The Use of High-Dose Corticosteroids Versus Low-Dose Corticosteroids With and Without Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS: This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS: In this cohort, 110 (54%) and 95 (46%) patients received high-dose (≥10 mg dexamethasone equivalent) and low-dose (<10 mg dexamethasone equivalent) corticosteroids for more than 3 consecutive days, respectively. Thirty-five patients (32%) in the high-dose group and 33 patients (35%) in the low-dose group survived to hospital discharge (P = 0.85). There was no difference in 28-day mortality in patients who received high-dose corticosteroids without tocilizumab compared with those who received low-dose corticosteroids with tocilizumab (n = 38/82, 46% vs n = 19/40, 48% P = 0.99); however, there was a higher mortality if patients received low-dose corticosteroids without tocilizumab (n = 39/55, 71%, P = 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS: In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.

Low-Dose Tocilizumab With High-Dose Corticosteroids in Patients Hospitalized for COVID-19 Hypoxic Respiratory Failure Improves Mortality Without Increased Infection Risk.

BACKGROUND: Severe hypoxic respiratory failure from COVID-19 pneumonia carries a high mortality risk. There is uncertainty surrounding which patients benefit from corticosteroids in combination with tocilizumab and the dosage and timing of these agents. The balance of controlling inflammation without increasing the risk of secondary infection is difficult. At present, dexamethasone 6 mg is the standard of care in COVID-19 hypoxia; whether this is the ideal choice of steroid or dosage remains to be proven. OBJECTIVES: The primary objective was to assess the impact on mortality of tocilizumab only, corticosteroids only, and combination therapy in patients with COVID-19 respiratory failure. METHODS: A multihospital, retrospective study of adult patients with severe respiratory failure from COVID-19 who received supportive therapy, corticosteroids, tocilizumab, or combination therapy were assessed for 28-day mortality, biomarker improvement, and relative risk of infection. Propensity-matched analysis was performed between corticosteroid alone and combination therapies to further assess mortality benefit. RESULTS: The steroid-only, tocilizumab-only, and combination groups showed hazard reduction in mortality at 28 days when compared with supportive therapy. In a propensity-matched analysis, the combination group (daily equivalent dexamethasone 10 mg and tocilizumab 400 mg) had an improved 28-day mortality compared with the steroid-only group (daily equivalent dexamethasone 10 mg; hazard ratio (95% CI) = 0.56 (0.38-0.84), P = 0.005] without increasing the risk of infection. CONCLUSION AND RELEVANCE: Combination of tocilizumab and corticosteroids was associated with improved 28-day survival when compared with corticosteroids alone. Modification of steroid dosing strategy as well as steroid type may further optimize therapeutic effect of the COVID-19 treatment.

Clinical Use of Cangrelor After Percutaneous Coronary Intervention in Patients Requiring Mechanical Circulatory Support.

BACKGROUND: Patients with cardiogenic shock after percutaneous coronary intervention (PCI) may require mechanical circulatory support (MCS). The combination of dual antiplatelet therapy with cangrelor and continuous anticoagulation required for MCS may increase the risk of bleeding. OBJECTIVE: The objective of the study is to describe the complications and outcomes of patients who received cangrelor during MCS following PCI. METHODS: This is a single-center, retrospective, observational case series of 17 patients who received cangrelor while on MCS from June 2017 to September 2019. RESULTS: In a case series of 17 patients, 8 patients (47%) were supported with an Impella device and 4 patients (24%) with venoarterial (VA) extracorporeal membrane oxygenation (ECMO); 5 required (29%) concomitant VA ECMO and Impella support in the setting of cardiogenic shock. All patients received triple antithrombotic therapy with aspirin, heparin, and cangrelor. Cangrelor was commonly initiated at a median dose of 0.75 (range 0.5-4) µg/kg/min. Cangrelor dose adjustments included changes in increments up to 0.25 µg/kg/min with review of P2Y12 levels. A total of 10 patients (59%) experienced a bleeding event, most commonly located at the peripheral cannulation site (40%) and in the gastrointestinal tract (30%). Seven (70%) and 3 (30%) of the bleeding complications were classified as major and minor, respectively. No patient developed in-stent thrombosis during the hospitalization; 14 (82%) patients survived their MCS course. CONCLUSION AND RELEVANCE: This case series suggests that cangrelor doses less than 0.75 µg/kg/min may be beneficial. Larger studies should evaluate alternative dosing regimens.

Is P&T Ready to Add Rapid Cycle Analytics to Formulary?

Purpose: The intent of this article is to evaluate a novel approach, using rapid cycle analytics and real world evidence, to optimize and improve the medication evaluation process to help the formulary decision making process, while reducing time for clinicians. Summary: The Pharmacy and Therapeutics (P&T) Committee within each health system is responsible for evaluating medication requests for formulary addition. Members of the pharmacy staff prepare the drug monograph or a medication use evaluation (MUE) and allocate precious clinical resources to review patient charts to assess efficacy and value. We explored a novel approach to evaluate the value of our intravenous acetaminophen (IV APAP) formulary admittance. This new methodology, called rapid cycle analytics, can assist hospitals in meeting and/or exceeding the minimum criteria of formulary maintenance as defined by the Joint Commission Standards. In this particular study, we assessed the effectiveness of IV APAP in total hip arthroplasty (THA) and total knee arthroplasty (TKA) procedures. We assessed the correlation to same-stay opioid utilization, average length of inpatient stay and post anesthesia care unit (PACU) time. Conclusion: We were able to explore and improve our organization's approach in evaluating medications by partnering with an external analytics expert to help organize and normalize our data in a more robust, yet time efficient manner. Additionally, we were able to use a significantly larger external data set as a point of reference. Being able to perform this detailed analytical exercise for thousands of encounters internally and using a data warehouse of over 130 million patients as a point of reference in a short time has improved the depth of our assessment, as well as reducing valuable clinical resources allocated to MUEs to allow for more direct patient care. This clinically real-world and data-rich analytics model is the necessary foundation for using Artificial or Augmented Intelligence (AI) to make real-time formulary and drug selection decisions.

Sedation Requirements in Patients on Venovenous or Venoarterial Extracorporeal Membrane Oxygenation.

Background:There is a paucity of data evaluating optimal dosing strategies of commonly utilized opioids and sedatives for patients on extracorporeal membrane oxygenation (ECMO) support where pharmacokinetic and pharmacodynamic variables of these administered agents are altered. Objective: To assess the daily dosing requirement of sedatives and analgesics for patients on venovenous (VV) and venoarterial (VA) ECMO after the initial ECMO cannulation period. Methods: We performed a retrospective, observational study of adult patients receiving sedation and analgesia while receiving ECMO support for at least 24 hours. Patients cannulated at an outside hospital more than 24 hours before transfer, those with a history of intravenous drug use or acute alcohol withdrawal, or those who died within 48 hours of ECMO initiation were excluded. Results: We evaluated 26 patients on ECMO, including 13 on VV and 13 on VA ECMO. The median dose of fentanyl was 140 µg/h, with the VV group requiring a higher dose compared with the VA group (167 vs 106 µg/h, P < 0.001). The median doses of dexmedetomidine and propofol were 0.7 µg/kg/h and 26 µg/kg/min, respectively, with no significant differences between groups (P = 0.38 and P = 0.24, respectively). The median daily doses of fentanyl, dexmedetomidine, and propofol did not significantly increase throughout the time on ECMO support. Conclusions and Relevance: We found that the overall opioid daily dosing requirements were lower than previously reported in the literature. Additionally, light sedation strategies with a target RASS of -1 to 0 are feasible in this patient population.

The Safety of Midline Catheters for Intravenous Therapy at a Large Academic Medical Center.

Background: Midline catheters (MCs) have arisen as alternatives to peripherally inserted central catheters (PICCs) for both general intravenous therapy and extended outpatient parenteral therapy. However, there is a lack of data concerning the safety of medication therapy through midline for extended durations. Objective: The purpose of this study is to evaluate the safety of MCs for extended intravenous use. Methods: This was a retrospective cohort study evaluating patients who received intravenous therapy through an MC at a tertiary care academic medical center. The primary end point was the incidence of composite catheter-related adverse events that included local events, catheter dislodgment, infiltration, catheter occlusion, catheter-related venous thromboembolism, extravasation, and line-associated infection. Results: A total of 82 MC placements and 50 PICC placements were included; 50 MCs were for outpatient parenteral antimicrobial therapy, and 32 were for inpatient intravenous use. There were 21 complications per 1000 catheter-days in the outpatient group and 7 complications per 1000 catheter-days in the PICC group (P = 0.91). The median time to complication in both groups was 8 days. The antimicrobial classes commonly associated with complications were cephalosporins, carbapenems, and penicillins. Conclusion and Relevance: Our results suggest that intravenous therapy with MCs is generally safe for prolonged courses that do not exceed 14 days as compared with PICC lines, which can be placed for months. There is still limited evidence for the use of MCs between 14 and 28 days of therapy. This study can help guide our selection of intravenous catheters for the purpose of outpatient antimicrobial therapy.

Evaluation of Meropenem Extended Versus Intermittent Infusion Dosing Protocol in Critically Ill Patients.

Extended infusion (EI) administration of ß-lactams can improve target attainment in critically ill patients with altered pharmacokinetics/pharmacodynamics. To optimize meropenem dosing in patients with severe sepsis/septic shock, our Antimicrobial Stewardship Program implemented a EI meropenem (EIM) protocol in an 18-bed Medical Intensive Care Unit in March 2014. In this retrospective study, we compared intensive care unit (ICU) mortality and clinical response in patients who received meropenem for ≥72 hours administered per EIM protocol of 1 g over 3 hours every 8 hours versus intermittent infusion (IIM) protocol of 500 mg over 30 minutes every 6 hours. Age, weight, comorbidities, severity of illness, and vasopressor use were comparable between groups (EIM protocol n = 52, IIM protocol n = 96). The IIM protocol group had higher rates of renal dose adjustment at meropenem initiation. Among 56 identified gram-negative (GN) pathogens, 94% had meropenem minimal inhibitory concentration ≤0.25 mg/L. The ICU mortality was lower (19 vs 37%; P = .032) and clinical response was higher (83% vs 46%; P < .01) in the EIM protocol versus IIM protocol group. Total vasopressor days were shorter (2 vs 3 days; P = .038), and white blood cell normalization rate was higher (87% vs 51%; P < .01) in the EIM protocol versus IIM protocol group. There was no difference in days of mechanical ventilation, duration of therapy, and ICU stay. The IIM protocol was also identified as an independent risk factor associated with ICU mortality (hazard ratio: 3.653, 95% confidence interval: 1.689-7.981; P = .001) after adjusting for Sequential Organ Failure Assessment score. In this cohort of patients with severe sepsis/septic shock and highly susceptible GN pathogens, there was improved mortality and clinical response in the EIM protocol group.

Evaluation of Pharmacy-Developed Antibiotic Desensitization Protocols.

BACKGROUND: Parameters within reconstitution, storage, stability, and administration may be optimized according to the unique pharmacokinetics of each antibiotic to ensure a successful desensitization. OBJECTIVE: The study aims to evaluate the successfulness and safety of antibiotic desensitization protocols developed by the pharmacy department at our institution. METHODS: A retrospective study was conducted at an 800-bed, urban, tertiary care, academic medical center. A total of 36 patients 18 years of age or older, admitted to our intensive care units between March 2013 and July 2017, who underwent antibiotic desensitization utilizing our pharmacy developed protocols were included. RESULTS: In 36 patients, 61 desensitization cases were identified and included; 17 (47%) were male, 27 (75%) were Caucasian, and the median age was 55 years (range 19-94). In all, 15 different antibiotics were administered for desensitization, with meropenem (n = 12, 20%), ampicillin (n = 7, 11%), piperacillin/tazobactam (n = 7, 11%), and penicillin (n = 7, 11%) being the most common; 59 (97%) of 61 desensitizations were completed successfully with or without experiencing reactions, and 53 (89%) of the successful desensitization cases were completed without reactions. Two cases were categorized as anaphylaxis, which was severe enough to terminate the desensitization process. Of the 59 cases successfully completed, the 6 (10%) cases that experienced reactions were managed successfully during desensitization with completion of the process. Conclusion and Relevance: The findings suggest that our pharmacy-developed antibiotic desensitization protocols are successful and safe and may be adapted by other institutions.

Safety of the Peripheral Administration of Vasopressor Agents.

Vasopressors are an integral component of the management of septic shock and are traditionally given via a central venous catheter (CVC) due to the risk of tissue injury and necrosis if extravasated. However, the need for a CVC for the management of septic shock has been questioned, and the risk of extravasation and incidence of severe injury when vasopressors are given via a peripheral venous line (PVL) remains poorly defined. We performed a retrospective chart review of 202 patients who received vasopressors through a PVL. The objective was to describe the vasopressors administered peripherally, PVL size and location, the incidence of extravasation events, and the management of extravasation events. The primary vasopressors used were norepinephrine and phenylephrine. The most common PVL sites used were the forearm and antecubital fossa. The incidence of extravasation was 4%. All of the events were managed conservatively; none required an antidote or surgical management. Vasopressors were restarted at another peripheral site in 88% of the events. The incidence of extravasation was similar to prior studies. The use of a PVL for administration of vasopressors can be considered in patients with a contraindication to a CVC.

Venous Thromboembolism Prophylaxis: A Narrative Review With a Focus on the High-Risk Critically Ill Patient.

Venous thromboembolism (VTE) is a major health concern associated with significant morbidity and mortality. Critically ill patients are at an increased risk of VTE compared to general medical patients due to unique risk factors: prolonged immobilization, invasive lines and devices, certain medications, and acquired thrombophilia. Furthermore, VTE in the critically ill is associated with increased duration of mechanical ventilation, increased length of intensive care unit and hospital stay, and a trend toward increased mortality. Clinical practice guidelines therefore recommend VTE prophylaxis with either subcutaneous heparin or low-molecular-weight heparin for all critically ill patients without contraindication. Yet, many patients will develop VTE despite appropriate pharmacologic prophylaxis, which has led to interest in risk-stratifying critically ill patients for more aggressive prophylaxis strategies. Recent research identified patients at highest risk of failure of thromboprophylaxis and provided insight into the pathophysiologic mechanisms. Obesity and the receipt of vasopressors are 2 risk factors consistently identified in observational studies; further clinical data support decreased absorption of anticoagulant administered via the subcutaneous route as the likely mechanism behind thromboprophylaxis failure in these patient populations. Several studies have investigated novel thromboprophylaxis strategies to circumvent pharmacokinetic limitations in patients who are obese or on vasopressors: increased fixed-dose, weight-based subcutaneous, or continuous intravenous infusion of a prophylactic dose of anticoagulant has shown promise in limited studies; however, the results have yet to demonstrate superiority compared to current standard-of-care. This review discusses observational studies identifying patients at risk of thromboprophylaxis failure and critiques clinical studies evaluating novel thromboprophylaxis strategies in high-risk, critically ill patients with a focus on their limitations. Future studies are currently being conducted that will provide further guidance into the appropriate use of individualized thromboprophylaxis.

Clinical effects of intravenous to oral amiodarone transition strategies in critically ill adult patients.

WHAT IS KNOWN AND OBJECTIVE: There is limited guidance on how to transition critically ill patients from intravenous (IV) to oral (PO) amiodarone. The objective of this study was to assess the impact of IV and PO amiodarone overlap on short-term tachyarrhythmia recurrence and adverse hemodynamic outcomes in the intensive care unit. METHODS: This is a retrospective, single-center analysis of critically ill adults who were treated with IV amiodarone for a supraventricular arrhythmia with rapid ventricular rate (RVR) and transitioned to PO amiodarone while inpatient. Patients were excluded if rate control was not achieved prior to the PO transition. Receipt of concomitant IV and PO therapy for ≤2 hours was considered no overlap (NOV) and >2 hours was considered overlap (OV). Tachyarrhythmia recurrence and adverse hemodynamic events were compared between groups. RESULTS: A total of 90 patients (45 NOV, 45 OV) were included in the analysis. The median overlap duration was 0.1 (-1.3 to 1.2) hours in the NOV arm and 4 (2.6-6.1) hours in the OV arm. Recurrence of RVR occurred in 9 (20%) patients in each arm (P = 1.0). The median time from IV discontinuation to return of tachyarrhythmia was 10.5 hours. There were no significant differences in amiodarone dosing, electrolyte abnormalities, volume status or concomitant cardiac medications at the time of IV to PO transition. Hypotension occurred in 13% and 20% (P = 0.369) and bradycardia in 9% and 13% (P = 0.502) of patients in the NOV and OV arms, respectively. WHAT IS NEW AND CONCLUSION: Providing IV and PO overlap of amiodarone for a median of 4 hours did not decrease the rate of early tachyarrhythmia recurrence. Future studies are warranted to evaluate the impact of alternative amiodarone dosing strategies on breakthrough tachyarrhythmia.

Evaluating Vasopressor Discontinuation Strategies in Patients With Septic Shock on Concomitant Norepinephrine and Vasopressin Infusions.

BACKGROUND: There is little data guiding clinicians on how to discontinue vasopressors among septic shock patients on concomitant norepinephrine (NE) and vasopressin (VP). OBJECTIVE: To determine the incidence of hypotension within 24 hours of discontinuing NE (NE DC first) versus VP (VP DC first) first in septic shock patients. METHODS: This retrospective study evaluated septic shock patients admitted to the medical intensive care unit (MICU) and surgical ICU (SICU) receiving concomitant NE and VP. Receipt of additional vasopressors, mixed shock states, expired or care withdrawn, and NE and VP discontinued simultaneously were exclusion criteria. The primary outcome was incidence of hypotension within 24 hours of first vasopressor discontinuation. Secondary outcomes included time to hypotension, hospital length of stay (LOS), ICU LOS, and ICU mortality. RESULTS: A total of 80 patients were included (NE DC first [n = 35]; VP DC first [n = 45]), with a median age of 73 years and median modified Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores of 21 and 7, respectively. More patients in the NE DC first group were in the SICU (42.9% vs 20.0%; P = 0.048) with more intra-abdominal infections (40.0% vs 15.6%; P = 0.021) and fewer appropriate empirical antibiotics (62.9% vs 86.7%; P = 0.018). Hypotension within 24 hours of first agent discontinuation was higher in the VP DC first group (28.6% vs 62.2%; P = 0.004), with similar hospital LOS and ICU mortality. Multivariate analysis identified VP DC first as an independent predictor of hypotension (odds ratio = 7.2; CI = 2.3-22.7). CONCLUSION: Among septic shock patients on concomitant NE and VP, discontinuation of VP first was associated with an increased incidence of hypotension; future prospective control trials are warranted.

Incidence of Adverse Events During Peripheral Administration of Sodium Chloride 3.

PURPOSE: Traditionally, sodium chloride 3% has been administered via a central venous line (CVL) because of the perceived risk of infiltration and tissue injury due to its high osmolarity. In clinical practice, sodium chloride 3% is commonly administered through peripheral venous catheters (PVCs) given the necessity of timely administration. However, there is no published data on the safety of administering sodium chloride 3% through PVCs in the adult population. The objective of this study was to evaluate the safety of peripheral venous administration of sodium chloride 3%. MATERIALS AND METHODS: A retrospective review was conducted in patients who received sodium chloride 3% in the intensive care unit (ICU). Patients were excluded if they had a CVL for the entire duration of the infusion or younger than 18 years at the time of administration. Baseline patient and infusion characteristics were collected. Infusion-related adverse events (IRAEs) were recorded, graded, and interventions required were noted. RESULTS: A total of 66 patients were included in the analysis. The most common indication was hyponatremia and majority of the patients were managed in the neurosurgical ICU. The most common risk factor for IRAEs was the presence of altered mental status. Four patients experienced an IRAE at an event rate of 6.1%. Patients who experienced an IRAE ranged from 38 to 82 years old. The IRAEs were grade 1 in severity, managed conservatively with removal of the PVC, and 2 of the 4 patients had their infusions restarted peripherally. The time to initial IRAE ranged from 2 to 94 hours. For the entire cohort, hospital and ICU length of stay were 8 and 4 days, respectively. CONCLUSIONS: The rate of IRAEs related to the infusion of sodium chloride 3% through PVCs appears to be similar to those reported with other hyperosmotic agents and could be considered for patients who need time-sensitive therapy.

Methylnaltrexone Versus Naloxone for Opioid-Induced Constipation in the Medical Intensive Care Unit.

BACKGROUND: Opioid-induced constipation (OIC) is common in critically ill patients; it leads to complications that can increase hospital stay and, rarely, bowel perforation. Opioid antagonists are considered a logical approach to treat OIC; however, the agent of choice has yet to be determined. OBJECTIVE: To assess the effectiveness and safety of enteral naloxone (NTX) versus subcutaneous methylnaltrexone (MNTX) for the treatment of OIC in the medical intensive care unit. METHODS: This retrospective review evaluated patients who received fentanyl continuous infusions for at least 72 hours and were initiated on NTX or MNTX. Active colitis, mechanical gastrointestinal obstruction, and inability to receive NTX orally were exclusion criteria. The primary outcome was time to first bowel movement (BM). Secondary outcomes included total number of BMs within 48 hours, opioid requirements after NTX or MNTX, and change in any of the following after the opioid antagonist: heart rates, mean arterial pressures, and level of sedation. A post hoc subgroup analysis of patients on vasopressors was conducted. RESULTS: Baseline characteristics were similar between patients receiving NTX (n = 52) and MNTX (n = 48), except the MNTX group required a higher median norepinephrine dose (0.22 vs 0.1 µg/kg/min, P = 0.001). The median times to first BM for NTX and MNTX were 30 and 24 hours ( P = 0.165). There was no difference in the primary outcomes for patients on vasopressors. Both groups did not require additional fentanyl equivalents, as evidenced by stable vitals and opioid requirements during treatment. CONCLUSIONS: Both agents appear to be effective and safe for the treatment of OIC; however, future controlled prospective trials are warranted.

Tolerability of Enteral Nutrition in Mechanically Ventilated Patients With Septic Shock Who Require Vasopressors.

PURPOSE: Enteral nutrition (EN) is often held in patients receiving vasopressor support for septic shock. The rationale for this practice is to avoid mesenteric ischemia. The objective of this study is to evaluate the tolerability of EN in patients with septic shock who require vasopressor support and determine factors associated with tolerance of EN. MATERIALS AND METHODS: This was a single-center retrospective review of adult patients admitted to the intensive care unit with a diagnosis of septic shock and an order for EN. The primary outcome was EN tolerance. Secondary outcomes included time to initiation of EN from the start of vasopressor(s), length of stay, and mortality. RESULTS: A total of 120 patients were included. Sixty-two percent of patients tolerated EN. The most common reason for intolerance of EN was gastric residuals > 250 mL (74%). No reports of mesenteric ischemia were observed. A multivariate analysis demonstrated that patients with septic shock initiating EN within 48 hours and receiving norepinephrine-equivalent doses of 0.14 µg/kg/min or less were more likely to tolerate EN. CONCLUSION: Based on our observation, early EN may be tolerated and safely administered in patients with septic shock who are adequately fluid resuscitated and receive doses of < 0.14 µg/kg/min of norepinephrine equivalents.

Dexmedetomidine for refractory adrenergic crisis in familial dysautonomia.

OBJECTIVE: Adrenergic crises are a cardinal feature of familial dysautonomia (FD). Traditionally, adrenergic crises have been treated with the sympatholytic agent clonidine or with benzodiazepines, which can cause excessive sedation and respiratory depression. Dexmedetomidine is a centrally-acting α 2-adrenergic agonist with greater selectivity and shorter half-life than clonidine. We evaluated the preliminary effectiveness and safety of intravenous dexmedetomidine in the treatment of refractory adrenergic crisis in patients with FD. METHODS: Retrospective chart review of patients with genetically confirmed FD who received intravenous dexmedetomidine for refractory adrenergic crises. The primary outcome was preliminary effectiveness of dexmedetomidine defined as change in blood pressure (BP) and heart rate (HR) 1 h after the initiation of dexmedetomidine. Secondary outcomes included incidence of adverse events related to dexmedetomidine, hospital and intensive care unit (ICU) length of stay, and hemodynamic parameters 12 h after dexmedetomidine cessation. RESULTS: Nine patients over 14 admissions were included in the final analysis. At 1 h after the initiation of dexmedetomidine, systolic BP decreased from 160 ± 7 to 122 ± 7 mmHg (p = 0.0005), diastolic BP decreased from 103 ± 6 to 65 ± 8 (p = 0.0003), and HR decreased from 112 ± 4 to 100 ± 5 bpm (p = 0.0047). The median total adverse events during dexmedetomidine infusion was 1 per admission. Median hospital length of stay was 9 days [interquartile range (IQR) 3-11 days] and median ICU length of stay was 7 days (IQR 3-11 days). CONCLUSIONS: Intravenous dexmedetomidine is safe in patients with FD and appears to be effective to treat refractory adrenergic crisis. Dexmedetomidine may be considered in FD patients who do not respond to conventional clonidine and benzodiazepine pharmacotherapy.

Elevated Anti-Xa in the Setting of Prophylactic Unfractionated Subcutaneous Heparin Administration.

Venous thromboembolism prophylaxis with subcutaneous unfractionated heparin or low molecular weight heparin is a common practice in hospitalized patients. Typically, prophylactic doses of these medications have poor bioavailability and thus do not reach therapeutic serum concentrations. However, in certain circumstances, heparin binding proteins may become saturated. Here we report a case series of 5 patients who had elevated anti-Xa levels while receiving prophylactic dosing of subcutaneous unfractionated heparin.

Low dose vs high dose tocilizumab in COVID-19 patients with hypoxemic respiratory failure.

PURPOSE: Tocilizumab has been shown to decrease mortality when used concomitantly with steroids in COVID-19 with 8 mg/kg (max 800 mg) being the standard dose. Our study sought to assess whether a low dose (400 mg) shows similar benefit compared to a high dose for COVID patients concurrently on the same median dose of steroids. MATERIALS/METHODS: A retrospective, multihospital observational study of COVID-19 patients who received tocilizumab in conjunction with steroids between March 2020 and August 2021 was conducted. RESULTS: A total of 407 patients were analyzed with low dose group being significantly more ill at baseline as a higher percentage of patients received vasopressors, were admitted to the ICU and on mechanical ventilation. In the propensity-matched analysis, both groups receiving a median dexamethasone equivalent dose of 10 mg showed no difference in 28-day mortality (p = 0.613). The high dose group had a higher rate of fungal and viral infections. CONCLUSION: Compared to low dose tocilizumab, the high dose did not provide additional efficacy and mortality benefit but resulted in higher fungal and viral infections. This study illustrates that low dose tocilizumab can be an alternative to high dose during a drug shortage of tocilizumab without compensating for efficacy and safety, conserving resources for more patients.

The incidence of propofol infusion syndrome in critically-ill patients.

PURPOSE: PRIS is a potentially fatal syndrome characterized by various clinical symptoms and abnormalities. Experts suggest that propofol treatment duration ≥48 h or dose ≥83 µg/kg/min is associated with developing PRIS. We hypothesized PRIS might be underdiagnosed due to the overlap of PRIS clinical manifestations with critical illnesses. MATERIALS AND METHODS: Multihospital, retrospective study of adult patients who received continuous propofol infusion ≥48 h or dose ≥60µg/kg/min for >24 h since admission were assessed for the development of PRIS. RESULTS: The incidence of PRIS was 2.9% with a PRIS-associated mortality rate of 36.8%. In PRIS patients, propofol was administered at a median dose of 36.4 µg/kg/min and over a median duration of 147.0 h. The development of PRIS was observed at a median of 125.0 h post-propofol initiation and a cumulative dose of 276.5 mg/kg. The development of metabolic acidosis (78.9%), cardiac dysfunction (52.6%), hypertriglyceridemia (100%), and rhabdomyolysis (26.3%) were observed in our PRIS patients. CONCLUSION: PRIS can often be overlooked and underdiagnosed. It is important to monitor for early signs of PRIS in patients who are on prolonged propofol infusion. Prompt recognition and interventions can minimize the dangers resulting from PRIS.