Is it Time for UK Obstetricians to Accept Fetal Scalp Lactate as an Alternative to Scalp ph?

Transcription

1 Is it Time for UK Obstetricians to Accept Fetal Scalp Lactate as an Alternative to Scalp ph? January 2015

2 Is it Time for UK Obstetricians to Accept Fetal Scalp Lactate as an Alternative to Scalp ph? 1. Background Since the introduction of cardiotocography (CTG) to monitor the fetus in labour, obstetricians have attempted to reduce its false-positive rate and therefore unnecessary intervention. The method used primarily is fetal blood sampling (FBS) to estimate fetal ph. To date, only one trial has compared the use of continuous CTG monitoring with or without fetal scalp blood sampling and its effect on the rate of caesarean section. In the group with scalp blood sampling, the total caesarean section rate was reduced from 18% to 11% and caesarean section indicated by fetal distress from 7% to 3%, when fetal scalp blood sampling was allowed. However, as only some 230 patients were included in each group, the study did not have power to show significance. 1 A Cochrane meta-analysis in 2013 looked at continuous fetal heart rate monitoring versus intermittent auscultation. Using a subgroup analysis between trials allowing scalp blood sampling for ph or not, they found significantly less neonatal acidosis but more instrumental deliveries in trials allowing scalp blood analysis. They concluded that access to fetal scalp blood sampling did not influence prespecified outcomes such as perinatal mortality or caesarean section. 2 However, this was an indirect analysis between studies with different populations and likely different management guidelines. An alternative method of establishing fetal condition in labour, fetal scalp lactate, has been introduced into obstetric practice in Sweden, France and Australia, but not the UK. The advantage claimed for lactate over ph is that sampling is easier to perform, yields results more often, can be performed at the bedside and is a better predictor of long-term neonatal condition. Since December 2014, lactate has been recommended by the National Institute for Health and Care Excellence, provided that trained staff and the relevant equipment are available. 3 This paper will review the evidence supporting fetal scalp ph as a predictor of short- and long-term fetal outcome and then review the evidence for fetal scalp lactate. It will discuss the Australian and Scandinavian experience with fetal lactate and offer an opinion on the implications for UK practice. 2. Fetal ph Originally introduced by Saling 4 in 1967, fetal scalp sampling was the first technique used to assess the fetal condition directly during the intrapartum period. In the original work by Saling, ph was equilibrated to a P CO 2 of 40 mmhg to eliminate the influence of respiratory acidaemia: i.e. to evaluate the metabolic acidaemia. For unknown reasons, the use of this equilibration disappeared over the years, probably due to the more complex laboratory work needed before analysis. Trials in the 1960s and 1970s suggested improvement in clinical outcomes when fetal scalp sampling to assess fetal ph was used. 5,6 This supposition was based on the premise that a lower than normal fetal ph is associated with shortand long-term neonatal morbidity. The strength of the association between low ph and morbidity is, however, beginning to be questioned. When neurological outcomes were compared in a cohort of babies with an umbilical cord ph ranging from , no significant difference was found. 7 A relationship between low ph and poorer long-term neurological outcome has been shown in a recent meta-analysis. 8 However, the relationship was thought most substantial only in those babies with a ph of 7 or below. In another recent observational study of over deliveries, it was found that in babies with a cord ph above 7.00 the association with neonatal morbidity was weak. Even for those babies with a cord ph below 7.00, the absolute risk of encephalopathy with seizures (and/or death) was only 2.95%. As one of its conclusions, this paper stated that the use of ph as a trigger for intervention to prevent poor long-term 2 of 6

3 neurological outcome, using current thresholds, will fail to prevent most adverse outcomes and at the cost of high rates of intervention. 9 Obtaining a fetal scalp sample for ph has been shown to take a significant amount of time and to be prone to failure. Tuffnell 10 and Westgren 11 found it to be a task which took approximately 20 minutes and failed in up to 20% of the attempts. 3. Lactate physiology and measurement In recent years, lactate has been shown to be a good predictor of adverse outcome in many areas of medicine. It is regularly used for the evaluation of the critically ill patient, both among adults and neonates. Lactate has also been tested to triage emergency patients with good results and included in diagnostic criteria for severe septicaemia. The mechanism of interest is not only tissue hypoxia but also tissue perfusion In the early years of fetal lactate studies, there was debate about whether the source of lactate measured in the fetus was maternal or fetal. Initially, the source was thought to be maternal skeletal muscles. 15 However, investigation over several years led to the conclusion that the fetus was the primary source of lactate measured in the fetal scalp and a marker of its increasing dependence on anaerobic metabolism in cases of intrapartum fetal hypoxia, as labour progresses. 16 Lactate is a metabolite produced during glucose metabolism as a result of tissue hypoxia. 17 The ph of blood within the fetal circulation is reduced by higher than normal levels of either carbonic acid (resulting from dissolved carbon dioxide) or lactic acid. Carbon dioxide levels rise when the fetus is unable to rid itself of carbon dioxide produced as a result of normal metabolism: for example, during a period of umbilical cord compression. Lactic acid production occurs when the fetus receives oxygen concentrations less than those required to maintain aerobic respiration, forcing a switch to anaerobic respiration. Lactate levels in the subcutaneous tissues have been shown to increase before ph decreases in the hypoxic process and therefore serve as an earlier marker. 18 This is explained by the buffering capacity within the tissue which can mop up the hydrogen ions, maintaining ph. With continued production of hydrogen ions (associated with prolonged hypoxia), this capacity decreases, the concentration of H + increases and ph falls. Fetal lactate estimation has long been recognised as an alternative method of establishing the presence of fetal metabolic acidaemia. Lactate as an indicator of prenatal oxygen deprivation has been known since the 1960s. 19 The ability to measure fetal lactate in blood from the fetal scalp during labour has been reported since the 1970s Fetal scalp blood lactate collected during labour and in umbilical artery blood at delivery has been shown to predict depressed newborns better than ph and/or base deficit Previously, lactate assays required microlitres of blood from the fetal scalp during labour and 1 ml of blood if taken after delivery from umbilical vein or artery. It is now possible to measure lactate at the bedside using an electrochemical microvolume device which requires a smaller fetal scalp sample of up to 5 microlitres of blood from the fetal scalp. 26 This technique employs the same sampling method as fetal ph but has a much lower failure rate. 27 This is primarily due to the much smaller volume of blood required. In addition, the test is performed at the bedside with no need to leave the labour room. It has to be emphasised that different lactate devices are available. They measure lactate levels and are calibrated differently, measuring lactate in different blood compartments (plasma, haemolysed blood or whole blood with intact erythrocytes). These facts influence the actual lactate level obtained which is likely to differ between devices used. 28 Several lactate sensors have been evaluated and have shown coefficients of variation of less than 4% of 6

4 4. Lactate versus ph Fetal scalp blood lactate has been shown to be superior in predicting hypoxic ischaemic encephalopathy (HIE), with a sensitivity of 67% and a specificity of 93% in predicting moderate to severe HIE versus 49% and 93% respectively for ph. 25 This has been supported by a more recent study showing cord blood lactate as a better predictor of low Apgar scores and HIE. 27 Women s experience of FBS during labour was examined as a pain score in a labour ward using both lactate and ph analyses. They found the procedure to be acceptable for most women. The median pain score was 3.5 out of During labour, the aim is to identify fetuses at risk for severe adverse outcome to be able to intervene before damage has occurred: i.e. to prevent and not predict adverse outcomes. In the observational data by Kruger et al. 25 the optimal cut-off value to predict an Apgar score of less than 4 at 5 minutes was 6.0 mmol/l. The corresponding value for moderate/severe HIE was 6.5 mmol/l. To be able to prevent these conditions, a cut-off value leading to intervention has to be set lower than these values. They therefore chose the 75th centile for scalp blood lactate (4.8 mmol/l) and 25th centile for ph (7.21) in this high-risk group of labours. This lactate value (4.8 mmol/l) was then suggested as the threshold for intervention as it was close to the recommended value 4 for scalp ph of 7.20 and below the predictive values quoted above. 25 A suggested clinical guideline for scalp blood determination and management is as follows: 25 Lactate value (mmol/l) Description Management < 4.2 Normal Continue labour Preacidaemia Repeat FBS between 20 and 30 minutes later > 4.8 Acidaemia Consider delivery Recently, a large randomised controlled trial compared the use of fetal scalp lactate versus scalp ph to manage the fetus during labour with nonreassuring CTG. 31 This demonstrated comparable results showing a similar level of acidaemia at birth: 3.2% in the lactate arm and 3.6% in the ph arm. As threshold values (centiles) for intervention were set at the same level, intervention rates were expected to be similar regardless as to whether lactate or ph was used. Similar intervention rates were also found in the trial. A Cochrane meta-analysis has compared analysis of lactate and ph in fetal scalp blood during labour and found no differences in fetal/neonatal outcome or operative interventions but a significantly higher success rate with lactate compared with ph (risk ratio 1.10; 95% CI ). 32 Only two trials are included in this metaanalysis and some 90% of the cases in this analysis emerge from the randomised controlled trial by Wiberg- Itzel et al. 31 However, in a recently published large observational study, where the above clinical guidelines were used, the FBS frequency was 11% and out of these 9% were acidaemic (greater than 4.8 mmol/l). This implies that only 1% of all deliveries had an FBS lactate indicating operative/instrumental delivery. 33 It has to be emphasised that FBS is useful in cases showing progressive deterioration of the CTG trace. In cases with bradycardia, FBS has no place. If fetal heart rate is not recovering, delivery has to be expedited regardless of analysis results. If it recovers, observation for at least 20 minutes is recommended as transient acidaemia is likely shortly after a bradycardic event. In obstetric catastrophies, for example, placental abruption, cord prolapse and uterine rupture, there is no place for FBS. 5. Swedish and Australian experience Australian obstetric units began to use lactate in the early 2000s. A paper published in the Australian and New Zealand Journal of Obstetrics and Gynaecology in 2004 presaged its widespread acceptance and use in the country of 6

5 Many large obstetric units in Australia recommend either ph or lactate to investigate cases of suspected intrapartum acidaemia; 35 indeed some have moved exclusively to using lactate. The latest Royal Australian and New Zealand College of Obstetricians and Gynaecologists guideline on intrapartum fetal surveillance recommends the use of scalp lactate rather than ph measurement because it is an easier and more affordable adjunct to electronic fetal monitoring for some units. 36 Lactate is used as an adjunct to electronic fetal monitoring in 41 out of 46 Swedish obstetric units Opinion Fetal lactate estimation in labour, from a fetal scalp sample using the latest bedside techniques, has been shown to be quicker and easier to perform and to yield results more often. To date, it has not been accepted into routine practice within the UK, although it is used in Sweden and Australia. Lactate deserves to be seen as at least equivalent to fetal ph when investigating the fetus with suspicious or pathological CTG in labour, as theoretically lactate is a better indicator of adverse outcome compared to ph and/or base deficit. References 1. Haverkamp AD, Orleans M, Langendoerfer S, McFee J, Murphy J, Thompson HE. A controlled trial of the differential effects of intrapartum fetal monitoring. Am J Obstet Gynecol 1979;134: Alfirevic Z, Devane D, Gyte GM. Continuous cardiotocography (CTG) as a form of electronic fetal monitoring (EFM) for fetal assessment during labour. Cochrane Database Syst Rev 2013;(5):CD National Institute for Health and Care Excellence. Intrapartum care: care of healthy women and their babies during childbirth. NICE clinical guideline 190. [Manchester]: NICE; Bretscher J, Saling E. ph values in the human fetus during labor. Am J Obstet Gynecol 1967;97: Garud MA, May DP, Simmons SC. Foetal blood sampling in the regional hospital. Br Med J 1969;i: Simmons SC, Lieberman B. The combined use of cardiotocography and fetal blood sampling in monitoring the fetus in labour. J Obstet Gynaecol Br Commonw 1972;79: Mittendorf R, Won SY, Gianopoulos JG, Pryde PG, Roizen N. Relationships between umbilical cord arterial blood ph levels at delivery and Bayley Psychomotor Development Index scores in early childhood. J Perinat Med 2008;36: Malin GL, Morris RK, Khan KS. Strength of association between umbilical cord ph and perinatal and long term outcomes: systematic review and meta-analysis. BMJ 2010;340:c Yeh P, Emary K, Impey L. The relationship between umbilical cord arterial ph and serious adverse neonatal outcome: analysis of consecutive validated samples. BJOG 2012;119: Tuffnell D, Haw WL, Wilkinson K. How long does a fetal scalp blood sample take? BJOG 2006;113: Westgren M, Kruger K, Ek S, Grunevald C, Kublickas M, Naka K, et al. Lactate compared with ph analysis at fetal scalp blood sampling: a prospective randomised study. Br J Obstet Gynaecol 1998;105: Fuller BM, Dellinger RP. Lactate as a hemodynamic marker in the critically ill. Curr Opin Crit Care 2012;18: Poukkanen M, Wilkman E, Vaara ST, Pettilä V, Kaukonen KM, Korhonen AM, et al.; the FINNAKI Study Group. Hemodynamic variables and progression of acute kidney injury in critically ill patients with severe sepsis: data from the prospective observational FINNAKI study. Crit Care 2013;17:R Nadeem M, Clarke A, Dempsey EM. Day 1 serum lactate values in preterm infants less than 32 weeks gestation. Eur J Pediatr 2010;169: Katz M, Lunenfeld E, Meizner I, Bashan N, Gross J. The effect of the duration of the second stage of labour on the acid-base state of the fetus. Br J Obstet Gynaecol 1987;94: Nordström L, Achanna S, Naka K, Arulkumaran S. Fetal and maternal lactate increase during active second stage of labour. BJOG 2001;108: Räiha NC. Organic acids in fetal blood and amniotic fluid. Pediatrics 1963;32: Engidawork E, Chen Y, Dell Anna E, Goiny M, Lubec G, Ungerstedt U, et al. Effect of perinatal asphyxia on systemic and intracerebral ph and glycolysis metabolism in the rat. Exp Neurol 1997;145; Daniel SS, Adamsons K Jr, James LS. Lactate and pyruvate as an index of prenatal oxygen deprivation. Pediatrics 1966;37: Yoshioka T, Roux JF. Correlation of fetal scalp blood ph, glucose, lactate and pyruvate concentrations with cord blood determinations at time of delivery and cesarean section. J Reprod Med 1970;5: Eguiluz A, López Bernal A, McPherson K, Parrilla JJ, Abad L. The use of intrapartum fetal blood lactate measurements for the early diagnosis of fetal distress. Am J Obstet Gynecol 1983;147: Smith NC, Soutter WP, Sharp F, McColl J, Ford I. Fetal scalp blood lactate as an indicator of intrapartum hypoxia. Br J Obstet Gynaecol 1983;90: Heinis AM, Spaanderman ME, Gunnewiek JM, Lotgering FK. Scalp blood lactate for intra-partum assessment of fetal metabolic acidosis. Acta Obstet Gynecol Scand 2011;90: Wiberg N, Källén K, Herbst A, Olofsson P. Relation between umbilical cord blood ph, base deficit, lactate, 5-minute Apgar score and development of hypoxic ischemic encephalopathy. Acta Obstet Gynecol Scand 2010;89: Kruger K, Hallberg B, Blennow M, Kublickas M, Westgren M. Predictive value of fetal scalp blood lactate concentration and ph as markers of neurologic disability. Am J Obstet Gynecol 1999;181: Shimojo N, Naka K, Uenoyama H, Hamamoto K, Yoshioka K, Okuda K. Electrochemical assay system with single-use electrode strip for measuring lactate in whole blood. Clin Chem 1993;39: Ramanah R, Martin A, Riethmuller D, Maillet R, Schaal JP. [Value of fetal scalp lactate sampling during labour: a comparative study with scalp ph]. Gynecol Obstet Fertil 2005;33: French. 28. Nordström L. Fetal scalp and cord blood lactate. Best Pract Res Clin Obstet Gynaecol 2004;18: of 6

6 29. Luttkus AK, Fotopoulou C, Sehouli J, Stupin J, Dudenhausen JW. Technical performance of lactate biosensors and a test-strip device during labour. Z Geburtshilfe Neonatol 2010;214: Liljeström L, Wikström AK, Skalkidou A, Åkerud H, Jonsson M. Experience of fetal scalp blood sampling during labor. Acta Obstet Gynecol Scand 2014;93: Wiberg-Itzel E, Lipponer C, Norman M, Herbst A, Prebensen D, Hansson A, et al. Determination of ph or lactate in fetal scalp blood in management of intrapartum fetal distress: randomised controlled multicentre trial. BMJ 2008;336: East CE, Leader LR, Sheehan P, Henshall NE, Colditz PB. Intrapartum fetal scalp lactate sampling for fetal assessment in the presence of a non-reassuring fetal heart rate trace. Cochrane Database Syst Rev 2010;(3):CD Holzmann M, Wretler S, Cnattingius S, Nordström L. Cardiotocography patterns and risk of intrapartum fetal acidemia. J Perinat Med 2014 Jun 10 [Epub ahead of print]. 34. Allen RM, Bowling FG, Oats JJ. Determining the fetal scalp lactate level that indicates the need for intervention in labour. Aust N Z J Obstet Gynaecol 2004;44: Women and Newborn Health Service. King Edward Memorial Hospital. 5 Intrapartum Care. 5.7 Management of Suspected Acute Fetal Compromise Fetal Scalp Blood Sampling. King Edward Memorial Hospital: Perth; 2011 [ kemh.health.wa.gov.au/development/manuals/o&g_ guidelines/sectionb/5/b5.7.2.pdf]. Accessed 2014 Apr The Royal Australian and New Zealand College of Obstetricians and Gynaecologists. Intrapartum Fetal Surveillance. Clinical Guideline Third Edition Melbourne: RANZCOG; Holzmann M, Nordström L. Follow-up national survey (Sweden) of routines for intrapartum fetal surveillance. Acta Obstet Gynecol Scand 2010;89: This Scientific Impact Paper was produced on behalf of the Royal College of Obstetricians and Gynaecologists by: Mr D Mowbray MRCOG, Hereford; Dr J Rafi, The Ipswich Hospital NHS Trust, Ipswich; Professor L Nordström, Karolinska Institutet, Stockholm, Sweden; Dr WN Ofunne, Hereford County Hospital, Hereford; and Dr S Akhtar, Hereford County Hospital, Hereford and peer reviewed by: British Maternal and Fetal Medicine Society; Mrs A Diyaf MRCOG, Barnstaple; RCOG Women s Network; Professor SC Robson MRCOG, Newcastle; Professor M Westgren, Karolinska Institutet, Stockholm, Sweden. The Scientific Advisory Committee lead reviewers were: Mr D Pasupathy MRCOG, London and Dr ZR Thurwell MRCOG, Manchester. Conflicts of interest: Mr Mowbray, Dr Rafi, Dr Ofunne and Dr Akhtar: none declared. Professor Nordström: Medexa AB, the Swedish company providing Lactate Pro, has supported previous clinical trials. The final version is the responsibility of the Scientific Advisory Committee of the RCOG. The review process will commence in 2018, unless otherwise indicated. 6 of 6