Local and Intra-articular Administration of Nonsteroidal Anti-inflammatory Drugs for Pain Management in Orthopedic Surgery.

BACKGROUND: Although growing evidence demonstrates the benefits of locally administered nonsteroidal anti-inflammatory drugs (NSAIDs) for postoperative pain management, there is ongoing debate regarding NSAID use in orthopedic surgery. AREAS OF UNCERTAINTY: Current data largely support a local site of NSAID action and suggest that effective pain control can be achieved with delivery of NSAIDs intra-articularly (IA) and/or locally at the site of injury, where they can block peripheral production of inflammatory mediators and may desensitize nociceptors. Improvements in postoperative pain control with locally administered NSAIDs have been widely reported in the total joint arthroplasty literature and may offer benefits in patient's undergoing arthroscopic procedures and those with osteoarthritis as well. The purpose of this review is to examine the available evidence in the literature regarding the efficacy and safety profile of the use of local and IA NSAIDs in orthopedic surgery. DATA SOURCES: Narrative literature review using keywords, expert opinion, either during or from live conference. THERAPEUTIC ADVANCES: Local and IA administration of NSAIDs for pain management in orthopedic surgery. CONCLUSION: There is convincing evidence that NSAIDs administered locally in and around the joint reduce postoperative pain scores and opioid consumption in patients undergoing total joint arthroplasty, yet further research is required regarding the risks of potential chondrotoxicity and the inhibition of bone and soft-tissue healing with locally administered NSAIDs.

Current Perspective on the Use of Opioids in Perioperative Medicine: An Evidence-Based Literature Review, National Survey of 70,000 Physicians, and Multidisciplinary Clinical Appraisal.

Objective: Opioids represent an important analgesic option for physicians managing acute pain in surgical patients. Opioid management is not without its drawbacks, however, and current trends suggest that opioids might be overused in the United States. An expert panel was convened to conduct a clinical appraisal regarding the use of opioids in the perioperative setting. Methods: The clinical appraisal consisted of the review, presentation, and assessment of current published evidence as it relates to the statement "Opioids are not overused in the United States, even though opioid adjunct therapy achieves greater pain control with less risk." The authors' evaluation of this statement was also compared with the results of a national survey of surgeons and anesthesiologists in the United States. Results: We report the presented literature and proceedings of the panel discussion. The national survey revealed a wide range of opinions regarding opioid overuse in the United States. Current published evidence provides support for the efficacy of opioid therapy in surgical patients; however, it is not sufficient to conclude unequivocally that opioids are-or are not-overused in the management of acute surgical pain in the United States. Conclusions: Opioids remain a key component of multimodal perioperative analgesia, and strategic opioid use based on clinical considerations and patient-specific needs represents an opportunity to support improved postoperative outcomes and satisfaction. Future studies should focus on identifying optimal procedure-specific and patient-centered approaches to multimodal perioperative analgesia.

Clopidogrel IBS Patients Have Higher Incidence of Gastrointestinal Symptoms Influenced by Age and Gender.

BACKGROUND: Clopidogrel is an irreversible antagonist of P2Y12 receptors (P2Y12Rs) used as an antiplatelet drug to reduce risk of thrombosis. P2Y12Rs are expressed in gastrointestinal (GI) tract where they might regulate GI function. AIM: To evaluate if blockade of P2Y12Rs by clopidogrel is associated with higher incidence of GI symptoms in patients with irritable bowel syndrome (IBS). METHODS: A retrospective analysis of our institutional database was conducted for a 13-year period. IBS patients were identified, and their demographics, GI symptoms and clopidogrel therapy were collected. Logistic regression models were used to characterize symptoms in clopidogrel versus no-clopidogrel IBS-groups, adjusting for Age and Sex differences. An additional study characterized the P2Y12R distribution in human gut. RESULTS: The search identified 7217 IBS patients (6761 no-clopidogrel/456 clopidogrel). There were a higher proportion of patients with GI symptoms on clopidogrel (68%) compared to controls (60%, p = 0.0011) that were Females (70 vs. 60%, p = 0.0003) not Males (61 vs. 60%; p = 0.8312). In Females, clopidogrel was associated with higher incidence of GI symptoms (Age adjusted; p < 0.0001) for pain, constipation, gastroparesis (p ≤ 0.0001) and psychogenic pain (p = 0.0006). Age or Sex (adjusted models) influenced one or more GI symptoms (i.e., pain, p < 0.0001; constipation, p < 0.0001/p = 0.008; diarrhea, flatulence, p = 0.01). P2Y12R immunoreactivity was abundant in human ENS; glial-to-neuron ratio of P2Y12Rs expressed in Females â‰« Males. CONCLUSIONS: Irreversible blockade of P2Y12R by clopidogrel is associated with higher incidence of GI symptoms in Female IBS patients, although Age or Sex alone contributes to symptomatology. Prospective studies can determine clinical implications of P2Y12Rs in IBS.

Perioperative Management of Dual-Antiplatelet Therapy in Patients With New-Generation Drug-Eluting Metallic Stents and Bioresorbable Vascular Scaffolds Undergoing Elective Noncardiac Surgery.

Dual-antiplatelet therapy (DAPT) is considered mandatory after new-generation drug-eluting coronary stent implantation to reduce ischemic complications such as stent thrombosis, but the need for DAPT makes the timing of elective surgery difficult. Interrupting DAPT places patients at risk for stent thrombosis, and surgery in the setting of DAPT may lead to bleeding. The 2016 American College of Cardiology/American Heart Association guideline recommends delaying elective noncardiac surgery for a minimum 6-month period to reduce ischemic risks after the implantation of a second-generation metallic drug-eluting stent (DES). However, the guideline fails to appropriately stratify surgical patients based on the indication for second-generation metallic DES implantation and other patient characteristics. The Absorb bioresorbable vascular scaffold (Abbott Vascular, Abbott Park, IL), which has a higher propensity for stent thrombosis compared with second-generation metallic DES, also produces DAPT management challenges in patients presenting for elective noncardiac surgery. Due to the novelty of bioresorbable vascular scaffold therapy, there are no guidelines available for the management of patients undergoing elective noncardiac surgery. This review addresses DAPT management in patients undergoing noncardiac surgery less than 12 months after new-generation metallic DES or bioresorbable vascular scaffold implantation and provides further guidance for anesthesiologists who encounter these challenging cases.

Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia: a systematic review.

The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

Sugammadex versus neostigmine for neuromuscular blockade reversal in outpatient surgeries: A randomized controlled trial to evaluate efficacy and associated healthcare cost in an academic center.

Introduction: Neuromuscular blockade is an essential component of the general anesthesia as it allows for a better airway management and optimal surgical conditions. Despite significant reductions in extubation and OR readiness-for-discharge times have been associated with the use of sugammadex, the cost-effectiveness of this drug remains controversial. We aimed to compare the time to reach a train-of-four (TOF) response of ≥0.9 and operating room readiness for discharge in patients who received sugammadex for moderate neuromuscular blockade reversal when compared to neostigmine during outpatient surgeries under general anesthesia. Potential reduction in time for OR discharge readiness as a result of sugammadex use may compensate for the existing cost-gap between sugammadex and neostigmine. Methods: We conducted a single-center, randomized, double arm, open-label, prospective clinical trial involving adult patients undergoing outpatient surgeries under general anesthesia. Eligible subjects were randomized (1:1 ratio) into two groups to receive either sugammadex (Groups S), or neostigmine/glycopyrrolate (Group N) at the time of neuromuscular blockade reversal. The primary outcome was the time to reverse moderate rocuronium-induced neuromuscular blockade (TOF ratio ≥0.9) in both groups. In addition, post-anesthesia care unit (PACU)/hospital length of stay (LOS) and perioperative costs were compared among groups as secondary outcomes. Results: Thirty-seven subjects were included in our statistical analysis (Group S= 18 subjects and Group N= 19 subjects). The median time to reach a TOF ratio ≥0.9 was significantly reduced in Group S when compared to Group N (180 versus 540 seconds; p = 0.0052). PACU and hospital LOS were comparable among groups. Postoperative nausea and vomiting was the main adverse effect reported in Group S (22.2% versus 5.3% in Group N; p = 0.18), while urinary retention (10.5%) and shortness of breath (5.3%) were only experienced by some patients in Group N. Moreover, no statistical differences were found between groups regarding OR/anesthesia, PACU, and total admission costs. Discussion: Sugammadex use was associated with a significantly faster moderate neuromuscular blockade reversal. We found no evidence of increased perioperative costs associated with the use of sugammadex in patients undergoing outpatient surgeries in our academic institution. Clinical trial registration: [https://clinicaltrials.gov/] identifier number [NCT03579589].

Postoperative Nausea and Vomiting After Craniotomy: An Evidence-based Review of General Considerations, Risk Factors, and Management.

One of the most common and distressing symptoms after craniotomy is postoperative nausea and vomiting (PONV). PONV could generate delayed postanesthesia care and hospitalization discharge, lower patient satisfaction, and an increase in overall hospitalization costs. The incidence of reported PONV after craniotomy is 22% to 70% without prophylaxis, and a multimodal regimen of medication has been recommended. We conducted a comprehensive literature review of the clinical evidence related to PONV prevention and management after craniotomy. All clinical trials in adult populations relevant to PONV after craniotomy available in English language and indexed in PubMed, Google Scholar and Cochrane Library databases from January 1997 up to September 2018 were retrieved using a combination of free-text words related to PONV in craniotomy. After screening manuscripts identified in the initial search, 23 clinical trials investigating systemic pharmacological intervention versus placebo or active control in patients undergoing craniotomy under general anesthesia met the criteria for inclusion in this comprehensive narrative review. The pathophysiology and mechanisms of PONV after craniotomy could be multifactorial in etiology. Therefore, based on current evidence, PONV management after craniotomy should focus on perioperative patient assessment, surgical, and anesthesia-related risk factors and the selection of systemic pharmacological considerations to reduce its incidence and complications. A multimodal regimen of medication targeting different chemoreceptors in the vomiting center is recommended. Ondansetron and dexamethasone, or their combination, are the most frequently used and effective agents. Further randomized clinical trials comparing different regimens that significantly reduce the incidence of PONV in craniotomy would provide relevant evidence-based data for PONV management in this patient population.

Enhanced Recovery After Surgery (ERAS): A Perspective Review of Postoperative Pain Management Under ERAS Pathways and Its Role on Opioid Crisis in the United States.

OBJECTIVES: The objective of this study was to review the current scientific evidence on the role of Enhanced Recovery After Surgery (ERAS) implementations in reducing postoperative opioid consumption and their potential association with the risk reduction for long-term opioid use, physical opioid dependency, and opioid addiction. METHODS: A literature search was conducted using the following medical subject heading keywords: "postoperative pain," "postoperative pain management," "multimodal analgesia," "ERAS," "Enhanced Recovery," "opioid-free analgesia," or "opioid crisis." DISCUSSION: Identification and management of pre-existing psychosocial factors, comorbid pain entities, and chronic opioid use have a significant impact on the severity of postoperative pain. Different multimodal analgesia approaches have been associated with reduced postoperative pain scores and opioid consumption. Health care providers, patients, and family members should recognize the advantages of opioid-free analgesia techniques in postoperative pain management. As part of ERAS protocols, transitional pain services may consider current therapeutic alternatives for acute and long-term pain management that include minimizing perioperative opioid use and establishing adequate opioid prescription practices.

Perioperative bleeding and non-steroidal anti-inflammatory drugs: An evidence-based literature review, and current clinical appraisal.

Patient satisfaction measures and the opioid epidemic have highlighted the need for effective perioperative pain management. Multimodal analgesia, including non-steroidal anti-inflammatory drugs (NSAIDs), have been shown to maximize pain relief and reduce opioid consumption, but are also associated with potential perioperative bleeding risks.A multidisciplinary panel conducted a clinical appraisal of bleeding risks associated with perioperative NSAID use. The appraisal consisted of review and assessment of the current published evidence related to the statement "In procedures with high bleeding risk, NSAIDs should always be avoided perioperatively." We report the presented literature and proceedings of the subsequent panel discussion and national pilot survey results. The authors' assessment of the statement based on current evidence was compared to the attempted national survey data, which revealed a wide range of opinions reflecting the ongoing debate around this issue in a small number of respondents.The appraisal concluded that caution is warranted with respect to perioperative use of NSAIDs. However, summarily excluding NSAIDs from perioperative use based on potential bleeding risks would be imprudent. It is recommended that NSAID use be guided by known patient- and procedure-specific factors to minimize bleeding risks while providing effective pain relief.

A prospective observational cohort study to evaluate patients' experience during sequential cataract surgery under monitored anesthesia care and topical anesthesia.

Cataract surgery is the most common ambulatory surgery at our outpatient surgery center. Several studies have shown that patients with bilateral cataracts may experience different levels of anxiety, pain, and awareness during the first and second cataract extraction.A prospective observational cohort study was conducted at The Ohio State University Wexner Medical Center Eye and Ear Institute in order to compare anxiety, general comfort, awareness, and pain levels in patients undergoing sequential cataract surgeries. Likert and numerical rating scale were used to assess the outcomes. Patients receiving monitored anesthesia care and topical anesthesia were included.A total of 198 patients were enrolled in this study, 116 patients (59%) were female and 157 patients (78%) were Caucasians with a median age of 67 years among participants. Patients with rating "no anxiety" or feeling "somewhat anxious" were significantly higher during surgery 2 (P =< .001). Most of the patients felt "extremely comfortable" during surgery 1 when compared to surgery 2 (54% vs 42.9%; P = .08). No significant differences were found between surgeries regarding intraoperative awareness (P = .16). Overall, patients experienced mild pain during both procedures (92.4% in surgery 1 compared to 90.4% in surgery 2; P = .55). During the postoperative visit, 54% of the patients associated surgery 2 with less anxiety levels, 53% with no differences in general comfort, 60% felt more aware, and 59% had no differences in pain levels.Previous exposure to surgery could have been associated with a significant reduction in anxiety levels reported during surgery 2. Non-pharmacological strategies aiming to reduce perioperative anxiety may be considered an alternative or additional approach to premedication in patients undergoing consecutive cataract surgeries.

Current perspectives on the opioid crisis in the US healthcare system: A comprehensive literature review.

INTRODUCTION: The administration of opioids has been used for centuries as a viable option for pain management. When administered at appropriate doses, opioids prove effective not only at eliminating pain but further preventing its recurrence in long-term recovery scenarios. Physicians have complied with the appropriate management of acute and chronic pain; however, this short or long-term opioid exposure provides opportunities for long-term opioid misuse and abuse, leading to addiction of patients who receive an opioid prescription and/or diversion of this pain medication to other people without prescription. Several reviews attempted to summarize the epidemiology and management of opioid misuse, this integrative review seeks to summarize the current literature related with responsible parties of this opioid abuse crisis and discuss potential associations between demographics (ethnicity, culture, gender, religion) and opioid accessibility, abuse and overdose. METHODS: We performed an extensive literature search in Google Scholar and Pub Med databases that were published between December 7, 1999 and January 9, 2018 in accordance with the Preferred Reporting Items for Systematic Reviews and meta-Analysis (PRISMA) guidelines. Searches were referenced using medical subject headings (MeSH) that included "opioids", "over-prescription", "opioid consumption", or "opioid epidemic". The final review of all data bases was conducted on July 24, 2018. RESULTS: A total of 7160 articles were originally identified. After 3340 duplicate articles were removed, 3820 manuscripts were removed after title and abstract screening. Following this, 120 manuscripts underwent eligibility selection with only 70 publications being selected as reliable full-texts addressing related factors surrounding the opioid crisis. CONCLUSION: With approximately 100 million people suffering from both chronic and acute pain in the United States (US) in 2016, opiates will continue to remain a prominent class of medication in healthcare facilities and homes across the US. Over 66% of total overdose episodes in 2016 were opioid-related, a figure that attests to the severity and wide-spread nature of this issue. A three-point approach accentuating the prevention, treatment, and rehabilitation of both those currently affected and at-risk in the future may be the comprehensive solution.

Potential role of pharmacogenomics testing in the setting of enhanced recovery pathways after surgery.

In 2001, a group of European academic surgeons created the Enhanced Recovery After Surgery (ERAS) study group and established the first official ERAS protocol. One of the most significant challenges during ERAS implementation is variability of drugs used throughout the perioperative period. Pharmacogenomic testing (blood or saliva) results (obtained within approximately 48 hrs) provide guidelines on how to prescribe the optimal drug with the optimal dosage to each patient based on an individual's unique genetic profile. Pharmacogenomic testing of various methods of multimodal analgesia is an essential element of ERAS protocols spanning the entire perioperative period to ultimately optimize postoperative pain control. The key goal for anesthetic management in ERAS protocols is to facilitate rapid emergence by using the shortest acting agents available, thus accelerating recovery and reducing length of stay, hospital expenses, and postoperative complications. Postoperative nausea and vomiting (PONV) is an additional challenge that should be overcome to ensure an enhanced recovery and shorter length of stay with the use of antiemetics. Postoperative ileus (POI) can result in longer hospital stay with increasing susceptibility to associated morbidities along with an increase in associated hospitalization costs. Genetics-guided pharmacotherapy and its impact on clinical outcomes should be thoroughly studied for better understanding and managing drug administration in the settings of ERAS.

Perioperative care of cannabis users: A comprehensive review of pharmacological and anesthetic considerations.

According to the 2015 National Survey on Drug Use and Health, marijuana continues to be the most common illicit recreational drug used in the US. Cannabis is associated with systemic reactions that potentially affect perioperative outcomes. We have reviewed the most important pharmacological aspects and pathophysiological effects that should be considered during the perioperative management of chronic cannabis/cannabinoids users. The synthetic analogues provide higher potency with increased risk for complications. High cannabinoid liposolubility favors rapid accumulation in fatty tissue which prolongs its elimination up to several days after exposure. The multi-systemic effects of cannabinoids and their pharmacological interactions with anesthetic agents may lead to serious consequences. Low doses of cannabinoids have been associated with increased sympathetic response (tachycardia, hypertension and increased contractility) with high levels of norepinephrine detected 30 min after use. High doses enhance parasympathetic tone leading to dose-dependent bradycardia and hypotension. Severe vascular complications associated with cannabis exposure may include malignant arrhythmias, coronary spasm, sudden death, cerebral hypoperfusion and stroke. Bronchial hyperreactivity and upper airway obstruction are commonly reported in cannabis users. Postoperative hypothermia, shivering and increased platelet aggregation have been also documented.

Negative pressure pulmonary edema postextubation following medial nerve repair with sural graft surgery in a young patient: A case report.

RATIONALE: Negative pressure pulmonary edema (NPPE) is a serious well-described pulmonary complication. It occurs after an intense inspiratory effort against an obstructed or closed upper airway and generates a large negative airway pressure, leading to severe pulmonary edema (transvascular fluid filtration and interstitial/alveolar edema) and hypoxemia. We present a case of NPPE following general anesthesia in a patient who underwent median nerve neurorrhaphy with graft from lower left limb (sural nerve) due to sharp injury. PATIENT CONCERNS: A 39-year-old Hispanic male was admitted to the Hospital Universitario de San José and scheduled to undergo a median nerve neurorrhaphy under general anesthesia. Preoperative vital signs, physical examination, and laboratory assessments were unremarkable. At the end of surgery, anesthetic agents were ceased after patient responded to commands and maintained eye contact. However, immediately after extubation, anesthesia care providers observed marked respiratory distress and rapid development of hypoxia. DIAGNOSES: After extubation, patient presented multiple episodes of hemoptysis, tachypnea (25 per minute), blood oxygen saturation (SpO2) of 82% and abundant bilateral pulmonary rales. A baseline chest x-ray revealed symmetric parenchymal opacities with ground-glass attenuation and bilateral multilobar consolidations patterns. The diagnosis of NPPE was established and supportive treatment was initiated. INTERVENTIONS: The patient received noninvasive mechanical ventilation with a PEEP at 10 cmH2O, intravenous furosemide (20 mg.) every 12 hours, and fluids restriction. Patient remained in PACU for continuing monitoring and laboratory/imaging follow-up testing until next morning. OUTCOMES: On postoperative day 1, patient responded satisfactorily to supportive treatment and transferred to the general care floor; oxygen supplementation was discontinued 12 hours after extubation time. On postoperative day 3, after the evaluation of a chest x-ray, patient was discharged to home in stable conditions LESSON:: The occurrence of NPPE in the perioperative setting could be successfully managed with supportive regimens, effective clinical team coordination, and awareness of the importance of its rapid diagnosis.

Cauda equina syndrome following an uneventful spinal anesthesia in a patient undergoing drainage of the Bartholin abscess: A case report.

RATIONALE: Neuraxial anesthesia is a commonly used type of regional anesthesia. Cauda equina syndrome is an unusual and severe complication of neuraxial anesthesia, and is caused by damage to the sacral roots of the neural canal. We present a case of cauda equina syndrome following spinal anesthesia in a patient who underwent Bartholin abscess drainage. PATIENT CONCERNS: A 23-year old female scheduled to undergo surgical drainage of Bartholin abscess. Spinal anesthesia was performed with bupivacaine and fentanyl. There were no perioperative adverse events reported. On postoperative day 1, the patient went to the emergency department describing bilateral weakness and pain of the lower extremities (LE). DIAGNOSES: Lumbar magnetic resonance imaging showed increased gadolinium accumulation in the neural sheath at the level of the cauda equina tracts, consistent with the diagnosis of arachnoiditis and the diagnosis of cauda equina was established. INTERVENTIONS: The patient received the following emergent treatment: 75 mg pregabalin (oral) every 12 hours, 20 mg (8 drops) tramadol (oral) every 8 hours, and 4 mg dexamethasone (intravenous) every 6 hours. On postoperative day 4, the patient still experienced bilateral flaccid paraparesis (accentuated in the left side), neuropathic pain in low extremities, and left brachial monoparesis. Hence, dexamethasone was instantly replaced with 1 g methylprednisolone (intravenous) for 5 days. OUTCOMES: After completing 5 days of methylprednisolone, on postoperative day 9, the patient experienced less pain in left extremities, osteotendinous reflexes were slightly diminished, and she was able to walk with difficulty for 3 to 5 minutes. Greater mobility was evidenced, with right proximal and distal low extremities Medical Research Council Scale grades of 2 and 3 and left proximal and distal low extremities Medical Research Council Scale grades 1 and 2, respectively. Oral prednisone was restarted. Consequently, she was discharged home in stable conditions on postoperative day 25 with a prescription for sertraline, clonazepam, pregabalin, paracetamol, and prednisone. LESSON: The early detection and treatment of complications after neuraxial anesthesia is essential to minimize the risk of permanent damage.

Post-acute Transitional Journey: Caring for Orthopedic Surgery Patients in the United States.

As the geriatric population in the United States continues to age, there will be an increased demand for total hip and total knee arthroplasties (THAs and TKAs). Older patients tend to have more comorbidities and poorer health, and will require post-acute care (PAC) following discharge. The most utilized PAC facilities following THA and TKA are skilled nursing facilities (SNFs), in-patient rehabilitation facilities (IRFs), and home with home health care (HHC). Coordination of care between hospitals and PACs, including the complete transfer of patient information, continues to be a challenge which impacts the quality of care provided by the PACs. The increased demand of hospital resources and PACs by the geriatric population necessitates an improvement in this transition of care process. This review aims to examine the transition of care process currently utilized in the United States for orthopedic surgery patients, and discuss methods for improvement. Employing these approaches will play a key role in improving patient outcomes, decreasing preventable hospital readmissions, and reducing mortality following THA and TKA. The extensive nature of this topic and the ramification of different types of healthcare systems in different countries were the determinant factors limiting our work.