Management of diabetic ketoacidosis in pregnancy_240704_013309 eidt.pdf

DOI: 10.1111/tog.12344 2017;19:55–62 The Obstetrician & Gynaecologist Review http://onlinetog.org Manageme...

DOI: 10.1111/tog.12344 2017;19:55–62 The Obstetrician & Gynaecologist Review http://onlinetog.org Management of diabetic ketoacidosis in pregnancy Manoj Mohan MBBS MRCOG,a,* Khaled Ahmed Mohamed Baagar MB BCh CABM MRCP,b Stephen Lindow MBChB c MMed (O&G) MD FRCOG FCOG(SA) FRCPI a Attending Physician, Department of Obstetrics and Gynaecology, Sidra Medical and Research Center, Doha, Qatar, PO Box 26999, and Assistant Professor of Clinical Obstetrics and Gynaecology, Weill Cornell Medical College, Doha, Qatar b Specialist Diabetologist, Diabetic Obstetric Service, Hamad General Hospital, Doha, Qatar c Head of the Division of Obstetrics, Sidra Medical and Research Center, Doha, Qatar Professor of Obstetrics and Gynecology, Weill College Medical College in Qatar *Correspondence: Manoj Mohan. Email: [email protected] Accepted on 31 May 2016 Key content Ethical issues  Diabetic ketoacidosis in pregnancy (DKP) is a serious  Despite adequate knowledge and care of patients with diabetes, is complication that poses several challenges with respect to DKA a major cause for concern? diagnosis, management and prevention.  To increase awareness, and reduce the perinatal morbidity and  This article covers the precipitating factors for DKP in pregnancy mortality associated with DKP. as well as diagnosis, management and prevention of Keywords: diabetes / diagnosis / management / pregnancy / the complication. prevention Learning objectives Linked resource: Single best answer questions are available for this  To manage the acute crisis of DKP. article at https://stratog.rcog.org.uk/tutorial/tog-online-sba-resource  To increase awareness of DKP.  To reduce the perinatal morbidity and mortality associated with DKP. Please cite this paper as: Mohan M, Baagar KAM, Lindow S. Management of diabetic ketoacidosis in pregnancy. The Obstetrician & Gynaecologist 2017;19: 55–62. associated with physiological changes that can predispose a Introduction pregnant woman with diabetes to diabetic ketoacidosis. Diabetic ketoacidosis in pregnancy (DKP) is a serious Some specific physiological reasons for DKP are complication that poses several challenges with respect to as follows:2,3 diagnosis, management and prevention. It develops because  Pregnancy is a state of respiratory alkalosis associated with of relative or absolute insulin deficiency and the a compensatory drop in bicarbonate levels; this impairs the simultaneous increase in counter-regulatory hormones buffering capacity and renders the pregnant woman more (cortisol, catecholamines, glucagon and growth hormone). prone to develop diabetic ketoacidosis. This causes significant changes in metabolism,1 such as  Relative insulin resistance in pregnancy along with lipolysis and proteolysis, which increase gluconeogenesis, and enhanced lipolysis and elevated free fatty acids form the together with glycogenolysis, contribute to the development base for DKP. of hyperglycaemia. This is accompanied by a decrease in  Hormonal changes including increased levels of human glucose uptake by peripheral tissues. Lipolysis provides excess placental lactogen, progesterone, and cortisol impair free fatty acids to the liver, enhancing the process of maternal insulin sensitivity. ketogenesis, with subsequent ketoacidosis.1 At present, most obstetric centres offer specialised care for DKP is more commonly observed along with type I diabetes in pregnancy, which reduces the chance of DKP diabetes, but can also be observed with type II diabetes and occurring. However, DKP does occur and can result in gestational diabetes. It is likely to be precipitated by specific significant morbidity and mortality for both the mother and factors such as protracted vomiting, hyperemesis gravidarum, the fetus. The rate of pregnancy associated with diabetes is starvation, infections, insulin non-compliance, medications rising, especially with the rise in obesity. Pregnancy is also precipitating DKP (e.g. beta sympathomimetic agents), ª 2017 Royal College of Obstetricians and Gynaecologists 55  Diabetic ketoacidosis in pregnancy steroid prophylaxis/steroid treatment, insulin pump failure  Blood glucose level more than 11.0 mmol/l or known (as pumps deliver rapid-acting insulin, interruption for a few diabetes mellitus hours completely deprives the patient of insulin) and  Bicarbonate level less than 15.0 mmol/l and/or venous pH conditions such as diabetic gastroparesis (Box 1).2 less than 7.3 Diagnosis of diabetic ketoacidosis in Management of diabetic ketoacidosis in pregnancy (DKP) pregnancy (DKP) (Figure 1) In pregnant women with any combination of the signs and DKP is considered as an emergency that needs to be managed symptoms specified in Box 2, DKP should be excluded; in at least Level 2 critical care units,5 such as a high-dependency occasionally, DKP may be the first presentation of diabetes unit (HDU) or intensive care unit (ICU), by a team of in pregnancy.2,3 professionals experienced in dealing with similar cases. This When DKP is suspected, laboratory investigation is team usually consists of an obstetrician, a diabetologist/ required to confirm the diagnosis, and to assess the severity endocrinologist, an obstetric anaesthesiologist, and well- of DKP and its possible cause (Box 3). The Joint British trained nursing staff/midwives.2 It is important to stabilise a Diabetes Societies Inpatient Care Group guidelines4 state the patient with DKP and insert large intravenous accesses or following diagnostic criteria for DKP: central venous line and continuous maternal monitoring with  Blood ketone level more than or equal 3.0 mmol/l (or) a cardiac monitor and pulse oximetry.6 The management urine ketone level more than 2+ incorporates six main aspects (Box 4), which should be carried out simultaneously. The six aspects are described below. Box 1. Precipitating factors for diabetic ketoacidosis in pregnancy Intravenous fluid therapy Protracted vomiting Fluid replacement should be commenced by infusing isotonic Hyperemesis gravidarum saline (0.9%), as most patients have a negative fluid balance Infections Insulin non-compliance of about 100 ml/kg of body weight.4 This represents a total Medications precipitating diabetic ketoacidosis in pregnancy fluid deficit of approximately 6–10 l. The intravenous (IV) Insulin pump failure infusion should be started at 10–15 ml/kg/h in the first hour,1 Conditions such as gastroparesis after which the rate should be adjusted according to the haemodynamic status of the patient, guided by monitoring of Box 2. Signs and symptoms blood pressure, urine output, and central venous pressure in selected cases.4 For example, in a healthy adult weighing Nausea or vomiting 70 kg, IV fluid therapy should be performed as follows: Abdominal pain If her systolic blood pressure (SBP) is less than 90 mmHg, Polyuria or polydipsia Blurred vision she should be resuscitated with 500 ml of normal saline Muscle weakness infusion over 10 to 15 minutes and if the SBP does not Drowsiness improve this can be repeated. Senior medical staff evaluation Lethargy should be undertaken to diagnose other causes of Change in mental status Hyperventilation (Kussmaul breathing)/pear drop odour hemodynamic instability such as sepsis.4 After stabilisation Tachypnoea of the SBP above 90 mmHg the patient can be maintained Hypotension with normal saline infusion of 1 l over 1 hour, then 500 ml/hr Tachycardia for 4 hours, followed by 250 ml/h for 8 hours, after which the Coma Shock infusion rate can be reduced to 150 ml/h.4 This fluid Abnormal fetal heart tracing Box 3. Investigation for diabetic ketoacidosis in pregnancy (DKP) Box 4. Management of diabetic ketoacidosis in pregnancy (DKP) Positive serum/urine ketones Multidisciplinary approach Lab glucose hyperglycaemia (≥ 11.0 mmol), but DKP can occur at lower 1. Intravenous fluid therapy glucose levels 2. Intravenous insulin therapy Low serum bicarbonate (12 5. Identification and treatment of any precipitating factors Elevated base deficit ≥4 mEq/l 6. Monitoring of maternal and fetal responses Potassium level may be falsely normal/elevated 56 ª 2017 Royal College of Obstetricians and Gynaecologists  Mohan et al. Figure 1. Algorithm. BUN = blood urea nitrogen; CBC = complete blood count; DKA = diabetic ketoacidosis; IV = intravenous; K = potassium; q = every (Latin quaque) maintenance regimen will be adequate for a patient who If the blood glucose level falls below 14 mmol/l (250 mg/dl), presents with an SBP more than or equal to 90 mmHg. The 10% dextrose should be added to the ongoing normal saline IV patient should be closely monitored by adjusting the IV fluid fluid therapy at a rate of 125 ml/h.4 Careful fluid management therapy according to her response. is imperative in patients with impaired heart or IV fluid therapy improves tissue perfusion, decreases stress kidney function.7 hormone levels, and causes haemodilution; this, in turn, lowers the hyperglycaemia and increases the response to Insulin therapy insulin therapy.2 Adequate perfusion should be ensured, The development of DKP could be attributed to absolute or taking into account fluid losses, through close monitoring of relative insulin deficiency. Therefore, IV insulin therapy not urine output. Urine output should be monitored using an only corrects the hyperglycaemia but also inhibits the ongoing indwelling catheter, and it should be more than or equal to synthesis of keto acids. IV therapy with regular insulin should 0.5 ml/kg/h to ensure that the patient is well hydrated.4 be commenced promptly in patients with serum potassium ª 2017 Royal College of Obstetricians and Gynaecologists 57  Diabetic ketoacidosis in pregnancy level more than or equal to 3.3 mmol/l.1 However, insulin Patients with a good urine output (at least 0.5 ml/kg/h) and administration should be postponed if serum potassium is low, serum potassium level less than 5.5 mmol/l should receive until it is corrected to more than or equal to 3.3 mmol/l, potassium chloride in order to maintain their potassium level because the insulin pushes the potassium into the intracellular in the range of 4–5 mmol/l, as the potassium starts to return space, which aggravates the existing hypokalaemia and may to the cells with the ongoing IV fluids and insulin therapy.2 precipitate fatal cardiac arrhythmias.1 Regular insulin infusion Failure to replace potassium may result in hypokalaemia with should be commenced at a fixed rate of 0.1 unit/kg/h, and it is life-threatening cardiac arrhythmias. recommended not to initially exceed 15 units/h.4 Priming with If the serum potassium level at presentation4 is more than an IV insulin bolus (0.1 unit/kg) is not required unless there is a 5.5 mmol/l potassium should not be added to the infused delay in the preparation of the fixed rate IV insulin infusion.4 If fluid. However, if the level is 3.5–5.5 mmol/l, 40 mmol/l of the metabolic targets (Box 5), primarily blood ketone levels, potassium chloride should be administered with IV normal cannot be achieved by the current infusion rate, the insulin saline. The National Patients Safety Agency and Irish infusion rate should be increased by 1 unit/h until ketones Medication Safety Network recommend not to infuse more reach the desired level.4 than 20 mmol potassium per hour.9,10 If the serum IV regular insulin has been compared with the new IV potassium is less than 3.3 mmol/l, review by a senior rapid-acting insulin analogues (in men and non-pregnant medical staff is important, as the patient may require a women), and both preparations have demonstrated the same higher-strength potassium infusion,4 which may require efficacy, without any difference in treatment duration or the central venous access. total number of insulin units administered.8 Therefore, regular insulin is adopted as it is more cost effective. If the Phosphate replacement patient is already maintained on basal insulin e.g. detemir or Although the whole body phosphate is decreased, glargine, then this should be prescribed and administered replacement is not recommended, unless the serum level is concomitantly with the IV insulin infusion.4 This ensures the less than 0.32 mmol/l (1 mg/dl) or the patient develops presence of insulin in case of interruption in the insulin cardiac impairment or respiratory depression.2,4 infusion and allows a smooth transition to the usual subcutaneous insulin regimen of the patient when he or Evaluation of the need for bicarbonate she is able to sufficiently eat and drink, and the period of administration ketoacidosis has resolved. The use of bicarbonate is not recommended,4 as there is no The fixed-rate infusion can be discontinued after DKP evidence of a beneficial effect with it, and it may be harmful resolution4 and after 30–60 minutes from the first dose of to the patient and the fetus. Bicarbonate inhibits the subcutaneous rapid acting insulin, administered with a meal, compensatory hyperventilation that washes out carbon as a part of the subcutaneous insulin regimen. This is to dioxide (CO2), leading to an increment in CO2 partial avoid rebound hyperglycemia or recurrence of DKP. pressure (PCO2), which may, in turn, decrease fetal oxygen When the DKP has resolved but still the patient cannot delivery.11 In addition, the patient may develop paradoxical reliably eat or drink, a transition of variable-rate (commonly cerebral acidosis, because the CO2 diffuses through the blood referred as sliding scale) IV insulin infusion4 with IV fluid brain barrier faster than the infused bicarbonate.12 Further, can be used to control the blood glucose level until the bicarbonate administration delays the wash out of ketones13 patient tolerates an oral diet and subcutaneous rapid acting and can worsen hypokalaemia. insulin can be given with discontinuation of the variable-rate infusion 30–60 minutes later. Identification and treatment of precipitating factors Recognition of the condition that precipitates DKP is Electrolyte correction: potassium replacement essential for its management, as any delay in the correction Although patients have a total potassium deficit of of the precipitating factor can worsen the prognosis and 3–5 mmol/kg4 the measured serum potassium is usually increase the risk of recurrence.2 A detailed history and normal or even high and this is related to the increased physical examination are very important to direct the osmolality and insulin deficiency, which cause trans-cellular investigations for the targeted treatment of precipitating shift of potassium outside the cells.1 factors. Elevated total white blood cell count is commonly observed; however, it does not always mean that the Box 5. Metabolic targets to be achieved using initial intravenous patient has an infection, as it can be secondary to insulin therapy dehydration. Nevertheless, a thorough clinical assessment Decrease in blood ketone levels by 0.5 mmol/l/h to exclude infection should be performed, and appropriate Increase in venous bicarbonate levels by 3 mmol/l/h treatment should be started if infection is suspected Decrease in capillary glucose levels by 3 mmol/l/h (54 mg/dl/h) or confirmed.3 58 ª 2017 Royal College of Obstetricians and Gynaecologists  Mohan et al. Monitoring of maternal and fetal response DKP, the fetal brain is susceptible to increased maternal 3BHB and lactate concentration, which lead to decreased glucose Maternal response uptake by the fetal brain.20 These events may increase the Capillary glucose should be monitored hourly during insulin chance of fetal brain injury and may have a long-term infusion. Blood ketones4 should also be monitored hourly for developmental impact.20,21 Future research may assist in the first 6 hours in order to ensure that ketone levels decrease at understanding the complete effect of DKP on the fetus. the required rate of at least 0.5 mmol/l. Other biochemical parameters such as pH, bicarbonate and serum potassium can Fetal monitoring and delivery in diabetic be monitored using venous gas samples every 2 hours in the ketoacidosis in pregnancy (DKP) first 6 hours,4 provided that a concomitant laboratory sample The fetal effects in DKP involve a combination of severe is taken at baseline to confirm the accuracy of serum potassium maternal dehydration with acidosis, which may be caused by levels. If a ketone meter is not available, the calculated anion reduced uteroplacental perfusion in an acidotic environment. gap (Box 6) helps in monitoring the patient response.1 In addition to this combined insult, severe maternal Measurement of arterial pH is not required (unless the electrolyte disturbances (particularly potassium) could patient is hypoxic or has an impaired level of consciousness), as result not only in maternal cardiac arrhythmias but also it is only 0.03 units higher than the venous pH.14 fetal cardiac arrhythmias, which may lead to fetal death.22 The bicarbonate level can be reliably used to evaluate the Fetal heart tracing performed in DKP may often demonstrate treatment response in the first 6 hours of management, as, fetal acidotic changes, representing the effect of maternal subsequently, aggressive hydration using 0.9% sodium metabolic acidosis on the fetus. This is often corrected with chloride could lead to the development of hyperchloraemic maternal hydration and correction of metabolic acidosis. acidosis associated with a normal anion gap, which tends to Normalisation of fetal heart tracing after correction of DKP lower the bicarbonate level.4 Ketoacidosis and may require 4–8 hours. Fetal biophysical profile and Doppler hyperchloraemic acidosis are two different types of studies may also reflect the fetal acidotic status. However, the metabolic acidosis associated with low serum bicarbonate decision to deliver should be individualised and should be levels. In ketoacidosis, the primary process is the increased primarily based on evaluation of the maternal clinical status production of keto acids. The body uses bicarbonate to to ensure a safe labour and delivery, fetal gestational age23,24 neutralise these keto acids; therefore, serum bicarbonate level and the results of fetal investigations such as fetal heart decreases and, subsequently, the anion gap increases. tracing. All these factors should be considered together with a Hyperchloraemic acidosis results from the administration multidisciplinary approach while making a decision of large volumes of normal saline with high chloride content regarding delivery. However, in the majority of cases of to the patient, which dilutes plasma bicarbonate, leading to DKP, the aim should be to monitor the fetus until the increased chloride with low bicarbonate, and, subsequently, maternal metabolic state is stabilised, without any immediate metabolic acidosis associated with a normal anion gap.2,4,15 plans for delivery, and to continue the pregnancy with Urinary ketones take time to clear, as the body excretes complete resolution of DKP. There is no consensus on ketones through metabolising the major ketone of DKP further fetal monitoring after complete resolution of DKP, (3-beta-hydroxybutyrate [3BHB]), which can be measured especially when the fetus is preterm. The best practice, on a bedside capillary sample, to acetoacetate, which is semi- however, is aimed at educating the patient to avoid further quantitatively measured in urine. Thus, ketonuria can persist recurrence of DKP, and an increased surveillance to ensure for a significant period after 3BHB has cleared and the adequate diabetic control and compliance with treatment. metabolic acidosis has resolved.16 The frequency of fetal monitoring is unknown and no definite recommendations are currently available. Therefore, Fetal response individualised care with a multidisciplinary approach is DKP may result in severe maternal complications such as acute recommended as a best practice option. renal failure, adult respiratory distress syndrome, cerebral oedema, coma and even death.2,11,17 The fetal mortality Resolution of diabetic ketoacidosis in associated with DKP ranges between 9% and 36%;1,18,19 pregnancy (DKP) however, considerably higher perinatal morbidity is observed with DKP, including hypoxia-related complications, which are Recovery from DKP is defined by a blood ketone level less than attributable to an increased rate of preterm delivery. During 0.6 mmol/l, a pH more than 7.3 and a serum bicarbonate more than 15 mmol/l (however, after 6 hours, bicarbonate may not Box 6. Anion gap calculation be a reliable indicator, as mentioned above).4 Moreover, normalisation of the anion gap (less than or equal to 12 mEq/l) Anion gap = (NA+ + K+) – (Cl + HCO3 ) helps to ensure that the patient has recovered from DKP ª 2017 Royal College of Obstetricians and Gynaecologists 59  Diabetic ketoacidosis in pregnancy (Box 6).1 Insulin infusion has no role in the management of she has hyperglycaemia or feels unwell. Patients should be hyperchloraemic acidosis. This condition is usually corrected educated regarding sick day rules. Ideally, a woman with by the kidney, and no intervention is required. diabetes should be in touch with her diabetes medical team to check her prepregnancy HbA1c level and to keep it below 6.5% (48 mmol/mol).30 Pregnancy should be Euglycaemic diabetic ketoacidosis in avoided if HbA1c level is above 10% (86 mmol/mol).30 pregnancy (DKP)  Prepregnancy counselling: A woman with diabetes should receive counselling from her primary care physician or at Euglycaemic (normoglycaemic) DKP is a rare situation where her diabetes clinic. Effective contraception to avoid the patient presents with normal or below normal, rather than unplanned pregnancy should be discussed. high, blood glucose levels with diabetic ketoacidosis.25 This can affect patients with type I diabetes, type II diabetes or gestational diabetes.2,26 The likely mechanisms are as follows:26 During pregnancy  the use of glucose by the fetoplacental unit, with decreased  Team: During pregnancy, the diabetes specialist nurse/ maternal glycogenolysis and gluconeogenesis midwife, diabetes specialist dietician and/or joint  increased renal loss of glucose as the renal blood flow obstetric-diabetes consultations will form a group of increases with increased glomerular filtration of glucose service providers for effective management. without a corresponding increase in tubular  Screening: Diabetes screening of the general obstetric glucose reabsorption population should be offered to exclude diabetes in  increase in estrogen and progesterone in pregnancy pregnancy as per the local diabetic guidelines, if accompanied by increased maternal usage of blood glucose available; otherwise, efforts should be made to formulate  dilutional effect on blood glucose because of the increased an effective diabetic local screening policy. plasma volume during pregnancy  Education: Women diagnosed with diabetes should be educated in a structured and impartial manner and in Moreover, starvation, which is associated with increased simple language about the precipitating factors and ketone production, is also accompanied by depletion of manifestations of DKP. glycogen stores and normoglycaemic DKP.27  Self-monitoring: Patients should continue to have a It is notable that the management of euglycaemic DKP glucose meter for self-monitoring, and those with type I follows the same principles. However, IV fluid therapy should diabetes should have a ketone meter to be used as involve the concomitant administration of 5% dextrose with previously described.30 IV saline via a separate line from the start of treatment to  Suspected DKP: Pregnant women with any type of diabetes avoid hypoglycaemia caused by IV insulin administration, should be advised to seek prompt attention at a medical which is necessary to stop the production of ketoacids.28,29 facility if their blood glucose level is persistently above 11.1 mmol/l (200 mg/dl), or if they have any signs of Prevention of diabetic ketoacidosis in infection or any other problems, as outlined in Box 1.2 pregnancy (DKP) They should be assessed for hospital admission.  Corticosteroid treatment: If a woman with diabetes Several strategies should be adopted during the requires antenatal corticosteroid therapy for the fetus, preconception period and during pregnancy to prevent DKP. e.g. for fetal lung maturation in a suspected preterm birth, her insulin dose should be gradually adjusted (usually, Prepregnancy insulin dose is increased by 25–40%).31  Education: As per National Institute for Health and Care  Tocolysis treatment: If tocolysis is required, it is preferable Excellence (NICE) guidlines,30 a woman with diabetes to avoid betamimetics (they increase susceptibility for should plan her pregnancy with support from her team of DKP) and use a different class of tocolytics. Tocolytics that diabetes experts; she should receive structured education are safer to use are the oxytocin receptor antagonist with explanation of the facts regarding the risks associated atosiban or a calcium channel blocker e.g. nifedipine.32 with uncontrolled blood glucose in pregnancy. This can reduce complications such as DKP as well as the maternal To prevent the recurrence of DKP, prior to discharge, it is and fetal risk associated with diabetes in pregnancy. necessary to:4  Self-monitoring: A woman with diabetes should be offered  educate the patient about how to identify and rectify the a glucose meter to check her blood glucose levels at home. precipitating factors; Women with type I diabetes should be provided a capillary  review the pre-admission diabetes control, injection ketone meter to check for blood ketonaemia, (or) at least technique, injection sites, glucometer reliability, and urine ketone test strips to check for urine ketonuria when storage of insulin with the patient; and 60 ª 2017 Royal College of Obstetricians and Gynaecologists  Mohan et al.  provide the patient with the contact information of the 4 Joint British Diabetes Societies Inpatient Care Group. The Management of Diabetic Ketoacidosis in Adults. Sept 2013. [http://www.diabetologists- diabetes team and a written plan of care. abcd.org.uk/JBDS/JBDS_IP_DKA_Adults_Revised.pdf]. 5 Department of Health. Comprehensive Critical care: A Review of Adult In addition, future fetal monitoring should also be planned Critical Care Services. UK: Department of Health; 2000 [http://webarchive. prior to discharge and a follow-up should be organised to nationalarchives.gov.uk/20130107105354/http:/www.dh.gov.uk/prod_ review both maternal and fetal antenatal progress, and to consum_dh/groups/dh_digitalassets/@dh/@en/documents/digitalasset/dh_ 4082872.pdf]. ensure continuation of care. 6 Wass J, Owen K. Diabetic hyperglycaemic emergencies. Oxford Handbook of Endocrinology and Diabetes. 3rd ed. Oxford: Oxford University Press; 2014. 7 Barrett EJ, DeFronzo RA. Diabetic ketoacidosis: diagnosis and treatment. Conclusion Hosp Pract (Off Ed) 1984;19(89–95):99–104. 8 Umpierrez GE, Jones S, Smiley D, Mulligan P, Keyler T, Temponi A, et al. DKP is a life-threatening condition; therefore, prompt Insulin analogs versus human insulin in the treatment of patients with diagnosis along with rapid initiation of acute care diabetic ketoacidosis: a randomized controlled trial. Diabetes Care management involving an experienced multidisciplinary 2009;32:1164–9. 9 National Patient Safety Agency. Potassium Solutions: Risks to Patients from team could help to reduce maternal and fetal mortality, Errors Occurring during Intravenous administration. London: National and morbidity. Patient education will form the main Patient Safety Agency; 2002 [http://www.nrls.npsa.nhs.uk/resources/? framework to reduce the risks associated with DKP. This entryid45=59882]. 10 Irish Medication Safety Network. Best Practice Guidelines for the Safe Use study intends to spread awareness regarding DKP among of Intravenous Potassium in Irish Hospitals. Dublin: Irish Medication Safety caregivers and to improve the quality of care in pregnancy. Network; 2013 [http://www.imsn.ie/images/guidelines/imns-july-2013- best-practice-guidance-for-iv-potassium-use.pdf]. 11 Parker JA, Conway DL. Diabetic ketoacidosis in pregnancy. Obstet Gynecol Disclosure of interests Clin North Am 2007;34:533–43, xii. There are no conflicts of interest. 12 Morris LR, Murphy MB, Kitabchi AE. Bicarbonate therapy in severe diabetic ketoacidosis. Ann Intern Med 1986;105:836–40. 13 Okuda Y, Adrogue HJ, Field JB, Nohara H, Yamashita K. Counterproductive Contribution to authorship effects of sodium bicarbonate in diabetic ketoacidosis. J Clin Endocrinol MM instigated, designed, drafted, and critically revised the Metab 1996;81:314–20. 14 Middleton P, Kelly AM, Brown J, Robertson M. Agreement between arterial intellectual content of the manuscript, and contributed to the and central venous values for pH, bicarbonate, base excess, and lactate. obstetric management of the study in the manuscript. 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