Reviving Decades-Old Wisdom: Longitudinal Analysis of Renin-Angiotensin System Inhibitors and Its Effects on Acute Ischemic Stroke to Improve Outcomes.

BACKGROUND: While renin-angiotensin system (RAS) inhibitors have a longstanding history in blood pressure control, their suitability as first-line in-patient treatment may be limited due to prolonged half-life and kidney failure concerns. METHODS: Using a cohort design, we assessed the impact of RAS inhibitors, either alone or in combination with beta-blockers, on mortality, while exploring interactions, including those related to end-stage renal disease and serum creatinine levels. Eligible subjects were Acute Ischemic Stroke (AIS) patients aged 18 or older with specific subtypes who received in-patient antihypertensive treatment. The primary outcome was mortality rates. Statistical analyses included cross-sectional and longitudinal approaches, employing generalized linear models, G-computation, and discrete-time survival analysis over a 20-day follow-up period. RESULTS: In our study of 3,058 AIS patients, those using RAS inhibitors had significantly lower in-hospital mortality (2.2%) compared to non-users (12.1%), resulting in a relative risk (RR) of 0.18 (95% CI: 0.12-0.26). Further analysis using G-computation revealed a marked reduction in mortality risk associated with RAS inhibitors (0.0281 vs. 0.0913, risk difference [RD] of 6.31% or 0.0631, 95% CI: 0.046-0.079). Subgroup analysis demonstrated notable benefits, with individuals having creatinine levels below and above 1.3 mg/dl exhibiting statistically significant RD (RD -0.0510 vs. -0.0895), and a significant difference in paired comparison (-0.0385 or 3.85%, CI 0.023-0.054). Additionally, longitudinal analysis confirmed a consistent daily reduction of 0.93% in mortality risk associated with the intake of RAS inhibitors. CONCLUSIONS: RAS inhibitors are associated with a significant reduction in in-hospital mortality in AIS patients, suggesting potential clinical benefits in improving patient outcomes.

Comparison of survival by vasoactive-inotropic score in patients receiving veno-arterial extracorporeal life support.

After the initiation of veno-arterial extracorporeal membrane oxygenation (V-A ECMO) for hemodynamic support, patients often require vasopressor and inotropic medications to support their blood pressure and cardiac contractility. The vasoactive-inotropic score (VIS) is a standardized calculation of vasopressor and inotrope equivalence, which uses coefficients for each medication to calculate a total value. This study evaluated the association between the 30-day survival of patients receiving V-A ECMO support and the VIS calculated 24 h after ECMO cannulation (VIS24). This was a single-center, retrospective, observational cohort study. The median VIS24 of the entire cohort was 6.0, and was determined as a cutoff for comparison. Patients with a VIS24 < 6.0 were assigned to a group, and those with a VIS24 ≥ 6.0 were assigned to a second group. Patients with a VIS24 < 6.0 had higher 30-day survival than those with a VIS24 ≥ 6.0 (54.5% vs 41.4%; p = 0.03). The group with a VIS24 < 6.0 also had significantly improved survival to decannulation of ECMO support; however, there was no difference in the survival to hospital discharge. We conducted a secondary analysis of quartiles and determined that individuals with a VIS24 > 11.4 had the lowest survival in the cohort. This finding may help identify patients with the lowest probability of 30-day survival in those receiving V-A ECMO for hemodynamic support.

Hemostatic efficacy of four factor prothrombin complex concentrate in intracerebral hemorrhage patients receiving warfarin vs. factor Xa inhibitors.

INTRODUCTION: 4-F PCC is administered for reversal of factor Xa inhibitor-associated coagulopathy despite a lack of quality evidence demonstrating hemostatic efficacy. The aim of this study was to evaluate the hemostatic efficacy of 4-F PCC in intracerebral hemorrhage patients who received factor Xa inhibitors versus warfarin. MATERIALS AND METHODS: This was a multi-center, retrospective, observational cohort study at a large healthcare system. Patients taking warfarin received 4-F PCC 25-50 units/kg based on the presenting INR, while patients taking a factor Xa inhibitor received 35 units/kg. The primary outcome was the percentage of patients with good or excellent hemostatic efficacy as assessed by modified Sarode scale, with neurologic outcomes assessed as a secondary endpoint. Patients were included in the primary outcome population if they had a repeat CT scan within 24 h. RESULTS: One hundred fifty-seven patients were included in the primary outcome population; [warfarin (n = 76), factor Xa inhibitors (n = 81)]. Hemostatic efficacy was 83 % in the warfarin group versus 75 % in the factor Xa inhibitor group (p = 0.24). The hemostatic efficacy risk difference between the groups was 7.6 % (95 % CI 5.1 %, 20.2 %). Good neurologic outcome (mRS 0-2) at discharge was 17 % in warfarin patients versus 12 % in the factor Xa inhibitor patients (p = 0.40). CONCLUSIONS: There was no significant difference in hemostatic efficacy or clinical outcomes between patients taking warfarin or a factor Xa inhibitor following reversal with 4-F PCC. This study provides further support that 4-F PCC can be used for the reversal of factor Xa inhibitor-associated coagulopathy.

Evaluation of Vasoactive-Inotropic Score and Survival to Decannulation in Adult Patients on Venoarterial Extracorporeal Life Support: An Observational Cohort Study.

Extracorporeal life support with venoarterial extracorporeal membrane oxygenation (VA-ECMO) is used to assist circulation in patients with severe cardiogenic shock or cardiac arrest. The vasoactive-inotropic score (VIS) is a standardized calculation of vasoactive medication support which uses coefficients for each medication that converts them to an equivalent value. The purpose of this study was to assess the VIS as an early prognostication tool for survival to decannulation patients on adult VA-ECMO support. This was a single-center, observational cohort study of adult patients who received VA-ECMO support compared based on their survival to decannulation. The primary endpoint was the VIS at hour 24 postcannulation. Among the 265 patients included in this study, 140 patients (52.8%) survived to decannulation of VA-ECMO. At 24 hours postcannulation, a lower VIS was observed in the group that survived decannulation (6.5 ± 7.5 vs. 12.3 ± 16.9; p < 0.001). Multivariate analysis performed also demonstrates an association between 24-hour VIS and survival to decannulation (odds ratio 0.95; 95% confidence interval, 0.91-0.95). This study suggests that the 24-hour VIS may be an early prognostic indicator in patients on VA-ECMO patients. http://links.lww.com/ASAIO/B39.

Clonidine for the Treatment of Agitation After Dexmedetomidine Discontinuation in Pediatric Patients: A Retrospective Cohort Study.

OBJECTIVE: Dexmedetomidine has become a widely used drug in PICUs for sedation. We aim to determine the effects of clonidine on pediatric patients after dexmedetomidine use. METHODS: This was a retrospective cohort study that evaluated all pediatric patients admitted to a tertiary PICU who received dexmedetomidine infusion for >48 hours. Outcomes in patients exposed to clonidine (CLON) were compared with those of patients who were not exposed (NoCLON). RESULTS: A total of 216 patients were included in this study (43 CLON and 173 NoCLON). The primary outcome, agitation, was less in the CLON cohort (9.3%) than in the NoCLON cohort (9.3% versus 29.5%, respectively; p < 0.01). Hospital LOS was longer in the CLON group (59 versus 20 days, p < 0.01), as was PICU LOS (37.4 versus 11.1 days, p < 0.01). There was no significant difference in the occurrence of increased heart rate or blood pressure between the 2 cohorts. Patients exposed to concurrent midazolam and opioid infusions had higher incidence of agitation when they did not receive clonidine (CLON 8% versus NoCLON 37%, OR 0.15; 95% CI, 0.05-0.51; p < 0.01). In contrast, there was no difference in the incidence of agitation for the CLON group versus the NoCLON group when dexmedetomidine was administered alone (25% versus 19%, OR 1.4; p = 0.99). CONCLUSIONS: Our study confirms the importance and effectiveness of clonidine to treat agitation after dexmedetomidine discontinuation. A validated withdrawal scoring tool can help better define dexmedetomidine withdrawal in pediatric patients.

Risk of pump thrombosis and stroke in patients with continuous-flow left ventricular assist devices and gastrointestinal bleeding.

Gastrointestinal (GI) bleeding is a common complication following the placement of continuous-flow left ventricular assist devices (LVADs) in patients with advanced heart failure. Secondary events arising as a result of GI bleeding have not been well-described. Furthermore, attribution of these events to bleeding is complicated by the interruption or de-intensification of antithrombotic therapy, while bleeding is controlled. The purpose of this study was to assess the incidence of pump thrombosis and ischemic stroke in patients with LVADs who experience GI bleeding, while on support. This was a single-center, retrospective, observational cohort study of consecutive patients with LVADs implanted from January 2012 to June 2018. Patients were assigned to comparator groups based on whether they experienced GI bleeding while on LVAD support. The primary endpoint assessed was the composite of pump thrombosis or ischemic stroke. Secondary endpoints assessed included incidence of pump thrombosis or ischemic stroke. A total of 250 patients were included after screening for exclusion criteria, 101 (40.4%) in the GI bleeding group, and 149 (59.6%) in the non-bleeding group. The incidence of pump thrombosis or ischemic stroke was not significantly greater in patients experiencing GI bleeding [23 (22.8%) vs. 21 (14.1%); P = .09]; however, the incidence of ischemic stroke alone was significantly greater [17 (16.8%) vs. 10 (6.7%); P = .01]. We conclude that GI bleeding in LVAD patients may be associated with a greater risk of ischemic stroke.

Improving Appropriate Dosing of Intravenous dilTIAZem in Patients With Atrial Fibrillation or Flutter With Rapid Ventricular Response in the Emergency Department.

INTRODUCTION: Atrial fibrillation and atrial flutter are common supraventricular arrhythmias in patients who present to the emergency department. Under the American Heart Association guidelines, dilTIAZem is the calcium channel blocker frequently used by many practitioners for rate control. Currently, institution-specific data have identified that many patients receiving dilTIAZem for atrial fibrillation or atrial flutter are given initial doses that exceed the recommended dose by more than 10%, resulting in hypotension in some patients. METHODS: ED personnel were surveyed to determine their current knowledge of appropriate intravenous dilTIAZem dosing and methods of prescribing intravenous dilTIAZem to determine the causes of higher dosing. Based on the baseline data, an intervention of adding a text alert when withdrawing dilTIAZem from the automated medication dispensing cabinet was implemented. RESULTS: Following the intervention, 29 patients received intravenous dilTIAZem for rate control of atrial fibrillation or flutter with rapid ventricular response. For the primary outcome, the incidence of high-dose dilTIAZem decreased by 19% (P = 0.03). There was no change in the secondary outcome of a reduction in hypotension (P = 0.3). DISCUSSION: The interventions of education and medication alerts resulted in a significant increase in the percentage of patients receiving appropriate doses of dilTIAZem and a nonsignificant decrease in the incidence of hypotension. This process-oriented intervention resulted in an improvement in appropriate dilTIAZem doses at our site. Rate control was not statistically significantly different between the 2 groups. Long-term sustainability of this intervention requires further study.

Comparison of Clevidipine and Nicardipine for Acute Blood Pressure Reduction in Patients With Stroke.

OBJECTIVE: The aim of this study was to determine whether clevidipine (CLEV) achieved faster blood pressure control compared to nicardipine (NIC) in patients presenting with either an acute ischemic stroke (AIS) or a spontaneous intracerebral hemorrhage (ICH). METHODS: This was a retrospective, observational, cohort study conducted in patients with AIS or ICH admitted to the emergency department of a Comprehensive Stroke Center from November 2011 to June 2013 who received CLEV or NIC continuous infusion for acute blood pressure management. RESULTS: The study included 210 patients: 70 in the CLEV group and 140 in the NIC group. There was no difference in mean time (standard deviation [SD]) from initiation of the infusion to goal systolic blood pressure (SBP), CLEV: 50 (83) minutes versus NIC: 74 (103) minutes, P = .101. Comparison of the 2 agents within diagnosis showed no difference. Hypotension developed in 5 (7.1%) CLEV patients versus 14 (10%) NIC patients (P = .003). There was no difference in the percentage change at 2 hours; CLEV: -20% (16%) versus NIC: -16% (16%), P = .058. Mean (SD) time to alteplase administration from admission was 56 (22) minutes in the CLEV group versus 59 (25) minutes in the NIC group (P = .684). CONCLUSIONS: There was no difference in the mean time from initiation of the infusion to the SBP goal between agents or in the secondary outcomes. Due to the lack of differences observed, each agent should be considered based on the patient care needs of the institution.

Evaluation of Bivalirudin's Effect on International Normalized Ratio to Determine an Appropriate Strategy for Transitioning to Warfarin.

Background: Direct thrombin inhibitors are recommended in confirmed or suspected heparin-induced thrombocytopenia. False elevation of the international normalized ratio (INR) occurs with these agents making bridging to warfarin challenging. There is limited data regarding bivalirudin's effect on INR. Objective: To evaluate bivalirudin's effect on the INR and determine a strategy for transitioning to warfarin. Methods: This was a retrospective observational study. Included patients were >18 years old receiving primary bridging therapy with overlapping bivalirudin and warfarin for at least 72 hours. Patients with administration of alternate anticoagulants during the transition interval or active major bleeding within 48 hours prior to bivalirudin initiation were excluded. The primary endpoint was to determine the effect on INR at first therapeutic activated partial thromboplastin time after bivalirudin initiation and prior to warfarin initiation. Secondary endpoints included change in INR 12 and 24 hours after bivalirudin initiation, change in INR 4 hours after bivalirudin cessation, and incidence of major bleeding or new thrombotic events. Results: Thirty-four patients met study criteria. For the primary endpoint, the change in INR at first therapeutic activated partial thromboplastin time was 0.37 (range = 0.28-0.48), which occurred at 8.4 hours (range = 4.6-14.2; n = 14). INR increased at 12 and 24 hours by a median of 0.55 and 0.5 from baseline, respectively. Median change in INR 4 to 8 hours post-bivalirudin cessation was -0.48. Conclusion: Targeting an INR > 2.5 when bridging to warfarin will account for this false elevation and maintain an INR above 2.0 on bivalirudin discontinuation.

In vitro efficacy of antibiotic beads in treating abdominal vascular graft infections.

OBJECTIVE: Abdominal aortic vascular graft infection often involves several different organisms. Antibiotic polymethyl methacrylate (PMMA) beads may be effective in controlling infection after débridement, but bacterial species identification and antibiotic susceptibility are often not available at the time of operation, generating a need for a broad-spectrum drug combination for empirical use. We sought to determine an effective antibiotic in PMMA beads for use in abdominal vascular graft infection. METHODS: PMMA beads were impregnated with combinations of antibiotics, consisting of daptomycin, tobramycin, and meropenem. Antibiotics were selected on the basis of activity spectrum and heat stability. Beads were placed on separate agar plates with vancomycin-resistant Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus epidermidis, and methicillin-resistant Staphylococcus aureus. Antibiotic inhibition was recorded by use of a modified agar-based disk-diffusion method. RESULTS: Daptomycin alone was not active against K. pneumoniae (average = 0 mm). Tobramycin alone was not active against vancomycin-resistant E. faecalis, K. pneumoniae, or methicillin-resistant S. aureus. Tobramycin and daptomycin in combination had moderate broad-spectrum activity with 8- to 14-mm mean inhibition halos. Meropenem showed strong activity against all tested organisms with >15-mm mean inhibition halos. The addition of daptomycin to meropenem provided improved coverage of gram-positive organisms. The presence of tobramycin reduced the efficacy of meropenem. CONCLUSIONS: Antibiotic PMMA beads containing 10% meropenem with 2.5% daptomycin had excellent in vitro activity against typical bacterial species associated with abdominal vascular graft infections. The addition of antibiotic beads may be a useful adjunct in managing such cases. Further studies are required to determine efficacy in clinical practice.

The impact of drug shortages on the pharmacy, nursing, and medical staff's ability to effectively care for critically ill patients.

Managing drug shortages has become a daily requirement for health care providers in the critical care environment. Drug shortages impact the practice of different disciplines in various ways, and the perceptions of the underlying causes and appropriate management of drug shortages vary among physicians, nurses, and pharmacists as well. Frequently, these differences can lead to tension between disciplines and feelings of frustration, anger, and helplessness. Understanding the reasons behind drug shortages, the role each discipline has in managing shortages, and establishment of an effective method of communication between disciplines is key to reducing the tension and frustration that can be associated with drug shortages.

Continuous infusion versus intermittent bolus dosing of vecuronium in patients receiving therapeutic hypothermia after sudden cardiac arrest.

STUDY OBJECTIVE: To compare the effects of vecuronium administered as an intravenous continuous infusion versus intermittent bolus doses in patients treated with therapeutic hypothermia after sudden cardiac arrest (SCA). Design. Retrospective medical record review. SETTING: Cardiac care unit of a university-affiliated, level I trauma center. PATIENTS: Of 123 adults treated with therapeutic hypothermia after SCA, 80 received continuous-infusion vecuronium 0.8 µg/kg/minute started 2 hours after cooling began or if shivering occurred (January 1, 2004-December 31, 2007), and 43 received intermittent boluses of vecuronium 0.05 mg/kg every 2 hours (January 1, 2008-September 30, 2009). MEASUREMENTS AND MAIN RESULTS: The degree of neuromuscular blockade was measured with a train-of-four (TOF) test. Primary outcomes evaluated were time to achieve goal TOF response and percentage of time the TOF response was maintained at goal. Secondary outcomes included total daily dose of vecuronium, the vecuronium dose needed to achieve goal TOF response, percentage of TOF measurements above or below goal, and time to return of spontaneous respirations and time to extubation after the last dose of vecuronium. The goal TOF response was achieved significantly earlier in the bolus group than the continuous-infusion group (mean 5.9 vs 11.3 hrs, p=0.008). The mean total daily dose of vecuronium administered in the bolus group was significantly lower than that in the continuous-infusion group (51.7 vs 76.9 mg, p=0.002). The mean percentage of TOF measurements above goal was higher in the continuous-infusion group (33% vs 16%, p<0.0001), and the mean percentage of TOF measurements below goal was higher in the bolus group (43% vs 29%, p<0.0001). The median time to return of spontaneous respirations (6 vs 11 hrs, p=0.017) and time to extubation (29.5 vs 89.5 hrs, p<0.0001) were significantly shorter in the continuous-infusion group than the bolus group. CONCLUSION: Intermittent boluses of vecuronium were more effective in reaching a goal TOF response earlier compared with continuous-infusion vecuronium in patients treated with therapeutic hypothermia. The two dosing strategies were equally effective at maintaining a goal TOF response despite patients receiving a significantly lower daily dose of vecuronium in the intermittent-bolus group.

Efficacy and safety of a furosemide continuous infusion following cardiac surgery.

OBJECTIVE: To review the literature regarding the efficacy and safety of continuous intravenous infusion of loop diuretics following cardiac surgery. DATA SOURCES: Articles were identified through a MEDLINE search (1966-March 2006) using the key words furosemide, bumetanide, torsemide, ethacrynic acid, loop diuretics, continuous infusions, intravenous infusions, surgery, cardiac surgery, cardiovascular surgery, and thoracic surgery. Search results were limited to studies in human subjects published in English. Additional references were identified through review of the bibliographies of the articles cited. STUDY SELECTION AND DATA EXTRACTION: All clinical trials and observational reports identified that evaluated or described the efficacy and/or safety of a continuous infusion of a loop diuretic in adult or pediatric patients who had undergone cardiac surgery were included in this review. DATA SYNTHESIS: Loop diuretics are often used to promote diuresis following cardiac surgery. Studies in patients who have undergone cardiac surgery have demonstrated that a more consistent and sustained diuresis is produced by a continuous infusion of furosemide compared with intermittent bolus doses of furosemide. However, there does not appear to be a significant difference in total urine output or change in serum electrolyte levels when furosemide is administered as a continuous infusion compared with intermittent bolus doses. CONCLUSIONS: A continuous infusion of furosemide is an effective and safe method of diuresis in patients undergoing cardiac surgery.