الفهرس 
Material and methodsOnly 14 pages are availabe for public view
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Abstract
Surgery evokes a series of well-characterized changes in hormonal
secretion and substrate mobilization, which are commonly referred to
as the ”stress response” to surgery. Anesthesia as well particulary
endotracheal intubation evokes cardiovascular response that can pass
without problems in normal persons, but in patients with compromised
cardiovascular system, it may be serious. Many anesthetic techniques
can modify part of cardiovascular response to intubation and part of
the hormonal and metabolic resonses to surgery, so knowledge of such
potential interactions is of importance.
Afferent neuronal impulses from the surgical site activate
hypothalamic-pituitary hormone secretion and the sympathetic
nervous system. Autonomic alTerent activity is of considerable
importance. There is now considerable evidence from studies with
epidural analgesia, both with local analgesics and with opioids, that
profound analgesia has only limited effect on the catabolic hormonal
response to surgery. It is only when autonomic blockade is added to
somatic blockade that complete block of the hormonal changes is
achieved.
The onset of surgery is associated with the rapid secretion of
hormones derived from the anterior and posterior pituitary Bendorphin,
adrenocorticotrophic hormone (ACTll), growth hormone
(GH), prolactin and arginine vasopressin (AVP) together with
activation of the sympathetic nervous system and the increases 111
circulating cortisol, aldosterone and rennin values. There IS
suppression of the important anabolic hormones; insulin and
testosterone.
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The increase in blood glucose. Found during and after surgery
is roughly proportional to the severity of the surgical trauma. There is
close association between activation of catecholamine secretion and
hyperglycaemia during the first few hours after the onset of surgery.
An increase in cortisol production and insulin suppression becomes of
increasing importance in perpetuating the glucose response in the
postoperative period. There is little evidence to support an important
role for glucagons in mediating the hyperglycaemic response to
surgery as the change in plasma levels is little during and after
uncoDlplicatedsurgery (Raja et al, 1988).
There are few changes in lipid mobilization associated with
surgery. In the operative and immediate postoperative pf’lrlodsthe key
hormones responsible for mobilization of non-esterified fatty acids are
catecbolamines (stimulatory) and insulin (inhibitory). However,
ketoQe body synthesis by the liver remains very lqw even when
circutllting non-esterified fatty acid values are high in a’ starved patient
with low insulin secretion (Hall et at, 1983).
Muscle protein loss is an inevitable accompaniment of any
major surgical operation. The amino acids released from muscle,
alanine and glutamine, are used for essential protein synthesis in the
liver, such as acute phase proteins ad for gluconeogensis in the liver
and renal cortex. It is the factors responsible for the loss of protein,
which are still not adequately elucidated interleukin-l, or a fragment
of this polypeptide, is a strong possibility, as are cortisol and insulin
(Fleck, 1980).
Trauma and inflammation of the tissues are associated with the
release of a polypeptide from the maerophllges and monocytes, which
is QOwknown as interleukin-l and is thought to be responsible for a
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variety of changes found after surgery. Furthermore, it has been
reported that interleukin-l enhanced messenger RNA and
somatostatin release in cultured hypothalamic neurons. The
importance of interleukin-l and similar peptides to the anesthetist lies
in the knowledge that their secretion occurs in response to tissue
damage and thus cannot be modified by any available anesthetic
technique (Michie et at, 1988).
Somatostatin, a peptide containing 14 amino acids bridged by a
sulph\lf-sulphur bond, was originally isolated form the pancreas and
the hypothalamus. Subsequent investigations have revealed that this
peptide is distributed widely in cells with functions other than the
regulation of growth hormone. Somatostatin is distributed extensively
within the nervous system, including parts of the brain pther than the
hypotllalamus, such as the cerebral cortex. Nerve fibers that produce
somatpstatin are present in the genitourinary system, heart, eye,
thyro4i, thymus and skin, somatostatin has also been found in
pancreatic islet D-cells, gastric and intestinal epithelium, intestinal
myenteron, salivary glands and the parafollicular cells of the thyroid.
Depending on its location, somatostatin seems to have different
action. It can act as a circulating hormone, as a paracrine (locally
acting) agent or as a neurocrine agent, released by somatostatinergic
neurons into the neuro - effector junction.
While receptors specific for somatostatin have been identified
in many tissues, somatostatin mechanism of action within the cells is
not known. It may cause calcium and potassium channel blockade or
may lIuppress production of cyclic AMP (Reub; and Maurer, 1986).
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The highly varied physiologic effects of Somatostatin are
primarily inhibitory. Somatostatin inhibits secretion and often inhibits
the target tissue as well.
Somatostatin inhibits the secretion of growth hormone,
thyrotropin, insulin, glucagons and gut hormones. It also decreases
gastrointestinal blood flow and motility and inhibits the secretion of
gastric acid and pepsin. Furthermore, somatostatin decreases
carbohydrate absorption, increases water and electrolyte absorption.
The ability of epidural analgesia with local analgesics to modify
the endocrine and metabolic response to pelvic surgery has been
investigated extensively. It has been found that an extensive epidural
blockade from dermatomes T4 to S5 inhibited completely the glucose
and cortisol response to pelvic surgery. This finding showed that not
only somatoic afferent but also sympathetic afferent blockade were
necesllary to prevent activation of pituitary secretion and hence
cortisol production.
The epidural and intrathecal administration of opiates is now
widely practiced because of the excellent postoperative analgesia it
provides. Epidural opiates have no effect on the metabolic response in
pelvic surgery, but some decrease in plasma cortisol is found
postoperatively. 10 upper abdominal surgery, there is no significant
metabolic effect but a small decline in catabolic hormones in found
postoperatively. It has been found that epidural local analgesia is
superior to epidural opiates in modifying the endocrine-metabolic
response to surgery. Thus, epidural opiates produce good analgesic by
virtue of their somatic afferent blockade, but because of their lack of
sympathetic blocking properties still permit afferent sutonomic
stimulation of the hypothalamus.
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There are multiplicities of receptors in the spinal cord, some of
which may be implicated in mediating analgesia preliminary studies
suggest that the epidural administratin of an appropriate ligand, such
as somatostatin, can profide analgesia after surgery.
The tetradecapeptided somatostatin was shown to be an
effective analgesic when given by the extradural route for treatment of
acute and chronic pain. Furthennore, somatostain wasreported to
produce segmental analgesia when injected into the extreadural space.
TIle analgesic effect of somatostatin has an early onset and short
duration without respiratory or cardiovascular side effects.
However, the exact mechanism of somatostatin - induced
analgesia remains unclear. It may inhibit the transmission of
nociceptive stimuli through its ulhibitory effect on substance P
relaesae.
It has been found that maintenance of analgesia in the early
poetoperative period requires continuous epidural somatostatin
infusion. The somatostatin requirement varies greatly from patient to
patient.
Although opiate receptors are involved in the mediation of
analgesia by somatostatin in rats, administratin of naloxone does not
reverse the analgesic effect of somatostatin, so it seems that
somatostatin acts on its own receptor sites.
In contradistinction, it has been found that epidural
administration of somatostatin is less likely to produce analgesia
because, unlike morphine, only small amounts of somatostatin
penetrate the dura mater, as the blood-brain barrier restricts peptide
penetration.
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Clinical usefulness of somatostatin is limited by its very short
half-life (about 2 - 3 minutes) and rebound hypersecretion of
hormones after cessation of the drug. Octreotide acetate (octreotide
acetate) was d signed to overcome these limitations while maximizing
clinical efficie cy. Octreotide acetate is a synthetic compound with
similar physio ogic actions so the native somatostatin but without its
drawbacks an was synthesized in 1980 by scientists at sandoz Ltd.,
Bases, Switzer and.
In the lood, octrcotide acetate is distributed mainly in the
plasma, whe given subcutaneously or intravenously. There is
approximately 65% protein bound, mainly to lipoproteins and to a
lower degree 0 albumin. Octreotide acetate is rapidly ilbsorbed from
us injection site. A peak serum concentration occurs
within 30 utes after subcutaneous adtninistration and within 4
minutes after a short (3 minutes) intravenous infusion. The apparent
elimination half-life of octreotide acetate from plasma IS
approximatel 1.5 hours. Approximately 32% of a subcutaneous dose
is excreted in the urine as unchanged octreotide acetate. Studies in
animals showed that biliary excretion and proteolysis are also
important metabolic pathways. A major metabolite has been identified
as the dipeptide d-tryptophan - L - lysine.
As re ards the side effects, no allergy or antibody production is
reported wi the use of octreotide acetate. It does not seem to cause
local preble s at the injection sites. Nausea occasionally occurs, but
no serious s de effects have been reported.
In tltis wo the effect of Somatostatin in modifying the mctabolic
and hormo at responses to surgery and hemodynamic and hormonl
responses t endotracheal intubation has been studied. Also
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Somatostatin has been used in patients receiving spinal analgesia to
assess its analgesic effect.
The study was conducted on 64 patients scheduled for elective lower
abdominal surgery of average duration 90 tol20 minutes. All were
ASA 1physical status. Their ages ranged between 20 and 40 years,
their body weight ranged between 60 and 70 kg and height between
160 and 170 cm. Informed consent was obtained from every patient.
None of the patients was receiving any medication known to interfere
with the metabolic or hormonal responses to surgery such as steroids
containing drugs, antihypertensive, oral hypoglycemic or insulin.
Patients suffering from organic diseases such as maturity onset
diabetes mellitus, hypertension or acromegaly were excluded from the
study as these might affect the parameters.
Patients were divided into two equal groups; each group was further
subdivided into two equal subgroups:
**Grpup I(32 patients):
.Subgroup I a (16 patients): Was given general anesthesia + I. V.
Fentanyl 1-2 microgram! kg given immediately before induction .
• Subgroup I b (16 patients): Was given general anesthesia + I.V.
Somatostatin 3.5 mierogramlkg given immediately before induction.
”Group II (32 patients):
.Subgroup Ila (16 patients):Was given spinal anesthesia using
Bupivacaine”heavy” 0.5% 3ml without the use of somatostatin
.Subgroup nb (16 patients): Was given spinal anesthesia using
Bup!vacaine”heavy” 0.5% 3ml + Intrathecal somatostatin 250
microgram (0.25 ml) bolus dose.
In group I general anesthesia was induced in all patients with a sleep
dOSGof thiopentone (3-5mglkg) and the trachea was intubated after
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administration of suxamethonimn Itng/kg. Maintenance of anesthesia
was done by using 1% halothane in oxygen and Atracurimn O.5mglkg.
Ventilation was adjusted to maintain end-tidal PC02 at 4.0-4.5 kpa
throughout the anesthetic procedure.
Venous blood samples were collected and recorded using sterile
syringes at pre-induction, post induction and 10min. after skin incision
for measuring of cortisol and glucose levels.
In addition, blood pressure and pulse rate readings were recorded at
the same intervals.
In-group n spinal anesthesia was induced in all patients at the level
between L2& L3 by spinal needle (22G), using Bupivllcaine ”heavy”
0.5%.
Venous blood samples were collected using sterile syringes at preinjection,
post injection and 10min. after skin incision for measuring
of cortisol and glucose levels.
In aWdition, blood pressure and pulse rate readings were recorded at
the same interval. .
Fluid therapy during operation was only in the form of 0.9 % sodium
chloride infusion at a rate of 6 ml/kg/h. Glucose solution and lactate
cotaining fluids were avoided to avoid possible effect on hormonal
and metabolic responses.
After the operation, the patients were closely observed in the recovery
room for any adverse reactions.
Differences between the studied groups were statistically assessed
using student ”t” test. The level ~f significance in the performed test is
atp<0.05.
In-group I (general anesthesia group), it was found that the
adnUnistration of Somatostatin during general anesthesia follow the
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same statistical pattern as fentanyl administration on stress response,
because of its intrinsic analgesic properties. Although it seems
unlikely that somatostatin will gain popularity as a specific analgesic
agent, we have shown that advantage can be taken of its analgesic
properties during anesthesia.
In-group II (spinal anesthesia group) it was found that the
administration of Somatostatin intrathecal plus heavy Bupivacaine
follow the same statistical pattern as administration of intrathecal
heavy Bupivacaine alone. However, addition of somatostatin to heavy
bupivacaine decreases the need for postoperative analgesia for six
hours after the end of operation.