Diabetic Ketoacidosis Shabana Kalladi ,MD Pediatric Endocrinology - PowerPoint PPT Presentation

Diabetic Ketoacidosis Shabana Kalladi ,MD Pediatric Endocrinology

Biochemical Criteria for Diagnosis of DKA ● Hyperglycemia [blood glucose (BG) >11 mmol/L (≈200 mg/dL) ● Venous pH < 7.3 or bicarbonate <15 mmol/L ● Ketonemia and ketonuria

DKA : Goals of Therapy ● Correct dehydration ● Correct acidosis and reverse ketosis ● Slowly correct hyperosmolality and restore BG to near normal

Fluid Replacement ● Fluid replacement should begin before starting insulin therapy ● Expand volume to restore peripheral circulation ● Calculate subsequent rate of fluid administration, including provision of maintenance fluid requirements, aiming to replace estimated fluid deficit evenly over 48 h (should seldom exceed 1.5–2 times daily maintenance requirement)

Insulin Therapy ● DKA: Deficiency of circulating insulin and increased levels of the counterregulatory hormones: catecholamines, glucagon, cortisol and growth hormone

Insulin Therapy ● DKA: Deficiency of circulating insulin and increased levels of the counterregulatory hormones: catecholamines, glucagon, cortisol and growth hormone ● Although rehydration alone frequently causes marked decrease in BG concentration, insulin therapy essential to restore normal cellular metabolism , normalize BG, suppress lipolysis and ketogenesis

Insulin Therapy ● Begin with IV insulin at 0.05–0.1 U/kg/h 1–2 h AFTER starting fluid replacement therapy Schade DS, Eaton RP. Dose response to insulin in man: differential effects on glucose and ketone body regulation. J Clin Endocrinol Metab 1977;44:1038–53.

Insulin Therapy ● Begin with IV insulin at 0.05–0.1 U/kg/h 1–2 h AFTER starting fluid replacement therapy ● Intravenous insulin at 0.1 unit/kg/hour → steady state plasma insulin levels ~ 100–200 mU/ml within 60 minutes ● → offset insulin resistance, inhibit lipolysis & ketogenesis Schade DS, Eaton RP. Dose response to insulin in man: differential effects on glucose and ketone body regulation. J Clin Endocrinol Metab 1977;44:1038–53.

To Bolus or Not to Bolus…?

To Bolus or Not to Bolus…? ● Half life of exogenous insulin 3.5 -4 mins → 5 half lives to achieve equilibrium serum level

To Bolus or Not to Bolus…? ● Half life of exogenous insulin 3.5 -4 mins → 5 half lives to achieve equilibrium serum level ● Giving insulin bolus activates sodium:hydrogen ion (H) exchanger--> gain of Na, loss of H in intracellular fluid compartment →

To Bolus or Not to Bolus…? ● Half life of exogenous insulin 3.5 -4 mins → 5 half lives to achieve equilibrium serum level ● Giving insulin bolus activates sodium:hydrogen ion (H) exchanger--> gain of Na, loss of H in intracellular fluid compartment → increased number of intracellular solutes, (exported H largely bound to intracellular buffers) ● → expand intracellular volume ( water moves rapidly across cell membranes to achieve osmotic equilibrium)

To Bolus or Not to Bolus…? ● Several early studies: insulin bolus → faster elimination of ketones

To Bolus or Not to Bolus…? ● Several early studies: insulin bolus → faster elimination of ketones ● Alberti, Fort : Time to metabolic normalcy no different with bolus ● Alberti et al: Bolus unnecessary given rapid rise of insulin levels with infusion, risk of further stimulation of counterregulatory hormones

To Bolus or Not to Bolus…?

To Bolus or Not to Bolus…? ISPAD Guidelines: ‘ An IV bolus should not be used at the start of therapy; it is unnecessary , may increase the risk of cerebral edema and can exacerbate hypokalemia.’

Fort et al. , 1980 19 children with 20 episodes of DKA treated by continuous low-dose ● insulin infusion - 0.1 unit/kg/hr ● Iv bolus of insulin administered prior to low-dose insulin infusion accelerated decline of BG during first hr of treatment, but differences not apparent thereafter ● Mean time for attaining "normoglycemia" (250 mg/dl) was similar

Fort et al. , 1980 Conclusion: ● Initial iv bolus of insulin may not be required /desirable in majority of children with DKA treated by standard low-dose insulin infusion regimen

Fort et al. , 1980 Conclusion: ● Initial iv bolus of insulin may not be required /desirable in majority of children with DKA treated by standard low-dose insulin infusion regimen (Data difficult to interpret - 35% : ‘compensated DKA’ with pH>7.35, Non random selection, 3 younger children received half insulin dose)

Aim To determine effect of an initial insulin bolus on immediate effect on plasma glucose , osmolality and duration of insulin therapy

Methods ● 38 children, 2-17 yrs ● 56 continuous episodes of DKA ● Randomly assigned to bolus vs non bolus

Results ● In severe acidosis: no appreciable effect ● Less severe acidosis: greater decline in avg glucose (199 vs 102) - not statistically significant ● Did not speed recovery/reduce hosp cost

Conclusion ● Did not result in a faster attainment of BG<250 or duration of insulin therapy

The Journal Of Pediatrics, May 2007

Hoorn et al Aim: To test whether a drop in effective plasma osmolality (PEff osm; 2 plasma sodium [PNa] X plasma glucose) during therapy of DKA is associated with an increased risk of cerebral edema (CE), and whether development of hypernatremia to prevent a drop in the PEff osm is dangerous.

Hoorn et al Method: Retrospective comparison of a CE group (n 12) and non-CE groups with hypernatremia (n 44) and without hypernatremia (n 13).

PEff osm dropped during first 8 hrs of therapy (after which hyperosmolar therapy was given to treat CE); remained constant /decreased minimally in control groups.

Hoorn et al Conclusion: ● CE was associated with a drop in PEff osm. ● Potential contributing factor : higher incidence of insulin bolus administration ● An adequate rise in PNa may be needed to prevent this drop in PEff osm.

Edge et al Aim ● To determine the impact of baseline biochemical factors and of treatment-related variables on risk of the development of cerebral oedema in children with DKA

Edge et al Methods: ● 2,940 episodes of DKA -- Identified 43 cases of cerebral oedema from records, 169 control subjects

Edge et al Results ● Calculated osmolality and baseline glucose were not significantly different. ● After allowing for severity of acidosis, insulin administration in the first hour (OR 12.7 [1.41–114.5], p =0.02) and volume of fluid administered over the first 4 h (OR 6.55 [1.38–30.97], p =0.01) were associated with risk.

Edge et al Conclusion ● Baseline acidosis , abnormalities of sodium, potassium , urea concentrations : important predictors of risk of cerebral oedema ● Additional risk factors : early administration of insulin , high volumes of fluid