Aminophylline and Cognitive Function After Sevoflurane Anaesthesia

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

Interventions

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.

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.

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.

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.

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.

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.

Sponsors & Collaborators

• King Faisal University

  lead OTHER

Principal Investigators

• Mohamed R El Tahan, M.D. · King Faisal University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-11-30

Primary Completion

2010-07-31

Completion

2010-08-31

Countries

• Saudi Arabia

Study Locations