Characterizing the Stability of Angiotensin II in 0.9% Sodium Chloride Using High Performance Liquid Chromatography and Liquid Chromatography Tandem Mass Spectrometry.

Purpose: The purpose of this study was to evaluate the stability of angiotensin II in 0.9% sodium chloride for up to 5 days. Methods: We prepared angiotensin II dilutions, by aseptically diluting 2.5 mg (1 mL) in 249 mL 0.9% sodium chloride creating a solution of 10 000 ng/mL. Admixtures were stored under refrigeration (5 ± 3°C). Stability of the dilution was assessed by: preservation of clarity, consistency of pH, and retention of concentration. Solutions were sampled at times 0, 24, 48, 72, 96, 120 hours. Solutions were analyzed via High-Performance Liquid Chromatography (HPLC-UV) and Liquid Chromatography Mass Spectrometry (LC-MS/MS). Retention of concentration was set a priori at > 90% of initial concentration. Results: Clarity, color, and pH at all sample time points remained constant. Both methods of analysis confirmed similar results. When stored under refrigeration, the concentration of angiotensin II solution remained above 90% of initial concentration throughout the entire sampling period. Conclusions: Angiotensin II in 0.9% sodium chloride stored in infusion bags under refrigeration (5 ± 3°C) maintained at least 90% of their original concentrations for up to 5 days. Stability was also demonstrated based on turbidity, color, and pH assessment.

Retrospective evaluation of LCP-tacrolimus (Envarsus XR) dosing in de novo kidney transplant.

INTRODUCTION: Tacrolimus is known to exhibit significant inter- and intra-patient pharmacokinetic (PK) and pharmacodynamic (PD) variability regarding therapeutic response. LCP-tacrolimus (LCPT-Envarsus XR) was approved in 2018 for use as a de novo immunosuppressive agent in kidney transplants, but there is limited evidence to guide de novo dosing of LCPT in patients with obesity. The primary objective of this study was to evaluate the impact of different calculated weight-based de novo LCPT dosing on early transplant outcomes. METHODS: This was a retrospective study of patients with obesity (BMI ≥ 30 kg/m2 ) who received a kidney transplant at the University of Illinois Hospital and Health System (UIH), between March 2019 and March 2021. Subjects were included if were age 18 years or older and received de novo LCPT throughout index hospitalization. The primary endpoint of this study was to compare correlations between the first tacrolimus trough level and dosing weight strategy (e.g., TBW, AdjBW, IBW). RESULTS: There was a statistically significant, though modest, correlation between all three dosing strategies and the first tacrolimus trough level (TBW correlation coefficient = .431, p < .001; AdjBW correlation coefficient = .455, p < .001; IBW correlation coefficient = .465; p < .001). In regression modeling for supratherapeutic levels each additional .01 mg/kg increase in dose by TBW, AdjBW, and IBW increased the odds of a supratherapeutic level by 1.46, 1.34, and 1.24, respectively (p < .001). CONCLUSIONS: The use of LCPT in kidney transplant recipients with obesity dosed using TBW demonstrated the strongest correlation with initial supratherapeutic tacrolimus levels. Larger prospective studies are needed to investigate the further impact of body weight on dosing regimens in the obese population.

Comparison of Vasopressor Duration in Septic Shock Patients With and Without Cirrhosis.

BACKGROUND: Patients with cirrhosis have immune dysfunction, altered inflammatory response, and hemodynamic changes which increase risk of septic shock and potentially prolong management with fluids, vasopressors, and other therapies. Due to limited available guidance, this study aimed to characterize vasopressor use in patients with cirrhosis in relation to patients without cirrhosis in septic shock. METHODS: This was a retrospective matched cohort analysis of 122 patients admitted to the intensive care unit (ICU) at an academic medical center from January 2015 to November 2017. Patients were grouped based on the presence or absence of cirrhosis and matched based on severity of illness scoring. The primary outcome was vasopressor duration. Secondary comparisons included total vasopressor requirement, length of hospital and ICU stay, in-hospital mortality, change in organ function, and discharge disposition. RESULTS: The group with cirrhosis had significantly longer median (interquartile range [IQR]) durations of vasopressor therapy compared with the group without cirrhosis (86.0 [42.0-164.5] vs 39.0 [14.5-82.0] hours; P = 0.003) leading to increased median (IQR) vasopressor exposure (71.7 [15.5-239.5] vs 24.7 [5.3-77.9] mg norepinephrine [NE] equivalents; P = 0.003). No difference was found in in-hospital mortality between groups. However, regression analysis showed vasopressor exposure was associated with in-hospital mortality. CONCLUSION AND RELEVANCE: Patients with cirrhosis in septic shock have increased vasopressor durations and overall requirements compared with patients without cirrhosis. Increased durations and requirements is associated with poorer outcomes independent of presence of cirrhosis. Future studies are needed to improve vasopressor treatment strategies and end points utilized in cirrhosis.

Safety of Immediate-Release Nifedipine.

Nifedipine immediate release (IR) is a short-acting dihydropyridine calcium channel blocker historically used for hypertensive crisis, but its use has decreased because of reports of adverse reactions such as myocardial infarction (MI), arrhythmias, and stroke. This was a retrospective evaluation of the safety of nifedipine IR in 122 patients at an academic medical center from January 1, 2009, to December 31, 2014. Patients were separated into high- and low-risk groups. High risk was defined as a medical history significant for arrhythmia, MI, or stroke. The primary outcome was a comparison of the composite incidence of nifedipine-associated adverse events including the following: new cardiology consultation, sentinel arrhythmia, stroke, MI, need for blood pressure support, transition to higher levels of care, or death. A per-dose incidence of 2.4% and per-patient incidence of 7.3% in this composite endpoint were found, with no differences between the groups. Patients received median doses of 10 mg and follow-up within 2.8 hours. There were no cases of death in either group. Although nifedipine IR may cause major adverse events, the incidence seems lower than previously believed. Future research is warranted to evaluate whether nifedipine IR may be an option to treat elevated blood pressure in hospitalized patients.

Pharmacokinetics and dialytic clearance of baricitinib during in vivo continuous venovenous haemodialysis in a patient with COVID-19.

OBJECTIVES: To date, there are no published pharmacokinetic (PK) data for baricitinib in critically ill patients requiring continuous renal replacement therapy. This paper describes in detail the plasma PK and dialytic clearance of baricitinib in a patient infected with coronavirus disease 2019 (COVID-19) requiring continuous renal replacement therapy in order to suggest dosing strategies in this population. METHODS: Baricitinib 2 mg daily was used for the treatment of COVID-19 in a critically ill patient on continuous venovenous haemodialysis (CVVHD). Prefiltration plasma drug concentrations of baricitinib were measured at hours 1, 2, 12, and 24 after drug administration. Postfiltration and ultrafiltrate concentrations were collected at hour 24. RESULTS: Plasma PK parameters of baricitinib in this patient were as follows: maximum plasma concentration (Cmax), 20.98 ng/mL; minimum plasma concentration (Cmin), 9.84 ng/mL; half-life (t1/2), 23.85 h; apparent volume of distribution at the steady state (Vss), 99.42 L; total clearance at the steady state (CLss), 2.89 L/h; and area under the concentration-time curve (AUC0-∞), 692.14 ng · h/mL. The saturation coefficient for baricitinib at 24 h after administration was 0.607. The transmembrane clearance of baricitinib by CVVHD running at a flow rate of 2 L/h was 1.21 L/h, representing 41.9% of the total clearance of baricitinib. CONCLUSIONS: In a critically ill COVID-19 patient on CVVHD, a 2-mg dose of baricitinib achieves a Cmax comparable with healthy subjects, but total clearance was reduced to about 20%. Larger studies exploring multiple patients and dialysis modes are needed to determine the optimal dosing strategy for baricitinib in this patient population.

Catecholamine Vasopressor Exposure Is Associated With Early Poor Allograft Function and Adverse Events in Living Donor Kidney Transplant Recipients.

BACKGROUND: Hypoperfusion leads to allograft injury during kidney transplantation. Catecholamine vasopressors are used to maintain blood pressure in the perioperative period but have demonstrated negative outcomes in the deceased-donor kidney transplant population. Little is known regarding living donor kidney transplants (LDKTs) and vasopressor use. The aim of this study is to describe the incidence of vasopressor use in LDKT and characterize its effects on allograft function and patient outcomes. METHODS: This retrospective, observational cohort study included adult patients who underwent an isolated LDKT between August 1, 2017, and September 1, 2018. Patients were divided into those who received perioperative vasopressors and those who did not. The primary objective was to compare allograft function between LDKT recipients that received vasopressors and those who did not. Secondary outcomes included safety endpoints and the identification of clinical variables associated with vasopressor use. RESULTS: A total of 67 patients received an LDKT during the study period. Of those, 25 (37%) received perioperative vasopressors, and 42 (62%) did not. Poor graft function, as defined by the development of slow or delayed graft function, occurred more frequently in patients receiving perioperative vasopressors compared with those who did not (6 [24%] vs 1 [2.4%], P = .016). In multivariable regression modeling, only perioperative vasopressors were statistically significantly associated with poor graft function. In addition, patients exposed to vasopressors experienced more postoperative arrhythmias (8 [32%] vs 1 [4.8%], P = .0025). CONCLUSION: Using perioperative vasopressors was independently associated with worsened early renal allograft function, including delayed graft function and adverse events in the LDKT population.

Comparison of thrombotic and clinical outcomes in SARS-CoV-2-pneumonia versus other viral pneumonia in an urban academic medical center.

BACKGROUND: Infection with viral pneumonia (PNA) is known to offset the coagulation cascade. Recent studies assessing novel SARS-CoV-2 infection observed a high frequency of systemic thrombotic events resulting in ambiguity if severity of infection or specific viral strain drive thrombosis and worsen clinical outcomes. Furthermore, limited data exists addressing SARS-CoV-2 in underrepresented patient populations. OBJECTIVES: Assess clinical outcomes events and death in patients diagnosed with SARS-CoV-2 pneumonia compared to patients with other types of viral pneumonia. METHODS: Retrospective cohort study evaluated electronic medical records in adult patients admitted to University of Illinois Hospital and Health Sciences System (UIHHSS) with primary diagnosis of SARS-CoV-2 PNA or other viral (H1N1 or H3N2) PNA between 10/01/2017 and 09/01/2020. Primary composite outcome was the following event incidence rates: death, ICU admission, infection, thrombotic complications, mechanical ventilation, renal replacement therapy, and major bleeding. RESULTS: Of 257 patient records, 199 and 58 patients had SARS-CoV-2 PNA and other viral PNA, respectively. There was no difference in primary composite outcome. Thrombotic events (n = 6, 3%) occurred solely in SARS-CoV-2 PNA patients in the ICU. A significantly higher incidence of renal replacement therapy (8.5% vs 0%, p=0.016) and mortality (15.6% vs 3.4%, p=0.048) occurred in the SARS-CoV-2 PNA group. Multivariable logistic regression analysis revealed age, presence of SARS-CoV-2, and ICU admission, aOR 1.07, 11.37, and 41.95 respectively, was significantly associated with mortality risk during hospitalization; race and ethnicity were not. CONCLUSION: Low overall incidence of thrombotic events occurred only in the SARS-CoV-2 PNA group. SARS-CoV-2 PNA may lead to higher incidence of clinical events than those observed in H3N2/H1N1 viral pneumonia, and that race/ethnicity does not drive mortality outcomes.

Treatment outcomes of heparin-induced thrombocytopenia in subarachnoid hemorrhage patients: a 4-year, retrospective single-center review.

INTRODUCTION: The treatment and outcomes of heparin-induced thrombocytopenia (HIT) are not well described in neurosurgery patients. This study reviewed the treatment for HIT in subarachnoid hemorrhage (SAH) patients, and compared outcomes in patients with isolated HIT (iHIT) and HIT with thrombotic syndrome (HITTS). METHODS: Adult patients with SAH discharged from the University of Illinois Hospital & Health Sciences System from 2006 to 2009 were included if they had at least one positive HIT antibody test. Patients were categorized with either iHIT or HITTS based on documented evidence of thrombosis. The primary outcome was the incidence of new thromboses prior to discharge. Secondary outcomes included the incidence of major bleeding, new thromboses up to 3 months after discharge, or hospice/death. Patients having any secondary outcome were defined as having a "poor treatment-related effect". RESULTS: A total of 176 patients were screened and 30 patients met inclusion criteria. Eighteen patients (60 %) were categorized with iHIT and 12 (40 %) with HITTS. Twelve patients (67 %) with iHIT received prophylaxis with fondaparinux and nine patients (75 %) with HITTS were treated with argatroban. There were no differences in the primary (11 vs. 25 %, p = 0.364) or secondary outcomes in the iHIT group versus the HITTS group. Patients with iHIT had a 5.5 % incidence of "poor treatment-related effects" compared to a 33.3 % incidence in patients with HITTS (p = 0.024). CONCLUSIONS: SAH patients with iHIT and HITTS did not differ in the incidence of new thromboses, incidence of hemorrhage, or hospice/death. Patients with iHIT had fewer "poor treatment-related effects" than HITTS patients.

Perioperative Vasopressors are Associated with Delayed Graft Function in Kidney Transplant Recipients in a Primarily Black and Hispanic Cohort.

Introduction: Negative outcome studies of vasopressors in kidney transplant have not focused on patient populations that are predominantly Black or Hispanic. Project Aims: The evaluation sought to investigate the independent impact of perioperative vasopressors on postoperative renal allograft function in a sample drawn from a primarily Black and Hispanic population. Design: Retrospective, observational, single-center evaluation of patients > 18 years old who underwent kidney transplantation comparing outcomes based on vasopressor exposure. Results: The study included 150 patients of which 60 received vasopressors. The primary outcome differed between groups with delayed graft function occurring in 17(28%) versus 11(12.2%) occurring more often in those that received perioperative vasopressors (P = 0.02). The serum creatinine at postoperative day 7 was higher (2.69 vs1.52 mg/dL, P = 0.004), postoperative day 7 eGFR was worse (27.3 vs 52.9 mL/min/1.73m2, P = 0.002) in patients who received vasopressors. Patients who received perioperative vasopressors experienced more postoperative arrhythmias (15% vs 8%, P = 0.007), insulin infusion therapy (26.7% vs 13.3%, P = 0.04), and increased hospital length of stay (6 days vs 5 days, P = 0.006). Using IPWRA, patients receiving vasopressors were more likely to experience delayed function, relative risk difference of 22% (95% CI:0.08-0.35;P = 0.002) and in multivariate logistic regression modeling, an increased odds ratio of 3.2 (95% CI:1.1-8.62;P = 0.022). Conclusions: The use of perioperative vasopressors was independently associated with worsened early renal allograft function including delayed graft function, increased adverse events such as postoperative arrhythmias, and longer ICU length of stay. Further investigation is needed surrounding vasopressor use in this population.

Safety and Efficacy of Apixaban For Therapeutic Anticoagulation in Critically Ill ICU Patients with Severe COVID-19 Respiratory Disease.

Introduction Despite the use of unfractionated heparin (UFH) or low molecular weight heparin (LMWH), rates of thromboembolic disease, and subsequent morbidity and mortality remain unacceptably high in patients with severe novel coronavirus disease 2019 (COVID-19) disease. Direct oral anticoagulants (DOACs), such as apixaban, have numerous purported benefits although the safety and efficacy of their use in intensive care unit (ICU) patients with severe COVID-19 has yet to be evaluated. Materials and Methods Single-center, retrospective cohort study of 21 ICU patients with severe COVID-19 respiratory disease treated with apixaban for atrial fibrillation (AFib), venous thromboembolism (VTE), catheter-induced thrombosis, and/or COVID-19-induced coagulopathy. The primary objective was to evaluate the incidence of bleeding events and secondary objectives included thromboembolic events, coagulation parameters, and mortality. Results Ninety percent of patients were non-White, 43% were obese, 90% had acute respiratory distress syndrome, and 76% required mechanical ventilation. Nearly half of (47.6%) also experienced renal dysfunction and required renal replacement therapy. Eighty-six percent of patients received prophylaxis or treatment with UFH or LMWH within the 24-hour period prior to apixaban initiation. Patients were initiated on apixaban for the treatment of suspected or confirmed VTE (67%) or AFib (33%). All coagulation parameters remained abnormal but stable throughout the 10-day monitoring period. No patients experienced any major bleeding events or thrombosis throughout the study period. There were four deaths during the follow-up period, all deemed unrelated to coagulopathy or bleeding. Conclusion Apixaban appeared safe and efficacious in ICU patients with severe COVID-19 disease. These data encourage future trials seeking to optimize anticoagulation strategies in patients with severe COVID-19.

A Pilot Study of End-Tidal Carbon Dioxide in Prediction of Inhospital Cardiac Arrests.

A validated means to predict inhospital cardiac arrest is lacking. The purpose of this study was to evaluate the changes in end-tidal carbon dioxide, as it correlates with the progression to inhospital cardiac arrest in ICU patients. DESIGN SETTING AND PATIENTS: Single-center, retrospective cohort study of mechanically ventilated ICU patients (age > 18 yr old) having inhospital cardiac arrest with advanced cardiac life support and continuous end-tidal carbon dioxide monitoring at a single academic center from 2014 to 2017. Demographics, clinical variables, and outcomes were collected. End-tidal carbon dioxide was collected from 5 to 2,880 minutes before inhospital cardiac arrest. Data were analyzed using descriptive statistics, and model estimates were generated using a repeated-measures categorical model with restricted maximum likelihood estimation and fully specified (autoregressive) covariance to assess the effect of time on changes in end-tidal carbon dioxide. MEASUREMENTS AND MAIN RESULTS: A total of 788 patients were identified and 104 met inclusion criteria, where 62% were male with an average age of 58.5 years. Seventy-four percent required vasopressors and 72% experienced pulseless electrical activity. Mean end-tidal carbon dioxide 5 minutes prior to inhospital cardiac arrest was significantly lower than all evaluated time points except 180 minutes (p < 0.05). One patient survived to hospital discharge. In multivariate logistic regression modeling for return of spontaneous circulation, a greater change in the prearrest end-tidal carbon dioxide maximum to prearrest end-tidal carbon dioxide minimum was associated with a decreased likelihood of return of spontaneous circulation (odds ratio 0.903; 95% CI, 0.832-0.979; p = 0.014). Additionally, a change from prearrest end-tidal carbon dioxide maximum to prearrest end-tidal carbon dioxide minimum greater than 17 mm Hg was associated with a decreased likelihood of return of spontaneous circulation and odds ratio 0.150; 95% CI, 0.036-0.66; p = 0.012). CONCLUSIONS: Mean end-tidal carbon dioxide is significantly lower immediately before inhospital cardiac arrest. The statistical and clinical significance of end-tidal carbon dioxide may highlight its utility for predicting inhospital cardiac arrest in ICU patients. Comparison analysis and modeling explorations in a larger cohort are needed.

Blood pressure variability in the management of hypertensive emergency: A narrative review.

Hypertensive emergencies (HTNe) primarily focus on decreasing the blood pressure to specific targets. However, there are emerging data surrounding the potential clinical effects of blood pressure variability (BPV) in patients with HTNe. This narrative review highlights the various definitions of BPV, the emerging role of BPV, and the clinical data surrounding BPV in the HTNe setting. Clinical studies were obtained from a PubMed search through October 2018 utilizing PICO methodology. Original research articles, systematic reviews, and meta-analyses were considered for inclusion. Articles were selected for inclusion based on the relevancy of the article investigating BPV in the HTNe setting. There is currently no accepted standard to express BPV in the acute care setting of HTNe, and various parameters have been reported. There are very limited data regarding BPV outside of the neurologic HTNe setting. In the acute treatment phase of neurologic HTNe, BPV is consistently associated with increased risk of unfavorable outcomes. In the HTNe setting, continuous infusion of calcium channel blockers may optimize BPV compared to other agents. Based on current data, BPV should be investigated in a prospective systemic fashion. Efforts should be taken to ensure that BPV is minimized in the acute phase of HTNe, especially for those patients with intracranial hemorrhage. This reduced BPV is associated with improved favorable outcomes, but further study investigating specific pharmacologic agents is needed.

The Future of Intensive Care Unit Sedation: A Report of Continuous Infusion Ketamine as an Alternative Sedative Agent.

This report describes a patient case utilizing a nontraditional sedative, continuous infusion ketamine, as an alternative agent for intensive care unit (ICU) sedation. A 27-year-old female presented for neurosurgical management of a coup contrecoup injury, left temporal fracture, epidural hemorrhage (EDH), and temporal contusion leading to sustained mechanical ventilation. The patient experienced profound agitation during mechanical ventilation and developed adverse effects with all traditional sedatives: benzodiazepines, dexmedetomidine, opioids, and propofol. Ketamine was titrated to effect and eliminated the need for other agents. This led to successful ventilator weaning, extubation, and transition of care. Given the unique side effect profile of ketamine, it is imperative that information is disseminated on potential utilization of this agent. More information is needed regarding dosing, monitoring, and long-term effects of utilizing ketamine as a continuous ICU sedative, but given the analgesia, anesthesia, and cardiopulmonary stability, future utilization of this medication for this indication seems promising.

A retrospective evaluation of fondaparinux for confirmed or suspected heparin-induced thrombocytopenia in left-ventricular-assist device patients.

BACKGROUND: Thrombotic events are a common complication of left ventricular assist device placement and warrant prophylactic anticoagulation. Heparin is the most common anticoagulant used for prophylaxis of thrombotic events in left ventricular assist device patients as a transition to oral anticoagulants but carries the risk of heparin-induced thrombocytopenia. Limited data is available for the treatment of heparin-induced thrombocytopenia in this patient population. We report an evaluation of 8 left ventricular assist device patients with suspected or confirmed HIT started on fondaparinux at the time of heparin-induced platelet-factor-4 antibody positivity. METHODS: Adult patients were reported if they were heparin-induced platelet antibody positive, tested via enzyme-linked immunusorbent assay, post-operative after left-ventricular assist device, and were initiated on fondaparinux at the time of heparin-induced platelet antibody positivity. Waiver of informed consent was granted from the institutional review board. Baseline demographics, clinical course of HIT, safety and efficacy variables were collected. RESULTS: Eight patients receiving fondaparinux were identified and included in this report. The patient group was on average 49 years old, weighing 95 kg, with calculated BMI 28.8 and consisted primarily of Caucasian males. Three patients developed new thromboses after initiation of fondaparinux for heparin-induced thrombocytopenia. Only one patient had a major bleeding event of an overt bleed after initiation of fondaparinux therapy. CONCLUSIONS: Given the lack of major bleeding in this evaluation, fondaparinux could be a potentially safe treatment option for left ventricular assist device patients that are heparin-induced platelet antibody positive pending confirmatory testing results. Given the development of new thromboses in 3 of 8 patients, concern exists about the efficacy of fondaparinux in this patient population. Significant limitations exist regarding these conclusions in this evaluation. Controlled, systematic evaluations are necessary to delineate safety and efficacy of fondaparinux for heparin-induced thrombocytopenia in this population.

Management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration.

PURPOSE: The management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration (CVVH) is reported. SUMMARY: A 46-year-old African-American woman with New York Heart Association class IV, American College of Cardiology- American Heart Association stage D heart failure arrived from an outside facility with complaints of dyspnea after minimal exertion, orthopnea, and lower-extremity edema. A transthoracic echocardiogram revealed an estimated left ventricular ejection fraction of 15%. The patient subsequently required left ventricular assist device placement on hospital day 5 as a potential bridge to transplantation. A total digoxin loading dose of 500 µg i.v. (8.2 µg/kg) was given in two divided doses six hours apart. The next morning, the serum digoxin concentration was 1.9 ng/mL, and the patient was started on a maintenance digoxin dosage of 125 µg i.v. daily. On postoperative day (POD) 20, the patient developed acute kidney injury, and CVVH was initiated. The sieving coefficient (Sc), transmembrane clearance (CLtm), digoxin concentration in ultrafiltration fluid (Cuf), and need for supplemental digoxin were determined to account for CVVH- associated digoxin loss. After 14 days of CVVH, the patient's clinical condition improved, and CVVH was transitioned to intermittent hemodialysis. On POD 66, the patient was discharged to an extended-care facility without adverse reactions related to digoxin therapy. CONCLUSION: Analysis of serum digoxin concentration and digoxin Cuf values suggested that digoxin was cleared by CVVH, allowed calculation of Sc and CLtm values, and facilitated determination of digoxin requirements in a critically ill patient requiring CVVH.

A Single-Center Review of Prescribing Trends and Outcomes of Corticosteroid Replacement Therapy in Critically Ill Children with Septic Shock.

Recently published consensus treatment guidelines for pediatric sepsis recommend initiating corticosteroid replacement therapy (CRT) for those critically ill children with adrenal insufficiency and refractory shock. The data to support this recommendation is limited, and multiple studies have demonstrated significant variation in both the diagnosis and treatment of adrenal insufficiency and refractory shock in children. In order to better define the variation in practice at our institution, we retrospectively reviewed the experience with CRT in critically ill children with refractory septic shock over a 1-year-period. In addition, as a secondary aim we compared outcomes in critically ill children treated with CRT for variable lengths of time. We found that the initiation of CRT at our center is relatively consistent. However, we noted significant variation in the duration of CRT and whether CRT was gradually tapered or stopped abruptly. The majority of the patients in our cohort received less than the currently recommended duration of 7 days of CRT. There were a higher number of treatment failures in those patients who received CRT for greater than 7 days, suggesting that CRT should be tapered gradually in these patients. There is significant variation in prescribing trends for CRT at our institution, which are likely to be compounded in any multi-center cohort study of CRT in critically ill children with septic shock. Practice variation in CRT should be standardized to address the impact of CRT in this population.