Considerations for Antiplatelet Management of Carotid Stenting in the Setting of Mechanical Thrombectomy: A Delphi Consensus Statement.

BACKGROUND AND PURPOSE: There are only few data and lack of consensus regarding antiplatelet management for carotid stent placement in the setting of endovascular stroke treatment. We aimed to develop a consensus-based algorithm for antiplatelet management in acute ischemic stroke patients undergoing endovascular treatment and simultaneous emergent carotid stent placement. MATERIALS AND METHODS: We performed a literature search and a modified Delphi approach used Web-based questionnaires that were sent in several iterations to an international multidisciplinary panel of 19 neurointerventionalists from 7 countries. The first round included open-ended questions and formed the basis for subsequent rounds, in which closed-ended questions were used. Participants continuously received feedback on the results from previous rounds. Consensus was defined as agreement of ≥70% for binary questions and agreement of ≥50% for questions with >2 answer options. The results of the Delphi process were then summarized in a draft manuscript that was circulated among the panel members for feedback. RESULTS: A total of 5 Delphi rounds were performed. Panel members preferred a single intravenous aspirin bolus or, in jurisdictions in which intravenous aspirin is not available, a glycoprotein IIb/IIIa receptor inhibitor as intraprocedural antiplatelet regimen and a combination therapy of oral aspirin and a P2Y12 inhibitor in the postprocedural period. There was no consensus on the role of platelet function testing in the postprocedural period. CONCLUSIONS: More and better data on antiplatelet management for carotid stent placement in the setting of endovascular treatment are urgently needed. Panel members preferred intravenous aspirin or, alternatively, a glycoprotein IIb/IIIa receptor inhibitor as an intraprocedural antiplatelet agent, followed by a dual oral regimen of aspirin and a P2Y12 inhibitor in the postprocedural period.

Antiplatelet Management for Stent-Assisted Coiling and Flow Diversion of Ruptured Intracranial Aneurysms: A DELPHI Consensus Statement.

BACKGROUND AND PURPOSE: There is a paucity of data regarding antiplatelet management strategies in the setting of stent-assisted coiling/flow diversion for ruptured intracranial aneurysms. This study aimed to identify current challenges in antiplatelet management during stent-assisted coiling/flow diversion for ruptured intracranial aneurysms and to outline possible antiplatelet management strategies. MATERIALS AND METHODS: The modified DELPHI approach with an on-line questionnaire was sent in several iterations to an international, multidisciplinary panel of 15 neurointerventionalists. The first round consisted of open-ended questions, followed by closed-ended questions in the subsequent rounds. Responses were analyzed in an anonymous fashion and summarized in the final manuscript draft. The statement received endorsement from the World Federation of Interventional and Therapeutic Neuroradiology, the Japanese Society for Neuroendovascular Therapy, and the Chinese Neurosurgical Society. RESULTS: Data were collected from December 9, 2019, to March 13, 2020. Panel members achieved consensus that platelet function testing may not be necessary and that antiplatelet management for stent-assisted coiling and flow diversion of ruptured intracranial aneurysms can follow the same principles. Preprocedural placement of a ventricular drain was thought to be beneficial in cases with a high risk of hydrocephalus. A periprocedural dual, intravenous, antiplatelet regimen with aspirin and a glycoprotein IIb/IIIa inhibitor was preferred as a standard approach. The panel agreed that intravenous medication can be converted to oral aspirin and an oral P2Y12 inhibitor within 24 hours after the procedure. CONCLUSIONS: More and better data on antiplatelet management of patients with ruptured intracranial aneurysms undergoing stent-assisted coiling or flow diversion are urgently needed. Panel members in this DELPHI consensus study preferred a periprocedural dual-antiplatelet regimen with aspirin and a glycoprotein IIb/IIIa inhibitor.

Quantitative assessment of haemolysis secondary to modern infusion pumps.

BACKGROUND: Although most studies have shown that little haemolysis is induced by infusion pumps, there are some notable exceptions. Only limited data are available on the actual infusion pumps that are most used in hospitals in Quebec and elsewhere, namely, the Infusomat® Space (peristaltic), Plum A+™ (piston) and Colleague® CXE (shuttle) pumps. METHODS: Haemolysis and potassium levels were compared before and after the use of the three different infusion pumps. Using 135 units of packed red blood cells (RBCs) aged from 10 to 28 days, 27 measurements were taken for each pump at various flow rates (30, 60, 150, 300 and 450 ml/h) and were compared with measurements taken before using the pumps. The range of flow rates was chosen to cover those of paediatric and adult transfusions. RESULTS: The shuttle- and piston-type pumps resulted in low haemolysis levels. The peristaltic-type pump produced significantly more haemolysis, which worsened at low flow rates, but the absolute value of haemolysis remained within the range recommended by the regulatory agencies in North America and Europe. Approximately two-thirds of the haemolysis produced by the peristaltic-type pump seemed to be secondary to the use of an antisiphon valve (ASV) on the transfusion line recommended by the manufacturer. Potassium levels did not increase with the use of the pumps. CONCLUSION: Modern infusion pumps widely used in hospitals in Quebec and elsewhere produce non-threatening levels of haemolysis during the transfusion of packed RBCs aged from 10 to 28 days. ASVs appear to induce additional haemolysis, and we do not recommend using them for blood transfusion.

Effect of warming and flow rate conditions of blood warmers on red blood cell integrity.

BACKGROUND AND OBJECTIVES: Fluid warmers are routinely used to reduce the risk of hypothermia and cardiac complications associated with the infusion of cold blood products. However, warming blood products could generate haemolysis. This study was undertaken to compare the impact of temperature of blood warmers on the per cent haemolysis of packed red blood cells (RBCs) heated at different flow rates as well as non-flow conditions. MATERIALS AND METHODS: Infusion warmers used were calibrated at 41·5°C ± 0·5°C and 37·5°C ± 0·5°C. Cold RBC units stored at 4°C in AS-3 (n = 30), aged 30-39 days old, were divided into half units before being allocated under two different scenarios (i.e. infusion pump or syringe). RESULTS: Blood warmers were effective to warm cold RBCs to 37·5°C or 41·5°C when used in conjunction with an infusion pump at flow rate up to 600 ml/h. However, when the warmed blood was held in a syringe for various periods of time, such as may occur in neonatal transfusions, the final temperature was below the expected requirements with measurement as low as 33·1°C. Increasing the flow with an infusion pump increased haemolysis in RBCs from 0·2% to up to 2·1% at a flow rate of 600 ml/h regardless of the warming device used (P < 0·05). No relevant increase of haemolysis was observed using a syringe. CONCLUSIONS: The use of a blood warmer adjusted to 41·5°C is probably the best choice for reducing the risk of hypothermia for the patient without generating haemolysis. However, we should be cautious with the use of an infusion pump for RBC transfusion, particularly at high flow rates.

Incidence of hypotension and acute hypotensive transfusion reactions following platelet concentrate transfusions.

BACKGROUND AND OBJECTIVES: Platelet concentrates (PCs) are associated with transfusion reactions involving hypotension, particularly bradykinin-mediated acute hypotensive transfusion reactions. This study aims to determine the incidence of hypotensive events and more specifically acute hypotensive transfusion reaction associated with PC transfusions. We also sought to ascertain whether these reactions are associated with elevated bradykinin levels. MATERIALS AND METHODS: This is a prospective descriptive study of PCs administered at Sainte-Justine Hospital over 28 months. All PCs administered during this period were screened for hypotension through review of all transfusion-associated reaction reports (TARRs) sent to the blood bank. All residual PC bags were returned to the blood bank. TARRs associated with hypotension were reviewed by adjudicators that established the imputability of the PC transfusion to the reaction. Bradykinin levels were sampled in the first 168 PC bags returned to the blood bank. Levels were compared between PCs associated with hypotension and control PCs not associated with hypotension. RESULTS: A total of 3672 PC bags were returned to the blood bank; 25 PCs were associated with hypotension. Adjudicators ascertained that five hypotensive events were imputable to PCs of which one was an acute hypotensive transfusion reaction (incidence: 0·03%). Bradykinin level in the latter PC was 10 pg/ml, whereas levels were 226·2 ± 1252 pg/ml in the 143 control PCs. CONCLUSION: Our results show a low incidence of hypotension after PC transfusion. We identified only one acute hypotensive transfusion reaction. No correlation between bradykinin level and the occurrence of acute hypotensive reactions could be observed given that only one event was identified.

Projection-free approximate balanced truncation of large unstable systems.

In this article, we show that the projection-free, snapshot-based, balanced truncation method can be applied directly to unstable systems. We prove that even for unstable systems, the unmodified balanced proper orthogonal decomposition algorithm theoretically yields a converged transformation that balances the Gramians (including the unstable subspace). We then apply the method to a spatially developing unstable system and show that it results in reduced-order models of similar quality to the ones obtained with existing methods. Due to the unbounded growth of unstable modes, a practical restriction on the final impulse response simulation time appears, which can be adjusted depending on the desired order of the reduced-order model. Recommendations are given to further reduce the cost of the method if the system is large and to improve the performance of the method if it does not yield acceptable results in its unmodified form. Finally, the method is applied to the linearized flow around a cylinder at Re = 100 to show that it actually is able to accurately reproduce impulse responses for more realistic unstable large-scale systems in practice. The well-established approximate balanced truncation numerical framework therefore can be safely applied to unstable systems without any modifications. Additionally, balanced reduced-order models can readily be obtained even for large systems, where the computational cost of existing methods is prohibitive.

Quality and safety of red blood cells stored in two additive solutions subjected to multiple room temperature exposures.

BACKGROUND AND OBJECTIVES: Many international standards state that red blood cell (RBC) products should be discarded if left out of controlled temperature storage for longer than 30 min to reduce the risk of bacterial growth and RBC loss of viability. This study aimed to verify whether repeated short-time exposures to room temperature (RT) influence RBCs quality and bacterial proliferation. MATERIALS AND METHODS: Saline-adenine-glucose-mannitol (SAGM) and AS-3 RBC units were split and exposed to RT for 30 or 60 min on day 2, 7, 14, 21, and 42 of storage while reference units remained stored at 1-6°C. Red blood cell in vitro quality parameters were evaluated after each exposure. In a second experiment, SAGM and AS-3 RBC units were split and inoculated with Staphylococcus epidermidis (5 CFU/ml), Serratia marcescens (1 CFU/ml), and Serratia liquefaciens (1 CFU/ml). Reference units remained in storage while test units were exposed as described previously. Bacterial concentrations were investigated after each exposure. RESULTS: No differences were noticed between reference and test units in any of the in vitro parameters investigated. S. epidermidis did not grow in either reference or exposed RBCs. While S. marcescens did not grow in AS-3, bacterial growth was observed in RT-exposed SAGM RBCs on day 42. Similar growth was obtained for S. liquefaciens in the two additive solutions for both reference and test units. CONCLUSION: Short-time exposures to RT do not affect RBC quality and do not significantly influence bacterial growth. An expansion of the '30-minute' rule to 60 min should be considered by regulatory agencies.

Overnight storage of whole blood: cooling and transporting blood at room temperature under extreme temperature conditions.

BACKGROUND AND OBJECTIVES: Many countries allow the overnight storage of whole blood (WB) at ambient temperature. Some countries, such as Canada, also require a rapid cooling of WB with an active cooling system. Given the significant operational constraints associated with current cooling systems, an alternative method for cooling and transporting WB at 20-24°C was evaluated. MATERIALS AND METHODS: Phase 22 cooling packs (TCP Reliable Inc., USA) were used in combination with vacuum-insulated panel (VIP) boxes. Temperature profiles of simulated WB units were studied in extreme temperatures (-35 and 40°C). The quality of blood components prepared using Phase 22 packs and CompoCool-WB (Fresenius HemoCare, Germany) was studied. RESULTS: Phase 22 packs reduced the temperature of simulated WB bags from 37 to 24°C in 1·7 ± 0·2 h. Used in combination with VIP boxes, Phase 22 packs maintain the temperature of bags between 20 and 24°C for 15 and 24 h, compared to 2 and 11 h with CompoCool-WB, when exposed at -35 and 40°C, respectively. The quality of platelet concentrates and plasma was comparable, regardless of the cooling system used. For red blood cell units, per cent haemolysis on day 42 was slightly higher in products prepared after cooling with Phase 22 packs compared to CompoCool-WB (0·33 ± 0·15% vs. 0·21 ± 0·06%; P < 0·05). CONCLUSIONS: Phase 22 packs combined with VIP boxes are an acceptable alternative to butane-1,4-diol cooling systems. This system allows blood manufacturers to transport WB to processing facilities in a broad range of environmental conditions.

[Chikungunya outbreak on Reunion Island in 2005/2006: role of hospital physicians in raising alert]. / L'epidémie de chikungunya de la Réunion 2005-2006; place du médecin hospitalier dans l'alerte et la gestion de l'epidémie.

The epidemic of chikungunya (CHIK) that swept through Reunion Island from late 2005 to mid 2006 affected 38.2% of the population, i.e., 300000 people. Although this outbreak took place in a French overseas department with high public health standards, failure to anticipate a large-scale epidemic associated with unprecedented severity and unexpectedly high mortality led to a major public health crisis. The purpose of this report is to provide a complete account of the experience of hospital intensive care physicians in addressing problems ranging from discovery of severe forms to management of a major health crisis. This report underlines the role of the head hospital physician and the necessity of mutual trust and collaboration with supervisory authorities.

[Outbreak of influenza A(H1N1)/2009: description of cases and crisis management in a ICU in Reunion Island]. / Épidémie de grippe A(H1N1/)2009 : description des cas et expérience de gestion de crise dans un service de réanimation réunionnais.

OBJECTIVES: to describe the characteristics, treatment and outcome of critically ill patients with influenza A(H1N1) infection at St Pierre Hospital in Reunion Island during the 2009 outbreak, as well as the measures of care reorganization implemented to face them. PATIENTS AND METHODS: prospective observational study of probable and confirmed cases of influenza A (H1N1)/2009 infection concerning hospitalized patients in a polyvalent intensive care unit (ICU). RESULTS: thirteen patients have been included between August and September 2009. Three (23 %) didn't have any medical history. The median age was 42 [22-69]. Eleven have required pulmonary ventilation for 10.3 days (± 8). Three (23 %) have developed an ARDS. Three patients (23 %) died. To cope with the influx of cases and considering our situation of geographic isolation, it has been needed to totally rework the organization of care: set-up of a specific welcoming channel, division into sectors of the department, opening of additional beds, new on-duty assignment, inter and intra hospital cooperation. CONCLUSION: reunion Island has been an experimental lab of crisis management during the H1N1/2009 epidemic, several months ahead of the mother country. To anticipate the reorganization of care in intensive care units during an outbreak period, particularly in small units or units isolated like ours, looks to us a must so to quietly face a sharp influx of patients.

Allergic transfusion reactions from blood components donated by IgA-deficient donors with and without anti-IgA: a comparative retrospective study.

BACKGROUND AND OBJECTIVES: IgA deficiency is common (1/500) and up to 40% of affected individuals will develop anti-IgA. A few studies suggested that passive transfusion of anti-IgA was not associated with an increased risk of allergic reactions. This study was designed to assess the safety of transfusing blood components containing anti-IgA. MATERIALS AND METHODS: IgA-deficient blood donors with and without anti-IgA were identified from Héma-Québec's (HQ) computerized database. IgA deficiency was confirmed by an ELISA method and the presence of anti-IgA by a passive hemagglutination assay. Blood donations from IgA-deficient donors issued to hospitals between March 1999 and December 2004 were retrieved. Medical charts of recipients were reviewed for the occurrence of a suspected transfusion reaction. Presence and nature of transfusion reactions were assessed blindly by an adjudicating committee. RESULTS: A total of 323 IgA-deficient blood products were issued by HQ to 55 hospitals. Of these, 48 agreed to participate [315 blood products (97.5%)]. A total of 272 products were transfused: 174 contained anti-IgA, and 98 did not. Only two minor allergic reactions occurred in each group. Incidence of allergic reactions was 1.15% in the anti-IgA group and 2.04% in the group without anti-IgA (P = 0.91). There was no anaphylactic reaction in either group. CONCLUSIONS: This study indicates that the proportion of allergic reactions does not appear to be greater in recipients of blood components containing anti-IgA compared to recipients of non-anti-IgA-containing components. Allowing donations from IgA-deficient donors with anti-IgA may therefore be contemplated.

Improved leucoreduction of red blood cell units prepared after a 24-h hold with the platelet-rich plasma method using newly developed filters.

BACKGROUND AND OBJECTIVES: A previous study indicated that the extension of whole blood (WB) storage from 8 to 24 h at 20-24 degrees C before the processing of platelet-rich plasma (PRP)-depleted red blood cell (RBC) units had a negative effect on the efficacy of leucoreduction filters. In this study, we further characterized the phenomenon and tested the leucoreduction capacity of two newly developed filters. MATERIALS AND METHODS: Whole blood was stored at 20-24 degrees C and processed at 4-h intervals between 8 and 24 h postcollection. Components were leucoreduced before storage. Efficacy of novel filters to leucoreduce 24-h-hold PRP-depleted RBC units was also evaluated. RESULTS: Using a conventional filter, the mean residual white blood cell (WBC) counts in leucoreduced PRP-depleted RBCs were comparable in units prepared within 12 h from collection but gradually increased upon extended preprocessing storage from 0.36 +/- 0.03 at 12 h to 0.46 +/- 0.21, 0.76 +/- 0.54 and 1.72 +/- 1.76 x 10(6) per unit at 16, 20 and 24 h, respectively. However, the mean residual WBC content in 24-h-hold RBCs was reduced to 0.60 +/- 0.39 x 10(6) and 0.46 +/- 0.13 x 10(6) per units using RC2D and the prototypes B-1582 rev B filters, respectively. CONCLUSION: For PRP-depleted RBC units, the extension of the WB room temperature storage from 8 to 24 h before processing is likely to require the introduction of newly developed filters having an increased leucoreduction capacity in order to meet the maximal residual WBC guideline in the RBCs.

Dietary protein level alters gentamicin-induced nephrotoxicity in rats.

Aminoglycosides (AG) such as gentamicin are antimicrobial drugs widely used in the hospital setting due to their efficacy in the treatment of severe gram-negative bacterial infections. However, all AG have the potential to cause nephrotoxicity. Two studies have been conducted (1) to assess the protein level of a diet that would give the best renal outcome with gentamicin administration, and (2) to get a better idea about the rhythms of food ingestion associated with the different protein levels. Adult female Sprague-Dawley rats fully adapted to a standard chow diet, the standard chow with 20% or 55% added casein were chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day, i.p.) or a saline solution. Food ingestion patterns of rats were recorded every hour using a Diet Scan system and gentamicin nephrotoxicity indices were measured. The second study used rats that were fed the same diets and given a sham injection. Corticosterone was assayed to quantify the stress of the animals. Results showed that chronic gentamicin treatment leads to a decrease in food intake and flattening of the rhythms of food ingestion. Also, chow feeding and the 20% casein diet were found to be more protective against gentamicin-induced nephrotoxicity than the 55% casein diet. Therefore, while a protein-rich diet can be protective against gentamicin-induced nephrotoxicity, the present study demonstrates that a diet too high in protein might rather be harmful to the kidneys.

Effect of sibutramine on macronutrient selection in male and female rats.

Sibutramine, a serotonin-noradrenaline reuptake inhibitor (SNRI), has been shown to be a safe and effective weight-loss drug. The purpose of the present study was to examine whether sibutramine has an effect on macronutrient selection in both female and male rats in addition to total food intake. Wistar rats of both sexes were divided into three groups, and each group was offered a different set of three sensorily contrasting macronutrient-specific diets, each set including carbohydrate-, protein-, and fat-rich diets. Sibutramine (10 mg/kg) was shown to consistently decrease carbohydrate and fat intake at all data points regardless of gender and diet. Intake of carbohydrate differed between male and female rats at 2 h post administration with 2.5 and 5 mg/kg of sibutramine. The effect of sibutramine on protein intake was diet- and gender-specific. All doses of sibutramine decreased total food intake regardless of gender and diet group beginning at 6 h post administration. In conclusion, sibutramine affected macronutrient selection and emphasis on dietary recommendations, as well as appropriate dosage according to gender should be considered during therapy.

Effect of melatonin on total food intake and macronutrient choice in rats.

Melatonin, a hormone secreted in a rhythmic manner over 24 h mainly by the pineal gland, is used to alleviate the symptoms of jetlag and treat sleeping problems. The objective of the present study was to examine the effects of a 7-h phase-shift from the natural peak of melatonin secretion on total food intake and macronutrient selection. Forty-eight adult Wistar rats of both sexes were divided in three dietary groups, each group offered a simultaneous and different choice of a carbohydrate- and a protein-rich diet. Macronutrient intakes following intraperitoneal administration of four doses of melatonin (3000, 6000, 10000 and 15000 pg/ml blood) at dark onset were examined. Melatonin increased short- (4 h postinjection) and long-term (12 h postinjection) nocturnal total food intake in both male and female rats, mainly with the two highest doses. This effect of melatonin was mainly due to a short-term increase of intake across all carbohydrate-rich diet preparations (dextrin/cornstarch, cornstarch, and sucrose/cornstarch) and across genders. This consistent effect of melatonin on the intake of carbohydrate-rich diets with contrasting sensory attributes rules out the possibility that melatonin acts on sensorymotor pathways, thus suggesting that melatonin's effect on food intake is controlled by the carbohydrate content of the diet. In contrast, melatonin could be affecting some sensory or motor processes peculiar to the ingestion of protein since it increased protein-rich diet intake inconsistently across the various preparations (casein, soy isolate, and egg protein) as well as genders. This evidence supports the view that melatonin acts as a time indicator, reinforcing the animals with a "night cue", and favors predominant carbohydrate intake normally occurring at the beginning of the activity period.

Dietary composition alters gentamicin-induced nephrotoxicity in rats.

Previous studies have shown temporal variations in gentamicin-induced renal toxicity characterized by a peak when administered during the resting period and a trough during the active period. This time-dependent toxicity was also altered according to the macronutrient composition of dietary regimens offered to female rats. In the present study, adult female Sprague-Dawley rats were adapted to semipurified isocaloric diets containing 20% casein or soy-protein (10% fat each) or to a standard chow diet (18.1% mixed proteins; 4.5% fat). The animals were then chronically treated for 10 days with a nephrotoxic dose of gentamicin sulfate (40 mg/kg/day ip) or a saline solution administered in the middle of their resting period (1200 h) or in the middle of their activity period (0000 h). Body weights of rats injected in the middle of their resting period decreased over the last 6 days of gentamicin treatment. Total 12-h light and 12-h dark food intakes were decreased in gentamicin-treated rats. Rats fed the standard chow diet had significantly lower corticocellular regeneration, serum creatinine and blood urea nitrogen compared to those fed the casein- and soy-containing diets. The present study demonstrates that chronic gentamicin-induced renal toxicity varies temporally according to the time of administration and that a mixed protein diet containing a lower fat level can protect against gentamicin-induced nephrotoxicity.

Biomechanics and neuropathology of adult and paediatric head injury.

The objective of this study was to understand the biomechanics in age-related primary traumatic brain injuries (TBI) causing initial severity and secondary progressive damage and to develop strategy reducing TBI outcome variability using biomechanical reconstruction to identify types of causal mechanisms prior to clinical trials of neuro-protective treatment. The methods included the explanation of TBI biomechanics and physiopathological mechanisms from dual perspectives of neurosurgery and biomechanical engineering. Scaling of tolerances for skull failure and brain injuries in infants, children and adults are developed. Diagnostic assumptions without biomechanical considerations are critiqued. Methods for retrospective TBI reconstruction for prevention are summarized. Mechanisms of TBI are based on the differences between the mechanical properties of the head and neck related to age. Skull fracture levels correlate with increasing cranial bone thickness and in the development of the cranial sutures in infants and in adults. Head injury tolerance levels at three age categories for cerebral concussion, skull fracture and three grades of diffuse axonal injuries (DAI) are presented. Brain mass correlates inversely for TBI caused by angular head motions and locations of injurious stresses are predictable by centripetal theory. Improved quantitative diagnosis of TBI type and severity levels depend primarily on age and biomechanical mechanisms. Reconstruction of the biomechanics is feasible and enables quantitative stratification of TBI severity. Experimental treatment has succeeded in preventing progressive damage in animal TBI models. In humans this has failed, because the animal model received biomechanically controlled TBI and humans did not. Clinical similarities of human TBI patients do not necessarily predict equivalent biomechanics because such trauma can be produced in various ways. We recommend 'reverse engineering' for in-depth reconstruction of the TBI injury mechanism for qualitative diagnoses and reduction of outcome variability.