Anthony H. Guarino

Perils of intravascular methylprednisolone injection into the vertebral artery. An animal study.

BACKGROUND Intravascular injection of particulate steroids during cervical nerve root blocks has been postulated to be a source of catastrophic neurologic complications that might be avoided with the use of non-particulate steroids. The objective of this study was to compare the effects of direct intravascular injection of particulate and non-particulate steroids on the spinal cord and central nervous system. METHODS Eleven adult pigs underwent direct injection, under fluoroscopic guidance, into the vertebral artery while under general anesthesia. A particulate steroid (methylprednisolone) was injected into four animals (Group 1), whereas seven animals received a non-particulate steroid (dexamethasone in four animals [Group 2] and prednisolone in three [Group 3]). Following injection, the animals were assessed by direct observation of physical activity and with magnetic resonance imaging. After the animals were killed, brain and spinal cord material was retrieved, fixed in paraformaldehyde for one week, and then subjected to histopathologic analysis. RESULTS All four animals in Group 1 failed to regain consciousness after the injection and required ventilatory support. The animals in Groups 2 and 3 recovered fully and demonstrated no evidence of neurologic injury. Magnetic resonance imaging revealed upper cervical cord and brain stem edema in Group 1, but not in Groups 2 and 3. Histologic analysis showed early evidence of hypoxic and ischemic damage-specifically, early eosinophilic neuronal necrosis, nuclear condensation, white-matter pallor, and extracellular edema-in Group 1 but not in Groups 2 and 3. CONCLUSIONS These data suggest that one etiology of neurologic complications following cervical nerve blocks may be inadvertent intravascular injection of particulate steroids, as all animals injected with methylprednisolone had neurologic deficits while none of the controls injected with non-particulate steroids were affected. To our knowledge, this study is the first to demonstrate that particulate steroids cause neurologic deficits and to suggest that use of non-particulate steroids might prevent such complications.

Can tapentadol cause a false-positive urine drug screen result for amphetamine?

Tapentadol (Nucynta ® Ortho-McNeil-Janssen Pharmaceuticals, Inc. Raritan, NJ.), is a newer, synthetic analgesic approved in the US in 2008 (immediate-release) and 2011 (extended-release) for acute or chronic management of moderate to severe pain. Tapentadol acts as both a mu opioid receptor agonist and norepinephrine reuptake inhibitor.1, 2 Activity at the alpha-2 adrenoreceptor may, directly or indirectly, contribute to its analgesic effect.3 In comparison to oxycodone, tapentadol has similar analgesia with fewer side effects, delayed tolerance, and reduced withdrawal symptoms.4, 5 Tapentadol (Fig. 1) is structurally similar to amphetamine (Fig. 2). Based upon our prior study showing frequent false positive amphetamine screens with other similar drugs such as bupropion,6 we sought to determine whether therapeutic use of tapentadol would be associated with false positive immunoassay amphetamine urine drug screens. Fig. 1 Structure of tapentadol. (Source: http://en.wikipedia.org). Fig. 2 Generic structure of amphetamine. (Source: http://en.wikipedia.org). We recruited patients from a pain management clinic and a rheumatology clinic into a prospective, IRB-approved study. We screened computerized clinic records to identify all patients with scheduled appointments in June through August 2011 and with recorded prescriptions for tapentadol. We met eligible patients on their scheduled appointment days and explained the purpose of the study. We excluded patients who were taking prescription amphetamines or bupropion, who admitted illicit amphetamine use, or who had not taken tapentadol within the 3 days before screening. Screened patients were explicitly allowed to opt out without stating a reason. Enrolled patients provided a spontaneously voided urine specimen on the day of their office visit, which we tested using the Siemens Syva EMIT II ™ immunoassay (Siemens Healthcare Diagnostics; Deerfield, IL). All positive immunoassays would then be confirmed by thin-layer chromatography. We recorded each patients prescribed dose and asked patients to report the number of doses taken on the study day and the two preceding days. We screened 21 patients taking tapentadol. We excluded 10 patients (3 had not taken the drug recently, 2 had excluding medications, 2 missed their appointments, 2 declined, 1 researcher unavailable). We enrolled 11 patients (8 women, 3 men) with ages ranging from 31 to 86 years (mean 49.5, median 50). Daily dose ranged from 50 mg/day to the maximum labeled dose of 600 mg/day (mean 268 mg/day, median 200 mg/day). All patients were taking the immediate-release formulation only. All urine specimens produced a negative immunoassay result for amphetamine in all 11 patients. We relied upon patient self-report for the quantity of tapentadol used in the days before study enrollment, and we did not confirm the presence of tapentadol metabolite in the urine. However, all the screened patients were aware of the purpose of the study and received no compensation for their participation, so we believe their self-reported recent doses to be accurate. Tapentadol shares structural similarities with both amphetamine and methadone. Although we found no amphetamine cross-reaction with the immunoassay, another recent study has demonstrated cross-reactivity with a similar immunoassay for methadone.7 We conclude that therapeutic use of tapentadol up to the maximum recommended dose of 600 mg/day does not produce a false positive urine amphetamine screen.

Opioids as a Treatment Option for MS Patients with Chronic Pain

Neuropathic and nociceptive pain are commonly observed in patients with MS. Among the analgesic options available for treating pain in MS, opioids may be too often avoided because of concerns about prescribing restrictions and addictive potential. However, when these fears are misplaced, they deny the patient of a powerful and potentially effective pain reduction option. Proper screening and management can help select appropriate patients for opioid therapy and maintain patients on long-term therapy while monitoring for signs of behaviors such as addiction or diversion. One such method involves entering into a “contract” with the patient with guidelines for renewing prescriptions. Although the literature contains few studies on opioids specific to MS patients, a number of studies support the use of this drug category in patients experiencing neuropathic pain syndromes.