Diabetic Emergencies

Sa’ad LahriRegistrar

Dept Of Emergency Medicine

Outline

• Hypoglycaemia

• Diabetic Ketoacidosis (DKA)

• Hyperglycemic Hyperosmolar state (HHS)

• Lactic Acidosis

• Case Study• 55 y old diabetic brought to ER with history of “L

CVA” by EMS crew.• Management en - route: “calmed and

reassured”• Glucose in ER = 1,1 mmol/l• Nurses records: “seen by Dr X and 50mls 50%

dextrose given IV. Patient now talking and moving all limbs freely”

Hypoglycaemia

• Definition: blood glucose level <2.5 mmol/l

Postgrad Med J 2007; 83:79-86

Principles of Disease

• Protection against hypoglycaemia :

• Cessation of insulin release and mobilisation of counter regulatory hormones – increase in glucose production and decrease glucose use.

Rosen’s Emergency Medicine 6th Ed

Causes of hypoglycaemiaHypoglycaemic admissions among diabetic patients in Soweto, South Africa

• A total of 51 episodes of biochemically confirmed hypoglycaemia (blood glucose < 2.2 mmol/l with coma or pre-coma, and requiring intravenous glucose) were observed in 43 patients.

• Important to check for sepsis, renal failure, heart failure, accidental overdose

Diabet Med. 1993 Mar;10(2):181-3

GIT upset 20%

Alcohol 22%

Gliclazide 33%

Missed meal 36%

Inappropiate Tx,18%

Gliclazide

Missed meal

Alcohol

GIT upset

Inappropiate Tx

Metformin and hypoglycaemia?

• Metformin – decreases hepatic production of glucose and increases insulin sensitivity.

• Symptoms of OD : nausea, vomiting, abdominal pain and lactic acidosis.

• Lactic acidosis can be fatal

Emergency Medicine Secrets 4th Ed

Hypoglycaemia due to OD

• OD – delayed hypoglycaemia

• Observation period – 12-16hrs

• Sulphonylurea – Octreotide

Emergency Medicine: Just the facts 2nd Ed

Diagnostic Strategies

• Cardinal test: blood glucose (before therapy)

• Finger prick : beware insufficient sample

• Other tests should address aetiology (eg sepsis)

• Factitious hypoglycaemia: low levels of C-peptide helpful

Rosen’s Emergency Medicine 6th Ed

Clinical Symptoms and signs

• Autonomic: (sweating, anxiety, nausea, palpitations and hunger) (3.3 – 3.6 mmol/l)

• Neuroglycopenia: confusion, drowsiness, altered behaviour and focal deficits. (<2.6 mmol/l)

• ABCD “EFG”

• Doctor “she is extending” (glucose 1mmol/l)

Postgrad Med J 2007; 83:79-86

Management

• Alert with mild symptoms – sugar containing food

• Unable to take po – IV 50 mls 50 % dextrose.

• 30% gel (hypostop) buccal mucosa

• Irritant to veins – venous sclerosis - rebound hypoglycaemia. Problem children

Rosen’s Emergency Medicine 6th Ed

Postgrad Med J 2007; 83:79-86

Dextrose 10% or 50%?

• Dextrose 10% or 50% in the treatment of hypoglycaemia out of hospital? A randomised controlled trial:

• Main outcome measures: To compare for each dextrose concentration the time to achieve a Glasgow Coma Scale (GCS) score of 15, and the dose required to obtain a blood glucose level of 4.5 mmol/l.

• Results:• No statistically significant differences in median time to

recovery • Dextrose 10 % lower post treatment glucose levels

Emerg Med J 2005; 22:512-515

• Thiamine if alcohol abuse

• No IV – 1mg Glucagon IM.

• Onset of action 10 -20 mins and peak response 30-60 mins.

• Ineffective if glycogen absent – alcohol induced hypoglycaemia.

Rosen’s Emergency Medicine 6th Ed

“Appropiate Disposition”

• Admit/observe – suicidal ; excessive amounts of oral hypoglycaemics or long – acting insulin. Persistent altered mental status.

• Hypoglycaemia uncomplicated by other disease – discharged if caused found and corrected.

• Give meal before discharge – ability to tolerate oral feeds and replenish glycogen stores.

Rosen’s Emergency Medicine 6th Ed

Emergency Medicine Secrets 4th ED

What about Non – diabetic Patients?

• Classify as Postprandial or fasting.• Postprandial: alimentary hyperinsulinism –

gastrectomy, fructose intolerance.• Fasting: imbalance production and use.

• Underproduction: hormone deficiencies, liver disease.

• Overuse: hyperinsulinism ; drugs, insulinoma, tumours.

Rosen’s Emergency Medicine 6th Ed

Case Study 2

• Referral letter from Primary Care:

• 19 y old male presents with hx of nausea, vomiting and abdominal pain.

• Notice him to be dehydrated with acidotic breathing

• Glucose … HI!

• Urine 3+ ketones

• Diagnosis … Diabetic ketoacidosis

DKA

• Triad of:• hyperglycaemia, ketosis and acidaemia.• Diagnostic criteria (ADA)• Blood glucose >14• Ph <7.30• Serum Bicarb <18mmol/l• Anion Gap >10• Ketonaemia

Postgrad Med J 2004; 80: 253-61

PrecipitantsQJ Med 2004;97:773 -780

• Infections and inadequate insulin doses.

• Most frequent dx infections: pneumonia and UTI. Check for meningism &PID

• Others include Myocardial infarction, CVA, pulmonary embolism

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History and Physical Exam

• DKA usually short time (<24hrs)

• Classic clinical picture: polyuria, polydipsia, weight loss, vomiting, abdominal pain, dehydration, weakness, mental stage change and coma.

Diabetes Care 2006;29: 2739 - 2747

Physical findings:

• Poor skin turgor• Kussmaul respirations• Tachycardia• Hypotension• Shock• Coma• Severe hypothermia poor prognostic sign.• Abdominal pain may be present – 50-75% resolves

correction of hyperglycaemia and acidosis.• Abdominal pain? – dehydration of muscle tissue,delayed

gastric emptying and ileus

Diabetes Care 2006;29: 2739 - 2747

Postgrad Med J 2004; 80: 253-61

Endocrinol Metab Clin N Am 35 (2006) 725–751

Laboratory Tests and Evaluation

• ABG not necessary – can use venous blood

• Lab: Na, K , Urea, Creatinine

• Serum ketones

• Culture of blood and urine if clinically indicated.

• ECG and CXR

• Preg test if femalePostgrad Med J 2004; 80: 253-61

Discussion of tests

• Leucocytosis common finding – stress and dehydration.

• Leukocytosis above 25000 suggests ongoing infection. Band neutrophils high sensitivity and specificity.

• Na : usually low osmotic flux of water.

• If high profound water loss.

• K: may be up due to extracellular shiftEndocrinol Metab Clin N Am 35 (2006) 725–751

Management Aims

Fluids Insulin Potassium

Correct Acidosis

HyperglycaemiaElectrolytesPrecipitant

Education

EMJ 2003, 20 :210-213

Fluid Therapy

• Controversy is rife!!!

• Which fluid?

• How much?

• At what rate?

Which Fluid?

• Current guidelines ADA – Initial Fluid 0.9% Saline

• Other’s prefer Hartmann’s. • 0.9% Saline – hyperchloraemiac

metabolic acidosis• Hartmann’s – 29mmol/l lactate. In DKA

high lactate to pyruvate ratio.• Hartmann’s – generate glucose from

lactate

BMJ 2007;334:1284-5

• Hartmann’s – 5mmol/l K. DKA patient may be hyperkalaemic

• 0.9% saline acidotic Ph 4.5

• Hartmann’s Ph 6,0

• Need a trial !

BMJ 2007;334:1284-5

Fluid replacement

• Aim to expand extracellular volume and restore renal perfusion.

• Rate of 15-20ml/kg hour or 1-1.5l 1st hour.

• Subsequent choice depends on state of hydration, serum electrolytes and urine output.

• O.45% NaCl at 4-14ml/kg/hr if hyperNa or euNa 0.9% if hypoNa

• Glucose <14 mmol/l 5% glucose containing solutions at 100-125mls/hr.

• Change in osmolality not exceed 3 mmol/kg/hr

CMAJ 2003;168(7) 859 -66

GF Jooste Clinical Guidelines 2007• Richardson, Meintjies and Burch:

• 1l N/S stat

• 1l over 1 1hr

• 1l over 2 hrs

• 1l over 4hrs

• 1 litre 6 hrly

Insulin

• Continous IV infusion • IV bolus 0.1 u/kg• Not subcut or IM for shocked. May used mild

DKA or no infusion available.• If K >3.3 0.1 U/kg per hour.• Gradual decline 3-4 mmol/l/hr.• If level not drop 3mmol in first hour infusion may

be doubled.• When Glucose level reaches 12-14 mmol/l

insulin rate may be decreased by 50% as 5% dextrose is added

Diabetes Care V 29:12 Dec 2006

GF Jooste Protocol

• Infusion 50 units Actrapid in 200mls Normal saline at 24mls/hr (6mls/hr)

• Visidex <15: change to rehydration fluid

• Visidex 10-15: 24 mls/hr• Visidex 4-10: 12mls/hr• Visidex <4: stop Actrapid 2 hrs and

50mls 50% dextrose

• Once the ketoacidosis has been corrected

• Glucose <11.0 mmol/l

• Serum Bicarb >18 mmol/l

• Venous Ph >7.3 and patient able to eat

• Multi dose insulin regimen may be started

Diabetes Care V 29:12 Dec 2006

Potassium

• Total body potassium depleted.

• May get hyperK because of acidosis.

• Give 20-30mmol K to each litre to maintain K - 4 and 5 mmol/l.

• If K < 3.3 mmol/l give K & delay insulin therapy to avoid arrhythmias

Diabetes Care V 29:12 Dec 2006

Bicarbonate therapy(could be a presentation on its own)

• Use remains controversial.

• Ph>7.0 insulin blocks lipolysis and resolves ketoacidosis.

• Disadvantages: Increased risk of hypokalaemia, decreased tissue oxygen uptake, cerebral oedema and may even augment ketone production.

Diabetes Care V 29:12 Dec 2006

Bicarb

• If Ph <7,0 ADA recommends 50mmol bicarb in 200mls sterile water with 10 mmol of K over 1 hr till ph >7,0.

• No studies PH <6.9. Risk of impaired myocardial contractility

• 100mmol bicarb in 400mls sterile water with 20 mmol K at 200mls/hr for 2 hrs until venous ph >7,0

Endocrinol Metab Clin N Am 35 (2006) 725–751

What about Phosphate and Magnesium?

• Phosphate: replacement not required for routine correction. May be harmful – hypocalcaemia.

• If potential complications of hypophosphatemia – replacement may be justified.

• Cydulka and Pennington in Rosen’s 6th Ed recommend Mg 0.35mEq/kg in fluids, 1st 3 -4 hrs.

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Treatment related complications

• Hypoglycaemia – poor monitoring

• Hypokalaemia – inadequate replacement

• Heart Failure – too much fluid

• Cerebral oedema – correct water and sodium deficits slowly. Suspect if comatose after reversal of acidosis

CMAJ 2003; 168 (7), Rosen’s Emergency Med 6th ed

• Non cardiogenic pulmonary oedema – due to increased water in lungs and reduced lung compliance.

• Hyperchloraemic metabolic acidosis: loss of ketanions necessary for bicarb regeneration, use of 0.9% saline.

• Acidosis: no adverse effects and corrects spontaneously

CMAJ 2003; 168 (7)

CASE STUDY 3

• 64 y old type 2 diabetic presents to EU with hx from family “doc, I had difficulty waking my mum this morning. She’s confused”

• Good doc, you check hgt = 48 mmol/l and notice her to be dehydrated.

• Diagnosis …

Hyperglycaemic hyperosmolar state

• HHS replaces “hyperosmolar non-ketotic coma”

• Alterations in sensoria may be present without coma.

• Mild to moderate ketosis is commonly present.

• Kitabchi et al …

Postgrad Med J 2004;80:253–261

Postgrad Med J 2004;80:253–261

Predisposing and precipitating factors

• Infection (eg, pneumonia, urinary tract infection, and sepsis) is the most common precipitating illness, occurring in up to 60% of cases

• others - provoke release of counter regulatory hormones and precipitate HHS include silent myocardial infarction, cerebrovascular accident, pulmonary embolism, and mesenteric thrombosis

Emerg Med Clin N Am 23 (2005) 629–648

Clinical Presentation

• Type 2 diabetics with more insidious onset.• Polyuria, polydipsia and weight loss over several

week’s duration.• May have focal neurological signs• Coma is associated with severe hypertonicity,

with serum osmolarity at 350 mOsm/L or greater, and usually more significant hypernatremia than hyperglycemia

• Dehydration

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hyponatraemia

Uraemia Drug od

sepsis

hypoglycaemia

Diff Diagnosis

Emerg Med Clin N Am 23 (2005) 629–648

• Calculate effective osmolarity, which reflects actual tonicity, the osmotic pressure of a solution.

• The normal serum osmolarity 275 to 295 mOsm/L. Levels above 320 mOsm/L - alteration in cognitive function

Emerg Med Clin N Am 23 (2005) 629–648

Lab investigations

• serum glucose, serum urea ,creatinine, electrolytes, serum ketones, osmolality, urinalysis

• complete blood count with differential.• arterial blood glasses if respiratory

compromise or acidosis is suspected.• Bacterial cultures of urine and blood

almost always are indicated.Emerg Med Clin N Am 23 (2005) 629–648

Sodium

• glucose osmotically shifts water into the extracellular space, sodium is diluted, and the measured value is decreased falsely.

• Corrected Na mmol/l = plasma Na + (1.6x{plasma glucose-5.6})/5.6

• Na high – water loss and dehydration

Emerg Med Clin N Am 23 (2005) 629–648

Other studies

• ECG - to look for signs of ischemia and infarction, and acute changes related to electrolyte deficiencies.

• CXR – check for pneumonia

Emerg Med Clin N Am 23 (2005) 629–648

Goals of therapy

Haemodynamic Stability

Electrolytehomeostasis

CorrectionOf hyperglycaemia&hyperosmolarity

Find precipitant Avoid complications

Emerg Med Clin N Am 23 (2005) 629–648

Fluids

• Replace one half of the fluid deficit in the first 12 hours and the remainder in the next 12 to 24 hours

• Initial replacement should be with isotonic crystalloid (eg, 0.9% sodium chloride).

• The ADA guidelines - corrected serum sodium. • If it is normal or elevated, 0.45% sodium chloride is

infused at 4 to 14 mL/kg per hour depending on hydration state

• If low, 0.9% sodium chloride is continued at the same rate

• Beware underlying disease states!

Emerg Med Clin N Am 23 (2005) 629–648

• Potassium – similar to DKA outlined earlier

• Low K greatest risk of complications including cardiac dysrhythmias, cardiac arrest, and respiratory muscle weakness.

Emerg Med Clin N Am 23 (2005) 629–648

Insulin

• Secondary role.

• Fluids always precede insulin administration.

• Insulin drives glucose, potassium, and water into cells, and administration of insulin alone could lead to circulatory collapse, shock, and even thromboembolism if fluid has not been replaced first.

• Dose similar to DKA outlined earlier

Emerg Med Clin N Am 23 (2005) 629–648

Complications

• Reasons for mortality – theories…see notes – click end show

• Elders – cardiac and renal disease.

• Thromboembolic events, cerebral edema, adult respiratory distress syndrome, and rhabdomyolysis may occur.

• Low dose subcut heparin - thrombosis

Rosen’s Emergency Med 6th Ed

Case Study 4

• 75 yold diabetic, hypertensive on oral hypoglycaemics presents to EU 2 day history of vomiting, abdominal pain.

• O/E: confused, restless found to be in Cardiac failure clinically.

• Hgt: 6,0• Gas: ph 6.96 PC02 5.4 P02 9,0 HCo3 14 BE: -12. lactate 7,0 mmol/l Diagnosis: ……………….

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Discussion:Diabetes and Lactic Acidosis

Definition:

• Severe lactic acidosis is defined as a high anion gap metabolic acidosis with a blood lactate concentration 5.0 mmol/l (normal 0.4–1.2 mmol/l).

• The pathological elevation of lactate and hydrogen ions may result from overproduction or delayed clearance of lactate, or a combination of both.

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Type A lactic acidosis (anaerobic/hypoxic)

• Type A lactic acidosis (anaerobic/hypoxic) occurs in states of profound tissue hypoxia such as myocardial infarction, cardiogenic shock, or profound sepsis.

• Anaerobic metabolism produces excess lactate that swamps the body’s capability to clear it and clearance of lactate may also be decreased.

• This situation is not peculiar to diabetes but people with diabetes (particularly type 2 diabetes) are at increased risk of hypoxic cardiovascular complications.

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Type B lactic acidosis (aerobic)

• Type B lactic acidosis (aerobic) is rarer and is associated with a number of systemic diseases (including diabetes), drugs, toxins, and inborn errors of metabolism.

• The biguanides metformin and phenformin, used in the treatment of type 2 diabetes, have both been associated with the development of type B lactic acidosis.

• Phenformin was withdrawn from the market because of this complication; the incidence of lactic acidosis is much lower with metformin, with an estimated incidence of 0.03 episodes per 1000 patient years.

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Metformin

• May be either type A lactic acidosis, where the acidosis is the result of concurrent complicating illness without the accumulation of metformin; type B arising from marked metformin accumulation without concurrent hypoxic factors; or mixed.

• 90% of absorbed metformin is excreted unchanged by the kidneys ; so - renal function that determines metformin clearance.

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Metformin

• The principal contraindication - is renal impairment: the American Diabetes Association recommends avoiding metformin use if serum creatinine concentration exceeds 125 mmol/l.

• Because of the accumulation of lactate in hypoxia, metformin is also contraindicated in conditions such as uncontrolled heart failure that predispose to lactic acidosis.

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Clinical Presentation

• Hyperpnoea (Kussmaul respiration), nausea, vomiting,diarrhoea, epigastric pain, anorexia, lethargy, thirst, and decreased level of consciousness.

• Hypotension, hypothermia, cardiac dysrhythmias, and respiratory failure may also occur in severe metformin-associated lactic acidosis.

• Blood glucose levels: low, normal, or high in diabetic subjects.

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Management

• Treatment of lactic acidosis includes appropriate supportive care (usually on an intensive care unit), treatment of any concomitant condition and elimination of any offending drug by renal excretion or dialysis.

• Bicarbonate therapy is still one of the principal management modalities for lactic acidosis despite conflicting reports as to its efficacy and even reports of potential adverse consequences.

• Metformin is a dialysable drug and the use of bicarbonate in combination with haemodialysis has been successful.

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summary

• Prognosis in lactic acidosis of all causes is poor with only between 12%–17% of patients surviving to discharge in one well conducted study. N Engl J Med 1992;327:1564–9.

• In summary, general management of the underlying condition, appropriate supportive care, bicarbonate therapy and haemodialysis are the key approaches to the management of severe lactic acidosis.

• Further trials needed before we can be clear as to what represents optimum care.

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Conclusion

“Many Cases of DKA and HHS can be prevented by better access to medical care, proper education and effective communication with the health care provider during the intercurrent illness”

Kitabchi et alDiabetes Care V 29 : 12 December 2006Hyperglycemic crises in adult patients with diabetes

Acknowledgements:Prof WallisProf PonsProf MattuProf Cydulka