Asokumar Buvanendran

Validation of proposed diagnostic criteria (the “Budapest Criteria”) for Complex Regional Pain Syndrome

&NA; Current IASP diagnostic criteria for CRPS have low specificity, potentially leading to overdiagnosis. This validation study compared current IASP diagnostic criteria for CRPS to proposed new diagnostic criteria (the “Budapest Criteria”) regarding diagnostic accuracy. Structured evaluations of CRPS‐related signs and symptoms were conducted in 113 CRPS‐I and 47 non‐CRPS neuropathic pain patients. Discriminating between diagnostic groups based on presence of signs or symptoms meeting IASP criteria showed high diagnostic sensitivity (1.00), but poor specificity (0.41), replicating prior work. In comparison, the Budapest clinical criteria retained the exceptional sensitivity of the IASP criteria (0.99), but greatly improved upon the specificity (0.68). As designed, the Budapest research criteria resulted in the highest specificity (0.79), again replicating prior work. Analyses indicated that inclusion of four distinct CRPS components in the Budapest Criteria contributed to enhanced specificity. Overall, results corroborate the validity of the Budapest Criteria and suggest they improve upon existing IASP diagnostic criteria for CRPS.

Multimodal analgesia for controlling acute postoperative pain.

Purpose of review Multimodal analgesia is needed for acute postoperative pain management due to adverse effects of opioid analgesics, which can impede recovery; a problem that is of increasing concern with the rapid increase in the number of ambulatory surgeries. Yet, the literature on multimodal analgesia often shows variable degrees of success, even with studies utilizing the same adjuvant medication. Recent findings Nonsteroidal anti-inflammatory drugs and selective cyclooxygenase-2 inhibitors consistently reduce postoperative opioid consumption. The N-methyl-D-aspartate antagonists have produced variable results in studies, which may be due to the dose and timing of drug administration. Alpha-2 adrenergic agonists have been useful as adjuvant for regional analgesia but not when administered orally. The alpha-2-delta receptor modulators such as gabapentin have shown early promising results in multimodal analgesia. Local anesthetic injection at the surgical site, though not as a preemptive analgesic, has recently been demonstrated to be beneficial in multimodal analgesia. No new adjuvants have appeared in the last year, which robustly reduce opioid consumption and opioid-related adverse effects. Summary There is a continuing need to explore new drug combinations to achieve all of the purported goals of multimodal anesthesia.

Perioperative Oral Pregabalin Reduces Chronic Pain After Total Knee Arthroplasty: A Prospective, Randomized, Controlled Trial

BACKGROUND: Despite the enormous success of total knee arthroplasty (TKA), chronic neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. We hypothesized that perioperative treatment with pregabalin, a chronic pain medication, would reduce the incidence of postsurgical neuropathic pain. METHODS: We performed a randomized, placebo-controlled, double-blind trial of pregabalin (300 mg) administered before TKA and for 14 days after TKA (150–50 mg twice daily). Patients were screened for the presence of neuropathic pain at 3 and 6 mo postoperatively using the Leeds Assessment of Neuropathic Symptoms and Signs scale. Secondary outcomes included postsurgical recovery and rehabilitation measures, including knee range of motion, opioid consumption, postoperative pain scores, sleep disturbance, and time to discharge as well as the occurrence of postoperative systemic complications. RESULTS: Of the 240 patients randomly assigned to the 2 treatment groups (120 in each), data for the primary outcome were obtained from 113 pregabalin patients and 115 placebo patients. At both 3 and 6 mo postoperatively, the incidence of neuropathic pain was less frequent in the pregabalin group (0%) compared with the placebo group (8.7% and 5.2% at 3 and 6 mo, respectively; P = 0.001 and P = 0.014). Patients receiving pregabalin also consumed less epidural opioids (P = 0.003), required less oral opioid pain medication while hospitalized (P = 0.005), and had greater active flexion over the first 30 postoperative days (P = 0.013). There were no differences in the actual recorded duration of hospitalization between the 2 groups, although time to achieve hospital discharge criteria was longer for placebo patients, 69.0 ± 16.0 h (mean ± sd), than that of pregabalin patients, 60.2 ± 15.8 h (P = 0.001). Sedation (P = 0.005) and confusion (P = 0.013) were more frequent on the day of surgery and postoperative day 1 in patients receiving pregabalin. CONCLUSION: Perioperative pregabalin administration reduces the incidence of chronic neuropathic pain after TKA, with less opioid consumption and better range of motion during the first 30 days of rehabilitation. However, in the doses tested, it is associated with a higher risk of early postoperative sedation and confusion.

Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans.

Background: The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E2 and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement. Methods: Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision. Results: Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E2 concentration after surgery; interleukin 1&bgr; and tumor necrosis factor &agr; were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1&bgr;; tumor necrosis factor &agr; decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E2. Conclusions: These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.

Intrathecal magnesium prolongs fentanyl analgesia: A prospective, randomized, controlled trial

Magnesium is a noncompetitive, N-methyl-d-aspartate receptor antagonist that does not effectively cross the blood-brain barrier when given IV. Intrathecal magnesium potentiates opioid antinociception in rats, and the safety of intrathecal magnesium has been demonstrated in animals. This is the first prospective human study evaluating whether intrathecal magnesium could prolong spinal opioid analgesia. Fifty-two patients requesting analgesia for labor were randomized to receive either intrathecal fentanyl 25 &mgr;g plus saline or fentanyl 25 &mgr;g plus magnesium sulfate 50 mg as part of a combined spinal-epidural technique. The duration of analgesia of the intrathecal drug combination was defined by the time of patient request for additional analgesia. There was significant prolongation in the median duration of analgesia (75 min) in the magnesium plus fentanyl group compared with the fentanyl alone group (60 min). There was no associated increase in adverse events in the group that received intrathecal magnesium. Larger doses of intrathecal magnesium were not studied in this group of patients because of the limitations on cephalad spread when hyperbaric solutions are injected in the sitting position. Our data indicate that intrathecal magnesium prolongs spinal opioid analgesia in humans and suggest that the availability of an intrathecal N-methyl-d-aspartate antagonist could be of clinical importance for pain management.

Preventing the Development of Chronic Pain After Orthopaedic Surgery with Preventive Multimodal Analgesic Techniques

The prevalences of complex regional pain syndrome, phantom limb pain, chronic donor-site pain, and persistent pain following total joint arthroplasty are alarmingly high. Central nervous system plasticity that occurs in response to tissue injury may contribute to the development of persistent postoperative pain. Many researchers have focused on methods to prevent central neuroplastic changes from occurring through the utilization of preemptive or preventive multimodal analgesic techniques. Multimodal analgesia allows a reduction in the doses of individual drugs for postoperative pain and thus a lower prevalence of opioid-related adverse events. The rationale for this strategy is the achievement of sufficient analgesia due to the additive effects of, or the synergistic effects between, different analgesics. Effective multimodal analgesic techniques include the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2 agonists, ketamine, alpha(2)-delta ligands, and opioids.

The Appropriate Use of Neurostimulation of the Spinal Cord and Peripheral Nervous System for the Treatment of Chronic Pain and Ischemic Diseases: The Neuromodulation Appropriateness Consensus Committee

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications.

The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases

The Neuromodulation Appropriateness Consensus Committee (NACC) of the International Neuromodulation Society (INS) evaluated evidence regarding the safety and efficacy of neurostimulation to treat chronic pain, chronic critical limb ischemia, and refractory angina and recommended appropriate clinical applications.

Characterization of a new animal model for evaluation of persistent postthoracotomy pain

Chronic pain after thoracotomy is common, although its basis and therapy have not been well characterized. In this study we characterize the allodynic responses (mechanical and cold) as well as the histopathologic changes after thoracotomy and rib retraction in rats. The antinociceptive effect of systemic and intrathecal analgesics was also evaluated. Male Sprague-Dawley rats were anesthetized and the right 4th and 5th ribs surgically exposed. The pleura was opened between the ribs and a retractor placed under both ribs and opened 8 mm. Retraction was maintained for 5, 30, or 60 min. Control animals had pleural incision only. Beginning Day 2 postsurgery, animals were tested for mechanical allodynia using calibrated von Frey filaments and cold allodynia using acetone applied to the incision site. Two weeks after surgery, animals were tested for reduction of allodynia with intraperitoneal and intrathecal injections of analgesics. Intercostal nerve histology was examined at 14 days postsurgery. Allodynia developed in 50% of the animals with 60 min retraction but in only 11% and 10% of animals when the retraction time was 5 and 30 min, respectively, and in none of the control animals. Allodynic animals showed extensive axon loss in the intercostal nerves of the retracted ribs. Allodynia appeared by Day 10 in the rib-retraction model and lasted at least 40 days. Systemic morphine sulfate (50% effective dose [ED50], 1.06 mg/kg) and gabapentin (ED50, 24.2 mg/kg), as well as intrathecal morphine (ED50, 1.19 nmol), gabapentin (ED50, 13.8 nmol), clonidine (ED50, 72.7 nmol), and neostigmine (ED50, 0.54 nmol) reduced allodynia. Rib-retraction in rats for 60 min produces allodynia that lasts more than 1 mo, and this allodynia is reduced by morphine, gabapentin, clonidine, and neostigmine. This new model may be useful for quantifying the efficacy of techniques to reduce the frequency and severity of long-term postthoracotomy pain.

Safeguards to Prevent Neurologic Complications after Epidural Steroid Injections: Consensus Opinions from a Multidisciplinary Working Group and National Organizations

Background: Epidural corticosteroid injections are a common treatment for radicular pain caused by intervertebral disc herniations, spinal stenosis, and other disorders. Although rare, catastrophic neurologic injuries, including stroke and spinal cord injury, have occurred with these injections. Methods: A collaboration was undertaken between the U.S. Food and Drug Administration Safe Use Initiative, an expert multidisciplinary working group, and 13 specialty stakeholder societies. The goal of this collaboration was to review the existing evidence regarding neurologic complications associated with epidural corticosteroid injections and produce consensus procedural clinical considerations aimed at enhancing the safety of these injections. U.S. Food and Drug Administration Safe Use Initiative representatives helped convene and facilitate meetings without actively participating in the deliberations or decision-making process. Results: Seventeen clinical considerations aimed at improving safety were produced by the stakeholder societies. Specific clinical considerations for performing transforaminal and interlaminar injections, including the use of nonparticulate steroid, anatomic considerations, and use of radiographic guidance are given along with the existing scientific evidence for each clinical consideration. Conclusion: Adherence to specific recommended practices when performing epidural corticosteroid injections should lead to a reduction in the incidence of neurologic injuries.