The Management Of Diabetic Ketoacidosis In Adults

Use of venous blood rather than arterial blood inblood gas analysers Increase the venous bicarbonate by 3 mmol/L/hour Monitoring of electrolytes on the blood gasanalyser with intermittent laboratory confirmation Potassium should be maintained between 4.0 and5.0 mmol/L Continuation of long acting insulin analogues(Lantus or Levemir ) as normalIf these rates are not achieved then the fixed rate IVIIrate should be increased (see Management of DKASection B, Action 2). Reduce capillary blood glucose by 3 mmol/L/hour Involvement diabetes specialist team as soon aspossibleIntravenous glucose concentrationThe management should be focussed on clearingketones as well as normalising blood glucose. It isoften necessary to administer an intravenous infusionof 10% glucose in order to avoid hypoglycaemia andpermit the continuation of a fixed rate IVII to suppressketogenesis. Introduction of 10% glucose isrecommended when the blood glucose falls below14 mmol/L. It is important to continue 0.9% sodiumchloride solution to correct circulatory volume. It maybe necessary to infuse these solutions concurrently(Section B, Action 2). Glucose should not bediscontinued until the patient is eating and drinkingnormally.General Management IssuesFluid administration and deficitsThere is universal agreement that the most importantinitial therapeutic intervention in DKA is appropriatefluid replacement followed by insulin administration.The main aims for fluid replacement are: Restoration of circulatory volume Clearance of ketones Correction of electrolyte imbalanceThe typical fluid and electrolyte deficits are shown inthe table below. For example, an adult weighing70kg presenting with DKA may be up to 7 litres indeficit. This should be replaced as crystalloid. Inpatients with kidney failure or heart failure, as well asthe elderly and adolescents, the rate and volume offluid replacement may need to be modified. The aimof the first few litres of fluid is to correct anyhypotension, replenish the intravascular deficit, andcounteract the effects of the osmotic diuresis withcorrection of electrolyte disturbance.Special patient groupsThe following groups of patients need specialist inputas soon as possible and special attention needs to bepaid to fluid balance. Elderly Pregnant Young people 18 to 25 years of age (see cerebraloedema)Typical Deficits in DKA:Water (ml/kg)100Sodium (mmol/kg)7-10Chloride (mmol/kg)3-5Potassium (mmol/kg))3-5The type of fluid to be used is discussed in detail inControversial Areas. Heart or kidney failure Other serious co-morbiditiesPatient considerationsPatients with diabetes who are admitted with DKAshould be counselled about the precipitating causeand early warning symptoms of DKA. Failure to do sois a missed educational opportunity. Things toconsider are:Insulin therapyA fixed rate IVII calculated on 0.1 units/ per kilograminfusion is recommended. It may be necessary toestimate the weight of the patient. See ControversialAreas. Insulin has the following effects: Identification of precipitating factor(s) e.g. infectionor omission of insulin injections Prevention of recurrence e.g. provision of writtensick day rules Suppression of ketogenesis Insulin ineffective e.g. the patient’s own insulinmay be expired or denatured. This should bechecked prior to reuse Reduction of blood glucose Correction of electrolyte imbalance Provision of handheld ketone meters andeducation on management of ketonaemiaMetabolic treatment targetsThe recommended targets are Reduction of the blood ketone concentration by0.5 mmol/L/hour7

Controversial Areasfor frequent arterial oxygen level measurements ormonitoring blood pressure in the critically unwellpatient.The clinical assessment and aims of treatment in themanagement of DKA are not controversial. However,there is still disagreement about the optimumtreatment regimen and where the evidence base isnot strong, recommendations are based onconsensus and experience. Some of the morecontroversial points will now be considered and goodpractice recommendations are made. Therecommendations are given first followed by therationale.2. Blood ketone measurement?Ketonaemia is the hallmark of DKA. Frequentrepeated measurement of blood 3-betahydroxybutyrate has only recently become a practicaloption due to the availability of meters which canmeasure blood ketone levels. Compelling evidencesupports the use of this technology for diagnosis andmanagement of DKA (Sheikh-Ali 2008, Bektas 2004,Vaneli 2003, Naunheim 2006). The resolution ofDKA depends upon the suppression of ketonaemiaand measurement of blood ketones now representsbest practice in monitoring the response totreatment.Recommendations1. Measure venous rather than arterial bicarbonateand pH2. Blood ketone meters should be used for nearpatient testing3. Crystalloid rather than colloid solutions arerecommended for fluid resuscitation3. Colloid versus crystalloid?Many guidelines suggest that in hypotensive patientsinitial fluid resuscitation should be with colloid.However, the hypotension results from a loss ofelectrolyte solution and it is more physiological toreplace with crystalloid. Moreover, a recent Cochranereview did not support the use of colloid inpreference to crystalloid fluid (Perel 2007).4. Cautious fluid replacement in young adults5. 0.9% sodium chloride solution is therecommended fluid of choice6. Subcutaneous long-acting analogue insulin shouldbe continued7. Insulin should be administered at a fixed rate IVIIcalculated on body weight8. Do not use a priming dose (bolus) of insulin4. Rate of fluid replacement?There is concern that rapid fluid replacement maylead to cerebral oedema in children and youngadults. National and international paediatricguidelines recommend cautious fluid replacementover 48 hours. Existing adult guidelines (ADA, ABCD,SIGN) all recommend rapid initial fluid replacement inthe first few hours. No randomised controlled trialsexist to guide decision making in this area. Wetherefore recommend cautious fluid replacement insmall young adults who are not shocked atpresentation.9. Bicarbonate administration is not recommendedroutinely10. Phosphate should not be supplemented routinely1. Arterial or venous measurements?Recent evidence shows that the difference betweenvenous and arterial pH is 0.02-0.15 pH units and thedifference between arterial and venous bicarbonate is1.88 mmol/L (Kelly 2006, Gokel 2000). This willchange neither diagnosis nor management of DKAand it is not necessary to use arterial blood tomeasure acid base status (Ma 2003). Venous bloodcan be used in portable and fixed blood gas analysersand therefore venous measurements (bicarbonate,pH and potassium) are easily obtained in mostadmitting units. Arterial line insertion should only beperformed if its use will influence management i.e.5. 0.9% sodium chloride solution or Hartmann’ssolution for resuscitation?There has been much debate recently about therelative merits of these two solutions (Dhatariya 2007and NPSA Alerts 2002, 2007).8

Infusion solutionAdvantagesDisadvantages0.9% sodium chloride Decades of clinical experience Hyperchloraemic metabolic acidosis Readily available in clinical areaswhich may cause renal arteriolar Commercially available ready mixedvasoconstriction leading to oliguriawith potassium at required concentrations,and a slowing of resolution of acidosis20mmol/L (0.15%) or 40mmol/L (0.3%) Supports safe practice with injectablepotassium (NPSA compliant (NPSA alert2002)Compound sodium Balanced crystalloid with minimaltendency to hyperchloraeamic metabolicacidosisIt is recommended that 0.9% sodium chloridesolution should be the fluid of choice for resuscitationin all clinical areas as it supports safe practice and isavailable ready to use with adequate ready-mixedpotassium. In theory replacement with glucose andcompound sodium lactate (Hartmann’s solution) withpotassium, would prevent hyperchloraemic metabolicacidosis, as well as allow appropriate potassiumreplacement. However, at present this is not readilyavailable as a licensed infusion fluid. Insufficient potassium if used alone Not commercially availablewith adequate pre-mixed potassium.Potassium addition in general clinicalareas is unsafe. (NPSA alert 2002) Unfamiliar and not routinely kept onmedical wardsthe ketone concentration is not falling fast enough,and/or the bicarbonate level is not rising fast enough.8. Initiating treatment with a priming dose(bolus) of insulin?A priming dose of insulin in the treatment in DKA isnot necessary provided that the insulin infusion isstarted promptly at a dose of at least 0.1 unit/kg/hour(Kitabchi 2008).9. Intravenous bicarbonate?Adequate fluid and insulin therapy will resolve theacidosis in DKA and the use of bicarbonate is notindicated (Morris 1986, Hale 1984). The acidosis maybe an adaptive response as it improves oxygendelivery to the tissues by causing a right shift of theoxygen dissociation curve. Excessive bicarbonate maycause a rise in the CO2 partial pressure in the cerebrospinal fluid (CSF) and may lead to a paradoxicalincrease in CSF acidosis (Ohman 1971). In addition,the use of bicarbonate in DKA may delay the fall inblood lactate: pyruvate ratio and ketones whencompared to intravenous 0.9% sodium chlorideinfusion (Hale 1984). There is some evidence tosuggest that bicarbonate treatment may beimplicated in the development of cerebral oedema inchildren and young adults (Glaser 2001).6. Continuation of long-acting insulinanalogues?In the last few years the use of long acting basalinsulin analogues (Levemir , Lantus ) has becomewidespread. Continuation of subcutaneous analoguesduring the initial management of DKA providesbackground insulin when the IV insulin isdiscontinued. This avoids rebound hyperglycaemiawhen IV insulin is stopped and should avoid excesslength of stay. This only applies to long actinganalogues and does not obviate the need to giveshort acting insulin before discontinuing theintravenous insulin infusion.7. Fixed-rate intravenous insulin infusion (fixedrate IVII) versus variable rate?Patient demographics are changing and patients withDKA are now more likely to be obese or sufferingwith other insulin-resistant states including pregnancy.Evidence has led to the re-emergence of fixed rate IVIIin adults in the USA and international paediatricpractice (Kitabchi 2009, BSPED 2009, ISPAD 2009).Fixed dose(s) per kilogram body weight enable rapidblood ketone clearance, which is readily monitoredusing bed-side ketone measurement. The fixed ratemay need to be adjusted in insulin resistant states if10. Use of intravenous phosphate?Whole-body phosphate deficits in DKA aresubstantial, averaging 1 mmol/kg of body weight.There is no evidence of benefit of phosphatereplacement (Wilson 1982) thus we do notrecommend the routine measurement or replacementof phosphate. However, in the presence of respiratoryand skeletal muscle weakness, phosphatemeasurement and replacement should be considered(Liu 2004).9

Serious complications of DKA andits treatmentHypokalaemia and hyperkalaemiaCerebral oedemaHypokalaemia and hyperkalaemia are potentiallylife-threatening conditions during themanagement of DKA. There is a risk of acute prerenal failure associated with severe dehydrationand it is therefore recommended that nopotassium be prescribed with the initial fluidresuscitation or if the serum potassium levelremains above 5.5 mmol/L. However, potassiumwill almost always fall as the DKA is treated withinsulin, thus it is recommended that 0.9% sodiumchloride solution with potassium 40 mmol/L(ready-mixed) is prescribed as long as the serumpotassium level is below 5.5 mmol/L and thepatient is passing urine. If the serum potassiumlevel falls below 3.5 mmol/L the potassiumregimen needs review. Where fluid balancepermits, an increase in rate of 0.9% sodiumchloride solution with potassium 40 mmol/Linfusion is possible. Otherwise, a moreconcentrated potassium infusion will be neededand to ensure safe practice, all aspects of its usemust comply with local and national guidance(NPSA 2002, 2009). Trusts need to ensure thatthey have local protocols in place which allow forthe safe administration of concentrated potassiumsolutions. This may require transfer to a higher careenvironment. Electrolyte measurements can beobtained from most modern blood gas analysersand should be used to monitor sodium, potassiumand bicarbonate levels.Cerebral oedema causing symptoms is relativelyuncommon in adults during DKA althoughasymptomatic cerebral oedema may be a commonoccurrence (Rosenbloom 1990). The observationthat cerebral oedema usually occurs within a fewhours of initiation of treatment has led to thespeculation that it is iatrogenic (Hillman 1987).However, this is disputed since subclinical cerebraloedema may be present before treatment isstarted (Hoffmann 1988). The exact cause of thisphenomenon is unknown; recent studies suggestthat cerebral hypoperfusion with subsequent reperfusion may be the mechanism operating (Glaser2001, Glaser 2008, Yuen 2008).Cerebral oedema associated with DKA is morecommon in children than in adults. In the UKaround 70 to 80% of diabetes-related deaths inchildren under 12 years of age are caused as aresult of cerebral oedema (Edge 1999). The UKcase control study of cerebral oedemacomplicating DKA showed that children whodeveloped cerebral oedema were more acidoticand, after severity of acidosis was corrected for,insulin administration in the first hour and volumeof fluid administered over the first 4 hours wereassociated with increased risk (Edge 2006).Pulmonary oedemaPulmonary oedema has only been rarely reportedin DKA. As with cerebral oedema, the observationthat pulmonary oedema usually occurs within afew hours of initiation of treatment has led to thespeculation that the complication is iatrogenic andthat rapid infusion of crystalloids over a shortperiod of time increases the likelihood of thiscomplication (Dixon 2006). Elderly patients andthose with impaired cardiac function are atparticular risk and monitoring of central venouspressure should be considered.HypoglycaemiaThe blood glucose may fall very rapidly asketoacidosis is corrected and a common mistake isto allow the blood glucose to drop tohypoglycaemic levels. This may result in a reboundketosis driven by counter-regulatory hormones.Rebound ketosis lengthens duration of treatment.Severe hypoglycaemia is also associated withcardiac arrhythmias, acute brain injury and death.Once the blood glucose falls to 14 mmol/Lintravenous glucose 10% needs to be commencedto prevent hypoglycaemia.10

DKA Care PathwayDiabetic Ketoacidosis is a medical emergency with asignificant morbidity and mortality. It should bediagnosed promptly and managed intensively. Thespecialist diabetes team should always be involved assoon as possible and ideally within 24 hours becausethis has been demonstrated to be associated with abetter patient experience and reduced length of stay.Assessment of severityIVII regimens will fail to accommodate for the veryobese or the pregnant patient and risks prematurereduction of insulin dosage. Where blood ketonemeasurements are available the adequacy of theinsulin regimen is determined by the rate of fall of theketones and will need revision if this is inadequate.If bedside ketone measurement is not available thebicarbonate level can be used to assess responseduring the first 6 hours, but may be less reliablethereafter. This is particularly important when glucoselevels are relatively normal. Supplementary glucosesolution may need to be infused at some stage intreatment to provide substrate. This will permit thefixed rate IVII to be maintained, avoid hypoglycaemiaand allow the full suppression of ketone production.The presence of one or more of the following mayindicate severe DKA and admission to a Level 2/HDU(High Dependency Unit) environment, insertion of acentral line and immediate senior review should beconsidered:A. Hour 1: Immediatemanagement upon diagnosis:0 to 60 minutes.For young people under the age of 18 years,contact your paediatric diabetes service and usethe BSPED DKA guidelines which can be foundat cs/DKAGuideline.pdf Blood ketones over 6 mmol/LT 0 at time intravenous fluids are commencedIf there is a problem with intravenous accesscritical care support should be requestedimmediately Bicarbonate level below 5 mmol/L Venous/arterial pH below 7.1 Hypokalaemia on admission (under 3.5 mmol/L)Aims Commence IV 0.9% sodium chloride solution GCS less than 12 or abnormal AVPU scale Oxygen saturation below 92% on air (assumingnormal baseline respiratory function) Commence a fixed rate IVII but only after fluidtherapy has been commenced Systolic BP below 90 mmHg Establish monitoring regime appropriate to patient;generally hourly blood glucose (BG) and hourlyketone measurement, with at least 2 hourly serumpotassium for the first six hours Pulse over 100 or below 60 bpm Anion gap above16 [Anion Gap (Na K ) –(Cl- HCO3-) ] Clinical and biochemical assessment of the patientProvision of care Involvement of the diabetes specialist diabetesteam at the earliest possible stageLocal care pathways should identify the units that areto care for DKA patients. Nursing staff appropriatelytrained in Level 2/HDU should take the lead in handson patient care.Action 1 - Intravenous access and initialinvestigations Rapid ABC (Airway, Breathing, Circulation)New principles Large bore iv cannulae and commence iv fluidreplacement (See action 2)The insulin infusion rate is calculated by weight,which may need to be estimated. Administration byweight allows insulin resistant states to beaccommodated. Reliance on standard variable rate Clinical assessmento Respiratory rate; temperature; blood pressure;pulse; oxygen saturation11

o Glasgow Coma Scale. NB: a drowsy patient in thecontext of DKA is serious and the patient requirescritical care input. Consider NG tube with airwayprotection to prevent aspirationo Full clinical examinationAction 2 – Restoration of circulatingvolumeAssess the severity of dehydration using pulse andblood pressure. As a guide 90mmHg may be usedas a measure of hydration but take age, genderand concomitant medication into account. Initial investigations should include:o Blood ketoneso Capillary blood glucoseo Venous plasma glucoseo Urea and electrolyteso Venous blood gaseso Full blood counto Blood cultureso ECGo Chest radiographo Urinalysis and culture Continuous cardiac monitoringSystolic BP (SBP) on admission below 90mmHgHypotension is likely to be due to low circulatingvolume, but consider other causes such as heartfailure, sepsis, etc. Give 500 ml of 0.9% sodium chlo

Diabetic ketoacidosis (DKA) is a complex disordered metabolic state characterised by hyperglycaemia, acidosis, and ketonaemia. DKA usually occurs as a consequence of absolute or relative insulin deficiency that is accompanied by an increase in counter-regulatory hormones (ie, glucagon, cortisol, growth hormone, epinephrine). This type of hormonal