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 the clearance of theophylline in 30 (20 males and 10 females) intubated critically ill adult patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The Mean (±SD) age was 57±17 years, creatinine clearance 86±36 ml/min, serum albumin 3.2±0.57 mg/dl and the median APACHE (acute physiology and chronic health evaluation) II score was 25 (with a range of 16 to 34). Critically ill patients who had met the diagnostic criteria for ALI/ARDS were enrolled on PEEP in low (5-9 cmH2O) and high (10-15 cmH2O) levels. All patients received the ordered dose of aminophylline infusion (3 mg/kg over 30 min and then 15 mg/h) after 2 h of initiating PEEP. Blood samples were collected after the loading dose, 2 and 6 h the aminophylline continuous infusion. Vital signs were recorded before and after 2 h of PEEP and each blood sampling interval. Cirrhotic patients and those who had received any drug which could interact with the metabolism and clearance of theophylline, were not included. The Mean (±SD) value of the pharmacokinetic key parameters of theophylline in high (n=17) and low (n=13) PEEP groups were as follows: Vd=0.42 (±0.15) L/kg and 0.54 (±0.13) L/kg, clearance = 0.035 (±0.024) L/h/kg and 0.056 (±0.025) L/h/kg. Mean measured theophylline concentrations following loading dose were 7.08 mg/L and 5.09 mg/L. The calculated volume of distribution (P<0.03), clearance (P<0.05) and theophylline serum concentration (P<0.05), in high versus low PEEP group, were found to be significantly different. Positive ventilation tends to reduce Vd and clearance of theophylline in critically ill patients.

Background: During gynecologic laparoscopy, pneumoperitoneum, and the position of the patient's head can lead to pathophysiologic changes in cardiovascular and respiratory systems, complicating the management of anesthesia in these patients. One of the strategies for improving the respiratory status of patients undergoing laparoscopy is the use of Positive End-Expiratory Pressure (PEEP). Objectives: This study aimed to evaluate the effect of different levels of PEEP on the respiratory status of patients undergoing gynecologic laparoscopy. Methods: In this clinical trial, 60 patients with ASA I were randomly assigned to three groups to control anesthesia: ZEEP (PEEP 0 cmH2O; 20 cases), PEEP5 (PEEP 5 cmH2O; 20 cases), and PEEP10 (PEEP 10 cmH2O; 20 cases). Respiratory and hemodynamic variables of patients were compared before general anesthetic induction and immediately after CO2 insufflation at intervals of 5, 10, 20, 30, and 60 min and the end of the operation in the three study groups. Results: The PEEP application improved pH, PaCO2, and PaO2 levels at the end of pneumoperitoneum compared to baseline when compared with the non-use of PEEP (ZEEP group). Also, the frequency of dysrhythmia in the use of PEEP in controlled ventilation was significantly lower in patients with PEEP10 (P < 0. 05). The application of PEEP5 resulted in similar effects to PEEP10 in the levels of respiratory variables. Conclusions: The PEEP application is associated with improved arterial blood gas in patients with gynecologic laparoscopy. The use of PEEP10 has a greater effect on the improvement of respiratory parameters and complications of pneumoperitoneum.

Background: The incidence of atelectasis after coronary artery bypass graft surgery is highly recommended due to the impact of different levels of PEEP to prevent these complications. The aim of this study was to investigate the effects of different levels of PEEP after coronary artery bypass graft surgery.Materials and Methods: This study was performed by clinical trial. The sample size in this study was 90 patients. Non-probability sampling was conducted in consecutive patients that using a stratified block randomized to intervention and control groups (each group n=45). In the control group of patients after surgery, upon arrival in the intensive care unit until tracheal extubation rates PEEP of 5 cm H2O received Patients in the intervention group after entering the intensive care unit for 4 hours average PEEP of 10 cm H2O received. Six hours after tracheal extubation atelectasis of the final diagnosis of chest radiographs, oxygen saturation and body temperature were used. For statistical analysis, chisquare test and t-test used.Results: The incidence of atelectasis in the intervention group, in 7 patients were about (15.6%) in the control group, and in 16 patients were about (35.6%) which was statistically significant difference (P=0.03). The mean arterial oxygen saturation was more higher in the intervention group rather than the control group and the difference was statistically significant (P=0.025).Conclusion: This study shows that the use of PEEP levels of 10 cm H2O after coronary artery bypass graft surgery can reduce the incidence of postoperative atelectasis. So, it is recommended to use this method in order to reduce the incidence of atelectasis.

known as a mainstay in respiratory management of ARDS patients. Pressure controlled - inverse ratio (PC-IRV) with I/E=2/1 ventilation is another technique which can be used for respiratory management of these patients. AS there is still controversy in which technique is the best for respiratory management in ARDS patients, this study was done to compare the effect of CMV+PEEP and PC-IRV on pulmonary and hemodynamic parameters in ARDS patients. Materials and Method: In this prospective randomized clinical trial study, 50 ARDS patients requiring mechanical ventilation were divided into two groups. 25 of them underwent mechanical ventilation with CMV+PEEP (group 1) and the other 25 were ventilated with PCV-IRV technique (group 2). Ventilatory parameters (Vt, RR, PEEP, FiO2) and inspiratory flow waveform were kept constant in both groups. Mean arterial blood press Peak Inspiratory Pressure (PIP), Mean Airway Pressure (MAP), Plateau Pessure (Pplat), Peak Inspiratory Pressure (PIP), ABG, and PaO2/FiO2 were measured at first and sixth hours after the start of mechanichal ventilation in both groups and the results were compared to those obtained at hour zero. Results: PaO2 and PaO2/FiO2 were both increased at first and sixth hour of ventilatory support in both groups, and the PaO2/FiO2 obtained at the first and 6th hour was significantly higher in patients on PC-IRV compared to patients on CMV+PEEP. PIP was significantly less in PC-IRV group when compared to CMV + PEEP group at the first and 6th hour of ventilation. Pplat remianed less than 30 cm of water in PC-IRV group. MAP was increased insignificantly at first and 6th hour PC-IRV group. Mean arterial pressure was decreased insignificantly in both groups. Decrease of pulse pressure was significantly less in PC-IRVgroup at hour 6th in comparison to hour zero. Conclusion: In comparison to CMV+PEEP, PC-IRV technique increases oxygenation and decreases PIP in ARDs patients.    

Positive ventilation has shown to have an influence on pharmacokinetic and disposition of some drugs. Beacause phenytoin with a narrow therapautic range, is the most commonly used drug for prophylaxis and treatment of early seizures after acute brain injuries, in the present study the effect of short term PEEP (5-10 cm H2O for at least 8 hours) on phenytoin serum concentration and pharmacokinetic parameters such as Vmax and clearance in brain injured patients under mechanical ventilation was examined. Ten patients with moderate to severe acute brain injury who were placed on mechanical ventilation with an initial PEEP level of 0-5 cm H2O were included in the study. Patients received phenytoin loading dose of 15 mg/kg followed by a maintenance daily dose of 3-7 mg/kg initiated within 12 hours of loading dose. Sampels were taken on two different occasions before and after PEEP elevation. Total phenytoin serum concentrations were determined by HPLC method. A time invarient Michaelis-Menten pharmacokinetic model was used to calculate Vmax and clearance for each patient. Derrived variables were calculated as follows: Vmax, 3.5-6.8 and 3.7-8.2 mg/kg/day; Clearance, 0.1-0.7 and 0.1-1.2 l/kg/day (before and after PEEP elevation, respectively). Our data have shown a wide range of variability (2.6-32.5 mg/l) in phenytoin serum concentrations. There were no statistically significant differences in the measured total concentrations (p=0.721) and calculated Vmax and clearance (p=0.285) before and after PEEP elevation. Administration of fluid and inotropic agents, limitation in application of higher levels of PEEP and drug interactions, shall be considered as possible explanations for these findings.

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.  

Background: The effects of positive ventilation on hepatic elimination of phenytoin with low extraction ratio characteristic have not yet been studied.Methods and Materials: In an observational prospective study, seven patients with traumatic brain injury (4 females and 3 males), old than 18 years old, GCS< 8, intubated with cute lung injury (Pao2/Fio2< 300) and without any history of hepatic (±SD) for age, CLcr and Alb were 45±58 ml/min and 3.7± 55 gm/dl. Results: The mean and range for height, weight, ideal body weight and APACHE II were 167 (160-175) cm, 64 (55-70) kg, 63 (54-73) kg and 21 (12-28) respectively. For our intubated and mechanically ventilated traumatic brain injury patients, we considered 0<PEEP≤5 H2O based on the patients pulmonary profile and attending decision. Supposing K3= 4 mg/L and Vd= 0.6 L/kg, the results were:MAP b.p.e= 108.72±10.62 mmHg, MAp2 a.p.e= 114.48±8.11 mmHg P value= 0.32 MAP= Mean arterial pressureCtrough b.p.e= 12.57±1.99 mg/l, Ctrough a.p.e= 10.42±3.63 mg/l           P value= 0.09 in the presence of MAP elevationCtrough b.p.e= 17.82±7.27 mg/l, Ctrough a.p.e= 22.95±4.43 mg/l         P value= 0.23 in thepresence of MAP reductionVmax= 6.85±0.23 mg/kg/d, Vmax a.p.e= 7.28±0.85 mg/kg/d               P value= 0.25 in thepresence of MAP elevationVmax b.p.e= 6.48±2.1 mg/kg/d, Vmax a.p.e= 6.15±1.81 mg/kg/d         P value= 0.41 in thepresence of MAP reductionConclusion: We concluded that although there is not any statistically significant correlation between mean arterial pressure (MAP) and pharmacokinetic key parameters of phenytoin following PEEP elevation (p<0.05) but clinically PEEP can cause MAP to be increased, Leading to increasing and decreasing of Vmax and Ctrough respectively and vice versa.

Introduction: Finding the probable governing pattern of PEEP and CVP changes is an area of interest for incharge physicians and researchers. Therefore, the present study was designed with the aim of evaluating the relationship between the mentioned pressures. Methods: In this quasi-experimental study, patients under mechanical ventilation were evaluated with the aim of assessing the effect of PEEP change on CVP. Non-trauma patients, over 18 years of age, who were under mechanical ventilation and had stable hemodynamics, with inserted CV line were entered. After gathering demographic data, patients underwent 0, 5, and 10 cmH2O PEEPs and the respective CVPs of the mentioned points were recorded. The relationship of CVP and PEEP in different cut points were measured using SPSS 21.0 statistical software. Results: 60 patients with the mean age of 73.95± 11.58 years were evaluated (68.3% male). The most frequent cause of ICU admission was sepsis with 45.0%.5 cmH2O increase in PEEP led to 2.47 ± 1.53 mean difference in CVP level. If the PEEP baseline is 0 at the time of 5 cmH2O increase, it leads to a higher raise in CVP compared to when the baseline is 5 cmH2O (2.47 ± 1.53 vs. 1.57 § 1.07; p = 0.039). The relationship between CVP and 5 cmH2O (p = 0.279), and 10 cmH2O (p = 0.292) PEEP changes were not dependent on the baseline level of CVP. Conclusion: The findings of this study revealed the direct relationship between PEEP and CVP. Approximately, a 5 cmH2O increase in PEEP will be associated with about 2.5 cmH2O raise in CVP. When applying a 5 cmH2O PEEP increase, if the baseline PEEP is 0, it leads to a significantly higher raise in CVP compared to when it is 5 cmH2O (2.5 vs. 1.6). It seems that sex, history of cardiac failure, baseline CVP level, and hypertension do not have a significant effect in this regard.