AN EVIDENCE AND RISK-BASED APPROACH TO A HARMONISED LABORATORY ALERT LIST. RCPA-AACB Working Party for High Risk result Management

Transcription

1 AN EVIDENCE AND RISK-BASED APPROACH TO A HARMONISED LABORATORY ALERT LIST RCPA-AACB Working Party for High Risk result Management

2 RCPA-AACB WORKING PARTY FOR HIGH RISKS RESULTS Craig Campbell Grahame Caldwell Penelope Coates Robert Flatman Andrew Georgiou Rita Horvath Que Lam Alan McNeil Hans Schneider

3 PROCESS FOR DECIDING THE ALERT THRESHOLDS The working party has designed a 6 step process for deciding alert thresholds. Process considers Evidence for thresholds Risk to patient - if no action taken Analytical aspects Workload implications

4 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence Low threshold 2.5 or 2.8 mmol/l? High threshold strong case for 6.2 mmol/l LOW K THRESHOLD Level 1 - Clinical Outcome Studies Level 2 - Recommended by Professional Bodies Laboratories and Clinicians Clinicians Laboratories 2.5 ( ) [3] 2.8 ( ) [3] Level 3 - Surveys 2.5 ( ) [1] 2.8 ( ) [11] Level 4 - Individual Institutions 2.75 ( ) [12] 2.5 ( ) [7] 2.8 ( ) [21] Limitations of Evidence Evidence mainly state of the art Search only retrieved evidence where laboratory terminology was used (i.e., critical results, panic values, etc). HIGH K THRESHOLD Level 1 - Clinical Outcome Studies Level 2 - Recommended by Professional Bodies Laboratories and Clinicians Clinicians Laboratories 6.2 ( ) [1] 6.3 ( ) [1] 7.0 ( ) [1] 6.2 ( ) [3] 6.2 ( ) [3] Level 3 - Surveys 6.0 ( ) [1] 6.2 ( ) [11] Level 4 - Individual Institutions 6.25 ( ) [12] 6.0 ( ) [7] 6.05 ( ) [22]

5 Retrospective can t select comparison groups K measurement and mortality - not subjective 48 hour/in-hospital/ 1 year mortality High K - cause or consequence? Mortality at different concentrations Big data needed for odds ratios with confidence intervals

6 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence - Results sorted into groups. - Group 1 = comparator. ~ Based on 873,000 test results Significant increase in risk of in-hospital mortality Significant decrease in risk of in-hospital mortality

7 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ Based on 873,000 test results Plots of 48-hour survival from first potassium measurement. Authors Conclusion 6.2 mmol/l appropriate for upper threshold. 2.8 mmol/l not conservative enough for lower threshold.

8 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 6,600 hyperkalaemic patients over 5 years High mortality rate Number of patients with k > 6.3 Review of every death within 8hrs of K > 6.3: hk was cause of death in very few cases High in-hospital mortality rate for patients with a hyperkalaemia discharge diagnosis code. Hyperkalaemia was judged to be responsible for only 4 deaths throughout 5 year period.

9 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 186 patients with potassium > 6.0 mmol/l. 14% mortality (16/111) in patients with K between 6 and 7 mmol/l. Absence of or early ECG changes in K between 6 and 7 mmol/l.

10 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence Working party decided that we need to also perform more targeted searches for Level 1 evidence. PubMed Search Keywords: hypokalemia, hyperkalemia, mortality.

11 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 923 patients with potassium > 6.5 mmol/l. High in-hospital mortality rate Mortality significantly associated with: severe underlying disease coexisting medical conditions severe hyperkalemia The comparator (AKI without CKD) was a strong predictor of mortality. Results imply that CKD protects against mortality caused by hyperkalaemia.

12 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 38,000 patients with potassium > 4.0 mmol/l. Associations adjusted for: age, race, gender, WBC, HCO3, BUN, creatinine, glucose, Deyo-Charlson Index, transfusions, patient type (medical versus surgical), sepsis, RRT, AKI, diabetes mellitus Significant increase in risk of inhospital mortality at K > 4.5 mmol/l.?? Odds ratios not rising when K goes above 5.5 mmol/l. Risk of mortality was negated in patients whose K declined by >1 mmol/l within 48 hrs of critical care initiation. ~ Effective Treatment

13 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 6,000 patients who died within 1 day of a blood draw for potassium. As severity of CKD increases, the risk of mortality (within 1 day of a hyperkalaemic event) reduces.?? Should we have a higher alert threshold for advanced CKD??

14 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 15,500 patients. Mortality follow-up: 23.5 years (on average). Why no long term mortality risk in diuretic-induced hypokalaemia? Perhaps an underlying disease (such as chronic illness or hyperaldosteronism) is the causal risk factor.

15 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 2,100 patients. Mortality follow-up: 8 years. Significantly increased risk of long term CVD mortality for K 3.5 to 3.8 mmol/l (low normal) compared to K 3.9 to 4.4 mmol/l (high normal). No increase in risk of long term CVD mortality for K 2.8 to 3.4 mmol/l (low) compared to K 3.5 to 3.8 mmol/l (low normal).

16 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence ~ 375 patients. In-hospital mortality. Very high mortality rate for severe hypokalaemia. 80% (32/40) of patients that died with severe hypokalaemia also had hypernatraemia. Was the hypernatremia responsible for mortality?

17 DECIDING POTASSIUM ALERT THRESHOLDS Steps 1 and 2 Review Literature / Rate Evidence What can we take from the literature review? Note that outcome studies were mainly retrospective: Labs still phoned critical potassiums Patients were treated for potassium imbalances as per normal No evidence to suggest that state of the art upper threshold (of 6.2 mmol/l) requires adjusting (based on cardiac related mortality). Based on limited evidence, hypokalemia (down to 2.5 mmol/l) may have a casual rather than causal relationship with the high rate of mortality. Insufficient evidence to justify the lower threshold of 2.5 mmol/l.

18 DECIDING POTASSIUM ALERT THRESHOLDS Steps 3 Risk Analysis 1. Identify potential harm and clinical intervention 2. Estimate likelihood and severity of potential harm, and urgency of clinical intervention 3. Evaluate whether routine reporting exposes patient to unacceptable risk

19 DECIDING POTASSIUM ALERT THRESHOLDS Steps 3 Risk Analysis Where can we get information on clinical intervention? Guideline Search: GIN (Guidelines International Network) The US National Guideline Clearing House etg (Electronic Therapeutic Guidelines, Australia) Online clinician decision support systems: BMJ Best Practice UpToDate PubMed Search: Keywords - (Hypokalemia OR Hyperkalemia OR Potassium) AND Guideline

20 DECIDING POTASSIUM ALERT THRESHOLDS Steps 3 Risk Analysis Hyperkalaemia - Essentially 3 Levels of Treatment 1. Calcium gluconate: Immediately administered to patients with symptoms or ECG changes ~ to stabilise the cardiac muscle. (Temporary effect) 2. Insulin and beta-2 agonists: Urgently administered to patients with symptoms, ECG changes, or moderate to severe hyperkalemia ~ to shift the potassium from the plasma to the cells. (Temporary effect) 3. Loop diuretics, ion-exchange resin, or dialysis: Urgency depends on severity and acuteness of hyperkalaemia; Administered to patients with severe, moderate or possibly mild hyperkalaemia ~ to eliminate excess potassium. (Permanent effect) Critical Risk

21 DECIDING POTASSIUM ALERT THRESHOLDS Steps 3 Risk Analysis Definitions for Severity of Hyperkalaemia 6.2 mmol/l is middle ground between 6.0 and 6.5 mmol/l What constitutes mild, moderate and severe hyperkalaemia is inconsistently defined in the literature. Source Sample Type Mild Hyperkalaemia Moderate Hyperkalaemia Severe Hyperkalaemia Emergency Treatment etg Australia Serum ECG helps determine urgency BMJ Best Practice Serum mmol/l UpToDate (Adult) Serum > 5.5 mmol/l > 6.5 mmol/l > 6.5 mmol/l UpToDate (Children) Serum or Plasma > 7.0 mmol/l > 7.0 mmol/l Emerg Med Pract Feb;14(2):1-17 Pharmacol Res Nov;113(Pt A): J Manag Care Spec Pharm Apr;23(4-a Suppl):S10- S19. Resuscitation 46 (2000) Am Fam Physician Sep 15;92(6): Serum mmol/l mmol/l > 7.5 mmol/l Insulin at > 6.5 mmol/l Serum Serum Serum > 5.0 mmol/l > 6.0 mmol/l > 7.0 mmol/l Serum > 6.5 mmol/l Ca at > 6.5 mmol/l; B2 agonist/insulin at > 6.0 mmol/l. Insulin/albuterol at > 6.0 mmol/l Insulin/albuterol/bicarb at > 6.0 mmol/l Prompt intervention at > 6.5 mmol/l

22 DECIDING POTASSIUM ALERT THRESHOLDS Steps 3 Risk Analysis Hypokalaemia Definitions and Treatment Definitions for severity of hypokalaemia are more consistent in the literature: Mild ~ < 3.5 mmol/l Moderate ~ < 3.0 mmol/l Severe ~ < 2.5 mmol/l Urgent treatment: IV administration of K with constant ECG monitoring Required in patients with symptoms or ECG changes Opinion varies on whether severe asymptomatic hypokalaemia requires urgent treatment Non-urgent treatment is typically an oral dose of K once daily.

23 DECIDING POTASSIUM ALERT THRESHOLDS Steps 3 Risk Analysis Conclusions Considering state of the art, mortality study findings and urgency of treatment, the critical risk alert thresholds for K should be: < 2.5 mmol/l AND > 6.2 mmol/l Laboratories should also monitor for sudden shifts in K levels away from the reference interval. More conservative significant risk thresholds may be needed for community based patients to enable earlier detection of acute hypo/hyperkalaemia.

24 K+ THRESHOLDS SO FAR K+ <2.5 mmol/l K+ >6.2 mmol/l

25 4. ASSESS TRANSFERABILITY AND CONSIDER THE PRE- AND POSTANALYTICAL ASPECTS OF THE ALERT THRESHOLD

26 POPULATION SPECIFIC ALERT THRESHOLDS PATIENTS ON DIALYSIS Should they have a higher hyperkalemia threshold? Can they be reliably identified? Not supported by clinical experience NEONATES & INFANTS Low renal excretion of potassium in first few months life AACB CRI 0-1 wk URL 6.5 mmol/l 2-26 wk URL 6.7 mmol/l UK NHS Neonatal Guidelines: Rx at K+> 7.0 mmol/l (& more aggressive Rx when >7.5 mmol/l) K+ Threshold >7.0 mmol/l for infants 0-6 months.

27 PREANALYTICAL CONSIDERATIONS EFFECT OF SAMPLE TYPE Plasma vs. serum Assumption that studies looking at K+ probably contained a mixture of specimen types. AACB CRI already accepts the mmol/l difference between serum and plasma. For adults, K+ 6.2 mmol/l serum ; 5.9 mmol/l plasma K+ 6.2 mmol/l plasma; 6.5 mmol/l serum For infants, Where plasma is preferred specimen, could reasonably lower threshold from 7.0mmol/L to 6.5 mmol/l

28 PSEUDOHYPERKALAEMIA Delayed separation is a significant issue for some laboratories.?any idea of magnitude of problem Approaches: Choose a higher threshold to accommodate these higher potassiums not recommended Assess potassium result on individual basis Ignore the issue H = 261 = 5.3% L = 165 = 3.4%

29 5. ASSESS THE IMPACT OF THE SELECTED THRESHOLDS ON THE FREQUENCY OF CRITICAL ALERTS

30 FLAGGING RATES Should not determine which threshold to use. However, where evidence is not strong, may provide useful information. Indicate the burden of notification. Absolute no. calls vs. % total. Degree of difficulty Outpatient vs. Inpatient notification Time of day notification is made Limitations of modelling Need data over a long time period. Need paediatric results to assess specific threshold. Need to assess all notifiable test results, not just one test in isolation.

31 K+ FLAGGING DATA Reported K+ results Mon 5 th Sun 11 th March. Public Hospital Laboratory 2 public hospitals n= 4906 (outpt:inpt 1:4) Private Pathology network 32 laboratories n = (outpt:inpt 7:3) Pathology Services asked to look at flagging rates and no. of actual calls (keeping with local instructions).

32 POTASSIUM FLAGGING RATE Hypokalemia < 2.5 mmol/l - guidelines < 2.8 mmol/l state of the art < 3.0 mmol/l - guidelines < 3.5 mmol/l significant risk Hyperkalemia > 5.5 mmol/l significant risk > 6.0 mmol/l guidelines > 6.2 mmol/l state of the art > 6.5 mmol/l - guidelines > 7.0 mmol/l paediatric*, and level at which ECG changes are more likely

33 HYPOKALEMIA K Threshold (mmol/l) Results flagged Abs. Calls Av. Calls per day. No. lab Highest burden lab Abs calls /day (total call/week) Inpt:Outpt <2.5 <2.8 <3.0 <3.5 1 (0.02%) (0) 0:0 1 (0.00 %) (0) 1:0 6 (0.12%) (5) 3:2 6 (0.00%) (1) 1:3 18 (0.37%) (15) 11:4 28 (0.00%) (6) 14:6 165 ( 3.4%) (141) 118: (2.14%) (109) 148:170

34 HYPERKALEMIA K Threshold (mmol/l) Results flagged Abs. Calls Av. Calls per day. No. lab Highest burden lab Abs calls /day (total call/week) >7.0 1 (0.02%) (1) 1:0 6 (0.00%) (1) 2:1 >6.5 1 (0.02%) (1) 4:1 15 (0.00%) (3) 5:2 > (0.34%) (15) 13:2 23 (0.01%) (7) 8:5 > (0.57%) (25) 20:5 Inpt:Outpt 46 (0.01%) (16) 17:13 > (2.3%) (99) 68: (0.07%) (87) 76:100

35 K+ THRESHOLDS SO FAR K+ <2.5 mmol/l? <3.0 mmol/l? K+ >6.2 mmol/l? >6.0 mmol/l? Paediatric: >7.0 mmol/l serum + plasma? >6.5 mmol/l plasma?

36 6. SEEK ENDORSEMENT FOR SELECTED THRESHOLDS FROM LABORATORIES AND CLINICAL GROUPS

37 ENDORSEMENT Laboratories Thresholds will be circulated for comment through AACB. Individual labs model flagging rate and compare to current thresholds. Clinicians Clinical groups medical colleges, representative societies/organisations. Indivdual labs consult their clinicians local guidelines survey ;?statewide?australasian

38 Survey of clinicians from all hospitals serviced by NSW Health Pathology laboratories (130 clinicians from 34 hospitals. 74% consultants). Online questionnaire Respondents were asked: whether they agreed with the thresholds in the list. If not, nominate alternate thresholds. The timeframe (immediately, within 8 hours or by the next business day) in which each of the critical risk results should be phoned.

39 Test Age Laboratory Threshold Clinician Agreement with Lab Threshold Clinician Proposed Alternate Threshold [if disagreed with lab] Mean (Range) [n] Immediate Phoning Required < 2.8 mmol/l 90.5% (86/95) 2.8 ( ) [9] 82.1% (69/84) Potassium 0 to < 28 days > 7.0 mmol/l 82.7% (81/98) 6.3 ( ) [14] 97.7% (84/86) PAEDIATRIC THESHOLDS For patients aged 0 to 1 month, 79% of survey respondents (53/67) agree with an upper alert threshold of >7.0 mmol/l. Among those that disagree, 6 have proposed a threshold of >6.2 mmol/l, while 4 suggested >6.5 mmol/l.

40 Test Age Laboratory Threshold Clinician Agreement with Lab Threshold Clinician Proposed Alternate Threshold [if disagreed with lab] Mean (Range) [n] Immediate Phoning Required Potassium 28 days to < 110 years < 2.5 mmol/l 89.8% (106/118) 2.9 ( ) [13] 83.8% (88/105) > 6.2 mmol/l 74.2% (89/120) 6.3 ( ) [33] 82.4% (84/102) ADULT THRESHOLDS For patients aged 28 days to 110 years, there was 71% agreement (57/79) for a threshold of >6.2 mmol/l. Alternative thresholds proposed by respondents for this age group include >6.0 mmol/l (9 respondents) and >6.5 mmol/l (9 respondents). What are the actionable thresholds? Is it preferable to be warned before the actionable level?

41 CONCLUSIONS POTASSIUM THRESHOLDS K+ <2.5 mmol/l? <2.8 mmol/l? <3.0 mmol/l? K+ >6.2 mmol/l? >6.0 mmol/l? >6.5 mmol/l? Paediatric: >7.0 mmol/l serum + plasma? >6.5 mmol/l plasma?

42 CONCLUSIONS - PROCESS 6 step process Hyperkalemia and hypokalemia as a example. Each step requires a lot of work. Plan to limit the number of thresholds we attempt Pros: less work, shorter timeframe Cons: Critical results fatigue (labs and clinicians).

43

44 POTASSIUM RESULTS MON 5 TH SUN 11 TH MARCH. PUBLIC HOSPITAL LABORATORY SERVICING 2 HOSPITALS. N=4906 H = 261 = 5.3% L = 165 = 3.4% More

45 No. of phone calls No. of phone calls POTASSIUM RESULTS MON 5 TH SUN 11 TH MARCH. PUBLIC HOSPITAL LABORATORY SERVICING 2 HOSPITALS. N=4906 K Threshold (mmol/l) > 7.0 >6.5 >6.2 paediatric, and level at which ECG changes are more likely guidelines state of the art Results flagged Calls Mad e Av. Calls per day. 1 (0.02%) :0 7 (0.14%) :1 17 (0.34%) :2 > (0.45%) :2 >6.0 Guidelines 28 (0.57%) :5 > (0.73%) :8 >5.5 significant risk Inpt:Outpt 112 (2.3%) : MON TUES WED THUR FRI SAT SUN