糖尿病酮體症的診斷與治療 - vm.ntu.edu.tw
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2010/8/14
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糖尿病酮體症的診斷與治療糖尿病酮體症的診斷與治療
蘇璧伶Bi-Ling Su
臨床動物醫學研究所獸醫專業學院獸醫專業學院台灣大學
National Taiwan University 2010
DM‐definition
• Is a metabolic disease
• An absolute or relative insulin deficiency that results in abnormal metabolism, particularly of glucose and fat.
• Prolonged hyperglycemia is the most obvious consequence of insulin deficiencyconsequence of insulin deficiency.
• Ketoacidosis can occur without therapy
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Insulin withdrawal
Protein catabolism Hyperglycemia
Hepatic lipogenesis&
ketogenesis
aminoacidemia
Urinary nitrogen
Glucosuria & osmotic diuresis
water & electrolyte loss
Dehydration
Peripheral circulatory failure
Ketonemia&ketouria
loss of Na & K
Adrenal stimulation
Hypotension hypoperfusion
Cardiovascular myocardial damage
Musculoskeletal lactic acid production
metabolic acidosis
GI bacterial translocation
Hepatic unable to remove bacteria and
toxinRenal ARF Pulmonary ARDS
Lypolysis Insulin resistance
Signalments
• Species: Canine
• Breeds: Chow chow
• Age: 3 y/o
• Sex: castrated male
• BW: 19.7 kg
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Chief complaint& history
• Polyuria noted since 1 month ago and h l i f d l t k t i t li ihyperglycemia found last week at private clinic
• Weight loss noted for 2 weeks and loss for 2 kg
• Loss appetite and decreased activity for 5 days
• No defecation for 3 days• No defecation for 3 days
• Urination once last night
Chief complaint& history
• Multiple skin abscess observed 2 months ago
– Treatment response: wax and wane
– Augmentin, Baytril, ketoconazole, lysozyme
– Ciprofloxacin
– Thyroxin 5 microgram/kg
– Prednisolone 0.2mg/kgPrednisolone 0.2mg/kg
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Physical exam
• BW:19.7kg
• BT:38.1℃
• HR: 156bpm RR:24/min
• weakness and weak pulse
• Bp: 60~62mmHg (5# right hindlimb)
• 6~8% dehydration
Insulin withdrawal
Protein catabolism Hyperglycemia
Hepatic lipogenesis&
ketogenesis
aminoacidemia
Urinary nitrogen
Glucosuria & osmotic diuresis
water & electrolyte loss
Dehydration
Peripheral circulatory failure
Ketonemia&ketouria
loss of Na & K
Adrenal stimulation
Hypotension hypoperfusion
Cardiovascular myocardial damage
Musculoskeletal lactic acid production
metabolic acidosis
GI bacterial translocation
Hepatic unable to remove bacteria and
toxinRenal ARF Pulmonary ARDS
Lypolysis Insulin resistance
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How to know the animal with DKA?
1. 呼吸時可以聞到水果味2 尿液試紙檢出含k b d 通常無氧代2. 尿液試紙檢出含keton body，通常無氧代謝有三種不同的酮體：acetoacetone, acetone and β‐hydroxybutyrate，但一般尿液試紙無法驗出β‐hydroxybutyrate
3. 計算anion gap可以用來幫忙診斷DKA。3. 計算anion gap可以用來幫忙診斷DKAAnion gap = (Na + K) ‐ (Cl +HCO3)，若AG>20則表示循環中有沒有測量的陰離子(ketoacids)
Blood gas analysis
12/22 Ref. value
10:00
pH(ven) 6 93 7 31 7 24pH(ven) 6.93 7.31‐7.24
HCO3(ven) 5.1 20‐29
PCO2(ven) 27 32‐49
AnGap 33.8
BE ‐24.2
tCO2(ven) 5.8 21‐31
PO2(ven) 67 24‐48 •Metabolic acidosis
21.57‐32.27
PO2(ven) 67 24 48
SO2(ven) 75%
Na 140 144‐160
K 3.6 3.5‐5.8
Cl 105 109‐122
•Metabolic acidosis• Ketoacidosis•Uremic acids•Lactatic acids
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Chronological approach of blood gas analysis
1 Determine the origin of the blood sample Arterial, venous, mixed
2 H A id i lk l i2 pH Acidemia, alkalemia
3 pCO2 Respiratory acidosis, respiratory alkalosis, normal
4 HCO3‐ Metabolic acidosis, metabolic alkalosis, normal
5 Base excess Increased, reduced, normal
6 Identify the primary pathology Metabolic imbalance, respiratory imbalance, mixed
7 Compensation Compensated, not compensated
Determine the origin of the blood sample
• Arterial: SaO2 more than 90%
• Mixed or venous: SaO2 less than 75%
– If there is any doubt over the origin of the sample, take a fresh from a vein and compare the data with that of the previous sample.
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Blood gas interpretation
1. pH: is the patient normal, acidemic (pH<7.35) or alkalemic (pH>7.45)?
2. Evaluate the respiratory component. Is the respiratory p y p p ycomponent normal or does that the patient have a respiratory alkalosis and hypocapnia(PaCO2 <35mmHg) or respiratory acidosis and hypercapnia(PaCO2>45mmHg)?
3. Evaluate the metabolic component. Is the metabolic component normal or does that the patient have a metabolic acidois(HCO3<18mmol/L or base deficit <‐metabolic acidois(HCO3<18mmol/L or base deficit <4mEq/L) or metabolic alkalosis(HCO3>24mmol/L or base deficit >+4mEq/L) ?
4. To determine which component (respiratory or metabolic) is the primary contributor.
Primary Changes & Compensatory Response for Acid-Base Disorders
Primary Disturbance pH Change Primary Change Compensatory Response
Metabolic Acidosis ↓ pH ↓ HCO3 / BE ↓ PCO2, 0.7mmHg decrement in Pco2 for each 1mEq/L decrement
in [HCO3]Metabolic Alkalosis ↑ pH ↑ HCO3 / BE ↑ PCO2, 0.7mmHg increment in
PCO2 for each 1mEq/L increment in [HCO3]
Acute Respiratory Acidosis
↓ pH ↑ PCO2 ↑ HCO3, 1.5mEq/L increment in HCO3
-for each 10mmHg
increment in PCO2
Chronic Respiratory Acidosis
↓ pH ↑ PCO2 ↑ HCO3, 3.5mEq/L increment in HCO3
-for each 10mmHg
increment in PCO2
Acute Respiratory Alkalosis
↑ pH ↓ PCO2 ↓ HCO3, 2.5mEq/L decrement in HCO3
-for each 10mmHg
decrement in PCO2
chronic Respiratory Alkalosis
↑ pH ↓ PCO2 ↓ HCO3, 5.5mEq/L decrement in HCO3
-for each 10mmHg
decrement in PCO2
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Blood gas analysis
12/22 Ref. value
10:00
pH(ven) 6 93 7 31 7 24pH(ven) 6.93 7.31‐7.24
HCO3(ven) 5.1 20‐29
PCO2(ven) 27 32‐49
AnGap 33.8
BE ‐24.2
tCO2(ven) 5.8 21‐31
PO2(ven) 67 24‐48 •Metabolic acidosis
21.57‐32.27
PO2(ven) 67 24 48
SO2(ven) 75% 93‐100
Na 140 144‐160
K 3.6 3.5‐5.8
Cl 105 109‐122
•Metabolic acidosis• Ketoacidosis•Uremic acids•Lactatic acids
Blood exam12/22 Ref.
Hb g/dL 16.6 12‐18
PCV % 46.9 37‐55
RBC 106/uL 7.68 5.5‐8.5
MCV fl 61.1 60‐77
12/22 Ref.
Albumin g/dL 3.5 2.3‐4.0
ALKP U/L 118 23‐212
ALT U/L 19 10‐100
MCH pg 21.6 19.5‐24.5
MCHC g/dL 35.4 32‐36
Platelets 103/uL 529 200‐900
WBC /uL 44000 6000‐17000
Band %
Seg % 9360‐77(3000‐
11400)
Eosino % 2‐10(100‐750)
Baso % 1
12 30(1000
AST U/L 68 0‐50
Bili. t NE 0‐0.9
BUN mg/dL 62 7‐27
Crea mg/dL 3.0 0.5‐1.8
Glucose mg/dL 839 74‐143
TP g/dL 6.3 5.2‐8.2
Ca. mg/dL 10.1 7.9‐12
Phospho mg/dL 7.2 2.5‐6.8
Lympho % 612‐30(1000‐
4800)
Mono % 3‐10(150‐1350)
NRBC
Toxic reaction cPL (+)
Na+ mmol/L 144‐160
K+ mmol/L 3.5‐5.8
Cl‐ mmol/L 109‐122
•Leukocytosis with toxic reation•AzotemiaHyperglycemia
• Hyperphophatemia
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Tentative diagnosis
DKADKAAcute
pancreatitis Acute
pancreatitis pp
Hypotension hypoperfusionHypotension hypoperfusion
Sepsis Sepsis
Acute renal failure
Acute renal failure
ARF -treatment• Correct underlying causes
Correct extracellular fluid volume• Correct extracellular fluid volume• Correct hyperkalemia• Correct acid-base imbalance• Restore urine output• Control vomitingControl vomiting• Nutrition • Dialysis: peritoneal or hemodialysis
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Correct underlying causes
• Acute pancreatitis• Diabetic ketoacidosis• Sepsis
Correct extracellular fluid volume
• Dehydrated because of vomiting, diarrhea d iand anorexia
• Overhydrated if they are anuric and have no way to excrete excessive fluid loads
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Clinical signs used to classify dehydration
Water loss(% body wt)
Dehydration status
signs
1-4 Very mild Non detectable
5-6 Mild Skin doughy, inelastic, slight loss of skin turgor; dry mucous membranes, conjunctiva injected
7-9 Moderate Definite loss of skin turgor, with slow return; enophthalmos; capillary refill time, ca 2-3 seconds,
10-12 Severe Pronounced loss of skin turgor, with incomplete return; peripheral vasoconstriction, cold extremities; CRT > 3 sec.
13-15 Very severe Vascular collapse, renal shutdown, death
Avoid of hyperhydrationClinical signs of hyperhydration
• Pulmonary edema (the terminal event of h d ti )overhydration)
• First:Increased serous nasal discharge• Followed by chemosis (結合膜水腫)• Finally, pulmonary congestion is
auscultated before edema developsauscultated before edema develops
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Correct extracellular fluid volumeCorrect hyperkalemia
Correct acid-base imbalance
Symptomatic therapy for hyperkalemia
Degree Management
Mild 5.5-6.5
Potassium-free fluid:0.9% NaCl5% dextrose
Moderate6.5-8
1. Potassium-free fluids2. Calcium gluconate: 0.5-1.0 mL 10% solution,
10-15 min slow IV (does not lower the K level, reverses toxic effects on the heart)reverses toxic effects on the heart)
3. Dextrose and insulin: 0.25-0.5IU/kg regular insulin, IM or IV + 2g dextrose per Unit insulin (shift K from ECF into ICF)
4. Sodium bicarbonate: based on blood gas analysis or 1-2 mEq/kg
Severe >8.0
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Metabolic acidosis• pH < 7.4, [HCO3-] <20 mEq/L, BE• Normal pCO2 (before respiratory compensation →
hyperventilation, causes this to decrease)• Causes:
– Gastrointestinal : vomiting, diarrhea, pancreatitis– Drugs and toxins: ethylene glycol
Renal failure hypoadrenocorticism– Renal failure, hypoadrenocorticism– Diabetic ketoacidosis– Anaerobic metabolism: exercise, shock, lactic acidosis
• HCO3- <15mEq/L should be treated with sodium bicarbonate
Restore urine output
• Normal urine output is 1-2 mL/kg/hr.Oli i & i• Oliguria & anuria– Furosemide (Lasix): 2-4mg/kg, or
0.66mg/kg/hr CRI– Low-dose dopamine: 3-5 μg/kg/min IV CRI– Mannitol: 0.25-0.5g/kg IV.
• Monitor the blood pressure– Dog: systolic 148;diastolic 87; MAP 102– Cat: systolic 125;diastolic 75; MAP 100
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Tentative diagnosis
DKADKAAcute
pancreatitis Acute
pancreatitis pp
Hypotension hypoperfusionHypotension hypoperfusion
Sepsis Sepsis
Acute renal failure
Acute renal failure
Sepsis mechanism
2nd HitImmune‐
1st Hit
Pro‐inflammatory mediators Anti‐inflammatory mediators
paralysis
HemostasisSIRS Infection
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Criteria for SIRS in dogs and cats
Criteria for SIRS (≥2 of the following)
Dogs Cats
Tachypnea >20 /min >40/min
Tachycardia (or in cats bradycardia)
>120 bpm <140, >225 bpm
Increased or decreased <38 or >39C <37.8 or >39 Crectal temperature
Increased or decreased WBC count
>18,000 or <5000 >19,000 or <5000
Physical parameters associated with sepsis
Early sepsis Late sepsis
Tachypnea Tachypnea
Bounding pulses Thready pulses
CRT <1 sec CRT > 2sec
Red mucous membranes Pale mucous membranes
Mental depression Stupor, coma
Hyperthermia Hypothermia
Organ failure
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Hematologic and biochemical parameters associated with sepsis
Early sepsis Late sepsis
Increased (early) or decreased blood HypoglycemiaIncreased (early) or decreased blood glucose
Hypoglycemia
Leukocytosis ( or leukopenia) Leukopenia (or leukocytosis)
Mild to moderate thrombocytopenia Thrombocytopenia
Hypercoagulability ( diagnosis difficult) Hypocoagulability (increased PT, aPTT)
lb h lbHypoalbuminemia Severe hypoalbuminemia
Evidence of organ dysfunction:Increased bilirubin, liver enzymesIncreased BUN/creatinineDecreased PaO2, increased PaCO2
Organ dysfunction in septic shock
• Respiratory dysfunction
– Acute lung injuryg j y
– Acute respiratory distress syndrome
• Renal dysfunction
– Acute renal failure
• Gastrointestinal and hepatic dysfunction
• Microcirculatory dysfunction
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Early sepsis
Hyperdynamic septic shock↑cardiac output↓systemic vascular resistence
Patient at risk
interventionsepsis
Development of sepsis
Mon
Vital
b
HR, RR, BT, MM color, CRT, Pulses
Treatmen
t
↓ ynormal to high BP
Death
Septic shock
nito
ring
Lab
Others
PCV, alb, TP,BUN, Glu, Eletro, blood gas
BP, pulse oximetry, urine outputHypodynamic septic shock
↓cardiac output↑systemic vascular resistence↓ BP
Treatments• Identify underlying causes
• Fluid therapy
• Antibiotics
• Hypotension
• Hypoglycemia
• Oxygen
GI• GI protectants
• Analgesics
• Nursing care
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Circulatory support
Fluid therapy Indication Comments
Isotinic crystalloids Intravascular volume replacementI t titi l fl id d fi it
May precipitate i t titi l d iInterstitial fluid deficits
Maintenance interstitial edema in patients with capillary leak or a low COP
Synthetic colloids (hetastarch, Dextran‐70)
Volume replacementColloid osmotic support
Dose‐relatedcoagulopathies have been documented
Human albumin Volume replacementColloid osmotic support
Monitor closely for reaction
Albumin supplementation
Fresh frozen plasma CoagulopathiesFactors deficienciesVolume replacementColloid osmotic support
Circulatory support
Fl id th I di ti C tFluid therapy Indication Comments
Packed red blood cells Anemia
Fresh whole blood AnemiaThrombocytopenia CoagulopathiesFactors deficienciesVolume replacementColloid osmotic support
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Antibiotics
Gram‐positive Gram‐negative
Drugs
Amikacin
Ampicillin
Ampicillin‐sulbactam
Azithromycin
Cefazolin
Cefotetan
Drugs
Amikacin
Ampicillin‐sulbactam
Azithromycin
Cefazolin
Cefotaxime
CefotetanCefotetan
Cefoxitin
Chloramphenicol
Clindamycin
Enrofloxacin
Gentamycin
Cefotetan
Cefoxitin
Ceftazidime
Enrofloxacin
Gentamycin
Antibiotics
Gram‐positive Gram‐negative
Drugs
Imipenem‐cilastatin
Meropenem
Vancomycin
Drugs
Imipenem‐cilastatin
Meropenem
Piperacillin‐tazobactam
Trimethoprim‐sulfamethoxazole
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Hypotension
Inotropes vasopressors
Drugs Dose
Dobutamine 5‐20g/kg/min in saline or D5W
Dopamine 2‐10g/kg/min in saline or D5W
Epinephrine D: 0.005‐0.05g/kg/min in saline or D W
Drugs Dose
Epinephrine D: 0.005‐0.05g/kg/min in saline or D5WC:0.01‐1.0g/kg/min in saline or D5W
saline or D5WC:0.01‐1.0g/kg/min in saline or D5W
Dobutamine
• A synthetic catecholamine
• Stimulates β1‐adrenergic receptors
• Increasing myocardial contractility
• Side effect:
– Exacerbate existing arrhythmias, esp. Ventricular arrhythmiasarrhythmias
– Produce new arrhythmias and increase heart rate
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Dobutamine • 12.5 mg/mL
• CRI=2‐40 μg/kg/minμg g
• Initiated at the lower dose and increased every 2‐10 min until desired effect
• BW × 0.24 ml in 50ml saline, 1ml/hr=1μg/kg/min, then can be increased as needed
• Should not be mixed with bicarbonate, heparin, hydrocortisone sodium succinate, cefalothin, penicillin or insulin
Dopamine
• Short‐term use in animals with systolic d f tidysfunction
• Management of acute oliguric renal failure (dog)
• Precursor of noradrenaline (norepinephrine)
• Stimulates cardiac α and β adrenergic• Stimulates cardiac α and β‐adrenergic receptors, as well as peripherally located dopaminergic receptors
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Dopamine
• 40mg/ml
• 1‐10 μg/kg/min, CRI
• BW × 0.075 ml in 50ml saline, 1ml/hr=1μg/kg/min, then can be increased as needed
• Inactivated when mixed with sodium bicarbonate or other alkaline IV solutionsbicarbonate or other alkaline IV solutions
Therapy of the dog
• Sodium bicarbinate supplement
– 0.3*19(BW)*24(BE)/0.7=195.43ml
• 40ml NaHCO3 + 10ml saline 25ml/hr
• Fluid therapy
– 0.9%saline +20mEq/L KCL 80ml/hr
• Actrapid®Actrapid®– 0.5IU/kg
• Augmentin 20mg/kg iv
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Blood gas analysis(after NaHCO3 infusion)
12/22 12/22 Ref. value
10:00 12:00
H( ) 6 93 6 99 31 24pH(ven) 6.93 6.99 7.31‐7.24
HCO3(ven) 5.1 7.3 20‐29
PCO2(ven) 27 33 32‐49
AnGap 33.8 37.3
BE ‐24.2 ‐21.3
tCO2(ven) 5.8 8.2 21‐31
PO2(ven) 67 38 24‐48PO2(ven) 67 38 24 48
SO2(ven) 75% ‐ 93‐100
Na 140 153 144‐160
K 3.6 2.5 3.5‐5.8
Cl 105 111 109‐122
Glucose 839 632 74‐143
time 10:30 10:40 10:50 11:00 11:10 11:20 11:50 12:10 12:20 13:20 14:00 14:30 15:30
HR 156 128 138 137 146 151 154 150 150 144 132 150 144
RR 24 42 48 48 36 42 42 42 42 42 54 42
Bp 60~62 60~62 70 64 60~62 60~62 60~62 60 70 68~70 68 70 64
BT 38 1 38 1 38 1 38 3 39 7 39 7 40 2
12/22
BT 38.1 38.1 38.1 38.3 39.7 39.7 40.2
Spo2 88~9495~96( on O2)
100 98 91
Na 140 153 152 155
K 3.6 2.5 2.5 2.9
Cl 105 111 107 115
Gucose 839 731 632
InsulinActrapid(A)
/A 0 25IU/kg
A 3IUInsulatardInsulin
0.5iu/kgA 0.25IU/kg Insulatard
(In)0.5IU/Kg
Fluid 1 NaHCO3 40ml
Fluid 2 NS(KCL20mEq/L) 60ml/hr NS(20mEq/L) 80ml/hr NS(40mEq/L) 60ml/hrNS(50mEq)50ml/hr
Dopa 3ml/hr
Fentanly2mcg/kr/hr
Urine UB size 4*3.4cmUB size 5*3.4cm
UB size 4*4cm
導尿管(16ml)
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12/22pmtime 15:30 16:00 16:30 17:00 17:30 18:00 18:30 19:00 19:30 20:00 20:30 21:00 22:00 23:00
HR 144 144 132 144 150 156 156 150 156 150 150 150 156
RR 42 48 48 54 48 54 48 36 48 42 48 48 44
Bp 64 72 70~72 66 70 70 66‐78 70 62~64 60 62 62 70Bp 64 72 70 72 66 70 70 66 78 70 62 64 60 62 62 70
BT 40.2 39.8 39.4 39.3 39.5 39.2 39.1 39.4 39.5 39.7
Spo2 91 97 95 97
Na 155 155 153 151
K 2.9 2.9 2.7 3.4
Cl 115 115 111 112
Gucose 419 446 369 209
Insulin A 0.5IU/kg In 0.4IU/kg
Fluid 1 LR 8ml/hr LR 48ml/hr
Fluid 2 NS(50mEq/L)50ml/hr NS(60mEq/L)30ml/hr NS(60mEq/L)20mlhrNS(60mEq/L)
20ml/hrNS(60mEq)25ml/hr
NS(50mEq/L)25ml/hr
Dopa 5mc/kg/hr
Fentanly 2ml/hr stop
Urine導尿管(16ml)
0ml/hr/kg
0.13ml/kg/hr 0.1ml/kg/hr 0.1ml/kg/hr
time 02:00 03:00 04:00 05:00 06:00 08:00 09:00 11:00 21:00 22:00 23:00 00:00
HR 165 120 132 174 162 186 176 150 156 156
RR 42 36 42 42 48 42 48 44 54
Bp 72 65 64 62 62 7276~78
62 70 70
BT 39 39.6 39.4 39.6 39.4 39.3 39.7 40.5
12/23
Spo2 99 97 96 96 97 98 95 97 98
Na 154 151 155
K 4.2 3.4 4
Cl 111 112 113
glucose 255 220 244 262 209 289
InsulinIn 0.5IU/kg
A 0.25IU/kg
fluid 1 LR 8ml/hr LR 48ml/hr LR25ml/hr
/NS(60mEq
/fluid 2
NS(50mEq)50ml/hr
NS(60mEq/L)20ml/hr
NS(60mEq)
25ml/hr
NS(50mEq/L)25ml/hr
stop
Dopa 5ml/hr
Fentanly 2ml/hr stop
urine <0.1 <0.1 <0.1 0.1ml/kg/hr <0.1ml/hr/kg
mannitol 1g/kg Lasix 2mg/kg iv
vomit vomit
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time 00:00 01:30 02:00 03:00 04:00 05:00 06:00 08:00 09:00 11:00 13:00 16:30
HR 156 156 165 120 132 174 162 186 176 156
RR 54 42 36 42 42 48 42 16
Bp 70 70 72 65 64 62 62 72 76~78 76
BT 40 5 39 39 6 39 4 39 6 39 4 39 3 39 9 38 4
12/23
BT 40.5 39 39.6 39.4 39.6 39.4 39.3 39.9 38.4
Spo2 98 99 97 96 96 97 98 95 95
Na 155 154 159
K 4 4.2 4.1
Cl 113 111 116
glucose 289 255 220 244 262 189 162 100
Insulin A 0.25IU/kg In 0.5IU/kg
fluid 1 LR25ml/hr LR15ml/hr
fluid 2 stop FFP10ml/hr
Dopa 5ml/hr
Fentanly
urine(ml/kg/hr)
0.1 <0.1 <0.1 <0.1
mannitol 1g/kg mannitol 0.5g/kg Lasix 2mg/kg iv
vomit vomit PD
38.5
39.0
39.5
40.0
40.5
41.0
80
100
120
140
160
180
200
13:30 16:30 17:00 19:30 22:00 0:00 7:00 13:00
Na 152 155 153 151 155 154 159
K 2.5 2.9 2.7 3.4 4 4.2 4.1
36.5
37.0
37.5
38.0
0
20
40
60
80
11:0012:0014:0014:3016:0017:0018:0019:0020:0021:0022:0000:0002:0003:0004:0005:0006:0008:0011:0016:3017:3018:30
RR
HR
BP
BT
Cl 107 115 117 112 113 117 116
Fluid rate
5o(50mEq/L)
330(60mEq/L)
30
17:30•Lasix 2mg/kg iv
18:30•Mannitol 0.5g/kg iv
20:00•Mannitol 0.5g/kg iv
8:00Mannitol 1g/kg
11:00Lasix 2mg/kg
PD placement
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Therapy of DKA
• Identify and treat the underlying disease process or stress factors that are contributing to theor stress factors that are contributing to the release of stress hormones or promoting insulin resistance and ketone production
• Reduce serum glucose level, which will halt osmotic diuresis and lower serum osmolality
• Replace fluid lostp
• Replace electrolytes lost
• Restore acid‐base balance
胰島素的選擇
• Insulinsu
– Actrapid (Novo Nordisk)(IV, IM, SC): neutral insulin, onset ½ hour, maximum effect: between 1st and 3rd hour, duration of action: 8 hour.
– Dosage:
• dog: 0 2‐0 5 IU/kg IM or IVdog: 0.2 0.5 IU/kg, IM or IV
• Cat: 0.1‐0.2 IU/kg, IM or IV
• 目標：血糖維持在200mg/dl 以下
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400
500
600
700
800
900
Glucose Glucose
0
100
200
300
10:00 12:00 14:30 16:45 17:20 18:30 19:30 22:00 23:30 0:00 1:00 2:00 4:00 6:00 7:00 9:00 11:00 13:00 15:00 16:30
Actrapid
Insulatard
13:30 16:30 17:00 19:30 22:00 0:00 7:00 13:00
Na 152 155 153 151 155 154 159
K 2.5 2.9 2.7 3.4 4 4.2 4.1
Cl 107 115 117 112 113 117 116
Fluid rate
5o(50mEq/L)
330(60mEq/L)
30
17:30•Lasix 2mg/kg iv
18:30•Mannitol 0.5g/kg iv
20:00•Mannitol 0.5g/kg iv
8:00Mannitol 1g/kg
11:00Lasix 2mg/kg
PD placement
Biochemical profile12/22am
12/22pm
12/23 Ref.
Albumin g/dL 3.5 2.3 2.3‐4.0
ALKP U/L 118 23‐212
12/23 12/23 Ref. value
8:15 13:30
pH(ven) 7.21 7.32 7.31‐7.24ALKP U/L 118 23‐212
ALT U/L 19 10‐100
AST U/L 68 0‐50
Bili. t NE 0‐0.9
BUN mg/dL 62 72 90 7‐27
Crea mg/dL 3.0 3.4 5.7 0.5‐1.8
Glucose mg/dL 839 74‐143
TP g/dL 6.3 5.2‐8.2
HCO3(ven) 9.6 12.8 20‐29
PCO2(ven) 26 27 32‐49
AnGap 37.2 34.6
BE ‐14.2 ‐8.9
tCO2(ven) 10.4 13.6 21‐31
PO2(ven) 67 64 24‐48
Ca. mg/dL 10.1 7.9‐12
Phospho mg/dL 7.2 2.5‐6.8
Na+ mmol/L 144‐160
K+ mmol/L 3.5‐5.8
Cl‐ mmol/L 109‐122
SO2(ven) 84 90 93‐100
Na 154 159 144‐160
K 4.2 4.1 3.5‐5.8
Cl 111 116 109‐122
Glucose 162 74‐143
2010/8/14
28
2nd ~ 4th day
ARF PD
Acute pancreatitis FFP
Hypoalbuminemia FFP
Hypotension Dopamine FFP
GI sign
Bacterial translocation
sepsis
Tienam
Augementin
metronidazole
GI protectants PPN
Force feeding
Clinic care
Baby food
12/23pm after PDtime 17:30 18:30 19:30 21:30 23:30 00:30 01:30 03:00 05:00 06:00 07:00
HR 162 186 174 144 160 148 164
RR 36 48 48 24 56 24 40
Bp 76 80 78 80 80 96 92 76
BT 38.8 39.7 39.6 39.3 39.4 38.7 39
Spo2 100 95 99 96 96 96Spo2 100 95 99 96 96 96
Na 157
K 4
Cl 115
glucose 105 174 97 83 97 96
Insulin In 0.5IU/kg
fluid 1LR
15ml/hr
fluid 2 FFP 10ml/hr Stopfluid 2 FFP 0ml/hr Stop
Dopa 5ml/hr 6ml/hr
Fentanly
urine(ml/kg/hr)
<0.1
diarrhea diarrhea
PD380ml for 40mins
400ml for 40mins
2010/8/14
29
3rd day12/22 12/24 Ref.
Hb g/dL 16.6 14.4 12‐18PCV % 46.9 37.9 37‐55
RBC 106/uL 7 68 6 78 5 5‐8 5 12/22 12/23 12/24 RefRBC 10 /uL 7.68 6.78 5.5‐8.5
MCV fl 61.1 55.9 60‐77MCH pg 21.6 21.2 19.5‐24.5MCHC g/dL 35.4 38.0 32‐36
Platelets 103/uL 529 314 200‐900
WBC /uL 44000 8600 6000‐17000
Band %
Seg % 93 73 60‐77(3000‐11400)
Eosino % 1 1 2‐10(100‐750)
/ / /
Albumin g/dL 3.5 2.3 2.3 2.3‐4
ALKP U/L 118 207 23‐2
ALT U/L 19 24 10‐1
AST U/L 68 474 0‐5
Bili. t NE 1.5 0‐0
BUN mg/dL 62 90 84 7‐2Eosino % 1 1 2 10(100 750)
Baso %
Lympho % 6 9 12‐30(1000‐4800)
Mono % 18 3‐10(150‐1350)
NRBCToxic
reactionToxic
reaction
Crea mg/dL 3.0 5.7 5.4 0.5‐1
Glucose mg/dL 839 92 74‐1
TP g/dL 6.3 5.1 5.2‐8
Ca. mg/dL 10.1 7.9‐
Phospho mg/dL 7.2 2.5‐6
12/24amtime 06:00 07:00 08:00 09:00 11:00 12:00 12:30 13:00 14:00 15:00 16:00
HR 164 152 135 144 144 148 138 120 120
RR 40 24 24 18 30 24 24 20
Bp 92 76 86‐92 84 76 106 88‐90 82‐86 100 100 98
BT 39 38 3 38 4BT 39 38.3 38.4
Spo2 96 95 96 95 96 97 99
Na 163 153
K 3.3 3.1
Cl 118 114
glucose 96 121 128 140
Insulin
fluid 1 PPN(2%glu) 15ml/hrPPN(2% glu+20mEqKCL)
15ml/hr
fluid 2 LR 19ml/hr FFP 10ml/hr
Dopa 6ml/hr 7ml/hr 5ml/hr
Fentanly 5ml/hr
urine(ml/kg/hr)
0.3 0.42 0.88 1.18
PD In 400ml Q40mins
diarrhea diarrhea diarrhea
2010/8/14
30
12/24 pmtime 16:00 17:00 18:00 19:00 20:00 21:00 22:00 00:00 03:00 06:00 08:00
HR 120 150 124 144 128 126
RR 20 18 18 30 20 30
Bp 98 108 106 90 102‐104 90
BT 38.5 38.5
Spo2 99 96 94Spo2 99 96 94
Na 154
K 2.8
Cl 112
glucose 212 104 104 225 140 121
InsulinIn
0.5IU/kg
fluid 1 PPN(2%glu+20mEq KCl) 15ml/hr PPN(2%glu+30mEq KCl) 25ml/hr
fluid 2 FFP 10ml/hr NO NS(20mEqKCL) 10m/hr 12ml/hr
Dopa 5ml/hr 3ml/hr
Fentanyl 2ml/hr stop
urine(ml/kg/hr)
2.8 3.8 4.15 3.36 2.55 2.18 1.89 1.76
PD In 400ml Q40mins
diarrhea diarrhea
Clinicare 20ml
4th day
12/24 12/25 Ref.
Albumin g/dL 2 3 2 4 2 3‐4 0
12/24 12/25 Ref.
Hb g/dL 14.4 13.2 12‐18
PCV % 37.9 36.7 37‐55 Albumin g/dL 2.3 2.4 2.3‐4.0
ALKP U/L 207 253 23‐212
ALT U/L 24 41 10‐100
AST U/L 474 437 0‐50
Bili. t 1.5 2.8 0‐0.9
BUN mg/dL 84 62 7‐27
Crea mg/dL 5.4 3.8 0.5‐1.8
Glucose mg/dL 92 44 74 143
PCV % 37.9 36.7 37 55
RBC 106/uL 6.78 6.5 5.5‐8.5
MCV fl 55.9 56.6 60‐77
MCH pg 21.2 20.3 19.5‐24.5
MCHC g/dL 38.0 36 32‐36
Platelets 103/uL 314 256 200‐900
WBC /uL 8600 12600 6000‐17000
Band %
Seg % 73 5260‐77(3000‐
11400) Glucose mg/dL 92 44 74‐143
TP g/dL 5.1 5.6 5.2‐8.2
Na mmol/L 154 155 144‐160
K mmol/L 2.8 2.8 3.5‐5.8
Cl mmol/L 112 115 109‐122
)
Eosino % 1 22‐10(100‐
750)
Baso %
Lympho % 9 1512‐30(1000‐
4800)
Mono % 18 313‐10(150‐1350)
Toxic reaction
2010/8/14
31
12/25 amtime 6:00 08:00 08:30 10:00 11:00 12:00 13:00 14:00
HR 128 126 134 148 138 144 128 148
RR 20 30 30 24 20 28 24 24
Bp 90 86 80 96 92‐98 98 98‐102Bp 90 86 80 96 92 98 98 98 102
BT 38.5 38.8
Spo2 94 99 99 97 98 96 96
Na 155
K 2.8
Cl 115
glucose 140 121 44 80 52 41 58
InsulinIn
0.5IU/kg
Feeding20mlc Glucose iv
Glucose iv bolusFeedinglinic bolus
Glucose iv bolus
fluid 1PPN(2%glu+30mEq KCl)
25ml/hr35ml/hr PPN(2%glu 40mEqKCl)
35ml/hrPPN(40mEqKCl+5%glu)
35ml/hrPPN(7%glu) 25ml/hr
PPN(10%glu)
fluid 2 NS(20mEqKCL) 12m/hr FFP 10ml/hr
Dopa 3ml/hr 5ml/hr
urine(ml/kg/hr)
1.89 1.76 3.6 6.1 5.65
PD In 400ml Q40mins
diarrhea
12/25 pmtime 14:00 15:00 16:00 17:00 18:00 19:00 20:00 22:00 00:00
HR 148 156 136 156 148 140 136 152 148
RR 24 30 20 28 28 36 20 24 30
Bp 98‐102 106 104‐108 142 114‐118 108‐110 114‐116 116‐120 92‐96
BT 38.7 38.9
Spo2 96 96 96 95 100 100 97 95 94
Na 152
K 2.9
Cl 113
glucose 58 100 76 68 78 67
Insulin
Feeding 10ml clinic 10ml clinic 20ml clinic 20ml clinic
fluid 1 PPN(10%glu) 25ml/hrfluid 1 PPN(10%glu) 25ml/hr
fluid 2 FFP 10ml/hr
Dopa 5ml/hr 4ml/hr
urine(ml/kg/hr)
2.83 3.83 2.57 3.08 2.98
PD Not smooth and stopped
diarrhea diarrhea diarrhea
2010/8/14
32
4th day
Time 11:00(after
12:00 13:00 14:30 15:30 17:30 22:00 24:00
bolus)
Glu 80 52 41 58 100 76 78 67
Bp 92~98 98~102
104~106 114~118 116~120 92~96
Fluid PPN5%
PPN 7%
PPN 10 %
Feed 15:00 21:00 24:00Clincare20ml
Clincare20ml
Clincare20ml
Therapy•PPN (10% glu+ 40mEq/L) •FFP 15ml/hr•Dapomine 3ml/hr•Feeding Q3H 20ml clincare
5th day
• Better activity and less frequency of diarrhea
• Normal urination output
• Still unwilling to eat by himself
• No vomiting noted
• Bp:90~110mmHg
2010/8/14
33
5th day
12/25 12/26 Ref.
Hb g/dL 13.2 13.2 12‐18
PCV % 36.7 39 37‐55
12/25 12/26 Ref.
Albumin g/dL 2 4 2 5 2 3‐4 0PCV % 36.7 39 37 55
RBC 106/uL 6.5 6.92 5.5‐8.5
MCV fl 56.6 56.4 60‐77
MCH pg 20.3 19.1 19.5‐24.5
MCHC g/dL 36 33.8 32‐36
Platelets 103/uL 256 192 200‐900
WBC /uL 12600 50700 6000‐17000
Band % 1
Seg % 52 6560‐77(3000‐
11400)
Albumin g/dL 2.4 2.5 2.3‐4.0
ALKP U/L 253 23‐212
ALT U/L 41 10‐100
AST U/L 437 0‐50
Bili. t 2.8 2.6 0‐0.9
BUN mg/dL 62 50 7‐27
Crea mg/dL 3.8 2.8 0.5‐1.8
Glucose mg/dL 44 104 74 143)
Eosino % 22‐10(100‐
750)
Baso %
Lympho % 15 412‐30(1000‐
4800)
Mono % 31 303‐10(150‐1350)
Glucose mg/dL 44 104 74‐143
TP g/dL 5.6 5.2‐8.2
Na mmol/L 155 160 144‐160
K mmol/L 2.8 2.5 3.5‐5.8
Cl mmol/L 115 111 109‐122
12/25amtime 01:00 03:00 06:00 07:00 08:00 10:00 12:00 13:30 14:00 15:30 16:00
HR 128 132 138 150 160 136 128
RR 24 30 24 20 36 28 30
Bp 118 102 108 120 128 124 94
BT 38.7 38.9
Spo2 96 98 98 98 99 96 95
Na 160
K 2.5
Cl 111
glucose 95 150 197 116 57 72 78
Insulin In 0.5IU/kg
Feeding 20ml clinic 20ml clinic 20ml clinic 20ml clinic 20ml clinic 20ml clinic
fluid 1PPN(10%glu 40mEqKcl) 40ml/hr
PPN30ml/hr
PPN 20ml/hrNS(20mEq) 10ml/hr
PPN 30ml/hr PPN(50mEq) 31ml/hr
fluid 2 FFP 10ml/hr
Dopa 4ml/hr 3ml/hr
urine(ml/kg/hr)
2.87 2.3 2.57 2.8 3.16
2010/8/14
34
12/26pmtime 14:00 15:30 16:00 17:00 18:00 19:00 20:00 21:00 22:00 23:00 00:00
HR 136 128 132 144 132 148 180 162
RR 28 30 28 28 30 30 30
Bp 124 94 74 102 98 104 90~96 94
BT 39.8 40
Spo2 96 95 97 99 98 97
Na 160
K 2.5
Cl 111
glucose 78 78 123 148 103
Insulin
Feeding 20ml clinic 20ml clini 20ml clinic 20ml clinic20ml clinicclinic
fluid 1 PPN(50mEq) 31ml/hr PPN 30ml/hr
fluid 2 FFP 10ml/hr no NewFFP 10ml/hr
Dopa 3ml/hr 4ml/hr
urine(ml/kg/hr)
3.16 2.57 1.57 1.160.75
Lasix 1mg/kg iv
5th dayTime 3:00 6:00 7:00 10:00 12:00 13:30 15:30 17:30 19:30 21:30
Glu 95 150 197 116 57 72 74 78 123 148
Bp 118 98‐102 120 128
Fluid FFP(5)PPN(35)
FFP(10)PPN(30)
FFP(10)PPN(20)Saline(10)
FFP(10)PPN(30)NS stop
FFP(10)PPN(30)
FFP(10)PPN(30)
Feed 20mlclincare
20mlclincare
20mlclincare
20mlclincare
20mlclincare
20mlclincare
25mlclincare
20mlclincare
Insulatard9 IU
•PPN+30mEq/L KCl
2010/8/14
35
8th ~9th day
12/27 12/28 12/29 12/30 Ref.
Hb g/dL 12.1 12.4 12.4 10.8 12‐18
PCV % 33.8 34.4 34.6 30.6 37‐55PCV % 33.8 34.4 34.6 30.6 37 55
RBC 106/uL 5.9 5.99 5.87 5.22 5.5‐8.5
MCV fl 57.3 57.4 58.7 58.6 60‐77
MCH pg 20.5 20.7 21.1 20.7 19.5‐24.5
MCHC g/dL 35.8 36 35.8 35.3 32‐36
Platelets 103/uL 197 310 266 323 200‐900
WBC /uL 110500 76300 39800 29900 6000‐17000
Band % 2
Seg % 86 93 93 9360‐77(3000‐
11400))
Eosino % 2 2‐10(100‐750)
Baso %
Lympho % 1 2 2 312‐30(1000‐
4800)
Mono % 10 5 5 23‐10(150‐1350)
Toxic reation
8th ~9th day
12/27 12/28 12/29 12/30 Ref.
Albumin g/dL 2.6 2.6 2.5 2.4 2.3‐4.0
ALKP U/L 670 23‐212
ALT U/L 54 10‐100
AST U/L 191 0‐50
Bili. t 4.1 2.6 1.2 0.8 0‐0.9
BUN mg/dL 35 21 18 25 7‐27
Crea mg/dL 1.8 1.2 1.0 1.9 0.5‐1.8
Glucose mg/dL 418 217 130 74‐143
TP g/dL 6.4 6.5 5.2‐8.2
Na mmol/L 158 163 166 160 144‐160
K mmol/L 2.9 3.3 3.4 4.2 3.5‐5.8
Cl mmol/L 115 119 121 118 109‐122
2010/8/14
36
12/27time 01:00 03:00 05:00 06:00 07:00 08:00 09:00 11:00 12:00 13:00 14:00 15:00
HR 144 168 144 172 168 160 162 144 156
RR 30 31 30 36 28 28 30 22 28
Bp 86 100 84 96 104 102 82
BT 40.1 39.8 39 39.2 40.3 39.2 39.1
Spo2 98 100 95 96 14 97 97
Na
K
Cl
glucose 152 396 447 254 129 368 386
Insulin In 0.5IU/kg In 0.5IU/kg
Feeding 20ml clinic 20ml clinic20ml clinic
20ml clinic
20ml clinicclinic clinic
fluid 1PPN 30ml/hr
NS(20mEqKCl)10ml/hrPPN 30ml/hr
PPN(5% glu 50mEqKcl) 30ml/hrNS(20mEqKcl)10ml/hr
PPN+NS stop
fluid 2 FFP stopped FFP 10ml/hr FFP stopRS(40mEq)40ml/hr
Dopa 4ml/hr 5ml/hr 4ml/hr
urine(ml/kg/hr) 2.19 2.19 1.2 2.76 4.08 1.56 3.23 2.45
pred 0.4mg/kg
12/27~12/28time 16:00 17:00 18:00 19:00 21:00 00:00
12/28 01:00
02:00 03:00 04:00 06:00 08:00 09:00
HR 132 132 150 120 120 110
RR 30 24 24 24 30 20RR 30 24 24 24 30 20
Bp 104 108 110 110 118 124
BT 38.2 38.4 38.3 38.1
Spo2 96 96 98 97 95 96
Na
K
Cl
glucose 408 210 185 170 131 71 125 156
Insulin In 0 2IU/kgInsulin In 0.2IU/kg
Feeding
20ml clinic 20ml clinic 20ml clinic 20ml clinic 20ml clinic 20ml clinic
fluid 1
fluid 2 RS(40mEq)40ml/hr
Dopa 4ml/hr
urine(ml/kg/hr)
2.55 1.63 1.48 2.44 2.19 3.1 1.8 10.5 2.3
2010/8/14
37
12/28time 10:00 12:00 13:00 14:00 15:00 16:00 17:00 18:00 20:00 21:00 22:00 24:00
HR 102 100 108 112 120 108 102
RR 16 20 24 20 24
Bp 114 108 114 116 120 128 108
BT 37.8 38.2 38.8
Spo2 97 95 96
Na
K
Cl
glucose 175 146 102 123 219
Insulin In 0.2u/kg
Feeding 20ml clinic 40ml clinic 40ml clinic 40ml clinic 40ml clinic
fl id 1 RS(40 E )40 l/hfluid 1 RS(40mEq)40ml/hr
Dopa 4ml/hr stop
urine(ml/kg/hr)
1.27 0.8 1.53 0.59 9.36 1.02 0.45 0.33
Lasix1mg/kgLasix0.5mg/
kg
Follow up
• Discharged at 13th Jan (23 days)
• Calories:560Kcal each meal
• Insulatrad :14IU (21.6kg; 0.65IU/kg)
2010/8/14
38
Feline DKA
Insulin withdrawal
Protein catabolism Hyperglycemia
Hepatic lipogenesis&
ketogenesis anorexia
aminoacidemia
Urinary nitrogen
Glucosuria & osmotic diuresis
water & electrolyte loss
Dehydration
Peripheral circulatory failure
Ketonemia&ketouria
loss of Na & K
Feline hepatic lipidosis
Adrenal stimulation
Hypotension hypoperfusion
Cardiovascular myocardial damage
Musculoskeletal lactic acid production
metabolic acidosis
GI bacterial translocation
Hepatic unable to remove bacteria and
toxinRenal ARF Pulmonary ARDS
Lypolysis Insulin resistance
Control of Diabetes mellitus
2010/8/14
39
治療與控制: 分類
Si l D• Simple Dm
• Diabetic ketoacidosis
• Possible non‐insulin dependent Dm in cats
• Secondary Dm• Secondary Dm
治療之基本原則
飲食的種類，附飲食的種類，附飲食的種類，附加作用之藥物飲食的種類，附加作用之藥物
胰島素的選擇胰島素的選擇動物及主人的配
合動物及主人的配
合
2010/8/14
40
動物及畜主的配合
• 動物的生活習慣 • 任食習慣之改變
• 主人的作息時間 • 打針及餵食時間
• 上下班時間
• 食物的適口性
胰島素分類
• 短效型 Regular Insulin ( RI )作用時間 5 ~ 7短效型 Regular Insulin ( RI ) 作用時間 5 7 小時
• 中效型 Isophane Insulin Suspension ( NPH ) 作用時間 18 ~ 24 小時
• 長效型 Extended Insulin Zinc Suspension 作用時間 24 ~ 36 小時
2010/8/14
41
商品化的胰島素製劑
– Caninsulin: 30% amorphous zinc insulin, 70% crystalline zinc insulin. 40IU/mL
– Insulatard (Novo Nordisk)= isophane insulin(NPH), onset 1 ½ hour, maximum effect: between 4th and 12th hour, duration of action:24 h 100IU/ Lhour. 100IU/mL
Caninsulin® dog
體重(kg) 依動物體重補充之
體重 初始劑量 • 每日施打一次重補充之劑量(IU)
<10 1 6 6+1=7
接近10 2 10 10+2=12
10‐20 3 16 16+3=19
超過 20 4 30 30+4=34
• 進食2次，第二次進食
為第一次進食及打針後7.5小時。即早上8:30打
及吃飯，下午四點吃第二餐。台灣經驗：晚上點吃及打 早上 點11點吃及打，早上 6點
半吃飯
2010/8/14
42
Caninsulin ® (cat)
血糖濃度 劑量
360 /dl 0 25IU/k• 貓需要一天打 2次，每
<360 mg/dl 0.25IU/kg
≥360 mg/kg 0.5 IU/kg12小時吃一次打一次
Insulatard®
Dog
• 一天打2次，吃 2次
Cat
• 一天打2次，吃 2次天打2次，吃 2次
• 起始劑量：0.5IU/kg
天打2次，吃 2次
• 起始劑量：0.25IU/kg
2010/8/14
43
貓的飲食原則
• 足夠的蛋白質及酯肪減量足夠的蛋白質及酯肪減量• 新的證據： high protein
• 糖類應使用多糖，盡量減少單糖• Increased dietary fiber may improve glycemic control by minimizing postprandial y g p pfluctuations in blood glucose
食物種類及量
– Dog (10‐15kg): 40‐60 Kcal/kg/day, divide to 2 g ( g) g ymeals
– Cat: 60‐70 Kcal/kg/day, divide to 2 meals
Dog (H) Dog (RC) Cat (H) Cat (H) Cat (RC)
正常體重 w/d Diabetic canine
m/d w/dm/d
Diabetic feline
過重 r/d Weight control
m/d r/dm/d
Obesity
過輕 i/d i/d i/dm/d
高酯血症 w/d r/d r/d
2010/8/14
44
Thank you for attention