Validation of cell-cycle arrest biomarkers for acute kidney injury using clinical adjudication.

RATIONALE: We recently reported two novel biomarkers for acute kidney injury (AKI), tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein 7 (IGFBP7), both related to G1 cell cycle arrest. OBJECTIVES: We now validate a clinical test for urinary [TIMP-2]·[IGFBP7] at a high-sensitivity cutoff greater than 0.3 for AKI risk stratification in a diverse population of critically ill patients. METHODS: We conducted a prospective multicenter study of 420 critically ill patients. The primary analysis was the ability of urinary [TIMP-2]·[IGFBP7] to predict moderate to severe AKI within 12 hours. AKI was adjudicated by a committee of three independent expert nephrologists who were masked to the results of the test. MEASUREMENTS AND MAIN RESULTS: Urinary TIMP-2 and IGFBP7 were measured using a clinical immunoassay platform. The primary endpoint was reached in 17% of patients. For a single urinary [TIMP-2]·[IGFBP7] test, sensitivity at the prespecified high-sensitivity cutoff of 0.3 (ng/ml)(2)/1,000 was 92% (95% confidence interval [CI], 85-98%) with a negative likelihood ratio of 0.18 (95% CI, 0.06-0.33). Critically ill patients with urinary [TIMP-2]·[IGFBP7] greater than 0.3 had seven times the risk for AKI (95% CI, 4-22) compared with critically ill patients with a test result below 0.3. In a multivariate model including clinical information, urinary [TIMP-2]·[IGFBP7] remained statistically significant and a strong predictor of AKI (area under the curve, 0.70, 95% CI, 0.63-0.76 for clinical variables alone, vs. area under the curve, 0.86, 95% CI, 0.80-0.90 for clinical variables plus [TIMP-2]·[IGFBP7]). CONCLUSIONS: Urinary [TIMP-2]·[IGFBP7] greater than 0.3 (ng/ml)(2)/1,000 identifies patients at risk for imminent AKI. Clinical trial registered with www.clinicaltrials.gov (NCT 01573962).

Discontinuation of mechanical ventilation at end-of-life: the ethical and legal boundaries of physician conduct in termination of life support.

End-of-life care in the ICU generally encompasses both the withholding and withdrawal of life support and the administration of palliative care. There is little practical distinction in the specific technology or life-support modality that is limited or removed with respect to the subsequent medical, ethical, or legal analysis. The important ethical issues pertinent to end-of-life care in the ICU at the point-of-life support discontinuation are: (1) the distinction between allowing patients to die in accordance with their wishes and causing them die, (2) the fine line between respecting a patient's wish to die with dignity and control and the risk of subsequent allegations of euthanasia or physician-assisted suicide, and (3) the adjunctive use of medications that simultaneously provide comfort but also may hasten death. The medical and legal issues are summarized, and an algorithm for the discontinuation of mechanical ventilatory support at the end of life is presented.

Legal issues in the practice of critical care medicine: a practical approach.

The intensive care unit is characterized by severely ill patients who frequently succumb to their disease, despite complex modern therapies and the best efforts of dedicated care teams. Although critical care is not historically characterized as a high-risk medical specialty with respect to litigation, the urgency, complexity, and invasive nature of intensive care unit care clearly increases legal risk exposure. Physicians do not practice in a vacuum. Instead, the practice of medicine is increasingly affected by government regulation, societal pressures, and pubic expectations. Law governs the interactions among the government, institutions, and individuals. Therefore, at a time when the practice of medicine itself is becoming increasingly more complex, physicians and other healthcare providers also face increasing administrative and legal challenges. Therefore, it is imperative that physicians develop an understanding of basic substantive and procedural law; first, so that their practices can be more focused and rewarding and less a fear of the unknown; second, that we can work proactively to minimize our legal risk; third, so that we can better communicate with risk managers, attorneys, and insurers; and finally, so that we can better understand and participate in future legal, legislative, regulatory, and public policy development. Accordingly, this general overview briefly addresses the substantive law of medical malpractice, informed consent, the law relating to research in critical care, Emergency Medical Treatment and Active Labor Act, the False Claims Act, peer review, state board disciplinary issues, and the Health Insurance Portability and Accountability Act; in addition, relevant procedural considerations will be briefly summarized.

Bacterial pericarditis and tamponade due to nonencapsulated Haemophilus influenzae complicating a case of adult community-acquired pneumonia.

We report a case of bacterial pericarditis in an immunologically competent adult female caused by nonencapsulated Haemophilus influenzae (H influenzae) that was complicated by the acute development of life-threatening pericardial tamponade. H influenzae is a gram-negative coccobacillus, a pathogen most frequently associated with childhood exanthema (otitis media, meningitis) and, less frequently, adult pneumonia. Encapsulated, type b, or typable H influenzae is the strain implicated in childhood infections. On the other hand, nonencapsulated or nontypable H influenzae is the specific strain most often associated with exacerbation of chronic obstructive airway disease. Bacterial pericarditis caused by either subtype of H influenzae is exceedingly rare. We have located only 15 previously reported cases of H influenzae pericarditis occurring in adults in the world medical literature, the majority of which date back to the pre-antibiotic era. In 12 of these 15 cases (the only cases in which typing could be accomplished), the encapsulated strain of H influenzae was cultured from the pericardial fluid. Thus, to the best of our knowledge, we are reporting here the first case of bacterial pericarditis caused by nonencapsulated H influenzae in an immunologically competent adult.

Monitoring pulmonary function with superimposed pulmonary gas exchange curves from standard analyzers.

OBJECTIVE: A repetitive graphic display of the single breath pulmonary function can indicate changes in cardiac and pulmonary physiology brought on by clinical events. Parallel advances in computer technology and monitoring make real-time, single breath pulmonary function clinically practicable. We describe a system built from a commercially available airway gas monitor and off the shelf computer and data-acquisition hardware. METHODS: Analog data for gas flow rate, O2, and CO2 concentrations are introduced into a computer through an analog-to-digital conversion board. Oxygen uptake (VO2) and carbon dioxide output (VCO2) are calculated for each breath. Inspired minus expired concentrations for O2 and CO2 are displayed simultaneously with the expired gas flow rate curve for each breath. Dead-space and alveolar ventilation are calculated for each breath and readily appreciated from the display. RESULTS: Graphs illustrating the function of the system are presented for the following clinical scenarios; upper airway obstruction, bronchospasm, bronchopleural fistula, pulmonary perfusion changes and inadequate oxygen delivery. CONCLUSIONS: This paper describes a real-time, single breath pulmonary monitoring system that displays three parameters graphed against time: expired flow rate, oxygen uptake and carbon dioxide production. This system allows for early and rapid recognition of treatable conditions that may lead to adverse events without any additional patient measurements or invasive procedures. Monitoring systems similar to the one described in this paper may lead to a higher level of patient safety without any additional patient risk.