Continuation of Newly Initiated Midodrine Therapy After Intensive Care and Hospital Discharge: A Single-Center Retrospective Study.

OBJECTIVES: Midodrine is an α1-agonist approved for orthostatic hypotension. Recently, it has received attention as an oral vasopressor to facilitate ICU discharge. The purpose of this study was to identify the incidence of continuation of newly initiated midodrine upon ICU and hospital discharge and identify risk factors associated with its occurrence. DESIGN: Single-center retrospective study. SETTING: ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. PATIENTS: Adult patients admitted to any ICU who received new midodrine for hypotension and survived to discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During the study period, 1,010 patients were newly started on midodrine and survived to ICU discharge. Midodrine was continued in 67% (672/1,010) of patients at ICU discharge. Admission to cardiovascular surgery ICU and mixed medical/surgical ICU was a risk factor for midodrine continuation at ICU discharge (odds ratio, 3.94 [2.50-6.21] and 2.03 [1.29-3.20], respectively). At hospital discharge, 34% (311/909) of patients were continued on midodrine therapy. History of congestive heart failure predicted midodrine continuation at hospital discharge (odds ratio, 1.49 [1.05-2.12]). Hypertension and use of mechanical ventilation were associated with a decreased odds of midodrine prescription at both ICU and hospital discharge. Of those discharged from the ICU or hospital on midodrine, 50% were concomitantly prescribed antihypertensives. Discharge from the ICU on midodrine was associated with a significantly shorter ICU length of stay (7.5 ± 8.9 vs 10.6 ± 13.4 d) and reduced risk of in-hospital mortality (hazard ratio, 0.47 [95% CI, 0.32-0.70]; p < 0.001), despite no difference in baseline severity of illness scores. In contrast, patients discharged from the hospital on midodrine had a higher risk of 1-year mortality (hazard ratio, 1.60 [95% CI, 1.26-2.04]; p < 0.001). CONCLUSIONS: This study established a high prevalence of midodrine continuation in transitions of care. The risks and benefits of this practice remain unclear. Future studies should explore the impact of this practice on patient outcomes and resource utilization. These insights could be used to model interventions for proper tapering, discontinuation, or follow-up of new start midodrine.

Trends in Use of Midodrine in the ICU: A Single-Center Retrospective Case Series.

OBJECTIVES: Midodrine is an oral alpha-agonist approved for orthostatic hypotension. The use of midodrine as a vasopressor sparing agent has steadily increased in the ICU despite limited evidence for its safety in that setting. We describe the trends in use and reported side effects and complications of midodrine in multidisciplinary ICUs of a tertiary care institution. DESIGN: Single-center retrospective case series. SETTING: Medical and surgical ICU patients from January 2011 to October 2016 at Mayo Clinic, Rochester. PATIENTS: Adult patients admitted to any ICU who received midodrine for hypotension were eligible. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We reviewed the mean arterial pressures and cumulative vasopressor dose before and after midodrine administration and assessed for reported complications. During the study period, a total of 1,119 patients were initiated on midodrine, 56% in surgical ICUs, 42% in medical ICUs, and 2% in a mixed medical and surgical neurology ICU. There was a significant decrease in the number of patients on vasopressors 24 hours after initiation of midodrine (663 to 344; p < 0.001); among the patients that remained on vasopressors, there was a significant decrease in the median cumulative vasopressor dose (p = 0.002). There was a significant increase in median mean arterial pressure 24 hours after initiation of midodrine among patients who were not on vasopressors (65-68; p < 0.01). Asymptomatic bradycardia (heart rate < 50 beats/min) was the most common side effect (n = 172 patients, median 39 beats/min). Two patients developed bowel ischemia after initiation of midodrine that prompted discontinuation of midodrine in one case. Evaluating trends of utilization, the off-label use of midodrine has increased steadily over the years across ICUs. CONCLUSIONS: Our results suggest that midodrine is being increasingly used as an adjunct to increase mean arterial pressure and facilitate weaning of vasopressors in the ICU. Prospective trials are required to further establish the appropriate timing, efficacy, safety, and cost-effectiveness of midodrine use in ICU patients.

New Decade, Old Debate: Blocking the Cytokine Pathways in Infection-Induced Cytokine Cascade.

OBJECTIVES: Our understanding of the immunopathogenesis of coronavirus disease 2019 is evolving; however, a "cytokine storm" has been implicated. Ongoing clinical trials are evaluating the value of anticytokine therapies to treat patients with coronavirus disease 2019. This review summarizes the existing literature evaluating the efficacy and safety of anticytokine therapy to tackle the dysregulated immune response to infectious pathogens, discusses potential reasons for failure, applicability to coronavirus disease 2019, and future direction. DATA SOURCES: Medline, PubMed, ClinicalTrials.gov, and media reports. STUDY SELECTION: The studies were included by author consensus. DATA EXTRACTION: Data were selected for inclusion after reviewing each study by author consensus. DATA SYNTHESIS: "Cytokine storm" is a nonspecific term, encompassing systemic inflammatory response to infectious pathogens, autoimmune conditions, cancers, trauma, and various chemotherapies. Like bacterial sepsis, viral pathogens may fuel immunopathogenesis by inducing a dysregulated autoamplifying cytokine cascade, ultimately leading to organ injury. This narrative review discusses what we know of the immune milieu of coronavirus disease 2019 versus noncoronavirus disease 2019 sepsis and/or acute respiratory distress syndrome, summarizes the existing literature on cytokine inhibitors in patients with sepsis and/or acute respiratory distress syndrome, and discusses possible reasons for recurrent failure. In doing so, it aims to assist decisions regarding the use of anticytokine therapy in patients with coronavirus disease 2019, as many regions of the world confront the second wave of the pandemic. CONCLUSIONS: As ongoing clinical trials determine the efficacy and safety of anticytokine therapy in patients with coronavirus disease 2019, clinicians should uphold caution when incorporating it into treatment protocols, while maintaining focus on established evidence-based practices and the mantra of "less is more."

Oral Midodrine Administration During the First 24 Hours of Sepsis to Reduce the Need of Vasoactive Agents: Placebo-Controlled Feasibility Clinical Trial.

Our preliminary data and observational studies suggested an increasing "off label" use of oral midodrine as a vasopressor sparing agent in various groups of critically ill patients, including those with sepsis. We designed this clinical trial to evaluate the feasibility of use of midodrine hydrochloride in early sepsis to reduce the duration for IV vasopressors and decrease ICU and hospital length of stay. DESIGN: Pilot, two-center, placebo-controlled, double blinded randomized clinical trial. SETTING: Medical ICUs at Mayo Clinic Rochester and Cleveland Clinic Abu Dhabi were the study sites. PATIENTS AND METHODS: Adult patients (≥ 18 yr old) were included within 24 hours of meeting the Sepsis-3 definition if the mean arterial pressure remained less than 70 mm Hg despite receiving timely antibiotics and initial IV fluid bolus of 30 cc/kg. INTERVENTION: Three doses of 10 mg midodrine versus placebo were administered. MEASUREMENTS AND MAIN RESULTS: Total 32 patients were randomized into midodrine (n = 17) and placebo groups (n = 15). There were no major differences in baseline variables between the groups except for higher baseline creatinine in the midodrine group (2.0 ± 0.9 mg/dL) versus placebo group (1.4 ± 0.6 mg /dL), p = 0.03. The median duration of IV vasopressor requirement was 14.5 ± 8.1 hours in midodrine group versus 18.8 ± 7.1 hours in the placebo group, p value equals to 0.19. Patients in the midodrine group needed 729 ± 963 norepinephrine equivalent compared with 983 ± 1,569 norepinephrine equivalent in the placebo group, p value equals to 0.59. ICU length of stay was 2.29 days (interquartile range, 1.65-3.9 d) in the midodrine group, compared with 2.45 days (interquartile range, 1.6-3.2 d) in the placebo group, p value equals to 0.36. No serious adverse events were observed in either group. CONCLUSIONS: Phase II clinical trial powered for clinical outcomes (duration of vasopressor use, need for central venous catheter, and ICU and hospital length of stay) is justified.

Severe Babesia microti infection presenting as multiorgan failure in an immunocompetent host.

A previously healthy 67-year-old farmer presented to an outside hospital after a 2-week history of non-specific respiratory symptoms. A certain diagnosis was not initially apparent, and the patient was discharged home on a regimen for presumed chronic obstructive pulmonary disease exacerbation. He re-presented to the emergency department with shock and hypoxaemic respiratory failure requiring prompt intubation and fluid resuscitation. He was then transferred to our institution due to multiorgan failure. On arrival, the patient demonstrated refractory shock and worsening acute kidney injury, severe anaemia and thrombocytopaenia. The peripheral smear revealed absence of microangiopathic haemolytic anaemia. A closer review of the smear displayed red blood cell inclusion bodies consistent with babesiosis. The patient was started on clindamycin and loaded with intravenous quinidine, and subsequently transitioned to oral quinine. A red cell exchange transfusion was pursued with improvement of the parasite load. The patient was discharged home on clindamycin/quinine and scheduled for outpatient intermittent haemodialysis.

Biomarkers for Early Detection of Acute Kidney Injury.

BACKGROUND: Acute kidney injury (AKI) is common in hospitalized patients and is associated with increased morbidity, mortality, and cost. Currently, AKI is diagnosed after symptoms manifest; available diagnostic tests (e.g., serum creatinine, urine microscopy, urine output) have limited ability to identify subclinical AKI. Because of the lack of treatment strategies, AKI typically is managed with supportive measures. However, strategies exist that may prevent renal insults in critically ill patients; therefore, early recognition of AKI is crucial for minimizing damage propagation. CONTENT: Experimental and clinical studies have identified biomarkers that may facilitate earlier recognition of AKI or even identify patients at risk of AKI. Such biomarkers might aid in earlier implementation of preventive strategies to slow disease progression and potentially improve outcomes. This review describes some of the most promising novel biomarkers of AKI, including neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (lL-18), liver-type fatty-acid-binding protein (L-FABP), insulin-like-growth-factor-binding protein 7 (IGFBP7), and tissue inhibitor of metalloproteinase 2 (TIMP-2). SUMMARY: We discuss biomarker test characteristics, their strengths and weaknesses, and future directions of their clinical implementation.

What Are We Doing? A Survey of United States Nephrology Fellowship Program Directors.

Interest in nephrology has been declining in recent years. Long work hours and a poor work/life balance may be partially responsible, and may also affect a fellowship's educational mission. We surveyed nephrology program directors using a web-based survey in order to define current clinical and educational practice patterns and identify areas for improvement. Our survey explored fellowship program demographics, fellows' workload, call structure, and education. Program directors were asked to estimate the average and maximum number of patients on each of their inpatient services, the number of patients seen by fellows in clinic, and to provide details regarding their overnight and weekend call. In addition, we asked about number of and composition of didactic conferences. Sixty-eight out of 148 program directors responded to the survey (46%). The average number of fellows per program was approximately seven. The busiest inpatient services had a mean of 21.5±5.9 patients on average and 33.8±10.7 at their maximum. The second busiest services had an average and maximum of 15.6±6.0 and 24.5±10.8 patients, respectively. Transplant-only services had fewer patients than other service compositions. A minority of services (14.5%) employed physician extenders. Fellows most commonly see patients during a single weekly continuity clinic, with a typical fellow-to-faculty ratio of 2:1. The majority of programs do not alter outpatient responsibilities during inpatient service time. Most programs (approximately 75%) divided overnight and weekend call responsibilities equally between first year and more senior fellows. Educational practices varied widely between programs. Our survey underscores the large variety in workload, practice patterns, and didactics at different institutions and provides a framework to help improve the service/education balance in nephrology fellowships.