Chris Droege

A Novel Approach to the Treatment of Orolingual Angioedema After Tissue Plasminogen Activator Administration

Orolingual angioedema is a rare adverse effect of tissue plasminogen activator (tPA), with an incidence of 1% to 5%. There are currently no published reports describing resolution of tPA-induced orolingual angioedema with complement inhibitor therapy. A 72-year-old man receiving home angiotensin-converting enzyme inhibitor therapy presented to the emergency department with newly developed orolingual angioedema after treatment with tPA for acute ischemic stroke. Therapy was initiated with intravenous methylprednisolone 125 mg, famotidine 20 mg, and diphenhydramine 50 mg, without significant improvement. Because of increased concern for airway protection, plasma-derived C1 esterase inhibitor was administered. Concerns about progressive and airway-threatening orolingual angioedema subsided 2 hours after administration, and invasive airway maneuvers were avoided. Orolingual angioedema is an infrequent, severe adverse effect of tPA for treatment of acute ischemic stroke. Complement inhibitors may be an additional therapeutic option for patients presenting with orolingual angioedema with potential airway compromise that is refractory to standard anaphylactic therapies.

Major publications in the critical care pharmacotherapy literature: January–December 2016

Purpose: To summarize select critical care pharmacotherapy guidelines and studies published in 2016. Summary: The Critical Care Pharmacotherapy Literature Update (CCPLU) Group screened 31 journals monthly for relevant pharmacotherapy articles and selected 107 articles for review over the course of 2016. Of those included in the monthly CCPLU, three guidelines and seven primary literature studies are reviewed here. The guideline updates included are as follows: hospital‐acquired pneumonia and ventilator‐associated pneumonia management, sustained neuromuscular blocking agent use, and reversal of antithrombotics in intracranial hemorrhage (ICH). The primary literature summaries evaluate the following: dexmedetomidine for delirium prevention in post‐cardiac surgery, dexmedetomidine for delirium management in mechanically ventilated patients, high‐dose epoetin alfa after out‐of‐hospital cardiac arrest, ideal blood pressure targets in ICH, hydrocortisone in severe sepsis, procalcitonin‐guided antibiotic de‐escalation, and empiric micafungin therapy. Conclusion: The review provides a synopsis of select pharmacotherapy publications in 2016 applicable to clinical practice. Highlights:Reviews pharmacotherapy‐focused guidelines (n = 3) and studies (n = 7)Articles selected based on applicability, relevance, and strength of study designCommentary provided by critical care pharmacists on clinical impact

995: METHADONE VERSUS SCHEDULED OPIOID THERAPY IN TIME TO CONTINUOUS INFUSION ANALGESIA DISCONTINUATION

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Patients in the intensive care unit (ICU) routinely experience pain. Scheduled opioids may be employed to facilitate weaning of continuous infusion (CI) analgesia in mechanically ventilated (MV) patients to avoid withdrawal. However, an optimum strategy has not been identified. Methadone may be an optimal choice as it possesses a long duration of action and has the ability to be administered intravenously and enterally. Methods: This single center, retrospective, cohort study included adult ICU patients on MV for 48 hours that received CI analgesia plus concomitant methadone or scheduled, enteral immediate release opioids (IRO). The primary outcome was comparison of time to CI analgesia discontinuation. Secondary outcomes included comparison of initial, 96-hour, and final methadone or IRO dose in oral morphine equivalents (OME) at CI analgesia discontinuation and prolonged QTc interval incidence at 96 hours. Logistic regression analyses were performed to determine independent predictors of methadone response. Results: Seventy-four patients were included in the analysis. Time to CI analgesia discontinuation was similar between the two treatment groups (methadone, 69 hours vs IRO, 57.5 hours; p = 0.527). CI analgesia dose at study drug initiation and maximum dose were similar between the two groups. The methadone group received statistically more daily OME at all time points analyzed (initiation, 90 vs 60 mg, p = 0.009; 96 hours, 90 vs 45 mg, p < 0.001; CI analgesia discontinuation, 90 vs 30 mg, p < 0.001). No difference in prolonged QTc interval at 96 hours was observed (methadone, 445 vs IRO, 460 ms; p = 0.110). Patients that received methadone were significantly more likely to discharged with a long-acting opioid prescription (51.4 vs 2.7%, p < 0.001). No independent predictors for methadone response were identified. Conclusions: Methadone was not associated with a quicker time to CI analgesia discontinuation when compared to scheduled IRO. Patients that received methadone were more likely to be discharged with a prescription for a long-acting opioid and received significantly more opioid analgesia until CI analgesia was discontinued.

Fentanyl Pharmacokinetics in Critically Ill Patients: A Demonstration of Mixed Effects.

240 www.ccmjournal.org January 2016 • Volume 44 • Number 1 have a delayed call? What particular patient and disease factors may contribute to the increased likelihood of being called late? For example, would those patients who have a terminal illness and have a perceived poor prognosis be more likely to have a delayed activation of a RRT? To understand the reasons behind delayed calls, an audit of those calls and root-cause analyses of the reasons behind them are a good start. Such studies will enable further intervention to improve compliance. Repeated education on the importance of, and logistics of, a RRS which targets both nurse and medical staff may also need to be considered. The message is this: timely activation of a RRS does save patients’ lives and willing is not enough, we must do.

581: CLINICAL IMPACT OF HYPERCHLOREMIA SECONDARY TO HYPERTONIC SODIUM CHLORIDE ADMINISTRATION

Learning Objectives: Itravenous (IV) hypertonic sodium chloride (HTS) has multiple clinical indications. Isotonic sodium chloride and subsequent hyperchloremia have been associated with acute kidney injury (AKI), prolonged hospital length of stay (LOS), and increased mortality. These associations have not been evaluated with HTS use. The primary objective of this study is to compare the incidence of AKI among peak serum chloride concentrations in patients receiving HTS. Methods: This single-center, retrospective, observational study analyzed adult patients admitted >72 hr and reveiving ≥15 grams of sodium chloride via IV HTS. Patients were divided into tertiles based on peak serum chloride: tertile 1 (T1) ≤108 mmol/L; tertile 2 (T2) 109–116 mmol/L; tertile 3 (T3) ≥117 mmol/L. AKI and in-hospital mortality rates were compared among tertiles. Multivariate logistic regression was performed to identify factors associated with AKI development or mortality. Results: 136 patients were included (T1, 43 [32%]; T2, 52 [38%]; T3, 41 [30%]). Baseline characteristics were similar among tertiles with the exception of T1 including fewer traumatic admissions (19 v 52 v 42%;p=0.003) and more hyponatremia diagnoses (14 v 4 v 0%;p=0.018). Increase in serum chloride from baseline was different among tertiles (6 v 9 v 16%;p<0.001). Rate of AKI increased with peak serum chloride (2 v 10 v 22%;p=0.015). Multivariate logistic regression identified that peak serum chloride independently predicted AKI development (OR 7.1, 95% CI 1–50;p=0.049). Hospital (13 v 16 v 13;p=0.053) and ICU (8 v 11 v 11;p=0.124) LOS (days) were similar among groups. Mortality rate increased with peak serum chloride (5 v 14 v 32%;p=0.003). No factors were identified as independent predictors of mortality. Conclusions: After adjusting for concurrent nephrotoxins and other confounding variables, increasing magnitude of serum chloride was associated with AKI among patients who received HTS. Prospective, multicenter studies are needed to confirm this relationship.

1004: EVALUATION OF ADHERENCE TO THE 2012 SURVIVING SEPSIS CAMPAIGN GUIDELINES AND ASSOCIATED OUTCOMES

Learning Objectives: The Surviving Sepsis Campaign (SSC) 2012 guidelines published updated bundles of care to guide healthcare providers in sepsis treatment. Updated bundle adherence and associated clinical outcomes have yet to be evaluated. Methods: This retrospective chart review included 110 patients who met ACCP/SCCM definition of sepsis, severe sepsis, or septic shock within the first six hours of emergency department admission. Patients were placed into predefined adherence tertiles based on percent bundle adherence (tertile 1: 0–33%, tertile 2: 34–66%, tertile 3: 67–100%). In-hospital mortality, resuscitation endpoints (e.g., lactate; mean arterial pressure; central venous pressure;central venous oxygen saturation), ICU length of stay (LOS), ventilator days, and Sequential Organ Failure Assessment (SOFA) scores were assessed at baseline, 24 hours, 72 hours, and discharge and compared between adherence tertiles. A multivariate logistic regression was performed in effort to identify predictors of mortality. Results: There was no difference in mortality seen between adherence groups in all patients (0%v 11.1% v. 6.7%, p=0.655) or those with severe sepsis or septic shock (0% v 13.3%v 0%, p=0.413). ICU length of stay and ventilator days was greater in patients in tertile 1 (3.1 v 0.4 v 0, p=0.039; 3.5 v 0 v 0, p=0.015). When morbidity endpoints were compared between patients admitted to the ICU and in those ventilated, no difference in ICU LOS or ventilator days was noted. No difference in ICU length of stay and ventilator days existed in patients in severe sepsis or septic shock. Median antibiotic administration time was 2.9 hours and 3.2 hours in all patients and patients with severe sepsis and septic shock, respectively. There was no difference in the amount of fluid given between groups. No predictors of mortality were identified. Conclusions: Adherence to 2012 SSC Bundles was relatively low. Bundle adherence did not improve clinical outcomes in emergency department patients with sepsis, severe sepsis, or septic shock.