Epidural blood patch in a patient receiving large dose enoxaparin (Lovenox).
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Biomedical subjects
Publications and source records attributed to Raymond Sinatra.
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PURPOSE OF REVIEW: The purpose of this review is to highlight the important recent advances in this fast developing field of pain mechanisms. It is now recognized that acute tissue and neural injuries can result in nociceptor sensitization (primary hyperalgesia) and spinal cord hyperexcitability or central sensitization that results in secondary hyperalgesia and allodynia. RECENT FINDINGS: New findings regarding peripheral and central sensitization are presented in this review. Newer ideas on pain modulation, pain states and pain syndromes, mechanisms of chronic pain, newer opioid and non opioid medications including newer N-methyl-D-asparate antagonists, cyclooxygenase-2 inhibitors and membrane stabilizing analgesics as well as pain control at the genetic level are discussed. SUMMARY: The research of the last decade has focused on the biochemical and structural plasticity of the nervous system following tissue and nerve injury. The mechanisms involved in the transition from acute to chronic pain are complex with the involvement of interacting receptor systems and intracellular ion flux, second messenger systems, new synaptic connections and apoptosis.
Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital stays as well as increased healthcare costs. Patient-controlled analgesia (PCA) has emerged as an effective way for patients to manage their pain, allowing self-administration of small doses of analgesics to maintain a certain level of pain control. PCA is most commonly delivered via an intravenous (IV) or epidural route, and while patient satisfaction is higher with PCA than with conventional methods of analgesic administration, the invasiveness, costs and risk of errors associated with currently available modalities may limit their utility. These systems also require significant healthcare resources, as nurses must manually program the pumps to deliver the correct amount of medication. Several new PCA modalities are being developed to address these limitations. These systems deliver drug through a variety of routes, including nasal transmucosal and transdermal. Most notably, a self-contained, credit card-sized, transdermal PCA system is currently in the final stages of development. The fentanyl HCl patient-controlled transdermal system (PCTS; IONSYS, Ortho-McNeil Pharmaceutical, Inc., Raritan, NJ) uses an imperceptible, low-intensity direct current to transfer fentanyl on demand across the skin into the systemic circulation. This compact system is patient-activated, can be applied to the patient's upper arm or chest, and is designed to manage moderate-to-severe pain requiring opioid analgesia. The system delivers a preprogrammed amount of fentanyl HCI over 10 minutes, for a total of 80 doses, or for 24 hours, whichever occurs first. The on-demand dosing and pharmacokinetics of this system differentiate it from the passive transdermal formulation of fentanyl designed for the management of chronic pain. Clinical studies have shown that the fentanyl HCl PCTS is effective in the management of acute postoperative pain. These studies have also demonstrated that the system is safe and well tolerated by patients.
PURPOSE: This study was undertaken because, although there is evidence that cyclooxygenase type 2 (COX)-2 inhibitors do not compromise platelets in healthy volunteers, many clinicians remain hesitant to administer them perioperatively without definitive evidence of intact platelet function during anesthesia and surgery. METHODS: In 20 patients scheduled for lower abdominal and pelvic surgery, 5 mL of blood were obtained for baseline platelet aggregometry. One hour prior to surgery, patients received an oral solution of either rofecoxib (ROF) 50 mg or placebo (PLAC) by randomized, double-blinded assignment. Approximately one hour after onset of anesthesia, an intraoperative blood sample was obtained. Baseline and postdrug samples were centrifuged to generate platelet-rich plasma, which was challenged with adenosine diphosphate (ADP) and arachidonic acid (AA). Aggregometry was performed with and without incubation with aspirin. The data in each subject were normalized to baseline aggregation in response to AA alone and ADP alone. Intergroup differences were assessed using paired t test; P < 0.05 was considered significant. RESULTS: Consistent with known effects of anesthesia on platelet function, both groups had approximately 25% intraoperative declines in aggregation in response to ADP (P = NS for PLAC vs ROF) and even greater declines in response to AA (P = NS for PLAC vs ROF). Aspirin eliminated aggregation in response to AA in both groups (P = NS), and it caused similar declines in PLAC and ROF groups during exposure to ADP (P = NS). CONCLUSION: This study provides strong evidence that ROF does not compromise platelet aggregation during anesthesia and surgery; nor does it interfere with the platelet inhibitory effect of aspirin.
Management of acute postoperative pain remains suboptimal: nearly 80% of patients report moderate to extreme pain following surgery. New pain management paradigms incorporate multimodal analgesia, using a combination of analgesics throughout the perioperative period to control nociceptive and centrally-stimulated pain. Nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) have a role in postoperative pain management, but concerns about increased bleeding and inhibited wound healing and bone fusion have limited their use. Cyclooxygenase (COX)-2-selective inhibitors (coxibs) offer the peripheral pain-relieving benefits of nonselective NSAIDs but with fewer adverse GI effects; they also may have a role in central sensitization. Clinical trials have demonstrated the efficacy and safety of celecoxib and rofecoxib for postoperative pain and for preemptive analgesia, and newer agents such as valdecoxib and etoricoxib also have demonstrated efficacy in these settings. In addition to their selectivity for the COX-2 isozyme overall, unique differences among the coxibs, such as in plasma half-life, may impart certain clinical advantages.
Primary care attitudes affecting the use of strong opioids in pain management have changed considerably in the last 3 decades. Forces that have shaped current attitudes and trends in opioid prescribing include historical influences, regulatory factors, and technologic and scientific advances. The article identifies for primary care physicians the current challenges and issues surrounding the use of opioid analgesics for noncancer pain and examines how new technology and expanding knowledge have been applied to existing opioids such as morphine, oxymorphone, and fentanyl to address continuing challenges in pain management.