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This protocol is intended as a guide – individual patient modifications may be necessary.PhysiologyDKA is the result of a lack of insulin production by the pancreas. This leads to a characteristic physiologic change in patients:1. The decreased insulin leads to an inability to draw glucose into cells. This in turn leads to increased serum glucose.A.A serum glucose level > 250 exceeds the kidney’s threshold, leading to spilling of glucose into the urine. The loss of glucose draws water with it and leads to polyuria.B.Polyuria leads to dehydration, which, in turn leads to polydipsia (which, as the patient gets sicker cannot keep up with the polyuria).i.As a result all patients with DKA are dehydrated2. The lack of glucose entry into cells leads to cellular energy deprivation.A.To overcome this, the body increases gluconeogenesis, a process to create more glucose in an attempt to provide energy to cells. The process of gluconeogenesis breaks down fats to create glucose.i.The glucose created is released into the serum and, because of lack of insulin, cannot enter cells and therefore leads to a further increase in serum glucose. An ideal rate of fall is by 50-100 mg/dl/hr.ii.As a by-product of breaking down fats ketoacids are produced – this leads to the acidosis of DKA.iii.To compensate for the acidosis the patients “blow off” CO2 by breathing deeply and rapidly (Kussmaul respirations).B.The lack of available energy leads to increased food consumption by the patients – polyphagia.3.Potassium physiologyA.The cells of the body are filled with potassium (positively charged ion).B.With increasing acidosis (i.e. an increase in hydrogen – also positively charged) hydrogen ions accumulate in the plasma.C.The hydrogen ions move down their concentration gradient into the cells in an attempt to buffer the acidosis.D.To keep the cell’s charge neutral, for each hydrogen ion that moves into the cell, a potassium ion is moved out into the plasma.E.To keep the plasma potassium concentration normal, the kidney will increase potassium losses into the urine.F.As the acidosis is corrected the process is reversed.i.The hydrogen ions move back out of the cellsii.The potassium moves back into the cells, BUT much has been lost in the urine, so the potassium level dropsG.Thus, the patient becomes total body potassium depleted.Criteria for admission to the PICU1. Venous pH less than 7.252. Bicarbonate less than 14 if the patient is vomiting3. Bicarbonate less than 124. Patient has evidence of shock, significantly altered mental status, or other concerning abnormalities5. Blood sugar > 700 mg/dlTreatmentGoals of Treatment1.Restore perfusion2.Stop ketogenesis (inhibit lipolysis and gluconeogenesis).3.Permit glucose transport into cells4.Correct dehydration and electrolyte disturbances5.Avoid complications of therapy – cerebral edema, hypoglycemia and hypokalemiaAssessment of the Patient1.Assess the patient with careful neurologic assessment – all patients with an altered mental status and/or severe dehydration and shock require immediate attending notification.2.Initial labs: VBG, electrolytes, BUN, creatinine, calcium, magnesium, phosphate, serum glucose, dextrostick, UA, CBC3. For new onset DKA patients: Obtain anti glutamic acid decarboxylase, anti islet cell, and anti insulin antibodies, anti tissue transglutaminase IGA, Total IGA, anto TPO antibodies, anti thyroglobulin antibodies, free T4 and TSH. If unsure about type of diabetes add serum insulin and c-peptide. Fluid TherapyTypes of Fluids1.Administer 10 cc/kg of normal saline (0.9%) over 30-60 minutes. If the patient is in shock the initial fluid bolus should be manually pushed. The PICU attending needs to be notified if the patient is in shock, as additional fluid boluses may be necessary to alleviate shock 2.The patient should be reevaluated after the initial 10 cc/kg fluid bolus and if no further boluses are needed, then fluids should be changed to:? normal saline + 20 mEq/L KCl + 20 mEq/L Kphos If the serum K+ is > 5, decrease the total K+ in the fluids to 20 mEq/LIf the serum K+ is > 5.5, omit the K+ from the fluids*A note on using buffer therapy with bicarbonate: sodium bicarbonate is almost never necessary in the treatment of DKA, and its use is associated with increased risk of cerebral edema. Therapy with sodium bicarbonate may be considered in cases of severe acidosis with shock. Any consideration of bicarbonate administration requires the input of the PICU attending. Fluid RateTo calculate the fluid needs for the patient: Body weight (BW) in KG1._____kgEstablish the extent of dehydration( decreased BP, tears, skin turgor, cap refill, increased BUN/Creatinine, increased hematocrit) in cc/kg (Most patients are mild to moderately dehydrated)Infants(up to one year)childrenMild5%=50cc/kg3%=30cc/kgModerate10%=100cc/kg6%=60cc/kgSevere15%=150cc/kg9%=90cc/kg2. _____ cc/kg3. Calculate the total fluid deficit multiple (1) x (2)3._____cc4. Add all fluids given to patient prior to arrival in the PICU4. _____cc5. Calculate the remaining fluid deficit by Subtract (3)-(4) to calculate the remaining fluid(this may be a negative number if excessive amounts of fluids were given)5. _____cc6. Calculate the Maintenance fluid requirements for the next 48 hours200cc/kg for the first 10 kg+100 cc/kg for the next 10kg+40cc/kg for the rest of the BW=6. ____cc/48hrs7. Calculate the total amount of fluid to be given over 48 hours: Add (5)+(6)7. ____cc/48hrs8. Calculate the hourly rate of fluid replacement: divide (7) by 48hours8. ____cc/hr(not to exceed 1.5 times Maintenance)Table: Two bag system methodDesired Dextrose Delivery ConcentrationTotal Rate (as %) of Bag A (D0)% Total Rate of Bag B (D10)GlucoseD0100 %Off>350D550%50%250-350D10Off 100% <250<150*Decrease the insulin drip with the PICU attending. *This fluid calculation is not to exceed 1.5 times maintenance, if it does discuss with the attending *For uncomplicated DKA, the total fluids (including boluses) should not exceed 4 L/m2/day* Continue to monitor urine output carefully, as significant polyuria may necessitate additional fluids – consult with attending.InsulinAfter the initial fluid bolus is finished or after the patient is out of shock, begin an insulin dripDose: 0.1 Units/kg/hr (greater than three yo)Concentration: 50 Units Regular insulin/500 cc normal salineNursing note: run 50 cc through tubing before connecting to patient to saturate binding sites in the tubing. The goal of insulin is to halt ketogenesis and stop gluconeogenesis – continue until the urine ketones are clearing, pH is improving (> 7.30), and the patient is able to eat.Note: In patient 3 or younger, start the insulin drip at 0.05 Unit/kg/hr.*If patient is hypoglycemic, may consider lowering the drip rate; however, the insulin drip should not be decreased below 0.05units/kg/hr. DextroseThe goal of dextrose management is to keep a serum glucose level of no less than 150. Remember the primary goal of treatment is to halt ketogenesis and gluconeogensis: not to treat hyperglycemia per se. The act of providing fluids alone will cause the glucose level to fall, as the patient continues to have glucosuria. Dextrosticks are monitored every 1 hour. When the glucose is <350, add dextrose at 5% (D5).Based on the hourly dextrosticks, the amount of glucose should be titrated up or down to maintain the serum glucose 150 – 300. This requires changing the glucose concentration hourly based on whether the patient’s glucose is falling too rapidly or rising again. Since the patient’s needs will change faster than the pharmacy can mix new fluid bags, the easiest way to alter the dextrose concentration that the patient receives is via the 2 bag system.2 Bag Fluid System to Allow Rapid Titration of DextroseThe fluids are ordered in 2 bags that are identical in electrolyte concentration: each bag will contain ? normal saline + 20 mEq KCl/L + 20 mEq Kphos/L.The first bag (A) will contain no dextrose. The second bag (B) will contain D10. A B The bags will run at the calculated fluid rate (Calculated rate minus the insulin drip rate). The relative rates of the 2 bags will be adjusted to change the amount of dextrose delivered to the patient from D0 all the way to D10. Thus: in the beginning of management, run Bag A at the full rate and keep Bag B off – this gives fluids with no dextrose.Increase dextrose by increasing the rate of Bag Band decreasing the rate of Bag ADecrease dextrose by decreasing the rate of Bag Band increasing the rate of Bag AHypoglycemia: First step will be decreasing the insulin drip, per PICU attending to no less than 0.05 u/kg/hr.If needed D12.5 can be ordered, however, with careful fluid management this should not be needed. Ongoing Monitoring?Never put the patient on autopilot?Check dextrose stick every 1 hour?Check VBG every 4-6 hours (more frequently if change in MS)?Check serum electrolytes every 4-6 hours?Make sure that Intake > Output?Consider foley catheter placement in patients in shock or if the resuscitation is not straightforward.?Check UA every 8 hours for glucose and ketonesNeurologic ComplicationsAll patient in DKA are at risk for cerebral edema and herniation. This is especially true for young patients, those that present with altered mental status and those with their first episode of DKA. All patients require frequent (at least q 1 hour) neuro checks. At this time we do not know what causes cerebral edema. Theories include a rapid change in osmolality (via drop in glucose), too much fluid and impaired cerebral compliance. An ominous warning sign is a serum sodium concentration that doses not increase as the patient is treated. A decreasing sodium level should trigger a decrease in the IV rate and a conversation with the attending. If there is a neurologic deterioration, mannitol is given (0.5 grams – 1 gram/kg) and the patient will be intubated.RecoveryOnce the ketones have cleared from the urine and ketogenesis has been halted, the insulin drip can be discontinued. If this occurs in the middle of night, continue the drip to until the morning, maintaining a serum glucose 150 – 300. Before discontinuation of the insulin drip, the patient must first receive subcutaneous insulin. Once the patient is feeding, the IV fluids can be discontinued. Insulin doses are then titrated to the patient’s need. Bicarbonate goal is 16. Subcutaneous insulin dosage:Many endocrinologists have treatment protocols for their patients. They should be consulted upon PICU admission and again prior to transitioning the patient to subcutaneous insulin. Ask their preference about long term care, as they will be managing these patients for years to come. Some typical examples are: Decide upon total daily insulin dose. Typically 0.5 – 1 Unit/kg/day depending upon age, pubertal status of and duration of diabetes.Decide upon insulin regimen, ie, Glargine Insulin + “log” or NPH + “log” or pumpFor Glargine/”log” regimen: ? of daily insulin dose is given as Glargine insulin, the remainder as log. Dose of “log” may be calculated by using an Insulin:Carbohydrate ratio and an Insulin sensitivity factor.I:C is often calculated by 500/total daily doseISF is often calculated by 1800 or 1500 /Total daily doseBoth need to be individualizedFor NPH / “log” regimen, usually 2/3 of daily insulin dose is given in with breakfast (typically 2/3 NPH and 1/3 “log”) and 1/3 of total daily insulin dose is given with dinner (typically 2/3 NPH and 1/3 “log” or ? NPH and ? “log”). Summary1.Prepare for the patient prior to their arrivalA.This protocol requires a minimum of 3 and perhaps 4 IV pumpsi.Insulin pumpii.2 pumps for fluids (1 for dextrose and 1 for non-dextrose containing fluids)iii.1 pump for additional fluid replacement if necessaryB.The following fluids are neededi.Normal Salineii.? NS + 20 mEq KCl/L + 20 mEq KPhos/Liii.D10 ? NS + 20 mEq KCl/L + 20 mEq Kphos/Liv.Insulin Drip mixed at 50 units of regular insulin in 500 cc NS2.Treat dehydration and shock with NS3.Begin ? NS with KCl and Kphos at calculated fluid rate not to exceed 1.5 times maintenance4.Begin Insulin drip at 0.1 units/kg/hr IV. 5. Add dextrose when dextrose stick falls below 3506.Titrate dextrose with 2 bag system to maintain dextrose stick 150-3007.Monitor I/O carefully 8.Monitor neurologic status closely 9.Endocrine consult early in the patient’s courseAppendix ATable: Two bag system method: calculating delivered dextrose.Desired Dextrose Delivery ConcentrationTotal Rate (as %) of Bag A (D0)% Total Rate of Bag B (D10)GlucoseD0100 %Off>350D550%50%250-350D10Off 100% <250<150*Decrease the insulin drip with the PICU attending ................
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