Diabetic Emergencies. Goals. Diabetic Ketoacidosis (DKA) 11/6/2008. James Hardy, MD

Transcription

1 Diabetic Emergencies James Hardy, MD Assistant Clinical Professor Department of Emergency Medicine, UCSF Goals DKA and Hyperosmolar hyperglycemic state (HHS) Treatment guidelines (Peds vs Adult) Interesting pathophysiology Cerebral Edema Controversies Diabetic Ketoacidosis (DKA) Hyperglycemia (glc>250) Metabolic Acidosis (ph <7.3)(HCO3<15) Ketonemia More typical of Type I DM, but can happen in Type II 1

2 Hyperosmolar Hyperglycemic State (HHS) High glucose (>600) High serum osmolality (>320mOsm/kg) No significant acidosis No or small amount of ketones More typical of Type II DM Disease continuum DKA<-->HSS DKA HHS Mild Moderate Severe Glucose (mg/dl) >250 mg/dl >250 mg/dl >250 mg/dl >600 mg/dl Arterial ph to <7.25 <7.00 >7.30 HCO3 (meq/l) to <15 <10 >15 Ketones Positive Positive Positive Small Serum Osm Variable Variable Variable >320 Anion gap >10 >12 >12 <12 Mental status Alert Alert/drowsy Stupor/coma Stupor/coma Why? QuickTime and a decompressor are needed to see this picture. Wolfsdorf, J, Glaser, N, Sperling, MA. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29: Wolfsdorf, J, Glaser, N, Sperling, MA. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:

3 Goals of Treatment ABCs Underlying Cause Volume deficit and dehydration Correct electrolytes, especially K+ Reverse acidosis and treat glucose Treat Cerebral edema Do no harm 16 y F h/o IDDM BP =153/84 P = 146 R = 30 T = 97 Sat = 97% Wt =175 lbs Glucometer = high Complains of pain all over Looks sick,?ams, smells of ketones ABC s and D IV, 02, Monitor Move to appropriate room in your ED What tests should I order? Why are they in DKA? How bad is the DKA? 3

4 Why? More on labs Urine Xrays Cultures/Lactate Tox? Pregnant? Ca, Mg, Phos EKG Beta hydroxybutyrate? ABG or VBG PE, MI, Pancreatitis,Thyroid, Zebras? VBG vs ABG What do you want to do? ph lower than arterial ph po instead of 100 pco2 - about 6 higher than arterial pco2 (46 rather than 40) 1. Insulin SQ, 1-2 liter NS bolus 2. Insulin IV bolus, 1-2 liter NS bolus 3. Insulin IV bolus followed by insulin drip, 1-2 liter NS bolus liter NS bolus, wait for study results for further care 4% 15% 59% 23% Insulin SQ, 1... Insulin IV bol... Insulin IV bol liter NS b... 4

5 ADA Protocol for Management of Adult DKA Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:2739. Fluids in DKA Part ml/kg = typical loss. Typical adult is 6 liters down Intravascular volume = Normal Saline For adults, start with 1 liter bolus over 1 hour. More if in shock, less if heart dz For kids, start with 10-20ml/kg bolus over 1 hr. Wolfsdorf, J, Glaser, N, Sperling, MA. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:

6 Goals of Treatment ABCs Underlying Cause Volume deficit and dehydration Correct electrolytes, especially K+ Total Body K+ is Low Vomiting Osmotic diuresis Hypovolemia-->hyperaldosteronism Typical deficit = 3-5mmol/kg But serum K+ is usually normal or high Due to insulin deficiency mostly Due to hyperosmolality Due to low ph Adroque et al, Medicine,

7 Know your serum K+ level before giving insulin Stat K+ EKG Must replete before insulin if K+ < 3.3 Hypokalemia Add 20mEq to 1 liter NS if hemodynamically unstable If stable, add 40-60mEq to 1 liter 1/2 NS and run over 2 hrs. Oral load? Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:2739. Hyperkalemia Best treatment is fluids and insulin Consider bicarb and calcium for life-threatening hyperkalemia (ekg changes) You will probably still have to give potassium later on! ADA Protocol for Management of Adult DKA If K+ is normal, add 20mEq to your IVF. Recheck lytes every 2 hours. Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:2739. Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:

8 Goals of Treatment ADA Protocol for Management of Adult DKA ABCs Underlying Cause Volume deficit and dehydration Correct electrolytes, especially K+ Reverse acidosis and treat glucose Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:2739. Insulin when K+ is OK 0.1unit/kg bolus for adults followed by 0.1unit/kg/hr drip Repeat bolus if glc not down by mg/dl in 1st hour (also consider ivf) Children do not get bolus just the drip When glc < , don t stop the insulin, add dextrose to the IVF. QuickTime and a decompressor are needed to see this picture. Wolfsdorf, J, Glaser, N, Sperling, MA. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:

9 Your Studies Come Back Wbc =31, Hgb =13.3, plt =422 Na =123, K =5.9, Cl =87, bicarb = 5, BUN = 20, Cr 1.3, glc = 812. Large acetone UA, preg, utox, LFTs, cxr = neg EKG = sinus tach, o/w neg Important Formulae Anion Gap = (Na) - (Cl) - (HCO3) Effective osmolality = 2xNa +glc/18 Corrected Na = Na + [(glc - 100) x 0.016] Alternative equation => Corrected Na = Na +[ SG 42] Correct the sodium it s not as low as it looks! Corrected serum Na = Measured serum Na + [ SG 42] where SG is the increment above normal in the serum glucose concentration (in mg/dl). So for our case Na = ( )/42 = 140 Gap and osms? Na =123, K =5.9, Cl =87, bicarb = 5, BUN = 20, Cr 1.3, glc = 812. Gap = = 31 (nl = 9-12) Effective osmolality = 2xNa +glc/18 =291 Effective osm > 300 abnl, >320 = clinical hyperosmolality 9

10 How s our Patient? Therapy so far = 2 liters NS BP = 120 s/70 s HR =130 s RR = 30 Altered? ph = pco2 = 9.7 PO2 = 126 Bicarbonate = 1.7 ABG What do you want to do? 1. One more liter NS, start insulin, give bicarb 50% 2. Two more liters NS, start insulin 3. NS at 200ml/hr, start insulin 30% 4. Give mannitol, send to CT scanner 7% 13% Cerebral Edema 0.3% to 1% of pediatric DKA 21% to 24% mortality 21% to 26% permanent neuro morbidity 57% to 87% of all DKA deaths One more liter... Two more liter... NS at 200ml/hr... Give mannitol,... 10

11 Symptoms and Signs of Cerebral Edema Headache Recurrence of vomiting Inappropriate slowing of heart rate Rising blood pressure Decreased oxygen saturation Change in neurological status: -Restlessness, irritability, increased drowsiness, incontinence -Specific neurologic signs, e.g., cranial nerve palsies, abnormal pupillary responses, posturing Should I get a CT? CE is clinical diagnosis CT will show subclinical swelling in many, Will appear normal in some kids with clinical sx. If you are really concerned, CT can help establish baseline or reveal other sequelae. Wolfsdorf, J, Glaser, N, Sperling, MA. Diabetic ketoacidosis in infants, children, and adolescents: A consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:1150. Muir et al, Diabetes Care, 2004 Krane et al, NEJM, 1985 Hoffman et al, American Journal of Neuroradiology, 1988 When does it happen? Subclinically present by CT in majority of children with DKA at presentation Typically becomes clinical 4-12 hours after initiation of treatment Some are already symptomatic when they arrive Krane et al, NEJM, 1985 Hoffman et al, American Journal of Neuroradiology, 1988 Who s at risk? Younger New onset dka (67%) Higher BUN Low pco2 Low ph Failure of Na to rise appropriately Glaser et al, NEJM, 2001 Edge et al, Diabetologia, 2006 Hoorn et al, J Pediatr, 2007 Lawrence et al, J Pediatr,

12 Osmotic Edema Theory Treatment drops intravascular osms-->water shifts into brain -->swelling Aggressive IVF and insulin BAD Edge et al, Diabetologia, 2006 Hoorn et al, J Pediatr, 2007 Levin et al, Pediatr Crit Care Med, 2008 Vasogenic Edema Theory Hypoperfusion-->injury-->reperfusion injury-->worsened by hypocapnea Supported by MRI studies No link between rate of fluid or insulin administration. Strong link with severity of illness Glaser et al, J Pediatr, 2004 Figueroa et al, Endocrine Research, 2005 Glaser et al, J Pediatr, 2008 Glaser et al, NEJM, 2001 Lawrence et al, J Pediatr, 2005 Hom et al, Annals Emerg Med, 2008 Pediatric Fluids--Part 2 Treat shock and sepsis with NS boluses If stable after 20ml/kg. Start NS (+/-K) at 1.5-2x maintenance Don t add in urine losses Switch to dextrose + NS or 1/2 NS (+K) when serum glc < 300. (4-6hrs of NS) Aim to keep glc between mg/dl Peds Hourly Maintenance IVF The 4,2,1 Rule 4mL/kg per hour for 1st 10kg 2ml/kg per hour for 2nd 10kg (11-20kg) 1ml/kg per hour for every kg over 20kg Example 55kg child = 4x10 + 2x10 + 1x35 =95ml/hr Wolfsdorg et al, Diabetes Care, 2006 Dunger et al, Pediatrics, 2004 Jeha et al, UpToDate,

13 Treatment of Cerebral Edema Mannitol g/kg bolus 3% NaCl 5-10mL/kg over 30 minutes Debate over when to treat Wolfsdorf et al, Diabetes Care, 2006 Dunger et al, Pediatrics, 2004 Jeha et al, UpToDate, 2008 Levin et al, Pediatr Crit Care Med, 2008 Symptoms and signs of Cerebral Edema Headache Recurrence of vomiting Inappropriate slowing of heart rate Rising blood pressure Decreased oxygen saturation Change in neurological status: * Restlessness, irritability, increased drowsiness, incontinence * Specific neurologic signs, e.g., cranial nerve palsies, abnormal pupillary responses, posturing Wolfsdorf et al, Diabetes Care, 2006 Muir et al, Diabetes Care, 2004 Diagnositic: Abnormal motor or verbal response to pain, Decorticate or decerebrate posturing, Cranial nerve palsy (espec III, IV, VI), Abnormal neurogenic repiratory pattern, (e.g. grunting, tachypnea, Cheyne-Stokes, apneusis Major: Altered mentation/fluctuating LOC, Sustained heart rate deceleration (decline > 20bpm) not 2/2 resusc, Age-inappropriate incontinence Minor: Vomiting, Headache, Lethargy, Diastolic BP > 90, Age < 5 Muir et al, Diabetes Care, % sensitivity, 96% specificity for: 1 Diagnostic Criterium 2 Major Criteria 1 Major + 2 Minor Would treat 5 for every 1 with CE 13

14 Adult Fluids--Part 2 Adult Fluids--Part 2 QuickTime and a decompressor are needed to see this picture. 1. Fill the tank 2. Add K+ appropriately 3. Can usually switch to 1/2NS when adding dextrose 4. Avoid hyperchloremic acidosis if possible Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:2739. Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:2739. Should I Give Bicarb? Do Not Give Bicarb to Peds Increased risk of cerebral edema No evidence that it helps Decreased oxygen to brain because shifts oxygen dissociation curve Paradoxical decreased ph in CSF Makes more CO2 ARF or diarrhea? Kitabchi, AE, Umpierrez, GE, Murphy, MB, Kreisberg, RA. Hyperglycemic crises in adult patients with diabetes: a consensus statement from the American Diabetes Association. Diabetes Care 2006; 29:

15 What about Adults? Mean Arterial Blood ph, Plasma Bicarbonate Concentrations, and Fractional Shortening of the Left Ventricle during Systole in 10 Patients before and after Correction of Ketoacidosis No evidence that it helps oxygen to brain because shifts oxygen dissociation curve Paradoxical decreased ph in CSF Makes more CO2 More convincing role in diarrheal losses or ARF Consider in low ph and severe cardiac dz Maury E et al. N Engl J Med 1999;341:1938 Yeah, but what about that ph? Treat perfusion problems with fluids Treat infection with fluids and abx Treat ketoacidemia with insulin Watch for hyperchloremic acidosis How is our Patient? 3 hours later 3.5 liters of NS, insulin gtt at 10units/hr BP =130/70 HR=120 s RR =30 s Na =129, K =6, Cl =98, C02 <5, glc = 621, gap = 26 Corrected Na = 141 (from 140) Mental status? 15

16 What if I have to intubate? Treat shock before intubating if possible Take your absolute Best shot Immediate blood gas Bicarb? Ventilation Goals Avoid hyperventilation May decrease intracranial blood flow and worsen cerebral edema Aim for pt s own pc02 Levin et al, Pediatr Crit Care Med, 2008 Phos? Central Line? Prospective studies have not shown clinical benefit from phosphate replacement; however, severe hypophospahtemia (<1mg/dl), which may manifest as muscle weakness, should be treated even in the absence of symptoms. Wolfsdorf et al, Diabetes Care, 2006 Children in DKA risk DVT DKA suggested prothrombotic state? Do it if you have to, avoid it if you can. Can use Kphos as part of the potassium replacement Phos replacement can drop calcium, so monitor. Worly et al, Pediatrics, 2004 Gutierrez, Crit Care Med, 2003 Carl et al, Endocr Res,

17 When are you done? Close the gap (bicarb may still be low) Eating and drinking Transition to SQ insulin A Quick Case 70 y m h/o Type II DM, htn, CAD Not getting out of bed last few days. Today confused. Glc = high BP =100/55 HR =115 RR =18 Temp =98F Sat =97% Looks dry 2nd verse same as the first ABC s IV, 02 sat, monitor Studies Treat underlying cause Start resuscitation with NS Studies WBC =18, Hgb =14, Plt =300 Na =135, K =5.5, Cl =105, Bicarb =20, BUN =50, Cr =2.2, Glc =1200 Lactate 2.5 Serum Ketones = small Everything else WNL 17

18 QuickTime and a decompressor are needed to see this picture. 11/6/2008 Do your calculations Gap = = 14 Effective osmolality = 2x /18 = 337 Corrected Na = ( )/42 = 161 Hyperosmolar Hyperglycemic State Rarer but more fatal than DKA 15% vs 2-5% Die of underlying or precipitated cause, not hypertonicity Develops over days to weeks 8-12 liter loss vs 5-6 liters in DKA More water loss than lytes, but still large electrolyte losses Nugent, Emergency Medicine Clinics of North America, 2005 Pathogenesis of DKA and HHS ADA Protocol for Management of HHS QuickTime and a decompressor are needed to see this picture. ITS=10&hits=10&RESULTFORMAT=&fulltext=Hyperglycemic+Crises+in+D iabetes&searchid=1&firstindex=0&sortspec=relevance&resourcetype= HWCIT 18

19 IVF and HHS Treat shock and establish urine output with NS bolus Calculate volume loss 150ml/kg or 12%- 15% of body wt (usu 8-12 liters) Replace 1/2 in first 12 hours, the remainder in next hours Switch to 1/2 NS if effective osms or sodium are high. (4-14mL/kg/hr) Summary ABCD s Find and treat underlying cause Fluid resuscitate No insulin until you know the K+ Treat the K+ Special Peds Considerations Expand volume with NS 10-20ml/kg bolus over 1-2 hours. Repeat x1 prn Gentle rehydration at x maintenance to avoid cerebral edema (maybe) No insulin bolus only use drip (usually 0.1unit/kg/hr) Avoid bicarb, central lines, ABG s (use venous or capillary samples) Monitor lytes carefully. K+ is king. Add Phos? Watch for appropriate rise in Na. Treat cerebral edema with mannitol or hypertonic saline (3%) 19