To the Editor: In their recent “Clinical Update” on adrenal insufficiency, Jung and Inder1 state:

The patient described in the case report2 was admitted with septic arthritis. His usual cortisone dose of 12.5 mg had been omitted that evening, and his morning dose of 25 mg was not given the next day until after he had returned from the operating theatre. Over the next 3 days, he became overtly septic, and returned to theatre for another knee washout. Cortisone was not given during this time. When he developed acute renal failure on Day 5, dehydration and gentamicin toxicity were listed as possible causes.

The article by Jung and Inder does not make it clear that the case report contains nothing of relevance to the management of patients with adrenal insufficiency who are fasting for routine surgical procedures, as this man’s hypotension and acute renal failure actually developed over 5 days in the context of sepsis, dehydration and possible gentamicin toxicity, in addition to prolonged withholding of cortisone and two operations.

To the Editor: The recent article by Jung and Inder1 provides sensible advice for the safe management of adults with adrenal insufficiency (AI) during illness and surgery, without risking adrenal crisis or excessive steroid dosing. However, the authors make no reference to paediatric practice and no guidelines have been provided for the body-size-related steroid doses required in paediatric patients with AI, either for routine steroid replacement or during illness and surgery. It is important that doctors be aware that the doses recommended by Jung and Inder are not suitable for children with AI.

In keeping with recent studies of daily cortisol production, daily hydrocortisone replacement doses of 6–8 mg/m2/day are now recommended for children with secondary AI (eg, due to adrenocorticotropic hormone deficiency), provided the patient has no hypoglycaemia or symptoms of cortisol deficiency.2 In children with primary AI, higher hydrocortisone doses are often necessary (up to 10–15 mg/m2/day) — for example, to minimise adrenal androgen secretion in children with congenital adrenal hyperplasia.3

During minor illness (as defined in Box 3 of Jung and Inder’s article1), a child’s usual daily oral dose of glucocorticoid should be doubled or tripled until recovery.3,4 However, for children with secondary AI who are on the lower doses of daily hydrocortisone (about 6–8 mg/m2/day), these multiples may not constitute adequate doses during stress. In these patients, per-m2 dosing is more accurate (ie, 30–40 mg/m2/day for minor illnesses).

During moderate-to-severe illness, for patients who are vomiting, those who have experienced trauma and those undergoing anaesthesia and surgery, the following doses of intravenous hydrocortisone are recommended:

• For children aged < 3 years: 25 mg initial dose then 25–30 mg/day;

• For children aged 3–12 years: 50 mg initial dose then 50–60 mg/day; and

• For adolescents and adults: 100 mg initial dose then 100 mg/day.

These doses are in keeping with national4 and international3 recommendations, and equate to doses of 60–100 mg/m2/day of hydrocortisone. The more accurate per-m2 dosing should be used for children who are not within the normal weight range for their age.

These recommendations for children are extrapolated from adult studies and also based on expert consensus. Attention to the specific body-size dose adjustments required in paediatric prescribing can provide safe levels of steroid cover while avoiding exposure to excessive steroid doses.

To the Editor: The excellent article by Jung and Inder1 in a recent issue of the Journal contains a detailed discussion of different regimens proposed for glucocorticoid supplementation in the perioperative period and makes recommendations for the use of hydrocortisone therapy according to the degree of “surgical stress”. It is worth noting that, in many cases, these recommendations and the detailed advice of endocrinologists regarding individual patients are rendered moot by the changes in routine perioperative antiemetic therapy that have occurred in the past decade.

The use of intravenous dexamethasone as an antiemetic has been the subject of much clinical research. The IMPACT study2 showed that it has an antiemetic efficacy similar to that of ondansetron or droperidol when given prophylactically. Dexamethasone is less expensive than either of these drugs and is ineffective as rescue therapy in the setting of postoperative nausea and vomiting (PONV), unlike the alternative drugs. As a result, it is used routinely on induction of anaesthesia in many cases of surgery associated with an increased risk of PONV or where PONV would pose a risk of injury or delayed discharge.

A range of doses of dexamethasone for antiemetic prophylaxis has been investigated without finding superior efficacy from higher doses (of up to 1.0 mg/kg).3 The dose typically used in clinical anaesthesia practice is 0.05–0.1 mg/kg. This is equivalent in glucocorticoid activity to more than the highest dose of hydrocortisone described in the guidelines of Jung and Inder1 and should provide a self-tapering effect over 2–3 days, consistent with their recommendations for hydrocortisone dosing.

In reply: We thank Woodforth for his interest in our article.1 The cited case report2 involved a patient with panhypopituitarism who had septic arthritis following a total knee replacement, requiring knee washout. As stated by Woodforth, the patient was without glucocorticoid replacement for 5 days, during which time he underwent two surgical procedures. Symptoms of cortisol deficiency were described on Days 1 and 2 postoperatively, with overt sepsis not manifesting until Day 3. The absence of adequate glucocorticoid replacement while the patient was under a “nil oral” instruction and suffering sepsis was undoubtedly a contributory factor in his decline, given that his condition improved significantly after he had received 24 hours of intravenous hydrocortisone treatment and other supportive care. It appears that the cortisone acetate was withheld because of concerns about administering it without food, as other medications were in fact given.

We stand by our assertion that patients with proven or suspected cortisol deficiency should receive adequate glucocorticoid replacement before and after surgery, according to the likely stress of the procedure. Often, for minor procedures, an oral route of administration will suffice. Doses of oral glucocorticoids given under these circumstances do not need to be taken with food. If there are sound clinical reasons for the patient not to have any medications orally, then parenteral administration is appropriate.1

Maguire and colleagues correctly point out that the glucocorticoid dosage recommendations in our article are suitable only for adults. They have made a significant contribution to the literature on the investigation and management of paediatric adrenal insufficiency and we would like to thank them for providing the appropriate glucocorticoid doses for paediatric patients under stress.

We are aware of the use of dexamethasone as a perioperative antiemetic, as outlined by Mitchell, although it is not clear how widespread this practice is. He is correct in stating that in cases in which dexamethasone is used for this purpose, the glucocorticoid dose thereby provided is likely to be more than adequate for adrenal replacement. However, dexamethasone has no mineralocorticoid activity, and this must be taken into account when treating patients with primary adrenal insufficiency. Doses of hydrocortisone greater than 50–75 mg per 24 hours provide adequate mineralocorticoid replacement. If dexamethasone is used for patients with primary adrenal insufficiency undergoing surgery, it is imperative that the patient continue to take oral fludrocortisone throughout the perioperative period to provide mineralocorticoid replacement. This highlights the need for good communication between the patient’s general practitioner, endocrinologist, surgeon and anaesthetist to ensure the best patient outcome.