Precision medicine is increasingly touted as a groundbreaking new paradigm in biomedicine. In the ICU, the complexity and ambiguity of critical illness syndromes have been identified as fundamental justifications for the adoption of a precision approach to research and practice. Inherently protean diseases states such as sepsis and acute respiratory distress syndrome have manifestations that are physiologically and anatomically diffuse, and that fluctuate over short periods of time. This leads to considerable heterogeneity among patients, and conditions in which a “one size fits all” approach to therapy can lead to widely divergent results. Current ICU therapy can thus be seen as imprecise, with the potential to realize substantial gains from the adoption of precision medicine approaches. A number of challenges still face the development and adoption of precision critical care, a transition that may occur incrementally rather than wholesale. This article describes a few concrete approaches to addressing these challenges.
First, novel clinical trial designs, including registry randomized controlled trials and platform trials, suggest ways in which conventional trials can be adapted to better accommodate the physiologic heterogeneity of critical illness. Second, beyond the “omics” technologies already synonymous with precision medicine, the data-rich environment of the ICU can generate complex physiologic signatures that could fuel precision-minded research and practice. Third, the role of computing infrastructure and modern informatics methods will be central to the pursuit of precision medicine in the ICU, necessitating close collaboration with data scientists. As work toward precision critical care continues, small proof-of-concept studies may prove useful in highlighting the potential of this approach.
Hudson K, Lifton R, Patrick-Lake B, Burchard EG, Coles T, Collins R, Conrad A, Desmond-Hellmann S, Dishman E, Giusti K, et al. The precision medicine initiative cohort program: building a research foundation for 21st century medicine. Bethesda: National Institutes of Health; 2105. https://acd.od.nih.gov/reports/DRAFT-PMI-WG-Report-9-11-2015-508.pdf. Accessed 13 Mar 2017
Antman EM, Loscalzo J. Precision medicine in cardiology. Nat Rev Cardiol. 2016;13:591-602.
Sweeney TE, Shidham A, Wong HR, Khatri P. A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set. Sci Transl Med. 2015;7(287):287ra71.
Walley KR, Thain KR, Russell JA, Reilly MP, Meyer NJ, Ferguson JF, et al. PCSK9 is a critical regulator of the innate immune response and septic shock outcome. Sci Transl Med. 2015;6(258):258ra143.
Sapru A, Liu KD, Wiemels J, Hansen H, Pawlikowska L, Poon A, et al. Association of common genetic variation in the protein C pathway genes with clinical outcomes in acute respiratory distress syndrome. Crit Care. 2016;20(1):151. doi: 10.1186/s13054-016-1330-5.
Russell JA. Genomics and pharmacogenomics of sepsis: so close and yet so far. Crit Care. 2016:1–4.
Famous KR, Delucchi K, Ware LB, Kangelaris KN, Liu KD, Thompson BT, et al. ARDS subphenotypes respond differently to randomized fluid management strategy. Am J Respir Crit Care Med. 2017;195(3):331–338. PubMed
Van de Klundert N, Holman R, Dongelmans DA, De Keizer NF. Data resource profile: the Dutch National Intensive Care Evaluation (NICE) Registry of Admissions to Adult Intensive Care Units. Int J Epidemiol. 2015;44:1850-h. CrossRef
InFACT Global H1N1 Collaboration. InFACT: a global critical care research response to H1N1. Lancet. 2010;375(9708):11–3.
Berry SM, Connor JT, Lewis RJ. The platform trial: an efficient strategy for evaluating multiple treatments. JAMA. 2015:1–2.
Rogers AJ, McGeachie M, Baron RM, Gazourian L, Haspel JA, et al. Metabolomic derangements are associated with mortality in critically ill adult patients. PLoS ONE. 2014;9(1):e87538. doi: 10.1371/journal.pone.0087538.
Gale SC, Shanker B-A, Coyle SM, Macor MA, Choi CW, Calvano SE, et al. Continuous enteral and parenteral feeding each reduces heart rate variability but differentially influences monocyte gene expression in humans. Shock (Augusta, Ga). 2012;38:255–61. CrossRef
Norris P R, Canter JA, Jenkins JM, Moore JH, Williams AE, Morris JA. Personalized medicine: genetic variation and loss of physiologic complexity are associated with mortality in 644 trauma patients. Ann Surg. 2009;250:524–530. PubMed
Bhuvaneshwar K, Belouali A, Singh V, Johnson RM, Song L, Alaoui A, et al. G-DOC Plus—an integrative bioinformatics platform for precision medicine. BMC Bioinformatics. 2016:1–13.
Schrimpf D, Haag M, Pilz LR. Possible combinations of electronic data capture and randomization systems. Methods of Inf Med. 2014;53(3):202–207. http://doi.org/10.3414/ME13-01-0074.
- A path to precision in the ICU
David M. Maslove
John C. Marshall
Daren K. Heyland
- BioMed Central
Neu im Fachgebiet AINS
Meistgelesene Bücher aus dem Fachgebiet AINS
Mail Icon II