Treatment of severe metformin-associated lactic acidosis with renal replacement therapy and tris-hydroxymethyl aminomethane: a case report.

BACKGROUND: Type B lactic acidosis is a rare but serious side effect of metformin use. The risk of metformin-associated lactic acidosis is elevated in renal or liver impairment, heart failure and in metformin overdose. Metformin-associated lactic acidosis is treated with renal replacement therapy although this can be limited by metformin's large volume of distribution and a patient's hemodynamic instability. Tris-hydroxymethyl aminomethane is a buffer that rapidly equilibrates in liver cells and increases the intracellular pH of hepatocytes. Intracellular alkalosis increases lactate uptake by the liver and can promote gluconeogenesis which results in increased lactate metabolism and decreased lactate production. Unlike intravenous bicarbonate which can worsen acidosis due to carbon dioxide retention and hypocalcemia, tris-hydroxymethyl aminomethane does not generate large amounts of carbon dioxide and can improve cardiac contractility in experimental models. CASE PRESENTATION: We present a case of a 43-year-old African American male who intentionally ingested 480,000 g of metformin. He developed severe metformin-associated lactic acidosis that was refractory to 21 hours of high flux hemodialysis. This was followed by an additional 12 hours of high flux hemodialysis augmented by continuous intravenous infusion of tris-hydroxymethyl aminomethane. After initiating tris-hydroxymethyl aminomethane, the patient had rapid reversal of lactic acidosis and was weaned off vasopressors and mechanical ventilation. CONCLUSIONS: While metformin-associated lactic acidosis can be treated with renal replacement therapy, severe cases of lactic acidosis may not be amenable to renal replacement therapy alone. Through its unique buffer mechanisms, tris-hydroxymethyl aminomethane can be used in conjunction with dialysis to rapidly improve acidosis associated with metformin.

Rapid Intensive Care Unit Onboarding in Response to a Pandemic.

BACKGROUND: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, hospital resources have been stretched to their limits. We introduced an innovative course to rapidly on-board a group of non-intensive care unit (ICU) nurse practitioners as they begin to practice working in a critical care setting. OBJECTIVE: To assess whether a brief educational course could improve non-ICU practitioners' knowledge and comfort in practicing in an intensive care setting. METHODS: We implemented a multi-strategy blended 12-week curriculum composed of bedside teaching, asynchronous online learning and simulation. The course content was a product of data collected from a targeted needs assessment. The cognitive learning objectives were taught through the online modules. Four simulation sessions were used to teach procedural skills. Bedside teaching simultaneously occurred from critical care faculty during daily rounds. We assessed learning through a pre and post knowledge multiple choice question (MCQ) test. Faculty assessed learners by direct observation and review of clinical documentation. We evaluated learner reaction and comfort in critical practice by comparing pre and post surveys. RESULTS: All 7 NPs were satisfied with the course and found the format to work well with their clinical schedules. The course also improved their self-reported comfort in managing critically ill patients in a medical ICU. There was an increase in the mean group score from the pre-to the post-course MCQ (60% vs 73%). CONCLUSIONS: The COVID-19 Critical Care Course (CCCC) for NPs was implemented in our ICU to better prepare for an anticipated second surge. It focused on delivering practical knowledge and skills as learners cared for critically ill COVID-19 patients. In a short period of time, it engaged participants in active learning and allowed them to feel more confident in applying their education.

Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial.

Importance: Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective: To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants: This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions: Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures: The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results: Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, -0.2% [95% CI, -5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance: Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration: ClinicalTrials.gov: NCT04332991.

High flow nasal oxygen therapy utilization: 7-year experience at a community teaching hospital.

OBJECTIVE: To examine the use of high flow nasal cannula oxygen therapy (HFNC) between 2008 and 2014 in patients 18 years or older at a community teaching hospital. METHODS: Yearly utilization rates of HFNC, noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) were calculated among admissions with a set of cardiopulmonary diagnoses (heart failure, COPD, asthma or pneumonia). RESULTS: Among the 41,711 admissions with at least one of the above cardiopulmonary condition, HFNC was utilized in 1,128 or 27.0/1000; NIV was used in an average of 169/1000 and IMV in 231/1000. HFNC was accompanied by IMV or NIV 71.3% of the time. From 2008 to 2014 HFNC utilization increased an average of 17.5% annually; NIV increased by 10.2% annually while IMV's utilization increased by 1.6% annually. The highest rate of change in HFNC use was among admissions with pneumonia and those with COPD. CONCLUSION: HFNC utilization increased steadily over a 7-year period at our hospital. Frequently, HFNC therapy was used in combination with other ventilatory modes to support patients' respiration. Similar with other technologies in healthcare, the uptake of HFNC has preceded the evidence from robust clinical trials.

The Economic and Humanistic Burden of Severe Sepsis.

Sepsis and severe sepsis in particular remain a major health problem worldwide. Their cost to society extends well beyond lives lost, as the impact of survivorship is increasingly felt. A review of the medical literature was completed in MEDLINE using the search phrases "severe sepsis" and "septic shock" and the MeSH terms "epidemiology", "statistics", "mortality", "economics", and "quality of life". Results were limited to human trials that were published in English from 2002 to 2014. Articles were classified by dominant themes to address epidemiology and outcomes, including quality of life of both patient and family caregivers, as well as societal costs. The severity of sepsis is determined by the number of organ failures and the presence of shock. In most developed countries, severe sepsis and septic shock account for disproportionate mortality and resource utilization. Although mortality rates have decreased, overall mortality continues to increase and is projected to accelerate as people live longer with more chronic illness. Among those who do survive, impaired quality of life, increased dependence, and rehospitalization increase healthcare consumption and, along with increased mortality, all contribute to the humanistic burden of severe sepsis. A large part of the economic burden of severe sepsis occurs after discharge. Initial inpatient costs represent only 30 % of the total cost and are related to severity and length of stay, whereas lost productivity and other indirect medical costs following hospitalization account for the majority of the economic burden of sepsis. Timeliness of treatment as well as avoidance of intensive care unit (ICU)-acquired illness/morbidity lead to important differences in both cost and outcome of treatment for severe sepsis and represent areas where improvement in care is possible. The degree of sophistication of a health system from a national perspective results in significant differences in resource use and outcomes for patients with serious infections. Comprehensive understanding of the cost and humanistic burden of severe sepsis provides an initial practical framework for health policy development and resource use.