Alexander Avidan

Multicenter comparison of cortisol as measured by different methods in samples of patients with septic shock

PurposeTo compare inter-laboratory and inter-assay measurements of total cortisol in patients with septic shock and to evaluate current recommendations for diagnosis of corticosteroid insufficiency in septic shock.MethodsIn the multinational CORTICUS study duplicate serum samples were taken before and after corticotropin stimulation tests in patients with septic shock. Serum cortisol was measured in paired samples, one being measured by the chemical laboratory of each participating site and the other by a central laboratory using an electrochemiluminescence immunoassay. Cortisol levels measured by tandem mass spectrometry were used as a ‘gold standard’ reference method in a subset of samples.ResultsA total of 425 corticotropin tests (850 cortisol samples) were available for comparison of local and central laboratory measurements. The concordance correlation coefficient between central laboratoty immunoassay and local hospital assays was 0.98 (CI 0.97–0.99) when the immunoassay of one manufacturer was used and 0.60 (CI 0.54–0.65) when immunoassays of different manufacturers were used. The comparison with the reference method of mass spectrometry showed concordance correlation coefficients ranging from 0.43 to 0.97 depending on the assay under study. Diagnosis of corticosteroid insufficiency was diverging due to inter-assay variations in up to 27% of cases.ConclusionIn samples taken from patients in septic shock, there was a high inter-assay variation of total serum cortisol. Comparisons with a reference method revealed both over- and underestimations of true cortisol levels. These inter-assay variations in samples of patients with septic shock complicate the diagnosis of corticosteroid insufficiency.

Seeking Worldwide Professional Consensus on the Principles of End-of-Life Care for the Critically Ill. The Consensus for Worldwide End-of-Life Practice for Patients in Intensive Care Units (WELPICUS) Study

Great differences in end-of-life practices in treating the critically ill around the world warrant agreement regarding the major ethical principles. This analysis determines the extent of worldwide consensus for end-of-life practices, delineates where there is and is not consensus, and analyzes reasons for lack of consensus. Critical care societies worldwide were invited to participate. Country coordinators were identified and draft statements were developed for major end-of-life issues and translated into six languages. Multidisciplinary responses using a web-based survey assessed agreement or disagreement with definitions and statements linked to anonymous demographic information. Consensus was prospectively defined as >80% agreement. Definitions and statements not obtaining consensus were revised based on comments of respondents, and then translated and redistributed. Of the initial 1,283 responses from 32 countries, consensus was found for 66 (81%) of the 81 definitions and statements; 26 (32%) had >90% agreement. With 83 additional responses to the original questionnaire (1,366 total) and 604 responses to the revised statements, consensus could be obtained for another 11 of the 15 statements. Consensus was obtained for informed consent, withholding and withdrawing life-sustaining treatment, legal requirements, intensive care unit therapies, cardiopulmonary resuscitation, shared decision making, medical and nursing consensus, brain death, and palliative care. Consensus was obtained for 77 of 81 (95%) statements. Worldwide consensus could be developed for the majority of definitions and statements about end-of-life practices. Statements achieving consensus provide standards of practice for end-of-life care; statements without consensus identify important areas for future research.

Short Term Morphine Exposure In Vitro Alters Proliferation and Differentiation of Neural Progenitor Cells and Promotes Apoptosis via Mu Receptors

Background Chronic morphine treatment inhibits neural progenitor cell (NPC) progression and negatively effects hippocampal neurogenesis. However, the effect of acute opioid treatment on cell development and its influence on NPC differentiation and proliferation in vitro is unknown. We aim to investigate the effect of a single, short term exposure of morphine on the proliferation, differentiation and apoptosis of NPCs and the mechanism involved. Methods Cell cultures from 14-day mouse embryos were exposed to different concentrations of morphine and its antagonist naloxone for 24 hours and proliferation, differentiation and apoptosis were studied. Proliferating cells were labeled with bromodeoxyuridine (BrdU) and cell fate was studied with immunocytochemistry. Results Cells treated with morphine demonstrated decreased BrdU expression with increased morphine concentrations. Analysis of double-labeled cells showed a decrease in cells co-stained for BrdU with nestin and an increase in cells co-stained with BrdU and neuron-specific class III β-tubuline (TUJ1) in a dose dependent manner. Furthermore, a significant increase in caspase-3 activity was observed in the nestin- positive cells. Addition of naloxone to morphine-treated NPCs reversed the anti-proliferative and pro-apoptotic effects of morphine. Conclusions Short term morphine exposure induced inhibition of NPC proliferation and increased active caspase-3 expression in a dose dependent manner. Morphine induces neuronal and glial differentiation and decreases the expression of nestin- positive cells. These effects were reversed with the addition of the opioid antagonist naloxone. Our results demonstrate the effects of short term morphine administration on the proliferation and differentiation of NPCs and imply a mu-receptor mechanism in the regulation of NPC survival.

Blood Cultures at Central Line Insertion in the Intensive Care Unit: Comparison with Peripheral Venipuncture

ABSTRACT Blood cultures are a key diagnostic test for intensive care unit (ICU) patients; however, contaminants complicate interpretations and lead to unnecessary antibiotic administration and costs. Indications for blood cultures and central venous catheter (CVC) insertions often overlap for ICU patients. Obtaining blood cultures under the strict sterile precautions utilized for CVC insertion might be expected to decrease culture contamination. This retrospective study compared the results of blood cultures taken at CVC insertion, at arterial line insertion, and from peripheral venipuncture in order to validate the advantage of CVC insertion cultures. Cultures from indwelling lines were excluded. Results of 14,589 blood cultures, including 2,736 (19%) CVC, 1,513 (10%) arterial line, and 10,340 (71%) peripheral cultures taken over 5.5 years in two ICUs (general and medical) were analyzed. CVC cultures were contaminated more frequently than arterial line or peripheral cultures (225/2,736 [8%] CVC, 48/1,513 [3%] arterial line, and 378/10,340 (4%) peripheral cultures [P < 0.001 for CVC versus peripheral and CVC versus arterial line cultures]). True pathogens were found more frequently in CVC insertion cultures (334/2,736 [12%] CVC, 155/1,513 [10%] arterial line, and 795/10,340 [8%] peripheral cultures [P < 0.001 for CVC versus peripheral cultures; P = 0.055 for CVC versus arterial line cultures; P < 0.001 for peripheral versus arterial line cultures]). Contamination and true-positive rates were similar for culture sets from the two ICUs for each given culture source. Despite superior sterile precautions, cultures taken at the time of central line insertion had a higher contamination rate than did either peripheral or arterial line blood cultures. This may be related to the increased manipulations required for CVC insertion.

An internet web site as a data collection platform for multicenter research.

The Internet can be an effective alternative for data collection for multicenter studies. It has major advantages over the “classical” method of using paper and traditional (“snail”) mail. We developed an Internet site and implemented collection of data for a multicenter study of ethical decision-making. The Web site was built with Microsoft FrontPage as the authoring tool. Database management was performed with Microsoft Access. Security issues were the major concerns for the web design. Thirty-seven European centers enrolled 4248 patients during 1.5 yr using the Internet site. The use of this Internet site for data acquisition was highly effective, and the investigators were able to use the system without training. Overall satisfaction of the investigators was high. After security issues, interactivity and user-friendly design are the main cornerstones for the success of such a system.

Pain management and regional anaesthesia in the trauma patient.

Purpose of the review Treatment of the trauma patient has evolved rapidly in the past decade. Nevertheless, the treatment of pain as part of overall trauma management has been relatively neglected. This update reviews recent publications related to pain relief in the trauma patient. Recent findings Although recent publications suggest that the assessment and treatment of pain in trauma have improved, most studies still document inadequate analgesia. We discuss the use of different analgesia strategies in the prehospital and emergency room settings. Summary Educating the emergency room staff to perform early routine assessment of pain and to be familiar with the administration of analgesia are key elements to improved pain management in trauma. Peripheral nerve block techniques should be practised by emergency room staff. If simple techniques are chosen, competence can be achieved with short, focused training sessions. Further developments are needed in order to provide safer and more effective analgesia to the trauma patient.

Nerve root inflammation demonstrated by magnetic resonance imaging in a patient with transient neurologic symptoms after intrathecal injection of lidocaine.

TRANSIENT neurologic symptoms after intrathecal injection of lidocaine are common. The main symptoms are severe pain and dysesthesia in the buttocks and legs after recovery from spinal anesthesia. The symptoms typically resolve within 1 week. No definitive etiology has been established until now. We report findings on magnetic resonance imaging (MRI) of a patient with transient neurologic symptoms after spinal anesthesia with lidocaine that indicated a local inflammatory process as the possible etiology for this symptom.

Appearance of white urine during propofol anesthesia.

Reference 6 addresses rotating the needle using postmortem dura mater that was “clamped so as to be flat but not stretched” prior to contact with the needle. The dura in this investigation is grossly dissimilar to the dura in the epidural space as seen in a clinical practice. In the epiduroscopy investigations (ref. 7, 14 autopsy subjects, and ref. 8, 10 patients), the Tuohy needle was not rotated. In the 10 patients the following resulted: 1) “A complete examination was possible in eight subjects.” 2) “In 2 of the 10 subjects a moderate bleeding impaired the view and made complete examination impossible.” 3) “Smaller bleeding occurred in three other subjects.” To hopefully prove that rotating a needle in the epidural is dangerous, Bromage appears to be “hanging his hat” on epiduroscopy. However, knowing the results in patients, is not conducting a prospective major clinical epiduroscopy investigation with statistical significant data minuscule? Would anesthesiologists volunteer for such an investigation or submit their patients to one simply to determine the outcome of rotating a needle in the epidural space? “What you don’t want done to yourself, do not do unto others” (Confucianism-Sixth Century B.C.). This is perhaps the oldest ethical proposition of mankind. To conclude, Bromage’s letter is resplendently cloaked with terms such as 1) “would seem to be true,” 2) “potential,” 3) “brings us very close,” 4) “perhaps,” 5) “may,” and 6) “it comes as close as one can get.” These reveal his letter to be speculation. Therefore, my statement about rotation of a needle in the epidural space, namely “All of us are theorizing,” (3) is still valid! Neither this response, the letter by Bromage, nor the letters of others (4,5) will alter an anesthesiologist’s technique of performing an epidural block. With or without rotating a needle in the epidural space, its bevel will occasionally enter a blood vessel, the subdural space, or the subarachnoid space, and the therapeutic dose of local anesthetic will be injected. Of greatest importance if these occur is that the anesthesiologist immediately recognizes the problem, treats it promptly and correctly, and thereby avoids a catastrophic sequela.

Anesthesiologists' ability in calculating weight-based concentrations for pediatric drug infusions: an observational study.

STUDY OBJECTIVES To assess the ability of anesthesiologists to calculate weight-specific drug concentrations for continuous drug administration in children, and to evaluate the acceptance of an inhouse-developed, computer-based application for calculating drug infusions for pediatric cardiac surgery. DESIGN Observational study. SETTING Anesthesiology department of a tertiary-care medical center in Israel. PARTICIPANTS 45 anesthesiology department staff members (attendings and residents). MEASUREMENTS Anesthesiologists were asked to calculate the weight-based amount of drug and the corresponding amount in mL to be drawn from a standard vial and added to a 50-mL syringe in order to reach an infusion rate, where 1 mL/hr corresponds to 1 μg x kg(-1) x min(-1). The time it took to reach the result was measured. Staff members were also asked to rate the user-friendliness and usability of the program. MAIN RESULTS 41 of the original 42 participants returned the completed questionnaire. Only 6 (15%) of 41 anesthesiologists provided all the correct answers. The mean calculation time required was 205 (±53) seconds. There was no difference in success rate between attendings and residents. Incorrect calculations ranged from a drug concentration 50 times too low up to 56 times too high. Most staff members believed that the computer-based application to perform these calculations reduced errors (65%) and workload (81%), and improved patient treatment (71%). This application was rated as very user-friendly. CONCLUSIONS Anesthesiologists have difficulty calculating pediatric drug concentrations for continuous drug infusions. The correct calculations are time-consuming. Incorrect calculations may lead to dangerously high or low doses. A computer-based application to calculate drug concentrations was rated as very useful and user-friendly.

Peripheral nerve block for ambulatory surgery and postoperative analgesia.

Purpose of review With this article we intend to increase the awareness of the efficiency and efficacy of peripheral nerve block as a treatment option for outpatient surgical anesthesia and postoperative home-based analgesia. Recent findings Current investigations have demonstrated that peripheral nerve block is associated with a superior outcome (reduced pain, nausea and vomiting) and more efficient patient turnover than general anesthesia. Continuous peripheral nerve block and patient controlled peripheral nerve block lead to further improvement in postoperative analgesia and patient satisfaction. Summary The recent advances and techniques described indicate that peripheral nerve block is both a valid and frequently a preferred option for ambulatory surgery.