33 Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP. Risk of uterine rupture during labor among ... A chest x ray showed interstitial shadowing but no focal ...
Clinical review
Recent developments in obstetrics Andrew H Shennan
Guy’s, King’s, and St Thomas’s School of Medicine, St Thomas’s Hospital, London SE1 7EH Andrew H Shennan professor of obstetrics
Two of the most challenging areas in antenatal care are prematurity and pre-eclampsia. Between them they affect one in 10 of all pregnant women, and their prevalence is static. Until recently management options have been limited. Improved understanding of the basic pathophysiology is changing this.
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Sources and selection
Pre-eclampsia affects around 3% of pregnant women and accounts for 25% of all babies with a very low birth weight ( < 1500 g). Doppler ultrasound of the uterine artery can identify women at risk
This article describes those advances that have made an impact on the management of prematurity and pre-eclampsia. Another major concern in obstetrics is the rising number of interventions, particularly caesarean sections, without obvious benefit to mother or baby. Recent research has highlighted several simple but effective strategies that could help influence this trend. These include management of previous caesarean sections and breech presentation and more appropriate use of fetal monitoring and epidurals in labour; knowledge of these will be valuable to any clinician who comes into contact with pregnant women. The articles selected are from relevant searches in English from Pubmed and the Cochrane Collaboration, as well as the author’s own experience through research and reviewing.
Low dose aspirin (75 mg) given prophylactically will reduce the chance of developing pre-eclampsia by 15%, with a similar reduction in fetal death. This should be considered in women at risk
Pre-eclampsia
There is no evidence that asymptomatic women with abnormal vaginal flora benefit from antimicrobials
The current structure of antenatal care developed around detecting pre-eclampsia. The detection of hypertension and proteinuria, the defining signs of this syndrome, is the key aim of frequent surveillance in pregnancy. Pre-eclampsia occurs in about 3% of pregnant women and results in around 100 000 maternal deaths per year worldwide. The fetus is also affected, directly through placental insufficiency and indirectly through iatrogenic delivery; this accounts for 25% of all infants with a very low birth weight ( < 1500 g). The onset and course of pre-eclampsia are unpredictable, and it therefore results in enormous use of health resources. Accurate prediction and targeted preventive measures would have enormous benefit. Prediction Many biochemical substances, principally of placental and endothelial origin, increase in pre-eclampsia. However, their predictive value to detect susceptible women before clinical presentation is poor. As the disorder originates in the placenta, blood flow in the uterine artery is abnormal in most women destined to present with the syndrome. A population at risk can be 604
Recent developments
The second trimester use of vaginal ultrasound to measure cervical length and the detection of vaginal fetal fibronectin are better predictors of preterm delivery than previous history Although infection has a key role in the aetiology of early preterm delivery, evidence regarding the use of prophylactic antibiotics is contradictory since benefit may be related to the choice, route, and timing of treatment
Women with a breech presentation at term who plan a vaginal delivery have a 3% increased risk of death or serious morbidity to their baby. External cephalic version should therefore be offered Intrapartum intervention can be reduced by avoiding unnecessary electronic fetal monitoring, encouraging vaginal delivery with previous caesarean section, and using low dose epidurals targeted for intervention (fig 1) by using Doppler ultrasound to measure blood flow in the uterine artery in the second trimester. This biophysical test is currently the best predictor of pre-eclampsia. Positive predictive values are similar in both high and low risk groups, so 20% of women with an abnormal Doppler result will develop pre-eclampsia.1 2 Prevention Aspirin at low dosage has been evaluated extensively as an agent to prevent pre-eclampsia, with a sound BMJ VOLUME 327
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Clinical review sounds and needs confirmation in other groups before widespread use of vitamins C and E can be recommended.6 However, the combination of predicting women at risk and targeting them with a safe intervention seems to be a sound strategy to limit the number needed to treat to prevent one case.
Fig 1 Flow velocity waveforms in the uterine artery as shown by Doppler analysis. a: abnormal flow velocity waveforms—high resistance index, early diastolic match. b: normal flow velocity waveforms—low resistance index, no match
No of patients needed to treat
rationale of reversing the imbalance of prostacyclin and thromboxane that is found in women with the disease. In 32 randomised controlled trials including nearly 30 000 women, low dose aspirin results in a 15% decrease in pre-eclampsia, with a similar reduction in the chance of fetal death.3 4 Babies are also less likely to be delivered prematurely, and the benefit is independent of risk status. Few interventions in perinatal medicine actually reduce the risk of the baby dying. Targeting women with an abnormal Doppler ultrasound can reduce the number needed to treat (NNT) considerably. Figure 2 shows how the positive predictive value of a test and the reduction in relative risk of an intervention will influence the number needed to treat. Even with a positive predictive value of around 20% (as found with uterine Doppler ultrasound) and a relative risk reduction of 15%, the number needed to treat can still be reduced substantively and make clinical application worth while. The value of screening women at low risk has, however, not been established. The benefit of the intervention may also be better in women identified by abnormal Doppler results. In five randomised controlled trials including women treated with aspirin after abnormal uterine Doppler ultrasounds, the reduction of relative risk in preeclampsia was nearer 45%.5 Recently antioxidants in the form of high dosages of vitamins C (1000 mg) and E (400 IU) have also been used successfully in reducing pre-eclampsia by more than 50%.6 Figure 2 also shows the numbers needed to treat when the intervention results in a relative risk reduction of 50%. Again the rationale for using these vitamins is scientifically sound as oxidative stress seems to be a key feature of the pathophysiology. This study was performed in women principally identified by abnormal Doppler ultra70 15% RRR 60 50% RRR 50 40 30 20 10 0 10
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Screening test positive predictive value
Fig 2 Influence of positive predictive value and relative risk reduction (RRR) on the number needed to treat (NNT)
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Management The management of pre-eclampsia entails close surveillance and delivery. Otherwise it is empirical, aimed at reducing morbidity or mortality. It includes antihypertensive agents, which can be used to halve severe hypertension (relative risk reduction 0.52, confidence interval 0.41 to 0.64).7 This is likely to reduce the risk of cerebral haemorrhage, which occurs in half the women who die.8 Controlling blood pressure does not, however, alter progression of the disease. The eclampsia trial showed that magnesium sulphate was the drug of choice to prevent further fits after eclampsia,9 but the value of prophylactic treatment with anticonvulsant drugs has been uncertain. As large numbers of women would need to be treated the benefits of prophylactic treatment are important to ascertain. The Magpie study compared giving magnesium sulphate with giving placebo to more than 10 000 women with pre-eclampsia.10 The chance of eclampsia was 0.8% if allocated magnesium sulphate compared with 1.9% in the controls; this represented 11 fewer fits per 1000 women treated. No benefit to the baby was found, although placental abruption may be less common in the group treated with magnesium sulphate. An eclamptic fit indicates serious underlying disease and is usually self limiting and not inherently life threatening, although undesirable. The importance of these findings will therefore depend on previous practice and the population treated. For example, in the United States where magnesium sulphate is used extensively in women at relatively low risk its use may now decline. However, women at high risk are likely to benefit as a trend has become obvious towards fewer maternal deaths in the Magpie study (relative risk 0.55, 95% confidence interval 0.26 to 1.14), and there are physiological reasons why magnesium sulphate might benefit other aspects of sequelae of pre-eclampsia.
Prematurity Preterm delivery accounts for 65% of neonatal deaths and 50% of neurological disability in childhood. Spontaneous preterm labour or prelabour rupture of the membranes account for 80% of preterm deliveries. Prematurity rates have not changed in recent decades. Prediction A short cervix identified on vaginal ultrasound has a good predictive value for early delivery, even in a low risk group, and a cervical length of less than 15 mm will result in a 50% chance of delivery before 32 weeks’ gestation.11 The predictive value in multiple pregnancies is similar.12 Identifying fetal fibronectin in vaginal secretions after 22 weeks’ gestation also has a strong association with preterm delivery.13 Both these tests perform far better than previous history as predictors of preterm delivery, which has traditionally been the way to identify a group at risk, as most women with recurrent prematurity will achieve a term pregnancy in 605
Clinical review their subsequent pregnancy. Although it is impractical to screen all women, populations at risk could be targeted with these tests to identify groups for intervention. Prevention Few agents can stop uterine contractions effectively, and acute tocolysis has never been shown to reduce perinatal mortality. Delivery may be prevented in the short term, which will allow steroids to be given to the mother or enable transfer to a suitable neonatal unit. A new tocolytic, atosiban (an oxytocin antagonist), is no more effective than agonists but has fewer side effects and is therefore likely to be safer.14 Treatment has therefore focused on prophylactic measures. Cervical cerclage—Elective cervical cerclage has previously shown only marginal benefit in preventing preterm delivery, and attention is now focused on cerclage in women identified at risk from a short cervix. Preliminary results show that this may be beneficial, although they are based on very small numbers.15 Some retrospective evidence shows that transabdominal cerclage may have a role in cases where transvaginal cerclage has failed.16 Antibiotics—Although preterm labour is multifactorial, it is often associated with and caused by infection, particularly if very preterm. Both bacterial vaginosis and vaginal infection with group B streptococci increase the risk of preterm delivery. Unfortunately randomised controlled trials have shown that using metronidazole in women at low risk who are positive for bacterial vaginosis does not reduce this risk.17 Targeting women at risk has shown variable results, but some randomised controlled trials show that antibiotics can even increase the risk of preterm delivery.18 More recently oral clindamycin given early to women with abnormal vaginal flora has shown some value in reducing late miscarriage and preterm delivery.19 Therefore the timing, type, and population targeted may determine if treatment is beneficial. The ORACLE trial considered if antibiotics were valuable in preterm labour and prelabour rupture of the membranes.20 Erythromycin significantly reduced the chance of delivery within one week while improving neonatal outcome in women with prelabour rupture of the membranes.20 Importantly co-amoxiclav increased the risk of necrotising enterocolitis and is not recommended with prelabour rupture of the membranes. Asymptomatic bacteruria should be treated as the treatment reduces prematurity. Tocolytic agents—Although acute tocolysis is of limited benefit, its use is generally restricted by unwanted side effects. Atosiban can be given for prolonged periods, and its use as a prophylactic agent is now being assessed. Calcium channel blockers such as nifedipine also have fewer side effects and are equally efficacious to atosiban, although they are unlicensed for use in pregnancy. Non-steroidal antiinflammatory drugs can cause renal and ductal problems in the fetus. Current studies are evaluating the cyclo-oxygenase-2 inhibitors, which theoretically may be as efficacious at preventing delivery while limiting these unwanted side effects, thus allowing their use as a prophylactic measure. Other strategies—Progesterone, given either intramuscularly or by vaginal pessary to women at risk, has 606
shown some benefit in reducing preterm delivery in at risk women, and confirmatory trials are eagerly awaited.21 22 Initial reports show that fish oils may reduce the incidence of preterm labour in women with a previous history, although the scientific rationale underpinning this has not been robustly tested.23 Confirmation is required in prospective trials. In the mean time the biggest impact to prevent prematurity is probably simple: avoid smoking.24
Breech presentation at term and external cephalic version At term, 3-4% of all babies will present by the breech. The recent term breech trial showed a notable increase in perinatal mortality and morbidity when a vaginal delivery is planned, providing unequivocal evidence that women with a breech presentation at term who plan a caesarean section will have a baby less likely to die or have a serious outcome.25 Women who plan a vaginal delivery will have a 1% increased risk of perinatal death and a 2.4% increased risk of serious neonatal morbidity. Caesarean section is, however, associated with a small increase risk of maternal morbidity (relative risk 1.29, 95% confidence interval 1.03 to 1.61).26 External cephalic version for breech at term will reduce non-cephalic births by nearly 60% but is not offered universally.27 A need therefore exists to implement this simple, apparently safe, alternative to the planned caesarean section in all obstetric units and offer it universally.28 A planned caesarean section with its increased maternal morbidity should not be the first or only obstetric intervention for the term breech.
Reducing operative deliveries Trial of scar Concerns have arisen that the rate of caesarean sections has been increasing steadily over the past two decades; the results of the term breech trial will be an added pressure on this. The National Sentinel Caesarean Section Audit Report in 2001 (www.rcog.org.uk) showed that in the United Kingdom, 21.3% of women now deliver by caesarean section, a similar rate to the United States. This rate has almost doubled in the past decade. The audit commission has estimated that every 1% increase in the rate of caesarean sections costs the NHS an additional £5m ($8m; €7m). Even elective caesarean sections, which are recognised to be the safest, probably have at least a doubling in risk of maternal death.8 Research has therefore recently focused on the safety of a vaginal delivery after a previous caesarean section and in what circumstances it should be encouraged. Some 80% of women will achieve a vaginal delivery after a previous caesarean section, even when the cause of the original operation was well defined cephalopelvic disproportion.29 Reasonable retrospective evidence now supports the commonly held belief that both the interval between pregnancies ( > 6 months) and a previous vaginal delivery reduce the risk of scar failure.30 31 The chance of successful vaginal delivery is, however, reduced to 60% if labour is induced.32 Rupture of the scar occurs more commonly in these women (1 in 50 women induced with prostaglandins, compared with 1 in 200 if the labour is spontaneous).33 This study of BMJ VOLUME 327
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Clinical review more than 20 000 women with one prior caesarean section defined outcome accurately; only one in 20 scar ruptures caused fetal death. Therefore the overall fetal mortality associated with a trial of scar is extremely small and comparable to the risk of an intrapartum stillbirth in all women (1 in 1500), assuming safe intrapartum management. Only a minority of women with ruptured scars require a hysterectomy (4.4%) and other serious morbidity such as infection, bladder injury, or paralytic ileus occurs in fewer than 10% of women. These data support the policy of encouraging women to deliver vaginally after one previous caesarean section, which is probably the single most important intervention to prevent caesarean section rates escalating further. Intrapartum care The recent increase in operative intervention has not been associated with improved perinatal morbidity or mortality. Increasing expectations and medicolegal fears probably contribute to iatrogenic morbidity in pregnancy. Routine investigations in all women are known to increase intervention, sometimes without clear benefit. An example of this is the routine use of electronic fetal monitoring, which is now not recommended in women at low risk. A cardiotocogram performed on admission in women at low risk was assumed to be desirable to identify fetuses at risk. A recent randomised controlled trial comparing this with Doppler auscultation has shown that cardiotocograms result in a notable increase in intervention, including oxytocin augmentation and use of epidurals, and cause an increase in operative deliveries without any evidence of improvement in the wellbeing of the newborn. Given the number of women involved in this intervention, withdrawing the routine use of the cardiotocogram on admission is likely to reduce unnecessary intervention considerably. Where available, more than one in five women will request epidurals for pain relief in labour. These are associated with longer labours, more use of oxytocin, and increased operative vaginal deliveries.34 Low dose epidurals are being used increasingly, which allow some mobility while maintaining adequate analgesia. This is achieved by adding opiates and reducing the bupivacaine dose. A recent randomised controlled trial has shown that low dose epidurals reduce the need for operative vaginal deliveries, so that one in four could be prevented.35 Several studies have also shown that women prefer them, so there seems little justification in continuing to use the higher dose procedure.
Additional educational resources http://www.cemach.org.uk/—The new Confidential Enquiry into Maternal and Child Health (CEMACH) was launched in April 2003. It was founded on the Confidential Enquiry into Maternal Deaths (CEMD) and the Confidential Enquiry into Stillbirths and Deaths in Infancy (CESDI) and is part of a strategy for the development of the national confidential enquiries being implemented by the National Institute for Clinical Excellence (NICE). CEMACH has a wider brief to include children up to the age of 16 years and its aim is to improve future care of mothers, babies, and children. www.rcog.org.uk—Royal College of Obstetricians and Gynaecologists. The RCOG is dedicated to the encouragement of the study and the advancement of the science and practice of obstetrics and gynaecology www.bapm.org.uk—British Association of Perinatal Medicine, aims to improve the standard of perinatal care in the British Isles. www.nice.org.uk—National Institute for Clinical Excellence, set up as a special health authority for England and Wales on 1 April 1999. It is part of the National Health Service (NHS), and its role is to provide patients, health professionals, and the public with authoritative, robust, and reliable guidance on current best practice. www.nelh.nhs.uk—The National Electronic Library for Health programme is working with NHS libraries to develop a digital library for NHS staff, patients, and the public. www.apec.org.uk—Action on Pre-eclampsia (APEC) is a UK charity set up in 1991 to ease and prevent suffering from pre-eclampsia and improve care and understanding of the condition. www.tommys.org—Charity that funds a national programme of research, education, and information aimed at understanding and preventing premature birth, miscarriage, and stillbirth. www.bmfms.org.uk—The British Maternal and Fetal Medicine Society aims to provide a forum where issues of relevance to obstetricians and other professionals involved in problem pregnancy care are discussed, to encourage improved standards of care.
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Competing interests: None declared. 1
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Mires GJ, Williams Fl, Leslie J, Howie PW. Assessment of uterine arterial notching as a screening test for adverse pregnancy outcome. Am J Obstet Gynecol 1998;179:1317-23. Coleman MA, McCowan LM, North RA. Mid-trimester uterine artery Doppler screening as a predictor of adverse pregnancy outcome in high risk women. Ultrasound Obstet Gynecol 2000;15:4-6. Duley L, Henderson-Smart D, Knight M, King J. Antiplatelet durgs for prevention of pre-eclampsia and is consequences: systematic review. BMJ 2001;322:329-33. Knight M, Duley L, Henderson-Smart DJ, King JF. Antiplatelet agents for preventing and treating pre-eclampsia. Cochrane Database Syst Rev 2000;(2):CD000492. Coomarasamy A, Papaioannou S, Gee H, Khan KS. Aspirin for the prevention of pre-eclampsia in women with abnormal uterine artery Doppler: a meta-analysis. Obstet Gynaecol 2001;98:861-6. Chappell LC, Seed PT, Briley AL, Kelly FJ, Hunt BJ, Parmar K, et al. Effect of antioxidants on the occurrence of pre-eclampsia in women at increased risk: a randomised trial. Lancet 1999;354:810-6.
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Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev 2001;(2):CD002252. Confidential Enquiry into Maternal Deaths in the United Kingdom. Why mothers die, report for 1997-1999. London: RCOG Press, 2001. Which anti-convulsant for women with eclampsia? Evidence from the collaborative eclampsia trial. Lancet 1995;345:1455-63. Duley L. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie trial: a randomised placebocontrolled trial. Lancet 2002;359:1877-90. Hassan SS, Romero R, Berry SM, Dang K, Blackwell SC, Treadwell MC, et al. Patients with an ultrasonographic cervical length < or = 15 mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol 2000;182:1458-67. Guzman ER, Walters C, O’Reilly-Green C, Meirowitz NB, Gipson K, Nigam J, et al. Use of cervical ultrasonography in prediction of spontaneous preterm birth in triplet gestations. Am J Obstet Gynecol 2000;183:1108-13. Heath VC, Daskalakis G, Zagaliki A, Carvalho M, Nicolaides KH. Cervicovaginal fibronectin and cervical length at 23 weeks of gestation: relative risk of early pre-term delivery. Br J Obstet Gynaecol 2000;107:1276-81. Effectiveness and safety of the oxytocin antagonist atosiban versus betaadrenergic agonists in the treatment of preterm labour. The Worldwide Atosiban versus Beta-agonists Study Group. Br J Obstet Gynaecol 2001;108:133-42. Althuisius SM, Dekker GA, van Geijn HP, Bekedam D, Kuik D, van Geijn H. Cervical incompetence prevention randomized cerclage trial (CIPRACT): study design and preliminary results. Am J Obstet Gynecol 2001;183:823-9. David G, Berghella V, Talucci M, Wapner RJ. Patients with a prior failed transvaginal cerclage: a comparison of obstetric outcomes with either transabdominal or transvaginal cerclage. Am J Obstet Gynaecol 2000;183:836-9. Carey JC, Klebanoff MA, Hauth JC, Hillier SL, Thom EA, Ernest JM, et al. Metronidazole to prevent preterm delivery in pregnant women with asymptomatic bacterial vaginosis. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med 2000;342:534-40. Odendaal HJ, Popov I, Schoeman J, Smithy M, Grove D. Preterm labour—is bacterial vaginosis involved? S Afr Med J 2002;92:231-4. Ugwumadu A, Manyonda I, Reid F, Hay P. Effect of early oral clindamycin on late miscarriage and preterm delivery in asymptomatic women with abnormal vaginal flora and bacterial vaginosis: a randomised controlled trial. Lancet 2003;361:983-88. Kenyon SL, Taylor DJ, Tarnow-Mordi W, for the ORACLE Collaborative Group. Broad-spectrum antibiotics for preterm, prelabour rupture of fetal membranes: the ORACLE I randomised trial. Lancet 2001;357:979-88.
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Clinical review 21 Meis PJ, Klebanoff M, Thom E, Dombrowski MP, Sibai B, Moawad AH, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Prevention of recurrent preterm delivery by 17 alpha-hydroxyprogesterone caproate. N Engl J Med 2003;348:2379-85. 22 Da Fonesca EB, Bittar RE, Carvalho MHB, Zugaib M. Prophylactic adminstration of progesterone by vaginal suppository to reduce the incidence of spontaneous preterm birth in women at increased risk: A randomised placebo-controlled double blind study. Am J Obstet Gynecol 2003;188:419-24. 23 Olsen SF, Secher NJ, Tabor A, Weber T, Walker JJ, Gluud C. Randomised clinical trials of fish oil supplementation in high risk pregnancies. Fish Oil Trials in Pregnancy (FOTIP) Team. Br J Obstet Gynaecol 2000;107:382-95. 24 Shah NR, Bracken MB. A systematic review and meta-analysis of prospective studies on the association between maternal cigarette smoking and preterm delivery. Am J Obstet Gynecol 2000;182:465-72. 25 Hannah ME, Hannah WJ, Hewson SA, Hodnett ED, Saigal S, Willan AR, for the Term Breech Trial Collaborative Group. Planned caesarean section versus planned vaginal birth for breech presentation at term: a randomised multicentre trial. Lancet 2000;356:1375-83. 26 Hofmeyr GJ, Hannah ME. Planned caesarean section for term breech delivery. Cochrane Database Syst Rev 2002;(2):CD000184.
27 Hofmeyr GJ, Kulier R. External cephalic version for breech presentation at term. Cochrane Database Syst Rev 2002;(2):CD000184. 28 Shennan A, Bewley S. How to manage term breech deliveries. BMJ 2001;323:244-5. 29 Impey L, O’Herlihy C. First delivery after cesarean delivery for strictly defined cephalopelvic disproportion. Obstet Gynecol 1998;92:799-803. 30 Esposito MA, Menihan CA, Malee MP. Association of interpregnancy interval with uterine scar failure in labor: a case-control study. Am J Obstet Gynecol 2000;183:1180-3. 31 Zelop CM, Shipp TD, Repke JT, Cohen A, Lieberman E. Effect of previous vaginal delivery on the risk of uterine rupture during a subsequent trial of labor. Am J Obstet Gynecol 2000;183:1184-6. 32 Sims EJ, Newman RB, Hulsey TC. Vaginal birth after cesarean: to induce or not to induce. Am J Obstet Gynecol 2001;184:1122-4. 33 Lydon-Rochelle M, Holt VL, Easterling TR, Martin DP. Risk of uterine rupture during labor among women with a prior cesarean delivery. N Engl J Med 2001;345:3-8. 34 Howell CJ. Epidural versus non-epidural analgesia for pain relief in labour. Cochrane Database Syst Rev 2000;(2):CD000331. 35 Effect of low-dose mobile versus traditional epidural techniques on mode of delivery: a randomised controlled trial. Lancet 2001;358:19-23.
Lesson of the week Spurious hyperglycaemia and icodextrin in peritoneal dialysis fluid Stephen G Riley, James Chess, Kieron L Donovan, John D Williams Metabolites of new peritoneal dialysis fluids may cause spurious hyperglycaemia and inappropriate insulin treatment Institute of Nephrology, University Hospital of Wales, Heath Park, Cardiff CF14 4XN Stephen G Riley specialist registrar James Chess locum appointment for training Kieron L Donovan consultant nephrologist John D Williams consultant nephrologist Correspondence to: S G Riley steveriley65@ hotmail.com BMJ 2003;327:608–9
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Diabetes mellitus, in particular type 2, has become more common, and the trend is likely to continue.1 Associated comorbidity is also more common—for example, diabetes is now the most common cause of dialysis dependent renal failure in the Western world.2 In the United Kingdom between 1991 and 1998, the incidence of new patients on dialysis increased from 67 to more than 90 patients per million population, and the prevalence of diabetes in people receiving dialysis has increased from 16% to 19%.3 The increasing demand for dialysis and slower growth in capacity for haemodialysis has reinforced the need for an integrated approach to providing dialysis. Peritoneal dialysis is the preferred option for a proportion of patients with end stage renal failure.4 A subgroup of patients has difficulties with removing fluid. This can be improved with an alternative osmotic agent based on a polymer of glucose—icodextrin.5 We report a severe potentially clinical consequence of using icodextrin in a diabetic patient, which although mentioned in a specialist journal is still not widely recognised. This issue is even more important given the increasing number of diabetic patients with end stage renal failure. About 500 patients in the United Kingdom use icodextrin daily.
Case report A 76 year old Sudanese man presented to the emergency department with a four day history of general malaise and shortness of breath. On the day of presentation he developed a cough, which produced white sputum. He had type 2 diabetes controlled with insulin and control of his diabetes had been erratic in the few days before admission. He had been using peritoneal dialysis for four years with icodextrin for the previous year to help maintain ultrafiltration.
In the emergency department the man seemed comfortable at rest but was feverish with a temperature of 37.2°C. His pulse was 85 beats/min and blood pressure 160/80 mm Hg. Oxygen saturation was 94% on air. He had a raised jugular venous pressure and heard crackles at the base of both lungs. A chest x ray showed interstitial shadowing but no focal consolidation. The finger stick glucose reading was 17 mmol/l. The team diagnosed him as having chest infection and transferred him to a sister hospital. During transfer the patient’s consciousness decreased: he became sweaty and developed slurred speech. On arrival at the new hospital, the patient had a grand mal seizure. Finger stick glucose testing gave a reading of 15.4 mmol/l. He was given 5 mg diazepam and the fit subsided. Soon after, laboratory blood tests found that venous glucose concentration was only 1.2 mmol/l. On treatment with intravenous glucose the patient recovered. The admitting doctors started antibiotics and insulin using a sliding scale. Two hours later, the patient had another grand mal seizure and they gave further bolus of diazepam. The glucose finger stick reading had increased again, to 14 mmol/l, but venous glucose concentration was 1.5 mmol/l. They gave further intravenous glucose and the patient recovered. A sample of blood on test sticks from two different machines gave readings of 15.6 and 16.8 mmol/l. A laboratory sample at the same time, however, gave 5.5 mmol/l. The sliding scale was stopped, and the patient was transferred to the renal unit, where he recovered uneventfully.
Discussion Peritoneal dialysis fluid usually contains glucose as an osmotic agent to enable water to pass across the peritoneum. Some patients lose the osmotic effect of glucose quickly, but large icodextrin molecules, which are not easily transported across the peritoneal BMJ VOLUME 327
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