Indian Journal of Anaesthesia 2007; 51 (5) : 389-393

Special Article

Steroid Therapy Current Indications in Practice

V. K. Grover 1, Ramesh Babu2 , S. P. S. Bedi3 Summary
Steroids are a widely used group of drugs in anaesthesia practice, sometimes with definite indication and sometimes without indication. When used judiciously they have proved to be of immense help. There has been a renewed interest in the use of steroids in modern day perioperative medicine. In the following article the recent trends, relevance and consensus issues on the use of steroids as adjunct pharmacological agents in relation to anaesthesia have been discussed, along with emphasis on important clinical aspects of their perioperative usefulness.

Key words Steroids; Replacement therapy; Hyper-reactive airway; Anaphylaxis; Post- operative nausea & vomiting; Day care surgery; Septic shock; Cerebral oedema; Spinal cord oedema; Anti- inflammatory. The steroids are among the most widely used class of drugs and their role in the therapy of pulmonary, inflammatory, dermatological and oncological diseases has been well described. There is an increasing application of steroid therapy during perioperative period for various purposes. Some of the current indications are:1. 2. 3. 4. 5. 6. 7. 8. Perioperative replacement therapy. Anti-inflammatory uses and hyper-reactive airway Post operative nausea and vomiting (PONV) Analgesia adjunct Day care surgery Anaphylaxis Septic shock Other indications like cerebral oedema, spinal cord injury, various surgical causes.

Steroids in replacement therapy

Steroid administration is necessary in perioperative period in patients treated for hypoadrenocorticism or in a patient with separation of pituitary adrenal axis owing to present or previous steroid intake. The increase in circulating cortisone levels in response to surgical trauma is one of the important components of stress response of our body. In perioperative setting this response is essential to avoid haemodynamic instability, metabolic, electrolyte, and fluid imbalances. In a well controlled study of glucocorticoid replacements in animals the investigators clearly defined the life threatening events, from haemodynamic fluctuations to addisonian crisis leading to death that can be associated with inadequate replacement of cortisol in perioperative setup 2. Table 1 Comparison of various corticosteroids
Compound AntiNa inflammat- retaining ory potency potency 1 0.8 4 4 5 5 25 1 0.8 0 0.8 0.8 0.5 0 0 Duration of action S S L I I I I L Equivalent dose 20 25 0.75 5 5 4 4 0.75

Steroids have different effects on different tissues, which are dose dependent. The reason for varied effect of steroids lies in its mechanism of action. Tissue specificity of steroid hormone action is achieved by tissue specific expression of steroid receptors and transcription factors. Natural and synthetic steroids display varied receptor-binding affinities and pharmacokinetic features. The relative potency of different steroids has generally been defined on the basis of pituitary ACTHsuppressive effect in the morning after single dose of oral steroids1. Equivalent doses apply only to oral or intravenous preparations- Short (8-12 Hrs), L- Long (36-72 Hrs), IIntermediate (12-36 Hrs)

Cortisol Cortisone Prednisone Prednisolone 6-methyl Prednisolone Triamcinolone Betamethasone

Dexamethasone 25

The specific duration and dose of steroid that can produce pituitary adrenal axis suppression is controver-

1. Professor, MD,MNAMS, 2. Senior Resident,MD, 3. Senior Resident, MD,DNB Department of Anaesthesia & Intensive Care Post Graduate Institute of MedicalEducation and Research Chandigarh, Correspondence to : Prof. V K Grover, H. No. 53 Sector 24A, Chandigarh160023. E-mail-vinodkgrover@gmail.com Accepted for publication on:1.8.07

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Indian Journal of Anaesthesia, October 2007 sial. The time required for the recovery from the suppression due to steroid intake varies from 2-5 days 3 to nine months4. Certainly more suppression may be expected in the setting of higher and longer duration of steroid therapy. Evaluation of the status of HPA axis and the adrenal reserve of the patients who have received steroid therapy should be based on biochemical testing, if available. A conservative estimate is to consider perioperative steroid therapy in all patients who have received steroids for at least one month in the past 6-12 months. There is no fixed steroid replacement protocol which is widely accepted. The amount of steroid supplementation dose and the duration should be based on the magnitude of surgical stress as well as preoperative steroid dose and the degree of HPA suppression. One of the widely practiced steroid replacements in perioperative setting is given by Kehlet, Symreng et al and Salem et al5, 6, 7(Table 2). Patients taking steroids for immunosuppression in organ transplantation need same high supraphysiological dosage during perioperative period to prevent deterioration in the transplanted organ function. These patients do not need additional steroid coverage since immunosuppressive doses are more than sufficient to maintain cardiovascular stability. It is important to note that the oral steroids must be supplemented by parenteral steroids in equivalent doses. For example, a patient who is taking 60 mg prednisolone per day requires 250mg hydrocortisone infusion over 24 hours during perioperative period till oral intake is established. minished secretion of lipolytic and proteolytic enzymes, decreased extravasation of leucocytes to area of injury. The net effect of these actions on various immune cells, results in a diminished inflammatory response. Anti-inflammatory property is usually seen with higher doses. For their anti-inflammatory actions common perioperative indications are (a) Hyper-reactive airways: asthma, foreign body, and trauma. (b)Anaphylactic reactions: drug allergies, blood transfusion reactions. (c)Transplantation of solid organs. (d) Spinal cord injuries (within 8 hours of injury).Connective tissue disorders or autoimmune disorders. Table 2 Perioperative steroid replacement therapy
Patient currently <10 mg per day Assume normal Additional steroid taking steroid (Prednisolone) HPA response cover not requi red >10 mg per day Minor surgery 25 mg hydrocort isone at induction Moderate surgery Usual preoperat ive steroid+25 mg hydrocortisone at i nduc ti o n+ 1 0 0 mg/day for 24 hrs Major surgery Usual preopera tive steroid+25 mg hydrocorti sone at induc tion+100 mg/day for 48-72 hrs High dose immunosuppr essive Give usual immunosuppressive dose during perioperative period Treat as if on steroids No perioperative steroids necessary

Patient stopped < 3 months taking steroid > 3 months

Steroids as anti-inflammatory
Steroids profoundly alter both the cellular and humoral immune responses. These can prevent or suppress inflammation in response to multiple inciting events including radiation, mechanical, chemical, infectious and immunological stimuli. Multiple mechanisms are involved in the suppression of inflammation by steroids. They inhibit the production of various inflammatory factors which are critical in generating and propagating the inflammatory response like interleukins, cytokines, and chemotactic agents. As a result there is a decreased release of vasoactive and chemo-attractive factors, di390

Steroids in hyper-reactive airway

Although steroids are not true bronchodilator, they have well established usefulness in hyper-reactive airway. Their action is mainly by virtue of their anti-inflammatory action leading to decreased mucosal oedema and prevention of release of broncho-constricting substances. They are also said to have a permissive role for bronchodilator medication i.e. they enhance efficacy of bronchodilator medication. They are useful in both acute as well as chronic hyper-reactive diseases. For this purpose they can be administered orally, parenterally or in aerosol form. The most commonly encoun-

V.K. Grover et al. Steroid therapy current indications in practice tered hyper-reactive states in anaesthetic practice are patients with history of asthma, recent upper respiratory tract infection, difficult airway, multiple intubation attempts, aspiration, foreign body bronchus, airway surgeries and COPD. In these settings, usually, steroid is given in anti-inflammatory doses to have their beneficial role of preventing inflammatory mediated airway oedema as well as broncho-constriction. may be due to their anti-inflammatory action resulting in decrease of production of various inflammatory mediators that play a major role in amplifying and maintenance of pain perception. They have also been seen to increase the endorphin levels and mood elevation15

Steroids and day care surgery

Various studies of steroids in perioperative setting have shown that they are beneficial in preventing factors which delay the patients discharge in ambulatory surgeries. Steroids decrease the incidence of PONV, postoperative pain, establish early oral intake, produce euphoric effect by decreasing level of prostaglandins, and elevating those of endorphins Aasboe et al used betamethasone 12 mg intramuscularly, 30 minutes prior to ambulatory hemorrhoidectomy or hallux valgus correction and they found significantly less postoperative pain, less PONV, and better patient satisfaction 16.

Steroids and PONV

Recently various studies have been conducted to evaluate the efficacy of steroids in managing PONV8. Steroids have been commonly used in chemotherapy for prevention of nausea along with other anti-emetic agents. Optimum dose was found to be 10mg of dexamethasone, and same dose was found to be highly effective when given immediately before induction rather than at the end of anaesthesia9. In meta-analysis of randomized trials, Hirayama et al found that dexamethasone was more effective than either droperidol or metoclopramide in the prevention of PONV induced by morphine after surgery10. Tzeng et al reported that dexamethasone alone did not reduce the incidence of PONV in women receiving general anaesthesia for dilatation and curettage, but it did appear to enhance the antiemetic effect of droperidol11. Studies have been done to know the synergy between 5HT3 receptor antagonist and dexamethasone. Fujii et al investigated the antiemetic efficacy of granisetron with or without dexamethasone given immediately prior to induction in patients undergoing laparoscopic cholecystectomy or thyroidectomy. There was significant decreased incidence of PONV in combination group compared to granisetron alone group. This suggests that dexamethasone and 5HT3 receptor antagonist act at different sites and overall combination is superior to individual drug alone. The mechanism by which it reduces PONV is not known, but is thought to be due to decrease in production of inflammatory mediators which are known to act on the CTZ area as well as improve the blood-brain barrier function, it is also known to act synergistically with 5HT3receptors antagonists.

Steroids and anaphylactic/ allergic reaction.

Steroids cannot be the mainstay of therapy in anaphylaxis because of the delayed onset of action,so they are used as adjunct after initial treatment with epinephrine ( adults) : 0.5 ml of 1:1000 intramuscular or subcutaneous ,which may be used every 15 min for upto 3 times. Glucocorticoids can supplement primary therapy to suppress manifestations of allergic diseases of a limited duration like Hay fever, serum sickness,urticaria, contact dermatitis, drug reactions, bee stings, and angioneurotic edema. In very severe diseases intravenous methylprednisolone 125mg every 6 hours, or equivalent can be used. In less severe diseases antihistaminics form the first choice.

Steroids and sepsis/septic shock

Patients having severe sepsis or in septic shock were found to have occult or unrecognized adrenal insufficiency, incidence may be has high as 28% in seriously ill patients 17. Clinically it has been shown that in sepsis with adrenal insufficiency, steroid supplementation was associated with significantly higher rate of success in the withdrawal of vassopressor therapy. Some studies have suggested steroid therapy in sepsis is not only associated with no clinicalimprovement, but may be harmful18. However, River et al found that steroids may not be beneficial in all septic patients but for an identifiable subgroup of patients they can be useful.
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Steroids and analgesia

There are studieswhich haveshown steroids do exert analgesic effects. Various routes of administration of steroids include parentral12, local infiltration at operated site13, as an adjuvant in nerve blocks14 and central-neuraxial blockade. The mode of analgesic effect is ill defined, it

Indian Journal of Anaesthesia, October 2007 Usually steroids are administered in this setting to meet the steroid requirement of body, for fighting the ongoing stressful condition. The commonly used steroid is hydrocortisone 100-125mg.day -1. cantly low in steroid group,the author suggested that improvement may be because of suppression of local edema leading to improved microcirculation at operative site and reduction in tissue injury due to inflammation mediated substances. Saureland et al in their review of 51 studies of the patients receiving high dose methylprednisolone (15 -30 mg.kg-1) or placebo prior to surgery, found to have a non significant more GIT bleed and wound complication in steroid group 21. The only significant finding was a greater reduction in perioperative pulmonary complication in steroid group.

Other purposes
1. Cerebral oedema: Steroids are of value in reduction or prevention of cerebral oedema associated with parasitic infections and neoplasms. The mechanism by which steroids influence vasogenic oedema are thought to include one or more of the following 3: (1) stabilization of cerebral endothelium, leading to a decrease in plasma filtration; (2) increase in lysosomal activity of cerebral capillaries; (3) inhibition of release of potentially toxic substances such as free radicals, fatty acids, and prostaglandins; (4) electrolyte shifts favoring transcapillary efflux of fluid; and (5) increase in local and global cerebral glucose use, leading to improved neuronal function. In the management of patient with malignant brain tumour, it is not uncommon for subjects who are somnolent or stuporous on admission, to respond within hours, to a loading dose of dexamethasone (8 to 32mg) and to appear alert and without neurological deficits by the following day. 2. Spinal cord injury: The use of steroids remains controversial for cord injuries because improvement is minimal and difficult to document. A suggested protocol for traumatic cord injury includes the use of high dose methyl prednisolone with an intravenous bolus of 30mg.kg -1 followed by 5.4mg.kg. -1hr -1 infusion for 23 hours 19. Steroids must be used within 8 hrs of cord insult to be of any benefit. Some of the partial cord syndromes have been reported to respond favorably and prompted the maintenance of steroids through a sub acute interval of one week, followed by weaning. 3. Steroids in surgery: High and long term steroids tend to produce adverse effects on GIT, wound healing, and also cause increase in infection. However anti-inflammatory action of steroids have beneficial role to play in surgery. Shimada et al in their retrospective study of patients undergoing resection of esophageal carcinoma,reported that those patients who received methylprednisolone 250mg prior and two days following surgery had low morbidity rates from anastomotic leakage an d liv er d ysf un ctio n 20. Th e in flammato ry mediators,body temperature and heart rate were signifi392

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14. Movafegh A ,Razazian M, Hajimohamandi F , Meyamie A. Dexamethasone added to lidocaine prolongs brachial plexus blockade. Anesth Analg 2006;102:263-7. 15. Coloma M, Duffy LL, White PF,et al .Dexamethasone facilitates discharge after outpatient anorectal surgery. Anesth Analg 2001; 92:85-88. 16. Aasboe V, Raeder JC, Groegaard B. Betamethasone reduces postoperative pain and nausea after ambulatory surgery .Anesth Analg 1988; 87:319-323. 17. Rivers EP,Gasspari M, Saad GA, et al. Adrenal insufficiency in

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