Steroid Therapy – Current Indications in Practice V. K. Grover

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.
Perioperative replacement therapy.
2.
Anti-inflammatory uses and hyper-reactive airway
3.
4.
Post operative nausea and vomiting (PONV)
Analgesia adjunct
5.
Day care surgery
6.
Anaphylaxis
7.
Septic shock
8.
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
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)
Compound
AntiNa
inflammat- retaining
ory potency potency
Duration
of
action
Equivalent
dose
Cortisol
1
1
S
20
Cortisone
0.8
0.8
S
25
Dexamethasone 25
0
L
0.75
Prednisone
4
0.8
I
5
Prednisolone
4
0.8
I
5
6-methyl
Prednisolone
5
0.5
I
4
Triamcinolone
5
0
I
4
Betamethasone
25
0
L
0.75
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. [email protected]
Accepted for publication on:1.8.07
389
Indian Journal of Anaesthesia, October 2007
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.
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.
Table 2 Perioperative steroid replacement therapy
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).
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
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.
High dose
immunosuppr
essive
Patient stopped < 3 months
taking steroid
> 3 months
Give usual
immunosuppressive dose
during
perioperative
period
Treat as if
on steroids
No perioperative steroids
necessary
Steroids in hyper-reactive airway
Steroids as anti-inflammatory
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-
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
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.
Steroids and analgesia
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.
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
391
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.
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