High-performance liquid chromatographic method for the determination of atracurium and laudanosine in human plasma. Application to pharmacokinetics

A high-performance liquid chromatographic method coupled with fluorimetric detection has been developed for the determination of atracurium and its major metabolite, laudanosine, in human plasma. The detection is performed at 240 nm for excitation and 320 nm for emission. Verapamil was used as the internal standard. The proposed technique, involving the direct precipitation of plasma proteins is reproducible, selective and sensitive. Linear detector responses were observed for the calibration curve standards in the range of 40 to 2000 ng/ml. Precision, expressed as C.V., was in the range 1 to 14%. The limit of quantification for both atracurium and laudanosine was 40 ng/ml. The method has been validated and stability tests under various conditions have been performed. This method has been used to determine the pharmacokinetic profile of atracurium and laudanosine in patients with acute respiratory distress syndrome.     

High-performance liquid chromatographic determination of cefepime in human plasma and in urine and dialysis fluid using a column-switching technique

A high-performance liquid chromatographic method with UV absorbance was developed for the analysis of cefepime in human plasma and urine, and in dialysis fluid. Detection was performed at 280 nm. The assay procedure for cefepime in plasma involves the addition of an internal standard (cefpirome) followed by treatment of the samples with trichloracetic acid, acetonitrile and dichloromethane. To quantify cefepime in diluted urine (1:20) and in the dialysis fluid, samples spiked with the internal standard (cefpirome) were analysed using a column-switching technique. The HPLC column, Nucleosil C18, was equilibrated with an eluent mixture composed of acetonitrile-ammonium acetate (pH 4). Linear detector responses were observed for the calibration curve standards in the range 0.5 to 100 microg/ml, which spans what is currently thought to be the clinically relevant range for cefepime concentrations in body fluids. The limit of quantification was 0.5 microg/ml in the three matrices. Extraction recoveries proved to be more than 84%. Precision, expressed as %RSD, was in the range 1.5 to 9%. Accuracy ranged from 93 to 105%. This method was used to follow the time course of the concentration of cefepime in plasma, urine and dialysate outlet samples after a 10-min infusion period of 2 g of this drug in patients with acute renal failure undergoing hemodiafiltration.     

Junior versus senior physicians for informing families of intensive care unit patients

To compare the effectiveness of information delivered to family members of critically ill patients by junior and senior physicians, we performed a prospective randomized multicenter trial in 11 French intensive care units. Patients (n = 220) were allocated at random to having their family members receive information by only junior or only senior physicians throughout the intensive care unit stay; there were 92 and 93 evaluable cases in the junior and senior groups, respectively, with no significant differences in baseline characteristics. Between Days 3 and 5, one family representative per patient was evaluated for comprehension of the diagnosis, prognosis, and treatment in the patient; satisfaction with information and care; and presence of symptoms of anxiety and depression. No significant differences were found between the two groups for any of these three criteria. Family members informed by a junior physician were more likely to feel they had not been given enough information time (additional time wanted: 3 [0-6.5] vs. 0 [0-5] minutes, p = 0.01) and to have sought additional explanations from their usual doctor (48.9 vs. 34.4%, p = 0.004). Specialty residents, if given opportunities for acquiring experience, can become proficient in communicating with families and share this task with senior physicians.     

Short term effects of hypertonic saline during severe sepsis and septic shock

OBJECTIVE: Assessment of haemodynamic effects of 250 ml hypertonic saline 7.5% (HS) perfusion in critically ill patients with severe sepsis or septic shock. STUDY DESIGN: Observational study. PATIENTS: Twelve mechanically ventilated patients with severe sepsis or septic shock requiring a pulmonary artery catheter and volume loading. INTERVENTION: Two hundred and fifty millilitres HS were given over 15 min. Were measured: heart rate (HR), mean arterial pressure (MAP) and pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), cardiac index (CI), indexed systemic vascular resistance (ISVR), indexed pulmonary vascular resistance (IPVR), plasma sodium, chloride, protein and haemoglobin concentrations and arterial blood lactate. Studied parameters were assessed at baseline (T(0)) and 5 (T(0)) and 105 min (T(120)) after the end of HS infusion. RESULTS: MAP, HR and RAP were not altered. HS increased PAPM (25 +/- 5-30 +/- 6 mmHg), PCWP (13 +/- 3-18 +/- 4 mmHg) and CI (3.5 +/- 1.2-4.6 +/- 1.1 l/min per m(2)) at T(20) (P < 0.05). ISVR and IPVR were decreased at T(20). Protein and haemoglobin were decreased at T(20). Sodium and chloride were increased at T(20) (from 136 +/- 4 to 147 +/- 4 and from 110 +/- 6 to 123 +/- 6 mmol/l, respectively, P < 0.01) and T(120). CONCLUSION: In patients with severe sepsis or septic shock, 250 ml HS transiently (<120 min) increases CI and PCWP and induces an increase in sodium and chloride concentrations.     

Pharmacokinetic-pharmacodynamic modeling of atracurium in intensive care patients

The authors have studied 10 critically ill patients with acute respiratory distress syndrome who required a neuromuscular blocking drug to assist mechanical ventilation. Patients received a bolus dose of 1 mg/kg of atracurium followed by a constant infusion rate of 1 mg/kg/h of this drug for 72 hours. Neuromuscular block was monitored using an accelerograph. Blood samples were obtained over a 96-hour period. A preliminary independent analysis was done to estimate the individual pharmacokinetic parameters; data were consistent with a one-compartment model. The pharmacodynamic data analysis was then performed using the changes in train-of-four (TOF) count as an index of the therapeutic effect of atracurium. Pharmacokinetic-dynamic variables were calculated using the Sheiner model and the Hill equation. The elimination half-life of atracurium averaged 22 minutes. Mean volume of distribution and plasma clearance were 217 ml/kg and 550 ml/min, respectively. There was a significant hysteresis loop when the TOF count was plotted against predicted plasma atracurium concentrations. The mean sigmoidicity factor, gamma, was 4.04. The concentration producing 50% of the Emax was 1.36 micrograms/mL, and the mean ke0 was 0.059 min-1. Recovery time ranged from 30 to 80 minutes, and none of the patients of this study had residual paralysis.     

Ophthalmic Regional Anesthesia: Medial Canthus Episcleral (Sub-Tenon) Anesthesia Is More Efficient than Peribulbar Anesthesia: A Double-blind Randomized Study

Background: Regional anesthesia and especially peribulbar anesthesia commonly is used for cataract surgery. Failure rates and need for reinjection remains high, however, with peribulbar anesthesia. Single-injection high-volume medial canthus episcleral (sub-Tenon's) anesthesia has proven to be an efficient and safe alternative to peribulbar anesthesia.

Methods: The authors, in a blind study, compared the effectiveness of both techniques in 66 patients randomly assigned to episcleral anesthesia or single-injection peribulbar anesthesia. Motor blockade (akinesia) was used as the main index of anesthesia effectiveness. It was assessed using an 18-point scale (0-3 for each of the four directions of the gaze, lid opening, and lid closing, the total being from 0 = normal mobility to 18 = no movement at all). This score was compared between the groups 1, 5, 10, and 15 min after injection and at the end of the surgical procedures. Time to onset of the blockade also was compared between the two groups, as was the incidence of incomplete blockade with a need for supplemental injection and the satisfaction of the surgeon, patient, and anesthesiologist.

Results: Episcleral anesthesia provided a quicker onset of anesthesia, a better akinesia score, and a lower rate of incomplete blockade necessitating reinjection (0 vs. 39%;P < 0.0001) than peribulbar anesthesia. Even after supplemental injection, peribulbar anesthesia had a lower akinesia score than did episcleral anesthesia. Peribulbar anesthesia began to wear off during surgery, whereas episcleral anesthesia did not.