Clinical Outcomes Associated With Diltiazem Use in Heart Failure With Reduced Ejection Fraction After Implementation of a Clinical Support System.

BACKGROUND: Despite atrial fibrillation guideline recommendations, many patients with heart failure with reduced ejection fraction (EF) continue to receive IV diltiazem for acute rate control. OBJECTIVE: Our institution recently implemented a clinical decision support system (CDSS)-based tool that recommends against the use of diltiazem in patients with an EF ≤ 40%. The objective of this study was to evaluate outcomes of adherence to the aforementioned CDSS-based tool. METHODS: This multi-hospital, retrospective study assessed patients who triggered the CDSS alert and compared those who did and did not discontinue diltiazem. The primary outcome was the occurrence of clinical deterioration. The primary endpoint was compared utilizing a Fisher's Exact Test, and a multivariate logistic regression model was developed to confirm the results of the primary analysis. RESULTS: A total of 246 patients were included in this study with 146 patients in the nonadherent group (received diltiazem) and 100 patients in the adherent group (did not receive diltiazem). There was a higher proportion of patients experiencing clinical deterioration in the alert nonadherence group (33% vs 21%, P = 0.044), including increased utilization of inotropes and vasopressors, and higher rate of transfer to ICU. CONCLUSION AND RELEVANCE: In patients with heart failure with reduced EF, diltiazem use after nonadherence to a CDSS alert resulted in an increased risk of clinical deterioration. This study highlights the need for improved provider adherence to diltiazem clinical decision support systems.

Basiliximab induction versus no induction in adult heart transplantation.

BACKGROUND: Induction immunosuppression in heart transplant recipients varies greatly by center. Basiliximab (BAS) is the most commonly used induction immunosuppressant but has not been shown to reduce rejection or improve survival. The objective of this retrospective study was to compare rejection, infection, and mortality within the first 12 months following heart transplant in patients who received BAS or no induction. METHODS: This was a retrospective cohort study of adult heart transplant recipients given BAS or no induction from January 1, 2017 to May 31, 2021. The primary endpoint was incidence of treated acute cellular rejection (ACR) at 12-months post-transplant. Secondary endpoints included ACR at 90 days post-transplant, incidence of antibody-mediated rejection (AMR) at 90 days and 1 year, incidence of infection, and all-cause mortality at 1 year. RESULTS: A total of 108 patients received BAS, and 26 patients received no induction within the specified timeframe. There was a lower incidence of ACR within the first year in the BAS group compared to the no induction group (27.7 vs. 68.2%, p < .002). BAS was independently associated with a lower probability of having a rejection event during the first 12-months post-transplant (hazard ratio (HR) .285, 95% confidence interval [CI] .142-.571, p < .001). There was no difference in the rate of infection and in mortality after hospital discharge at 1-year post-transplant (6% vs. 0%, p = .20). CONCLUSION: BAS appears to be associated with greater freedom from rejection without an increase in infections. BAS may be a preferred to a no induction strategy in patients undergoing heart transplantation.

Evaluation of Newly Integrated Bivalirudin Titration Protocol in Patients With Mechanical Circulatory Support.

BACKGROUND: Patients with cardiogenic shock or end-stage heart failure can be maintained on mechanical circulatory support (MCS) devices. Once a patient undergoes placement of a device, obtaining and maintaining therapeutic anticoagulation is vital. Guidelines recommend the use of institutional protocols to assist in dosing and titration of anticoagulants. OBJECTIVE: The purpose of this study was to characterize the use of bivalirudin before and after the implementation of a standardized titration protocol in patients with MCS. METHODS: A retrospective review of patients who received bivalirudin for MCS (VA ECMO [veno-arterial extracorporeal membrane oxygenation], Impella, or LVAD [left ventricular assist device]) before and after the implementation of the titration protocol into the electronic health record (EHR) was conducted. The primary outcome was to compare the proportion of therapeutic activated partial thromboplastin time (aPTT). Secondary outcomes included number of subtherapeutic and supratherapeutic aPTTs, incidence of bleeding and clotting events, bivalirudin titrations per day, and percentage of patients with therapeutic aPTT level. RESULTS: A total of 100 patients were included (precohort = 67; postcohort = 33). The proportion of therapeutic aPTTs was significantly higher in the postcohort than that in the precohort (62% vs 48%; P < 0.001). The postcohort had 0% of patients failing to achieve therapeutic aPTT levels. The number of titrations per day was significantly lower in the postcohort, with 1.20 titrations per day versus 1.93 in the precohort (P < 0.001). CONCLUSIONS: Implementation of the bivalirudin titration nomograms within the EHR significantly increased the number of therapeutic aPTTs, reduced the number of patients who never achieved a therapeutic aPTT, and reduced the required number of titrations per day.

Outcomes of systemic bivalirudin and sodium bicarbonate purge solution for Impella 5.5.

BACKGROUND: Impella 5.5 (Abiomed; Danvers, MA) (IMP5) is a commonly used, surgically implanted, tMCS device that requires systemic anticoagulation and purge solution to avoid pump failure. To avoid heparin-induced thrombocytopenia (HIT) from unfractionated heparin (UFH) use, our program has explored the utility of bivalirudin (BIV) for systemic anticoagulation and sodium bicarbonate-dextrose purge solution (SBPS) in IMP5.5. METHODS: This single center, retrospective study included 34 patients supported on IMP5.5 with BIV based AC and SBPS between December 1st 2020 to December 1st 2021.The efficacy and safety end points were incidence of development of HIT, Tissue Plasminogen Activator (tPA) use for suspected pump thrombosis, stroke, and device failure as well as clinically significant bleeding. RESULTS: The median duration of IMP5.5 support was 9.8 days (IQR: 6-15). Most patients were bridged to HTX (58%) followed by recovery (27%) and LVAD implantation (15%). Patients were therapeutic on bivalirudin for 64% of their IMP5.5 support. One patient (2.9%) suffered from ischemic stroke and 26.5% (9) patients developed clinically significant bleeding. tPA was administered to 7(21%) patients. One patient in the entire cohort developed HIT. CONCLUSIONS: Our experience supports the use of systemic BIV and SBPS as a method to avoid heparin exposure in a patient population predisposed to the development of HIT.

Risk factors of bronchial dehiscence after primary lung transplantation.

BACKGROUND: Although the incidence of bronchial dehiscence following lung transplantation has decreased significantly due to improvements in perioperative managements and surgical techniques, it remains a devastating postoperative complication associated with high morbidity and mortality. METHODS: We retrospectively reviewed 811 lung transplantation performed at our institution between January 2011 and December 2020. Bronchial dehiscence was confirmed with flexible bronchoscopy, computed tomography (CT) scan, or clinical findings grade using International Society for Heart and Lung Transplantation recommendations. RESULTS: Bronchial dehiscence was diagnosed in 38 patients (4.7%). The overall survival rates of the patients with bronchial dehiscence were significantly worse than those of the patients without bronchial dehiscence (p = .003). Multivariate analysis identified use of our basiliximab induction protocol (odds ratio = 3.03, p = .008) as an independent predictive factor of postoperative airway dehiscence in our multivariable model, along with total ventilator duration (odds ratio = 1.02, p = .002). CONCLUSIONS: Based on our analysis, patients that underwent our basiliximab induction protocol for lung transplantation experienced a higher rate of postoperative bronchial dehiscence when compared with patients who receive alemtuzumab induction. We believe this may be associated with a higher steroid exposure in this population. Additional studies are necessary to further characterize the relationship between different induction protocols and bronchial dehiscence following transplantation.

Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients.

BACKGROUND: Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. METHODS: A single-center, retrospective study of patients who received isavuconazole (September 2015-February 2018) or voriconazole (September 2013-September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. RESULTS: Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). CONCLUSIONS: Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

Comparison of Anticoagulation Strategies in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: Heparin Versus Bivalirudin.

OBJECTIVES: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective cohort study. SETTING: Single-center, cardiothoracic ICU. PATIENTS: Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. INTERNVENTIONS: IV bivalirudin or IV unfractionated heparin. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. CONCLUSIONS: Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.

Dabigatran reversal with idarucizumab prior to lung transplantation.

BACKGROUND: When the transplant candidates are receiving oral anticoagulation therapy before transplantation, it is crucial to have an urgent reversal strategy to prevent hemorrhagic complications perioperatively. The aim of this study was to present the experience with idarucizumab to reverse the anticoagulant activity of dabigatran prior to lung transplantation. METHODS: A single-center retrospective study was performed to analyze the clinical outcomes of idarucizumab use before lung transplantation. RESULTS: Between July 2016 and June 2019, six patients were on dabigatran at the time of transplantation. Out of the six patients, four patients received idarucizumab. These four recipients received a median of 3 units (range 0-4 units) of packed red blood cells (pRBCs) and 450 ml (range 250-1500 ml) of intraoperative salvage of shed blood (cell saver blood) during the lung transplant. The two patients who were not administered idarucizumab received 5 units and 13 units of pRBCs and 900 ml and 3600 ml of cell saver blood, respectively. There was no grade 3 primary graft dysfunction (PGD) at 72 hours after transplantation or in-hospital mortality in idarucizumab group. In the group without idarucizumab, there was one case of grade 3 PGD without any in-hospital mortality. CONCLUSION: Dabigatran reversal with idarucizumab provides reasonable hemostasis during lung transplantation.

An Evaluation of Continuous Infusion Rocuronium for Sustained Neuromuscular Blockade in Critically Ill Adults.

BACKGROUND: Recent medication shortages of the neuromuscular blocking agent (NMBA) cisatracurium have forced the prescribing of aminosteroidal agents such as rocuronium. There are limited data on the use and dosing of continuous infusion (CI) rocuronium in critically ill patients outside of the operating room. OBJECTIVE: We sought to describe the use of CI rocuronium for sustained neuromuscular blockade in intensive care unit (ICU) patients by characterizing the dosing, utilization, and safety profile in patients with multiple organ failure (MOF) and non-MOF. METHODS: This was a retrospective review of patients in mixed ICUs from 2 tertiary medical centers who received CI rocuronium between January 2018 and July 2019. RESULTS: A total of 46 unique rocuronium infusions were utilized for 40 patients during the evaluation period. Of these, 37% had MOF, and 41% had at least 1 organ fail during the rocuronium infusion. The median starting and maximum dose was 8 µg/kg/min. Overall, 64% of train of 4 (TOF) measurements were a TOF 0 (T0) or TOF 1 (T1), with a higher percentage of T0 or T1 in the MOF group compared with the non-MOF group (75% vs 50%). The median time to recovery was more than twice as long for the MOF compared with the non-MOF group (10 vs 4.6 hours). ICU-acquired weakness was diagnosed in 27% of survivors. CONCLUSION AND RELEVANCE: In ICU patients with MOF, continuous rocuronium infusions were associated with deep levels of paralysis and prolonged recovery times. If neuromuscular blockade is required for critically ill patients, alternative strategies could be considered.

Population Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients.

Isavuconazole (ISA) is a triazole antifungal with activity against yeasts and molds. We established a population pharmacokinetic (pop PK) model of intravenous (i.v.) ISA to identify covariates that affect pharmacokinetics, using plasma samples from solid-organ transplant (SOT) recipients receiving peritransplant prophylaxis. Samples (n = 471) from 79 SOT recipients were utilized for pop PK analysis using nonlinear mixed-effect modeling NONMEM software. ISA (i.v.) PK parameters were best described by a two-compartment model. Significant covariates were sex on clearance (∼53% higher in women than men) and body mass index on peripheral volume of distribution. Incorporating drug exposure into Monte Carlo simulations, we demonstrated that standard ISA dosing is likely to attain the PK-pharmacodynamic (PD) target (area under the concentration curve/MIC ratio [AUC/MIC]) for treatment effectiveness against almost all infections caused by Aspergillus fumigatus isolates exhibiting MICs of ≤0.5 µg/ml (modal MIC). In contrast, standard dosing is predicted to attain PK-PD targets against <20% of infections caused by Candida albicans and Candida glabrata isolates exhibiting MICs of ≥0.016 and ≥0.5 µg/ml, respectively (modal MICs). These data are consistent with our SOT program's experience with ISA breakthrough infections, where 3 of 4 were caused by C. glabrata for which probabilities of PK-PD target attainment (PTA) were only 70% and 0% for isolates with MICs of 0.25 µg/ml and 1 µg/ml. Our findings provide important new insights into how ISA use might be optimized following SOT.

Achievement of clinical isavuconazole blood concentrations in transplant recipients with isavuconazonium sulphate capsules administered via enteral feeding tube.

BACKGROUND: Isavuconazole is a triazole antifungal available in IV and capsule formulation. Prescribing information states that capsules should not be chewed, crushed, dissolved or opened because the drug was not studied in this manner. However, considering the pharmacokinetics of the capsules, we theorized opening and sprinkling the contents into an enteral feeding tube (EFT) would result in adequate absorption and systemic concentrations of isavuconazole. OBJECTIVES: To determine whether patients receiving isavuconazonium sulphate capsules via EFT would achieve clinical blood concentrations of isavuconazole. METHODS: Nineteen solid organ and HCT recipients receiving isavuconazole via EFT for prevention or treatment of invasive fungal infection (IFI) were prospectively identified at four academic medical centres in the USA. Patients were included in this evaluation if they received isavuconazole via EFT for at least 5 days and therapeutic drug monitoring (TDM) was performed. RESULTS: TDM was performed after a median of 7 days (range 6-17) following EFT administration and 15 days (range 7-174) of isavuconazole therapy overall. Median isavuconazole concentration was 1.8 µg/mL (range 0.3-5.2). Median isavuconazole concentrations in patients with or without prior IV administration were 1.8 µg/mL (range 0.3-5.2) and 2.2 µg/mL (range 0.8-3.6; P = 0.896), respectively. Concentrations achieved with the EFT route were similar to or greater than the corresponding concentrations via the IV route in six patients who had TDM performed during both routes of administration. CONCLUSIONS: It is reasonable to consider opening isavuconazonium sulphate capsules and administering the contents enterally for prevention and treatment of IFI.

Pharmacokinetics of Intravenous Isavuconazole in Solid-Organ Transplant Recipients.

Isavuconazole may be useful in treating and preventing fungal infections in solid-organ transplant (SOT) recipients due to its safety profile and activity against Aspergillus and some Mucorales Isavuconazole has favorable pharmacokinetics based on clinical trials in various patient populations, but data are limited in SOT recipients. We evaluated the steady-state pharmacokinetics of isavuconazole in 26 SOT recipients receiving the drug intravenously for prophylaxis. There was moderate interpatient variability in isavuconazole pharmacokinetic parameters (coefficients of variation of 51% for the area under the plasma concentration-versus-time curve [AUC] and 59% for the trough plasma concentration [Ctrough]). AUC and steady-state Ctrough were significantly lower in women, patients with a body mass index of ≥18.5 kg/m2, and those receiving hemodialysis. Trough plasma concentrations were highly correlated with AUCs (R2 = 0.94) and can serve as a suitable measure of isavuconazole exposure in patients. In conclusion, moderate interpatient variability in isavuconazole exposure, the identification of factors associated with lower exposure, the recognition that Ctrough is a surrogate marker for AUC, and the availability of a simple analytical method suggest that therapeutic drug monitoring (TDM) may be useful for guiding treatment in at least some SOT recipients. Future studies are needed to correlate isavuconazole exposure with patients' clinical outcomes and to determine the clinical role of TDM.

Pharmacokinetics of Azole Antifungals in Cystic Fibrosis.

Defects in mucociliary clearance predispose cystic fibrosis (CF) patients to airway colonization and infection by various fungi, especially Aspergillus fumigatus. Although the clinical significance of airway fungal colonization is not clear, several studies have suggested its association with worsening lung function and increased risk of CF exacerbations. Antifungal triazole agents have been used in CF patients with airway fungal colonization or infections with varying results. Limited pharmacokinetic studies to date have demonstrated high inter-subject variability of triazole levels among CF patients. This review discusses the basic principles of pharmacokinetics, the pharmacokinetic changes associated with CF and the effect of CF on the pharmacokinetic principles of azole antifungals. The inconsistent azole serum levels in CF patients may be associated with sub-therapeutic (thus risk of therapeutic failure and/or emergence of azole-resistant fungi) or supratherapeutic exposures (thus potential risk of azole toxicity), suggesting that therapeutic dose monitoring is necessary in CF patients.

Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid-Organ Transplant Patients.

We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, the tacrolimus concentration/dose ratio normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable interpatient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly but, rather, be guided by therapeutic drug monitoring.

Association Between Train-of-Four Values and Gas Exchange Indices in Moderate to Severe Acute Respiratory Distress Syndrome.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is associated with a mortality rate of approximately 40%. Neuromuscular blockade is associated with an improvement in oxygenation and a reduction in mortality in ARDS. OBJECTIVE: The goal of this evaluation was to determine if the depth of paralysis, determined by train-of-four (TOF) monitoring, correlates with gas exchange in moderate to severe ARDS. METHODS: This was a retrospective review of moderate to severe ARDS patients who were prescribed >12 hours of continuous infusion cisatracurium between January 1, 2013, and December 31, 2014, with a PaO2:FiO2 ratio <150 and documented TOF and arterial blood gases. Patients were evaluated for inclusion at 12, 24, and 48 hours after initiation of neuromuscular blockade. RESULTS: A total of 378 patients were screened for inclusion, with 107 evaluable patients meeting criteria at baseline. Poor correlation existed between TOF and oxygenation index (OI) at 12 (τ = 0.03), 24 (τ = 0.15) and 48 hours (τ = 0.08). When controlling for proning and baseline OI, the depth of paralysis did not have a significant effect on OI at 12, 24, or 48 hours. CONCLUSIONS: This evaluation demonstrates that the use of TOF monitoring for neuromuscular blockade does not correlate with gas exchange markers in moderate to severe ARDS.

Drug Class Combination-Associated Acute Kidney Injury.

OBJECTIVE: To evaluate the quality of available evidence of drug class combinations and their association with the development of acute kidney injury (AKI). DATA SOURCES: A search of MEDLINE and Embase databases was completed using the following terms: "risk factor AND (acute kidney injury or acute kidney failure) AND (drug or medication)." STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria were the following: English language, full-text availability, and at least 1 drug-combination. Each citation was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. The literature was evaluated using the quality of evidence component of GRADE. No standardized definition of AKI was applied throughout.. DATA SYNTHESIS: Out of 2139 total citations, 151 were assessed for full-text review, with 121 citations (6%) meeting inclusion criteria, producing76 unique drug class combinations. Overall, 56 combinations (73.7%) were considered very low quality; 12 (15.8%) were considered low quality. There were 8 (10.5%) of moderate quality, and no combination was considered high quality. 58 (76%) combinations that had a single citation,with a mean of 1.6 citations per drug class combination. The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) and diuretics was reported in 10 citations, the largest number of citations. CONCLUSIONS: Our study demonstrates a lack of well-designed studies addressing drug class combination-associated AKI. The combination of NSAIDs and diuretics with or without additional renin-angiotensin aldosterone agents had the strongest level of evidence. Despite limitations, the information included in this review may result in additional scrutiny about combining certain individual nephrotoxic drugs.

Safety and Efficacy of Warfarin Reversal with Four-Factor Prothrombin Complex Concentrate for Subtherapeutic INR in Intracerebral Hemorrhage.

BACKGROUND: The use of vitamin K antagonists is an independent risk factor for the development of intracerebral hemorrhage (ICH). Four-factor prothrombin complex concentrate (4F-PCC) is recommended for urgent reversal of anticoagulation in this setting. The safety and efficacy of 4F-PCC in ICH with subtherapeutic levels of anticoagulation is yet to be determined. METHODS: This was a retrospective, observational study of 4F-PCC administration data from September 2013 to July 2015. Patients with spontaneous or traumatic ICH with initial INR 1.4-1.9 were compared to those with INR 2-3.9. A Fisher's exact test was used to compare the difference between the two groups in the effectiveness of 4F-PCC in reversing the INR to ≤1.3 and in the occurrence of thrombotic events within 7 days of administration. RESULTS: A total of 131 patients with a presenting INR between 1.4 and 3.9 received 4F-PCC during the study period. Twenty-three of 29 patients (79 %) in the INR <2 group achieved an INR reduction to ≤1.3 after 4F-PCC administration compared to 47 of 92 patients (51 %) in the INR 2-4 group, p = 0.03. There was no difference in thrombotic complications within 7 days after administration (6.7 % in INR 1.4-1.9 group, 10 % in INR 2-3.9 group, p = 0.73). CONCLUSION: The use of 4F-PCC in patients with INR between 1.4 and 1.9 results in an effective reduction in INR with similar thrombotic risks compared to patients presenting with an INR of 2-3.9.

An evaluation of intravenous vitamin k for warfarin reversal: are guideline recommendations being followed?

BACKGROUND: Vitamin K antagonists (eg, warfarin) remain the mainstay of anticoagulation therapy in the United States, with over 22 million prescriptions being filled annually. Unfortunately, warfarin therapy is difficult to manage and increases bleeding risk. The 2012 American College of Chest Physicians guidelines created a warfarin reversal algorithm that suggested the stringent use of intravenous vitamin K. OBJECTIVE: The purpose of this evaluation was to determine the rates of adherence with guideline recommendations in clinical practice. METHOD: A convenience sample of 3 months of intravenous vitamin K medication administration data (September to November 2013) was obtained to conduct a retrospective review. Patients with underlying hepatic dysfunction or lack of warfarin therapy were excluded. Vitamin K use was evaluated for consistency with the 2012 guidelines. RESULTS: A total of 364 patients were reviewed and 119 were included. Vitamin K utilization was consistent with guideline recommendations for a total of 30 (25.2%) patients. The most common site of active bleeding requiring reversal was head bleeds, consisting of 56.6% of bleeds. A single dose of 10 mg of vitamin K was the most frequently used dosing strategy. Fresh frozen plasma (73.3%) and four-factor prothrombin complex concentrate (36.7%) were the most commonly used factor products. CONCLUSION: This evaluation demonstrates that there is a difference between clinical judgment and guideline adherence. True adherence with the guidelines may not be necessary; however, there is room for improvement in both the appropriateness and safety of intravenous vitamin K use.