Efficacy of Rivastigmine in the Management of Toxic Anticholinergic Delirium: A Prospective Study at Alexandria Poison Center
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Change in Glasgow Coma Scale (GCS) Score.
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- •Non-Toxic Delirium: Delirium of multifactorial origin or other medical causes (e.g., sepsis, hepatic encephalopathy, alcohol withdrawal, or metabolic disturbances).
- •Cardiac Contraindications: Baseline bradycardia, Atrioventricular (AV) block, or significant QTc prolongation.
- •Patients who experienced pulmonary aspiration as a complication of overdose, necessitating endotracheal intubation and mechanical ventilation
- •Severe Organ Impairment: Known severe renal or hepatic impairment.
- •Neurological Conditions: History of pre-existing seizure disorders or epilepsy.
- •Respiratory Conditions: Severe asthma or Chronic Obstructive Pulmonary Disease (COPD) due to the risk of bronchoconstriction.
- •Obstructions: Mechanical bowel obstruction or urinary tract obstruction.
- •Hypersensitivity: Known history of hypersensitivity to rivastigmine or other carbamates.
- •Pregnancy/Lactation: Pregnant or lactating women.
研究组 & 干预措施
Rivastigmine Treatment Group
A total of 100 patients presenting with anticholinergic delirium (including both hyperactive and hypoactive variants) were enrolled. Each participant received rivastigmine according to the established clinical titration protocol.
干预措施: Rivastigmine (Drug)
结局指标
主要结局
Change in Glasgow Coma Scale (GCS) Score.
时间窗: 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
时间窗: 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.
次要结局
- Post-Resolution Clinical Stability and Safety Profile.(From initial administration up to 6 hours post-resolution of delirium.)
- Median Time to Clinical Resolution.(From the time of initial administration until the achievement of clinical resolution.)
- Resolution of Peripheral Antimuscarinic Features.(From initial administration up to the point of CNS manifestation resolution (variable, typically within 2-12 hours).)
- The requirement for Additional Interventions(From Initiation of Rivastigmine Treatment Until 6 Hours After Recovery of Consciousness)
- Time to Clinical Resolution.(From the time of initial administration until the achievement of clinical resolution.)
研究者
shimaa Gaber
Assistant lecturer of forensic medicine and clinical toxicology
Alexandria University