Peri-Operative Diabetic Patient
Management
Larry Field, MD
Critical Care Anesthesiologist
Medical University of South Carolina
April 20, 2010
Objectives
• Update our knowledge of different
insulin preparations
• Update our knowledge of non-insulin
(oral and injectable) agents
• Set reasonable goals for perioperative
glycemic control
• Suggest recommendations for
achievement of glycemic goals
• Disclaimers: None
Diabetes Mellitus
• Metabolic diseases characterized by
hyperglycemia resulting from defects in
insulin secretion, insulin action, or both
• Affects 8% of general population
• 20% of persons aged 65 to 74
• 30-40% of those born this past decade
JAMA 2003;290:1884–90
Curr Opin Anaesthesiol 22:718–724
Insulin Regimens
Humalog/
Novolog
Humalin/
Novolin
Lantus
Levemir
(detemir)
Non-insulin Agents
Alpha-glucosidase inhibitors
• Acarbose (Precose), miglitol (Glyset)
• Inhibit oligosaccharide and disaccharide
uptake at intestinal (brush border) level
• If NPO, doesn’t do anything
Biguanide
• Metformin (Glucophage)
• Inhibition of gluconeogenesis in the kidneys
and liver
• Bind to the Mitochondrial membranes,
leading to decreased ATP and increased
AMP
• Limited hypoglycemia potential
• Lactic acidosis black box warning
• Classically hold for 48hrs
• Eliminated by kidneys
Diabetes Care 2004; 27:1791-1793
Sulfonylureas
• Endogenous insulin
release from beta cells
• Can cause
hypoglycemia
• Hold on morning of
surgery
www.endotext.org
Meglitinides
• Nateglinide (Starlix), repaglinide (Prandin),
repaglinide/metformin (PrandiMet)
• Induce endogenous insulin release similar
to sulfonureas
• Hypoglycemic risk reduced?
• Quick/short action
• Taken prior to each meal
Thiozolidinediones (glitazones)
• Troglitazone (Rezulin), rosiglitazone (Avandia),
pioglitazone (Actos)
• Transcription factor (PPAR)agonist
 Insulin receptor sensitization
• Also improves lipid profiles
• No lactic acidosis
• Limited potential for hypoglycemia
• Hepatotoxicity and fluid retention concerns
• Short plasma half-life; Long duration of action
Combination Pills
Incretin hormones?
• GI hormones released in response
enteral carbohydrate load
• Glucose-dependent insulinotropic
polypeptide (GIP)
• Increased insulin release from beta cells
prior to hyperglycemia
• Glucagon-like peptide 1 (GLP-1)
• Neuroendocrine signal
GLP-1
• Alpha cells:
• Glucose-dependent glucagon inhibition
• Beta cells:
• Primes glucose-dependent insulin release
• Increases beta cell numbers
• Increases insulin biosynthesis
• Reduces appetite; slows gastric emptying
Dipeptidyl peptidase IV
• Ubiquitous
• Involved in hormone degredation
• GLP-1, VIP, GHRH, neuropeptide Y
• GLP-1 is quickly degraded
• Involved in immune cell messaging
Amylin
• Produced by pancreatic beta cells
similar to insulin
• Independent/additive effects to insulin
• Glucose-dependent glucagon
suppression
• Satiety and delayed gastric emptying
Newest Agents
SQ
PO
SQ
Little anesthetic experience with these agents
Based on physiology and pharmacology
Anesth Analg 2009;108:1803–10
Surgery as a Metabolic Challenge
• Stress hormones – catecholamines,
cortisol, growth hormone
• Cytokines – IL-6 and TNF-alpha
• Hyperglycemia proportional to insult
• Superficial: 10-20 mg/dl
• Major vascular/cardiac: 50-100 mg/dl
Stress-induced hyperglycemia
• Adaptive response
• Brain and red blood cell uptake is
increased
• Independent risk factor for morbidity
and mortality
Hyperglycemia
• Impaired collagen production
• Impaired neutrophil chemotaxis,
phagocytosis, and bacterial killing
• Increased platelet aggregation
• Infectious complications
Clinical Diabetes 2009; 27:82-85
Hypoglycemia
• Sympatho-adrenal activation
• Diaphoresis, tachycardia, hypertension
• Weakness/fatigue  AMS  Coma
• Common in Type 1 diabetics
• Uncommon in Type 2 diabetics
Intraoperative Glucose
Control Data
• Sparse data on outpatient procedures
• Critical care data
• Van den Berghe 2001  80-110 goal
• NICE-SUGAR  140-180 goal
• Cardiac/surgical data
• Very tight vs good vs poor glucose control
Insulin Benefits
• Decreases endothelial activation
• Improved lipid profiles
• Decreases pro-inflammatory cytokine
production
• Benefits thought due to glycemic control
Treatment Goal
• Try to mimic normal metabolism as
closely as possible:
• Avoiding hypoglycemia
• Avoiding excessive hyperglycemia
• Avoid ketoacidosis
• Avoid electrolyte/fluid disturbances
• Avoid large fluctuations
Consensus Recommendations
Typical daily insulin regimen
(DM Type 1: about 50% of daily insulin is basal)
Consensus Statement, SAMBA 2010
Consensus Recommendations
Consensus Statement, SAMBA 2010
Consensus Statement, SAMBA 2010
Consensus Recommendations
Consensus Statement, SAMBA 2010
Consensus Recommendations
Consensus Statement, SAMBA 2010
Consensus Recommendations
Consensus Statement, SAMBA 2010
Consensus Recommendations
Consensus Statement, SAMBA 2010
POC testing can be
off by +/- 20%
• 20% of capillary
• 7% of whole
blood samples
Mayo Clinic Proc. 2008; 83:394-397
Consensus Recommendations
Insulin admin: IV gtt vs IV bolus vs SQ bolus?
Consensus Statement, SAMBA 2010
Insulin Dosing
• Use 1500 rule for regular insulin
• Use 1800 rule for rapid-acting insulin
Current opinion in anesthesiology 2009; 22:718-724
Consensus Recommendations
Consensus Statement, SAMBA 2010
Current opinion in anesthesiology 2009; 22:718-724
Other Anesthetic Considerations
for Diabetes Mellitus
• Diabetic comorbidities not covered today
• Periop/stress steroids
 Hyperglycemia within a couple of hours
• Starvation increases insulin resistance
 Preop carb loading may help
• Beta-blockers can blunt catecholamineinduced hyperglycemia
Other Anesthetic Considerations
for Diabetes Mellitus
• Etomidate can blunt steroid-induced
hyperglycemia of stress
• Volatile anesthetics impair insulin release
and increase insulin resistance (dosedependent)
• Regional anesthesia/local anesthetics can
blunt/abolish periop hyperglycemia
• High-dose opioids also blunt
A Final Thought
Continuous glucose monitoring
will (soon) be awesome!