Systemic Effects of Epidural Corticosteroid Injection

Systemic Effects of Epidural Corticosteroid Injection Myth: Transforaminal and interlaminar epidural injections of corticosteroids can be administered without concern for systemic effects because the doses used are small and intermittent. Fact: The doses of corticosteroids administered in interventional spine procedures have systemic effects, especially when the patient has a steroid-dependent condition such as diabetes mellitus or has multiple exposures to steroids. Transforaminal and interlaminar epidural injections of corticosteroids are used to treat radicular pain. The presumed rationale is that the corticosteroid suppresses inflammation of the affected nerve root, which is responsible wholly or partly for the generation of pain. Once injected, the corticosteroid is absorbed through the epidural plexus of veins and can exert systemic effects. The risk of side effects is dependent on the dose used and the number of injections given over time. The nature of systemic effects depends on the systems affected and the duration of exposure to steroids. Pharmacology The corticosteroids used in spinal pain management are glucocorticoids. They act by binding to glucocorticoid receptors, which are present in virtually all human tissues and control carbohydrate metabolism. Synthetic corticosteroids have substantially higher affinity for glucocorticoid receptors than does natural cortisol. Glucocorticoid drugs have a weak, but not negligible, affinity for mineralocorticoid receptors. Glucocorticoids are metabolized in the liver to inactive glucuronides and sulfates and are excreted mainly by the kidneys, but also in feces. The half-lives of glucocorticoids vary, but are of the order of several days. For example, the half-life of dexamethasone is 36 to 54 hours. The half-lives of these agents determine the durations of their acute side effects. Dose For transforaminal injection of steroids (TFIS), dexamethasone has become the preferred agent because it does not form particles. Typical doses range from 5 mg to 7.5 mg and 15 mg. Equivalent doses of other agents, such as triamcinolone or betamethasone, have been used in the past. For interlaminar epidural injections, similar or larger doses have been used. For either type of procedure, larger doses are sometimes used when more than one nerve root is the target. There are no published data comparing the incidence, severity, or duration of systemic adverse effects with different doses of any of the glucocorticoid steroids administered epidurally. Consequently, any inferences drawn about systemic side effects can only be qualitative in nature. Systemic Side Effects Corticosteroids principally influence the metabolism of carbohydrates, fats, proteins, and purine, but they can also affect electrolyte and water balance; they may affect the functions of the central nervous system and of the cardiovascular, renal, endocrine, reproductive, and immune systems, as well as of bones and muscles. The short-term systemic effects of the corticosteroids reported are listed in Table 1. Table 1 A list of the short-term systemic side effects of corticosteroids that can occur after transforaminal or interlaminar epidural administration     Glucose Metabolism  Cardiovascular System  Hyperglycemia  Fluid retention, edema  Hepatic gluconeogenesis  Hypertension  Inhibition of glucose uptake in muscle and adipose tissue  Aggravation of arrhythmias  Increased appetite    Loss of appetite  Immunological    Allergic reactions    Reduced resistance to infection  Nervous system  Delayed healing  Mood changes    Restlessness or irritability Euphoria or even mania Depression  OtherGastrointestinal effects  Insomnia Vasomotor flushing  (face, neck and chest)  Reflux Heartburn Gastritis  Headache  Menstrual irregularities  Malaise  Vaginal bleeding  Balance disturbance, vertigo  Raised intraocular pressure  Nausea, vomiting    Seizures        Glucose Metabolism  Cardiovascular System  Hyperglycemia  Fluid retention, edema  Hepatic gluconeogenesis  Hypertension  Inhibition of glucose uptake in muscle and adipose tissue  Aggravation of arrhythmias  Increased appetite    Loss of appetite  Immunological    Allergic reactions    Reduced resistance to infection  Nervous system  Delayed healing  Mood changes    Restlessness or irritability Euphoria or even mania Depression  OtherGastrointestinal effects  Insomnia Vasomotor flushing  (face, neck and chest)  Reflux Heartburn Gastritis  Headache  Menstrual irregularities  Malaise  Vaginal bleeding  Balance disturbance, vertigo  Raised intraocular pressure  Nausea, vomiting    Seizures    Long-term systemic side effects may arise if corticosteroids are administered on a continuing basis or given repeatedly at intervals too short for the body to have cleared the previous dose(s). Long-term effects may be caused directly by excess glucocorticoid in the circulation or indirectly through suppression of the hypothalamic-pituitary axis (HPA). Suppression of the HPA, resulting in low-serum cortisol, has been seen following a single epidural steroid injection and may persist anywhere from two to 52 weeks. Higher doses of epidural methyprednisolone suppress the HPA axis more frequently and for a longer duration than lower doses. Serial epidural steroid injections may result in higher frequencies of HPA suppression. A recent study showed that of patients presenting to a university pain management center and considered for epidural steroid injections, more than 44% already had significant steroid exposure within the previous six months. The longer-term effects of the epidural steroids reported include persistence of the short-term effects (Table 1). Other longer-term systemic steroid side effects that potentially could occur but have not been reported explicitly after epidural injections include hyperinsulinemia, increased adiposity, hypokalemic alkalosis, reduced gonadal function and infertility, abnormal intraocular pressure, cataracts, osteoporosis, myopathy, and cardiomyopathy (each caused by excess glucocorticoid), and hypoglycemia, hypoinsulinemia, loss of appetite, hyponatremia, hyperkalemia, and hypothyroidism (each caused by effects on the HPA). Lymphocytosis or lymphocytopenia, monocytosis or monocytopenia, and eosinophilia or eosinopenia can also occur. Implications The practical implications of the pharmacology of corticosteroids are that unwanted effects should be taken into account when planning the administration of steroids by any route. The risks should be explained to patients before any intervention in which a steroid is to be administered so that they can give properly informed consent. Precautions should be taken for anticipated effects, such as hyperglycemia, in patients with impaired glucose tolerance. If steroid injections are to be repeated, shorter-acting agents should be administered at intervals of no less than two weeks to prevent accumulation of the drug in the body and HPA suppression. If a longer-acting, depot steroid is to be used, a three-week or even four-week interval may be appropriate. Injected doses should be in accordance with published data. Every effort should be made to determine if patients have received other glucocorticoid steroids. Acknowledgments The authors express appreciation to the other members of the Patient Safety Committee who served as peer reviewers for this FactFinder, in particular Dr. Adrian Popescu and Dr. Byron Schneider, and to Mrs. Belinda Duszynski, who coordinated the project. Funding sources: No funds were received in support of this manuscript. Conflicts of interest: None of the authors has any financial conflicts of interest to disclose. An extended version of this FactFinder with complete references is available on the Spine Intervention Society Website at https://c.ymcdn.com/sites/www.spineintervention.org/resource/resmgr/factfinder/FactFinder_2017-06-01_System.pdf. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pain Medicine Oxford University Press

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Blackwell Publishing Inc.
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© 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
ISSN
1526-2375
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1526-4637
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Abstract

Myth: Transforaminal and interlaminar epidural injections of corticosteroids can be administered without concern for systemic effects because the doses used are small and intermittent. Fact: The doses of corticosteroids administered in interventional spine procedures have systemic effects, especially when the patient has a steroid-dependent condition such as diabetes mellitus or has multiple exposures to steroids. Transforaminal and interlaminar epidural injections of corticosteroids are used to treat radicular pain. The presumed rationale is that the corticosteroid suppresses inflammation of the affected nerve root, which is responsible wholly or partly for the generation of pain. Once injected, the corticosteroid is absorbed through the epidural plexus of veins and can exert systemic effects. The risk of side effects is dependent on the dose used and the number of injections given over time. The nature of systemic effects depends on the systems affected and the duration of exposure to steroids. Pharmacology The corticosteroids used in spinal pain management are glucocorticoids. They act by binding to glucocorticoid receptors, which are present in virtually all human tissues and control carbohydrate metabolism. Synthetic corticosteroids have substantially higher affinity for glucocorticoid receptors than does natural cortisol. Glucocorticoid drugs have a weak, but not negligible, affinity for mineralocorticoid receptors. Glucocorticoids are metabolized in the liver to inactive glucuronides and sulfates and are excreted mainly by the kidneys, but also in feces. The half-lives of glucocorticoids vary, but are of the order of several days. For example, the half-life of dexamethasone is 36 to 54 hours. The half-lives of these agents determine the durations of their acute side effects. Dose For transforaminal injection of steroids (TFIS), dexamethasone has become the preferred agent because it does not form particles. Typical doses range from 5 mg to 7.5 mg and 15 mg. Equivalent doses of other agents, such as triamcinolone or betamethasone, have been used in the past. For interlaminar epidural injections, similar or larger doses have been used. For either type of procedure, larger doses are sometimes used when more than one nerve root is the target. There are no published data comparing the incidence, severity, or duration of systemic adverse effects with different doses of any of the glucocorticoid steroids administered epidurally. Consequently, any inferences drawn about systemic side effects can only be qualitative in nature. Systemic Side Effects Corticosteroids principally influence the metabolism of carbohydrates, fats, proteins, and purine, but they can also affect electrolyte and water balance; they may affect the functions of the central nervous system and of the cardiovascular, renal, endocrine, reproductive, and immune systems, as well as of bones and muscles. The short-term systemic effects of the corticosteroids reported are listed in Table 1. Table 1 A list of the short-term systemic side effects of corticosteroids that can occur after transforaminal or interlaminar epidural administration     Glucose Metabolism  Cardiovascular System  Hyperglycemia  Fluid retention, edema  Hepatic gluconeogenesis  Hypertension  Inhibition of glucose uptake in muscle and adipose tissue  Aggravation of arrhythmias  Increased appetite    Loss of appetite  Immunological    Allergic reactions    Reduced resistance to infection  Nervous system  Delayed healing  Mood changes    Restlessness or irritability Euphoria or even mania Depression  OtherGastrointestinal effects  Insomnia Vasomotor flushing  (face, neck and chest)  Reflux Heartburn Gastritis  Headache  Menstrual irregularities  Malaise  Vaginal bleeding  Balance disturbance, vertigo  Raised intraocular pressure  Nausea, vomiting    Seizures        Glucose Metabolism  Cardiovascular System  Hyperglycemia  Fluid retention, edema  Hepatic gluconeogenesis  Hypertension  Inhibition of glucose uptake in muscle and adipose tissue  Aggravation of arrhythmias  Increased appetite    Loss of appetite  Immunological    Allergic reactions    Reduced resistance to infection  Nervous system  Delayed healing  Mood changes    Restlessness or irritability Euphoria or even mania Depression  OtherGastrointestinal effects  Insomnia Vasomotor flushing  (face, neck and chest)  Reflux Heartburn Gastritis  Headache  Menstrual irregularities  Malaise  Vaginal bleeding  Balance disturbance, vertigo  Raised intraocular pressure  Nausea, vomiting    Seizures    Long-term systemic side effects may arise if corticosteroids are administered on a continuing basis or given repeatedly at intervals too short for the body to have cleared the previous dose(s). Long-term effects may be caused directly by excess glucocorticoid in the circulation or indirectly through suppression of the hypothalamic-pituitary axis (HPA). Suppression of the HPA, resulting in low-serum cortisol, has been seen following a single epidural steroid injection and may persist anywhere from two to 52 weeks. Higher doses of epidural methyprednisolone suppress the HPA axis more frequently and for a longer duration than lower doses. Serial epidural steroid injections may result in higher frequencies of HPA suppression. A recent study showed that of patients presenting to a university pain management center and considered for epidural steroid injections, more than 44% already had significant steroid exposure within the previous six months. The longer-term effects of the epidural steroids reported include persistence of the short-term effects (Table 1). Other longer-term systemic steroid side effects that potentially could occur but have not been reported explicitly after epidural injections include hyperinsulinemia, increased adiposity, hypokalemic alkalosis, reduced gonadal function and infertility, abnormal intraocular pressure, cataracts, osteoporosis, myopathy, and cardiomyopathy (each caused by excess glucocorticoid), and hypoglycemia, hypoinsulinemia, loss of appetite, hyponatremia, hyperkalemia, and hypothyroidism (each caused by effects on the HPA). Lymphocytosis or lymphocytopenia, monocytosis or monocytopenia, and eosinophilia or eosinopenia can also occur. Implications The practical implications of the pharmacology of corticosteroids are that unwanted effects should be taken into account when planning the administration of steroids by any route. The risks should be explained to patients before any intervention in which a steroid is to be administered so that they can give properly informed consent. Precautions should be taken for anticipated effects, such as hyperglycemia, in patients with impaired glucose tolerance. If steroid injections are to be repeated, shorter-acting agents should be administered at intervals of no less than two weeks to prevent accumulation of the drug in the body and HPA suppression. If a longer-acting, depot steroid is to be used, a three-week or even four-week interval may be appropriate. Injected doses should be in accordance with published data. Every effort should be made to determine if patients have received other glucocorticoid steroids. Acknowledgments The authors express appreciation to the other members of the Patient Safety Committee who served as peer reviewers for this FactFinder, in particular Dr. Adrian Popescu and Dr. Byron Schneider, and to Mrs. Belinda Duszynski, who coordinated the project. Funding sources: No funds were received in support of this manuscript. Conflicts of interest: None of the authors has any financial conflicts of interest to disclose. An extended version of this FactFinder with complete references is available on the Spine Intervention Society Website at https://c.ymcdn.com/sites/www.spineintervention.org/resource/resmgr/factfinder/FactFinder_2017-06-01_System.pdf. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Journal

Pain MedicineOxford University Press

Published: Feb 1, 2018

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