Clinical outcomes after 4F-PCC for warfarin-associated ICH and baseline GCS less than or equal to 8.

PURPOSE: There is limited evidence describing the mortality benefit of utilizing 4-factor prothrombin complex concentrate (4F-PCC) in patients presenting with a warfarin-associated intracerebral hemorrhage (ICH) and a Glasgow Coma Scale (GCS) of ≤8. The aim of this study is to determine the potential mortality benefit of 4F-PCC in this patient population. METHODS: This was a retrospective chart review, performed at a comprehensive stroke center from October 2013 through August 2020. Patients were included if they were ≥ 18 years of age, experienced a spontaneous ICH with baseline GCS ≤ 8, treated with warfarin prior to admission, had a baseline INR ≥ 1.7, and received 4F-PCC for INR normalization due to warfarin-associated ICH. The primary outcome was in-hospital mortality at 30 days. RESULTS: A total of 252 patients received 4F-PCC in the specified time period. Of those patients, 25 patients met inclusion criteria. Sixteen patients (64%) experienced in-hospital mortality. When compared to a historical estimated 80% mortality rate in the studied patient population, there was no statistically significant difference (p = 0.208) in mortality when 4F-PCC was utilized to reverse INR. CONCLUSION: The administration of 4F-PCC in patients presenting with warfarin-related ICH and GCS ≤ 8 did not result in statistically significant mortality benefit. Our results are limited by study design and sample size. Thus, larger studies are needed to determine if a benefit exists for 4F-PCC in this patient population. Although the results are not statistically significant, our small study suggests that there may be a clinically significant mortality benefit when 4F-PCC is utilized.

Factor Xa Inhibitor-Related Intracranial Hemorrhage: Results From a Multicenter, Observational Cohort Receiving Prothrombin Complex Concentrates.

BACKGROUND: Since the approval of the oral factor Xa inhibitors, there have been concerns regarding the ability to neutralize their anticoagulant effects after intracranial hemorrhage (ICH). Multiple guidelines suggest using prothrombin complex concentrates (PCCs) in these patients on the basis of research that includes a limited number of patients with ICH. Given this, we aimed to evaluate the safety and efficacy of PCCs for factor Xa inhibitor-related ICH in a large, multicenter cohort of patients. METHODS: This was a multicenter, retrospective, observational cohort study of patients with apixaban- or rivaroxaban-related ICH who received PCCs between January 1, 2015, and March 1, 2019. The study had 2 primary analysis groups: safety and hemostatic efficacy. The safety analysis evaluated all patients meeting inclusion criteria for the occurrence of a thrombotic event, which were censored at hospital discharge or 30 days after PCC administration. Patients with intracerebral, subarachnoid, or subdural hemorrhages who had at least 1 follow-up image within 24 hours of PCC administration were assessed for hemostatic efficacy. The primary efficacy outcome was the percentage of patients with excellent or good hemostasis on the basis of the modified Sarode criteria. Secondary outcomes included an evaluation of in-hospital mortality, length of stay, infusion-related reactions, and thrombotic event occurrence during multiple predefined periods. RESULTS: A total of 663 patients were included and assessed for safety outcomes. Of these, 433 patients met criteria for hemostatic efficacy evaluation. We observed excellent or good hemostasis in 354 patients (81.8% [95% CI, 77.9-85.2]). Twenty-five (3.8%) patients had a total of 26 thrombotic events, of which 22 occurred in the first 14 days after PCC administration. One patient had documentation of an infusion-related reaction. For the full cohort of patients, in-hospital mortality was 19.0%, and the median intensive care unit and hospital lengths of stay were 2.0 and 6.0 days, respectively. CONCLUSIONS: Administration of PCCs after apixaban- and rivaroxaban-related ICH provided a high rate of excellent or good hemostasis (81.8%) coupled with a 3.8% thrombosis rate. Randomized, controlled trials evaluating the clinical efficacy of PCCs in patients with factor Xa inhibitor-related ICH are needed.

Stress-Related Gastrointestinal Bleeding in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter Retrospective Observational Study.

BACKGROUND/OBJECTIVE: Stress-related mucosal bleeding (SRMB) occurs in approximately 2-4% of critically ill patients. Patients with aneurysmal subarachnoid hemorrhage (aSAH) have a (diffuse) space-occupying lesion, are critically ill, often require mechanical ventilation, and frequently receive anticoagulation or antiplatelet therapy after aneurysm embolization, all of which may be risk factors for SRMB. However, no studies have evaluated SRMB in patients with aSAH. Aims of the study were to determine the incidence of SRMB in aSAH patients, evaluate the effect of acid suppression on SRMB, and identify specific risk factors for SRMB. METHODS: This was a multicenter, retrospective, observational study conducted across 17 centers. Each center reviewed up to 50 of the most recent cases of aSAH. Patients with length of stay (LOS) < 48 h or active GI bleeding on admission were excluded. Variables related to demographics, aSAH severity, gastrointestinal (GI) bleeding, provision of SRMB prophylaxis, adverse events, intensive care unit (ICU), and hospital LOS were collected for the first 21 days of admission or until hospital discharge, whichever came first. Descriptive statistics were used to analyze the data. A multivariate logistic regression modeling was utilized to examine the relationship between specific risk factors and the incidence of clinically important GI bleeding in patients with aSAH. RESULTS: A total of 627 patients were included. The overall incidence of clinically important GI bleeding was 4.9%. Of the patients with clinically important GI bleeding, 19 (61%) received pharmacologic prophylaxis prior to evidence of GI bleeding, while 12 (39%) were not on pharmacologic prophylaxis at the onset of GI bleeding. Patients who received an acid suppressant agent were less likely to experience GI bleeding than patients who did not receive pharmacologic prophylaxis prior to evidence of bleeding (OR 0.39, 95% CI 0.18-0.83). The multivariate regression analysis identified any instance of elevated intracranial pressure, creatinine clearance < 60 ml/min and the incidence of cerebral vasospasm as specific risk factors associated with GI bleeding. Cerebral vasospasm has not previously been described as a risk for GI bleeding (OR 2.5 95% CI 1.09-5.79). CONCLUSIONS: Clinically important GI bleeding occurred in 4.9% of patients with aSAH, similar to the general critical care population. Risk factors associated with GI bleeding were prolonged mechanical ventilation (> 48 h), creatinine clearance < 60 ml/min, presence of coagulopathy, elevation of intracranial pressure, and cerebral vasospasm. Further prospective research is needed to confirm this observation within this patient population.

Association of Longitudinal Glycemia with Diffusion Weighted Imaging Lesions in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: Higher glycemia on admission has been associated with diffusion weighted imaging (DWI) lesions in patients with spontaneous intracerebral hemorrhage (sICH). However, the influence of longitudinal glycemia after admission and during a patient's hospitalization on DWI lesions in sICH has not been studied. Our aim was to compare longitudinal glycemia in sICH patients with and without DWI lesions. MATERIAL AND METHODS: Glycemia measurements were abstracted on participants enrolled in a prospective observational study examining predictors for DWI lesions in sICH. Univariate analysis was used to compare mean longitudinal glycemia in sICH patients with and without DWI lesions. Logistical regression was used to determine whether mean longitudinal glycemia was predictive of DWI lesions. RESULTS: DWI lesions were found in 60 of the 121 (49.6%) participants. Mean time-to-MRI was 99.6 h (SD ± 89). During this time interval, 2,101 glucose measurements were analyzed with a median number of 7 (IQR 12, 1-261) measurements per patient. Mean longitudinal glycemia was higher in the DWI positive group compared to the DWI negative group until time-to-MRI (132 mg/dL vs 122 mg/dL, p = 0.03). Mean longitudinal glycemia was found to be predictive of DWI lesions (OR 1.02, 95% CI 1.005 to 1.035, p = 0.011). CONCLUSIONS: Mean longitudinal glycemia was higher in sICH patients with DWI lesions compared to those without DWI lesions. Future research into the association between higher glycemia and DWI lesions in sICH may provide insight into a pathophysiologic mechanism.

Eptifibatide use following emergent carotid stenting in acute anterior circulation ischemic stroke with tandem occlusion.

BACKGROUND: Early revascularization of the extracranial internal carotid artery in acute anterior circulation ischemic stroke (ACIS) is feasible and may improve clinical outcome. When a stent is deployed, antithrombotic agents should be administered peri-procedurally to ensure stent patency. Our institution implemented a protocol for the use of eptifibatide as a means of maintaining stent patency in the treatment of ACIS associated with cervical internal carotid artery occlusion. METHODS: Our internal database was queried for patients who received emergent endovascular therapy (ET) for ACIS with stent placement and eptifibatide administration between July 2016 and 2019. RESULTS: Twenty nine patients met the study criteria. The etiology was large artery atherosclerosis in 26 cases. Two patients had a dissection (7%), and one had a carotid occlusion related to a recent carotid endarterectomy. Mean NIHSS was 14. Sixteen patients received IVrtPA. Extracranial-intracranial tandem occlusion (TO) was present in 21 of cases. All patients received an eptifibatide bolus followed by an infusion for approximately 24 hours post stent deployment. Head CT was obtained prior to initiation of oral dual antiplatelet therapy with aspirin and clopidogrel. Successful recanalization was achieved in all patients with no evidence of downstream embolization. Symptomatic intracerebral hemorrhage occurred in one patient. Stent occlusion occurred in two patients, only one of which was symptomatic. Favorable clinical outcome with mRS ≤ 2 at 3 months was achieved in seventeen patients. CONCLUSIONS: The use of eptifibatide post procedure was associated with low risk of symptomatic intracranial hemorrhage, including in patients treated with rtPA.

Dual intraventricular plus systemic antibiotic therapy for the treatment of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae ventriculitis.

OBJECTIVE: To report a case of Klebsiella pneumoniae carbapenemase (KPC)-producing K pneumoniae ventriculitis successfully treated with dual intraventricular plus systemic antibiotic therapy. CASE SUMMARY: A 43-year-old woman with a ventriculoperitoneal shunt was transferred from a nursing home with fever, altered mental status, and leukocytosis. She was found to have KPC-producing K pneumoniae ventriculitis. Combination intraventricular antibiotic therapy with colistin and gentamicin plus systemic colistin and amikacin led to the resolution of infection. DISCUSSION: Utilization of intraventricular or intrathecal antibiotics has been described in the literature for multidrug resistant (MDR) Gram-negative central nervous system (CNS) infections; however, none of the cases were caused by a KPC-producing organism. Given the pathogenicity and limited treatment options for this resistant organism, we utilized intraventricular colistin 10 mg and intraventricular gentamicin 10 mg in combination with systemic colistin and amikacin. An extensive literature search revealed several case reports and case series of documented MDR Acinetobacter baumanii CNS infections successfully treated with intraventricular colistin or aminoglycoside therapy with good tolerability. Additionally, recent pharmacokinetic analyses suggest improved cerebrospinal fluid (CSF) concentrations with direct CNS antimicrobial administration in combination with systemic therapy. Although our patient's cerebral spinal fluid cultures were cleared with dual intraventricular plus systemic therapy, she continued to deteriorate clinically because of her comorbid conditions and required hospice admission. CONCLUSIONS: This describes the first reported case of KPC-producing K pneumoniae ventriculitis microbiologically cured based on negative blood and CSF cultures with a combination of intraventricular and systemic therapy.

Comparison of nimodipine formulations and administration techniques via enteral feeding tubes in patients with aneurysmal subarachnoid hemorrhage: A multicenter retrospective cohort study.

BACKGROUND: Nimodipine improves outcomes following aneurysmal subarachnoid hemorrhage (aSAH) and current guidelines suggest that patients with aSAH receive nimodipine for 21 days. Patients with no difficulty swallowing will swallow the whole capsules or tablets; otherwise, nimodipine liquid must be drawn from capsules, tablets need to be crushed, or the commercially available liquid product be used to facilitate administration through an enteral feeding tube (FT). It is not clear whether these techniques are equivalent. The goal of the study was to determine if different nimodipine formulations and administration techniques were associated with the safety and effectiveness of nimodipine in aSAH. METHODS: This was a retrospective multicenter observational cohort study conducted in 21 hospitals across North America. Patients admitted with aSAH and received nimodipine by FT for ≥3 days were included. Patient demographics, disease severity, nimodipine administration, and study outcomes were collected. Safety end points included the prevalence of diarrhea and nimodipine dose reduction or discontinuation secondary to blood pressure reduction. Predictors of the study outcomes were analyzed using regression modeling. RESULTS: A total of 727 patients were included. Administration of nimodipine liquid product was independently associated with higher prevalence of diarrhea compared to other administration techniques/formulations (Odds ratio [OR] 2.28, 95% confidence interval [CI] 1.41-3.67, p-value = 0.001, OR 2.76, 95% CI 1.37-5.55, p-value = 0.005, for old and new commercially available formulations, respectively). Bedside withdrawal of liquid from nimodipine capsules prior to administration was significantly associated with higher prevalence of nimodipine dose reduction or discontinuation secondary to hypotension (OR 2.82, 95% CI 1.57-5.06, p-value = 0.001). Tablet crushing and bedside withdrawal of liquid from capsules prior to administration were associated with increased odds of delayed cerebral ischemia (OR 6.66, 95% CI 3.48-12.74, p-value <0.0001 and OR 3.92, 95% CI 2.05-7.52, p-value <0.0001, respectively). CONCLUSIONS: Our findings suggest that enteral nimodipine formulations and administration techniques might not be equivalent. This could be attributed to excipient differences, inconsistency and inaccuracy in medication administration, and altered nimodipine bioavailability. Further studies are needed.

Under the Microscope: A Look Into the Role of Critical Care Pharmacists During the COVID-19 Pandemic.

Among disciplines, the COVID-19 pandemic has reinforced the importance of critical care pharmacists in assuming responsibility for managing medication therapy in direct patient care settings. Historically, pharmacists have been relied upon for prospective evaluation of drug therapy for appropriate indications, dosage, drug interactions, and drug allergies; monitoring patients' pharmacotherapeutic regimens for effectiveness and adverse effects; providing drug information to providers; and educating health professionals regarding drug therapies. Specific to COVID-19, pharmacists have been an integral member of the multidisciplinary rounding team, assisting with drug shortages and strategies for drug conservation; participating in emergencies, such as advanced cardiac life support (ACLS) and rapid sequence intubations; and creating as well as integrating evidence-based guidelines and pathways during the pandemic into clinical practice. The purpose of this article is to demonstrate the various roles of critical care pharmacists among the healthcare team in caring for critically ill COVID-19 patients.

Efficacy of an opioid-sparing analgesic protocol in pain control after less invasive cranial neurosurgery.

INTRODUCTION: Opioid overuse in postoperative patients is a worrisome trend, and potential alternatives exist which warrant investigation. Nonsteroidal anti-inflammatory drug use in treating postoperative cranial surgery pain has been hampered by concern for inadequate pain control and increased risk of hemorrhagic complications. A safe and effective alternative to opioid-based pain management is critical to improving postoperative care. OBJECTIVE: The objective of this retrospective study was to determine whether an NSAID-based opioid-sparing pain management protocol (OSP) is effective in analgesic control of less invasive cranial surgery patients at 6-, 12-, and 24-hour postoperatively. Secondary aims included investigating differences in hemorrhagic complications. METHODS: Five hundred sixty-six consecutive patients who underwent cranial surgery before and after implementation of the celecoxib-based OSP were eligible. Propensity score matching was used to match patients in each cohort. RESULTS: The opioid-sparing cohort had lower pain scores at 6 hours (3.45 vs 4.19, P = 0.036), 12 hours (3.21 vs 4.00, P = 0.006), and 24 hours (2.90 vs 3.59, P = 0.010). Rates of postoperative hemorrhage were not significantly different (5% intervention vs 8% control, P = 0.527). The opioid-sparing pain management protocol provided comparable or better pain control in the first 24 hours after less invasive cranial surgery. Hemorrhage rates did not change with the use of an NSAID-based OSP. CONCLUSION: An effective alternative to the current standard opioid-based pain management is feasible for less invasive cranial surgery. Determinations of hemorrhage risk and more complex cranial surgery will require larger prospective randomized trials.

Reversal of Warfarin-Associated Major Hemorrhage: Activated Prothrombin Complex Concentrate versus 4-Factor Prothrombin Complex Concentrate.

BACKGROUND: Warfarin-associated major hemorrhage is frequently treated with prothrombin complex concentrates to correct international normalized ratio (INR). OBJECTIVE: This article aims to investigate the efficacy of activated prothrombin complex concentrate (aPCC) versus 4-factor prothrombin complex concentrate (4PCC) for vitamin K antagonist reversal in patients with warfarin-associated major hemorrhage. MATERIALS AND METHODS: This was a multicenter, retrospective cohort study. Patients included were age ≥ 18 years with pretreatment INR of > 1.5. Exclusion criteria were patients treated for urgent procedures without hemorrhage, treated but not taking warfarin, unavailable INR values, and pregnant patients. Patients were stratified into two groups: aPCC or 4PCC. The primary outcome was achievement of INR ≤ 1.5 at the posttreatment INR sampling. Secondary outcomes focused on thrombotic events and mortality. RESULTS: Of 342 patients, 237 patients received aPCC and 105 patients received 4PCC. After 1:1 propensity score matching, 86 patients remained in each group. In the matched cohort, the proportion of patients who achieved target INR ≤ 1.5 was greater with 4PCC (aPCC = 61 [70.9%] vs. 4PCC = 76 [88.4%]; 95% confidence interval [CI] -29.2% to -5.7%) and groups had comparable in-hospital thrombotic events and mortality. In the unmatched cohort, achievement of target INR ≤ 1.5 was greater with 4PCC (aPCC = 151 [63.7%] vs. 4PCC = 92 [87.6%]; 95% CI -32.7% to -15.1%). CONCLUSION: In the treatment of warfarin-associated major hemorrhage, 4PCC compared with aPCC was associated with greater achievement of INR ≤ 1.5 with comparable thrombotic events and mortality. Further controlled studies are needed to confirm these findings and determine the optimal dosing strategy that maximizes efficacy and safety.

Outcome following intracranial hemorrhage associated with novel oral anticoagulants.

The emergence of dabigatran, rivaroxaban and apixaban has changed the approach to anticoagulation for patients worldwide. Continued approval of novel oral anticoagulants (NOAC) for non-valvular atrial fibrillation and venous thromboembolism will result in increasing use of these medications over warfarin. Morbidity and mortality of anticoagulant related intracranial hemorrhage (ICH) is relatively high and there is concern that outcomes may be worse with NOAC as there is a lack of specific antidotes for these agents with a greater risk for hematoma expansion. Unfortunately, the evidence supporting effective reversal strategies is lacking. Therefore, to gain further insight into the outcome after the management of NOAC related ICH, we present our experience with two patients with NOAC-induced ICH.

Outcomes associated with transdermal nicotine replacement therapy in a neurosurgery intensive care unit.

PURPOSE: The outcomes associated with transdermal nicotine replacement therapy (NRT) in a neurosurgery intensive care unit (ICU) were studied. METHODS: Data from pharmacy records, neurosurgery ICU admission logs, and computerized patient charts at the University of Illinois Medical Center at Chicago from January 2001 through August 2008 were reviewed for patients older than 18 years who were admitted to the neurosurgery ICU for neurologic insults. Patients were categorized into three groups: smokers who received transdermal NRT (n = 114), smokers who did not receive transdermal NRT (n = 113), and nonsmokers (n = 113). The primary outcome of this study was unfavorable disposition at discharge from the hospital. Secondary outcomes measured included overall mortality; lengths of hospital and neurosurgery ICU stays; and rates of subarachnoid hemorrhage (SAH) rebleeding, angiographic vasospasm, intracerebral hemorrhage rebleeding, and ischemic stroke. RESULTS: Overall, there was no difference in unfavorable discharge disposition among the three groups (p = 0.17). However, the group who received NRT had higher admission rates of SAH, smoked more cigarettes for a longer period of time, and had longer stays in the neurosurgery ICU and hospital compared with the other groups. All patients who received NRT had prolonged hospital (p = 0.014) and neurosurgery ICU (p = 0.006) stays compared with those who did not receive NRT. There were no differences in other secondary outcomes among the groups. CONCLUSION: There was no significant difference in unfavorable discharge disposition among neurosurgery ICU patients who were smokers treated with NRT, smokers not treated with NRT, and nonsmokers not treated with NRT.