Narelle Hadlow, Peter Ward, Ken Sikaris

Transcription

1 Narelle Hadlow, Peter Ward, Ken Sikaris

2 Analytes for consideration Vascular, renal and Na and water changes Consider physiology and review data Na, K, Cl, Urea, Cr, Osm Acid base status Consider physiology and review data Anion gap, bicarbonate

3 Data sources Published ranges Klajnbard, 2010 Clin Chem Lab Med, Danish, 801-subset, 6x in Preg, 391 no Cx,(Plasma, Vitros 950, Cobas Integra 400) Larsson, 2008, BJOG, Swedish, 52 normals, 9x in Preg, (Plasma, Abbott Archi) Lockitch 41 normal + Lit review, (Serum Ektachem 700) Gronowski various publications Abbassi-Ghanavati, 2009, ObsGyn, Database review-above and others Up to Date- various publications (Larsson, Lockitch, Bacq (LFT s), Ardawi, Davison (Osm) PathWest RI KEMH Vitros, Tertiary, Plasma Sonic data RI Serum. SEALS data RI

4 Important Information Sources 1. Normal pregnancies. 801 to 391 Normals, 6 samplings, Plasma, 2.5 and 97.5 percentiles and 90% CI 52 Normal, 9 samplings each Plasma Calc. Lower 2.5 percentile and Upper 97.5 percentile and 90% CI Nordic Ref Int Proj comparisons

5 Important Information Sources 2. Published Texts. Pregnancy RI Textbooks 41 normals studied, plus Literature review Data presented as follows with % of nonpregnant also given

6 Important Information Sources 3. Data Mining -SONIC Tests Thousands S Sodium: S Potassium: S Chloride: S Bicarbonate: S Urea: S Creatinine: S egfr: S Anion Gap: Haemolysis S Bilirubin: S C Bilirubin: S U Bilirubin: S ALP: S GGT: S ALT: S AST: S Total Protein: S Albumin: S Calcium: S Corr Calcium: S Phosphate: S Uric Acid: S LDH: P Glu Fast P Glu AM P Glu PM S Glu Fast S Glu AM S Glu PM

7 Na -Sonic

8 Vascular, renal and Na and water Physiology changes Data Proposed ranges Na, K, Cl, Bicarb, Urea, Cr

9 Vascular, renal and Na and water changes GFR % to 170 ml/min/1.73 m2 from cardiac output & renal Blood flow Creatinine Clearance 50% Creatinine and Urea 30% Eg Creatinine umol/l Sodium 3-5 mmol/l Osmolality up to 10 mmol/kg (nadir 10/40) Eg falls to ~ 270 mmol/kg median

10 Changes driven by Relaxin (Deng et al, Danielson et al, Conrad et al, Davison et al) Osmolality threshold Vasopressin secreted at lower Osm Thirst at lower Osmolality + Nitric Oxide + Endothelial Rec-NO pathway RELAXIN ILGF-from ovary corpus luteum Vasc. Resistance Renal Vasodilation (? Other effects on relaxin on afferent arteriole JGA myoendocrine cells- reduced stretch) RAS activation Systemic vasodilation Sympathetic activity water & Na ~-900 mmol plasma volume (1.5 L) Renal Blood Flow ~60% hcg GFR ~ 50% Creatinine HypoNa, Osmolality

11 Data summary Sodium SODIUM Bias assessment outcome No sign. method bias Summary Data: AACB mmol/l PREGNANT Non Pregnant Weeks Klanjbard mmol/l Larsson mmol/l Up to date mmol/l Lockitch mmol/l Gronowski N/P PathWest mmol/L Sonic Serum mmol/l SEALS mmol/l NOTE:Not Provided = N/P Note different starting points of Klanjbard and Larsson - higher Sonic ** T1: 0 97 days T2: days T3: days

12 Summary - SODIUM ( mmol/L AACB) Agreement Slightly lower, not much change (98% of Non Preg) ~ 2 mmol/l drop average- at upper and lower RI ( or last meeting suggested ) T1-T3 much the same Although minimal might be clinically significant ie provide reassurance

13 Data summary Potassium POTASSIUM Bias assessment outcome No sign. method bias Summary Data: AACB mmol/l Non Pregnant PREGNANT Weeks Klanjbard mmol/l Larsson mmol/l Up to date mmol/l Lockitch mmol/l Gronowski N/P PathWest mmol/l N/P Sonic Serum mmol/l SEALS mmol/l NOTE: Not Provided = N/P Klajnbard, Plasma Sep d < 4 hrs Larsson Plasma Lockitch Serum PathWest Plasma Sonic Serum

14 Summary -POTASSIUM ( mmol/l) P or S Slight drop ( ) begins early pregnancy 95% of NP with slight recovery later. T1-T3 much the same 0.2 would give Previously Proposed at AACB Harmonisation : mmol/l in serum Notes from last AACB Only 5% of 40,000 pregnant women had potassium about 4.5. Only 5% of 40,000 pregnant women had potassium below 3.6 URL of 4.8 includes the rise of potassium in 3 rd trimester (unknown mechanism).

15 Other analytes for Break Out discussion

16 Chloride CHLORIDE Bias assessment outcome No sign. method bias Summary Data: AACB mmol/l PREGNANT Non Pregnant Weeks Klanjbard N/P N/P Larsson mmol/l Up to date mmol/l Lockitch mmol/l Gronowski N/P PathWest mmol/l N/P Sonic Serum mmol/l SEALS mmol/l NOTE: Not Provided = N/P Slight Drop in Chloride

17 Summary CHLORIDE ( mmol/l S/P) Possible v small drop early, Slight rise later-? Clinically significant or not T1 T3 same Proposed last AACB meeting: mmol/l Serum Notes from last meeting Slightly lower for consistency - if everything else drops due to a dilutional effect, why doesn t chloride? RI based on acknowledging this trend and being pragmatic Drop in chloride is commensurate with bicarbonate decreasing.

18 Urea UREA Bias assessment outcome Summary Data: AACB No agreed range PREGNANT Non Pregnant Weeks Klanjbard mmol/l Larsson mmol/l Up to date 7-20 mg/dl Lockitch mmol/l Gronowski N/P PathWest 3-8 mmol/l Sonic Serum mmol/l SEALS mmol/l NOTE: Not Provided = N/P Significant decrease to 65-75% of normal

19 Summary UREA mmol/l Significant decrease to 63-75% of normal? Clinical significance Persistent over T1-T3 Proposed Last AACB meeting: mmol/l Tolerant interval Confirm with reanalysis of data plus contributed data for other platforms

20 Creatinine CREATININE Bias assessment outcome No sign. method bias Summary Data: AACB umol/l PREGNANT Non Pregnant Weeks Klanjbard umol/l Larsson umol/l Up to date mg/dl Lockitch umol/l Gronowski N/P PathWest umol/l <80 <75 <90 Sonic Serum umol/l SEALS umol/l NOTE: Not Provided = N/P Significant decrease to 70% of normal

21 Summary -CREATININE (45-90 umol/l S/P) Significant decrease over pregnancy -~70% of usual, Consistent T1-T3 Previous Discussion at AACB Lower creatinine in 2 nd trimester of pregnancy is less concerning than the similar trend for urea? Proposed: µmol/l Confirm with reanalysis of data plus contributed data for other platforms

22 Physiology of Acid Base changes Progesterone sensitivity to pco2 in medulla - respiration and ventilation Later gravid uterus, lung capacity mild hyperventilation Chronic mild respiratory alkalosis with metabolic compensation pco2 from 40 mm Hg to mm Hg Compensatory renal excretion of bicarbonate HCO 3 from 25 to 22 mmol/l ( 2-4 mmol/l) ph slightly alkalotic Pa O 2 maintained normal to sl.

23 Anion Gap ANION GAP Bias assessment outcome Summary Data: AACB - No agreed range PREGNANT Non Pregnant Weeks Klanjbard N/P N/P Larsson N/P N/P Up to date 7-16 mmol/l Lockitch mmol/l Gronowski N/P PathWest mmol/l S N/P Sonic Serum mmol/l(+k) SEALS NOT REPORTED NOT REPORTED NOTE: Not Provided = N/P Limited Data Steady or some report increase

24 Bicarbonate BICARBONATE Bias assessment outcome Summary Data: AACB mmol/l PREGNANT Non Pregnant Weeks Klanjbard N/P N/P Larsson N/P N/P Up to date mmol/l Lockitch mmol/l Gronowski N/P PathWest mmol/l Sonic Serum mmol/l SEALS mmol/l NOTE:Not Provided = N/P Decrease to 85 % of normal

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26 Summary - ANION GAP and BICARBONATE (Bicarbonate mmol/l, P/S) Bicarbonate drops significantly 85% of non pregnant Over all T1-T3 Anion Gap Median is relatively steady (Lockitch suggests slight rise) Past discussion at AACB Proposed: Anion Gap Confirm with reanalysis of data plus contributed data for other platforms Proposed: Bicarb mmol/l Effect of hyperventilation in pregnancy Appears constant over pregnancy We need more data

27 Suggested Reference Intervals last AACB meeting Non Pregnant 1st / 2 nd / 3rd Trimester Little evidence of major trimester specific changes Sodium Potassium Chloride Bicarbonate Anion Gap Urea Creatinine

28 Thank you!

29 Uric Acid Normal handling complex free filtered, reasb pct, resecretion and re-absorption. Only 10% of filtered is excreted 8-16/40 UA clearance (? 2 nd to GFR) so levels ~ 25% After 20 weeks - Uric acid levels due to tubular reabsorption

30 Uric Acid URIC ACID Bias assessment outcome Summary Data: AACB Nil agreed PREGNANT Non Pregnant Weeks Klanjbard umol/l Larsson umol/l Up to date mg/dl Lockitch umol/l Gronowski umol/l PathWest mmol/l Specifically designed to accommodate 3rd trimester but no Pregnancy RI Sonic Serum mmol/l <0.31 <0.32 <0.33 <0.34 <0.35 <0.36 SEALS mmol/l NOTE: Not Provided = N/P

31 Klajnbard

32 Sonic Urate Sonic Urate T1 (0-97 days): mmol/l T2 ( days): mmol/l T3 ( days): mmol/l T3 ( days): mmol/l T3 ( days): mmol/l T3 ( days): mmol/l T3 ( days): mmol/l T3 ( days): mmol/l T3 ( days): mmol/l T3 ( days): mmol/l

33 Summary URIC ACID Significant change in UA Fall in UA early on -68% to later rise -106% T1 and T3 Different!! Rule of thumb 30/40 UA < /40 < 0.31 etc After 30 weeks, data agrees with clinician opinion Bhattacharaya analysis supports a rise of 0.01 mmol/l per week up to 38 weeks Proposed decision points: Up to 30 weeks <0.30 mmol/l weeks <0.36 mmol/l Urate in 1 st and 2 nd trimesters is predictive of where it will end up in 3 rd trimester Confirm with reanalysis of data plus contributed data for other platforms.

34 Osmolarity (mosm/kg H 2 O) OSMOLARITY Bias assessment outcome Summary Data: PREGNANT Non Pregnant Weeks Klanjbard N/P N/P Larsson N/P N/P Up to date mosmol/kg Lockitch N/P (+/- 4) Gronowski N/P PathWest NIL available Sonic Serum mosmol/kg (from Chart Data) SEALS mmol/kg NOTE: Not Provided = N/P PathWest Measured Sonic calculated (1.85(Na+K)+Urea+Gluc)