Diagnosis and Management

Case presentation

N.E , Female 17 year old student

Origin of burkina faso- speaks french

she has been in Nigeria for 1 week

Date of presentation- 14th August, 2016.

Presenting complaint

High grade fever for 2/7

Progressive weakness for 2/7 Positive history of abdominal pain
No vomiting, no loss of consciousness. No
urinary symptoms, cough, breathlessness
nor diarrhea
History of polyuria, polydipsia and
polyphagia could not be ascertained at
time of presentation in view of language
barrier
3

Past medical history /family

and social history

She was diagnosed with type 1 diabetes

mellitus(DM) a year ago

Commenced on soluble and intermediate

acting insulin initially but patient stopped
insulin in july 2016- thought disease has
been cured

No family history of diabetes mellitus.

History of frequent ingestion of products
made with refined sugar

continued

She does not take alcohol

Physical findings

Restless and in painful distress, though

conscious; mildly pale and moderately
dehydrated.
Bedside glucose test was 406mg/dl
Vital signs:
blood pressure-150/100mmhg,
respiratory rate 44cpm, pulse-124bpm
(small volume and regular). Spo2- 96%

Physical findings

Abdomen-slightly distended and moves with

respiration
-Globally tender with marked epigastric
tenderness. Deep palpation limited by
pain
Other systems- normal findings

Laboratory findings

Full blood count : pcv 38%, wbc

16,600cells/ul (neutrophils 53%,
lymphocyte 39%)

C reactive protein 115.5mg/l(2.5-10)

Lipid profile- cholesterol 39.5mmol/l(1.35.5), triglycerides 7.38mmol/l(0.57-2.1), low

density lipoprotein-LDL 34.4mmol/l(<4.2),
high density lipoprotein- HDL
1.76mmol/l(1.42-10)
8

Laboratory findings
Repeat lipid profile day 2 of admission
was still deranged but on day 6, cholesterol
and triglycerides were 2.4mmol/l, LDL was
17.7mmol/l
Urinalysis
glucose +
red blood cell ++
ketone +
protein trace
Repeat urinalysis day 3 of admission was not
remarkable

Laboratory findings

Serum electrolyte, urea and creatinine

14/8/16- lipaemic sample
Creatinine-unrecordable
urea-19.7mmol/l(1.7-7.5)
sodium 402 meq/l(132-145)
chloride 362meq/l(92-108)
pottasium 23.9meq/l(3.2-5.5)
Bicarbonate 23.9meq/l(22-32)
10

Continued

Pancreatic amylase result was in the

value i.e -298u/l and repeat was
-283u/l(0-50)

11

Sample

12

Laboratory findings

Serum electrolyte, urea and creatinine 17/8/16

Creatinine-56umol(44.2-106)
urea-11.7mmol/l(1.7-7.5)
sodium 150 meq/l(132-145)
chloride 313meq/l(92-108)
pottasium 4.7meq/l(3.2-5.5)
Bicarbonate 27meq/l(22-32)

Glycosylated hemoglobin 16.9%(4.4-6.7)

Malaria parasite was 1+

13

Laboratory finding

Malaria parasite +

14

Assesment and plan

Initial diagnosis by the admitting doctor was

hyperglyecemic hyperosmolar state in type 1
DM Patient .
She was commenced on the following-intravenous fluid(ivf) normal saline(n/s) at
2litres stat then 1litre 6hrly
-subcutaneous soluble insulin 10iu stat
-parenteral omeprazole and hyoscine
Other plan included: hourly bedside glucose
monitoring; input/output chart; close monitoring
of vital signs
15

5hours post admission

Latest bedside glucose level (Bgl) was

193mg/dl or 10.7mmol/l
Vital signs- blood pressure130/100mmhg, pulse 120bpm,
respiration 26cpm
She was commenced on parenteral
artesunate and ceftriaxone
Infusion was adjusted: ivf n/s 1litre 8hrly
and add pottasium chloride(kcl) 10mmol
into each 500ml of ivf
16

12hr post admission

Latest bgl was 352mg/dl

Bp 160/110mmhg, spo2 98%, pulse
120bpm. Respiration 28cpm
Sensorium was altered
She was commenced on soluble insulin
30iu in 500ml of N/S to run over 4hrs
Iv soluble insulin 10iu push
Hourly monitoring of bgl until <-12mol/l
17

15hrs post admission

Bgl 176mg/dl
She was lethargic and stuporous
Pulse 118bpm, bounding and regular with
moderate volume
Bp 140/87mmhg, respiration
40cpm(acidotic breathing)
Cardiovascular system s1 and s2
Chest- harsh breath sounds on left middle
zone/left lower zone/right upper zone
posteriorly
18

continued
Abdomen- flat and moves with respiration
and not distended. No palpable
organomegaly. Bowel sounds normoactive
Assesment was still Diabetic ketoacidosis
Plan
- Nil per oral
- Pass catether with strict input and output
chart
- Fasting lipid profile
- Parenteral artesunate and omeprazole
were continued

19

Continued

Second iv line set up as 0.9% saline 1l

12hrly
Previous ivf to continue as 500mls saline +
30iu soluble insulin + 10mmol kcl to run as
500mls 4hrly
When random blood sugar is <12mmol/l ,
switch to 5%d/s 500mls+ 10mmol kcl +
30iusoluble insulin to run as 500mls 4hrly
If>-12mmol/l(216mg/dl), switch back to
500mls ivf normal saline + 30iu soluble
insulin+10mmol kcl at 500mls 4hrly
20

Continued

2hrs after above review bgl dropped

from 352mg/dl to 176mg/dl
She was now coherent and
communicating
Abdominal and chest pain had subsided
and decision was to continue present
plan

21

Day 2 of admission
Patient had a dip in blood sugar
3.4mmol/l(61mg/dl) which necessitated
titrating the insulin infusion to 10iu soluble
insulin in 5%dextrose saline(d/s); +10mmol kcl
Catheter was removed after sustained
satisfactory input/output chart.
She was commenced on oral feeds and insulin
infusion was continued
Subcutaneous soluble insulin was
commenced, while insulin infusion was still
ongoing, at 20iu 8hrly before each meal and
bgl done before each insulin injection

22

Continued
-Following above she had
hypoglycemia:43mg/dl(2.4mmol/l)
Glucose/pottasium/insulin infusion was
stopped and she was told to eat
Next dose of subcutaneous insulin was
reduced to 15iu

23

Day 4 of admission

Bgl was 147mg/dl

Vital signs were stable
Patient not cooperating with timing of
eating and insulin administration and
she strongly counselled
Subcutaneous insulin continued and at
15iu 8am, 4pm and 12am
Ivf saline+ 5mmol kcl was maintained
24

Day 5

Bgl 167mg/dl
She was stable and bgl chart was fair
She was educated on insulin self
injection technique and identification of
symptoms of hypoglycemia

25

Day 6

Bgl done at midnight 12am was 481mg/dl

Patient took tuwo prepared from maize
flour
She was given soluble insulin at 30iu stat
before meal
Recheck bgl 6hrs later was 103mg/dl
Patient was discharged same day and
taught on diabetic diet
She was also advised to get a personal
glucometer and directed on how to give
insulin based on random blood sugar level
26

Continued

<70mg/dl
take 2units
70-130mg/dl
4units
131-180
8units
181-240
12units
241- 300
16units
301-350
20units
351-400
24units
>400
24units and come to
hospital
27

DISCUSSION/INTRODUCT
ION

Diabetic ketoacidosis is an acute major life

threatening complication of diabetes
mellitus(DM)
Mainly occurs with type 1 DM but not
uncommon with some patients with type 2
It is a complex disordered metabolic state
characterized by hypergycemia,
ketoacidosis and ketonuria
Most common early symptom of DKA are
increase in polydipsia and polyuria of
sudden onset

28

Continued

It is a primary reason for admission to

the hospital for patients with diabetes

It is counted among metabolic

emergencies that may require
management in the intensive care unit
setting

29

Continued

DKA imposes a heavy burden in terms of

economic and patient outcomes
Often requires intensive care unit
management with resultant use of
healthcare resources incurring high cost
Significant morbidity and mortality
associated with DKA in the range 2% to
14% in developed countries
Morbidity associated with DKA relates to
the severity of acid-base balance and
electrolyte disturbances that if left untreated
can result in coma and death
30

Continued

DKA accounts for 14% of all hospital

admissions of patients with diabetes and
16% of all diabetes-related fatalities.
Almost 50% of diabetes-related
admissions in young persons are related
to DKA.
DKA frequently is observed during the
diagnosis of type 1 diabetes and often
indicates this diagnosis.
31

continued

The incidence of diabetic ketoacidosis in

developing countries is not known, but it
may be higher than in industrialized
nations.

32

33

Continued

Insulin deficiency causes the body to

metabolize triglycerides and amino acids
instead of glucose for energy.
Serum levels of glycerol and free fatty
acids (FFAs) rise because of
unrestrained lipolysis, as does alanine
because of muscle catabolism.
Glycerol and alanine provide substrate
for hepatic gluconeogenesis, which is
stimulated by the excess of glucagon
that accompanies insulin deficiency..
34

Continued

Glucagon also stimulates mitochondrial

conversion of FFAs into ketones.
Insulin normally blocks ketogenesis by
inhibiting the transport of FFA
derivatives into the mitochondrial matrix,
but ketogenesis proceeds in the
absence of insulin

35

Continued

. The major ketoacids produced,

acetoacetic acid and -hydroxybutyric
acid, are strong organic acids that
create metabolic acidosis.
Acetone derived from the metabolism of
acetoacetic acid accumulates in serum
and is slowly disposed of by respiration

36

Continued

Hyperglycemia due to insulin deficiency

causes an osmotic diuresis that leads to
marked urinary losses of water and
electrolytes.
Urinary excretion of ketones obligates
additional losses of Na and K.
Serum sodium(Na) may fall from
natriuresis or rise due to excretion of
large volumes of free water.
37

continued

Pottassium(K) is also lost in large

quantities, sometimes > 300 mEq/24 h.
Despite a significant total body deficit of
K, initial serum K is typically normal or
elevated because of the extracellular
migration of K in response to acidosis

38

Definition of Diabetic
Ketoacidosis*
Acidosis

*
Ketosis
Hyperglycemia
.
39

Diabetic Ketoacidosis:
Pathophysiology
Unchecked gluconeogenesis

Hyperglycemia

Osmotic diuresis

Dehydration

Unchecked ketogenesis

Ketosis

Dissociation of ketone bodies into

hydrogen ion and anions

Anion-gap metabolic
acidosis

Often a precipitating event is identified (infection, lack of insulin

administration)

40

Insulin Deficiency

Hyperglycemia
Hyperosmolality

Glycosuria

Dehydration
Renal Failure
Shock

Electrolyte
Losses
CV
Collapse

41

Insulin Deficiency

Hyperglycemia
Hyperosmolality

Glycosuria

Lipolysis

FFAs
Ketones

Dehydration
Renal Failure
Shock

Electrolyte
Losses

Acidosis

CV
Collapse

42

Insulin Deficiency
Lipolysis

FFAs
Ketones
Acidosis

CV
Collapse

43

44

Clinical Presentation of
Diabetic Ketoacidosis
History
Thirst
Polyuria
Abdominal pain
Nausea and/or vomiting
Profound weakness

Physical exam
Kussmaul respirations
Fruity breath
Relative hypothermia
Tachycardia
Supine hypotension,
orthostatic drop of blood
pressure
Dry mucous membrane

45

Lab Findings in DKA

Severe hyperglycemia
Increased blood and urine ketones
Low bicarbonate
High anion gap
Low arterial pH
Low PCO2 (respiratory compensation)

46

Electrolyte and Fluid

Deficits in
Parameter
DKA*
DKA
Water, mL/kg

100 (7 L)

Sodium, mmol/kg

7-10 (490-700)mmol/l

Potassium, mmol/kg

3-5 (210-300) mmol/l

Chloride, mmol/kg

3-5 (210-350) mmol/l

Phosphate, mmol/kg

1-1.5 (70-105)mmol/l

Magnesium, mmol/kg

1-2 (70-140)mmol/l

Calcium, mmol/kg

1-2 (70-140)mmol/l

Estimate for a 70kg man

.
47

Initial Laboratory Evaluation

of DKA

Comprehensive metabolic profile

Serum osmolality
Serum and urine ketones
Arterial blood gases
CBC
Urinalysis
ECG
Blood cultures
48

Laboratory Diagnostic
Criteria of
DKA

Parameter

Normal range

DKA

70-100

250

7.35-7.45

7.30

22-28

15

275-295

320

<12

>12

Serum ketones

Negative

Moderate to high

Urine ketones

Negative

Moderate to high

Plasma glucose, mg/dL

Arterial pH

Serum bicarbonate, mmol/L

Effective serum osmolality, mmol/kg
Anion gap, mmol/L

Calculation: Na+ - (Cl- + HCO3-).

.
49

Formulas for Estimating

Serum Osmolality and Effective
Osmolality
Osmolality
2 x [Na+ mEq/L]
+ [glucose mg/dL] / 18

Effective Osmolality
2 x [Na+ mEq/L]
+ [glucose mg/dL] / 18

+ [BUN mg/dL] / 2.8

= Sosm (mosm/Kg H2O)

= Sosm (mosm/Kg H2O)

50

Differential diagnosis

Hyperglycemic hyperosmolar state(HHS)

Acute pancreatitis
Other causes of metabolic acidosis
alcohol ketoacidosis
lactic acidosis
uremic acidosis
starvation ketoacidosis
Hypoglycemia
51

Characteristics of DKA and

HHS
Diabetic Ketoacidosis (DKA)

Hyperglycemic Hyperosmolar State

(HHS)

Absolute (or near-absolute) insulin

deficiency, resulting in
Severe hyperglycemia
Ketone body production
Systemic acidosis

Severe relative insulin deficiency,

resulting in
Profound hyperglycemia and
hyperosmolality (from urinary free
water losses)
No significant ketone production or
acidosis

Develops over hours to 1-2 days

Develops over days to weeks

Most common in type 1 diabetes, but

increasingly seen in type 2 diabetes

Typically presents in type 2 or

previously unrecognized diabetes
Higher mortality rate
52

DKA and HHS

Diabetic Ketoacidosis (DKA)

Hyperglycemic Hyperosmolar State

(HHS)

Plasma glucose >250 mg/dL

Plasma glucose >600 mg/dL

Arterial pH <7.3

Arterial pH >7.3

Bicarbonate <15 mEq/L

Bicarbonate >15 mEq/L

Moderate ketonuria or ketonemia

Minimal ketonuria and ketonemia

Anion gap >12 mEq/L

Serum osmolality >320 mosm/L

53

Diabetic Ketoacidosis
(DKA)

Hyperglycemic Hyperosmolar State

(HHS)

Younger, type 1 diabetes

Older, type 2 diabetes

No hyperosmolality

Hyperosmolality

Volume depletion

Volume depletion

Electrolyte disturbances

Electrolyte disturbances

Acidosis

No acidosis

54

continued
Features

DKA

Alcohol
Ketoacid
osis

Starvatio Uraemic
n
acidosis
ketoacido
sis

Lactic
ketoacido
sis

PH

Plasma
glucose

Anion gap
Serum
ketones

Serum
osmolarity

55

56

Treatment With IV Fluids

and Dextrose

For severe hypovolemia, during the first 1-2 hours (in

absence of cardiac compromise), give 1-1.5 L 0.9%
NaCl
After initial volume resuscitation, or for more mild
dehydration, use intravenous fluid rate of 250-500
mL/hr
Compute corrected serum Na
For every 100 mg/dL BG elevation, add 1.6 mEq/L to Na

value

Use 0.45% NaCl if corrected Na normal

Use 0.9% NaCl if corrected Na <135

When BG(Blood glucose) reaches 200 mg/dL (DKA)

change to 5% dextrose with 0.45% NaCl at
150-250 mL/hr (ie, clamping blood glucose until anion
gap has closed in DKA)
57

Conventional Insulin
Guidelines

Initiate the correction of hypovolemic shock

with fluids, and correct hypokalemia if present,
before starting insulin
When starting insulin, initially infuse 0.1 to
0.14 units/kg/h
If plasma glucose does not decrease by 50-75
mg in the first hour, increase the infusion rate
of insulin
Continue insulin infusion until anion gap closes
Initiate subcutaneous insulin at least 2 h
before interruption of insulin infusion

.
58

Insulin drip adjustment

Glucose 60-90mg/dl
and/or if glucose falls
by > 75mg/dl
between two serial
readings
Glucose within range
Target -100-175mg/dl

Drip rate- U/hr

Decrease by U/hr

<2

0.5

2-9

10-20

2.0

>20

4.0

Continue current drip

Continue current drip

59

Insulin drip adjustment

Glucose > 175mg/dl

Drip rate- U/hr

increase by U/hr

<2

0.5

2-9

10-20

2.0

>20

4.0

>30

Call a senior doctor

60

Glucose monitoring

Aim for 100-175mg/dl

Monitor glucose level
-1hr after start of drip
- 1hr after any change in drip rate
-Every 2hrs if no change after two serial
1hr check
-Every 4hrs if no change after two serial
2hr check
61

When to Transition From

IV
Insulin
Infusion
to
SC
BG <200 mg/dL and 2 of
the following
Insulin
HCO3 15 mEq/L

Venous pH >7.3
Anion gap 12 mEq/L

62

Potassium Repletion in
DKA

Life-threatening hypokalemia can develop

during insulin treatment
Potassium reenters cells with insulinization
and correction of acidosis
The small extracellular compartment
experiences a precipitous drop of
potassium concentration
Anticipatory potassium replacement during
treatment of DKA is almost always required

63

Potassium Balance in
DKA

Potassium is dominantly intracellular

Urinary losses occur during evolution of DKA (due to
glycosuria)
Total body potassium stores are greatly reduced in any
patient with DKA
Potassium moves from inside the cell to the
extracellular space (plasma)
During insulin deficiency
In presence of high blood glucose
As cells buffer hydrogen ions

Blood levels of potassium prior to treatment are usually

high but may drop precipitously during therapy
64

Potassium Repletion in
DKA

K+ >5.2 mEq/L

Do not give K+ initially, but check serum K + with

basic metabolic profile every 2 h

Establish urine output ~50 mL/hr

K+ <3.3 mEq/L
Hold insulin and give K + 20-30 mEq/hr until

K+ >3.3 mEq/L

K+ = 3.3-5.2 mEq/L
Give 20-30 mEq K+ in each L of IV fluid to

maintain serum K+ 4-5 mEq/L

65

Causes of Morbidity and

Mortality in DKA

Shock
Hypokalemia during
treatment
Hypoglycemia
during treatment
Cerebral edema
during treatment
Hypophosphatemia

Acute renal failure

Adult respiratory
distress syndrome
Vascular thrombosis
Precipitating illness,
including MI, stroke,
sepsis, pancreatitis,
pneumonia

66

DKA Management Pitfalls

Not assessing for and/or treating underlying

cause of the DKA
Not watching K+ closely enough and/or not
replacing K+ aggressively enough
Following serial serum ketone concentrations
Following serum bicarbonate instead of the
anion gap, with misinterpretation of expansion
acidosis as persistent ketoacidosis
Interrupting IV insulin too soon (eg, patient not
yet eating, anion gap not yet closed)

67

DKA Management Pitfalls

Occurrence of rebound ketosis

consequent to inadequate insulin dosing
at transition (eg, failure to give SC insulin
when glucose is low or injudicious use
of sliding scale insulin)
Inappropriate extension of hospitalization
to fine-tune an outpatient regimen
Inadequate patient education and training
Inadequate follow-up care
68

69

Possible Precipitating Causes or

Factors in DKA: Type 1 Diabetes

Nonadherence to insulin regimen or

psychiatric issues
Insulin error or insulin injection/pump
malfunction
Poor sick-day management
Infection (intra-abdominal, pyelonephritis, flu)
Myocardial infarction
Pancreatitis
Other endocrinopathy (rare)
Steroid therapy, other drugs or substances
70

Possible Precipitating Causes or

Factors in DKA: Type 2 Diabetes

Nonadherence to medication regimen

Poor sick-day management
Dehydration
Renal insufficiency
Infection (intra-abdominal,
pyelonephritis, flu)
Myocardial infarction, stroke
Steroid therapy, other drugs or
substances
71

Predischarge Checklist

Diet information
Glucose monitor and strips
(and associated prescription)
Medications, insulin, needles
(and associated prescription)
Treatment goals
Contact phone numbers
Medic-Alert bracelet
Survival Skills training

72

Education in Type 1 Diabetes

to Prevent DKA

Recognize symptoms and findings that

require contact with a healthcare provider
Prevent ketoacidosis through selfmanagement skills:
Glucose testing
Appropriate use of urine testing
Appropriate maintenance of insulin on sick days
Use of supplemental insulin during illness

Address social factors

73

Summary

DKA is a life-threatening emergencies

Management involves
Attention to precipitating cause
Fluid and electrolyte management
Insulin therapy
Patient monitoring
Prevention of metabolic complications during

recovery
Transition to long-term therapy

Patient education and discharge planning

should aim at prevention of recurrence
74

References

Kitabchi AE, et al. Diabetes Care.

2009;32:1335-1343
Devi R, et al. Diabetes Manage.
2011;1:397-412
Kitabchi AE, Fisher JN. Diabetes
Mellitus. In: Glew RA, Peters SP, ed.
Clinical Studies in Medical Biochemistry.
New York, NY: Oxford University Press;
1987:105
75

References

American Association of Clinical

Endocrinologists. https://www.aace.com/

76