Aminophylline and Cognitive Function After Sevoflurane Anaesthesia

NCT01022151 | Completed Phase 2

• 2 other identifiers: 23/20072007
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Anaesthesia

Keywords

Aminophylline; sevoflurane; anaesthesia; recovery; cognitive function; entropy

Outcome Measures

Primary Outcomes (1)

• early postoperative cognitive function

  The SOMCT is a patient-based test designed to assess cognitive function in terms of level of orientation, memory, and concentration.

  30 min before induction and 30, 60 and 90 minutes after extubation.

Secondary Outcomes (1)

• changes in entropy variables, and end-tidal concentration (EtSevo) of sevoflurane, heart rate (HR), and mean arterial blood pressure (MAP) and recovery pattern

  1 min after administration of the study drug (T0) for 15 min.

Study Arms (6)

Placebo [group P]

PLACEBO COMPARATOR

Drug: Placebo [group P]

Aminophylline 2 mg/Kg [group A2]

ACTIVE COMPARATOR

Drug: 0.2 mL/kg of aminophylline 10 mg/mL [group A2]

Aminophylline 3 mg/Kg [group A3]

ACTIVE COMPARATOR

Drug: 0.2 mL/kg of aminophylline 15 mg/mL [group A3]

Aminophylline 4mg/Kg [group A4]

ACTIVE COMPARATOR

Drug: 0.2 mL/kg of aminophylline 20 mg/mL [group A4]

Aminophylline 5 mg/Kg [group A5]

ACTIVE COMPARATOR

Drug: 0.2 mL/kg of aminophylline 25 mg/mL [group A5]

Doxapram 1 mg/kg [group D]

ACTIVE COMPARATOR

Drug: Doxapram 1 mg/kg [group D]

Interventions

Placebo [group P] DRUG

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.

Placebo [group P]

0.2 mL/kg of aminophylline 10 mg/mL [group A2] DRUG

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.

Aminophylline 2 mg/Kg [group A2]

0.2 mL/kg of aminophylline 15 mg/mL [group A3] DRUG

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.

Aminophylline 3 mg/Kg [group A3]

0.2 mL/kg of aminophylline 20 mg/mL [group A4] DRUG

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.

Aminophylline 4mg/Kg [group A4]

0.2 mL/kg of aminophylline 25 mg/mL [group A5] DRUG

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.

Aminophylline 5 mg/Kg [group A5]

Doxapram 1 mg/kg [group D] DRUG

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.

Doxapram 1 mg/kg [group D]

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• ASA I-II patients
• aged 18-55 years
• scheduled for elective ambulatory surgery
• duration \>1 h under general anaesthesia

You may not qualify if:

• cardiovascular diseases
• respiratory diseases
• neurological diseases
• psychiatric diseases
• pregnancy
• obesity
• adverse reaction to aminophylline or sevoflurane
• receiving xanthines, ß-agonist, anticholinergic
• history of cognitive dysfunction
• cerebrovascular disease
• recent history of infection or recent fever
• adverse reaction to aminophylline or sevoflurane
• alcoholism
• drug dependence
• those receiving xanthines, ß-agonist, anticholinergic, tranquilizers, anticonvulsants or antidepressants

Sponsors & Collaborators

• King Faisal University: lead

Study Sites (1)

King Faisal University

Khobar, Eastern Province, 31952, Saudi Arabia

Location

Related Publications (1)

• El Tahan MR. Effects of aminophylline on cognitive recovery after sevoflurane anesthesia. J Anesth. 2011 Oct;25(5):648-56. doi: 10.1007/s00540-011-1190-8. Epub 2011 Jul 14.

  PMID: 21755342 DERIVED

MeSH Terms

Interventions

Aminophylline; Doxapram

Intervention Hierarchy (Ancestors)

Ethylenediamines; Diamines; Polyamines; Amines; Organic Chemicals; Theophylline; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Mohamed R El Tahan, M.D.

  King Faisal University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: November 26, 2009
• First Posted: December 1, 2009
• Study Start: November 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: August 1, 2010
• Last Updated: November 19, 2010

Record last verified: 2010-11

Locations

SA (1)