Determinants of Vancomycin Trough Concentration in Patients Receiving Continuous Veno-Venous Hemodialysis.

BACKGROUND: Vancomycin pharmacokinetics are altered in the critically ill and are further distorted by renal replacement therapy. Limited literature is available evaluating vancomycin dosing in continuous veno-venous hemodialysis (CVVHD). OBJECTIVE: The goal of this analysis was to identify factors that affect vancomycin trough concentration in patients on CVVHD and to determine an appropriate dosing strategy. METHODS: This was a single-center, retrospective cohort study of adult inpatients admitted to the Cleveland Clinic from May 2016-December 2017. Patients in the intensive care unit who received ≥ 2 doses of vancomycin during CVVHD were included. Patients with interruptions of CVVHD inappropriately timed troughs, a change in dialysate rate, and those who received different vancomycin dosages were excluded. Multivariable linear regression including age, sex, weight, Sequential Organ Failure Assessment score, albumin, 24-hour urine output (UOP), dialysate rate, filter type, and vancomycin dose was run to determine predictors of vancomycin concentration. RESULTS: A total of 160 patients were included. The median vancomycin dose was 12.6 mg/kg with a trough of 24.6 mcg/mL. Weight, 24-hour UOP, vancomycin dose (mg/kg), and dialysate rate (mL/kg/h) were all determined to be independent predictors of vancomycin trough level. Patients who received <10 mg/kg doses of vancomycin (N=18) achieved a median trough of 21.5 mcg/mL, with 83% being therapuetic. In patients who received >10 mg/kg (N=142), the median trough was 25.5 mcg/mL, with 47% being therapeutic. CONCLUSION AND RELEVANCE: Vancomycin dose, dialysate rate, UOP, and weight are independently associated with vancomycin trough concentration. In CVVHD patients, vancomycin dosed at 10 mg/kg every 24 hours may be an appropriate recommendation.

Anticoagulation with temporary Impella device in patients with heparin-induced thrombocytopenia: A case series.

The Impella device is a percutaneous ventricular assist devices that requires administration of heparin via a continuous purge solution. Patients on Impella device support may experience hemolysis with accompanying thrombocytopenia generating suspicion for heparin-induced thrombocytopenia (HIT). However, data and recommendations for use of non-heparin anticoagulants with Impella device are lacking. Therefore, we performed a retrospective cohort analysis of patients requiring bivalirudin during Impella device support to describe the safety and efficacy of bivalirudin as an alternative anticoagulant during Impella device support. Nine patients were included in the evaluation which analyzed Impella device purge flow and purge pressure along with bivalirudin dosing requirements, incidence of thrombosis, and incidence of pump failure. All patients had a positive platelet factor-4 IgG ELISA test, and the serotonin release assay was positive in four patients. After initiation of bivalirudin, the median (15th, 85th percentile) nadir purge flow decreased by 76% (5%, 88%) and the median (15th, 85th percentile) peak purge pressure increased by 86% (21%, 143%). At the time of bivalirudin discontinuation, the median final purge flow and pressure were 2.4 mL/h (74% decrease) and 969 mmHg (89% increase), respectively. Zero patients experienced catastrophic pump failure. Adding low concentration bivalirudin to the purge solution along with systemic bivalirudin may be a reasonable approach.

Evaluation of a hospital-wide vancomycin-dosing nomogram in patients with continuous-flow left ventricular assist devices.

INTRODUCTION: Hemodynamic derangements due to heart failure are associated with alterations in pharmacokinetics. Although use of mechanical circulatory support mitigates such derangements, little evidence is available regarding pharmacokinetics in patients with LVADs. A previous pharmacokinetic analysis of vancomycin among patients with LVADs observed a reduced volume of distribution and clearance compared with estimates based on population kinetics. METHODS: A total of 28 adult patients with LVADs hospitalized between January 2014 and May 2018 who received vancomycin through a pharmacist dosing consult were included. Internal medicine patients without heart failure receiving vancomycin were enrolled in a 2:1 fashion to make a control group. Exclusion criteria were unstable renal function, ESRD, acute decompensation, cardiac surgery within the preceding 5 days, or weight >110 kg. RESULTS: No difference was observed in the proportion achieving goal trough (64% of LVAD patients vs 71% control patients, p = 0.50). However, mean trough was significantly higher among LVAD patients (23.4 mg/L vs 17.7 mg/L, p = 0.017). Furthermore, there was a significant difference in the distribution of trough levels (p = 0.025) with LVAD patients being more likely to attain levels >25 mg/L (32% vs 14%) and less likely to have troughs <10 mg/L (4% vs 14%). A numerically greater number of LVAD patients experienced nephrotoxicity but this did not reach statistical significance (32% vs 18%, p = 0.14). CONCLUSION: The use of vancomycin in LVAD patients may result in higher trough levels when compared to internal medicine patients. Increased monitoring or conservative dosing may be warranted to improve safety and efficacy.

Prescribing Practices of Valproic Acid for Agitation and Delirium in the Intensive Care Unit.

BACKGROUND: Analgesics, sedatives, and antipsychotics are commonly prescribed for agitation and delirium in the intensive care unit (ICU), but their use is limited by adverse effects and lack of efficacy. Valproic acid is an alternative treatment option. OBJECTIVE: The primary objective of this study was to describe valproic acid prescribing in our institution's ICUs when used for agitation or delirium. Measures of effectiveness and safety were also assessed. METHODS: This was a single-center, retrospective, institutional review board-approved cohort study of adult inpatients admitted to the ICU between January 2018 and August 2018. Patients who received valproic acid for the treatment of agitation or delirium for ≥24 hours were included. Prescribing practices were evaluated for dose, frequency, and route of administration. Effectiveness was assessed via agitation and delirium assessment tools and quantity of adjunctive agents used. RESULTS: A total of 80 patients were included, with 35 receiving valproic acid alone and 45 in conjunction with antipsychotics. The most common valproic acid regimen was 250 mg orally 3 times daily. Delirium resolution occurred in 55% of patients: 24 in the valproic acid monotherapy group and 20 in the valproic acid plus antipsychotic group (69% vs 44%; P = 0.03). The incidence of delirium decreased from valproic acid day 0 to day 3 (93% vs 68%; P < 0.01), with no change in agitation (64% vs 63%; P = 0.28). CONCLUSION AND RELEVANCE: Valproic acid is frequently prescribed in agitated, delirious patients at our institution and may have a role in the management of ICU delirium.

Effectiveness, Safety, and Economic Comparison of Inhaled Epoprostenol Brands, Flolan and Veletri, in Acute Respiratory Distress Syndrome.

Background: No previous studies exist examining 2 inhaled epoprostenol formulations in an acute respiratory distress syndrome (ARDS) patient population. Objective: The study aim was to evaluate a formulary conversion from inhaled Flolan to Veletri to determine the impact on effectiveness, safety, and cost in patients with ARDS. Methods: This was a single-center, retrospective, matched cohort observational study at a tertiary care academic medical center. Patients included were mechanically ventilated, adult patients with ARDS receiving inhaled Flolan or Veletri for ≥1 hour in the intensive care unit. Results: A total of 132 patients were included in the matched cohort. There was no difference detected in change in partial pressure of arterial O2/fraction of inspired O2 (PaO2/FiO2) ratio after 1 hour of therapy between the inhaled Flolan and Veletri groups (27.2 ± 46.2 vs 30 ± 68 mm Hg, P = 0.78). Significant differences in secondary outcomes included incidence of hypotension (83% vs 95.5%, P = 0.04) and thrombocytopenia (9.1% vs 29.5%, P < 0.01) in the inhaled Flolan and Veletri groups, respectively, with no difference in cost per duration of therapy (P = 0.29). Conclusions and Relevance: There was no difference in the change in PaO2/FiO2 ratio after 1 hour of therapy between inhaled Flolan and Veletri in an ARDS patient population. The formulary conversion from inhaled Flolan to Veletri was likely justified.

Prothrombin Complex Concentrates for Warfarin Reversal Before Heart Transplantation.

BACKGROUND: Anticoagulation therapy with warfarin is common before heart transplantation and complicates perioperative management. METHODS: This single-center, noninterventional, retrospective cohort study evaluated heart transplant patients before and after institution of a prothrombin complex concentrates-based preoperative warfarin reversal protocol for heart transplantation. Patients with international normalized ratio (INR) greater than 1.5 who received prothrombin complex concentrate (PCC) before heart transplant surgery were compared with a control group before implementation of a PCC protocol. Coprimary endpoints were utilization of individual blood products. Secondary endpoints included in-hospital mortality, reoperation for bleeding, delayed sternal closure, thromboembolic events, duration of chest tube use, time to extubation, intensive care unit length of stay, and hospital length of stay. RESULTS: The study included 106 consecutive heart transplant patients (PCC cohort = 57, historical control cohort = 49). There was a significant reduction in fresh frozen plasma utilization in the PCC cohort (6 units versus 8 units, p = 0.002). Rates of packed red blood cells and platelet transfusion were similar between groups. There was a significant increase in the incidence of cryoprecipitate utilization in the PCC cohort, which can likely be attributed to decreased antifibrinolytic utilization. There were no differences in secondary endpoints between groups, including thromboembolic events. CONCLUSIONS: This study found that a PCC-based warfarin reversal protocol significantly reduced fresh frozen plasma utilization compared with historical controls without affecting other clinically important surgical outcomes. These data suggest that PCC is a valuable tool for INR normalization that could safely reduce fresh frozen plasma administration and offer a practical alternative to traditional approaches for INR reversal before heart transplantation.

Acute kidney injury in postoperative shock: is hyperoncotic albumin administration an unrecognized resuscitation risk factor?

BACKGROUND: The use of hyperoncotic albumin (HA) for shock resuscitation is controversial given concerns about its cost, effectiveness, and potential for nephrotoxicity. We evaluated the association between early exposure to hyperoncotic albumin (within the first 48 h of onset of shock) and acute organ dysfunction in post-surgical patients with shock. METHODS: This retrospective, cohort study included 11,512 perioperative patients with shock from 2009 to 2012. Shock was defined as requirement for vasopressors to maintain adequate mean arterial pressure and/or elevated lactate (> 2.2 mmol/L). Subsets of 3600 were selected after propensity score and exact matching on demographics, comorbidities, and treatment variables (> 30). There was a preponderance of cardiac surgery patients. Proportional odds logistic regression, multivariable logistic regression or Cox proportional hazard regression models measured association between hyperoncotic albumin and acute kidney injury (AKI), hepatic injury, ICU days, and mortality. RESULTS: Hyperoncotic albumin-exposed patients showed greater risk of acute kidney injury compared to controls (OR 1.10, 95% CI 1.04, 1.17. P = 0.002), after adjusting for imbalanced co-variables. Within matched patients, 20.3%, 2.9%, and 4.4% of HA patients experienced KDIGO stages 1-3 AKI, versus 19.6%, 2.5%, and 3.0% of controls. There was no difference in hepatic injury (OR 1.16; 98.3% CI 0.85, 1.58); ICU days, (HR 1.05; 98.3% CI 1.00, 1.11); or mortality, (OR 0.88; 98.3% CI 0.64, 1.20). CONCLUSIONS: Early exposure to hyperoncotic albumin in postoperative shock appeared to be associated with acute kidney injury. There did not appear to be any association with hepatic injury, mortality, or ICU days. The clinical and economic implications of this finding warrant further investigation.

Evaluation of Prophylactic Antibiotic Use for Delayed Sternal Closure After Cardiothoracic Operation.

BACKGROUND: Clinical practice guidelines provide recommendations for surgical prophylaxis in patients undergoing cardiothoracic procedures. However, currently no recommendations guide the management of antibiotic prophylaxis in patients who require delayed sternal closure after cardiothoracic operation. METHODS: This is a single-center, retrospective analysis. Data were extracted from The Society of Thoracic Surgery database and electronic medical record from July 2011 through January 2016. Patients included are adults (≥18 years old) after cardiothoracic operation with delayed sternal closure. RESULTS: A total of 167 patients were included for analysis. The majority of patients (131, 78.4%) were continued on routine antibiotics and 36 patients (21.6%) were switched to broad-spectrum antibiotics for prophylaxis. Of patients on routine antibiotic prophylaxis, 6 (4.6%) experienced a sternal surgical site infection, whereas 3 patients (8.3%) switched to broad-spectrum agents before chest closure experienced a sternal surgical site infection (p = 0.407). Eleven patients (6.6%) received an abbreviated duration of antibiotics, 52 patients (31.1%) were continued on antibiotics until the time of sternal closure, and 104 patients (62.3%) were continued on antibiotics past the time of sternal closure. The incidence of infection based on duration of prophylactic antibiotic was 0, 1 (1.9%), and 8 (7.7%), respectively (p = 0.352). CONCLUSIONS: Substantial variation was found in the duration and selection of antibiotic prophylaxis for patients with delayed sternal closure after cardiothoracic operation. Broad-spectrum antimicrobial agents and extended durations of antibiotic prophylaxis were not associated with benefits in the incidence of sternal wound infection and may increase the risk of adverse effects.

Low-dose 3-factor prothrombin complex concentrate for warfarin reversal prior to heart transplant.

BACKGROUND: Anticoagulation with warfarin is common in patients presenting for heart transplant. Prior to surgery, anticoagulation reversal is necessary to avoid significant intraoperative and perioperative bleeding complications. Commonly, warfarin reversal is achieved with vitamin K and fresh frozen plasma (FFP); however, these therapies have significant limitations. An alternative to FFP for reversal exists with prothrombin complex concentrate (PCC). A warfarin reversal protocol prior to heart transplant was implemented using low-dose PCC at our institution. OBJECTIVE: To assess blood product use, effectiveness, and safety post-low-dose PCC administration in patients needing warfarin reversal prior to heart transplant compared with historical controls. METHODS: This was a single-center, retrospective cohort study. The PCC cohort included patients undergoing heart transplant presenting with an international normalized ratio ≥1.5 on warfarin therapy and who received at least 1 dose of PCC. Blood product use was measured from postoperative day 0 to 2. RESULTS: The PCC and historical control cohorts included 16 and 50 patients, respectively. There was a significant reduction in the use of FFP (4 vs 8 units, P = 0.0239) in the PCC cohort compared with the historical control cohort. No differences were identified in the use of other blood products as well as other secondary efficacy or safety end points. CONCLUSIONS: Use of PCC, per the reversal protocol, prior to heart transplant reduced FFP use and showed a non-statistically significant trend toward reductions in the use of other blood products in the intraoperative and perioperative setting, with no difference identified in thrombotic or embolic complications compared with historical controls.

Safe use of hemodialysis for dabigatran removal before cardiac surgery.

OBJECTIVE: To describe a case in which hemodialysis was performed before cardiac transplantation in an attempt to reverse the effects of dabigatran and reduce the risk of bleeding associated with surgery. CASE SUMMARY: A 59-year-old female with heart failure and atrial fibrillation was admitted for orthotropic heart transplant. She had been stable at home with continuous milrinone therapy 0.25 µg/kg/min, amiodarone 200 mg twice daily, and dabigatran 150 mg twice daily for stroke prevention secondary to atrial fibrillation. Upon notification of organ availability, the patient was admitted to the hospital for transplant surgery, with her last dose of dabigatran taken approximately 36 hours before admission. Coagulation studies indicated normal activated partial thromboplastin time, slightly elevated international normalized ratio of 1.2, and elevated thrombin time (TT) of 90.6 seconds (upper limit of normal 19.9 seconds). A hemodialysis catheter was emergently placed and dialysis was initiated. One hour after initiation, TT decreased to 65.5 seconds. After 2.5 hours of dialysis, TT further decreased to 60.2 seconds; at that time, the patient underwent transplantation with no abnormal bleeding during or following surgery. DISCUSSION: Minimal data exist on techniques to reverse the effects of dabigatran in cases of bleeding or emergent surgery. This case examines the efficacy of hemodialysis to decrease dabigatran's effect on clotting assays prior to surgery to reduce the risk of bleeding. In this case, a TT of 60.2 seconds with recent dabigatran administration did not result in abnormal bleeding associated with cardiac surgery. CONCLUSIONS: To our knowledge, this case report represents the first published data on the effects of hemodialysis on dabigatran removal and reversal of anticoagulation associated with dabigatran before surgery. The routine use of preoperative hemodialysis in patients on dabigatran is not recommended; however, the potential efficacy in such circumstances is supported by the successful results in this case.