Perioperative corticosteroid supplementation: supported by evidence
Otto-Minasian, A.G., Boer, J.M.M. de
Locatie(s): Auditorium 1
Categorie(ën): Plenaire sessie; Presentations "Schop de Heilige Huisjes omver!"
Moderator:
Mw. dr. H.A.H. Kaasjager, Arnhem
Panelleden
Mw. dr. P.C. Oldenburg, Amersfoort
Mw. W.E.M. Schouten, Amsterdam
Dr. F.L.J. Visseren, Utrecht
Introduction: Long-term use of corticosteroids may result in suppression of the hypothalamic-pituitary-adrenal axis (corticosteroid induced adrenal insufficiency).[1-3] During periods of physical stress, like surgery, the adrenal glands of patients on chronic corticosteroid therapy might produce insufficient amounts of cortisol. It is therefore generally believed that these patients require supplemental perioperative (stress) doses of corticosteroids to prevent adrenal insufficiency and subsequently cardiovascular collapse during the stressful period.[1-3] Since the publication of two case reports in the early 1950s of postoperative cardiovascular collapse and death in two corticosteroid-dependent patients whose preoperative steroids were abruptly discontinued before surgery[4-5], stress doses of corticosteroids up to 200-300 mg hydrocortisone per 24 h have become routine in the perioperative management of patients receiving long-term corticosteroid therapy. Subsequently, many corticosteroid supplementation strategies have been developed since then.[1-3] Nowadays, however, it is questionable whether supraphysiological doses of corticosteroids are necessary to prevent perioperative adrenal insufficiency and hemodynamic instability. Moreover, high doses of corticosteroids may have potential detrimental effects that can influence surgical outcomes. These include reduced tissue repair, immunosuppression, increased susceptibility to infections, hyperglycaemia, hypertension, fluid retention, psychological symptoms, and disturbances of electrolytes.[2,6]
Clinical question: Is supplemental perioperative corticosteroid therapy required in adult patients receiving long-term corticosteroid therapy to prevent corticosteroid induced adrenal insufficiency and hemodynamic instability?
Methods: A literature search was conducted using PubMed. The entered search terms were:
- [‘corticosteroid’ OR ‘glucocorticosteroid’ OR ‘steroid’]
- [‘perioperative’ OR ‘surgery’]
- [‘adrenal insufficiency’]
- Limitations: English language
The titles and abstracts of 777 articles were screened and 5 articles (3 reviews[7-9] and 2 recent retrospective studies[10,11]) were selected to answer the clinical question. These articles were selected because they gave the best overall picture of the studies published on this subject in the last decades.
Results and discussion: A Cochrane review of 2 randomized controlled trials (RCTs) (n = 37) was published in 2009 and updated in 2012.[7] The studies compared the use of supplemental perioperative steroids to placebo in adult patients on maintenance doses of corticosteroids who required surgery. There was no difference in the hemodynamic profile between patients receiving supplemental perioperative steroids compared with patients receiving only their usual daily dose of corticosteroids. Both studies were graded as having a high risk of bias and the authors concluded that owing to the small number of patients the results might not be representative. Available evidence was insufficient to support or refute the use of supplemental perioperative corticosteroids for patients with adrenal insufficiency during surgery. However, the authors found it to be likely that in the majority of adrenally suppressed patients undergoing surgery, administration of the patient’s daily maintenance dose of corticosteroid may be sufficient and that supplemental doses may not be required.
In their systematic review of the literature Marik and Varon[8] discussed the 2 RCTs described above, as well as 7 cohort studies (6 prospective, 1 retrospective) that enrolled a total of 315 patients who underwent 389 surgical procedures. In the 5 cohort studies in which patients continued to receive their usual daily dose of corticosteroids without the addition of stress doses, no patient developed unexplained hypotension or adrenal crisis. One patient in each of the 2 cohort studies (5% and 1% respectively) in which the usual daily dose of corticosteroids was discontinued 48 and 36 hours before surgery did develop unexplained hypotension; both patients responded to hydrocortisone and fluid administration. The authors concluded that patients receiving therapeutic doses of corticosteroids (with exclusion of those with primary adrenal insufficiency) who undergo a surgical procedure do not routinely require stress doses of corticosteroids so long as they continue to receive their usual daily dose of corticosteroids.
Similar conclusions were put forward in the review of de Lange and Kars[9] who argued that the current and rather defensive strategy of perioperative supraphysiological corticosteroid supplementation is not supported by evidence.
Recently, 2 retrospective studies have been published on this issue. Zaghiyan et al.[10] performed a retrospective analysis of 74 corticosteroid-treated patients with inflammatory bowel disease (IBD) who underwent a total of 97 major colorectal surgery’s (49% were on corticosteroids at the time of the surgery while 51% were off corticosteroids but had been previously treated with corticosteroids < 1 year before surgery). There were no significant differences in hemodynamic instability or surgical outcomes when treated with low-dose steroids (LDS, i.e. 30 mg bolus and 100 mg/24h hydrocortisone for patients on corticosteroids at the time of the surgery and no perioperative corticosteroids for patients off corticosteroids at the time of the surgery) versus high-dose steroids (HDS, i.e. 100 mg bolus and 300 mg/24h hydrocortisone). Hemodynamic instability, defined as heart rate > 100 or < 60 beats/min or systolic blood pressure < 90 mmHg, was more frequent in a subgroup of patients on corticosteroids at the time of the surgery receiving perioperative LDS versus HDS (100% vs. 72%, p = 0.02). However, these episodes of hemodynamic instability were clinically unimportant, because in all but 3 cases, hemodynamic instability resolved with simple measures. In the 3 patients who were treated with vasopressors, hemodynamic instability was due to other causes rather than adrenal insufficiency. No patient required rescue HDS because of adrenal insufficiency. This study was mainly limited by its retrospective nature and selection bias. Finally, another publication of this study group showed no clinically significant hemodynamic instability in corticosteroid-treated patients (n = 26) with IBD undergoing 32 surgical procedures who were treated with perioperative LDS.[11]
Conclusion: In conclusion, the current practice of perioperative supraphysiological corticosteroid supplementation in patients on chronic corticosteroid therapy is not supported by evidence. Small retrospective, prospective, and randomized controlled trials, though all methodologically flawed, have suggested that corticosteroid-treated patients undergoing surgery who are at risk of developing corticosteroid induced adrenal insufficiency may be safely treated with only their baseline corticosteroid doses in the perioperative period. Moreover, excessive doses of corticosteroids may be harmful due to the known adverse effects of these medications. Large RCTs of high quality in various surgical settings are warranted to further assess the requirement for supplemental perioperative corticosteroids and the dose required to prevent adrenal insufficiency in patients receiving long-term corticosteroid therapy.
