Procalcitonin: A promising tool or just another overhyped test?

Sepsis is the leading cause of death worldwide. Timely administration of antibiotics is recognized as the cornerstone in the management of sepsis. However, inappropriate use of antibiotics may lead to adverse effects and the selection of drug-resistant pathogens. Microbiological cultures remain the gold standard to diagnose infection despite their low sensitivity and the intrinsic delay to obtain the results. Certain biomarkers have the benefit of rapid turnover, potentially providing an advantage in timely diagnosis leading to accurate treatment. Over the last few decades, there is an ongoing quest for the ideal biomarker in sepsis. Procalcitonin (PCT), when used alone or alongside additional clinical information, has shown to be a promising tool to aid in the diagnosis and management of patients with sepsis. In February 2017, the Food and Drug Administration (FDA) approved the use of PCT to guide antibiotic treatment in lower respiratory tract infections and sepsis. Despite a good negative predictive value for bacterial infection, the utility of PCT-guided antibiotic initiation is conflicting at best. On the other hand, the use of PCT-guided antibiotic discontinuation has shown to reduce the duration of antibiotic use, the associated adverse effects, and to decrease the overall mortality. The current review discusses the history and pathophysiology of procalcitonin, synthesizes its utility in the diagnosis and management of sepsis, highlights its limitations and compares it with other biomarkers in sepsis.

Enhancing Sepsis Outcomes: A 7-Year Multidisciplinary Endeavor.

Regulatory bodies in the United States have implemented quality metrics aimed at improving outcomes for patients with severe sepsis and septic shock. The current study was a quality improvement (QI) project in a community-based academic center aimed at improving adherence to sepsis quality metrics, time to antibiotic administration, and patient outcomes. Electronic health record systems were utilized to capture sepsis-related data. Regular audits and feedback sessions were conducted to identify areas for improvement, with a focus on the timely administration of antibiotics. Interventions included improving access to antibiotics, transitioning from intravenous piggyback to intravenous push formulations, and providing continuous staff education and training. This multidisciplinary QI initiative led to significant improvements in the mortality index, length of stay index, and direct cost index for patients with sepsis. Targeted multidisciplinary QI interventions resulted in improved quality metrics and patient outcomes.

Serum Bicarbonate: Reconsidering the Importance of a Neglected Biomarker in Predicting Clinical Outcomes in Sepsis.

Background Despite being an important pathophysiological component, information on the predictive value of serum bicarbonate level in sepsis is limited. Study design and method This is a single-centered retrospective study involving 4176 patients admitted to the medical ICU (MICU) with a diagnosis of sepsis. Patients were divided into two groups based on the presence or absence of chronic kidney disease (CKD) on admission: CKD and non-CKD, respectively. Each group was then divided into three sub-groups based on serum bicarbonate level at presentation (in mEq/l)- low (<22), normal (22-28), and high (>28). We compared the clinical outcomes between the sub-groups in each group, with in-hospital mortality as the primary endpoint. Secondary endpoints included vasopressor-free days, ventilator-free days, ICU-free days, and hospital-free days. Result In both the CKD and non-CKD groups, low serum bicarbonate was associated with significantly increased in-hospital mortality. There was no difference in the mortality between the sub-groups with normal and high serum bicarbonate. When adjusted for other known predictors of mortality, the association of low serum bicarbonate with increased in-hospital mortality was statistically significant only in the patient group with a Sequential Organ Failure Assessment (SOFA) score of ≥9. Additionally, the SOFA score had a better predictive value for in-hospital mortality, ICU-free days, and ventilator-free days when the serum bicarbonate level was <22. Interpretation Serum bicarbonate is a good predictor of clinical outcomes in sepsis and can be used along with other markers of sepsis to predict clinical outcomes.

Mechanical Power: A New Concept in Mechanical Ventilation.

Mechanical ventilation is a potentially life-saving therapy for patients with acute lung injury, but the ventilator itself may cause lung injury. Ventilator-induced lung injury (VILI) is sometimes an unfortunate consequence of mechanical ventilation. It is not clear however how best to minimize VILI through adjustment of various parameters including tidal volume, plateau pressure, driving pressure, and positive end expiratory pressure (PEEP). No single parameter provides a clear indication for onset of lung injury attributable exclusively to the ventilator. There is currently interest in quantifying how static and dynamic parameters contribute to VILI. One concept that has emerged is the consideration of the amount of energy transferred from the ventilator to the respiratory system per unit time, which can be quantified as mechanical power. This review article reports on recent literature in this emerging field and future roles for mechanical power assessments in prospective studies.

Low Yield of Thyroid-Function Tests in Adult Hospitalized Patients - A Retrospective Analysis.

BACKGROUND: In the US, serum thyroid-stimulating hormone (TSH) and thyroxine measurements are the fourth- and tenth-commonest laboratory tests ordered, respectively. Diagnosis of thyroid disorder requires clinical suspicion supported by laboratory values. However, in the setting of acute illness, both the clinical and laboratory pictures can be confounded. OBJECTIVE: To study clinical outcomes and derangement patterns of inpatient thyroid-function tests. DESIGN: This retrospective study was conducted at an academic center on admissions aged ≥18 years and TSH tests performed over a 1-year period. Admissions with active pregnancy and/or prior thyroid-related diagnosis were excluded. MAIN OUTCOMES: Clinical outcomes were divided based on new diagnosis of thyroid-related disorder, newly prescribed thyroxine replacement, or antithyroid drugs/ endocrinology referrals, or both. In order to analyze the derangement patterns of abnormal TSH, only the results of the first test ordered were considered (as some admissions had multiple TSH tests ordered). RESULTS: A total of 7,204 admissions aged ≥18 years had TSH tests done. Of these, 1,912 were excluded. Of the 5,292 admissions with no prior thyroid disorder or active pregnancy, 183 (3.46%) were assigned a new diagnosis of thyroid-related disorder, 54 (1.02%) received treatment/referral, and 46 (0.87%) received both a new diagnosis and treatment/referral. Based on the TSH results (reference range 0.42-4.0 mIU/L) of the 5,292 admissions, 4,312 (81.5%) and 980 (18.5%) admissions were flagged normal and abnormal, respectively. Of the 980 admissions with one or more abnormal TSH results, 21 (2.14%) had first ordered TSH <0.05 mIU/L, 855 (87.25%) admissions had first TSH result between 0.05-10 mIU/L, and lastly 104 (10.61%) were >10 mIU/L. CONCLUSION: There is low value in testing inpatients for thyroid disorders, and testing comes at significant expense to the health-care system.

Acute Liver and Renal Failure: A Rare Adverse Effect Exclusive to Intravenous form of Amiodarone.

Amiodarone is an antiarrhythmic drug which is highly effective against a wide spectrum of ventricular tachyarrhythmias making it irreplaceable in certain group of patients. We report an unusual case of acute liver and renal failure within 24 hours of initiation of intravenous (IV) amiodarone which resolved after stopping the medication. The mechanism of acute liver and renal toxicity is not clearly known but is believed to be secondary to amiodarone induced (relative) hypotension, idiosyncratic reaction to the drug, and toxicity of the vector that carries the medication, polysorbate-80. In this case review, we discuss the hyperacute drug toxicity caused by IV amiodarone being a distinctly different entity compared to the adverse effects shown by oral amiodarone and support the suggestion that oral amiodarone can be safely administered even in patients who manifest acute hepatitis with the IV form.

A Hematological Menace: Multiple Venous Thrombosis Complicated by Acquired Factor VIII Deficiency.

BACKGROUND: Acquired hemophilia A (AHA) classically presents with spontaneous bleeding of mucosal sites, GI tract, and subcutaneous tissues, often leading to large hematomas and ecchymosis. Among documented cases, 50% are idiopathic and few have been associated with trauma or surgery. We present a case of life-threatening bleeding caused by AHA, following trauma and complicated by multiple venous thrombi. CASE REPORT: A 21-year-old man presented with multiple injuries secondary to trauma leading to extensive life-saving surgery. Two weeks post-operatively, he developed multiple deep venous thrombi and was started on anticoagulation. Twenty-four days post-operatively, he started bleeding from multiple mucosal sites and developed an abdominal hematoma. Anticoagulation was stopped, with administration of fresh frozen plasma and vitamin K. Diagnosis of AHA was made based on low factor VIII level and presence of factor VIII inhibitors after an appropriate battery of tests ruled out other possible diagnoses. He was started on steroids and recombinant factor VIIa, leading to immediate improvement. Once stable, Rituximab infusions resulted in decreasing factor VIII inhibitor levels, with gradual normalization of PTT. CONCLUSIONS: AHA remains a diagnostic challenge because of its rarity, leading to delay in diagnosis and causing significant morbidity and mortality. Elevated PTT relative to PT/INR is a strong clue which should be followed by mixing studies. Very few cases have been associated with surgery or trauma and relatively few large, controlled trials have compared different treatment modalities for AHA. Growing evidence supports anti-CD20 (Rituximab) as an effective treatment option, as in this case.