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Gas Reference Intervals

The Struggle Continues

Roger Ashton Pathlab Whakatane Walking on eggshells

Riding on the shoulders of those who have tried before

Lynne Clarke – Waikato Tony Mace - Pathlab

And many others including : RCPA ARQAG AACB

Blood Gas Reference Intervals

Lyn Clarke Dip MLT, BBS June2016 Analysers in New Zealand

 Radiometer – majority of large volume sites  41 ABL800  11 ABL80  25 ABL90  iSTAT – Large numbers in low volume sites  Siemens – A few sites APPROX 9  GEM At least 2  ? Others e.g. Epoch, Roche, Novastat 12 New Zealand Locations Reality

 Few Laboratories have references in their methods. • Some use vendor ranges.

 There is a lot of data on cord bloods

 Plenty of data on animals

 Very little data on adults

 Text books often have no references or reference each other e.g Tietz, Sigaard-Andersen, Wallach, New England Medical Journal

 Still cannot get agreement on UNITS

Klaestrup et al 2011

 182 patients  Medical Students and health professionals

 118 medical students practising on each other  76% <40 yrs (138)  Age range 20-76 yrs  Radiometer analyser

Conclusions 2015

 CLSI now allows for Consensus Ranges

 Logically the ranges should be the same throughout the country.

 Get buy in from Pathologists

 Set up a meeting of the participants

iSTAT Comparison of Reference Intervals

REFERENCE RANGES LITERATURE Tietz 4th ed ABBOTT Klaestrup et Widdop Cousineau et al Test Age 2006 ISTAT Radiometer al (2011) (2002) ( 2006) Helwig (1996) Yeomans (1985) Victory (2004) Shirley (1996) Number in study ? ? ? 182 126 16060 146 20456 53 pH Arterial 1 Day 7.29-7.45 7.35 - 7.45 7.35-7.45 Male 7.376 -7.455

Female 7.35-7.45 7.384-7.468 Female/Male 7.35 - 7.45 7.382 - 7.462 pH Venous Adult 7.32-7.43 7.31 - 7.41 60-90 7.31-7.42 pH - Capillary 36-60 hours 7.312-7.473 pH Cord Blood- Arterial 7.28±0.05 7.10-7.38 7.15-7.43 7.17-7.31 pH Cord Blood - Venous 7.35±0.05 7.20-7.46 7.24-7.49 7.27-7.45 54-95 mmHg pO2 Arterial 1 Day 7.18-12.64 kPa

83-108 mmHg 83-108 mmHg >1 Day 11.04-14.36 kPa 11.07-14.4 kPa 11.1-15.5 kPa pO2 Venous pO2 Capillary 36-60 hours 32.8- 61.2 mmHg 80 -105 mmHg pO2 Cord Blood- Arterial 6.7 -14 kPa 6-30 mmHg 3.8-33.8 mmHg pO2 Cord Blood - Venous 16-43 mmHg 15.4-48.2 mmHg 27-40 mmHg pCO2 Arterial Newborn 3.59-5.32 kPa 35-48 35-48 mmHg 35-45 mmHg mmHG(M/F) Adult Male 4.66-6.38 kPa 4.67 - 6.0 kPa 4.67-6.40 kPa 4.5-6.0 kPa 32-45 mmHg 35-45 mmHg Adult Female 4.26 - 5.99 kPa 4.67 - 6.0 kPa 4.1 - 5.6 kPa Female/Male 4.3-6.0 kPa 0.8-0.83 kPa Higher than 41-51 mmHg pCO2 Venous arterial 5.47 - 6.8 kPa Where we are currently

 pH

 Tietz (2006) 7.35 – 7.45  Wallach (1996) 7.36 – 7.44  Radiometer, Siemens iSTAT 7.35 – 7.45  Klaestrup et al (2011) 7.382 – 7.462

pH

 Propose 7.35 - 7.45 pO2

Adult

KPA mmHg Semantics and conversion factors 1 7.5 2 15 3.5 26.25 mmHg 4 30 6 45 160 6.7 50.25 KPA mmHg 140 7 52.5 1 7.5 7.6 57 2 15 120 8 60 4 30 9.34 70.05 6 45 100 9.5 71.25 8 60 80 10 75 10 75 10.65 79.875 12 90 60 10.66 79.95 14 105 40 10.67 80.025 16 120 11.34 85.05 20 18 135 11.4 85.5 20 150 0 12 90 0 5 10 15 20 25 13.3 99.75 14 105 16 120 18 135 • Do we want our Reference Range to be exact? 20 150 • To how many decimals? • Or Memorable? • Or close enough? • Or Clinically Significant NUMERICAL CREEP 11 KPa = 82.5 mmHg “ Let’s call it 83” 83 mmHg = 11.1 KPa “must be exact”

80 ~ 10.7 85 ~ 11.4

100 ~ 13.3 108 ~ 14.4 PO2 Adult

 Low 70 – 85 mmHg = 9.3 – 11.4 KPa

 High 100 - 108 mmHg = 13.3 - 14.4 Kpa

 9.3 - 14.4 Kpa ?? Too wide, and not referenced ??  ORIGINAL PROPOSAL  Tietz 83 - 108 mmHg = 11.0 to 14.4 KPa

P O 2

 ARQAG Proposal

 75 - 105 mmHg 10 - 14 KPa PCO2

Wider variation depending on source Tried looking at Low & High separately Some sources had different Male and Female

Test Age Range ADHB Christchurch Waikato Wellington WDHB Hawkes Bay Whakatane pCO2 Arterial 4.6-6.0 kPa 24-30.0 mmHg 4.5-6.0 kPa 35-45 mmHg 4.6 -6.0 KPA 35-45 4.67 - 6.00 kPa pCO2 Venous 5.0-6.4 kPa 25-33.0 mmhg 5.0-6.4 kpa 38-48 mmHg 41-51 5.47 - 6.8 kPa

PCO2 Adult  Low MALE 32 – 37 mmHg = 4.3 – 4.9 KPa  Low FEMALE 27 – 32 = 3.6 – 4.3 Kpa  LOW limit NZ LABS 24 – 30 = 3.4 – 4.0 Kpa

 High MALE 45 – 48 = 6.0 – 6.66  High FEMALE 43 – 45 = 5.6 – 6.0  High limit NZ LABS 30 – 48 = 4.0 – 6.67 Kpa

 DO WE NEED GENDER SPECIFIC RANGES ??

PCO2 Adult

 Tietz  Male 35 – 48 mmHg = 4.7 – 6.4 KPa  Female 32 – 45 mmHg = 4.3 – 6.0 KPa

 ARQAG PROPOSAL  35 - 45 mmHg 4.7 - 6.0 KPa

Consensus Recommendation NZPOCTQAG / ARQAG NSW Pathology • source  pH 7.35 - 7.45 Tietz

 PO2 75 - 105 mmHg = 10.0 to 14.0 Kpa Tietz / ARQAG

 PCO2 35 – 45 mmHg = 4.7 to 6.0 KPa Tietz / ARQAG  HCO3 22 to 28 mmol/L  -3 to +3 mmol/L  Lactate less than 2.0 mmol/L

Cord Bloods Agreed 2018 What is next?

 HAEMOGLOBIN  HaemQAG RCPA

 Haematology nationwide recommendations 2014  Needed “pruning” to give 10 age related for use in POC Number of significant figures

 The reference intervals are rounded regardless of the number of decimals in the original source.  pH: Rounded to 2 decimal places.  pCO2: Rounded to 0 decimal place for mmHg and 1 decimal place for kPa.  pO2: Rounded to 0 decimal place for mmHg and 1 decimal place for kPa.  ctHb: Rounded to 0 decimal place. (1 decimal for g/dl )  sO2: Rounded to 0 decimal place for % and 2 decimal places for fraction. Laboratories may choose to report to a higher number of Decimals, but Ranges should be rounded  Other parameters  (, Metabolites, & Co-oximetry)  Generally follow ARQAG

 Do we need separate ranges?  Serum, Plasma, Whole Blood?

 Potassium Venous Ranges

 To be discussed in more detail by Rita  Currently before ARQAG

Where to next?

 Propose pH , PCO2, PO2 ranges to

 NZPOCTQAG  ARQAG  PATHOLOGISTS  Other Quality Groups

 Suggest need for haste and assertiveness. onions References

 B.E. Statland, Clinical Decision Levels for Lab Tests (Oradell, NJ: Medical Economic Books, 1987).  P.C. Painter, J.Y. Cope, J.L. Smith, “Reference Ranges, Table 41–20” in Tietz Textbook of Clinical Chemistry—Second Edition, C.A. Burtis and E.R. Ashwood, eds. (Philadelphia: W.B. Saunders Company, 1994).  CLSI Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory – Third Edition v28 n30 Base Excess??

 Standard Base Excess ?? SBE  Actual Base Excess ?? ABE

 HCO3  Plasma  Standardized  K 3.5-5.2 mmol/L  Na 135-145 mmol/L  Cl 95-110 mmol/L  pH 7.30-7.40  PO2 No RR  PCO2 5.0-6.4 Kpa 40-50 mmHg  HCO3 22-28 mmol/L  Lactate < 2.0 mmol/L  Ionized Ca 1.15-1.30 mmol/L