The importance of acidosis in asphyxia Janet M Rennie Senior Lecturer in Neonatal Medicine Institute for Women s Health, UCL, London Clinical negligence seminar, 1 Crown Office Row
Objectives To review the criteria for establishing the probability of a damaging intrapartum hypoxic ischaemic insult To define the acidosis criteria in detail and examine its pitfalls To teach the interpretation of blood gas results
Causes of cerebral palsy Intrauterine infection CNS maldevelopment genetic, toxic, Intracranial haemorrhage Intracranial thrombus or embolus (stroke) Kernicterus Perinatal hypoxia-ischaemia Meningitis, cytokine damage from other postnatal sepsis Periventricular leukomalacia IUGR, postnatal, others (prenatal cytokines) Twin-twin transfusion, death of co-twin
International consensus statement/acog criteria Essential criteria: evidence of a metabolic acidosis (fetal, cord or very early neonatal) with ph <7.0 and base deficit >-12 mmol/l; early onset of encephalopathy in infants of > 34 weeks CP of the spastic quadriplegic or dyskinetic type Exclusion of other identifiable aetiologies, such as trauma, coagulation disorders, infectious conditions or genetic disorders*. Source: MacLennan A et al BMJ 1999 319:1054-9 * Added by ACOG in 2003 ISBN 0-915473-91-7
Secondary criteria Sentinel hypoxic event occurring immediately before or during labour; sudden, rapid and sustained deterioration of CTG where the pattern was previously normal; Apgar 0-6 for >5 minutes; (ACOG 0-3 ) early evidence of multisystem involvement (ACOG within 72 hours of birth); early imaging evidence of acute cerebral abnormality (ACOG an acute non focal abnormality ).
Consensus statement: criticisms Only relevant to acute profound hypoxic ischaemia; Rigid rules with no room for inference from missing data, paradoxes or exceptions; Lack of input from neonatal neurophysiology (EEG), ultrasound or early MRI; Lack of consideration of the considerable experience with end-stage MRI. Rosenbloom L Rennie JM BMJ (correspondence) 2000;320:1076 Dear P, Rennie J, Newell S, Rosenbloom L 2000 Clinical Risk 6:143-144
Essential criterion 1; why is metabolic acidosis important? Energy systems Aerobic (requires oxygen) ATP is the essential energy currency A TP is not stored Anaerobic Sufficient oxygen is required without oxygen ATP is for the cell mitochondria to make ATP made from stored glycogen efficiently from carbohydrate, fat and protein and lactic acid accumulates
Anaerobic metabolism Only carbohydrates (glycogen or blood sugar) can be used anaerobically Anaerobic ATP synthesis involves to the formation of lactate from glucose via pyruvate This is a rapid but less efficient process and lactic acid accumulates in the blood (oxygen debt)
Normal fetal and neonatal lactate values usually less than 5 mmol/l Fetal scalp lactate < 5mmol/L (1.7 ± 0.8) Umbilical artery lactate <5 mmol/l (2.7/3.7 ± 1.2) Neonatal lactate at 30 minutes <5 mmol/l (>9 HIE, and often >7.5 with delayed clearance) Sources: Kruger, K. 1999 Am J Obs and Gynecol 181, 1072-1078. Shah, S 2004 Journal of Perinatol, vol. 24, pp. 16-20. Da Silva 2000 Acta Paed 89:320-3.
Interpreting a blood gas result Bicarbonate & Base excess Are Calculated Not measured
From Pomerance JF 2004 Interpreting umbilical cord blood gases: BNMG Pasadena http://www.cordgases.com Essential criterion 1; Acidosis Normal cord blood results range derived from mean and 2 standard deviations Venous blood Arterial blood ph 7.25-7.45 7.18-7.38 (H+) concentration 56-36 64-43 PCO2 (mmhg) 26.8-49.2 32.3-65.8 (kpa) 3.57-6.56 4.30-8.77 PO2 (mmhg) 17.2-40.8 5.6-30.8 (kpa) 2.29-5.44 0.74-4.1 HCO3 (mmol/l) 15.8-24.2 17-27 Base excess -8 to 0-8 to 0
Acidosis = more hydrogen ions An acid is a proton donor [H + ] A base is a proton acceptor ph = -log 10 [H + ] Buffering the Henderson Hasselbalch equation H + + HCO 3 - = H 2 O + CO 2
Interpretation of change in acid-base balance Modi N in Rennie JM Ed Textbook of Neonatology 4th Ed
Acidosis :quality data no significant change in ph and blood gases in arterial blood in a clamped vessel stored at room temperature for up to one hour; but lactate increases Armstrong, L. & Stenson, B. 2006, Archives of Disease in Childhood, vol. 91, no. 5, pp. 342-345.
Acidosis: quality data Westgate JA et al 1994 Br J O&G 101: 1054-1063 ph difference >0.02 and/or umbilical PCO2 should be > 4mm Hg greater than the venous PCO2. Pomerance JJ 2004 www.cordgases.com ph difference 0.03-0.04
Acidosis - example Large difference between arterial and venous ph
Acid-base differences With acute fetal hypoxaemia, there may not be enough time for fetal and placental blood to equilibrate before delivery and acids produced by the fetus may not be removed across the placenta. This will be particularly so for acids like lactic acid, for their placental transfer is much slower than for the volatile carbonic acid. As a result it will take some time for the placental extracellular fluid compartment to become saturated with lactic acid from the fetus. It is probable that large arterial-venous BD differences (high arterial BD, low venous BD) reflect an acute onset of fetal metabolic acidosis. In contrast, if both the artery and the vein have a high BD the fetal acid load has saturated placental buffering capacity and equilibration has occurred so that acidosis is not acute. Westgate J, Garibaldi JM Greene KR 1994 Umbilical cord blood gas analysis at delivery: a time for quality data. British Journal of Obstetrics and Gynaecology 101:1054-1063
Arterio-venous difference how long does it last? Umbilical vein uteroplacental function Umbilical atery fetal and uteroplacental status Reducing rapidly after 30 min and virtually gone at 0.7h Naeye & Shaffer 2005 J Perinatol 25:664-668
Acidosis - example Abnormal CTG scalp ph 7.24 One hour later repeated; ph 7.31 PCO2 28 mmhg PO2 142 mmhg BE -11 mmol/l At delivery cord ph 6.81 BE -23
Acidosis air bubble effect Important to examine all parameters of the result, not just the ph Contamination with air bubbles, including many small air bubbles, drives the oxygen level up, the carbon dioxide level down and elevates the ph. The base excess remains valid Source: Pomerance JJ Interpreting umbilical cord blood gases
Sample quality
Acidosis is it essential? Fetal lambs Occlusion of the maternal common iliac artery Lactate increased from around 2 to around 15 mmol/l De Haan et al 1993 AJOG 169: 1493-1501
Acidosis example cases 1340 ROM - syntocinon late decelerations 1800 Scalp ph 7.28, 7.29, 7.28 1925 Scalp ph 7.24, 7.24, 7.26 2025 Scalp ph 7.25, 7.44 (disregarded) 2223 Ventouse delivery cord ph 7.29
Acidosis rate of recovery Spontaneous labour, admission CTG normal cervix 4 cm dilated at 2400 Cervix 8 cm dilated at 0110 0400 still 8 cm ; synto from 0620-0710 Delivery at 0740 Apgar 2 1 7 5 arterial ph 7.18 venous ph 7.22 MRI and clinical picture borderzone damage If the damage was caused between 0620 0710 could the acidosis have recovered by 0740?
Rate of recovery 1400h scalp ph 7.26 1825h birth. Apgar 6 and 6 stunned 1930h Cap ph 7.26 CO2 4.1 bicarb 14 base excess -12 1955h Cap ph 7.26 CO2 3.28 bicarb 12 base excess -14 Bhutani 1997 Seminars Neonatol :1-12
Acidosis key messages Ideally both artery and vein sampled, with all parameters available; Lactate and early neonatal values helpful; Check for internal inconsistency, transposed values, impossibly high oxygen levels; Use the appropriate normal ranges; Genuine absence of a metabolic acidosis is evidence against damaging hypoxic ischaemia (apart from total cord occlusion).
Conclusion Some CP is acquired as a result of intrapartum hypoxia; in some the injury is potentially preventable; The Consensus (and other criteria) are a useful basis for analysis, but the problem is not as simple as these documents suggest and only applies to acute profound hypoxia