CHAPTER 1 THEORY: NON-TOXIC MULTINODULAR GOITER INTRODUCTION Multinodular non-toxic goiter is the most prevalent thyroid pathology characterized

y unilateral or ilateral thyroid gro!th !ith morphologically and"or #unctionally trans#ormed een reported$ +eside morphologic varia ility& lac, o# #ollicles and euthyroidism$ %t thyroid sonography in unselected populations& '( to )( * incidence o# thyroid nodules has hyperstimulation in the ma-ority o# the multiplicated #ollicles is the hallmar, o# the disorder$ Most nodular goiters gro! slo!ly and undergo di##erent morphologic changes& encompassing di##use hyperplastic enlargement in the early phase& development o# large #ollicles loaded !ith a undant colloid and !ith increasing age& #ormation o# #unctionally autonomous tissue$ %nnual gro!th potential o# approximately '( * can e assumed$ The pathogenesis o# nodular goiter is multi#actorial and pro a ly di##ers #rom patient to patient$ In contrast to the endemic goiter& iodine de#iciency is not a primary causal #actor$ .nvironmental #actors such as natural goitrogens& iodine inta,e& malnutrition& drugs& stress& pollution or in#ections& constitutional #actors such as #emale gender and several genetic #actors& i$e$ circulating thyroid gro!th #actors contri ute to di##erent degree to the development o# nodular thyroid enlargement$ %lso controversially de ated& thyroid-stimulating hormone /T012 presuma ly has an important role in the maintenance o# thyroid gro!th and goitrogenesis$ The o servation that T01-suppressive treatment may cause a reduction o# goiter volume underlines the role o# T01 as goitrogen #actor$ 1.1. Anatomy

The thyroid gland is a utter#ly-shaped organ and is composed o# t!o cone-li,e lo es or !ings& lobus dexter /right lo e2 and lobus sinister /le#t lo e2& connected via the isthmus$ The organ is situated on the anterior side o# the nec,& lying against and around the larynx and trachea& reaching posteriorly the oesophagus and carotid sheath$ It starts cranially at the o li4ue line on the thyroid cartilage /-ust elo! the laryngeal prominence& or 5%dam5s %pple52& and extends in#eriorly to approximately the #i#th or sixth tracheal ring$ It is di##icult to demarcate the gland5s upper and lo!er order !ith verte ral levels ecause it moves position in relation to these during s!allo!ing$ The thyroid gland is covered y a #i rous sheath& the capsula glandulae thyroidea& composed o# an internal and external layer$ The external layer is anteriorly continuous !ith the lamina pretrachealis fasciae cervicalis and posteriorolaterally continuous !ith the carotid sheath$ The gland is covered anteriorly !ith in#rahyoid muscles and laterally !ith the sternocleidomastoid muscle also ,no!n as sternomastoid muscle$ On the posterior side& the gland is #ixed to the cricoid and tracheal cartilage and cricopharyngeus muscle y a thic,ening o# the #ascia to #orm the posterior suspensory ligament o# +erry$ The thyroid gland5s #irm attachment to the underlying trachea is the reason ehind its movement !ith s!allo!ing$ In varia le extent& 6alouette5s 7yramid& a pyramidal extension o# the thyroid lo e& is present at the most anterior side o# the lo e$ In this region& the recurrent laryngeal nerve and the in#erior thyroid artery pass next to or in the ligament and tu ercle$ +et!een the t!o layers o# the capsule and on the posterior side o# the lo es& there are on each side t!o parathyroid glands$ The thyroid isthmus is varia le in presence and size& can change shape and size& and can encompass a cranially extending pyramid lo e / lobus pyramidalis or processus pyramidalis2& remnant o# the thyroglossal duct$ The thyroid is one o# the larger endocrine glands& !eighing ') grams in neonates and 38-9( grams in adults& and is increased in pregnancy$ The thyroid is supplied !ith arterial lood #rom the superior thyroid artery& a ranch o# the external carotid artery& and the in#erior thyroid artery& a ranch o# the thyrocervical trun,& and sometimes y the thyroid ima artery& ranching directly #rom the rachiocephalic trun,$ The venous lood is drained via superior thyroid veins& draining in the internal -ugular vein& and via in#erior thyroid veins& draining via the plexus thyroideus impar in the le#t rachiocephalic vein$

'

6ymphatic drainage passes #re4uently the lateral deep cervical lymph nodes and the preand parathracheal lymph nodes$ The gland is supplied y parasympathetic nerve input #rom the superior laryngeal nerve and the recurrent laryngeal nerve$

1.2. Histo o!y %t the microscopic level& there are three primary #eatures o# the thyroid: "#at$%# D#s&%i'tion

The thyroid is composed o# spherical #ollicles that selectively a sor iodine /as iodide ions& I-2 #rom the lood #or production o# thyroid reast& hormones& ut also #or storage o# iodine in thyroglo ulin& in #act iodine is necessary #or other important iodine-concentrating organs as ;ollicles stomach& salivary glands& thymus etc$ /see iodine in iology2$ T!enty-#ive percent o# all the ody5s iodide ions are in the thyroid gland$ Inside the #ollicles& colloid serves as a reservoir o# materials #or thyroid hormone production and& to a lesser extent& acts as a reservoir #or the hormones themselves$ Colloid is rich in a protein calledthyroglo ulin$ The #ollicles are surrounded y a single layer o# thyroid epithelial cells& Thyroid epithelial cells !hich secrete T) andT=$ >hen the gland is not secreting T)"T= /inactive2& /or <#ollicular cells<2 the epithelial cells range #rom lo! columnar to cu oidal cells$ >hen active& the epithelial cells ecome tall columnar cells$ 7ara#ollicular /or <C cells<2 cells 0cattered among #ollicular cells and in spaces secrete calcitonin$ et!een the spherical #ollicles are another type o# thyroid cell& para#ollicular cells& !hich

1.(. D#)inition

?oitre is an enlargement o# the thyroid gland$ The gland can e generally enlarged or have multiple gro!ths /nodules2 leading to enlargement o# the !hole thyroid gland$ The latter is termed multinodular goitre (MNG). There are t!o #orms o# multinodular goitre: 32 nontoxic MNG and '2 toxic MNG. I# the goiter ma,es normal amounts o# thyroid hormone& it is ,no!n as a nontoxic MN?$ I# the goiter ma,es higher than normal amounts o# thyroid hormone leading to a suppressed T01& it is ,no!n as a toxic MN?$ The exact causes o# thyroid nodules or multinodular goitres are un,no!n$ In general& the development o# goitre is due to a complex mix o# genetic and environmental #actors$ Iodine de#iciency as a cause o# goitre is rare in North %merica and most o# .urope$ 1o!ever& even in areas o# iodine de#iciency most patients do not develop goitres$ 1.*. Etio o!y The #irst comprehensive theory a out the development o# multinodular goitre !as proposed y David Marine and studied #urther y 0el!yn Taylor& and can e considered one o# the classics in this #ield$ Nodular goitre may e the result o# any chronic lo!-grade& intermittent stimulus to thyroid hyperplasia$ In response to iodide de#iciency& the thyroid #irst goes through a period o# hyperplasia as a conse4uence o# the resulting T01 stimulation& ut eventually& possi ly ecause o# iodide repletion or a decreased re4uirement #or thyroid hormone& enters a resting phase characterized y colloid storage and the histologic picture o# a colloid goitre$ Repetition o# these t!o phases o# the cycle !ould eventually result in the #ormation o# nontoxic multinodular goitre$ 0tudies y Taylor o# thyroid glands removed at surgery led him to elieve that the initial lesion is di##use hyperplasia& ut that !ith time discrete nodules develop$ +y the time the goitre is !ell developed& serum T01 levels and T01 production rates are usually normal or even suppressed$ ;or example& Dige-7etersen and 1ummer evaluated asal and TR1-stimulated serum T01 levels in 3@ patients !ith di##use goitre and =A patients !ith nodular goitre$ They #ound impairment o# TR1-induced T01 release in 'A* o# the patients !ith nodular goitre& suggesting thyroid autonomy& ut in only 3 o# the 3@ !ith di##use goitre$ 0meulers et al & studied clinically euthyroid !omen !ith multinodular goitre and #ound that there !as an inverse relationship et!een the increment o# T01 a#ter administration o# TR1& and size o# the thyroid gland $ It !as also #ound that& !hile eing still !ithin the normal range& the mean serum T) concentration o# the group !ith impaired T01 secretion !as signi#icantly higher than

the normal mean& !hereas the mean value o# serum T= levels !as not elevated$ These and other results are consistent !ith the hypothesis that a di##use goitre may precede the development o# nodules$ They are also consistent !ith the clinical o servation that& !ith time& autonomy may occur& !ith suppression o# T01 release& even though such goitres !ere originally T01 dependent$ "a&to%s t+at may ,# in-o -#. in t+# #-o $tion o) m$ tino.$ a% !oit#%. PRIMARY "ACTOR/

;unctional heterogeneity o# normal #ollicular cells& most pro a ly due to genetic and ac4uisition o# ne! inherita le 4ualities y replicating epithelial cells$ ?ender /!omen2 is an important #actor$

0u se4uent #unctional and structural a normalities in gro!ing goiters$

/ECONDARY "ACTOR/

.levated T01 /induced y iodine de#iciency& natural goitrogens& in orn errors o# thyroid hormone synthesis2

0mo,ing& stress& certain drugs Other thyroid-stimulating #actors /I?;-3 and others2 .ndogenous #actor /gender2

1.0. Pat+o o!y %lthough it is rare to o tain pathological examination o# thyroid glands in the early phase o# development o# multinodular goitres& such glands should sho! areas o# hyperplasia !ith considera le variation in #ollicle size$ The more typical specimen coming to pathologists is the goitre that has developed a nodular consistency$ 0uch goitres characteristically present a variegated appearance& !ith the normal homogeneous parenchymal structure de#ormed y the presence o# nodules$ The nodules may vary considera ly in size /#rom a #e! millimeters to several centimeters2B in outline /#rom sharp encapsulation in adenomas to poorly de#ined margination #or ordinary nodules2B and in architecture /#rom the solid #ollicular adenomas to the gelatinous& colloid-rich nodules or degenerative cystic structures2$ The graphic term C7uddingstone goitreD has een applied$ ;re4uently the nodules have degenerated and a cyst has

#ormed& !ith evidence o# old or recent haemorrhage& and the cyst !all may have 0cattered

ecome

calci#ied$ O#ten there is extensive #i rosis& and calcium may also e deposited in these septae$ et!een the nodules are areas o# normal thyroid tissue& and o#ten-#ocal areas o# lymphocytic in#iltration$ Radioautography sho!s a variegated appearance& !ith R%I localized sometimes in the adenomas and sometimes in the paranodular tissue$ Occasionally& most o# the radioactivity is con#ined to a #e! nodules that seem to dominate the meta olic activity o# the gland$ I# care#ul sections are made o# numerous areas& =-3A* o# these glands removed at surgery !ill e #ound to har or microscopic papillary carcinoma$ The varia le incidence can most li,ely e attri uted to the di##erent criteria used y the pathologists and the asis o# selection o# the patients #or operation y their physicians$ 1.1. Nat$%a Histo%y o) t+# Dis#as# Multinodular goitre is pro a ly a li#elong condition that has its inception in adolescence or at pu erty$ Minimal di##use enlargement o# the thyroid gland is #ound in many teenage oys and girls& and is almost a physiologic response to the complex structural and hormonal changes occurring at this time$ It usually regresses& ut occasionally /much more commonly in girls2 it persists and undergoes #urther gro!th during pregnancy$ This course o# events has not een documented as !ell as might e desired in sporadic nodular goitre& ut it is the usual evolution in areas !here mild endemic goitre is #ound$ 7atients !ith multinodular goitre see, medical attention #or many reasons$ 7erhaps most commonly they consult a physician ecause a lump has een discovered in the nec,& or ecause a gro!th spurt has een o served in a goiter ,no!n to e present #or a long time$ 0ometimes the increase in the size o# the goitre !ill cause pressure symptoms& such as di##iculty in s!allo!ing& cough& respiratory distress& or the #eeling o# a lump in the throat$ Rarely& an area o# particularly asymmetrical enlargement may impinge upon or stretch the recurrent laryngeal nerve$ Commonly the goitre is discovered y a physician in the course o# an examination #or some other condition$ %n important scenario is #or the patient to see, medical attention ecause o# cardiac irregularities or congestive heart #ailure& !hich proves to e the result o# slo!ly developing thyrotoxicosis$ Many times the goitre gro!s gradually #or a period o# a #e! too many years& and then ecomes sta le !ith little tendency #or #urther gro!th$ It is rare #or any note!orthy spontaneous reduction in the size o# the thyroid gland to occur& ut patients o#ten descri e

#luctuation in the size o# the goitres and the symptoms they give$ These are usually su -ective occurrences& and more o#ten than not the physician is una le to corro orate the changes that the patient descri es$ On the other hand& it could e that changes in lood #lo! through the enlarged gland account #or the symptoms$ Occasionally& a sudden increase in the size o# the gland is associated !ith sharp pain and tenderness in one area$ This event suggests haemorrhage into a nodular cyst o# the goiter& !hich can e con#irmed y ultrasound$ >ithin )-= days the symptoms su side& and !ithin '-) !ee,s the gland may revert to its previous dimensions$ In such a situation& acute thyrotoxicosis may develop and su side spontaneously$ Rarely& i# ever& do the patients ecome hypothyroid and i# they do& the diagnosis is more pro a ly 1ashimotoEs thyroiditis than nodular goitre$ I# the goitre is present #or long time& thyrotoxicosis develops in a large num er o# patients$ In a series collected many years ago at the Mayo Clinic& 9(* o# patients !ith MN? over 9( !ere thyrotoxic$ The average duration o# the goitre e#ore the onset o# thyrotoxicosis !as 3A yearsB the longer the goitre had een present the greater !as the tendency #or thyrotoxicosis to develop$ This condition appears to occur ecause !ith the passage o# time& autonomous #unction o# the nodules develops$ In a study o# patients !ith euthyroid multinodular goitre& thyroid #unction !as autonomous in 9= and normal in '9$ %#ter a mean #ollo!-up o# @$( years /maximum 3' years2 38 patients !ith autonomous thyroid #unction ecame overtly hyperthyroid and in 9 patients !ith primarily normal thyroid #unction autonomy develope$ Thyroid #unction tests is illustrated in a patient !ith multinodular goitre starting #rom complete euthyroidism on to overt thyrotoxicosis$ Occasionally a single discrete nodule in the thyroid gland ecomes su##iciently active to cause thyrotoxicosis and to suppress the activity o# the rest o# the gland$ I# these patients are given thyroid hormone& continued #unction o# nodules can e demonstrated y radioiodine scanning techni4ues$ Thus& these nodules have ecome independent o# pituitary control$ >hen patients !ith euthyroid multinodular goiter are #re4uently tested& it appears that in some o# them occasional transient increases o# serum T) and " or T= are seen$ In several areas o# the !orld previously iodine de#iciency the introduction o# iodine supplementation lead to an increase o# hyperthyroidism /non-autoimmune2 possi ly y excessive thyroid hormone production y ChotD thyroid nodules$ 1.2. Dia!nosis

3$A$3$ 0igns and 0ymptoms Many o# the symptoms o# multinodular goitre have already een descri ed$ They are chie#ly due to the presence or an enlarging mass in the nec, and its impingement upon the ad-acent structures$ There may e dysphagia& cough& and hoarseness$ 7aralysis o# recurrent laryngeal nerve may occur !hen the nerve is stretched taut across the sur#ace o# an expanding goiter& ut this event is very unusual$ >hen unilateral vocal cord paralysis is demonstrated& the presumptive diagnosis is cancer$ 7ressure on the superior sympathetic ganglions and nerves may produce a 1ornerEs syndrome$ %s the gland gro!s it characteristically enlarges the nec,& ut #re4uently the gro!th occurs in a do!n!ard direction& producing a su sternal goitre$ % history sometimes given y an older patient !here a goitre once present in the nec, has disappeared may mean that it has #allen do!n into the upper mediastinum& !here its upper limits can e #elt y care#ul deep palpation$ 1emorrhage into this goitre can produce acute tracheal o struction$ 0ometime su sternal goitres are attached only y a #i rous and to the goitre in the nec, and extend do!n!ard to the arch o# the aorta$ They have even een o served as deep in the mediastinum as the diaphragm$ Occasionally the s,illed physician can detect a su sternal goiter y percussion& particularly i# there is a hint #rom tracheal deviation& or the presence o# a nodular mass in the nec, a ove the manu rial notch$ 0ymptoms suggesting constriction o# the trachea are #re4uent& and displacement o# the trachea is commonly #ound on physical examination$ Computer Tomography examination is use#ul in de#ining the extent o# tracheal deviation and compression$ Compression is #re4uently seen ut rarely is #unctionally signi#icant have expected to #ind so#tened tracheal cartilage a#ter the removal o# some large goiters& ut tracheomalacia has een o served only on the rarest occasion$ 7atients may endemic goiter areas o# the !orld$ It is generally agreed that& thyroid isotope or ultrasound scanning are o# little or no use in the diagnosis o# carcinoma in a multinodular goiter$ T!o aspects are important in the di##erentiation #rom malignancy$ ;irst& the clinical presentation& i# the goiter is o# longstanding& sho!ing little or no gro!th& a sence o# a dominant node& #amilial& !hile e remar,a ly tolerant o# nodular goiter even !hen the enlargement is stri,ing$ This #inding is especially true in the

there is no nec, irradiation in the past& especially in childhood& no hoarse voice& and no suspicious lymphnodes in the nec,& there is little #ear #or carcinoma$ 3$A$'$ 6a oratory investigation The choice o# tests to investigate the #unctional status o# a patient !ith a simple di##use goitre or multinodular goitre may di##er depending on the geographic areas o# the !orld$ Recent surveys conducted in the %merican& .uropean and 6atin %merican Thyroid %ssociations have indicated that the North %merican thyroidologists are 4uite restrictive in the choice o# la oratory tests$ Most o# the experts& ho!ever& !ould per#orm a serum T01 and serum ;ree T= test$ In other settings Total T= and Total T) are also included ecause o# the pre#erential secretion o# T) over T= in mild iodine de#iciency$ %nti odies against thyro-peroxidase /anti-T7O2 and thyroglo ulin /anti-T?2 are measured& routinely& y most .uropeans and 6atin %mericans thyroidologists$ This seems to e relevant ecause thyroid auto anti odies are #ound approximately in 3(* o# the population and& conse4uently& autoimmunity may coexist !ith a goiter$ %lso di##use or #ocal lymphocytic in#iltration in an enlarged gland may represent chronic autoimmune thyroiditis$ %lthough serum T? correlates !ith the iodine status and the size o# the enlarged thyroid gland it has little or no value in the diagnosis o# goiter$ 3$A$)$ Diagnostic imaging Nec, palpation is notoriously imprecise !ith regard to thyroid morphology and size estimation$ 0everal imaging methods are availa le in most settings: scintilography /!ith radioiodine& technetium2& ultrasonography& computed tomography scans& magnetic resonance imaging and& less #re4uently used& positron emission tomography /7.T2$ 3$A$)$3$ Ultrasonography o# the thyroid The main reasons #or the !idespread use o# thyroid sonography are availa ility /several porta le models are !idely availa le at a relatively a##orda le price2& the lo! cost o# the procedure /i# per#ormed in the o##ice or in the thyroid clinic2& limited discom#ort #or the patient& and the non ionizing nature o# the method$ Ultrasonography may detect non palpa le nodules cysts& !ill estimate

nodule and goiter size /volume2& !ill monitor the changes #ollo!ing therapy and !ill guide the ;ine Needle %spiration +iopsy /;N%+2$ %#ter the introduction o# ultrasonography it has ecome clear that nodules in the thyroid gland are very prevalent& ranging #rom 3A* to 9(* i# older people are included in the study$ 1ypoechogenicity& micro-calci#ications& indistinct nodular #lo! /visualized orders increased y DO776.R2 may have predictive value in

distinguishing malignant #rom enign nodules /even in Multinodular ?oiters2$ The possi ility o# measuring thyroid volume is another highly use#ul #eature o# ultrasonographic studies particularly a#ter therapy !ith 6-T= or radioiodine a lation$ The volume o# the goiter is usually ased on the ellipsoid method /length& !idth depth G pi"92$ This has an o server coe##icient o# variation o# more than 3(*$>hen compared to CT planimetry the ellipsoid method underestimate the goiter volume y '(*$ Ultrasonography can not evaluate a multinodular goiter that has partially migrated to the upper mediastinum$ 3$A$=$ 0cintigraphy /isotope imaging2 It !as used routinely in the past ut at present has little place in the evaluation o# a multinodular goiter /3(3-3(@2$ It is help#ul in the determination o# the #unctionality o# the various nodules o# a MN?$ Thyroid scintigrams have een used through many years #or measurement o# the thyroid volume ut compared to other methods is very inaccurate$ 3$A$@$ Computed tomography /CT2 and Magnetic resonance /MR2 CT and MR provide high-resolution visualization o# the goiter /0imple di##use& multinodular2$ The ma-or strength o# CT and MR is their a ility to diagnose and assess the extent o# su sternal goiters$ %nother advantage o# the CT is the possi ility #or planimetric volume estimations& 4uite use#ul in irregularly enlarged multinodular goiter$ Recently the ionizing radiation delivered y a CT procedure has een source o# concern #or oth clinicians and radiologists$ There#ore the use o# CT as an imaging method should compression$ e reserved #or intra thoracic multinodular goiters& !ith tracheal

3(

1.3. Di))#%#ntia Dia!nosis

o o o o o

%denoma Cyst Carcinoma Multinodular goitre 1ashimotoEs thyroiditis 0u acute thyroiditis .##ect o# prior operation or 3)3I therapy Thyroid hemiagenesis Metastasis 7arathyroid cyst or adenoma Thyroglossal cyst Nonthyroidal lesions In#lammatory or neoplastic nodes Cystic hygroma %neurysm +ronchocele 6aryngocele

1.4. T%#atm#nt Unli,e ?raves disease& Multinodular goitre /MN?2 is not an autoimmune disease and rarely& i# ever& remits$ There#ore& patients !ho have autonomously #unctioning nodules should e treated de#initely !ith radioactive iodine or surgery$ The %merican Thyroid %ssociation and %merican %ssociation o# Clinical .ndocrinologists have released guidelines #or the management o# hyperthyroid and other causes o# thyrotoxicosis& including the use o# radioactive iodine or surgery to treat toxic multinodular goitre$ 7atients !ith su clinical hyperthyroidism should e monitored closely #or overt disease$ 0ome suggest that elderly patients& !omen !ith osteopenia& and patients !ith ris, #actors #or atrial #i rillation should e treated& even those !ho have su clinical disease$ 3$F$3$ Na3)3 I treatment 33

Radioactive iodine is considered the treatment o# choice #or Toxic MN?$ .xcept #or pregnancy& there are no a solute contraindications to radioiodine therapy$
o

% single dose o# radioiodine therapy has a success rate o# 8@-3((* in patients !ith TN?$ Radioiodine therapy may reduce the size o# the goiter y up to =(*$ ;ailure o# initial treatment !ith radioactive iodine has #actors may present a need #or higher doses o# Na3)3 I$ een associated !ith

increased goiter size and higher T) and #ree T= levels& !hich suggests that these % positive correlation exists et!een radiation dose to the thyroid and decrease in thyroid volume$ In patients !ith upta,e o# less than '(*& pretreatment !ith lithium& 7TU& or recom inant T01 can increase the e##ectiveness o# iodine upta,e and treatment$ This treatment may surgery is considered high ris,$
o

e valua le in elderly patients in !hom

Complications

1ypothyroidism occurs in 3(-'(* o# patientsB this is similar to the incidence rate a#ter surgery and is su stantially less than in the treatment o# ?raves disease$ Tracheal compression due to thyroid s!elling a#ter radiation therapy is no longer thought to e a ris,$ Mild thyrotoxic symptoms a#ter radioiodine occur in a out one-third o# patients& and a out =* o# patients develop a clinically signi#icant radiation-induced thyroiditis$ These patients should e treated symptomatically !ith eta loc,ers$

.lderly patients may have exacer ation o# congestive heart #ailure and atrial #i rillation$ 7retreat elderly patients !ith antithyroid drugs$ Thyroid storm is a rare complication& particularly in patients !ith rapidly enlarging goiters or high total T) levels$ 7atients !ith these conditions should receive pretreatment !ith antithyroid drugs$

3$F$'$ 7harmacotherapy

3'

%ntithyroid drugs and eta loc,ers are used #or short courses in the treatment o# MN?B they are important in rendering patients euthyroid in preparation #or radioiodine or surgery and in treating hyperthyroidism !hile a!aiting #ull clinical response to radioiodine$ 7atients !ith su clinical disease at high ris, o# complications /eg& atrial #i rillation& osteopenia2 may e given a trial o# lo! dose methimazole /@-3@ mg"d2 or eta loc,ers and should e monitored #or a change in symptoms or #or disease progression that re4uires de#initive treatment$
o

Thioamides - The role o# therapy !ith thioamides /eg& 7TU& methimazole2 is to achieve euthyroidism prior to de#initive treatment !ith 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 = days prior to radioiodine therapy in order to maximize the radioiodine e##ect$

%ntithyroid drugs and eta loc,ers have side e##ects& the most common eing pruritic rash& #ever& gastrointestinal upset& and arthralgias$ More serious potential side e##ects include agranulocytosis& drug-induced lupus and other #orms o# vasculitis& and liver damage$ 7TU is considered to e a second-line drug therapy& except in patients !ho are allergic to or intolerant o# methimazole& or in !omen !ho are in the #irst trimester o# pregnancy$ Rare cases o# em ryopathy& including aplasia cutis& have een reported !ith methimazole during pregnancy$ The ;D% recommends the #ollo!ing criteria e considered #or prescri ing 7TU:

Reserve 7TU use during #irst trimester o# pregnancy& or in patients !ho are allergic to or intolerant o# methimazole$ Closely monitor 7TU therapy #or signs and symptoms o# liver in-ury& especially during the #irst 9 months a#ter initiation o# therapy$ ;or suspected liver in-ury& promptly discontinue 7TU therapy& evaluate the patient #or evidence o# liver in-ury& and provide supportive care$ 7TU should not e used in pediatric patients unless the patient is allergic to or intolerant o# methimazole and no other treatment options are availa le$

3)

Counsel patients to promptly contact their health care provider #or the #ollo!ing signs or symptoms: #atigue& !ea,ness& vague a dominal pain& loss o# appetite& itching& easy yello!ing o# the eyes or s,in$ ruising& or

+eta-adrenergic receptor antagonists - These drugs remain use#ul in the treatment o# symptoms o# thyrotoxicosisB they may e used alone in patients !ith mild thyrotoxicosis or in con-unction !ith thioamides #or treatment o# more severe disease$

7ropranolol& a nonselective eta loc,er& may help to lo!er the heart rate& control tremor& reduce excessive s!eating& and alleviate anxiety$ 7ropranolol is also ,no!n to reduce the conversion o# T= to T)$ In patients !ith underlying asthma& eta-3 selective antagonists& such as atenolol or metoprolol& !ould e sa#er options$ In patients !ith contraindications to eta loc,ers /eg& moderate to severe asthma2& calcium channel antagonists /eg& diltiazem2 may e used to help control the heart rate$

0urgical therapy is usually reserved #or young individuals& patients !ith 3 or more large nodules or !ith o structive symptoms& patients !ith dominant non#unctioning or suspicious nodules& patients !ho are pregnant& patients in !hom radioiodine therapy has #ailed& or patients !ho re4uire a rapid resolution o# the thyrotoxic state$

0u total thyroidectomy results in rapid cure o# hyperthyroidism in F(* o# patients and allo!s #or rapid relie# o# compressive symptoms$ Restoring euthyroidism prior to surgery is pre#era le$ Complications o# surgery include the #ollo!ing:
o

In patients !ho are treated surgically& the #re4uency o# hypothyroidism is similar to that #ound in patients treated !ith radioiodine /3@-'@*2$ Complications include permanent vocal cord paralysis /'$)*2& permanent hypoparathyroidism /($@*2& temporary hypoparathyroidism /'$@*2& and signi#icant postoperative leeding /3$=*2$

Other postoperative complications include tracheostomy& !ound in#ection& !ound hematoma& myocardial in#arction& atrial #i rillation& and stro,e$

3=

The mortality rate is almost zero$

1.15. Com' i&ations

1yperthyroid complications
o o

The most important complications are related to the heart$ Cardiomyopathy resulting in severely depressed #unction may e o served !ith hyperthyroidism& possi ly in relation to persistent tachycardia$ ;ortunately& cardiomyopathy resolves remar,a ly !ith resolution o# the hyperthyroid state$ Using anticoagulants to treat patients exhi iting atrial #i rillation remains controversial& although it is recommended y many authorities$ %trial #i rillation o# long duration that is associated !ith other anatomical de#ects o# the heart should e treated !ith !ar#arin or another suita le anticoagulant$

1.11. P%o!nosis Most treated patients have a good prognosis$ % !orse prognosis is related to untreated hyperthyroidism$ I# le#t untreated& hyperthyroidism may lead to osteoporosis& arrhythmia& heart #ailure& coma& and death$ Regular assessment o# thyroid #unction is important in monitoring disease$ Na3)3 I a lation may result in continued hyperthyroidism& !ith some patients /up to A)* in some studies& depending on the size o# the goiter and the dosing o# radioiodine2 re4uiring repeated treatment or surgical removal o# the gland$ 1ypothyroidism a#ter radioiodine a lation has een reported in (-)@* o# individuals$ $ 0urgical treatment usually consists o# a lo ectomy o# the hyper#unctioning nodule$ The rate o# hypothyroidism associated !ith this procedure is very lo!$ Rates o# hyperthyroidism recurrence !ith surgery have een reported to e as lo! as (-F*$ 6arger& multinodular goiters may re4uire total thyroidectomy$ CHAPTER 2 THEORY: GENERAL ANE/THE/IA INTRODUCTION

3@

%nesthesia is an important #ield o# medicine that has made complicated surgeries possi le$ It involves the administration o# su stances or drugs to patients !hich causes loss o# consciousness& loss o# ver al a ility& a sence o# recall and loss o# protective re#lexes e$g$ cough& gag and !ithdra!al #rom pain$ %nesthesia means C!ithout #eelingD /no sensation2& !hereas analgesia means C!ithout painD$ %lthough a patient is anesthetized ut !ithout proper analgesia& there !ill e evidence o# pain such as tachycardia and hypertension$ Thus& one must not thin, that a person !ill not #eel pain !hen he is anesthetized$ ?eneral anesthesia /?%2 is the state produced !hen a patient receives medications #or amnesia& analgesia& muscle paralysis& and sedation$ %n anesthetized patient can e thought o# as eing in a controlled& reversi le state o# unconsciousness$ %nesthesia ena les a patient to tolerate surgical procedures that !ould other!ise in#lict un eara le pain& potentiate extreme physiologic exacer ations& and result in unpleasant memories$ The com ination o# anesthetic agents used #or general anesthesia o#ten leaves a patient !ith the #ollo!ing clinical constellation: 3$ Unarousa le even secondary to pain#ul stimuli '$ Una le to remem er !hat happened /amnesia2 )$ Una le to maintain ade4uate air!ay protection and"or spontaneous ventilation as a result o# muscle paralysis =$ Cardiovascular changes secondary to stimulant"depressant e##ects o# anesthetic agents$ 2.1. G#n#%a An#st+#sia ?eneral anesthesia uses intravenous and inhaled agents to allo! ade4uate surgical access to the operative site$ % point !orth noting is that general anesthesia may not al!ays e the est choiceB depending on a patientEs clinical presentation& local or regional anesthesia may e more appropriate$ %nesthesia providers are responsi le #or assessing all #actors that in#luence a patient5s medical condition and selecting the optimal anesthetic techni4ue accordingly$ %ttri utes o# general anesthesia include the #ollo!ing: %dvantages
o

Reduces intraoperative patient a!areness and recall

39

o o o o o o

%llo!s proper muscle relaxation #or prolonged periods o# time ;acilitates complete control o# the air!ay& reathing& and circulation Can e used in cases o# sensitivity to local anesthetic agent Can e administered !ithout moving the patient #rom the supine position Can e adapted easily to procedures o# unpredicta le duration or extent Can e administered rapidly and is reversi le Re4uires increased complexity o# care and associated costs Re4uires some degree o# preoperative patient preparation Can induce physiologic #luctuations that re4uire active intervention %ssociated !ith less serious complications such as nausea or vomiting& sore throat& headache& shivering& and delayed return to normal mental #unctioning %ssociated !ith malignant hyperthermia& a rare& inherited muscular condition in !hich exposure to some / ut not all2 general anesthetic agents results in acute and potentially lethal temperature rise& hypercar ia& meta olic acidosis& and hyper,alemia

Disadvantages
o o o o

>ith modern advances in medications& monitoring technology& and sa#ety systems& as !ell as highly educated anesthesia providers& the ris, caused y anesthesia to a patient undergoing routine surgery is very small$ Mortality attri uta le to general anesthesia is said to occur at rates o# less than 3:3((&((($ Minor complications occur at predica le rates& even in previously healthy patients$ The #re4uency o# anesthesia-related symptoms during the #irst '= hours #ollo!ing am ulatory surgery is as #ollo!s:

Homiting - 3(-'(* Nausea - 3(-=(* 0ore throat - '@* Incisional pain - )(*

2.2. P%#'a%ation )o% G#n#%a An#st+#sia 0a#e and e##icient anesthetic practices re4uire certi#ied personnel& appropriate medications and e4uipment& and an optimized patient$

3A

Minimum in#rastructure re4uirements #or general anesthesia include a !ell-lit space o# ade4uate sizeB a source o# pressurized oxygen /most commonly piped in2B an e##ective suction deviceB standard %0% /%merican 0ociety o# %nesthesiologists2 monitors& including heart rate& lood pressure& .C?& pulse oximetry& capnography& temperatureB and inspired and exhaled concentrations o# oxygen and applica le anesthetic agents$ +eyond this& some e4uipment is needed to deliver the anesthetic agent$ This may e as simple as needles and syringes& i# the drugs are to e administered entirely intravenously$ In most circumstances& this means the availa ility o# a properly serviced and maintained anesthetic gas delivery machine$ %n array o# routine and emergency drugs& including Dantrolene sodium /the speci#ic treatment #or malignant hyperthermia2& air!ay management e4uipment& a cardiac de#i rillator& and a recovery room sta##ed y properly trained individuals completes the picture$ 2.(. P%#'a%in! t+# 'ati#nt 7reoperative evaluation allo!s #or proper la oratory monitoring& attention to any ne! or ongoing medical conditions& discussion o# any previous personal or #amilial adverse reactions to general anesthetics& assessment o# #unctional cardiac and pulmonary states& and development o# an e##ective and sa#e anesthetic plan$ It also serves to relieve anxiety o# the un,no!n surgical environment #or patients and their #amilies$ Overall& this process allo!s #or optimization o# the patient in the perioperative setting$ 7hysical examination associated !ith preoperative evaluations allo! anesthesia providers to #ocus speci#ically on expected air!ay conditions& including mouth opening& loose or pro lematic dentition& limitations in nec, range o# motion& nec, anatomy& and Mallampati presentations$ +y com ining all #actors& an appropriate plan #or intu ation can e outlined and extra steps& i# necessary& can e ta,en to prepare #or #i eroptic ronchoscopy& video laryngoscopy& or various other di##icult air!ay interventions$ %ir!ay management

7ossi le or de#inite di##iculties !ith air!ay management include the #ollo!ing: 0mall or receding -a! 7rominent maxillary teeth

38

0hort nec, 6imited nec, extension 7oor dentition Tumors o# the #ace& mouth& nec,& or throat ;acial trauma Interdental #ixation 1ard cervical collar 1alo traction Harious scoring systems have een created using oro#acial measurements to predict

di##icult intu ation$ The most !idely used is the Mallampati score& !hich identi#ies patients in !hom the pharynx is not !ell visualized through the open mouth$ The Mallampati assessment is ideally per#ormed !hen the patient is seated !ith the mouth open and the tongue protruding !ithout phonating$ In many patients intu ated #or emergent indications& this type o# assessment is not possi le$ % crude assessment can opening and the li,elihood that the tongue and oropharynx may intu ation$ e per#ormed !ith the patient in the supine position to gain an appreciation o# the size o# the mouth e #actors in success#ul

Mallampati classi#ication$ 1igh Mallampati scores have een sho!n to e predictive o# di##icult intu ations$

1o!ever& no one scoring system is near 3((* sensitive or 3((* speci#ic$ %s a result& practitioners rely on several criteria and their experience to assess the air!ay$

3F

>hen suspicion o# an adverse event is high ut a similar anesthetic techni4ue must e used again& o taining records and previous anesthetic records #rom previous operations or #rom other institutions may e necessary$ Other re4uirements The need #or coming to the operating room !ith an empty stomach is to reduce the ris, o# pulmonary aspiration during general anesthesia !hen a patient loses his or her a ility to voluntarily protect the air!ay$ 7atients should continue to ta,e regularly scheduled medications up to and including the morning o# surgery$ .xceptions may include the #ollo!ing:

%nticoagulants to avoid increased surgical leeding Oral hypoglycemics /;or example& met#ormin is an oral hypoglycemic agent that is associated !ith the development o# meta olic acidosis under general anesthesia$2 Monoamine oxidase inhi itors +eta loc,er therapy /1o!ever& eta loc,er therapy should e continued perioperatively #or high-ris, patients undergoing ma-or noncardiac surgery2

2.*. T+# '%o&#ss o) an#st+#sia '$=$3$ 7remedication This is the #irst stage o# a general anesthetic and usually conducted in the surgical !ard or in a preoperative holding area$ The goal o# premedication is to have the patient arrive in the operating room in a calm& relaxed #rame o# mind$ Most patients do not !ant to have any recollection o# entering the operating room$ The most commonly used premedication is midazolam& a short-acting enzodiazepine$ ;or example& midazolam syrup is o#ten given to children to #acilitate calm separation #rom their parents prior to anesthesia$ In anticipation o# surgical pain& nonsteroidal anti-in#lammatory drugs or acetaminophen can e administered preemptively$ >hen a history o# gastroesophageal re#lux exists& 1' loc,ers and antacids may e administered$ Drying agents /eg& atropine& scopolamine2 are no! only administered routinely in anticipation o# a #i eroptic endotracheal intu ation$

'(

'$=$'$ Induction This is the critical part o# the anesthesia process$ Usually& the mnemonic D%MMI0 can e used to remem er !hat to chec, / D rugs& A ir!ay e4uipment& M achine& M onitors& I H& / uction2$ This stage can e achieved y intravenous in-ection o# induction agents /drugs that !or, rapidly& such as propo#ol2& y the slo!er inhalation o# anesthetic vapors delivered into a #ace mas,& or y a com ination o# oth$ ;or the most part& contemporary practice dictates that adult patients and most children aged at least 3( years e induced !ith intravenous drugs& this eing a rapid and minimally unpleasant experience #or the patient$ 1o!ever& sevo#lurane& a !ell-tolerated anesthetic vapor& allo!s #or elective inhalation induction o# anesthesia in adults$ In addition to the induction drug& most patients receive an in-ection o# an opioid analgesic& such as #entanyl /a synthetic opioid many times more potent than morphine2$ Many synthetic and naturally occurring opioids !ith di##erent properties are availa le$ Induction agents and opioids !or, synergistically to induce anesthesia$ In addition& anticipation o# events that are a out to occur& such as endotracheal intu ation and incision o# the s,in& generally raises the lood pressure and heart rate o# the patient$ Opioid analgesia helps control this undesira le response$ The next step o# the induction process is securing the air!ay$ This may e a simple matter o# manually holding the patient5s -a! such that his or her natural reathing is unimpeded y the tongue& or it may demand the insertion o# a prosthetic air!ay device such as a laryngeal mas, air!ay or endotracheal tu e$ Harious #actors are considered !hen ma,ing this decision$ The ma-or decision is !hether the patient re4uires placement o# an endotracheal tu e$ 7otential indications #or endotracheal intu ation under general anesthesia may include the #ollo!ing:
o

7otential #or air!ay contamination /#ull stomach& gastroesophageal I?.J re#lux& gastrointestinal I?IJ or pharyngeal leeding2 0urgical need #or muscle relaxation 7redicta le di##iculty !ith endotracheal intu ation or air!ay access /eg& lateral or prone patient position2 0urgery o# the mouth or #ace

o o

'3

7rolonged surgical procedure

Not all surgery re4uires muscle relaxation$ I# surgery is ta,ing place in the a domen 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 o# reathing$ There#ore& the patient5s lungs must e ventilated under pressure& necessitating an endotracheal tu e$ 7ersons !ho& #or anatomic reasons& are li,ely to e di##icult to intu ate are usually intu ated electively at the eginning o# the procedure& using a #i eroptic ronchoscope or other advanced air!ay tool$ This prevents a situation in !hich attempts are made to manage the air!ay !ith a lesser device& only #or the anesthesia provider to discover that oxygenation and ventilation are inade4uate$ %t that point during a surgical procedure& s!i#t intu ation o# the patient can e very di##icult& i# not impossi le$ '$=$)$ Maintenance phase %t this point& the drugs used to initiate the anesthetic are eginning to !ear o##& and the patient must e ,ept anesthetized !ith a maintenance agent$ ;or the most part& this re#ers to the delivery o# anesthetic gases /more properly termed vapors2 into the patient5s lungs$ These may e inhaled as the patient reathes spontaneously or delivered under pressure y each mechanical reath o# a ventilator$ The maintenance phase is usually the most sta le part o# the anesthesia$ 1o!ever& understanding that anesthesia is a continuum o# di##erent depths is important$ % level o# anesthesia that is satis#actory #or surgery to the s,in o# an extremity& #or example& !ould e inade4uate #or manipulation o# the o!el$ %s the procedure progresses& the level o# anesthesia is altered to provide the minimum amount o# anesthesia that is necessary to ensure ade4uate anesthetic depth$ Traditionally& this has een a matter o# clinical -udgment& ut ne! processed ..? machines give the anesthesia provider a simpli#ied output in real time& corresponding to anesthetic depth$ These devices have yet to ecome universally accepted as vital e4uipment$ I# muscle relaxants have not een used& inade4uate anesthesia is easy to spot$ The patient moves& coughs& or o structs his air!ay i# the anesthetic is too light #or the stimulus eing given$ I# muscle relaxants have een used& then clearly the patient is una le to

''

demonstrate any o# these phenomena$ In these patients& the anesthesia provider must rely on care#ul o servation o# autonomic phenomena such as hypertension& tachycardia& s!eating& and capillary dilation to decide !hether the patient re4uires a deeper anesthetic$ This re4uires experience and -udgment$ The specialty o# anesthesiology is !or,ing to develop relia le methods to avoid cases o# a!areness under anesthesia$ .xcessive anesthetic depth& on the other hand& is associated !ith decreased heart rate and lood pressure& and& i# carried to extremes& can -eopardize per#usion o# vital organs or e #atal$ 0hort o# these serious misadventures& excessive depth results in slo!er a!a,ening and more adverse e##ects$ %s the surgical procedure dra!s to a close& the patient5s emergence #rom anesthesia is planned$ .xperience and close communication !ith the surgeon ena le the anesthesia provider to predict the time at !hich the application o# dressings and casts !ill e complete$ In advance o# that time& anesthetic vapors have een decreased or even s!itched o## entirely to allo! time #or them to e excreted y the lungs$ .xcess muscle relaxation is reversed using speci#ic drugs and an ade4uate long-acting opioid analgesic to ,eep the patient com#orta le in the recovery room$ I# a ventilator has een used& the patient is restored to reathing y himsel#& and& as anesthetic drugs dissipate& the patient emerges to consciousness$ Removal o# the endotracheal tu e or other arti#icial air!ay device is only per#ormed !hen the patient has regained su##icient control o# his or her air!ay re#lexes$ '$=$=$ Reversal It is a process o# discontinuation o# anesthetic agents at the end o# surgery to allo! return o# consciousness and recovery #rom muscle paralysis !hile maintaining analgesia$ Holatile agents are discontinued #irst and later the nitrous oxide$ 7atient is given 3((* oxygen$ >ait #or return o# spontaneous reathingB this can e o served on capnography and can also e #elt !ith reservoir ag i# patient is manually ventilated$ %dminister reversal agent such as neostigmine /anticholinesterase2 or glycopyrrolate to counteract non-depolarizing muscle relaxantB atropine is usually given to counteract the parasympathetic e##ects o# anticholinesterase$

')

Reversal agent is given !hen there is evidence o# spontaneous e#ore attempting extu ation$ 2.0. Posto'#%ati-# Ca%#

reathing e##ort$

7atientEs tidal volume has to e ensured that it is ade4uate and a le to control o!n air!ay

The anesthesia should conclude !ith a pain-#ree a!a,ening and a management plan #or postoperative pain relie#$ This may e in the #orm o# regional analgesia& oral& transdermal or parenteral medication$ Minor surgical procedures are amena le to oral pain relie# medication such as paracetamol and N0%IDs such as i upro#en$ Moderate levels o# pain re4uire the addition o# mild opiates such as tramadol$ Ma-or surgical procedures may re4uire a com ination o# modalities to con#er ade4uate pain relie#$ 7arenteral methods include patient-controlled analgesia /7C%2 involving a strong opiate such as morphine& #entanyl or oxycodone$ To activate a syringe device& patient !ill press a utton and receive a preset dose or olus o# the drug /eg: 3mg o# morphine2$ The 7C% device then loc,s out #or a preset period to allo! drug to ta,e e##ect$ I# the patient ecomes too sleepy or sedated& they ma,e no more morphine re4uests$ This con#ers a #ail sa#e aspect !hich is lac,ing in continuous opiate in#usion techni4ues$ 0hivering is a #re4uent occurs in the post operative period$ %part #rom causing discom#ort and exacer ating post operative pain& shivering has een sho!n to increase oxygen consumption& cathecolamine release& cardiac output& heart rate& lood pressure and intra ocular pressure$ There are num er o# techni4ues used to reduce this occurrence& such as increasing the am ient temperature in theatre& using conventional or #orced !arm air intravenous #luids$ 2.1. Common An#st+#ti& D%$!s The main group o# drugs commonly used in general anesthesia are roadly classi#ied into induction agents& muscle relaxants& analgesics and reversal agents$ Induction agents then are #urther classi#ied into inhalational and parenteral !hile the muscle relaxants can e divided into depolarizers and non depolarizers$ '$9$3$ Inhalational %naesthetic %gents lan,ets and using !armed

'=

It exists as gaseous #orm /nitrous oxide2 or volatile li4uids /iso#lurane2$ 1alothane is a halogenated al,ane derivative$ Other modern volatile agents are halogenated methyl ether derivatives /en#lurane& iso#lurane2$ Controlla ility is y pulmonary administration and is delivered via vaporizers$ The commonly used inhalational agents are li4uids at room temperature and there#ore they need to e converted to the gaseous state #or administration to patients$ Haporizers is a device #or producing a clinically use#ul and sta le concentration o# an anesthetic vapour in a carrier gas / oxygen and nitrous oxide2$ The aim o# inhalational anaesthesia is the development o# an appropriate tension or partial pressure o# anesthetic agent !ithin the rain$ - ?aseous anaesthetic agents Nitrous oxide o It is stored in steel cylinders as a li4uid under pressure in e4uili rium !ith the gas phase at normal room temperature$ o N'O is a colorless gas !ithout apprecia le odour or taste and non explosive$ o It is a potent analgesic ut a !ea, anaesthetic agents o It cause depress hematopoietic #unction / megalo lastic anemia& throm ocytopenia and leucopenia2& thus not advisa le #or administration o# more than '= hours$ o It is !idely used as an ad-uvant to lo!er the M%C o# volatile anesthetics$ >ith inhalation o# A(* N'O " )(* O' M%C value are reduced /K)@*- =@*2 - Holatile %nesthetic agents 1alothane 1alothane is a haloal,ane and has a M%C value o# A(*$ It can e used #or induction o# anesthesia in children$ 1alothane is a non speci#ic Ca 'L in#lux inhi itor and it may cause radycardia$ It increases the automaticity o# the heart and !hen com ined !ith adrenaline it may cause tachyarrythmias$ One o# the important side e##ects is haBothane hepatotoxicity$ The diagnosis o# halothane hepatitis is y exclusion$ This may progress into #ulminant hepatic #ailure !ith a '@

high mortality$ O ese middle aged !omen having repeat halothane exposures are at ris,$ 1alothane hepatitis may occur #ollo!ing a single exposure$ Iso#lurane It causes a dose dependent reduction in lood pressure$ The decrease in lood pressure is due to vasodilatation and decreased total peripheral resistance$ The heart rate is increased via re#lex mechanisms ut arrhythmias are uncommon$ Iso#lurane does not a##ect ventricular conduction and does not increase the excita ility o# ventricular myocardium$ Induction o# anesthesia is di##icult !ith iso#lurane due to its pungent odour and preanesthetic concentration o# iso#lurane may cause an air!ay re#lex stimulation& !ith increased secretions and"or coughing and laryngospasm$ 0evo#lurane It is a ne! inhalational agent and more expensive than others$ It has pleasant odour and can e used as induction agents in paediatric and adult patients$ It has rapid onset o# induction and recovery o# anesthesia ecause it is less solu le in lood than iso#lurane$ It has a mild negative inotropic e##ect$ It also decreases systemic vascular resistance #or daycare surgery$ '$9$'$ Intravenous induction agents Criteria #or ideal intravenous anesthetic agents: Induction o# anesthesia should e rapid& smooth and sa#e It should have limited e##ects on cardiovascular and respiratory systems It should possess analgesic activity$ Consciousness should return rapidly& smoothly and predicta ly$ ut does not cause re#lex tachycardia$ 0evo#lurane is less arrythmogenic !hen compared to halothane and it is suita le

a$ 0odium thiopental /7entothal2

'9

Thiopental is the only intravenous ar iturate eing used today and is classi#ied under an ultra short acting ar iturate$ It is prepared as a '$@* solution& !ater solu le& p1 o# 3($@ and sta le #or up to 3-' !ee,s i# re#rigerated$ Mechanism of action: Depress the reticular activating system& re#lecting the a ility o# ar iturates to decrease the rate o# dissociation o# the inhi itory neurotransmitter ?%+% #rom its receptors Pharmacokinetics 0hort duration o# action /@-3( minutes2 #ollo!ing IH olus re#lects high lipid solu ility and redistri ution #rom the rain to inactive tissues$ 7rotein inding parallels lipids solu ility& decreased protein inding increases drug sensitivity$ ;at is the only compartment in !hich thiopental continues to accumulate )( minutes a#ter in-ection Thiopental is meta olized in the liver slo!ly$ Its hepatic excretion ratio is ($3@ It has an anticonvulsant e##ect and is a use#ul drug #or cere ral protection in head in-ury$ It also has an analgesics e##ect$ In the presence o# inade4uate anaesthesia& air!ay manipulation may result in ronchospasm and laryngospasm$ Cardiovascular e##ects o# ar iturate include decrease in lood pressure due to vasodilatation and direct myocardial depression$ There is a compensatory increased in heart rate$ It should e used cautiously in haemodynamically unsta le patients and is contraindicated in hypovolaemia and hypotensive patients$ Induction dose is )@mg",g in a healthy adult$ $ 7ropo#ol It is '&9- diisopropyl-phenol& under group o# hindered phenol& an al,ylphenol derivative$ ;ormulated in a solution !ith 3(* soy and a!a,ening are prompt and complete a#ter even prolonged in#usions$ ean oil& hydropho ic nature$ It has rapid onset and short duration o# action$ .mergence

'A

Mechanism of action: 7ropo#ol increases the inhi itory neurotransmission mediated y gammaamino utyric acid$ It has extensive meta olism does not has antianalgesic activity$ 7ropo#ol is an ideal drug #or total intravenous anesthesia$ The target controlled induction /TCI2 and maintenance o# anesthesia can e achieved no!adays !ith propo#ol y a special TCI pump$ 7ropo#ol also can e used to provide sedation in ICU& #or minor procedures or in com ination !ith regional anesthesia$ Effects on organ system Cardiovascular : decrease in arterial lood pressure secondary to a drop in systemic vascular resistance& contractility& and preload$ 1ypotension is more pronounced than !ith thiopental$ 7ropo#ol mar,edly impairs the normal arterial arore#lex response to hypotension$ Respiratory: propo#ol causes pro#ound respiratory depression$ 7ropo#ol induced depression o# the upper air!ay re#lexes exceeds that o# thiopental Cere ral: decreases cere ral lood #lo! and intracranial pressure$ Induction dose: 3$@-) mg" ,g in a healthy adult$ y hepatic and extrahepatic$ It has no cumulative e##ects& has antiemetic property and suita le #or daycare surgery$ It

c$ Metamine It is a phenicyclidine derivative$ It produces dissociative anesthesia resulting in catatonia& amnesia and analgesia$ 7atient may appear a!a,e and reactive ut does not response to sensory stimuli Mechanism of action: It acts on NMD% receptor$ It loc,s polysynaptic re#lexes in the spinal cord& inhi iting excitatory neurotransmitter e##ects$ It has oth anesthetic and analgesic properties$ It causes postoperative psychic phenomena- emergence delirium& vivid dreams& hallucination$ There#ore it is not suita le #or adults$ These e##ects can enzodiazepines$ Clinical usage: e minimized y com ination !ith

'8

Induction o# anesthesia in poor ris, patients /eg: hypotension or ronchial asthma2 %s sole agent in dressing o# urns& radiological procedures in children& mass casualties in the #ield$ In the management o# unresponsive severe ronchospasm It is contraindicated in raised intracranial pressure& per#orating eye

surgery& hypertension& heart #ailure& recent myocardial in#arction& aneurysm and valvular heart disease$ Dosage: o IH 3$@-' mg",g& onset )( sec$ duration @-3(min$

o IM 3( mg",g& onset )-8min& duration 3(-'(min ystemic effects: Increase intracranial and intraocular pressures 7ostoperative nausea and vomiting Increased salivation$ %n antisialagogue is recommended e#ore used 7reservation o# air!ay re#lexes and produces rochodilatation Increased in cathecolamines secretion Metamine has cardiovascular e##ects: increases heart rate& lood pressure and pulmonary arterial pressure$ It is most li,ely due to direct stimulation o# the sympathetic nervous system$ '$9$)$ Neuromuscular loc,ing agents Muscle relaxants are generally classi#ied into t!o groups& depending on their mechanism o# action$ 3$ Depolarizing muscle relaxants$ a$ .xample: succinylcholine '$ Non depolarizing muscle relaxants a$ Intermediate acting: vecuronium& atracurium& rocuronium $ 6ong acting: pancuronium 3$ Depolarizing muscle relaxants

'F

Used to provide s,eletal muscle relaxation to #acilitate tracheal intu ation and optimal surgical condition$ Hentilation must e provided as the diaphragmatic muscle !ould also e paralysed$ There is no CN0 activity and the pro lem o# a!areness egin !ith introduction induction o# muscle relaxants$ ;actors that in#luence inclusion o# muscle relaxants in general anesthesia are types o# surgical procedures /anatomic location and patient position2& anesthetic techni4ues and patient #actors /%0% class& o ese& exreme o# age2$ Succinylcholine The only depolariser drug that is used clinically$ It consists o# t!o molecules o# acetylcholine lin,ed together$ It acts on nicotinic receptors at neuromuscular -unction /NMN2 to cause sustained depolarization that prevents propagation o# action potential$ The net e##ect o# 0Ch induced depolarization is uncoordinated s,eletal muscle activity that is seen as #asciculation$ It remains a use#ul muscle relaxants ecause o# its rapid onset and short duration o# muscular relaxation that cannot e achieved y any other availa le nondepolarising muscle relaxants$ % dose o# 3-' mg",g produces pro#ound muscle relaxation !ithin one minute$ ;ull recovery is 3(-3' minutes$ It is used in emergency surgery as rapid se4uence induction techni4ue and in situation o# di##icult air!ay management$ ide effects It may cause cardiac dysarryhmias such as children$ 1yper,alemia O at ris, patients / urns& extensively trauma& unrecognized muscular dystrophy and denervation in-uries$ Increased intragastric pressure /o##set y even greater increase in lo!er oesophageal sphincter2 Increased intraocular pressure /due to cycloplegic action o# succinylcholine2 7rolonged response in presence o# atypical cholinesterase )( radycardia especially in

 '

Increased intracranial pressure Muscle pain and myoglo inuria

Non depolarizing muscle relaxant %cts on nicotinic receptors in a competitive #ashion to produce loc,ade- a sence od depolarization$ Can e antagonized y

neuromuscular

anticholinesterase drugs$ They are used to #acilitate endotracheal intu ation& controlled ventilation and maintenance o# muscle relaxation during surgical procedures$ a$ %tracurium It is an intermediate acting enzyliso-4uinolinium type NDMR$ The intu ation dose is ($@-($9mg",g$ It presents as 3(mg"ml solution in '@mg or @(mg glass ampoules and is stored at = PC$ 1istamine release may occur in suscepti le patients ut anaphylactoid reaction is very rare$ $ Hecuronium It is an aminosteroid group and presents as #reezed dried po!der and diluted !ith sterile !ater e#ore used$ There is no histamine release and devoid o# cardiovascular side e##ects$ It does not antagonize #entanyl induced radycardia$ It is meta olized y liver and also excreted unchanged in ile$ The intu ation dose is ($(8-($3 mg",g$ c$ Rocuronium It is an aminosteroid group$ Its rapid onset o# action ma,es it a potential replacement #or 0Ch !hen rapid tracheal intu ation is needed$ Its duration o# action is similar to vecuronium and has similar pharmaco,inetic characteristic$ It has minimal cardiovascular side e##ects and very lo! potential #or histamine release$ Dosage #or endotracheal intu ation is ($9 mg",g$ d$ 7ancuronium It is a long acting NDMR !ith a steroid structure /+isamino4uaternary steroid2$ It increases heart rate and lood pressure and cardiac output due to cardiac vagal loc,ade$ 1istamine release is very rare and ronchospasm is extremely uncommon$

)3

%ssessment o# neuromuscular loc,ade 3$ Clinical assessment a$ % ility to li#t up head #or @ second $ 1and grip #or @ second c$ % ility to produce vital capacity reath Q 3( ml",g d$ Tongue protrusion '$ Responses to electrical stimulation o# a peripheral nerve stimulator %nticholinesterase %nticholinesterase is used to reverse non depolarizers$ It inhi its the action o# acetylcholinesterase and increase the concentration o# acetylcholine at the neuromuscular -unction$ It also acts at parasympathetic nerve endings$ In excessive doses& acetylcholineesterase inhi itors can paradoxically potentiate a nondepolarizing neuromuscular loc,ade and prolong the depolarization loc,ade o# succinylcholine$ %nticholinesterase increases acetylcholine at oth nicotinic and muscarinic

receptors$ Muscarinic e##ects can e loc,ed y administration o# atropine or glycopyrolate$ '$9$=$ Opioid analgesics ;e! examples o# this drugs are morphine& pethidine& #entanyl and nal uphine$ This drugs act on opioid receptors and classi#ied as #ull agonist& antagonist& or mixed agonist-antagonist depending on the actions on the opioid receptors$ Three main receptors are mu& ,appa and delta$ Classi#ication o# opioid receptors Mu receptors: morphine is the prototype exogenous ligand$ Mu-3: the main action at this reseptors is analgesia& ut also responsi le #or miosis& nausea"vomiting& urinary retention and pruritus$ The endogenous ligands are en,ephalins$ Mu-': respiratory depression& euphoria& radycardia& ileus and physical dependence are elicited y inding at this receptor$

)'

Mappa: Metocyclazocine and dynorphin are the prototype exogenous and endogenous ligands respectively$ %nalgesia& sedation& dysphoria and psychomimetic e##ects are produced y this receptor$ +inding to ,appa receptor can inhi it release o# vasopressin and thus promote dieresis$

Delta:

It is a modulation o# Mu receptor$ 1as high selective #or the endogenous

en,ephalins& ut opioid drugs still ind /leuen,ephalin and eta-endorphin2$ Morphine pharmacokinetics!

.limination hal#times #or morphine #ollo!ing ecause:

olus administration is a out 3$A-=$@

hours$ ;ollo!ing olus administration onset time is relatively slo! /3@-)( minutes2 3$ morphine exhi its relatively lo! lipid solu ility a out '$@* o# #entanyl /0u limaze2 '$ at physiological p1& morphine& a !ea, ase !ith the pMa o# a out 8$(& is primarily ionized$ The ionized #orm does not #avor passage through the lipid mem raneB accordingly& only a out 3(*-'(* o# molecules are un-ionized$

Relatively high plasma clearance /3@-=( ml",g"minute2 has implicated extrahepatic clearance mechanisms& most li,ely renal$

"entanyl ( ublima#e) pharmacokinetics!

;entanyl /0u limaze2 is signi#icantly more lipid-solu le& compared morphine and& relative to morphine& has a more rapid onset o# action /#entanyl /0u limaze2 is also a !ea, ase and at physiological p1 only a out 3(* o# molecules are un-ionized2$

Clearance o# a out 3(-'( ml",g"minute is consistent !ith a primary hepatic mechanism$ ;entanyl /0u limaze25s short duration o# action #ollo!ing explained olus administration is y rapid redistri ution #rom rain to other compartments such as s,eletal

muscle and #at$ I#& ho!ever& #entanyl /0u limaze2 is administered y continuous IH in#usion or multiple IH dosing& other non-CN0 compartments !ill saturated and remaining CN0 #entanyl !ill contri ute to postoperative ventilatory depression$

%ction o# opioid drugs:

))

%$ Central nervous system: %nalgesia& sedation& euphoria& nausea& vomiting& miosis& depression o# ventilation& pruritus and s,eletal muscle rigidity$ +$ Respiratory system: ronchospasm in suscepti le patients and depressed cough re#lex C$ Cardiovascular system: radycardia /#entanyl2 or tachycardia / pethidine2 D$ 0,in: pruritus may e due to histamine release or action on opioid receptor$ .$ ?astrointestinal tract: constipation& delays gastric emptying& increased tone o# the common ile duct and sphincter o# Oddi$ ;$ Urinary tract: increased sphincter tone and retention o# urine$ Use o# opioids in anesthesias 7remedication drugs Induction o# anaesthesia +lunt haemodynamic reactions to noxious stimulation Intraoperative analgesia 7ostoperative analgesia Used in ICU as analgesia to #acilitate mechanical ventilation Drug Morphine 7ethidine ;entanyl Naloxone It is an antagonist at all opioid receptors o# pure opioid antagonist$ It reverse all opioid actions including analgesia$ It has short duration o# action / 3-= hours2 and has limited action against partial or mixed actions opioids$ % rupt reversal o# opioid analgesia can result in sympathetic stimulation /tachycardia& ventricular irrita ility& hypertension and pulmonary oedema2$ Doses
2.5 - 5 mg (IV), 15 - 30 mg (oral)

@( to 3(( mg 0$C$& I$M or in reduced doses I$H$ repeated every ) to = hours

25 - 50 g (IV), 150 - 300 g (oral)

Dosage :

)=

+olus: o %dult: ($(= mg IH in titrated olus every ') minutes until the desired e##ects o Child: 3-=mcg",g titrated

Tramadol

Continuous in#usion: @mcg",g"hr IH !ill prevent respiratory depression !ithout altering the analgesia produced y neuraxial opioids$

It is an opioid agonist at mu receptor and inhi its noradrenaline reupta,e and release o# @hydroxytryptamine /monoaminergic path!ays2$ It is given intravenously !ith the dose o# 3-' mg",g and Non o'ioi.s Use o# non steroidal anti-in#lammatory drugs as analgesics /eg: Metorolac& Diclo#enac2$ It loc, synthesis o# prostaglandins y inhi iting cyclooxygenase enzyme$ It reduces pain y peripheral action and centrally y reducing input o# nociceptive in#ormation in spinal cord$ Metorolac and Metopru#en has opioid sparing e##ects$ ide effects: Reduced platelet aggregation may increase leeding O it is not advisa le #or neurosurgical and ophthalmic surgery$ It may cause damage to gastric mucosa causing ulceration and leeding$ +ronchospasm O patients !ith asthma have an increased incidence o# sensitivity to aspirin Renal #ailure- inhi ition o# renal prostaglandin synthesis may inter#ere !ith maintenance o# renal lood #lo!$ Drug Holtaren /Diclo#enac2 7aracetamol 0yn#lex Doses 3((-'(( mg daily ' x @((mg =-9 hourly Initially @@( mg then 'A@ mg 9-8 hrly CHAPTER ( CA/E: PERIOPERATI6E A//E//MENT )@ also can e given orally /good ioavaila ility2$ It produces less respiratory depression in e4uivalent dose i# compared !ith morphine$

(.1. P%#o'#%ati-# Ass#ssm#nt )$3$3$ Case 1istory ID.NTI;IC%TION D%T% Name 0ex %ge Nationality"Tri e Religion %ddress Marital 0tatus Occupation %dmission Date C1I.; COM76%INT This )F-year old Malay lady !as admitted to surgical !ard o# 1ospital Tuan,u ;auziah !ith a chie# complaint o# right anterior nec, s!elling associated !ith shortness o# reath since one !ee, ago$ 1I0TORR O; 7R.0.NTIN? I66N.00 7atient is a ,no!n case o# goitre #or the past t!o years$ The goitre& !hich is a right sided anterior nec, s!elling& painless& and gradually increases in size$ 0ometimes& the patient experienced hand tremor& palpitation and heat intolerance$ No!& she !as having o structive symptoms such as shortness o# reath and occasionally orthopnoea since 3 !ee, ago$ Ultrasound !as done on =th May '(33& !ith the impression o# Multinodular ?oitre$ ;ine Needle %spiration Cytology /;N%C2 !as also done on ' nd Nune '(33& !ith the impression o# nodular goitre !ith cystic degeneration$ Other!ise& she has no dysphagia& no diarrhea& no constipation& no a dominal pain& no upper respiratory tract in#ection or urinary tract in#ection& and no stridor$ : %nita inti Rahaya : ;emale : )F years old : Malaysian"Malay : Islam : Mangar& 7erlis : Married : 1ouse!i#e :3Ath May '(3'& 33$3@ am

)9

7%0T M.DIC%6 1I0TORR 0he has no ,no!n o# other medical condition$ 7%0T %N%.0T1.TIC 1I0TORR 7atient has never gone through any surgical or anaesthetic procedures$ DRU? 1I0TORR 7atient is not on any medication$ ThereEs no history o# drug or #ood allergy$ 7atient claimed sheEs not ta,ing any traditional medication or over the counter drug$ 7%0T O+0T.TRIC S ?RN.CO6O?R 1I0TORR 7atient has never had any pro lem regarding o stetric and gynecology$ 0he had her menarche at the age o# 3) years old and claimed to have a regular menstrual cycle& around A to 8 days every month$ 1o!ever& she has mild dysmenorrhea$ ;%MI6R 1I0TORR The patientEs #ather has thyroid cancer$ Mother is healthy$ 0OCI%6 1I0TORR 7atient is a house!i#e& married& and having = children$ Currently& sheEs living !ith her hus and and children$ 0heEs a non-smo,er and non-alcoholic$ 0he denied o# any high-ris, ehavior$ )$3$'$ 7hysical .xamination ?.N.R%6 .G%MIN%TION 7atient !as conscious and alert& lying com#orta ly on the ed$ 0he doesnEt loo, ill& not in pain& and not in respiratory distress$ 1er nutritional status is o esity& and her hydrational status is #air$ ThereEs no gross de#ormity& no any involuntary or a normal movement& and thereEs a rannula attached at her le#t !rist$ HIT%6 0I?N0

)A

Hital signs Temperature +lood pressure 7ulse rate Respiratory rate 7ain score 1eight >eight +ody Mass Index

Halue )APC 3)@"A( mm1g A' pm 38x"minute ("3( 39' cm 8= ,g )' ,g"m'

Interpretation %#e rile Normal Normal Normal Not in pain O esity

1.%D& N.CM S .GTR.MITI.0 .G%MIN%TION On the general examination /extremities2& the palm !as moist& no pallor& no palmar erythema and the temperature !as normal$ ThereEs no clu ing #inger& and no luish discolouration o# the nail$ No leuconychia or ,oilonychia noted$ ThereEs no #ine tremor or #lapping tremor$ ThereEs also no pedal edema at oth lo!er extremities$ .xamination o# the head did not reveal pallor o# the con-unctiva& no -aundice o# the sclera& no exophthalmus& no arcus senilis and no xanthelasma$ ThereEs also no discoloration o# the lips and the tongue$ The dental hygiene !as #air$ ;or nec, examination& on inspection& thereEs a right anterior nec, s!elling that moves upon deglutition& ut does not move !ith tongue protrusion$ Other!ise& thereEs no redness& no s,in changes& no discharge& no surgical scar and no prominent vein$ On palpation& itEs a nontender s!elling !ith normal temperature$ The size is )x' cm$ The s!elling has a smooth sur#ace& #irm in consistency& round in shape& mo ile and has a !ell-de#ined margin$ The lo!er order o# luish

)8

the s!elling can e #elt upon deglutition$ There is a tracheal deviation to!ards the le#t side$ Other!ise& the s!elling is not attached to underlying structures or overlying s,in& no #luctuation and thereEs no pulsation can e appreciated$ On percussion& thereEs no retrosternal extension o# the s!elling& and on auscultation& thereEs no ruit can e heard$ R.07IR%TORR 0R0T.M .G%MIN%TION ;rom air!ay assessment& patient !as classi#ied as Mallampati class II& and the thyromental distance !as more than 9$@ cm or three #ingers !ide$ 7atient has no history or symptoms o# upper respiratory tract in#ection$ On examinationB on inspection& the chest moved symmetrically !ith respiration& !ith thoraco-a dominal reathing pattern$ The chest shape !as normal and there !as no de#ormity or scar noted on oth anterior and posterior chest !all$ There !ere also no signs o# respiratory distress$ On palpation& the chest expansion and tactile vocal #remitus !ere symmetrical on oth anterior and posterior chest$ On percussion& it !as a symmetrical resonance sounds& and thereEs no retrosternal extension o# the goiter$ On auscultation& no !heezing or crepitation heard$ %ir entry !as e4ual on oth sides$ C%RDIOH%0CU6%R 0R0T.M .G%MIN%TION The peripheral pulses !ere palpa le& e4ual and regular$ There !as no surgical scar seen on the chest$ There !as neither heave nor thrill can e palpated$ %pex eat !as palpa le at le#t midclavicular line et!een =th and @th intercostal space$ Normal 3st and 'nd heart sounds !ere heard and there !ere no additional sounds or murmurs heard in the mitral& tricuspid& aortic and pulmonary area$ %+DOMIN%6 .G%MIN%TION On inspection& the a domen !as not distended& moves !ith each respiration$ The um ilicus is centrally located$ Other!ise& there is no surgical scar& no visi le peristalsis or pulsation& no s,in discolouration and no cough impulse$ On palpation& the a domen is so#t and non-tender$ No mass can e appreciated and no hepatomegaly or splenomegaly$ The ,idney !as non- allota le$ The percussion gives tympanic sound& and thereEs no shi#ting dullness$ On auscultation& the o!el sound !as present and no renal ruit heard$

)F

C.NTR%6 N.RHOU0 0R0T.M .G%MIN%TION 7atient !as alert& and !ell oriented to person& time and place$ ?lasgo! Coma 0cale !as 3@"3@$ ;acial expression !as symmetry$ %ll cranial nerves !ere intact$ MU0CU6O0M.6.T%6 0R0T.M .G%MIN%TION 7atient has a normal muscle ul,& strength& tone and po!er #or oth upper and lo!er extremities$ The shape o# verte ral spine is normal$ No de#ormities noted$ ?ait !as normal$ 71R0IC%6 0T%TU0 %0% score is 3$ 7atient !as healthy !ith no systemic disease& and the surgery !as an elective surgery$ )$3$)$ Investigation o ;ull lood count: Components >hite lood cell Red lood cell 1aemoglo in 1aematocrit M#an &# -o $m# M#an &# +a#mo! o,in MC1C 7latelet Di##erential: Neutrophils 6ymphocytes Monocytes Eosino'+i s ;aso'+i s Halue 8$8 /3(F"62 =$A /3(9"62 3'$( /g"d62 )A$8 /*2 35.1 7)L8 20.* 7'!8 )3$A /g"d62 'F8 /3()"u62 =$A@ /3()"u62 '$F( /3()"u62 ($)@ /3()"u62 5.25 715(<$L8 5.55 715(<$L8 Normal Range =$( O 33$( )$8 O =$8 3'$( O 3@$( )9$( O =9$( 3(.5 9 151.5 22.5 9 (2.5 )3$@ O )=$@ 3@( O =@( '$( O A$( 3$( O )$( ($' O 3$( 5.52 9 5.05 5.52 9 5.15 Interpretation Normal Normal Normal Normal Lo: Lo: Normal Normal Normal Normal Normal Hi!+ Lo:

=(

o Renal pro#ile Components 0odium 7otassium Urea Creatinine o Coagulation: Components 7rothrom in time INR %7TT test %7TT ratio Halue 33$A /sec2 ($FF '8$@ /sec2 3$( Normal Range 3($= O 3)$' ($F O 3$3 '($3 O )=$F Interpretation Normal Normal Normal Halue 3)8 /mmol"62 )$A /mmol"62 )$A /mmol"62 93 /umol"62 Normal Range 3)@ O 3=@ )$) O @$) 3$A O 8$) TFA Interpretation Normal Normal Normal Normal

o Thyroid #unction test: Components T01 ;ree T= o Urine ;.M.: =3 Halue 3$A'( /uIU"m62 3@$F9 /pmol"62 Normal Range ($'A O =$'( 3' - '' Interpretation Normal Normal

Components Urine glucose +iliru in Metone 0peci#ic gravity +lood Urine p1 7rotein Uro ilinogen Nitrite 6eucocyte Color Tur idity Urine 7T .M?: o 0inus rhythm o No ischemic changes o Interpretation: Normal Chest G-Ray:

Halue Normal Negative Negative 3$((( Negative @$( Negative )$' Negative Negative 6ight yello! Clear Negative

Interpretation Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal

o Tracheal deviated to the le#t side o 6ung: Normal o No cardiomegaly o +ones: Intact o 0o#t tissues: Normal Indirect 6aryngoscope: o +oth vocal #old mo ile e4ually o No anterior compression o Impression: Normal vocal cord )$3$=$ 0ummary % )F years old malay lady& a ,no!n case o# multinodular goitre diagnosed in '(3(& presented !ith right anterior nec, s!elling associated !ith shortness o# reath since 3 !ee, ='

e#ore 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$ ;rom the chest G-ray& thereEs a tracheal deviation to the le#t side$ Other!ise& thereEs no any signi#icant #inding in any other system$

)$3$@$ 7reoperative Diagnosis o +ilateral multinodular goitre )$3$9$ 7lan o Right hemithyroidectomy MIH total thyroidectomy o To ,eep nil y mouth y 3' midnight /8 hours prior to surgery2 o To in4uire in#ormed consent #or the surgery and anaesthetic procedures o 0end lood #or lood crossmatch o To plan #or general anaesthesia"intermittent positive pressure volume (.2. Int%ao'#%ati-# Ass#ssm#nt %naesthesia : +alanced general anaesthesia !ith intermittent positive pressure ventilation /I77H2$ ;asting : 7atient !as ,ept nil y mouth 8 hours prior to operation$ 7remedication : Not given to patient )$'$3$ %naesthesia 7rocedures : I$ 7reoperative assessment !as done and consent !as ta,en #rom the patient$ II$ ?% machine !as chec,ed and anaesthetic drug !as prepared e#ore patient !as entered into the operation room$ III$ Intravenous assessed !as esta lished y inserting IH catheter 38? and patient !as preloaded !ith normal saline$ IH$ 7rocedures !ere done in a #ull aseptic techni4ue& scru surgery$ HI$ 7atient !as preoxygenated !ith 3((* oxygen #or ) minutes at 8am$ =) ed& gloved and go!ned$ H$ 7atient nec, !as #ully extended and given sand ag to get the etter vie! #or the

HII$ %dministration o# intravenous ;entanyl 3((mcg and intravenous sodium thiopentan '$@* 3A@mg$ HIII$ 6oss o# consciousness !as assessed y loss o# eyelash re#lex$ IG$ Test ventilate e#ore give muscle relaxant$ G$ Then& IH atracurium )(mg !as given and mas, ventilate !ith oxygen and volatile #or )minutes$ GI$ 6aryngoscopy and intu ation !ere then per#ormed circuit$ GIII$ .TT positioned !as con#irmed y auscultation and end tidal volume CO'$ GIH$ The vital sign !hich are oxygen saturation& rain tissue car on dioxide& respiratory rate& lood pressure& heart rate& any lood loss and urine output !as monitored during the operation$ GH$ No lood trans#usion !as done during the operation$ )ml"hour and morphine )mg "hour$ GHII$ Reversal !ith intravenous %tropine 3mg and Neostigmine '$@mg$ GHIII$ .TT !as removed and mouth !as cleared under direct vision once patient spontaneously reathing$ GIG$ Oxygen !as administered y #ace mas, and patient !as trans#erred to recovery room to e reassessed$ )$'$'$ Drugs : )$'$'$3$ Intravenous : a$ ;entanyl 3((mcg $ 0odium thiopentate '$@* 3A@mg c$ %tracorium )(g d$ Morphine )mg e$ %trocorium in#usion )ml"hour #$ %tropine 3mg g$ Neostigmine '$@mg GHI$ %naesthesia !as maintained !ith 0evo#lurane and top up atracurium in#usion y using UarmoredE .TT tu e$ GII$ .TT cu## o# A$@ cm and angle at 3@cm !as in#lates and connected to reathing

==

)$'$'$'$ ?ases : 3$ Oxygen " air /6"min2

8$'( am 3:3

8$@(am 3:3 3$A

F$'(am 3:3 3$A

F$@(am 3:3 3$A

'$ Holatile : 0evo#lurane /M%C *23$A

)$'$)$ Monitoring : Time 0aturation O' /3((*2 Respiratory rate /x"min2 7 t CO' 8$'(am 3(( * 38x"min )= 8$@(am 3((* 38"min )= F$'(am FF* 39x"min )= F$@(am 3((* 38x"min )9

+lood 7ressure and 1eart Rate : +lood pressure !as monitored every @ minutes during the !hole operation procedure$ The systole reading range !as pressure !as et!een 9( O 38(mm1g$ 1eart rate !as monitored every @minutes and noted to e in normal range !hich !as !ithin F( O 3(( eats per minutes$
200 150 100 50 0
10 .0 5 10 .1 5 8. 05 8. 15 8. 25 8. 35 8. 45 8. 55 9. 05 9. 15 9. 25 9. 35 9. 45 9. 55

et!een 3=( O 38( mm1g and diastolic

+lood 7ressure monitoring :

S ystole d iastolic

105 100 95 90 85 80 75 8.05 8.15 8.25 8.35

1eart rate monitoring

H ea rt ra te

=@
8.45 8.55 9.05 9.15 9.25 9.35 9.45 9.55 10.1 10.2

)$'$=$ 0ummary : 7atient !as hemodynamically sta le !ith minimal lood loss during the operation thus no lood trans#usion !as needed$ Upon operation& the surgeon only did right hemithyroidectomy and not done total thyroidectomy ecause the nodule at the le#t side is small /3cm2 near the recurrent laryngeal nerve and not removed$ +oth recurrent laryngeal nerve identi#ied and preserved and parathyrois gland identi#iend and preserved$ 0,in closed !ith su cuticular$ 7atient reversed !ith atropine and neostigmine and !as trans#erred to recovery !ard e#ore discharging to !ard$ (.(. Post O'#%ati-# Ass#ssm#nt %#ter extu ation& patient !as sta le and supplemental oxygen via #ace mas, /@6"min2$ 7atient !as trans#erred to the recovery area a#ter the surgery !as done$ 7atient !as still dro!sy lethargic ut there !as no sign o# respiratory distressed seen$ Non-invasive lood pressure /NI+72 monitor& .C? monitoring and pulse oximeter !ere set-up$ 7atient !as put elo! radiant !armer to prevent hypothermia$ 7ain !as minimal and there !ere no complaints o# headache& nausea or vomiting$ Other!ise& no other post-operative complications noted$ 6ita /i!ns +lood pressure 7ulse rate Respiratory rate Temperature 0pO' R#a.in! 33F"8( mm1g 83 x"min '(x" min )APC 3((* Int#%'%#tation Normal Normal Normal %#e rile Normal egan to reathe spontaneously !ith

=9

7ain score

'"3(

Mild pain

7ost-operative anaesthesia recovery score Pa%am#t#%s %ctivity Respiration Circulation /i!ns % le to li#t the head or has a good hand grip Consciousness Colour None o# the a ove % le to reathe and cough easily Dyspnoeic or apnoeic +7 !ithin '(* o# pre-operative level +7 a ove or elo! '(* o# pre-operative level 7ulse regular rate& !ithin '(* o# preoperative level 7ulse irregular& a ove or elo! '(* o# preoperative level %rousa le Not responding 7in, ( 1 /&o%# 1 ( 1 ( 1 (

1 ( 1 ( 1<1

Dus,y Tota s&o%#

Note: 0core @ or more may e coming home !ith the conditions o# operation" action possi le 0core = to the treatment room !hen the reathing value is 3 0core ) or less to ICU

Operative #indings: Multinodular goitre& right lo e is larger than the le#t lo e Only 3 small nodule is noted& measuring a out 3cm on the le#t side& situated near the recurrent laryngeal nerve& not removed +oth recurrent laryngeal nerves are identi#ied and preserved 7arathyroid glands are identi#ied and preserved

=A

7lan: /i2 To trans#er patient to the surgical !ard a#ter )( minutes and regularly monitor the vital signs in the !ard /ii2 /iii2 /iv2 /v2 /vi2 Continue to give supplemental oxygen /@6"min2 via #ace mas, In#use ) pints o# dextrose @* and ' pints normal saline ($F* in '= hours Meep nil y mouth #or 9-8 hours To give C$ Tramal @(mg 7RN To give ta $ 7aracetamol 3g VID

)$)$3$ ;ollo!-up 38th o# May '(3' /3'$(( pm2 0u -ective 7atient complain o# pain over the incision site and throat discom#ort& pain score )"9 7atient !as a le to spea,& can tolerate small volume o# li4uid /'-) spoon#ul2 orally Other!ise& there is no num ness& hoarseness o# voice& shortness o# reath& tremor or palpitation O -ective %nalysis 7lan 7atient is alert& conscious ut mildly lethargic 0,in is pin,& hydration is ade4uate +7: 338"8( mm1g 7ulse rate: 8(x"min Respiratory rate: '(x"min Temperature: )AC 0urgical scar: clean& no discharge is seen& not in#ected 6ungs: Hesicular reath sound& no additional sound CH0: Dual rhythm no murmur % domen: so#t non tender

7ost- right hemithyroidectomy #or multinodular goitre Continue vital signs monitoring every = hours =8

Meep nil y mouth #or a out 9-8 hours& then encourage #luid inta,e orally /set an inta,e" output chart2 ?ive C$ Tramal @(mg 7RN and T$ 7aracetamol VID #or pain To complete IH drip: ' pints o# normal saline and ) pints o# Dextrose @* in '= hours

=F

3Fth o# May '(3' /'$(( pm2 0u -ective 7atient complain o# pain over the incision site and throat discom#ort& pain score '"9 7atient !as a le to spea, !ith slight hoarseness& can tolerate small volume o# li4uid orally Other!ise& there is no num ness& shortness o# reath& tremor or palpitation O -ective %nalysis 7lan 7atient is alert& conscious and com#orta le 0,in is pin,& hydration is ade4uate +7: 339"8( mm1g 7ulse rate: A9x"min Respiratory rate: 3Ax"min Temperature: )AC 0urgical scar: clean and healing& no discharge is seen& not in#ected 6ungs: Hesicular reath sound& no additional sound CH0: Dual rhythm no murmur

% domen: so#t non tender 7ost- right hemithyroidectomy #or multinodular goitre Continue vital signs monitoring every = hours .ncourage #luid inta,e orally /set an inta,e" output chart2 ?ive C$ Tramal @(mg 7RN and T$ 7aracetamol VID #or pain O## IH drip !hen completed and ade4uate oral inta,e To discharge patient !hen no complication and condition is sta le$ 7lan #or #ollo!-up in 0O7D

@(

CHAPTER * PERIOPERATI6E DI/CU//ION 7CA/E8 *.1. P%#-o'#%ati-# Dis&$ssion There are #e! criteria that need to e considered in the pre-operation e#ore a patient undergone surgery& !hich are:

@3

o To access the condition o# the patient #rom the history and physical examination$ ;rom physical examination& it is important to ma,e a thorough assessment o# air!ay& cardiovascular system& and respiratory system$ 0ince this patient has no pro lem in her cardiovascular and respiratory system& the assessment !ould e #ocused more on her air!ay& to determine i# there !ould e any di##iculty !hen the intu ation is per#ormed$ o To decide the anaesthetic plan #or the patient either y general or regional anaesthesia$ o The need o# in#ormed consent #or oth surgery and anaesthetic procedures$ o 7atient is not given any premedication such as: %nti iotic: Thyroidectomy is considered as a clean surgery& prophylactic anti iotic is not needed$ %nxiolytic: 7atientEs anxiety is not severe enough to e treated using medication$ %ntiemetic: Ris, o# aspiration is reduced y ,eeping patient N+M e#ore surgery$ %nalgesic: Not given to our patient ecause she is not in pain prior to the surgery

o To ,eep the patient nil y mouth 8 hours prior to surgery 3$ ;or this patient& she does not have any past medical history such as asthma& or any evidence o# recent upper respiratory tract in#ection& !hich suggesting the use o# general anaesthesia is not contradicting$ 1o!ever& this is her #irst surgical experience& thus thereEs no any record o# allergy to anaesthetic agents$ ;rom assessment o# Mallampati class& this patient is in class II& and the thyromental distance is ) #inger readth& !hich suggesting the di##iculty o# air!ay #or intu ation is not present$ '$ In this patient !hom undergone right hemithyroidectomy surgery& !hich involves the upper air!ay regionB general anaesthesia is the est option$ It is unethical to use regional anaesthesia and ,eeps the patient a!a,e #or this type o# surgery$ )$ +ased on %merican 0ociety o# %naesthesiology grade& the patient classi#ied into class I /!ith the mortality rate o# ($(9*-($(8*2& ecause she is per#ectly healthy and thus& the operation ris, is minimal$ 1o!ever& there are also other predictors !hich play roles in determining the ris, and mortality o# an operation& such as operation type and surgical s,ill o# the operator$ @'

=$ The patient gave her consent to go through hemithyroidectomy surgery$ The consent given a#ter the anaesthesia and surgical teams explained a out the nature o# surgical and anaesthetic procedures$ Their consent is ta,en and is documented in the anaesthesia and surgery consent #orms$ %ll 4uestions as,ed y the patient& ans!ered y anaesthesiologist$ @$ The patient !as ,eep nil y mouth y 3' midnight& 8 hours e#ore she undergone the surgery& to allo! su##icient time #or gastric emptying o# ingested #ood and li4uid at the time o# induction o# anaesthesia$ It is elieved that #asting can limit the severity o# aspiration pneumonitis syndrome in the event o# aspiration o# gastric content$ The gastric emptying o# #luid is very rapidB F@* o# ingested li4uids are emptied in 3 hour& !hile solids are emptied only !hen it is trans#ormed into a li4ue#ied #orm& !hich re4uires unpredicta le time /up to 3' hours2$ *.2. Int%ao'#%ati-# Dis&$ssion 3$ 7atient !as given alanced general anaesthesia !ith intermittent positive air!ay pressure ventilation not y spontaneous ventilation$ +alanced anaesthesia mean that ) component o# anaesthesia !as given !hich mean hypnotic& analgesia& and muscle relaxant$ It is sa#er to use ) types o# drug in sa#ety doses than 3 type that re4uire higher dose to get other e##ect ut can harm the patient$ I77H !as chosen ecause the surgery involves the air!ay& at the nec, region& and re4uires endotracheal intu ation$ 0pontaneous ventilation !as not chosen #or this patient ecause it usually #or super#icial surgeries and surgery that doesnEt involve the air!ay$ '$ 7atient !as given special type o# endotracheal tu e !hich is UarmoredE endotracheal tu e that are cu##ed& !ire- rein#orced silicone ru polyvinyl chloride tu e& er tu es that are much more #lexi le than ut they are di##icult to compress or ,in,$ This type o#

endotracheal tu e is use#ul !hen the trachea is anticipated to remain intu ated #or a prolonged duration and the nec, to remain #lexed during surgery$ .TT is indicated #or

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surgery that used I77H and muscle relaxant& to secure the air!ay& and #or unusual surgical position$ )$ 7atient !as given ' types o# opioid #or the surgery !hich are IH ;entanyl and IH morphine$ ;entanyl !as given 3-'mcg",g& so #or this patient is 8( O 39(mcg$ 7atient !as given 3((mcg !hich is 3 ampoule$ ;entanyl !as used as an induction agent ecause the onset o# action o# #entanyl is almost immediately !hen given intravenously than morphine$ ;entanyl is more potent than morphine due to its high lipophilicity& !hich ma,e it penetrates the CN0 more easily$ It inds to mu opioid ? protein couple receptor !hich inhi its pain neurotransmitter released y decreasing intracellular Ca'L levels$ Morphine is used as maintenance #or analgesia during the intraoperation period ecause it is long acting$ Morphine is used than ,etorolac ecause it is a gold standard drug and patient does not have contraindication to it$ Metorolac may not improve analgesia due to its ceiling e##ect ut may increase the un#avora le e##ect$ ;urthermore& ,etorolac increased the ris, o# surgical leeding and increased ?I leeding$ =$ 7atient !as given !ith sodium thiopental /0T72 !hich is an intravenous ar iturate /)@mg",g2& ut #or this patient !as given 3A@mg$ 0T7 !as given to sedate the patient so it is given slo!ly !ith other volatile gas !hich can give synergistic e##ect and is stopped !hen the patient has een sedated$ That is !hy patient it is only given 3A@mg$ 0T7 is cost e##ective compared to propo#ol$ Unli,e propo#ol& 0T7 induces histamine release !hich !ill e dangerous in asthmatic patient$ 0T7 is considered to e sa#e #or our patient since she doesnEt have asthma$ 0T7 causes less pain !hen itEs in-ected compared to propo#ol$ 0T7 is an ultra-short acting ar iturate due to its rapid distri ution !hich is used as an induction that acts directly to ?%+% receptor and causes sedative e##ect$ %#ter 0T7 !as given& ventilation test needs to e done to ma,e sure that !e can ventilate the patient y monitoring the capnograph$ @$ %tracurium is a muscle relaxant given to the patient a#ter test ventilate !as done$ ;or this patient !as given )( mg$ It is non depolarizing muscle relaxant that acts on nicotinic receptor in competitive #ashion to produce neuromuscular loc,ade so that depolarization

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not occur$ It is used to #acilitate endotracheal intu ation& and controlled ventilation$ It is spontaneously degraded y 1o#mann elimination$ %s maintenance& atracurium sustains muscle relaxation during surgical$ Usually atracurium not given as in#usion #or thyroid surgery ut #or this patient& atracurium in#usion !as given ecause the anaesthesiologist predicted that the surgery !ill e long& ut the operation is not complicated and tends to e short surgery& so it is stopped !ithin W hour e#ore the surgery !as done$ %#ter the atracurium !as given& mas, ventilation has to e done #or ) minutes to allo! the onset o# action o# atracurium$ 9$ 0evo#lurane is a volatile anaesthetic agent that is used #or this patient$ It is used ecause it is less solu le in lood !hich !ill cause patient to gain her consciousness #aster #rom anaesthesia$ ;urthermore& it is pre#erred agent #or mas, delivery due to its less irritation to mucous mem rane$ It causes immo ility that is measured y minimum alveolar concentration /M%C2 o# anaesthesia re4uired to suppress movement to a surgical incision in @(* o# patient$ It has mild negative inotropic e##ect !hich can lo!er the lood pressure in this patient during surgery$ A$ 7atient !as given IH atropine 3mg and IH neostigmine '$@mg #or reversal a#ter operation$ Neostigmine is an anticholinesterase that inhi its acethylcholinesterase so that the enzyme can no longer rea, do!n the acethycholine molecules e#ore they reach the postsynaptic mem rane receptor$ %tropine is given to counteract the parasympathetic e##ects o# anticholinesterase$ 8$ Monitoring o# intraoperative is to see any rapid changes in patient status during anaesthesia$ The patientEs oxygenation& ventilation& circulation and temperature are continuously monitored$ Clinical signs li,e colour& pulse rate and volume& rate and depth o# respiration& lood pressure& #luid status& temperature& urine output& lood trans#usion are also monitored$ %ll the important vital sign are documented$ ;or this patient all the vital sign are in the normal state except that her lood pressure !hich is higher than normal$ 0evo#lurane can reduce the lood pressure during the operation$ ;urthermore& it

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is normal #or lood pressure to elevate during intu ation and extu ation ecause o# ody response and it !ill reduce later$ F$ ;luid replacement is divided into ) components& !hich are: #or maintenance& de#icit& and the #luid loss /insensi le S leeding2$ Intraoperative #luid administration has to e given to maintain ade4uate oxygen delivery& normal electrolyte concentration& and to normal lood glucose level$ ;or the maintenance: 3st 3(,g o# +> : 3((ml",g"'=h =ml",g"h 7atient :8(,g /3(,g x= X =(ml2 nd ' 3(,g o# +> : @(ml",g"'=h 'ml",g 3(,g /3( ,g x'X '(ml2 .ach ,g a ove '(,g : '(ml",g"'=h 3ml",g"h 9(,g /9(,g x3X 9(ml2 Maintenance O =( ml L '(ml L 9(ml X 3'(ml"hour 7reexisting de#icit: maintenance x num ers o# hour o# #asting$ Replace hal# in the 3 st hour& 4uarter in 'nd and )rd hours O 8hour x 3'(ml X F9(ml /replace =8( in 3st hour& '=( in 'nd and )rd hours 2 Ongoing loss : #rom the lood loss and the evaporative loss #rom the surgical #ield / minor X 3- 'ml",g"h& moderate X )- =ml",g"h& ma-or X 9- 8 ml",g"h2 7atient X minor O 3 x 8( X 8(ml"h 3st hour X 3'( ml L =8( ml L 8(ml X 98( ml"h 'nd and )rd hour X 3'(ml L '=(ml L 8( ml X ==(ml"h =th hour on!ard X 3'(ml L8( X '((ml"h The choice o# #luid given is crystalloid ecause it is rapidly distri uted into the extracellular #luid component$ It is use#ul to provide maintenance !ater and electrolytes and #or intravascular volume expansion $ ;or this patient& normal saline !as chosen /($F* NaCl2 $ *.(. Post-o'#%ation .is&$ssion 3$ 7atient should not leave the operation room unless they have a sta le and patent air!ay /indicated y the presence o# cough and gag re#lex along !ith spontaneous reathing2& ade4uate ventilation and oxygenation& and are hemodynamically sta le$ '$ Continuing care in the recovery room: @9

)$ 7hase 3: ?ained consciousness !ith intact pharyngeal re#lexes$ % le to sustain a @ seconds head li#t& cough and deep reath$ =$ 7hase ': Recovers the a ility to thin, clearly and movement returns$ Can e trans#erred to the !ard$ @$ 7hase ): %t the end o# this phase all the e##ects o# anaesthetics should disappear$ 9$ The most #re4uent pro lems in the recovery room are: A$ Nausea and vomiting /might electrolyte loss can also happen2$ 8. Inade4uate pain relie# /pain !ill activate the sympathetic activity vasoconstriction less per#usion to the tissue delayed !ound healing2 F$ shivering due to hypothermia /patient should e placed near a !armer and covered !ith lan,et2 3($ 1ypoxemia /to prevent this& pre-oxygenation via #ace mas, should immediately a#ter extu ation2 33$ +leeding #rom the surgical site or !ound in#ection / leeding and s!elling can compromise the air!ay$ I# this occurs& remove s,in clips"sutures and strap muscle sutures and call #or help$ 3'$ 1oarseness o# voice might post thyroidectomy might e due to iatrogenic in-ury to the recurrent laryngeal nerve& or simply due to s!elling around the nerves /this !ill resolve !ith time2$ 7atient should e !arned that their voice !ill e di##erent #or a #e! days postop ecause o# intu ation and local edema$ 3)$ Most patients !ho have mild to moderate pain #ollo!ing surgery can e managed !ith oral COG inhi itors& opiods& or a com ination$ Our patient !as given 7aracetamol /3g VID2 ta let and Tramadol hydrochloride capsule /@(mg 7RN2 as soon as patient !as a le to tolerate orally$ 7aracetamol /acetaminophen2 has the #e!est side e##ects ut is a hepatotoxin at very high doses$ Isoniazid& zidovudine& and toxicity$ Tramadol is a synthetic oral opioid that also loc,s neuronal reupta,e o# ar iturates can potentiate acetaminophen e continued e the e##ect o# opioids analgesics& !hich !ill cause increased intracranial pressure& resulting in headache& altered consciousness$ ;luid and

norepinephrine and serotonin$ It appears to have the same e##icacy as the com ination @A

o# codeine and acetaminophen ut is associated !ith signi#icantly less respiratory depression and has little e##ect on gastric emptying$

RE"ERENCE/ +asri& M$& %ri##& 6u,man& M$& 1adi& %$& %zrina& '((F$ ?eneral %naesthesia$ $naesthesiology for Medical %ndergraduatesB )A-@($

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Desai& %$M$& Macario& %$& ?reen& R$& Talavera& ;$& Mrugman& M$& Raghavendra& M$& '(33$ ?eneral %naesthesia$ %vaila le #rom: http:""emedicine$medscape$com"article"3'A3@=)overvie! I %ssessed 3F May '(3'J ;rilling& %$& 6iu& C$& >e er& ;$& '((=$ +enign Multinodular ?oiter$ candinavian &ournal of urgery& Hol$F): 'A8-'83 Neto& ?$M$& '(3($ Multinodular Goiter' Thyroid Disease Manager$ %vaila le #rom: http:""!!!$thyroidmanager$org"chapter"multinodular-goiter" I%ssessed 38 May '(3'J$ The %merican %ssociation o# .ndocrine 0urgeons& '((A . (enign )hyroid Enlargement (non* toxic multinodular goiter)$ %vaila le #rom: http:""endocrinediseases$org"thyroid"goiterYsymptoms$shtml I %ssessed 38 May '(3'J

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