Administration Of Reversal Agents Research Articles

Dedicated anticoagulation management protocols in fragility femoral fracture care – a source of significant variance and limited effectiveness in improving time to surgery: The hip and femoral fracture anticoagulation surgical timing evaluation (HASTE) study

IntroductionApproximately 20 % of femoral fragility fracture patients take anticoagulants, typically warfarin or Direct Oral AntiCoagulant (DOAC). These can impact timing of surgery affecting patient survival. Due to several possible approaches and numerous factors to consider in the preoperative workup of anticoagulated patients, potential for variations in clinical practice exist. Some hospitals employ dedicated anticoagulation management protocols to address this issue, and to improve time to surgery. This study aimed to determine the proportion of hospitals with such protocols, compare protocol guidance between hospitals, and evaluate the effectiveness of protocols in facilitating prompt surgery. MethodsData was prospectively collected through a collaborative, multicentre approach involving hospitals across the UK. Femoral fragility fracture patients aged ≥60 years and admitted to hospital between 1st May to 31st July 2023 were included. Information from dedicated anticoagulation management protocols were collated on several domains relating to perioperative care including administration of reversal agents and instructions on timing of surgery as well as others. Logistic regression was used to evaluate effects of dedicated protocols on time to surgery. ResultsDedicated protocols for management of patients taking warfarin and DOACs were present at 41 (52.6 %) and 43 (55.1 %) hospitals respectively. For patients taking warfarin, 39/41 (95.1 %) protocols specified the dose of vitamin k and the most common was 5 milligrams intravenously (n=21). INR threshold values for proceeding to surgery varied between protocols; 1.5 (n=28), 1.8 (n=6), and 2 (n=6). For patients taking DOACs, 35/43 (81.4 %) and 8/43 (18.6 %) protocols advised timing of surgery based on renal function and absolute time from last dose respectively. Analysis of 10,197 patients from 78 hospitals showed fewer patients taking DOACs received surgery within 36 h of admission at hospitals with a dedicated protocol compared to those without (adjusted OR 0.73, 95% CI 0.54–0.99, p=0.040), while there were no differences among patients taking warfarin (adjusted OR 1.64, 95% CI 0.75–3.57, p=0.219). ConclusionsAround half of hospitals employed a dedicated anticoagulation management protocol for femoral fragility fracture patients, and substantial variation was observed in guidance between protocols. Dedicated protocols currently being used at hospitals were ineffective at improving the defined targets for time to surgery.

Coagulation Tests and Reversal Agents in Patients Treated with Oral Anticoagulants: The Challenging Scenarios of Life-Threatening Bleeding and Unplanned Invasive Procedures.

In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients' conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents.

Time to oral anticoagulant reversal in intracranial hemorrhage with an emergency medicine pharmacist presence

PurposeIntracranial hemorrhage (ICH) is associated with high morbidity and mortality, with mortality rates up to 65%. Oral anticoagulants (OAC) are a major risk factor for ICH. Since these patients are usually diagnosed in the emergency department (ED), emergency medicine (EM) pharmacists can help ensure appropriate selection and delivery of medications in urgent situations including reversal agents for OAC-associated bleeding. The purpose of this study was to determine the impact EM pharmacist presence has on time to OAC reversal in patients presenting with an ICH. ProceduresThis was a retrospective, single-center cohort study evaluating time to reversal of OAC-associated ICH at a level one trauma center between November 2016 and September 2022. Patients 18 years or older who presented to the ED with an OAC-associated ICH and received at least one dose of an emergent reversal agent were included. Patients were excluded if their ICH was diagnosed at an outside facility, if they received emergent reversal agents for other indications, or if they had do not resuscitate orders upon admission. The primary outcome was time to administration of reversal agent with or without an EM pharmacist present, represented as median [interquartile range]. Secondary outcomes included hematoma expansion, hospital length of stay, intensive care unit LOS, and in-hospital mortality. ResultsOf the 157 patients evaluated, 83 met criteria for inclusion. Majority of patients presented with warfarin-associated ICH (55%) and the most common indication for OAC was atrial fibrillation (66%). The most common type of ICH was intracerebral hemorrhage (35%). The median time to emergent reversal agent administration was significantly shorter in the EM pharmacist group (50 min [31–65] vs. 85 min [51–121], p < 0.01). No significant differences in secondary outcomes existed. ConclusionsThe presence of an EM pharmacist at the bedside of patients who present to the ED with ICH was associated with a decrease in the time to OAC reversal by 36 min. Presence of an EM pharmacist was not associated with improved clinical outcomes for ICH in our study. Larger trials are warranted to determine whether the presence of an EM pharmacist is associated with improved functional and clinical outcomes in patients with OAC-associated ICH and whether time to newer reversal agents, other than 4F-PCC, has an effect on outcomes.

Predictors of direct oral anticoagulant concentrations in the trauma population

IntroductionDirect oral anticoagulant (DOAC) use is becoming more prevalent in patients presenting after trauma. We sought to identify the prevalence and predictors of subtherapeutic and therapeutic DOAC concentrations and hypothesized...

Utilization of International Normalized Ratio-Derived Formula to Predict Plasma Rivaroxaban Level - Validation Study and Real-World Experience

Introduction: Specific assay of plasma rivaroxaban level are not always readily available with short turn-around-time which hampered the management of urgent clinical situations. The response of routine coagulation screening tests show huge lot-to-lot differences with the plasma rivaroxaban level. International normalized ratio (INR) is a standardized measurement taking into account of lot-to-lot variations of PT reagents. In this study, we aimed to build a predictive formula of plasma rivaroxaban levels from INR value and validated in real world clinical situations. Method: The study period was 1 st January 2018 to 31 st December 2021. Ninety-four patients who taking rivaroxaban participated in the study. Patients were randomized into testing cohort and validation cohorts. The prediction formula was built from the testing cohort and then validated in validation cohort. The predictive performance was further validated on real-world clinical requests. Results: The baseline characteristics of both cohorts were well-balance. There was significant correlation between the plasma rivaroxaban level and PT in both the testing and validation cohorts (Testing cohort: R square 0.838, p &amp;lt; 0.01; Validation cohort: R square 0.836, p &amp;lt; 0.01). The plasma rivaroxaban level showed significant correlation with APTT in both the testing and validation cohorts (Testing cohort: R square 0.744, p &amp;lt; 0.01; Validation cohort: R square 0.654, p &amp;lt; 0.01). There was also significant correlation between INR and plasma rivaroxaban levels in both the testing and validation cohorts (Testing cohort: R square 0.819, p &amp;lt;0.01; Validation cohort: R square 0.816, p &amp;lt; 0.01). Both INR and plasma rivaroxaban levels were undergone natural logarithmic transformation. We choose the quadratic model to determine the relationship between the natural log of plasma rivaroxaban level and the natural log of INR as it had highest R square value (R square 0.850, p&amp;lt;0.01). The formula is: ln (plasma rivaroxaban level) = 2.96+7.87 X ln (INR) - 5.04X (ln (INR))^2. The root mean square error (RMSE) of the predictive formula for the testing and validation cohorts were 61.81 ng/ml and 69.32 ng/ml, respectively. We received a total of 43 requests for plasma rivaroxaban assay involved 29 patients during the study period (Table 1). Three patients had multiple requests for plasma DOAC level assays during this period. The cut-off INR value was 1.3 for administration of antidote for rivaroxaban, which corresponded to a rivaroxaban level of 75 ng/ml. The sensitivity and specificity for using this INR cut-off value to determine the threshold plasma rivaroxaban level (75 ng/ml) for administration of reversal agents were 95% (95%CI: 85.4 -100%) and 87.5% (95%CI:71.3-100%) respectively in real world clinical situations (Table 2). Conclusion: Plasma rivaroxaban level can be calculated from prediction formula by INR value with satisfactory accuracy and the INR cut-off value derived from it can be used to guide the decision for administration of reversal agents with excellent sensitivity and specificity.

Four-factor prothrombin complex concentrate versus andexanet alfa for direct oral anticoagulant reversal

BackgroundOptimal reversal agent for direct oral anticoagulant (DOAC)–associated major bleeding has not been described. Before the approval of andexanet alfa (AA) in 2018, 4-factor prothrombin complex concentrate (4F-PCC) was recommended by major guidelines. Currently, AA is recommended as the first-line agent by most guidelines. With a paucity of literature comparing the 2 agents, there is clinical value in assessing hemostatic efficacy and safety of the 2 agents. ObjectiveThis study aimed to evaluate hemostatic efficacy and safety of AA and 4F-PCC in all DOAC-associated major bleedings. MethodsA multicenter, retrospective chart review was performed of adult subjects who were admitted for a DOAC-associated major bleeding and received 4F-PCC from February 2018 to May 2019 or AA from May 2019 to September 2021. Some of the exclusion criteria included not receiving a DOAC, receiving multiple reversal agents during the same hospitalization, receiving reversal for any nonmajor bleeding indication, and not receiving the full dose of a reversal agent. The primary outcome was hemostatic efficacy 24 hours after the end of the reversal agent administration. Secondary outcomes included time to administration, hospital mortality, length of stay, need for surgery, and need for additional blood product. Safety outcome was incidence of thrombotic events. ResultsThere were 99 subjects included in the 4F-PCC group and 84 subjects in the AA group. Hemostatic efficacy was achieved in 69 subjects (69.7%) in the 4F-PCC group and 63 subjects (75%) in the AA group (P = 0.927). In-hospital mortality was seen in 20 subjects (20.2%) in the 4F-PCC group and 10 subjects (11.9%) in the AA group. Thrombotic events were seen in 7 subjects (7.1%) in the 4F-PCC group and 6 subjects (7.1%) in the AA group. ConclusionsThere were no significant differences in hemostatic efficacy, in-hospital mortality, and number of thrombotic events between 4F-PCC and AA.

Comparison of neostigmine and sugammadex for hemodynamic parameters in neurointerventional anesthesia.

Hemodynamic stability is important during neurointerventional procedures. However, ICP or blood pressure may increase due to endotracheal extubation. The aim of this study was to compare the hemodynamic effects of sugammadex and neostigmine with atropine in neurointerventional procedures during emergence from anesthesia. Patients undergoing neurointerventional procedures were allocated to the sugammadex group (Group S) and the neostigmine group (Group N). Group S was administered IV 2 mg/kg sugammadex when a train-of-four (TOF) count of 2 was present, and Group N was administered neostigmine 50 mcg/kg with atropine 0.2 mg/kg at a TOF count of 2. We recorded heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure (MAP), and peripheral arterial oxygen saturation during administration of the reverse agent and at 2, 5, 10, 15, 30, 120 min, and 24 h thereafter. The primary outcome was blood pressure and heart rate change after the reversal agent was given. The secondary outcomes were systolic blood pressure variability standard deviation (a measure of the amount of variation or dispersion of a set of values), systolic blood pressure variability-successive variation (square root of the average squared difference between successive blood pressure measurements), nicardipine use, time-to-TOF ratio ≥0.9 after the administration of reversal agent, and time from the administration of the reversal agent to tracheal extubation. A total of 31 patients were randomized to sugammadex, and 30 patients were randomized to neostigmine. Except for anesthesia time, there were no significant differences in any of the clinical characteristics between the two groups. The results demonstrated that the increase in MAP from period A to B was significantly greater in Group N than in Group S (regression coefficient = -10, 95% confidence interval = -17.3 to -2.7, P = 0.007). The MAP level was significantly increased from period A to B in the neostigmine group (95.1 vs. 102.4 mm Hg, P = 0.015), but it was not altered in Group S. In contrast, the change in HR from periods A to B was not significantly different between groups. We suggest that sugammadex is a better option than neostigmine in interventional neuroradiological procedures due to the shorter extubation time and more stable hemodynamic change during emergence.

Rate of residual neuromuscular block using single-dose rocuronium in general anesthesia for ENT surgery: a retrospective cohort study

IntroductionNMB facilitates intubating conditions in general anesthesia. However, it is associated with significant residual postoperative paralysis and morbidity.ObjectiveTo investigate the rate of underdiagnosed residual NMB based on two TOFR criteria (< 0.91 and < 1.00).MethodsWe performed a retrospective study adhering to STROBE guidelines. We included patients undergoing ENT surgery using single-dose neuromuscular block for balanced general anesthesia from June to December 2018. We collected demographic and anthropometric data, ASA score, NMBA dose, TOFR recordings at 5, 30 and 60 min and end of the surgery, anesthesia and surgery time, and administration of reversal agent. Statistical analysis included descriptive and dispersion measures statistics, curve and cross tables for residual NMB on different TOFR criteria with sub-analysis for AR, RR, and OR in patients over 65 years old.ResultsWe included 57 patients, mean age 41; 43 females and 14 males. Mean anesthetic and surgical time were 139.4 and 116.1 min, respectively. All the patients received rocuronium under a mean ponderal single-dose of 0.48 mg/kg. Residual NMB rates were 29.9 and 49.1% for a TOFR < 0.91 and < 1.00, respectively. Older adults had an OR of 6.08 for residual NMB.ConclusionsThe rate of residual NMB was 29.9 to 49.1%, depending on the criteria used (TOFR < 0.91 and < 1.00, respectively). Patients above 65 years old had an increased risk of residual NMB (6.08 OR) and clinical symptoms related to residual NMB (11.75 OR). We recommend future research aiming to provide a specific surveillance protocol for patients above 65 years old, including shorter-action NMB, early reversal, and prolonged surveillance using the TOFR criteria of < 1.00 to identify patients at risk of residual NMB readily.

The Role of Thromboelastography in Identifying Coagulopathy Among Geriatric Traumatic Brain Injury Patients.

Background The geriatric population has the highest incidence of head injury, and those who are anticoagulated have an increased risk of traumatic intracranial hemorrhage (ICH). The availability of viscoelastic coagulation studies has coincided with the development of many anticoagulation reversal agents. In this study, our objective was to assess whether the thromboelastography (TEG) assay affected clinical decision-making regarding reversal agent administration among geriatric patients with ICH caused by blunt head trauma. Methodology We prospectively screened adults aged 65 and older with head trauma presenting to the emergency departments of two level-one trauma centers. International Classification of Diseases, Tenth Revision codes S00-09 were used to identify the diagnosis of head injury. Patients with CT head imaging positive for acute ICH were included. Each patient was assessed for home use of antiplatelet or anticoagulant medications, as well as in-hospital use of any reversal agents. Reversal agent administration and mortality were compared between patients who received TEG and those who did not. Results A total of 680 patients had acute ICH on head CT, and 324 (48%) patients received TEG. More patients screened with TEG were transfused platelets (30.2% vs. 10.7%, p < 0.001). This remained significant for patients taking anticoagulants, antiplatelets, or neither. There were no differences in the administration of other reversal agents (prothrombin complex concentrate or fresh frozen plasma) or mortality whether or not TEG was performed. Conclusions Patients who had TEG performed were more likely to receive platelet reversal agents, regardless of antiplatelet medication usage. Among elderly adults with ICH, TEG is a rapid screening test that may help identify patients with platelet function abnormalities requiring reversal.

The Use of Andexanet Alfa Vs. Four-Factor Prothrombin Complex Concentrates in the Reversal of Life-Threatening Intracranial Hemorrhage

Background/objective Andexanet alfa (AA) is a novel reversal agent for life threatening bleeding associated with oral Xa inhibitors, but there is uncertainty regarding the benefit compared to 4-factor prothrombin complex concentrate (4F-PCC). We investigated the clinical outcomes and cost differences between these two reversal agents in life threatening intracranial hemorrhage (ICH). Methods We retrospectively reviewed patients at our institution who received anticoagulation reversal for life-threatening ICH with either AA or 4F-PCC between 9/1/2013 - 4/20/2020 and had an anti-Xa level greater than 0.6 IU/L. The primary outcome was 30-day mortality after administration of either 4F-PCC or AA. Secondary outcomes included progression of ICH based on imaging, ICU length of stay, hospital length of stay, disposition at discharge, functionality at discharged, and financial cost. Safety outcomes evaluated included thrombosis after administration of reversal agent. Results 89 patients were included in this study. There were no differences in 30-day mortality (p = 0.14, Figure 1), radiographic resolution of ICH (p = 0.93), objective volume change in ICH(p = 0.18), progression of ICH (p = 0.74), hospital and ICU length of stay (p=0.66, 0.50), discharge disposition (p=0.40), or thrombosis after administration of reversal agent (p=0.17) between the two groups. Modified Rankin at discharge was slightly higher for the AA group (p=0.02), while cost was 2.8 times higher for AA. Conclusion Given the lack of statistically significant differences in clinical outcomes and the high cost of AA, the results validate the use of 4F-PCCs as an alternative to AA, based on similar efficacy and safety. Multi-center prospective studies are needed to further evaluate novel anticoagulation reversal agents. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis

BackgroundA recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions.MethodsPubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences.ResultsData from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups.ConclusionConsidering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future.

Pharmacology and pharmacokinetics of fentanyl toxicity reversal by anti‐fentanyl monoclonal antibodies in combination with naloxone

AIMWidespread access to illicit fentanyl has contributed to an ongoing epidemic of fatal drug overdoses in the United States. The incidence of fatal overdoses in the United States accelerated during the COVID‐19 pandemic, with over 100,000 deaths recorded by April 2021. Fentanyl‐specific monoclonal antibodies (mAb) offer a prophylactic and therapeutic intervention against opioid overdose by binding and sequestering fentanyl in serum, and reducing distribution to the brain. Here, the kinetics of overdose reversal by anti‐fentanyl mAb alone or in combination with naloxone were explored, and the dose‐response relationship between naloxone and high doses of fentanyl in the presence of mAb was evaluated.METHODSTo evaluate the kinetics of fentanyl reversal, fentanyl 0.1 mg/kg was administered to male Sprague‐Dawley rats, and mAb or naloxone was administered fifteen minutes after exposure. Oxygen saturation was monitored constantly for ten minutes following administration of reversal agent. To evaluate duration and extent of protection from further fentanyl exposures, rats were pre‐treated with mAb, naloxone, or a combination, and challenged with increasing doses of fentanyl up to 0.5 mg/kg. Finally, to determine whether the presence of mAb would increase efficacy of naloxone against a lethal dose of fentanyl, 2.25 mg/kg fentanyl was administered, followed by naloxone 0.01 to 1.0 mg/kg.RESULTSThe most rapid reversal of fentanyl toxicity was achieved by intravenous administration of a combination of anti‐fentanyl mAb and naloxone (&lt;1 min). Intravenous naloxone reversed fentanyl toxicity more quickly than subcutaneous naloxone, and intravenous mAb was effective against fentanyl within 4 minutes, similar to subcutaneous NLX. Against further challenges of fentanyl, both mAb and 0.1 mg/kg naloxone were effective against 0.1‐0.2 mg/kg fentanyl, and the combination of mAb and naloxone was effective against doses of 0.5 mg/kg fentanyl or higher. Prophylactic administration of mAb enhanced efficacy of naloxone in reversing a potentially lethal challenge of 2.25 mg/kg fentanyl. Finally, mAb sequestered high concentrations of both fentanyl and its metabolite norfentanyl in serum, and reduced brain concentrations of fentanyl in pre‐exposure scenarios.CONCLUSIONSThese results support translation of mAb as medical countermeasures to prevent and reverse opioid overdose related to fentanyl and its analogs.

Outcomes of a Stroke Response Team on the Emergent Management of Intracerebral Hemorrhage.

Spontaneous intracerebral hemorrhage results in high patient mortality or poor functional outcomes. Early access to specialty care allows for rapid implementation of evidence-based strategies that improve the patient's long-term outcomes. The aim of this study was to determine the impact of a dedicated stroke response team on timeliness of blood pressure control, administration of anticoagulation reversal agents, and emergency department arrival to a critical care bed. A stroke response team was developed from the neuro intensive care unit that compliments the hospital's current rapid response team. Development of an algorithm guides the implementation of key interventions for intracerebral hemorrhages. Widespread education targeting care of patients with hemorrhagic stroke provided the stroke response team and emergency department staff with knowledge to implement the plan of care. Baseline time interval data were collected on 70 consecutive patients with intracerebral hemorrhage. After implementation of a dedicated stroke response team, time interval data on 70 consecutive patients with intracerebral hemorrhage were collected for comparison with the baseline measurement. A significant decrease was seen in the time to control the patient's systolic blood pressure (median of 130 to 56 minutes, P = .000) and emergency department arrival to a critical care bed (240 to 132 minutes, P = .000). Patient arrival to anticoagulation reversal agent administration decreased from a mean of 98 to 72 minutes (P = .32). Implementation of a stroke response team increased the knowledge of the care team, improved the timeliness of blood pressure control, and decreased the time for emergency department arrival to a critical care bed, and to anticoagulation reversal agent administration.

Neurosurgical Treatment of Patients with Posterior Fossa Acute Subdural Hematoma Right after Cardiac Surgery.

As posterior fossa acute subdural hematoma (ASDH) right after cardiac surgery is extremely rare, the clinical course and optimal treatment strategy remain undetermined. We performed a retrospective analysis of patients with posterior fossa ASDH right after cardiac surgery requiring neurosurgical treatment at our institution over a 7-year period and, in this study, discussed the neurosurgical strategy and clinical course. Collected data included clinical history, laboratory results, time course, symptoms, neurosurgical treatment, outcome at discharge, and imaging studies. All six patients were women who had no history of head trauma and had received antithrombotic therapy during the perioperative period of cardiac surgery. All patients showed lower platelets count and were diagnosed with ASDH within 3 days (longest time 64 h) right after cardiac surgery. After discontinuation of anticoagulation therapy and administration of reversal agents, they underwent emergency hematoma evacuation craniotomy (n = 5) or burr hole drainage surgery (n = 1), which were performed in the prone (n = 4) or lateral (n = 2) positions. Four of these patients showed favorable outcomes, and two showed poor outcomes. One of the poor-outcome patients received three antithrombotic therapies, and another developed rapidly progressive ASDH. Posterior fossa ASDH associated with antithrombotic therapy right after cardiac surgery is frequently found in women, and emergent neurosurgical treatment with anticoagulation discontinuation and reversal agent administration can be performed safely. Burr hole drainage surgery might be acceptable in nonsevere cases. By contrast, we must pay attention to cases receiving both anticoagulant and antiplatelet drugs and rapid progression cases.

476 Does Anticoagulation or Antiplatelet Therapy Increase Risk of Traumatic Subarachnoid Hemorrhage Progression?

INTRODUCTION: Isolated traumatic subarachnoid hemorrhage (tSAH) is a common finding of mild traumatic brain injury that often results in the transfer to a tertiary center. This is often done out of concern for patients on blood thinners (BT) who are thought to be at higher risk of clinical worsening. METHODS: A retrospective analysis identified patients over the age of 18 with isolated tSAH and a GCS of 15 on admission. Clinical information including use of BT, administration of reversal agents, radiographic progression, and need for neurosurgical intervention were collected. Patients on BT were divided into AP, AC and AP/AC groups based on drug type. RESULTS: 384 patients were included with 203 in the non-BT group and 181 in the BT group. 2.1% had worsening scans and none required neurosurgical intervention. There was no difference in radiographic worsening between the non-BT and BT group (2.4% vs. 1.6%; p = 1.00). Crosswise comparison revealed no difference between the non-BT group and each BT subtype (AP, AP/AC, AC). The non-BT group was more likely to have radiographic improvement than the BT group (45.8% vs. 30.9%; p = 0.002). CONCLUSION: Neurologically intact patients on BT with isolated tSAH are not at increased risk of radiographic progression or need for neurosurgical management. Consequently, the presence of BT should not influence management decisions for increased surveillance.

Half-Dose Sugammadex After Neostigmine Versus Neostigmine as a Routine Reversal Agent: A Pilot Randomized Trial

PurposeThe use of sugammadex at a lower dose after a routine reversal dose of neostigmine may prevent residual neuromuscular blockade (rNMB). Our goal was to investigate the effects of the use of half-dose sugammadex for reversing rNMB after administration of neostigmine, and compare these effects to a routine full-dose of neostigmine. DesignProspective, single-blinded, randomized trial. MethodsNinety-eight patients having lower abdominal tumor resection surgery under general anesthesia were randomized into two groups. Group N (Neostigmine) (n = 48) patients received standard reversal dose of intravenous neostigmine 0.05 mg/kg and atropine 0.02 mg/kg before extubationl Group N + S (Neostigmine + Sugammadex) (n = 50) patients received 1 mg/kg of intravenous sugammadex three minutes after a standard neostigmine reversal dose. The primary end-point was the incidence of a train-of-four (TOF) ratio less than 0.9 at tracheal extubation. Secondary end-points were periods between the start of administration of reversal agents and extubation or operating room discharge in minutes to achieve recovery of TOF ratio < 0.9 to 0.7 and TOF ratio ≥ 0.9. FindingsThe demographic data were not different between the two groups (P > .005). The incidence of rNMB presented as TOF ratio < 0.9 to 0.7 was present in 52% of Group N patients compared to 8% in Group N + S patients (P < .0001). The time to recovery between administering reversal and extubation as well as operating room discharge in Group N were; 18.52 ± 6.34 minutes and 23.27 ± 6.95 minutes, respectively, whereas; in Group N + S, they were; 12.86 ± 5.05 and 17.82 ± 4.99 minutes, respectively. (P < .0001, P < .0001, respectively). Adverse events were similar between groups (P > .05). ConclusionsA half-dose sugammadex (1 mg/kg) after full-dose reversal of neostigmine provides a lower incidence of rNMB and shorter recovery times as compared to full-dose neostigmine reversal agent. This practice is safe and effective in case of rNMB.

Does Pre-existing Anticoagulation or Antiplatelet Therapy Increase the Risk of Traumatic Subarachnoid Hemorrhage Progression?

Isolated traumatic subarachnoid hemorrhage (tSAH) is a common finding in mild traumatic brain injury that often results in transfer to a tertiary center. Patients prescribed blood-thinning medications (BTs) are believed to be at higher risk of clinical or radiographic worsening. To compare the rates of radiographic progression and need for neurosurgical intervention in patients with tSAH who are on anticoagulation (AC) and antiplatelet (AP) therapies with those who are not. Analysis using a retrospective cohort design identified patients older than 18 years with isolated tSAH and a Glasgow Coma Scale of 15 on admission. Clinical information including use of BTs, administration of reversal agents, radiographic progression, and need for neurosurgical intervention was collected. Patients on BTs were divided into AP, AC, and AP/AC groups based on drug type. Three hundred eighty-four patients were included with 203 in the non-BT group and 181 in the BT group. Overall, 2.1% had worsening scans, and none required operative intervention. There was no difference in radiographic worsening between the non-BT and BT groups (2.4% vs 1.6%; P = 1.00). Crosswise comparison revealed no difference between the non-BT group and each BT subtype (AP, AP/AC, or AC). The non-BT group was more likely to have radiographic improvement than the BT group (45.8% vs 30.9%; P = .002). Neurologically intact patients on BTs with isolated tSAH are not at increased risk of radiographic progression or neurosurgical intervention. The presence of BTs should not influence management decisions for increased surveillance.

Comparison of recovery after sugammadex or neostigmine reversal of rocuronium in geriatric patients undergoing spine surgery: a randomized controlled trial

AimTo evaluate the effect of sugammadex compared with neostigmine on speed and quality of recovery after rocuronium neuromuscular blockade (NMB) in geriatric patients undergoing posterior lumbar spine surgery.MethodsThis randomized controlled study at a tertiary academic medical center involved 40 patients (age ≥65 years, ASA PS II/III) scheduled for elective surgery under general anesthesia. Patients were randomized to sugammadex or neostigmine for reversal of moderate NMB with rocuronium. The primary outcome was recovery time from NMB after surgery to a train-of-four (TOF) ratio ≥0.9 measured at the adductor pollicis (TOF-Watch® SX). Secondary outcomes included hemodynamic change after administration of reversal agent (heart rate, blood pressure, dysrhythmia), time to extubation, pain medication requirement, time to first ambulation, and length of postanesthesia care unit (PACU) and total hospital stay.ResultsSugammadex (4 ± 2.2 min) compared with neostigmine reversal (26.3 ± 17.5 min) was on average 22 min faster (95% CI 14.1-30.5; P <0.001) with less variability (range 2-11 min vs 5-72 min). The groups significantly differed in time for tracheal extubation, response to verbal commands (open eyes, squeeze hand, lift head), and operating room exit. However, they had similar PACU stay, time to first ambulation, total hospital stay, postoperative pain, and opioid use. Sugammadex had less hemodynamic variability than neostigmine. No patient developed treatment-emergent dysrhythmias.ConclusionSugammadex reversal significantly hastened NMB recovery compared with neostigmine reversal in geriatric patients. It significantly decreased operating room time but not PACU time or hospital stay.ClinicalTrial.gov identification numberNCT03112993

Evaluation of the effects of a dexmedetomidine-midazolam-ketamine combination administered intramuscularly to captive red-footed tortoises (Chelonoidis carbonaria).

To evaluate the effects of a dexmedetomidine-midazolam-ketamine (DMK) combination administered IM to captive red-footed tortoises (Chelonoidis carbonaria). 12 healthy adult red-footed tortoises. In a prospective experimental study, DMK (0.1, 1.0, and 10 mg/kg, respectively) was administered IM as separate injections into the right antebrachium. Atipamezole (0.5 mg/kg, IM) and flumazenil (0.05 mg/kg, SC) were administered into the left antebrachium 60 minutes later. Times to the first treatment response and maximal treatment effect after DMK administration and time to recovery after reversal agent administration were recorded. Vital signs and reflexes or responses to stimuli were assessed and recorded at predetermined intervals. DMK treatment produced deep sedation or light anesthesia for ≥ 20 minutes in all tortoises. Induction and recovery were rapid, with no complications noted. Median times to first response, maximum effect, and recovery were 4.5, 35, and 14.5 minutes, respectively. Two tortoises required additional reversal agent administration but recovered < 20 minutes after the repeated injections. Mean heart and respiratory rates decreased significantly over time. All animals lost muscle tone in the neck and limbs from 35 to 55 minutes after DMK injection, but other variables including palpebral reflexes, responses to mild noxious stimuli (eg, toe pinching, tail pinching, and saline ([0.9 NaCl] solution injection), and ability to intubate were inconsistent. DMK administration produced deep sedation or light anesthesia with no adverse effects in healthy adult red-footed tortoises. At the doses administered, deep surgical anesthesia was not consistently achieved. Anesthetic depth must be carefully evaluated before performing painful procedures in red-footed tortoises with this DMK protocol.

Utilization of anti-factor Xa levels to guide reversal of oral factor Xa inhibitors in the emergency department.

PurposeOral factor Xa inhibitors (FXaIs) are increasingly utilized for outpatient anticoagulation therapy; however, laboratory monitoring is not routinely used to assess the safety and efficacy of these agents. We aimed to evaluate the role of chromogenic anti–factor Xa (anti-Xa) assays in the emergency department (ED) in the setting of patients with an acute bleed or requiring emergent procedures.MethodsA retrospective review of anti-Xa levels obtained in the ED between June 1, 2019, and April 30, 2020, was completed. Data were collected to describe the clinical setting of anti-Xa level collection, oral FXaIs used before admission, administration of reversal agents, and patient disposition to further characterize the role of anti-Xa levels in the management of rivaroxaban and apixaban reversal.ResultsThirty anti-Xa levels were included in the final analysis. The median time from sample collection to anti-Xa assay result was 45.9 minutes (interquartile range, 35.3-54.7 minutes). Eleven patients (37%) received anticoagulation reversal after their anti-Xa levels were determined. Anticoagulation reversal agents included either activated prothrombin complex concentrates (aPCCs) or prothrombin complex concentrates (PCCs). Anti-Xa levels were collected in 2 patients who had received PCCs before arrival at our ED. Of the patients with anti-Xa levels below 30 ng/mL, none received aPCCs or PCCs after their anti-Xa levels were determined. Anti-Xa assays were used to rule out the presence of FXaIs in 3 patients.ConclusionThis study illustrates the novel role of anti-Xa levels in managing patients with an emergent need for reversal in the ED. The assay may be used to rule out the presence of oral FXaIs and avoid unnecessary administrations of anticoagulation reversal agents.