 140 hospitals were included in this study. The prevalence rate for the use of at least one restraint over a 30-day period was 8.7% (n = 2577), with mechanical restraints representing the highest proportion of restraint type used (55.0%, n = 1417). The main reason for restraint use was fall prevention (43.8%, n = 1129), followed by confusion or delirious behaviour (20.4%, n = 525). In 64.3% of the cases (n = 1657), restraint use was documented in the patient file. Regular evaluation occurred in 42.9% of the cases (n = 1105). Care dependency had the strongest association with restraint use (odds ratio [OR] 25.00, 95% confidence interval [CI] 21.01–29.78 for completely dependant patients in comparison to completely independent patients), followed by mental and behavioural disorders (OR 2.36, 95% CI 2.15–2.59). ConclusionsRestraints are often utilised in hospitals in complex care situations such as with patients at risk of falling or with delirium. When using restraints the consideration of processes like documentation and evaluation shows great potential for improvement. Standardisation of these processes and education of the interprofessional team could be beneficial for raising awareness and for the sustainable reduction of restraint use.Tweetable abstract: In hospitals restraints are often used in complex care situations. However, their use seems to be insufficiently documented and evaluated.

Transient blindness associated with mild encephalitis/encephalopathy with a reversible splenial lesion (MERS): a case report and review of literature

BackgroundMild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinical-radiological syndrome that can be related to infectious and non-infectious conditions. The most prominent neurological symptoms are disturbance of consciousness, abnormal speech, delirious behavior, seizures, muscle weakness, ophthalmoplegia, facial nerve paralysis and headache. Here we report the case of a child with MERS presenting with the unusual symptom of bilateral transient blindness.Case presentationA 4-year-old female patient, with a history of fever, abdominal pain, loss of appetite and cough lasted for a few days, experienced 3 episodes of transient bilateral loss of vision with difficulty in walking. Her physical examination showed absence of focal neurological and meningeal irritation signs, although responsiveness was slightly impaired. The ophthalmologic evaluation, including a fundus oculi examination, was negative.The electroencephalogram showed slow activity in the temporo-occipital regions, more evident in the right hemisphere. A lumbar puncture was performed and cerebrospinal fluid analysis revealed normal glycorrhachia, cell counts, protein levels and IgG index.Magnetic resonance imaging of the brain showed a signal alteration in the splenium of the corpus callosum, without contrast enhancement. This finding was suggestive of a reversible cytotoxic lesion. Empiric antiviral treatment with acyclovir and intravenous dexamethasone was initiated. Polymerase chain reaction search for neurotropic viral nucleic acid sequences in the cerebrospinal fluid was negative, while a low number of HHV-6 DNA copies was detected in the blood.Electroencephalograms were repeated in the following days, showing a progressive normalization of the pattern. The child was discharged without symptoms after 10 days of treatment with oral corticosteroids. After 40 days, brain magnetic resonance imaging showed a complete normalization of the signal alteration in the splenium of the corpus callosum.ConclusionTransient blindness was reported as an initial symptom of MERS in a few children. To date, there is no evidence of effective treatment methods. Nonetheless, MERS diagnosis provides pediatricians with valuable prognostic information in order to reassure patients and their families about the good outcome of this disease.

Nationwide survey of influenza-associated acute encephalopathy in Japanese adults

BackgroundKnowledge of adult patients with influenza-associated acute encephalopathy (IAE) is limited. We conducted a detailed survey to investigate the prevalence, clinical features, associated outcomes, and prognostic factors in adult IAE patients. MethodA nationwide questionnaire on IAE patients was sent to the departments of Internal Medicine, Neurology, Neurosurgery, and Emergency and Critical Care at all hospitals with ≥200 beds in Japan. Results118 patients were diagnosed with IAE during the 2013/14 to 2015/16 influenza seasons, and the estimated annual incidence of IAE in Japanese adults was 0.98/1000,000 population. 44 patients were subsequently enrolled in the detailed study. 93% of patients exhibited disturbance of consciousness. Convulsions and delirious behavior were present in 26% and 40% of patients, respectively. 65% of patients received pulse corticosteroid therapy with methylprednisolone and 21% of patients received intravenous gamma-globulin therapy. 63% of patients achieved a good recovery, but 7% died. Multiple logistic regression analysis revealed that plasma glucose level demonstrated a statistically significant association with poor outcome.Conclusion: This nationwide survey provided data for the annual incidence and clinical features of IAE in Japanese adults. Hyperglycemia was indicated as an independent predictor of poor prognosis in IAE patients and reflected systemic hypercytokinemia in IAE pathogenesis.

Mild encephalitis/encephalopathy with a reversible splenial lesion in children.

We aimed to present clinical and radiologic characteristics of mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in children. Eight children (5 boys and 3 girls; median age, 5.9 years; age range, 8 months to 14.1 years) diagnosed with MERS between September 2015 and June 2017 were included in the study. We reviewed the patient's data, including demographic characteristics, prodromal and neurologic symptoms, neurologic examination, magnetic resonance imaging and electroencephalography findings, laboratory findings, treatment, and prognosis. Prodromal symptoms were nausea and vomiting (n=6), diarrhea (n=6), and fever (n=3). Initial neurologic symptoms were seizures (n=4), delirious behavior (n=1), drowsiness (n=1), ataxia (n=1), transient blindness (n=2), abnormal speech (n=2), and headache (n=1). Two patients had a suspected infective agent: urinary tract infection caused by Escherichia coli and gastroenteritis caused by rotavirus. Seven patients had type I lesions, comprising characteristic symmetric ovoid (n=6) and band-shaped (n=1) T2-weighted hyperintense lesions at the spenium of corpus callosum, and one patient had type II lesion with additional symmetric posterior periventricular lesions. The lesions were isointense to mildly hypointense on T1-weighted imaging and did not show enhancement. All lesions displayed restricted diffusion. In all patients, neurologic symptoms completely normalized < 48 hours from the onset of symptoms without any sequelae. MERS has characteristic imaging features and favorable outcome.

Mild encephalopathy with a reversible splenial lesion in a girl with acute pyelonephritis.

We report the case of a 12-year-old girl who had mild encephalopathy with a reversible splenial lesion (MERS) associated with acutepyelonephritis caused by Escherichia coli. The patient was admitted with a high fever, and she was diagnosed with acute pyelonephritis based on pyuria and the results of urine culture, which detected cefotaxime-sensitive E. coli. Although intravenous cefotaxime and tobramycin were administered, her fever persisted and her C-reactive protein level increased to 307 mg/L. On day 3 of admission, she demonstrated abnormal neuropsychiatric symptoms, such as delirium, ataxia, and word salad. Magnetic resonance imaging (MRI) of the brain performed on day 4 showed marked hyperintensities in the bilateral corpus callosum and deep white matter on diffusion-weighted images, with corresponding diffusion restriction on apparent diffusion coefficient mapping. No abnormalities or pathogens were detected in the cerebrospinal fluid; however, lipopolysaccharides (LPS, endotoxin) were detected in plasma (41.6 pg/mL), associated with acute neurological deterioration. Her clinical condition gradually improved, and no neurological abnormalities were observed on day 6. Follow-up brain MRI performed 2 weeks later showed near-disappearance of the previously noted hyperintense lesions. In this patient, we first proved endotoxemia in a setting of MERS. The release of LPS following antibiotic administration might be related to the development of MERS in this patient. The possibility of MERS should be considered in patients who present with acute pyelonephritis and demonstrate delirious behavior.

Clozapine: Since the very beginning?

IntroductionPsychosis in childhood and adolescence could be defined as having hallucinations, with the hallucinations occurring in the absence of insight. A broader definition includes symptoms such as delirious thoughts, disorganized speech, disorganized behavior, cognitive and mood symptoms and what is called negative symptoms. Several researches have been done focused in the treatment of first episode of psychosis showing clozapine as a keystone in the treatment of psychosis, especially in refractory first episodes.ObjectivesClozapine has unique efficacy in improving treatment-resistant patients with chronic schizophrenia but the moment of instauration remains unclear. There have always been doubts about the right moment to start clozapine, after two or more previous anti-psychotics or as first option.Materials and methodsWe report a 18-year- old woman with family history of severe psychosis. Her mum reasserted patient's symptoms contributing to a longer period of non-treating psychosis (about 10 months). Auditory hallucinations, incongruent mood and incoherent language appeared for the first time at the age of 17. High doses of two consecutive anti-psychotics were tried without remission and finally clozapine was initiated with clinical improvement.DiscussionIn clinical practice, a subgroup of psychotic patients experience, significant ongoing positive symptoms despite of using first line anti-psychotic medication.ConclusionMost recent research; suggest that clozapine may have an important role in the early treatment of first-episode patients, even becoming a first line option to consider.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion Associated with Rhinovirus Infection

We report a 7-year-old patient with mild encephalopathy with a reversible splenial lesion (MERS) presenting with recurrent delirious behavior, hallucinations and seizures following common cold.

Influenza-Associated Delirious Behavior

Dr Millichap has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Investigators from Japan retrospectively reviewed the medical records of children with influenza-associated delirious behavior (DB) to assess their clinical course.1 Children were eligible if they were admitted for treatment of rapid-antigen detection assay-confirmed influenza at the study hospital from 2009–2013, were diagnosed with DB, and had an MRI and EEG within 96 hours of DB onset. DB was defined as the presence of 1 or more of the following components: visual hallucinations, nonvisual sensory misperceptions, unexpected emotional changes, incoherent speech, purposeless …

Donepezil-Induced Onset of Rheumatoid Arthritis: Case Report and Literature Review

Donepezil has been approved for treatment of Alzheimer's disease. The common adverse reactions of donepezil in the treatment of Alzheimer's disease include diarrhea and nausea. However, there are also some other rare clinical cases been reported on administration of donepezil, such as mania and delirious behavior. Here, we report a patient with Alzheimer’s disease who was induced the onset of rheumatoid arthritis upon treatment with donepezil.

Clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination

We retrospectively collected three patients with clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination, and reviewed five patients, including two patients previously reported. The five patients (all males, aged 1 to 9) presented with fever, vomiting, or headache as the initial symptoms (day 0), suggesting meningitis, at 13 to 21days after mumps vaccination. Consciousness disturbance, delirious behavior, seizures, or dysarthria was observed on days 1 to 3, which had completely resolved before day 11. Hyponatremia was observed in all patients. A cerebrospinal fluid study showed pleocytosis, and confirmed the vaccine strain genome. MRI revealed reduced diffusion in the splenium of the corpus callosum on days 2 to 4, which had completely disappeared on the follow-up studies performed on days 7–15. EEG showed high voltage slow wave in three patients, which later normalized. These findings led to a diagnosis of MERS after mumps vaccination. MERS after mumps vaccination may be more common than previously considered. MERS is suspected when a male patient after mumps vaccination presents with neurological symptoms with hyponatremia, following symptoms of aseptic meningitis, and MRI would be performed to examine the splenium of the corpus callosum.

Alterations in the functional connectivity of frontal lobe networks preceding emergence delirium in children.

This study aimed to characterize the electroencephalogram in children who emerged with emergence delirium (ED) compared with children without ED using methods that involved the assessment of cortical functional connectivity. Children aged 5 to 15 yr had multichannel electroencephalographic recordings during induction and emergence from anesthesia during minor surgical procedures. Of these, five children displayed ED after sevoflurane anesthesia. Measures of cortical functional connectivity previously used to evaluate anesthetic action in adults were compared between ED and age-, sex-, and anesthetic-matched non-ED children during emergence from anesthesia. At the termination of sevoflurane anesthesia, the electroencephalogram in both ED and control patients showed delta frequency slowing and frontally dominant alpha activity, followed by a prolonged state with low-voltage, fast frequency activity (referred to as an indeterminate state). In children with ED, arousal with delirious behavior and a variety of electroencephalogram patterns occurred during the indeterminate state, before the appearance of normal wake or sleep patterns. The electroencephalogram in children without ED progressed from the indeterminate state to classifiable sleep or drowsy states, before peaceful awakening. Statistically significant differences in frontal lobe functional connectivity were identified between children with ED and non-ED. ED is associated with arousal from an indeterminate state before the onset of sleep-like electroencephalogram patterns. Increased frontal lobe cortical functional connectivity observed in ED, immediately after the termination of sevoflurane anesthesia, will have important implications for the development of methods to predict ED, the design of preventative strategies, and efforts to better understand its pathophysiology.

Differential diagnosis of delirious behavior in children with influenza.

Delirious behavior (DB) in children infected with influenza virus is an important symptom associated with encephalopathy. As children with influenza-associated DB with encephalopathy may require therapy whereas children with influenza-associated DB without encephalopathy do not, distinguishing between these conditions is essential. To clarify these differences and identify the most common features of acute encephalopathy, we retrospectively reviewed the clinical course, laboratory data, magnetic resonance imaging (MRI) and electroencephalography (EEG) findings, therapy, and prognosis of 48 children with influenza exhibiting DB. Of the 48 children, 37 and 11 were diagnosed with influenza A and B, respectively. Moreover, 40 were diagnosed with DB without encephalopathy (DBNE group) and 8, with DB with encephalopathy (DBE group). Reversible splenial lesion (RESLE) was detected in 7 patients in the DBNE group, mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) in 2 patients, and a mild form of acute encephalopathy with biphasic seizures and late reduced diffusion in 1 patient in the DBE group. Serum sodium levels <136mEq/L were observed in 28 cases. Disturbance of consciousness was observed in 25 cases, seizure in 20, and slow waves on EEG in 22. Methylprednisolone pulse therapy was administered in 8 cases. No cases of neurological sequelae were observed. Although most of the clinico-radiological features of the DBNE and DBE groups did not differ substantially, marked differences were observed in the age at onset, initial neurological symptoms, duration of DB, rate of seizure, and slowing of background activity on EEG. These differences should be considered when distinguishing between DBNE and DBE in children.

Delirious behavior or mild reduction of consciousness mimicking influenza‐associated encephalopathy

During the A/H1N1 pandemic, patients suffered from impaired consciousness. They were suspected of or diagnosed as having influenza-associated encephalopathy (IAE) in an emergency situation. Their symptoms resembled those of a recently described 'unique clinical group', which were reported to have a favorable prognosis. We retrospectively examined 46 patients and divided them into two groups. Group IC contained the 26 patients with persisting impaired consciousness. The remainder of the patients were categorized into group R, consisting of patients with only neurological symptoms without impaired consciousness. Male predominance (22 male/four female) was noted in group IC. Patient age ranged from 5 to 12 years old (mean ± SD, 7.7 ± 2.3 years). Impaired consciousness such as delirious behavior or mild reduction of consciousness lasted continuously or intermittently from 5 min to 2.5 days. On electroencephalogram, semi-rhythmic high-voltage slow waves in the parieto-occipital regions and diffuse high-voltage slow waves were observed in eight and in two patients, respectively. In group R, there was no gender predominance. Patient age ranged from 1 to 9 years old (mean ± SD, 4.1 ± 2.5 years). All group R patients were clinically diagnosed with febrile seizure. Some of the characteristics in group IC resembled those of the unique clinical group, and are part of a continuous clinical spectrum. Some patients may have favorable outcome without specific treatment.

Marked elevation of interleukin-6 in mild encephalopathy with a reversible splenial lesion (MERS) associated with acute focal bacterial nephritis caused by Enterococcus faecalis

This report describes two cases of mild encephalitis/encephalopathy with reversible splenial lesion (MERS) associated with acute focal bacterial nephritis (AFBN). The patients, who presented with fever and delirious behavior, exhibited hyponatremia and markedly elevated interleukin (IL)-6 in cerebrospinal fluid (CSF) and serum. Enterococcus faecalis was detected in the urine culture. After ampicillin treatment, their consciousness improved without neurological sequelae. Moreover, a diffusion-weighted MRI abnormality, i.e., intensified signals in splenium of the corpus callosum, disappeared. MERS is a possible complication of AFBN. Elevated CSF IL-6 levels suggest that remote activation of intracerebral immune response through the immune–neuroendocrine pathway might play an important role in the pathophysiology of MERS.

Clinico-radiological spectrum of reversible splenial lesions in children

Recently, many cases of children presenting reversible splenial lesions during febrile illness (RESLEF) have been reported; however, their overall clinico-radiological features are unclear.To describe the clinico-radiological features, we retrospectively reviewed the etiology (pathogen), clinical course, laboratory data, magnetic resonance imaging and electroencephalography (EEG) findings, therapy, and prognosis of 23 episodes in 22 children (1 child recurred) who presented neurological symptoms, with RESLEF.The etiologies (pathogens) varied. Seizure occurred in 7 episodes, disturbance of consciousness (DC) in 13, and delirious behavior in 18. Serum sodium levels <136mEq/L were observed in 18 episodes. Lesions outside the splenium were found in 4 cases. Slow waves were observed on EEG in 10 episodes. Methylprednisolone pulse therapy was given in 7 cases. No case resulted in neurological sequelae. Among 23 episodes, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) was diagnosed in 6 episodes, whereas non-MERS was observed in 17 episodes. No difference was observed in almost all the clinico-radiological features’ data between the 2 groups. The largest differences were observed in the rate of purposeless movement, DC, extension of the abnormal lesions outside the splenium, and marked slowing of background activity on EEG.RESLEF exhibit a spectrum of clinico-radiological features. These results suggest that non-MERS and MERS both are a part of a larger pathological condition, which we have termed as RESLEF spectrum syndrome. Given the view that such a syndrome exists, the clinical characteristics and position of non-MERS and MERS become clear.

Influenza-Related Postinfectious Encephalomyelitis Complicated by a Perforated Peptic Ulcer

Influenza virus infection is extremely common and raises global concern due to the increasing prevalence of pandemic H1N1 infection. Influenza may occasionally be associated with neurologic complications and, also, rarely with gastrointestinal complications. Here, we report a rare case complicated with appendicitis, duodenum perforation, and transient delirious behavior after influenza A viral infection in a pediatric patient aged 14 years. The transient delirious behavior could be attributed to postinfectious encephalopathy. The perforated peptic ulcer could have resulted from influenza infection, could have been an adverse event related to oseltamivir administration, or could have been a complication of preceding gastroenteritis. Our case highlights the importance of pediatric healthcare workers to be aware of possible complications arising from both influenza infection and oseltamivir therapy, even though some of these complications may be relatively rare.

Late-Onset Delirium After an Overdose of Acetaminophen in a Case of Benzodiazepine Dependence

Back to table of contents Previous article Next article LettersFull AccessLate-Onset Delirium After an Overdose of Acetaminophen in a Case of Benzodiazepine DependenceYutaro Suzuki, M.D., Ph.D., Keita Shinada, M.D., Naoki Orime, M.D., and Toshiyuki Someya, M.D., Ph.D.Yutaro SuzukiSearch for more papers by this author, M.D., Ph.D., Keita ShinadaSearch for more papers by this author, M.D., Naoki OrimeSearch for more papers by this author, M.D., and Toshiyuki SomeyaSearch for more papers by this author, M.D., Ph.D.Published Online:1 Oct 2013https://doi.org/10.1176/appi.neuropsych.12100243AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: A 42-year-old man with depression overdosed on acetaminophen 37.5g and was admitted to our hospital. He had been taking flunitrazepam 12 mg, etizolam 5 mg, clotiazepam 15 mg, lormetazepam 6 mg, every day for over a year. He was diagnosed with acetaminophen intoxication and benzodiazepine (BZD) withdrawal. Gastric lavage was carried out, and N-acetylcysteine was administered, with mild hepatic dysfunction. Because his delirium did not improve, he was admitted to the psychiatric ward on Day 5. Although his delirium became aggravated after an attack of grand mal convulsions on Day 6, his delirium completely disappeared on Day 10. Electroencephalographic examination (EEG) on Day 12 was normal; hepatic dysfunction had also improved upon biochemical testing carried out on Day 14, with no observation of other abnormalities, and discharge from the hospital was planned. However, disorientation and visual hallucinations were observed from Day 18, with no contributing factors, and the patient returned to a state of delirium state once again. No abnormalities were observed on the head CT scan and blood/biochemical testing on Day 20. Slowing of brain waves was observed on EEG compared with that of Day 12. Subsequently, although his delirium continued for over 2 weeks, the delirium completely disappeared on Day 40, and slowing of brainwaves was improved upon EEG. The delirium did not recur after then, and the patient left the hospital.Various types and amounts of BZD withdrawal and acetaminophen intoxication may be considered as the cause for the initial delirium. Delirium and seizures are well known as major withdrawal symptoms of BZD. Acetaminophen can cause delirium in pediatric patients,1 but there are very few reports on the effects of acetaminophen on the central nerves in adults. The lethal dose of acetaminophen is 13g to 25g, but an amount exceeding this was taken in this case, and it cannot be ruled out that intoxication due to acetaminophen caused the delirium. However, the cause of the second delirium episode should be open to discussion. The first delirium was completely clinically improved, and EEG on Day 12 was normal. Afterward, delirium occurred again, even though other new physical complications did not occur. There have been no reports in which withdrawal delirium from BZD occurred after once recovering. Furthermore, delirium was prolonged for a long period of time in elderly patients and dementia patients;2 however, there are no reports similar to this case, in which withdrawal delirium from BZD continued for a total of 40 days, combining the first and second episodes, in a relatively young patient with no underlying physical disorders. Therefore, we believe that the lethal dose of acetaminophen intoxication caused the second delirium. Because acetaminophen intoxication can cause delirium, clinicians should pay attention to side effects other than its liver dysfunction.Dept. of PsychiatryNiigata University Graduate School of Medical and Dental SciencesNiigata, JapanCorrespondence: Dr. Suzuki; e-mail: [email protected]niigata-u.ac.jpThe study was funded by a Grants-in-Aid for Scientific Research (Kakenhi) from the Japan Society for the Promotion of Research (JSPS, #17591199 and #19591344), Mitsubishi Pharma Research Foundation, and Health and Labour Sciences Research Grants (Research on Psychiatric and Neurological Diseases and Mental Health, H17-kokoro-002) to Toshiyuki Someya, and a Grant-in-Aid for Scientific Research (Kakenhi) from JSPS (#20591362) to Yutaro Suzuki. The funding sources played no role in study design; in the collection, analysis, and interpretation of data; in the writing of the report, or in the decision to submit the paper for publication.Conflict of interest: Dr Someya has received research support and honoraria from Asahi Kasei, Astellas Pharma, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical, Pfizer Japan, Shionogi, Takeda Pharmaceutical, and Yoshitomiyakuhin. The other authors have no conflicts of interest to disclose.References1 Okumura A, Fukumoto Y, Hayakawa F, et al.: Antipyretics and delirious behavior during febrile illness. Pediatr Int 2006; 48:40–43Crossref, Medline, Google Scholar2 Mittal V, Muralee S, Williamson D, et al.: Review: delirium in the elderly: a comprehensive review. Am J Alzheimers Dis Other Demen 2011; 26:97–109Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited ByBenzodiazepines/paracetamol15 November 2014 | Reactions Weekly, Vol. 1527, No. 1 Volume 25Issue 4 Fall 2013Pages E28-E29 Metrics PDF download History Published online 1 October 2013 Published in print 1 October 2013