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Paper Information

Journal:   JOURNAL OF IRANIAN SOCIETY ANAESTHESIOLOGY AND INTENSIVE CARE   2003 , Volume 23 , Number 42; Page(s) 26 To 34.
 
Paper: 

THE EFFECT OF POSITIVE END EXPIRATORY PRESSURE ON PHARMACOKINETIC BEHAVIOR OF AMINOPHYLLINE IN PATIENTS WITH ACUTE LUNG INJURY

 
 
Author(s):  NAJAFI A., SHARIAT MOHARARI R., MOJTAHEDZADEH M., KHAJAVI M.R., HADAVAND N., SADRAEI SIMA
 
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Abstract: 

The effect of positive end expiratory pressure (PEEP) on the hepatic elimination of low to moderate extraction ratio drugs has not been clearly defined.

We prospectively investigated the effect of PEEP on pharmacokinetic behavior of aminophylline in 30 (20 males, 10 females) critically ill adult patients with acute lung injury / acute respiratory distress syndrome. Based on their ventilation and oxygenation profiles, patients were decided to either low PEEP (5-9cmH2O) or high PEEP (10-15 cmH2O), supervised by attending physicians. All patients received the ordered dose of aminophylline infusion (3mg/kgin over 30 minutes and

then 15mg/h)after 2 hours of initiating PEEP. Blood samples were collected after loading dose, 2 and 6 hours into the aminophylline continuous infusion. Cirrhotic patients and those who received any drugs that could interacted with metabolism and clearance of aminophylline were not included. Vital signs were recorded before and after 2 hours of PEEP and each time of blood sampling.

Mean (±SD) of the pharmacokinetic key parameters of aminophylline in high (n=17) and low (n=13) PEEP groups were as followed: volume of distribution (Vd) = 0.42 (±o.15) L/Kg & 0.54(±0.13) L/Kg and aminophylline clearance =0.035) (±0.024) L/Kg/h & 0.056 (±0.025) L/Kg/h. Mean measured aminophylline concentration after 6 hours of loading dose were 6.24 (±3.50) mg/L and 3.98 (±1.04) mg/L. The calculated volume of distribution (p<0.03), clearance (p<0.05) and aminophylline serum concentration (p<0.05) in high versus low peep groups, were found to be significantly different. We also found that patients who had higher aminophylline serum concentration after 6 hours, had higher level of PaO2/FiO2 too (p=0.09). However this difference was not statistically significant, but clinically it was very important. And in patients with lower arterial pH, volume of distribution were greater however it was not significant either. (p=0.43).

Because of significant difference in calculated volume of distribution and aminophylline clearance in high and low PEEP group, this study showed that positive ventilation tends to reduce Vd and clearance of aminophylline in critically ill patients. Therapeutic drug monitoring of aminophylline, must be applied to reduce the likely-hood of therapeutic failure among

critically ill patients.

 

 
Keyword(s): ACUTE RESPIRATORY DISTRESS SYNDROME, ACUTE LUNG INJURY, POSITIVE END EXPIRATORY PRESSURE, AMINOPHYLLINE, PHARMACOKINETIC
 
References: 
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