Sick Day Management Ragnar Hanas, MD, PhD, Department of Pediatrics, Uddevalla, Sweden.

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1 Sick Day Management Ragnar Hanas, MD, PhD, Department of Pediatrics, Uddevalla, Sweden

2 R Hanas, CWD 2006 00;18 Pediatric and adolescent diabetes in Sweden - Sparsely populated with large geographical distances - High diabetes incidence (3 rd in the world after Finland and Sardinia) - ~7000 children and adolescents up to the age of 20 ~700 new cases/year (0 -18 years)

3 R Hanas, CWD 2006 00;18 How do we care for our patients? - Almost everyone is cared for at pediatric departments, the majority by a pediatric diabetologist - None are seen by GP:s - 40 centers, the largest with ~ 500 patients, but most have 75 -150 - Some travel 150 - 200 km to see their diabetologist - 50 -100 patients / diabetologist - 75 - 150 patients / diabetes nurse - Teams with dietician, psychologist, counselor (social worker)

4 R Hanas, CWD 2006 00;18 Modern treatment of childhood diabetes Traditional approach - Insulin, diet, and exercise ”To dare is to lose foothold for a short while - not to dare is to lose yourself” Sören Kierkegaard Danish philosopher 1813-55 Diabetes treatment today - Insulin, love and care - Prof. Johnny Ludvigsson - Knowledge - There is nothing that is forbidden, you can always try something and find out what works for you

5 R Hanas, CWD 2006 00;18 What goals do we have? - The family is encouraged to take active part in diabetes and adjusting doses - ”It is no fun having diabetes - but you must be able to have fun even if you have diabetes” - Prof. Johnny Ludvigsson -Must know more than the average doctor to manage your diabetes

6 R Hanas, CWD 2006 00;18 Important to learn for life... - After one year you will have experienced most things - “ Then we want to learn from you!” - The clinic will function as an “intelligence center” with input from all families ”Give a man a fish and he will not go hungry that day. Teach him how to fish and he will not be hungry for the rest of his life.” Chinese saying

7 R Hanas, CWD 2006 00;18 Try to keep on living as usual in the family... - It is our job to adjust the insulin doses to the child, not the other way around - Your job is to continue with important things you used to do, like mountain-biking, going for skiing vacation or a trip on the sea - It is important to come back to your ordinary parent-child rules in the family

8 R Hanas, CWD 2006 00;18 Healthy - Start with the need of food in your body - Take insulin to the food - Adjust the dose according to the carbohydrate content Healthy or sick? Sick - Start with the need of insulin in your body - Take food and drink to the insulin - Eat and drink to give the insulin sugar “to work with”, for example sweet drinks in small but frequent sips.

9 R Hanas, CWD 2006 00;18 - The child usually eats less but the fever requires more insulin - Begin by taking the same insulin doses as usual - 100° F - often 25% increase of doses 102° F - up to 50% increase of doses Sick with fever - Monitor BG before and after each meal Urine ketones at every voiding & in blood if positive - Check blood/urine ketones if vomiting or nauseous

10 R Hanas, CWD 2006 00;18 Illness that raises BG - Increase doses if needed: High BG prior to a meal -  premeal dose by 1 - 2 U or according to correction factor Multiple inj. -  next day basal insulin by 1-2 U Pump -  basal rate by 10-20% (if needed up to 40-50%) High BG 1 - 2 h. after a meal -  next day premeal dose by 1 - 2 U Insulin during sick days - Adjust doses according to body weight - Persons in remission phase may need to increase up to 1 unit/kg/day very quickly!

11 R Hanas, CWD 2006 00;18 - Vomiting or nausea? - Caused by lack of insulin?!? - High blood glucose? Ketones in blood or urine ? Beware of vomiting when having diabetes! - When a child with diabetes vomits it should always be considered a sign of insulin deficiency until the opposite is proven! - Vomiting from gastroenteritis should be considered only when a lack of insulin has been excluded!

12 R Hanas, CWD 2006 00;18 - Vomiting with diarrhea or only diarrhea - Low blood glucose levels - Always check for ketones in blood or urine! - Vicious circle with ketones - nausea - eats less - more ketones Gastroenteritis - Decrease doses if needed: Low BG prior to the meal -  premeal dose by 1 - 2 U or according to correction dose Multiple inj. -  next day basal insulin by 2-4 U Pump -  basal rate by 20-40% Low BG 1-2 h. after a meal -  next premeal dose by 1 - 2 U

13 R Hanas, CWD 2006 00;18 - Give drinks containing sugar (not Light) in small and frequent portions (several sips every 10-15 min.) - Sweet ice cream or yoghurt may work well - Never miss a chance to give something containing sugar! Gastroenteritis - Keep records of how much the child has had to drink - Begin with solid foods as soon as the vomiting stops or decreases - Mini-doses of glucagon work well when everything else fails 2 years:1 “unit”/year up to 15 “units” (0.15 mg) Repeat after 1 hour or more if needed Haymond MW. Diabetes Care 2001;24:643-45.

14 R Hanas, CWD 2006 00;18 - Relative insulin deficiency if doses are not increased - Nausea/vomiting makes it difficult to eat - Therefore it may be difficult to increase insulin doses Increased risk of ketoacidosis when ill - Small insulin depot with a pump - insulin deficiency develops quickly if there is a pump failure when you are ill - Drink more to prevent dehydration! Sugar-free fluids if BG is > ~220 mg/dl Fluids containing carbohydrates if BG ~220 mg/dl Fluids containing carbohydrates if BG < ~220 mg/dl (~12 mmol/l)

15 R Hanas, CWD 2006 00;18 High blood glucose and ketones Repeated BG > 270 mg/dl (15 mmol/l) and ketones - Risk of developing ketoacidosis!! - 0.1 U/kg with pen or syringe (preferably Humalog/NovoLog) - Risk of over-correction - hypoglycemia - Check BG and ketones every hour If BG is not decreasing: Repeat dose every 1-2 hours (/2-3 hours with regular insulin) - The blood ketone level may increase after 1 hour but should be much lower after 2 hours - Urine ketones stay elevated for many hours

16 R Hanas, CWD 2006 00;18 Insulin from the pancreas Vad happens to the carbohydrates from the food? - - - Fat/muscle cell Stored sugar in the liver (glycogen) Carbohydrates from food

17 R Hanas, CWD 2006 00;18 A healthy cell Insulin O2O2O2O2 CO 2 WaterEnergy Urine test shows Glucose Ketones 0 0 0 0 Bloodvessel Cell

18 R Hanas, CWD 2006 00;18 Starvation (Insulin) in liver Fatty acids Ketones Urine test shows Glucose Ketones 0 + 0 + Bloodvessel Cell

19 R Hanas, CWD 2006 00;18 Diabetes - lack of insulin Cell in liver Fatty acids Ketones Urine test shows Glucose Ketones +++ +++ +++ +++ Bloodvessel

20 R Hanas, CWD 2006 00;18 Ketone bodies in a healthy person Liver cell Fatty acids Blood vessel Mitochondrion Fatty acyl CoA Acetoacetate Acetoacetate Ketones + Beta-hydroxybutyrate Beta-hydroxybutyrate Starvation Low insulin High fat diet Ketone bodies are used by the heart, kidneys, muscles, and brain as fuel AcetoneAcetone

21 R Hanas, CWD 2006 00;18 Starvation ketones in people without diabetes - 15 prepubertal children 10 adult men 10 adult women - Children fasted for 30 h. (part of clinical evaluation for hypoglycemia symptoms) Adults fasted for 86 h. - Children had much higher ketone levels than adults 0 12 24 36 48 60 72 84 Time, hours Blood ketones (Beta-hydroxybutyrate) mmol/l children men women

22 R Hanas, CWD 2006 00;18 Ketone bodies increase when there is a lack of insulin Liver cell Fatty acids Blood vessel Mitochondrion Fatty acyl CoA Acetoacetate Acetoacetate Ketones +++ +++ Fruity breath (Kussmaul breathing) Beta-hydroxybutyrate Beta-hydroxybutyrate Low insulin AcetoneAcetone

23 R Hanas, CWD 2006 00;18 Urine ketones can be false neagative! Liver cell Fatty acids Blood vessel Mitochondrion Fatty acyl CoA Acetoacetate Acetoacetate Ketones 0 Beta-hydroxybutyrate Beta-hydroxybutyrate Low insulin Ketones can only be detected by blood testing

24 R Hanas, CWD 2006 00;18 Urine ketones decrease slowly after insulin treatment Liver cell Fatty acids Blood vessel Mitochondrion Fatty acyl CoA AcetoacetateAcetoacetateKetones +++ +++ Beta-hydroxybutyrate Beta-hydroxybutyrate High insulin Acetone Acetone is deposited in fat tissue Acetone

25 R Hanas, CWD 2006 00;18 Effects of insulin treatment - Blocked production of ketones in the liver - Blocked production of glucose in the liver - Increased uptake of glucose in tissue Increased dose needed DeFronzo RA et al. Diabetes Reviews 1994;2:209-38. How is the blood glucose decreased when treating ketoacidosis?

26 R Hanas, CWD 2006 00;18 Blood ketones and ketoacidosis 55 children, age 10.4 ± 3.9 y. with BG > 11.1 mmol/l (200 mg/dl) and ketones in urine. 37 had ketoacidosis (pH 11.1 mmol/l (200 mg/dl) and ketones in urine. 37 had ketoacidosis (pH < 7.30) - Good correlation between patient method and lab. method Ham MR et. al. Ped Diab 2004;5:39-43. Lab  -hydroxybutyrate - Blood ketones > 1.5 mmol/l - 85% had ketoacidosis but only 2 pat. with blood ketones 1.5 mmol/l - 85% had ketoacidosis but only 2 pat. with blood ketones < 2.9 mmol/l had ketoacidosis.

27 R Hanas, CWD 2006 00;18 Measuring ketones in blood vs. urine >100,000 episodes of DKA annually in the U.S. - 86 children, ages 2-18 (>0.5 units insulin/kg/day) unless 0.3 units/kg/day. Slide from S Brink - 73 children on intensified insulin regimes and 18 used pumps. - 3900 concurrent pairs of blood and urine ketone tests were obtained. - 7783 concurrent pairs of BG and blood ketone tests were obtained. Laffel LMB. Diabetes 2002;51(suppl 1):A105.

28 R Hanas, CWD 2006 00;18 Measuring ketones in blood Precision Xtra meter - Accuracy has been well demonstrated Cembrowski GS,Diabetes 1999;48.Suppl:Abstract 265. Byrne HA, Diabetes Care 2000;23:500-503. - Linear response 0.0-6.0 mmol/L beta-hydroxybutyrate (  -OHB) - 5 µL blood sample - Results in 30 seconds - No interference by acetoacetate, acetone, lipids, etc. - No interference by common therapeutic agents (Captopril, L-DOPA, vitamin C, etc.)

29 R Hanas, CWD 2006 00;18 Measuring ketones in urine KetoStix - It detects acetoacetate. - Results read from a color chart are Negative, trace (5 mg/dL), small (15 mg/dL), moderate (40 mg/dL), and large (80-160 mg/dL). - User timing is required. Read color at exactly 15 seconds after removing reagent strip from urine. - Proper read time is critical for optimal results. Must ignore color changes that occur after 15 seconds. - False-negative results when sticks have been exposed to air och after eating much vitamin C (acidic urine)

30 R Hanas, CWD 2006 00;18 Measuring ketones in blood vs. urine Relationship between blood and urine ketones Slide from S Brink - On 15 occasions blood ketones were moderate to large but the urine ketones were negative!

31 R Hanas, CWD 2006 00;18 Measuring ketones in blood vs. urine - Relationship between blood and urine ketones Slide from S Brink

32 R Hanas, CWD 2006 00;18 Measuring ketones in blood vs. urine Slide from S Brink

33 R Hanas, CWD 2006 00;18 Measuring ketones in blood vs. urine Slide from S Brink

34 R Hanas, CWD 2006 00;18 Measuring ketones in blood vs. urine - conclusions - Use of urine ketones may lead to inappropriate decisions regarding the severity of illness in insulin-treated children. - The advantages of monitoring blood ketones include: - Real-time direct measurement of the predominant ketone body -Patient acceptance and improved compliance - Real-time direct measurement of the predominant ketone body -Patient acceptance and improved compliance - Careful monitoring of BG and blood ketones, plus supplemental insulin and hydration, may enhance sick-day guidelines and help to prevent ketoacidosis in children.

35 R Hanas, CWD 2006 00;18 Measuring ketones in blood vs. urine - conclusions 123 children aged 3-22 years - Check ketones: When blood glucose was consistently > 13.9 mmol/l (250 mg/dl) During acute illness or stress - 6 months follow-up: 21548 days 578 sick days Laffel LMB. Diab Med 2005;23:278-84. 60% fewer hospitalizations 40% fewew emergency assessments Frequency of ketone measurements

36 R Hanas, CWD 2006 00;18 How should blood ketones be interpreted? KetonesBG 180-270 270-400 mg/dl>400 mg/dl < 0.5 mmol/lNo problems Test again after 1-2 hours 0.5 - 0.9 mmol/l Test again 0.05 U/kg0.1 U/kg 1.0 - 1.4 mmol/lEat and take 0.1 U/kg0.1 U/kg, x 1-2 0.05 U/kg Samuelsson, Diabetes Tech. 2002 Laffel, poster 426, ADA 2002 - Every pump user should be able to test blood ketones - Also very helpful for younger children 1.5 - 3 mmol/lEat and take 0.1 U/kg. x 1-2 0.1 U/kg. x 1-2 0.1 U/kg > 3 mmol/lEat and take 0.1 U/kg, x 1-2 0.1 U/kg, x 1-2 0.1 U/kg Contact your diabetes team or emergency ward!!

37 R Hanas, CWD 2006 00;18 How should blood ketones be interpreted? Ketones BG 400 mg/dl < 0.6 mmol/lNo change 5%10% 0.6 - 0.9 mmol/l No change 5%10% 1.0 - 1.4 mmol/l0-5%10%15% ≥ 1.5 mmol/l0-10%15-20%20% Laffel LMB. Diab Med 2005;23:278-84. - Extra insulin to be given in percentage of total daily insulin dose - Don´t use % of daily dose when in remission phase!

38 R Hanas, CWD 2006 00;18 Sick day rules - Monitor glucose (with adult supervision even in adolescents) every 3-4 h. and occasionally every 1-2 h. with results recorded in a log book - Test for ketones every 2-4 h. Check blood ketones if positive in urine - Continue monitoring in the middle of the night (no matter how tired the child or parent is) Stu Brink. Diab. Nutr. Metab. 1999;12:122-35 - Increased salty fluid intake to combat dehydration. Always drink something containing sugar - Check weight every 8-12 h. to monitor for clinical dehydration - Necessary medical treatment for underlying condition (antibiotics for tonsillitis, otitis, urinary tract infection)

39 R Hanas, CWD 2006 00;18 Sick day rules - Antipyretics (acetaminophen) to treat fever - Antiemetics if severe vomiting prevents adequate fluid intake Stu Brink. Diab. Nutr. Metab. 1999;12:122-35 - Continue to give insulin and administer extra doses for as long as blood glucose and/or ketones are high - Recognize of when insulin dose (rarely) needs to be temporarily decreased due to hypoglycemia (needs more sugar intake) - Contact your health team or hospital if symtoms persist, worsen or do not get better. - All too frequently a physician or nurse advises omission of insulin because the child is ill and not eating!!!

40 R Hanas, CWD 2006 00;18 When do you need to go to the hospital? - Large or repeated vomiting - Increasing levels of ketones or laboured breathing - Continued high BG level > 270 mg/dl (15 mmol/l) despite extra insulin - Unable to keep BG > 70 mg/dl (3.5 mmol/l) Adapted from Silink M. (Ed.) APEG handbook 1996 - The underlying condition is unclear - Severe or unusual abdominal pain - The child is confused or his/her general well-being is affected

41 R Hanas, CWD 2006 00;18 When do you need to go to the hospital? Adapted from Silink M. (Ed.) APEG handbook 1996 - The child is young (< 2 - 3 years) or has another disease besides diabetes - Exhausted patients/relatives, for example due to repeated nighttime waking - Always call if you are in the least unsure about how to manage the situation

42 R Hanas, CWD 2006 00;18 Diabetes and surgery - Schedule surgery first thing in the morning - I.v. insulin best for major surgery with general anesthesia - For minor surgery with local anesthesia, take only basal insulin (Lantus or pump) - - Emergency surgery: I.v. insulin to bring down BG before surgery - Ketoacidosis can give abdominal pain of the same magnitude as appendicitis - - Parents are the “diabetes experts” when their child is at a pediatric surgery ward!

43 R Hanas, CWD 2006 00;18 Insulin resistance in changed by the BG level High level due to infection - Õ insulin resistance a Blood glucose level Increased doses - lower BG a After a couple of days BG will be lower - doses need to be lowered a Back to normal insulin resistance again a 1-2 weeks a

44 R Hanas, CWD 2006 00;18 Insulin requirements increase with fever Cold with fever a Insulin requirements Increased insulin resistance due to fever a Infection cured a Continued insulin resistance a

45 R Hanas, CWD 2006 00;18 Insulin requirements decrease when having gastroenteritis Gastroenteritis with vomiting, diarrhea a Insulin requirements Decreased insulin resistance due to low BG levels a Infection cured a Continued low insulin resistance due to low BG a

46 R Hanas, CWD 2006 00;18 - Vomiting or nausea? - Caused by lack of insulin?!? Especially true when using an insulin pump!! - Vomiting caused by pump problems may easily be mistaken for illness!! Beware of vomiting when using a pump! - When a child with a pump vomits it should always be considered as a pump problem until the opposite is proven!

47 R Hanas, CWD 2006 00;18 Insulin kinetics increseases ketoacidosis risk 20 adults with type 1 diabetes Short-acting 125 I-insulin CSII with infusion in the abdomen Hildebrandt P, Diabetic Medicine 1988;5:434-40 2.24U/h 1.12U/h

48 R Hanas, CWD 2006 00;18 How quickly will the ketones rise? - 10 adults with pump, crossover with Velosulin and Humalog - Pump stopped between 7AM and 12 AM. - Blood glucose was ~ 5 mmol/l higher with Humalog after 5 hours Guerci B et al. J Clin Endo Met 1999;84:2673-78. 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0 Betahydroxy-buturate, mmol/l Humalog Velosulin - All patients with pumps have blood ketone meters

49 R Hanas, CWD 2006 00;18 - Blood glucose will rise quickly when insulin supply is interrupted - Always check ketones in the urine when you are not feeling well Increased risk of ketoacidosis with pump Needle came loose New needle inserted Ketones!! 2018161412108642 8 10 12 2 4 6 8 10 12 2 4 6 8 AM PM AM Time 8 10 12 2 4 6 8 10 12 2 4 6 8 AM PM AM Time Blood glucose mmol/L x x x x x x x x x x x x Example of pump problems: Time 10 AM 122 PM pH7.287.317.36 Ketones3.63.00.2 BGhigh450305 mg/dl 3603242882522161801441087236 mg/dl

50 R Hanas, CWD 2006 00;18 Diabetes equipment to bring on the trip - Extra insulin pen and/or syringes (pre-filled pens are handy for this) - Store in separate hand luggage - Thermometer to check the temperature of the refrigerator - Test strips + meter - Extra meter 1 mmol/l = 18 mg/dl - Finger-pricking device + lancets - Test strips for ketones (blood and/or urine)

51 R Hanas, CWD 2006 00;18 Diabetes equipment to bring on the trip - Dextrose/glucose tablets and gel - Glucagon - Clinical thermometer - Fever suppressing drugs: Paracetamol/acetaminophen and/or aspirin /salicylic acid (adults only) - Oral rehydration solution - ID indicating that you have diabetes and a necklace/bracelet - Telephone and fax. numbers for your diabetes clinic at home - Insurance documents

52 R Hanas, CWD 2006 00;18 Always call your home team - You are never longer away from home than a telephone call - Ask for a doctor’s contact before leaving home Check www.ispad.org for names of doctors www.ispad.org - Staying at a hospital where you don’t understand the language is a difficult experience - Try to find a children’s hospital in an emergency situation - With glucagon and frequent monitoring you can prevent most emergencies!

53 R Hanas, CWD 2006 00;18 Preventing “The revenge of Montezuma” - Antibiotics for diarrhea when travelling to Asia, Africa, Latin/South America or Southern Europe: - Lexinor ® (norfloxacine) Not for children younger than 12 years old or pregnant women. - Dose: 200 mg twice daily for prophylactic use or 400 mg twice daily for 3 days if you are having acute diarrhea. - Co-trimoxazole ®, Colizole ® (trimethoprim + sulphamethoxazole) or similar for children younger than 12 years old.