Evaluation of Insulin Dosing Strategies for Hyperkalemia Management at an Academic Medical Center.

PURPOSE: While intravenous (IV) insulin is often administered at a fixed dose of 10 units for acute hyperkalemia, optimal dosing for minimizing hypoglycemia while effectively reversing hyperkalemia has not been established. The purpose of this analysis was to evaluate the effect of insulin dosing strategies on hypoglycemia in patients with hyperkalemia. METHODS: Adult patients presenting to an academic medical center who received IV insulin for hyperkalemia between 2016 and 2020 were retrospectively identified. Patients treated with 10 units of insulin (fixed) were compared to those who received < 10 units (reduced). The primary outcome was the incidence of hypoglycemia (blood glucose < 70 mg/dL) within 12 hours of insulin administration. Secondary outcomes included the incidence of severe hypoglycemia (blood glucose < 40 mg/dL) and change in potassium. Multivariable analyses were used to assess for risk factors for hypoglycemia and severe hypoglycemia. FINDINGS: Of the 2576 patients included, 305 (11.8%) received reduced dosing and 2271 (88.2%) received fixed dosing. Hypoglycemia occurred in 16.7% of the reduced group and 15.9% of the fixed group (P = 0.70). Severe hypoglycemia occurred in 2.3% of the reduced group and 2.5% of the fixed group (P = 0.86). Median potassium reduction from baseline to first check post-insulin was less with reduced dosing (-0.6 mEq/L vs -0.8 mEq/L, P < 0.001). On multivariable regression analysis, greater weight-based insulin dose and ED location were significant predictors for hypoglycemia and severe hypoglycemia. Location in the intensive care unit was associated with a decreased risk of hypoglycemia. Higher pre-insulin glucose was protective for hypoglycemia and severe hypoglycemia. IMPLICATIONS: The incidence of hypoglycemia was similar among both groups. Greater weight-based insulin dose was a significant risk factor for hypoglycemia, while higher baseline glucose levels were associated with a decreased risk, indicating that patient-specific insulin dosing for hyperkalemia may be warranted.

Safety of Intravenous Push Valproate Compared with Intravenous Piggyback at a Tertiary Academic Medical Center.

BACKGROUND AND OBJECTIVES: Data are limited regarding the safety associated with administering valproate sodium by intravenous push (IVP) compared with intravenous piggyback (IVPB). The objective of this retrospective pre-post analysis was to compare the safety profile of valproate administration via IVPB from March to May 2022 and IVP from June to August 2022. METHODS: A total of 890 IVPB and 440 IVP administrations were included. The major endpoint of this analysis was the incidence of infusion site reactions (infiltration or phlebitis). RESULTS: The incidence of documented intravenous (IV) site reactions demonstrated minimal differences between both IVPB and IVP administration cohorts. Based on the Naranjo algorithm, all IVPB and IVP infusion site reactions were classified as possible or doubtful. Additional safety endpoints included bradycardia, hypotension, or sedation attributable to valproate sodium administration. Similar safety profiles were observed, including valproate-associated bradycardia, hypotension, and sedation events. All safety events were further classified as possible or doubtful by the Naranjo algorithm. Time from pharmacist verification to valproate administration was also collected. The mean time from pharmacist order verification to valproate administration was significantly faster in the IVP cohort compared to the IVPB cohort. CONCLUSION: IVP valproate administration may be considered safe, allowing for more optimal clinical and operational outcomes in the acute care setting.

Evaluating the incidence of acute kidney injury and gentamicin synergy dosing for endocarditis.

Objectives: Current infective endocarditis guidelines recommend two different gentamicin synergy dosing strategies for selected Gram-positive organisms. The purpose of this analysis was to evaluate the incidence of acute kidney injury (AKI) with gentamicin synergy dosing, comparing divided-daily and once-daily dosing strategies for infective endocarditis (IE). Methods: Groups were split into patients who received gentamicin divided-daily dosing and once-daily (3 mg/kg) dosing for Gram-positive IE. The primary outcome was the incidence of AKI defined by RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria after starting gentamicin. A multivariable logistic regression analysis was performed to identify possible independent predictors of developing AKI. Notable secondary outcomes included hospital length of stay, need for gentamicin dose adjustments based on therapeutic drug monitoring, and assessment of each case of AKI using the Naranjo algorithm. Results: The incidence of AKI was significantly higher in the divided-daily group compared with the once-daily group (52.5% versus 13%, P < 0.01). The divided-dosing group had significantly longer median [IQR] hospital length of stay (19 days [12:29] versus 13.5 days [9:22], P < 0.01) and a greater number of patients who required dose adjustments (76.2% versus 21.7%, P < 0.01). The multivariable regression analysis showed that the divided-dosing strategy, duration and institution were independently associated with incidence of AKI. Conclusions: This analysis suggests a lower incidence of AKI in the treatment of endocarditis with gentamicin synergy dosed once-daily compared with a divided-daily dosing. Further studies are warranted to assess if there is a difference in efficacy between gentamicin synergy dosing strategies and in gentamicin compared with no gentamicin regimens for IE.

Comparison of Early Versus Late Adjunctive Vasopressin and Corticosteroids in Patients With Septic Shock.

BACKGROUND: Vasopressin (VP) and hydrocortisone (HC) have been shown to improve outcomes in patients with septic shock. However, there is very little literature addressing the impact of the timing of the combination. OBJECTIVE: This study was conducted to evaluate the impact of early versus late initiation of both VP and HC on time to shock reversal in septic shock patients. METHODS: This was a retrospective study conducted at a tertiary academic medical center. Data were collected from system-generated reports, which were used to identify patients with septic shock who were admitted to an intensive care unit (ICU) and received both VP and HC. The primary endpoint was time to shock reversal. Patients were divided into the "early" group if both VP and HC were initiated within 12 hours of vasopressor initiation or into the "late" group if either VP or HC (or both agents) were initiated after 12 hours of vasopressor initiation. RESULTS: A total of 122 patients were included in the analysis. Early initiation was associated with a shorter time to shock reversal (34 hours vs 65 hours; P = 0.012) compared to late initiation. There were no differences in ICU length of stay, mortality, the number patients requiring renal replacement therapy, or the duration of mechanical ventilation in either group. CONCLUSION AND RELEVANCE: Our study addressed a major gap in the literature and suggests that adding the combination of VP and HC within 12 hours of septic shock may be associated with improved patient outcomes.

A Narrative Review on the Administration of Inhaled Prostaglandins in Critically Ill Adult Patients With Acute Respiratory Distress Syndrome.

OBJECTIVE: To describe the effect of inhaled prostaglandins on both oxygenation and mortality in critically ill patients with acute respiratory distress syndrome (ARDS), with a focus on safety and efficacy in coronavirus disease 2019 (COVID-19)-associated ARDS and non-COVID-19 ARDS. DATA SOURCES: A literature search of MEDLINE was performed using the following search terms: inhaled prostaglandins, inhaled epoprostenol, inhaled nitric oxide, ARDS, critically ill. All abstracts were reviewed. STUDY SELECTION AND DATA EXTRACTION: Relevant English-language reports and studies conducted in humans between 1980 and June 2023 were considered. DATA SYNTHESIS: Data regarding inhaled prostaglandins and their effect on oxygenation are limited but show a benefit in patients who respond to therapy, and data pertaining to their effect on mortality is scarce. Concerns exist regarding the formulation of inhaled epoprostenol (iEPO) utilized in addition to modes of medication delivery; however, the limited data surrounding their use have shown a reasonable safety profile. Other avenues and beneficial effects may exist with inhaled prostaglandins, such as use in COVID-19-associated ARDS or non-COVID-19 ARDS patients undergoing noninvasive mechanical ventilation or during patient transport. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: The use of inhaled prostaglandins can be considered in critically ill patients with COVID-19-associated ARDS or non-COVID-19 ARDS who are experiencing difficulties with oxygenation refractory to nonpharmacologic strategies. CONCLUSIONS: The use of iEPO and other inhaled prostaglandins requires further investigation to fully elucidate their effects on clinical outcomes, but it appears these medications may have a potential benefit in COVID-19-associated ARDS and non-COVID-19 ARDS patients with refractory hypoxemia but with little effect on mortality.

Prevalence, risk factors, and outcomes associated with delayed second doses of antibiotics in sepsis at a large academic medical center.

Objective: To evaluate the prevalence, risk factors, and clinical impact of delays in second doses of antibiotics in patients with sepsis. Design: Single-center, retrospective, observational study. Setting: Large teaching hospital. Patients: Adult patients who triggered an electronic sepsis alert in the emergency department (ED), received ≥2 doses of vancomycin or an antipseudomonal beta-lactam, and were discharged with an ICD-10 sepsis code. Methods: We assessed the prevalence of delays in second doses of antibiotics by ≥25% of the recommended dose interval and conducted multivariate regression analyses to assess for risk factors for delays and in-hospital mortality. Results: The cohort included 449 patients, of whom 123 (27.4%) had delays in second doses. In-hospital death occurred in 31 patients (25.2%) in the delayed group and 71 (21.8%) in the non-delayed group (p = 0.44). On multivariate analysis, only location in a non-ED unit at the time second doses were due was associated with delays (OR 2.75, 95% CI 1.20-6.32). In the mortality model, significant risk factors included malignant tumor, respiratory infection, and elevated Sequential Organ Failure Assessment (SOFA) score but not delayed second antibiotic doses (OR 1.19, 95% CI 0.69-2.05). In a subgroup analysis, delayed second doses were associated with higher mortality in patients admitted to non-intensive care units (ICUs) (OR 4.10, 95% CI 1.32-12.79). Conclusions: Over a quarter of patients with sepsis experienced delays in second doses of antibiotics. Delays in second antibiotic doses were not associated with higher mortality overall, but an association was observed among patients admitted to non-ICUs.

Evaluation of Dexmedetomidine as an Adjunct to Phenobarbital for Alcohol Withdrawal in Critically Ill Patients.

INTRODUCTION: Dexmedetomidine (DEX) is commonly used with benzodiazepines for the management of alcohol withdrawal syndrome (AWS), but limited data exist regarding its use with phenobarbital (PHB). This analysis evaluated the utility of DEX in addition to PHB for AWS in adult patients admitted to the intensive care unit (ICU). METHODS: This was a single-center, retrospective cohort analysis of critically ill adult patients who received PHB plus either DEX or different adjunctive therapies (NO-DEX) for AWS between 2018 and 2021. Patients were excluded if they had underlying altered mental status or seizure disorder unrelated to AWS or received PHB at outside hospitals. Coarsened exact matching (CEM) was performed to match patients on baseline characteristics in a 1:1 ratio. The primary outcome was ICU length of stay (LOS). A multivariate linear regression analysis was performed to assess the effects of DEX on ICU LOS when accounting for confounders. Secondary outcomes included days with delirium and incidence of mechanical ventilation after PHB administration. RESULTS: Of the 606 encounters evaluated, 197 met criteria for inclusion. After CEM, 56 encounters remained in each group for analysis. The median ICU LOS was 97.2 [50.1:139.5] hours for the DEX group and 47.5 [28.8:88.1] hours for the NO-DEX group (P = .002). The multivariate linear regression analysis showed the use of DEX (P = .008) was independently associated with an increased ICU LOS by 49.8 h. The DEX group had higher rates of total delirium days (208 vs 143 days, P < .001) and a higher incidence of mechanical ventilation after PHB administration (32% vs 9%, P < .001). CONCLUSION: This analysis suggests the use of adjunctive DEX with PHB for AWS was associated with a prolonged ICU LOS. Additional studies are needed to further understand the role of adjunctive DEX in the treatment of AWS in critically ill patients.

Evaluation of Rocuronium Continuous Infusion in Critically Ill Patients During the COVID-19 Pandemic and Drug Shortages.

Background: Limited data exist to support the use of rocuronium continuous infusions in the intensive care unit (ICU). Objective: To evaluate the dosing and monitoring of adult patients who received rocuronium for hypoxemic respiratory failure during the Coronavirus Disease 2019 (COVID-19) pandemic. Methods: This was a retrospective, single-center study from March 1, 2020 to May 31, 2020. We identified all adult patients admitted to any ICU who received rocuronium via continuous infusion. Patients were excluded if they received rocuronium for <6 hours. The main outcome of this study was to determine the median rocuronium maintenance continuous infusion rate in the ICU. Secondary outcomes of this study included the initial continuous infusion rate, duration of therapy, cumulative dose, frequency and median of rocuronium boluses, time to resolution of neuromuscular blockade, and the relationship between the hourly administration rates of rocuronium and train-of-four (TOF) assessments. Results: Seventy-one patients and 97 paralytic infusions were included. Fifty-nine patients (83%) were positive for SARS CoV-2. Of the 97 rocuronium infusions, the median dose at initiation was 3 (3-5) mcg/kg/min and duration of infusion was 45 (23.6-92.5) hours. The median continuous infusion maintenance rate was 4.3 (2.8-7.2) mcg/kg/min. There was a negligible correlation between the dose of rocuronium and the TOF results (r = .04). A total of 1775 TOFs were assessed, of which 46.2% were over-paralyzed, 35.7% well-paralyzed, and 18.1% under-paralyzed. Conclusions: The initial and maintenance infusion doses in our analysis were lower than what have been previously referenced.

Naloxone Versus Methylnaltrexone for Opioid-Induced Constipation in Critically Ill Patients.

BACKGROUND: Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for managing OIC. OBJECTIVE: The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients. METHODS: A retrospective analysis was conducted on adult patients who received NLX or MNTX and a continuous opioid infusion for at least 48 hours. The primary end point was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of an opioid antagonist. Reversal of analgesia was assessed by comparing the total number of morphine milligram equivalents (MME) 24 hours preopioid and postopioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours. RESULTS: Baseline characteristics were similar between patients receiving NTX (n = 89) and MNTX (n = 71). However, the time to the first BM with NLX was 18 hours compared with 41 hours with MNTX (P = 0.004). There was no difference in MME requirements 24 hours pre/post NLX or MNTX administration. Naloxone administration was identified as a statistically significant predictor of BM within 48 hours (odds ratio [OR] = 2.68 [1.33-5.38]). CONCLUSION AND RELEVANCE: The time to first BM was shorter with enteral NLX. Both NLX and MNTX appear to be effective for the management of OIC without causing reversal of analgesia. Future controlled, prospective trials comparing these agents are warranted.

Managing Clinical Programs in Pharmacy at an Academic Medical Center in the United States.

Managing clinical pharmacy programs requires communication, coordination, and organization to provide the best possible care to patients and to support staff members. While different areas of pharmacy have slight variations in management style, there are core concepts that all clinical managers should address. These include training, staff evaluation and  support, assessment and improvement of policies and processes and research. Standardized training performed by high performing members of  staff is essential in providing the framework for strong employees and clinical  pharmacists. Routine communication, evaluation, and discussion of reward and promotion will provide support to staff and recognition of high-quality  work. Continued evaluation and improvement of policies and processes will  bring attention to areas of improvement and how the change can be agreed  upon and implemented. Research is necessary to advance the healthcare  practice and improve patient outcomes. Managers and administrators should tailor their approach based on what is best for their practice setting,  institution, and staff to promote strong and capable pharmacists, policies, and workflow to provide the best possible care to patients.

La gestión de los programas de Farmacia Clínica requiere comunicación, coordinación y organización para brindar la mejor atención  posible a los pacientes y apoyar a los profesionales de los servicios de  farmacia. Si bien existen ligeras variaciones entre los estilos de gestión de los  diferentes ámbitos de la farmacia hospitalaria, existen algunos conceptos  básicos que todos los gestores clínicos deben abordar. Estos incluyen  formación, evaluación y apoyo al personal, evaluación y mejora de políticas y  procesos, e investigación y docencia. La formación reglada impartida por  personal cualificado es esencial para proporcionar un marco de actuación sólido encaminado a fortalecer las competencias del personal en general y de  los farmacéuticos clínicos en particular. La comunicación, evaluación y  discusión continuas sobre recompensas y promociones sirven para intensificar el apoyo al personal y reconocer la excelencia profesional. La  evaluación y mejora continuas de políticas y procesos ayudan a identificar  posibles áreas de mejora y a consensuar e implementar los cambios  necesarios. La investigación es necesaria para optimizar la atención sanitaria y  mejorar los resultados en salud. Los gerentes y responsables hospitalarios  deben adaptar sus métodos de trabajo en función de las necesidades de su  práctica asistencial, de las características de la institución en la que trabajan y  de los profesionales que ejercen sus funciones en ella. De este modo, podrá  promoverse el desarrollo de profesionales farmacéuticos, políticas y rutinas de  trabajo que permitan ofrecer a los pacientes la más alta calidad asistencial.

Gestión de programas clínicos en farmacia en un hospital docente de los Estados Unidos / Managing Clinical Programs in Pharmacy at an Academic Medical Center in the United States

La gestión de los programas de Farmacia Clínica requiere comunicación,coordinación y organización para brindar la mejor atención posiblea los pacientes y apoyar a los profesionales de los servicios de farmacia. Sibien existen ligeras variaciones entre los estilos de gestión de los diferentesámbitos de la farmacia hospitalaria, existen algunos conceptos básicos quetodos los gestores clínicos deben abordar. Estos incluyen formación, evaluacióny apoyo al personal, evaluación y mejora de políticas y procesos,e investigación y docencia. La formación reglada impartida por personalcualificado es esencial para proporcionar un marco de actuación sólidoencaminado a fortalecer las competencias del personal en general y delos farmacéuticos clínicos en particular. La comunicación, evaluación y discusióncontinuas sobre recompensas y promociones sirven para intensificarel apoyo al personal y reconocer la excelencia profesional. La evaluacióny mejora continuas de políticas y procesos ayudan a identificar posiblesáreas de mejora y a consensuar e implementar los cambios necesarios. Lainvestigación es necesaria para optimizar la atención sanitaria y mejorarlos resultados en salud. Los gerentes y responsables hospitalarios debenadaptar sus métodos de trabajo en función de las necesidades de su prácticaasistencial, de las características de la institución en la que trabajany de los profesionales que ejercen sus funciones en ella. De este modo,podrá promoverse el desarrollo de profesionales farmacéuticos, políticas yrutinas de trabajo que permitan ofrecer a los pacientes la más alta calidadasistencial.

Managing clinical pharmacy programs requires communication, coordination,and organization to provide the best possible care to patients andto support staff members. While different areas of pharmacy have slightvariations in management style, there are core concepts that all clinicalmanagers should address. These include training, staff evaluation and support,assessment and improvement of policies and processes and research.Standardized training performed by high performing members of staff isessential in providing the framework for strong employees and clinical pharmacists.Routine communication, evaluation, and discussion of reward andpromotion will provide support to staff and recognition of high-quality work.Continued evaluation and improvement of policies and processes will bringattention to areas of improvement and how the change can be agreed uponand implemented. Research is necessary to advance the healthcare practiceand improve patient outcomes. Managers and administrators shouldtailor their approach based on what is best for their practice setting, institution,and staff to promote strong and capable pharmacists, policies, andworkflow to provide the best possible care to patients.

Safety and efficacy of transitioning from intravenous to subcutaneous insulin in critically ill patients.

Background Intravenous (IV) insulin is commonly used for the management of hyperglycemia in critically ill patients. However, an assessment of real-world practices for the transition process from IV to Subcutaneous (SC) is lacking. Objective The objective of this study was to describe the real-world practice during insulin transition from IV to SC in intensive care unit (ICU) patients. Setting ICUs at a tertiary medical center. Methods This was a retrospective cohort study. Data were obtained from electronic medical records for all ICU patients for whom insulin infusions were ordered between Nov 2017-2018. Adult ICU patients were included if they were transitioned to a SC insulin regimen after spending at least 6 h on IV insulin infusion. Data collected include blood glucose readings, transition percentage, and the type of insulin regimen used after transition. Main outcome measure Assessment of the transition percentage and dysglycemic events during the insulin transition process from IV to SC. Results Two hundred patients with 4702 blood glucose checks were included. Of the included patients, 65% (130/200) were transitioned to a basal insulin-containing regimen. The median transition percentage in those patients was 45% [IQR: 28 - 69]. In the overall cohort, the number of patients who developed moderate and severe hypoglycemia was significantly higher prior to transition, while hyperglycemia was significantly higher after insulin transition. Conclusion We observed that patients were converted to SC therapy using a lower transition percentage than previously described. More data are needed to optimize the transition process in critically ill patients.

Protocol for assessing and predicting acute respiratory decline in hospitalized patients.

This protocol aids both new and experienced researchers in designing retrospective clinical and translational studies of acute respiratory decline in hospitalized patients. This protocol addresses (1) the basics of respiratory failure and electronic health record research, (2) defining patient cohorts as "mild, progressive, or severe" instead of "ICU versus non-ICU", (3) adapting physiological indices, and (4) using biomarker trends. We apply these approaches to inflammatory biomarkers in COVID-19, but this protocol can be applied to any progressive respiratory failure study. For complete details on the use and execution of this protocol, please refer to Mueller et al. (2020).

Intravenous levothyroxine stewardship program at a tertiary academic medical center.

PURPOSE: Based on the pharmacokinetic profile of levothyroxine, a 3-day hold guideline for adult patients ordered for intravenous (IV) levothyroxine was implemented at a tertiary academic medical center. The purpose of this study was to evaluate the impact of the implementation of an IV levothyroxine hold guideline. METHODS: This single-center, retrospective analysis identified patients ordered for IV levothyroxine during a 13-week period before and after implementation of the guideline. The primary outcome was guideline adherence, defined as full implementation of the 3-day hold. Secondary outcomes included the number of IV levothyroxine administrations avoided in the post-guideline group, extrapolated yearly cost avoidance (EYCA) after guideline implementation, reasons for guideline non-adherence, and number of safety reports involving IV levothyroxine. RESULTS: A total of 166 and 134 patients met inclusion criteria for the pre- and post-guideline groups, respectively. Guideline adherence was observed in 94 (70.1%) patients, resulting in 276 vials saved in the 13-week post-guideline period, which translated to an EYCA of $139,877. Forty orders (29.9%) were non-adherent to the guideline, with the most common reason stated as nil per os (NPO). No difference in safety outcomes was seen between the pre- and post-guideline groups, as evidenced by 1 safety report in each group. CONCLUSION: We observed a high rate of adherence to an IV levothyroxine hold guideline. This was associated with a substantial cost savings over the study period with no increase in reported safety events. To our knowledge, this is the first published report of an inpatient IV levothyroxine 3-day hold guideline.

Evaluation of Desmopressin in Critically Ill Patients with Hyponatremia Requiring 3% Hypertonic Saline.

BACKGROUND: Desmopressin (DDAVP) is often used for hyponatremia management but has been associated with increases in hospital length of stay and duration of hypertonic saline use. The purpose of this study was to evaluate hyponatremia management strategies and their effect on sodium correction in critically ill patients requiring 3% hypertonic saline (3HS). METHODS: This retrospective, single-center study included critically ill patients with hyponatremia (serum sodium ≤ 125 mEq/L) receiving 3HS from May 31 2015, to May 31 2019. Patients were divided into those who received 3HS for hyponatremia management (HTS) and those who received proactive or reactive DDAVP in addition to 3HS (D-HTS). Patients in either group could receive rescue DDAVP. The primary outcome was the percentage of patients achieving goal sodium correction of 5-10 mEq/L 24 h after 3HS initiation. RESULTS: Goal sodium correction was achieved in 52.5% of patients in HTS compared to 65.6% of patients in D-HTS (p = 0.21). Patients in HTS had a shorter duration of 3HS infusion (p = 0.0022) with no difference in ICU length of stay, free water intake, urine output, or serum sodium increases 12 and 24 h after receiving 3HS. Overcorrection during any 24- or 48 h period was not statistically different between groups. CONCLUSION: Patients in HTS and D-HTS had similar rates of achieving goal sodium correction at 24 h. A proactive or reactive DDAVP strategy led to an increase in 3HS duration and total amount with no significant difference in rates of overcorrection. Prospective, randomized studies assessing standardized strategies for hyponatremia management and DDAVP administration are warranted.

Evaluation of Delirium in Critically Ill Patients Prescribed Melatonin or Ramelteon.

BACKGROUND: An impaired sleep-wake cycle may be one factor that affects the development of delirium in critically ill patients. Several small studies suggest that exogenous melatonin or ramelteon may decrease the incidence and/or duration of delirium. OBJECTIVE: To compare the effect of prophylactic administration of melatonin, ramelteon, or no melatonin receptor agonist on the development of delirium in the intensive care unit (ICU). METHODS: This was a single-center, retrospective, observational cohort study of nondelirious patients in the ICU who received melatonin, ramelteon, or no melatonin receptor agonist. The primary end point was the incidence of delirium. Secondary end points included assessments of daily level of sedation and daily utilization of antipsychotic, sedative, and opioid agents. RESULTS: No difference was observed in the incidence of delirium among the melatonin, ramelteon, and placebo cohorts (18.7% vs 14.3% vs 13.8%; P = 0.77). A difference was observed in the rate of agitation and sedation among the 3 groups, with the greatest observed in the melatonin cohort. Additionally, there was a difference in the use of propofol, dexmedetomidine, and opioids. Overall, there was no difference in clinical outcomes, including duration of mechanical ventilation and ICU or hospital length of stay. CONCLUSION AND RELEVANCE: Therapy with melatonin, ramelteon, and no melatonin receptor agonist resulted in similar rates of delirium in a mixed ICU population. Despite significant differences in agitation, sedation, and medication utilization, there was no differences in the clinical outcomes evaluated.

Characterization of Nocturnal Neuroactive Medication Use and Related Sleep Documentation in Critically Ill Adults.

We retrospectively characterized scheduled, newly initiated, nocturnal neuroactive medication use, and related clinician documentation, in a cohort of consecutive adults admitted greater than or equal to 24 hours to seven different medical/surgical ICUs at two academic centers who had not received a scheduled nocturnal neuroactive medication prior to admission, over a 5-month period (April 1, 2017, to August 31, 2017). A total of 207 different newly initiated, scheduled nocturnal neuroactive medication orders were written (melatonin agonist 101 [48.8%], antipsychotic 80 [38.6%], antidepressant 17 [8.2%], benzodiazepine 9 [4.3%]) in 189 (9.7%) of the 1,955 patients. Among the 1,553 nights, the 189 patients spent in the ICU, a scheduled nocturnal neuroactive medication was administered on 1,103 (71%), an "as needed" nocturnal neuroactive medication was solely administered on 183 (11.8%), delirium occurred on 736 (47.4%), and nurses were twice as likely as physicians (28.8% vs 11.4%; p < 0.0001) to document a note about sleep quality. Among the 69.8% of patients discharged to the floor, and the 64.5% from the hospital, the scheduled nocturnal neuroactive medication was continued in 85.6% and 87.3%, respectively. Scheduled nocturnal neuroactive medication initiation is common, often continued beyond hospital discharge, and poorly documented.

Evaluation of Hypertriglyceridemia in Critically Ill Patients With Coronavirus Disease 2019 Receiving Propofol.

OBJECTIVES: To report the prevalence of, and evaluate risk factors for, the development of hypertriglyceridemia (defined as a serum triglyceride level of > 400 mg/dL) in patients with coronavirus disease 2019 who received propofol. DESIGN: Single-center, retrospective, observational analysis. SETTING: Brigham and Women's Hospital, a tertiary academic medical center in Boston, MA. PATIENTS: All ICU patients who with coronavirus disease 19 who received propofol between March 1, 2020, and April 20, 2020. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The major outcome of this analysis was to report the prevalence of, and risk factors for, the development of hypertriglyceridemia in patients with coronavirus disease 19 who received propofol. Minor outcomes included the development of acute pancreatitis and description of propofol metrics. Of the 106 patients that were included, 60 (56.6%) developed hypertriglyceridemia, with a median time to development of 46 hours. A total of five patients had clinical suspicion of acute pancreatitis, with one patient having confirmatory imaging. There was no difference in the dose or duration of propofol in patients who developed hypertriglyceridemia compared with those who did not. In the patients who developed hypertriglyceridemia, 35 patients (58.5%) continued receiving propofol for a median duration of 105 hours. Patients who developed hypertriglyceridemia had elevated levels of inflammatory markers. CONCLUSIONS: Hypertriglyceridemia was commonly observed in critically ill patients with coronavirus disease 2019 who received propofol. Neither the cumulative dose nor duration of propofol were identified as a risk factor for the development of hypertriglyceridemia. Due to the incidence of hypertriglyceridemia in this patient population, monitoring of serum triglyceride levels should be done frequently in patients who require more than 24 hours of propofol. Many patients who developed hypertriglyceridemia were able to continue propofol in our analysis after reducing the dose.

The Incidence of Propofol-Induced Hypertriglyceridemia and Identification of Associated Risk Factors.

OBJECTIVES: The objective of this study was to describe the incidence of propofol-induced hypertriglyceridemia and the risk factors associated with hypertriglyceridemia in mechanically ventilated ICU patients while receiving propofol. DESIGN: This was a single-center case-control study. SETTING: Brigham and Women's Hospital, a tertiary academic medical center in Boston, MA. SUBJECTS: Adult ICU patients who received continuous infusion propofol for at least 24 hours from May 1, 2019, to December 31, 2019, were included. Patients were excluded if they were diagnosed with acute pancreatitis upon admission or did not have any serum triglyceride levels evaluated during propofol administration. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The major outcome was the incidence and risk factors associated with the development of propofol-induced hypertriglyceridemia, defined as triglyceride level greater than or equal to 400 mg/dL. Minor outcomes included the prevalence of acute pancreatitis. A hybrid multivariate logistic regression analysis was used to evaluate the relation between individual risk factors and the dependent variable of hypertriglyceridemia. During the study period, 552 patients were evaluated for inclusion, of which 136 were included in the final analysis. A total of 38 patients (27.9%) developed hypertriglyceridemia with a median time to hypertriglyceridemia of 47 hours. The only significant independent risk factor for development of hypertriglyceridemia identified was the cumulative propofol dose (odds ratio, 1.04; 95% CI, 1.01-1.08; p = 0.016). Two of the 38 hypertriglyceridemia patients (5.3%) were diagnosed with acute pancreatitis. CONCLUSIONS: In our analysis, approximately one third of patients developed hypertriglyceridemia with cumulative propofol dose identified as a significant predictor of the development of hypertriglyceridemia. Despite a high incidence of hypertriglyceridemia, a significant number of patients continued propofol therapy, and a relatively low prevalence of pancreatitis was observed. Future analyses are warranted to further investigate these results.

Evaluation of the Efficacy and Safety of Inhaled Epoprostenol and Inhaled Nitric Oxide for Refractory Hypoxemia in Patients With Coronavirus Disease 2019.

OBJECTIVES: The objectives of this study were to evaluate the efficacy and safety of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019. DESIGN: Retrospective single-center study. SETTING: ICUs at a large academic medical center in the United States. PATIENTS: Thirty-eight adult critically ill patients with coronavirus disease 2019 and refractory hypoxemia treated with either inhaled epoprostenol or inhaled nitric oxide for at least 1 hour between March 1, 2020, and June 30, 2020. INTERVENTIONS: Electronic chart review. MEASUREMENTS AND MAIN RESULTS: Of 93 patients screened, 38 were included in the analysis, with mild (4, 10.5%), moderate (24, 63.2%), or severe (10, 26.3%), with acute respiratory distress syndrome. All patients were initiated on inhaled epoprostenol as the initial pulmonary vasodilator and the median time from intubation to initiation was 137 hours (68-228 h). The median change in Pao2/Fio2 was 0 (-12.8 to 31.6) immediately following administration of inhaled epoprostenol. Sixteen patients were classified as responders (increase Pao2/Fio2 > 10%) to inhaled epoprostenol, with a median increase in Pao2/Fio2 of 34.1 (24.3-53.9). The mean change in Pao2 and Spo2 was -0.55 ± 41.8 and -0.6 ± 4.7, respectively. Eleven patients transitioned to inhaled nitric oxide with a median change of 11 (3.6-24.8) in Pao2/Fio2. A logistic regression analysis did not identify any differences in outcomes or characteristics between the responders and the nonresponders. Minimal adverse events were seen in patients who received either inhaled epoprostenol or inhaled nitric oxide. CONCLUSIONS: We found that the initiation of inhaled epoprostenol and inhaled nitric oxide in patients with refractory hypoxemia secondary to coronavirus disease 2019, on average, did not produce significant increases in oxygenation metrics. However, a group of patients had significant improvement with inhaled epoprostenol and inhaled nitric oxide. Administration of inhaled epoprostenol or inhaled nitric oxide may be considered in patients with severe respiratory failure secondary to coronavirus disease 2019.