Evaluation if Physostigmine Reduces Symptoms in Patients Who Has Developed a Delirium in Intensive Care After a Surgery

Study Overview
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Brief Summary
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Evaluation if physostigmine reduces symptoms in patients who has developed a delirium in Intensive care after a surgery

Official Title
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Monocenter, Double Blind, Randomised, Placebo Controlled Study to Evaluate Physostigmine for the Treatment of Delirium in Perioperative Intensive Care Medicine

Conditions
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Suspected Delirium After Elective or Emergency Heart Surgery, CAM-ICU Diagnosed Delirium

Intervention / Treatment
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* Drug: Physostigmine
* Other: Sodium Chloride solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients of both genders aged > 18 years, < 85 years of ICU C1 after elective or emergency heart surgery with or without extracorporeal circulation (heart-lung machine and/or extracorporeal membrane oxygenation), with suspected delirium. (May be suspected if a patient does not show adequate improvement of vigilance 24 h after adequate reduction or stop of sedative medicine) Patients (>18a, <85a) with CAM-ICU diagnosed delirium Patients of legal capacity and patients with appointed representative Exclusion Criteria: Asthma hypersensitivity against Physostigmine salicylate, Sodium metabisulfite, Nitrogen gangrene mechanical obstipation mechanical urinary retention Dystrophia myotonica Depolarization block after depolarising muscle relaxants Intoxications with irreversibly acting cholinesterase inhibitors closed head trauma obstructions at gastro-intestinal tract and at urinary tract neurological diseases left ventricular ejection fraction < 40% Simultaneous Participation in other clinical trials or participation ind other clinical trials in the last 30 days untreated coronary heart disease wish to have children, pregnancy or nursing patients with addictive disorder in medical history

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Physostigmine<br>Physostigmine administered intravenously at a dose of 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram | Drug: Physostigmine<br> <br> * Other names: Anticholium;|
| Placebo Comparator: Sodium Chloride solution<br>solution administered intravenously 24 mg + 25 min a 0,04 mg/kg milligram(s)/kilogram | Other: Sodium Chloride solution<br> <br> * Other names: NaCl solution as Placebo comparator;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change of vigilance or symptoms of the delirium measured by Richmond Agitation Sedation Score (RASS) |  | baseline to 48 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| reduction of weaning time at mechanical ventilator of patients with symptoms of delirium |  | baseline to 48 hours after administration | 
| change in the spontaneous EEG and auditory evoked potentials | for the spontaneous EEG, we expect a shift in the frequency characteristics, measure is the spectrogram, more precisely the amplitude per frequency (band) and the phase information derived via Fourier Transform and Wavelet transformation The paradigm of the auditory stimulation is a roving paradigm (Science 13 May 2011: Vol. 332 no. 6031 pp. 858-862 DOI: 10.1126/science.1202043 •Report Preserved Feedforward But Impaired Top-Down Processes in the Vegetative State Melanie Boly1,2,*, Marta Isabel Garrido2, Olivia Gosseries1, Marie-Aurélie Bruno1, Pierre Boveroux3, Caroline Schnakers1, Marcello Massimini4, Vladimir Litvak2, Steven Laureys1, Karl Friston2) Measures will be differences in the mismatch negativity and in the phase synchronization between electrodes | baseline to 48 hours after administration | 
| impact of the variability of heart rate | heart rate variability is a dimensionless parameter, assessing the variability of the heart rate from ECG measures (Heart Rate Variability Conny M. A. van Ravenswaaij-Arts, MD; Louis A. A. Kollee, MD, PhD; Jeroen C. W. Hopman, MSc; Gerard B. A. Stoelinga, MD, PhD; and Herman P. van Geijn, MD, PhD [+-] Article and Author Information Ann Intern Med. 1993;118(6):436-447. doi:10.7326/0003-4819-118-6-199303150-00008 ) | baseline to 48 hours | 
| change in development of muscular force | muscular force is measured with a force gauge, measured in [Newton] | baseline up to 48 hours | 
| Occurence of Adverse events |  | baseline to 4 weeks after treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Delirium, CAM-ICU