Aminophylline and Cognitive Function After Sevoflurane Anaesthesia

This study has been completed.
Sponsor:
Information provided by:
King Faisal University
ClinicalTrials.gov Identifier:
NCT01022151
First received: November 26, 2009
Last updated: November 18, 2010
Last verified: November 2010
  Purpose

Early postoperative recovery of neurologic and cognitive functions is especially advantageous after fast-tracking ambulatory procedures to hasten home discharge after surgery.1 It is well known that volatile anaesthetic agents may generate adverse postoperative cognitive effects and even traces of it may affect task performance in healthy volunteers.2Hence, rapid elimination of the volatile anaesthetics may help reduce postoperative confusion and cognitive impairment in surgical patients by facilitating a faster recovery from general anaesthesia.3 Sevoflurane has been advocated for the routine anesthesia for ambulatory surgery patients. It activates adenosine A1 receptors in primary rat hippocampal cultures through the liberation of adenosine secondary to the interaction of with adenosine transport or key enzymes in adenosine metabolism.4 However; sevoflurane anaesthesia is associated with slower emergence and delayed early postoperative cognitive recovery than desflurane5 and xenon2 anaesthesia.

Aminophylline, which is a hydrophilic cyclic adenosine mono-phosphate (cAMP) dependent phosphodiesterase inhibitor has been used for long time to antagonize the sedative effects of morphine, diazepam, and barbiturates.6-7Aminophylline in doses of 2-5 mg/kg shortens the recovery from sevoflurane anaesthesia and improves bispectral index scores (BIS) with concurrent increases in heart rate which might have a detrimental effect in patients with ischaemic heart disease.8-11However, the use of smaller doses of 2-3 mg/kg is associated with less increases in heart rate. 10-11 The use of 1 mg/kg of Doxapram is comparable to 2 mg/kg of aminophylline in improvement of early recovery from sevoflurane anaesthesia secondary to its central nervous system stimulating effect rather than increased ventilatory elimination of sevoflurane.11 Currently, there is no available published studies have investigated the effects of either theophylline or doxapram on early postoperative cognitive recovery after balanced anaesthesia with sevoflurane.

We hypothesized that the use of small doses of aminophylline [2-3 mg/kg] may be comparable to larger doses in improvement of the early postoperative cognitive recovery from sevoflurane anaesthesia with associated non-significant increases in heart rate.

The present study investigated the effects of 1 mg/kg of doxapram, and 2, 3, 4, and 5 mg/kg of aminophylline on the early postoperative cognitive recovery using the Short Orientation Memory Concentration Test (SOMCT), response entropy (RE) state entropy (SE), difference between RE and SE (RE-SE), end-tidal sevoflurane concentration, haemodynamics, the times to eyes opening and to extubation and degree of sedation after sevoflurane anaesthesia in patients undergoing ambulatory surgery.


Condition Intervention Phase
Anaesthesia
Drug: Placebo [group P]
Drug: 0.2 mL/kg of aminophylline 10 mg/mL [group A2]
Drug: 0.2 mL/kg of aminophylline 15 mg/mL [group A3]
Drug: 0.2 mL/kg of aminophylline 20 mg/mL [group A4]
Drug: 0.2 mL/kg of aminophylline 25 mg/mL [group A5]
Drug: Doxapram 1 mg/kg [group D]
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Aminophylline Improves Early Postoperative Cognitive Recovery After Sevoflurane Anaesthesia: A Dose-Dependent Study

Resource links provided by NLM:


Further study details as provided by King Faisal University:

Primary Outcome Measures:
  • early postoperative cognitive function [ Time Frame: 30 min before induction and 30, 60 and 90 minutes after extubation. ] [ Designated as safety issue: Yes ]
    The SOMCT is a patient-based test designed to assess cognitive function in terms of level of orientation, memory, and concentration.


Secondary Outcome Measures:
  • changes in entropy variables, and end-tidal concentration (EtSevo) of sevoflurane, heart rate (HR), and mean arterial blood pressure (MAP) and recovery pattern [ Time Frame: 1 min after administration of the study drug (T0) for 15 min. ] [ Designated as safety issue: Yes ]

Enrollment: 180
Study Start Date: November 2007
Study Completion Date: August 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo [group P] Drug: Placebo [group P]
receive intravenous injection of 0.2 mL/kg of saline 0.9%L [group P]. All study solutions were injected within 1 min at T0 after discontinuation of sevoflurane. No stimulation was applied to patients during this period.
Active Comparator: Aminophylline 2 mg/Kg [group A2] Drug: 0.2 mL/kg of aminophylline 10 mg/mL [group A2]
receive intravenous injection of 0.2 mL/kg of aminophylline 10 mg/mL [group A2]. All study solutions were injected within 1 min at T0 after discontinuation of sevoflurane. No stimulation was applied to patients during this period.
Active Comparator: Aminophylline 3 mg/Kg [group A3] Drug: 0.2 mL/kg of aminophylline 15 mg/mL [group A3]
receive intravenous injection of 0.2 mL/kg of aminophylline 15 mg/mL [group A3]. All study solutions were injected within 1 min at T0 after discontinuation of sevoflurane. No stimulation was applied to patients during this period.
Active Comparator: Aminophylline 4mg/Kg [group A4] Drug: 0.2 mL/kg of aminophylline 20 mg/mL [group A4]
receive intravenous injection of 0.2 mL/kg of aminophylline 20 mg/mL [group A4]. All study solutions were injected within 1 min at T0 after discontinuation of sevoflurane. No stimulation was applied to patients during this period.
Active Comparator: Aminophylline 5 mg/Kg [group A5] Drug: 0.2 mL/kg of aminophylline 25 mg/mL [group A5]
receive intravenous injection of 0.2 mL/kg of aminophylline 25 mg/mL [group A5]. All study solutions were injected within 1 min at T0 after discontinuation of sevoflurane. No stimulation was applied to patients during this period.
Active Comparator: Doxapram 1 mg/kg [group D] Drug: Doxapram 1 mg/kg [group D]
receive intravenous injection of 0.2 mL/kg of doxapram 5 mg/mL [group D]. All study solutions were injected within 1 min at T0 after discontinuation of sevoflurane. No stimulation was applied to patients during this period.

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  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. ASA I-II patients
  2. aged 18-55 years
  3. scheduled for elective ambulatory surgery
  4. duration >1 h under general anaesthesia

Exclusion Criteria:

  1. cardiovascular diseases
  2. respiratory diseases
  3. neurological diseases
  4. psychiatric diseases
  5. pregnancy
  6. obesity
  7. adverse reaction to aminophylline or sevoflurane
  8. receiving xanthines, ß-agonist, anticholinergic
  9. history of cognitive dysfunction
  10. cerebrovascular disease
  11. recent history of infection or recent fever
  12. adverse reaction to aminophylline or sevoflurane
  13. alcoholism
  14. drug dependence
  15. those receiving xanthines, ß-agonist, anticholinergic, tranquilizers, anticonvulsants or antidepressants
  16. those who has habitual coffee consumption exceeding 2 cups per day
  17. unable to read
  18. suffering from serious hearing or vision impairment
  19. those who had not completed primary school
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01022151

Locations
Saudi Arabia
King Faisal University
Khobar, Eastern, Saudi Arabia, 31952
Sponsors and Collaborators
King Faisal University
Investigators
Principal Investigator: Mohamed R El Tahan, M.D. King Faisal University
  More Information

No publications provided by King Faisal University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mohamed R. El-Tahan, Department of Anaesthesia and Surgical ICU, Faculty of Medicine, King Faisal University, Dammam, KSA
ClinicalTrials.gov Identifier: NCT01022151     History of Changes
Other Study ID Numbers: 23/2007, 2007
Study First Received: November 26, 2009
Last Updated: November 18, 2010
Health Authority: Saudi Arabia: Ethics Committee

Keywords provided by King Faisal University:
Aminophylline
sevoflurane
anaesthesia
recovery
cognitive function
entropy

Additional relevant MeSH terms:
Aminophylline
Doxapram
Anesthetics
Sevoflurane
Cardiotonic Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Protective Agents
Central Nervous System Depressants
Central Nervous System Agents
Central Nervous System Stimulants
Platelet Aggregation Inhibitors
Hematologic Agents
Anesthetics, Inhalation
Anesthetics, General

ClinicalTrials.gov processed this record on July 29, 2014