DIABETIC COMA clinical features and ma

1. DIABETIC COMA clinical features and management

3. HYPOGLYCEMIA

4. DEFINITION Hypoglycemia or low blood glucose is a clinical state associated with < 50mg/dl or low plasma glucose with typical symptoms. Whipples triad = venous plasma glucose <50mg/dl. Classical symptoms. Relief of symptoms with glucose.

5. DCCT Definition Event resulting in seizure,coma ,confusion or symptoms like sweating,palpitation,hunger with finger stick glucose < 50 mg/dl and amelioration of symptom by elevation of blood glucose. Prodromal symptoms occuring before the event are well remembered. Severe hypoglycemic symptoms requiring hospital admission and treatment with IV glucose or glucagon.

6. Mechanisms for fasting hypoglycemia Under production hormone deficiencies enzyme defects substrate deficiency chronic infections. drugs Over utilization hyper insulinism insulinoma exogeneous insulin overdose. auto immunity Normal insulin level extra pancreatic tumour carnitine def, cachexia.

7. Fed state hypoglycemia Early(alimentary)within 2-3 hours after meals Alimentary hyperinsulinism Postgastrectomy Functional(increased vagal tone) Hereditary fructose intolerance Galactosemia Leucine sensitivity Late(occult diabetic) 3-5 hours after meals Delayed insulin release due to beta cell dysfunction Counter regulatory deficiency of growth hormone,glucagon, cortisone,autonomic response,epinephrine.

8. Factors that precipitate hypoglycaemia Excessive insulin or SU administration- - Error by patient or doctor. - Poor matching to patient�s lifestyle. Increased insulin bioavailability- -Exercise. -Injecting into abdomen. -Change to human insulin/analogs -Insulin antibodies. -Mismatch of syringes

9. Risk factors for severe hypo Intensive insulin therapy & tight glycemic control. Hypoglycemia unawareness �acute & chronic. Long duration of diabetes. Increasing age. Sleep. Excessive alcohol. Renal failure/ Hepatic failure Hypothyroidism/ Hypopituitarism/ Hypoadrenalism

10. Hypoglycemia in non diabetic scenario ZE syndrome -Whipple�s triad, diarrhea ,muscle wasting,tiredness. May be associated with neurofibroma. 5 hour OGGT shows < 50mg/dl. Serum insulin level-20micro units /ml, increased proinsulin level. Hereditary fructose intolerance � enlarged liver,jaundice,cirrhosis,albuminurIa, aminoaciduria,mental retardation. Ingestion of fruit leading to vomiting and hypoglycemia.

11. Common symptoms Autonomic Neuroglycopenic General Adrenergic Sweating confusion nausea Palpitation drowsiness headache Tremor speech problems Hunger incoordination atypical behaviour diplopia

12. Grading of Hypoglycaemia Grade 1 or mild : patient can recognize hypo and able to self treat Grade 2 or moderate : severe hypo prevents patient from self treating but with assistance oral treatment is possible. Grade 3 or severe : severe degree of neuroglycopenia requiring parenteral glucagon/dextrose.

13. Sequence of responses to decrements in plasma glucose mg/dl 70 Counter regulation 60 Adrenergic symptoms 50 Neuroglycopenic symptoms 40 Lethargy 30 Coma 20 Convulsions 10 Permanent Damage Death 0

14. Hierarchy of Glucoregulation Insulin (83 + 9 mg) Glucagon (68 + 2 mg) Epinephrine (68 + 2 mg) Growth hormone (66 + 2 mg) Cortisol (58 + 6 mg) Symptoms of hypoglycemia (53 + 2) Cognitive dysfunction (49 + 2)

15. Nocturnal Hypoglycemia Is common (biochem hypos occur frequently). Asymptomatic/morning headache/hangover. Often identified by partner: sweating, fretting. May lead to sudden death. Unsatisfactory time action profile of certain insulins; physio defences against hypo reduced in flat position; sympathetic responses to hypo reduced in slow wave sleep Dawn phenomenon vs Somogyi effect.

16. Morbidity of Hypoglycemia CNS � Coma/convulsions/transient deficits/ataxia/brain damage/ intellectual impairment. Psycho � Cognitive disorders/personality changes/ behavioural disorders/ automatism/ psychosis. CVS � Arrhythmia/MI/TIA/stroke. Eye � Vitreous haemorrhage Musculoskeletal � Fracture/accidental injury.

17. Hypoglycaemic mortality Causes Severe brain damage Hypostatic pneumonia Acute vascular events �Dead in Bed� Cardiac arrhythmia

18. Hypoglycaemic Unawareness Absence of classical adrenergic warning symptom, More vulnerable to develop severe hypoglycaemia Counter-regulatory failure : Glucagon failure - 5 yr.to20 yr. Adrenaline failure - follows then 25 times higher risk for severe hypoglycaemia

19. Hypoglycemia unawareness Perception of early warning symptoms impaired. Is not an all-or-none phenomenon. Affects one quarter of Type 1 diabetic patients. Correlates with glycemic control ? Duration of diabetes ? May be Acute or Chronic (Central autonomic failure).

20. Hypoglycaemia in DiabetesHypothyroidism Insulin degradation is less Insulin sensitivity is more Decreased appetite Decreased GH Decreased glycogenolysis

21. Hypoglycaemia in DiabetesHypocortisolism Decreased gluconeogenesis By decreasing substrate By decreasing PEPCK By decreasing Glu-6-phosphatase. Decreased permissive effect on glucagon and epinephrine Decreased appetite

22. Hypoglycaemia in DiabetesDiabetic Nephropathy Decreased catabolism of insulin Proteinuria Decreased appetite Nausea and vomiting Impaired absorption Impaired gluconeogenesis

23. Alcohol and hypoglycemia Reduced gluconeogenesis Reduced hypo awareness Reduced tremors

24. DD of hypoglycemic and hyperglycemic coma Symptoms,signs and hypoglycemic coma hyperglycemic coma laboratory findings Physical findings pulse rate increased increased pulse volume full weak temperature may be decreased may be decreased respiration shallow or normal rapid and deep blood pressure normal,may be increased decreased skin clammy,sweating dry Tongue moist dry tissue turgor normal reduced eyeball tension normal reduced breath no acetone acetone may be present reflex brisk reflexes diminished reflexes

25. Symptoms,signs and hypoglycemic coma hyperglycemic coma laboratory findings Laboratory tests urine glucose -ve to +ve depending +ve on time of last voiding plasma glucose -ve to +ve +ve greater than 200mg/dl plasma acetone -ve usually present plasma bicarbonate normal low less than 20mg/litre plasma CO2 normal diminished blood pH normal less than 7.35

26. MANAGEMENT ALGORITHM

27. CAUTION Glucagon may lose effect with repeated use. Glucagon is contraindicated in SU induced hypos. SU induced hypoglycemia may be very prolonged.It can be more fatal than insulin induced hypoglycemia. Duration of treatment depends on cause of hypo

28. Measures to avoid hypoglycemia in patients on insulin and/or sulfonylureas Do not delay,skip or reduce food intake. Take a snack before physical exercise. Avoid insulin injections in the limb which is actively involved in the exercise. Avoid exercise during the peak time period of insulin action. When on human insulins,the time gap between insulin and food should be 15 minutes. When on analogs, keep the time gap less than 5 minutes Do not use sulfonylureas in patients with hepatic/ renal insufficiency. Ask the patient to avoid alcohol. In older diabetics do not insist on very tight control of blood glucose;prefer short acting sulfonylureas Regularly monitor blood glucose.

29. Drugs causing hypo Increase in SU effect Salicylates, probenecid, sulfonamides, nicoumalone, fluconazole [inhibits CYP2C9 which metabolizes glimepiride], ketoconazole, ciprofloxacin [inhibits CYP3A4 which metabolizes glibenclamide], gatifloxacin Direct hypoglycemic effect ACE(I), disopyramide, SSRIs, quinine, sulfamethoxazole, mefloquine, pentamidine, doxycycline, ethanol

30. Neonatal hypoglycemia Hypoglycemia in the immediate postpartum period needs recognition,as this phenomenon is transient. Every newborn of diabetic mothers must be given a 5% glucose infusion for the first six hours and subsequently blood glucose monitored to prevent potentially fatal hypoglycemic convulsions.

31. Take home message Single most important limiting factor in maintaining strict glycemic control. Can be life threatening Delicate balance needs to be kept between tight control & hypoglycemia. BE ON THE LOOK OUT FOR HYPO ALL THE TIME

32. Dhanya vaad Have a safe journey back home

33. ETIOLOGY GLYCEMIA-RELATED Hypoglycemia Ketoacidosis HHNKC NON-GLYCEMIA RELATED Meningitis Stroke SDH Associated encephalopathy

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35. DKA: Clinical features Common cause of death in type 1 diabetics Can occur in type 2 as well Hyperketonemia/significant ketosis Metabolic acidosis Hyperglycemia Ppt factors: infection, inadequate insulinization, stress, MI, new cases

36. BHARTI HOSPITAL EXPERIENCE 10 April to 16 May 2004 20 patients; 7 aged less than 18 yrs 10 with BG �Hi�; 14 with large UK; 7 with clinical acidosis; 4 with altered sensorium [ 1 not responding to pain]; 2/2 with BK �Hi� OPD management for 3 [successful in 2 with 30 U insulin each, unsuccessful in 1] ADA recommends admission for moderate ketosis

37. Age/gender distribution

38. Precipitating factors [Bharti Hospital, 10 Apr to 16 May, 2004]

39. Ketosis: Symptoms Polyuria, nocturia, thirst Rapid weight loss Muscular weakness Visual disturbance Air hunger Abdominal pain, nausea, vomiting Leg cramps Altered sensorium

40. Ketosis: Signs Acetone breath Air hunger Impaired consciousness Hyperglycemia, osmolarity Cerebral edema if sensorium worsens during treatment Hypotension: due to peripheral vasodilatation due to acidosis Hypothermia Succussion splash May mimic surgical emergency

41. Presentation [Bharti Hospital]

42. D/D Hyperosmolar non-ketotic coma Hypoglycemia Lactic acidosis Associated CNS pathology Other metabolic encephalopathies Acute pancreatitis

43. Cardinal principles Replace insulin Replace fluids Correct electrolytes Treat the cause Supportive treatment Prevent complications

44. Insulin Begin IV infusion of NS and regular insulin Monitor BG hourly Shift to 5D + insulin when BG = 200 � 250 mg% Try 0.1 � 0.2 U insulin/ kg body wt/ hour initially; reduce gradually Check BG after every 2nd to 3rd bottle of IV fluid Give first few vacs �fast� until patient regains consciousness/ BG comes down from �Hi�/BK come down from �Hi�

45. Insulin Give continuous IV regular insulin to produce steady high physio or supraphysio insulin that adequately corrects biochemical derangements High doses are required to counter catabolic hormones/cytokines in infective/stressful states Insulin aims to Inhibit lipolysis; inhibit ketogenesis Inhibit hepatic gluconeogenesis Enhance disposal of glucose and ketone bodies by peripheral tissues

46. SC insulin Begin as soon as patient is fit to eat Inject at least 30 min before stopping IV insulin Always begin with regular or short-acting analogue

47. Electrolyte balance Focus on K Total body K is low even if plasma report is high Insulin and rising pH both stimulate entry of extracellular K into cells Aim for K > 3.5 mEq/l Average req = 20 mmol of K per 1000 ml of NS Do not give K in first hour unless K < 3.5 Reduce if anuria/renal failure ECG monitoring can help

48. Fluids 1000 ml/hour x first 2-3 hrs, thereafter adjust acc to need, hydration status NS, N/2 saline, 5D Consider NaHCO3 if pH < 7.0 Avoid N/2S as it is hypotonic, and promotes rapid movement of water into cells; may ppt cerebral edema

49. Bicarbonate Beneficial ONLY if patient is severely acidotic or nearing cardiorespiratory collapse HCO3 + H = carbonic acid = H2O + CO2 in ECF CO2 readily enters cells, where reverse reaction occurs, i.e., H is produced intracellularly, leading to intracellular acidosis Hypokalemia Paradoxical acidosis of CSF Adverse effects on oxyHb dissociation curve: tissue hypoxia Overshoot alkalosis Acceleration of ketogenesis by raising pH Cerebral edema Local necrosis

50. Management Always count insulin, fluid, KCl requirement to make your patient is conscious/ ketone-free Correlate with ppt factor, other variates Average requirement is 100 U insulin in 4 l fluid over 24 hours Keep BG 150 � 200 mg% Requirement varies acc to ppt factor, duration of ketosis

51. Management Avoid recurrent ketosis: stopping IV infusion for few minutes can revert patient to ketotic state Maintain IV infusion (5D + insulin) until at least 2 urine samples are ketone-negative Keep separate IV line for IV antibiotic infusions Give SC NPH insulin b.d.; give first dose as soon as patient is reasonably hydrated

52. Management Check BG hourly initially, then 2 � 4 hourly If patient is on 5D infusion, stop the drip 15 � 30 mins prior to test; take blood from contralateral arm Keep a glass bottle of NS + 2 units insulin; give 100 ml after completing 5D infusion; check BG after that

53. Our experience Insulin req: 14 to 410 U [mean 115.53 U] minimum: 14, 32, 38 U maximum: 260, 410 U all others: 48 to 146 U Per kg body wt: 0.71 to 14.6 U [mean 3.6 U/kg] minimum: 0.53, 0.71 maximum: 5.91, 8.5, 14.6 all others: 1.2 to 3.8

54. Our experience Fluid req: 1500 ml to 17 000 ml minimum 1500 ml in 4 patients maximum 9500, 17000 ml Per kg body wt: 25 to 607 ml/kg [mean 128] minimum 25, 25, 30 maximum 607 ml/kg till ketone-free

55. Complications Cerebral edema Incr intracellular osmolarity in CNS neurone [glucose, ketones, idiogenic osmoles] Sudden fall in ECF osmolarity [insulin hypotonic fluids] Increased gradient Increased entry of water into CNS CEREBRAL EDEMA ARDS Thromboembolism DIC Rhinocerebral mucormycosis

56. Prevention/treatment of c. edema Slow rate of IV infusion Avoid hypotonic fluids Slow insulin replacement IV mannitol dose 0.2 to 1 g/kg

57. Reading lab tests First capillary BG may be low because of dehydration; next value can be higher inspite of insulin Initial TLC/DLC, bl urea may be high due to hemoconcentration; OT/PT, se amylase high Initial Na is low, K may be high If in doubt, repeat the next day

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