Breakout Session C: Harmonisation of the Alert Table.

Transcription

1 Breakout Session C: Harmonisation of the Alert Table.

2 RCPA-AACB High Results Working Party Andrew Georgiou Craig Campbell Grahame Caldwell Hans Schneider Penelope Coates Que Lam Rita Horvath Robert Flatman

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4 Alert Table is a list containing: Critical Tests Alert thresholds for Critical- and Significant- Results Laboratories and Clinicians must be confident that these results require notification for timely clinical action. Common goal and common tests lend themselves to Harmonisation. Beyond Harmonisation; evidence-based.

5 Points of discussion Alert Table must be solid enough to resist customisation. Individual variations are unworkable for the laboratory, and for clinicians who use multiple laboratory services. Choice of analytes & thresholds must be evidence-based. We need to state the source and strength of the evidence. Can we have one value for all methods? Start with analytes with AACB Common Reference Intervals We can t be too simplistic; what conditions do we need to consider? Inpatients vs. Community patients, after hours vs. working hours, patient groups (pregnancy, paediatric), refer to clinical notes, serum vs. plasma. Do we need to be pragmatic? Do we want to look at every analyte abnormality? Should we start with a small list and look to expand later?

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7 Published 12 th April 2015

8 Management (CLSI GP47) Hazard Identification Analysis estimation Evaluation Control Analyte value Potential harm associated with result Clinical intervention that can reduce the risk of harm Probability: Is there reasonable likelihood of harm in absence of intervention? Severity: Is there reasonable likelihood of severe damage if harm occurs? Urgency: Is immediate intervention necessary to reduce risk of harm? of Process Failure: Is there reasonable likelihood that routine reporting would not permit timely intervention? Is the risk of process failure greater than the clinically acceptable risk, given the estimation of potential harm? Category of abnormal result (critical risk vs. significant risk)

9 Hierarchy of Evidence Strength of Evidence Laboratory AND clinicians Laboratories OR clinicians Level 1 alert thresholds established by clinical outcome studies 1A 1B Source of Data Level 2 Level 3 Level 4 alert thresholds recommended by professional bodies alert thresholds from surveys of laboratories or clinicians alert thresholds reported by individual institutions 2A 3A 4A 2B 3B 4B Notes 1. Number of studies classification is based on should appear after the classification in ().

10 Elements of the Alert Table Displayed on Alert Table: Analyte Sample type Alert threshold (including delta) values Clinical setting Accompanying information for laboratory: (potential harm) of this result Probability of Harm Immediacy of Intervention Time to Escalation Level of Evidence Source Strength of Evidence

11 Laboratory abnormalities identified as High. C. Campbell and consensus. (sample type is serum/plasma unless specified) Potassium Potassium Sodium Sodium Glucose Glucose Calcium(Total) Calcium (Ionised) Calcium (Total) Calcium (Ionised) Magnesium Magnesium Phosphate Phosphate creatinine Urea Uric Acid in Pregnancy CK Cortisol CRP Bicarbonate Bicarbonate ph ph po2 pco2 Lactate Lipase Albumin ALT Ammonia Digoxin Lithium Carbamazepine Phenytoin Gentamicin (pre-dose) Paracetamol Valproate Vancomycin Bilirubin (Total) in neonate Bilirubin (Direct) in neonate freet4 freet4 TSH TSH iron in child iron in adult Urine Total Protein in Pregnancy Triglycerides Troponin Vitamin B12

12 The Plan Review evidence Define thresholds Ask laboratories if they agree Compare to current list Look at potential rates of notification. Ask clinicians if they agree Does this fit with clinical practice. Seek endorsement from laboratory and clinical groups

13 The Reality Review evidence Define thresholds Ask laboratories if they agree Compare to current list Look at potential rates of notification. Ask clinicians if they agree Does this fit with clinical practice. Seek endorsement from laboratory and clinical groups

14 Sodium Hans Schneider

15 Hypernatremia (serum/plasma) Analysis Hazard Threshold 155 Hypernatremia estimation Evaluation Control Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process > clinically acceptable risk? Category (critical vs. significant) Hyperosmolar Coma Treatment with iv Dextrose or other iv therapy Critical Level of Evidence: 1A (Craig Campbell Literature) Discussion: Currently few outcome studies- see later slides What outcome? Death? Intervention? Hospital length of stay? Clinical conditions?

16 Hyponatremia(serum/plasma) Analysis Hazard Threshold 120 Hyponatremia estimation Evaluation Control Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process > clinically acceptable risk? Category (critical vs. significant) Hypoosmolar coma, osmotic demyelination Hypertonic saline Critical Level of Evidence: 1A (see later) Discussion: Currently few outcome studies- see later slides What outcome? Death? Intervention? Hospital length of stay? Clinical conditions?

17 Natremia studies critical serum and whole blood sodium a 6-month period clinical responses and patient outcomes 615 (0.6%) were critical < 120 mmol/l, > 155 mmol/l 166 critically ; 447 critically (0.6%) the lengths of stay were increased above our average clinicians responded > 50% of results within 4 hours mortality rates of hyponatremic and hypernatremic inpatients were 19% and 48% Guerin MD, Martin AH, Sikaris KA. Change in plasma sodium concentration associated with mortality. Clin Chem Feb;38(2):317. Howanitz JH, Howanitz PJ. Evaluation of serum and whole blood sodium critical values. Am J Clin Pathol Jan;127(1):56-9.

18 Doering TA, Plapp F, Crawford JM. Establishing an evidence base for critical laboratory value thresholds. Am J Clin Pathol Nov;142(5): efigure 3 G 1.00 Survival From First Test Result: High Sodium 0.98 Fraction Surviving Hours Low Near-Critical Group High Near-Critical Group Low Critical Group High Critical Group

19 Doering TA, Plapp F, Crawford JM. Establishing an evidence base for critical laboratory value thresholds. Am J Clin Pathol Nov;142(5): Doering 48 efigure 3 K 1.00 Survival From First Test Result: Low Sodium Fraction Surviving Hours High Near-Critical Group Low Near-Critical Group High Critical Group Low Critical Group

20 Doering TA, Plapp F, Crawford JM. Establishing an evidence base for critical laboratory value thresholds. Am J Clin Pathol Nov;142(5): supplementary material from C Campbell Group Odds Ratio Relative to Group #1 Lower 95% CI Upper 95% CI p value Group Odds Ratio Relative to Group #1 Lower 95% CI Upper 95% CI p value High Sodium First Excursion Low Sodium First Excursion Group # < Group # < Group # < Group # Group # < Group # Maximal Excursion Maximal Excursion Group # < Group # < Group # < Group # < Group # < Group # Final Excursion Final Excursion Group # < Group # < Group # < Group # < Group # < Group # < 0.001

21 Change in Sodium Uptodate Among patients with hyponatremia lasting more than two to three days, or with hyponatremia of unknown duration, we recommend that the serum sodium be raised by less than 6 to 8 meq/l in any 24-hour period to prevent ODS (Osmotic demyelination syndrome) (Grade 1B). When correcting the serum sodium in patients with hyponatremia, careful monitoring of the serum sodium concentration (initially, every two to three hours) is essential to avoid overly rapid correction in patients at increased risk for ODS. The urine volume should also be monitored for the emergence of a water diuresis. Outcome studies Klinck J et al. Predictors and outcome impact of perioperative serum sodium changes in a - risk population. British Journal of Anaesthesia 114 (4): (2015) Ahn SY et al. Association Between Small Decrease in Serum Sodium Concentration within the Normal Range and All-Cause and Cardiovascular Mortality in Elderly Adults over 5 Years. J Am Geriatr Soc Mar;64(3):510-7.

22 Potassium Robert Flatman

23 Potassium Severe elevations or reductions in potassium can cause life threatening changes in excitability of skeletal and cardiac muscle Hyperkalaemia may by relatively asymptomatic up to 7.0 mmol/l already at or above life threatening levels Intervention usually successful if high/low potassium recognised and actioned promptly

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28 Low potassium (serum/plasma) Analysis estimation Evaluation Control Hazard Threshold Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process failure > clinically acceptable risk? Category (critical vs. significant) Hypokalemia <2.5 mmol/l Arrhythmias and sudden cardiac death Replacement of potassium Critical Level of Evidence: 3A No Outcome studies Strong evidence (also supported by consensus)

29 Low potassium Relatively few outcome studies for hypokalaemia General agreement it is a critical risk parameter Almost universal that labs have a low potassium critical value Very good agreement in results between labs Excellent QAP agreement Good uptake of AACB recommended common reference intervals

30 Low potassium Serum Vs Plasma Consistently slightly higher serum values Public Vs Private labs Reference interval work in recent years showed surprisingly little variation in patient populations Many private labs centrifuge at point of collection

31 Low potassium Critical Recommendation: < 2.5 mmol/l

32 Low potassium (serum/plasma) Analysis estimation Evaluation Control Hazard Threshold Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process failure > clinically acceptable risk? Category (critical vs. significant) Hypokalemia <2.5 mmol/l Arrhythmias and sudden cardiac death Replacement of potassium Critical Level of Evidence: 3A No Outcome studies Strong evidence (also supported by consensus)

33 High potassium (serum/plasma) Analysis estimation Evaluation Control Hazard Threshold Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process failure > clinically acceptable risk? Category (critical vs. significant) Hyperkalemia >6.2 mmol/l Arrhythmias and sudden cardiac death Correction of hyperkalaemia Critical Level of Evidence: 1A 3 Outcome Studies

34 High potassium Excellent QAP agreement Some discussion (previously) around upper limit for harmonised potassium reference interval Artefact more likely than low values

35 High potassium Recognising artefact is a particular challenge Correction for haemolysis is feasible and may reduce notification time and reduce need for recollections in critical care Blood gases Haemolysis difficult to detect in whole blood Need to ensure escalation mechanisms also apply for blood gas results

36 High potassium of chronic hyperkalaemia in CKD considered separately by working party based available evidence Rarely while GFR>15 ml/min Neonates special consideration for expected higher values?

37 High potassium Critical Recommendation: > 6.2 mmol/l

38 High potassium (serum/plasma) Analysis estimation Evaluation Control Hazard Threshold Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process failure > clinically acceptable risk? Category (critical vs. significant) Hyperkalemia >6.2 mmol/l Arrhythmias and sudden cardiac death Correction of hyperkalaemia Critical Level of Evidence: 1A 3 Outcome Studies

39 Calcium Penelope Coates

40 Hypocalcemia Analysis estimation Evaluation Control Hazard Threshold Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process failure > clinically acceptable risk? Category (critical vs. significant) Hypocalcaemia </= 1.9mmol/L (corrected total calcium if albumin >20 g/l)?< 0.85 mmol/l (ionised calcium) Tetany; Long QT; Seizure; Laryngospasm; Death Replacement of calcium Critical Level of Evidence: 1A (2 outcome studies) Discussion: Corrected calcium vs. measured ionised calcium Threshold for ionised calcium

41 Hypercalcemia Analysis estimation Evaluation Control Hazard Threshold Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process failure > clinically acceptable risk? Category (critical vs. significant) Hypercalcaemia mmol/l (corrected total calcium) >/=3.5 mmol/l (corrected total calcium) >1.55 mmol/l (ionised calcium) Renal damage; Neurological (coma); Arrhythmia; Heart failure; Death Rehydration; possible bisphosphonate; treat primary cause Critical Level of Evidence: 1A (3 outcome studies) Discussion: Threshold- 3.0 vs 3.5 mmol/l Potential bias of mortality data due to hypercalcaemia of malignancy

42 References SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypocalcaemia in adult patients. SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypercalcaemia in adult patients. Zhang Z et al. (2014) Predictive value of ionized calcium in critically ill patients: an analysis of a large clinical database MIMIC II. Sauter TC et al (2015). Calcium disorders in the emergency department: independent risk factors for mortality. Lutsey et al. (2014) Serum magnesium, phosphorus, and calcium are associated with risk of incident heart failure: the Atherosclerosis in Communities (ARIC) study. Am J Clin Nutr 100;

43 Glucose Rita Horvath

44 Hypoglycaemia Most commonly due to inappropriate dosage of diabetic medication. Other causes include: drugs hepatic, renal or cardiac failure sepsis, trauma, burns deficiency in cortisol, glucagon or adrenaline Non-islet cell tumours Insulinoma noninsulinoma pancreatogenous hypoglycemia (NIPHS) post gastric bypass hypoglycemia

45 Hypoglycaemia Analysis Hazard Threshold Hypoglycemia. Glucose < 2.5 mmol/l Potential harm Neurologic symptoms: anxiety, tremor, nausea, palpitations, tachycardia. Neuroglycopaenic symptoms: confusion, dizziness, lethargy, seizure, loss of consciousness, coma. Clinical intervention Immediate reversal of hypoglycaemia by: - carbohydrate ingestion at 15 minute intervals until hyopglycaemia is resolved. - administration of parental glucose if patient unable to ingest carbohydrate or if hypoglycaemia is severe.

46 Hypoglycaemia estimation Probability harm High probability of brain damage and death if severe hypoglycaemia is unresolved. Severity permanent brain damage or death Urgency immediate intervention required of Process Failure routine reporting would cause an unacceptable delay in treatment. Evaluation of process > clinically acceptable risk? Control Category (critical vs. significant) Critical

47 Hypoglycaemia Problem with Outcome Studies

48 Hypoglycaemia Problem with Outcome Studies Current studies don t establish the temporal relationship were the patients already dying? Few databases record cause specific mortality thus the relationship between hypoglycaemia and outcome is unclear. Is the hypoglycaemia itself harmful, or just indicative of a glucose control feature that is harmful?

49 Hypoglycaemia Problem with Outcome Studies 12 month prospective study - Harlem Hospital. 125 ED visits for symptomatic hypoglycaemia. Obtundation, stupor or coma in 65 patients. There was little correlation between cause, blood glucose level and symptoms. 11% mortalilty, but only 1 death due to hypoglycaemia. 4 survivors had residual focal neurological symptoms.

50 Hypoglycaemia Strength of Evidence Laboratory AND clinicians Laboratories OR clinicians Level 1 alert thresholds established by clinical outcome studies 1A 1B Source of Data Level 2 Level 3 Level 4 alert thresholds recommended by professional bodies alert thresholds from surveys of laboratories or clinicians alert thresholds reported by individual institutions 2A 2.64 mmol/l (n=3) 3A 4A 2.50 mmol/l (n=11) 2B 2.22 mmol/l (n=3) 3B 2.50 mmol/l (n=10) 4B 2.50 mmol/l (n=23)

51 Hypoglycaemia SEALS Survey of Clinicians (Still running) Yo ur o p inio n o f this thre sho ld : Answe r Op tio ns I a g re e with this thre sho ld I p re fe r a d iffe re nt thre sho ld Pre fe rre d thre sho ld Resp o nse Co unt Gluco se ra nd o m [28 days to < 110 years]: < 2.5 mmo l/l , 3.0, and W he n sho uld this re sult b e p ho ne d? Answe r Op tio ns Gluco se ra nd o m [28 days to < 110 years]: < 2.5 mmo l/l Gluco se ra nd o m [28 days to < 110 years]: > 25.0 mmo l/l Imme d ia te ly W ithin 8 ho urs o f a na lysis By the ne xt b usine ss d a y Resp o nse Co unt

52 Phenytoin Craig Campbell

53 Phenytoin Commonly prescribed anticonvulsant. Narrow therapeutic index; non-linear pharmacokinetics, even in therapeutic range. Largely protein-bound. Consider measuring free levels in hypoalbuminaemia, renal failure, critical illness.

54 Phenytoin Analysis Hazard Threshold Potential harm Clinical intervention Acute toxicity due to overdose/decreased metabolism of phenytoin. Plasma Phenytoin (trough) > 25 mg/l CNS effects: drowsiness, fatigue, dizziness, confusion, visual disturbances, nystagmus, ataxia, phenytoin induced seizure, coma. > 20 mg/l: far lateral nystagmus > 30 mg/l: 45 O lateral gaze nystagmus and ataxis > 40 mg/l: decreased mentation > 100 mg/l: death NOTE: thresholds vary widely between individuals. Cardiovascular effects: hypotension, bradyarrhythmias and arrest. Phenytoin therapy stopped. Activated charcoal within 24 hours (unless altered conscious state). Observation and supportive measures to treat symptoms. Phenytoin induced seizure can be treated with benzodiazepines.

55 Phenytoin estimation Probability harm CNS effects: very common, reversible. Coma: very uncommon. Phenytoin induced seizure: very uncommon, brief in duration. Cardiovascular effects: uncommon (and only occur in intravenous administration, due to propylene glycol solvent). Severity Common adverse effects = No; Uncommon adverse effects =. Urgency of Process Failure failure to halt dose. Phenytoin result not needed to initiate observation/treatment of symptoms. Evaluation of process > clinically acceptable risk? Control Category (critical vs. significant) Critical

56 Phenytoin Level of Evidence: 2A CC1

57 Slide 56 CC1 Original guidelines released in Craig Campbell, 8/05/2017

58 Level of Evidence: 2A Phenytoin

59 Phenytoin Strength of Evidence Laboratory AND clinicians Laboratories OR clinicians Level 1 alert thresholds established by clinical outcome studies 1A 1B Source of Data Level 2 Level 3 Level 4 alert thresholds recommended by professional bodies alert thresholds from surveys of laboratories or clinicians alert thresholds reported by individual institutions 2A = 25 mg/l (2) 3A 4A = 30 mg/l (2) 2B 3B = 25 mg/l (3) 4B = 29 mg/l (6) Notes 1. Number of studies classification is based on should appear after the classification in ().

60 Phenytoin SEALS Survey of Clinicians (Still running) What is your specialty? Answer Options Emergency Psychiatry Endocrinology Paediatrics Haematology Infectious Diseases Neurology Anaesthetics General Medicine Oncology Renal Obstetric Medicine Paediatric Endocrinology Paediatric Renal Toxicology Other (please specify) answered question Resp o nse Co unt Yo ur o p inio n o f this thre sho ld : Answe r Op tio ns I a g re e with this thre sho ld I p re fe r a d iffe re nt thre sho ld p re fe rre d thre sho ld Resp o nse Co unt Phenytoin - trough [0 to < 110 years]: > 25 mg/l W he n sho uld this re sult b e p ho ne d? Answe r Op tio ns Imme d ia te ly W ithin 8 ho urs o f a na lysis By the ne xt b usine ss d a y Resp o nse Co unt Phenytoin - trough [0 to < 110 years]: > 25 mg/l

61 Creatinine Alan McNeil

62 Elevated creatinine (serum/plasma) Analysis estimation Evaluation Control Hazard Threshold Potential harm Clinical intervention Probability harm Severity Urgency of Process Failure of process > clinically acceptable risk? Category (critical vs. significant) Acute kidney failure. Single result: 1. egfr < 12 ml/min (creatinine > 350 umol/l in women or > 450 umol/l in men). 2. Creatinine > 150 umol/l in woman years or child. Previous result available: If current result > 150 umol/l and > 50% increase over previous result. Death from hyperkalaemia or other complications of acute kidney failure. Dialysis Critical

63 Elevated creatinine (serum/plasma) Single creatinine result (no previous available) Discussion: 1. There is wide variation in the thresholds recommended by different groups. 2. Creatinine > 350 umol/l = Stage 3 acute kidney injury, AKI (KDIGO 2012). 3. Given that creatinine varies with age and sex, egfr might be a more useful measure than creatinine. Creatinine > 350 umol/l in women equates to > 450 umol/l in men and egfr < 12 ml/min (see plot). 4. Special consideration should be given to children and pregnant women where AKI is unusual and the consequences may be more serious. We use creatinine > 150 umol/l in children and women of reproductive age. 5. Changes in K and bicarbonate may help assess severity of acute metabolic derangement.

64 Elevated creatinine (serum/plasma) Previous result is available Discussion: Current criteria use calculations based on previous result, current result, absolute change, relative change and time between specimens. The first two were cited in Campbell et al Flynn et al. Previous creatinine > 50 umol/l and increase > 50 umol/l. Comment: This flags too many people and is of limited value when crea nine is (e.g umol/l). 2. Mathew et al. Previous creatinine > 97 umol/l and increase > 20%. Comment: Flags fewer results than #1. 3. KDIGO Stage 1 acute kidney injury creatinine increase fold or increase > 26 umol/l. Comment: No absolute creatinine concentration specified. The fold increase seems reasonable but the > 26 umol/l increase very.

65 Case. 62 year-old woman Date 27/04/17 01/05/17 Creatinine egfr Four day interval Creatinine increase = 81 umol/l (1.85 fold) egfr decrease = 29 ml/min (53%) Should these results be phoned? 1. Flynn et al. Previous creatinine > 50 umol/l and increase > 50 umol/l. 2. Mathew et al. Previous creatinine > 97 umol/l and increase > 20%. No 3. KDIGO Stage 1 acute kidney injury creatinine increase fold or increase > 26 umol/l.

66 Summary Analyte Threshold Notes Sodium Sodium Potassium Potassium >155 mmol/l <120 mmol/l >6.2 mmol/l <2.5 mmol/l Calcium (Total) </= 1.9 mmol/l (corrected T Ca if Alb >20 g/l) Calcium (Ionised)?<0.85 mmol/l Calcium (Total) mmol/l (corrected T Ca if Alb >20 g/l) Calcium (Total) >/= 3.5 mmol/l (corrected T Ca if Alb >20 g/l) Calcium (Ionised) Glucose >1.55 mmol/l <2.5 mmol/l Phenytoin > 25 mg/l trough egfr or Creatinine <12 ml/min/1.73m2 Or M>450, W>350 umol/l Creatinine >150 umol/l woman years or child. Creatinine > 150 umol/l & > 50% increase over previous result. Previous result available

67 Summary Alert Table design Choice of Tests/abnormalities Hierarchy of Evidence Review of Evidence Clinical consultation Laboratory consultation Endorsement