Periop management of diabetes

INSULINDR.SANDEEP

NMCH, NELLORE

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

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

Insulin is 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.

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.

INSULIN RECEPTORBinding sites

Cellmembrane

Tyrosin kinase

Intracellularspace

Schematic diagram of the two-phase release of Insulin in response to a constant glucose infusion.

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.

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

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

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!)

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

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

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.

TYPES “Natural” Insulin and four modified Insulins

are used clinically:

Regular (Natural) Insulin Insulin Lispro, Aspart Insulin LenteNPH Insulin Insulin Glargine

CLASSIFICATION

Rapid-acting - Humalog ®, Novolog ®

Short-acting - Regular

Intermediate - Lente, NPH

Long-acting - Ultralente, Glargine (Lantus)

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)

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).

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

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.

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.

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.

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Glargine

24

Time Activity of Human Insulins

INSULINSNPH

LenteUltralente

Onset (hr)0.5-11-23-4

Maximum (hr)2-3

4-1010-15

Duration (hr)6-8

12-1818-26

ANALOGUES Onset (min/hr) Maximum (hr) Duration (hr)

Lisproglargine

0.15-15 (min)3-4 (hr)

0.5-1missing

3-530

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

GLYCEMIC GOALSType I DM-

Before meals- 70 to 120 mg/dlAfter meals- <150mg/dlBed time- 100 to 130 mg/dl3 A.M- >70 mg/dl

Type II DM-FBS & PPBS- 90-130mg/dlPeak PPBS - <180 mg/dlHbA1C -<7%

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

HUMULIN - NPH70/REG30

NOVOLOG- ASPRAT PROT70/REG30

HUMALOG- LISPRO PROT75/REG25

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

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

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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

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

ORAL HYPOGLYCEMIC AGENTS

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

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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

Meglitinide AnalogsSulphonylureas

Thiazolindinediones

Metformin (Biguanides)

Alpha Glucosidase Inhibitors

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Sulfonylureas (Oral Hypoglycemic drugs)

Tolbutamide AcetohexamideTolazamide

Chlorpropamide GlipizideGlyburide(Glibenclamide)Glimepiride

Short acting

First generation

Intermediateacting

Longacting

Longacting

Short acting

Second generation

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Tolbutamid short-acting

Acetohexamideintermediate-

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

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GlipizideShort- acting

Glibenclamide(Glyburide)Long-acting

GlimepirideLong-acting

Absorption Well Well WellMetabolism Yes Yes YesMetabolites Inactive Inactive InactiveHalf-life 3 – 4 hrs Less than 3 hrs 5 - 9 hrsDuration of action

10 – 16 hrs 12 – 24 hrs 12 – 24 hrs

Excretion Urine Urine Urine

SECOND GENERATION SULPHONYLUREA COMPOUNDS

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) Hypoglycaemia3) Dilutional hyponatraemia &

water intoxication (Chlorpropamide)

4) Disulfiram-like reaction with alcohol (Chlorpropamide)

5) Weight gain 6)Inhibits protective response

on heart

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 kidney3) Pregnancy, lactation4) Major stress

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MEGLITINIDES (Repaglinide, Nateglinide)

PK:Rapidly absorbed ( Peak in1hr ), Metabolized by

livert1/2 = 1 hr, Duration of action 4-5 hr

MECHANISM OF ACTION

Bind to the same KATP Channel to cause Insulin release from β-cells.

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MEGLITINIDES (Contd.)

CLINICAL USEApproved as monotherapy and in combination with

metformin in type 2 diabetesTaken before each meal, 3 times / dayDoes not offer any advantage over sulfonylureas;

Advantage: Pts. allergic to sulfur or sulfonylurea

SIDE EFFECTS:HypoglycemiaWt gain ( less than SUs )

Caution in pts with renal & hepatic impairment.

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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 utilization2. Inhibits gluconeogenesis3. Impaired absorption of glucose from the gut4. Dec plasma TG & LDL & CH

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 46

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1. Hepatic impairment

2. Renal impairment3. Alcoholism4. Heart failure

BIGUANIDES (Contd.)

CONTRAINDICATIONS

1. Obese patients with type II diabetes

2. Alone or in combination with sulfonylureas

INDICATIONS

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α-GLUCOSIDASE INHIBITORS (Acarbose)

Pk:-

Not absorbed from intestine except small amountt1/2 3 - 7 hr

Excreted with stool

MOA:-

Inhibits intestinal alpha-glucosidases and

delays carbohydrate absorption, reducing postprandial increase in blood glucose

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α-GLUCOSIDASE INHIBITORS (Contd.)

MECHANISM OF ACTION

50

SIDE EFFECTSFlatulenceLoose stool or diarrheaAbdominal painAlone 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)

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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 )

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ADVERSE EFFECTS- Mild to moderate edema- Wt gain- Headache- Myalgia - Hepatotoxicity

THIAZOLIDINEDIONE DERIVATIVES

INDICATIONSType II diabetes aloneor in combination with metformin or sulfonylurea

or Insulin in patients resistant to Insulin treatment.

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)

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

Dipeptyl- peptidase inhibitors Sitagliptin Vildagliptin Saxagliptin Septagliptin Allogliptin

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

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 ofactive incretinsGLP-1 and GIP Blood glucose

in fasting and postprandial

states

Ingestion of food

Glucagon(GLP-1)

Hepatic glucose

production

GI tract

DPP-4 enzym

e

InactiveGLP-1

XSitagliptin

(DPP-4 inhibitor)

Insulin(GLP-1 and

GIP)

Glucose-dependent

Glucose dependent

Pancreas

InactiveGIP

β cells

α cells

Glucose uptake by peripheral

tissues

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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.

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

THE NATURE OF INSULIN REGIMEN DEPENDS ON

Glycemic state and goals

Nature and severity of surgery

Minor

Major

Emergency

Presence or absence of complications

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

PRE -OP If patient is on Insulin pump

Over night rate- 70% of basal rate

Morning- continue same rate as usualStop continuous Insulin infusion s/c Glargine and discontinue pump in 60 to 90 min

PRE -OPIf patient is on Glargine and

aspartNight

2/3rd of GlargineEntire aspart/lispro

MorningStop all

PRE-OPIf patient is on OHA

Stop SulfonylureasIt blocks myocardial K-ATP channel and inhibit ischemic preconditioning , a cardioprotective mechanism.

So it should be stopped 24 to 48 hrs prior to surgery.

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.

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.

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.

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.

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

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

If BG(mg/dl)

<100 – D51/2 NS 150ml/hr 101-150 – 75 ml/hr151-200 - 50 ml/hr>200 – keep vein open

INSULIN/DEXTROSE REGIMENS: The two widely used regimens are the

Insulin sliding scale andThe ‘Alberti’ regimen.

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).

SLIDING SCALE Blood sugar

mg/dlRegular Insulin

150-200 2U

200-250 4U

250-300 6U

300-350 8U

Above 350 10U

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

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.

•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

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

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

HIRSCH REGIMEN

Classic "Non-Tight Control" RegimenAim: 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

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.

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.

TIGHT CONTROL" REGIMEN 2 :-

Aim:- same as for TCR-1Protocol:- obtain feedback mechanical pancreas &

set controls for the desired plasma glucose regimen

institute 2 IV lines

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.

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

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

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%)

• Measures to decrease lossa) Running about 50 ml of infusate rapidly

through the tubing to saturate the sitesb) Add small amount of protein to the infusate

8. Higher Insulin dose required in case of administration of RL during surgery

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%

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

THANK YOU