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Steroid cover for dental patients on long-termsteroid medication: proposed clinical guidelinesbased upon a critical review of the literatureN. Gibson1 and J. W. Ferguson2

Based to a great extent upon mainly anecdotal case reports and theory, there is a general acceptance that patients on long-term systemic steroid medication should receive supplementary glucocorticoids or ‘steroid cover’ when undergoing certaintypes of stressful treatment including dentistry. The theoretical basis to this practice is that exogenous steroids suppressadrenal function to an extent that insufficient levels of cortisol can be produced in response to stress, posing the risk of acuteadrenal crisis with hypotension and collapse. The purpose of this paper is to review relevant literature and propose clinicalguidelines for dental practitioners. Of numerous reported cases of adrenal crisis following procedural interventions, fewstand up to critical evaluation. Other reviewers have reached similar conclusions. A number of studies confirm the lowlikelihood of significant adrenal insufficiency even following major surgical procedures. Various authors have suggestedmodified guidelines for management of patients on steroid medications. Patients on long-term steroid medication do notrequire supplementary ‘steroid cover’ for routine dentistry, including minor surgical procedures, under local anaesthesia.Patients undergoing general anaesthesia for surgical procedures may require supplementary steroids dependent upon thedose of steroid and duration of treatment.

1Registrar in Oral and Maxillofacial Surgery and MedicalStudent, Royal Dental Hospital and University ofMelbourne, 711 Elizabeth Street, Melbourne, Australia3000; 2*Director Oral and Maxillofacial Surgery Unit,Western Hospital, Gordon Street, Footscray, Victoria 3011and Professorial Fellow, University of Melbourne, 711Elizabeth Street, Melbourne, Australia, 3000*Correspondence to: J. W. FergusonE-mail: johnferg@bigpond.net.au

Refereed Paperdoi:10.1038/sj.bdj.4811857Received 02.12.02; Accepted 14.11.03© British Dental Journal 2004; 197: 681–685

INTRODUCTIONGlucocorticoids were first introduced inthe 1940s and have become a widely pre-scribed class of drugs. Subsequently, con-cern developed regarding the potential ofexogenous steroids to suppress normaladrenal gland function. This resulted indevelopment of recommendations foradditional glucocorticoid supplementa-tion, or ‘steroid cover', for management ofpatients undergoing stressful situations

such as surgery or dentistry.1–3 It has thusbecome common for standard textbooksin dentistry to recommend the administra-tion of oral or intravenous steroids priorto even minor dental procedures such asconservative dentistry.4 With theincreased understanding of adrenal func-tion and knowledge of glucocorticoidsduring the last 20 years, it is timely toreview this knowledge with reference towhether accepted guidelines for steroidcover remain appropriate. A literaturesearch was conducted through the Nation-al Library of Medicine PubMed database,using the search terms adrenal crisis,adrenal collapse, adrenal suppression,Addisonian crisis, steroid cover, coveringliterature up to December 2002. All identi-fied publications were considered for thepresent review, excluding however thosepapers which did not add materially to thepreviously published body of knowledgeon the subject.

REVIEW OF LITERATURE

Physiology of glucocorticoidsThe cortex of the adrenal gland producesboth sex (androgens) and corticoid hor-mones, the latter being divided into miner-alocorticoid (aldosterone) and glucocorti-coid (cortisol) steroids. Glucocorticoids areprincipally concerned with glucose metab-olism, have a ‘permissive role’ affectingmany physiological processes, and also alimited mineralocorticoid effect alteringelectrolyte and fluid balance by increasingsodium and water retention.5 Glucocorti-coids play a critical role in the body'sresponse to stress. Stress results in releaseof cytokines, and in particular the cytokineinterleukin-1, which causes cortisol levelsto rise thereby mobilising the body's glyco-gen and fat stores.6

Control of cortisol release is modulatedthrough the hypothalamic-pituitary-adre-nal (HPA) axis, whereby secretion of corti-

This paper :● Reviews the physiology of glucocorticoids. ● Provides an update on the therapeutic applications of steroid drugs. ● Provides an understanding of the theoretical basis for adrenal crisis and collapse. ● Provides the dental practitioner with guidelines for management of patients being treated

with steroid drugs.

I N B R I E F

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cotrophin-releasing hormone (CRH) fromthe hypothalamus in turn modulatesrelease of adreno-corticotrophic hormone(ACTH) from the anterior pituitary gland.Cortisol release is in direct response to theaction of ACTH. Cortisol, as well as exoge-nous glucocorticoids, functions to providenegative feedback on CRH release from thehypothalamus and thus ACTH.5

Glucocorticoid insufficiency Thomas Addison, in 1855, described theclinical syndrome associated with diseaseof the adrenal glands. Primary Addison'sdisease follows destruction of the adrenalgland, resulting in decreased mineralocor-ticoid and glucocorticoid levels.7 Autoim-mune disease has now superseded tubercu-losis as the most common cause of primaryAddison's disease, while other causes aremetastatic cancer, haemorrhage and fungaldisease,8 and an identical clinical state willalso arise following adrenalectomy. Sec-ondary Addison's disease results from defi-ciency of ACTH due to disease of the ante-rior pituitary gland, but may also resultfrom the action of exogenous glucocorti-coids in suppressing ACTH release. Thisleads to decreased glucocorticoid levelsonly, mineralocorticoid levels being notaffected as they are controlled by therenin-angiotensin system.7,9 Addison's dis-ease may present either as a chronic illness,or as an Addisonian or adrenal crisis asso-ciated with a stressful event when cortisollevels fail to meet the body's increasedrequirements.

Adrenal or Addisonian crisisUntreated adrenal failure is incompatiblewith life,10,11 and acute adrenal insufficien-cy is primarily a state of mineralocorticoiddeficiency.12 However, patients takingexogenous steroids may sometimes devel-op coexistent autoimmune adrenal disease,and experience Addisonian crisis due to themineralocorticoid deficiency alone.12 Threeclinical states associated with adrenal fail-ure are considered to occur.

1. Acute adrenal crisis, with insufficiencyof mineralocorticoids and glucocorti-coids, is a medical emergency. Thepatient presents with abdominal pain,weakness, hypotension, dehydration,nausea and vomiting.13 Laboratory find-ings may include decreased sodium(hyponatraemia), elevated potassium(hyperkalaemia), decreased blood glu-cose (hypoglycemia), acidosis anduraemia. Few patients have all thesefindings, with hypotension and nauseabeing most common.14

2. Patients with secondary Addison's dis-ease present less acutely, because miner-alocorticoid function is normal. The

most typical presentation is of hypoten-sion, and hyponatraemia without vol-ume depletion.9 Additional symptomsmay include fatigue, weakness, arthral-gia, nausea, and orthostatic dizzinessassociated with hypotension.

3. Patients taking exogenous glucocorti-coids. Exogenous glucocorticoids cancause adrenal gland suppression andresultant atrophy. With atrophy of theadrenal glands there is a decreased glu-cocorticoid response to stress, and thismay precipitate an adrenal crisis.7

Adrenal crisis and surgeryThe stress of surgery may precipitate adre-nal crisis in patients. Since 1952, fifty-seven cases have been reported of patientssuffering fatal circulatory collapse follow-ing surgery, believed to be due to cortisolinsufficiency, and these cases have beenreviewed and summarised in the paper bySalem et al.15 In reviewing these reports,firm evidence of definite adrenal insuffi-ciency was however identified for onlythree cases, while in three further casesadrenal insufficiency was the likely cause.The remaining cases were inconclusive ornot likely to have been related to cortisollevels. Cope21 has stated that most reportedcases of adrenal insufficiency ‘were a fail-ure of medical diagnostic skills not theadrenal glands.’ It could thus reasonably beconcluded that adrenal insufficiency lead-ing to acute adrenal crisis is considerablyover reported.

In oral and maxillofacial surgery twocases of adrenal crisis following dentalextractions have been reported. In the casedescribed by Cawson and James16 a 49-year-old male, taking 5 mg prednisolonedaily for rheumatoid arthritis, underwentgeneral anesthesia for 15 dental extrac-tions. The patient doubled his prednisolonedose on the day of the operation. Post-operatively he was referred to hospital withpersistent bleeding and found to haveblood pressure of 60 mm Hg systolic and40 mm Hg diastolic. Blood pressure rosefollowing administration of hydrocorti-sone, thus the hypotension was attributedto an adrenal crisis. In the case of Broutsasand Seldin17 a 53-year-old woman, taking37.5 mg cortisone (equivalent 7.5 mg pred-nisolone) for primary Addison's disease,had seven teeth extracted under generalanesthesia. Additional doses of 100 mgcortisone were administered 12 and 6hours preoperatively. Post-operatively shehad low blood pressure and signs of shockthat were attributed to adrenal crisis.

Both of these patients presented withlow blood pressure post-operatively, whichresponded to the administration of hydro-cortisone 100 mg at regular intervals overthe following 2 days. However, the admin-

istration of intravenous hydrocortisonewill produce a rise in blood pressure inhealthy patients, and cannot thus beregarded in these two cases as prima facieevidence of acute adrenal insufficiency.19

Hypotension following general anaesthesiacan have numerous causes, including nau-sea and failure to restore volume followingpre-operative fasting. Furthermore, neithercortisol levels nor electrolytes wereassessed, and the patients were not workedup for other causes of hypotension. It iscorrespondingly inconclusive that adrenalcrisis was the cause of hypotension ineither case.

A further case of adrenal crisis wasreported by Scheitler et al.,18 involving a43-year-old man undergoing tooth extrac-tion under local anaesthesia. However thispatient, who had well-documented second-ary Addison's disease subsequent to pitu-itary surgery and radiotherapy, had a reac-tion involving high fever and raised bloodpressure inconsistent with acute adrenalinsufficiency. This case therefore does notmeet any reasonable criteria for adrenalcrisis.

Exogenous glucocorticoids and adrenalsuppression Every day, 24 to 30 mg of cortisol (equiva-lent to 5–7.5 mg prednisolone) is releasedin a rhythmic pulsatile fashion. Understress this may increase to 300 mg (60 mgprednisolone equivalent) per day.22 Theexistence of adrenal suppression can betested by measuring the cortisol responseto ACTH or insulin.23

Bromberg et al.24 evaluated 60 trans-plant patients at the time of admission forsurgery or for serious medical conditions.The patients had all been taking 5 to 10 mgprednisolone for longer than 3 months andhad received no additional steroids. Com-pared with controls, the test group showedcomparative cortisol levels in response tostress. However a study by Schlaghecke etal.,25 of 279 patients receiving steroids,found a correlation between resting corti-sol levels and dose of steroids, but littlecorrelation between steroid dose and poorcortisol response to stress testing. Somepatients on low doses of steroid did notmount an increased cortisol level afteradministration of insulin or ACTH. There isno explanation for why this last study con-flicts with other published works, and gen-erally it is accepted that adrenal suppres-sion correlates with dose of glucocorticoidsand length of treatment.7,11

It is well established that patients withdocumented suppression of adrenal func-tion can undergo surgical treatment with-out event.27 Glowniak and Loriaux28 con-ducted a double blind study of 18 patientswith proven HPA suppression undergoing

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moderate to major surgery. The test groupreceived supplementation of 200 mg corti-sol for the first 24 hours followed by100 mg the second day and 50 mg the thirdday, while the control group received onlytheir regular steroid dose. Blood pressureperi-operatively was monitored, and nodifference found between the two groups.One patient in each group developed post-operative hypotension but both respondedto volume replacement. It may be that test-ing of cortisol response to ACTH or insulinis an unreliable surrogate end point foradrenal suppression, in other words the cri-teria measured are not a reflection or markerof the clinical situation.

In another study by Bromberg et al.,29

52 renal patients receiving between 10 and15 mg prednisolone daily underwent mod-erate surgery without additional steroids.Monitoring of cortisol levels showed anincrease in cortisol perioperatively and nopatients had signs of adrenal crisis. Kehletand Binder30 studied 104 patients whoceased taking their regular dose of exoge-nous glucocorticoids 36 hours prior to sur-gery, and whose bloodpressure and cortisollevels were monitored throughout surgery.The majority of these patients maintained anormal adrenal cortical response.

Patients who exhibited lower restingcortisol levels than controls did not devel-op hypotension, when compared withpatients with normal cortisol levels.

Seven patients experienced unexplainedhypotension, four of whom had normalcortisol levels and three slightly decreasedcortisol levels. The hypotension correctedspontaneously or following fluid replace-ment. It thus appears that HPA suppres-sion does not correlate with the ability ofthe adrenal glands to respond to stress.

Dluhy,31 in a review of inhaled steroidsand glucocorticoid activity, concluded thatinhaled steroids in high doses for a longterm could lead to suppression of the HPAaxis, possibly indicating the use of supple-mentary steroids during stress challenges.Recent case reports, well documented withrespect to measuring cortisol levels andundertaking stress testing, have confirmedthat high doses of inhaled steroids such asfluticasone and budesonide can causeadrenal suppression culminating in adrenalcrisis.32,33 Dluhy further concluded that therisk of adrenal insufficiency in patientstaking low to medium doses of inhaledsteroid was minimal, and did not indicateuse of supplementary steroids.

Glucocorticoid dose and HPA suppressionGenerally it is accepted that the degree ofHPA suppression is related to the length oftreatment and dose of steroids.7,11,26 Longterm steroid treatment, with doses equiva-lent to 10 mg prednisolone or greater, is

mostly likely to cause HPA suppression.26

This group of patients may develop symp-toms of fatigue, weakness, arthralgia, nau-sea, and orthostatic dizziness if theyabruptly stop steroids.9 Salem15 reviewedthe literature on this topic, concluding thatblanket recommendations for steroid coverwere not supported by evidence and thatmore significance should be attached to thedose and duration of therapeutic steroidtreatment. He additionally points out thatpatients taking doses above 50 mg pred-nisolone are close to the innate maximumcortisol level seen in patients whenstressed, therefore maintenance of theusual steroid dose is more critical than sup-plementary steroid doses, a view supportedby Glowniak.28

Daily doses of steroids at or below 5–7mg prednisolone a day are considered bysome authors to be under the physiologicalthreshold for causing adrenal suppression.There is however no consensus as towhether HPA suppression can occur inpatients taking low doses of steroids.34

In summary, adrenal suppression via theHPA axis is most likely to occur with highdoses of steroids, however such suppres-sion does not necessarily eliminate the nor-mal cortisol stress response.

Recovery from HPA suppressionHPA recovery, following cessation of highdose short to medium term steroids, occurswithin 2 months. Spiegel et al.35 evaluatedrenal transplant patients who received40–100 mg prednisolone daily for 2–4weeks, demonstrating that all had recov-ered normal adrenal function by 7 days.Webb and Clark36 evaluated cortisol levelsin patients who received 40 mg pred-nisolone daily for 3 weeks and found corti-sol levels normal after 4 days. Levic et al.37

studied 10 multiple sclerosis patientsadministered 1000 mg methylprednisolone(equivalent to 1200 mg prednisolone) for 7 days, and found no HPA suppression 10 days after ending the therapy.

The natural history of recovery follow-ing prolonged suppression of the HPA axisis manifested as a depressed response toACTH testing for 9 months or more.38 How-ever, as previously stated, this will not nec-essarily reflect the functional status of theHPA axis which in most instances will benormal.

Adrenocortical response to stress

AnxietyStudies have evaluated what constitutesstress and causes increases in cortisol levels.Surprisingly, in both the study by Banks39

of oral and maxillofacial surgery patients,and that of Udelsman et al.41 of general sur-gery patients, it was demonstrated that

apprehension about surgery is not a stimu-lus for adrenal cortical secretion.

AnaesthesiaNo cases of adrenal insufficiency havebeen reported in patients undergoing pro-cedures under local anaesthesia. In a studyby Bunch et al.51 of patients having thirdmolar teeth removed under local anaesthe-sia, significant increases of cortisol levelsdid not occur. Similarly, in a small studyShepherd et al.50 assessed cortisol levels inpatients undergoing periodontal surgeryunder local anaesthesia alone or with con-scious sedation. Cortisol levels fell duringthe 90 minutes procedure, a more signifi-cant fall occurring in the patients receivingconscious sedation.

Hempenstall et al.52 compared cortisollevels in patients having either a generalanaesthetic or sedation for surgical removalof third molar teeth. Cortisol levels remainedunchanged in the sedation group but rosesignificantly after surgery in patients whohad a general anaesthetic.

General anaesthesia alone will cause anincrease in cortisol levels. Oyama et al. 46,47

measured cortisol levels in patients undergeneral anaesthesia for 45 minutes prior tosurgery, and found a steady increase incortisol with a peak in the recovery phase.It has been shown by Crozier49 that certainanaesthetic drugs may cause a fall in corti-sol levels during the peri-operative phase,but rapid recovery to normal levels follows.Udelsman et al.41 reported that reversal ofgeneral anaesthesia and extubation com-prised a major stimulus to increase in corti-sol levels, although levels were minimallyaltered during anaesthesia and surgery.

SurgeryKehlet and Binder30 measured cortisol lev-els in 74 patients previously treated withglucocorticoids, who underwent major sur-gery without steroid supplementation.Eighteen patients developed post-operativehypotension, but in all cases the hypoten-sion corrected spontaneously. Three ofthese patients were considered to have mildadrenocortical deficiency based on meas-ured cortisol levels. These authors conclud-ed that cortisol levels were not the primarydeterminant of hypotension in glucocorti-coid-treated patients, and that acute stress-induced adrenocortical deficiency in suchpatients was likely to be infrequent. Naitoet al.45 studied the changes in plasma corti-sol levels during and following majorabdominal surgery, demonstrating theexpected elevations and defining themechanisms involved. Complete normali-sation of cortisol levels after major surgerymay take up to 72 hours, with significantelevation occurring only in the first 48hours. King et al.48 measured cortisol levels

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in patients undergoing laminectomy, withcomparable findings of a modest increaseimmediately following surgery. Crozier etal.49 studied patients undergoing minororthopedic procedures, with similar find-ings, cortisol levels returning to normal by6 hours. Chernow et al.53 demonstrated adirect correlation between the degree ofsurgical stress and elevation of plasma cor-tisol, with minor procedures having a neg-ligible effect compared with major surgery,with return to normal levels usually within24 hours.

DentistryThere is a relative paucity of studiesexamining whether routine dental treat-ment has an effect on plasma cortisol lev-els. However some studies have examinedsalivary cortisol levels as these are con-sidered by some authors to correlate wellwith plasma cortisol levels,54 althoughother studies55 have suggested a bettercorrelation of urinary cortisol levels withthose of plasma. Investigations byBrand,55 Miller et al.56 and Akyuz et al.57

have shown an increase in salivary corti-sol levels both before and during restora-tive dental treatment. Additionally, thestudy by Brand demonstrated persistentelevated urinary levels of cortisol follow-ing treatment.

Banks39 studied 50 healthy patientsundergoing general anaesthesia for thirdmolar surgery, mandibular osteotomies ordental clearances. In these patients cortisollevels rose approximately 4 hours after sur-gery and returned to base line levels by 24hours. On the basis of these findings Banksconcluded that routine oral and maxillofa-cial surgery constituted minor surgery andwould not warrant more than 1 day ofsteroid supplementation.

A more recent study by Thomason et al.40

examined the need for supplementarysteroids in organ transplant patients under-going gingival surgery. This well-designedstudy identified no differences between onegroup receiving supplementary hydrocorti-sone 100 mg and another receiving placebo,when assessed by measurement of bloodpressure and ACTH levels.

PROPOSED CLINICAL GUIDELINES

Glucocorticoid supplementation or‘steroid cover’General dental procedures for patientsreceiving long-term steroid medication donot warrant supplementation with addi-tional glucocorticoids.

Patients undergoing minor surgical pro-cedures under local anaesthesia are at verylow risk, if any, for developing adrenal crisis. Although opinions conflict onwhether any significant suppression of

adrenal function occurs in patients takinglow doses of steroids (under 7.5 mg pred-nisolone) available evidence suggests thatsupplementation is unnecessary for localanaesthetic procedures. These patientsshould simply maintain their usual dose ofglucocorticoids. However those patientstaking high doses of steroid should doublethe usual dose on the day. Unexplainedhypotension in patients on exogenoussteroids should be investigated for otherpossible causes, because adrenal crisis israre and patients on glucocorticoids are athigh risk of various other medical compli-cations. If adrenal insufficiency is suspect-ed, follow-up with an endocrinologist isimportant, as secondary adrenal diseaseneeds to be ruled out.

For surgical procedures under generalanaesthesia, the need for peri-operativeglucocorticoid supplementation, forpatients on exogenous steroids, should bedetermined by the severity of the surgeryand the pre-existing glucocorticoid dose,and there is no evidence that glucocorti-coid supplementation exceeding physio-logical levels of cortisol induced by stress isbeneficial. Thus, for patients undergoinggeneral anesthesia for minor surgery100 mg hydrocortisone intramuscularlyshould be administered and the usual glu-cocorticoid medications maintained. Formajor surgery 100 mg hydrocortisonedelivered as a bolus pre-operatively fol-lowed by 50 mg 8-hourly for 48 hours isadequate.

An alternative regimen for surgicalpatients is that proposed and successfullytrialled by Lloyd42 for orthopaedic patients,where hydrocortisone was given asrequired based on measurement of post-operative levels of blood pressure and pulserate. It was found that 78% of patientsrequired no supplementation, and surpris-ingly small doses for those who did. A fur-ther option is to undertake pre-operativestress testing by assessing cortisol responseto insulin or ACTH challenge.

The risks of excess glucocorticoidadministration are relatively small, involv-ing mainly impaired electrolyte balanceand hypertension,10 however pharma-cotherapy should be based on current sci-entific and clinical knowledge, thusdecreasing overtreatment and inconven-ience to patient and practitioner.

SUMMARYPatients with primary Addison's disease aremost at risk of acute adrenal insufficiency.The risk of clinically significant adrenalinsufficiency is low in patients takinglong-term steroid medication. For this latter group of patients, performance ofroutine dentistry including minor surgicalprocedures under local anaesthesia does

not require supplementary steroids. Forpatients undergoing surgery under generalanaesthesia, provision of supplementalglucocorticoids needs to be balancedagainst the dose and duration of treatmentwith steroid drugs and the severity of theplanned surgery.

1. Plumpton F S, Besser G M, Cole P V. Corticosteroidtreatment and surgery. Anaesthesia 1969; 24: 3-18.

2. Kalkwarf K L, Hinrichs J E, Shaw D H. Management ofthe dental patient receiving corticosteroidmedications. Oral Surg Oral Med Oral Pathol 1982; 54:396-400.

3. Luyk N H, Anderson J, Ward-Booth R P. Corticosteroidtherapy and the dental patient. Br Dent J 1985; 159;12-17.

4. Scully C, Cawson R A. Medical problems in dentistry.4th ed. p 272. Oxford: Wright, 1998.

5. Moffett D E, Moffett S, Schauf C L. Human physiology.Foundations and Frontiers. 2nd ed. pp 96-135. StLouis: Mosby, 1993.

6. Naito Y, Tamai S, Shingu K, et al. Responses of plasmaadrenocortioctropic hormone, cortisol, and cytokinesduring and after upper abdominal surgery.Anesthesiol 1992; 77: 426-431.

7. Edwards C R, Baird J D, Frier B M, Shepherd J, Toft A D.Endocrine and metabolic diseases, including diabetesmellitus. In Edwards C R, Bouchier I A, Haslett C,Chilvers E R (eds) Davidson's principles and practice ofmedicine. 17th ed. pp 706-719. Edinburgh: ChurchillLivingstone, 1995.

8. Stoffer S S. Addison's Disease. How to improvepatients' quality of life. Postgrad Med 1993; 93: 265-266, 271-278.

9. Byyny R L. Preventing adrenal insufficiency duringsurgery. Postgrad Med 1980; 67: 219-228.

10. Swingle W W, Remington J W, Drill V S, Kleinberg W.Differences among adrenal steroids with respect totheir efficacy in protecting the adrenalectomized dogagainst circulatory failure. Am J Physiol 1942; 136:567-576.

11. Swingle W W, Hays H W, Remington J W. The effect ofprimary doses of desoxycorticosterone acetate inpreventing circulatory failure and shock in theadrenalectomized dog. Am J Physiol 1949 ; 132: 249-258.

12. Cronin C C, Callaghan N, Kearney P J, Murnaghan D L,Shanahan F. Addison disease in patients treated withglucocorticoid therapy. Arch Intern Med 1997; 157:456-458.

13. Jordan R M. Endocrine emergencies. Med Clin NorthAm 1983; 67: 1193-1213.

14. Gilliland P F. Endocrine emergencies. Adrenal crisis,myxedema coma and thyroid storm. Postgrad Med1983; 74: 215-220.

15. Salem M, Tainsh R E, Bromberg J, Loriaux D L,Chernow B. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of aproblem. Ann Surg 1994; 219: 416-425.

16. Cawson R A, James J. Adrenal crisis in a dental patienthaving systemic corticosteroids. Br J Oral Surg 1973;10: 305-309.

17. Broutsas M G, Seldin R. Adrenal crisis after toothextractions in an adrenalectomized patient: report ofcase. J Oral Surg 1972; 30: 301-302.

18. Scheitler L E, Tucker W M, Christian D C. Adrenalinsufficiency: report of case. Spec Care Dent 1984; 4:22-24.

19. Mattingly D, Tyler C. Plasma 11-hydroxycorticoidlevels in surgical stress. Proc R Soc Med 1965; 58:1010-1012.

20. Whitworth J A. Adrenocorticotrophin and steroid-induced hypertension in humans. Kidney Int Suppl1992; 37: S34-37.

21. Cope C L. The adrenal cortex in internal medicine. I. Br Med J 1966; 2: 847-853.

22. Montgomery M T, Hogg J P, Roberts D L, Redding S W.The use of glucocorticosteroids to lessen theinflammatory sequelae following third molar surgery.J Oral Maxillofac Surg 1990; 48: 179-187.

23. Talwar V, Lodha S, Dash R J. Assessing the

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BRITISH DENTAL JOURNAL VOLUME 197 NO. 11 DECEMBER 11 2004 685

hypothalamo-pituitary-adrenocortical axis usingphysiological doses of adrenocorticotropic hormone.Q J Med 1998 ; 91: 285-290.

24. Bromberg J S, Alfrey E J, Barker C F, et al. Adrenalsuppressioon and steroid supplementation in renaltransplant recipients. Transplantation 1991; 51: 385-390.

25. Schlaghecke R, Kormely E, Santen R T, Ridderskamp P.The effect of long-term glucocorticoid therapy onpituitary-adrenal responses to exogenouscorticotropin-releasing hormone. N Engl J Med 1992;326: 226-230.

26. Bell N H The glucocorticoid withdrawal syndrome.Adv Expl Med Biol 1984; 171: 293-299.

27. Knudsen L, Christiansen L A, Lorentzen J E.Hypotension during and after operation inglucocorticoid-treated patients. Br J Anaesth 1981;53: 295-301.

28. Glowniak J V, Loriaux D L. A double-blind study ofperioperative steroid requirements in secondaryadrenal insufficiency. Surg ery 1997; 121: 123-129.

29. Bromberg J S, Baliga P, Cofer J B, Rajagopalan P R,Friedman RJ. Stress steroids are not required forpatients receiving a renal allograft and undergoingoperation. J Am Coll Surg 1995; 180: 532-536.

30. Kehlet H and Binder C. Adrenocortiocal function andclinical course during and after surgery inunsupplemented glucocorticoid-treated patients. BrJ Anaesth 1973; 45: 1043-1048.

31. Dluhy R G. Clinical relevance of inhaledcorticosteroids and HPA axis suppression. J AllergyClin Immunol 1998; 101: S447-450.

32. Todd G R, Acerini C L, Buck J J et al. Acute adrenalcrisis in asthmatics treated with high-dosefluticasone propionate. Eur Respir J 2002; 19: 1207-1209.

33. Dunlop K A, Carson D J, Shields M D. Hypoglycemiadue to adrenal suppression secondary to high-dosenebulized corticosteroid. Pediatr Pulmonol 2002; 34:85-86.

34. Bahn S L . Glucocorticosteroids in dentistry. J Am DentAssoc 1982; 105: 476-481.

35. Spiegel R J, Vigersky R A, Oliff A I, Echelberger C K,

Bruton J, Poplack D G. Adrenal suppression aftershort-term corticosteroid therapy. Lancet 1979; 1:630-633.

36. Webb J, Clark T J. Recovery of plasma corticotrophinand cortisol levels after three-week course ofprednisolone. Thorax 1981; 36: 22-24.

37. Levic Z, Micic D, Nikolic J et al. Short-term high dosesteroid therapy does not affect the hypothalamic-pituitary-adrenal axis in relapsing multiple sclerosispatients. Clinical assessment by the insulin tolerancetest. J Endocrinol Invest 1996; 19: 30-34.

38. Livanou T, Ferriman D, James V H. Recovery ofhypothalamo-pituitary-adrenal function aftercorticosteroid therapy. Lancet 1967; 2: 856-859.

39. Banks P. The adreno-cortical response to oral surgery.Br J Oral Surg 1970; 8: 32-44.

40. Thomason J M, Girdler N M, Kendall-Taylor P, WastellH, Weddel A, Seymour R A. An investigation into theneed for supplementary steroids in organ transplantpatients undergoing gingival surgery. A double-blind,split-mouth, cross-over study. J Clin Periodontol1999; 26: 577-582.

41. Udelsman R, Norton J A, Jelenich S E, et al. Responsesof the hypothalamic-pituitary-adrenal and renin-antiotensin axes and the sympathetic system duringcontrolled surgical and anesthetic stress. J ClinEndocrinol Metab 1987; 64: 986-994.

42. Lloyd E L. A rational regimen for perioperative steroidsupplements and a clinical assessment of therequirement. Ann R Coll Surg Engl 1981; 63: 54-57.

43. Reding R, Michel L A, Donckier J, de Canniere L, andJamart J. Surgery in patients on long-term steroidtherapy: a tentative model for risk assessment. Br JSurg 1990; 77: 1175-1178.

44. Fraser C G, Preuss F S, Bigford W D. Adrenal-atrohyand irreversible shock associated with cortisonetherapy. J Am Med Assoc 1952; 148: 1542.

45. Naito Y, Fukata J Tamai S, et al. Biphasic changes inhypothalamo-pituitary-adrenal function during theearly recovery period after major abdominal surgery. J Clin Endocrinol Metab 1991; 73: 111-117.

46. Oyama T, Takiguchi M, Nakai Y, Imura H. Plasma levelsof ACTH and cortisol in man during droperidol-

pentazocine anesthesia and surgery. Anesth Analg1972; 51: 726-730.

47. Oyama T, Takiguchi M. Plasma levels of ACTH andcortisol in man during halothane anesthesia andsurgery. Anesth Analg 1970; 49: 363-366.

48. King L R, McLaurin R L, Lewis H P, Knowles HC Jr.Plama cortisol levels after head injury. Ann Surg 1970;172: 975-984.

49. Crozier T A, Beck D, Schlaeger M, Wuttke W, Kettler D.Endocrinological changes following etomidate,midazolam or methohexital for minor surgery.Anesthesiol 1987; 66: 628-635.

50. Shepherd S R, Sims T N, Johnson B W, Hershman J M.Assessment of stress during periodontal surgery withintravenous sedation and with local anesthesia only. J Periodontol 1988; 59: 147-154.

51. Bunch F L, Allen G D, Jorgensen N B. Analysis of bloodcortisol levels in oral surgery patients given variouslevels of intravenous medication. J Dent Res 1975;54: 965-967.

52. Hempenstall P D ,Campbell J P S ,Bajurnow A T,Preade P C, McGrath B, Harrison L C. Cardiovascular,biochemical, and hormonal responses to intravenoussedation with local analgesia versus generalanesthesia in patients undergoing oral surgery. J OralMaxillofac Surg 1986; 44: 441-446.

53. Chernow B, Alexander H R, Smallridge R C et al.Hormonal responses to graded surgical stress. ArchIntern Med 1987; 147: 1273-1278.

54. Groschl M, Wagner R, Rauh M, Dorr H G. Stability ofsalivary steroids: the influences of storage, food anddental care. Steroids 2001; 66: 737-741.

55. Brand H S. Anxiety and cortisol excretion correlateprior to dental treatment. Int Dent J 1999; 49: 330-336.

56. Miller C S, Dembo J B, Falace D A, Kaplan A L. Salivarycortisol response to dental treatment of varyingstress. Oral Surg Oral Med Oral Pathol Oral RadiolEndod 1995; 79: 436-441.

57. Akyuz S, Pince S, Hekin N. Children's stress during arestorative dental treatment: assessment usingsalivary cortisol measurements. J Clin Pediatr Dent1996; 20: 219-223.

British Dental Journal

Fatal Delights of ‘Gas’

According to the daily Press, at an inquest on a married woman who had been suffocated bycoal-gas, it was stated that about a week before her death the deceased had had a tooth extractedunder nitrous oxide, and she had done nothing but talk about the delightful sensation ever since,regretting that she had not another bad tooth.

She said she had a delightful dream, and it was thought not at all unlikely that she fanciedcoal-gas would give her a similarly pleasant sensation. The jury found that the deceased diedfrom coal-gas suffocation; but the motive they left an open question.

Br Dent J 1904

One Hundred Years Ago

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