Incidence of Hypertriglyceridemia in Patients on Propofol, Clevidipine, or Both.

BACKGROUND: Propofol and clevidipine (PC) are commonly used in the treatment of critically ill patients. While both medications are lipid emulsions, there is limited evidence concerning the incidence of hypertriglyceridemia (HTG) when these agents are used individually or concurrently. OBJECTIVE: The objective of this study is to determine the effects of propofol, clevidipine, or concurrent PC on triglycerides (TGs) and related outcomes in critically ill adults. METHODS: This was a retrospective cohort study conducted at an academic medical center. Patients were included if they received ≥24 hours of continuous propofol and/or clevidipine. Excluded were those without TG levels after ≥24 hours of infusion, baseline HTG, acute pancreatitis at admission, or receiving total parenteral nutrition with lipids. The primary outcome was incidence of HTG (defined as a TG level >400 mg/dL). Secondary outcomes included median and peak TG levels, hospital length of stay, intensive care unit length of stay, total lipid infused, time to peak TG level, peak lipase level, and development of pancreatitis. RESULTS: In total, 190 patients were studied: 109 in the propofol group, 50 in the clevidipine group, and 31 in the PC group. Incidence of HTG was similar (19 [17.4%] vs 6 [12%] vs 4 [12.9%] patients, P = 0.6246). Peak and median TG levels were similar for propofol, clevidipine, and PC groups (216 mg/dL vs 189.5 mg/dL vs 205 mg/dL, P = 0.7069; 177 mg/dL vs 185.5 mg/dL vs 177 mg/dL, P = 0.6791). CONCLUSIONS AND RELEVANCE: There was a similar incidence of HTG in all groups. The results of this study suggest that the concurrent use of PC should not modify the frequency of TG level monitoring.

Major Bleeding Postadministration of Tenecteplase Versus Alteplase in Acute Ischemic Stroke.

BACKGROUND: Tenecteplase is a genetically engineered fibrinolytic with growing interest in the treatment of acute ischemic stroke. Compared to alteplase, tenecteplase is effective for neurologic improvement following ischemic stroke in patients with large vessel occlusions who are eligible for thrombectomy and for mild ischemic strokes with National Institutes of Health Stroke Scale of 0 to 5. OBJECTIVE: The purpose of this study is to determine if safety outcomes are different in patients receiving tenecteplase and alteplase for acute ischemic stroke. METHODS: This retrospective cohort reviewed all patients who received alteplase or tenecteplase from January 2019 to December 2020. Patients admitted before April 28, 2020, received alteplase intravenous bolus over 1 minute followed by an infusion over 1 hour, for a total of 0.9 mg/kg. Patients admitted after this date received tenecteplase 0.25 mg/kg as an intravenous bolus over 5 to 10 seconds. Any patient transferring from an outside facility was excluded. The primary outcome was major bleeding. RESULTS: There was no significant difference in major bleeding between alteplase and tenecteplase (40 [18%] vs 21 [18.1%], P = 0.985). There was no significant difference in all-cause inpatient mortality for alteplase versus tenecteplase (10 [5%] vs 5 [4%], P = 0.934) or in adverse events between the groups (22 [9%] vs 14 [12%], P = 0.541) for alteplase and tenecteplase, respectively. CONCLUSIONS AND RELEVANCE: Tenecteplase had similar rates of major bleeding versus alteplase and may be a reasonable alternative in the treatment of acute ischemic stroke.

Activated Prothrombin Complex Concentrates for the Treatment of Factor Xa Inhibitor-Associated Spontaneous Intracerebral Hemorrhage.

Background: Anticoagulant-associated intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality. Despite approval of a specific reversal agent for factor Xa inhibitors, there is still much interest in nonspecific reversal agents, such as activated prothrombin complex concentrates (aPCCs). Objective: The objective of this study was to describe ICH expansion in a cohort of patients with factor Xa inhibitor-associated ICH who were treated with aPCC. Methods: This was a retrospective cohort study conducted at an academic medical center designated as a comprehensive stroke center. Consecutive patients admitted for ICH who reported use of apixaban or rivaroxaban prior to admission were considered for inclusion in the study. Patients were treated with 25 to 50 units/kg of aPCC. Intracerebral hemorrhage volume was measured before administration of aPCC and then again within 36 hours of aPCC administration. Results: A total of 40 patients were included in the final analysis. Overall, the cohort was predominantly male (24 [60%]), white (27 [67.5%]), and the mean age was 75.3 ± 10.5 years. Most patients reported taking apixaban prior to admission (31 [77.5%]) and a large proportion were also taking aspirin (13 [32.5%]). The mean change in ICH volume was 1.12 ± 6.03 mL (P = 0.2475). Conclusions and Relevance: There was a nonsignificant change in mean ICH volume and no reported cases of thromboembolism. Due to the relatively high proportion of patients with significant hematoma expansion, more studies are needed on which patient population would best benefit from treatment with aPCC.

Incidence of thrombotic complications related to weight-based dosing of activated prothrombin complex concentrate (aPCC) for reversal of apixaban and rivaroxaban in obese patients.

Factor eight inhibitor bypassing activity (aPCC) is recommended as a non-specific reversal agent for direct oral anticoagulants (DOACs) according to the 2017 American College of Cardiology (ACC) guidelines for reversal of anticoagulation. Factor eight inhibitor bypassing activity carries a black box warning for thrombotic events such as stroke, pulmonary embolism, deep vein thrombosis, and myocardial infarction, particularly at high doses. This was a retrospective, single-center, cohort investigation that included patients who received a weight-based dose of aPCC for reversal of apixaban and rivaroxaban between January 1, 2015, and December 31, 2020. Patients were grouped by BMI as obese (BMI ≥ 30 kg/m2) or non-obese (BMI < 30 kg/m2) for analysis. The primary outcome of this investigation was the occurrence of thrombotic complications [venous thromboembolism (VTE), myocardial infarction, stroke] documented in the medical record at any point during hospitalization after administration of aPCC. Secondary outcomes included bleeding complications, in-hospital mortality, ICU and hospital length of stay. Patients in the obese group were younger [76.4 years (SD +/- 11.3 years) vs. 69.6 years (SD +/- 12.4 years); p < 0.0001] and a higher proportion had a diagnosis of diabetes mellitus prior to admission [37 (19.2%) vs. 35 (36.8%); p = 0.0011]. There was no difference in the primary outcome of thrombotic events between non-obese and obese patients [12 (6.2%) vs. 5 (5.3%); p = 0.75], or for any of the secondary outcomes of bleeding, in-hospital mortality or length of stay. This investigation did not reveal a difference in rates of thrombosis or bleeding events between obese and non-obese patients who received aPCC for reversal of apixaban and rivaroxaban.

Impact of Factor Xa Inhibitor Reversal with Prothrombin Complex Concentrate in Patients with Traumatic Brain Injuries.

BACKGROUND: Anticoagulant use prior to trauma has been associated with increased incidence of traumatic brain injury (TBI), intracranial hemorrhage (ICH) progression, and mortality. Prothrombin complex concentrates (PCCs) are commonly used as off-label treatments for factor Xa inhibitor-associated life-threatening hemorrhage. At this time, there is no consensus regarding appropriate indication, target dose, or outcomes of PCC administration in patients presenting with traumatic ICH. This study seeks to evaluate the impact of reversal with PCC on hemorrhage progression and outcomes in patients with TBI on preinjury factor Xa inhibitors. METHODS: This single-center retrospective cohort study included patients ≥ 18 years presenting with an acute TBI of any severity on apixaban or rivaroxaban from September 1, 2016, to September 1, 2019. Patients were grouped on the basis of receipt of PCCs for reversal (i.e., reversal or no reversal). Exclusion criteria included spontaneous ICH or known coagulopathy. Propensity score matching was conducted with the following variables: age, Abbreviated Injury Scale (head) score, and Charlson Comorbidity Index score. The primary outcome was hemorrhage stability within 48 h. Secondary outcomes included degree of hemorrhage progression, in-hospital mortality, discharge disposition, and incidence of thromboembolic events. RESULTS: Of the 115 patients meeting inclusion criteria, 84 were included in the propensity score matched data set. Baseline characteristics, comorbidities, and TBI severity were similar. The majority of patients in the reversal group (35 [83.3%]) and the no reversal (NR) group (40 [95.2%]) experienced a mild TBI (admission Glasgow Coma Scale score of 14 to 15). In the reversal group, patients received 34.3 units/kg activated PCC, 30.5 units/kg four-factor PCC, or 54.9 units/kg four-factor PCC and activated PCC on average. There was no difference observed in the incidence of hemorrhage progression (10.8% NR vs. 15.0% reversal; p = 0.739) or in median change in ICH volume (0 mL NR vs. 1 mL reversal; p = 0.2199) between groups. Additionally, reversal did not affect in-hospital mortality (3 [7.1%] NR vs. 4 [9.5%] reversal; p > 0.999). One patient in the reversal group developed a deep vein thrombosis (DVT) during the hospitalization; however, this did not result in a statistically significant difference in the occurrence of DVT (p > 0.999). CONCLUSIONS: This study demonstrated that PCC used for the treatment of factor Xa inhibitor-associated ICH related to mild TBI did not significantly impact the incidence or degree of hemorrhage progression, and PCC treatment did not result in increased thromboembolic events.

23.4% Sodium Chloride Versus Mannitol for the Reduction of Intracranial Pressure in Patients With Traumatic Brain Injury: A Single-Center Retrospective Cohort Study.

BACKGROUND: Intermittent doses of mannitol or hypertonic saline are recommended to treat elevated intracranial pressure (ICP). However, it is unclear if one agent is more effective than the other. Previous studies have compared mannitol and hypertonic saline in reduction of ICP, with conflicting results. However, no study thus far has compared 23.4% sodium chloride with mannitol. OBJECTIVE: The objective of this study was to determine the difference in absolute reduction of ICP 60 minutes after infusion of 23.4% sodium chloride versus mannitol. METHODS: This was a single-center retrospective cohort study that included patients at least 16 years old admitted to the trauma/surgical intensive care unit between August 8, 2016, and August 30, 2018, who received either 23.4% sodium chloride 30 mL and/or mannitol 0.5 g/kg and had an ICP monitor or external ventricular drain in place. The primary outcome was absolute reduction in ICP 60 minutes after infusion of hyperosmolar therapy. RESULTS: In all, 31 patients and 162 doses of hyperosmolar therapy were included in the analysis. There was no statistically significant difference in the primary end point of absolute reduction of ICP 60 minutes after infusion of hyperosmolar therapy comparing 23.4% sodium chloride 30 mL with 0.5 g/kg mannitol (P = 0.2929). There was no statistically significant difference found for any secondary end points. CONCLUSION AND RELEVANCE: No difference was found for absolute reduction of ICP at 30, 60, and 120 minutes, respectively, after infusion of hyperosmolar agent or time to next elevated ICP. Patient-specific parameters should be used to guide the choice of hyperosmolar agent to be administered.

Impact of Obesity on Warfarin Reversal With Fixed-Dose Factor VIII Inhibitor Bypassing Activity (aPCC).

BACKGROUND: Data are limited addressing anticoagulant reversal in obese patients using activated prothrombin complex concentrate (aPCC). OBJECTIVE: Assess the impact of obesity on INR reversal with fixed aPCC dosing. METHODS: Institutional review board-approved, retrospective cohort conducted in a large academic medical center. Patients 18 years or older who received fixed-dose aPCC for warfarin-associated hemorrhage were included. Patients who received aPCC for any other indications or who had no follow-up INR after aPCC administration were excluded. Patients with an INR of 5 or greater received 1000 units aPCC, whereas those with INR less than 5 received 500 units aPCC, per institutional protocol. Patients were stratified into obese and nonobese based on body mass index. Primary end point was INR reversal, defined as repeat INR of 1.4 or less within 4 hours following aPCC treatment, without a repeated dose. Secondary end points included percentage change in INR, proportion of patients requiring an additional dose of aPCC, bleeding complications, thrombotic complications, hospital length of stay, and in-hospital mortality. RESULTS: 259 patients were included, of whom 83 were obese (32%). A significantly higher proportion of nonobese patients achieved an INR of 1.4 or less within 4 hours of treatment (169 [96.02%] vs 69 [83.13%]; P = 0.0004). There were no differences in any secondary end points. CONCLUSION AND RELEVANCE: When fixed-dose aPCC is used for warfarin reversal, obesity is associated with a significantly lower rate of INR reversal, without increased bleeding. This study adds to the limited amount of literature on aPCC dosing in obesity.

INR Response to Low-Dose Vitamin K in Warfarin Patients.

BACKGROUND: Literature suggests that 2 mg of vitamin K intravenously (IV) provides a similar effect as 10 mg to reverse warfarin. Doses <5 mg haven't been studied in depth. OBJECTIVE: The objective was to determine the international normalized ratio (INR) reduction effect of ultra low-dose (ULD) IV vitamin K. METHODS: This retrospective, observational cohort study compared IV vitamin K doses of 0.25-0.5 mg (ULD) versus 1-2 mg (standard low dose [SLD]). The primary outcome assessed ΔINR at 36 hours; secondary outcomes assessed ΔINR at 12 hours and 30-day venous thromboembolism (VTE) and mortality rates. RESULTS: Of 88 patients identified (median baseline INR [IQR], 5.1 [3.1, 7.3] vs 4.5 [2.8, 8.2], ULD vs SLD, respectively), 59 had an INR at 12 hours. The ULD had fewer 12-hour INR values <2, with no statistical difference in the ΔINR at 12 hours between the ULD and SLD cohorts (median ΔINR, 2.2 [1.1, 3.4] vs 2.2 [1.1, 6.3]; P = 0.54; median INR, 2.3 vs 1.8). A total of 41 patients had both a 12- and 36-hour INR. No significant difference in the ΔINR between the 12- and 36-hour values occurred (median ΔINR, 0.52 [0.2, 0.91] vs ΔINR, 0.46 [0.18, 0.55]; P = 0.61), suggesting no rebound or excessive reversal and no difference in 30-day rates of VTE (P > 0.99) or death (P = 0.38). CONCLUSION AND RELEVANCE: ULD IV vitamin K reversed INR similarly to doses of 1-2 mg without rebound. A ULD strategy may be considered in patients requiring more cautious reversal.

Identification of Risk Factors for Refractory Status Epilepticus.

Objective: The objective of this study is to identify risk factors for the development of refractory status epilepticus (RSE). Methods: This was an IRB-approved, retrospective case control study that included patients admitted with status epilepticus between August 1, 2014, and July 31, 2017. Cases were defined as those with RSE, and controls were those who did not develop RSE. A bivariate analysis was conducted comparing those with RSE and those without RSE. A stepwise logistic regression model was constructed predicting for progression to RSE. Risk factors for progression to RSE were extrapolated from this model. Results: A total of 184 patients met inclusion criteria for the study (99 controls and 49 cases). After adjusting for covariates in the logistic regression, patients with convulsive seizures had a lower odds of developing RSE (odds ratio [OR] = 0.375; 95% CI = 0.148 to 0.951; P = 0.0388). Treatment with benzodiazepines plus levetiracetam had a higher odds of developing RSE (OR = 3.804; 95% CI = 1.523 to 9.499; P = 0.0042). Conclusion and Relevance: This study found that patients with convulsive seizures had a lower odds of developing RSE. In addition, patients treated with benzodiazepines and levetiracetam had a higher odds of developing RSE. This information can be used to potentially identify patients at higher risk of developing RSE, so that treatment can be modified to reduce morbidity and mortality. These results may warrant further investigation into the effectiveness of levetiracetam as a first-line agent for the treatment of SE.

Rescheduling hydrocodone combination products: Impact on patients receiving long-term HCP therapy in a large chain pharmacy-A statewide assessment.

OBJECTIVE: This study aimed to evaluate the rescheduling of hydrocodone combination products (HCPs) from schedule III (CIII) to schedule II (CII) in patients receiving chronic HCP therapy. METHODS: This study was a retrospective cohort analysis of administrative pharmacy data from 118 statewide pharmacies from a retail chain in Tennessee. HCP filling histories were analyzed on patients meeting enrollment criteria from July 1, 2014, to October 1, 2015. The average number of tablets dispensed, daily average of the number of tablets dispensed, and monthly average of morphine milligram equivalents (MME) dispensed were compared for the periods of July 1, 2014, to October 5, 2014 (enrollment period before schedule change) and October 6, 2014, to October 1, 2015 (period following schedule change) using a pooled t test. RESULTS: A total of 4536 patients met the inclusion criteria. Of these 4536 patients, 60.6% were female, and 40.4% were male, with an average age of 58 years (patients included in this study were between the ages of 18 and 99 years). The total number of hydrocodone tablets dispensed in the 12 periods after the schedule change dropped from 467,217 to 259,327, a 45.5% reduction (P < 0.001). Total MME decreased from 4.11 to 2.29 million, a 45.3% reduction (P < 0.001). The number of study participants still receiving an HCP at the end of the study decreased to an average of 2736 across the 12 periods following the schedule change, a 40% reduction. CONCLUSION: HCP dispensing and use decreased among patients receiving chronic opioid treatment from a large corporate statewide community pharmacy in Tennessee after a schedule change from CIII to CII. Monthly sums of total tablets dispensed, average daily tablets dispensed, MME, and average daily MME calculated from July 1, 2014, to October 1, 2015, all experienced statistically significant reductions.

Current Practices of Intraventricular Antibiotic Therapy in the Treatment of Meningitis and Ventriculitis: Results from a Multicenter Retrospective Cohort Study.

BACKGROUND: Central nervous system (CNS) infections are particularly prevalent in the adult neurocritical care patient population and are associated with significant morbidity and mortality. Factors relevant to the nature of CNS infections pose significant challenges to clinicians treating afflicted patients. Intraventricular (IVT) administration of antibiotics may offer several benefits over systemic therapy; however, the outcomes and current practices of such treatments are poorly described in the literature. OBJECTIVE: To describe current practices and outcomes of patients receiving intraventricular antibiotic treatment for CNS infections in neurological intensive care units of academic medical centers nationwide. METHODS: A retrospective cohort study was conducted on patients admitted to intensive care units who received IVT antibiotic treatment at participating centers in the USA between January 01, 2003, and December 31, 2013. Clinical and laboratory parameters, microbiology, surgical and antimicrobial management, and treatment outcomes were collected and described. RESULTS: Of the 105 patients included, all received systemic antimicrobial therapy along with at least one dose of IVT antimicrobial agents. Intraventricular vancomycin was used in 52.4% of patients. The average dose was 12.2 mg/day for a median duration of 5 days. Intraventricular aminoglycosides were used in 47.5% of the patients, either alone or in combination with IVT vancomycin. The average dose of gentamicin/tobramycin was 6.7 mg/day with a median duration of 6 days. Overall mortality was 18.1%. Cerebrospinal fluid (CSF) culture sterilization occurred in 88.4% of the patients with a rate of recurrence or persistence of positive cultures of 9.5%. CONCLUSION: Intraventricular antimicrobial agents resulted in a high CSF sterilization rate. Contemporary use of this route typically results in a treatment duration of less than a week. Prospective studies are needed to establish the optimal patient population, as well as the efficacy and safety of this route of administration.

Activated Prothrombin Complex Concentrate Versus 4-Factor Prothrombin Complex Concentrate for Vitamin K-Antagonist Reversal.

OBJECTIVES: To compare the international normalized ratio normalization efficacy of activated prothrombin complex concentrates and 4-factor prothrombin complex concentrates and to evaluate the thrombotic complications in patients treated with these products for warfarin-associated hemorrhage. DESIGN: Retrospective, Multicenter Cohort. SETTING: Large, Community, Teaching Hospital. PATIENTS: Patients greater than 18 years old and received either activated prothrombin complex concentrate or 4-factor prothrombin complex concentrate for the treatment of warfarin-associated hemorrhage. We excluded those patients who received either agent for an indication other than warfarin-associated hemorrhage, pregnant, had a baseline international normalized ratio of less than 2, received a massive transfusion as defined by hospital protocol, received plasma for treatment of warfarin-associated hemorrhage, or were treated for an acute warfarin ingestion. INTERVENTIONS: Patients in the activated prothrombin complex concentrate group (enrolled from one hospital) with an international normalized ratio of less than 5 received 500 IU and those with an international normalized ratio greater than 5 received 1,000 IU. Patients in the 4-factor prothrombin complex concentrate (enrolled from a separate hospital) group received the Food and Drug Administration approved dosing algorithm. MEASUREMENTS AND MAIN RESULTS: A total of 158 patients were included in the final analysis (activated prothrombin complex concentrate = 118; 4-factor prothrombin complex concentrate = 40). Those in the 4-factor prothrombin complex concentrate group had a higher pretreatment international normalized ratio (2.7 ± 1.8 vs 3.5 ± 2.9; p = 0.0164). However, the posttreatment international normalized ratio was similar between the groups. In addition, even when controlling for differences in the pretreatment international normalized ratio, there was no difference in the ability to achieve a posttreatment international normalized ratio of less than 1.4 (odds ratio, 0.753 [95% CI, 0.637-0.890]; p = 0.0009). Those in the activated prothrombin complex concentrate group did have higher odds of achieving a posttreatment international normalized ratio of less than 1.2 (odds ratio, 3.23 [95% CI, 1.34-7.81]; p = 0.0088). There was only one posttreatment thrombotic complication reported. CONCLUSIONS: A low, fixed dose of activated prothrombin complex concentrate was as effective as standard dose 4-factor prothrombin complex concentrate for normalization of international normalized ratio. In addition, we did not see an increase in thrombotic events.

Intracerebral hemorrhage after external ventricular drain placement: an evaluation of risk factors for post-procedural hemorrhagic complications.

BACKGROUND: The objective of this study was to evaluate and identify the risk factors for developing a new or enlarged intracranial hemorrhage (ICH) after the placement of an external ventricular drain. METHODS: A single center, nested case-control study of individuals who received an external ventricular drain from June 1, 2011 to June 30, 2014 was conducted at a large academic medical center. A bivariate analysis was conducted to compare those individuals who experienced a post-procedural intracranial hemorrhage to those who did not experience a new bleed. The variables identified as having a p-value less than 0.15 in the bivariate analysis were then evaluated using a multivariate logistic regression model. RESULTS: Twenty-seven of the eighty-one study participants experienced a new or enlarged intracranial hemorrhage after the placement of an external ventricular drain. Of these twenty-seven patients, 6 individuals received an antiplatelet within ninety-six hours of external ventricular drain placement (p = 0.024). The multivariate logistic regression model identified antiplatelet use within 96 h of external ventricular drain insertion as an independent risk factor for post-EVD ICH (OR 13.1; 95% CI 1.95-88.6; p = 0.008). CONCLUSION: Compared to those study participants who did not receive an antiplatelet within 96 h of external ventricular drain placement, those participants who did receive an antiplatelet were 13.1 times more likely to exhibit a new or enlarged intracranial hemorrhage.

Treatment of Hyponatremia in Patients with Acute Neurological Injury.

BACKGROUND: Little data exist regarding the practice of sodium management in acute neurologically injured patients. This study describes the practice variations, thresholds for treatment, and effectiveness of treatment in this population. METHODS: This retrospective, multicenter, observational study identified 400 ICU patients, from 17 centers, admitted for ≥48 h with subarachnoid hemorrhage (SAH), traumatic brain injury (TBI), intraparenchymal hemorrhage, or intracranial tumors between January 1, 2011 and July 31, 2012. Data collection included demographics, APACHE II, Glascow Coma Score (GCS), serum sodium (Na+), fluid rate and tonicity, use of sodium-altering therapies, intensive care unit (ICU) and hospital length of stay, and modified Rankin score upon discharge. Data were collected for the first 21 days of ICU admission or ICU discharge, whichever came first. Sodium trigger for treatment defined as the Na+ value prior to treatment with response defined as an increase of ≥4 mEq/L at 24 h. RESULTS: Sodium-altering therapy was initiated in 34 % (137/400) of patients with 23 % (32/137) having Na+ >135 mEq/L at time of treatment initiation. The most common indications for treatment were declining serum Na+ (68/116, 59 %) and cerebral edema with mental status changes (21/116, 18 %). Median Na+ treatment trigger was 133 mEq/L (IQR 129-139) with no difference between diagnoses. Incidence and treatment of hyponatremia was more common in SAH and TBI [SAH (49/106, 46 %), TBI (39/97, 40 %), ICH (27/102, 26 %), tumor (22/95, 23 %); p = 0.001]. The most common initial treatment was hypertonic saline (85/137, 62 %), followed by oral sodium chloride tablets (42/137, 31 %) and fluid restriction (15/137, 11 %). Among treated patients, 60 % had a response at 24 h. Treated patients had lower admission GCS (12 vs. 14, p = 0.02) and higher APACHE II scores (12 vs. 10, p = 0.001). There was no statistically significant difference in outcome when comparing treated and untreated patients. CONCLUSION: Sodium-altering therapy is commonly employed among neurologically injured patients. Hypertonic saline infusions were used first line in more than half of treated patients with the majority having a positive response at 24 h. Further studies are needed to evaluate the impact of various treatments on patient outcomes.

The Insertion and Management of External Ventricular Drains: An Evidence-Based Consensus Statement : A Statement for Healthcare Professionals from the Neurocritical Care Society.

External ventricular drains (EVDs) are commonly placed to monitor intracranial pressure and manage acute hydrocephalus in patients with a variety of intracranial pathologies. The indications for EVD insertion and their efficacy in the management of these various conditions have been previously addressed in guidelines published by the Brain Trauma Foundation, American Heart Association and combined committees of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. While it is well recognized that placement of an EVD may be a lifesaving intervention, the benefits can be offset by procedural and catheter-related complications, such as hemorrhage along the catheter tract, catheter malposition, and CSF infection. Despite their widespread use, there are a lack of high-quality data regarding the best methods for placement and management of EVDs to minimize these risks. Existing recommendations are frequently based on observational data from a single center and may be biased to the authors' view. To address the need for a comprehensive set of evidence-based guidelines for EVD management, the Neurocritical Care Society organized a committee of experts in the fields of neurosurgery, neurology, neuroinfectious disease, critical care, pharmacotherapy, and nursing. The Committee generated clinical questions relevant to EVD placement and management. They developed recommendations based on a thorough literature review using the Grading of Recommendations Assessment, Development, and Evaluation system, with emphasis placed not only on the quality of the evidence, but also on the balance of benefits versus risks, patient values and preferences, and resource considerations.

Management of apixaban-associated subdural hematoma: a case report on the use of factor eight inhibitor bypassing activity.

OBJECTIVE: We report a case of a patient receiving apixaban who developed a spontaneous subdural hematoma and declining mental status that improved after administration of a single dose of factor eight inhibitor bypassing activity. DESIGN: Case report. SETTING: Comprehensive Stroke Center, Neurocritical Care Unit. PATIENT: A 76-year-old man presented to an outside facility with a chief complaint of headache and pain behind his right eye. A CT scan of his head revealed a subdural hematoma. The patient was transferred to our facility with worsening clinical status. INTERVENTIONS: After a confirmatory cranial CT scan revealed a worsening subdural hematoma with midline shift, a single dose of factor VIII inhibitor bypassing activity (25 U/kg) was administered. MEASUREMENTS AND MAIN RESULTS: Coagulation tests following the administration of factor VIII inhibitor bypassing activity and a follow-up CT scan confirmed hemostasis. The patient was discharged home with no focal deficits. CONCLUSIONS: Factor VIII inhibitor bypassing activity may be a viable, nonspecific reversal agent for life-threatening bleeding associated with apixaban.

Evaluation of the Hemodynamic Effects of Intravenous Amiodarone Formulations During the Maintenance Phase Infusion.

BACKGROUND: Two of the excipients in intravenous formulations of amiodarone, polysorbate 80 and benzyl alcohol, have been shown to cause hypotension. A newer formulation of amiodarone, which contains cyclodextrin, is devoid of these excipients. OBJECTIVE: To evaluate the change in mean arterial pressure when utilizing 2 intravenous amiodarone formulations. METHODS: This was a retrospective cohort analysis conducted at an academic medical center. Patients received intravenous amiodarone containing either polysorbate 80/benzyl alcohol (control) or cyclodextrin (cyclodextrin). Patients received these formulations based on a standard institutional protocol of 1 mg/min for 6 hours, followed by 0.5 mg/min for at least 18 hours or until discontinued by the provider. All data were collected from the medical record and included changes in blood pressures, time to lowest systolic blood pressure, concurrent antihypertensive use, and number of patients requiring treatment for hypotension. RESULTS: A total of 160 patients (120 control, 40 cyclodextrin) were included. There was a statistically significant difference in mean arterial pressure between the groups receiving the control formulation of amiodarone compared with the cyclodextrin formulation across the 24-hour maintenance phase infusion (P < 0.001). There was a significant difference between formulations with regard to the change in mean arterial pressure during the 0- to 6-hour and 12- to 18-hour time blocks. There was a statistically significant difference in the number of patients receiving fluid boluses for treatment of hypotension (P = 0.001). CONCLUSIONS: The excipients in the formulation of intravenous amiodarone may have a significant role in the hypotensive effects seen throughout the duration the maintenance phase infusion.

Long-term comparison of GOS-E scores in patients treated with phenytoin or levetiracetam for posttraumatic seizure prophylaxis after traumatic brain injury.

BACKGROUND: Much debate exists on the optimal medication for posttraumatic seizure prophylaxis after traumatic brain injury (TBI). There is some evidence that levetiracetam (LEV) could be neuroprotective and provide long-term benefits in this patient population. OBJECTIVE: The primary objective was to compare the Glasgow Outcome Scale-Extended (GOS-E) 6 months or more after severe TBI. Secondary end points were presence of early seizures (0 to 7 days post-TBI) or late seizures (8 days post-TBI to phone interview), use of anticonvulsant medication when interviewed, medication-related hospital complications, and a summary of phenytoin (PHT) and LEV dosing regimens. METHODS: This was an IRB-approved, single-center, prospective cohort analysis. Patients were identified by cross-referencing a list of patients receiving LEV or PHT, with a list of patients with ICD-9 code consistent with TBI. After study inclusion, patients were contacted by telephone, and the GOS-E was administered. Data for secondary end points were gathered by retrospective chart review. RESULTS: In all, 19 patients were included in the final analysis. There was no difference in the GOS-E score assessed ≥6 months after injury (5.07±1.69 vs 5.60±2.07, P=0.58). There was no difference in the secondary end points of early seizures (P=0.53) or late seizures (P=0.53). However, the PHT group experienced a higher rate of hospital days with recorded fever (0.20±0.22 vs 0±0; P=0.014). CONCLUSIONS: Long-term functional outcome in patients who experienced a TBI was not affected by treatment with PHT or LEV; however, patients treated with PHT had a higher incidence of fever during hospitalization.

Thromboelastographic changes in patients experiencing an acute ischemic stroke and receiving alteplase.

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 hemorrhage. 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.

Outcomes Associated With Levetiracetam Use After Spontaneous Intracerebral Hemorrhage.

Background and Purpose: The purpose of this study was to assess the incidence of seizures in patients with spontaneous intracerebral hemorrhage (ICH) who received prophylactic levetiracetam. Methods: This was a retrospective cohort study evaluating the use of levetiracetam in patients without a history of seizures who experienced a spontaneous intracerebral hemorrhage. Patients were excluded if they were younger than 18 years of age, had a documented history of a seizure disorder, or had an antiseizure drug documented on their home medication list. Patients were based on their exposure to levetiracetam. The primary outcome was incidence of seizure during hospital admission. Secondary outcomes included occurrence of adverse events, intensive care unit (ICU) length of stay (LOS), and hospital LOS. Results: Of the 229 patients included in the final analysis, 21 were in the levetiracetam group (LEV) and 208 were in the no levetiracetam group (no LEV). No statistical difference in seizure incidence was observed when comparing the LEV and no LEV groups (1 [4.8%] LEV vs 3 [1.4%] no LEV; P = .32). There was also no statistical difference in the median ICU LOS (2 days [1 day, 5 days] LEV vs 2 days [1 day, 3 days] no LEV; P = .27), median hospital LOS (6 days [2 days, 8 days] LEV vs 6 days [3 days, 9 days] no LEV; P = .27), or adverse events. Conclusions: This study does not support the use of levetiracetam prophylaxis in patients who have experienced an ICH.