Supervised by : Dr. Rasha Bondok Assistant professor of anesthesia and intensive care Presented by : Lamya Elsayed Resident of anesthesia and intensive care case scenario : 23 yrs old female, IDDM for 15 yrs. Presents with disturbed level of consciousness ,confusion, looks very unwell after having a normal vaginal delivery without anesthesia. Vital data: BP 90/60 mmHg, Pulse 132 bpm, RR 32 breath/m with deep breaths (Kussmauls) Examinaton: dry mucous membrane, mild epigastric tenderness, fruity breath odour and no fever. Case scenario : Labs: Hb 14gm/dl, WBC 20,000, Plt 312,000 S. glucose 400mg/dl. Na = 137mEq/L, K = 3.8mEq/L, Cl = 101mEq/L. ABG: pH = 7.15, pCo2 = 23 mmHg, Hco3 = 8 mmol/L & pO2 = 100 mmHg. Blood chemistry shows: BUN 40, creatinine 2 mg/dl. Urine: Glucose +4, Ketone +3 . What Does The ABG Tells Us ? ( PH = 7.15, PCO2 = 23, HCO3 = 8 & PO2 = 100) o pH = 7.15 therefore acidosis (severe). o pCO2 = 23 therefore not resp. acidosis. o HCO3 = 8 therefore metabolic acidosis o Anion gap = Na + K – (Cl + HCO3 ) =137 + 5 – (101+ 8) = 33 (>14) - - High anion gap metabolic acidosis with respiratory compensation Ketonemia / ketonuria hyperglycemia DKA Metabolic acidois Questions : Can serum glucose be normal in DKA ? What are the cut off values for PH and HCO3 in DKA ? Is there any other types of acidosis in DKA ? Who is at risk of DKA ? More common in IDDM esp. in pts on insulin pump. why ?! Can still happen in NIDDM. When ?! 1/5 of cases are 1st time presenters Most of cases are precipitated by certain factors : stress of surgery, infection, trauma or a serious underlying medical illness e.g. stroke, MI No underlying precipitating factors can be detected in small percentage of cases. Pathophysiology of DKA INSULIN COUNTERREGULATORY HORMONES DKA is considered an extension of the physiological state desinged to overcome starvation. in this case the relative carbohyrate unavailability caused by lack of insulin mimics a state of starvation. Both lack of insulin and excess glucagon contribute to the 2 main processes taking place in DKA : hyperglycemia and ketosis Mechanism of hyperglycemia 1. Lack of insulin : inhibit glycolysis , stimulate glycogenolyis and gluconeogenesis. 2. Excess glucagon : inhibit glycolysis. How ? It inhibits formation of fructose 2,6 biphosphate which is an extremely potent allosteric regulator of a major rate limitting enzyme in the pathway of glycolysis (phosphofructokinae enzyme) Effects of hyperglycemia : o Hyperglycemia leads to hyperosmolarity that in turn cause osmotic diuresis and loss of water and electrolytes in urine and although hyperosmolarity shifts water to ECF, hypervolemia doesn’t occur dt concomitant osmotic diuresis. o severe dehydration, dehydration is augmented by vomiting and later DCL decreasing fluid intake. Mechanism of ketosis : 1. Lack of insulin : stimulates lipolysis that deliver FFA used for ketogenesis. 2. Excess glucagon : Citric acid (the product of krebs cycle I.e. glucose metabolism that Is inhibited by glucagon as decribed before) is responsible for regulation of activity of acetyl coA carboxylase. The later synthesize malony coA in the liver which turn off carnitine acyl transferase 1 that is the rate limitting enzyme in ketogenesis. ( so turn off the supply of substrate into krebs cycle and ketogenesis is automatically turned on ). Effects of ketosis : Metabolic acidosis increasing anion gap Draws out intracelluar cations a sodium and potasium Vomiting that aggravates dehydration Total body stores of K are depleted due to urinary loss however s.K maybe intially elevated due to acidosis pulling intacellular K out. It markedly decrease with insulin therapy that stimuate the influx of K into the cells and with correction of acidosis. fat cell DKA: Pathophysiology Glucose Insulin + PFK TG Ketoacids Insulin + HSL FFA Liver Cell Pyruvate Kreb’s Cycle Acetyl-CoA + Fatty Acyl-CoA Glucagon Insulin + VLDL (TG) Clinical manifestations of DKA Polyuria, Polydipsia, Polyphagia Dehydration + orthostasis Vomiting (50-80%) Abdominal pain present in at least 30%. Küssmaul respiration if pH < 7.2 Temperature usually normal or low, if elevated think infection! Lethargy, delirium How to manage a case of DKA ? Broad lines of treatment : Rehydration Insulin therapy DKA Electrolyte repletion Management of complications and evaluation of therapy Priority is given to correction of the state of hyperosmolarity and dehdration. rehydration should be done gradually to prevent overshooting of s.NA levels. Insulin therapy is started only after support of heamodynamics to prevent latent shock of rehydration Potassium replacement is started even with normal levels as it is expected to dramatically drop with insulin therapy. 100 % O2 is given to all cases of DKA even if the saturation is 100 % on RA. rehydration Rehydration Volume! Volume! Volume Objectives: 1- Restore intravascular volume. 2- Reduce blood glucose level. 3- Reduce counter regulatory hormones. (catecholamines, glucagon) Augment insulin sensitivity. How much fluid will you give ? 15 – 20 ml/kg . (1-2 L ) in 1st hour 500 ml/h for next 2 hours or 1L /h if in shock 500-250 ml/h according to hydration status ( UOP & renal functions). maintainence fluids should be provided. How much fluid will you give ? Subsequent choice for IV fluids depends on: 1-Corrected serum Na (Nac) 2- Effective serum osmolarity (E osm) o If E osm > 320 mOsm/L or Nac is normal/elevated 0.45% NaCl 4-14 ml/Kg/hr o If E osm <320 mOsm/L or Nac is low 0.9% NaCl at a similar rate of 4-14 ml/Kg/hr. S.NA is a good marker for hyperosmolarity and intracellular dehydration but it might be inaccurate in case of DKA as hyperosmolarity is predominantely caused by hyperglycemia so scaling s.NA in relation to s.glucose (corrected s.NA) is a better judge of free water deficit. Osmolarity is a the conc. Of an osmolar fluid while effective osmolarity (tonicity) is the osmolar pressure of this solution. it calculates only the effective molecules able to draw water across cell membrane (mannitol , glucose) and excludes freely diffusible substances (urea) that produce no effect on tonicity . Corrected serum Na + (Nac) = measured Na + [1.6×serum glucose mg/dl -100] 100 Serum osmolarity mOsm/L = 2×Na (mEq/L) + s.glucose(mg/dl) + BUN(mg/dl) 18 2.8 E osm (mOsm/L) = 2×Na (mEq/L) + s.glucose (mg/dl) 18 Successful progress is judged by : Haemodynamic monitoring (pulse-BP) Adequate urine output. Improved mental status. Monitoring the decrease in E osm. ( should not exceed 3 mOsm/L/hr ) caution Gradual rehydration over 36 - 48 hours. why ? 1.avoid iatrogenic fluid overload and cerebral oedema (how) 2.overly aggressive fluid replacement leads to overshooting of NA levels leading to further increase in plasma osmolarity increasing risk of pontine myelinolysis. Insulin therapy insulin therapy aims at controlling hyperglycemia and reversing lipolysiss. It should be delayed at least 1 hr after fluid therapy to prevent latent shock of rehydration and it can be delayed further more if serum levels of K is below normal. There is no evidence that that the IV route is better than the SC route except in cases of shock. How to supply insulin ? A Loading dose 0.1U/Kg IV bolus Then maintainence rate of infusion U/hr = s.glucose mg/dl 150 or 100 if Steroids Infection Overweight Infusion rate is doubled for an hr if insulin resistense is suspected and s.glucose is rechecked in an hr. • Once s. glucose falls to 250 mg/dl, add DW5% at a rate of 50 ml/hr to maintain stable glucose level (i.e to allow continuation of insulin infusion till reversal of lipolysis without episodes of therapy induced hypoglycemia). Maximum rate of glucose decline/ hr is 75-100 mg/dl regardless the dose of insulin. Failure of s.glucose level to fall by 75-100 mg/dl/hr implies inadequate volume administration or impaired renal function rather than insulin resistance. serum HCO3 < 20 mEq/L even with normal glucose level implies continued need for glucose-insulin inf. till reversal of lipolysis (decreased s.HCO3 is an indicator of persistent ketosis as HCO3 regeneration automatically occurs when insulin sensitivity is restored . This occurs via renal and hepatic mechanisms. hepatic mechanism uses ketones as a substarate). How to stop Insulin infusion ? Sliding scale has to be started at least 2 hrs prior to discontinuation of insulin infusion . Total daily intake : total req. of insulin in insulin infusion per day / total insulin dose calculated by sliding scale per day . Either dose is divided into 1/3 and 2/3 and given by the usual SC regimen. Electrolyte replacement Total K stores are depleted due to renal loss (osmotic diuresis) even if serum levels are high or normal (shift of K outside the cell due to hyperosmolarity). insulin therapy causes shift of K inside cells so s.K falls further more reaching its peak in 2-4 hrs (1 meq/L / 0.1 unit ) . 20-40 meq /L are given if s.K is equal to or less than 5.5 meq/L. max. rate of infusion is 0.5 meq/kg/hr. should bicarbonate be given ? The use of NAHCO3 in DKA remains controversial. There is no doubt that PH is markedly improved but at the expense of worsening intracellular acidosis and other side effects that overshadow any potenial benefits such as CO2 production, rebound alkalosiss, hypovolemia and volume overload. Also in the context of DKA ,it might delay clearence of ketones and may further enhance hepatic production. In PH less than 6.9, most authors recommend use of bicarbonate to partially correct acidosis, the threshold of NAHCO3 use is debatable between 6.9 and 7.1 Management of complications and evaluation of therapy cerebral oedema It maybe subclinical at the beginning of therapy and the CSF pressure is normal. Classically, labs are improving and there is no way to predict who is going to have this complication. it occur typically in the 1t 24 hrs of therapy with no way to see it coming. o Mechanism : Brain conserves water by producing osmoprotective molecules (taurine). Osmolarity becomes disproportionately higher in the brain than other tissues. Sudden fall in serum osmolarity during rapid rehydration moves fluid across the blood-brain barrier. Brain becomes relatively hypervolemic. So Cerebral edema is a complication of therapy, not a progression of DKA. Pathophysiology of cerebral oedema EC glucose rises causing loss of water from IC space which is lost in osmotic diuresis Later the brain generates idiogenic osmoles which serve to draw water back into the cerebrum Presentation of cerebral oedema • Initial complaint of headache,Progresses to decreasing level of consciousness, hypertension, papilledema, blurring of vision and bradycardia. Coma and death soon follow • Diagnosis is available with CT scan. • The best therapy is to prevent it with careful rehydration Therapy for acute episode: Intubation and hyperventilation IV Mannitol 0.5 - 1.0 Gram/Kg ( bolus) . IV sedation. Slow the rate of osmolar correction. Management of cerebral oedema The best therapy is to prevent it with careful rehydration. Diagnosis is available with CT scan. Therapy for acute episode: Intubation and hyperventilation IV Mannitol 0.5 - 1.0 Gram/Kg as bolus. IV sedation. Slow the rate of osmolar correction. Evaluation of therapy Controlled reduction in serum glucose. Correction of acidosis “closing the gap”. Clearing of serum ketones. Clinical improvement : fall in respiratory rate improved perfusion improving mental status.