Intracardiac injection of potassium chloride as ... - Wiley Online Library

DOI: 10.1111/j.1471-0528.2007.01639.x

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Intracardiac injection of potassium chloride as method for feticide: experience from a single UK tertiary centre L Pasquini, V Pontello, S Kumar Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital, Imperial College, London, UK Correspondence: Dr S Kumar, Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital, Du Cane Road, London W12 0HS UK. Email [email protected] Accepted 27 November 2007.

We report our experience with intracardiac administration of potassium chloride as safe and effective method for late termination of pregnancy (TOP) and to document the indications for feticide in a major tertiary unit. During the study period (January 2000 and December 2005), 239 late terminations of pregnancy were performed at a median gestational age of 22+6 weeks (range 20+6 to 36+3 weeks). The most frequent indication was represented by aneuploidy (24.3%), followed by brain abnormalities (17.6%). Maternal indications were responsible for 2.9% of the total number of terminations. No maternal

complications occurred and complete asystole was achieved in all cases with a median volume of potassium chloride of 4.7 ml (range 2–10 ml). Potassium chloride injected directly in the left ventricle induces immediate asystole, and it is a safe and effective method of TOP. Interestingly, despite the widespread introduction of aneuploidy screening, chromosomal abnormalities, particularly trisomy 21, still represent the major indication for late TOP. Keywords Abortion, feticide, potassium chloride, termination of

pregnancy.

Please cite this paper as: Pasquini L, Pontello V, Kumar S. Intracardiac injection of potassium chloride as method for feticide: experience from a single UK tertiary centre. BJOG 2008;115:528–531.

Introduction Termination of pregnancy (TOP) in England and Wales has been legal since 1929 and is now governed by the Abortion Act of 1967, which was amended in 1990.1,2 It can only be performed if two registered medical practitioners support the offer/request as justified and sign the appropriate (blue) form. There are five statutory grounds (A to E) and a further two emergency situations (F+G) when termination is permitted. Grounds A, B and E have no gestational age limit. Ground E of the Act stipulates that when ‘there is a substantial risk that if the child was born it would suffer from such physical or mental abnormalities as to be seriously handicapped’ TOP can be carried out. If there is ‘risk to the life of the pregnant woman greater than if the pregnancy were terminated’ or ‘the termination is necessary to prevent permanent injury to the physical or mental health of the pregnant women’ grounds A and B are used respectively. Ground C states that the ‘continuance of the pregnancy would involve risk, greater than if the pregnancy were terminated, of injury to the physical or mental health of the pregnant woman’. This is by far the most common indication for early TOP.

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Late TOP is a very difficult issue not only for women and healthcare professionals but also for society as a whole. The introduction of high-resolution ultrasound and prenatal diagnostic techniques has allowed early diagnoses of aneuploidy and fetal abnormalities and subsequent early TOP if appropriate. However, sometimes, prenatal diagnosis of fetal abnormalities is made late in pregnancy or evolution of fetal prognosis only becomes clear as the pregnancy progresses or life-threatening maternal conditions may manifest at gestations when the fetus is just viable and therefore late TOP is requested. We report our experience of late TOP (‡20+6 weeks) in a single UK tertiary referral centre, and we document the indications for termination.

Methods All cases of feticide (>20+6 weeks of gestation) between January 2000 and December 2005 were retrieved from the fetal medicine database at the Centre for Fetal Care, Queen Charlotte’s and Chelsea Hospital, London. This is a tertiary referral centre for Fetal and Maternal Medicine. The maternal

ª 2008 The Authors Journal compilation ª RCOG 2008 BJOG An International Journal of Obstetrics and Gynaecology

Intracardiac administration of potassium chloride for feticide

notes were reviewed to obtain details about the pregnancy. All cases of multiple pregnancy reduction were excluded. In our unit, the indications for TOP were always discussed and reviewed by a multidisciplinary team (fetal medicine specialists, neonatologists, paediatric cardiologist, paediatric surgeon, neurologist and geneticist). Pretermination counselling was offered to all women. Feticide was only performed by fetal medicine consultants and subspecialty fellows of at least 6 months experience (and always with consultant supervision). The procedure was performed under aseptic conditions with continuous ultrasound guidance. Local anaesthetic (10 ml of 1% lignocaine) was used to infiltrate the maternal skin before a 15-cm 20-G needle (Cook Ob/Gyn, Spencer, IN, USA) was inserted into the fetal left ventricle. After aspirating 1 ml of fetal blood to confirm correct placement of the needle, strong potassium chloride (15%, 20 mM/10 ml; Phoenix Pharma Ltd, Gloucester, UK) was injected. In all cases, 2–3 ml of potassium chloride was injected first before a further dose (if necessary) to achieve fetal asystole. A decision whether or not to inject a further volume of potassium chloride was taken after 1 minute if asystole had not occurred. The volume administered depended on the fetal heart rate, but in general, a further 1–2 ml was injected if the heart rate was above 100/minute. Cardiac activity was then observed for at least 2 minutes to confirm permanent asystole. In line with department protocol, a repeat scan was performed 30 minutes later to confirm fetal demise. Anti-D immunoglobulin prophylaxis was given to all RhD-negative women. After feticide, women were given mifepristone (600 mg) followed by induction of labour 48 hours later with intravaginal misoprostol. Karyotyping and fetal postmortem examinations were offered in appropriate cases. Indications for TOP were subdivided into the following categories: aneuploidy, brain abnormalities, cardiac abnormalities, renal/urinary tract abnormalities, thoracic abnormalities, severe facial abnormalities, neural tube defects (NTDs), skeletal dysplasia, multiple major malformations, severe intrauterine growth retardation, severe early-onset oligo/anhydramnios, hydrops, infections and maternal medical conditions. The category multiple major malformations was defined when two or more abnormalities were present (in the absence of aneuploidy).

Results During the study period, 239 women underwent feticide. The median gestational age at diagnosis/referral was 22+0 weeks (range 11+0 to 36+6 weeks) and at termination 22+6 weeks of gestation (range 20+5–37+5 weeks). The most frequent indication for termination was aneuploidy (24.3%), followed by brain abnormalities (17.6%), multiple abnormalities (14.6%), cardiac abnormalities (9.6%), renal abnormalities (7.5%) and

NTDs (7.5%). Maternal medical indications were responsible for 2.9% of cases (five severe pre-eclampsia and two major psychiatric disorders). The indications for all cases are reported in Table 1. Thirty-eight percent of cases had postmortem examinations, and fetal karyotype was obtained in 84% of cases. Trisomy 21 was the most common indication for aneuploidy (21/58, 36.2%), followed by trisomy 18 (13/58, 22.4%), Turner syndrome (4/58, 6.9%) and 47XXY (3/58, 5.2%). The average amount of potassium chloride injected into the left ventricle required to cause fetal asystole was 4.7 ml (range 2–10 ml), and the dose did not exceed 10 ml in any case. Complete cessation of heart activity was confirmed in all cases within 2 minutes. No women required a second needle insertion. In all women, the entire procedure (from needle insertion to removal) took no longer than 5 minutes. No live births occurred, and there were no maternal complications. Two hundred and twenty-nine (95.8%) procedures were performed under ground E, five (2.1%) under ground B and 5 (2.1%) under ground C. One hundred and thirteen cases (47.3%) were performed beyond 24+0 weeks of gestation. Twenty-seven of these cases (23.9%) were for brain malformations, 23 (20.3%) for aneuploidy, 17 (15%) for multiple abnormalities, 11 (9.7%) for cardiac malformations, 6 (5.3%) for NTD, 4 (3.5%) for skeletal dysplasia, 7 (6.2%) for renal abnormalities, 4 (3.5%) for thoracic malformations, 5 (4.4%) for severe growth restriction, 4 (3.4%) for maternal, 2 (1.8%) for hydrops, 2 (1.8%) for infections and 1 (1.8%) for severe anhydramnios.

Discussion The vast majority of termination of pregnancies (88%) in England and Wales in 2004 were carried out at less than 13 weeks of gestation, usually under ground C of the Abortion Act.3 Feticide was performed in approximately 1900 pregnancies (1%). This figure has remained fairly constant since 2002 when feticide registration was first introduced. In 2004, 124 pregnancies were terminated beyond 24 weeks of gestation in the UK. Comparing this figure with our data, it is clear that feticide is still under-reported nationally. We performed 43 feticides in 2004, 23 of which were performed after 24 weeks. It is unlikely that our unit alone is responsible for almost 20% of nationally reported terminations beyond 24 weeks of gestation. In addition, although the vast majority of feticides are performed within National Health Service units, it is well known that some procedures are carried out within the private sector. Accurate reporting of these procedures is important for both the medical profession and public. Despite significant advances in imaging and prenatal diagnostic techniques, late diagnosis of fetal abnormalities remains an issue for many women. The reasons for this


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Table 1. Indications for late TOP Indication

Aneuploidy Brain Multiple abnormalities Cardiac abnormalities NTD Urinary system Skeletal dysplasia IUGR Severe early-onset anhydramnios Maternal conditions Thorax abnormalities Hydrops Infections Severe facial abnormalities

Incidence (%)

Median GA at diagnosis (range) (weeks)

Median GA at termination (range) (weeks)

58 (24.3) 42 (17.6) 35 (14.6) 23 (9.6) 18 (7.5) 18 (7.5) 11 (4.6) 8 (3.3) 7 (2.9) 7 (2.9) 6 (2.5) 3 (1.2) 2 (0.8) 1 (0.4)

2211 (1215 to 3612) 2116 (1315 to 3616) 2116 (1511 to 3613) 2116 (1513 to 2812) 2212 (1314 to 2813) 2114 (1713 to 2614) 2115 (1110 to 2310) 2210 (1614 to 2515) 2211 (2012 to 2414) 2313 (1714 to 3210) 2211 (2016 to 2214) 2414 (2112 to 2910) 2216 (1212 to 2112) 2213

2313 (2111 to 3613) 2513 (2016 to 3712) 2315 (2110 to 3715) 2313 (2015 to 2816) 2312 (2016 to 2815) 2216 (2110 to 2814) 2314 (2210 to 2610) 2512 (2213 to 2615) 2213 (2113 to 2611) 2413 (2210 to 3212) 2215 (2215 to 2616) 2714 (2310 to 3215) 2816 (2512 to 3213) 2213

GA, gestational age; IUGR, intrauterine growth retardation.

includes late presentation, delayed diagnosis because of the nature of the abnormality or missed diagnosis at earlier scans. For some abnormalities, complex investigations are required before the diagnosis and hence prognosis becomes clearer. Some maternal medical diseases (pre-eclampsia and cardiac abnormalities) present late in pregnancy, and TOP may be necessary to safe guard the life of the mother. The technique of feticide using intracardiac potassium chloride appears to be safe and effective in our hands. We have not had any maternal complications related to the procedure, and rapid fetal asystole was achieved in all cases. Other authors have proposed intrafunicular administration of potassium chloride rather than intracardiac. In our opinion, this is unnecessary as asystole is achieved very rapidly with the intracardiac approach. Cordocentesis usually takes longer to perform and may be complicated by needle displacement, arterial spasms and haematoma. In addition, it is not always effective: Gill et al.4 reported a success rate of 86.7% and Bhide et al.5 95.2% with this technique. Furthermore, in the study by Bhide et al., there was one case of failed feticide in the cordocentesis group that resulted in the delivery of a fetus with signs of life. The authors also had a second case requiring additional administration of intracardiac potassium chloride.5 In the study by Gill et al.,4 13.3% of cases required additional cardiocentesis after cordocentesis. That study also reported the birth of a live baby after attempted feticide by cordocentesis. We are also aware of a few more recent cases of failed feticide. Clearly, such situations have enormous emotional implications for women and significant financial consequences for the hospitals concerned. Senat et al.6 proposed administration of sulfentanil and lignocaine by cordocentesis for feticide instead of potassium chloride.

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However, with this technique, in three cases, cardiocentesis was necessary and in one case additional intracardiac potassium chloride was required. In our view, these complications are avoidable and unnecessary if direct intracardiac administration of potassium chloride is performed appropriately in the first instance. The average amount of potassium chloride required in our study was 4.7 ml (range 2–10 ml), much less than the amounts reported by other authors. In the series of Bhide et al.,5 the average amount of potassium chloride used was 10 ml. This is significantly higher than our experience. We believe that if the needle is correctly positioned in the left ventricle, minimal amount of potassium chloride is required to achieve asystole as the potassium chloride is injected rapidly into the coronary circulation inducing immediate asystole. Although it is certainly possible for inadvertent maternal injection or maternal absorption of potassium chloride during feticide, this would be extremely rare if correct fetal placement of the needle is confirmed prior to the procedure. Hyperkalemia can cause cardiac arrhythmias or asystole, and if there is any concern about maternal cardiac risk, a postprocedure electrocardiogram should be considered and potassium levels checked. For some conditions, there is a significant lag between diagnosis and subsequent termination. For many cases, the delay is as a result of further investigations being performed or evolution of the fetal condition before prognosis becomes clearer or most importantly patient choice. In our population, the main indication for late TOP was chromosomal abnormalities (24.3%), with trisomy 21 and 18 accounting for 56.4% of all cases. Brain abnormalities represented the second largest indication for feticide in our study.


Intracardiac administration of potassium chloride for feticide

Because of the uncertainty about long-term neurodevelopmental outcome for many brain abnormalities, many women opt for TOP. This is in contrast to major cardiac malformations in that many women choose to continue the pregnancy despite being aware of the risks of neonatal open heart surgery. Cardiac abnormalities are the most common congenital malformation among live births, 6.5 times greater than chromosomal anomalies and four times than of NTDs. However, they are not the most frequent indication for late TOP. Despite major advances in prenatal diagnosis, fetal therapy and obstetric care, in some cases, late TOP is a necessary option. Feticide is a specialised procedure that should really be undertaken in tertiary fetal medicine units after comprehensive evaluation of the fetus and pregnancy. Given the legal and ethical implications raised by late TOP, we believe it is important that a multidisciplinary team of specialists discuss contentious cases before a final offer is made to the woman. In many institutions, this practice is already established. Potassium chloride injected directly into the left ventricle induces immediate asystole, and it is a safe and effective method of TOP. No maternal or fetal complications were associated with the procedure in our series. However, it is important to follow a strict protocol to confirm fetal asystole as the consequences for failed feticide are significant. In our view, all cases should be discussed by a multidisciplinary team

to ensure that the indications for late TOP are sound and in accordance with the law. This approach also serves to deflect any potential criticism that might be levelled at any one medical practitioner.

Contribution to authorship S.K. conceived the idea for this paper and together with L.P. wrote the first draft. L.P. and V.P. helped review the notes and collected and analysed the data. All authors contributed to the final draft. j

References 1 Abortion Act 1967. London: HMSO; 1967. 2 Human Fertilisation and Embryology Act 1990. London: HMSO; 1990. 3 Department of Health. Abortion Statistics, England and Wales: 2002. Statistical Bulletin 2003/23. London: Department of Health, 2003. 4 Gill P, Cyr D, Afrakhtah M, Mack L, Easterling T. Induction of fetal demise in advanced pregnancy terminations: report on a funic potassium chloride protocol Fetal Diagn Ther 1994;9:278–82. 5 Bhide A, Sairam S, Hollis B, Thilaganathan B. Comparison of feticide carried out by cordocentesis versus cardiac puncture. Ultrasound Obstet Gynecol 2002;20:230–2. 6 Senat MV, Fisher C, Bernard JP, Ville Y. The use of lidocaine in late termination of pregnancy. BJOG 2003;110:296–300.


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