Anticholinergic Delirium, Antipsychotic Toxicity, Clozapine Poisoning, CNS Depression, Hypoactive Delirium, Procyclidine Induced Delirium, Tricyclic Antidepressant Poisoning
Conditions
Keywords
Rivastigmine, Clozapine, Quetiapine, Carbamazepine, Procyclidine, Cyproheptadine, Acetylcholinesterase Inhibitors, CNS depression, Hypoactive dilirium, Anticholinergic delirium
Brief summary
This study aims to evaluate the clinical efficacy and safety of rivastigmine in reversing the full spectrum of anticholinergic delirium including hypoactive delirium which is presented with CNS depression and hyperactive or agitated delirium. The study was conducted on 100 patients at the Poison Control Center of Alexandria University Main Hospital. The primary objective is to assess the effectiveness of rivastigmine in restoring consciousness and improving cognitive function in patients presenting with delirium and depressed mental status using GCS and RASS score.
Detailed description
This prospective clinical study assess the efficacy of rivastigmine in reversing the full spectrum of anticholinergic delirium. The study encompasses both hyperactive (agitated) and hypoactive (depressed mental status/CNS depression) presentations, with a specific focus on the hypoactive variant. While anticholinergic toxicity is traditionally associated with agitation, this research highlights its role in causing hypoactive delirium and assesses how rivastigmine facilitates the recovery of consciousness and cognitive function. Participants: The study includes 100 patients (aged ≥18 years) with Anticholinergic delirium-induced by exposure to drugs with anticholinergic properties-manifests either as agitated delirium (characterized by confusion, agitation, disorientation, and hallucinations) or hypoactive delirium (characterized by CNS depression). Patient status was assessed using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS) upon admission to the Poison Control Center of Alexandria University Main Hospital (AUMH). Intervention Protocol: Administration: An initial enteral dose of 6 mg is administered orally or by nasogastric tube. Transdermal patch was administered when nasogastric route was non-feasible. Dosing: Additional 6 mg doses are administered every 2 hours until achieving GCS 15 /RASS 0 Assessment & Resolution: Awareness, cognition, consciousness, and the level of agitation or sedation were evaluated using the Glasgow Coma Scale (GCS) and the Richmond Agitation-Sedation Scale (RASS). These assessments were performed at baseline, 2 hours, and 6 hours for both the oral and transdermal groups, and at 12 hours exclusively for the transdermal group. Clinical success was defined as achieving a GCS score of 15 and a RASS score of 0.
Interventions
DRUGRivastigmine
Initial Dose: A starting dose of 6 mg is administered either orally or via a Nasogastric Tube (NGT) for patients with impaired swallowing or depressed consciousness. Titration: Additional 6 mg doses are repeated every 2 hours based on clinical need until the resolution of delirium. Alternative Route: Transdermal patches (9.5 mg/24h) are applied in cases where enteral administration is not feasible or based on clinical judgment.
Sponsors
Alexandria University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
This is an open-label study in which all participants received the active intervention. Blinding was not feasible due to the clinical status of the participants, who presented with significantly impaired consciousness or toxic delirium (including CNS depression and coma). This clinical state rendered the participants unaware of the intervention at the time of administration. Furthermore, the emergency nature of the toxicological intervention and the need for rapid clinical assessment made masking impractical.
Intervention model description
This is a single-arm, open-label prospective study involving 100 patients who met the inclusion criteria for toxic anticholinergic delirium. All enrolled participants received the intervention (rivastigmine) following a standardized titration protocol. The study uniquely focuses on the reversal of CNS depression and hypoactive delirium, in addition to agitated states. Clinical response and level of arousal were quantitatively monitored using the Glasgow Coma Scale (GCS) to assess the degree of consciousness and the Richmond Agitation-Sedation Scale (RASS) to evaluate the degrees of sedation and agitation, ensuring a comprehensive assessment of the drug's efficacy across the full spectrum of delirium.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Exposure: acute exposure to anticholinergic agents (e.g., clozapine, tricyclic antidepressants). Clinical Presentation: Presence of anticholinergic delirium either hyperactive/agitated or hypoactive/CNS depression/coma).
Exclusion criteria
1. Non-Toxic Delirium: Delirium of multifactorial origin or other medical causes (e.g., sepsis, hepatic encephalopathy, alcohol withdrawal, or metabolic disturbances). 2. Cardiac Contraindications: Baseline bradycardia, Atrioventricular (AV) block, or significant QTc prolongation. 3. Patients who experienced pulmonary aspiration as a complication of overdose, necessitating endotracheal intubation and mechanical ventilation 4. Severe Organ Impairment: Known severe renal or hepatic impairment. 5. Neurological Conditions: History of pre-existing seizure disorders or epilepsy. 6. Respiratory Conditions: Severe asthma or Chronic Obstructive Pulmonary Disease (COPD) due to the risk of bronchoconstriction. 7. Obstructions: Mechanical bowel obstruction or urinary tract obstruction. 8. Hypersensitivity: Known history of hypersensitivity to rivastigmine or other carbamates. 9. Pregnancy/Lactation: Pregnant or lactating women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glasgow Coma Scale (GCS) Score. | Baseline (0 hour), 2 hours post-administration (all patients), 6-8 hours, and 12 hours (transdermal group). For patients receiving additional oral/NGT doses, assessments were repeated 2 hours after each supplemental dose up to 6 hours after resolution. | The Glasgow Coma Scale (GCS) is a clinical scale used to assess a patient's level of consciousness. The total score was recorded for all participants at baseline and subsequent intervals to evaluate the clinical response to rivastigmine. The GCS score ranges from a minimum of 3 to a maximum of 15, where higher scores indicate a better neurological outcome (improved consciousness). For the oral/NGT group, assessments were performed 2 hours after the initial dose and after each supplemental dose. For the transdermal group, monitoring included a 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a GCS score of 15 and a RASS score of 0. |
| Change in Richmond Agitation-Sedation Scale (RASS) Score | Baseline, 2h (all), 6-8h & 12h (patch group), and up to 6h post-resolution (both groups) | The Richmond Agitation-Sedation Scale (RASS) is used to evaluate the clinical response to rivastigmine. The RASS is a 10-point scale ranging from a minimum value of -5 (denoting unarousable/deep sedation) to a maximum value of +4 (denoting combative/extreme agitation). A score of 0 represents an alert and calm state, which indicates the best clinical outcome for this study. Scores were recorded for all participants at baseline and 2 hours to evaluate the initial response. For the oral/NGT group, additional assessments were performed 2 hours after each supplemental dose. For the transdermal group, monitoring focused on the 6 to 8-hour window and at 12 hours. Clinical resolution is defined as reaching a RASS score of 0 and a GCS score of 15. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-Resolution Clinical Stability and Safety Profile. | From initial administration up to 6 hours post-resolution of delirium. | Monitoring for potential adverse effects related to rivastigmine, including cardiac complications (e.g., bradycardia, arrhythmias) and cholinergic side effects (e.g., excessive secretions, vomiting). Safety is further assessed by the absence of relapse during a mandatory 6-hour observation period following the resolution of delirium and CNS depression. Patients are deemed clinically stable if they remain symptom-free throughout this period prior to discharge. |
| Time to Clinical Resolution. | From the time of initial administration until the achievement of clinical resolution. | The duration (measured in hours) elapsed from the initial dose of rivastigmine until the patient achieves clinical resolution, defined as reaching a Glasgow Coma Scale (GCS) score of 15 and a Richmond Agitation-Sedation Scale (RASS) score of 0. |
| Resolution of Peripheral Antimuscarinic Features. | From initial administration up to the point of CNS manifestation resolution (variable, typically within 2-12 hours). | Monitoring the normalization of heart rate and the resolution of urinary retention (without the requirement for catheterization) in patients presenting with these features at baseline. |
| The requirement for Additional Interventions | From Initiation of Rivastigmine Treatment Until 6 Hours After Recovery of Consciousness | The percentage of patients requiring rescue therapy or escalation of care after receiving rivastigmine. This includes the need for benzodiazepines for sedation, the use of physical restraints, or clinical escalation to endotracheal intubation and intensive care unit (ICU) admission. |
Countries
Egypt
Contacts
STUDY_CHAIRNaima A Sherif, Professor of Forensic Medicine
University of Alexandria
STUDY_CHAIRRagaa T Darwish, Professor of Forensic Medicine
University of Alexandria
STUDY_CHAIRSahar Y Issa, Assoc Prof Forensic Med
University of Alexandria
Outcome results
None listed