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SCALP BLOOD GAS ANALYSIS
ANTEPARTUM AND INTRAPARTLJM FETAL ASSESSMENT
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SCALP BLOOD GAS ANALYSIS Keith R. Greene, MD, FRCOG
The fetal blood sample (FBS) was introduced into clinical practice for pH measurements by Saling38 in 1962 as the first invasive fetal monitoring tool. This methodology was an important step forward for understanding the effect of labor on blood gas homeostasis of the human fetus and for defining the importance of fetal heart rate (FHR) patterns*rz5 revealed by continuous FHR measurement techniques, which were introduced at about the same time.I8 Although the use of FBS has been widely advocated to improve the specificity of FHR monitoring, it remains an unpopular procedure7 because it is inconvenient for both the clinician and mother and invasive for the mother and fetus. Consequently, the frequency of its use varies dramatically from Europe to North America, from unit to unit, and even within the same unit dependent on individual clinicians. Physicians who embrace it in their practices would gladly give it up; however, it currently remains the only inexpensive practical procedure (with a physiologic basis and an evidence base) to clarify complex and uncertain patterns found on continuous FHR monitoring. PHYSIOLOGIC RATIONALE FOR FETAL BLOOD SAMPLING
Prior to labor, fetal acid-base status is largely determined by the acid-base status of the mother. During active labor, as the uterus contracts with intrauterine pressures exceeding 30 mm Hg, the arteries
From the Plymouth Perinatal Research Group, Postgraduate Medical School, University of Plymouth; and the Derriford Hospitals NHS Trust, Plymouth, United Kingdom
OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA VOLUME 26 * NUMBER 4 DECEMBER 1999
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supplying the intervillous space of the placenta are constricted so that there is temporarily little flow and therefore temporarily little exchange of oxygen to the fetus or carbon dioxide from it. This decrease can be accommodated by the healthy fetoplacental unit provided that the uterine contractions last no more than 60 seconds and there is sufficient respite (2 minutes) between them. If this does not occur, there will be a progressive accumulation of CO, (hypercapnia) and a shortage of oxygen (hypoxemia). The former state causes a respiratory acidosis, whereas the latter may produce a metabolic acidemia (Fig. 1). Any factor that affects placental blood flow and gaseous exchange in labor affects fetal blood gas homeostasis and, potentially, pH. Dramatic acute events such as abruption and cord prolapse have an impact Decreased placental blood flow (for whatever reason)
t PCO2
.1 Oxygen saturation
I
If
& Oxygen Delivery
Respiratory acidosis ( COP + H20 LS H2C03 + [H'] + HC03 )
Anaerobic metabolism
Metabolic acidosis (pyruvic 8 lactic acid)
I
Asphyxia
Figure 1. Pathophysiology of metabolic and respiratory acidosis.
SCALP BLOOD GAS ANALYSIS
643
on both sides of Figure 1, as does hypertonus. Cord compression or entanglement and supine hypotension affect blood gas homeostasis more subtly, producing a respiratory acidosis sometime before a metabolic acidosis. Any decrease in FHR results in a decreased cardiac output, decreased CO, transfer, and CO, accumulation so that prolonged or repetitive bradycardias result in a respiratory acidosis, which commonly occurs in the second stage. How soon a metabolic acidosis develops depends on the particular insult and the individual fetal reserve and ability to compensate. The fetus normally derives its metabolic needs by the oxidation of glucose (or glycogen) to water and carbon dioxide in the presence of oxygen, with the generation of 38 units of ATP; aerobic metabolism. The healthy fetus is able to adjust to short episodes of hypoxemia to maintain aerobic metabolism by a synchronized response that involves behavioral, cardiovascular, metabolic, and hormonal adjustment^.'^ The most important cardiovascular response is the centralization of blood flow to the heart, brain, and adrenals, with increased oxygen extraction at the placental bed and tissues. If these adjustments fail to maintain adequate oxygen supply to the central organs, aerobic metabolism is supplemented by anaerobic metabolism of glucose and glycogen as far as lactic acid in the Kreb cycle, with the generation of 3 units of ATP to maintain cell and organ function. Clearly, anaerobic metabolism is much less efficient than aerobic metabolism but is a very important survival mechanism, particularly to maintain cardiac and brain function during hypoxemia / asphyxia. Anaerobic metabolism is largely dependent on the pre-asphyxia1 glycogen content of the myocardium and liver,8,39 the long-term stores of glucose, which are depleted in this process (Fig. 2). In anaerobic metabolism, the accumulation of pyruvic and lactic acid causes an increase in hydrogen ions [H’], resulting in a metabolic acidosis. Free intracellular hydrogen ions are toxic to cells and are buffered by bicarbonate, hemoglobin, and plasma protein. When these buffers are saturated, there is a marked increase in free [H+]ions and a fall in pH, with acidosis. This saturation occurs sometime after the onset of hypoxemia. Hydrogen ions can also accumulate in respiratory acidosis via the accumulation of CO, by the equation: CO,
+ H,O+H,CO,--’
[H’]
+ HCO,
The shift in the balance of the equation to the right also reduces the availability of bicarbonate to buffer metabolic acidosis. Figure 1 shows that a respiratory acidosis occurs before a metabolic acidosis. The former is less significant than a metabolic acidosis because it need not be associated with tissue oxygen lack. Generally, situations that create a metabolic acidosis also cause a respiratory acidosis so that the resultant acidosis is then mixed. The degree of metabolic acidosis can be expressed by changes in buffering capacity expressed as base deficit (BD) or buffer base (BB) calculated from the measurements of pH and pC0,. Because acidosis in
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'
Oxygen canylng 9availability capacity @02) (hemoglobin)
Oxyg"" saturation
blood-flow
OXYGEN SUPPLY
AEROBIC METABOLISM
OXYGEN REQUIREMENT
tissue maSS
obligatory functions
physical activity
Not balanced Supplementedby ANAEROBIC METABOLISM
i1
BUFFERS
H'+ HCO,
H++ HbH'+ h o t
>< < >>< -
H2C03 HHb HProt
1 Base deficit increase
H'rise (pH fall)
Figure 2. Physiologic background to aerobic and anaerobic metabolism.
SCALP BLOOD GAS ANALYSIS
645
the fetus is usually of mixed origin, the relatively high pC02 and the increased extracellular fluid volume compared with the values in an adult can unduly influence calculations of BD or BB.4O It is increasingly argued37,48 that buffering capacity in the perinatal period should be calculated in the extracelluIar fluid and not blood and expressed as BDecf. For example, the difference in the case of a mixed acidosis with a pH less than 7.20 is a 30% higher BDblood than the B D ~ c ~ . ~ ~ pH is a logarithmic function of the [H+]concentration. A decrease in pH from 7.30 to 7.20 is not as significant as a decrease from 7.10 to 7.00. The change is exponential such that, in the latter situation, there are about twice as many free [H'] generated. In assessing the significance of a particular FBS result, one should ideally use BD or BB (in extracellular fluid) as well as pH to determine the relative contributions of respiratory and metabolic components. Blood gas analyzers can be programmed to produce this calculation using the Siggaard-Andersen nomogram.40 EVIDENCE BASE
The normal cardiotocogram (CTG), that is, the normal baseline with rest / activity cycles and reactivity, is associated with a good outcome, and, conversely, a persistent bradycardia is associated with a poor outcome. Unfortunately, between these extremes, various patterns of change occur that do not provide reassurance. Decelerations occur in 50% of cases monitored by CTG,I9 and because at least 50% of labors are monitored by electronic fetal monitoring (EFM) in Europe and North America, this is a major clinical problem. Although there is an association of lower cord gas pH" and increased BDM with increasingly abnormal CTG features and the duration of these features,l* the CTG with tachycardia, late decelerations, and decreased baseline variation has only about a 50% incidence of low pH.2 Beard and co-workers2have concluded "that if continuous CTG monitoring was used on its own in clinical practice, a number of false-positive diagnoses of fetal asphyxia are likely to be made." They advocate further assessment of pH by FBS before intervention. Table 1 illustrates the CTG classifications that require a second variable (e.g., FBS) at the author's center. The interpretation of EFM patterns by expert clinicians is improved by the additional use of FBS as another variable. In the author's study of interobserver and intraobserver error in the interpretation of 50 representative CTGs by 17 nominated experts from 16 institutions, the one individual who elected not to use FBS in the practical decision making regarding intervention was the least consistent in the repeat decisions 1 month later and had the least agreement with peers.22 Twelve randomized trials have compared intrapartum EFM with intermittent auscultation performed around the world.+ The trials have *References1517, 23, 2629, 32, 36, 46, and 52.
<5 bpm in the absence of sedation and no accelerations
180 bpm
Persistent bradycardia, no accelerations exceeding 100 bpm, with the belief that this will persist
Abnormal
Preterminal
Severe variable$ Late
Action Continue recording Any two 2 3 0 minutes, FBS Repeat 1 hourt Any one >30 minutes, FBS Any two >15 minutes, FBS Repeat 1 hourt Deliver immediately
Decelerations None Early Mild variable*
*<60 Dropped beats, <60-second duration. tFBS earlier if cardiotocogram deteriorates. $>60 Dropped beats, >60 seconds. FBS = Fetal blood sample; bpm = beats per minute. Dafa from Westgate J, Harris M, Cumow JSH, et a1 Plymouth randomized trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring: 2400 Cases. Am J Obstet Gynecol 169:1151-1160, 1993.
10-25 bpm >25 bpm <5 bpm
Variabilitv
110-160 bpm 100-110 bpm 160-180 bpm
Baseline
Normal Intermediate
Classification
Table 1. CARDIOTOGRAM CLASSIFICATION CRITERIA TO ILLUSTRATE SITUATIONS IN WHICH A SECOND VARIABLE (e.g., FBS) IS REQUIRED
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differed in their entry criteria (variously including high-risk or low-risk pregnancies for all or most women) and in whether FBS for pH estimation was available as an adjunctive method of assessment of fetal wellbeing. Meta-analy~is'~, 31,43 is greatly influenced by the large Dublin trial that specifically excluded cases with meconium and oligohydramnios.28 The only clear benefit to be demonstrated from the routine use of CTG is a reduction in neonatal seizures. Thacker's meta-analysis4j also found a significant decrease in low 1-minute Apgar score (<4) associated with continuous EFM (relative risk [RR], 0.82; 95% confidence interval [CI] 0.65 to 0.98) in the seven studies in which this was recorded. This protective effect was apparent only in trials performed outside of the United States and had not been reported previously. The decrease in neonatal seizures and low 1-minute Apgar score occurred at the expense of a significantly increased operative delivery rate by cesarean section and instrumental vaginal delivery, although this rate has decreased with time. ELECTRONIC FETAL MONITORING WITH AND WITHOUT SCALP BLOOD GAS ANALYSIS
The results of meta-analysis of the three trials in which intermittent auscultation was compared with EFM used without FBS for pH15,16, 23 show a fourfold increase in the odds of cesarean section for fetal distress (odds ratio [OR], 4.14; CI, 2.29 to 7.51) in comparison with the intermittent auscultation group without improvement in fetal outcome. In contrast, EFM with the option of FBS showed a less marked increase in cesarean section rate when compared with intermittent auscultation (OR, 1.98; CI, 1.33 to 2.94), although the greatest impact was on postponing intervention to the second stage (Table 2). Only in the trials with the FBS option was there a decrease in neonatal c o n v ~ l s i o n s . ~ ~ On the basis of these findings, the 26th study group of the UK Royal College of Obstetricians and Gynaecologists35recommended in Table 2. COMPARISON OF ODDS RATIO WITH CONFIDENCE INTERVALS FOR INPACT ON MATERNAL AND NEONATAL OUTCOME FOR INTERMITENT AUSCULTATION VERSUS ELECTRONIC FETAL MONITORING WITH AND WITHOUT FETAL BLOOD SAMPLE Trials of EFM Versus IA
EFM without FBS' EFM with FBSt
Cesarean Section Rate (OR [Cll)
Neonatal Convulsions (OR P I )
4.14 (2.29-7.51) 1.98 (1.33-2.94)
0.79 (0.21-2.97) 0.49 (0.29-0.82)
EFM = Electronic fetal monitoring; FBS = fetal blood sample; IA = intermittent auscultation; OR [CI] = odds ratio (confidence intervals). 'References 15, 16, and 23. tReferences 15, 27,28,32, and 36. Data from Murphy KW, Johnson Moorcraft J, et al: Birth asphyxia and the intraparturn cardiotograph. Br J Obstet Gynaecol 97470-479, 1990; and Thacker SB, Stroup DF, Peterson HB:Efficacy and safety of intrapartum fetal monitoring: An update. Obstet Gynecol 8661?-620, 1995.
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1993 that EFM should not be used without the facility for fetal blood pH measurements, a statement similar to that made 14 years earlier in the report of the US National Institute of Child Health and Human Development Consensus Task Despite these findings and recommendations, there has been no evidence of any increase in the use of FBS in clinical practice. The increased operative delivery rate (by cesarean section and instrumental vaginal delivery) has decreased with time.43The degree to which this lowered intervention is the result of increased use of FBS, better education, or the use of some other modality such as stimulation testing is uncertain. The Plymouth randomized controlled trial of CTG alone versus CTG plus electrocardiography49 showed that the use of the ST waveform of the electrocardiogram as an additional variable improved the interpretation of the CTG and halved the incidence of operative intervention (P
FETAL BLOOD SAMPLING TECHNIQUE
Fetal blood sampling is limited to the skin covering the fetal presenting part. Although animal studies have shown a good correlation for pH between scalp blood samples and carotid arterial blood' and between blood from the fetal scalp in the second stage and blood from the umbilical vessel^,^ there are several situations in which scalp pH measurements are inaccurate (e.g., edema, caput succedaneum) or are misinterpreted. The technique of FBS must be appropriate. Fetal blood can be obtained only with ruptured membranes and the cervix 2- to 3-cm dilated. Samples should be taken with the mother in the lateral position to avoid supine hypotension, which can produce a profound bradycardia with hypoxemia and hypercarbia, producing a short-lasting mixed acidosis (Fig. 3 ) that may prompt unnecessary delivery. An amnioscope is passed into the vagina and through the cervix to rest on the presenting part of the fetus with sufficient pressure to exclude amniotic fluid (which would otherwise contaminate the sample and cause a falsely high pH) but insufficientto cause stasis of capillary flow. Fetal skin is cleaned with a swab then smeared with silicone gel so that when the skin is punctured with a 2-mm blade, a droplet of blood forms rather than runs across the surface. An ethyl chloride spray produces a reactive hyperemia, which aids in bleeding. The droplet of blood is allowed to flow into a glass capillary tube pretreated with heparin, preferably by capillary action. The sample is then transferred to a blood gas analyzer for immediate measurement. Contemporary blood gas analyzers can perform a full analysis on a 40-kL sample to produce a value for pC0, pH, and the calculated BD. As recommended earlier, the complete acid-base balance should be assessed to differentiate between respiratory and metabolic acidosis.
SCALP BLOOD GAS ANALYSIS pn
7.a
1.w
I
1
649
n
7. 1
,
I
am
Figure 3. Short-term effect of supine hypotension caused by fetal blood sample (pH 7.28) in lithotomy inappropriately done for early decelerations. Delay in getting anesthetists allowed further FBS in lateral position to document resolution of respiratory acidosis coincident with an improved and reactive cardiotocogram. A normal delivery occurred 3 hours later. (Break in trace is of 15 minutes’ duration, paper speed run at 1 cm/min).
PRACTICAL INTERPRETATION
Apart from the inconvenience and practical difficulties of obtaining an accurately measured sample, a major problem of FBS is that it is intermittent. Because of the physiology of hypoxemia and acidosis, a sigruficant decrease in pH can occur a short time after a normal sample has been obtained. Care must be taken in assuming that a single-point measurement is the gold standard of hypoxemia/ asphyxia. Unfortunately, attempts over the last decades to produce a continuous pH measurement have continued to prove unsuccessful. The acid-base status of the fetus during labor usually mirrors that of the mother, but at 0.10 of a pH unit less than the maternal venous blood value.@Measurement of this pH difference was used clinically in the past but is no longer carried out. In several situations, consideration of the maternal and fetal acid-base status could be helpful. If the laboring patient is hyperventilating (usually without an epidural and with ineffective pain relief), she expires more C 0 2 and sustains a respiratory alkalosis with a potential blood pH value of 7.50 or greater. This condition raises the fetal pH level and may confound the confirmation of hypoxemia/ acidosis. Similarly, if the woman has a prolonged labor with a ketoacidosis, an infusion acidosis may occur in the fetus, lowering its pH level without hypoxemia. In these situations, a fetomaternal pH difference of more than 0.20 of a pH unit should be taken as indicative of fetal acidemia. It is also good practice to plot serial pH measurements to observe and interpret the trend in conjunction with any FHR abnormalities and the expected duration of labor. Significant hypoxemia produces a progressive acidemia that can be recognized earlier by such repeated measurements. If the trend is projected to the expected time of delivery
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from the partogram, a decision might be made some hours before significant acidemia occurs (Fig. 4).Maternal samples can also facilitate earlier decision making. A clear divergence in the graph of fetal versus maternal pH (see Fig. 4) suggests accumulating fetal [H'] and a significant hypoxemia. In other circumstances, the use of FBS is potentially misleading. Equipment can be poorly calibrated, and, in some situations, the fetal problem is not hypoxemia/asphyxia; a fall in fetal pH can be a late event in fetal sepsis. There are also occasions in clinical practice when heart rate changes are so abnormal that an FBS should not be part of the investigation because it would be a waste of valuable time. In these situations, there is no substitute for knowledge and experience in interpretation of the CTG and FBS in clinical context. FETAL SCALP BLOOD ANALYSIS FOR LACTATE
As explained previously (see Fig. 2), there are good physiologic reasons to measure lactate as a direct marker of anaerobic metabolism. A simple technique for the measurement of lactate in whole blood has recently been developed using just 5 pL of blood on a test strip, provid-
Maternal
b) Diverging materno-fetal pH difference
0.10
v..-.. -..
0.18
-.. -..
PH
-.. ---..
. '.. . -.. \.... '.. a) Projection of pH to estimated time of delivery
7.10
1
I
I
I
0
1
2
3
-..
..
'..\*
Fetal
I
I
I
I
4
5
6
7
Time (h)
Figure 4. Serial fetal blood samples illustrate extrapolation of the trend of serial samples to the predicted time of delivety that could have avoided a fourth sample and acidosis (a) or use of comparison with a paired maternal venous blood pH detecting diverging pH values (b).
SCALP BLOOD GAS ANALYSIS
651
ing a result within 1 minute by a hand-held, bedside electrochemical device.33 In a recent prospective randomized controlled trial (RCT), FBS lactate analysis was compared with pH in 341 cases with ominous FHR patterns.50A sufficient quantity of blood for lactate analysis was obtained significantly more often than for pH analysis. The failure rate for pH was inversely related to the degree of cervical dilation. The lactate group required fewer scalp incisions to obtain a sample, and the result was obtained sooner than in the pH group (2 minutes compared with just under 4 minutes). There was no difference in the predictive value for perinatal outcome in this small study. Because the reluctance to perform FBS12,51 is largely related to the difficulties of obtaining and measuring the sample, lactate analysis using the simple disposable test strip may increase the utility of FBS and even encourage serial use as a simple monitoring procedure. Further studies in other centers are required. EFFICACY
The effectiveness of FBS in clinical practice is another problem. Despite the use of a strict protocol during a research trial in the author's 39% of cases had FBS performed unnecessarily, and 33% of cases did not have it performed when it was indicated. In a study at Oxford, Murphy and c o - w ~ r k e r sexperienced ~~ similar problems with the selection and timing of FBS in a review of 38 cases of birth asphyxia. FBS and the CTG are not independent monitoring methods, and the decision to obtain a FBS depends on the interpretation of the CTG. If the level of CTG interpretation is suboptimal, the value of monitoring by FBS is limited. Some centers45advocate high FBS rates, and there is evidence that higher rates of sampling are associated with higher mean cord arterial pH at delivery? There is no evidence that this 'approach results in a reduction in birth asphyxia. Many opportunities exist for the misinterpretation of FBS results, and an increase in FBS rates without an improvement in knowledge of how to interpret and use the information is unlikely to be successful. There is an urgent need for adequate training, knowledge, and expertise in the interpretation of CTG changes in the context of the individual instance of labor, with intelligent use of FBS or some other ancillary method of fetal surveillance. Contrary to the RCT data, some large units with low intervention rates seldom perform FBS, perhaps relying on fetal stimulation testing7,12,34 FETAL STIMULATION RESPONSE AND pH SAMPLING
Despite the evidence suggesting that it is useful to assess the FHR response to stimulation to reduce the need for fetal scalp ampl ling,^, 6, lo
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which is in keeping with current understanding of the physiology of behavioral adjustments to hypoxemia, the evidence is not sufficiently robust to suggest that either scalp or acoustic fetal ~timulation~~ can entirely replace FBS. FBS may be avoided in 51% of nonreassuring FHR patterns when a positive FHR response to stimulation of 15 beats per minute (bpm) for 15 seconds is elicited.6 This percentage might be increased to 73% of cases if an acceleration were redefined as 10 bpm for 10 seconds and if heart rate variation was normal prior to the stimulation.1° In trying to replicate these results in a large database, the author has found it very difficult to judge an acceleration of 15 bpm for 15 seconds in some of the many traces with fluctuating baselines yet normal FBS r e s ~ l t s This . ~ difficulty has caused considerable intraobserver and interobserver inconsistencies, particularly for the traces (not normal, not abnormal) that required further definition, and is likely to cause interpretative problems in widespread clinical practice. Physiologically, it is surprising that the scalp stimulation studies have found such a clear separation of positive and negative FHR response about an FBS value of 7.20-a figure originally derived for FBS decision making from statistics derived from the population data of Saling and not from any physiologic data. In sheep at least, fetal brain function as measured by evoked response is preserved to lower pH values. Although the literature is generally supportive of stimulation testing, there are increasing reportsg,20, 21 of false-negative findings (i.e., accelerations with a pH <7.20), and these findings do not seem to be explained by the presence of respiratory rather than metabolic acidosis.21 For these reasons, stimulation testing seems unlikely to replace the need for FBS or some other variable in worldwide clinical practice, although it has apparently reduced the need to rely on FBS in some units in North America that maintain low intervention rates.I2 Despite the convenience of the stimulation test, a large randomized control trial seems justified. CONCLUSION
Much has been learned about intraparturn monitoring over the last few decades. There is a much better understanding of the physiologic integrity and responses of the fetus. It is seldom verbalized that what the obstetrician really hopes to achieve from fetal monitoring is the reassurance to allow labor to continue. It is easy to identify the healthy fetus at the onset of labor and to employ low-key monitoring strategies. When concerns arise, continuous EFM by CTG remains the principal means of surveillance, not only because it is a robust signal that can be obtained noninvasively, but also because cardiac output and therefore oxygen delivery are largely determined by heart rate. Although it is possible to derive much information about neurodevelopmental integration and the cardiovascular responses to stress and hypoxia from the CTG, even experienced clinicians fre-
SCALP BLOOD GAS ANALYSIS
Singleton, cephalic, 37-41 weeks' gestation, clear amniotic fluid, spontaneous labor, no major antenatal complications
653
All Other Cases
I Admission CTG 20-40 minutes
not normal
normal
\
/
I
Intermittent Auscultation
not normal or meconium, epidural, - antepartum hemorrhage, oxytocin administration
EFM (External or Internal)
+
I
I
not normal
1 Response to Stimulation'
normal
not normal
1 ST waveform or future proven modality
not normal
T
Continue Intermittent Auscultation
I
Continue EFM
I
I
or FBs deliver
I
Figure 5. Proposed clinical management of fetal monitoring based on current research evidence. 'Fetal heart rate responses should be assessed continuously once electronic fetal monitoring (EFM) is commenced and the fetal electrocardiogram continuously assessed once the scalp clip is applied.
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quently need more data to determine the best course of clinical action when there are uncertain patterns of CTG change. The addition of another variable improves the reliability of interpretation. FBS has traditionally been the second variable used to judge the level of acidosis, whereas the evoked response is widely used in North America. The electrocardiographic waveform has shown considerable promise, and pulse oximetry is increasingly being investigated. The relationship of these possible monitoring strategies to the processes of hypoxemia and asphyxia is much clearer and requires a thoughtful stepwise process of investigation based on the evidence and dependent on individual needs (Fig. 5). It is possible with this approach that intermittent FBS could be confined to a small number of fetuses for whom decision making remains uncertain. In the future, lactate analysis performed on a sequential basis may be useful to examine change over time. These issues are best resolved by further well-designed clinical trials. References 1. Adamsons K, Beard RW, Myers RE: Comparison of the composition of arterial, venous and capillary blood of the fetal monkey during labor. Am J Obstet Gynecol 1 0 7 4 3 5 440, 1970 2. Beard RW, Filshie GM, Knight CA, et al: The significance of the changes in the continuous fetal heart rate in the first stage of labour. J Obstet Gynaecol Br Commonw 78:865881, 1971 3. Bowe ET, Beard RW, Finster M, et al: Reliability of fetal blood sampling. Am J Obstet Gynecol 107279-287, 1970 4. Bretscher J, Saling E: pH values in the human fetus during labour. Am J Obstet Gynecol97906-911, 1967 5. Clark SL, Gimovsky ML, Miller FC: Fetal heart rate response to scalp blood sampling. Am J Obstet Gynecol 144706708, 1982 6. Clark SL, Gimovsky ML, Miller FC: The scalp stimulation test: A clinical alternative to fetal scalp sampling. Am J Obstet Gynecol 148:274-277, 1984 7. Clark SL, Paul RH: Intrapartum fetal surveillance: The role of fetal scalp blood sampling. Am J Obstet Gynecol 153:717-720, 1985 8. Dawes GS, Mott JC, Shelley HJ: The importance of cardiac glycogen for the maintenance of life in foetal lambs and newborn animals during anoxia. J Physiol 146516538, 1959 9. Dixon M, Harris M, Greene KR: Computer analysis of fetal heart rate response to intrapartum scalp stimulation around the time of fetal blood sampling. J Obstet Gynaecol 19(suppl 1):550, 1999 10. Eliman A, Figueroa R, Tejani N: Intrapartum assessment of fetal well-being: A comparison of scalp stimulation with scalp blood pH sampling. Obstet Gynecol 89:373-376, 1997 11. Fleischer A, Schulman H, Jagani N, et al: The development of fetal acidosis in the presence of an abnormal fetal heart rate tracing. 1. The average for gestational age fetus. Am J Obstet Gynecol 144:5540, 1982 12. Goodwin TM, Milner-Masterson L, Paul R Elimination of fetal scalp blood sampling on a large clinical service. Obstet Gynecol 83:971-973, 1994 13. Grant A Monitoring the fetus during labour. In Chalmers I, Enkin M, Keirse MJNC (eds): Effective Care in Pregnancy and Childbirth. New York, Oxford University Press, 1989, pp 8464382 14. Greene KR, R o s h KG: Intrapartum asphyxia. In Levene MI, Lilford RJ (eds): Fetal
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and Neonatal Neurology and Neurosurgery. New York, Churchill Livingstone, 1995, pp 389-404 15. Haverkamp AD, Orleans M, Langendoerfer S, et al: A controlled trial of the differential effects of intraparturn fetal monitoring. Am J Obstet Gynecol 134:399-409, 1979 16. Haverkamp AD, Thompson HE, McFee JG, et al: The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy. Am J Obstet Gynecol 125310-317, 1976 17. Herbst A, Ingemarsson I: Intermittent versus continuous electronic fetal monitoring in labour: A randomized study. Br J Obstet Gynaecol 101:663-668,1994 18. Hon E H Instrumentation of fetal heart rate and fetal electrocardiography. 11. A vaginal electrode. Am J Obstet Gynecol 86772-784, 1963 19. Ingermarsson E: Routine electronic fetal monitoring during labour. Acta Obstet Gynecol Scand Suppl994-29, 1981 20. Ingemarsson I, Arulkumaran S Reactive fetal heart rate response to vibroacoustic stimulation in fetuses with low scalp blood pH. Br J Obstet Gynaecol96:562-565, 1989 21. Irion 0, Stuckelberger P, Moutquin J-M, et al: Is intrapartum vibratory acoustic stimulation a valid alternative to fetal scalp p H determination? Br J Obstet Gynaecol103642647, 1996 22. Keith RDF, Beckley S, Garibaldi JM, et al: A multicentre comparative study of 17 experts and an intelligent computer system for managing labour using the cardiotocogram. Br J Obstet Gynaecol 102688-700, 1995 23. Kelso IM, Parsons RJ, Lawrence GF, et al: An assessment of continuous fetal heart rate monitoring in labor: A randomized trial. Am J Obstet Gynecol 131:526-531, 1978 24. Krebs HB, Petres RE, Dunn LJ, et al: Intrapartum fetal heart rate monitoring. I. Classification and prognosis of fetal heart rate patterns. Am J Obstet Gynecol 133:762772, 1979 25. Kubli FW, Hon EH, Khazin AF, et al: Observations on heart rate and pH in the human fetus during labour. Am J Obstet Gynecol 104119(r1206, 1969 26. Leveno KJ, Cunningham FG, Nelson S, et al: A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies. N Engl J Med 315:615619, 1986 27. Luthy DA, Shy KK, van Belle G, et al: A randomized trial of electronic fetal monitoring in pretenn labor. Obstet Gynecol 69:687-695, 1987 28. MacDonald D, Grant A, Sheridan-Pereira M, et al: The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol 152:524-539, 1985 29. Mahomed K, Nyoni R, Mulambo T, et al: Randomised controlled trial of intrapartum fetal heart rate monitoring. BMJ 308:497-500, 1994 30. Murphy KW, Johnson P, Moorcraft J, et al: Birth asphyxia and the intrapartum cardiotocograph. Br J Obstet Gynaecol97470-479, 1990 31. Neilson JP, Grant AM. The randomised trials of intrapartum electronic fetal heart rate monitoring. In Spencer JAD, Ward RHT (eds): Intrapartum Fetal Surveillance. London, RCOG Press, 1993, pp 77-93 32. Neldam S, Osler M, Hansen PK, et al: Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: A controlled clinical trial. Eur J Obstet Gynecol Reprod Biol 23:l-11, 1986 33. Nordstrom L, Ingemarsson I, Kublickas M, et al: Scalp blood lactate: A new test strip method for monitoring fetal well-being in labour. Br J Obstet Gynaecol 102894-899, 1995 34. Perkins Rp: Perinatal observations in a high-risk population managed without intrapartum fetal pH studies. Am J Obstet Gynecol 149:327-334, 1984 35. Recommendations arising from 26th RCOG study group: Intrapartum fetal surveillance. In Spencer JAD, Ward RHT (eds): Intrapartum Fetal Surveillance. London, RCOG Press, 1993, pp 387-393 36. Renou F, Chang A, Anderson I, et al: Controlled trial of fetal intensive care. Am J Obstet Gynecol 126:470-476, 1976 37. Ros6n KG, Murphy K How to assess fetal metabolic acidosis from cord samples. J Perinat Med 19221-226, 1991 38. Saling E: Neues Vorgehen zur Untertesuchung des Kindes unter der Geburt-Einfiihrung, Technik, Grundlagen. Arch Gynak 197108-122,1962
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39. Shelley HJ: Glycogen reserves and their changes at birth. Br Med Bull 17137-143,1961 40. Siggaard-Andersen 0: An acid base chart for arterial blood with normal and pathophysiological reference areas. Scand J Clin Lab Invest 27239-245, 1971 41. Smith CV,Nguyen HN, Phelan JP, et al: Intrapartum assessment of fetal wellbeing: A comparison of fetal acoustic stimulation during the abnormal or equivocal biophysical profile. Am J Obstet Gynecol 155:726-728, 1986 42. Steer PJ: Fetal scalp blood analysis current practice. In Spencer JAD, Ward RHT (eds): Intraparturn Fetal Surveillance. London, RCOG Press, 1993, pp 127-138 43. Thacker SB, Stroup DF, Peterson HB:Efficacy and safety of intraparturn fetal monitoring: An update. Obstet Gynecol 86:613-620, 1995 44. Towel1 ME: The rationale for biochemical monitoring of the fetus. J Perinat Med 16(s~ppl1):49-54, 1988 45. van den Berg P, Schmidt S, Gesche J, et al: Fetal distress and the condition of the newborn using cardiotocography and fetal blood analysis during labour. Br J Obstet Gynaecol 94:72-75, 1987 46. Vintzileos AM, Antsaklis A, Varvarigos I, et al: A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent ausculation. Obstet Gynecol 815399-907, 1993 47. Westgate J, Greene KR: How well is fetal blood sampling used in clinical practice. Br J Obstet Gynaecol 101:25(r251, 1994 48. Westgate J, RosCn KG: Add base balance at birth. In van Geijin HP, Copray FJA (eds): A Critical Appraisal of Fetal Surveillance. Amsterdam, Elsevier, 1994, pp 595-603 49. Westgate J, Harris M, Cumow JSH, et al: Plymouth randomized trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring: 2400 Cases. Am J Obstet Gynecol 1693151-1160, 1993 50. Westgren M, h g e r K, Ek S, et a1 Lactate compared with pH analysis at fetal scalp blood sampling: A prospective randomised study. Br J Obstet Gynaecol105:29-33,1998 51. Wheble AM, Gillmer MDG, Spencer JAD, et al: Changes in fetal monitoring practice in the UK: 1977-1984. Br J Obstet Gynaecol 96:114&1147, 1989 52. Wood C, Renou P, Oats J, et al: A controlled trial of fetal heart rate monitoring in a low-risk obstetric population. Am J Obstet Gynecol 141:527-534, 1981 53. Zuspan FP, Quilligan EJ, Iams JD,et al: Predictors of intrapartum fetal distress: The role of electronic fetal monitoring. Report of the National Institute of Child Health and Human Development Consensus Task Force. Am J Obstet Gynecol 135:287-291, 1979 Address reprint requests to Keith R. Greene, MD, FRCOG Plymouth Perinatal Research Group Department of Obstetrics and Gynaecology Derriford Hospital Plymouth, Devon United Kingdom PL6 8DH
0889-8545/99 $8.00
+ .OO
SCALP BLOOD GAS ANALYSIS Keith R. Greene, MD, FRCOG
The fetal blood sample (FBS) was introduced into clinical practice for pH measurements by Saling38 in 1962 as the first invasive fetal monitoring tool. This methodology was an important step forward for understanding the effect of labor on blood gas homeostasis of the human fetus and for defining the importance of fetal heart rate (FHR) patterns*rz5 revealed by continuous FHR measurement techniques, which were introduced at about the same time.I8 Although the use of FBS has been widely advocated to improve the specificity of FHR monitoring, it remains an unpopular procedure7 because it is inconvenient for both the clinician and mother and invasive for the mother and fetus. Consequently, the frequency of its use varies dramatically from Europe to North America, from unit to unit, and even within the same unit dependent on individual clinicians. Physicians who embrace it in their practices would gladly give it up; however, it currently remains the only inexpensive practical procedure (with a physiologic basis and an evidence base) to clarify complex and uncertain patterns found on continuous FHR monitoring. PHYSIOLOGIC RATIONALE FOR FETAL BLOOD SAMPLING
Prior to labor, fetal acid-base status is largely determined by the acid-base status of the mother. During active labor, as the uterus contracts with intrauterine pressures exceeding 30 mm Hg, the arteries
From the Plymouth Perinatal Research Group, Postgraduate Medical School, University of Plymouth; and the Derriford Hospitals NHS Trust, Plymouth, United Kingdom
OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA VOLUME 26 * NUMBER 4 DECEMBER 1999
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supplying the intervillous space of the placenta are constricted so that there is temporarily little flow and therefore temporarily little exchange of oxygen to the fetus or carbon dioxide from it. This decrease can be accommodated by the healthy fetoplacental unit provided that the uterine contractions last no more than 60 seconds and there is sufficient respite (2 minutes) between them. If this does not occur, there will be a progressive accumulation of CO, (hypercapnia) and a shortage of oxygen (hypoxemia). The former state causes a respiratory acidosis, whereas the latter may produce a metabolic acidemia (Fig. 1). Any factor that affects placental blood flow and gaseous exchange in labor affects fetal blood gas homeostasis and, potentially, pH. Dramatic acute events such as abruption and cord prolapse have an impact Decreased placental blood flow (for whatever reason)
t PCO2
.1 Oxygen saturation
I
If
& Oxygen Delivery
Respiratory acidosis ( COP + H20 LS H2C03 + [H'] + HC03 )
Anaerobic metabolism
Metabolic acidosis (pyruvic 8 lactic acid)
I
Asphyxia
Figure 1. Pathophysiology of metabolic and respiratory acidosis.
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643
on both sides of Figure 1, as does hypertonus. Cord compression or entanglement and supine hypotension affect blood gas homeostasis more subtly, producing a respiratory acidosis sometime before a metabolic acidosis. Any decrease in FHR results in a decreased cardiac output, decreased CO, transfer, and CO, accumulation so that prolonged or repetitive bradycardias result in a respiratory acidosis, which commonly occurs in the second stage. How soon a metabolic acidosis develops depends on the particular insult and the individual fetal reserve and ability to compensate. The fetus normally derives its metabolic needs by the oxidation of glucose (or glycogen) to water and carbon dioxide in the presence of oxygen, with the generation of 38 units of ATP; aerobic metabolism. The healthy fetus is able to adjust to short episodes of hypoxemia to maintain aerobic metabolism by a synchronized response that involves behavioral, cardiovascular, metabolic, and hormonal adjustment^.'^ The most important cardiovascular response is the centralization of blood flow to the heart, brain, and adrenals, with increased oxygen extraction at the placental bed and tissues. If these adjustments fail to maintain adequate oxygen supply to the central organs, aerobic metabolism is supplemented by anaerobic metabolism of glucose and glycogen as far as lactic acid in the Kreb cycle, with the generation of 3 units of ATP to maintain cell and organ function. Clearly, anaerobic metabolism is much less efficient than aerobic metabolism but is a very important survival mechanism, particularly to maintain cardiac and brain function during hypoxemia / asphyxia. Anaerobic metabolism is largely dependent on the pre-asphyxia1 glycogen content of the myocardium and liver,8,39 the long-term stores of glucose, which are depleted in this process (Fig. 2). In anaerobic metabolism, the accumulation of pyruvic and lactic acid causes an increase in hydrogen ions [H’], resulting in a metabolic acidosis. Free intracellular hydrogen ions are toxic to cells and are buffered by bicarbonate, hemoglobin, and plasma protein. When these buffers are saturated, there is a marked increase in free [H+]ions and a fall in pH, with acidosis. This saturation occurs sometime after the onset of hypoxemia. Hydrogen ions can also accumulate in respiratory acidosis via the accumulation of CO, by the equation: CO,
+ H,O+H,CO,--’
[H’]
+ HCO,
The shift in the balance of the equation to the right also reduces the availability of bicarbonate to buffer metabolic acidosis. Figure 1 shows that a respiratory acidosis occurs before a metabolic acidosis. The former is less significant than a metabolic acidosis because it need not be associated with tissue oxygen lack. Generally, situations that create a metabolic acidosis also cause a respiratory acidosis so that the resultant acidosis is then mixed. The degree of metabolic acidosis can be expressed by changes in buffering capacity expressed as base deficit (BD) or buffer base (BB) calculated from the measurements of pH and pC0,. Because acidosis in
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'
Oxygen canylng 9availability capacity @02) (hemoglobin)
Oxyg"" saturation
blood-flow
OXYGEN SUPPLY
AEROBIC METABOLISM
OXYGEN REQUIREMENT
tissue maSS
obligatory functions
physical activity
Not balanced Supplementedby ANAEROBIC METABOLISM
i1
BUFFERS
H'+ HCO,
H++ HbH'+ h o t
>< < >>< -
H2C03 HHb HProt
1 Base deficit increase
H'rise (pH fall)
Figure 2. Physiologic background to aerobic and anaerobic metabolism.
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645
the fetus is usually of mixed origin, the relatively high pC02 and the increased extracellular fluid volume compared with the values in an adult can unduly influence calculations of BD or BB.4O It is increasingly argued37,48 that buffering capacity in the perinatal period should be calculated in the extracelluIar fluid and not blood and expressed as BDecf. For example, the difference in the case of a mixed acidosis with a pH less than 7.20 is a 30% higher BDblood than the B D ~ c ~ . ~ ~ pH is a logarithmic function of the [H+]concentration. A decrease in pH from 7.30 to 7.20 is not as significant as a decrease from 7.10 to 7.00. The change is exponential such that, in the latter situation, there are about twice as many free [H'] generated. In assessing the significance of a particular FBS result, one should ideally use BD or BB (in extracellular fluid) as well as pH to determine the relative contributions of respiratory and metabolic components. Blood gas analyzers can be programmed to produce this calculation using the Siggaard-Andersen nomogram.40 EVIDENCE BASE
The normal cardiotocogram (CTG), that is, the normal baseline with rest / activity cycles and reactivity, is associated with a good outcome, and, conversely, a persistent bradycardia is associated with a poor outcome. Unfortunately, between these extremes, various patterns of change occur that do not provide reassurance. Decelerations occur in 50% of cases monitored by CTG,I9 and because at least 50% of labors are monitored by electronic fetal monitoring (EFM) in Europe and North America, this is a major clinical problem. Although there is an association of lower cord gas pH" and increased BDM with increasingly abnormal CTG features and the duration of these features,l* the CTG with tachycardia, late decelerations, and decreased baseline variation has only about a 50% incidence of low pH.2 Beard and co-workers2have concluded "that if continuous CTG monitoring was used on its own in clinical practice, a number of false-positive diagnoses of fetal asphyxia are likely to be made." They advocate further assessment of pH by FBS before intervention. Table 1 illustrates the CTG classifications that require a second variable (e.g., FBS) at the author's center. The interpretation of EFM patterns by expert clinicians is improved by the additional use of FBS as another variable. In the author's study of interobserver and intraobserver error in the interpretation of 50 representative CTGs by 17 nominated experts from 16 institutions, the one individual who elected not to use FBS in the practical decision making regarding intervention was the least consistent in the repeat decisions 1 month later and had the least agreement with peers.22 Twelve randomized trials have compared intrapartum EFM with intermittent auscultation performed around the world.+ The trials have *References1517, 23, 2629, 32, 36, 46, and 52.
<5 bpm in the absence of sedation and no accelerations
Persistent bradycardia, no accelerations exceeding 100 bpm, with the belief that this will persist
Abnormal
Preterminal
Severe variable$ Late
Action Continue recording Any two 2 3 0 minutes, FBS Repeat 1 hourt Any one >30 minutes, FBS Any two >15 minutes, FBS Repeat 1 hourt Deliver immediately
Decelerations None Early Mild variable*
*<60 Dropped beats, <60-second duration. tFBS earlier if cardiotocogram deteriorates. $>60 Dropped beats, >60 seconds. FBS = Fetal blood sample; bpm = beats per minute. Dafa from Westgate J, Harris M, Cumow JSH, et a1 Plymouth randomized trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring: 2400 Cases. Am J Obstet Gynecol 169:1151-1160, 1993.
10-25 bpm >25 bpm <5 bpm
Variabilitv
110-160 bpm 100-110 bpm 160-180 bpm
Baseline
Normal Intermediate
Classification
Table 1. CARDIOTOGRAM CLASSIFICATION CRITERIA TO ILLUSTRATE SITUATIONS IN WHICH A SECOND VARIABLE (e.g., FBS) IS REQUIRED
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differed in their entry criteria (variously including high-risk or low-risk pregnancies for all or most women) and in whether FBS for pH estimation was available as an adjunctive method of assessment of fetal wellbeing. Meta-analy~is'~, 31,43 is greatly influenced by the large Dublin trial that specifically excluded cases with meconium and oligohydramnios.28 The only clear benefit to be demonstrated from the routine use of CTG is a reduction in neonatal seizures. Thacker's meta-analysis4j also found a significant decrease in low 1-minute Apgar score (<4) associated with continuous EFM (relative risk [RR], 0.82; 95% confidence interval [CI] 0.65 to 0.98) in the seven studies in which this was recorded. This protective effect was apparent only in trials performed outside of the United States and had not been reported previously. The decrease in neonatal seizures and low 1-minute Apgar score occurred at the expense of a significantly increased operative delivery rate by cesarean section and instrumental vaginal delivery, although this rate has decreased with time. ELECTRONIC FETAL MONITORING WITH AND WITHOUT SCALP BLOOD GAS ANALYSIS
The results of meta-analysis of the three trials in which intermittent auscultation was compared with EFM used without FBS for pH15,16, 23 show a fourfold increase in the odds of cesarean section for fetal distress (odds ratio [OR], 4.14; CI, 2.29 to 7.51) in comparison with the intermittent auscultation group without improvement in fetal outcome. In contrast, EFM with the option of FBS showed a less marked increase in cesarean section rate when compared with intermittent auscultation (OR, 1.98; CI, 1.33 to 2.94), although the greatest impact was on postponing intervention to the second stage (Table 2). Only in the trials with the FBS option was there a decrease in neonatal c o n v ~ l s i o n s . ~ ~ On the basis of these findings, the 26th study group of the UK Royal College of Obstetricians and Gynaecologists35recommended in Table 2. COMPARISON OF ODDS RATIO WITH CONFIDENCE INTERVALS FOR INPACT ON MATERNAL AND NEONATAL OUTCOME FOR INTERMITENT AUSCULTATION VERSUS ELECTRONIC FETAL MONITORING WITH AND WITHOUT FETAL BLOOD SAMPLE Trials of EFM Versus IA
EFM without FBS' EFM with FBSt
Cesarean Section Rate (OR [Cll)
Neonatal Convulsions (OR P I )
4.14 (2.29-7.51) 1.98 (1.33-2.94)
0.79 (0.21-2.97) 0.49 (0.29-0.82)
EFM = Electronic fetal monitoring; FBS = fetal blood sample; IA = intermittent auscultation; OR [CI] = odds ratio (confidence intervals). 'References 15, 16, and 23. tReferences 15, 27,28,32, and 36. Data from Murphy KW, Johnson Moorcraft J, et al: Birth asphyxia and the intraparturn cardiotograph. Br J Obstet Gynaecol 97470-479, 1990; and Thacker SB, Stroup DF, Peterson HB:Efficacy and safety of intrapartum fetal monitoring: An update. Obstet Gynecol 8661?-620, 1995.
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1993 that EFM should not be used without the facility for fetal blood pH measurements, a statement similar to that made 14 years earlier in the report of the US National Institute of Child Health and Human Development Consensus Task Despite these findings and recommendations, there has been no evidence of any increase in the use of FBS in clinical practice. The increased operative delivery rate (by cesarean section and instrumental vaginal delivery) has decreased with time.43The degree to which this lowered intervention is the result of increased use of FBS, better education, or the use of some other modality such as stimulation testing is uncertain. The Plymouth randomized controlled trial of CTG alone versus CTG plus electrocardiography49 showed that the use of the ST waveform of the electrocardiogram as an additional variable improved the interpretation of the CTG and halved the incidence of operative intervention (P
FETAL BLOOD SAMPLING TECHNIQUE
Fetal blood sampling is limited to the skin covering the fetal presenting part. Although animal studies have shown a good correlation for pH between scalp blood samples and carotid arterial blood' and between blood from the fetal scalp in the second stage and blood from the umbilical vessel^,^ there are several situations in which scalp pH measurements are inaccurate (e.g., edema, caput succedaneum) or are misinterpreted. The technique of FBS must be appropriate. Fetal blood can be obtained only with ruptured membranes and the cervix 2- to 3-cm dilated. Samples should be taken with the mother in the lateral position to avoid supine hypotension, which can produce a profound bradycardia with hypoxemia and hypercarbia, producing a short-lasting mixed acidosis (Fig. 3 ) that may prompt unnecessary delivery. An amnioscope is passed into the vagina and through the cervix to rest on the presenting part of the fetus with sufficient pressure to exclude amniotic fluid (which would otherwise contaminate the sample and cause a falsely high pH) but insufficientto cause stasis of capillary flow. Fetal skin is cleaned with a swab then smeared with silicone gel so that when the skin is punctured with a 2-mm blade, a droplet of blood forms rather than runs across the surface. An ethyl chloride spray produces a reactive hyperemia, which aids in bleeding. The droplet of blood is allowed to flow into a glass capillary tube pretreated with heparin, preferably by capillary action. The sample is then transferred to a blood gas analyzer for immediate measurement. Contemporary blood gas analyzers can perform a full analysis on a 40-kL sample to produce a value for pC0, pH, and the calculated BD. As recommended earlier, the complete acid-base balance should be assessed to differentiate between respiratory and metabolic acidosis.
SCALP BLOOD GAS ANALYSIS pn
7.a
1.w
I
1
649
n
7. 1
,
I
am
Figure 3. Short-term effect of supine hypotension caused by fetal blood sample (pH 7.28) in lithotomy inappropriately done for early decelerations. Delay in getting anesthetists allowed further FBS in lateral position to document resolution of respiratory acidosis coincident with an improved and reactive cardiotocogram. A normal delivery occurred 3 hours later. (Break in trace is of 15 minutes’ duration, paper speed run at 1 cm/min).
PRACTICAL INTERPRETATION
Apart from the inconvenience and practical difficulties of obtaining an accurately measured sample, a major problem of FBS is that it is intermittent. Because of the physiology of hypoxemia and acidosis, a sigruficant decrease in pH can occur a short time after a normal sample has been obtained. Care must be taken in assuming that a single-point measurement is the gold standard of hypoxemia/ asphyxia. Unfortunately, attempts over the last decades to produce a continuous pH measurement have continued to prove unsuccessful. The acid-base status of the fetus during labor usually mirrors that of the mother, but at 0.10 of a pH unit less than the maternal venous blood value.@Measurement of this pH difference was used clinically in the past but is no longer carried out. In several situations, consideration of the maternal and fetal acid-base status could be helpful. If the laboring patient is hyperventilating (usually without an epidural and with ineffective pain relief), she expires more C 0 2 and sustains a respiratory alkalosis with a potential blood pH value of 7.50 or greater. This condition raises the fetal pH level and may confound the confirmation of hypoxemia/ acidosis. Similarly, if the woman has a prolonged labor with a ketoacidosis, an infusion acidosis may occur in the fetus, lowering its pH level without hypoxemia. In these situations, a fetomaternal pH difference of more than 0.20 of a pH unit should be taken as indicative of fetal acidemia. It is also good practice to plot serial pH measurements to observe and interpret the trend in conjunction with any FHR abnormalities and the expected duration of labor. Significant hypoxemia produces a progressive acidemia that can be recognized earlier by such repeated measurements. If the trend is projected to the expected time of delivery
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from the partogram, a decision might be made some hours before significant acidemia occurs (Fig. 4).Maternal samples can also facilitate earlier decision making. A clear divergence in the graph of fetal versus maternal pH (see Fig. 4) suggests accumulating fetal [H'] and a significant hypoxemia. In other circumstances, the use of FBS is potentially misleading. Equipment can be poorly calibrated, and, in some situations, the fetal problem is not hypoxemia/asphyxia; a fall in fetal pH can be a late event in fetal sepsis. There are also occasions in clinical practice when heart rate changes are so abnormal that an FBS should not be part of the investigation because it would be a waste of valuable time. In these situations, there is no substitute for knowledge and experience in interpretation of the CTG and FBS in clinical context. FETAL SCALP BLOOD ANALYSIS FOR LACTATE
As explained previously (see Fig. 2), there are good physiologic reasons to measure lactate as a direct marker of anaerobic metabolism. A simple technique for the measurement of lactate in whole blood has recently been developed using just 5 pL of blood on a test strip, provid-
Maternal
b) Diverging materno-fetal pH difference
0.10
v..-.. -..
0.18
-.. -..
PH
-.. ---..
. '.. . -.. \.... '.. a) Projection of pH to estimated time of delivery
7.10
1
I
I
I
0
1
2
3
-..
..
'..\*
Fetal
I
I
I
I
4
5
6
7
Time (h)
Figure 4. Serial fetal blood samples illustrate extrapolation of the trend of serial samples to the predicted time of delivety that could have avoided a fourth sample and acidosis (a) or use of comparison with a paired maternal venous blood pH detecting diverging pH values (b).
SCALP BLOOD GAS ANALYSIS
651
ing a result within 1 minute by a hand-held, bedside electrochemical device.33 In a recent prospective randomized controlled trial (RCT), FBS lactate analysis was compared with pH in 341 cases with ominous FHR patterns.50A sufficient quantity of blood for lactate analysis was obtained significantly more often than for pH analysis. The failure rate for pH was inversely related to the degree of cervical dilation. The lactate group required fewer scalp incisions to obtain a sample, and the result was obtained sooner than in the pH group (2 minutes compared with just under 4 minutes). There was no difference in the predictive value for perinatal outcome in this small study. Because the reluctance to perform FBS12,51 is largely related to the difficulties of obtaining and measuring the sample, lactate analysis using the simple disposable test strip may increase the utility of FBS and even encourage serial use as a simple monitoring procedure. Further studies in other centers are required. EFFICACY
The effectiveness of FBS in clinical practice is another problem. Despite the use of a strict protocol during a research trial in the author's 39% of cases had FBS performed unnecessarily, and 33% of cases did not have it performed when it was indicated. In a study at Oxford, Murphy and c o - w ~ r k e r sexperienced ~~ similar problems with the selection and timing of FBS in a review of 38 cases of birth asphyxia. FBS and the CTG are not independent monitoring methods, and the decision to obtain a FBS depends on the interpretation of the CTG. If the level of CTG interpretation is suboptimal, the value of monitoring by FBS is limited. Some centers45advocate high FBS rates, and there is evidence that higher rates of sampling are associated with higher mean cord arterial pH at delivery? There is no evidence that this 'approach results in a reduction in birth asphyxia. Many opportunities exist for the misinterpretation of FBS results, and an increase in FBS rates without an improvement in knowledge of how to interpret and use the information is unlikely to be successful. There is an urgent need for adequate training, knowledge, and expertise in the interpretation of CTG changes in the context of the individual instance of labor, with intelligent use of FBS or some other ancillary method of fetal surveillance. Contrary to the RCT data, some large units with low intervention rates seldom perform FBS, perhaps relying on fetal stimulation testing7,12,34 FETAL STIMULATION RESPONSE AND pH SAMPLING
Despite the evidence suggesting that it is useful to assess the FHR response to stimulation to reduce the need for fetal scalp ampl ling,^, 6, lo
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which is in keeping with current understanding of the physiology of behavioral adjustments to hypoxemia, the evidence is not sufficiently robust to suggest that either scalp or acoustic fetal ~timulation~~ can entirely replace FBS. FBS may be avoided in 51% of nonreassuring FHR patterns when a positive FHR response to stimulation of 15 beats per minute (bpm) for 15 seconds is elicited.6 This percentage might be increased to 73% of cases if an acceleration were redefined as 10 bpm for 10 seconds and if heart rate variation was normal prior to the stimulation.1° In trying to replicate these results in a large database, the author has found it very difficult to judge an acceleration of 15 bpm for 15 seconds in some of the many traces with fluctuating baselines yet normal FBS r e s ~ l t s This . ~ difficulty has caused considerable intraobserver and interobserver inconsistencies, particularly for the traces (not normal, not abnormal) that required further definition, and is likely to cause interpretative problems in widespread clinical practice. Physiologically, it is surprising that the scalp stimulation studies have found such a clear separation of positive and negative FHR response about an FBS value of 7.20-a figure originally derived for FBS decision making from statistics derived from the population data of Saling and not from any physiologic data. In sheep at least, fetal brain function as measured by evoked response is preserved to lower pH values. Although the literature is generally supportive of stimulation testing, there are increasing reportsg,20, 21 of false-negative findings (i.e., accelerations with a pH <7.20), and these findings do not seem to be explained by the presence of respiratory rather than metabolic acidosis.21 For these reasons, stimulation testing seems unlikely to replace the need for FBS or some other variable in worldwide clinical practice, although it has apparently reduced the need to rely on FBS in some units in North America that maintain low intervention rates.I2 Despite the convenience of the stimulation test, a large randomized control trial seems justified. CONCLUSION
Much has been learned about intraparturn monitoring over the last few decades. There is a much better understanding of the physiologic integrity and responses of the fetus. It is seldom verbalized that what the obstetrician really hopes to achieve from fetal monitoring is the reassurance to allow labor to continue. It is easy to identify the healthy fetus at the onset of labor and to employ low-key monitoring strategies. When concerns arise, continuous EFM by CTG remains the principal means of surveillance, not only because it is a robust signal that can be obtained noninvasively, but also because cardiac output and therefore oxygen delivery are largely determined by heart rate. Although it is possible to derive much information about neurodevelopmental integration and the cardiovascular responses to stress and hypoxia from the CTG, even experienced clinicians fre-
SCALP BLOOD GAS ANALYSIS
Singleton, cephalic, 37-41 weeks' gestation, clear amniotic fluid, spontaneous labor, no major antenatal complications
653
All Other Cases
I Admission CTG 20-40 minutes
not normal
normal
\
/
I
Intermittent Auscultation
not normal or meconium, epidural, - antepartum hemorrhage, oxytocin administration
EFM (External or Internal)
+
I
I
not normal
1 Response to Stimulation'
normal
not normal
1 ST waveform or future proven modality
not normal
T
Continue Intermittent Auscultation
I
Continue EFM
I
I
or FBs deliver
I
Figure 5. Proposed clinical management of fetal monitoring based on current research evidence. 'Fetal heart rate responses should be assessed continuously once electronic fetal monitoring (EFM) is commenced and the fetal electrocardiogram continuously assessed once the scalp clip is applied.
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quently need more data to determine the best course of clinical action when there are uncertain patterns of CTG change. The addition of another variable improves the reliability of interpretation. FBS has traditionally been the second variable used to judge the level of acidosis, whereas the evoked response is widely used in North America. The electrocardiographic waveform has shown considerable promise, and pulse oximetry is increasingly being investigated. The relationship of these possible monitoring strategies to the processes of hypoxemia and asphyxia is much clearer and requires a thoughtful stepwise process of investigation based on the evidence and dependent on individual needs (Fig. 5). It is possible with this approach that intermittent FBS could be confined to a small number of fetuses for whom decision making remains uncertain. In the future, lactate analysis performed on a sequential basis may be useful to examine change over time. These issues are best resolved by further well-designed clinical trials. References 1. Adamsons K, Beard RW, Myers RE: Comparison of the composition of arterial, venous and capillary blood of the fetal monkey during labor. Am J Obstet Gynecol 1 0 7 4 3 5 440, 1970 2. Beard RW, Filshie GM, Knight CA, et al: The significance of the changes in the continuous fetal heart rate in the first stage of labour. J Obstet Gynaecol Br Commonw 78:865881, 1971 3. Bowe ET, Beard RW, Finster M, et al: Reliability of fetal blood sampling. Am J Obstet Gynecol 107279-287, 1970 4. Bretscher J, Saling E: pH values in the human fetus during labour. Am J Obstet Gynecol97906-911, 1967 5. Clark SL, Gimovsky ML, Miller FC: Fetal heart rate response to scalp blood sampling. Am J Obstet Gynecol 144706708, 1982 6. Clark SL, Gimovsky ML, Miller FC: The scalp stimulation test: A clinical alternative to fetal scalp sampling. Am J Obstet Gynecol 148:274-277, 1984 7. Clark SL, Paul RH: Intrapartum fetal surveillance: The role of fetal scalp blood sampling. Am J Obstet Gynecol 153:717-720, 1985 8. Dawes GS, Mott JC, Shelley HJ: The importance of cardiac glycogen for the maintenance of life in foetal lambs and newborn animals during anoxia. J Physiol 146516538, 1959 9. Dixon M, Harris M, Greene KR: Computer analysis of fetal heart rate response to intrapartum scalp stimulation around the time of fetal blood sampling. J Obstet Gynaecol 19(suppl 1):550, 1999 10. Eliman A, Figueroa R, Tejani N: Intrapartum assessment of fetal well-being: A comparison of scalp stimulation with scalp blood pH sampling. Obstet Gynecol 89:373-376, 1997 11. Fleischer A, Schulman H, Jagani N, et al: The development of fetal acidosis in the presence of an abnormal fetal heart rate tracing. 1. The average for gestational age fetus. Am J Obstet Gynecol 144:5540, 1982 12. Goodwin TM, Milner-Masterson L, Paul R Elimination of fetal scalp blood sampling on a large clinical service. Obstet Gynecol 83:971-973, 1994 13. Grant A Monitoring the fetus during labour. In Chalmers I, Enkin M, Keirse MJNC (eds): Effective Care in Pregnancy and Childbirth. New York, Oxford University Press, 1989, pp 8464382 14. Greene KR, R o s h KG: Intrapartum asphyxia. In Levene MI, Lilford RJ (eds): Fetal
SCALP BLOOD GAS ANALYSIS
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and Neonatal Neurology and Neurosurgery. New York, Churchill Livingstone, 1995, pp 389-404 15. Haverkamp AD, Orleans M, Langendoerfer S, et al: A controlled trial of the differential effects of intraparturn fetal monitoring. Am J Obstet Gynecol 134:399-409, 1979 16. Haverkamp AD, Thompson HE, McFee JG, et al: The evaluation of continuous fetal heart rate monitoring in high-risk pregnancy. Am J Obstet Gynecol 125310-317, 1976 17. Herbst A, Ingemarsson I: Intermittent versus continuous electronic fetal monitoring in labour: A randomized study. Br J Obstet Gynaecol 101:663-668,1994 18. Hon E H Instrumentation of fetal heart rate and fetal electrocardiography. 11. A vaginal electrode. Am J Obstet Gynecol 86772-784, 1963 19. Ingermarsson E: Routine electronic fetal monitoring during labour. Acta Obstet Gynecol Scand Suppl994-29, 1981 20. Ingemarsson I, Arulkumaran S Reactive fetal heart rate response to vibroacoustic stimulation in fetuses with low scalp blood pH. Br J Obstet Gynaecol96:562-565, 1989 21. Irion 0, Stuckelberger P, Moutquin J-M, et al: Is intrapartum vibratory acoustic stimulation a valid alternative to fetal scalp p H determination? Br J Obstet Gynaecol103642647, 1996 22. Keith RDF, Beckley S, Garibaldi JM, et al: A multicentre comparative study of 17 experts and an intelligent computer system for managing labour using the cardiotocogram. Br J Obstet Gynaecol 102688-700, 1995 23. Kelso IM, Parsons RJ, Lawrence GF, et al: An assessment of continuous fetal heart rate monitoring in labor: A randomized trial. Am J Obstet Gynecol 131:526-531, 1978 24. Krebs HB, Petres RE, Dunn LJ, et al: Intrapartum fetal heart rate monitoring. I. Classification and prognosis of fetal heart rate patterns. Am J Obstet Gynecol 133:762772, 1979 25. Kubli FW, Hon EH, Khazin AF, et al: Observations on heart rate and pH in the human fetus during labour. Am J Obstet Gynecol 104119(r1206, 1969 26. Leveno KJ, Cunningham FG, Nelson S, et al: A prospective comparison of selective and universal electronic fetal monitoring in 34,995 pregnancies. N Engl J Med 315:615619, 1986 27. Luthy DA, Shy KK, van Belle G, et al: A randomized trial of electronic fetal monitoring in pretenn labor. Obstet Gynecol 69:687-695, 1987 28. MacDonald D, Grant A, Sheridan-Pereira M, et al: The Dublin randomized controlled trial of intrapartum fetal heart rate monitoring. Am J Obstet Gynecol 152:524-539, 1985 29. Mahomed K, Nyoni R, Mulambo T, et al: Randomised controlled trial of intrapartum fetal heart rate monitoring. BMJ 308:497-500, 1994 30. Murphy KW, Johnson P, Moorcraft J, et al: Birth asphyxia and the intrapartum cardiotocograph. Br J Obstet Gynaecol97470-479, 1990 31. Neilson JP, Grant AM. The randomised trials of intrapartum electronic fetal heart rate monitoring. In Spencer JAD, Ward RHT (eds): Intrapartum Fetal Surveillance. London, RCOG Press, 1993, pp 77-93 32. Neldam S, Osler M, Hansen PK, et al: Intrapartum fetal heart rate monitoring in a combined low- and high-risk population: A controlled clinical trial. Eur J Obstet Gynecol Reprod Biol 23:l-11, 1986 33. Nordstrom L, Ingemarsson I, Kublickas M, et al: Scalp blood lactate: A new test strip method for monitoring fetal well-being in labour. Br J Obstet Gynaecol 102894-899, 1995 34. Perkins Rp: Perinatal observations in a high-risk population managed without intrapartum fetal pH studies. Am J Obstet Gynecol 149:327-334, 1984 35. Recommendations arising from 26th RCOG study group: Intrapartum fetal surveillance. In Spencer JAD, Ward RHT (eds): Intrapartum Fetal Surveillance. London, RCOG Press, 1993, pp 387-393 36. Renou F, Chang A, Anderson I, et al: Controlled trial of fetal intensive care. Am J Obstet Gynecol 126:470-476, 1976 37. Ros6n KG, Murphy K How to assess fetal metabolic acidosis from cord samples. J Perinat Med 19221-226, 1991 38. Saling E: Neues Vorgehen zur Untertesuchung des Kindes unter der Geburt-Einfiihrung, Technik, Grundlagen. Arch Gynak 197108-122,1962
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39. Shelley HJ: Glycogen reserves and their changes at birth. Br Med Bull 17137-143,1961 40. Siggaard-Andersen 0: An acid base chart for arterial blood with normal and pathophysiological reference areas. Scand J Clin Lab Invest 27239-245, 1971 41. Smith CV,Nguyen HN, Phelan JP, et al: Intrapartum assessment of fetal wellbeing: A comparison of fetal acoustic stimulation during the abnormal or equivocal biophysical profile. Am J Obstet Gynecol 155:726-728, 1986 42. Steer PJ: Fetal scalp blood analysis current practice. In Spencer JAD, Ward RHT (eds): Intraparturn Fetal Surveillance. London, RCOG Press, 1993, pp 127-138 43. Thacker SB, Stroup DF, Peterson HB:Efficacy and safety of intraparturn fetal monitoring: An update. Obstet Gynecol 86:613-620, 1995 44. Towel1 ME: The rationale for biochemical monitoring of the fetus. J Perinat Med 16(s~ppl1):49-54, 1988 45. van den Berg P, Schmidt S, Gesche J, et al: Fetal distress and the condition of the newborn using cardiotocography and fetal blood analysis during labour. Br J Obstet Gynaecol 94:72-75, 1987 46. Vintzileos AM, Antsaklis A, Varvarigos I, et al: A randomized trial of intrapartum electronic fetal heart rate monitoring versus intermittent ausculation. Obstet Gynecol 815399-907, 1993 47. Westgate J, Greene KR: How well is fetal blood sampling used in clinical practice. Br J Obstet Gynaecol 101:25(r251, 1994 48. Westgate J, RosCn KG: Add base balance at birth. In van Geijin HP, Copray FJA (eds): A Critical Appraisal of Fetal Surveillance. Amsterdam, Elsevier, 1994, pp 595-603 49. Westgate J, Harris M, Cumow JSH, et al: Plymouth randomized trial of cardiotocogram only versus ST waveform plus cardiotocogram for intrapartum monitoring: 2400 Cases. Am J Obstet Gynecol 1693151-1160, 1993 50. Westgren M, h g e r K, Ek S, et a1 Lactate compared with pH analysis at fetal scalp blood sampling: A prospective randomised study. Br J Obstet Gynaecol105:29-33,1998 51. Wheble AM, Gillmer MDG, Spencer JAD, et al: Changes in fetal monitoring practice in the UK: 1977-1984. Br J Obstet Gynaecol 96:114&1147, 1989 52. Wood C, Renou P, Oats J, et al: A controlled trial of fetal heart rate monitoring in a low-risk obstetric population. Am J Obstet Gynecol 141:527-534, 1981 53. Zuspan FP, Quilligan EJ, Iams JD,et al: Predictors of intrapartum fetal distress: The role of electronic fetal monitoring. Report of the National Institute of Child Health and Human Development Consensus Task Force. Am J Obstet Gynecol 135:287-291, 1979 Address reprint requests to Keith R. Greene, MD, FRCOG Plymouth Perinatal Research Group Department of Obstetrics and Gynaecology Derriford Hospital Plymouth, Devon United Kingdom PL6 8DH