Reduction of Plasma Fibrinogen, Immunoglobulin G, and Immunoglobulin M Concentrations by Immunoadsorption Therapy with Tryptophan and Phenylalanine Adsorbents

Abstract Immunoadsorption (1A) therapy with tryptophan (TR-350) or phenylalanine (PH-350) adsorbents has been used to reduce the concentration of serum antibodies in human lymphocyte antigen (HLA)-immunized patients. Other forms of plasma purification have been reported to reduce the level of fibrinogen, which affects the blood properties. In this study we investigated the effects of IA therapy using both adsorbents on plasma fibrinogen and immunoglobulins G and M in 13 patients (8 patients were treated with TR-350, and 5 patients were treated with PH-350). During each session 1 plasma volume (2.8 ± 0.4 L of plasma) was processed through the immunocolumn and then returned to the patient together with the blood cells. Compared with the pretreatment values, the plasma fibrinogen, IgG, and IgM concentrations were significantly reduced after IA therapy (p < 0.01 for TR-350; p < 0.04 for PH-350). There was a positive correlation between the degree of reduction of plasma proteins and the number of IA treatments given. A nonpara-metric test (Wilcoxon's signed-rank test or the Mann-Whitney test) was used for statistical analysis. We conclude from our study that IA therapy effectively lowers the plasma levels of fibrinogen, IgG, and IgM and thus can be considered a valuable alternative to other blood purification methods.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

The multiply injured child

Blunt trauma is the principal cause of childhood death in many developed countries. This review outlines the differences between adults and children with respect to resuscitation and treatment of orthopaedic injuries in a child with polytrauma. Recent advances in techniques of fracture stabilization are reported.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.     

Intravenous endotoxin does not increase tissue extravasation of albumin in rats

Background : It is unclear whether activation of the inducible nitric oxide synthase (iNOS) increases or decreases the extravasation of plasma.
Methods : Chloralose anaesthetised male Wistar rats received E. coli lipopolysacharide (LPS), 3 mg kg^-1 i.v., or the corresponding volume of saline, 3 or 5 h before the end of the experiment. Mean arterial pressure (MAP) and heart rate (HR) were recorded. Tissue clearance of radio-labelled albumin, during the last 2 h of each experiment, was determined by a double-isotope method. In separate animals, the serum concentration of nitrite and nitrate was determined, 5 h after LPS or the solvent.
Main Results : LPS initially decreased MAP and lastingly increased HR. In the 3-h LPS animals (n=8), tissue plasma clearance was lower in the heart and calf muscle and increased only in diaphragm, compared to corresponding control animals (n=8). In the 5-h LPS rats, clearance was lowered (n=8) in the entire gastrointestinal tract and in testes, compared to controls (n=8). The serum nitrite/nitrate concentration was higher in animals given LPS (n=6) than in controls (n=6).
Conclusion : After LPS, tissue clearance of albumin was not increased in any major tissue, in spite of increased serum levels of NO end products. Apparently, after activation of iNOS, the augmented release of NO is not necessarily associated with increased albumin extravasation.     

Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery: A randomised, double-blind, cross-over study with and without adrenaline

Background: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. Methods: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml · h^?1 of bupivacaine 1 mg · ml^?1, fentanyl 2 μg · ml^?1, and adrenaline 2 μg · ml^?1 were included. On the 1^st and 2^nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. Results: The number of hypaesthetic dermatomal segments decreased (P <0.001) and pain intensity at rest and when coughing increased (P <0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15–20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng · ml^?1 (P <0.01), and there was more sedation during the period without adrenaline. Conclusions: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.     

Development of Selective Low-Density Lipoprotein (LDL) Apheresis System: Immobilized Polyanion as LDL-Specific Adsorption for LDL Apheresis System

Abstract: Low-density lipoprotein (LDL) is widely recognized as one of the major risk factors for developing coronary heart diseases. Despite intensive development of LDL-lowering drugs, there still exist those patients with refractory hyperlipidemia whose plasma LDL levels are not sufficiently lowered by drugs. LDL apheresis, direct removal of plasma LDL from circulating blood, is thought to be the most promising treatment for such refractory patients. Various techniques, such as the use of an im-munoadsorbent utilizing an anti-LDL antibody, have been used in an attempt to achieve the selective removal of LDL. However, none were widely used because of complications, poor selectivity, and so forth. To establish a safe and effective LDL apheresis system, we chose a synthetic affinity adsorbent as the LDL-removing device. Synthetic polyanion compounds were used as the affinity ligands for LDL adsorbent to simulate the anion-rich sequence of LDL binding sites in the human LDL receptor. Among various polyanion compounds, those polyanions with sulfate or sulfonate groups and hydrophilic backbone were found to have strong affinity for LDL. In contrast, polyanions with carboxyl groups showed poor affinity. Dextran sulfate (DS) was selected as the affinity ligand of LDL adsorbent for its high affinity and low toxicity. The influence of its charge density and molecular weight on its affinity for LDL was suitable. The affinity rapidly increased as the charge density increased, then, reached a constant value. Little affinity was found for either the DS monomer (glucose sulfate) or DS with a molecular weight higher than 10⁴ daltons whereas DS with molecular weights in the midrange showed strong affinity. DS with a midrange molecular weight was immobilized on cellulose hard gel to give LDL adsorbent clinical application. The adsorbent demonstrated an excellent selectivity for LDL and very low density lipoprotein (VLDL) in vitro. Adsorption of high-density lipoprotein and major plasma proteins was almost negligible. Additional study of the LDL-binding mechanism revealed that DS directly interacts with positively charged sites on LDL, which demonstrates that the nature of the interaction is the same as that of LDL receptor. An LDL adsorption column (Liposorber) packed with an LDL adsorbent and polysulfone hollow-fiber plasma separator (Sulflux) was developed as an efficient LDL apheresis system. Clinical investigation proved that this system is capable of intensively lowering the plasma LDL level without affecting major plasma components.     

Artificial organs 2010: a year in review

In this Editor's Review, articles published in 2010 are organized by category and briefly summarized. As the official journal of The International Federation for Artificial Organs, The International Faculty for Artificial Organs, and the International Society for Rotary Blood Pumps, Artificial Organs continues in the original mission of its founders "to foster communications in the field of artificial organs on an international level."Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide such meaningful suggestions to the author's work whether eventually accepted or rejected and especially to those whose native tongue is not English. Without these excellent and dedicated reviewers the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, Wiley-Blackwell, for their expert attention and support in the production and marketing of Artificial Organs. In this Editor's Review, that historically has been widely received by our readership, we aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. We look forward to recording further advances in the coming years.     

Avaliação do clube de revista de anestesiologia por meio de mudanças semânticas

Background and objectives

The interactive approach of a journal club has been described in the medical education literature. The aim of this investigation is to present an assessment of journal club as a tool to address the question whether residents read more and critically.

Methods

This study reports the performance of medical residents in anesthesiology from the Clinics Hospital – University of São Paulo Medical School. All medical residents were invited to answer five questions derived from discussed papers. The answer sheet consisted of an affirmative statement with a Likert type scale (totally disagree–disagree–not sure–agree–totally agree), each related to one of the chosen articles. The results were evaluated by means of item analysis – difficulty index and discrimination power.

Results

Residents filled one hundred and seventy three evaluations in the months of December 2011 (n = 51), July 2012 (n = 66) and December 2012 (n = 56). The first exam presented all items with straight statement, second and third exams presented mixed items. Separating “totally agree” from “agree” increased the difficulty indices, but did not improve the discrimination power.

Conclusions

The use of a journal club assessment with straight and inverted statements and by means of five points scale for agreement has been shown to increase its item difficulty and discrimination power. This may reflect involvement either with the reading or the discussion during the journal meeting.     

Utilisation des médicaments prokinétiques en réanimation : indications et limites ?

Enteral feeding is often limited by gastric and intestinal motility disturbances in critically ill patients, particularly in patients with shock. So, promotility agents are frequently used to improve tolerance to enteral nutrition. This review summaries the pathophysiology, presents the available pharmacological strategies, the clinical data, the counter-indications and the principal limits. The clinical data are poor. No study demonstrates a positive effect on clinical outcomes. Metoclopramide and erythromycin seems to be the more effective. Considering the risk of antibiotic resistance, the first line use of erythromycin should be avoided in favor of metoclopramide.     

Lymphocytapheresis

Abstract: Leukocytapheresis has long been performed with the centrifugal method. But in 1989 in Japan, the Asahi Medical Co. developed the extracorporeal leukocyte-removal filter, Cellsorba. This filter consists of non-woven fabric, which can remove leukocytes from whole blood during extracorporeal circulation. In the incipient stage, this filter was applied to collagen diseases, rheumatoid arthritis, and systemic lupus erythematosus. During the following studies, this filter has been found to have an immunosuppressive effect. Now, it is beginning to be applied to various kinds of autoimmune diseases. Moreover, this filter has recently been recognized to be effective in inflammatory bowel diseases, ulcerative colitis, and Crohn's disease. The outline of Cellsorba and the application of this filter is described here.     

Soluble TNFα Receptors Are Increased in Chronic Renal Insufficiency and Hemodialysis and Inhibit Neutrophil Priming by TNFα

Abstract: The oxidative burst of neutrophils from azotemic patients is refractory to priming by tumor necrosis factor-α (TNFα). Soluble TNFα binding proteins (TNFR) accumulate in the plasma of azotemic patients. To test the hypothesis that these increased sTNFR concentrations inhibit TNFa priming of oxidative burst activity, we measured plasma sTNFR concentrations in nondialyzed azotemic patients, hemodialysis patients, and normal subjects, and determined TNFa priming of fMet-Leu-Phe-stimulated superoxide production in neutrophils incubated in plasma with differing levels of sTNFR. These sTNFR concentrations increased significantly as creatinine clearance decreased and were significantly greater in hemodialysis patients than could be accounted for by loss of renal function alone. TNFα primed superoxide production by normal neutrophils in normal plasma, but this effect was significantly reduced in plasma with increased concentrations of sTNFR. Neutrophils from azotemic and hemodialysis patients were refractory to priming by TNFα in autologous plasma, and incubation in normal plasma only partially corrected this defect. We conclude that sTNFR accumulate as a result of the loss of renal function and hemodialysis and inhibit TNFα priming of neutrophils in azotemic and hemodialysis patients, but that these cells also have an intrinsic functional defect.     

Anesthésie générale chez l’enfant : quid des pratiques en 2010 ?

Introduction

The practice of pediatric anesthesia requires a regular update of scientific knowledge and technical skills. To provide the most adequate Continuing Medical Education programs, it is necessary to assess the practices of pediatric anesthesiologists. Thus, the objective of this survey was to draw a picture of the current clinical practices of general anesthesia in children, in France.

Material and methods

One thousand one hundred and fifty questionnaires were given to anesthesiologists involved in pediatric cases. These questionnaires collected information on various aspects of clinical practice relative to induction, maintenance, recovery from general anaesthesia and also classical debated points such as children with Upper Respiratory Infection (URI), emergence agitation, epileptoid signs or anaesthetic management of adenoidectomy. Differences in practices between CHG (general hospital), CHU (teaching hospital), LIBERAL (private) and PSPH (semi-private) hospitals were investigated.

Results

There were 1025 questionnaires completed. Fifty-five percent of responders worked in public hospitals (CHG and CHU); 77% had a practice that was 25% or less of pediatric cases. In children from 3 to 10 years: 72% of respondents used always premedication and two thirds performed inhalation induction in more than 50% of cases. For induction, 53% used sevoflurane (SEVO) at 7 or 8%. Respondents from LIBERAL used higher SEVO concentrations. Tracheal intubation was performed with SEVO alone (37%), SEVO and propofol (55%) and SEVO with myorelaxant (8%), 93% of respondents used a bolus of opioid. For maintenance, the majority of respondents used SEVO associated with sufentanil; desflurane and remifentanil were more frequently used in CHU. Two thirds of respondents used N₂O. Depth of anesthesia was commonly assessed by hemodynamic changes (52%), end tidal concentration of halogenated (38%) or automated devices based on EEG (7%). In children with URI, 98% of respondents used SEVO for anesthesia. To control the airway 42% used a tracheal tube, 30% a laryngeal mask and 20% a facial mask. Emergence agitation was an important concern for two thirds of respondents, while epileptoid signs were considered as important by only 20%. Eighty-nine percent of respondents practiced anesthesia for adenoidectomy. Anesthesia was induced by inhalation of SEVO 7–8% (41%), 6% (39%) or 4% (12%), 66% put an intravenous line (less frequently in LIBERAL). 67% of the responders managed adenoidectomy without any device to control the airway (more frequently in LIBERAL), 32% administrated a bolus of opioid (less frequently in LIBERAL).

Discussion

This survey demonstrated that the practices regarding general anesthesia in children are relatively homogenous. Most of the differences appeared between LIBERAL and the others structures; the anaesthetic management for adenoidectomy illustrates these findings.     

Intérêt d’une rééducation précoce pour les patients neurologiques

Rehabilitation improves the functional prognosis of patients after a neurologic lesion, and tendency is to begin rehabilitation as soon as possible. This review focuses on the interest and the feasibility of very early rehabilitation, initiated from critical care units. It is necessary to precisely assess patients’ impairments and disabilities in order to define rehabilitation objectives. Valid and simple tools must support this evaluation. Rehabilitation will be directed to preventing decubitus complications and active rehabilitation. The sooner rehabilitation is started; the better functional prognosis seems to be.     

Risiko Schlaganfall — Öffentlichkeitsarbeit und Aufklärung dringend erforderlich

Zusammenfassung Das wesentliche — und zugleich noch wenig ausgeschöpfte — Potenzial der Schlaganfallmedizin liegt in der langfristigen Prophylaxe. Durch Beeinflussung von Lifestylefaktoren wie Ernährungsgewohnheiten, Zigarettenkonsum und körperlichem Training durch entsprechende Aufklärung ließe sich ein erheblicher Teil an zerebralen Ereignissen vermeiden. Ein weiterer in Deutschland noch zu wenig beachteter Faktor ist die konsequente Blutdruckeinstellung. Breitgestreute Aufklärung könnte außerdem potenziellen Patienten helfen, bereits auftretende Warnsymptome wie die transiente ischämische Attacke richtig einzuschätzen, um eine rechtzeitige Behandlung zu ermöglichen.