Impact of C-reactive Protein on Anticoagulation Monitoring in Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the impact of inflammation on anticoagulation monitoring for patients supported with extracorporeal membrane oxygenation (ECMO). DESIGN: Prospective single-center cohort study. SETTING: University-affiliated tertiary care academic medical center. PARTICIPANTS: Adult venovenous and venoarterial ECMO patients anticoagulated with heparin/ MEASUREMENTS AND MAIN RESULTS: C-Reactive protein (CRP) was used as a surrogate for overall inflammation. The relationship between CRP and the partial thromboplastin time (PTT, seconds) was evaluated using a CRP-insensitive PTT assay (PTT-CRP) in addition to measurement using a routine PTT assay. Data from 30 patients anticoagulated with heparin over 371 ECMO days was included. CRP levels (mg/dL) were significantly elevated (median, 17.2; interquartile range [IQR], 9.2-26.1) and 93% of patients had a CRP of ≥5. The median PTT (median 58.9; IQR, 46.9-73.3) was prolonged by 11.3 seconds compared with simultaneously measured PTT-CRP (median, 47.6; IQR, 40.1-55.5; p < 0.001). The difference between PTT and PTT-CRP generally increased with CRP elevation from 2.7 for a CRP of <5.0 to 13.0 for a CRP between 5 and 10, 17.7 for a CRP between 10 and 15, and 15.1 for a CRP of >15 (p < 0.001). In a subgroup of patients, heparin was transitioned to argatroban, and a similar effect was observed (median PTT, 62.1 seconds [IQR, 53.0-78.5 seconds] vs median PTT-CRP, 47.6 seconds [IQR, 41.3-57.7 seconds]; p < 0.001). CONCLUSIONS: Elevations in CRP are common during ECMO and can falsely prolong PTT measured by commonly used assays. The discrepancy due to CRP-interference is important clinically given narrow PTT targets and may contribute to hematological complications.

Perioperative Implications of the 2020 American Heart Association Scientific Statement on Drug-Induced Arrhythmias-A Focused Review.

The recently released American Heart Association (AHA) scientific statement on drug-induced arrhythmias discussed medications commonly associated with bradycardia, supraventricular tachycardias, and ventricular arrhythmias. The foundational data for this statement were collected from general outpatient and inpatient populations. Patients undergoing surgical and minimally invasive treatments are a unique subgroup, because they may experience hemodynamic changes associated with anesthesia and their procedure, receive multiple drug combinations not given in either inpatient or outpatient settings, or experience postprocedural inflammatory syndromes. Accordingly, the generalizability of the AHA scientific statement to this perioperative population is unclear. This focused review highlights important aspects of the new AHA scientific statement and their application to the perioperative setting. The authors review medications frequently encountered and given by anesthesiologists and their risk of drug-induced arrhythmias and discuss common anesthetic and adjunctive medications and their associated risks of bradycardia, atrial fibrillation, torsades de pointes, and drug-induced Brugada syndrome. In many instances, the risk of arrhythmia reported by the AHA scientific statement in the general population appeared to be higher than found in perioperative arenas. Furthermore, the authors discuss the arrhythmia risk of additional medications commonly ordered or administered by anesthesiologists that are not included in the AHA scientific statement. As patient and procedural complexity increases and novel anesthetic combinations propagate, further research and observational studies will be required to delineate further perioperative risks for drug-induced arrhythmia.

Predictors of Functional Outcome After Subdural Hematoma: A Prospective Study.

BACKGROUND: Although the incidence of subdural hematoma (SDH) has increased in the US in the last decade, limited prospective data exist examining risk factors for poor outcome. METHODS: A prospective, observational study of consecutive SDH patients was conducted from 7/2008 to 11/2011. Baseline clinical data, hospital and surgical course, complications, and imaging data were compared between those with good versus poor 3-month outcomes (modified Rankin Scores [mRS] 0-3 vs. 4-6). A multivariable logistic regression model was constructed to identify independent predictors of poor outcome. RESULTS: 116 SDH patients (18 acute, 56 mixed acute/subacute/chronic, 42 subacute/chronic) were included. At 3 months, 61 (53 %) patients had good outcomes (mRS 0-3) while 55 (47 %) were severely disabled or dead (mRS 4-6). Of those who underwent surgical evacuation, 54/94 (57 %) had good outcomes compared to 7/22 (32 %) who did not (p = 0.030). Patients with mixed acuity or subacute/chronic SDH had significantly better 3-month mRS with surgery (median mRS 1 versus 5 without surgery, p = 0.002) compared to those with only acute SDH (p = 0.494). In multivariable analysis, premorbid mRS, age, admission Glasgow Coma Score, history of smoking, and fever were independent predictors of poor 3-month outcome (all p < 0.05; area under the curve 0.90), while SDH evacuation tended to improve outcomes (adjusted OR 3.90, 95 % CI 0.96-18.9, p = 0.057). CONCLUSIONS: Nearly 50 % of SDH patients were dead or moderate-severely disabled at 3 months. Older age, poor baseline, poor admission neurological status, history of smoking, and fever during hospitalization predicted poor outcomes, while surgical evacuation was associated with improved outcomes among those with mixed acuity or chronic/subacute SDH.

The Role of Platelet Activation and Inflammation in Early Brain Injury Following Subarachnoid Hemorrhage.

BACKGROUND: Early brain injury (EBI) following aneurysmal subarachnoid hemorrhage (SAH) is an important predictor of poor functional outcome, yet the underlying mechanism is not well understood. Animal studies suggest that platelet activation and inflammation with subsequent microthrombosis and ischemia may be a mechanism of EBI. METHODS: A prospective, hypothesis-driven study of spontaneous, SAH patients and controls was conducted. Platelet activation [thromboelastography maximum amplitude (MA)] and inflammation [C-reactive protein (CRP)] were measured serially over time during the first 72 h following SAH onset. Platelet activation and inflammatory markers were compared between controls and SAH patients with mild [Hunt-Hess (HH) 1-3] versus severe (HH 4-5) EBI. The association of these biomarkers with 3-month functional outcomes was evaluated. RESULTS: We enrolled 127 patients (106 SAH; 21 controls). Platelet activation and CRP increased incrementally with worse EBI/HH grade, and both increased over 72 h (all P < 0.01). Both were higher in severe versus mild EBI (MA 68.9 vs. 64.8 mm, P = 0.001; CRP 12.5 vs. 1.5 mg/L, P = 0.003) and compared to controls (both P < 0.003). Patients with delayed cerebral ischemia (DCI) had more platelet activation (66.6 vs. 64.9 in those without DCI, P = 0.02) within 72 h of ictus. At 3 months, death or severe disability was more likely with higher levels of platelet activation (mRS4-6 OR 1.18, 95 % CI 1.05-1.32, P = 0.007) and CRP (mRS4-6 OR 1.02, 95 % CI 1.00-1.03, P = 0.041). CONCLUSIONS: Platelet activation and inflammation occur acutely after SAH and are associated with worse EBI, DCI and poor 3-month functional outcomes. These markers may provide insight into the mechanism of EBI following SAH.

Withdrawal of Life-Sustaining Therapy in Patients With Intracranial Hemorrhage: Self-Fulfilling Prophecy or Accurate Prediction of Outcome?

OBJECTIVES: Withdrawal of life-sustaining therapy may lead to premature limitations of life-saving treatments among patients with intracranial hemorrhage, representing a self-fulfilling prophecy. We aimed to determine whether our algorithm for the withdrawal of life-sustaining therapy decision would accurately identify patients with a high probability of poor outcome, despite aggressive treatment. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Tertiary-care Neuro-ICU. PATIENTS: Intraparenchymal, subdural, and subarachnoid hemorrhage patients. INTERVENTIONS: Baseline demographics, clinical status, and hospital course were assessed to determine the predictors of in-hospital mortality and 12-month death/severe disability among patients receiving maximal therapy. Multivariable logistic regression models developed on maximal therapy patients were applied to patients who underwent withdrawal of life-sustaining therapy to predict their probable outcome had they continued maximal treatment. A validation cohort of propensity score-matched patients was identified from the maximal therapy cohort, and their predicted and actual outcomes compared. MEASUREMENTS AND MAIN RESULTS: Of 383 patients enrolled, there were 128 subarachnoid hemorrhage (33.4%), 134 subdural hematoma (35.0%), and 121 intraparenchymal hemorrhage (31.6%). Twenty-six patients (6.8%) underwent withdrawal of life-sustaining therapy and died, 41 (10.7%) continued maximal therapy and died in hospital, and 316 (82.5%) continued maximal therapy and survived to discharge. The median predicted probability of in-hospital death among withdrawal of life-sustaining therapy patients was 35% had they continued maximal therapy, whereas the median predicted probability of 12-month death/severe disability was 98%. In the propensity-matched validation cohort, 16 of 20 patients had greater than or equal to 80% predicted probability of death/severe disability at 12 months, matching the observed outcomes and supporting the strength and validity of our prediction models. CONCLUSIONS: The withdrawal of life-sustaining therapy decision may contribute to premature in-hospital death in some patients who may otherwise have been expected to survive to discharge. However, based on probability models, nearly all of the patients who underwent withdrawal of life-sustaining therapy would have died or remained severely disabled at 12 months had maximal therapy been continued. Withdrawal of life-sustaining therapy may not represent a self-fulfilling prophecy.

The Role of FEIBA in Reversing Novel Oral Anticoagulants in Intracerebral Hemorrhage.

BACKGROUND: Activated prothrombin complex concentrates factor eight inhibitor bypassing activity (FEIBA) has been recommended for reversing novel oral anticoagulants (NOAC) in the context of intracerebral hemorrhage (ICH), though few clinical studies report its use. METHODS: A prospective study of patients with spontaneous ICH was conducted from May 2013 to May 2015. Hospital complications including hemorrhage (gastrointestinal bleeding, anemia requiring transfusion, and surgical site bleeding) and thrombosis (pulmonary embolus, deep vein thrombosis, ischemic stroke, and myocardial infarction) were recorded. All ICH patients underwent baseline head CT and a follow-up stability scan in 6 h. NOAC taken within 48 h of presentation was reversed with FEIBA (50 u/kg) per protocol. Three-month outcomes were assessed using the modified rankin score (mRS). RESULTS: Of 127 ICH patients enrolled, 6 (5 %) had NOAC-related ICH including: oral factor XA inhibitor N = 5 (4 %; N = 4 rivaroxaban, N = 1 apixaban] and direct thrombin inhibitor N = 1 (0.8 %; dabigatran). The indication for NOAC was atrial fibrillation in all patients and the median CHADS2-VASC score was 4 (range 2-5). The median admission NIHSS was 2 (range 0-14) and the median ICH volume was 8 mL (range 1-20). Five patients (3 rivaroxaban, 1 apixaban, 1 dabigatran) presented within 48 h and received FEIBA within a median of 13 h (range 10-29 h) from their last NOAC dose and 8 h (range 4.5-20) from the time last known well. None of the patients had ICH expansion, hemorrhagic, or thrombotic complications. Three-month median mRS was 1 (range 0-6). CONCLUSION: In this small case series, reversal of NOAC with FEIBA was not associated with ICH expansion or any thrombotic or hemorrhagic complications.

Superbug Meets Opportunistic Infection: A Case Report of Mobilized Colistin Resistance-1-Positive Klebsiella pneumoniae and Candida lusitaniae in a Complex Surgical Patient.

Infection with either mobilized colistin resistance-1 gene-positive gram-negative bacteria or invasive Candida lusitaniae occurs rarely throughout the United States. Here we report the existence of both invasive infections occurring in a single, complex patient who initially presented with necrotizing pancreatitis and gastrointestinal bleeding. We detail the patient's history and perioperative course for enterocutaneous fistulae takedown and ureteral stenting, describe a template of preventative steps taken in the perioperative environment to prevent nosocomial pathogen transmission, and provide a brief overview of both the mobilized colistin resistance-1 gene and C lusitaniae.

Dural Traction a Possible Cause of Hemodynamic Changes During Single-Level Transforaminal Lumbar Interbody Fusion.

BACKGROUND: Lumbar spinal surgery may be associated with electrophysiologic and hemodynamic abnormalities during the procedure. CASE DESCRIPTION: A 58-year-old man with grade II L4-5 spondylolisthesis and degenerative changes underwent single-level transforaminal lumbar interbody fusion. During decompression of the L4 foramina, distraction of the disc space, and placement of the interbody cage and pedicle screws, episodes of extreme bradycardia with up to 5 seconds of asystole were detected on electrocardiogram and invasive hemodynamic monitoring. The events correlated with and possibly could have been a result of traction on the dura mater. CONCLUSIONS: Anesthesia providers should be aware of electrophysiologic and hemodynamic abnormalities during lumbar spinal surgery and the need to respond appropriately with sympathomimetic or vagolytic interventions.