Download DKA and HHS

DKA and HHS
By; Dr. Sisay H.(EMCC specialist , AaBET Hospital)
8/17/2022
1
Outlines
- Introduction
- Definition
- Epidemiology
- Pathogenesis
- Clinical features
- Diagnosis
- Management options
8/17/2022
2
Diabetes mellitus
 Diabetes mellitus is the most common endocrine disease.
It comprises a heterogeneous group of hyperglycemic disorders characterized by high
serum glucose and disturbances of carbohydrate and lipid metabolism.
And can have both acute n chronic complications
Acute include hypoglycemia,(DKA), and hyperglycemic hyperosmolar non-ketotic
coma (HHNC).
Long-term complications include disorders of blood vessels, especially the
microvasculature.
8/17/2022
3
Definition
 DKA is a syndrome in which insulin deficiency and glucagon excess
combine to produce a hyperglycemic, dehydrated, acidotic patient with
profound electrolyte imbalance
Hyperglycemic hyperosmolar nonketotic coma (HHNC) represents a
syndrome of acute diabetic decompensation characterized by marked
hyperglycemia, hyperosmolarity and dehydration, and decreased mental
functioning that may progress to frank coma with minimal or absent ketosis
and acidosis.
8/17/2022
4
Epidemiology
 ED visits for DKA was 64 per 10,000
 Mortality to <5% of reported episodes inexperienced centers.
 Mortality is higher in the elderly due to underlying renal disease or
coexisting infection and in the presence of coma or hypotension.
 Women>men
8/17/2022
5
Pathophysiology
- Two hormonal abnormalities are largely responsible for the development of
hyperglycemia and ketoacidosis in patients with uncontrolled diabetes are
interrelated and are
1-Insulin deficiency and/or resistance.
2-Glucagon excess, which may result from removal of the normal
suppressive effect of insulin
8/17/2022
6
Cont’d
 As serum glucose concentration increases, an osmotic gradient develops,
attracting water from the intracellular space into the intravascular
compartment, causing cellular dehydration. The initial increase in
intravascular volume is accompanied by a temporary increase in the
glomerular filtration rate.
8/17/2022
7
Cont’d
As serum glucose concentration increases, the capacity of the kidneys to
reabsorb glucose is exceeded, and glucosuria and osmotic diuresis occur.
During osmotic diuresis, significant urinary loss of sodium and potassium, as
well as more modest losses of calcium, phosphate, and magnesium may occur
8/17/2022
8
Cont’d
As volume depletion progresses, renal perfusion decreases, and the
glomerular filtration rate is reduced.
Renal tubular excretion of glucose is impaired, which further worsens
hyperglycemia.
A sustained osmotic diuresis may result in total body water losses that often
exceed 20% to 25% of total body weight, or approximately 8 to 12 L in a 70kg patient
8/17/2022
9
Cont’d
This osmotic diuresis combined with poor intake and vomiting produces the
profound dehydration and electrolyte imbalance associated with DKA.
The hyperosmolarity produced by hyperglycemia and dehydration is the most
important determinant of the patient’s mental status
8/17/2022
10
8/17/2022
11
DKA/HHS
Pathogenesis
Absolute
Insulin
Deficiency
Glucagon
Catecholamines
Cortisol
Growth Hormone
Lipolysis
Proteolysis
FFAs
Gluconeogenic
Substrates
Ketogenesis
Ketoacidosis
Triglycerides
Hyperlipidemia
8/17/2022
Precipitating Factors
Gluconeogenesis
Hyperglycemia
Relative
Insulin
Deficiency
Minimal Lipolysis
Glycogenolysis
Hyperosmolality
Glucosuria
(Osmotic Diuresis)
Decreased GFR
Loss of Water
& Electrolytes
Dehydration
12
DKA/HHS Ketone Body Formation in Liver
Fatty Acids
Insulin
Glucose
Fatty Acyl-CoA
Triglycerides
Fatty Acyl-CoA
Acetyl-CoA
Acetoacetyl-CoA
b-Hydroxy-b-methylglutaryl CoA
Acetoacetate
AcetoneNADH
8/17/2022
b -Hydroxybutyrate
NAD
13
Clinical features
Usually requires precipitants or pt might not have precipitant n the precipitant
includes
 Omission or reduced daily insulin injections
 Dislodgement/occlusion of insulin pump catheter
 Infection
 Pregnancy
 Hyperthyroidism, pheochromocytoma, Cushing’s syndrome
 Substance abuse (cocaine)
 Medications: steroids, thiazides, antipsychotics, sympathomimetics
8/17/2022
14
Con’d
 Heat-related illness
 Cerebrovascular accident
 GI hemorrhage
 Myocardial infarction
 Pulmonary embolism
 Pancreatitis
 Major trauma
 Surgery
8/17/2022
15
Con’d
The clinical manifestations of DKA are related directly to hyperglycemia,
volume depletion, and acidosis and includes
 Polyuria
 Polydipsia
 Weight loss
 Nausea
 Vomiting
 Abdominal pain: common in DKA
 Impaired mental status: common in HHS
8/17/2022
16
C/F
The earliest symptoms of marked hyperglycemia are polyuria, polydipsia, and weight
loss.
As the degree or duration of hyperglycemia progresses, neurologic symptoms,
including lethargy, focal signs, and obtundation, can develop.
This can progress to coma in later stages.
Neurologic symptoms are most common in HHS, while hyperventilation and
abdominal pain are primarily limited to patients with DKA.
8/17/2022
17
Abdominal pain in DKA
Abdominal pain …………. 46 percent of patients with DKA
Abdominal pain was associated with the severity of the metabolic acidosis
but did not correlate with the severity of hyperglycemia or dehydration.
Possible causes of abdominal pain include
Delayed gastric emptying and
Ileus induced by the metabolic acidosis and associated electrolyte abnormalities
8/17/2022
18
Physical examination
Signs of volume depletion are common in both DKA and HHS and include
Decreased skin turgor,
Dry axillae and oral mucosa,
Low jugular venous pressure,
Tachycardia, and, if severe, hypotension.
Neurologic findings, noted above, also may be seen, particularly in patients with
HHS.
Patients with DKA may have
A fruity odor and
Deep respirations reflecting the compensatory hyperventilation (called Kussmaul respirations).
8/17/2022
19
Diagnosis
DKA is diagnosed with
 A blood glucose level >250 milligrams/dL (13.8 mmol/L)
 An anion gap >10 mEq/L (>10 mmol/L)
 A bicarbonate level <15 mEq/L (<15 mmol/L), and
 PH <7.3 with moderate ketonuria or ketonemia
8/17/2022
20
DKA
Factors that contribute to the lesser degree of hyperglycemia in DKA,
compared with HHS
Patients with DKA often present earlier in the course of their acute disease with
symptoms of ketoacidosis (such as shortness of breath, abdominal pain, and nausea and
vomiting), rather than late with symptoms due to hyperosmolality.
Patients with DKA tend to be younger and to have a higher glomerular filtration
rate………. glucosuria
8/17/2022
21
Con’d
HHS is “defined” by
 Severe hyperglycemia with serum glucose usually >600 milligrams/dL
(>33.3 mmol/L),
 An elevated calculated plasma osmolality of >315 mOsm/kg (>315
mmol/kg),
 Serum bicarbonate >15 mEq/L (>15 mmol/L),
 An arterial pH >7.3, and
 Serum ketones that are negative to mildly positive
8/17/2022
22
Euglycemic DKA
Blood glucose level ≤ 300 mg/dL has been reported in up to 18% of patients.
 RBS might be normal (euglycemic DKA) in
Patients presenting shortly after receiving insulin
Type 1 diabetics who are young and vomiting
Patients with impaired gluconeogenesis
Low caloric intake/starvation
Depression
Pregnancy
Patients treated with the class of drugs that block the sodium/glucose cotransporter 2
(SGLT2 inhibitors).
8/17/2022
23
Laboratory Testing
 Rapid bedside glucose
determination
 A urine test strip
 An electrocardiogram to check for
hyperkalemia
 Obtain a CBC
 Serum electrolytes
 BUN and creatinine
 Urinalysis
8/17/2022
 Venous blood gas, and
 Phosphate/magnesium/calcium
levels
Calculate the anion gap. Blood
cultures
24
Laboratory abnormalities
CBC:
 Leukocytosis is often present because of hemoconcentration and stress.
 However, a WBC count >25,000 mm3 and/or
 An absolute band count of 10,000 mm3 or more is suggestive of infection.
 sensitivity of 100% and specificity of 80%
Elevation of C-reactive protein
U/A :ketonuria
8/17/2022
25
Ketone Bodies
 In DKA, elevated serum levels of βHB and AcAc cause acidosis and
ketonuria (ketonemia).
 The nitroprusside reagent normally used to detect urine and serum ketones
only detects AcAc;
 Acetone is only weakly reactive and βHB not at all.
 Gas chromatography can be used to detect serum acetone but is expensive
and time-consuming.
(AcAc + NADH = βHB + NAD).
 A new point-of-care capillary blood ketone test for βHB levels.
8/17/2022
26
Acid-Base Abnormalities
 Wide-anion-gap metabolic acidosis.
 Hyper-chloremic acidosis
 Aggressively rehydrated with normal saline.
 Vomiting was sufficient to cause a concomitant metabolic alkalosis
8/17/2022
27
Con’d
 Serum electrolyte
 Na:decreased due to Osmotic diuresis
 K:serum potassium level is normal or elevated ,Despite total body k depletion due
to extracellular shift of potassium secondary to acidemia and increased intravascular
osmolarity caused by hyperglycemia
 Phosphorous, calcium, and magnesium : initially elevated due to hemoconcentration but later become decreased due to renal lose.
8/17/2022
28
Serum potassium
 Patients presenting with DKA or HHS have a potassium deficit that averages 300 to
600 mEq.
 A number of factors contribute to this deficit, particularly
increased urinary losses due both to the glucose osmotic diuresis and to the excretion of
potassium ketoacid anion salts…….. volume contraction-related secondary hyperaldosteronism
Gastrointestinal losses and the loss of potassium from the cells due to glycogenolysis and
proteolysis
 Despite these total body potassium deficits, hypokalemia is observed in only
approximately 5 percent of cases.
8/17/2022
29
cont...
 Patients presenting with DKA or HHS have a potassium deficit that averages
300 to 600 mEq.
 A number of factors contribute to this deficit, particularly
 increased urinary losses due both to
 The glucose osmotic diuresis and
 The excretion of potassium ketoacid anion salts (the ketoacid anions are filtered as sodium salts, but
some of the sodium is reabsorbed in the distal renal tubule in exchange for potassium as a result of
volume contraction-related secondary hyperaldosteronism).
 Gastrointestinal losses and the loss of potassium from the cells due to glycogenolysis
and proteolysis also may play a contributory role.
8/17/2022
30
cont...
Despite these large total body potassium deficits, the serum potassium
concentration is usually normal or, in one-third of patients, elevated on
admission. This is mainly due to hyperosmolality and insulin deficiency.
The rise in plasma osmolality causes osmotic water movement out of the cells.
Potassium also moves into the ECF as a result of at least two mechanisms:
The contraction of the ICF space increases intracellular potassium concentration and
favors passive potassium exit through potassium channels in the cell membrane
The frictional forces between solvent (water) and solute result in potassium being
carried out through the water pores in the cell membrane (this process is called solvent
drag)
Insulin normally promotes potassium uptake by the cells. Therefore, insulin deficiency
contributes to elevated serum potassium levels.
8/17/2022
31
Serum phosphate
Patients with uncontrolled hyperglycemia are typically in negative phosphate
balance because of
decreased phosphate intake,
an acidosis-related shift of phosphate into the extracellular fluid (ECF) when metabolic
acidosis exists, and
phosphaturia caused by osmotic diuresis.
Despite phosphate depletion, the serum phosphate concentration at
presentation is usually normal or even high because both
insulin deficiency and metabolic acidosis cause a shift of phosphate out of the cells and
as a result of ECF volume contraction.
8/17/2022
32
Con’d
 Cr: might be elevated due to pre renal azotemia
 CXR : might be normal or features of precipitant like pneumonia, PE
 HgA1C- elevated
8/17/2022
33
Serum amylase and lipase
Acute pancreatitis may precipitate or complicate DKA.
Each of these enzymes is often elevated in patients with DKA who do
not have any other clinical or radiological evidence of pancreatitis.
Therefore, the diagnosis of pancreatitis in patients with DKA should be
primarily based upon clinical findings and imaging.
8/17/2022
34
Leukocytosis
The majority of patients with hyperglycemic emergencies present with
leukocytosis, which is proportional to the degree of ketonemia.
Leukocytosis unrelated to infection may occur as a result of
hypercortisolemia and increased catecholamine secretion.
However, a white blood cell count greater than 25,000/microL or more than
10 percent bands increases suspicion for infection and should be evaluated.
8/17/2022
35
8/17/2022
36
Severity of DKA
mild
moderate
severe
Mental status
Alert
Alert/drowsy
Stupor/coma
Arterial pH
7.25-7.30
7.00-7.24
<7.00
Serum bicarbonate (mEq/L)
15-18
10 to <15
<10
Urine ketones*
Positive
Positive
Positive
Serum ketones*
Positive
Positive
Positive
Effective serum osmolality
(mOsm/kg)•
Variable
Variable
Variable
Anion gap
>10
>12
>12
8/17/2022
37
cont...
 ESO = 2[measured Na (mEq/L)] + glucose (mg/dL)/18.
 AG = (Na+) - (Cl- + HCO3-) (mEq/L).
8/17/2022
38
cont...
Be Aware of Conditions that may make DKA Diagnosis Difficult
Mixed acid base disorder (eg. vomiting may raise the bicarbonate)
 Pregnancy  normal to minimally elevated glucose levels
 Normal AG due to loss of ketones from osmotic diuresis
 Negative serum ketones due to β-hydroxybutarate
  AG + negative serum ketones = order serum β-hydroxybutarate
 Always order both urine and serum ketones
8/17/2022
39
DDx
Alcoholic ketoacidosis
Starvation ketoacidosis
Renal failure
Lactic acidosis
Ingestions
-Salicylates
-Ethylene glycol
-Methanol
8/17/2022
40
TREATMENT
 Place patients on a cardiac monitor and begin at least one large-bore (16- to 18-gauge)
IV infusion of normal saline.
 A second IV line with 0.45% normal saline at minimal rate to keep the IV line open can
be considered.
8/17/2022
41
Treatment
The goals of therapy are
(1) volume repletion,
(2) reversal of the metabolic consequences of insulin insufficiency,
(3) correction of electrolyte
(4) recognition and treatment of precipitating causes; and
(5) avoidance of complications.
The goal of treatment is
 Glucose <200 milligrams/dL (<11.1 mmol/L),
 Bicarbonate ≥18 mEq/L (≥18 mmol/L), and
 Venous pH >7.3.
8/17/2022
42
cont....
The order of therapeutic priorities is
 Volume first and foremost,
 Correction of potassium deficits, and
 Then insulin administration.
Metabolic disturbances should be corrected at the approximate rate of
occurrence or over 24 to 36 hours.
8/17/2022
43
Volume repletion




Restore intravascular volume and normal tonicity
Perfuse vital organs,
Improve GFR and lower serum glucose and ketone level
Improves the response to low dose insulin therapy.
8/17/2022
44
DKA/HHS
Typical Water and Electrolyte Deficits
Total Water
Water (ml/kg)
Na+ (mEq/kg)
Cl- (mEq/kg)
K+ (mEq/kg)
PO4 (mmol/kg)
Mg++ (mEq/kg)
Ca++ (mEq/kg)
8/17/2022
DKA
HHS
6
50-100
7-10
4-7
3-12
1
1
1
9
100-200
5-13
5-15
4-6
3-7
1-2
1-2
45
Cont’d
 The average adult patient has a water deficit of 100 mL/kg (5 to 10 L) and a
sodium deficit of 7 to 10 mEq/kg
 NS is the preferred fluid. WHY Is NS preferred?
 Before initial electrolyte results, administer the initial fluid bolus of
isotonic saline at a rate of 15 to 20 mL/kg/h during the first hour
Estimated (corrected) plasma sodium* =
Measured plasma or serum sodium concentration + (2 *
(Serumglucose - 100) / 100)
8/17/2022
46
Fluid
 After the second or third hour, optimal fluid replacement depends upon the
state of hydration, serum electrolyte levels, and the urine output.
 The most appropriate IV fluid composition is determined by the sodium
concentration "corrected" for the degree of hyperglycemia.
If the "corrected" serum sodium concentration is :
Less than 135 mEq/L, isotonic saline should be continued at a rate of approximately
250 to 500 mL/hour.
Normal or elevated, the IV fluid is generally switched to one-half isotonic saline at a
rate of 250 to 500 mL/hour in order to provide electrolyte-free water.
8/17/2022
47
8/17/2022
48
Con’d
 After the initial bolus,
 Administer normal saline at 250 to 500 cc/h in hyponatremic patients, or
 Give 0.45% normal saline at 250 to 500 cc/h for eunatremic and hypernatremic
patients.
OR
The first 2 L are administered rapidly over 0 to 2 hours,
the next 2 L over 2 to 6 hours, and
then an additional 2 L over 6 to 12 hours.
This will replace 50% of the volume lost and the next 50 % will be
administered over the next 12 hrs.
8/17/2022
49
Con’d
 When the blood glucose level is 250 milligrams/dL (13.8 mmol/L), change to
5%dextrose in 0.45% normal saline
 During this phase of treatment we may consider
 Central venous pressure or
 Pulmonary artery wedge pressure monitoring in the elderly or in those with heart or
renal disease, for excess fluid may contribute to the development of adult respiratory
distress syndrome and cerebral edema.
 The mean plasma glucose concentration has been noted to drop by 18% after
the administration of saline solution without insulin.
8/17/2022
50
Potassium Replacement
 Total-body potassium deficits in the range of 3 to 5 mEq/kg due to
Insulin deficiency,
Metabolic acidosis,
Osmotic diuresis, and
Frequent vomiting
 The initial serum concentration is usually normal or high because of
The intracellular exchange of potassium for hydrogen ions during acidosis,
The total-body fluid deficit, and
Diminished renal function
 Initial hypokalemia indicates severe total-body potassium deficits, and large
amounts of replacement potassium are usually necessary in the first 24 to 36
hours.
Although the actual incidence of initial hypokalemia in DKA is not known, a few
studies report an occurrence of 4% to 6%.
8/17/2022
51
cont...
During initial therapy for DKA, the serum potassium concentration may fall
rapidly, primarily due to
The action of insulin promoting reentry of potassium into cells and,
To a lesser degree, the dilution of extracellular fluid,
Correction of acidosis, and
Increased urinary loss of potassium.
If these changes occur too rapidly, precipitous hypokalemia may result in fatal
cardiac arrhythmias, respiratory paralysis, paralytic ileus, and rhabdomyolysis.
The rapid development of severe hypokalemia is potentially the most lifethreatening electrolyte derangement during the treatment of DKA.
8/17/2022
52
Con’d
 Replacement depends on initial serum k+
 If initial [K+] >5.2 initiate IV infusion of regular insulin at 0.1-0.14 units/kg/hr*.
Repeat [K+] STAT in 2 hours
 If initial [K+] is >3.3 and <5.2 add 20-30 mEq of K+ to each liter of fluid and insulin
drip.
 However, potassium replacement must be done cautiously if renal function remains
depressed and/or urine output does not increase to a level >50 mL/hour.
 The decrease in serum potassium during therapy is reported to be about 1.5 mEq/L
(1.5 mmol/L) and parallels the drop in glucose and the dose of insulin.
8/17/2022
53
Con’d
 If initial [K+] is <3.3 hold insulin drip and give K+ @20-30 mEq/h until
[K+] is >3.3 then initiate insulin drip
 The rate of KCL infussion is at a rate no faster than
10 mEq/h via peripheral IV or
20 mEq/h via central line access
During the first 24 hours, 100 to 200 mEq or of KCl is usually required
 TARGET;; to raise the serum potassium concentration into the normal range
of 4 to 5 mEq/L.
Insulin therapy should be delayed until the serum potassium is above
3.3 mEq/L to avoid complications such as cardiac arrhythmias, cardiac
arrest, and respiratory muscle weakness.
8/17/2022
54
cont...
Because the most rapid changes occur during the first few hours of therapy,
measure the plasma potassium level initially every 2 hours.
If oliguria or renal insufficiency is present, withhold or decrease potassium
replacement.
8/17/2022
55
cont...
 What is the drug of choice if concomitant hypophosphatemia?
 Potassium chloride,
 Potassium phosphate
8/17/2022
56
cont...
 What is the preferred route?
Oral potassium replacement is safe and effective and is the preferred route of
replacement as soon as the patient can tolerate oral fluids.
In DKA, initial potassium replacement is usually by an intravenous line.
8/17/2022
57
cont...
How do u treat a DKA patient if the K level is 8.2 and had
A. ECG manifestation?
B. No ECG manifestation?
8/17/2022
58
Magnesium
Magnesium deficiency is a common problem in patients with DKA without
renal disease.
Both the initial pathophysiologic process and therapy for DKA induce
profound magnesium diuresis.
Magnesium deficiency may exacerbate vomiting and mental changes,
promote hypokalemia and hypocalcemia, and/or induce fatal cardiac
dysrhythmia.
If there is concern for hypomagnesemia, we recommend adding magnesium
8/17/2022
to the IV fluids, with the typical adult patient requiring 1 to 3 g for repletion.
59
Sodium
Osmotic diuresis leads to excessive renal losses of sodium chloride in the
urine.
However, the presence of hyperglycemia tends to artificially lower the serum
sodium levels.
Standard teaching is that
1.6 mEq (1.6 mmol) should be added to the reported sodium value for every 100
milligrams (5.55 mmol) of glucose >100 milligrams/dL (>5.5 mmol/L).
However, the correction factor is probably 2.4, especially for blood glucose levels
>400 milligrams/dL (>22.2 mOsm/L).
 Estimated (corrected) plasma sodium* =
Measured plasma or serum sodium concentration
8/17/2022
+ (2 * (Serumglucose - 100) / 100)
60
Insulin
 Insulin therapy lowers the serum glucose concentration (by
Decreasing hepatic glucose production, the major effect, and
Enhancing peripheral utilization, a less important effect),
Diminishes ketone production (by reducing both lipolysis and glucagon secretion), and
May augment ketone utilization.
 Inhibition of lipolysis requires a much lower level of insulin than that
required to reduce the serum glucose concentration.
 Therefore, if the administered dose of insulin is reducing the glucose
concentration, it should be more than enough to stop ketone generation.
8/17/2022
61
cont...
 The current initial therapy of choice, as recommended by the ADA, is regular
insulin infused at 0.1 units/ kg/hr up to 5 to 10 units/hr, mixed with IV fluids.
 Because the half-life of regular insulin is 3 to 10 minutes, insulin should be
administered IV by constant infusion rather than by repeated bolus.
The half-life of IV insulin is 4 to 5 minutes, with an effective biologic halflife at the tissue level of approximately 20 to 30 minutes.
8/17/2022
62
INSULIN
 Once hypokalemia ([K+] <3.3 mEq/L [<3.3 mmol/L]) is excluded regular
insulin can be administered after the initial fluid bolus, or simultaneously in a
second IV line
 At a rate of 0.1 to 0.14 unit/kg/h rate of drop of RBS expected/hr is 5075 mg/dl,
 If the drop is < expected give a 0.14 unit/kg bolus and resume insulin drip
rate.
Another option is to increase the insulin infusion rate by 1 unit/h.
The incidence of nonresponse to low-dose continuous IV insulin
administration is 1% to 2%, with infection being the primary reason for failure
to respond.
8/17/2022
63
cont...
In HHS or moderate to severe DKA, treatment can be initiated with
An IV bolus of regular insulin (0.1 units/kgbody weight) followed within 5 minutes by
A continuous infusion of regular insulin of 0.1 units/kg/hour (equivalent to
7 units/hour in a 70-kg patient)
An IV loading dose of insulin is not recommended in
 Children and
 New-onset young adult diabetics and is optional in adults
8/17/2022
64
cont...
Higher doses do not generally produce a more prominent hypoglycemic
effect, probably because the insulin receptors are fully saturated and
activated by the lower doses .
However, if the serum glucose does not fall by at least 50 to 70 mg/dL (2.8 to
3.9 mmol/L) from the initial value in the first hour, check the IV access to be
certain that the insulin is being delivered and that no IV line filters that may
bind insulin have been inserted into the line.
After these possibilities are eliminated, the insulin infusion rate should be
doubled every hour until a steady decline in serum glucose of this magnitude
is achieved.
8/17/2022
65
Con’d
 Resolution of hyperglycemia usually occurs earlier than resolution of the
anion gap, So once the serum glucose is 200 milligrams/dL add dextrose to
the IV fluids and reduce the insulin drip rate to 0.02 to 0.05 unit/kg/h
 Maintain the serum glucose between 150 and 200 milligrams/dL (8.3 and 11
mmol/L) until the resolution of DKA.
Occasionally a 10% dextrose solution may be needed to maintain glucose
levels
 In patients with euglycemic DKA, dextrose should be added to the IV fluids
at the start of insulin therapy.
8/17/2022
66
cont...
Continue the insulin infusion until the resolution of DKA
glucose <200 milligrams/dL (<11 mmol/L) and
two of the following:
a serum bicarbonate level >15 mEq/L,
a venous pH >7.3, and/or
a normal calculated anion gap.
Monitor laboratory values every 1 to 2 hours to ensure that insulin is being
administered in the desired amount.
8/17/2022
67
Precipitant
 The most common events are
 infection (often pneumonia or
urinary tract infection) and
 discontinuation of or
inadequate insulin therapy.
8/17/2022
68
Monitoring
 The serum glucose should initially be measured every hour until stable,
 While serum electrolytes, blood urea nitrogen (BUN), creatinine, and venous
pH (for DKA) should be measured every two to four hour, depending upon
disease severity and the clinical response.
 Beta-hydroxybutyrate can then be measured every two hours depending on
the clinical response.
8/17/2022
69
Transition from IV Insulin
The American Diabetes Association (ADA) guidelines for DKA recommend that IV
insulin infusion be tapered and a multiple-dose, subcutaneous insulin schedule be
started when the blood glucose is <200 mg/dL (11.1 mmol/L) and at least two of the
following goals are met :
Serum anion gap <12 mEq/L (or at the upper limit of normal for the local laboratory)
 Serum bicarbonate ≥15 mEq/L
 Venous pH >7.30
 If the patient is unable to eat, it is preferable to continue the IV insulin infusion
8/17/2022
70
cont...
 Can consider switch to SC insulin when
 AG normalized
 BS < 250 mg/dl
 Insulin IV requirements < 2U/h
 Patient able to eat
 Hemodynamically stable
8/17/2022
71
cont...
 The method of insulin transition varies, and there is no set protocol
 In patients who can eat, the transition should include a short-acting and longacting insulin given when DKA has resolved.
One method consists of giving 10 units of SC regular insulin 30 to 60 minutes
before the insulin infusion is stopped and 80% of the usual long-acting insulin
dose 1 to 2 hours before discontinuing the IV insulin infusion
8/17/2022
72
Con’d
 Another method is to give 50% of the usual long-acting insulin dose 2 hours
before the IV insulin infusion is stopped.
 If the patient is a newly diagnosed diabetic, one can estimate a starting dose
of long-acting insulin at 0.1 to 0.2 unit/kg.
 Additional glucose coverage can be provided with short-acting insulin as
needed.
 Continue glucose checks every hour for 2 hours.
8/17/2022
73
SC Insulin
In uncomplicated mild to moderate DKA, the use of rapid acting SC insulin
may be another treatment option, although the standard treatment remains
continuous IV insulin.
The dose of SC rapid-acting insulin is
 an initial injection of 0.2 unit/kg followed by 0.1 unit/kg every hour, or
 an initial dose of 0.3 unit/kg followed by 0.2 unit/kg every 2 hours until blood glucose
is <250 milligrams/dL (<13.8 mmol/L).
Then, the insulin dose is decreased by half and administered every 1 or 2
hours until resolution of DKA.
This can avoid intensive care admissions and lower hospital costs, but still
requires close nursing monitoring that is difficult to accomplish in the ED or
in a regular hospital bed.
8/17/2022
74
HYPOPHOSPHATEMIA
Serum phosphate levels often are normal or increased on presentation of DKA
and do not reflect the total-body phosphate deficits secondary to enhanced
urinary losses.
Phosphate (similar to glucose and potassium) reenters the intracellular space
during insulin therapy, resulting in low phosphate concentrations.
Hypophosphatemia is usually most severe 24 to 48 hours after the start of
insulin therapy.
8/17/2022
75
cont...
Hypophosphatemia is usually most severe 24 to 48 hours after the start of
insulin therapy.
Acute phosphate deficiency (<1.0 milligram/dL) can result in
 Hypoxia,
 Skeletal muscle weakness,
 Rhabdomyolysis,
 Hemolysis,
 Respiratory failure, and
 Cardiac dysfunction.
8/17/2022
76
cont....
 No established role for initiating IV K2PO4 for DKA in the ED.
 In general, do not give IV phosphate unless the serum phosphate
concentration is <1.0 milligram/dL (0.323 millimol/L).
If absolutely necessary (a phosphate level <1.0 milligram/dL early in
therapy), IV phosphate replacement should be administered as
IV K2PO4, 2.5 to 5 milligrams/kg (0.08 to 0.16 millimol/kg).
Monitor serum calcium level if giving supplemental phosphate.
8/17/2022
77
cont...
Undesirable side effects from IV phosphate administration include
 Hyperphosphatemia,
 Hypocalcemia,
 Hypomagnesemia,
 Metastatic soft tissue calcifications,
 Hypernatremia, and
 Volume loss from osmotic diuresis.
8/17/2022
78
HYPOMAGNESEMIA
Osmotic diuresis may cause hypomagnesemia and deplete magnesium stores
from bone.
Hypomagnesemia may inhibit parathyroid hormone secretion, causing
hypocalcemia and hyperphosphatemia.
If the serum magnesium concentration is <2.0 mEq/L (<1.0 mmol/L) or
symptoms are suggestive of hypomagnesemia, give magnesium sulfate 2
grams IV over 1 hour.
Obtain serum magnesium and calcium levels on presentation and 24 hours
into therapy.
Monitor levels every 2 hours if there is initial hypomagnesemia or
hypocalcemia or if symptoms suggestive of hypomagnesemia or hypocalcemia
occur
8/17/2022
79
Bicarbonate and metabolic acidosis
 Give bicarbonate if the initial pH is ≤6.9, but do not give bicarbonate if
the pH is ≥7.0.
Severe metabolic acidosis is associated with numerous
 Cardiovascular(impaired contractility, vasodilation, and hypotension) and
 Neurologic (cerebral vasodilation and coma) complications.
 Selected patients who benefit from cautious alkali therapy, including those
with
Decreased cardiac contractility and peripheral vasodilatation, and
Patients with life-threatening hyperkalemia and coma
8/17/2022
80
cont....
HCO3-
if ph is <7 at a dose of 100 mEq of sodium bicarbonate in 400 mL of water with 20 mEq KCl at
200 mL/h for 2 hours until the venous pH >7.0 and
If the pH remains <7.0 despite the infusion, repeat the infusion until pH >7.0
ADA recommendation
If PH 6.9-7.0
 50mEq of NaHCo3
+ 200ml sterile water+10mEq KCl over 1 hour
If Ph <6.9
 100mEq of NaHCo3 + 400ml sterile water+10mEq KCl over 2 hours
 Repeat dose of bicarbonate every 2 hours till PH>7.
 Check [K+] every 2 hours.
8/17/2022
81
cont...
Metabolic acidosis refractory to routine therapy may be
Secondary to unrecognized infection (lactic acidosis)
 Rarely insulin antibodies, or
 Improper preparation or administration of the insulin drip.
8/17/2022
82
Advantage of bicarbonate
More of theoretical advantage
 In case of severe acidosis
-Improve myocardial contractility
- Improve catecholamine tissue response
- Decrease work of breathing
 In case of Hyperkalemia
-Elevate ventricular fibrillation threshold
8/17/2022
83
Disadvantages
Severe & worsening hypokalemia
Paradoxical CNS acidosis
Impair oxyhemoglobin dissociation
Hyper tonicity
Sodium overload
8/17/2022
84
Identify and Treat the Precipitating factor
Insulin omission – MOST COMMON CAUSE of DKA
New diagnosis of diabetes
Infection / Sepsis
Myocardial infarction
Small rise in troponin may occur without overt ischemia
ECG changes may reflect hyperkalemia
Thyrotoxicosis
Drugs
8/17/2022
85
8/17/2022
DKA & HHS by KDA
86
DISEASE COMPLICATIONS
8/17/2022
87
PROGNOSIS
In general, the greater the initial serum osmolality, BUN, and blood glucose
concentrations, and the lower the serum bicarbonate level (<10 mEq/L), the
greater the mortality.
Infection and myocardial infarction are the main contributors to
mortality. Additional factors that increase morbidity include
Old age,
Severe hypotension,
Coma, and
Underlying renal and cardiovascular disease.
Severe volume depletion leaves the elderly at risk for deep venous
thrombosis.
8/17/2022
88
cont...
Mortality in DKA results mainly from
sepsis
pulmonary and cardiovascular complications in the elderly
fatal cerebral edema in children and young adults
8/17/2022
89
Complications of Therapy
Hypoglycemia
Hypokalemia or Hyperkalemia
Fluid Overload
Hyperchloremic Acidosis
Cerebral Edema
ARDS
Thromboembolic Episodes
8/17/2022
90
Acute respiratory distress syndrome
is a rare complication of therapy
But can develop, particularly in the elderly and those with impaired
myocardial contractility.
Overly aggressive fluid therapy Is a risk factor.
8/17/2022
91
Cerebral edema
In very young children, new-onset diabetics, and adolescents with DKA
Cerebral edema generally occurs 6 to 10 hours after the initiation of therapy;
there are no warning signs, and the associated mortality rate is 90%.
Premonitory symptoms are
 Severe headache, incontinence, change in arousal or behavior, pupillary changes, blood
pressure changes, seizures, bradycardia, or disturbed temperature regulation.
8/17/2022
92
Best Practice to Prevent Cerebral Edema
8/17/2022
93
cont...
Any change in neurologic function early in therapy is an indication for IV
mannitol (1 to 2 grams/kg).
Mannitol should be given before respiratory failure or obtaining confirmatory
CT scans because serious morbidity and mortality may be prevented.
Hypertonic saline (3%), 5 to 10 mL/kg over 30 minutes, may be an alternative
to mannitol.
Intubation and fluid restriction are generally necessary.
There are no data supporting glucocorticoid use in DKA-related cerebral
edema
8/17/2022
94
shock
Shock that is unresponsive to aggressive fluid therapy suggests
 Gram-negative bacteremia or
 Silent myocardial infarction
8/17/2022
95
Special populations
RECURRENT DKA PATIENTS
- insulin noncompliance
- cocaine use are the commonest causes
 Patients Benefit from drug rehabilitation and social workers
8/17/2022
96
Con’d
PATIENTS WITH INSULIN PUMPS
Their pumps disconnected and turned off and should be treated just like
any other patient.
Reinstitution of pump therapy should start in the same time frame as
switching over to SC insulin in the non–pump user.
8/17/2022
97
Con’d
DKA IN PREGNANCY
Pregnant women prone to DKA due to relative insulin deficiency , vomiting
and urinary tract infections.
8/17/2022
98
cont...
The mortality from DKA was
 90% in historical controls before the development of exogenous insulin and
 50% after insulin was introduced;
 with appropriate supportive therapy, it has reached the current levels of 5%
to 7%.
8/17/2022
99
cont...
Morbidity in DKA is largely iatrogenic
Hypokalemia from inadequate potassium replacement,
Hypoglycemia from inadequate glucose monitoring,
Failure to replenish glucose in IV solutions when the serum glucose concentration drops
below 250 to 300 mg/dL,
Alkalosis from overaggressive bicarbonate replacement, and
Pulmonary edema from overaggressive hydration.
The primary causes of death remain
Infection, especially pneumonia,
Arterial thromboses, and
Shock
8/17/2022
100
DKA/HHS
Poor Prognostic Indicators
Advanced Age
Low pH
Hypotension
Marked Hyperosmolality
High BUN
Associated Diseases
8/17/2022
101
HYPERGLYCEMIC HYPEROSMOLAR STATE
8/17/2022
102
HHS
HHS represents a syndrome of acute diabetic decompensation characterized
by marked hyperglycemia, hyperosmolarity, dehydration, and decreased
mental function that may progress to frank coma.
Hyperosmolar hyperglycemic non-ketotic state/coma/syndrome and nonketotic hyperglycemic coma
 Typically found in a debilitated patient with poorly controlled or undiagnosed
type 2 diabetes mellitus, limited access to water, and commonly, a
precipitating illness.
8/17/2022
103
HHS
HHS is “defined” by severe hyperglycemia with
 Serum glucose usually >600 milligrams/dL (>33.3 mmol/L),
 An elevated calculated plasma osmolality of >315 mOsm/kg (>315
mmol/kg),
 Serum bicarbonate>15 mEq/L (>15 mmol/L),
 An arterial pH >7.3, and serum ketones that are negative to mildly positive
in a 1:2 dilution (by nitroprusside method).
8/17/2022
104
cont....
The development of HHS is attributed to three main factors:
(1) insulin resistance and/or deficiency;
(2) an inflammatory state with marked elevation in proinflammatory
cytokines (C-reactive protein, interleukins, tumor necrosis factors) and
counterregulatory hormones (growth hormone, cortisol) that cause increased
hepatic gluconeogenesis and glycogenolysis; and
(3) osmotic diuresis followed by impaired renal excretion of glucose.
8/17/2022
105
Pathogenesis of DKA &
HHS
8/17/2022
106
Diagnostic Criteria for (DKA) and (HHS)
8/17/2022
107
cont...
A sustained osmotic diuresis may result in total body water losses that often
exceed 20% to 25% of total body weight, or approximately 8 to 12 L in a 70kg patient.
8/17/2022
108
cont....
The relative lack of severe ketoacidosis in HHS is poorly understood and has
been attributed to three possible mechanisms:
(1) higher levels of endogenous insulin than are seen in diabetic
ketoacidosis, which inhibits lipolysis;
(2) lower levels of counterregulatory “stress” hormones; and
(3) inhibition of lipolysis by the hyperosmolar state itself.
8/17/2022
109
Conditions That May Precipitate HHS
8/17/2022
110
Clinical Features
 The prodrome of HHS is significantly longer than that of DKA.
 Clinically, extreme dehydration, hyperosmolarity, volume depletion, and
CNS findings predominate.
 If they are awake, patients may complain of fever, thirst, polyuria, or
oliguria.
 Complaints are often nonspecific and may include weakness, anorexia,
fatigue, dyspnea, or chest or abdominal pain.
8/17/2022
111
Some Drugs That May Predispose Individuals to the
Development of HHS
8/17/2022
112
8/17/2022
113
references
Uptodate
Tintinali
Rosen
8/17/2022
114