Remote Continuous Glucose Monitoring With a Computerized Insulin Infusion Protocol for Critically Ill Patients in a COVID-19 Medical ICU: Proof of Concept.

OBJECTIVE: The use of remote real-time continuous glucose monitoring (CGM) in the hospital has rapidly emerged to preserve personal protective equipment and reduce potential exposures during coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: We linked a hybrid CGM and point-of-care (POC) glucose testing protocol to a computerized decision support system for continuous insulin infusion and integrated a validation system for sensor glucose values into the electronic health record. We report our proof-of-concept experience in a COVID-19 intensive care unit. RESULTS: All nine patients required mechanical ventilation and corticosteroids. During the protocol, 75.7% of sensor values were within 20% of the reference POC glucose with an associated average reduction in POC of 63%. Mean time in range (70-180 mg/dL) was 71.4 ± 13.9%. Sensor accuracy was impacted by mechanical interferences in four patients. CONCLUSIONS: A hybrid protocol integrating real-time CGM and POC is helpful for managing critically ill patients with COVID-19 requiring insulin infusion.

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 a 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 patient's 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 exist, 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.

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.

Comparison of Computer-Guided Versus Standard Insulin Infusion Regimens in Patients With Diabetic Ketoacidosis.

BACKGROUND: This study was performed to investigate the efficacy of Glucommander (GM) (Glytec®), a computer-based algorithm versus standard (paper form-based) continuous insulin infusion (CII) in the treatment of patients with diabetic ketoacidosis (DKA). METHODS: This was a retrospective multicenter study involving 2665 patients with DKA treated with either GM (n = 1750) or standard protocols (n = 915) across 34 institutions in the United States. GM estimates the rate of CII using an insulin sensitivity factor referred to as a "multiplier" that ranges between 0.01 and 0.03. Outcomes of interest were differences in time to resolve DKA (blood glucose [BG] <200 mg/dL and bicarbonate < 18 mmol/L) and number of hypoglycemic events defined as a BG <70 mg/dl. RESULTS: Treatment with GM was associated with lower rates of hypoglycemia during the time of the insulin drip (12.9% vs 35%, P = .001), faster time to normalization of blood glucose (9.7 ± 8.9 vs 10.97 ± 10.2 hours, P = .0001) and resolution of metabolic acidosis (13.6 ± 11.8 vs 17.3 ± 19.6 hours, P = .0001), and shorter hospital length of stay (3.2 ± 2.9 vs 4.5 ± 4.8 days, P = .01) compared to standard care. Best treatment outcomes were achieved with an initial multiplier of 0.01 and a glucose target range between 120 and 180 mg/dl. CONCLUSION: The GM algorithm in DKA treatment resulted in lower rates of hypoglycemia and faster DKA resolution over standard paper-based algorithms. Prospective randomized clinical trials comparing the efficacy and cost of computer-based algorithms versus standard CII regimens are warranted.

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.

Pharmacokinetic and Pharmacodynamic Evaluation of Doripenem in Critically Ill Trauma Patients with Sepsis.

BACKGROUND: Doripenem is approved by the Food and Drug Administration for the treatment of patients with complicated intra-abdominal infections and complicated urinary tract infections. While studies have described the pharmacokinetics/pharmacodynamics (PK/PD) of doripenem in the critically ill, no study has described the probability of target attainment profile among trauma patients with sepsis. PATIENTS AND METHODS: This study was a prospective, open-label, pharmacokinetic study in the surgical intensive care unit (SICU) at Grady Health System. Thirty trauma patients with sepsis admitted to the SICU received doripenem 1 g infused over 4 hours every 8 hours for three doses. Blood samples were taken just before and after the third dose. A two-compartment model was fit to the data using non-parametric population PK modeling software. Embedded with the final PK model, a Monte Carlo Simulations (MCS) was performed to determine the PK/PD profile of doripenem 1 g, infused over 4 hours, every 8 hours after administration of the first and fourth doses. RESULTS: Overall, the model fit the data well, and mean (standard deviation) clearance and volume of the central compartment were 16.9 (11.4) L/h and 28.5 (16.0) L, respectively. In the MCS analyses, doripenem 1 g, infused over 4 hours, administered every 8 hours, conferred >90% probabilities of achieving 30-50% time greater than the minimum inhibitory concentration (30-50% T>MIC) for MICs ≤2 mg/L after infusion of both the first and fourth doses. The MCS indicated that more intensive doripenem dosing schemes should be considered for organisms with MIC values in excess of 2 mg/L. CONCLUSIONS: This is the first study to describe the doripenem PK/PD in critically ill patients with trauma. Among these patients, the MCS analyses suggest that current dosing strategies may be ineffective when the MIC value for the infecting pathogen is expected to be above 2 mg/L.

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.

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.