Anaesthesia in Endocrine Disorders Diabetes Mellitus Diabetes Mellitus (DM) is a metabolic defect due to absolute or relative lack of insulin. The aims of peri-operative management of patients with diabetes should include near normal metabolism as possible, with a simple regimen with low likelihood for errors. The diabetic surgical patient is at high risk, not only from the point of view of the management of diabetes, but also because of co-morbid diseases. Anaesthesia should be modified according to the biological age of the patient. Biological age is increased depending on degree of control and target organ disease. CLASSIFICATION OF DIABETES Classification is based on the patho-physiological process and not the treatment. Type 1 : Autoimmune destruction of pancreatic cells in the young resulting in absence of insulin, needing insulin therapy, and also prone to ketosis (formerly IDDM). Type II : Insulin resistance or relative deficiency, maturity onset, familial, obese, treated with diet, oral hypoglycaemics, insulin or a combination (formerly NIDDM). DIAGNOSTIC CRITERIA FOR DIABETES Random blood sugar (RBS)::. 11.1 mmol/L (200mg/dL) HbA1C > 6.5% Fasting blood sugar (FBS)::. 7.0 mmol/L (126mg/dL) Postprandial (PPBS)::. 11.l mmol/L at 2h during a 75g oral glucose tolerance test (Conversion of mmol/L to mg /dL, multiply by 18) BIOCHEMICAL EFFECTS OF INSULIN Conversion of glucose to fatty acids and glycogen Facilitation of glucose and potassium transport into cells Inhibition of glycolysis, gluconeogenesis, glycogenolysis, lipolysis, ketogenesis Promotion of anabolism, wound healing and phagocytosis METABOLIC EFFECTS OF SURGERY Surgical stress causes increased release of glucagons, corticosteroids, growth hormone, and catecholamines, all of which are known to increase insulin resistance. This leads to worsened glycaemic control in the previously well controlled individual and a tendency to ketoacidosis in the previously poorly controlled individual.
PROBLEMS DUE TO EFFECTS OF DIABETES ON ORGAN FUNCTION Microangiopathy: results in neuropathy, nephropathy and retinopathy. Macroangiopathy: hypertension, coronary, cerebral and peripheral arterial disease. Cardiovascular system • Hypertension, ischaemic heart disease (silent or undeclared), cardiomyopathy • Atherosclerosis with poor autoregulation, and intolerance of hypotension • Peripheral vascular disease • Postural hypotension, tachy I bradycardia, due to autonomic neuropathy Central and peripheral nervous system • Prone to cerebro-vascular accidents • Peripheral neuropathy ("glove and stocking type") • Autonomic neuropathy (see below) • Reduced hypoxic ventilatory drive Respiratory system Chest infections common. Difficult airway due to limited joint mobility, prayer sign (see page 4.5) Gastro-intestinal dysfunction Gastric stasis and reflux due to autonomic neuropathy Renal dysfunction Diabetic nephropathy (earliest sign is microalbuminuria) Sepsis Increased tendency to infection and poor wound healing AUTONOMIC NEUROPATHY Signs Postural hypotension, gustatory sweating, gastroparesis, gastric reflux, nocturnal and post-prandial diarrhoea, diuresis, Na loss, impotence, silent MI, night sweats, signs of hypoglycaemia Jost, flushing, warm extremities Tests 1. Measure BP : supine and then standing (sympathetic compensation absent). Abnormal decrease by >20mmHg (normal by < lOmmHg) 2. Measure heart rate: response to 6 deep breaths/min (parasympathetic block) ECG Maximum I minimum R-R interval variability reduced. Sinus arrhythmia absent : inspiratory increase < 10 bpm (normal > 15) 3. Valsalva Manoeuvre: (sympathetic and parasympathetic block) "Blocked Valsalva" : No rise in BP or tachycardia during phase II No after-shoot of BP or post-valsalva bradycardia.
PROBLEMS DUE TO DIABETIC STATUS Control is more difficult in the peri operative period due to a tendency to : 1. Hypoglycaemia due to fasting and residual effects of hypoglycaemic agents. Hypoglycaemia< 4mmol/l or< 70mg/dl is more life-threatening in the short term. 2. Hyperglycaemia due to the stress response to surgery (increased resistance to insulin) causes hyperosmolarity, glycosuria, electrolyte and acid base disorders. Hyperglycaemia predisposes to poor wound healing, infection and catabolism. Indicators of control • Frequency and severity of hypoglycaemic attacks • Control of blood sugar and need for alteration in the daily dose regime • FBS 4-8 mmol/L (70-140 mg/di) and PPBS < 14 mmol/L (good control) • HbAlc <7% (controlled), >9% (uncontrolled), >12% (prone to ketoacidosis) • If uncontrolled (BS >15mmol/L), exclude ketoacidosis (urine for ketones) Lack of control maybe due to drugs (steroids, thiazide, oestrogen), thyroid disease, obesity, pregnancy, stress. Measure RBS 4 hrly for patients on insulin and 8 hrly for those on oral agents. HYPOGLYCAEMIC AGENTS • Oral hypoglycaemic agents: Check duration of action and omit before surgery. Sulphonylureas (enhance insulin secretion) Tolbutamide 8h, glibenclamide, gliclazide 12h. Omit on day of surgery Long acting chlorpropamide 24-72h. Omit 3 days prior to surgery. Biguanides (decrease insulin resistance in liver): metformin 12h. Thiazolidinediones (insulin sensitizers) eg. pioglitazone, resiglitazone 24h a glucosidase inhibitors (delay glucose absorption) eg. acarbose 8h Meglitinides (stimulate~ cells) eg. repaglinide 6h • Insulin : Check dose, frequency and type of insulin. Type Onset Peak Duration Rapid acting 5-15min 30-90min 3 -5 h (Actrapid) Short acting 1/2 -lh 2-4h 6-8 h (Regular) Intermediate 1-2 h 6-8 h 10-16 h (70/30 lente) Long acting 4-6h 18 h 24-36 h (Ultra lente)
PRE-OPERATIVE PERIOD ASSESSMENT AND OPTIMIZATION A careful history, examination and investigations should assess: 1. The diabetic status 2. Organ dysfunction which is the common cause of mortality and morbidity Both should be optimized prior to surgery. Airway assessment is also important (see page 4.5) INVESTIGATIONS Diabetic status Blood sugar: FBS, PPBS HbAlc Urine for sugar, albumin, casts and ketones Organ dysfunction ECG, telechest, echo and stress test if indicated Blood urea I serum creatinine, electrolytes PREMEDICA TION Give ranitidine and metoclopramide orally 2 hours before surgery. (see page 4.29) Ensure a light solid meal 8 hours before surgery, and clear fluids up to 3 hours before surgery to avoid ketoacidosis. Continue drug therapy for co-morbid diseases till morning of surgery. CONTROL OF BLOOD SUGAR IN THE PERI-OPERATIVE PERIOD • Adequate glucose should be provided to satisfy basal requirements and additional demands of the stress response (5-1 Og/h). It prevents hypoglycaemia, ketosis and protein breakdown. • Insulin is essential to prevent hyperglycaemia, lipolysis, ketogenesis and protein catabolism. Insulin infusions are more physiological than bolus doses, as they produce stable blood levels especially for major surgery. • Check duration of action of oral drug, and discontinue or replace with soluble insulin or short acting glibenclamide. • If uncontrolled pre-operatively, use a prophylactic insulin regime which aims to match the insulin requirement of the patient e.g. if hyperglycaemia occurs after lunch increase the next morning dose. • Post operatively a similar prophylactic regime should be used with regular monitoring of BS since control of BS may be more difficult. • The regime used for control of BS depends on the resources available, and what is considered the safe practice in that particular hospital.
Which regime for my patient? AIM : Glycaemic control, balancing the risks of hypoglycaemia vs reduction m mortality and morbidity. BS 6-10 mmoVL or 100-180mg /dL is recommended. THE REQUIRED REGIME depends on the : 1. Type of Surgery 2. Treatment Regime 3. Degree of Control Major (oral feeds not possible within 4 hours post-op.) Minor (oral feeding possible within 4 hours post-op.) On insulin On oral hypoglycaemic drugs Poor control : RBS > 10 mmol/L Good control : RBS < 10 mmoVL • Pre-operatively : The blood sugar should be well controlled with short acting oral drugs or s.c. insulin, and taken as usual the day prior to surgery. If uncontrolled and surgery is urgent, revert to the major surgery regime. Blood sugar tests should be done the day prior, lh pre-op., 1-2 hourly intra-op., 2 hourly post-op. till feeding, and 4 hourly, till stabilized. • All diabetics should be first on the surgical list to minimize fasting. No patient should be taken up for elective surgery if the fasting BS is >200 mg% (even if they are on diabetic diet or drugs). MINOR SURGERY for patients controlled on oral drugs Pre-op. RBS > lOmmol/l Pre-op. RBS <lOmmol/l Day of surgery After surgery Treat as for major surgery (see below) omit oral drugs (see page 8.3 ). restart oral drugs with first meal. MINOR SURGERY for patients controlled on insulin Pre-op. RBS > lOmmol/l Treat as for major surgery (see below) Pre-op. RBS <lOmmol/l, will miss only 1 meal, and very minor surgery : Day of surgery After surgery No breakfast, no insulin ifFBS < 7mmoVL Give s.c. insulin half usual dose ifFBS>7mmoVL Restart usual s.c. insulin with first meal.
MAJOR SURGERY (all types of diabetes) Day of surgery Omit oral and s.c. insulin, and use the GIK regime. After surgery Type I Stop infusion with the first meal. Give soluble insulin (1/3 total daily dose tds) When stabilized, restart the usual regime. Type II : Restart oral drugs with the first meal. GLUCOSE INSULIN POTASSIUM (GIK) Infusions Measure morning blood sugar. Start the infusion in the OT on the day of surgery whatever the time of surgery and give insulin according to the morning BS and algorithm. • Fixed rate insulin (mixed infusion) (Alberti & Thomas regime modified) Danger of hypoglycaemia is reduced as both glucose and insulin are in one infusion, but more wasteful when doses have to be altered. 1. 5% dextrose with KC! (lOmmol I 500ml) and insulin according to algorithm. 2. Infuse at the rate of 100 ml/ h till oral feeding commences. 3. Discard first 50 ml to minimize effects of adsorption of insulin by plastic. • Variable rate insulin infusion allows alteration of insulin dose with changes of BS unlike that of the mixed infusion, but danger of hypoglycaemia is greater. Insulin and KC! in 5% dextrose (at a fixed rate of lOOml I h) is infused via separate lines using the same cannula via a syringe pump or burette. Syringe pump : 50 units of soluble insulin added to 50 ml of normal saline Burette (if no infusion pump) : o Add 50 units of soluble insulin to 500 ml of saline and take 100 ml into the burette. Give according to the BS. (10 microdrops I minute =1 unit insulin/h) or o Take 100 ml of 5% dextrose and KC! into the burette hourly and add the soluble insulin based on the BS. If difficult to control, increase the rate or give Actrapid bolus 3-5 units. Algorithm for GIK regime BS (mmol/l) <4 4-7 7.1 -11 11.1-17 17.1-22 >22 (mg/di) <72 72-126 127-199 200-299 300-400 >400 Insulin dose (units /h) 0.5 l 2 4 8 10
Acute Emergencies in Diabetes Mellitus These are life threatening medical emergencies. Surgery however urgent should be postponed in the presence of ketoacidosis. Dehydration and hyper-osmolarity must be corrected pre-operatively. 1. HYPOGLYCAEMIA (<4mmol/L) Signs : Sweating, tremors, confusion, pallor, tachycardia due to sympathetic activity (does not occur with beta blockade and autonomic neuropathy). Drowsy, lethargic, altered consciousness, and delayed recovery from GA Treatment : 50ml of 25% dextrose followed by a 5% dextrose infusion. Alternative: Glucagon 1 mg i.m./ i.v. (slow action) or sweetened drinks 2. HYPERGLYCAEMIA (>10mmol/L) Differential Diagnosis 1. Ketoacidosis 2. Hyperosmolar Hyperglycaemic Non ketotic Syndrome (HHNS) 3. Non-ketotic lactic acidosis (NKLA) Ketoacidosis HHNS NKLA BS >15 mmol/L > 15 mmol/L variable Ketones +++ 0 + O+ Dehydration +++ +++ O+ Hyperventilation +++ -+++ Anion gap >10 mmol/L normal >lOmmol/L Monitoring Pulse, BP, ECG, CVP, ABG, urine output, serum electrolytes, ketone bodies, blood lactate, serum creatinine HYPEROSMOLAR HYPERGLYCAEMIC NON-KETOTIC SYNDROME Occurs mainly in Type II DM due to missed doses of insulin or other medication, acute infection or illness, intake of sugary food or fluids. Ketones are not common. No acetone in the breath. No acidosis. Treatment: (see page 8.9) NON-KETOTIC LACTIC ACIDOSIS Occurs in diabetic patients with poor renal function on metforrnin. Blood lactate >5mmol/L, serum creatinine > l.25mmol/L Symptoms: Anorexia , nausea, vomiting, abdominal pain, Treatment : Stop metformin, correct acidosis, hydrate, circulatory support
KETO ACIDOSIS Diagnosis Anorexia, nausea, vomiting, thirst, polyuria, severe dehydration, abdominal pain (mimics acute abdomen), hyperventilation, acetone in the breath, impending coma High BS, high K, high anion gap, ketonuria, metabolic acidosis, respiratory alkalosis. MANAGEMENT OF KETOACIDOSIS AND HHNS 1. Rapid rehydration with saline (112 N saline for HHNS if serum sodium is high) 1st litre in the first 30 minutes. 2"d litre in 1 hour, 3rd litre in 2 hours 4th litre in 3 hours and 500ml 2 -4 hourly (4 -10 litres may be required). Pulse, BP, urine output, CVP should guide the management of re-hydration. 2. Insulin Therapy • Soluble insulin IOU i. v. stat, followed by 0.1 U/kg/h via an infusion pump, or SOU of insulin in 500 ml of isotonic saline at a rate of 50 ml/hr (lml/kg/h). • The optimal rate of glucose decline is 100 mg/dL/h and should not fall to 200mg/dL in< 4-5h. • When BS falls to <12mmol/L, replace saline with 5% dextrose. Reduce insulin according to GIK algorithm (see page 8.6). Monitor BS closely for hypoglycaemia. • Once recovered (eating I drinking) change to s.c. insulin. 3. Correct potassium depletion (with hourly serum Kand ECG monitoring). • Potassium supplements : if K (mmol/L) <5 : 10 mmol/h, <4 : 20mmol/h via cental venous access • Stop supplements if serum K >5mmol/L. • Monitoring must continue even after infusion is stopped as hypokalaemia can recur 4. Acidosis Correct only if pH is <7, with 50ml 8.4% NaHC03 in IOOrnl saline. Repeat every half hour if necessary. 5. Coma : Airway protection, nasogastric tube, 02, and good nursing care essential. 6. Treat cause : Search for site of infection. Early surgery may be necessary. Complications : DVT, ARDS, sepsis, acute dilatation of stomach, cerebral oedema MANAGEMENT OF KETOACIDOSIS • Rehydrate first and fast • Insulin therapy avoiding hypoglycaemia • Identify and treat hypokalaemia • Airway protection and nursing care • Treat the cause