Chalmers, Sarah

Abstract Purpose We describe the case of a 22-year-old male who developed thyroid storm necessitating therapeutic plasma exchange (TPE). The patient’s past medical history was complicated by epilepsy, for which he took lacosamide. Little evidence was available to guide lacosamide dosing during TPE. Because of an exacerbation of the patient’s underlying epilepsy in the context of the thyroid storm, we conducted therapeutic medication monitoring of lacosamide concentrations to guide management. Summary We arranged for measurement of the lacosamide concentration immediately before TPE (5.1 μg/mL) and 2.5 hours after the initial measurement (3.4 μg/mL) to determine the amount of lacosamide removed by TPE. Utilizing population pharmacokinetic parameters, we calculated the expected concentration and compared this to the measured concentration. The difference between these values was used to determine the percentage removed via TPE compared to the expected post-TPE concentration. We found that one TPE session removed an additional 20% of serum lacosamide. Conclusion TPE appeared to remove an additional 20% of lacosamide when compared to the expected post-TPE concentration.

Objective:To describe the current prescribing practices of direct oral anticoagulants (DOACs) in intensive care unit (ICU) patients and the associated clinical outcomes, including the incidence of major bleeding episodes and the need for intervention (endoscopic, surgical, or interventional radiology guided). Design:Observational, retrospective chart review. Setting and Participants:Single large academic center study. Participants included patients with critical illness who were admitted to the intensive care units (ICU) at Mayo Clinic from January 1st, 2012, until May 4th, 2018. Adult ICU patients with a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) listed as one of the active medications at the time of hospital admission were included. Results:37 249 patients in medical and surgical intensive care units were screened for the study period. After excluding patients who did not qualify, 558 unique encounters were included. The median age was 69 (IQR 59-78) years; most patients were male, white Caucasians, and had a median SOFA score of 4. After excluding the patients who had major bleeding episodes in the first 24 hours, 188 (39%) were continued on the same DOAC therapy, 204 (42%) were discontinued without transitioning to another agent, and 95 (20%) were transitioned to another agent. Finally, 410 (84%) were dismissed on DOAC therapy at the end of hospitalization. The difference in the continuation rate of the same DOAC agent beyond 24 hours, discontinuation without transition to an alternate agent, or discontinuation of DOAC with a transition to an alternate anticoagulation agent was not statistically significant ( P = .60). A total of 52 major bleeding events were identified. Gastrointestinal bleeding was the most common bleeding complication [n (%): 34 (65)], followed by intra-abdominal and peri-procedural bleeding [7 (13.5) and 7 (13.5)]. Thirty-three (65%) patients had a major bleeding complication requiring intervention. Conclusions:Our single-center retrospective study describes the current prescribing practices and preliminary outcomes in ICU patients with prehospital use of DOACs. Up to 20% of the patients were transitioned to a different agent within 24 hours of ICU admission, whereas a significant proportion of patients (42%) had anticoagulation discontinued altogether. Most patients who suffered a major bleeding episode required either endoscopic or surgical intervention to control bleeding.

Abstract ObjectivePrevious studies suggested that hypernatremia or hyperosmolarity may have protective effects in lung injury. We hypothesized that hypernatremia and/or hyperosmolarity would prevent ARDS in those at risk of lung injury and associated with favorable outcomes in ARDS patients.SubjectsAll admissions at medical, surgical, and multidisciplinary intensive care units in Mayo Clinic, Rochester from the year of 2009 to 2019.DesignRetrospective cohort study. The occurrence of ARDS was identified using a validated computerized search strategy. The association between serum sodium/osmolarity and the occurrence of ARDS was analyzed using a multivariable logistic regression model. The relationship between serum sodium/osmolarity and outcomes of ARDS was analyzed using linear and logistic regression models.ResultsAmong 50,498 patients, the serum sodium level on admission did not have a significant association with the occurrence of ARDS, with an adjusted odds ratio of 0.95 [95% CI (0.86, 1.05)]. There was no significant association between calculated serum osmolarity and the occurrence of ARDS, with an adjusted odds ratio of 1.03 [95% CI (1.00, 1.07)]. 1560 patients developed ARDS during the ICU stay. Their serum sodium level did not have a significant association with their outcomes [adjusted estimated difference in 28-day ICU-free days, 0.08 days, 95% CI (-0.85, 1.02), adjusted estimated difference in 28-day ventilator-free days, -0.02, 95% CI (-0.62, 0.58), adjusted odds ratio of 28-day mortality 1.02, 95%CI (0.84, 1.24)]. There was no significant association between their calculated serum osmolarity and their outcomes [adjusted estimated difference in 28-day ICU-free days, -0.26, 95% CI, (-0.63, 0.12); adjusted estimated difference in 28-day ventilator-free days, -0.05, 95% CI (-0.28, 0.19); adjusted odds ratio of 28-day mortality, 1.07, 95% CI (0.99, 1.15)].ConclusionsAdmission serum sodium or serum osmolarity were not associated with the occurrence or outcomes of ARDS in ICU.

BACKGROUND: Several markers of oxygenation are used as prognostic markers in acute hypoxemic respiratory failure. Real-world use is limited by the need for invasive measurements and unreliable availability in the electronic health record. A pragmatic, reliable, and accurate marker of acute hypoxemic respiratory failure is needed to facilitate epidemiologic studies, clinical trials, and shared decision-making with patients. F IO 2 is easily obtained at the bedside and from the electronic health record. The F IO 2 trajectory may be a valuable marker of recovery in patients with acute hypoxemic respiratory failure. METHODS: This was a historical cohort study of adult subjects admitted to an ICU with acute hypoxemic respiratory failure secondary to community-acquired pneumonia and/or ARDS. RESULTS: Our study included 2,670 subjects. F IO 2 and S pO 2 were consistently more available than was P aO 2 in the electronic health record: (F IO 2 vs S pO 2 vs P aO 2 : 100 vs 100 vs 72.8% on day 1, and 100 vs 99 vs 21% on day 5). A worsening F IO 2 trajectory was associated with reduced ventilator-free days. From days 2 to 5, every increase in F IO 2 by 10% from the previous day was associated with fewer ventilator-free days (on day 2: adjusted mean –1.25 [95% CI –1.45 to –1.05] d, P < .001). The S pO 2 /F IO 2 trajectory also provided prognostic information. On days 3 – 5, an increase in S pO 2 /F IO 2 from the previous day was associated with increased ventilator-free days (on day 3: adjusted mean 2.09 (95% CI 1.44–2.74) d; P < .001). S pO 2 /F IO 2 models did not add predictive information compared with models with F IO 2 alone (on day 2: adjusted F IO 2 vs S pO 2 /F IO 2 R2 0.122 vs 0.119; and on day 3: 0.153 vs 0.163). CONCLUSIONS: F IO 2 and S pO 2 /F IO 2 are pragmatic and readily available intermediate prognostic markers in acute hypoxic respiratory failure. The F IO 2 trajectory in the first 5 d of ICU admission provided important prognostic information (ventilator-free days). Although the S pO 2 /F IO 2 trajectory was also associated with ventilator-free days, it did not provide more information than the F IO 2 trajectory alone.

Current guidelines suggest screening all patients with idiopathic pulmonary arterial hypertension for genetic aberrations, particularly mutations in Bone Morphogenic Protein Receptor Type II (BMPR2), the gene most commonly implicated in the pathogenesis of PAH. Herein, we present a novel technique used to identify a pathogenic germline BMPR2 alteration in a 36‐year‐old female and family members with hereditary pulmonary arterial hypertension who each screened negative by standard cytogenetics and molecular genetics testing.

OBJECTIVES: Accurate identification of acute respiratory distress syndrome is essential for understanding its epidemiology, patterns of care, and outcomes. We aimed to design a computable phenotyping strategy to detect acute respiratory distress syndrome in electronic health records of critically ill patients. DESIGN: This is a retrospective cohort study. Using a near real-time copy of the electronic health record, we developed a computable phenotyping strategy to detect acute respiratory distress syndrome based on the Berlin definition. SETTING: Twenty multidisciplinary ICUs in Mayo Clinic Health System. SUBJECTS: The phenotyping strategy was applied to 196,487 consecutive admissions from year 2009 to 2019. INTERVENTIONS: The acute respiratory distress syndrome cohort generated by this novel strategy was compared with the acute respiratory distress syndrome cohort documented by clinicians during the same period. The sensitivity and specificity of the phenotyping strategy were calculated in randomly selected patient cohort (50 patients) using the results from manual medical record review as gold standard. MEASUREMENTS AND MAIN RESULTS: Among the patients who did not have acute respiratory distress syndrome documented, the computable phenotyping strategy identified 3,169 adult patients who met the Berlin definition, 676 patients (21.3%) were classified to have severe acute respiratory distress syndrome (Pao 2/Fio 2 ratio ≤ 100), 1,535 patients (48.4%) had moderate acute respiratory distress syndrome (100 < Pao 2/Fio 2 ratio ≤ 200), and 958 patients (30.2%) had mild acute respiratory distress syndrome (200 < Pao 2/Fio 2 ratio ≤ 300). The phenotyping strategy achieved a sensitivity of 94.4%, specificity of 96.9%, positive predictive value of 94.4%, and negative predictive value of 96.9% in a randomly selected patient cohort. The clinicians documented acute respiratory distress syndrome in 1,257 adult patients during the study period. The clinician documentation rate of acute respiratory distress syndrome was 28.4%. Compared with the clinicians’ documentation, the phenotyping strategy identified a cohort that had higher acuity and complexity of illness suggested by higher Sequential Organ Failure Assessment score (9 vs 7; p < 0.0001), higher Acute Physiology and Chronic Health Evaluation score (76 vs 63; p < 0.0001), higher rate of requiring invasive mechanical ventilation (99.1% vs 71.8%; p < 0.0001), higher ICU mortality (20.6% vs 16.8%; p < 0.0001), and longer ICU length of stay (5.1 vs 4.2 d; p < 0.0001). CONCLUSIONS: Our rule-based computable phenotyping strategy can accurately detect acute respiratory distress syndrome in critically ill patients in the setting of high clinical complexity. This strategy can be applied to enhance early recognition of acute respiratory distress syndrome and to facilitate best-care delivery and clinical research in acute respiratory distress syndrome.