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

R Hanas, CWD ;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)

R Hanas, CWD ;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 Some travel km to see their diabetologist patients / diabetologist patients / diabetes nurse - Teams with dietician, psychologist, counselor (social worker)

R Hanas, CWD ;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 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

R Hanas, CWD ;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

R Hanas, CWD ;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

R Hanas, CWD ;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

R Hanas, CWD ;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.

R Hanas, CWD ;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

R Hanas, CWD ;18 Illness that raises BG - Increase doses if needed: High BG prior to a meal -  premeal dose by 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 h. after a meal -  next day premeal dose by 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!

R Hanas, CWD ;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!

R Hanas, CWD ;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 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 U

R Hanas, CWD ;18 - Give drinks containing sugar (not Light) in small and frequent portions (several sips every 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:

R Hanas, CWD ;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)

R Hanas, CWD ;18 High blood glucose and ketones Repeated BG > 270 mg/dl (15 mmol/l) and ketones - Risk of developing ketoacidosis!! 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

R Hanas, CWD ;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

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

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

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

R Hanas, CWD ;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

R Hanas, CWD ;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 Time, hours Blood ketones (Beta-hydroxybutyrate) mmol/l children men women

R Hanas, CWD ;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

R Hanas, CWD ;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

R Hanas, CWD ;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

R Hanas, CWD ;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: How is the blood glucose decreased when treating ketoacidosis?

R Hanas, CWD ;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: 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.

R Hanas, CWD ;18 Measuring ketones in blood vs. urine >100,000 episodes of DKA annually in the U.S 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 concurrent pairs of blood and urine ketone tests were obtained concurrent pairs of BG and blood ketone tests were obtained. Laffel LMB. Diabetes 2002;51(suppl 1):A105.

R Hanas, CWD ;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: Linear response 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.)

R Hanas, CWD ;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 ( 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)

R Hanas, CWD ;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!

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

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

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

R Hanas, CWD ;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.

R Hanas, CWD ;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: days 578 sick days Laffel LMB. Diab Med 2005;23: % fewer hospitalizations 40% fewew emergency assessments Frequency of ketone measurements

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

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

R Hanas, CWD ;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: 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)

R Hanas, CWD ;18 Sick day rules - Antipyretics (acetaminophen) to treat fever - Antiemetics if severe vomiting prevents adequate fluid intake Stu Brink. Diab. Nutr. Metab. 1999;12: 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!!!

R Hanas, CWD ;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 The underlying condition is unclear - Severe or unusual abdominal pain - The child is confused or his/her general well-being is affected

R Hanas, CWD ;18 When do you need to go to the hospital? Adapted from Silink M. (Ed.) APEG handbook The child is young (< 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

R Hanas, CWD ;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!

R Hanas, CWD ;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

R Hanas, CWD ;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

R Hanas, CWD ;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

R Hanas, CWD ;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!

R Hanas, CWD ;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: U/h 1.12U/h

R Hanas, CWD ;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: Betahydroxy-buturate, mmol/l Humalog Velosulin - All patients with pumps have blood ketone meters

R Hanas, CWD ;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!! AM PM AM Time 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 pH Ketones BGhigh mg/dl mg/dl

R Hanas, CWD ;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)

R Hanas, CWD ;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

R Hanas, CWD ;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 for names of doctors - 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!

R Hanas, CWD ;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.