PERIOPERATIVE

STRESS RESPONSE
TO SURGERY AND ANESTHESIA

Vina Yanti Susanti

Endocrinology Departement
Sardjito Hospital/ Faculty of Medicine UGM
 Epidemiology

§ Diabetes affects more than 10% of people undergoing

surgery

§ People with diabetes undergoing surgery have

§ An increased length of stay (9 vs. 7 days)

§ Increased incidence of pneumonia (12.1 vs. 5.4%)

§ Increased incidence of wound infection (5 vs. 2.3%)

§ Increased incidence of myocardial infarction (2.6 vs.

1.2%)

National Diabetes Inpatient Audit (NaDIA) 2010. 2011. Available at

http://www.diabetes.nhs.uk/ourpublications/reports_and_guidance/diabetes_information_and_Data
Frisch et al Prevalence and Clinical Outcome of Hyperglycemia in the Perioperative Period in Noncardiac Surgery Diabetes
Care 2010; 33(8): 1783–1788
Impact of surgery

Persistent hyperglycaemia is a risk factor for perioperative

complications:

§ endothelial dysfunction
§ postoperative sepsis
§ impaired wound healing

Stress response (counterregulatory hormones)

Volume contraction (nausea, vomiting, osmotic diuresis)

Dagogo-Jack S, George K, Alberti. Management of Diabetes Mellitus in Surgical Patients. Diabetes

Spectrum 2002, 15(1): 44-48
 Impact of surgery and general anaesthesia

§ Physiological stress- counter-regulatory hormone

release
§ Increased insulin resistance
§ Decreased insulin secretion
§ Decreased peripheral glucose utilisation
§ Transient hyperglycaemia possible in non-diabetes patients
§ Insufficient reserve to compensate in type 1 (no insulin
secretion) and type 2 diabetes (relative secretion defect)

Dhatarya K et al NHS diabetes guideline for the perioperative management of the adult patient with diabetes
Diabetic Medicine 2012; 29:420-433
Aärimaa et al Glucose tolerance and insulin response during and after elective skeletal surgery.
Ann Surg. 1974;179(6):926
Respon Endokrin dan Metabolik pada Pasien Diabetes yang Menjalani
Pembedahan
•Endokrin
Peningkatan hormon kontra regulasi insulin : katekolamin, glukagon, dan kortisol – hormon
katabolik utama dan hormon pertumbuhan
Penurunan sekresi insulin menyebabkan hilangnya efek antikatabolik insulin
Penurunan kerja insulin yang disebabkan oleh meningkatnya resistensi insulin sekunder akibat
hormon kontra regulasi
•Metabolik
Hiperglikemia
Penurunan penggunaan glukosa
Meningkatnya produksi glukosa sekunder akibat glikogenolisis dan glukoneogenesis
Meningkatnya katabolisme protein
Meningkatnya variabel pada lipolisis dengan formasi benda keton
Meningkatnya laju metabolik dan katabolisme
•Efek segera dan jangka panjang
Dehidrasi dan ketidakstabilan hemodinamik yang disebabkan oleh diuresis osmotik
Berkurangnya massa lemak tubuh, keseimbangan nitrogen negatif, kegagalan penyembuhan luka,
penurunan resistensi untuk terjadinya infeksi
Berkurangnya jaringan adiposa dan cadangan energi dari asam lemak
Defisiensi asam amino esensial, vitamin dan mineral
Sympatho-adrenal response to surgery

§ The stress response to surgery causes an increased production

of hormones with catabolic function
§ Cortisol: cortisol secretion is increased as a result of adrenal
cortical stimulation by means of ACTH.
§ A greater ACTH and cortisol plasma concentrations may be
detected few minutes after the start of the surgery and its
increase is related to the intensity of surgical stimulus.
§ Other than its known metabolic effects, cortisol exerts anti-
inflammatory activity by reducing inflammatory mediators’
production.
§ The physiological feedback mechanism that leads to ACTH
synthesis inhibition due to increased cortisol concentration is
disrupted during surgery whereas the cortisol secretion may
be reduced by anesthetic drugs
§ PRL: PRL is a protein hormone of 199 amino acids with a
structure similar to that of growth hormone.
§ Secretion of PRL is increased as part of the stress response
to surgery. It has a little metabolic activity.
§ The physiological effects of increased secretion of PRL
during surgery are unknown.
§ However, PRL is supposed to regulate T-lymphocyte
proliferation
Activation of the stress response

§ The cytokines have local effects of mediating and

maintaining the inflammatory response to tissue injury, and
are also implicated in some of systemic changes.
§ After major surgery, the main released cytokines are
interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) and
IL-6.
§ The initial reaction is the release of IL-1 and TNF-α from
activated macrophages and monocytes in the damaged
tissues.
§ This process stimulates production and release of further
cytokines, in particular, IL-6, the main cytokine responsible
for inducing the systemic changes known as acute phase
response
§ The cytokines increase the cortisol secretion by stimulating
ACTH release as a result of surgical stimulus but cortisol
response to surgery suppresses cytokine production due to
a negative feedback system

§ It has been demonstrated that IL-6 secretion, but not other

stress hormones production, may be reduced using less
invasive surgical techniques (e.g. laparoscopic approach)
§ Anaesthetic drugs exert a variable action on response of
HPA axis to surgical trauma and only little effects on
cytokine production linked to tissue trauma. It is essential
to blunt the stress hormones secretion in order to prevent
postoperative complications, such as delirium

§ the use of drug at dose known to produce adequate

anaesthesia and the support of neuro-monitoring may help
to prevent an excessive HPA axis activation
§ Review of the etomidate mechanism shows suppressed
adrenocortical function mediated by blocking the activity of
11-beta-hydroxylase, ultimately causing decreased
steroidogenesis
§ Acute adrenocortical insufficiency and crisis may occur after
a standard induction dose of etomidate. However, due to
diminished cortisol secretion, etomidate triggers a
subsequent decrease in the hyperglycemic response to
surgery.
§ Additionally, if used in high doses during surgery,
benzodiazepines decrease ACTH secretion.
§ Benzodiazepines also stimulate release of growth hormone,
while reducing sympathetic stimulation.
§ Opiates given in high doses such as during the
postoperative recovery phase block the sympathetic
nervous system as well as the hypothalamic-pituitary axis,
essentially abolishing the hyperglycemic response to
surgery.

§ In vitro studies revealed that volatile anesthetic agents

such as halothane and isoflurane inhibit normal insulin
production triggered by glucose in a dose dependent
fashion, essentially resulting in a hyperglycemic response
Aim of perioperative management in
diabetes patients

§ Avoid hypoglycaemia
§ Avoid severe hyperglycaemia, volume depletion, electrolyte
abnormalities

§ Ensure adequate nutrition

§ Assess educational needs
Summary

§ Surgery is common in patients with diabetes

§ Hyperglycaemia is associated with adverse outcomes
§ Hypoglycaemia is associated with adverse outcomes
§ All patients on insulin, and most on oral agents, require
perioperative insulin

§ IL-6, TNF, IL-8, acute phase proteins are responsible

§ Each patient should be considered individually and treated
appropriately
TERIMA KASIH