Selective Inhibition of NaV1.8 with VX-548 for Acute Pain.

BACKGROUND: The NaV1.8 voltage-gated sodium channel, expressed in peripheral nociceptive neurons, plays a role in transmitting nociceptive signals. The effect of VX-548, an oral, highly selective inhibitor of NaV1.8, on control of acute pain is being studied. METHODS: After establishing the selectivity of VX-548 for NaV1.8 inhibition in vitro, we conducted two phase 2 trials involving participants with acute pain after abdominoplasty or bunionectomy. In the abdominoplasty trial, participants were randomly assigned in a 1:1:1:1 ratio to receive one of the following over a 48-hour period: a 100-mg oral loading dose of VX-548, followed by a 50-mg maintenance dose every 12 hours (the high-dose group); a 60-mg loading dose of VX-548, followed by a 30-mg maintenance dose every 12 hours (the middle-dose group); hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. In the bunionectomy trial, participants were randomly assigned in a 2:2:1:2:2 ratio to receive one of the following over a 48-hour treatment period: oral high-dose VX-548; middle-dose VX-548; low-dose VX-548 (a 20-mg loading dose, followed by a 10-mg maintenance dose every 12 hours); oral hydrocodone bitartrate-acetaminophen (5 mg of hydrocodone bitartrate and 325 mg of acetaminophen every 6 hours); or oral placebo every 6 hours. The primary end point was the time-weighted sum of the pain-intensity difference (SPID) over the 48-hour period (SPID48), a measure derived from the score on the Numeric Pain Rating Scale (range, 0 to 10; higher scores indicate greater pain) at 19 time points after the first dose of VX-548 or placebo. The main analysis compared each dose of VX-548 with placebo. RESULTS: A total of 303 participants were enrolled in the abdominoplasty trial and 274 in the bunionectomy trial. The least-squares mean difference between the high-dose VX-548 and placebo groups in the time-weighted SPID48 was 37.8 (95% confidence interval [CI], 9.2 to 66.4) after abdominoplasty and 36.8 (95% CI, 4.6 to 69.0) after bunionectomy. In both trials, participants who received lower doses of VX-548 had results similar to those with placebo. Headache and constipation were common adverse events with VX-548. CONCLUSIONS: As compared with placebo, VX-548 at the highest dose, but not at lower doses, reduced acute pain over a period of 48 hours after abdominoplasty or bunionectomy. VX-548 was associated with adverse events that were mild to moderate in severity. (Funded by Vertex Pharmaceuticals; VX21-548-101 and VX21-548-102 ClinicalTrials.gov numbers, NCT04977336 and NCT05034952.).

Treatment of drug-resistant fibromyalgia symptoms using high-intensity laser therapy: a case-based review.

Fibromyalgia is a chronic musculoskeletal condition characterized by widespread pain in the body and is associated with tender points at the shoulder, back and hip regions. A wide variety of pharmacologic drugs and dietary supplements have been used with limited success in treating the musculoskeletal pain. Early clinical studies with low level laser therapy (LLLT) alone or in combination with drugs commonly used to treat fibromyalgia suggested that LLLT may be effective in reducing musculoskeletal pain and stiffness, as well as the number of tender locations. However, a sham-controlled study reported that LLLT was not significantly better than the sham treatment and kinesiotape. Preliminary studies with high-intensity laser therapy (HILT) suggest that it may be more effective than LLLT for treating chronic pain syndromes. Therefore, we evaluated low (1 W), intermediate (42 W) and high level (75 W) HILT in a woman with long-standing fibromyalgia syndrome which was resistant to both standard pharmacotherapy and treatment in an interdisciplinary pain management program. The patient received a series of treatments with a HILT device (Phoenix Thera-lase) at a wavelength of 1275 nm administered at both the paraspinous region and tender points in the shoulder and hip regions. Although the 1 W treatment produced minimal symptom relief, both the 42 and the 75 W treatments produced a dramatic reduction in her overall pain, improved quality of sleep, and increased her level of physical activity for 4-10 days after these treatment sessions. This case illustrates the potential beneficial effects of using higher power levels of HILT for patients with fibromyalgia syndrome who have failed to respond to conventional interdisciplinary treatment regimens.

An update on the management of postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) remain common and distressing complications following surgery. PONV and PDNV can delay discharge and recovery and increase medical costs. The high incidence of PONV has persisted in part because of the tremendous growth in ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major operations. Pharmacological management of PONV should be tailored to the patients' risk level using the PONV and PDNV scoring systems to minimize the potential for these adverse side effects in the postoperative period. A combination of prophylactic antiemetic drugs should be administered to patients with moderate-to-high risk of developing PONV in order to facilitate the recovery process. Optimal management of perioperative pain using opioid-sparing multimodal analgesic techniques and preventing PONV using prophylactic antiemetics are key elements for achieving an enhanced recovery after surgery. Strategies that include reductions of the baseline risk (e.g., adequate hydration, use of opioid-sparing analgesic techniques) as well as a multimodal antiemetic regimen will improve the likelihood of preventing both PONV and PDNV.

An update on pain management for elderly patients undergoing ambulatory surgery.

PURPOSE OF REVIEW: The aim of this review is to provide an overview of the drugs and techniques used for multimodal postoperative pain management in the older population undergoing surgery in the ambulatory setting. RECENT FINDINGS: Interest has grown in the possibility of adding adjuncts to a single shot nerve block in order to prolong the local anesthetic effect. The rapid and short-acting local anesthetics for spinal anesthesia are potentially beneficial for day-case surgery in the older population because of shorter duration of the motor block, faster recovery, and less transient neurologic symptoms. Another recent advance is the introduction of intravenous acetaminophen, which can rapidly achieve rapid peak plasma concentration (<15 min) following infusion and analgesic effect in ∼5 min with a duration of action up to 4 h. SUMMARY: The nonopioid analgesic therapies will likely assume an increasingly important role in facilitating the recovery process and improving the satisfaction for elderly ambulatory surgery patients. Strategies to avoid the use of opioids and minimize opioid-related side-effects is an important advance as we expand on the use of ambulatory surgery for the aging population.

Anesthesia for the elderly outpatient.

PURPOSE OF REVIEW: As the number of ambulatory surgery procedures continues to grow in an aging global society, the implementation of evidence-based perioperative care programs for the elderly patients will assume increased importance. RECENT FINDINGS: Increasing evidence supports the expanded use of ambulatory surgery for managing elderly patients undergoing elective surgery procedures. SUMMARY: This review article describes the demographics of ambulatory surgery in the elderly population. This review article describes the effects of aging on the responses of geriatric patients to anesthetic and analgesic drugs used during ambulatory surgery. Important considerations in the preoperative evaluation of elderly outpatients with co-existing diseases, as well as the advantages and disadvantages of different anesthetic techniques on a procedural-specific basis, and recommendations regarding the management of common postoperative side-effects (including delirium and cognitive dysfunction, fatigue, dizziness, pain, and gastrointestinal dysfunction) after ambulatory surgery. Finally, we discuss the future challenges related to the continued expansion of ambulatory surgery practice in this growing segment of our surgical population. The role of anesthesiologists as perioperative physicians is of critical importance for optimizing surgical outcomes for elderly patients undergoing ambulatory surgery. Providing high-quality, evidence-based anesthetic and analgesic care for elderly patients undergoing elective operations on an ambulatory basis will assume greater importance in the future.

Effect of local anaesthetic infiltration with bupivacaine and ropivacaine on wound healing: a placebo-controlled study.

Infiltration of surgical wounds with long-acting local anaesthetics (LA) is used to reduce postoperative incisional pain. We hypothesised that infiltration with LA interferes with wound healing in rats. Seventy-two rats were allocated into nine groups. After intraperitoneal anaesthesia, the interscapular dorsal region was infiltrated with equivolumes of saline, 0·5% bupivacaine or ropivacaine, in a randomised double-blind fashion. A standardised incision was performed in the infiltrated area and sutured closed. The rats were euthanised on the 3rd or 14th day after the operation and tissue from the incision site was subjected to histochemical analyses and mechanical testing (MT). Compared with the control group, bupivacaine displayed a significant increase in the macrophage number on day 3 (+63% versus +27% for ropivacaine). The transforming growth factor ß-1 expression had a significant increase in the LA (versus saline) groups, +63% in ropivacaine group and +115% in bupivacaine group on day 3 (P < 0·05). The collagen fibres as measured by dyed area were significantly higher in the bupivacaine group on day 3 (+56%, P < 0·01 versus +15% for ropivacaine). CD34 was reduced in bupivacaine group (-51%, P < 0·05 versus +3% for ropivacaine). On day 14, no statistical differences were observed in either LA group (versus saline) with respect to histopathologic or inflammatory mediators. MT on day 14 showed no differences between the LA and saline groups. The LA-induced increases in histological markers did not extend beyond the third day, suggesting that wound infiltration with long-acting LA does not impair the wound healing process in rats.

Use of herbal medication in the perioperative period: Potential adverse drug interactions.

Use of herbal medications and supplements has experienced immense growth over the last two decades, with retail sales in the USA exceeding $13 billion in 2021. Since the Dietary Supplement Health and Education Act (DSHEA) of 1994 reduced FDA oversight, these products have become less regulated. Data from 2012 shows 18% of U.S. adults used non-vitamin, non-mineral natural products. Prevalence varies regionally, with higher use in Western states. Among preoperative patients, the most commonly used herbal medications included garlic, ginseng, ginkgo, St. John's wort, and echinacea. However, 50-70% of surgical patients fail to disclose their use of herbal medications to their physicians, and most fail to discontinue them preoperatively. Since herbal medications can interact with anesthetic medications administered during surgery, the American Society of Anesthesiologists (ASA) and the American Association of Nurse Anesthetists (AANA) recommend stopping herbal medications 1-2 weeks before elective surgical procedures. Potential adverse drug effects related to preoperative use of herbal medications involve the coagulation system (e.g., increasing the risk of perioperative bleeding), the cardiovascular system (e.g., arrhythmias, hypotension, hypertension), the central nervous system (e.g., sedation, confusion, seizures), pulmonary (e.g., coughing, bronchospasm), renal (e.g., diuresis) and endocrine-metabolic (e.g., hepatic dysfunction, altered metabolism of anesthetic drugs). During the preoperative evaluation, anesthesiologists should inquire about the use of herbal medications to anticipate potential adverse drug interactions during the perioperative period.

Intrathecal transplantation of bone marrow stromal cells attenuates blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury in rabbits.

OBJECTIVE: Intrathecal administration of bone marrow stromal cells has been found to produce beneficial effects on ischemia-reperfusion injury to the spinal cord. The blood-spinal cord barrier is critical to maintain spinal cord homeostasis and neurologic function. However, the effects of bone marrow stromal cells on the blood-spinal cord barrier after spinal cord ischemia-reperfusion injury are not well understood. This study investigated the effects and possible mechanisms of bone marrow stromal cells on blood-spinal cord barrier disruption induced by spinal cord ischemia-reperfusion injury. METHODS: This was a prospective animal study conducted at the Central Laboratory of the First Affiliated Hospital, China Medical University. The study used 81 Japanese white rabbits (weight, 1.8-2.6 kg). Spinal cord ischemia-reperfusion injury was induced in rabbits by infrarenal aortic occlusion for 30 minutes. Two days before the injury was induced, bone marrow stromal cells (1 × 10(8) in 0.2-mL phosphate-buffered saline) were transplanted by intrathecal injection. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histologic examination. The permeability of the blood-spinal cord barrier was examined using Evans blue (EB) and lanthanum nitrate as vascular tracers. The expression and localization of tight junction protein occludin were assessed by Western blot, real-time polymerase chain reaction, and immunofluorescence analysis. Matrix metalloproteinase-9 (MMP-9) and tumor necrosis factor-α (TNF-α) expression were also measured. RESULTS: Intrathecal transplantation of bone marrow stromal cells minimized the neuromotor dysfunction and histopathologic deficits (P < .01) and attenuated EB extravasation at 4 hours (5.41 ± 0.40 vs 7.94 ± 0.36 µg/g; P < .01) and 24 hours (9.03 ± 0.44 vs 15.77 ± 0.89 µg/g; P < .01) after spinal cord ischemia-reperfusion injury. In addition, bone marrow stromal cells treatment suppressed spinal cord ischemia-reperfusion injury-induced decreases in occludin (P < .01). Finally, bone marrow stromal cells reduced the excessive expression of MMP-9 and TNF-α (P < .01). CONCLUSIONS: Pre-emptive intrathecal transplantation of bone marrow stromal cells stabilized the blood-spinal cord barrier integrity after spinal cord ischemia-reperfusion injury in a rabbit model of transient aortic occlusion. This beneficial effect was partly mediated by inhibition of MMP-9 and TNF-α and represents a potential therapeutic approach to mitigating spinal cord injury after aortic occlusion. CLINICAL RELEVANCE: Clinical thoracoabdominal aorta surgery may trigger spinal cord ischemia-reperfusion injury, resulting in paraplegia as well as bladder, bowel, and sexual dysfunction. Transplantation of bone marrow stromal cells has attracted increasing attention in the field of nervous system protection, but its mechanisms have not been elucidated completely. The blood-spinal cord barrier plays a crucial role to maintain normal spinal cord function. This study suggested that intrathecal transplantation of bone marrow stromal cells stabilized blood-spinal cord barrier integrity through inhibiting the upregulation of matrix metalloproteinase-9 and tumor necrosis factor-a and ameliorated spinal cord ischemia-reperfusion injury. This may provide a novel train of thought to enhance the protective effects of bone marrow stromal cells on spinal cord injury.

Use of a disposable acupressure device as part of a multimodal antiemetic strategy for reducing postoperative nausea and vomiting.

BACKGROUND: There is still controversy regarding the optimal strategy for managing postoperative nausea and vomiting (PONV) in high-risk surgical populations. Although acustimulation at the P6 acupoint has been demonstrated to be effective in preventing PONV, the effect of this nonpharmacologic therapy on the patient's recovery with respect to resumption of normal activities of daily living has not been previously assessed when it is used as part of a multimodal antiemetic regimen. Therefore, we designed this randomized, sham-controlled, and double-blind study to assess the efficacy of a disposable acupressure device (Pressure Right®; Pressure Point Inc., Grand Rapids, MI) on the incidence of emetic episodes and quality of recovery when used in combination with ondansetron and dexamethasone for antiemetic prophylaxis. METHODS: One hundred ASA physical status I and II patients undergoing major laparoscopic procedures were randomly assigned to either a control group (n = 50) receiving a "sham" acustimulation device or an acupressure group (n = 50) receiving a disposable Pressure Right device placed bilaterally at the P6 point 30 to 60 minutes before induction of anesthesia. All patients received a standardized general anesthetic. A combination of ondansetron, 4 mg IV, and dexamethasone, 4 mg IV, was administered during surgery for antiemetic prophylaxis in both study groups. The incidence of nausea and vomiting and the need for "rescue" antiemetic therapy were assessed at specific time intervals for up to 72 hours after surgery. The recovery profiles and quality of recovery questionnaires were evaluated at 48 hours and 72 hours after surgery. Patient satisfaction with the management of their PONV was assessed at the end of the 72-hour study period. RESULTS: The 2 study groups did not differ in their demographic characteristics or risk factors for PONV. The incidence of vomiting at 24 hours was significantly decreased in the acupressure group (10% vs 26%, P = 0.04, 95% confidence interval for absolute risk reduction 1%-31%). The overall incidence of vomiting from 0 to 72 hours after surgery was also significantly decreased from 30% to 12% in the acupressure group (P = 0.03, 95% confidence interval 2%-33%). Furthermore, adjunctive use of the acupressure device seemed to enhance patient satisfaction with their PONV management and quality of recovery at 48 hours after surgery. However, the recovery times to hospital discharge, resumption of normal physical activities, and return to work did not differ significantly between the 2 study groups. CONCLUSION: Use of the Pressure Right acupressure device in combination with antiemetic drugs provided a reduction in the incidence of vomiting from 0 to 72 hours after surgery with an associated improvement in patient satisfaction with their PONV management. However, recovery and outcome variables failed to demonstrate any improvement with the addition of the acupressure device.

Perioperative care for the older outpatient undergoing ambulatory surgery.

As the number of ambulatory surgery procedures continues to grow in an aging global society, the implementation of evidence-based perioperative care programs for the elderly will assume increased importance. Given the recent advances in anesthesia, surgery, and monitoring technology, the ambulatory setting offers potential advantages for elderly patients undergoing elective surgery. In this review article we summarize the physiologic and pharmacologic effects of aging and their influence on anesthetic drugs, the important considerations in the preoperative evaluation of elderly outpatients with coexisting diseases, the advantages and disadvantages of different anesthetic techniques on a procedural-specific basis, and offer recommendations regarding the management of common postoperative side effects (including delirium and cognitive dysfunction, fatigue, dizziness, pain, and gastrointestinal dysfunction) after ambulatory surgery. We conclude with a discussion of future challenges related to the growth of ambulatory surgery practice in this segment of our surgical population. When information specifically for the elderly population was not available in the peer-reviewed literature, we drew from relevant information in other ambulatory surgery populations.

The effects of oral ibuprofen and celecoxib in preventing pain, improving recovery outcomes and patient satisfaction after ambulatory surgery.

BACKGROUND: Nonsteroidal antiinflammatory drugs have become increasingly popular as part of multimodal analgesic regimens for pain management in the ambulatory setting. We designed this randomized, double-blind, placebo-controlled study to evaluate the effect of postoperative administration of either a nonselective nonsteroidal antiinflammatory drug (ibuprofen) or the cyclooxygenase-2 selective inhibitor (celecoxib when administered as part of a multimodal analgesic regimen) on the severity of pain, the need for rescue analgesics, and clinically relevant patient outcomes after ambulatory surgery. The primary end point was the time to resumption of normal activities of daily living. METHODS: One hundred eighty patients undergoing outpatient surgery were randomly assigned to 1 of 3 treatment groups: group 1 (control) received either 2 placebo capsules (matching celecoxib) or 1 placebo tablet (matching ibuprofen) in the recovery room and 1 placebo tablet at bedtime on the day of surgery, followed by 1 placebo capsule or tablet 3 times a day for 3 days after discharge; group 2 (celecoxib) received celecoxib 400 mg (2 capsules) orally in the recovery room and 1 placebo capsule and tablet at bedtime on the day of surgery, followed by celecoxib 200 mg (1 capsule) twice a day + placebo capsule every day at bedtime for 3 days after surgery; or group 3 (ibuprofen) received ibuprofen 400 mg (1 tablet) orally in the recovery room and 400 mg orally at bedtime on the day of surgery, followed by 400 mg orally 3 times a day for 3 days after surgery. Recovery times, postoperative pain scores, and the need for rescue analgesics were recorded before discharge. Follow-up evaluations were performed at 24 hours, 48 hours, 72 hours, 7 days, and 30 days after surgery to assess postdischarge pain, analgesic requirements, resumption of normal activities, opioid-related side effects, as well as quality of recovery and patient satisfaction with their postoperative pain management using a 5-point verbal rating scale. RESULTS: The 3 groups did not differ with respect to their demographic characteristics. Compared with the placebo treatment, both celecoxib and ibuprofen significantly decreased the need for rescue analgesic medication after discharge (P < 0.05). The effect sizes (celecoxib and ibuprofen versus control group) were 0.73 to 1 and 0.3 to 0.8, respectively. Quality of recovery scores and patient satisfaction with their postoperative pain management were also improved in the celecoxib and ibuprofen groups compared with the control group (P < 0.05, effect size [vs control group] = 0.67). The incidence of postoperative constipation was significantly higher in the control group (28%) compared with the celecoxib (5%) and ibuprofen (7%) groups, respectively (P < 0.05). Both active treatments were well tolerated in the postdischarge period. However, the time to resumption of normal activities of daily living was similar among the 3 groups. CONCLUSIONS: Both ibuprofen (1200 mg/d) and celecoxib (400 mg/d) significantly decreased the need for rescue analgesic medication in the early postdischarge period, leading to an improvement in the quality of recovery and patient satisfaction with their pain management after outpatient surgery.

Impact of chronic medications in the perioperative period -anesthetic implications (Part II).

Background: This review article discusses the pharmacodynamic effects of the most commonly used chronic medications by patients undergoing elective surgical procedures, namely cardiovascular drugs (e.g., beta blockers, alpha-2 agonist, calcium channel blockers, ACE inhibitors, diuretics, etc.), lipid-lowering drugs, gastrointestinal medications (H2-blockers, proton pump inhibitors), pulmonary medications (inhaled ß-agonists, anticholinergics,), antibiotics (tetracyclines, clindamycin and macrolide, linezolid.), opioids and non-opioids analgesics (NSAIDs, COX-2 inhibitors, acetaminophen), gabapentanoids, erectile dysfunction (ED) drugs, psychotropic drugs (tricyclic antidepressants [TCAs], monoamine oxidase inhibitors [MAOI], selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs], and cannabinol-containing drugs).  In addition, the potential adverse drug-interactions between these chronic medications and commonly used anesthetic drugs during the perioperative period will be reviewed. Finally, recommendations regarding the management of chronic medications during the preoperative period will be provided.Materials and Methods: An online search was conducted from January 2000 through February 2021 with the Medline database through PubMed and Google Scholar using the following search terms/keywords: "chronic medications in the perioperative period", and "chronic medications and anesthetic implications." In addition, we searched for anesthetic side effects associated with the major drug groups.Results and Conclusions: An understanding of the pharmacodynamic effects of most used chronic medications is important to avoid untoward outcomes in the perioperative period. These drug interactions may result in altered efficacy and toxicity of the anesthetic medications administered during surgery. These drug-drug interactions can also affect the morbidity, mortality, recovery time of surgical patients and acute relapse of chronic illnesses which could lead to last minute cancellation of surgical procedures. Part II of this two-part review article focuses on the reported interactions between most commonly taken chronic medications by surgical patients and anesthetic and analgesic drugs, as well as recommendations regarding the handling these chronic medications during the perioperative period.

Impact of chronic medications in the perioperative period: mechanisms of action and adverse drug effects (Part I).

Background: This review article discusses the pharmacology of the most commonly used chronic medications in patients undergoing elective surgical procedures. The mechanism of action and adverse side effects of cardiovascular medications (e.g., beta blockers, alpha-2 agonist, calcium channel blockers, ACE inhibitors, diuretics), lipid-lowering drugs, gastrointestinal medications (H2-blockers, proton pump inhibitors), pulmonary medications (inhaled ß-agonists, anticholinergics,), antibiotics (tetracyclines, clindamycin and macrolide, linezolid), opioids and non-opioids analgesics (NSAIDs, COX-2 inhibitors, acetaminophen), gabapentanoids, erectile dysfunction (ED) drugs, and psychotropic drugs (tricyclic antidepressants [TCAs], monoamine oxidase inhibitors [MAOI], selective serotonin reuptake inhibitors [SSRIs], serotonin norepinephrine reuptake inhibitors [SNRIs], and cannabinol-containing drugs) will be reviewed.Materials and Methods: An online search was conducted from January 2000 through February 2021 with the Medline database through PubMed and Google Scholar using the following search terms/keywords: "chronic medications in the perioperative period", and "chronic medications and anesthetic implications." In addition, we searched for anesthetic side effects associated with the major drug groups.Results and Conclusions: An understanding of the pharmacology and pharmacokinetics of most used chronic medications is important to avoid untoward outcomes in the perioperative period. These drug interactions may result in altered efficacy and toxicity of the anesthetic medications administered during surgery. These drug-drug interactions can also effect the morbidity, mortality, and recovery time of surgical patients. Part I of this two-part review article focuses on the mechanisms of action and adverse side effects of the chronic medications most commonly taken by surgical patients in the preoperative period.

The use of prolonged peripheral neural blockade after lower extremity amputation: the effect on symptoms associated with phantom limb syndrome.

BACKGROUND: Phantom limb syndrome (PLS) is common after limb amputations, involving up to 90% of amputees. Although many different therapies have been evaluated, none has been found to be highly effective. Therefore, we evaluated the efficacy of a prolonged perineural infusion of a high concentration of local anesthetic solution in preventing PLS. METHODS: A perineural catheter was placed immediately before or during surgery in 71 patients undergoing lower extremity amputation. A continuous infusion of 0.5% ropivacaine was started intraoperatively at 5 mL/h using an elastomeric (nonelectronic) pump, and continued for 4 to 83 days after surgery. PLS was evaluated on the first postoperative day and then 1, 2, 3, and 4 weeks, and 3, 6, 9, and 12 months after surgery. To evaluate the presence and severity of PLS while the patient was receiving the ropivacaine infusion, it was discontinued for 6 to 12 hours before each assessment period (i.e., until the sensation in the extremity returned). The severity of phantom limb and stump pain was assessed using a 5-point verbal rating scale (VRS), with 0 = no pain to 4 = intolerable pain, and "phantom" sensations were recorded as present or absent. If the VRS score was >1 or significant phantom sensations were present, the ropivacaine infusion was immediately restarted at 5 mL/h. If the VRS score remained at 0 to 1 and the patient had not experienced phantom sensations for 48 hours, the infusion was permanently discontinued and the catheter was removed. RESULTS: Median duration of the local anesthetic infusion was 30 days (95% confidence interval, 25-30 days). On postoperative day 1, 73% of the patients complained of severe-to-intolerable pain (visual analog scale >2). However, the incidence of severe-to-intolerable phantom limb pain was only 3% at the end of the 12-month evaluation period. At the end of the 12-month period, the percentage of patients with VRS pain scores were 0 = 84%, 1 = 10%, 2 = 3%, 3 = 3%, and 4 = none. However, phantom limb sensations were present in 39% of patients at the end of the 12-month evaluation period. All patients were able to manage the elastomeric catheter infusion system at home. CONCLUSION: Use of a prolonged postoperative perineural infusion of ropivacaine 0.5% seems to be an effective therapy for the treatment of phantom limb pain and sensations after lower extremity amputation.

The role of multimodal analgesia in pain management after ambulatory surgery.

PURPOSE OF REVIEW: As outpatient (day-case) surgery had continued to grow throughout the world, many more complex and potentially painful procedures are being routinely performed in the ambulatory setting. Opioid analgesics, once considered the standard approach to preventing acute postoperative pain, are being replaced by a combination of nonopioid analgesic drugs with diverse modes of action as part of a multimodal approach to preventing pain after ambulatory surgery. This review will provide an update on the topic of multimodal pain management for ambulatory (day-case) surgery. RECENT FINDINGS: Efficacy of multimodal analgesic regimens continues to improve; opioid analgesics are increasingly taking on the role of 'rescue analgesics' for acute pain after day-case surgery. The use of multimodal analgesia is rapidly becoming the 'standard of care' for preventing pain after ambulatory procedures at most surgery centers throughout the world. SUMMARY: This article discusses recent evidence from the peer-reviewed literature regarding the role of local anesthetics, NSAIDs, gabapentinoids, and acetaminophen, as well as alpha-2 agonists, ketamine, esmolol, and nonpharmacologic approaches (e.g., transcutaneous electrical stimulation) as parts of multimodal pain management strategies in day-case surgery.

Management strategies for the treatment and prevention of postoperative/postdischarge nausea and vomiting: an updated review.

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) remain common and distressing complications following surgery. The routine use of opioid analgesics for perioperative pain management is a major contributing factor to both PONV and PDNV after surgery. PONV and PDNV can delay discharge from the hospital or surgicenter, delay the return to normal activities of daily living after discharge home, and increase medical costs. The high incidence of PONV and PDNV has persisted despite the introduction of many new antiemetic drugs (and more aggressive use of antiemetic prophylaxis) over the last two decades as a result of growth in minimally invasive ambulatory surgery and the increased emphasis on earlier mobilization and discharge after both minor and major surgical procedures (e.g. enhanced recovery protocols). Pharmacologic management of PONV should be tailored to the patient's risk level using the validated PONV and PDNV risk-scoring systems to encourage cost-effective practices and minimize the potential for adverse side effects due to drug interactions in the perioperative period. A combination of prophylactic antiemetic drugs with different mechanisms of action should be administered to patients with moderate to high risk of developing PONV. In addition to utilizing prophylactic antiemetic drugs, the management of perioperative pain using opioid-sparing multimodal analgesic techniques is critically important for achieving an enhanced recovery after surgery. In conclusion, the utilization of strategies to reduce the baseline risk of PONV (e.g. adequate hydration and the use of nonpharmacologic antiemetic and opioid-sparing analgesic techniques) and implementing multimodal antiemetic and analgesic regimens will reduce the likelihood of patients developing PONV and PDNV after surgery.

Improvement in psychosocial outcomes in chronic pain patients receiving intrathecal morphine infusions.

BACKGROUND: When conventional multimodal analgesic therapy is unsuccessful, more aggressive analgesic treatments are required for patients with intractable chronic pain. Despite extensive clinical experience with implanted morphine pumps, there is still controversy regarding the psychosocial effects of this invasive analgesic therapy. In this prospective study, we evaluated the impact of intrathecal (IT) morphine infusions on pain perception and psychosocial functionality. A secondary objective of this pilot study was to assess the effect of IT morphine infusion on the patient's level of functional activity. METHODS: Thirty patients with chronic nonmalignant pain that failed to respond to multimodal analgesic regimens were evaluated using the McGill Pain Questionnaire before and at 3-, 12-, and 24-mo intervals after implantation of an IT morphine infusion pump. At each clinic visit, the patient's level of pain was assessed using an 11-point visual analog scale, with 0 = no pain and 10 = worse pain imaginable. The mean initial morphine infusion rate was 0.23 +/- 0.14 mg/day (with a range from 0.09 to 0.75 mg/day) and was subsequently adjusted to maintain their pain score at a value <50% of the initial value. Adverse side effects and complications, as well as activity levels, were recorded at each clinic visit. RESULTS: Both evaluative and affective components of the pain assessment demonstrated a significant improvement over the 24-mo study period. The evaluative component of the McGill Pain Questionnaire improved 66%, the affective component 59%, and the sensory component 32%. The average morphine infusion rate increased to 0.44 +/- 0.29, 0.66 +/- 0.39, and 0.80 +/- 0.45 mg/day at the 3-, 12-, and 24-mo follow-up intervals (P < 0.05). The reduced level of chronic pain leads to improved social, work, and family relationships and quality of life. Among 13 patients of working age, 12 returned to work full time, and among 17 retired patients, 14 had a reduced need for assistance. CONCLUSIONS: IT infusion of morphine using an implantable pump was helpful in improving psychosocial function in patients with intractable pain that had failed to respond to standard multimodal analgesic therapy.