1. INSULIN
DR.SANDEEP
NMCH, NELLORE

2. INSULIN
 Insulin is a protein which contains two chains (A and
B) linked by disulfide bridges
 First protein whose sequence was identified (1955)
 51 amino acids;
 6-10 mg stored in the pancreas
 ~ 2 mg released per day (40 units/day)/1 unit per hour
 1 unit of Insulin decrease 25 to 30 mg of glucose

4.  It is released from pancreatic B cells at a low basal rate
and at much higher stimulated rate in response to a
variety of stimuli, especially glucose.
 ProInsulin -->Insulin and C-peptide
 Plasma concentration of C- peptide reflects the
pancreatic activity of beta cells
 Symp and parasymp systems innervate beta cells
 Alpha – dec
 Beta and parasymp – increases basal sec of Insulin

5. Insulinis destroyed in the GIT, and must be given parenterally
(s.c., i.v., i.m.). Pulmonary absorption occurs and inhalation of an
aerosol is a new route of administration. t1/2 is 10 min.
 Degradation :- liver and kidney remove Insulin by
hydrolysis of the disulfide connection between the A and
B chains through Insulinase. Further degradation by
proteolysis occurs.
 The liver normally clears 60% of the Insulin released
from the pancreas as the terminal of portal vein blood
flow, with the kidney removing 35-40% of the
endogenous hormone.

6. THE INSULIN RECEPTOR
 Receptor consists of two heterodimers, each containing an
alpha subunit, which is entirely extracellular and constitues
the recongition site, and a beta subunit, which spans the
membrane.
 The beta subunit contains a tyrosine kinase. When Insulin
binds to alpha subunit at the outside surface of the cells,
tyrosine kinase activity is stimulated in the beta portion
 Self-phosphorylation of the beta portion results in
translocation of certain proteins such as glucose transporter
from sequestered sites within adipocytes and muscle cells to
exposed locations on the cell surface. Finally, the Insulin-
receptor complex is internalised.

7. INSULIN RECEPTOR
Binding sites
Cell
membrane
Tyrosin kinase
Intracellular
space
Schematic diagram of the two-phase release of Insulin
in response to a constant glucose infusion.

8. CASCADE OF INSULIN STIMULATION
Translocation of Glut 4 transpoters to plasma
membranes, where by
 Facilitate glucose diffusion into the cells
 Facilitates glycogenisis
 Stimulates cellular uptake of aminoacids, Phoshates,
K+, Mg2+.
 Stimulates protein synthesis and inhibits proteolysis
 Regultes gene expression via Insulin regulatory
elements in target DNA.

9. EFFECTS OF INSULIN ON ITS TARGETS
1.Action of Insulin on glucose
transporters
 It has an important effect on several transport
molecules that facilitate glucose movement across
cell membranes (GLUT 1-GLUT 4)
 GLUT-4 (inserted into the membranes of muscle
and adipose cells) is responsible for Insulin-
mediated uptake of glucose
 GLUT-2 (B-cells of pancreas) mediates transport of
glucose into pancreatic B-cells. Its defects may
contribute to the reduced Insulin secretion that
characterizes DM2

10. Effects on liver
 Anabolic
 Promotes glycogenesis
 Increases synthesis of
triglycerides, cholesterol, and
VLDL
 Increases protein synthesis
 Promotes glycolysis
 Anticatabolic
 Inhibits glycogenolysis
 Inhibits ketogenesis
 Inhibits gluconeogenesis
Effects on muscle
 Promotes protein synthesis
 Increases amino acid transport
 Promotes glycogen synthesis
 Increases glucose transport
 Inhibits activity of glycogen
phosphorylase
Effects on fat
 Promotes triglyceride storage
 Induces lipoprotein lipase, making
fatty acids available for absorption
into fat cells
 Increases glucose transport into fat
cells, thus increasing availability of -
glycerol phosphate for triglyceride
synthesis
 Inhibits intracellular lipolysis

11. INSULIN PREPARATIONS AND
DELIVERY:
 Therapeutic Insulin used to be purified from porcine
or bovine pancreas =>functionally active, but many
patients developed an immune response
 Today, human Insulin is produced by recombinant
DNA technology
 Main side effect: Hypoglycemia (requires immediate
attention!)

12.  The potency of Insulin is based on the ability to
decrease the BG and is expressed in units.
 The potency of Insulin is 22 to 26 U per mg
 Insulin U-100(100U per ml) is most commonly used
preparation

13. INSULIN ANALOGUES
 Alteration of the Insulin peptide provides an
opportunity to change the absorption rate of the
molecule
 Eg:- Insulin lispro (ultra-short acting Insulin) and
glargine ultra-long acting Insulin are the first to
use

14.  Normally 6 monomers units associate with Zn and
form a hexamer.
 Once this hexamer dissociates and form a
monomer they can be absorbed.
 Thus regular Insulin has a peak action of 2 to 4
hours after its s/c inj.

15. TYPES
 “Natural” Insulin and four modified Insulins are used
clinically:
 Regular (Natural) Insulin
 Insulin Lispro, Aspart
 Insulin Lente
 NPH Insulin
 Insulin Glargine

16. CLASSIFICATION
 Rapid-acting - Humalog ®, Novolog ®
 Short-acting - Regular
 Intermediate - Lente, NPH
 Long-acting - Ultralente, Glargine (Lantus)

17. REGULAR (NATURAL)
INSULIN
 Unmodified human Insulin
 Rapid acting with short duration (half-life 9 min)
 Only one that can be given IV (infusions, since
injections are too brief acting)
 Useful for emergencies (hyperglycemic coma)

18. INSULIN LISPRO
 Ultra-short acting Insulin-
 Monomeric Insulin produced by recombinant technology, in
which two aminoacids (proline and lysine) have been reversed
in their position 28 and 29 of beta chain without any influence
on receptor binding.
 The advantage is rapid absorption. Peak serum value is
reached in 1 hr. Its use is associated with significantly
improved post-glycemic control (without increasee incidence
of hypoglycemia).
 Used for emergency (ketoacidosis), for rapid
response (surgery).

19. INSULIN LENTE
 Mixed with zinc => forms micro-precipitates
=>Takes longer to absorb => longer acting
 Only for s.c. Administration
 It is a mixture of 30% semilente - an amorphous
precipitate of Insulin with zinc ions in acetate
buffer that has a relatively rapid onset of action +
70% of ultralente Insulin

20. ULTRALENTE INSULIN
 A poorly soluble crystal zinc Insulin that has a
delayed onset and prolonged duration of action.
 This is needed in typeI patients to achieve
basal Insulin concentratin throughout the 24 hrs
that are comparable to those achieved in
normal subjects by basal endogenous
secretion.

21. NEPHAN INSULIN
 Regular Insulin mixed with Protamine
(0.005mg/U) (large positively charged
protein)
 (NPH, neutral protamine Hagedorn or
isophane Insulin) is an intermediate Insulin
with the delayed onset of action achieved by
combining appropriate amount of Insulin
and protamine.

22. INSULIN GLARGINE (LANTUS®)
 Amino acid asparagine at position A21 is
replaced by glycine and two arginines are added
to the C-terminus of the B-chain
 After injection into the subcutaneous tissue, the
acidic solution is neutralized, leading to
formation of microprecipitates from which small
amounts of Insulin Glargine are slowly released,
resulting in a relatively constant
concentration/time profile over 24 hours with no
pronounced peak.

23. Glargine

24. 24
Time Activity of
Human Insulins

25. INSULINS
NPH
Lente
Ultralente
Onset (hr)
0.5-1
1-2
3-4
Maximum (hr)
2-3
4-10
10-15
Duration (hr)
6-8
12-18
18-26
ANALOGUES Onset (min/hr) Maximum (hr) Duration (hr)
Lispro
glargine
0.15-15 (min)
3-4 (hr)
0.5-1
missing
3-5
30

26. INSULIN ADMINISTRATION:
• Subcutaneously (oral application impossible
due to degradation)
• Only Regular Insulin can be given IV if
needed
• Jet injectors
• Pen injectors
• Implantable Insulin pumps
• Intranasal Insulin - mucosal atrophy
(abandoned)
• Pulmonary Insulin (inhalation) - in clinical
trial

27. GLYCEMIC GOALS
 Type I DM-
 Before meals- 70 to 120 mg/dl
 After meals- <150mg/dl
 Bed time- 100 to 130 mg/dl
 3 A.M- >70 mg/dl
 Type II DM-
 FBS & PPBS- 90-130mg/dl
 Peak PPBS - <180 mg/dl
 HbA1C -<7%

28. 50
150
6 9 12 3 6 9 12 3
 
Two doses:
The usual dosing commonly used.
Initial Insulin therapy
50
150
6 9 12 3 6 9 12 3
   
Four doses:
Brittle diabetic patient.
Pregnant mothers specially type 1.
50
150
6 9 12 3 6 9 12 3
  

Four doses:
Brittle diabetic patient.
Pregnant mothers specially type 1.
Motivated patients.
50
150
6 9 12 3 6 9 12 3
  
Three doses:
Used for active patients.
Patients taking two main meals.
INSULIN THERAPYConventional therapy
Intensive therapy

29.  HUMULIN - NPH70/REG30
 NOVOLOG- ASPRAT PROT70/REG30
 HUMALOG- LISPRO PROT75/REG25

30. 0
10
20
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Cause:
Counter regulatory hormones response to
hypoglycemia at mid-night.
Increase in hepatic glucose production.
Insulin resistance because of the Counter
regulatory hormones.
Treatment:
Decrease pre-supper intermediate Insulin.
Defer the dose to 9 PM.
Change or start pre-bed snack.
SOMOGYI PHENOMENON
Rebound hyperglycemia in response to hypoglycemia

31. 0
10
20
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Cause:
Less Insulin at bed time.
More food at bed time.
Not using NPH at night.
Release of counterregulatory harmones
Treatment:
Use enough dose.
Reduce bed time snack.
Add NPH pre-supper.
DAWN PHENOMENON
Increases in BG in the morning

32. COMPLICATIONS OF INSULIN THERAPY
1. Severe Hypoglycemia (< 50 mg/dl )– Life threatening
Overdose of Insulin
Excessive (unusual) physical exercise
A meal is missed
2. Weight gain
3. Local or systemic allergic reactions (rare)
4. Lipodystrophy at injection sites
5. Insulin resistance
6. Hypokalemia

33. DRUG INTERACTIONS
 Drugs(harmones) that counter hypoglycemic effects-
 ACTH , estrogen, glucagon
 Epinephrine inhibits the secretion of Insulin and
stimulates glycogenolysis
 Antibiotics (tetracycline and chloramphenicol)
salicylates, and phenylbutazone increases the
duration of action of Insulin and may have a direct
hypoglycemic effects
 Hypoglycemic effect potentiated by MAOI

34. ORAL HYPOGLYCEMIC
AGENTS

35. ORAL HYPOGLYCEMICS
Pts with type II diabetes have two
physiological defects:
1. Abnormal Insulin secretion
2. Resistance to Insulin action in target tissues
associated with decreased number of Insulin
receptors

36. MODES OF ACTION
 Secretogogues (sulphonylureas and biguanides)-
inc Insulin availability
 Biguanides – dec or inhibit excess hepatic glucose
release
 Glitazones – inc Insulin sensitivity
 Alpha glucosidase inhibitors- dec gastric glucose
absorption

37. Meglitinide Analogs
Sulphonylureas
Thiazolindinediones
Metformin (Biguanides)
Alpha Glucosidase
Inhibitors

38. Sulfonylureas (Oral Hypoglycemic drugs)
Tolbutamide Acetohexamide
Tolazamide
Chlorpropamide Glipizide
Glyburide
(Glibenclamide
Glimepiride
Short
acting
First generation
Intermediate
acting
Long
acting
Long
acting
Short
acting
Second generation

39. Tolbutamid
short-acting
Acetohexamide
intermediate-
acting
Tolazamide
intermediate-
acting
Chlorpropamide
long- acting
Absorption Well Well Slow Well
Metabolism Yes Yes Yes Yes
Metabolites Inactive* Active +++ ** Active ++ ** Inactive **
Half-life 4 - 5 hrs 6 – 8 hrs 7 hrs 24 – 40 hrs
Duration of
action
Short
(6 – 8 hrs)
Intermediate
(12 – 20 hrs)
Intermediate
(12 – 18 hrs)
Long
( 20 – 60 hrs)
Excretion Urine Urine Urine Urine
FIRST GENERATION SULPHONYLUREA COMPOUNDS
** Pts with renal impairment can expect long t1/2

40. Glipizide
Short-
acting
Glibenclamide
(Glyburide)
Long-acting
Glimepiride
Long-acting
Absorption Well Well Well
Metabolism Yes Yes Yes
Metabolites Inactive Inactive Inactive
Half-life 3 – 4 hrs Less than 3 hrs 5 - 9 hrs
Duration of
action
10 – 16 hrs 12 – 24 hrs 12 – 24 hrs
Excretion Urine Urine Urine
SECOND GENERATION SULPHONYLUREA COMPOUNDS

41. MECHANISM OF
ACTION
Closes K -ATP Channel-
exocytosis of Insulin sec
granules
1) Release of Insulin from β-cells
2) Reduction of serum glucagon
concentration
3) Potentiation of Insulin action
on target tissues
SIDE
EFFECTS
1) Nausea, vomiting, abdominal
pain, diarrhea
2) Hypoglycaemia
3) Dilutional hyponatraemia &
water intoxication
(Chlorpropamide)
4) Disulfiram-like reaction with
alcohol (Chlorpropamide)
5) Weight gain
6)Inhibits protective response on
heart

42. SIDE EFFECTS OF SULPHONYLUREAS (contd.)
6) Blood dyscrasias
(not common; less than 1% of patients)
- Agranulocytosis
- Haemolytic anaemia
- Thrombocytopenia
7) Cholestatic obstructive jaundice (uncommon)
8) Dermatitis (Mild)
9) Muscle weakness, headache, vertigo
CONTRAINDICATIONS:-
1) Type 1 DM ( Insulin dependent)
2) Parenchymal disease of the liver or kidney
3) Pregnancy, lactation
4) Major stress

43. MEGLITINIDES (Repaglinide,
Nateglinide)
PK:
Rapidly absorbed ( Peak in1hr ), Metabolized by liver
t1/2 = 1 hr, Duration of action 4-5 hr
MECHANISM OF ACTION
Bind to the same KATP Channel to cause Insulin release
from β-cells.

44. MEGLITINIDES (Contd.)
CLINICAL USE
Approved as monotherapy and in combination with metformin in
type 2 diabetes
Taken before each meal, 3 times / day
Does not offer any advantage over sulfonylureas;
Advantage: Pts. allergic to sulfur or sulfonylurea
SIDE EFFECTS:
Hypoglycemia
Wt gain ( less than SUs )
Caution in pts with renal & hepatic impairment.

45. BIGUANIDES(Metformin)
PK:-
Does Not bind to plasma proteins, Not metabolized
Excreted unchanged in urine
t 1/2 2 hr
MOA:-
1. Increase peripheral glucose utilization
2. Inhibits gluconeogenesis
3. Impaired absorption of glucose from the gut
4. Dec plasma TG & LDL & CH

46. Advantages of Metformin over SUs
Does not cause hypoglycemia
Does not result in wt gain ( Ideal for obese pts )
SIDE EFFECTS
 1. Metallic taste in the mouth
 2. Gastrointestinal (anorexia, nausea, vomiting,
diarrhea, abdominal discomfort)
 3. Vitamin B 12 deficiency (prolonged use)
 4. Lactic acidosis

47. 1. Hepatic impairment
2. Renal impairment
3. Alcoholism
4. Heart failure
BIGUANIDES (Contd.)
CONTRAINDICATIONS
1. Obese patients with
type II diabetes
2. Alone or in
combination with
sulfonylureas
INDICATIONS

48. α-GLUCOSIDASE INHIBITORS
(Acarbose)
Pk:-
Not absorbed from intestine except small amount
t1/2 3 - 7 hr
Excreted with stool
MOA:-
Inhibits intestinal alpha-glucosidases and
delays carbohydrate absorption, reducing postprandial
increase in blood glucose

49. α-GLUCOSIDASE INHIBITORS (Contd.)
MECHANISM OF ACTION

50. SIDE EFFECTS
Flatulence
Loose stool or diarrhea
Abdominal pain
Alone does not cause hypoglycemia
INDICATIONS
α-GLUCOSIDASE INHIBITORS
Patients with Type II inadequately controlled by diet with or
without other agents( SU, Metformin)
Can be combined with Insulin
May be helpful in obese Type II patients
(similar to Metformin)

51. THIAZOLIDINEDIONE DERIVATIVES
(Rosiglitazone, Pioglitazone)
PK:-
- 99% absorbed, Metabolized by liver
- 99% of drug binds to plasma proteins
- Half-life 3 – 4 h, Eliminated via the urine 64% and feces 23%
MOA:-
- Increase target tissue sensitivity to Insulin by:
reducing hepatic glucose output & increase glucose
uptake & oxidation in muscles & adipose tissues.
They do not cause hypoglycemia (similar to metformin
and acarbose )

52. ADVERSE EFFECTS
- Mild to moderate edema
- Wt gain
- Headache
- Myalgia
- Hepatotoxicity
THIAZOLIDINEDIONE DERIVATIVES
INDICATIONS
Type II diabetes alone
or in combination with
metformin or sulfonylurea or
Insulin in patients resistant
to Insulin treatment.

53. WHAT ARE THE INCRETINS
 GIP: Glucose-dependent Insulinotrophic polypeptide
Small effect in Type 2 diabetes.
 GLP-1(glucagon-like peptide 1)
augmented in the presence of hyperglycaemia.
Action less at euglycaemia and in normal subjects.
 Pituitary Adenylate Cyclase Activating Peptide (PACAP)

54. GLP-1 LOCALISATION
 Cleaved from proglucagon in intestinal L-cells
(and neurons in hindbrain / hypothalamus)
 Secreted in response to meal ingestion
 Cleared via the kidneys
 GLP-1 is short-acting
 t½=2.6 minutes
 Native GLP-1 is rapidly degraded by DPP-IV

55. Dipeptyl- peptidase inhibitors
Sitagliptin
Vildagliptin
Saxagliptin
Septagliptin
Allogliptin

57. SITAGLIPTIN
•1st approved member of a new class of OAHA - DPP-4
inhibitor
•Potent, highly selective, reversible and competitive
inhibitor of DPP-4 enzyme
•Tmax (median): 1 to 4 hours postdose
•Apparent t½ (mean): 12.4 hours

58. MECHANISM OF ACTION OF SITAGLIPTIN
Incretin hormones GLP-1 and GIP are released by the intestine
throughout the day, and their levels increase in response to a meal.
Concentrations of the active intact hormones are increased by sitagliptin, thereby increasing and
prolonging the actions of these hormones.
Release of
active incretins
GLP-1 and GIP  Blood glucose
in fasting and
postprandial
states
Ingestion
of food
 Glucagon
(GLP-1)
 Hepatic
glucose
production
GI tract
DPP-4
enzyme
Inactive
GLP-1
XSitagliptin
(DPP-4
inhibitor)
 Insulin
(GLP-1 and
GIP)
Glucose-
dependent
Glucose
dependent
Pancreas
Inactive
GIP
β cells
α cells
 Glucose
uptake by
peripheral
tissues
30

59. ANAESTHETIC MANAGEMENT
The main aims of perioperative diabetic management are
to:
 avoid hypoglycaemia/hyperglycaemia
 aim for prompt return to oral intake
 avoid dehydration
 avoid hypokalaemia
 prevent ketoacidosis.

60. METABOLIC EFFECTS OF SURGERY:
 The normal stress response to surgery affects the
patient‟s Insulin requirements and depends on the
nature and length of surgery.
 Increased production of catabolic hormones (e.g.
catecholamines, cortisol, growth hormone, thyroid
hormones) and a decrease in the production and
action of Insulin

61. THE NATURE OF INSULIN REGIMEN
DEPENDS ON
 Glycemic state and goals
 Nature and severity of surgery
 Minor
 Major
 Emergency
 Presence or absence of complications

62. PRE -OP
 Night before surgery- two thirds of total night dose
 Morning of sugery - NPH/2 of usual dose and full
dose of regular Insulin
 Start 5%D with 0.45% of NS i.v at 1.5 ml/kg/hr
(100ml/hr)
 If infusion is going on – BG/150 U iv and D5W @ 1
ml/kg/hr

63. PRE -OP
 If patient is on Insulin pump
 Over night rate- 70% of basal rate
 Morning-
 continue same rate as usual
Stop continuous Insulin infusion
s/c Glargine and discontinue pump in
60 to 90 min

64. PRE -OP
If patient is on Glargine and aspart
 Night
2/3rd of Glargine
Entire aspart/lispro
 Morning
Stop all

65. PRE-OP
If patient is on OHA
 Stop Sulfonylureas
It blocks myocardial K-ATP
channel and inhibit ischemic
preconditioning , a
cardioprotective mechanism.
So it should be stopped 24 to 48
hrs prior to surgery.

66. PRE-OP
 If for minor surgery and well controlled DM -2 – no
need of Insulin
 If poorly controlled type 2 DM, all type I minor surg
and major surg- needs Insulin
 Major surg with
 BG >270mg/dl –delay surgery with rapid control
 If 400 mg/dl – surgery postponed and metabolic state
reestablished.

67. PATIENTS UNDERGOING MINOR SURGERY:
 Type 1 diabetes
 First on morning list.
 Insulin adjustments
 If blood glucose is 12 mmol/litre (200mg/dl) or more
start Insulin/dextrose/potassium regimen.
 Take blood glucose measurements 1 hour
preoperatively, hourly intraoperatively, and 2 hourly
postoperatively until the patient is eating and
drinking.
 The normal Insulin regimen can be given once the
patient is eating and drinking.

68. MINOR SURGERY
 Type 2 diabetes
 Omit oral hypoglycaemic on morning of surgery
except metformin, omitted much before.
 Measure blood glucose as above.
 Restart oral hypoglycaemics with first meal.

69. PATIENTS UNDERGOING MAJOR SURGERY:
 Major surgery is that not falling into the above
category and emergency surgery. Type 1 and type
2 diabetes are treated the same.
 Insulin managment
 Start Insulin/dextrose/potassium regimen according
to blood glucose.
 Measure blood glucose 2 hourly during infusion and
hourly during surgery.

70. INTRA-OP
 Avoid hyperglycemia and hypoglycemia
 Ideally
 Start continuous Insulin infusion 2hrs prior to surgery
 If BG > 200 to 250 no use of s/c Insulin
 Maintain BG 120 to 180 mg/dl

71. INTRA OP
 Typical rate is 0.02U/kg/hr or 1.4 U/hr in 70 kg individual
 If CABG- 0.06mg/kg/hr
 If on steroids /severe infection-0.04 U/kg/hr
 If pt on hyperalimentation / vasopressor infusion –D51/2
NS with 20 mEqKCl at 100 to 150 ml/hr
 Monitor glucose hourly& every 30 min if pt underwent
CABG

72. If BG(mg/dl)
 <100 – D51/2 NS 150ml/hr
 101-150 – 75 ml/hr
 151-200 - 50 ml/hr
 >200 – keep vein open

73. INSULIN/DEXTROSE REGIMENS:
 The two widely used regimens are the
 Insulin sliding scale and
 The „Alberti‟ regimen.

74. INSULIN SLIDING SCALE
 Insulin sliding scale uses 50 U of soluble Insulin
diluted up to 50 ml with normal saline and run at a
rate according to the patient‟s blood glucose.
 Dextrose and potassium also need to be infused
concurrently (e.g. 500 ml of 10% dextrose plus 10
mmol potassium chloride at 100 ml/hour).

75. SLIDING SCALE
Blood sugar
mg/dl
Regular Insulin
150-200 2U
200-250 4U
250-300 6U
300-350 8U
Above 350 10U

76. SLIDING SCALE
 The amount of Insulin
administered can be
altered easily without
having to make up a
new mixture.
 Risk of a failure to
administer dextrose
due to blockage,
disconnection or
backflow.
Advantage Disadvantage

77. THE ALBERTI REGIMEN
 Combines Insulin, dextrose and potassium to
remove the risk of accidental Insulin infusion
without dextrose.
 The amount of Insulin added to each bag depends
on the patient‟s blood glucose level, so new
mixtures of Insulin and dextrose have to be made
up each time a change in Insulin dose is required.

78. •Glucose – Potassium – Insulin infusion
• Alberti and Thomas regimen (1979)
To commence on the morning of surgery:
500ml 10% glucose
+ 10U Insulin + 1o mmol Kcl
@ 100ml / hr
Blood sugar every 2-3hrs
Blood sugar
<5mmol / L (90mg/dl)
Insulin ↓ to 5u
Blood sugar
>10mmol / L (180-
270mg/dl)
Insulin ↑ to 15

79.  Combines
Insulin, dextrose and
potassium to remove
the risk of accidental
Insulin infusion without
dextrose.
 Costly and inefficient
because it may have to
be done every hour in
some patients.
Advantage Disadvantage

80. Modified alberti regimen
GIK sol
500ml of 10%dextrose +
10mmols/L of KCL +15 U
Insulin @ 100ml/hr
Cont new GIK sol
at adjusted conc
Inc Insulin by 5 U Dec Insulin by 5 U
Measure
BG every 2
hrs
BG<120mg/
dl
BG >200mg/dl
BG 120-200mg
continue @ same
rate

81. HIRSCH REGIMEN

82.  Classic "Non-Tight Control" Regimen
Aim:
 To prevent hypoglycemia, ketoacidosis, and hyperosmolar
states.
protocol:
 1. On the day before surgery, the patient should be kept NPO
after midnight.
 2. At 6 AM on the day of surgery, infuse a solution of IV fluids
containing 5% dextrose at a rate of 125 mL/hr/70 kg body
weight.
 3. After starting the IV infusion, give half the usual morning
Insulin dose (and the usual type of Insulin) subcutaneously.
 4. Continue 5% dextrose solutions through the operative
period and give at least 125 mL/hr/70kg body weight.
 5. In the recovery room, monitor blood glucose
concentrations and treat on a sliding scale

83. Tight Control" Regimen 1 :-
Aim:
 To keep plasma glucose levels at 79 to 120 mg/dL.
protocol:
 1. On the evening before surgery, determine the preprandial
blood glucose level.
 2. begin an IVinfusion of 5% dextrose at a rate of 50 mL/hr/70
kg body weight.
 3. "Piggyback" an infusion of regular Insulin (50 U in 250 mL of
0.9% sodium chloride) to the dextrose infusion with an infusion
pump). Before attaching this piggyback line to the dextrose infusion, flush the line with
60 mL of infusion mixture and discard the flushing solution. This approach saturates
Insulin binding sites on the tubing.
 4. infusion rate: Insulin (U/hr) = plasma glucose(mg/dL)/150.
(Note: The denominator should be 100 if the patient is taking
corticosteroids.

85. 6. On the day of surgery, intraoperative fluids and electrolytes
are managed by continued administration of non-dextrose-
containing solutions, as described in steps 3 and 4.
7. Determine the plasma glucose level at the start of surgery and
every 1 to 2 hours for the rest of the 24-hour period. Adjust the
Insulin dosage appropriately.
5. 4th hourly measure blood glucose and adjust Insulin
appropriately to obtain blood glucose levels of 100 to 200
mg/dL.

86. TIGHT CONTROL" REGIMEN
2 :-
Aim:-
same as for TCR-1
Protocol:-
 obtain feedback mechanical pancreas & set
controls for the desired plasma glucose regimen
 institute 2 IV lines

87. POST-OP
 Measure blood glucose hourly for 4 hours postoperatively or
until stable, whichever is longer, and then 2 hourly.
 For type I patients stop the infusion once they are eating and
drinking.
 Calculate the total dose of Insulin in the last 24 hours and
divide it into three daily doses and administer this as
subcutaneous soluble Insulin.
 Adjust the dose until the patient is stable, aiming to return to
their normal regimen.
 For type 2 patients, stop the infusion and restart oral
hypoglycaemics once they are eating and drinking.

88. EMERGENCY SURGERY
 Patient will be in DKA/HHS
 Large volume of NS and Insulin is given
 Insulin
 Bolus – 0.1u/kg
 Infusion-0.1u/kg/hr
 Check – BG hrly and electrolytes 2nd hrly
 If BG <250 – add dextrose
 Continue infusion till acidosis decreases

89. IMPORTANT POINTS TO BE NOTED WHILE
GIVING INSULIN
1. Absorption of Insulin is highly variable (type,
species, site and blood flow )
2. 1 U of Insulin = 25-30 mg%
3. Daycare patients should have preceeding evening
Insulin reduced by 10-20% to prevent
hypoglycemia early morning

90. 4. Insulin sliding scales have no benefit in poorly
controlled surgical patients
5. Intravenous Insulin is the most precise means of
managing hyperglycemia perioperatively and
several regimes are recommended
6. Interruption of Insulin infusion suddenly leads to
sudden metabolic decompensation
7. Insulin is adsorbed to glassware as well as plastic
ware. (around 30%)

91. • Measures to decrease loss
a) Running about 50 ml of infusate rapidly through
the tubing to saturate the sites
b) Add small amount of protein to the infusate
8. Higher Insulin dose required in case of
administration of RL during surgery

92. MISC…….
• BZD‟s – if given by
continous infusion,
decreases blood glucose (
by decreasing the ACTH,
decreases cortisol )
• High dose opiate – abolish
hyperglycemia by blocking
sympathetic response
• Halothane, Enflurane and
Isoflurane in vitro, inhibit the
Insulin response to glucose
in a reversible and dose
dependent manner.
 General medical/surgical
Fasting : 90-126 mg%
Random: < 200 mg%
 Cardiac surgery
< 150 mg%
 Critically ill
< 150 mg%
 Acute neurologic disorders
80 – 140 mg%

93. REFERENCES
 Anaesthetic management of the diabetic patient. Simon
Webster Nicola Lewis, ANAESTHESIA AND INTENSIVE
CARE MEDICINE, 2005
 Harrison‟s principles of Internal medicine, 17th edition
 Miller‟s Anesthesia 6th edition.
 Stoelting‟s anesthesia & coexisting diseases, 4th & 5th edition
 ISACON 2007, CME lectures.
 Morgan anesthesia

94. THANK YOU