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| REVIEW ARTICLE |
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| Year : 2017 | Volume
: 7
| Issue : 1 | Page : 41-44 |
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Pulse therapy – A newer approach
Karuna Suran1, Suran Pushpa2
1 Department of Oral Medicine and Radiology, Government Dental College, Ballari, Karnataka, India
2 Department of Conservative, Government Dental College, Ballari, Karnataka, India
| Date of Web Publication | 30-Jun-2017 |
Correspondence Address:
Karuna Suran
Department of Oral Medicine and Radiology, Government Dental College Ballari, Karnataka
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijmd.ijmd_69_16
Pulse therapy is defined as discontinuous/intermittent intravenous infusion of very high doses of corticosteroids along with certain immunosuppressive agents over a short period. It has gained its popularity since last three decades due to the advantage of minimizing the adverse effects of conventional corticosteroid therapy, and their action is supposed to be mediated through nongenomic actions within the cell. The aim of pulse therapy is to achieve a faster response and stronger efficacy and to decrease the need for long-term use of systemic corticosteroids. This paper intends to review the various available pulse therapy regimens with dosages, indications, contraindications, and adverse effects. Keywords: Azathioprine, cyclophosphamide, high-dose corticosteroid
How to cite this article:
Suran K, Pushpa S. Pulse therapy – A newer approach. Indian J Multidiscip Dent 2017;7:41-4 |
| Introduction | |  |
Pulse therapy was first introduced by Pasricha and Ramji in 1984.[1] Pulse therapy means the administration of large (suprapharmacologic) doses of drugs in an intermittent manner to enhance the therapeutic effects and reduce the side-effects.[2],[3],[4],[5],[6] The first reported use of pulse administration of corticosteroids is attributed to Kountz and Cohn who used it to prevent renal graft rejection in 1973.[2],[5],[6]
| Definition | | |
Pulse therapy refers to discontinuous intravenous (IV) infusion of high doses of the medication, arbitrarily defined as treatment with more than 250 mg prednisone or its equivalent per day, for one or more days.[2],[7]
| Drugs Used in Pulse Therapy | | |
- Corticosteroids
- Immunosuppressive
- Antifungal
- Antibiotics.
| Pulse Corticosteroid Therapy | | |
Pulse therapy refers to discontinuous infusion of high-dose glucocorticoids in short bursts. In the context of corticosteroids, pulse therapy refers to discontinuous IV infusion of high doses of the medication.[7] There are no guidelines of administration; which therefore includes single boluses, daily boluses given for 3 days in a row, or on alternate days for up to 12 days.[3],[4],[7]
| Medications Used | | |
Methylprednisolone pulse therapy
Methylprednisolone is an intermediate acting, potent, anti-inflammatory agent with a low tendency to induce sodium and water retention compared with hydrocortisone. Its biological half-life is 12–36 h, potency 1.25 times compared with prednisolone.
Dosage
Methylprednisolone is administered at a dose of 20–30 mg/kg (500–1000 mg/m 2) per pulse up to a maximum dose of 1 g.[2],[4],[7]
Dexamethasone pulse therapy
It is a fluoridated glucocorticoid, is a long-acting agent half-life of 36–72 h. It is 6.7 times more potent than prednisolone, has negligible mineralocorticoid effect with almost no sodium retaining tendency and a small equipotent volume.
Dosage
Dexamethasone is administered at a dose of 4–5 mg/kg (100–200 mg) per pulse.[2],[3],[4]
Administration of pulse therapy
Initially, the duration of infusion was 10–20 min. However, rapid infusions are known to be associated with a higher risk of hemodynamic abnormalities, nowadays, the corticosteroid preparation is dissolved in 150–200 ml of 5% dextrose and infused IV, slowly over 2–3 h.[3],[8]
| Advantage of Corticosteroid as a Pulse Therapy | | |
- An immediate, profound anti-inflammatory effect is achieved, and the toxicities seen with conventional high-dose oral therapy are low. Faster clinical recovery from symptoms than with oral therapy, the clinical improvement is seen to last about 3 weeks after one pulse
- No prolonged suppressive effect on the hypothalamic-pituitary axis.[8],[9],[10]
| Rationale for the Use of High-dose Intravenous Glucocorticoids | | |
The aim of pulse therapy is getting quicker and stronger efficacy and decreasing the need for long-term use of steroids. The paradox here is that administration of high-dose steroids is used to achieve the steroid sparing effect. The largest experience with pulse therapy has been reported in patients with pemphigus. Pasricha described steroid-sparing effects and long-term remission extending up to 9 years.[4]
| Mechanism of Action | | |
Glucocorticoids exert a variety of immunosuppressive, anti-inflammatory, and anti-allergic effects. They mediate their actions through genomic and nongenomic methods.[11] Buttgereit et al. have postulated three “modules” of glucocorticoid effect on cells resulting from different concentrations:[12]
- Low concentrations mediate effects through genomic events
- Medium concentrations bind to cell surface receptors, which activate cross membrane signal transmission for genomic and nongenomic intracellular events
- At very large concentrations steroids dissolve in the cell membrane resulting in greater membrane stability and reduced nongenomic cell function. Overall, effects of corticosteroid pulses appear to include downregulation of activation of immune cells and proinflammatory cytokine production. These effects are qualitatively similar to those seen with antitumor necrosis factor-alpha therapy.[13]
| Indications | | |
Commonly used:[2]
- Rheumatoid arthritis
- Juvenile rheumatoid arthritis
- Systemic lupus erythematosus
- Polymyositis
- Severe form vasculitis
- Steroid-resistant nephritic syndrome
- Crescentic glomerulonephritis
- Acute allograft rejection
- Pemphigus vulgaris
- Bullous dermatitis herpetiformis.
Infrequently used:
- Psoriatic arthritis
- 2.Ankylosing spondylitis
- Kawasaki disease
- Lupus nephritis
- Severe Steven Johnson syndrome
- Myasthenia gravis
- Severe ulcerative colitis
- Exfoliative dermatitis.
| Contraindication in Pulse Therapy | | |
[2],[3],[4],[6]
- Systemic infections, fungal sepsis, uncontrolled hypertension, and hypersensitivity to the steroid preparation
- Absolutely contraindicated in pregnant, lactating, and unmarried patients
- The therapy is also contraindicated in patients with known hypersensitivity to the steroid preparation.
| Adverse Effects | | |
The most significant serious effects in children are:
- Increased blood pressure in already hypertensive children during and after the infusion
- Seizures, particularly in systemic lupus erythematosus, which may be related to rapid flux in electrolytes
- Anaphylactic shock after even one prior infusion, usually associated with the succinate ester of Methylprednisolone.[3]
| Laboratory Monitoring | | |
Before starting the therapy
As a routine, it is mandatory to admit every patient enrolled for pulse therapy. Hemogram, serum electrolytes, renal and liver function tests, blood sugar (including hemoglobin A1C), urine microscopic examination, chest X-ray, electrocardiogram, and pregnancy test are some of the preliminary laboratory tests to be done at the first visit. Blood sugar, serum electrolytes, urine microscopic examination, body weight, and blood pressure should be monitored at baseline and each visit of the patient.
During and following therapy
Careful record of heart rate, respiratory rate, and blood pressure every 15–30 min should be maintained. If an arrhythmia is suspected, the infusion is discontinued; an electrocardiogram and blood levels of sodium, potassium, calcium, and magnesium are obtained and abnormalities are rectified. Careful screening for occurrence or exacerbation of infections should be done. Estimate blood levels of sugar and electrolytes every other day.[3],[4],[6]
| Dexamethasone Cyclophosphamide Pulse Therapy | | |
Dexamethasone-cyclophosphamide pulse (DCP) therapy is divided into four phases:[3],[6]
First phase
Dexamethasone 100 mg in 5% dextrose as a slow IV infusion over 2 h for three consecutive days along with cyclophosphamide 500 mg infusion on one of the days is instituted. DCPs are repeated every 28 days until no new lesions appear between pulses. Cyclophosphamide 50 mg/day is given orally on the remaining days. During this phase, the patient may develop recurrences in between the DCPs and conventional doses of oral corticosteroids can be given to achieve quicker clinical recovery. After the skin and mucous membrane, lesions have subsided completely, and the additional medications are withdrawn, the patient is considered to have entered Phase II.
Second phase
The phase of remission while on therapy. DCP schedule is given for the duration of 9 months.
Third phase
Monthly pulses are terminated, and oral cyclophosphamide is continued for the duration of 9 months.
Fourth phase
Treatment is stopped and patients are followed-up for the next 10 years.
| Modifications of Dexamethasone Cyclophosphamide Pulse Therapy | | |
There are following modifications of DCP therapy
Dexamethasone azathioprine pulse therapy
Cyclophosphamide is known to cause oligo/azoospermia and amenorrhea. For unmarried patients who have not completed their family, cyclophosphamide was replaced by 50 mg of azathioprine daily during the first three phases.[3]
Dexamethasone methotrexate pulse therapy
Cyclophosphamide was replaced by 7.5 mg of methotrexate weekly given orally, during the first three phases of pulse therapy.[3]
Dexamethasone cyclophosphamide pulse therapy in children
DCP therapy can be given to patients of all ages, but the doses have to be reduced to half for children below the age of 12 years.[5],[6]
Dexamethasone cyclophosphamide pulse therapy in systemic diseases
Diabetic patients need to be given 10 units of soluble insulin for every 500 ml bottle of 5% dextrose dissolved in the same drip. In addition, patient's regular treatment for diabetes mellitus is continued. Similarly, patients having concomitant diseases such as hypertension and tuberculosis must receive the respective medication.[6] If there is serious infection, the pulse may be delayed for a week or two until the infection is under control.[4]
| Conclusion | | |
Pulses of high doses of corticosteroids have a significant but transient anti-inflammatory effect. Not all effects are well understood, and some effects may have unique pharmacologic properties not related to exaggerating mechanisms obtained with lower doses. When used in appropriate diseases and circumstances, large IV pulses of corticosteroid are cumulatively less toxic than sustained steroid treatment at lower quantitative dosage, but no evidence exists that by themselves they can cure or alter long-term outcomes in diseases. More information is needed to define the specific diseases to be treated, the optimal steroid to be used, and the optimal timing of pulses to avoid chronic toxicity and obtain maximum benefit.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Kaul R, Sanjay CJ. Review on pulse therapy: A novel approach in treatment of pemphigus vulgaris. J Indian Acad Oral Med Radiol 2010;22:211-4.  [Full text] |
| 2. | Panat SR, Aggarwal A, Joshi A. Pulse therapy: A boon or bane. J Dent Sci Oral Rehabil 2012;3:1-3. |
| 3. | Gupta G, Jain A, Narayanasetty NK. Steroid pulse therapies in dermatology. Muller J Med Sci Res 2014;5:155-8. [Full text] |
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| 6. | Mittal R, Sudha S, Murugan S, Adikrishnan, Shobana S, Anandan S. Pulse therapy in dermatology. Sri Ramachandra J Med 2007;1:44-6. |
| 7. | Tarani S. Pulse therapy: A decisive treatment modality in dermatological disorders. Indian J Appl Res 2016;6:26-9. |
| 8. | Novak E, Stubbs SS, Seckman CE, Hearron MS. Effects of a single large intravenous dose of methylprednisolone sodium succinate. Clin Pharmacol Ther 1970;11:711-7. |
| 9. | Gallant C, Kenny P. Oral glucocorticoids and their complications. A review. J Am Acad Dermatol 1986;14(2 Pt 1):161-77. |
| 10. | Miura M, Ohki H, Yoshiba S, Ueda H, Sugaya A, Satoh M, et al. Adverse effects of methylprednisolone pulse therapy in refractory Kawasaki disease. Arch Dis Child 2005;90:1096-7. |
| 11. | Schimmer BP, Parker KL. Adrenocorticotropic hormones; adrenocortical steroids and their synthetic analogs; inhibitors of the synthesis and actions of adrenocortical hormones. In: Brunton LL, Lazo JS, Parker KL, editors. Goodman and Gilman's the Pharmacological Basis of Therapeutics. 11 th ed. New York: McGraw-Hill Professional; 2006. p. 1587-612. |
| 12. | Buttgereit F, Saag KG, Cutolo M, da Silva JA, Bijlsma JW. The molecular basis for the effectiveness, toxicity, and resistance to glucocorticoids: Focus on the treatment of rheumatoid arthritis. Scand J Rheumatol 2005;34:14-21. |
| 13. | Smith MD, Ahern MJ, Roberts-Thomson PJ, Youssef PP. Similar effects of pulse corticosteroid and tumor necrosis factor alpha blockade in rheumatoid arthritis: Comment on the article by Taylor et al. Arthritis Rheum 2001;44:245-6. |
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