Marina Rabinovich

Azithromycin-induced liver injury

PURPOSE A case of azithromycin-induced hepatotoxicity in a 69-year-old woman with no history of liver disease is reported. SUMMARY After receiving four days of high-dose azithromycin for the treatment of suspected bronchitis, a 69-year-old woman arrived at the emergency room with nausea, vomiting, diarrhea, elevated liver enzyme values, and visible signs of pruritus and jaundice. Her medical history included hypertension, hypothyroidism secondary to Graves disease, depression, dyslipidemia, and chronic obstructive pulmonary disease. She had no history of liver, cardiac, genitourinary, and renal diseases. Causes of primary liver injury, including metabolic, viral, and autoimmune liver diseases, were excluded. Her International Normalized Ratio was elevated, and substantial transaminitis was noted. There was no evidence of portal vein thrombosis on ultrasound, and extrahepatic obstruction was unlikely. Liver injury associated with right heart failure was unlikely, as right ventricular function was relatively preserved and right atrial pressure was not severely elevated. Ischemic hepatitis was also ruled out. After exclusion of other causes of liver disease, drug-induced hepatotoxicity was considered. A careful review of her medications prior to admission was conducted. A temporal relationship between initiation of azithromycin and the onset of clinical signs and symptoms was noted. The Naranjo et al. probability scale indicated a possible relationship between azithromycin and hepatotoxicity; however, two scales specifically used for evaluating drug-induced liver disease indicated a probable adverse drug-associated event. CONCLUSION A 69-year-old woman developed cholestatic hepatitis after four days of therapy with high-dose azithromycin for the treatment of suspected bronchitis.

Probable Amlodipine-Induced Angioedema

Objective: To report a case of angioedema likely associated with amlodipine administration in a patient with a right thalamic hemorrhagic stroke. Case Summary: A 50-year-old female experienced angioedema during hospitalization for s right thalamic hemorrhagic stroke. She had no past history of angioedema and all of her medications were assessed for risk of angioedema. After careful evaluation, case reports linking calcium channel blockers (CCBs) and angioedema led to further examination of amlodipine as a cause. Amlodipine therapy had been initiated 24 hours prior to the development of angioedema, which then resolved 72 hours after discontinuation of the drug. In total, the patient experienced oropharyngeal swelling for 10 days. Discussion: In determining a cause for the patients angioedema we eliminated genetic, allergic, physically induced, thyroid autoimmune disease-associated, and medication-induced causes. Three case reports describing 7 patients have linked the CCBs verapamil, diltiazem, and nifedipine with angioedema. The onset and resolution of symptoms in our patient were very similar to those seen in other case reports. Application of the Naranjo probability scale found a probable link between amlodipine and angioedema. Conclusions: Although few reports of CCB-induced angioedema exisi, to our knowledge, this is the first reported case to suggest a link between angioedema and amlodipine therapy. Clinicians should consider amlodipine as a potential cause of angioedema.

Effect of Electronic Health Record Implementation in Critical Care on Survival and Medication Errors

Background: Electronic health records (EHR) with computerized physician order entry have become exceedingly common and government incentives have urged implementation. The purpose of this study was to ascertain the effect of EHR implementation on medical intensive care unit (MICU) mortality, length of stay (LOS), hospital LOS and medication errors. Materials and Methods: Prospective, observational study from July 2010‐June 2011 in MICU at an urban teaching hospital in Atlanta, Georgia of 797 patients admitted to the MICU; 281 patients before the EHR implementation and 516 patients post‐EHR implementation. Results: Compared with the preimplementation period (N = 43 per 281), the mortality risk at 4 months post‐EHR implementation (N = 41 per 247) and at 8 months post‐EHR implementation (N = 26 per 269) significantly decreased (P < 0.001). In addition, the mean MICU LOS statistically decreased from 4.03 ± 1.06 days pre‐EHR to 3.26 ± 1.06 days 4 months post‐EHR and to 3.12 ± 1.05 days 8 months post‐EHR (P = 0.002). However, the mean hospital LOS was not statistically decreased. Although medication errors increased after implementation (P = 0.002), this was attributable to less severe errors and there was actually a decrease in the number of severe medication errors (both P < 0.001). Conclusions: We report a survival benefit following the implementation of EHR with computerized physician order entry in a critical care setting and a concomitant decrease in the number of severe medication errors. Although overall hospital LOS was not shortened, this study proposes that EHR implementation in a busy urban hospital was associated with improved ICU outcomes.

Risk of Hypoglycemia During Insulin Infusion Directed by Paper Protocol Versus Electronic Glycemic Management System in Critically Ill Patients at a Large Academic Medical Center

Background: Insulin infusions are commonly utilized to control hyperglycemia in critically ill patients and decrease hyperglycemia associated complications. Safety concerns have been raised in trials evaluating methods of glycemic control regarding the incidence of hypoglycemia and its relationship to increased mortality. Electronic glycemic management systems (eGMS) may result in less variable blood glucose (BG) control and less hypoglycemia. This study aimed to compare BG control, time in target BG range, and the rate of hypoglycemia when critically ill patients were managed with an insulin infusion guided by paper-based protocol (PBP) versus eGMS. Methods: This retrospective review compared critically ill patients ≥ 18 years old that received insulin infusion from March to May 2015 (PBP group) and October to January 2017 (eGMS group). The primary outcome was the incidence of hypoglycemia. Secondary outcomes included frequency and severity of hypoglycemia, duration in glycemic target, length of insulin therapy, as well as ICU and hospital length of stay. Results: Fifty-four patients were evaluated, 27 in each group. Percentage of days with BG <70 mg/dL was significantly reduced after eGMS implementation (21.5% v 1.3%, P < .0001) including the frequency of severe hypoglycemia (BG < 40 mg/dL) (5.4% v 0.01%, P < .0001). Patients in the eGMS group spent a greater amount of time in target BG range (31.5% v 63.7%, P < .0001). Conclusions: An eGMS has the potential to address many of the unmet needs of an optimal glycemic control strategy, minimizing hypoglycemia, and glycemic variability in a heterogeneous critically ill population.

A review of current agents for anticoagulation for the critical care practitioner

There has been a tremendous boom in the arena of anticoagulant therapy recently. Although the indications for these agents reside in the noncritical care environment, over time, the impact of these agents have infiltrated the critical care environment particularly due to devastating complications with associated use. With so many newer agents on the market or coming down the pipeline, it is easy to become overwhelmed. It is important that the critical care practitioner does not ignore these agents but becomes familiar with them to better prepare for the management of patients on one or more anticoagulant agents in the intensive care unit. To equip the critical care practitioners with the knowledge about commonly used anticoagulants, we provide an extensive review of the pharmacology, indications, and adverse effects related to these agents as well as suggestions on preventing or managing complications.

913: EVALUATION OF CRITICAL CARE PHARMACIST-TO-PATIENT RATIOS IN INTENSIVE CARE UNITS

www.ccmjournal.org Critical Care Medicine • Volume 46 • Number 1 (Supplement) Learning Objectives: The justification of critical care pharmacist positions is a common challenge in part due to limited data regarding ideal pharmacist-to-patient ratio. A variety of ideal pharmacistto-patient ratios in the ICU setting are identified with a range around 1:15. The lack of agreement among reported ratios is due to the various methods of determination including patient census, unit location, and illness acuity. The purpose of this study was to characterize pharmacist allocation practices across the southeast region of the United States. Methods: This cross-sectional study surveyed pharmacist members of the Southeast Chapter of Society of Critical Care Medicine and consisted of three areas of assessment: (1) institution demographics; (2) individual demographics; (3) perceived appropriateness of current pharmacistto-patient ratios. Descriptive statistics were used for analysis. Results: The initial response rate was 18% with 12 pharmacists representing 12 different institutions. All institutions were teaching hospitals with 58% (7/12) having greater than 600 beds. All institutions reported decentralized pharmacy services. Evening critical care services were offered at 5/12 (42%) of institutions, and 1 institution (8%) had a designated ICU float position. Pharmacist-to-patient ratios greater than 1:15 were reported in 92% (11/12) of respondents and a ratio greater than 1:25 in 7/12 (58.3%). Additional non-patient care activities (i.e. research) was reported in 9/12 (75%) respondents for at least 30% of the workday. Concerns regarding the appropriateness of current workload and the ability to provide appropriate patient care were expressed in 6 respondents (50%). Conclusions: Pharmacists reported higher daily pharmacist to patient ratios than the recognized recommendations. A majority of pharmacists reported concern regarding workload and patient safety. Despite high rates of involvement with patient care and non-patient care activities, many institutions do not have standardized practices to evaluate or manage pharmacist to patient ratio, minimize cross coverage, or provide evening services.

Evaluation of medication errors with implementation of electronic health record technology in the medical intensive care unit

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Case Report: Persistent Elevation in Creatine Phosphokinase Associated With High-Dose Daptomycin Therapy

Objective To report a persistent elevation in creatine phosphokinase (CPK) associated with high-dose daptomycin therapy that did not resolve following discontinuation of daptomycin. Summary A 34-year-old male with HIV/AIDS and stage IV Burkitt lymphoma was admitted for pain management. The patients initial hospital course was complicated by left brachial deep vein thrombosis (DVT), Clostridium difficile colitis, and pancytopenia. The patient later developed severe sepsis and septic shock secondary to methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Candida albicans, and Escherichia coli infection. High-dose daptomycin (12 mg/kg) was initiated to treat MRSA and VRE bacteremia. The patients baseline CPK was 118 U/L, which increased to 327 U/L following 2 days of therapy. The patients CPK continued to increase to 1648 U/L on day 10 of daptomycin, thereby necessitating a discontinuation of daptomycin and the initiation of linezolid. Six days after discontinuation of therapy, the patients CPK remained elevated at 1940 U/L. Discussion A Naranjo scale score of 6 was calculated, indicating that daptomycin was the probable cause for the increase in CPK. Although daptomycin is known to cause elevations in CPK, there are limited published data describing this adverse event with high-dose daptomycin therapy. Conclusion High-dose daptomycin is becoming more frequently used in clinical practice, so clinicians should monitor for and report any adverse events associated with this dosing strategy.

Paricalcitol versus Calcitriol in the Treatment of Secondary Hyperparathyroidism in Hemodialysis Patients

Purpose A mainstay treatment of secondary hyperparathyroidism has been the administration of vitamin D analogs. Paricalcitol is a vitamin D analog thought to reduce parathyroid hormone (PTH) levels with fewer effects on calcium (Ca) and phosphorous (P) levels than intravenous calcitriol. However, there are limited data directly comparing the 2 agents. The primary objective was to compare the efficacy of paricalcitol to calcitriol in hemodialysis patients. Secondary objectives evaluated the safety and direct costs associated with these agents. Methods This was a retrospective study of hemodialysis patients who received at least 8 weeks of both therapies from 2002 to 2004. Primary outcomes included the percentage of patients achieving greater than or equal to 50% reduction in baseline PTH levels; the change in PTH levels from baseline to the end of therapy; and time to achieve greater than or equal to 50% reduction in baseline PTH concentrations. Secondary outcomes included the percentage of patients experiencing hypercalcemia, hyperphosphatemia, or elevated Ca and P product; and the percentage of patients hospitalized secondary to these side effects. Results Calcitriol-treated patients showed a median reduction in PTH concentrations from baseline to the end of treatment phase of 8.3% versus paricalcitol reduction of 1.5%. This result was not statistically significant (P = 0.08); however, it should be examined in a study powered to detect this difference. A similar number of patients in both treatment groups were able to achieve a greater than or equal to 50% reduction in baseline PTH concentrations but calcitriol-treated patients were more likely to achieve this primary end point faster than the paricalcitol-treated group (166 days vs 207 days, respectively, P = 0.18). The incidence of side effects between the agents was similar. There was a substantial difference in the annual drug cost between paricalcitol and calcitriol. Conclusion Paricalcitol did not seem to result in clear efficacy and safety benefit over calcitriol in this study. However, due to the studys retrospective design and potential for a type 2 error, as well as limited published data comparing this agent to calcitriol, additional research is required before paricalcitol becomes the standard of care in patients with chronic kidney disease and secondary hyperparathyroidism.