CME INDIA Presentation by Dr. Amit A Saraf, MD FRCP (London) FRCPE (Edinburgh) FRCP (Glasgow) FACP (Philadelphia) FCPS, Director Department of Internal Medicine Jupiter Hospital, Head Quality Control Jupiter Hospital, International Adviser India for RCP London MRCP London Examiner-Associate Professor of Medicine MUHS, DNB Teacher and MD Examiner, Mumbai.

Based on a presentation at APICON-2023 at Ahmedabad.

Defining Concepts of Hyper & Hypoglycemia in Hospitalized Patients

• Hyperglycemia in hospitalized patients is defined as any blood glucose greater than 140 mg/dl.
• It can occur in a patient previously diagnosed with diabetes, in an undiagnosed diabetic patient or it can be a transient hyperglycemia linked to the hospitalization, in which case blood sugar levels normalizes after discharge.
• The differentiation between undiagnosed diabetes and transient hospital hyperglycemia can be done by determining glycated hemoglobin.
• Hospital hypoglycemia is defined as blood glucose below 70 mg/dl.
• Severe hypoglycemia in a hospitalized patient is defined as blood glucose below 40 mg/dl.

Why Is Peri-Operative Diabetes Control Essential?

Perioperative Morbidity & Mortality

• The presence of diabetes or hyperglycemia in surgical patients has been shown to lead to increased morbidity and mortality, with perioperative mortality rates up to 50% greater than the non-diabetic population.

The reasons for these adverse outcomes are multifactorial, but include:

Why Is Peri-Op Management of Diabetes Important?

• Surgical procedures may result in several metabolic perturbations that can alter normal glucose homeostasis.
• The resulting hyperglycemia due to abnormal glucose balance is a risk factor for postoperative sepsis, endothelial dysfunction, cerebral ischemia and impaired wound healing.
• In addition, the stress response may also precipitate DKA and HHS during surgery or postoperatively.
• Unmanaged hypoglycemia may result in several neurological complications.
• In general, complications from surgical wounds are more prevalent in diabetics and healing is impaired when glycemic levels are not well managed.
• Unmanaged hypoglycemia may result in several neurological complications.
• In general, complications from surgical wounds are more prevalent in diabetics and healing is impaired when glycemic levels are not well managed.

The Metabolic Response to Surgery in A Diabetic

• Metabolic effects of Starvation.
• Period of starvation induces a catabolic state.
• It will stimulate secretion of counter-regulatory hormones.
• Metabolic effects of Major Surgery.
• It causes neuro-endocrine stress response with release of counter-regulatory hormones (Epinephrine, Glucagon, Cortisol & Growth hormones) and of Inflammatory cytokines IL6 and Tumor Necrosis Factor-Alpha.
• Hypoglycemia exacerbates the catabolic effect of surgery.
• These Neuro-Hormonal changes result in metabolic abnormalities including:
• Increased insulin resistance.
• Decreased peripheral glucose utilization.
• Impaired insulin secretion.
• Increased lipolysis.
• Protein catabolis.
• Hyperglycemia and even ketosis.

How Does Hyperglycaemia Affect Operative Outcomes?

The mechanism by which hyperglycemia influences perioperative morbidity and mortality.

Credit: Verde i, armean p. Current perioperative management of diabetic patients from general surgery wards. Acta medica transilvanica september 2014;2(3):243-247.

Perioperative Assessment & Management Goals

• Reduction of overall patient morbidity and mortality.
• Avoidance of severe hyperglycemia or hypoglycemia.
• Maintenance of physiological fluid and electrolyte balance.
• Prevention of ketoacidosis.
• Establishment of certain glycemic target levels, less than 180mg/dL in critical patients and less than 140mg/dL in stable patients.

Pre-operative evaluation

• Determine the type of diabetes and its management.
• Ensure that the patient’s sugars are well controlled.
• Review of medications.
• Consider the presence of complications of diabetes that might be adversely affected by or that might adversely impact upon the outcome of the proposed procedure.
• Identify high risk patients requiring critical care management.
• To Assess: History/ Examination/Investigation.
• Blood sugar control
  • Hypo/Hyperglycemic episodes, Hospitalization, Medical compliance.
  • BS-F & PP, HbA1C.
• Nephropathy
  • H/O – HTN, Swelling over body, Recurrent UTI.
  • Urine R/M (To exclude albuminuria and UTI), RFT.
• Cardiac status
  • H/O- Angina/ MI, Swelling of feet, Exercise intolerance.
  • ECG, CXR, ECHO, TMT.
• PVD
  • H/O Intermittent claudication, Blanching of feet, Non- Healing Ulcer.
• Retinopathy
  • H/O Visual disturbances.
  • Fundus Examination.
• ANS
  • Early satiety, abdominal distension, anhidrosis, impotence, orthostatic hypotension.
  • Postural change in BP, HR variability with exercise.
• Metabolic & Electrolyte
  • H/O – Starvation, infections, signs of DKA.
  • ABG, Urinary Ketones, Sr. Electrolytes.
• Airway
  • Scleroderma, Stiff joint syndrome (Prayer Sign, Palm Print test).
  • X-ray Cervical Spine – AP & LATERAL.

Pre-Operative DM Management

Pre-Operative Glycemic Management

• During pre-operative evaluation the type of diabetes is to be ascertained.
• Just before admission, patients should monitor blood glucose levels vigilantly including before and after meals as well as before sleeping.
• Additionally, finger stick glucose monitoring HGT should be completed every 4 to 6 hours in any patient who is Nil by Mouth (NBM).
• Long-acting insulin is discontinued 2 to 3 days prior to surgery; glucose levels are instead stabilized by a combination of intermediate insulin (NPH) with short-acting insulin twice daily or regular insulin before meals and intermediate-acting insulin at bedtime.
• The presences of complications of diabetes that might be adversely affected by or that might adversely impact upon the outcome of the proposed procedure have to be considered.
• Glycemic control is to be ensured pre-operatively.

What is the Acceptable Upper Limit of A1c For Patients Undergoing Elective Surgery?

• Diabetes UK Position Statements and Care Recommendations states that there is insufficient evidence to recommend an upper limit of HbA1c prior to elective surgery and the risks associated with poor glycemic control should be balanced against the necessity for surgery.
• HbA1c between 8% and 9% (mean plasma glucose of 185-210 mg%) is acceptable, depending on individual circumstances.

ERAS guidelines (Enhanced recovery after Surgery)

• Carbohydrate loading can be safely used in noninsulin dependent diabetics.
• In insulin dependent diabetics, a preoperative carbohydrate load has not been shown to result in hyperglycemia or delayed gastric emptying. However, monitoring of blood glucose levels should be carried out at regular intervals.

Intra-Operative DM Management

• Keeping glucose levels between 150 and 200 mg/dL (8 to 11mmol/L) during surgery.
• Clinicians must take the approximate length of time required to complete a procedure into consideration when determining an intraoperative glycemic control strategy.
• For more complex procedures, variable rate IV insulin infusion has been highlighted as a more effective method for achieving glycemic control.
• In patients with Type I Diabetes the insulin infusion rate begins at roughly 0.5–1 U/hour (mix 100U short-acting insulin in 100mL normal saline, i.e., 1U = 1 mL), whereas infusion rates are typically increased in Type II Diabetics to approximately 2-3 U/hour or higher.

Regimes

Vellore Regimen

• All patients had blood glucose measured at 6am on the day of procedure.
• For those patients whose operation started in the early morning (7.30 am to 9am), no glucose or insulin was given in the ward.
• All other patients receive a glucose insulin infusion (regular insulin 5U in 500 ml of 5% dextrose) in the ward, if their blood glucose is more than 100 mg/dl.

Alberti’s or GKI Regimen

• Blood sugar to be stabilized 2-3 days prior to surgery.
• Start GKI Infusion at 100 to 125 ml/hr.

Variable Rate Intravenous Insulin Infusion (VRIII)

• 50 ml syringe with 50 units of soluble human insulin in 49.5ml of 0.9% sodium chloride solution. This makes the concentration of insulin 1 unit per ml.
• The rate of fluid must be set to deliver the hourly fluid requirements of the individual.
• Delivery of the substrate solution and VRIII must be via a single cannula with appropriate one-way and anti-siphon valves.

Fluid Management

• Aims of fluid management:
  • Provide glucose as substrate to prevent proteolysis, lipolysis and ketogenesis.
  • Maintain blood glucose level between 100-150 mg/dl where possible.
  • Optimize intravascular volume status.
  • Maintain Serum electrolytes within normal ranges.
• The daily requirement of the healthy adult is:
  • 1.5-2.5 liters of Water.
  • 50-100 mmol of Sodium.
  • 40-80 mmol of Potassium.
  • 180 gms of Glucose is needed to prevent catabolism (particularly in DM).
  • Diabetic patients may require Magnesium, Phosphate.

Fluid Management for Patients Requiring a Variable Rate Intravenous Insulin Infusion VRIII

• The substrate solution to be used alongside the VRIII should be based on Sr electrolytes measured daily and selected from:
  • 0.45% saline with 5% glucose and 0.15% Potassium chloride (KCl) or
  • 0.45% saline with 5% glucose and 0.3% KCl.
• Very occasionally, the patient may develop hyponatremia without signs of fluid or salt overload, in such cases 0.45% saline is replaced by 0.9% saline with dextrose and potassium.
• Hypovolemia/Hypotension to be treated with Crystalloids such as 0.9% Normal saline, Harttman solution.
• Aims of Fluid Management:
  • Provide intravenous fluids as required according to individual need until the patient has recommenced oral intake.
  • Maintain Sr electrolytes within the normal ranges.
  • Avoid Hyperchloremic metabolic acidosis.
• Recommendations:
  • Hartman’s solution should be used in preference to 0.9% saline.
  • Glucose containing solutions should be avoided unless the blood glucose is low.

Post-Operative DM Management

• The Society of Thoracic Surgeons as well as the AACE/ADA consensus recommended a postoperative glycemic range between 140 and 180mg/dL.
• If blood glucose levels remain low after surgery, a dextrose infusion rate of 5–10 g of glucose per hour should prevent hypoglycemia and concomitant ketosis.
• Additionally, if a patient is unable to tolerate oral nourishment for a prolonged period of time, total parenteral nutrition (TPN) should be considered.
• Physiologic replacement of insulin can be mediated by a long-acting basal insulin dose, short or rapid acting insulin dose following meals and rapid acting supplemental insulin to combat hyperglycemia if needed.
• In non-critically ill hospitalized Type II diabetics, use of basal/bolus insulin protocols offers significantly better glycemic control than supplemental-scale insulin alone.
• The basal insulin dosage can be calculated using the Miami 4/12 rule or approximated to 50–80% of the intraoperative IV insulin total.
• Patients treated with intraoperative IV insulin; it may be easiest to continue IV insulin alongside a dextrose infusion until the patient can tolerate food without difficulty.
• Supplemental insulin dose for hyperglycemic patients can be approximated by dividing the total daily insulin (TDI) dose by 30 for every 50 mg/dL (3mmol/L) above the glycemic goal.
• For example:
  • Take a patient with a TDI dose of 150U with a blood glucose reading of 350mg/dL. Subtracting the upper end of a normal glucose measurement (200mg/dL) from the patients reading and diving by 50mg/dL yields 3 [(350 − 200)/50 = 3]. Simply multiply this number by the TDI/30 (150/30 = 5) to determine the patient requires an additional 15U of rapid acting insulin to restore blood glucose levels back into target range.

Switching To Subcutaneous Insulin

• The recommendation on the frequency of finger stick testing is as follows:
  • If the patient is being fed enterally or parenterally, blood glucose monitoring by glucometer is recommended every 4-6 h if a rapid-acting insulin analog is used and every 6 h if regular insulin is used.
  • If the patient is eating orally, blood glucose monitoring by glucometer should be performed before meals and at bedtime.

Special Operative Conditions

• Minor outpatient surgeries, Type I or Type II diabetes can be managed on their regular daily anti-diabetes medications.
• For emergency surgery situations, blood glucose should be monitored more frequently.
• Physicians should also note when the last dose of a sulphonyl urea drug was taken, as progressive absorption may disturb glycemic control.
• Insulin requirements are generally much higher in cardiac procedures; recent studies suggest improved patient outcomes with tight glycemic control during and after cardiac surgery.
• Perioperative blood glucose levels must be carefully monitored in patients undergoing cesarean section.
• Hyperglycemia should be avoided during cesarean section to reduce the risk of neonatal hypoglycemia or wound infections in the mother.
• Before induction of labor, patients should follow their normal diabetic regimen; however, if labor is prolonged and blood glucose levels fall below 100 mg/dL, a 5% dextrose infusion should be initiated.

Anaesthesia And Diabetes

Pre-Op Fasting

• At least 6 hrs. for solid foods.
• Patients with gastroparesis, 12 hrs. may be needed. Such patients are given H2 receptor blocker (Ranitidine) and prokinetics (Metoclopramide).
• When fasting exceeds 8-10 hrs. then insulin – glucose infusion has to be started to prevent catabolism.

Concerns

• DM affects oxygen transport by causing glucose binding to Hb.
• DM is considered CAD equivalent.
• Chronic Kidney Disease CKD is asymptomatic in diabetes and usually advanced.
• Autonomic dysfunction causing:
  • Exaggerated Hypotension.
  • Risk of Hypothermia.
  • Sympathetic responses are blunted.
  • Silent MI.
  • Delayed gastric emptying.
• Difficult Airway
  • Restricted joint movement (Atlanto-Occipital).
  • Obesity.
• Therapy related
  • Sulphonylureas – Hypoglycemia.
  • Metformin – Lactic acidosis.
  • Incretins & Amylin – Delays gastric emptying, nausea.

Pharmacology of Anaesthetics and DM

• Propofol – Lipid loading leads to impaired metabolism in DM, decreased lipid clearance.
• Etomidate – Decreases adrenal steroidogenesis → decreased glycemic response to surgery.
• Ketamine – May cause significant hyperglycemia.
• Midazolam – Decreases ACTH & Cortisol → decreased sympathoadrenal stimulation → decreased glycemic response to surgery.
• Alpha – 2 adrenergic agonist – Decreases sympathetic outflow from hypothalamus, decrease ACTH → decreases glycemic control.
• Opioids – Offers hemodynamic, metabolic, hormonal stability. Blocks entire sympathetic nervous system & Hypothalamic-Pituitary axis.
• Inhalation agents – Halothane, Isoflurane, Enflurane inhibit the insulin response to glucose in reversible and dose dependent manner.
• Dexamethasone – Increases blood sugar.
• NSAIDS – Aggravate gastritis, aggravates renal dysfunction.

CME INDIA Learning Points

(By Dr. Saraf)

CME INDIA Tail Piece

Credit: New guidance on the perioperative management of diabetes Bonnie Grant and Tahseen a Chowdhury. DOI: https://doi.org/10.7861/clinmed.2021-0355 Clin Med January 2022.

Guideline for perioperative adjustment of non-insulin diabetes medication before surgery

Acarbose Take as normal Omit morning dose if not eating. Give morning dose if eating.

Meglitinide (repaglinide or nateglinide) Take as normal. Omit morning dose if not eating. Give morning dose if eating.

Metformin (AND eGFR >60 ml/min/1.73m2 OR procedure not requiring use of contrast media)-Take as normal If taken once or twice a day – take as normal.

If taken three times per day, omit lunchtime dose.

If taken once or twice a day – take as normal.

If taken three times per day, do not take lunchtime dose.

Sulphonyl urea (e.g., glibenclamide, gliclazide, glipizide, glimepiride)

Take as normal Omit on morning of surgery.

If taken twice daily, take evening dose if eating.

Do not take on day of surgery.

Pioglitazone Take as normal Take as normal. Take as normal.

DPP4 inhibitor (e.g., sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin).

Take as normal.

GLP-1 Receptor Agonist (e.g., exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide) Daily/Weekly administration.

Take as normal.

SGLT-2 inhibitors (e.g., dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) SGLT2 inhibitors must be discontinued 3–4 days before surgery. (ADA-2023)

References:

1. Verde i, armean p. Current perioperative management of diabetic patients from general surgerywards. Acta medica transilvanica september 2014;2(3):243-247.
2. Barker Et Al. Guidelines ON Peri-operative Management Of The Surgical Patient With Diabetes 2015. Anaesthesia .Doi:10.1111/Anae.13233
3. Verde i, armean p. Current perioperative management of diabetic patients from general surgerywards. Acta medica transilvanica september 2014;2(3):243-247.
4. S Sudhakaran, S.R.Surani. Guidelines for Perioperative Management of the Diabetic Patient.Surgery Research and Practice.2015; Article ID 284063, 8 pages
5. Salam R. Perioperative management of diabetes mellitus. J Med Soc 2014;28:4-8.
6. Management of adults with diabetes undergoing surgery and elective procedures: improving standards-nhs(national institute for health and clinical excellence) April 2011
7. Dogra P, Jialal I. Diabetic Perioperative Management. [Updated 2022 Jun 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK540965/
8. New guidance on the perioperative management of diabetesBonnie Grant and Tahseen A Chowdhury.DOI: https://doi.org/10.7861/clinmed.2021-0355 Clin Med January 2022
9. Centre for Perioperative Care. Guideline for perioperative care for people with diabetes mellitus undergoing elective and emergency surgery. CPOC, 2021. https://cpoc.org.uk/sites/cpoc/files/documents/2021-03/CPOC-Diabetes-Guideline2021_0.pdf

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