Comparison of 2 different inhaled epoprostenol dosing strategies for acute respiratory distress syndrome in critically ill adults: Weight-based vs fixed-dose administration.

PURPOSE: Inhaled epoprostenol (iEPO) is a viable, temporizing option for acute respiratory distress syndrome (ARDS), although the optimal iEPO dosing strategy remains inconclusive. The purpose of this study was to evaluate oxygenation and ventilation parameters in a comparison of weight-based and fixed-dose iEPO in adult patients with moderate-to-severe ARDS. METHODS: A retrospective cohort study was conducted at 2 academic medical centers in adult intensive care unit (ICU) patients administered either fixed-dose or weight-based iEPO for moderate-to-severe ARDS. The primary endpoint was the highest recorded change in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) within 4 hours of baseline. Secondary analyses compared responder rates within 4 hours of initiation, oxygenation and ventilation parameters, in-hospital mortality rates, mechanical ventilation duration, length of stay (ICU and hospital), and tracheostomy rates between the study groups. RESULTS: A total of 294 patients were included, n = 194 with 100 (34.0%) and 194 (66.0%) in the weight-based and fixed-dose iEPO groups, respectively. The mean (SD) change in the highest recorded PaO2/FiO2 value from baseline up to 4 hours after initiation in the fixed-dose and weight-based groups was 81.1 (106.0) and 41.0 (72.5) mm Hg, respectively (P = 0.0015). The responder rate at 4 hours after iEPO initiation was significantly higher in the fixed-dose group (69.9%) than in the weight-based group (30.1%) (P = 0.02). The only predictor of response was fixed-dose administration (odds ratio, 3.28; 95% confidence interval, 1.6-6.7; P = 0.0012). Clinical outcomes were comparable between the groups. CONCLUSION: Fixed-dose iEPO was associated with significantly higher response rates then weight-based iEPO during the first 4 hours of therapy. Fixed-dose iEPO is a more convenient strategy than weight-based approaches.

Incidence of Hypotension Associated With Two Different Vasopressin Discontinuation Strategies in the Recovery Phase of Septic Shock.

Introduction: Safe and effective vasopressor withdrawal strategies during the recovery phase of septic shock lack consensus and are not addressed in clinical practice guidelines. The purpose of this study was to compare the incidence of clinically relevant hypotension associated with different vasopressin (AVP) discontinuation strategies. Methods: This was a single-center, retrospective, cohort study, conducted at a university medical center over a three-year period. Adult patients ≥18 years with septic shock were included in the study. Patients were stratified into two groups; patients incrementally weaned from AVP and patients in which AVP was abruptly discontinued. The primary endpoint was to compare the incidence of clinically relevant hypotension between study groups up to 24 hours following discontinuation. Secondary analyses included the incidence of any hypotensive event up to 24 hours after AVP cessation, intensive care unit and hospital length of stay, and in-hospital mortality. Results: A total of 74 patients (n = 46 AVP wean and n = 28 AVP no-wean) met inclusion criteria and were included in the study. The primary outcome was not statistically different between groups. Clinically relevant hypotension occurred in 24 patients (52.3%) and 16 patients (57.1%) in the AVP wean and AVP no-wean groups, respectively (P = .68). There were no significant differences in any secondary clinical outcome between the two study groups. Conclusion: No differences were found in the incidence of clinically relevant hypotension, length of stay, or mortality between AVP weaning and no-weaning discontinuation strategies. These findings suggest incremental weaning and abrupt withdrawal of AVP are both acceptable discontinuation strategies.

Vancomycin With Concomitant Piperacillin/Tazobactam vs. Cefepime or Meropenem Associated Acute Kidney Injury in General Ward Patients: A Multicenter Propensity Score-Matched Study.

Background: Concurrent administration of vancomycin and piperacillin/tazobactam (VAN+PTZ) may increase the risk of acute kidney injury (AKI) in hospitalized patients. Comprehensive characterization of VAN+PTZ associated AKI and recovery patterns remains lacking in previous reports. Objective: To compare the incidence of AKI associated with VAN+PTZ compared to either cefepime (CEF) or meropenem (MER) with VAN in adult general ward patients. Methods: A multicenter, retrospective, propensity score cohort study was conducted in non-critically ill adult patients. Included patients were concurrently administered VAN+PTZ or VAN+CEF/MER. Patients developing AKI ≤48 hours following combination therapy were excluded. The primary endpoint was to compare the incidence of AKI between study groups. Multivariable Cox regression modeling in predicting AKI was also conducted. Results: A total of 3199 patients met inclusion criteria and were evaluated. The incidence of AKI in VAN+PTZ and VAN+CEF/MER groups were 16.4% and 8.7%, respectively (P < .001). The onset to AKI was 1.8 days earlier with VAN+PTZ compared to VAN+CEF/MER (P < .001). Multivariable prediction model showed concomitant VAN+PTZ was identified as an independent risk factor of developing AKI (HR 2.34, 1.82-3.01, P < .001). The VAN+PTZ group experienced significantly higher rates of severe AKI (stage II or III) compared to the VAN+CEF/MER group (P = .002). No differences in the AKI recovery patterns were found between study groups. Conclusions: Concomitant VAN+PTZ in adult general ward patients was independently associated with an increased risk of AKI overall. More severe AKI was also associated with VAN+PTZ.

Vancomycin with concomitant piperacillin/tazobactam vs. cefepime or meropenem associated acute kidney injury in the critically ill: A multicenter propensity score-matched study.

PURPOSE: The risk of acute kidney injury (AKI) associated with concomitant vancomycin and piperacillin/tazobactam in the intensive care unit (ICU) remains controversial. The aim of this study was to compare the AKI incidence associated with concomitant vancomycin and piperacillin/tazobactam compared to either cefepime or meropenem with vancomycin in the ICU. MATERIALS AND METHODS: A multicenter, retrospective, propensity score-matched cohort study was conducted in adult ICU patients administered vancomycin in combination with either piperacillin/tazobactam, cefepime, or meropenem were included. Patients developing AKI ≤48 h following combination therapy initiation were excluded. The primary endpoint was to compare the incidence of AKI associated with concomitant antimicrobial therapy. Multivariable Cox regression modeling in predicting AKI was also conducted. RESULTS: A total of 1044 patients were matched. The AKI incidence in vancomycin- piperacillin/tazobactam and vancomycin-cefepime/meropenem groups were 21.9% and 16.8%, respectively (p = 0.068). Multivariable prediction models showed concomitant vancomycin-piperacillin/tazobactam was an independent risk factor of AKI using serum creatinine only (HR 1.52, 1.10-2.10, p = 0.011) and serum creatinine with urine output-based KDIGO criteria (HR 1.77, 1.18-2.67, p = 0.006). No significant differences between groups were observed for AKI recovery patterns or mortality. CONCLUSION: Concomitant vancomycin and piperacillin/tazobactam administration in adult ICU patients was independently associated with an increased risk of AKI.

Comparison of Fixed-Dose Inhaled Epoprostenol and Inhaled Nitric Oxide for Acute Respiratory Distress Syndrome in Critically Ill Adults.

PURPOSE: Several reports have demonstrated similar effects on oxygenation between inhaled epoprostenol (iEPO) compared to inhaled nitric oxide (iNO) for acute respiratory distress syndrome (ARDS). Previous studies directly comparing oxygenation and clinical outcomes between iEPO and iNO exclusively in an adult ARDS patient population utilized a weight-based dosing strategy. The purpose of this study was to compare the clinical and economic impact between iNO and fixed-dosed iEPO for ARDS in adult intensive care unit (ICU) patients. METHODS: This retrospective cohort study was conducted at a major academic medical center between January 1, 2014, and October 31, 2018. Patients ≥18 years of age with moderate-to-severe ARDS were included. The primary end point was to compare the mean change in partial arterial oxygen pressure to fraction of inspired oxygen (Pao 2: Fio 2) at 4 hours from baseline between iEPO and iNO. Other secondary aims were total acquisition drug costs, in-hospital mortality, ICU and hospital length of stay, and duration of mechanical ventilation. RESULTS: A total of 239 patients were included with 139 (58.2%) and 100 (41.8%) in the iEPO and iNO groups, respectively. The mean change in Pao 2: Fio 2 at 4 hours from baseline in the iEPO and iNO groups were 31.4 ± 54.6 and 32.4 ± 42.7 mm Hg, respectively (P = .88). The responder rate at 4 hours was similar between iEPO and iNO groups (64.7% and 66.0%, respectively, P = .84). Clinical outcomes including mortality, overall hospital and ICU length of stay, and mechanical ventilation duration were similar between iEPO and iNO groups. Estimated annual cost-savings realized with iEPO was USD1 074 433. CONCLUSION: Fixed-dose iEPO was comparable to iNO in patients with moderate-to-severe ARDS for oxygenation and ventilation parameters as well as clinical outcomes. Significant cost-savings were realized with iEPO use.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Utilization and Associated Costs in General Ward Patients.

BACKGROUND: Inappropriate albumin use in clinical practice remains problematic. Health-systems face continued challenges in promoting cost-appropriate use. OBJECTIVE: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin use in general ward patients. METHODS: A retrospective cohort study evaluated all adult (≥18 years) general ward patients administered ≥1 dose of albumin at a university medical center over a 2-year period. The intervention consisted of a clinical pharmacist-led strategy intervening on all albumin orders not in accordance with institutional guidelines. The primary end point was to compare inappropriate albumin utilization before and after implementation. Secondary end points compared the rates of inappropriate albumin use adjusted for hospital admission and patient-days as well as associated costs by appropriateness between study periods. RESULTS: A total of 4420 patients were screened, with 1971 (44.6%) patients meeting inclusion criteria. The clinical pharmacist strategy significantly reduced inappropriate albumin (grams) utilization by 86.0% (P < 0.001). A 7-fold reduction of inappropriate albumin administered adjusted for the number of patient admissions was found from the preimplementation period following clinical pharmacist intervention strategy implementation (415.3 ± 83.2 vs 57.5 ± 34.2 g per 100 general ward hospital admissions, respectively; P < 0.001). Also, the adjusted inappropriate albumin rate was reduced from 62.2 ± 12.3 to 8.6 ± 5.2 g per 100 patient-days in the preimplementation and postimplementation periods, respectively (P < 0.001). Annual cost savings were $421 455 overall, with $341 930 resulting from mitigation of inappropriate use. CONCLUSION AND RELEVANCE: Clinical pharmacist-led interventions significantly reduced inappropriate albumin use and costs in hospitalized patients.

Hyperoncotic Albumin Reduces Net Fluid Loss Associated With Hemodialysis.

Purpose: The purpose of this study was to compare the volume of fluid removal associated with and without 25% albumin administration in conjunction with hemodialysis. Methods: This retrospective, cohort study was conducted at a large academic medical center over a 6-month period to compare the net fluid amount removed (mL) during hemodialysis between patients administered 25% albumin and those without albumin. Results: A total of 238 patients consisting of 973 unique hemodialysis sessions were evaluated. The mean overall net fluid removed by hemodialysis in the 25% albumin and no albumin groups were 1242 mL and 1899 mL, P < .001, respectively. No albumin group had significantly higher mean fluid losses compared with 25% albumin for a total dose of either 25 g (P = .001) or 50 g (P = .001). There were no significant differences in mean fluid loss between the no albumin group and patients receiving 75 g or 100 g of albumin. Post hoc analysis failed to demonstrate a dose-dependent response in those patients receiving 25% albumin and no albumin. Conclusion: Hyperoncotic albumin administered during hemodialysis sessions reduced net fluid loss associated with hemodialysis. The findings of this study do not support the routine use of 25% albumin to improve fluid removal during dialysis.

Adverse Hemodynamic Events Associated With Concomitant Dexmedetomidine and Propofol for Sedation in Mechanically Ventilated ICU Patients.

PURPOSE: Nonbenzodiazepines are preferred for continuous sedation in mechanically ventilated intensive care unit (ICU) patients. Although dexmedetomidine and propofol have blood pressure lowering properties, limited data exist about the hemodynamic effects of concomitant administration. The purpose of this study was to compare the adverse hemodynamic event rate with concomitant dexmedetomidine and propofol compared to either agent alone in mechanically ventilated ICU patients. METHODS: This retrospective cohort study was conducted at a university medical center. Adult ICU patients (≥18 years) admitted between October 20, 2015, and January 25, 2018, and administered concurrent dexmedetomidine and propofol or either agent alone for ≥24 hours were included. Mean arterial pressure, heart rate, and sedative dosing requirements were assessed from initiation to 72 hours after initiation. The primary end point was comparing the incidence of hypotension among study groups. Secondary aims compared the incidence of tachycardia and bradycardia as well as clinical outcomes. RESULTS: Overall, 276 patients were included among combination (n = 93), dexmedetomidine (n = 91), and propofol (n = 92) groups. The incidence of hypotension was significantly higher in patients administered concomitant dexmedetomidine and propofol (62.4%) compared to those administered dexmedetomidine (23.1%) or propofol (23.9%) alone (P < .0001). Adjunctive dexmedetomidine with propofol was also associated with higher rates of clinically relevant hypotension requiring treatment (P = .048). The tachycardia incidence in the concomitant, dexmedetomidine, and propofol groups were 30.1%, 28.6%, and 14.1%, respectively (P = 02). Only 1.4% (n = 4) of all study patients developed bradycardia. Concomitant therapy was an independent risk factor of hypotension compared to either dexmedetomidine (odds ratio [OR]: 6.7, 95% confidence interval [CI]: 2.61-17.3, P < .0001) or propofol (OR: 2.89, 95% CI: 1.24-6.74, P = .014) monotherapy. Patients experiencing hypotension were associated with worse clinical outcomes. CONCLUSION: Concomitant dexmedetomidine and propofol use in mechanically ventilated patients increased the risk of hypotensive events. Adjunctive dexmedetomidine with propofol administration in the critically ill warrants caution.

Clinical Pharmacist-Led Impact on Inappropriate Albumin Use and Costs in the Critically Ill.

Background:Optimal albumin use in the intensive care unit (ICU) remains challenging with inappropriate use approaching 50%. No published reports have described clinical pharmacist impact aimed at mitigating inappropriate albumin use in the ICU. Objective: To evaluate the clinical and economic impact of a clinical pharmacist-led intervention strategy targeting inappropriate albumin in the ICU. Methods: A retrospective cohort study evaluated all adult (≥18 years) ICU patients administered albumin at an academic medical center over a 2-year period. Institutional guidelines were developed with clinical pharmacists targeting inappropriate albumin use. The primary end point was to compare inappropriate use of albumin administered before and after pharmacist intervention implementation. Secondary analyses compared the overall albumin use between study periods. In-hospital mortality, length of stay, and albumin-related costs between study periods were also compared. Results: A total of 4419 patients were identified, with 2448 (55.4%) critically ill patients included. The pharmacist-led strategy resulted in a 50.9% reduction of inappropriate albumin use (P < 0.001). The rate of inappropriate albumin use was 44.3 ± 10.5 and 5.5 ± 2.9 g per patient-day in the preimplementation and postimplementation periods, respectively (P < 0.001). Costs associated with overall and inappropriate albumin use in the ICU decreased by 34.8% and 87.1%, respectively. Total annual cost-savings was $355 393 in the ICUs. No differences in clinical outcomes were found. Conclusion and Relevance: Clinical pharmacist-led interventions reduced overall and inappropriate albumin use and costs without negatively affecting clinical outcomes.