CHAPTER 1

THEORY: NON-TOXIC MULTINODULAR GOITER

INTRODUCTION

Multinodular non-toxic goiter is the most prevalent thyroid pathology characterized by

unilateral or bilateral thyroid growth with morphologically and/or functionally transformed

follicles and euthyroidism. At thyroid sonography in unselected populations, 20 to 30 %

incidence of thyroid nodules has been reported. Beside morphologic variability, lack of

hyperstimulation in the majority of the multiplicated follicles is the hallmark of the disorder.

Most nodular goiters grow slowly and undergo different morphologic changes, encompassing

diffuse hyperplastic enlargement in the early phase, development of large follicles loaded with

abundant colloid and with increasing age, formation of functionally autonomous tissue. Annual

growth potential of approximately 20 % can be assumed.

The pathogenesis of nodular goiter is multifactorial and probably differs from patient to

patient. In contrast to the endemic goiter, iodine deficiency is not a primary causal factor.

Environmental factors such as natural goitrogens, iodine intake, malnutrition, drugs, stress,

pollution or infections, constitutional factors such as female gender and several genetic factors,

i.e. circulating thyroid growth factors contribute to different degree to the development of

nodular thyroid enlargement. Also controversially debated, thyroid-stimulating hormone (TSH)

presumably has an important role in the maintenance of thyroid growth and goitrogenesis. The

observation that TSH-suppressive treatment may cause a reduction of goiter volume underlines

the role of TSH as goitrogen factor.

1.1. Anatomy

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The thyroid gland is a butterfly-shaped organ and is composed of two cone-like lobes or

wings, lobus dexter (right lobe) and lobus sinister (left lobe), connected via the isthmus. The

organ is situated on the anterior side of the neck, lying against and around the larynx and trachea,

reaching posteriorly the oesophagus and carotid sheath. It starts cranially at the oblique line on

the thyroid cartilage (just below the laryngeal prominence, or 'Adam's Apple'), and extends

inferiorly to approximately the fifth or sixth tracheal ring.  It is difficult to demarcate the gland's

upper and lower border with vertebral levels because it moves position in relation to these during

swallowing.

The thyroid gland is covered by a fibrous sheath, the capsula glandulae thyroidea,

composed of an internal and external layer. The external layer is anteriorly continuous with

the lamina pretrachealis fasciae cervicalis and posteriorolaterally continuous with the carotid

sheath. The gland is covered anteriorly with infrahyoid muscles and laterally with

the sternocleidomastoid muscle also known as sternomastoid muscle. On the posterior side, the

gland is fixed to the cricoid and tracheal cartilage and cricopharyngeus muscle by a thickening of

the fascia to form the posterior suspensory ligament of Berry.  The thyroid gland's firm

attachment to the underlying trachea is the reason behind its movement with swallowing. In

variable extent, Lalouette's Pyramid, a pyramidal extension of the thyroid lobe, is present at the

most anterior side of the lobe. In this region, the recurrent laryngeal nerve and the inferior

thyroid artery pass next to or in the ligament and tubercle.

Between the two layers of the capsule and on the posterior side of the lobes, there are on

each side two parathyroid glands.

The thyroid isthmus is variable in presence and size, can change shape and size, and can

encompass a cranially extending pyramid lobe (lobus pyramidalis or processus pyramidalis),

remnant of the thyroglossal duct. The thyroid is one of the larger endocrine glands, weighing 2-

3 grams in neonates and 18-60 grams in adults, and is increased in pregnancy.

The thyroid is supplied with arterial blood from the superior thyroid artery, a branch of

the external carotid artery, and the inferior thyroid artery, a branch of the thyrocervical trunk, and

sometimes by the thyroid ima artery, branching directly from the brachiocephalic trunk. The

venous blood is drained via superior thyroid veins, draining in the internal jugular vein, and

via inferior thyroid veins, draining via the plexus thyroideus impar in the left brachiocephalic

vein.

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Lymphatic drainage passes frequently the lateral deep cervical lymph nodes and the pre-

and parathracheal lymph nodes. The gland is supplied by parasympathetic nerve input from

the superior laryngeal nerve and the recurrent laryngeal nerve.

1.2. Histology

At the microscopic level, there are three primary features of the thyroid:

Feature Description

Follicles

The thyroid is composed of spherical follicles that selectively absorb

iodine (as iodide ions, I-) from the blood for production of thyroid

hormones, but also for storage of iodine in thyroglobulin, in fact iodine

is necessary for other important iodine-concentrating organs as breast,

stomach, salivary glands, thymus etc. (see iodine in biology).

Twenty-five percent of all the body's iodide ions are in the thyroid gland.

Inside the follicles, colloid serves as a reservoir of materials for thyroid

hormone production and, to a lesser extent, acts as a reservoir for the

hormones themselves. Colloid is rich in a protein calledthyroglobulin.

Thyroid   epithelial   cells

(or "follicular cells")

The follicles are surrounded by a single layer of thyroid epithelial cells,

which secrete T3 andT4. When the gland is not secreting T3/T4 (inactive),

the epithelial cells range from low columnar to cuboidal cells. When

active, the epithelial cells become tall columnar cells.

Parafollicular cells

(or "C cells")

Scattered among follicular cells and in spaces between the spherical

follicles are another type of thyroid cell, parafollicular cells, which

secrete calcitonin.

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1.3. Definition

Goitre is an enlargement of the thyroid gland. The gland can be generally enlarged or

have multiple growths (nodules) leading to enlargement of the whole thyroid gland. The latter is

termed multinodular goitre (MNG). There are two forms of multinodular goitre: 1) nontoxic

MNG and 2) toxic MNG. If the goiter makes normal amounts of thyroid hormone, it is known as

a nontoxic MNG. If the goiter makes higher than normal amounts of thyroid hormone leading to

a suppressed TSH, it is known as a toxic MNG. The exact causes of thyroid nodules or

multinodular goitres are unknown. In general, the development of goitre is due to a complex mix

of genetic and environmental factors. Iodine deficiency as a cause of goitre is rare in North

America and most of Europe. However, even in areas of iodine deficiency most patients do not

develop goitres.

1.4. Etiology

The first comprehensive theory about the development of multinodular goitre was

proposed by David Marine and studied further by Selwyn Taylor, and can be considered one of

the classics in this field. Nodular goitre may be the result of any chronic low-grade, intermittent

stimulus to thyroid hyperplasia. In response to iodide deficiency, the thyroid first goes through a

period of hyperplasia as a consequence of the resulting TSH stimulation, but eventually, possibly

because of iodide repletion or a decreased requirement for thyroid hormone, enters a resting

phase characterized by colloid storage and the histologic picture of a colloid goitre. Repetition of

these two phases of the cycle would eventually result in the formation of nontoxic multinodular

goitre. Studies by Taylor of thyroid glands removed at surgery led him to believe that the initial

lesion is diffuse hyperplasia, but that with time discrete nodules develop.

By the time the goitre is well developed, serum TSH levels and TSH production rates are

usually normal or even suppressed. For example, Dige-Petersen and Hummer evaluated basal

and TRH-stimulated serum TSH levels in 15 patients with diffuse goitre and 47 patients with

nodular goitre. They found impairment of TRH-induced TSH release in 27% of the patients with

nodular goitre, suggesting thyroid autonomy, but in only 1 of the 15 with diffuse goitre.

Smeulers et al , studied clinically euthyroid women with multinodular goitre and found that there

was an inverse relationship between the increment of TSH after administration of TRH, and size

of the thyroid gland . It was also found that, while being still within the normal range, the mean

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serum T3 concentration of the group with impaired TSH secretion was significantly higher than

the normal mean, whereas the mean value of serum T4 levels was not elevated. These and other

results are consistent with the hypothesis that a diffuse goitre may precede the development of

nodules. They are also consistent with the clinical observation that, with time, autonomy may

occur, with suppression of TSH release, even though such goitres were originally TSH

dependent.

Factors that may be involved in the evolution of multinodular goiter.

PRIMARY FACTORS

Functional heterogeneity of normal follicular cells, most probably due to genetic and

acquisition of new inheritable qualities by replicating epithelial cells. Gender (women) is an

important factor.

Subsequent functional and structural abnormalities in growing goiters.

SECONDARY FACTORS

Elevated TSH  (induced by iodine deficiency, natural goitrogens, inborn errors of thyroid 

hormone synthesis)

Smoking, stress, certain drugs

Other thyroid-stimulating factors (IGF-1 and others)

Endogenous factor (gender)

1.5. Pathology

Although it is rare to obtain pathological examination of thyroid glands in the early phase

of development of multinodular goitres, such glands should show areas of hyperplasia with

considerable variation in follicle size. The more typical specimen coming to pathologists is the

goitre that has developed a nodular consistency.  Such goitres characteristically present a

variegated appearance, with the normal homogeneous parenchymal structure deformed by the

presence of nodules. The nodules may vary considerably in size (from a few millimeters to

several centimeters); in outline (from sharp encapsulation in adenomas to poorly defined

margination for ordinary nodules); and in architecture (from the solid follicular adenomas to the

gelatinous, colloid-rich nodules or degenerative cystic structures). The graphic term

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“Puddingstone goitre” has been applied. Frequently the nodules have degenerated and a cyst has

formed, with evidence of old or recent haemorrhage, and the cyst wall may have become

calcified. Often there is extensive fibrosis, and calcium may also be deposited in these septae.

Scattered between the nodules are areas of normal thyroid tissue, and often-focal areas of

lymphocytic infiltration. Radioautography shows a variegated appearance, with RAI localized

sometimes in the adenomas and sometimes in the paranodular tissue. Occasionally, most of the

radioactivity is confined to a few nodules that seem to dominate the metabolic activity of the

gland.  If careful sections are made of numerous areas, 4-17% of these glands removed at surgery

will be found to harbor microscopic papillary carcinoma. The variable incidence can most likely

be attributed to the different criteria used by the pathologists and the basis of selection of the

patients for operation by their physicians.

1.6. Natural History of the Disease

Multinodular goitre is probably a lifelong condition that has its inception in adolescence

or at puberty. Minimal diffuse enlargement of the thyroid gland is found in many teenage boys

and girls, and is almost a physiologic response to the complex structural and hormonal changes

occurring at this time. It usually regresses, but occasionally (much more commonly in girls) it

persists and undergoes further growth during pregnancy. This course of events has not been

documented as well as might be desired in sporadic nodular goitre, but it is the usual evolution in

areas where mild endemic goitre is found.

Patients with multinodular goitre seek medical attention for many reasons. Perhaps most

commonly they consult a physician because a lump has been discovered in the neck, or because a

growth spurt has been observed in a goiter known to be present for a long time. Sometimes the

increase in the size of the goitre will cause pressure symptoms, such as difficulty in swallowing,

cough, respiratory distress, or the feeling of a lump in the throat. Rarely, an area of particularly

asymmetrical enlargement may impinge upon or stretch the recurrent laryngeal nerve.

Commonly the goitre is discovered by a physician in the course of an examination for some other

condition. An important scenario is for the patient to seek medical attention because of cardiac

irregularities or congestive heart failure, which proves to be the result of slowly developing

thyrotoxicosis. Many times the goitre grows gradually for a period of a few too many years, and

then becomes stable with little tendency for further growth. It is rare for any noteworthy

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spontaneous reduction in the size of the thyroid gland to occur, but patients often describe

fluctuation in the size of the goitres and the symptoms they give. These are usually subjective

occurrences, and more often than not the physician is unable to corroborate the changes that the

patient describes. On the other hand, it could be that changes in blood flow through the enlarged

gland account for the symptoms.

Occasionally, a sudden increase in the size of the gland is associated with sharp pain and

tenderness in one area. This event suggests haemorrhage into a nodular cyst of the goiter, which

can be confirmed by ultrasound. Within 3-4 days the symptoms subside, and within 2-3 weeks

the gland may revert to its previous dimensions. In such a situation, acute thyrotoxicosis may

develop and subside spontaneously.    Rarely, if ever, do the patients become hypothyroid and if

they do, the diagnosis is more probably Hashimoto’s thyroiditis than nodular goitre. If the goitre

is present for long time, thyrotoxicosis develops in a large number of patients. In a series

collected many years ago at the Mayo Clinic, 60% of patients with MNG over 60 were

thyrotoxic. The average duration of the goitre before the onset of thyrotoxicosis was 17 years;

the longer the goitre had been present the greater was the tendency for thyrotoxicosis to develop.

This condition appears to occur because with the passage of time, autonomous function of the

nodules develops. In a study of patients with euthyroid multinodular goitre, thyroid function was

autonomous in 64 and normal in 26. After a mean follow-up of 5.0 years (maximum 12 years) 18

patients with autonomous thyroid function became overtly hyperthyroid and in 6 patients with

primarily normal thyroid function autonomy develope. Thyroid function tests is illustrated in a

patient with multinodular goitre starting from complete euthyroidism on to overt thyrotoxicosis.

Occasionally a single discrete nodule in the thyroid gland becomes sufficiently active to cause

thyrotoxicosis and to suppress the activity of the rest of the gland. If these patients are given

thyroid hormone, continued function of nodules can be demonstrated by radioiodine scanning

techniques. Thus, these nodules have become independent of pituitary control. When patients

with euthyroid multinodular goiter are frequently tested, it appears that in some of them

occasional transient increases of serum T3 and / or T4 are seen. In several areas of the world

previously iodine deficiency the introduction of iodine supplementation lead to an increase of

hyperthyroidism (non-autoimmune) possibly by excessive thyroid hormone production by “hot”

thyroid nodules.

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1.7. Diagnosis

1.7.1. Signs and Symptoms

Many of the symptoms of multinodular goitre have already been described. They

are chiefly due to the presence or an enlarging mass in the neck and its impingement

upon the adjacent structures. There may be dysphagia, cough, and hoarseness. Paralysis

of recurrent laryngeal nerve may occur when the nerve is stretched taut across the surface

of an expanding goiter, but this event is very unusual. When unilateral vocal cord

paralysis is demonstrated, the presumptive diagnosis is cancer. Pressure on the superior

sympathetic ganglions and nerves may produce a Horner’s syndrome.

As the gland grows it characteristically enlarges the neck, but frequently the

growth occurs in a downward direction, producing a substernal goitre. A history

sometimes given by an older patient where a goitre once present in the neck has

disappeared may mean that it has fallen down into the upper mediastinum, where its

upper limits can be felt by careful deep palpation. Hemorrhage into this goitre can

produce acute tracheal obstruction. Sometime substernal goitres are attached only by a

fibrous band to the goitre in the neck and extend downward to the arch of the aorta. They

have even been observed as deep in the mediastinum as the diaphragm. Occasionally the

skilled physician can detect a substernal goiter by percussion, particularly if there is a

hint from tracheal deviation, or the presence of a nodular mass in the neck above the

manubrial notch.

Symptoms suggesting constriction of the trachea are frequent, and displacement

of the trachea is commonly found on physical examination. Computer Tomography

examination is useful in defining the extent of tracheal deviation and compression.

Compression is frequently seen but rarely is functionally significant have expected to find

softened tracheal cartilage after the removal of some large goiters, but tracheomalacia has

been observed only on the rarest occasion. Patients may be remarkably tolerant of

nodular goiter even when the enlargement is striking. This finding is especially true in the

endemic goiter areas of the world.

It is generally agreed that, thyroid isotope or ultrasound scanning are of little or

no use in the diagnosis of carcinoma in a multinodular goiter. Two aspects are important

in the differentiation from malignancy. First, the clinical presentation, if the goiter is of

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longstanding, showing little or no growth, absence of a dominant node, familial, while

there is no neck irradiation in the past, especially in childhood, no hoarse voice, and no

suspicious lymphnodes in the neck, there is little fear for carcinoma.

1.7.2. Laboratory investigation

The choice of tests to investigate the functional status of a patient with a simple

diffuse goitre or multinodular goitre may differ depending on the geographic areas of the

world. Recent surveys conducted in the American, European and Latin American

Thyroid Associations have indicated that the North American thyroidologists are quite

restrictive in the choice of laboratory tests. Most of the experts, however, would perform

a serum TSH and serum Free T4 test. In other settings Total T4 and Total T3 are also

included because of the preferential secretion of T3 over T4 in  mild iodine deficiency.

Antibodies against thyro-peroxidase (anti-TPO) and thyroglobulin (anti-TG) are

measured, routinely, by most Europeans and Latin Americans thyroidologists. This seems

to be relevant because thyroid auto antibodies are found approximately in 10% of the

population and, consequently, autoimmunity may coexist with a goiter. Also diffuse or

focal lymphocytic infiltration in an enlarged gland may represent chronic autoimmune

thyroiditis.

Although serum TG correlates with the iodine status and the size of the enlarged

thyroid gland it has little or no value in the diagnosis of goiter.

1.7.3. Diagnostic imaging

Neck palpation is notoriously imprecise with regard to thyroid morphology and

size estimation. Several imaging methods are available in most settings: scintilography

(with radioiodine, technetium), ultrasonography, computed tomography scans, magnetic

resonance imaging and, less frequently used, positron emission tomography (PET).

1.7.3.1. Ultrasonography of the thyroid

The main reasons for the widespread use of thyroid sonography are

availability (several portable models are widely available at a relatively affordable

price), the low cost of the procedure (if performed in the office or in the thyroid

clinic), limited discomfort for the patient, and the non ionizing nature of the

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method. Ultrasonography may detect non palpable nodules cysts, will estimate

nodule and goiter size (volume), will monitor the changes following therapy and

will guide the Fine Needle Aspiration Biopsy (FNAB). After the introduction of

ultrasonography it has become clear that nodules in the thyroid gland are very

prevalent, ranging from 17% to 60% if older people are included in the study.

Hypoechogenicity, micro-calcifications, indistinct borders increased

nodular flow (visualized by DOPPLER) may have predictive value in

distinguishing malignant from benign nodules (even in Multinodular Goiters).

The possibility of measuring thyroid volume is another highly useful

feature of ultrasonographic studies particularly after therapy with L-T4 or

radioiodine ablation. The volume of the goiter is usually based on the ellipsoid

method (length, width depth X pi/6). This has an observer coefficient of variation

of more than 10%.When compared to CT planimetry the ellipsoid method

underestimate the goiter volume by 20%. Ultrasonography can not evaluate a

multinodular goiter that has partially migrated to the upper mediastinum.

1.7.4. Scintigraphy (isotope imaging)

It was used routinely in the past but at present has little place in the evaluation of

a multinodular goiter (101-105). It is helpful in the determination of the functionality of

the various nodules of a MNG. Thyroid scintigrams have been used through many years

for measurement of the thyroid volume but compared to other methods is very inaccurate.

1.7.5. Computed tomography (CT) and Magnetic resonance (MR)

CT and MR provide high-resolution visualization of the goiter (Simple diffuse,

multinodular). The major strength of CT and MR is their ability to diagnose and assess

the extent of substernal goiters. Another advantage of the CT is the possibility for

planimetric volume estimations, quite useful in irregularly enlarged multinodular goiter.

Recently the ionizing radiation delivered by a CT procedure has been source of

concern for both clinicians and radiologists. Therefore the use of CT as an imaging

method should be reserved for intra thoracic multinodular goiters, with tracheal

compression.

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1.8. Differential Diagnosis

Adenoma

Cyst

Carcinoma

Multinodular goitre

Hashimoto’s thyroiditis

Subacute thyroiditis

Effect of prior operation or 131I therapy

Thyroid hemiagenesis

Metastasis

Parathyroid cyst or adenoma

Thyroglossal cyst

Nonthyroidal lesions

o Inflammatory or neoplastic nodes

o Cystic hygroma

o Aneurysm

o Bronchocele

o Laryngocele

1.9. Treatment

Unlike Graves disease, Multinodular goitre (MNG) is not an autoimmune disease and

rarely, if ever, remits. Therefore, patients who have autonomously functioning nodules should be

treated definitely with radioactive iodine or surgery. The American Thyroid Association and

American Association of Clinical Endocrinologists have released guidelines for the management

of hyperthyroid and other causes of thyrotoxicosis, including the use of radioactive iodine or

surgery to treat toxic multinodular goitre.

Patients with subclinical hyperthyroidism should be monitored closely for overt disease.

Some suggest that elderly patients, women with osteopenia, and patients with risk factors for

atrial fibrillation should be treated, even those who have subclinical disease.

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1.9.1. Na131 I treatment

Radioactive iodine is considered the treatment of choice for Toxic MNG. Except

for pregnancy, there are no absolute contraindications to radioiodine therapy.

o A single dose of radioiodine therapy has a success rate of 85-100% in patients

with TNG. Radioiodine therapy may reduce the size of the goiter by up to 40%.

o Failure of initial treatment with radioactive iodine has been associated with

increased goiter size and higher T3 and free T4 levels, which suggests that these

factors may present a need for higher doses of Na131 I.

o A positive correlation exists between radiation dose to the thyroid and decrease in

thyroid volume. In patients with uptake of less than 20%, pretreatment with

lithium, PTU, or recombinant TSH can increase the effectiveness of iodine uptake

and treatment. This treatment may be valuable in elderly patients in whom

surgery is considered high risk.

o Complications

Hypothyroidism occurs in 10-20% of patients; this is similar to the

incidence rate after surgery and is substantially less than in the treatment

of Graves disease.

Tracheal compression due to thyroid swelling after radiation therapy is no

longer thought to be a risk.

Mild thyrotoxic symptoms after radioiodine occur in about one-third of

patients, and about 4% of patients develop a clinically significant

radiation-induced thyroiditis. These patients should be treated

symptomatically with beta blockers.

Elderly patients may have exacerbation of congestive heart failure and

atrial fibrillation. Pretreat elderly patients with antithyroid drugs.

Thyroid storm is a rare complication, particularly in patients with rapidly

enlarging goiters or high total T3 levels. Patients with these conditions

should receive pretreatment with antithyroid drugs.

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1.9.2. Pharmacotherapy

Antithyroid drugs and beta blockers are used for short courses in the treatment of MNG;

they are important in rendering patients euthyroid in preparation for radioiodine or surgery and in

treating hyperthyroidism while awaiting full clinical response to radioiodine. Patients with

subclinical disease at high risk of complications (eg, atrial fibrillation, osteopenia) may be given

a trial of low dose methimazole (5-15 mg/d) or beta blockers and should be monitored for a

change in symptoms or for disease progression that requires definitive treatment.

o Thioamides - The role of therapy with thioamides (eg, PTU, methimazole) is to

achieve euthyroidism prior to definitive treatment with either surgery or

radioiodine therapy. Data suggest that pretreated patients have decreased response

to radioiodine. The general recommendation is to stop antithyroid agents at least 4

days prior to radioiodine therapy in order to maximize the radioiodine effect.

Antithyroid drugs and beta blockers have side effects, the most common

being pruritic rash, fever, gastrointestinal upset, and arthralgias. More

serious potential side effects include agranulocytosis, drug-induced lupus

and other forms of vasculitis, and liver damage.

PTU is considered to be a second-line drug therapy, except in patients who

are allergic to or intolerant of methimazole, or in women who are in the

first trimester of pregnancy. Rare cases of embryopathy, including aplasia

cutis, have been reported with methimazole during pregnancy. The FDA

recommends the following criteria be considered for prescribing PTU:

Reserve PTU use during first trimester of pregnancy, or in patients

who are allergic to or intolerant of methimazole.

Closely monitor PTU therapy for signs and symptoms of liver

injury, especially during the first 6 months after initiation of

therapy.

For suspected liver injury, promptly discontinue PTU therapy,

evaluate the patient for evidence of liver injury, and provide

supportive care.

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PTU should not be used in pediatric patients unless the patient is

allergic to or intolerant of methimazole and no other treatment

options are available.

Counsel patients to promptly contact their health care provider for

the following signs or symptoms: fatigue, weakness, vague

abdominal pain, loss of appetite, itching, easy bruising, or

yellowing of the eyes or skin.

o Beta-adrenergic receptor antagonists - These drugs remain useful in the treatment

of symptoms of thyrotoxicosis; they may be used alone in patients with mild

thyrotoxicosis or in conjunction with thioamides for treatment of more severe

disease.

Propranolol, a nonselective beta blocker, may help to lower the heart rate,

control tremor, reduce excessive sweating, and alleviate anxiety.

Propranolol is also known to reduce the conversion of T4 to T3.

In patients with underlying asthma, beta-1 selective antagonists, such as

atenolol or metoprolol, would be safer options.

In patients with contraindications to beta blockers (eg, moderate to severe

asthma), calcium channel antagonists (eg, diltiazem) may be used to help

control the heart rate.

Surgical therapy is usually reserved for young individuals, patients with 1 or more large nodules

or with obstructive symptoms, patients with dominant nonfunctioning or suspicious nodules,

patients who are pregnant, patients in whom radioiodine therapy has failed, or patients who

require a rapid resolution of the thyrotoxic state.

Subtotal thyroidectomy results in rapid cure of hyperthyroidism in 90% of patients and

allows for rapid relief of compressive symptoms.

Restoring euthyroidism prior to surgery is preferable.

Complications of surgery include the following:

o In patients who are treated surgically, the frequency of hypothyroidism is similar

to that found in patients treated with radioiodine (15-25%).

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o Complications include permanent vocal cord paralysis (2.3%), permanent

hypoparathyroidism (0.5%), temporary hypoparathyroidism (2.5%), and

significant postoperative bleeding (1.4%).

o Other postoperative complications include tracheostomy, wound infection, wound

hematoma, myocardial infarction, atrial fibrillation, and stroke.

o The mortality rate is almost zero.

1.10. Complications

Hyperthyroid complications

o The most important complications are related to the heart.

o Cardiomyopathy resulting in severely depressed function may be observed with

hyperthyroidism, possibly in relation to persistent tachycardia. Fortunately,

cardiomyopathy resolves remarkably with resolution of the hyperthyroid state.

o Using anticoagulants to treat patients exhibiting atrial fibrillation remains

controversial, although it is recommended by many authorities. Atrial fibrillation

of long duration that is associated with other anatomical defects of the heart

should be treated with warfarin or another suitable anticoagulant.

1.11. Prognosis

Most treated patients have a good prognosis. A worse prognosis is related to untreated

hyperthyroidism. If left untreated, hyperthyroidism may lead to osteoporosis, arrhythmia, heart

failure, coma, and death. Regular assessment of thyroid function is important in monitoring

disease.

Na131 I ablation may result in continued hyperthyroidism, with some patients (up to 73%

in some studies, depending on the size of the goiter and the dosing of radioiodine) requiring

repeated treatment or surgical removal of the gland. Hypothyroidism after radioiodine ablation

has been reported in 0-35% of individuals. .

Surgical treatment usually consists of a lobectomy of the hyperfunctioning nodule. The

rate of hypothyroidism associated with this procedure is very low. Rates of hyperthyroidism

recurrence with surgery have been reported to be as low as 0-9%. Larger, multinodular goiters

may require total thyroidectomy.

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CHAPTER 2

THEORY: GENERAL ANESTHESIA

INTRODUCTION

Anesthesia is an important field of medicine that has made complicated surgeries

possible. It involves the administration of substances or drugs to patients which causes loss of

consciousness, loss of verbal ability, absence of recall and loss of protective reflexes e.g. cough,

gag and withdrawal from pain.

Anesthesia means “without feeling” (no sensation), whereas analgesia means “without

pain”. Although a patient is anesthetized but without proper analgesia, there will be evidence of

pain such as tachycardia and hypertension. Thus, one must not think that a person will not feel

pain when he is anesthetized.

General anesthesia (GA) is the state produced when a patient receives medications for

amnesia, analgesia, muscle paralysis, and sedation. An anesthetized patient can be thought of as

being in a controlled, reversible state of unconsciousness. Anesthesia enables a patient to tolerate

surgical procedures that would otherwise inflict unbearable pain, potentiate extreme physiologic

exacerbations, and result in unpleasant memories.

The combination of anesthetic agents used for general anesthesia often leaves a patient with

the following clinical constellation:

1. Unarousable even secondary to painful stimuli

2. Unable to remember what happened (amnesia)

3. Unable to maintain adequate airway protection and/or spontaneous ventilation as a result

of muscle paralysis

4. Cardiovascular changes secondary to stimulant/depressant effects of anesthetic agents.

2.1. General Anesthesia

General anesthesia uses intravenous and inhaled agents to allow adequate surgical access

to the operative site. A point worth noting is that general anesthesia may not always be the best

choice; depending on a patient’s clinical presentation, local or regional anesthesia may be more

appropriate.

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Anesthesia providers are responsible for assessing all factors that influence a patient's

medical condition and selecting the optimal anesthetic technique accordingly. Attributes of

general anesthesia include the following:

Advantages

o Reduces intraoperative patient awareness and recall

o Allows proper muscle relaxation for prolonged periods of time

o Facilitates complete control of the airway, breathing, and circulation

o Can be used in cases of sensitivity to local anesthetic agent

o Can be administered without moving the patient from the supine position

o Can be adapted easily to procedures of unpredictable duration or extent

o Can be administered rapidly and is reversible

Disadvantages

o Requires increased complexity of care and associated costs

o Requires some degree of preoperative patient preparation

o Can induce physiologic fluctuations that require active intervention

o Associated with less serious complications such as nausea or vomiting, sore

throat, headache, shivering, and delayed return to normal mental functioning

o Associated with malignant hyperthermia, a rare, inherited muscular condition in

which exposure to some (but not all) general anesthetic agents results in acute and

potentially lethal temperature rise, hypercarbia, metabolic acidosis, and

hyperkalemia

With modern advances in medications, monitoring technology, and safety systems, as

well as highly educated anesthesia providers, the risk caused by anesthesia to a patient

undergoing routine surgery is very small. Mortality attributable to general anesthesia is said to

occur at rates of less than 1:100,000. Minor complications occur at predicable rates, even in

previously healthy patients. The frequency of anesthesia-related symptoms during the first 24

hours following ambulatory surgery is as follows:

Vomiting - 10-20%

Nausea - 10-40%

Sore throat - 25%

Incisional pain - 30%

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2.2. Preparation for General Anesthesia

Safe and efficient anesthetic practices require certified personnel, appropriate

medications and equipment, and an optimized patient.

Minimum infrastructure requirements for general anesthesia include a well-lit space of

adequate size; a source of pressurized oxygen (most commonly piped in); an effective suction

device; standard ASA (American Society of Anesthesiologists) monitors, including heart rate,

blood pressure, ECG, pulse oximetry, capnography, temperature; and inspired and exhaled

concentrations of oxygen and applicable anesthetic agents.

Beyond this, some equipment is needed to deliver the anesthetic agent. This may be as

simple as needles and syringes, if the drugs are to be administered entirely intravenously. In most

circumstances, this means the availability of a properly serviced and maintained anesthetic gas

delivery machine.

An array of routine and emergency drugs, including Dantrolene sodium (the specific

treatment for malignant hyperthermia), airway management equipment, a cardiac defibrillator,

and a recovery room staffed by properly trained individuals completes the picture.

2.3. Preparing the patient

Preoperative evaluation allows for proper laboratory monitoring, attention to any new or

ongoing medical conditions, discussion of any previous personal or familial adverse reactions to

general anesthetics, assessment of functional cardiac and pulmonary states, and development of

an effective and safe anesthetic plan. It also serves to relieve anxiety of the unknown surgical

environment for patients and their families. Overall, this process allows for optimization of the

patient in the perioperative setting.

Physical examination associated with preoperative evaluations allow anesthesia providers

to focus specifically on expected airway conditions, including mouth opening, loose or

problematic dentition, limitations in neck range of motion, neck anatomy, and Mallampati

presentations. By combining all factors, an appropriate plan for intubation can be outlined and

extra steps, if necessary, can be taken to prepare for fiberoptic bronchoscopy, video

laryngoscopy, or various other difficult airway interventions.

18

Airway management

Possible or definite difficulties with airway management include the following:

Small or receding jaw

Prominent maxillary teeth

Short neck

Limited neck extension

Poor dentition

Tumors of the face, mouth, neck, or throat

Facial trauma

Interdental fixation

Hard cervical collar

Halo traction

Various scoring systems have been created using orofacial measurements to predict

difficult intubation. The most widely used is the Mallampati score, which identifies patients in

whom the pharynx is not well visualized through the open mouth.

The Mallampati assessment is ideally performed when the patient is seated with the

mouth open and the tongue protruding without phonating. In many patients intubated for

emergent indications, this type of assessment is not possible. A crude assessment can be

performed with the patient in the supine position to gain an appreciation of the size of the mouth

opening and the likelihood that the tongue and oropharynx may be factors in successful

intubation.

Mallampati classification.

19

High Mallampati scores have been shown to be predictive of difficult intubations.

However, no one scoring system is near 100% sensitive or 100% specific. As a result,

practitioners rely on several criteria and their experience to assess the airway.

When suspicion of an adverse event is high but a similar anesthetic technique must be

used again, obtaining records and previous anesthetic records from previous operations or from

other institutions may be necessary.

Other requirements

The need for coming to the operating room with an empty stomach is to reduce the risk of

pulmonary aspiration during general anesthesia when a patient loses his or her ability to

voluntarily protect the airway.

Patients should continue to take regularly scheduled medications up to and including the

morning of surgery. Exceptions may include the following:

Anticoagulants to avoid increased surgical bleeding

Oral hypoglycemics (For example, metformin is an oral hypoglycemic agent that is

associated with the development of metabolic acidosis under general anesthesia.)

Monoamine oxidase inhibitors

Beta blocker therapy (However, beta blocker therapy should be continued perioperatively

for high-risk patients undergoing major noncardiac surgery)

2.4. The process of anesthesia

2.4.1. Premedication

This is the first stage of a general anesthetic and usually conducted in the surgical

ward or in a preoperative holding area. The goal of premedication is to have the patient arrive

in the operating room in a calm, relaxed frame of mind.

Most patients do not want to have any recollection of entering the operating room.

The most commonly used premedication is midazolam, a short-acting benzodiazepine. For

example, midazolam syrup is often given to children to facilitate calm separation from their

parents prior to anesthesia. In anticipation of surgical pain, nonsteroidal anti-inflammatory

drugs or acetaminophen can be administered preemptively. When a history of

20

gastroesophageal reflux exists, H2 blockers and antacids may be administered. Drying agents

(eg, atropine, scopolamine) are now only administered routinely in anticipation of a

fiberoptic endotracheal intubation.

2.4.2. Induction

This is the critical part of the anesthesia process. Usually, the mnemonic DAMMIS

can be used to remember what to check ( D  rugs, A  irway equipment, M  achine, M 

onitors, I  V, S uction).

This stage can be achieved by intravenous injection of induction agents (drugs that

work rapidly, such as propofol), by the slower inhalation of anesthetic vapors delivered into a

face mask, or by a combination of both.

For the most part, contemporary practice dictates that adult patients and most children

aged at least 10 years be induced with intravenous drugs, this being a rapid and minimally

unpleasant experience for the patient. However, sevoflurane, a well-tolerated anesthetic

vapor, allows for elective inhalation induction of anesthesia in adults.

In addition to the induction drug, most patients receive an injection of an opioid

analgesic, such as fentanyl (a synthetic opioid many times more potent than morphine).

Many synthetic and naturally occurring opioids with different properties are available.

Induction agents and opioids work synergistically to induce anesthesia. In addition,

anticipation of events that are about to occur, such as endotracheal intubation and incision of

the skin, generally raises the blood pressure and heart rate of the patient. Opioid analgesia

helps control this undesirable response.

The next step of the induction process is securing the airway. This may be a simple

matter of manually holding the patient's jaw such that his or her natural breathing is

unimpeded by the tongue, or it may demand the insertion of a prosthetic airway device such

as a laryngeal mask airway or endotracheal tube. Various factors are considered when

making this decision. The major decision is whether the patient requires placement of an

endotracheal tube. Potential indications for endotracheal intubation under general anesthesia

may include the following:

o Potential for airway contamination (full stomach, gastroesophageal [GE] reflux,

gastrointestinal [GI] or pharyngeal bleeding)

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o Surgical need for muscle relaxation

o Predictable difficulty with endotracheal intubation or airway access (eg, lateral or

prone patient position)

o Surgery of the mouth or face

o Prolonged surgical procedure

Not all surgery requires muscle relaxation. If surgery is taking place in the abdomen

or thorax, an intermediate or long-acting muscle relaxant drug is administered in addition to

the induction agent and opioid. This paralyzes muscles indiscriminately, including the

muscles of breathing. Therefore, the patient's lungs must be ventilated under pressure,

necessitating an endotracheal tube.

Persons who, for anatomic reasons, are likely to be difficult to intubate are usually

intubated electively at the beginning of the procedure, using a fiberoptic bronchoscope or

other advanced airway tool. This prevents a situation in which attempts are made to manage

the airway with a lesser device, only for the anesthesia provider to discover that oxygenation

and ventilation are inadequate. At that point during a surgical procedure, swift intubation of

the patient can be very difficult, if not impossible.

2.4.3. Maintenance phase

At this point, the drugs used to initiate the anesthetic are beginning to wear off, and

the patient must be kept anesthetized with a maintenance agent. For the most part, this refers

to the delivery of anesthetic gases (more properly termed vapors) into the patient's lungs.

These may be inhaled as the patient breathes spontaneously or delivered under pressure by

each mechanical breath of a ventilator.

The maintenance phase is usually the most stable part of the anesthesia. However,

understanding that anesthesia is a continuum of different depths is important. A level of

anesthesia that is satisfactory for surgery to the skin of an extremity, for example, would be

inadequate for manipulation of the bowel.

As the procedure progresses, the level of anesthesia is altered to provide the minimum

amount of anesthesia that is necessary to ensure adequate anesthetic depth. Traditionally, this

has been a matter of clinical judgment, but new processed EEG machines give the anesthesia

22

provider a simplified output in real time, corresponding to anesthetic depth. These devices

have yet to become universally accepted as vital equipment.

If muscle relaxants have not been used, inadequate anesthesia is easy to spot. The

patient moves, coughs, or obstructs his airway if the anesthetic is too light for the stimulus

being given. If muscle relaxants have been used, then clearly the patient is unable to

demonstrate any of these phenomena. In these patients, the anesthesia provider must rely on

careful observation of autonomic phenomena such as hypertension, tachycardia, sweating,

and capillary dilation to decide whether the patient requires a deeper anesthetic. This requires

experience and judgment.

The specialty of anesthesiology is working to develop reliable methods to avoid cases

of awareness under anesthesia. Excessive anesthetic depth, on the other hand, is associated

with decreased heart rate and blood pressure, and, if carried to extremes, can jeopardize

perfusion of vital organs or be fatal. Short of these serious misadventures, excessive depth

results in slower awakening and more adverse effects.

As the surgical procedure draws to a close, the patient's emergence from anesthesia is

planned. Experience and close communication with the surgeon enable the anesthesia

provider to predict the time at which the application of dressings and casts will be complete.

In advance of that time, anesthetic vapors have been decreased or even switched off entirely

to allow time for them to be excreted by the lungs. Excess muscle relaxation is reversed

using specific drugs and an adequate long-acting opioid analgesic to keep the patient

comfortable in the recovery room. If a ventilator has been used, the patient is restored to

breathing by himself, and, as anesthetic drugs dissipate, the patient emerges to consciousness.

Removal of the endotracheal tube or other artificial airway device is only performed

when the patient has regained sufficient control of his or her airway reflexes.

2.4.4. Reversal

It is a process of discontinuation of anesthetic agents at the end of surgery to allow

return of consciousness and recovery from muscle paralysis while maintaining analgesia.

Volatile agents are discontinued first and later the nitrous oxide. Patient is given

100% oxygen. Wait for return of spontaneous breathing; this can be observed on

capnography and can also be felt with reservoir bag if patient is manually ventilated.

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Administer reversal agent such as neostigmine (anticholinesterase) or glycopyrrolate

to counteract non-depolarizing muscle relaxant; atropine is usually given to counteract the

parasympathetic effects of anticholinesterase.

Reversal agent is given when there is evidence of spontaneous breathing effort.

Patient’s tidal volume has to be ensured that it is adequate and able to control own airway

before attempting extubation.

2.5. Postoperative Care

The anesthesia should conclude with a pain-free awakening and a management plan for

postoperative pain relief. This may be in the form of regional analgesia, oral, transdermal or

parenteral medication. Minor surgical procedures are amenable to oral pain relief medication

such as paracetamol and NSAIDs such as ibuprofen. Moderate levels of pain require the addition

of mild opiates such as tramadol. Major surgical procedures may require a combination of

modalities to confer adequate pain relief.

Parenteral methods include patient-controlled analgesia (PCA) involving a strong opiate

such as morphine, fentanyl or oxycodone. To activate a syringe device, patient will press a

button and receive a preset dose or bolus of the drug (eg: 1mg of morphine). The PCA device

then locks out for a preset period to allow drug to take effect. If the patient becomes too sleepy or

sedated, they make no more morphine requests. This confers a fail safe aspect which is lacking in

continuous opiate infusion techniques.

Shivering is a frequent occurs in the post operative period. Apart from causing discomfort

and exacerbating post operative pain, shivering has been shown to increase oxygen consumption,

cathecolamine release, cardiac output, heart rate, blood pressure and intra ocular pressure. There

are number of techniques used to reduce this occurrence, such as increasing the ambient

temperature in theatre, using conventional or forced warm air blankets and using warmed

intravenous fluids.

2.6. Common Anesthetic Drugs

The main group of drugs commonly used in general anesthesia are broadly classified into

induction agents, muscle relaxants, analgesics and reversal agents. Induction agents then are

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further classified into inhalational and parenteral while the muscle relaxants can be divided into

depolarizers and non depolarizers.

2.6.1. Inhalational Anaesthetic Agents

It exists as gaseous form (nitrous oxide) or volatile liquids (isoflurane).

Halothane is a halogenated alkane derivative. Other modern volatile agents are

halogenated methyl ether derivatives (enflurane, isoflurane). Controllability is by

pulmonary administration and is delivered via vaporizers. The commonly used

inhalational agents are liquids at room temperature and therefore they need to be

converted to the gaseous state for administration to patients. Vaporizers is a

device for producing a clinically useful and stable concentration of an anesthetic

vapour in a carrier gas ( oxygen and nitrous oxide). The aim of inhalational

anaesthesia is the development of an appropriate tension or partial pressure of

anesthetic agent within the brain.

- Gaseous anaesthetic agents

Nitrous oxide

o It is stored in steel cylinders as a liquid under pressure in equilibrium

with the gas phase at normal room temperature.

o N2O is a colorless gas without appreciable odour or taste and non

explosive.

o It is a potent analgesic but a weak anaesthetic agents

o It cause depress hematopoietic function ( megaloblastic anemia,

thrombocytopenia and leucopenia), thus not advisable for

administration of more than 24 hours.

o It is widely used as an adjuvant to lower the MAC of volatile

anesthetics. With inhalation of 70% N2O / 30% O2 MAC value are

reduced (~35%- 45%)

- Volatile Anesthetic agents

Halothane

Halothane is a haloalkane and has a MAC value of 70%. It can be used

for induction of anesthesia in children. Halothane is a non specific Ca2+ influx

inhibitor and it may cause bradycardia. It increases the automaticity of the heart

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and when combined with adrenaline it may cause tachyarrythmias. One of the

important side effects is ha;othane hepatotoxicity. The diagnosis of halothane

hepatitis is by exclusion. This may progress into fulminant hepatic failure with a

high mortality. Obese middle aged women having repeat halothane exposures are

at risk. Halothane hepatitis may occur following a single exposure.

Isoflurane

It causes a dose dependent reduction in blood pressure. The decrease in

blood pressure is due to vasodilatation and decreased total peripheral resistance.

The heart rate is increased via reflex mechanisms but arrhythmias are uncommon.

Isoflurane does not affect ventricular conduction and does not increase the

excitability of ventricular myocardium. Induction of anesthesia is difficult with

isoflurane due to its pungent odour and preanesthetic concentration of isoflurane

may cause an airway reflex stimulation, with increased secretions and/or

coughing and laryngospasm.

Sevoflurane

It is a new inhalational agent and more expensive than others. It has

pleasant odour and can be used as induction agents in paediatric and adult

patients. It has rapid onset of induction and recovery of anesthesia because it is

less soluble in blood than isoflurane. It has a mild negative inotropic effect. It also

decreases systemic vascular resistance but does not cause reflex tachycardia.

Sevoflurane is less arrythmogenic when compared to halothane and it is suitable

for daycare surgery.

2.6.2. Intravenous induction agents

Criteria for ideal intravenous anesthetic agents:

Induction of anesthesia should be rapid, smooth and safe

It should have limited effects on cardiovascular and respiratory systems

It should possess analgesic activity.

Consciousness should return rapidly, smoothly and predictably.

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a. Sodium thiopental (Pentothal)

Thiopental is the only intravenous barbiturate being used today and is

classified under an ultra short acting barbiturate. It is prepared as a 2.5% solution,

water soluble, pH of 10.5 and stable for up to 1-2 weeks if refrigerated.

Mechanism of action: Depress the reticular activating system, reflecting the

ability of barbiturates to decrease the rate of dissociation of the inhibitory

neurotransmitter GABA from its receptors

Pharmacokinetics

Short duration of action (5-10 minutes) following IV bolus reflects high lipid

solubility and redistribution from the brain to inactive tissues.

Protein binding parallels lipids solubility, decreased protein binding increases

drug sensitivity.

Fat is the only compartment in which thiopental continues to accumulate 30

minutes after injection

Thiopental is metabolized in the liver slowly. Its hepatic excretion ratio is 0.15

It has an anticonvulsant effect and is a useful drug for cerebral protection

in head injury. It also has an analgesics effect. In the presence of inadequate

anaesthesia, airway manipulation may result in bronchospasm and laryngospasm.

Cardiovascular effects of barbiturate include decrease in blood pressure due to

vasodilatation and direct myocardial depression. There is a compensatory

increased in heart rate.

It should be used cautiously in haemodynamically unstable patients and is

contraindicated in hypovolaemia and hypotensive patients. Induction dose is 3-

5mg/kg in a healthy adult.

b. Propofol

It is 2,6- diisopropyl-phenol, under group of hindered phenol, an

alkylphenol derivative. Formulated in a solution with 10% soy bean oil,

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hydrophobic nature. It has rapid onset and short duration of action. Emergence

and awakening are prompt and complete after even prolonged infusions.

Mechanism of action: Propofol increases the inhibitory neurotransmission

mediated by gammaaminobutyric acid.

It has extensive metabolism by hepatic and extrahepatic. It has no

cumulative effects, has antiemetic property and suitable for daycare surgery. It

does not has antianalgesic activity.

Propofol is an ideal drug for total intravenous anesthesia. The target

controlled induction (TCI) and maintenance of anesthesia can be achieved

nowadays with propofol by a special TCI pump. Propofol also can be used to

provide sedation in ICU, for minor procedures or in combination with regional

anesthesia.

Effects on organ system

Cardiovascular : decrease in arterial blood pressure secondary to a drop in

systemic vascular resistance, contractility, and preload. Hypotension is more

pronounced than with thiopental. Propofol markedly impairs the normal arterial

baroreflex response to hypotension.

Respiratory: propofol causes profound respiratory depression. Propofol

induced depression of the upper airway reflexes exceeds that of thiopental

Cerebral: decreases cerebral blood flow and intracranial pressure.

Induction dose: 1.5-3 mg/ kg in a healthy adult.

c. Ketamine

It is a phenicyclidine derivative. It produces dissociative anesthesia

resulting in catatonia, amnesia and analgesia. Patient may appear awake and

reactive but does not response to sensory stimuli

Mechanism of action: It acts on NMDA receptor. It blocks polysynaptic

reflexes in the spinal cord, inhibiting excitatory neurotransmitter effects. It has

both anesthetic and analgesic properties. It causes postoperative psychic

phenomena- emergence delirium, vivid dreams, hallucination. Therefore it is not

28

suitable for adults. These effects can be minimized by combination with

benzodiazepines.

Clinical usage:

Induction of anesthesia in poor risk patients (eg: hypotension or bronchial

asthma)

As sole agent in dressing of burns, radiological procedures in children,

mass casualties in the field.

In the management of unresponsive severe bronchospasm

It is contraindicated in raised intracranial pressure, perforating eye

surgery, hypertension, heart failure, recent myocardial infarction, aneurysm and

valvular heart disease.

Dosage:

o IV 1.5-2 mg/kg, onset 30 sec. duration 5-10min.

o IM 10 mg/kg, onset 3-8min, duration 10-20min

Systemic effects:

Increase intracranial and intraocular pressures

Postoperative nausea and vomiting

Increased salivation. An antisialagogue is recommended before used

Preservation of airway reflexes and produces brochodilatation

Increased in cathecolamines secretion

Ketamine has cardiovascular effects: increases heart rate, blood pressure

and pulmonary arterial pressure. It is most likely due to direct stimulation of the

sympathetic nervous system.

2.6.3. Neuromuscular blocking agents

Muscle relaxants are generally classified into two groups, depending on

their mechanism of action.

1. Depolarizing muscle relaxants.

a. Example: succinylcholine

2. Non depolarizing muscle relaxants

a. Intermediate acting: vecuronium, atracurium, rocuronium

b. Long acting: pancuronium

29

1. Depolarizing muscle relaxants

Used to provide skeletal muscle relaxation to facilitate tracheal intubation

and optimal surgical condition. Ventilation must be provided as the diaphragmatic

muscle would also be paralysed. There is no CNS activity and the problem of

awareness begin with introduction induction of muscle relaxants.

Factors that influence inclusion of muscle relaxants in general anesthesia

are types of surgical procedures (anatomic location and patient position),

anesthetic techniques and patient factors (ASA class, obese, exreme of age).

Succinylcholine

The only depolariser drug that is used clinically. It consists of two

molecules of acetylcholine linked together. It acts on nicotinic receptors at

neuromuscular junction (NMJ) to cause sustained depolarization that

prevents propagation of action potential. The net effect of SCh induced

depolarization is uncoordinated skeletal muscle activity that is seen as

fasciculation.

It remains a useful muscle relaxants because of its rapid onset and

short duration of muscular relaxation that cannot be achieved by any other

available nondepolarising muscle relaxants.

A dose of 1-2 mg/kg produces profound muscle relaxation within

one minute. Full recovery is 10-12 minutes. It is used in emergency

surgery as rapid sequence induction technique and in situation of difficult

airway management.

Side effects

It may cause cardiac dysarryhmias such as bradycardia especially in

children.

Hyperkalemia – at risk patients (burns, extensively trauma, unrecognized

muscular dystrophy and denervation injuries.

Increased intragastric pressure (offset by even greater increase in lower

oesophageal sphincter)

Increased intraocular pressure (due to cycloplegic action of

succinylcholine)

30

Prolonged response in presence of atypical cholinesterase

Increased intracranial pressure

Muscle pain and myoglobinuria

2 Non depolarizing muscle relaxant

Acts on nicotinic receptors in a competitive fashion to produce

neuromuscular blockade- absence od depolarization. Can be antagonized by

anticholinesterase drugs. They are used to facilitate endotracheal intubation,

controlled ventilation and maintenance of muscle relaxation during surgical

procedures.

a. Atracurium

It is an intermediate acting benzyliso-quinolinium type NDMR. The

intubation dose is 0.5-0.6mg/kg. It presents as 10mg/ml solution in 25mg or 50mg

glass ampoules and is stored at 4 °C. Histamine release may occur in susceptible

patients but anaphylactoid reaction is very rare.

b. Vecuronium

It is an aminosteroid group and presents as freezed dried powder and

diluted with sterile water before used. There is no histamine release and devoid of

cardiovascular side effects. It does not antagonize fentanyl induced bradycardia. It

is metabolized by liver and also excreted unchanged in bile. The intubation dose

is 0.08-0.1 mg/kg.

c. Rocuronium

It is an aminosteroid group. Its rapid onset of action makes it a potential

replacement for SCh when rapid tracheal intubation is needed. Its duration of

action is similar to vecuronium and has similar pharmacokinetic characteristic. It

has minimal cardiovascular side effects and very low potential for histamine

release. Dosage for endotracheal intubation is 0.6 mg/kg.

d. Pancuronium

It is a long acting NDMR with a steroid structure (Bisaminoquaternary

steroid). It increases heart rate and blood pressure and cardiac output due to

31

cardiac vagal blockade. Histamine release is very rare and bronchospasm is

extremely uncommon.

Assessment of neuromuscular blockade

1. Clinical assessment

a. Ability to lift up head for 5 second

b. Hand grip for 5 second

c. Ability to produce vital capacity breath > 10 ml/kg

d. Tongue protrusion

2. Responses to electrical stimulation of a peripheral nerve stimulator

Anticholinesterase

Anticholinesterase is used to reverse non depolarizers. It inhibits the action of

acetylcholinesterase and increase the concentration of acetylcholine at the neuromuscular

junction. It also acts at parasympathetic nerve endings.

In excessive doses, acetylcholineesterase inhibitors can paradoxically potentiate a

nondepolarizing neuromuscular blockade and prolong the depolarization blockade of

succinylcholine. Anticholinesterase increases acetylcholine at both nicotinic and muscarinic

receptors. Muscarinic effects can be blocked by administration of atropine or glycopyrolate.

2.6.4. Opioid analgesics

Few examples of this drugs are morphine, pethidine, fentanyl and nalbuphine.

This drugs act on opioid receptors and classified as full agonist, antagonist, or mixed

agonist-antagonist depending on the actions on the opioid receptors. Three main receptors

are mu, kappa and delta.

Classification of opioid receptors

Mu receptors: morphine is the prototype exogenous ligand.

Mu-1: the main action at this reseptors is analgesia, but also responsible for

miosis, nausea/vomiting, urinary retention and pruritus. The endogenous ligands

are enkephalins.

32

Mu-2: respiratory depression, euphoria, bradycardia, ileus and physical

dependence are elicited by binding at this receptor.

Kappa: Ketocyclazocine and dynorphin are the prototype exogenous and endogenous

ligands respectively. Analgesia, sedation, dysphoria and psychomimetic effects are

produced by this receptor. Binding to kappa receptor can inhibit release of vasopressin

and thus promote dieresis.

Delta: It is a modulation of Mu receptor. Has high selective for the endogenous

enkephalins, but opioid drugs still bind (leuenkephalin and beta-endorphin).

Morphine  pharmacokinetics:

Elimination halftimes for morphine following bolus administration is about 1.7-4.5

hours.  Following bolus administration onset time is relatively slow (15-30 minutes)

because:

1. morphine exhibits relatively low lipid solubility about 2.5% of fentanyl

(Sublimaze)

2. at physiological pH, morphine, a weak base with the pKa of about 8.0, is

primarily ionized.  The ionized form does not favor passage through the lipid

membrane; accordingly, only about 10%-20% of molecules are un-ionized.

Relatively high plasma clearance (15-40 ml/kg/minute) has implicated extrahepatic

clearance mechanisms, most likely renal.

Fentanyl (Sublimaze) pharmacokinetics:

Fentanyl (Sublimaze) is significantly more lipid-soluble, compared morphine and,

relative to morphine, has a more rapid onset of action (fentanyl (Sublimaze) is also a

weak base and at physiological pH only about 10% of molecules are un-ionized).

Clearance of about 10-20 ml/kg/minute is consistent with a primary hepatic mechanism. 

Fentanyl (Sublimaze)'s short duration of action following bolus administration is

explained by rapid redistribution from brain to other compartments such as skeletal

muscle and fat. If, however, fentanyl (Sublimaze) is administered by continuous IV

infusion or multiple IV dosing, other non-CNS compartments will saturated and

remaining CNS fentanyl will contribute to postoperative ventilatory depression.

33

Action of opioid drugs:

A. Central nervous system: Analgesia, sedation, euphoria, nausea, vomiting, miosis,

depression of ventilation, pruritus and skeletal muscle rigidity.

B. Respiratory system: bronchospasm in susceptible patients and depressed cough reflex

C. Cardiovascular system: bradycardia (fentanyl) or tachycardia ( pethidine)

D. Skin: pruritus may be due to histamine release or action on opioid receptor.

E. Gastrointestinal tract: constipation, delays gastric emptying, increased tone of the

common bile duct and sphincter of Oddi.

F. Urinary tract: increased sphincter tone and retention of urine.

Use of opioids in anesthesias

Premedication drugs

Induction of anaesthesia

Blunt haemodynamic reactions to noxious stimulation

Intraoperative analgesia

Postoperative analgesia

Used in ICU as analgesia to facilitate mechanical ventilation

Drug Doses

Morphine 2.5 - 5 mg (IV), 15 - 30 mg (oral)

Pethidine 50 to 100 mg S.C., I.M or in reduced doses I.V.

repeated every 3 to 4 hours

Fentanyl 25 - 50 µg (IV), 150 - 300 µg (oral)

Naloxone

It is an antagonist at all opioid receptors of pure opioid antagonist. It reverse all opioid

actions including analgesia. It has short duration of action ( 1-4 hours) and has limited action

against partial or mixed actions opioids. Abrupt reversal of opioid analgesia can result in

sympathetic stimulation (tachycardia, ventricular irritability, hypertension and pulmonary

oedema).

34

Dosage :

Bolus:

o Adult: 0.04 mg IV in titrated bolus every 23 minutes until the desired

effects

o Child: 1-4mcg/kg titrated

Continuous infusion: 5mcg/kg/hr IV will prevent respiratory depression without

altering the analgesia produced by neuraxial opioids.

Tramadol

It is an opioid agonist at mu receptor and inhibits noradrenaline reuptake and release of 5-

hydroxytryptamine (monoaminergic pathways). It is given intravenously with the dose of 1-2

mg/kg and also can be given orally (good bioavailability). It produces less respiratory

depression in equivalent dose if compared with morphine.

Non opioids

Use of non steroidal anti-inflammatory drugs as analgesics (eg: Ketorolac, Diclofenac). It

block synthesis of prostaglandins by inhibiting cyclooxygenase enzyme. It reduces pain by

peripheral action and centrally by reducing input of nociceptive information in spinal cord.

Ketorolac and Ketoprufen has opioid sparing effects.

Side effects:

Reduced platelet aggregation may increase bleeding – it is not advisable for neurosurgical

and ophthalmic surgery.

It may cause damage to gastric mucosa causing ulceration and bleeding.

Bronchospasm – patients with asthma have an increased incidence of sensitivity to

aspirin

Renal failure- inhibition of renal prostaglandin synthesis may interfere with maintenance of

renal blood flow.

Drug Doses

Voltaren (Diclofenac) 100-200 mg daily

Paracetamol 2 x 500mg 4-6 hourly

Synflex Initially 550 mg then 275 mg

6-8 hrly

35

CHAPTER 3

CASE: PERIOPERATIVE ASSESSMENT

3.1. Preoperative Assessment

3.1.1. Case History

IDENTIFICATION DATA

Name : Anita binti Yahaya

Sex : Female

Age : 39 years old

Nationality/Tribe : Malaysian/Malay

Religion : Islam

Address : Kangar, Perlis

Marital Status : Married

Occupation : Housewife

Admission Date :17th May 2012, 11.15 am

CHIEF COMPLAINT

This 39-year old Malay lady was admitted to surgical ward of Hospital Tuanku Fauziah

with a chief complaint of right anterior neck swelling associated with shortness of breath since

one week ago.

HISTORY OF PRESENTING ILLNESS

Patient is a known case of goitre for the past two years. The goitre, which is a right sided

anterior neck swelling, painless, and gradually increases in size. Sometimes, the patient

experienced hand tremor, palpitation and heat intolerance. Now, she was having obstructive

symptoms such as shortness of breath and occasionally orthopnoea since 1 week ago.

Ultrasound was done on 4th May 2011, with the impression of Multinodular Goitre. Fine

Needle Aspiration Cytology (FNAC) was also done on 2nd June 2011, with the impression of

nodular goitre with cystic degeneration.

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Otherwise, she has no dysphagia, no diarrhea, no constipation, no abdominal pain, no

upper respiratory tract infection or urinary tract infection, and no stridor.

PAST MEDICAL HISTORY

She has no known of other medical condition.

PAST ANAESTHETIC HISTORY

Patient has never gone through any surgical or anaesthetic procedures.

DRUG HISTORY

Patient is not on any medication. There’s no history of drug or food allergy. Patient

claimed she’s not taking any traditional medication or over the counter drug.

PAST OBSTETRIC & GYNECOLOGY HISTORY

Patient has never had any problem regarding obstetric and gynecology. She had her

menarche at the age of 13 years old and claimed to have a regular menstrual cycle, around 7 to 8

days every month. However, she has mild dysmenorrhea.

FAMILY HISTORY

The patient’s father has thyroid cancer. Mother is healthy.

SOCIAL HISTORY

Patient is a housewife, married, and having 4 children. Currently, she’s living with her

husband and children. She’s a non-smoker and non-alcoholic. She denied of any high-risk

behavior.

3.1.2. Physical Examination

GENERAL EXAMINATION

Patient was conscious and alert, lying comfortably on the bed. She doesn’t look ill, not in

pain, and not in respiratory distress. Her nutritional status is obesity, and her hydrational status is

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fair. There’s no gross deformity, no any involuntary or abnormal movement, and there’s a

brannula attached at her left wrist.

VITAL SIGNS

HEAD, NECK & EXTREMITIES EXAMINATION

On the general examination (extremities), the palm was moist, no pallor, no palmar

erythema and the temperature was normal. There’s no clubbing finger, and no bluish

discolouration of the nail. No leuconychia or koilonychia noted. There’s no fine tremor or

flapping tremor. There’s also no pedal edema at both lower extremities.

Examination of the head did not reveal pallor of the conjunctiva, no jaundice of the

sclera, no exophthalmus, no arcus senilis and no xanthelasma. There’s also no bluish

discoloration of the lips and the tongue. The dental hygiene was fair.

For neck examination, on inspection, there’s a right anterior neck swelling that moves

upon deglutition, but does not move with tongue protrusion. Otherwise, there’s no redness, no

skin changes, no discharge, no surgical scar and no prominent vein. On palpation, it’s a non-

tender swelling with normal temperature. The size is 3x2 cm. The swelling has a smooth surface,

firm in consistency, round in shape, mobile and has a well-defined margin. The lower border of

the swelling can be felt upon deglutition. There is a tracheal deviation towards the left side.

Otherwise, the swelling is not attached to underlying structures or overlying skin, no fluctuation

Vital signs Value Interpretation

Temperature 37°C Afebrile

Blood pressure 135/70 mmHg Normal

Pulse rate 72 bpm Normal

Respiratory rate 18x/minute Normal

Pain score 0/10 Not in pain

Height 162 cm -

Weight 84 kg -

Body Mass Index 32 kg/m2 Obesity

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and there’s no pulsation can be appreciated. On percussion, there’s no retrosternal extension of

the swelling, and on auscultation, there’s no bruit can be heard.

RESPIRATORY SYSTEM EXAMINATION

From airway assessment, patient was classified as Mallampati class II, and the

thyromental distance was more than 6.5 cm or three fingers wide.

Patient has no history or symptoms of upper respiratory tract infection. On examination;

on inspection, the chest moved symmetrically with respiration, with thoraco-abdominal breathing

pattern. The chest shape was normal and there was no deformity or scar noted on both anterior

and posterior chest wall. There were also no signs of respiratory distress. On palpation, the chest

expansion and tactile vocal fremitus were symmetrical on both anterior and posterior chest. On

percussion, it was a symmetrical resonance sounds, and there’s no retrosternal extension of the

goiter. On auscultation, no wheezing or crepitation heard. Air entry was equal on both sides.

CARDIOVASCULAR SYSTEM EXAMINATION

The peripheral pulses were palpable, equal and regular. There was no surgical scar seen

on the chest. There was neither heave nor thrill can be palpated. Apex beat was palpable at left

midclavicular line between 4th and 5th intercostal space. Normal 1st and 2nd heart sounds were

heard and there were no additional sounds or murmurs heard in the mitral, tricuspid, aortic and

pulmonary area.

ABDOMINAL EXAMINATION

On inspection, the abdomen was not distended, moves with each respiration. The

umbilicus is centrally located. Otherwise, there is no surgical scar, no visible peristalsis or

pulsation, no skin discolouration and no cough impulse.

On palpation, the abdomen is soft and non-tender. No mass can be appreciated and no

hepatomegaly or splenomegaly. The kidney was non-ballotable.

The percussion gives tympanic sound, and there’s no shifting dullness. On auscultation,

the bowel sound was present and no renal bruit heard.

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CENTRAL NERVOUS SYSTEM EXAMINATION

Patient was alert, and well oriented to person, time and place. Glasgow Coma Scale was

15/15. Facial expression was symmetry. All cranial nerves were intact.

MUSCULOSKELETAL SYSTEM EXAMINATION

Patient has a normal muscle bulk, strength, tone and power for both upper and lower

extremities. The shape of vertebral spine is normal. No deformities noted. Gait was normal.

PHYSICAL STATUS

ASA score is 1. Patient was healthy with no systemic disease, and the surgery was an

elective surgery.

3.1.3. Investigation

o Full blood count:

Components Value Normal Range Interpretation

White blood cell 8.8 (109/L) 4.0 – 11.0 Normal

Red blood cell 4.7 (106/L) 3.8 – 4.8 Normal

Haemoglobin 12.0 (g/dL) 12.0 – 15.0 Normal

Haematocrit 37.8 (%) 36.0 – 46.0 Normal

Mean cell volume 80.1 (fL) 83.0 – 101.0 Low

Mean cell

haemoglobin

25.4 (pg) 27.0 – 32.0 Low

MCHC 31.7 (g/dL) 31.5 – 34.5 Normal

Platelet 298 (103/uL) 150 – 450 Normal

Differential:

Neutrophils

Lymphocytes

Monocytes

Eosinophils

Basophils

4.75 (103/uL)

2.90 (103/uL)

0.35 (103/uL)

0.70 (103/uL)

0.00 (103/uL)

2.0 – 7.0

1.0 – 3.0

0.2 – 1.0

0.02 – 0.50

0.02 – 0.10

Normal

Normal

Normal

High

Low

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o Renal profile

Components Value Normal Range Interpretation

Sodium 138 (mmol/L) 135 – 145 Normal

Potassium 3.7 (mmol/L) 3.3 – 5.3 Normal

Urea 3.7 (mmol/L) 1.7 – 8.3 Normal

Creatinine 61 (umol/L) <97 Normal

o Coagulation:

Components Value Normal Range Interpretation

Prothrombin time 11.7 (sec) 10.4 – 13.2 Normal

INR 0.99 0.9 – 1.1 Normal

APTT test 28.5 (sec) 20.1 – 34.9 Normal

APTT ratio 1.0

o Thyroid function test:

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Components Value Normal Range Interpretation

TSH 1.720 (uIU/mL) 0.27 – 4.20 Normal

Free T4 15.96 (pmol/L) 12 - 22 Normal

o Urine FEME:

Components Value Interpretation

Urine glucose Normal Normal

Bilirubin Negative Normal

Ketone Negative Normal

Specific gravity 1.000 Normal

Blood Negative Normal

Urine pH 5.0 Normal

Protein Negative Normal

Urobilinogen 3.2 Normal

Nitrite Negative Normal

Leucocyte Negative Normal

Color Light yellow Normal

Turbidity Clear Normal

Urine PT Negative Normal

EKG:

o Sinus rhythm

o No ischemic changes

o Interpretation: Normal

Chest X-Ray:

o Tracheal deviated to the left side

o Lung: Normal

o No cardiomegaly

o Bones: Intact

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o Soft tissues: Normal

Indirect Laryngoscope:

o Both vocal fold mobile equally

o No anterior compression

o Impression: Normal vocal cord

3.1.4. Summary

A 39 years old malay lady, a known case of multinodular goitre diagnosed in 2010,

presented with right anterior neck swelling associated with shortness of breath since 1 week

before her admission to the hospital. Occasionally she has tremor, palpitation and heat

intolerance. On physical examination, patient is clinically euthyroid and not in respiratory

distress. From the chest X-ray, there’s a tracheal deviation to the left side. Otherwise, there’s no

any significant finding in any other system.

3.1.5. Preoperative Diagnosis

o Bilateral multinodular goitre

3.1.6. Plan

o Right hemithyroidectomy KIV total thyroidectomy

o To keep nil by mouth by 12 midnight (8 hours prior to surgery)

o To inquire informed consent for the surgery and anaesthetic procedures

o Send blood for blood crossmatch

o To plan for general anaesthesia/intermittent positive pressure volume

3.2. Intraoperative Assessment

Anaesthesia : Balanced general anaesthesia with intermittent positive pressure ventilation

(IPPV).

Fasting : Patient was kept nil by mouth 8 hours prior to operation.

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Premedication : Not given to patient

3.2.1. Anaesthesia Procedures :

I. Preoperative assessment was done and consent was taken from the patient.

II. GA machine was checked and anaesthetic drug was prepared before patient was

entered into the operation room.

III. Intravenous assessed was established by inserting IV catheter 18G and patient was

preloaded with normal saline.

IV. Procedures were done in a full aseptic technique, scrubbed, gloved and gowned.

V. Patient neck was fully extended and given sand bag to get the better view for the

surgery.

VI. Patient was preoxygenated with 100% oxygen for 3 minutes at 8am.

VII. Administration of intravenous Fentanyl 100mcg and intravenous sodium thiopentan

2.5% 175mg.

VIII. Loss of consciousness was assessed by loss of eyelash reflex.

IX. Test ventilate before give muscle relaxant.

X. Then, IV atracurium 30mg was given and mask ventilate with oxygen and volatile

for 3minutes.

XI. Laryngoscopy and intubation were then performed by using ‘armored’ ETT tube.

XII. ETT cuff of 7.5 cm and angle at 15cm was inflates and connected to breathing

circuit.

XIII. ETT positioned was confirmed by auscultation and end tidal volume CO2.

XIV. The vital sign which are oxygen saturation, brain tissue carbon dioxide, respiratory

rate, blood pressure, heart rate, any blood loss and urine output was monitored during

the operation.

XV. No blood transfusion was done during the operation.

XVI. Anaesthesia was maintained with Sevoflurane and top up atracurium infusion

3ml/hour and morphine 3mg /hour.

XVII. Reversal with intravenous Atropine 1mg and Neostigmine 2.5mg.

XVIII. ETT was removed and mouth was cleared under direct vision once patient

spontaneously breathing.

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XIX. Oxygen was administered by face mask and patient was transferred to recovery room

to be reassessed.

3.2.2. Drugs :

3.2.2.1. Intravenous :

a. Fentanyl 100mcg

b. Sodium thiopentate 2.5% 175mg

c. Atracorium 30g

d. Morphine 3mg

e. Atrocorium infusion 3ml/hour

f. Atropine 1mg

g. Neostigmine 2.5mg

3.2.2.2. Gases : 8.20 am 8.50am 9.20am 9.50am

1. Oxygen / air (L/min) 1:1 1:1 1:1 1:1

2. Volatile : Sevoflurane (MAC %)1.7 1.7 1.7 1.7

3.2.3. Monitoring :

Time 8.20am 8.50am 9.20am 9.50am

Saturation O2 (100%) 100 % 100% 99% 100%

Respiratory rate (x/min) 18x/min 18/min 16x/min 18x/min

Pbt CO2 34 34 34 36

Blood Pressure and Heart Rate :

Blood pressure was monitored every 5 minutes during the whole operation

procedure. The systole reading range was between 140 – 180 mmHg and diastolic

pressure was between 60 – 180mmHg.

Heart rate was monitored every 5minutes and noted to be in normal range which

was within 90 – 100 beats per minutes.

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Blood Pressure monitoring :

Heart rate monitoring

3.2.4. Summary :

Patient was hemodynamically stable with minimal blood loss during the operation

thus no blood transfusion was needed. Upon operation, the surgeon only did right

hemithyroidectomy and not done total thyroidectomy because the nodule at the left side is

small (1cm) near the recurrent laryngeal nerve and not removed. Both recurrent laryngeal

nerve identified and preserved and parathyrois gland identifiend and preserved. Skin closed

with subcuticular. Patient reversed with atropine and neostigmine and was transferred to

recovery ward before discharging to ward.

3.3. Post Operative Assessment

After extubation, patient was stable and began to breathe spontaneously with

supplemental oxygen via face mask (5L/min).

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Patient was transferred to the recovery area after the surgery was done. Patient was still

drowsy lethargic but there was no sign of respiratory distressed seen.

Non-invasive blood pressure (NIBP) monitor, ECG monitoring and pulse oximeter were

set-up.

Patient was put below radiant warmer to prevent hypothermia.

Pain was minimal and there were no complaints of headache, nausea or vomiting.

Otherwise, no other post-operative complications noted.

Vital Signs Reading Interpretation

Blood pressure 119/80 mmHg Normal

Pulse rate 81 x/min Normal

Respiratory rate 20x/ min Normal

Temperature 37°C Afebrile

SpO2 100% Normal

Pain score 2/10 Mild pain

Post-operative anaesthesia recovery score

Parameters Signs Score

Activity Able to lift the head or has a good hand grip

None of the above

1

0

Respiration Able to breathe and cough easily

Dyspnoeic or apnoeic

1

0

Circulation BP within 20% of pre-operative level

BP above or below 20% of pre-operative

level

Pulse regular rate, within 20% of pre-

operative level

Pulse irregular, above or below 20% of pre-

operative level

1

0

1

0

Consciousness Arousable 1

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Not responding 0

Colour Pink

Dusky

1

0

Total score 6/6

Note:

Score 5 or more may be coming home with the conditions of operation/ action possible

Score 4 to the treatment room when the breathing value is 1

Score 3 or less to ICU

Operative findings:

Multinodular goitre, right lobe is larger than the left lobe

Only 1 small nodule is noted, measuring about 1cm on the left side, situated near the

recurrent laryngeal nerve, not removed

Both recurrent laryngeal nerves are identified and preserved

Parathyroid glands are identified and preserved

Plan:

(i) To transfer patient to the surgical ward after 30 minutes and regularly monitor the vital

signs in the ward

(ii) Continue to give supplemental oxygen (5L/min) via face mask

(iii) Infuse 3 pints of dextrose 5% and 2 pints normal saline 0.9% in 24 hours

(iv) Keep nil by mouth for 6-8 hours

(v) To give C. Tramal 50mg PRN

(vi) To give tab. Paracetamol 1g QID

3.3.1. Follow-up

18th of May 2012 (12.00 pm)

Subjective Patient complain of pain over the incision site and throat

discomfort, pain score 3/6

Patient was able to speak, can tolerate small volume of liquid

(2-3 spoonful) orally

Otherwise, there is no numbness, hoarseness of voice, shortness

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of breath, tremor or palpitation

Objective Patient is alert, conscious but mildly lethargic

Skin is pink, hydration is adequate

BP: 118/80 mmHg

Pulse rate: 80x/min

Respiratory rate: 20x/min

Temperature: 37°C

Surgical scar: clean, no discharge is seen, not infected

Lungs: Vesicular breath sound, no additional sound

CVS: Dual rhythm no murmur

Abdomen: soft non tender

Analysis Post- right hemithyroidectomy for multinodular goitre

Plan Continue vital signs monitoring every 4 hours

Keep nil by mouth for about 6-8 hours, then encourage fluid

intake orally (set an intake/ output chart)

Give C. Tramal 50mg PRN and T. Paracetamol QID for pain

To complete IV drip: 2 pints of normal saline and 3 pints of

Dextrose 5% in 24 hours

19th of May 2012 (2.00 pm)

Subjective Patient complain of pain over the incision site and throat

discomfort, pain score 2/6

Patient was able to speak with slight hoarseness, can tolerate

small volume of liquid orally

Otherwise, there is no numbness, shortness of breath, tremor

or palpitation

Objective Patient is alert, conscious and comfortable

Skin is pink, hydration is adequate

BP: 116/80 mmHg

Pulse rate: 76x/min

Respiratory rate: 17x/min

Temperature: 37°C

Surgical scar: clean and healing, no discharge is seen, not

infected

Lungs: Vesicular breath sound, no additional sound

CVS: Dual rhythm no murmur

Abdomen: soft non tender

Analysis Post- right hemithyroidectomy for multinodular goitre

Plan Continue vital signs monitoring every 4 hours

Encourage fluid intake orally (set an intake/ output chart)

Give C. Tramal 50mg PRN and T. Paracetamol QID for pain

Off IV drip when completed and adequate oral intake

To discharge patient when no complication and condition is

stable. Plan for follow-up in SOPD

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CHAPTER 4

PERIOPERATIVE DISCUSSION (CASE)

4.1. Pre-operative Discussion

There are few criteria that need to be considered in the pre-operation before a patient

undergone surgery, which are:

o To access the condition of the patient from the history and physical examination. From

physical examination, it is important to make a thorough assessment of airway,

cardiovascular system, and respiratory system. Since this patient has no problem in her

cardiovascular and respiratory system, the assessment would be focused more on her

airway, to determine if there would be any difficulty when the intubation is performed.

o To decide the anaesthetic plan for the patient either by general or regional anaesthesia.

o The need of informed consent for both surgery and anaesthetic procedures.

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o Patient is not given any premedication such as:

- Antibiotic: Thyroidectomy is considered as a clean surgery, prophylactic

antibiotic is not needed.

- Anxiolytic: Patient’s anxiety is not severe enough to be treated using medication.

- Antiemetic: Risk of aspiration is reduced by keeping patient NBM before surgery.

- Analgesic: Not given to our patient because she is not in pain prior to the surgery

o To keep the patient nil by mouth 8 hours prior to surgery

1. For this patient, she does not have any past medical history such as asthma, or any

evidence of recent upper respiratory tract infection, which suggesting the use of general

anaesthesia is not contradicting. However, this is her first surgical experience, thus

there’s no any record of allergy to anaesthetic agents. From assessment of Mallampati

class, this patient is in class II, and the thyromental distance is 3 finger breadth, which

suggesting the difficulty of airway for intubation is not present.

2. In this patient whom undergone right hemithyroidectomy surgery, which involves the

upper airway region; general anaesthesia is the best option. It is unethical to use regional

anaesthesia and keeps the patient awake for this type of surgery.

3. Based on American Society of Anaesthesiology grade, the patient classified into class I

(with the mortality rate of 0.06%-0.08%), because she is perfectly healthy and thus, the

operation risk is minimal. However, there are also other predictors which play roles in

determining the risk and mortality of an operation, such as operation type and surgical

skill of the operator.

4. The patient gave her consent to go through hemithyroidectomy surgery. The consent

given after the anaesthesia and surgical teams explained about the nature of surgical and

anaesthetic procedures. Their consent is taken and is documented in the anaesthesia and

surgery consent forms. All questions asked by the patient, answered by anaesthesiologist.

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5. The patient was keep nil by mouth by 12 midnight, 8 hours before she undergone the

surgery, to allow sufficient time for gastric emptying of ingested food and liquid at the

time of induction of anaesthesia. It is believed that fasting can limit the severity of

aspiration pneumonitis syndrome in the event of aspiration of gastric content. The gastric

emptying of fluid is very rapid; 95% of ingested liquids are emptied in 1 hour, while

solids are emptied only when it is transformed into a liquefied form, which requires

unpredictable time (up to 12 hours).

4.2. Intraoperative Discussion

1. Patient was given balanced general anaesthesia with intermittent positive airway pressure

ventilation not by spontaneous ventilation. Balanced anaesthesia mean that 3 component

of anaesthesia was given which mean hypnotic, analgesia, and muscle relaxant. It is safer

to use 3 types of drug in safety doses than 1 type that require higher dose to get other

effect but can harm the patient. IPPV was chosen because the surgery involves the

airway, at the neck region, and requires endotracheal intubation. Spontaneous ventilation

was not chosen for this patient because it usually for superficial surgeries and surgery that

doesn’t involve the airway.

2. Patient was given special type of endotracheal tube which is ‘armored’ endotracheal tube

that are cuffed, wire- reinforced silicone rubber tubes that are much more flexible than

polyvinyl chloride tube, but they are difficult to compress or kink. This type of

endotracheal tube is useful when the trachea is anticipated to remain intubated for a

prolonged duration and the neck to remain flexed during surgery. ETT is indicated for

surgery that used IPPV and muscle relaxant, to secure the airway, and for unusual

surgical position.

3. Patient was given 2 types of opioid for the surgery which are IV Fentanyl and IV

morphine. Fentanyl was given 1-2mcg/kg, so for this patient is 80 – 160mcg. Patient was

given 100mcg which is 1 ampoule. Fentanyl was used as an induction agent because the

onset of action of fentanyl is almost immediately when given intravenously than

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morphine. Fentanyl is more potent than morphine due to its high lipophilicity, which

make it penetrates the CNS more easily. It binds to mu opioid G protein couple receptor

which inhibits pain neurotransmitter released by decreasing intracellular Ca2+ levels.

Morphine is used as maintenance for analgesia during the intraoperation period because it

is long acting. Morphine is used than ketorolac because it is a gold standard drug and

patient does not have contraindication to it. Ketorolac may not improve analgesia due to

its ceiling effect but may increase the unfavorable effect. Furthermore, ketorolac

increased the risk of surgical bleeding and increased GI bleeding.

4. Patient was given with sodium thiopental (STP) which is an intravenous barbiturate (3-

5mg/kg), but for this patient was given 175mg. STP was given to sedate the patient so it

is given slowly with other volatile gas which can give synergistic effect and is stopped

when the patient has been sedated. That is why patient it is only given 175mg. STP is

cost effective compared to propofol. Unlike propofol, STP induces histamine release

which will be dangerous in asthmatic patient. STP is considered to be safe for our patient

since she doesn’t have asthma. STP causes less pain when it’s injected compared to

propofol. STP is an ultra-short acting barbiturate due to its rapid distribution which is

used as an induction that acts directly to GABA receptor and causes sedative effect. After

STP was given, ventilation test needs to be done to make sure that we can ventilate the

patient by monitoring the capnograph.

5. Atracurium is a muscle relaxant given to the patient after test ventilate was done. For this

patient was given 30 mg. It is non depolarizing muscle relaxant that acts on nicotinic

receptor in competitive fashion to produce neuromuscular blockade so that depolarization

not occur. It is used to facilitate endotracheal intubation, and controlled ventilation. It is

spontaneously degraded by Hofmann elimination. As maintenance, atracurium sustains

muscle relaxation during surgical. Usually atracurium not given as infusion for thyroid

surgery but for this patient, atracurium infusion was given because the anaesthesiologist

predicted that the surgery will be long, but the operation is not complicated and tends to

be short surgery, so it is stopped within ½ hour before the surgery was done. After the

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atracurium was given, mask ventilation has to be done for 3 minutes to allow the onset of

action of atracurium.

6. Sevoflurane is a volatile anaesthetic agent that is used for this patient. It is used because it

is less soluble in blood which will cause patient to gain her consciousness faster from

anaesthesia. Furthermore, it is preferred agent for mask delivery due to its less irritation

to mucous membrane. It causes immobility that is measured by minimum alveolar

concentration (MAC) of anaesthesia required to suppress movement to a surgical incision

in 50% of patient. It has mild negative inotropic effect which can lower the blood

pressure in this patient during surgery.

7. Patient was given IV atropine 1mg and IV neostigmine 2.5mg for reversal after

operation. Neostigmine is an anticholinesterase that inhibits acethylcholinesterase so that

the enzyme can no longer break down the acethycholine molecules before they reach the

postsynaptic membrane receptor. Atropine is given to counteract the parasympathetic

effects of anticholinesterase.

8. Monitoring of intraoperative is to see any rapid changes in patient status during

anaesthesia. The patient’s oxygenation, ventilation, circulation and temperature are

continuously monitored. Clinical signs like colour, pulse rate and volume, rate and depth

of respiration, blood pressure, fluid status, temperature, urine output, blood transfusion

are also monitored. All the important vital sign are documented. For this patient all the

vital sign are in the normal state except that her blood pressure which is higher than

normal. Sevoflurane can reduce the blood pressure during the operation. Furthermore, it

is normal for blood pressure to elevate during intubation and extubation because of body

response and it will reduce later.

9. Fluid replacement is divided into 3 components, which are: for maintenance, deficit, and

the fluid loss (insensible & bleeding). Intraoperative fluid administration has to be given

to maintain adequate oxygen delivery, normal electrolyte concentration, and to normal

blood glucose level.

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For the maintenance:

1st 10kg of BW : 100ml/kg/24h 4ml/kg/h Patient :80kg (10kg x4 = 40ml)

2nd 10kg of BW : 50ml/kg/24h 2ml/kg 10kg (10 kg x2= 20ml)

Each kg above 20kg : 20ml/kg/24h 1ml/kg/h 60kg (60kg x1= 60ml)

Maintenance – 40 ml + 20ml + 60ml = 120ml/hour

Preexisting deficit: maintenance x numbers of hour of fasting. Replace half in the 1 st

hour, quarter in 2nd and 3rd hours – 8hour x 120ml = 960ml (replace 480 in 1st hour,

240 in 2nd and 3rd hours )

Ongoing loss : from the blood loss and the evaporative loss from the surgical field

( minor = 1- 2ml/kg/h, moderate = 3- 4ml/kg/h, major = 6- 8 ml/kg/h)

Patient = minor – 1 x 80 = 80ml/h

1st hour = 120 ml + 480 ml + 80ml = 680 ml/h

2nd and 3rd hour = 120ml + 240ml + 80 ml = 440ml/h

4th hour onward = 120ml +80 = 200ml/h

The choice of fluid given is crystalloid because it is rapidly distributed into the

extracellular fluid component. It is useful to provide maintenance water and electrolytes

and for intravascular volume expansion . For this patient, normal saline was chosen

(0.9% NaCl) .

4.3. Post-operation discussion

1. Patient should not leave the operation room unless they have a stable and patent airway

(indicated by the presence of cough and gag reflex along with spontaneous breathing),

adequate ventilation and oxygenation, and are hemodynamically stable.

2. Continuing care in the recovery room:

3. Phase 1: Gained consciousness with intact pharyngeal reflexes. Able to sustain a 5

seconds head lift, cough and deep breath.

4. Phase 2: Recovers the ability to think clearly and movement returns. Can be transferred

to the ward.

5. Phase 3: At the end of this phase all the effects of anaesthetics should disappear.

6. The most frequent problems in the recovery room are:

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7. Nausea and vomiting (might be the effect of opioids analgesics, which will cause

increased intracranial pressure, resulting in headache, altered consciousness. Fluid and

electrolyte loss can also happen).

8. Inadequate pain relief (pain will activate the sympathetic activity vasoconstriction

less perfusion to the tissue delayed wound healing)

9. shivering due to hypothermia (patient should be placed near a warmer and covered with

blanket)

10. Hypoxemia (to prevent this, pre-oxygenation via face mask should be continued

immediately after extubation)

11. Bleeding from the surgical site or wound infection (bleeding and swelling can

compromise the airway. If this occurs, remove skin clips/sutures and strap muscle sutures

and call for help.

12. Hoarseness of voice might post thyroidectomy might be due to iatrogenic injury to the

recurrent laryngeal nerve, or simply due to swelling around the nerves (this will resolve

with time). Patient should be warned that their voice will be different for a few days post-

op because of intubation and local edema.

13. Most patients who have mild to moderate pain following surgery can be managed with

oral COX inhibitors, opiods, or a combination. Our patient was given Paracetamol (1g

QID) tablet and Tramadol hydrochloride capsule (50mg PRN) as soon as patient was able

to tolerate orally.

Paracetamol (acetaminophen) has the fewest side effects but is a hepatotoxin at very

high doses. Isoniazid, zidovudine, and barbiturates can potentiate acetaminophen

toxicity.

Tramadol is a synthetic oral opioid that also blocks neuronal reuptake of

norepinephrine and serotonin. It appears to have the same efficacy as the combination

of codeine and acetaminophen but is associated with significantly less respiratory

depression and has little effect on gastric emptying.

56

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Basri, M., Ariff, Lukman, M., Hadi, A., Azrina, 2009. General Anaesthesia. Anaesthesiology for

Medical Undergraduates; 37-50.

Desai, A.M., Macario, A., Green, R., Talavera, F., Krugman, M., Raghavendra, M., 2011.

General Anaesthesia. Available from: http://emedicine.medscape.com/article/1271543-

overview [ Assessed 19 May 2012]

Frilling, A., Liu, C., Weber, F., 2004. Benign Multinodular Goiter. Scandinavian Journal of

Surgery, Vol.93: 278-281

Neto, G.M., 2010. Multinodular Goiter, Thyroid Disease Manager. Available from:

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http://www.thyroidmanager.org/chapter/multinodular-goiter/ [Assessed 18 May

2012].

The American Association of Endocrine Surgeons, 2007. Benign Thyroid Enlargement (non-

toxic multinodular goiter). Available from:

http://endocrinediseases.org/thyroid/goiter_symptoms.shtml [ Assessed 18 May 2012]

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