Co-creating critical limits for enhanced acute care: proven need and web knowledge base. Part 1: A call to action!

Editors Note

A few months ago, I sent Dr. Kost, who serves as the reviewer of the Table of Critical Limits that appears in MLO’s annual publication Clinical Laboratory Reference (CLR), a question from a reader, in the hopes that he would respond to it for MLO‘s recurring “Tips from the Clinical Experts” column. The question was this: “What are critical values for routine coagulation testing (i.e. PT and PTT) for therapeutic and diagnostic testing?”

Dr. Kost responded with a discussion of scope far beyond that of typical “Tips” answers: A two-part discussion with a call to action—on the broader topic of standardized critical limits for enhanced acute care. I enthusiastically took Dr. Kost up on his offer to address this important topic for MLO once again, as he did for the magazine with a colleague more than 20 years ago (he explains below). MLO is pleased to run Part 1 in this December 2015 issue; Part 2 will follow in the January 2016 issue.

History of critical limits

With the teamwork of Ms. Gloria Lew-Peck, a gifted survey expert, and student researchers in the Point-of-Care Center for Teaching and Research (POCT•CTR), we conducted the first national surveys of critical limits in the 1980s. Our goals were to capture quantitative critical limits, qualitative critical values, and underlying policies, then describe patterns of use and relationships to outcomes in hospitals randomly selected and geographically distributed across America.

We obtained and worked directly from hospital policies; while we communicated with hospital staff, there was no data transcription by respondents and no forms to be completed, that is, no possibility of selection bias or transcription errors in the surveys.

We observed that hospitals essentially had innovated a consensus-like process whereby critical values were implemented widely for approximately 15 years following their inception, and then adjusted to meet laboratory and clinical needs in the course of uncountable urgent notifications of critical test results across the nation. The practice had become a de facto standard of care, so our first surveys codified that standard.

We published this collaborative evidence in several journals, as follows: a) in 1990 for adult hospitals in the Journal of the American Medical Association (JAMA)¹; b) in 1991 for children’s hospitals in Pediatrics²; and c) in 1993 in the Archives of Pathology and Laboratory Medicine³ for ionized (free) calcium (Ca⁺²). In 1993 a cover article in Medical Laboratory Observer (MLO)⁴ was the first to graphically link critical limits and outcomes in critical care, while summarizing the previously published survey data.

The MLO article has been used widely throughout the United States and often is cited during legal proceedings. Since 1992, tables with accompanying notes updated annually have appeared every April in MLO’s Clinical Laboratory Reference (CLR),⁵ which is accessible online at http://www.clr-online.com/CLR20152016-Table-of-Critical-Limits.pdf. The journal publications, web presence, and recommended harmonization⁶ led to other countries adopting the concept of urgent critical results notifications to improve quality and patient outcomes, including Canada,⁷ China^8-11 (where we consulted for investigators), and Italy.^12,13

Subsequently, professional organizations published subscriber/membership polls of critical values in 2002¹⁴ and 2007.^15,16 A web-based survey of laboratories associated with the Accreditation Council for Graduate Medical Education pathology residency programs for drugs appeared in 2011.¹⁷ Of note, a survey of the North American Specialized Coagulation Laboratory Association in 2011¹⁸ documented an International Normalized Ratio (INR) critical limit of 5.0. A study of hematology critical values performed in Canada in 2015 unfortunately did not include coagulation tests.¹⁹ A study of INR critical values processes published in 2015 cited, “anticoagulant warfarin…as the second most frequent drug responsible for serious, disabling, and fatal adverse drug events in the United States.”²⁰ Hence, the high risk warrants timely notification and also justifies critical limits for point-of-care testing (POCT).

These membership/subscriber surveys often use “fill-in” questionnaires for respondent entries, which may artificially exclude specialized “alerts” and categorical triggers that should be captured in order to appreciate the full breadth and depth of urgent notifications of life-and-death test results. Now, 25 years after the first national surveys, we propose that each hospital post its list of critical values and associated policy to its web page, in order to co-create an original national and international resource in the public domain for everyone to use. It is the natural thing to do to progress the standard of care beyond where it is now.

Rationale

The sidebar “Logical reasons for co-creating a web knowledge base of critical limits” below outlines our rationale, and, under each bullet point, presents advantages that will help improve global practice. Others agree that practices need improvement. For example, the authors of the 2015 hematology study in Canada¹⁹ concluded, “There is a lack of consensus for critical values reporting in hematology. As critical value reporting is crucial for patient safety, standardization of this practice would be beneficial.” The authors of the 2015 INR study²⁰ stated, “Critical value INR results were reported within the time frame established by the laboratory for 93.4% of 2,604 results, but 1.0% of results were not reported.” Hence, the coagulation discipline provides an excellent example of good and bad processes and practices that should be improved. Transparency will enhance practice.

Strategic call to action

Future improvement comprises two fundamental strategies: 1) risk mitigation, in which laboratories are engaging already as part of individualized quality control plans (IQCP) due early 2016 by the Centers for Medicare and Medicaid Services (CMS), and for which the 2015 INR paper²⁰ provides many targeted, excellent, and sometimes shocking revelations that can become part of IQCPs; and importantly, 2) transparent access achieved through web postings of hospital critical limit lists and critical values policies, so that shared practice and the standard of care can evolve more efficiently and effectively.

Thus, this article is a call to action! We explain here why the time for harmonization has come, not just for coagulation but for all disciplines, including especially POCT, and for the broad spectrum of analyte tests deemed potentially to produce critical life-threatening quantitative and qualitative results.

Web consensus INR critical limits—proof of feasibility

Web consensus. Based on our web survey conducted in the U.S. during August and September of 2015, we found relatively consistent critical limits for INR, with a mean INR of 5.0 (SD 0.6); median, 5.0; mode, 5.0; and range, 4.0 to 7.0. These results derive from 37 (92.5 percent) INR listings present in 40 unique critical values lists captured via the web. Of those 37 INR listings, 46 percent (17/37) listed an INR critical limit of 5.0 (the mean, median, and mode). By definition, at or above this INR, test results indicate a potential life-threatening coagulation condition that demands immediate (<1 hr) notification of responsible clinicians, who are capable of adjusting therapy appropriately and if necessary, also of initiating life-saving medical rescue.

Regarding POCT, 8.1 percent (three of 37 web-captured INR listings) reported INR critical limits, which were 4.5, 5, and 8. Despite the small sample size, these listings suggest that more evidence will be discovered. Listings of critical limits for POCT represent a novel finding of legal significance in view of the fact that a new facet of the standard of care is arising, and hospitals could be held to it in litigation proceedings. After all, if a critical test result emerges at the point of care, it must be communicated and dealt with promptly like all others that threaten the lives of patients, wherever patients may be located. Surely, this new finding will capture the attention of The Joint Commission (TJC) and eventually filter into the National Patient Safety Goals (NPSG).

In this current survey, other coagulation critical limits, such as prothrombin time (PT) and activated PTT (aPTT), were not consistent, which makes a strong case for harmonization through this call to action, especially in view of potential litigation in the case of hospitals inadvertently using outlier critical limits that can precipitate or be associated with adverse patient outcomes. For example, a very high PTT or aPTT critical limit could mean that warnings of excessive therapeutic anticoagulation doses come too late. The 40 captured lists also illustrated that several new qualitative critical values unassociated with coagulation tests had been added over the past 25 years, raising the question of diminished impact because of overuse of urgent notifications (“crying wolf”).

Proof of feasibility. Despite its limitations, the current survey confirms the feasibility of using the web to sample and directly capture original critical limits lists and policies without transcription of data or the intervention of intermediaries. This is important, because our call to action recommends the web as a public domain knowledge base. However, critical limit lists we obtained often had no dates documented, so they need to be “cleaned up,” and the results reported here have not been validated by contacting hospitals pending additional work. The Director of the Institutional Review Board at the University of California Davis has assured us that no ethics review is necessary, because the goal is not to capture personal data, just lists and policies.

Limitations of this present work comprise a) no direct questioning of laboratory personnel to resolve discrepancies, such as one hospital that listed “aPTT/PTT;” b) no investigation of potentially missed POCT critical limits, which when listed often were instrument-specific; c) no explanation of one hospital that stated “lot specific” for INR and did not list an INR value; d) unsolved controversies, such as one hospital that listed a critical value of 15 minutes for bleeding time while another stated “none, obsolete test;” and e) in some cases, lack of clarity regarding critical limits postings for anticoagulated versus non-anticoagulated patients.

Challenges selecting PTT/aPTT critical values—proof of need

Question from a reader. In the case of coagulation critical values and in response to one MLO reader who queried recently, “What are critical values for routine coagulation testing (e.g., PT and PTT) for therapeutic and diagnostic testing?” it is relatively easy to establish that an INR of 5.0 represents a reasonable standard of care based on the web data collected, albeit preliminary and subject to change as more data are gathered.

Common sense. The INR critical limit of 5.0 makes clinical common sense—it is a level at and above which there is serious risk from bleeding. Apparently, this article is the first report of a web-based INR of 5.0 as an implied standard of care. It is consistent with the data reported in the 2015 INR study,²⁰ wherein the authors reported only “bins” and populations comprising INR 2.6-3.5, 12 values; 4.0-4.4, 28; 4.5-4.7, 16; 5.0-5.7, 27; and 6.0-10.0, 13, respectively. Nonparametric analysis of these bin data leads to an estimated median of 5.0. While this INR numerical value is not the “end-all,” it certainly represents a good preventative measure to mitigate risk.

Link with outcomes. Statistically, here the INR critical limit of 5.0 reflects simultaneously the mean, median, and mode, so there is little issue of parametric versus non-parametric statistics, although the high outlier of 7.0 we observed in the survey certainly could raise legal eyebrows, because 5.0, two points below, or five points below the even higher high of 10 reported in the 2015 INR study,²⁰ already is thought to be associated with excessive bleeding episodes and substantial patient risk. Hence, hospitals using high INR values, above two times the INR standard deviation (ignoring non-normality) in the web survey (i.e., >6.2), should design individualized quality control plans and initiate risk mitigation to be self-assured that they have selected clinically and therapeutically appropriate and meaningful values for their institutions.

Additionally, only two hospitals listed INR values linked to therapy—one for “non therapy” (>1.8) and one for “not anticoagulated” (>3). Hence, such a listing would be considered optional under the apparent standard of care, assuming this low frequency persists as additional national data are gathered. For values in the low range of high INR critical limits, none fell below 4.0—probably there is not too much wasted effort with unnecessary calls. However, calling frequency, per se, is not generally considered by courts to be an adequate criterion for selecting critical limits, although laboratory personnel will often take it into consideration.

Out of 40 captured critical limits lists, only seven reported values for PT, and four of the seven also listed critical limits for INR, which were all 5.0. In contrast to INR, consistency did not appear in the PTT and aPTT listings, for which the web survey showed “noisy” and discrepant values with lack of a consistent relationship to assumed anticoagulant therapeutic brackets of 1.5 to 2.5 times the upper limits of normal, typically not the same for PTT and aPTT. Ideally, web postings should include normal and therapeutic ranges, in part because patients themselves should be able to access this type of information.

Proof of need. Policies should be crystal clear about defining clinical needs and actual tests, whether for therapy or non-therapy, and if at the point of care. Thus, for PTT and aPTT, establishing a knowledge base as delineated in the sidebar will help alleviate these incongruities, because it is hoped that participating hospitals clarify their listings (e.g., is it really PTT or maybe aPTT?) and collectively drift into more of a consensus over time. Meanwhile, the reader can review the following web survey results (and other studies available) to decide for him- or herself in consultation with hospital peers what numerical values should be used.

In this web survey, then, the mean (SD), median, mode, and range (in seconds) found for PTT (N=21) and aPTT (N=17) were, respectively: 108(26), 100, 100 (nine at this level), and 68.9-200; and 129(29), 125, 150 (four at this level), and 85-200. As noted above, it was not clear if some hospitals considered PTT and aPTT synonymous insofar as the listings were considered, and if they did, then overall analysis for 38 captured lists showed: 117(29), 100, 100 (11 at this level), and 60-200 seconds. Note that listings for point-of-care and laboratory coagulation tests may not agree.

Beware inconsistencies. These inconsistencies obfuscate selection of appropriate PTT and aPTT critical limits, deprecate the standard of care, and, potentially, can lead to patient harm and expensive litigation, which is to say that these results prove beyond a doubt the need for a transparent consensus process based on actual evidence (i.e., critical values policies hospitals use on a daily basis) that could be achieved through web postings, public access, and the actions delineated in the sidebar.

Conclusions for Part 1

This new round of web-based assessment should not be limited to coagulation critical limits; it should encompass all analytes deemed critical enough to warrant listing, and in fact, the ability to gather raw data (i.e., hospital lists) will help accomplish that. Then the availability of shared practices will make it easier to discern the standard of care. Thus, in Part 2, we will define “standard of care,” then discuss the legal ramifications of selecting appropriate critical limits, what the courts think about the process, the consequences of a hospital being an “outlier,” and how the proposed public posting of critical values on the web can enhance patient care.

This work was supported by the Point-of-Care Testing Center for Teaching and Research (POCT•CTR) and by Dr. Kost, Director. Spatial Care Path is a trademark by William Ferguson and Gerald Kost, Knowledge Optimization, Davis, CA. The sidebar was provided courtesy and permission of Knowledge Optimization, Davis, California, and Visual Logistics, a division of Knowledge Optimization.

References

1. Kost GJ. Critical limits for urgent clinician notification at US medical centers. Journal of the American Medical Association. 1990;263:704-707.
2. Kost GJ. Critical limits for emergency clinician notification at United States children’s hospitals. Pediatrics. 1991;88:597-603.
3. Kost, GJ. The significance of ionized calcium in cardiac and critical care: Availability and critical limits at US medical centers and children’s hospitals. Archives of Pathology and Laboratory Medicine. 1993;117:890-896.
4. Kost, GJ. Using critical limits to improve patient outcome. Medical Laboratory Observer. 1993;25:22-27.
5. Table of critical limits. Medical Laboratory Observer Clinical Laboratory Reference. Available at http://www.clronline.com/CLR20152016-Table-of-Critical-Limits.pdf. Accessed September 18, 2015.
6. Kost GJ, Hale KN. Global trends in critical values practices and their harmonization. Clin Chem Lab Med. 2011;49:167-176.
7. Gong Y, Adeli K. A national survey on pediatric critical values used in clinical laboratories across Canada. Clin Biochem. 2009;42:1610-1615.
8. Zeng R, Wang W, Wang Z. National survey on critical values notification of 599 institutions in China. Clin Chem Lab Med. 2013;51:2099-2107.
9. Yang D, Zhou Y, Yang C. Analysis of laboratory repeat critical values at a large tertiary teaching hospital in China. PLoS One. 2013;8(3):e59518. doi:\ 10.1371/journal.pone. 0059518. Epub 2013 Mar 14.
10. Niu A, Yan X, Wang L, Min Y, Hu C. Utility and necessity of repeat testing of critical values in the clinical chemistry laboratory. PLoS One. 2013 Nov 19;8(11):e80663. doi: 10.1371/journal.pone.0080663. eCollection 2013.
11. Zhou F, Zhao B, Gu D. Evaluation of laboratory critical serum potassium values and their association with clinical symptoms in Chinese Han patients. J Int Med Res. 2015 Sep 18. pii: 0300060515576011. [Epub ahead of print]
12. Lippi G, Giavarina D, Montagnana M, Luca Salvagno G, Cappelletti P, et al. National survey on critical values reporting in a cohort of Italian laboratories. Clin Chem Lab Med. 2007;45:1411-1413.
13. Piva E, Sciacovelli L, Laposata M, Plebani M. Assessment of critical values policies in Italian institutions: comparison with the US situation. Clin Chem Lab Med. 2010 Apr;48(4):461-468.
14. Howanitz PJ, Steindel SJ, Heard NV. Laboratory critical values and procedures: a college of American Pathologists Q-Probes Study in 623 institutions. Arch Pathol Lab Med. 2002;126:663-669.
15. Wagar EA, Stankovic AK, Wilkinson DS, et al. Assessment monitoring of laboratory critical values: a College of American Pathologists Q-Tracks study of 180 institutions. Arch Pathol Lab Med. 2007;131:44-49.
16. Wagar EA, Friedberg RC, Souers R, Stankovic AK. Critical values comparison. A College of American Pathologists Q-Probes survey of 153 clinical laboratories. Arch Pathol Lab Med. 2007;131:1769–1775.
17. McClain CM, Owings R, Bornhorst JA. Heterogeneity of publicly accessible online critical values for therapeutic drugs. J Pathol Inform. 2011;2:53-62.
18. Pai M, Moffat KA, Plumhoff E, Hayward CP. Critical values in the coagulation laboratory: results of a survey of the North American Specialized Coagulation Laboratory Association. Am J Clin Pathol. 2011;136:836-841.
19. McFarlane A, Aslan B, Raby A, Bourner G, Padmore R. Critical values in hematology. Int J Lab Hematol. 2015;37:36-43.
20. Howanitz PJ, Darcy TP, Meier FA, Bashleben CP. Assessing clinical laboratory quality: A College of American Pathologists Q-Probes study of prothrombin time INR structures, processes, and outcomes in 98 laboratories. Arch Pathol Lab Med. 2015;139:1108-1114.