What We Already Know about This Topic Dantrolene effectively treats malignant hyperthermia, but there are discrepant recommendations for dantrolene availability in facilities that stock succinylcholine for airway rescue but do not use volatile anesthetics. What This Article Tells Us That Is New The authors performed an analysis of data from three databases and a systematic literature review. Providers frequently use succinylcholine, including during difficult mask ventilation. Succinylcholine given without volatile anesthetics triggered 24 malignant hyperthermia events, 13 of which were treated with dantrolene. Fourteen patients experienced substantial complications, and one died. Delayed dantrolene treatment worsened patient outcomes. Background: Although dantrolene effectively treats malignant hyperthermia (MH), discrepant recommendations exist concerning dantrolene availability. Whereas Malignant Hyperthermia Association of the United States guidelines state dantrolene must be available within 10 min of the decision to treat MH wherever volatile anesthetics or succinylcholine are administered, a Society for Ambulatory Anesthesia protocol permits Class B ambulatory facilities to stock succinylcholine for airway rescue without dantrolene. The authors investigated (1) succinylcholine use rates, including for airway rescue, in anesthetizing/sedating locations; (2) whether succinylcholine without volatile anesthetics triggers MH warranting dantrolene; and (3) the relationship between dantrolene administration and MH morbidity/mortality. Methods: The authors performed focused analyses of the Multicenter Perioperative Outcomes Group (2005 through 2016), North American MH Registry (2013 through 2016), and Anesthesia Closed Claims Project (1970 through 2014) databases, as well as a systematic literature review (1987 through 2017). The authors used difficult mask ventilation (grades III and IV) as a surrogate for airway rescue. MH experts judged dantrolene treatment. For MH morbidity/mortality analyses, the authors included U.S. and Canadian cases that were fulminant or scored 20 or higher on the clinical grading scale and in which volatile anesthetics or succinylcholine were given. Results: Among 6,368,356 queried outcomes cases, 246,904 (3.9%) received succinylcholine without volatile agents. Succinylcholine was used in 46% (n = 710) of grade IV mask ventilation cases (median dose, 100 mg, 1.2 mg/kg). Succinylcholine without volatile anesthetics triggered 24 MH cases, 13 requiring dantrolene. Among 310 anesthetic-triggered MH cases, morbidity was 20 to 37%. Treatment delay increased complications every 10 min, reaching 100% with a 50-min delay. Overall mortality was 1 to 10%; 15 U.S. patients died, including 4 after anesthetics in freestanding facilities. Conclusions: Providers use succinylcholine commonly, including during difficult mask ventilation. Succinylcholine administered without volatile anesthetics may trigger MH events requiring dantrolene. Delayed dantrolene treatment increases the likelihood of MH complications. The data reported herein support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used.

Background Educational research projects are often developed and implemented at a single institution. However, the research project methods and results may not be generalizable and able to be replicated successfully at other institutions. The aim of this study was to investigate the process of replicating an effective educational Objective Structured Clinical Examination (OSCE) event at multiple other institutions. Methods An OSCE event was initially designed and implemented at the primary institution to assess the skill level of junior residents on the performance of basic anesthesia tasks. After the initial implementation, additional institutions were recruited to participate in a replication of this OSCE event at their own institutions. The primary institution provided the OSCE scenarios, assessment tools, rater training, and resident participant instructions. The participating secondary institutions' (n = 4) event managers obtained Institutional Review Board [IRB] approval, developed the event schedule, assigned faculty evaluators, and organized the simulation space at their own medical centers. The events were assessed by the secondary institutions' resident and faculty participants via an anonymous survey regarding the event's content and their perception of its educational value. Results We replicated a complex educational OSCE event, developed and implemented at 1 institution, at 4 other institutions. Resident participants (n = 60), participating faculty (n = 24), and event directors (n = 4) indicated a high level of appreciation for the OSCE event. Conclusion Using a structured approach, educational OSCE events can be successfully replicated at multiple institutions. Organization of multi-institutional studies and collaborative efforts is complex. This study illustrates 1 example of how to successfully approach multi-institutional educational projects.

Background: Thromboelastography is a method of measuring whole-blood coagulation changes and has been used to guide therapy and monitor changes in a variety of disease states. However, few studies have investigated the thromboelastographic changes experienced in a patient who has received alteplase for an acute ischemic stroke. This pilot study sought to describe the effect of alteplase on the thromboelastogram tracings of patients experiencing an acute ischemic stroke. Methods: This was an institutional review board-approved prospective cohort study. Patients who presented to the emergency department with symptoms of acute ischemic stroke and received intravenous alteplase were evaluated for inclusion. Blood samples were obtained before alteplase administration and at 30, 60, 90, 120, and 150 minutes after alteplase administration. In addition, baseline variables collected included patient age, sex, prothrombin time, partial thromboplastin time, and the use of pretreatment anticoagulants or antiplatelet agents. Patients were also followed throughout their hospital stay for development of intracranial he. Results: A total of 7 patients were included in the analysis. At baseline, thromboelastogram parameters of all patients were within the normal range. The maximum inhibition of fibrin buildup was seen at 30 minutes after the start of alteplase infusion, and the lowest clot strength was observed at 60 minutes after initiation of alteplase. Most patients return to near baseline parameters within 150 minutes of alteplase initiation; however, 2 patients did not return to their baseline values within the 150-minute time frame. Conclusions: Our study suggests that thromboelastogram (TEG) is a useful tool for determining changes in the coagulation system of patients whom have received recombinant tissue plasminogen activator (rt-PA). Further study is needed to determine if TEG can be used to predict those patients who may be at higher risk of adverse events because of rt-PA. (C) 2014 by National Stroke Association

BACKGROUND:Aspirin-resistant platelet activation in whole blood is attributable to a transcellular pathway not detected by isolated platelet aggregometry. Aspirin resistance as defined by urinary thromboxane levels is associated with increased risk for myocardial infarction or cardiac death. Whole blood point-of-care assays may also detect aspirin resistance. METHODS:We compared PlateletMapping® with VerifyNow® for detecting aspirin resistance in 200 patients undergoing invasive cardiac procedures. This included 10 patients not receiving aspirin therapy for comparison. The assay results were correlated with urinary 11-dehydro-thromboxane B2 collected 2 to 8 hours after the procedure. RESULTS:PlateletMapping detected aspirin resistance in 32% of patients. VerifyNow detected aspirin resistance in 6% of patients. A patient's compliance with aspirin therapy was confirmed by a <20% aggregation response to arachidonic acid by light transmission aggregometry. Aspirin-resistant patients as determined by PlateletMapping had significantly (P<0.001) higher urinary 11-dehydro-thromboxane B2 levels than aspirin-sensitive patients but significantly (P=0.001) lower levels than patients not receiving aspirin therapy. There was no significant difference in urinary 11-dehydro-thromboxane B2 for aspirin-resistant compared with aspirin-sensitive patients as determined by VerifyNow, but the confidence intervals were wide. There was no significant correlation of resistance as defined by PlateletMapping with aspirin dose. However, there was significant increased aspirin sensitivity with clopidogrel (0.0006) or statin (0.004) cotherapies. There also was a significant correlation of smoking with aspirin resistance. CONCLUSIONS:These results indicate that PlateletMapping could be a useful point-of-care assay to identify aspirin-resistant patients for better perioperative risk stratification and management.

Background Limited data are available regarding the perioperative management of cardiac rhythm management devices (CRMDs) exposed to intraoperative electromagnetic interference. We postulated that implementation of a simple, standardized approach to CRMD management using our own institution's Pacing And Cardioverting Electronic Devices peri-Operative Protocol (the PACED-OP protocol) would be associated with a reduction in the amount of device reprogramming without an increase in CRMD-related complications. Methods Records of patients with CRMDs undergoing 497 consecutive surgical procedures were analyzed retrospectively. Roughly half (51%, n=254) of these procedures occurred before implementation of the PACED-OP protocol, when patients were generally treated according to the American Society of Anesthesiologists' 2005 guidelines. These cases were compared to the remaining surgeries that occurred after implementation of the PACED-OP protocol. Records were screened for evidence of intraoperative CRMD malfunction that was directly associated with the use of electrocautery. Postoperative complications that could be indirectly or possibly linked to electrocautery-mediated CRMD malfunction were also identified. Results Implementation of the PACED-OP protocol was associated with a significant reduction in the odds of device reprogramming (adjusted odds ratio [aOR] 0.19, P<0.001). There was no direct evidence of CRMD malfunction in either cohort. The rate of postoperative complications that could be indirectly or possibly linked with electrocautery-mediated CRMD damage did not differ significantly between cohorts (aOR=1.37, 95% confidence interval 0.563.3, P=0.49). Conclusion The PACED-OP protocol implementation was associated with a significant reduction in the odds of device reprogramming without a significant difference in the odds of CRMD-related complications.

INTRODUCTION:We have previously defined aspirin resistance detected by TEG PlateletMapping using arachidonic acid (AA). This aspirin resistance is observed as platelet activation (>20%) by AA in whole blood, even though the isolated platelets are inhibited by aspirin. This platelet activation in whole blood is due to a transcellular pathway mediated by platelets and leukocytes.METHODS:To determine if this PlateletMapping assay of aspirin resistance on pre-procedure blood samples correlated with an in vivo response we assayed the first voided urine samples collected 2-8 hours post interventional cardiology procedures for 11-dehydro thromboxane B2.RESULTS AND CONCLUSIONS:We detected 27 aspirin resistant patients out of a total of 81 (33%), in agreement with our previous study. All of these patients were on aspirin therapy, confirmed by a <20% aggregation response to AA by light transmission platelet aggregometry using isolated platelet rich plasma. Aspirin resistant patients urine samples (14 out of a total of 60 patients analyzed) contained significantly (P=0.008) higher 11-dehydro thromboxane B2 levels than the other 46 aspirin sensitive patients urine samples. Since our previous study implicated 12- and 15-lipoxygenases in this pathway, we also assayed for polymorphisms to determine any correlation with aspirin resistance. A correlation was found in a polymorphism affecting the lipoxygenase domain of platelet 12-lipoxygenase. This result indicates that aspirin resistance detected in whole blood by the TEG PlateletMapping assay correlates with a physiological consequence in terms of thromboxane formation. This is the first report of such a correlation.

Posttraumatic coagulopathy is a major cause of morbidity. This prospective study evaluated the thrombelastography (TEG) system and PlateletMapping (Haemoscope Corporation, Niles, III) values posttrauma, and it correlated those values with transfusions and fatalities. After institutional review board approval, assays were performed on 161 trauma patients. One citrated blood sample was collected onsite (OS), and 1 citrate and 1 heparinized sample were collected within 1 h of arrival to the emergency department (ED). Paired and unpaired t-testing was performed for nominal data with chi square testing for categorical values. Except for a slight increase in clot strength (maximal amplitude (MA)), there were no significant changes from OS to the ED. None of the TEG parameters were significantly different for the 22 patients who required transfusion. PlateletMapping showed lower platelet adenosine diphosphate (ADP) responsiveness in patients who needed transfusions (MA = 22.7 +/- 17.1 vs MA = 35.7 +/- 19.3, P = 0.004) and a correlation of fibrinogen < 100 mg/dL with fatalities (P = 0.013). For the 14 fatalities, TEG reaction (R) time was 3703 +/- 11,618 versus 270 +/- 393 s (P = < 0.001), and MA was 46.4 +/- 22.4 versus 64.7 +/- 9.8 mm (P < 0.001). Hyperfibrinolysis (percent fibrinolysis after 60 min (LY60) > 15%) was observed in 3 patients in the ED with a 67% fatality rate (P = < 0.001 by chi-square testing). PlateletMapping assays correlated with the need for blood transfusion. The abnormal TEG System parameters correlated with fatality. These coagulopathies were already evident OS. The TEG assays can assess coagulopathy, platelet dysfunction, and hyperfibrinolysis at an early stage posttrauma and suggest more effective interventions. (Translational Research 2009; 154:34-39)

Study Objective: To validate a Thromboelastograph (Haemoscope Corporation, Niles, IL) assay for functional fibrinogen.Design: Correlation study of the Thromboelastograph assay with two conventional fibrinogen assays by the standard Clauss method.Setting: Research laboratory of a university medical center.Participants and Interventions: Blood samples were obtained from 19 healthy volunteers.Measurement and Main Results: Thromboelastograph assays, using heparinized whole blood from 19 healthy donors, indicated that reptilase-XIIIa mixture (Activator(f))-generated clot shear elasticity in dynes per square centimeter (G(f)) correlated with fibrinogen (mg/dL). Blood from four donors was used to define the contribution of hematocrit (Het) to G(f) by titration with platelet-rich plasma. The G(f) versus Hct gave linear correlations (r(2) = 0.746) with G(f) = 1258 - 17.8 x % Hct. A commercial collection of 19 normal, 10 borderline, and one deficient for functional fibrinogen-citrated plasmas was assayed for G(f) after recalcification using Activator(f). Of the 30 plasma samples, four were from factor X- or factor VII-deficient donors and one was from a coumadin-treated donor. There was a linear correlation of Activatorf Gf with functional fibrinogen (r(2) = 0.940) with G(f) = -730 + 9.21 x fibrinogen (mg/dL).Conclusion: Thrombelastography with Activatorf may be used to determine fibrinogen levels in whole blood. (c) 2008 Elsevier Inc. All rights reserved.

The anticoagulant effect of enoxaparin is readily observed by Thrombelastography (TEG), particularly on the reaction time (R) to form a clot, and is completely reversed by heparinase. In this study, recalcified citrated whole blood with heparinase (CNHR) and without (CNR), along with TEG R time, was used to derive a delta R (CNR-CNHR). This delta R (DeltaR) was then used to measure enoxaparin anticoagulation, which was correlated by linear regression (r(2)=0.806) with plasma anti-Xa in 48 thrombophilic pregnancy patients. In a follow up study whole blood from 15 thrombophilic and 15 normal pregnancy subjects was titrated ex vivo with enoxaparin and TEG DeltaR determined. Linear dose responses (all r(2)>0.9) of DeltaR versus plasma enoxaparin concentration were obtained for each subject. A large variation in slope was observed for both thrombophilic (>7 fold, 217 to 1,588 s DeltaR/unit anti-Xa) and normal (>3 fold, 788 to 2,758) pregnancy subjects. The average slope for the thrombophilic group (710 s DeltaR/unit anti-Xa) was significantly (P=0.002) lower than the normal pregnancy group (1,354 s), indicating resistance to enoxaparin anticoagulation in the thrombophilic group. This technique may help gauge the appropriate dose of enoxaparin for each individual, check for residual anticoagulation before invasive procedures, and perhaps help screen for thrombophilic subjects.

Clinically monitoring recovery from clopidogrel and nonsteroidal anti-inflammatory drug (NSAID) inhibition requires whole blood assays corresponding to a standard methodology such as platelet-rich plasma aggregation monitored optically (OPA). We compared OPA, using an ED50 dose of adenosine diphosphate activation, with 2 whole blood assays, Plateletworks (PWA) and modified Thrombelastograph (TEG). Two sets of assays were performed on 43 surgery patients while on clopidogrel and off clopidogrel to determine the reversal of absolute and relative inhibition. The modified TEG had Spearman correlations with OPA for absolute (p =.424; P =.006) and relative inhibition (p =.742; P <.0001). PWA correlations with OPA gave absolute (p =.28; P =.08) and relative inhibition (p =.46; P =.004) values. Bland-Altman analysis indicated agreement of both tests with OPA, showing constant biases of about 18% and some dependency on mean magnitude error. Cohen effect size thresholds defined nonresponders as < 7.7% clopidogrel inhibition relative to baseline recovery of full platelet function. Apparent nonresponse to clopidogrel or lack of platelet recovery did not correlate with statin or NSAID therapies. These PWA and modified TEG whole blood assays could prove useful for monitoring the reversal of clopidogrel and NSAID inhibition before surgery. More important, these assays done at baseline and after beginning clopidogrel therapy could monitor the effectiveness for the individual patients with cardiovascular disease and help identify the need for alternative therapies.

Optical platelet aggregation (OPA) with platelet-rich plasma (PRP) was compared with a Thrombelastograph (TEG) whole blood assay for monitoring arachidonic acid (AA)-induced platelet activation. Assays were performed on 47 interventional cardiology and 24 general surgery patients receiving aspirin therapy for cardiovascular disease, as well as 48 volunteers asked to take nonsteroidal anti-inflammatory drugs (NSAIDs) or 12 volunteers on chronic NSAID therapy unrelated to diagnosed cardiovascular disease. Whole blood TEG monitoring of NSAID inhibition detected NSAID-insensitive AA activation of platelets in a significantly higher number of cardiology (23%) and surgery (25%) patients and normal volunteers on chronic NSAID (25%) therapy relative to normal subjects not on chronic NSAID therapy (0%). Whole blood NSAID insensitivity was observed with cyclooxygenase-I inhibitors, such as aspirin and ibuprofen; was not affected by Celebrex, a cyclooxygenase-II inhibitor; but was completely inhibited by thromboxane-receptor antagonists. This was not due to platelet NSAID insensitivity, because complete inhibition of AA-activation responses in PRP was observed with either TEG or OPA assays. We confirmed that thromboxane B-2 formation in PRP from NSAID-insensitive subjects was completely inhibited by NSAIDs. However, significant amounts were formed in whole blood from NSAID-insensitive subjects, but not in whole blood from NSAID-sensitive subjects. Thromboxane formation after AA addition was not found in washed blood cells with 90% reduced platelet counts or in leukocyte-rich buffy coat fractions, but could be restored by addition of PRP. NSAID-insensitive activation was inhibited by nordihydroguaiaretic acid, with an IC50 of 30 mu mol implicating 12- and/or 15-lipoxygenases in this transcellular pathway.

Flow cytometry, singlet platelet counting, and optical aggregation have been used to monitor clopidogrel and glycoprotein IIb/IIIa (GPIIb/IIIa) platelet antagonists. Optical aggregation is considered the gold standard, but neither it nor flow cytometry is convenient in larger-scale clinical studies or point-of-care systems. Singlet platelet counting, a point-of-care assay correlated with optical platelet aggregation, only provides a measurement of platelet function at a single point in time. The Thrombelastograph is used to assay whole blood for thrombin-generated maximal clot-shear elasticity, referred to as the maximal amplitude (MA). Although platelet dysfunction, thrombocytopenia, and the in vitro effect of strong inhibitors such as IIb/IIIa antagonists can be observed, with thrombin generation milder platelet inhibitors cannot be assessed. We modified the Thromboelastograph assay, using reptilase and factor XIIIa, to form a clot, without thrombin generation, in heparinized whole blood. The resulting clot MA is dependent on added platelet agonists such as ADP or arachidonic acid, is sensitive to platelet antagonists, and provides a continuous measure of platelet function more analogous and better correlated with optical aggregation. This novel modification of the Thromboelastograph assay should prove to be a useful point-of-care whole-blood assay with which to monitor the effects of GPIIb/IIIa, ADP, and thromboxane A(2)-receptor-inhibiting drugs in patients.

Platelet function was evaluated before and after clopidogrel therapy in 50 cardiology candidates scheduled for intervention; results were averaged from optical platelet aggregation with 2 significantly correlated point-of-care instruments, Thrombelastograph and Ichor PlateletWorks. Although this was a limited study with few complications, the failure of clopidogrel therapy (30% nonresponders with <10% average platelet inhibition) was not correlated with clinical pretreatment variables, including atorvastatin therapy, postintervention bleeding complications, or major adverse coronary events.

Platelets play a major role in thrombus formation, as well as in the pathogenesis of atherothrombosis. Inhibition of platelet function is now emphasised more than ever for prevention and treatment of almost all vascular diseases, since thrombosis is established as the key pathogenic event causing acute ischaemic coronary and cerebrovascular syndromes. Although acetylsalicylic acid (aspirin) has been shown to reduce the incidence of myocardial infarction and stroke, its effect is weak and more effective antithrombotic agents are required to manage patients at high-risk for recurrent vascular events. Platelet glycoprotein IIb/IIIa receptor (GPIIb/IIIa) blockade represents a significant advance in interventional cardiology and treatment of acute ischaemic syndromes. The past several years have seen the introduction of many platelet GPIIb/IIIa blockers into the clinical arena targeting the unique platelet GPIIb/IIIa receptor for the adhesive proteins, fibrinogen and von Willebrand Factor. Platelet GPIIb/IIIa blockers administered intravenously have proven efficacious in mitigating arterial thrombosis in acute coronary syndromes (unstable angina and non-ST-elevation myocardial infarction) and percutaneous coronary interventions (PCI) such as balloon dilatation and stent implantation. Currently, orally-active platelet GPIIb/IIIa blockers are being developed to provide additional benefits for primary and secondary prevention of thrombosis as chronic treatment, especially in high-risk patients. Lotrafiban (SmithKline Beecham) is a member of the latest generation of orally-active platelet GPIIb/IIIa blockers undergoing Phase III clinical trials to test the relative effectiveness versus other oral platelet inhibitors for ischaemic conditions including unstable angina, restenosis after PCI and stroke. Lotrafiban is converted from an esterified prodrug by plasma and liver esterases to a peptidomimetic of the arginine-glycine-aspartic acid amino acid sequence. This sequence itself mimics the binding site of fibrinogen and von Willebrand Factor to the platelet GPIIb/IIIa receptor. Preliminary results of the clinical trial APLAUD (antiplatelet useful dose) show that lotrafiban is clinically safe and well-tolerated in patients with recent myocardial infarction, unstable angina, transient ischaemic attack (TIA), or stroke when added to aspirin therapy. With lotrafiban, a worldwide large-scale Phase III clinical trial BRAVO (blockage of the GPIIb/IIIa receptor to avoid vascular occlusion) is currently underway. In general, GPIIb/IIIa blockade seems clinically very promising. A number of unresolved issues, however, remain to be elucidated.