Wieruszewski, Patrick M

Abstract Rationale The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. Objectives To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. Methods This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as 1) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, 2) new pulmonary opacities on chest imaging, and 3) exclusion of an infectious or cardiac etiology to explain the clinical presentation. Results Of 3,473 patients undergoing autologous HCT, 167 (4.8%) developed PERDS. Radiographic changes preceded engraftment in 77% of cases. In a multivariable regression model, risk factors for PERDS included female sex (odds ratio [OR], 1.73; P = 0.001), the number of preengraftment platelet transfusions (OR, 1.22; P = 0.002), and more rapid engraftment (OR, 0.72 per day longer; P < 0.001). PERDS cases were more likely to be admitted to the intensive care unit (47.3% vs. 9.5%, P < 0.001) and require intubation (20.4% vs. 1.6%, P < 0.001). In an adjusted 100-day death analysis, those diagnosed with PERDS were more likely to die (hazard ratio, 3.1; 95% confidence interval, 1.5–6.2; P = 0.002). Conclusions PERDS is a common complication of autologous HCT and is associated with increased mortality and healthcare use. Radiographic evidence of pulmonary involvement precedes hematopoietic recovery. A larger number of platelet transfusions and more rapid engraftment appear to increase risk for PERDS.

Background: Clozapine is an atypical antipsychotic with potent alpha-adrenergic blocking properties when administered at high dosages, resulting in vasodilatory shock in overdose settings. Case Summary: A 39-year-old man presented with profound catecholamine- and vasopressin-refractory vasodilatory shock following massive clozapine ingestion. Angiotensin II was initiated when the patient was requiring 2.2 µg/kg/min norepinephrine equivalents of vasopressor support, resulting in a prompt increase in the perfusion pressure. All vasopressors were liberated within 18 hours of angiotensin II initiation, and the patient was discharged with no deficits. Conclusions: Synthetic angiotensin II may represent a therapeutic option for refractory hypotension resulting from high dosages of clozapine or other potent alpha-adrenergic blocking medications.

Antithrombotic optimization with a glycoprotein IIb/IIIa inhibitor has been used for the treatment of suspected pump thrombosis, but available literature with tirofiban is lacking. This study aims to describe the use of tirofiban for suspected pump thrombosis. This was a single-center cohort study of left ventricular assist device patients who received tirofiban for the treatment of suspected pump thrombosis from January 1, 2016 to July 31, 2017. Tirofiban was initiated at 0.1 μg/kg/min in patients with normal renal function and subsequent dose adjustments for altered renal function or history of bleeding were employed. Success was defined as resolution of lactate dehydrogenase back to patients’ known baseline. Fourteen patients were included for 16 total instances of tirofiban use during the time period. Tirofiban was continued for a median of 5 days (range: 0.3–35 days). Successful treatment was achieved in 12 of the 16 tirofiban uses (75%). Seven bleeding events occurred while on therapy, two major and five minor. This study showed a majority of patients achieved success with tirofiban for suspected pump thrombosis. For patients who are not current candidates for pump exchange or transplant, tirofiban may be considered a therapeutic medical management option.

AbstractBackgroundTrace‐element contamination of contemporary parenteral nutrition (PN) components exists in unknown quantities and, in combination with excessive amounts of certain trace elements provided in commercially available adult, pediatric, and neonatal multitrace‐element (MTE) products, could result in eventual accumulation and toxicity. This study aims to quantify trace‐element contamination in components used for PN compounding to further inform recommendations for MTE product reformulation and individualized trace‐element prescribing in PN.MethodsA total of 32 unique components (65 products) available for PN compounding were tested for manganese, chromium, selenium, zinc, and copper contamination, utilizing inductively coupled plasma mass spectrometry. Theoretical adult, pediatric, and neonatal PNs were formulated to assess the impact of macronutrient and micronutrient component doses on PN trace‐element contamination.ResultsTrace‐element contamination was detected in 24 (75%) components tested. Chromium and manganese were common, present in 65.6% and 51.5% of all components, respectively. Eight components did not contain detectable trace‐element contamination, most notably sterile water, concentrated dextrose, and lipid emulsion. Manganese contamination in theoretical adult, pediatric, and neonatal PN was 25.18, 9.92, and 1.37 µg, respectively. Chromium contamination was 4.85, 1.5, and 0.28 µg, respectively.ConclusionTrace‐element contamination was prevalent in components used to compound PN. Our findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to eliminate chromium, decrease manganese, and supply full daily physiologic requirements of selenium, zinc, and copper. Future study is needed to assess the additional contamination that could occur through the compounding and storage processes.

AbstractDisruptions in the medication supply chain and consequent drug product shortages, including shortages of parenteral products used for parenteral nutrition (PN) compounding, have become an increasingly common occurrence. The amino acid solution shortage that resulted from the devastating impact of Hurricanes Maria and Irma on manufacturing facilities in Puerto Rico in 2017 necessitated a rapid, coordinated shift from use of compounded PN to commercial multichamber‐bag PN (MCB‐PN) at our hospitals. We describe our experience operationalizing this intervention via a framework that may be adapted for addressing other drug product shortages to promote rapid yet safe use of therapeutic alternatives.

Background: Corticosteroid therapy is a well-recognized risk factor for Pneumocystis pneumonia (PCP); however, it has also been proposed as an adjunct to decrease inflammation and respiratory failure. Objective: To determine the association between preadmission corticosteroid use and risk of moderate-to-severe respiratory failure at the time of PCP presentation. Methods: This retrospective cohort study evaluated HIV-negative immunosuppressed adults diagnosed with PCP at Mayo Clinic from 2006 to 2016. Multivariable regression models were used to evaluate the association between preadmission corticosteroid exposure and moderate-to-severe respiratory failure at presentation. Results: Of the 323 patients included, 174 (54%) used preadmission corticosteroids with a median daily dosage of 20 (interquartile range: 10-40) mg of prednisone or equivalent. After adjustment for baseline demographics, preadmission corticosteroid therapy did not decrease respiratory failure at the time of PCP presentation (odds ratio: 1.23, 95% confidence interval: 0.73-2.09, P = .38). Additionally, after adjusting for inpatient corticosteroid administration, preadmission corticosteroid use did not impact the need for intensive care unit admission ( P = .98), mechanical ventilation ( P = .92), or 30-day mortality ( P = .11). Conclusions: Corticosteroid exposure before PCP presentation in immunosuppressed HIV-negative adults was not associated with a reduced risk of moderate-to-severe respiratory failure.