Background: Four-factor prothrombin complex concentrate (4F-PCC) is indicated for vitamin K antagonist (VKA) reversal but is associated with thrombotic events (TE). In 2018, the institution revised 4F-PCC dosing for VKA reversal from INR and weight-based dosing to a fixed-dose of 1500 units. Objective: The purpose of this study was to compare hemostatic efficacy and TE rate of fixed-dose 4PCC to weight-based dosing. Methods: This was a retrospective, single-center, quasi-experimental study of adult patients who received 4F-PCC for VKA reversal from January 2014 through May 2016 (INR and weight-based dosing) or April through October 2018 (fixed-dosing). The primary endpoint was hemostatic efficacy, defined by achieving an INR of ≤1.4, or an INR of ≤1.7 with evidence of hemostasis. The key secondary endpoint was TE within 14 days of 4F-PCC administration. Data were analyzed using descriptive statistics, chi-squared for nominal data and Mann-Whitney U for ordinal and continuous data. Results: The study included 163 patients who received weight-based dosing and 45 who received fixed-dose 4F-PCC. Hemostatic efficacy was 76.9% of patients in the weight-based group and 77.4% of patients in the fixed-dose group (P = .229). TE occurred in 13.5% of the weight-based vs 6.7% of the fixed-dose group (P = .181). Conclusion: This study found no difference in hemostatic efficacy with fixed-dose 4F-PCC for VKA reversal compared to INR and weight-based dosing. The occurrence of TE was reduced by 50% with the 4F-PCC fixed-dose strategy; however, this difference was not statistically significant. Further randomized studies are needed to confirm these results.

When medication administration record (MAR) “hold” capability is enabled in the electronic health record (EHR) during patient transfers, medication doses appear as “held” rather than due. We sought to quantify the incidence of delayed and missed doses of critical medications during MAR hold periods and to implement and evaluate interdisciplinary efforts and technical interventions to reduce missed medication doses during these periods. A list of critical medications was identified. MAR data were collected in patients with at least 1 critical medication dose due during the MAR hold period. MAR times were used to determine if delayed doses or missed doses occurred. Our interventions included: (1) implementation of a patient list indicator to retrospectively identify recently “held” medication doses, and (2) a report for operating room pharmacists to prospectively identify upcoming doses and ensure they were administered on time. Pre- and post-intervention period data were compared using a chi-squared test. During the pre-intervention study period, there were 1044 instances of delayed or missed doses during MAR hold. Most MAR times evaluated were on MAR hold during perioperative patient transfers. Delayed, missed, and multiple missed doses were defined in accordance with internal medication administration policies. There was no significant difference in the incidence of delayed and missed doses (69% vs 66%, P = .31), however, there was a significant reduction in the number of critical medication doses missed multiple times (0.8% vs 6.7%, P < .001) and all missed doses (35% vs 42%, P = .05) between the pre- and post-intervention period. As demonstrated across in both the pre- and post-intervention period of our study, MAR hold is commonly associated with dose delays and missed doses, which has potential negative consequences on patient outcomes. Future considerations will include implementation of a best practice alert (BPA) that directs users to a MAR tab highlighting doses held during transfers.

Introduction: Maximal vasopressor dosing is driven by institutional policy and may vary between intensive care units (ICUs) within an institution. The purpose of this project was to characterize use of and evaluate outcomes associated with high-dose norepinephrine (defined as norepinephrine ≥ 1 mcg/kg/min). Methods: This was a retrospective, observational cohort study of adult ICU patients at two academic medical centers over five years. Patients who received high-dose norepinephrine for ≥ 1 hour were included. Subsequent hospitalizations were excluded. Index ICU admission was defined as the ICU admission in which patients first received high-dose norepinephrine. Results: Among 1564 included patients, 277 (17.7%) survived to hospital discharge. The majority of patients were male (58.4%) and admitted to a medicine unit (75.6%). The median (IQR) age was 63 (53-76) years and the median (IQR) weight was 81.5 (67.1-99.3) kilograms. Patients received high-dose norepinephrine for a median (IQR) duration of 6.3 (3-15.9) hours with a median (IQR) maximum norepinephrine dose of 3 (1.6-3) mcg/kg/min. Patients who survived had a lower median (IQR) age compared to non-survivors [58 (48-68) vs. 65 (55-74) years, p < 0.0001], lower median (IQR) weight [72.8 (59.8-90.7) vs. 83.3 (68.8-100.8) kilograms, p < 0.0001], and received high-dose norepinephrine for a shorter median (IQR) duration [4.7 (2-13.0) vs. 6.6 (1.8-16.9) hours, p < 0.0001]. Survivors also required lower median (IQR) maximum doses [1.8 (1.4-3) vs. 3 (2-3) mcg/kg/min, p < 0.0001]. Among 857 patients that received norepinephrine ≥ 3 mcg/kg/min, 74 (8.6%) survived. On multivariable logistic regression, the odds of in-hospital survival were higher in patients who were less than 65 years (OR 2.14, 95% CI: 1.59-2.88, p < 0.001), had a maximum norepinephrine rate < 3 mcg/kg/min (OR 3.98, 95% CI: 1.9-4.16, p < 0.001) or achieved their maximum norepinephrine rate within 24 hours of index ICU admission (OR 2.83, 95% CI: 2.09-3.85, p < 0.001). Conclusions: Nearly one-fifth of patients survived to hospital discharge following administration of norepinephrine ≥ 1 mcg/kg/min. Younger age, lower maximum norepinephrine doses, and administration of high-dose norepinephrine earlier in the ICU course was associated with increased survival.

BACKGROUND:Levocarnitine deficiency has been observed in patients receiving parenteral nutrition (PN) and can cause or worsen hypertriglyceridemia. The objective was to characterize use of levocarnitine supplementation in PN and evaluate its effect on triglyceride levels in hospitalized adults.METHODS:This retrospective, single-center study included patients with triglyceride levels ≥175 mg/dl while receiving PN who had a subsequent reduction in lipid injectable emulsion dose. A piecewise linear regression was used to evaluate trends in triglyceride levels before and after the intervention, defined as initiation of levocarnitine in PN for the levocarnitine group, or reduction in lipid injectable emulsion alone for the control group.RESULTS:Two hundred sixty-one patients who received PN had an elevated triglyceride level and lipid injectable emulsion dose reduction, of which 97 (37.2%) received levocarnitine in PN. The median (IQR) levocarnitine dose added to PN was 8.0 (5.7-9.9) mg/kg. Triglyceride levels at 30 days post-intervention did not differ between groups (125 vs 176 mg/dl, P = .345). The addition of levocarnitine to PN was associated with a significantly greater rate of reduction in triglyceride levels pre-intervention to post-intervention compared with a reduction in lipid injectable emulsion alone (-11 vs -3 mg/dl per day; 95% CI, -15 to -2; P = .012).CONCLUSION:In hospitalized adults with hypertriglyceridemia who had a lipid injectable emulsion dose reduction, the addition of levocarnitine in PN was not associated with a difference in triglyceride levels at 30 days; however, a greater rate of improvement in pre-intervention to post-intervention triglyceride levels was observed.

Grucz, Traci1; Marengo, Christina2; Sugrue, David2; Jarrell, Andrew3; Crow, Jessica4; Mendez-Tellez, Pedro2 Author Information

Copyright © 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Sugrue, David1; Jarrell, Andrew1; Buzzalino, Franco1; Kiehle, Nicole2; Wolpaw, Jed1; Sapirstein, Adam3; Crow, Jessica1 Author Information

Background: At a tertiary referral and Level I trauma center, current institutional guidelines suggest initial aminoglycoside doses of gentamicin or tobramycin 4 mg/kg and amikacin 16 mg/kg for patients admitted to surgical intensive care units (SICUs) with suspected gram-negative infection. The objective of this study was to evaluate initial aminoglycoside dosing and peak serum drug concentrations in critically ill surgery patients to characterize the aminoglycoside volume of distribution (V-d) and determine an optimal standardized dosing strategy. Methods: This retrospective, observational, single-center study included adult SICU patients who received an aminoglycoside for additional gram-negative coverage. Descriptive statistics were used to evaluate the patient population, aminoglycoside dosing, and V-d. Multivariable linear regression was applied to determine variables associated with greater aminoglycoside V-d. The mortality rate was compared in patients who achieved adequate initial peak concentrations versus those who did not. Results: One hundred seventeen patients received an aminoglycoside in the SICUs, of whom 58 had an appropriately timed peak concentration measurement. The mean Acute Physiology, Age, and Chronic Health Evaluation (APACHE) II score was 27.8 +/- 8.9. The V-d in patients receiving gentamicin, tobramycin, and amikacin was 0.49 +/- 0.10, 0.41 +/- 0.09, and 0.53 +/- 0.13 L/kg, respectively. Together, the mean aminoglycoside V-d was 0.50 +/- 0.12 L/kg. Gentamicin or tobramycin 5 mg/kg achieved goal peak concentrations in 24 patients (63.2%), and amikacin 20 mg/kg achieved the desired concentrations in nine patients (50.0%). Net fluid status, Body Mass Index, and vasopressor use were not predictive of V-d. There was no difference in the in-hospital mortality rate in patients who achieved adequate peak concentrations versus those who did not (26.8% versus 26.7%; p = 0.99). Conclusion: High aminoglycoside doses are needed in critically ill surgery patients to achieve adequate initial peak concentrations because of the high V-d. Goal peak concentrations were optimized at doses of gentamicin or tobramycin 5 mg/kg, and amikacin 20 mg/kg.

Milkovits, Ashley; McAllister, Kelly; Sugrue, David; Faris, Jane; Schad, Jessica Author Information

Grucz, Traci1; Crow, Jessica2; Davis, Stephanie2; Gager, Erin3; Beattie, Jessica3; Shermock, Kenneth4; Sugrue, David1; Jarrell, Andrew1 Author Information

Milkovits, Ashley; McAllister, Kelly; Sugrue, David; Faris, Jane; Schad, Jessica Author Information

Critical Care Medicine: January 2020 - Volume 48 - Issue 1 - p 55 doi: 10.1097/01.ccm.0000618936.32164.c9

Background & aims: Current evidence and guidelines identify patient populations who may benefit from parenteral nutrition. Peripheral parenteral nutrition (PPN) may be indicated for a subset of patients; however, PPN therapy carries a risk of associated adverse effects. The purpose of this project was to assess appropriateness of current PPN prescribing practices at an academic medical center to determine whether additional guidance and oversight may be beneficial. Methods: Adult patients admitted from August 1, 2015 to November 30, 2015 with at least one order of PPN administered were included. PPN use was evaluated for appropriateness using definitions derived from clinical practice guidelines and standard of practice. Adverse events, including phlebitis and bacteremia, were also examined. Results: Of the 159 patients included, 51 (32.1%) received appropriate PPN therapy, in which all four criteria for appropriateness were met. In regards to the criteria for appropriateness, 128 (80.5%) had an appropriate indication, 85 (53.5%) had appropriate time to PPN initiation, 157 (98.7%) had an appropriate duration of therapy, and 112 (70.4%) achieved an appropriate percentage of goal daily calories. In terms of complications associated with PPN therapy, 69 (43.4%) patients had documented phlebitis and bacteremia occurred in 5 (3.1%) of the patients. Conclusion: During the study period, PPN was appropriately utilized in only one- third of patients and phlebitis occurred in almost half of all patients. Restrictions on PPN prescribing may allow nutrition support clinicians to prospectively evaluate patients to optimize nutrition therapy and minimize the incidence of inappropriate PPN use. Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.

Sugrue, David; Crow, Jessica; Jarrell, Andrew; Kruer, Rachel; Davis, Stephanie; Snyder, Sukyee; Tsui, Evelyn