Single Epidural Injection Research Articles

The pharmacokinetic profile of an extended-release liposomal formulation of bupivacaine administered via a single epidural injection

1Department of Anaesthesia and Intensive Care, University of Adelaide; 2SkyePharma Inc., San Diego, California, USA

(735): Epidural steroid injection efficacy is a function of the contrast dispersion pattern

Epidural steroid injections (ESI) may provide relief of radicular pain associated with lumbar disc herniations. Inflammation from a disc herniation occurs primarily in the ventral epidural space at the site of the disc injury. Epidural steroids should therefore, be deposited at the level of the disc lesion in the ventral epidural space. Epidural needle placement can be accomplished by one of three methods: caudal (C), translaminar (TL) or transforaminal (TF). The purpose of this study is to analyze epidurogram contrast dispersion patterns in the epidural space using the three routes of epidural needle placement. After patient informed consent and IRB approval, 60 patients with L5-S1 disc herniations were randomly assigned to have epidural steroid injections by one of three methods for epidural needle placement; caudal (n=20), translaminar (n=20) and transforaminal (n=20). Each procedure was performed with fluoroscopy using a 22 gauge Tuohoy needle. Each patient received 3 ml of iohexol 300 with 5 ml preservative saline with 40 mg of triamincolone in Groups TL and TF and 20 ml preservative saline with 40 mg steroid in Group C after proper needle placement was ascertained by epidurogram observation. Fluoroscopy was repeated at 30 min post injection. Statistical analysis was done using the Fisher Exact test with p <0.05 to reject the null hypothesis. Observed epidural contrast dispersion patterns were; V=ventral, AP =anterior-posterior and P= posterior; Caudal (n=20), V=0/20 (0%), AP=11/20(55%), P=9/20, (45%); Translaminar (n=20) V=2/20 (10%), AP= 8/20 (40%), P=10/20 (50%) and Transforaminal (n=20), V=18/20 (90%), AP, 2/20 (10%), P=0/20 (20%). Pain relief two weeks following the ESI was as follows: C, 9/20 (45%), TL, 10/20 (50%), TF, 15/20 (75%). Transforaminal ESI resulted in significantly (p<0.05) greater pain relief with a single epidural steroid injection which is attributed to a higher incidence of steroid placement within the ventral epidural space.

Antipruritic and antiemetic effect of epidural droperidol

This study was designed to investigate whether single epidural droperidol or continuous epidural droperidol inhibit pruritus and postoperative nausea and vomiting induced by postoperative continuous epidural fentanyl administration, and to identify the optimal method of administering epidural droperidol. 120 ASA I-II patients undergoing subtotal gastrectomy with general anaesthesia combined with epidural anaesthesia were randomly allocated into three groups: control (no droperidol), single injection (droperidol 2.5 mg) and continuous group (droperidol 2.5 mg 2 day(-1)). Postoperatively the frequency and severity of pruritus and postoperative nausea and vomiting in all groups were compared during 48 h. The frequency and severity of pruritus was significantly lower in both single injection and continuous groups than control group after epidural fentanyl administration (P < 0.05). The frequency and severity of postoperative nausea and vomiting was significantly lower in single injection group than control group after epidural fentanyl administration (P < 0.05). Epidural continuous droperidol is effective for reducing pruritus, and single epidural droperidol injection is effective for reducing pruritus and postoperative nausea and vomiting induced by postoperative continuous epidural fentanyl analgesia.

Pharmacology of Drugs Formulated with DepoFoam???

Lamellar liposome technology has been used for several decades to produce sustained-release drug formulations for parenteral administration. Multivesicular liposomes are structurally distinct from lamellar liposomes and consist of an aggregation of hundreds of water-filled polyhedral compartments separated by bi-layered lipid septa. The unique architecture of multivesicular liposomes allows encapsulating drug with greater efficiency, provides robust structural stability and ensures reliable, steady and prolonged drug release. The favourable characteristics of multivesicular liposomes have resulted in many drug formulations exploiting this technology, which is proprietary and referred to as DepoFoam. Currently, two formulations using multivesicular liposome technology are approved by the US FDA for clinical use, and many more formulations are at an experimental developmental stage. The first clinically available formulation contains the antineoplastic agent cytarabine (DepoCyt) for its intrathecal injection in the treatment of malignant lymphomatous meningitis. Intrathecal injection of DepoCyt reliably results in the sustained release of cytarabine and produces cytotoxic concentrations in cerebrospinal fluid (CSF) that are maintained for at least 2 weeks. Early efficacy data suggest that DepoCyt is fairly well tolerated, and its use allows reduced dosing frequency from twice a week to once every other week and may improve the outcome compared with frequent intrathecal injections of unencapsulated cytarabine. The second available formulation contains morphine (DepoDur) for its single epidural injection in the treatment of postoperative pain. While animal studies confirm that epidural injection of DepoDur results in the sustained release of morphine into CSF, the CSF pharmacokinetics have not been determined in humans. Clinical studies suggest that the use of DepoDur decreases the amount of systemically administered analgesics needed for adequate postoperative pain control. It may also provide superior pain control during the first 1-2 postoperative days compared with epidural administration of unencapsulated morphine or intravenous administration of an opioid. However, at this timepoint the overall clinical utility of DepoDur has yet to be defined and some safety concerns remain because of the unknown CSF pharmacokinetics of DepoDur in humans. The versatility of multivesicular liposome technology is reflected by the many agents including small inorganic and organic molecules and macromolecules including proteins that have successfully been encapsulated. Data concerning many experimental formulations containing antineoplastic, antibacterial and antiviral agents underscore the sustained, steady and reliable release of these compounds from multivesicular liposomes after injection by the intrathecal, subcutaneous, intramuscular, intraperitoneal and intraocular routes. Contingent on the specific formulation and manufacturing process, agents were released over a period of hours to weeks as reflected by a 2- to 400-fold increase in elimination half life. Published data further suggest that the encapsulation process preserves bioactivity of agents as delicate as proteins and supports the view that examined multivesicular liposomes were non-toxic at studied doses. The task ahead will be to examine whether the beneficial structural and pharmacokinetic properties of multivesicular liposome formulations will translate into improved clinical outcomes, either because of decreased drug toxicity or increased drug efficacy.

The PINE study of epidural steroids and local anaesthetics to prevent postherpetic neuralgia: a randomised controlled trial

Postherpetic neuralgia is the most frequent complication of herpes zoster. Treatment of this neuropathic pain syndrome is difficult and often disappointing. We assessed the effectiveness of a single epidural injection of steroids and local anaesthetics for prevention of postherpetic neuralgia in older patients with herpes zoster. We randomly assigned 598 patients older than 50 years, with acute herpes zoster (rash <7 days) below dermatome C6, to receive either standard therapy (oral antivirals and analgesics) or standard therapy with one additional epidural injection of 80 mg methylprednisolone acetate and 10 mg bupivacaine. The primary endpoint was the proportion of patients with zoster-associated pain 1 month after inclusion. Analyses were by intention-to-treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN32866390. At 1 month, 137 (48%) patients in the epidural group reported pain compared with 164 (58%) in the control group (relative risk [RR] 0.83, 95% CI 0.71-0.97, p=0.02). After 3 months these values were 58 (21%) and 63 (24%) respectively (0.89, 0.65-1.21, p=0.47) and, at 6 months, 39 (15%) and 44 (17%; 0.85, 0.57-1.13, p=0.43). We detected no subgroups in which the relative risk for pain 1 month after inclusion substantially differed from the overall estimate. No patient had major adverse events related to epidural injection. A single epidural injection of steroids and local anaesthetics in the acute phase of herpes zoster has a modest effect in reducing zoster-associated pain for 1 month. This treatment is not effective for prevention of long-term postherpetic neuralgia.

Emerging Techniques in the Management of Acute Pain: Epidural Analgesia

Epidural analgesia, often using opioids intraoperatively and postoperatively, is widely accepted as a valuable modality for perioperative pain management. In this review I present data from meta-analyses and recently published trials that evaluate the perioperative use of opioids administered epidurally or parenterally (as-needed or by patient-controlled analgesia) and their effect on outcome. Published effects of perioperative epidural techniques on cardiac and pulmonary function are reviewed. Clinical and practical issues associated with epidural anesthesia and analgesia include the existence of analgesic gaps (often related to technical difficulties with the pump or use of an indwelling catheter), the occurrence of hypotension, and compatibility with anticoagulation therapy. A new treatment option, a single epidural injection of morphine for continuous perioperative analgesia (DepoDur; Endo Pharmaceuticals Inc, Chadds Ford, PA), may reduce some of these problems. Data from recent clinical studies are presented.

Effect of betamethasone on neuropathic pain and cerebral expression of NF-κB and cytokines

Glucocorticoids have been used to treat neuropathic pain for many years, but the underlying mechanisms are still unknown. Recent studies indicate that pathological pain states may be mediated by cytokines. We, therefore, examined the effect of betamethasone on neuropathic pain and the relationship between pain behavior and the expression of cytokines in the brain. Rats were given epidural injections of betamethasone (Diprospan) after L5 spinal nerve transection. Mechanical allodynia and thermal hyperalgesia were evaluated on post-operative days 1, 3, 7, 14 and 21 with von Frey and Hargreaves tests. Cerebral expression of NF-κB, TNFα, IL-1β and IL-10 was quantified using electrophoretic mobility shift assay (EMSA) or enzyme-linked immunosorbent assay (ELISA). We found that spinal nerve injury caused long-lasting mechanical and thermal hyperalgesia in the hind paw and stimulated the expression of NF-κB, TNFα, IL-1β and IL-10 in the brain. A single epidural injection of betamethasone at the time of nerve injury partially inhibited the development of neuropathic hyperalgesia and reduced the subsequent elevated levels of pro-inflammatory cytokines in the brain, while stimulating the expression of the anti-inflammatory cytokine IL-10. These data support our hypothesis that pro-inflammatory cytokines in the brain may mediate the hyperalgesic effects of spinal nerve injury and that the long-acting anti-hyperalgesic effects of epidural glucocorticoid treatment are due to an inhibitory effect on pro-inflammatory cytokine levels and a stimulatory effect on anti-inflammatory cytokine levels in the brain.

Extended-Release Epidural Morphine (DepoDur™)

D a EPIDURAL MORPHINE HAS been administered by single and intermittent bolus doses, continuous infusion, and patient-controlled analgesia (PCA) for the management of postoperative pain for many years. All of these methods have proven to be safe and effective in controlling pain, but each also has its limitations. A single epidural injection of conventional morphine (Astramorph; AstraZeneca LP, Wilmington, DE) produces pain relief for as long as 24 hours, which may not be long enough for some patients after major surgery. Although continuous epidural infusion and patient-controlled epidural analgesia (PCEA) techniques provide prolonged relief, they require an indwelling catheter, which can impede mobility and carries the risk of intraspinal infection. In addition, guidelines for insertion and removal of indwelling epidural catheters must be carefully followed in patients receiving prophylactic anticoagulant therapy to prevent the occurrence of an epidural hematoma. However, the US Food and Drug Administration (FDA) has recently approved a unique formulation of epidural morphine called extended-release epidural morphine (EREM) (DepoDur; Endo Pharmaceuticals, Chadds Ford, PA) that may provide a better choice for pain control after some surgical procedures. A single epidural bolus of EREM is capable of providing pain relief for as long as 48 hours, which represents an exciting new postoperative pain management option for many patients undergoing major surgery.

Systemic effects of epidural betamethasone injection

A single epidural injection of a steroid may produce a suppression of the adrenocortical secretion. We aimed to evaluate systemic effects of a single epidural injection of betamethasone in this study. The study included 33 patients with low back pain. None of the patients had received local or systemic steroid therapy within 2 months before the injection. The epidural injection consisted of 10 mg of betamethasone diluted in 8 ml 0.25% bupivacaine. Injections were performed between 8:00 and 9:00 a. m. Before the injection in the same day (D0) cortisol, ACTH, fasting levels of glucose, triglycerides, cholesterol, sodium, and potassium were checked in the blood. The same assays were done again by the same laboratory at 15, 30, 45 min, and 7 (D7) and 21 (D21) days after the steroid injections. In all patients, cortisol and ACTH were normal at D0. ACTH and cortisol significantly decreased 45 min and at D7 after steroid injection, but returned to normal on D21. There were no significant changes in mean fasting glucose, sodium, potassium, triglycerides or cholesterol levels during the study. Blood pressure values were normal in all patients. As a result, it is concluded that a single epidural injection of betamethasone is associated with transient adrenal suppression.

Design issues for studies into prevention of chronic pain: lessons from post-herpetic neuralgia.

Design issues for studies into prevention of chronic pain: lessons from post-herpetic neuralgia.

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390

BackgroundPostherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients.Methods / designThe PINE study is an open, multicenter clinical trial in which 550 elderly (age ≥ 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness.ConclusionThe PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN.

Post cesarean analgesia

There are a variety of effective options for postcesarean analgesia. A single epidural injection of 4 mg of morphine provides 18 to 24 hours of good to excellent analgesia. A single spinal injection of 0.1 mg of morphine also provides 18 to 24 hours of analgesia. Continuous epidural catheter techniques can be effective, usually by relying on a combination of a short-acting opioid, such as fentanyl or sufentanil, and a local anesthetic, usually bupivacaine or ropivacaine. Occasionally, with this technique, motor block caused by the local anesthetic interferes with maternal ambulation. Patient-controlled techniques, either intravenous or epidural, also have proven effective. A variety of opioids (including morphine, meperidine, and fentanyl) have been used for intravenous patient-controlled analgesia with little to recommend one drug over the other. For epidural patient-controlled analgesia, opioid-local anesthetic combinations are usually used, with delivery parameters dependent on the exact concentration of the chosen solution. Regardless of the technique chosen, careful monitoring of patients in the early postoperative period (24 hours) is essential to avoid adverse effects and to ensure maternal satisfaction.

Combination Spinal Analgesic Chemotherapy: A Systematic Review

Combination Spinal Analgesic Chemotherapy: A Systematic Review

Combination spinal analgesic chemotherapy: a systematic review.

Combination spinal analgesic chemotherapy: a systematic review.

Comparison of Motor Block of 1.0% Ropivacaine and 0.5% Bupivacaine in Epidural Anesthesia for Hip Arthroplasty Surgery

Background: The purpose of this study was to compare the onset time, degree and duration of motor block, and the satisfaction of surgeons of given single epidural injections of 1.0% ropivacaine and 0.5% bupivacaine in patients undergoing hip arthroplasty surgery. Methods: In a double-blind randomized study involving 20 patients, patients randomly received 12 ml of 1.0% ropivacaine or 0.5% bupivacaine at the L2-3 or L3-4 interspace. Parameters measured were the onset time, duration and degree of motor block, and the satisfaction of the surgeons. Results: Mean onset time of Bromage scale 2 was significantly slower with 1% ropivacaine (14.6 1.3 min) than with 0.5% bupivacaine (15.7 . 2.0 min). However, each frequency of motor blockade (Bromage scale 1, 2 and 3) with 1.0% ropivacaine (10, 8 and 7) was greater than that seen with 0.5% bupivacaine (7, 6 and 1). For scales 1 and 2, 1.0% ropivacaine had a significantly longer duration than 0.5% bupivacaine and the overall duration of motor blockade with 1.0% ropivacaine was longer than 0.5% bupivacaine. Motor block was in 80% achieved satisfactorily of the ropivacaine group and 60% of the bupivacaine group by the surgeons. Conclusions: In conclusion this study demonstrated that 1.0% ropivacaine provides a more rapid onset time, greater degree and longer duration of motor block without unacceptable side effects than 0.5% bupivacaine for hip arthroplasty surgery. From these results, it may suggest that 1.0% ropivacaine may be useful for lower extremity orthopedic surgery requiring good muscle relaxation.

Effect of epidural liposomal morphine on the postoperative stress response in humans

O-26 Introduction: The prolonged release of morphine from high load liposomal formulations provides significant analgesia following neuraxial application. We investigated in this double-blind, randomized placebo-controlled trial whether such formulations were efficient for obtunding the postoperative stress response. Methods: The protocol was approved by the University Ethics Committee. Forty patients, ASA class II-III, scheduled for abdominal surgery, received a single epidural injection of 7 mL of either placebo (PL), plain morphine (1 mg mL−1, MOR), liposomal morphine 1 mg mL−1 (LIP1) or liposomal morphine 2 mg mL−1 (LIP2) after operation. All patients used i.v. PCA fentanyl for analgesia. Arterial samples were taken before anaesthesia and postoperatively before and at 4 and 24 h after drug administration. Catecholamine assays were performed using HPLC and results analysed with two-way ANOVA tests. Results: All groups (n = 10 per group) were comparable for age, weight, gender and pre-operative values of catecholamines. The epinephrine levels increased 6-fold in all groups after surgery. Concentrations decreased by 50% 4 h after drug application in the MOR and LIP1 groups and returned to preoperative values in the LIP2 group (P < 0.01). The norepinephrine levels remained higher in the PL group than in the MOR and LIP1 groups, and were lowest in the LIP2 group (PL: 612 (163, SEM) pg mL−1; LIP2: 397 (38) pg mL−1, P < 0.05) at 24 h. No difference was found between the MOR and LIP1 groups (MOR: 531 (61, SEM) pg mL−1; LIP1: 494 (59, SEM) pg mL−1). Conclusion: The neuraxial administration of a liposomal formulation with high morphine load (2 mg mL−1) provided a quicker return of epinephrine concentrations to preoperative values, and decreased the rise of norepinephrine concentrations after operation compared to the use of plain morphine or i.v. PCA fentanyl.

The Effects of Single Epidural Triamcinolone Injection on the Blood ACTH and Cortisol Level

The Effects of Single Epidural Triamcinolone Injection on the Blood ACTH and Cortisol Level

Hemostasis-altering drugs and central neural block. A survey of anesthetic practice in Scotland and the United Kingdom.

There is debate regarding the use of central neural block in the presence of hemostasis-altering drugs. This study aims to examine current practice. A survey was made of the members of the Scottish Society of Anaesthetists and the U.K. branch of the European Society of Regional Anaesthesia to determine the pattern of use of central neural block in patients who are receiving drugs known to alter hemostasis. Spinal anesthetics were considered safer than single epidural injections (P < .05) and single epidural injections safer than infusions via epidural catheters (P < .05). There is general agreement regarding contraindication of central neural block in the presence of full anticoagulation with either heparin or warfarin, but there is less consensus about the use of central neural block in the presence of low-dose subcutaneous heparin. There is some confusion about the role of aspirin and its duration of action.

Transpulmonary disposition of prilocaine, mepivacaine, and bupivacaine in humans in the course of epidural anaesthesia

The pulmonary first-pass kinetics of the amide-linked local anaesthetics prilocaine, mepivacaine and bupivacaine were studied in 33 patients after a single epidural injection. Drug concentrations were monitored before and after lung passage, i.e. in samples withdrawn simultaneously from mixed venous and arterial blood. In most cases, maximum plasma concentrations were observed 10 min after injection (range 2 to 30 min). Two min after injection the local anaesthetics were distinctly extracted by the lung (prilocaine 40%, mepivacaine 20%, and bupivacaine 12%). Prilocaine was retained by the lung more effectively than bupivacaine and mepivacaine. However, a transpulmonary concentration gradient could be observed only for a short time, i.e. maximum 15 min. Altogether, in the case of accidental fast absorption, e.g. inadvertent intravenous injection, arterial peak concentrations of these drugs will be attenuated by passage of the lung. However, the lung will not substantially lower the risk of toxicity by amide-linked local anaesthetics during normal conditions of regional anaesthesia where slow absorption occurs.

Preoperative Analgesia with Epidural Morphine

In a prospective double-blind study, we examined the effects of preoperative epidural morphine associated with general anesthesia (GA) on intra- and postoperative analgesic requirements over a 3-day postoperative period. Twenty patients scheduled for major intraabdominal surgery were randomly assigned to two groups: a control group (n = 10) and an epidural group (n = 10) which received an epidural injection of 5 mg of preservative-free morphine in 10 mL of 0.9% saline. Afterward, both groups received the same GA. Postoperative pain relief was achieved with intravenous (IV) boluses of morphine using a patient-controlled analgesia device. We found smaller opioid requirements in the epidural group than in the control group for intraoperative fentanyl (465 +/- 179 micrograms vs 983 +/- 682 micrograms), for postoperative morphine at 12 h (3.1 +/- 3 mg vs 21.4 +/- 13.8 mg) and 24 h (9.1 +/- 6.4 mg vs 20.6 +/- 9.8 mg), and for the cumulated needs over the 3-day postoperative period (37 +/- 24 mg vs 86 +/- 42 mg). The consumption of IV morphine by the control group decreased over time (P < 0.001, r = 0.44), whereas, in the epidural group, consumption remained constant and small during the 3 days. The maximum pain score was significantly lower in the epidural group than in the control group at 24 h (0.65 +/- 2.4 vs 3 +/- 2), at 36 h (0.3 +/- 0.6 vs 3 +/- 2.7), and at 60 h (0.1 +/- 0.3 vs 1.8 +/- 1.2) after surgery. These results suggest that a single epidural injection of 5 mg of morphine before major surgery produces intra- and postoperative pain relief for at least 3 days.