Final year medical student presenting for seminar presentation under supervision of emergency department specialist.

1. M E TA B O L I C E M E R G E N C I E S
P R E S E N T E D B Y
A U D I A D I B A H R A H M A N
N I K N O R L I Y A N A
N U R U L H I D A Y U I B R A H I M

2. WHAT IS METABOLIC EMERGENCIES?
Metabolic diseases can vary as much in clinical presentation as they can in
classification, and neonates and infants frequently present with symptoms similar
to those seen with other emergencies. Vomiting, alterations in neurologic status,
and feeding difficulties are the most prominent features of metabolic
emergencies.
Pediatric cases > Adult cases
It covers few aspects, including:
 Sodium
 Potassium
 Calcium
 Phosphate
 Magnesium
 Glucose
 Inborn Errors of Metabolism

3. OUTLINES
 HYPOGLYCEMIA
 HYPONATREMIA
 INBORN ERRORS OF METABOLISM
 METABOLIC ACIDOSIS
O U R F O C U S TO P I C S F O R TO DAY

4. H Y P O G LY C E M I A
“Low plasma glucose level (<4.0 mmol/L)”
“Development of autonomic or neuroglycopenic
symptoms in patients treated with insulin or OADs
which are reversed by caloric intake.”

5. INTRODUCTION
G LU C O S E H O M EO S TA S I S
Two major hormones regulating glucose
homeostasis are insulin (beta cells) and
glucagon (alpha cells). They work
together to promote homeostasis of
energy and metabolism of
carbohydrates and fats. There are also
other regulating hormones, such as
somatostatin, epinephrine and cortisol.
High blood glucose  stimulates insulin
release from pancreas  stimulates
glucose uptake from blood into skeletal
muscles and fat, stimulates glycogen
formation in liver, inhibits release of
glucagon

6. INTRODUCTION
G LU C O S E H O M EO S TA S I S

7. INTRODUCTION
G LU C O S E H O M EO S TA S I S

8. INTRODUCTION
G LU C O S E H O M EO S TA S I S
↓ blood
glucose
↑ blood
glucose

9. INTRODUCTION
H Y P O G LYC E M I A
Definition
Hypoglycaemia is defined by either one of the following two conditions:
a) Low plasma glucose level (<4.0 mmol/L).
b) Development of autonomic or neuroglycopenic symptoms in patients
treated with insulin or OADs which are reversed by caloric intake.
Plasma glucose <3.0 mmol/L (OXFORD HANDBOOK)
Blood glucose <3.5 mmol/L (DAVIDSON)
Can mimic any neurological presentation including coma, seizure, acute
confusion or isolated hemiparesis.
“Always exclude hypoglycemia in any patient with coma, altered behavior,
neurological symptoms or signs.” – OXFORD HANDBOOK OF ACCIDENT AND
EMERGENCY MEDICINE, 2ND EDITION

10. INTRODUCTION
H Y P O G LYC E M I A
Whipple’s Triad
 Fasting hypoglycemia (<2.2 mmol/L)
 Symptomatic hypoglycemia (autonomic and neuroglycemic symtoms)
 Relieve of symptoms after administration of glucose
When Whipple triad is mentioned, one classically thinks
of insulinomas, but these features are not specific for
insulinoma.
Insulinoma - a rare islet tumor of the pancreas that is
characterized by symptomatic hypoglycemia and
inappropriately increased plasma insulin during an
episode of spontaneous hypoglycemia. Insulinomas are
evenly distributed in the pancreas; that is one-third are
found in the head, one-third in the body and one-third
in the tail.
Management of insulinomas includes controlling
symptoms of hypoglycemia and surgical resection.
Hypoglycemia can be controlled through a combination
of diet and medication.

11. CLASSIFICATION

12. PREDISPOSING FACTORS
H Y P O G LYC E M I A
 Advancing age
 Poor health knowledge
 Hypoglycemia unawareness
 The most common cause of hypoglycemia is medications used to treat diabetes
mellitus such as insulin and sulfonylureas. Long standing insulin therapy.
 Risk is greater in diabetics who have eaten less than usual, exercised more than usual
or have drunk alcohol.
 Relative therapeutic insulin excess
 Reduce oral intake, missed meals
 Improve insulin sensitivity; eg. Increased physical activity, improved glycemic
control, weight loss
 Low blood sugar may occur in otherwise healthy babies who have not eaten for a few
hours.
 Other causes of hypoglycemia include kidney failure, certain tumors, such as
insulinoma, liver disease, hypothyroidism, starvation, inborn error of metabolism,
severe infections, reactive hypoglycemia and a number of drugs including alcohol.

13. CLINICAL FEATURES
AUTONOMIC NEUROGLYCOPENIA
 Trembling
 Palpitations
 Sweating
 Anxiety
 Hunger
 Nausea
 Tingling
 Difficulty concentrating
 Confusion
 Weakness
 Drowsiness
 Vision changes
 Difficulty speaking
 Headache
 Dizziness
Ta b l e 1 : S y m p t o m s o f H y p o g l y c e m i a

14. CLINICAL FEATURES
H y p o g l y c e m i c S y m p t o m s B a s e d o n B l o o d G l u c o s e L e v e l s
Adapted from Kedia N. Treatment of severe diabetic hypoglycemia with glucagon: an underutilized
therapeutic approach. Diabetes, metabolic syndrome and obesity: targets and therapy, 2011.

15. CLINICAL FEATURES
H y p o g l y c e m i c S y m p t o m s B a s e d o n B l o o d G l u c o s e L e v e l s

16. CLINICAL FEATURES
H y p o g l y c e m i c S y m p t o m s B a s e d o n B l o o d G l u c o s e L e v e l s

17. CLINICAL FEATURES
Ta b l e 2 : S e v e r i t y o f H y p o g l y c e m i a
Not all of the above manifestations occur in every case of hypoglycemia. There is no
consistent order to the appearance of the symptoms, if symptoms even occur. Specific
manifestations may also vary by age, by severity of the hypoglycemia and the speed of
the decline.
In both young and old patients, the brain may habituate to low glucose levels, with a
reduction of noticeable symptoms despite neuroglycopenic impairment.
In insulin-dependent diabetic patients this phenomenon is termed hypoglycemia
unawareness and is a significant clinical problem when improved glycemic control is
attempted.

18. CLINICAL FEATURES
 In young children, vomiting can sometimes
accompany morning hypoglycemia with
ketosis.
 In older children and adults, moderately
severe hypoglycemia can resemble mania,
mental illness, drug intoxication, or
drunkenness.
 In the elderly, hypoglycemia can produce focal
stroke-like effects or a hard-to-define malaise.
 In newborns, hypoglycemia can produce
irritability, jitters, myoclonic jerks, cyanosis,
respiratory distress, apneic episodes, sweating,
hypothermia, somnolence, hypotonia, refusal
to feed, and seizures. Hypoglycemia can
resemble asphyxia, hypocalcemia, sepsis, or
heart failure.

19. MANAGEMENT
C R I T E R I A F O R A D M I S S I O N
Patients without other indication for admission but at high risk of
prolonged/recurrent hypoglycemia should be considered for admission,
examples :
 Patients on glibenclamide who cannot tolerate orally (because of the long
half life, IV dextrose may be needed for days)
 Frail or elderly patients > 60 years old , especially if poor oral intake or poor
social support.
 Patients with significant renal or liver impairment
 Patients who presented with recurrent episodes of hypoglycemia within the
last 2 weeks
 Patients who are unable to self-care and unable to be discharged to an able
caregiver
 Patient with previous history of severe hypoglycemia.
Sarawak Handbook of Medical Emergencies

20. MANAGEMENT
A I M O F T R E A T M E N T S
The aims of treatment are to:
a) Detect and treat a low blood glucose level promptly.
b) Eliminate the risk of injury to oneself and to relieve symptoms
quickly.
c) Avoid overcorrection of hypoglycaemia especially in repeated
cases as this will lead to poor glycaemic control and weight
gain.
MALAYSIAN DIABETIC CPG 2015

21. MANAGEMENT
T R E A T M E N T S
A. Oral carbohydrate replacement
B. IV glucose/dextrose
C. Glucagon
D. Octreotide
E. Diazoxide

22. MANAGEMENT
1 .Treat o f Hyp oglycemic Ep is od es
Prevention is better than cure, and correction should be as quick as possible.
A. Fully conscious patients:
 In mild to moderate hypoglycaemia where the individual is able to self-
treat, he/she should ingest 15 grams of simple carbohydrate
(e.g 1 table spoon of honey, ¾ cup of juice, 3 tea spoon of table sugar)
 Repeat blood glucose after 15 minutes. If the level at 15 minutes is still <4.0
mmol/L, another 15 grams of carbohydrate should be taken.
 In severe hypoglycaemia where the individual is still conscious, he/she
should ingest 20 grams of carbohydrate and the above steps are repeated.
MALAYSIAN DIABETIC CPG 2015

23. MANAGEMENT
1 .Treat o f Hyp oglycemic Ep is od es
B. When mental function is impaired:
Medical emergency : Set IV line, turn patient to the left lateral position.
 In severe hypoglycaemia and unconscious individual, he/she should be given 20–50
mL of IV 50% dextrose 25-50 ml over 1-3 minutes followed by saline flush. Outside
the hospital setting, a tablespoon of honey should be administered into the oral
cavity.
 Once hypoglycaemia has been reversed, the patient should have the usual meal or
snack that is due at that time of the day to prevent repeated hypoglycaemia.
 When hypoglycemia is due to an overdose of long acting insulin or OADs, 10%
dextrose drip should be continued for 24-48 hours.
 Patients receiving anti-diabetic agents that may cause hypoglycaemia should be
counselled about strategies for prevention, recognition and treatment of
hypoglycaemia. Individuals may need to have their insulin regimen adjusted
appropriately to lower their risk.
MALAYSIAN DIABETIC CPG 2015

24. MANAGEMENT
1 .Treat o f Hyp oglycemic Ep is od es
B. When mental function is impaired:
 Glucagon, 1 mg IM or deep SC can be given to treat severe hypoglycemia
when IV access is difficult. This option can also be taught to relatives of
patients on insulin. As soon as patient regain consciousness after glucagon,
they are advised to eat/drink (followed procedure in (A)) as the
hyperglycemic action of glucagon lasts only for 10-15 min.
 Patient who remain unconscious after prolonged hypoglycemia may need to
be given treatment for cerebral edema with IV dexamethasone 4 mg 6
hourly or IV mannitol, or consider other causes of coma (e.g. stroke, drug
overdose)
Sarawak Handbook of Medical Emergencies

25. MANAGEMENT
2 . I nvestigate an d treat th e u n d erlyin g cau s e to p revent
recu rren ce :
A. Adjustment of drug therapy, diet and physical activity
If hypoglycemia recurs at a particular time of day, change the distribution and
timing of insulin injections.
If hypoglycemia is severe, prolonged, or unpredictable, reduce total dose.
Increase carbohydrates intake prior to increasing or prolonging
activity/exercise.
Avoid long acting sulfonylureas like glinbeclimide in elderly patient or patient
with renal impairment.
B. Educate patient on hypoglycemia recognition and management
C. For patients not known to have DM, please refer to endocrinologist for
formal workup of hypoglycemia.
Sarawak Handbook of Medical Emergencies

26. MANAGEMENT
O C T R EOT I D E
 Somatostatin analogue
 An antidote for sulfonylurea-induced hypoglycemia. Octreotide is a safe and
effective treatment for refractory sulfonylurea-induced hypoglycemia, reducing
additional hypoglycemic episodes.
 Provides more potent inhibition of growth hormone, glucagon, and insulin as
compared to endogenous somatostatin
 May reduce recurrent hypoglycemia as with dextrose-alone therapy
 Should be used with IV dextrose/oral carbohydrates
 It is reserved for patients that experience a recurrent episode of hypoglycemia
after standard dextrose therapy to prevent additional recurrences
 Dose: (ideal dose not well established)
SQ: 50-100 mcg, repeat every 6 hours PRN
IV: up to 125 mcg/hour has been used

27. MANAGEMENT
O C T R EOT I D E
 Warnings/precautions:
I. Cholelithiasis – may inhibit gallbladder contractility
II. Glucose regulation
III. Hypothyroidism – may suppress TSH secretion
IV. Pancreatitis – may change absorption of fats
 Adverse effects: bradycardia, dizziness, hyperglycemia, diarrhea, constipation

28. MANAGEMENT
D I A Z OX I D E
 Antidote for hypoglycemia due to hyperinsulinemia; vasodilator
 Opens ATP-dependent K+ channels on pancreatic beta cells 
hyperpolarization of the beta cell  inhibition of insulin release
 Binds to a different site on the potassium channel than the sulfonylureas
 Dose: 3-8 mg/kg/day PO in divided doses Q8H
Starting dose 3 mg/kg/day PO divided in 2-3 doses
 Contraindications: hypersensitivity to diazoxide or to other thiazides
 Warnings/precautions:
I. Heart failure – antidiuretic actions, may ↑ fluid retention
II. Gout – may cause hyperuricemia
III. Renal dysfunction
 Adverse effects: hypotension, hyperglycemia

29. MANAGEMENT
H OW TO P R E V E N T ?
To prevent future episodes of hypoglycemia
Note: Do not give correction insulin until next meal
Note: Basal insulin should never be held in patients with type 1 diabetes, but
dose may require reduction
 Identify and correct the cause of the initial hypoglycemic episode
 Adjust nutritional insulin dose to match caloric (carbohydrate) intake or below
goal pre-meal blood glucose.
 Document meals and snacks and ensure accurate and timely blood glucose
monitoring
 Evaluate for early signs/symptoms of hypoglycemia.
 Pay attention to the blood glucose trends: contact provider if unusual or rapid
downward blood glucose trend.
 Patients at high risk for severe hypoglycaemia should be informed of their risk
and counselled, along with their family members and friends. Patients at risk
of hypoglycaemia are discouraged from driving, riding, cycling or operating
heavy machineries, as these activities may endanger oneself and the public.

30. MANAGEMENT
MALAYSIAN DIABETIC CPG 2015

31. MANAGEMENT
AMERICAN DIABETES ASSOCIATION

32. SITUATION
Hypoglycaemia – blood glucose level <4mmol/L
• A potentially dangerous side effect of insulin therapy and sulphonylureas
• Prompt treatment is required
BACKGROUND
Common causes of hypoglycaemia
• Inadequate food intake, fasting, delayed or missed meals
• Too much insulin or sulphonylurea
• Insulin administration/drug administration at an inappropriate time
• Problems with insulin injection technique/injection site causing variable insulin absorption
• Increased physical activity
• Alcohol
At risk groups
• Strict glycaemic control, impaired hypoglycaemic awareness, cognitive impairment, extremes of age, breast feeding mother with
diabetes
Conditions that increase risk of hypoglycaemia
• Malabsorption, gastroparesis
• Abrupt discontinuation of corticosteroids, hypoadrenalism, renal or hepatic impairment, pancreatectomy
ASSESSMENT
Assess recent pattern of blood glucose levels i.e. last 48 hours.
• Establish when and what the patient last ate
• Check insulin/ diabetes medication is being prescribed and administered at correct dose, time, and in relation to food intake
• Check for signs of lipohypertrophy (lumpy areas at injection sites) which may affect insulin absorption
• Check credibility of blood glucose monitoring e.g. handwashing before testing
RECOMMENDATION
Treat hypoglycaemia as per protocol. Observe patient until recovery complete and provide information on hypoglycaemia
management. Consult diabetes team for advice if necessary.
• Establish the cause of hypoglycaemia and take action to prevent recurrence. Inform patient if medication dose is changed
• Do not omit insulin in type 1 diabetes - treat hypoglycaemia and administer insulin as usual after dose review
• Blood glucose is likely to be high following hypoglycaemia; additional correction doses should not be given
• If receiving IV insulin treatment, check blood glucose every 15 minutes until above 4.0 mmol/L, then re-start IV insulin after review
of infusion rates and requirement for IV insulin

33. Algorithm for the Treatment and Management of Hypoglycaemia in Adults with Diabetes Mellitus in Hospital
Hypoglycaemia is a serious condition and should be treated as an emergency regardless of level of consciousness. Hypoglycaemia is defined as blood
glucose of less than 4mmol/L (if not less than 4mmol/L but symptomatic give a small carbohydrate snack for symptom relief).
For further information see the full guideline “The Hospital Management of Hypoglycaemia in Adults with Diabetes Mellitus” at www.diabetes.nhs.uk
Severe
Patient unconscious/fitting or very
aggressive or nil by mouth (NBM)
Moderate
Patient conscious and able to
swallow, but confused, disorientated
or aggressive
If capable and cooperative, treat as for
mild hypoglycaemia
If not capable and cooperative but can
swallow give 1.5-2 tubes of GlucoGel®
(squeezed into mouth between teeth and
gums). If ineffective, use 1mg Glucagon
IM*.
Test blood glucose level after 10-15
minutes and if still less than 4 mmol/L
repeat above up to 3 times. If still
hypoglycaemic, call doctor and consider
IV 10% glucose at 100 ml/hr**.
Patient conscious, orientated and
able to swallow
Mild
Give 15-20 g of quick acting carbohydrate,
such as
5-7 Dextrosol® tablets or 4-5 Glucotabs®
or
90-120mls original Lucozade®,
or
150-200mls pure fruit juice**
Test blood glucose level after 15 minutes
and if still less than 4 mmol/L repeat up to
3 times. If still hypoglycaemic, call doctor
and consider IV 10% glucose at 100 ml/hr**
or 1mg Glucagon IM*.
Check ABC, stop IV insulin, contact
doctor urgently
Give IV glucose over 10 minutes as
75 ml 20% glucose or
150ml 10% glucose or
30ml 50% glucose (risk of extravasation
injury, only use if 10%, 20% not available)
or 1mg Glucagon IM *
Recheck glucose after 10 minutes and if
still less than 4mmol/L, repeat treatment.
Blood glucose level should now be above 4mmol/L.
Give 20g of long acting carbohydrate e.g. two biscuits / slice of bread / 200-300ml milk/ next
meal containing carbohydrate (give 40g if IM Glucagon has been used) .
Patients with enteral feeding tube Give 20g quick acting carbohydrate via enteral tube eg 50-
70ml Ensure Plus ®Juice or Fortijuice® or 100mls original Lucozade®, then flush. Check glucose
after 10-15 minutes. Repeat up to three times until glucose > 4.0mmol/L . See full guideline.
If glucose now above 4mmol/L, follow
up treatment as described on the left.
If NBM, once glucose >4.0mmol/L give
10% glucose infusion at 100ml/hr** until no
longer NBM or reviewed by doctor
*GLUCAGON MAY TAKE UP TO 15 MINUTES TO WORK AND MAY BE INEFFECTIVE IN UNDERNOURISHED PATIENTS, IN SEVERE LIVER
DISEASE AND IN REPEATED HYPOGLYCAEMIA. DO NOT USE IN ORAL HYPOGLYCAEMIC AGENT- INDUCED HYPOGLYCAEMIA.
**IN PATIENTS WITH RENAL/CARDIAC DISEASE, USE INTRAVENOUS FLUIDS WITH CAUTION. AVOID FRUIT JUICE IN RENAL FAILURE
DO NOT OMIT SUBSEQUENT DOSES OF INSULIN. CONTINUE REGULAR CAPILLARY BLOOD GLUCOSE MONITORING FOR 24 TO 48
HOURS. REVIEW INSULIN / ORAL HYPOGLYCAEMIC DOSES. GIVE HYPOGLYCAEMIA EDUCATION AND REFER TO DIABETES TEAM

34. REFERENCES
1. Sarawak Handbook of Medical Emergencies 3rd Edition
2. Malaysian Diabetes Mellitus CPG 2015
3. The Journal of Clinical Endocrinology & Metabolism : Evaluation and
Management of Adult Hypoglycemic Disorders: An Endocrine Society Clinical
Practice Guideline
4. National Health Service UK Website