systematic review on pharmacokinetic changes in critically ill patients role of extracorporeal, membrane oxygenation

Several factors including disease condition and different procedures could alter pharmacokinetic profile of drugs in critically ill patients. For optimizing patient's outcome, changing in dosing regimen is necessary. Extracorporeal Membrane Oxygenation [ECMO] is one of the procedures which could change pharmacokinetic parameters. The aim of this review was to evaluate the effect of ECMO support on pharmacokinetic parameters and subsequently pharmacotherapy. A systematic review was conducted by reviewing all papers found by searching following key words; extracorporeal membrane oxygenation, ECMO, pharmacokinetic and pharmacotherapy in bibliography database. Different drug classes have been studied; mostly antibiotics. Almost all of the studies have been performed in neonates [as a case series]. ECMO support is associated with altered pharmacokinetic parameters that may result in acute changes in plasma concentrations with potentially unpredictable pharmacological effect. Altreation in volume of distribution, protein binding, renal or hepatic clearance and sequestration of drugs by ECMO circuit may result in higher or lower doses requirement during ECMO. As yet, definite dosing guideline is not available. ECMO is extensively used recently for therapy and as a procedure affects pharmacokinetics profile along with other factors in critically ill patients. For optimizing the pharmacodynamic response and outcome of patients, drug regimen should be individualized through therapeutic drug monitoring whenever possible

Recombinant human erythropoietin reduces plasminogen activator inhibitor and ameliorates pro-inflammatory responses following trauma

Besides its hematopoietic effects, erythropoietin [EPO] by mobilization of iron and modulation of some inflammatory cytokines has antioxidant and anti-inflammatory properties. The purpose of this study was to evaluate these effects of erythropoietin and its impact on organ function in traumatized patients. Twenty-six ICU-admitted traumatized patients within 24 hrs after trauma were randomly assigned to the EPO [received EPO, 300 units/Kg/day] and Control [not received EPO] groups. The inflammatory biomarkers including Tumor Necrosis Factor alpha [TNF-alpha], Interleukin 1 [IL-1], Plasminogen Activator Inhibitor 1 [PAI-1] and Nitrotyrosine were recorded at the admission, 3, 6 and 9 days thereafter. Acute Physiology and Chronic Health Evaluation [APACHE II] and Sequential Organ Failure Assessment [SOFA] scores were also recorded. Results: Among 12 patients [EPO group] TNF-alpha level at the day of 9 [P=0.046], and within EPO group at the days of 3 [P=0.026 ameliorate], 6 [P=0.016], and 9 [P=0.052] were significantly lowered. Level of IL-1 and PAI-1 decreased significantly at days of 3, 6 and 9 post intervention. Also there were significant differences between two groups in the SOFA score during three measured time intervals [the first, third and seventh days]. From the results of this study it seems that injection of erythrocyte stimulating agent is well tolerated and inhibits the inflammatory response and oxidative stress following trauma

[Comparison between primary PCI and thrombolytic therapy results in patients with acute st-elevation MI]

Early revascularization is the main step in treatment of patients with acute MI which since a few years ago has been done via P-PCI. Since thrombolytic therapy is performed as a standard method of therapy of acute MI in all centers not equipped with angiography and angioplasty systems, we decided to compare these two methods in the university centers in Iran. This prospective study was conducted on STEMI [ST Elevation MI] patients referred to emergency department of Shohadaye Tajrish and Shahid Modarres Hospitals, in Tehran, for early revascularization using thrombolytic therapy or Primary PCI. We compared these two methods of revascularization based on the effects on ejection fraction, ST-resolution and complications. 287 patients [144 in T.T group and 143 in P-PCI group] were enrolled in our study. There were no differences in ejection fraction between the two groups, but STresolution was significantly better in the P-PCI group [P< 0.001]. The rate of complications was similar in both groups. It seems the P-PCI is more effective than T.T in patients with STEMI

Fentanyl supplement expedites the onset time of sensory and motor blocking in interscalene lidocaine anesthesia

Opioids are usually used in regional anesthesia, with or without local anesthetics to improve the regional block or postoperative pain control. Since no data are available on fentanyl's effect on the onset time of lidocaine interscalene anesthesia, the purpose of this study was to examine its effect on the onset time of sensory and motor blockade during interscalene anesthesia. In a prospective, randomized, double-blind study, ninety patients scheduled for elective shoulder, arm and forearm surgeries under an interscalene brachial plexus block .They were randomly allocated to receive either 30 ml of 1.5% lidocaine with 1.5 ml of isotonic saline [control group, n = 39] or 30 ml of 1.5% lidocaine with 1.5 ml [75 micro g] of fentanyl [fentanyl group, n = 41]. Then the onset time of sensory and motor blockades of the shoulder, arm and forearm were evaluated every 60 sec. The onset time of the sensory and motor blockades was defined as the time between the last injection and the total abolition of the pinprick response and complete paralysis. The duration of sensory blocks were considered as the time interval between the administration of the local anesthetic and the first postoperative pain sensation. Ten patients were excluded because of unsuccessful blockade or unbearable pain during the surgery. The onset time of the sensory block was significantly faster in the fentanyl group [186.54 +/- 62.71sec] compared with the control group [289.51 +/- 81.22, P < 0.01]. The onset times of the motor block up to complete paralysis in forearm flexion was significantly faster in the fentanyl group [260.61 +/- 119.91sec] than the control group [367.08 +/- 162.43sec, P < 0.01]. There was no difference in the duration of the sensory block between two groups. Results of the study showed that the combination of 75 micro g fentanyl and 1.5% lidocaine solution accelerated the onset of sensory and motor blockade during interscalene anesthesia

Effects of vitamin E administration on APACHE II score in ARDS patients

The acute respiratory distress syndrome [ARDS] is a common clinical disorder caused by injury to the alveolar epithelial and endothelial barriers of lung. In ARDS patients, oxidative stress is increased and plasma antioxidant levels are reduced. Vitamin E has an important role in antioxidant defense mechanisms. In this study the effect of vitamin E on decrease of APACHE II score in ARDS patients was investigated. Twenty patients [mean [SE]: age = 51.2 +/- 6.41 years] with ARDS were enrolled. After diagnosis based on inclusion and exclusion criteria, ten patients as treatment group received 600 IU vitamin E daily intramuscularly. Control group received normal saline as placebo. Plasma samples and Acute Physiology and Chronic Health Evaluation [APACHE] II score were obtained before administration, 4hrs and 12hrs after each intervention and repeated three days for each patient. Results were analyzed by use of an SPSS software package with a repeated-measures analysis of variance [ANOVA]. Significant changes were observed in APACHE II score from first to seventh measurement [p=0.0001] in treatment group, but vitamin E concentration altered significantly in only first to seventh measurement [p = 0.019]. From the results of this study, it seems that the use of vitamin E as a lipid-soluble antioxidant along with other supportive measures is beneficial in decreasing APACHE II score in ARDS patients

[Evaluation of phenytoin utilization based on key pharmacokinetic parameters in patients with head trauma]

Background: Phenytoin is commonly administered as an anticonvulsant agent to critically traumatic patients for seizure prophylaxis and treatment. It exhibits non-linear pharmacokinetic characteristic and requires frequent plasma level monitoring and dose adjustment. Based on the previous study, it is often difficult to achieve therapeutic levels in patients with head trauma using the recommended phenytoin dosing strategies. Therefore, we conducted a prospective, randomized study to evaluate pharmacokinetic parameters of phenytoin in patients with head trauma

Materials and methods: In this prospective randomized study, eighty-three patients were enrolled. The dosing regimen of phenytoin was designed and individualized for each patient based on available population pharmacokinetic data and was compared with the administered dose. The peak and trough concentrations of collected blood samples were determined by TDX

Results: Statistical analysis of the findings indicated that there were significant differences between administered doses of phenytoin and calculated doses based on peak and trough [P<0.0001]. Additonally, our findings indicate the significant difference between previous population Vmax and Vmax obtain from this study. Furthermore, this study showed that phenytoin plasma concentrations were sub therapeutic in the majority of cases [71 %]

Conclusions: It seems that blood level monitoring of phenytoin in patients with neurosurgical trauma on the basis of drug pharmacokinetic parameters such as Vmax is necessary

Evaluation of phenytoin utilization based on key pharmacokinetic parameters in patients with head trauma

Phenytoin is commonly administered as an anticonvulsant agent to critically traumatic patients for seizure prophylaxis and treatment. It exhibits non-linear pharmacokinetic characteristic and requires frequent plasma level monitoring and dose adjustment. Based on the previous study, it is often difficult to achieve therapeutic levels in patients with head trauma using the recommended phenytoin dosing strategies. Therefore, we conducted a prospective, randomized study to evaluate pharmacokinetic parameters of phenytoin in patients with head trauma. In this prospective randomized study, eighty-three patients were enrolled. The dosing regimen of phenytoin was designed and individualized for each patient based on available population pharmacokinetic data and was compared with the administered dose. The peak and trough concentrations of collected blood samples were determined by TDX. Statistical analysis of the findings indicated that there were significant differences between administered doses of phenytoin and calculated doses based on peak and trough [P<0.0001]. Additonally, our findings indicate the significant difference between previous population Vmax and Vmax obtained from this study. Furthermore, this study showed that phenytoin plasma concentrations were sub therapeutic in the majority of cases [71%].It seems that blood level monitoring ot phenytoin in patients with neurosurgical trauma on the basis of drug pharmacokinetic parameters such as Vmax is necessary

Role of magnesium loading test in detecting hypomagnsemia in critically ill Patients

Magnessium [Mg] deficiency has not usually been considered in clinical practice due to lack of relevant blood tests and because the symptoms are often vague and non-specific. Serum concentrations may not adequately reflect Mg status. Mg Loading Test [MLT] can provide information on total body Mg stores. We prosectively studied 21 critically ill patients [10 males, 11 females] admitted to the ICU, to investigate the prevalence of Mg deficiency. Their mean age was 50 +/- 21 years. To determine serum Mg, venous blood specmens were obtained just before the MLT. Mg sulfate [30 mmol] was infused during an 8-hr period and 24-hr urine samples were collected from the starting of Mg infusion. Although low serum Mg [<1.8 mmol/L] was present only in 2 patients, MLT showed Mg deficiency in 18 patients. MLT detected Mg deficiency in 13 out of 14 patients with normal serum Mg, in 2 out of 2 subjects with hypomagnesemia, and in 3 out of 5 cases with hypermagnesemia. Of 7 fetal cases, 6 occurred in individuals with hypomagnesemia [6/18] and 1 death occurred in the normomagnesemic group [1/3]. There was no relationship between Mg retention, age [r=0.33, p=0.63] and serum Mg concentrations [r=0.15, p=0.925]. There was a significant correlation between Mg uptake and APACHE II score [r=0.46, p=0.035]. In conclusion, Mg depletion is highly prevalent in ICU patients according to MLT. MLT is superior to serum Mg in determining actual Mg status in this group. Therefore, we suggest that MLT, and not serum Mg, should be carried out in patients when Mg deficiency is suspected