The peripartum management of diabetes

Learning objectives.

By reading this article you should be able to:

• •Describe the implications of diabetes in pregnancy on mother and baby.
• •Discuss the rationale for recommendations about glycaemic control in labour.
• •Identify the complications associated with the use of a variable rate insulin infusion.
• •Formulate a multidisciplinary plan for the safe intrapartum management of women with diabetes for operative delivery.

Key points.

• •Women with diabetes are more likely to require interventions in the intrapartum period.
• •Management of these patients requires a multidisciplinary approach.
• •There is controversy about the optimal target for intrapartum capillary blood glucose.
• •A target of 4–7 mmol L⁻¹ during labour and delivery is widely recommended.
• •A target capillary blood glucose of 5–8 mmol L⁻¹ during and after surgery may improve safety.

Hyperglycaemia in pregnancy affects an estimated 21.4 million women worldwide. In the UK alone, pre-existing diabetes and gestational diabetes mellitus (GDM) complicates 5% of pregnancies, approximately 35,000 per annum, but the prevalence varies between countries (Table 1).^1,2 GDM accounts for the majority of pregnant women with diabetes, followed by type 1 diabetes (T1DM) and type 2 diabetes (T2DM).¹ GDM typically arises in the second or third trimester of pregnancy. If detected in the first trimester, it is likely that the parturient had undiagnosed pre-existing diabetes.

Table 1.

Estimates of the prevalence of diabetes in pregnancy by country in 2013²

Country	Live births in women aged 20–49 yrs (1000s)	Cases (1000s)	Crude prevalence (%)
UK	719.5	164.3	22.8
USA	3,894.3	464.2	11.9
Canada	380.1	67.5	17.8
Australia	299.8	24.7	8.2
India	24,055.9	5,995.3	24.9

The prevalence of pre-existing diabetes in pregnancy in the UK has increased dramatically over the past 20 yrs. Between 1995 and 2012, the prevalence of T1DM in pregnancy increased from 1.56 to 4.09 per 1000 pregnancies. The increase has been even more evident for T2DM, increasing from 2.34 to 10.62 per 1000 pregnancies. Increasing maternal age and a higher BMI are likely to have contributed to these increases.³

Women with pre-existing diabetes and GDM in pregnancy are a high-risk group. Maternal hyperglycaemia is associated with increased perinatal morbidity such as macrosomia, birth injuries, premature delivery, and hyperbilirubinaemia.⁴ The UK Perinatal Confidential Enquiry identified that babies born to mothers with pre-existing diabetes have an increased risk of congenital anomalies, are five times more likely to be stillborn, and three times more likely to die in the first months of life. There is a higher requirement for Caesarean delivery in women with diabetes. Pre-existing conditions such as diabetic retinopathy and nephropathy may also be exacerbated by pregnancy. There is also a higher incidence of other comorbidities including sepsis and pre-eclampsia.^4,5 Management of these patients requires careful planning with a multidisciplinary approach involving obstetricians, diabetologists, anaesthetists, midwives, diabetes specialist nurse and dietitians.

Planning management for a diabetic parturient during labour and delivery is particularly challenging because of the demands of labour, dietary restrictions and potential for operative delivery. The main goals can be summarised as: ensuring the avoidance of maternal hypoglycaemia or hyperglycemia (which can increase the risk of neonatal hypoglycaemia), ensuring the safe use of measures to manage glycaemic control, for example variable rate i.v. insulin infusions (VRIIs) and the provision of effective analgesia for labour. This article focuses on the peripartum management of women with diabetes relevant to the anaesthetist.

Maternal glycaemic control in labour

Currently available international guidelines for the peripartum management of pregnant women with diabetes focus on rigorous intrapartum glycaemic control. In women with diabetes, maternal hyperglycaemia leads to hyperplasia of pancreatic β cells in the fetus and an increase in fetal insulin concentrations. When the continuous supply of glucose is stopped after delivery, the neonate is at risk of developing hypoglycaemia, which if untreated can have serious neurological consequences.⁶ The increase in fetal insulin also contributes to the excess growth of the fetus in mothers with hyperglycaemia.⁴ However, data supporting tight intrapartum maternal glucose control and its role in minimising neonatal hypoglycaemia have been inconsistent.

A systematic review examined the relationship between intrapartum maternal glycaemic control and neonatal hypoglycaemia.⁷ Twelve of the 23 studies included showed no association between intrapartum maternal glucose and neonatal hypoglycemia. The review highlighted the marked heterogeneity of the studies published between 1978 and 2016. The most recent study that showed an association between maternal glucose and neonatal hypoglycaemia, was published in 2002. The authors recommended that further work is necessary, given the inconsistent findings and the lack of high-quality studies.

A further potential concern relates directly to the woman. Pregnant women with diabetes may be at greater risk of hypoglycaemic episodes because awareness of the symptoms of hypoglycaemia is reduced, and this is further exacerbated by tight glycaemic control.⁸

In the UK, the National Institute for Health and Care Excellence (NICE) published clinical guidance on ‘Diabetes in pregnancy: management from preconception to the postnatal period’ in 2015. The recommendations for capillary blood glucose (CBG) control during the intrapartum period are shown in Box 1.

Box 1. NICE recommendations during the intrapartum period1.

• •Monitor CBG every hour during labour and birth in women with diabetes, and ensure that it is maintained between 4 and 7 mmol L⁻¹.
• •Use intravenous dextrose and insulin infusion during labour and birth for women with diabetes in whom CBG is not maintained between 4 and 7 mmol L⁻¹.

Alt-text: Box 1

The recommendations by NICE are based on 10 observational studies,9, 10, 11, 12, 13, 14, 15, 16, 17, 18 of which the most recent was published in 2006. In contrast to the systematic review, all 10 studies demonstrated an association between maternal hyperglycaemia and neonatal hypoglycaemia. However, only two studies showed that maintaining a maternal blood glucose concentration of <7 mmol L⁻¹ actually decreased this complication.^9,13 The target range for CBG of 4–7 mmol L⁻¹ is also recommended by the Canadian Clinical Practice Guidelines on diabetes in pregnancy.¹⁹

In 2017 the Joint British Diabetes Societies for Inpatient Care (JBDS-IP) published guidance on ‘Management of glycaemic control in pregnant women with diabetes on obstetric wards and delivery units’. This guideline also recommends a target CBG range between 4 and 7 mmol L⁻¹, consistent with the recommendations by NICE.⁷ In addition, this guidance provides an alternative pragmatic view on intrapartum glycaemic management for women with diabetes requiring operative delivery.²⁰ During these perioperative conditions, a slightly more relaxed CBG range of 5–8 mmol L⁻¹ has been proposed as a safer alternative for the woman. This would reduce the need for a VRIII and the associated iatrogenic complications.

Practical management of the parturient with diabetes

Women with diabetes should have their CBGs checked hourly during the intrapartum period. Appropriate equipment for monitoring and treating hypoglycaemia or hyperglycaemia such as a glucometer, infusion pumps, 20% glucose solution should be readily available in delivery units and obstetric theatres.

Both the UK and Canadian guidelines recommend the use of a VRII for women with diabetes whose CBG is not maintained between 4 and 7 mmol L⁻¹ in labour. Staff caring for patients should receive training on blood glucose management and the safe use of VRIIs. In the UK many midwives have entered the profession directly, without prior nursing experience and may therefore have limited experience of managing patients with diabetes. In line with the JBDS-IP recommendations, midwives should have at least 2 h of training and yearly updates on blood glucose management.

Safe use of variable rate intravenous insulin infusions

A VRII is used when the target CBG range is not achieved by modification of the patient's usual medications. A glucose containing substrate fluid is run alongside an i.v. insulin infusion, which acts to prevent gluconeogenesis, lipolysis, and the development of ketoacidosis. Basal insulin should be continued after a VRII has been started. Although the VRII is an effective way to achieve and maintain glycaemic control, its use may also be associated with various complications (Box 2). In 2010, the National Patient Safety Agency report on safer administration on insulin highlighted cases resulting in severe harm and death from dosing errors in insulin administrations.²²

Box 2. Complications associated with the use of VRIII21.

Equipment-related errors:

• •Errors in programming
• •Errors in i.v. cannula connection

Commencement errors:

• •Failure of administration of dextrose substrate alongside insulin infusion
• •Delayed commencement resulting in diabetic ketoacidosis (DKA)
• •Inadequate frequency of CBG monitoring resulting in poor titration

Errors in discontinuing.

• •Premature discontinuation before administration of insulin in patients with type 1 diabetes leading to DKA

Alt-text: Box 2

Of particular relevance in obstetric patients is the risk of hyponatraemia associated with the use of i.v. glucose as the substrate fluid. Severe hyponatraemia can lead to seizures and cerebral oedema.²³ Severe but asymptomatic maternal antepartum hyponatraemia has been described as a cause of neonatal seizures.²⁴ The use of oxytocin during labour can cause fluid retention, further exacerbating this problem.

The recommended substrate fluid when commencing a VRII is 5% glucose in 0.9% saline with pre-mixed 0.15% (20 mmol L⁻¹) potassium chloride or 0.30% (40 mmol L⁻¹) potassium chloride. The sodium-rich solution reduces the risk of developing hyponatraemia. It is recommended that the rate of substrate fluid be commenced at 50 ml h⁻¹ and adjusted according to the patient's fluid status and requirements.²⁰

Continuous subcutaneous insulin infusion

Women with T1DM may have their diabetes managed with a continuous subcutaneous insulin infusion (CSII). This is a small, battery-powered device that continuously delivers insulin subcutaneously. The pump can be programmed to deliver basal insulin infusion and insulin boluses. The basal infusion provides continuous delivery of insulin to maintain normoglycaemia and prevent ketogenesis. The insulin bolus is titrated at meal times by the patient according to the carbohydrate count. A retrospective study in women with T1DM showed that women who chose to continue on CSII during labour had better glycaemic control than women using CSII during pregnancy but who chose to convert to VRII during labour. There was no increase in maternal hypoglycemia, suggesting that the continuation of CSII during labour and delivery appears safe and efficacious.²⁵ The use of an insulin pump in the perioperative period has been discussed in detail in a previously published review.²⁶

During the intrapartum period, the CSII can be safely used to maintain normoglycaemia. Women can self-manage their insulin pumps if they prefer. CBG monitoring can either be continuous or intermittent depending on the device. In the antenatal period, these patients will receive input from the multidisciplinary diabetes team (endocrinologist and diabetes specialist nurse). This team will provide an individualised care plan with recommendations on the settings and methods for monitoring CBG during the intrapartum and postpartum period.

The JBDS recommends that if the CBG is more than 7 mmol L⁻¹ on more than two consecutive readings or if capillary blood ketones are more than 1.5 mmol L⁻¹, the insulin pump should be turned off and a VRIII should be commenced in an attempt to stabilise blood glucose and prevent ketogenesis.²⁰ A VRII can also replace the CSII pump if the woman is unable to manage her own insulin requirements. The same principle applies for women undergoing operative delivery.

Management of anaesthesia in women with diabetes

As a result of associated comorbidities such as pre-eclampsia and fetal macrosomia, women with diabetes are at higher risk of requiring intervention during the intrapartum period. The provision of neuraxial analgesia may offer specific advantages and reduce the risk of general anaesthesia being required in the event of operative delivery.

The incidence of hypotension after the initiation of neuraxial analgesia during labour is estimated to be about 10% and is similar whether it is initiated with combined spinal–epidural or epidural alone. Although it is no longer mandatory to use i.v. fluids before or when initiating neuraxial anaesthesia, an i.v. infusion of a crystalloid is generally started before establishing epidural analgesia. If a VRII is required to maintain CBG within the target range, a separate cannula for the VRII and substrate fluid is recommended. Treatment for both hyperglycaemia and hypoglycaemia should be prescribed on the drug chart.

Management is more complicated in patients with pre-eclampsia as they are likely to receive multiple i.v. infusions including VRIIs, substrate fluid, oxytocin, antihypertensive medication(s), and magnesium. Adequate venous access must be in place and infusions pumps must be clearly labelled. Close attention should be paid to fluid balance as management can be complicated by the development of pulmonary oedema, often caused by inappropriate fluid administration. Fluid restriction to 80 ml h⁻¹ is recommended in the UK by NICE unless there are ongoing fluid losses.^27,28

If a VRII is used to maintain a target CBG of less than 7 mmol L⁻¹ during labour (unless undergoing operative delivery where target range is 5–8 mmol L⁻¹), it may be appropriate to run it without substrate fluid for those with fluid restriction in place. This increases the risk of hypoglycaemia and should only be considered if other means of reducing fluid input have been attempted. Local pharmacy departments can provide advice on reducing the volume of drug infusions if the target fluid restriction rate cannot otherwise be achieved. Patients requiring operative delivery under general anaesthesia should have their CBG measured more frequently. Blood glucose homeostasis is disrupted as a result of the surgical stress response. There is also loss of neuroglycopenic awareness, increasing the risk of hypoglycaemic episodes occurring undetected. More frequent CBG measurements allow early detection and treatment of blood glucose outside the recommended range. The management of women with diabetes requiring operative delivery under regional and general anaesthesia is summarised in Box 3.

Box 3. Management of women with diabetes requiring operative delivery under regional and general anaesthesia.

• •Sufficient venous access must be available to accommodate additional i.v. infusions, e.g. fluids, phenylephrine and oxytocin.
• •The recommended CBG range is 5–8 mmol L⁻¹. CBG should be checked hourly (half-hourly if under general anaesthesia).
• •The recommended CBG range is 5–8 mmol L⁻¹. CBG should be checked hourly (half-hourly if under general anaesthesia).
• •Infusion pumps should be clearly marked. Care must be taken when altering the rate of infusions to ensure the correct pump is chosen.

Alt-text: Box 3

Hypoglycaemia (CBG <4 mmol L⁻¹) should be treated promptly with an infusion of 20% dextrose over 15 min. If a VRIII is ongoing, it should be stopped for 20 min. The CBG should be rechecked 10 min after the initial hypoglycaemic reading.²⁰

Postpartum management

In general, insulin requirements will decrease rapidly after delivery. The emphasis of management in the postpartum period is to avoid maternal hypoglycaemia. The target CBG range for patients with pre-existing diabetes is relaxed to 6–10 mmol L⁻¹. These postpartum management recommendations are in line with the guidance from the JBDS.²⁰

Pre-existing type 1 diabetes or insulin-dependent type 2 diabetes

If patient has been commenced on a VRIII, the rate should be decreased by 50% after delivery and can be stopped 30–60 min after the first meal. CBG should be monitored hourly until then and continued as per the patient's pre-pregnancy practice.

Subcutaneous insulin should be started as per the individual care plan. However, if one is not available, give 50% of the late pregnancy dose or seek advice from the diabetes specialist team.

If mothers are breastfeeding or expressing breast milk, increase in calorie requirements increases the risk of hypoglycaemia. Mothers should be made aware of increased nutritional needs and be advised to snack after each feed.

Pre-existing diabetes on oral glucose lowering therapy

If subcutaneous insulin was started during the antenatal period or if a VRIII was commenced during the intrapartum period, the insulin should be discontinued after delivery. CBG monitoring frequency can be reduced to every 4 h, until the first meal. Subsequent monitoring should be before meals and before bedtime or as per local trust policy.

Oral glucose-lowering drugs such as metformin and glibenclamide can be restarted as per pre-pregnancy dose. Any other drugs should be discussed with the diabetes specialist team.

Gestational diabetes

GDM is a risk factor for developing T2DM. Up to 50% of women with GDM will be diagnosed with T2DM within 5 yrs.¹ Those that are diagnosed with GDM in the first half of pregnancy are at increased risk of recurrent GDM in subsequent pregnancies and development of T2DM. Obesity and requirements for insulin for glycaemic control are also predisposing factors.²⁹

CSII

After delivery, the settings on the CSII pump must be changed to postnatal settings as per the patient's individual care plan. If the pump has been discontinued during the intrapartum period and the patient is on a VRIII, the pump should be restarted with postnatal settings. The VRIII should only be discontinued after an hour after restarting the CSII pump and the mother is able to manage her own pump. The target blood glucose is between 6 and 10 mmol L⁻¹.

If no documented care plan is available, the JBDS guidance has recommended the following pump settings:

• •Basal rates reduced to 0.5 units h⁻¹
• •Insulin/carbohydrate ratio of 1 unit of insulin per 15 g of carbohydrate
• •Insulin sensitivity increased to 4 mmol L⁻¹.

The diabetes specialist team should also be contacted as soon as possible.

Conclusion

Diabetes is associated with an increase in maternal and perinatal morbidity and mortality. As the incidence increases, we are more likely to encounter these patients on a regular basis. Management requires a multidisciplinary approach from the antenatal period through to the postnatal period with individualised plans. Daily multidisciplinary reviews should be encouraged when patients are admitted to the delivery unit.

This review has discussed the controversies with regard to the current national guidelines. There is a lack of high-quality data to support the view that tight glycaemic control during the intrapartum period reduces the risk of neonatal hypoglycaemia. In light of this, we recommend a less stringent intrapartum CBG range of 5–8 mmol L⁻¹ for patients undergoing operative delivery. This approach will reduce the risk of maternal hypoglycaemia and hyponatraemia associated with the inappropriate use of a VRIII.

Declaration of interest

Dr A Modi was one of the co-authors of the section 'Appendix 3' in the Joint British Diabetes Societies (JBDS) document on glycaemic control on pregnant women with diabetes referenced in this article.

MCQs

The associated MCQs (to support CME/CPD activity) will be accessible at www.bjaed.org/cme/home by subscribers to BJA Education.

Biographies

Yeng Yap FRCA is a specialty registrar in anaesthesia in the East of England deanery.

Aditi Modi FRCA is a consultant obstetric anaesthetist at West Suffolk Hospital. She is the secretary of the East Anglian Obstetric Anaesthetists group and co-organiser of seminars on diabetes for the Association of Anaesthetists.

Nuala Lucas FRCA is a consultant anaesthetist at Northwick Park Hospital and lead for maternity anaesthesia. Between 2014 and 2018, she was honorary secretary of the OAA and currently chairs the education subcommittee. She is a senior editor of the International Journal of Obstetric Anaesthesia and joint anaesthetics lead for MBRRACE-UK.

Matrix codes: 1A01, 1A02, 2B02, 2B03, 2B04, 3B00