Postoperatieve endocriene verwikkelingen
Chantal Mathieu UZ Gasthuisberg, KULeuven
The diabetic patient for surgery
ADA criteria for diagnosis of diabetes mellitus (2005) NORMAAL
Diabetes
Gestoorde glucosetolerantie
________________________________________________________________________ Nuchter
<100 mg/dl
≥126 mg/dl
≥100 en <126 mg/dl
OGTT
<140 mg/dl
≥200 mg/dl
≥140 en <200 mg/dl
(2h na 75g glucose)
Random staal
≥200 mg/dl
________________________________________________________________________ * In afwezigheid van klinische decompensatietekens (polyurie, polydipsie,...) moet voor de diagnose met zekerheid mag gesteld worden de test op een andere dag herhaald worden.
The diabetic patient for surgery Diabetes, a growing problem Diabetes, a changing population Diabetes, changes in treatment
Diabetes in the hospital
Occupation of beds DARTS UZ GHB Periphery VU
8.2% (0.5+7.7) 8.4% 8.2% 5.8%
LOS 7 vs 3d 12/10 vs 7.9d 11.7vs 7.4d 11.5 vs 8d
Why are diabetic patients admitted into hospital? DARTS, retrospective cohort study RR for type 2 diabetic patients for hospitalisation Amputation PVD Renal faillure MI Stroke
RR 5.79 4.27 3.99 2.05 1.94
Peri-operatieve glycemic control: The problem Operative stress:
Hyperglycemia in vitro
Insulin resistance
Chemotaxis Phagocytosis Killing Toxisc radicals
Hyperglycemia
Peri-operative glycemic control: The dilemma Strict glycemic control:
Less strict control:
Intensive work Risk of hypoglycemia
Less work No risk of hypoglycemia Risk of hyperglycemia
Consequences of hyperglycemia Protein catabolism Impaired woundhealing Impaired defence against infections Fluid and electrolyte imbalance Hyperosmolarity (type 2) Ketoacidosis (type 1) ↑ cardiovascular mortality
The diabetic patient for surgery Diabetes, a growing problem Diabetes, a changing population Diabetes, changes in treatment
Diabetes, not all patients are the same Carefull history of diabetic complications Cardiovascular risk? Renal status? Eye disease? Neuropathy?
Diabetes, not all patients are the same Carefull history of diabetic complications Cardiovascular risk? Renal status? Eye disease? Neuropathy?
Carefull history of medications Antihypertensives, statins, aspirin,… OAD Insulins
The diabetic patient for surgery Diabetes, a growing problem Diabetes, a changing population Diabetes, changes in treatment
Oral antidiabetics Insulin-augmenting agents
Insulin-assisting agents
Sulfonylurea
Biguanides (Metformin)
“Glinids”
Alpha-glucosidase inhibitoren
Thiazolidinediones
Characteristics of commonly used sulfonylurea Generic name
Brand name
Posology
Duration of action
Excretion
(h) (Tolbutamide)
Rastinon
(Tolazamide)
Tolinase
Chlorpropamide Diabinese
125-250mg/d
60
Renal
Glibenclamide
2.5-15mg/d
60
Renal
2.5-20mg/d
24
Renal 80%
Daonil Euglucon
Glipizide
Glibenese Minidiab
Gliquidone
Glurenorm
30-90mg/d
7
Hepatic 95%
Gliclazide
Diamicron
40-120mg/d
24
Renal 70%
Glimepiride
Amarylle
1-8mg/d
24
Renal 60%
Characteristics of Metiglinides Generic name
Brand name
Posology
Duration of action
Excretion
(h)
Repaglinide
Novonorm
2-12mg/d
6
Hepatic
Characteristics of Available Agents that Enhance the Effectiveness of Insulin
Class and generic name
Approved daily dosage range
Duration of action (hours)
Clearance
Glucophage Liver, muscle
500 - 2550 mg
6 to 12 (?)
Renal
Glucobay
Intestine
25 - 300 mg
<4
Not absorbed
Actos Avandia Resulin
Fat, muscle 15 - 45 mg Fat, muscle 4 - 8 mg Fat, muscle 200 - 600 mg
Weeks (?) Weeks (?) Weeks (?)
Hepatic Hepatic Hepatic
Brand name Site of action
Biguanide Metformin
α-Gluc. Inhibitor Acarbose
Thiazolidinedione Pioglitazone Rosiglitazone Troglitazone
Combination drugs Glucovance
Metformin + Glibenclamide 500mg 500mg
Avandamet
2.5mg 5mg
Metformin + Rosiglitazone 500mg 500mg
1mg 2mg
The Incretin Effect: difference in Insulin Response to Oral vs IV Glucose 2.0
Oral glucose (50 g) or isoglycemic infusion
200
*
C-Peptide Peptide* (nmol/L)
Plasma Glucose (mg/dL)
IV glucose Oral glucose
100
1.5 *
*
*
*
1.0
*
*
0.5 0.0
0 0
60
120
180
0
Time (min)
60
120
180
Time (min)
*C-peptide measure is a marker for endogenous insulin production in the liver IV = Intravenous Adapted from Nauck MA, et al. J Clin Endocrinol Metab. 1986;63:492–498.
19
The incretins GLP-1: glucagon-like peptide-1 H A E G T F T S D V S S Y L E G Q A A A I F E K K L R V W G G GIP: glucose-dependent insulinotropic peptide A
E G T F I S D Y S I A M D K I H Q K K G K A L L W N V F D Q D N W Q K T Q I N H Y
Amino acids shown in gold are homologous with the structure of glucagon
-
Solutions for exploitation of the incretin system GLP-1 mimetics - Homologue: Exenatide - Analogue: Liraglutide, Taspoglutide
DPP IV inhibitors -
Sitagliptin Vildagliptin Saxagliptin …..
GLP-analogues
Exenatide
Byetta® 2x5µg 2x10µg
Characteristics of Gliptines Generic name
Brand name
Posology
Duration of action
Excretion
(h)
Sitagliptine
Januvia
Vildagliptine Galvus
100mg/d
24
Renal
2x50mg/d
12-14
Renal
Some numbers on type 2 diabetes 53% of patients with type 2 diabetes treated with SU need insulin by 6 years of follow up 80% of patients with type 2 diabetes treated with SU need insulin by 9 years of follow up
Hayward et al. JAMA 1997,278; Wright et al. Diabetes Care 2002,25; Turner et al. JAMA 1999,281, DeWitt et al. JAMA 2003,289
Current insulin preparations and their pharmacokinetics following s.c. injection Insulin
Onset of action
Peak of action
Duration of action
Soluble 30-60 minutes Lispro/Aspart 5-15 minutes Glulisine NPH 1-2 hours
2-4 hours
6-8 hours
1-2 hours
4-5 hours
5-7 hours
13-18 hours
Lente
1-3 hours
4-8 hours
13-20 hours
Ultralente
2-4 hours
8-10 hours
18-30 hours
Glargine Levemir
1-2 hours 1-2 hours
peakless dose-dependent
Adapted from Burge and Schade. 1997
>24 hours 20-24 hours
Insulin Profiles Aspart, Lispro, Glulisine (4–5 hr) Regular (6–8 hr) Plasma Insulin Levels
NPH (12–16 hr) Ultralente (~16 ~16––20 hr ) Glargine (~24 hr) Levemir (~20 ~20-24 hr)
0
2
4
6
8
10
12
14
16
18
20
22
24
Hours Based on Rosenstock J, Wyne K. In: Goldstein BJ, Muller-Wieland D, eds. Textbook of Type 2 Diabetes. 2003. Ch. 11:131-154.
Standard therapy of type 1 diabetic patients: Basal bolus therapy 70 Normal free insulin levels (Mean)
Insulin (mU/l)
60
Simulated s.c. injected Humalog/NovoRapid + Glargine (Lantus)
50 40
Meals
30 20 10 0 0600
0900
1200
1500
1800
2100
2400
Time of day Breakfast Adapted from Polonsky et al. 1988
Lunch
Dinner
Bedtime
0300
0600
Variable Basal Rate: CSII Program
Plasma insulin
Breakfast
Lunch
Dinner
Bolus Bolus
Bolus
Basal infusion 4:00
8:00
12:00
16:00
Time
20:00
24:00
4:00
8:00
Diabetes: messages for surgeons Be aware Contraindication: ketoacidosis- all others go ahead Type 1 and short duration operation: basal insulin or basal pump- IV access Type 1 and long duration: IV drip Type 2: depends on therapy and duration of surgery
Diabetes: messages for surgeons Type 2 diabetes: -
Metformin: officially stop (potential lactic acidosis SU: stop (hypoglycemia) TZD continue DPP4 inhibitors continue Insulin: similar type 1
Thyroid Avoid hyperthyroidism preop Determine thyroid function postop
Definitie thyreotoxische “storm” • Levensbedreigende complicatie van hyperthyreoïdie – Geen enkele test of testcombinatie is diagnostisch
• Klinische diagnose! – Labowaarden ~ ongecompliceerde thyreotoxicosis
Klinische diagnose • T° > 38.5 ° C • Tachycardie > 140/ min Congestief hartfalen • Bewustzijnsstoornissen – tremor, rusteloosheid, emotionele labiliteit – agitatie, psychose apathie, coma
• Gastro-intestinale verschijnselen – diarree - buikpijn, nausea, braken – leverstoornissen, icterus
Behandeling “storm” 4 domeinen Bestrijding van overmaat schildklierhormoon Remming van de perifere effecten van schildklierhormoon Handhaving van homeostase Bestrijding van uitlokkende ziekte
Bestrijding overmaat sk hormoon Remming hormoonsynthese Thyreo-inhibitoren (ATD) hoge doses PTU: oplaaddosis van 600-1000mg, dan tot 200 mg/4h Strumazol tot 20 mg/6h (IV: methimazol in UZ apotheek)
Remming hormoonvrijzetting Jodiumtoediening: 1 uur na start ATD Lugol 8 druppels (0,5 ml)/6h po (IV NaI 1g/12h)
Bestrijding overmaat sk hormoon Remming hormoonsynthese Remming hormoonvrijzetting Jodiumtoediening = tweesnijdend zwaard: snelle remming van hormoonvrijzetting vs. uitstel van diagnostiek en ev. 131I-therapie
Reductie circulerend hormoon (zelden) peritoneaal dialyse of plasmaferese hemoperfusie door hars/actieve kool cholestyramine po • (onderbreking enterohepatische recirculatie)
Remming perifere effecten Remming perifere conversie T4 T3 Hydrocortisone 3 x 100 mg IV/d (+ i.v.m. onaangepast lage cortisolemie)
PTU (hoge doses); propranolol 40-80mg/4h
Bètablokkade (op zich onvoldoende) • densiteit van β-receptoren in thyreotoxicosis
Propranolol 40-80 mg po/4h (IV propranolol 1-3 mg over 10 min/4-6 h) (IV esmolol oplaaddosis 0,25-0,5 mg/kg over 10 min, infuus:0,05-0,1 mg/kg/min)
Handhaven homeostase Intensieve zorgen - supportief Correctie hydratatietoestand (CV collaps) • cf. zweten, diarree, braken • centrale katheter, ev. Swan-Ganz
Nutritioneel (glucose, B-vitamines) Afkoelen • antipyretica: paracetamol (geen salicylaten) • mechanisch (ijs,…)
O2, monitoring elektrolyten, glucose, leverset, (plasma cortisol)
Therapie Opereer geen hyperthyroide patiënten Denk eraan Roep de endocrinoloog…..
Acute bijnierinsufficiëntie Addison’s disease
Diagnose acute bijnierinsufficiëntie Patiënt onder stress (ICU) (hypotensie, hypoxie, koorts, hypoglycemie) random cortisol < 25 µg/dl geen ACTH-testing nodig voor diagnose
Niet-hypotensieve patiënt (ICU) cortisol na LD-ACTH < 25 µg/dl (Synacthen-test) random cortisol < 20 µg/dl + tekens
Behandeling Hydrocortisone: 100mg IV/6h eerste dag, dan afbouwend tot 2x50mg per dag, dan afhankelijk van pathologie, per os.
Therapie Denk eraan Roep de endocrinoloog…..
