Mechanisms and Preventative Strategies for Persistent Pain following Knee and Hip Joint Replacement Surgery: A Narrative Review.

Chronic postsurgical pain (CPSP) following total knee arthroplasty (TKA) and total hip arthroplasty (THA) is a prevalent complication of joint replacement surgery which has the potential to decrease patient satisfaction, increase financial burden, and lead to long-term disability. The identification of risk factors for CPSP following TKA and THA is challenging but essential for targeted preventative therapy. Recent meta-analyses and individual studies highlight associations between elevated state anxiety, depression scores, preoperative pain, diabetes, sleep disturbances, and various other factors with an increased risk of CPSP, with differences observed in prevalence between TKA and THA. While the etiology of CPSP is not fully understood, several factors such as chronic inflammation and preoperative central sensitization have been identified. Other potential mechanisms include genetic factors (e.g., catechol-O-methyltransferase (COMT) and potassium inwardly rectifying channel subfamily J member 6 (KCNJ6) genes), lipid markers, and psychological risk factors (anxiety and depression). With regards to therapeutics and prevention, multimodal pharmacological analgesia, emphasizing nonopioid analgesics like acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), has gained prominence over epidural analgesia. Nerve blocks and local infiltrative anesthesia have shown mixed results in preventing CPSP. Ketamine, an N-methyl-D-aspartate (NMDA)-receptor antagonist, exhibits antihyperalgesic properties, but its efficacy in reducing CPSP is inconclusive. Lidocaine, an amide-type local anesthetic, shows tentative positive effects on CPSP. Selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) have mixed results, while gabapentinoids, like gabapentin and pregabalin, present hopeful data but require further research, especially in the context of TKA and THA, to justify their use for CPSP prevention.

Postoperative analgesic options after spine surgery: finding the optimal treatment strategies.

INTRODUCTION: Spine surgery is one of the most common types of surgeries performed in the United States; however, managing postoperative pain following spine surgery has proven to be challenging. Patients with spine pathologies have higher incidences of chronic pain and resultant opioid use and potential for tolerance. Implementing a multimodal plan for postoperative analgesia after spine surgery can lead to enhanced recovery and outcomes. AREAS COVERED: This review presents several options for analgesia following spine surgery with an emphasis on multimodal techniques to best aid this specific patient population. In addition to traditional therapeutics, such as acetaminophen, non-steroidal anti-inflammatory medications, and opioids, we discuss intrathecal morphine administration and emerging regional anesthesia techniques. EXPERT OPINION: Several adjuncts to improve analgesia following spine surgery are efficacious in the postoperative period. Intrathecal morphine provides sustained analgesia and can be instilled intraoperatively by the surgical team under direct visualization. Local anesthetics deposited under ultrasound guidance by an anesthesiologist trained in regional techniques also provide the opportunity for single injections or continuous analgesia via an indwelling catheter.

Delirium after Cardiac Surgery-A Narrative Review.

Postoperative delirium (POD) after cardiac surgery is a well-known phenomenon which carries a higher risk of morbidity and mortality. Multiple patient-specific risk factors and pathophysiologic mechanisms have been identified and therapies have been proposed to mitigate risk of delirium development postoperatively. Notably, cardiac surgery frequently involves the use of an intraoperative cardiopulmonary bypass (CPB), which may contribute to the mechanisms responsible for POD. Despite our greater understanding of these causative factors, a substantial reduction in the incidence of POD remains high among cardiac surgical patients. Multiple therapeutic interventions have been implemented intraoperatively and postoperatively, many with conflicting results. This review article will highlight the incidence and impact of POD in cardiac surgical patients. It will describe some of the primary risk factors associated with POD, as well as anesthetic management and therapies postoperatively that may help to reduce delirium.

Perioperative utility of amisulpride and dopamine receptor antagonist antiemetics-a narrative review.

Despite advances in antiemetics and protocolized postoperative nausea vomiting (PONV) management, it remains one of the most common postoperative adverse events. In patients who developed PONV despite antiemetic prophylaxis, giving a rescue treatment from the same class of medication is known to be of limited efficacy. Given the widespread use of 5-HT3 antagonists as PONV prophylaxis, another class of effective intravenous rescue antiemetic is in dire need, especially when prophylaxis fails, and rescue medication is utilized. Dopamine antagonists were widely used for the treatment of PONV but have fallen out of favor due to some of their side effect profiles. Amisulpride was first designed as an antipsychotic medication but was found to have antiemetic properties. Here we will review the historical perspective on the use of dopamine receptor antagonist antiemetics, as well as the evidence on the efficacy and safety of amisulpride.

Taming Postoperative Delirium with Dexmedetomidine: A Review of the Therapeutic Agent's Neuroprotective Effects following Surgery.

Postoperative delirium (POD) represents a perioperative neurocognitive disorder that has dreaded ramifications on a patient's recovery from surgery. Dexmedetomidine displays multiple mechanisms of neuroprotection to assist in preventing POD as a part of a comprehensive anesthetic care plan. This review will cover dexmedetomidine's pharmacological overlap with the current etiological theories behind POD along with pre-clinical and clinical studies on POD prevention with dexmedetomidine. While the body of evidence surrounding the use of dexmedetomidine for POD prevention still requires further development, promising evidence exists for the use of dexmedetomidine in select dosing and circumstances to enhance recovery from surgery.

The validity and applications of the analgesia nociception index: a narrative review.

Pain refers to the subjective, unpleasant experience that is related to illness or injury. In contrast to pain, nociception refers to the physiological neural processing of noxious stimuli, such as intra-operative surgical stimuli. One novel device, the Analgesia Nociception Index (ANI), aims to objectively measure intra-operative nociception by analyzing the heart rate variability in patients undergoing surgery. Through this method of nociceptive monitoring, the ANI device aims to provide an objective, continuous evaluation of patient comfort levels and allow anesthesiologists to better manage surgical stress and patient analgesia, perhaps with even better efficacy than current practices used to assess nociception. Additionally, ANI may have clinical application in settings outside of the operating room, such as in the intensive care unit. In this narrative review, we compiled and summarized the findings of many studies that have investigated ANI's validity and applications in different clinical settings. Currently, the literature appears mostly supportive of ANI's ability to detect nociception in both surgical and non-surgical settings. However, the ability for ANI to provide clinical benefits, such as decreased intra-operative opioid use, post-operative opioid use, and post-operative pain compared to standard practices appear controversial. Because of the wide variety of methodology, clinical settings, patient populations, and limitations in these studies, more investigation of ANI is needed before any firm conclusions can be drawn on its clinical benefits.

Caudal block vs. transversus abdominis plane block for pediatric surgery: a systematic review and meta-analysis.

Background: The caudal block and transversus abdominis plane block (TAP) are commonly used in combination with general anesthesia for pediatric lower abdominal, inguinal, and genitourinary surgeries. There is limited data directly comparing the impact of these techniques on recovery. In this meta-analysis, we compare the duration of postoperative analgesia between these two techniques. Objective: This review examined the duration of analgesia in pediatric patients (age 0-18 years) undergoing surgery who received caudal or TAP block after induction of general anesthesia. The primary outcome was duration of analgesia, defined as the time to first rescue analgesic dose. Secondary outcomes included number of rescue analgesic doses, acetaminophen usage within 24 h postoperatively, 24 h pain score area under the curve, and postoperative nausea and vomiting. Evidence review: We systematically searched Pubmed, Central, EMBASE, CINAHL, Google Scholar, Web of Science citation index, the US clinical trials register, and abstracts from prominent 2020-2022 anesthesia conferences for randomized controlled trials that compared these blocks and reported analgesia duration. Findings: Twelve RCTs inclusive of 825 patients were identified. TAP block was associated with longer analgesia duration (Mean difference = 1.76 h, 95% CI: 0.70-2.81, p = 0.001) and reduced doses of rescue analgesic within 24 h (Mean difference = 0.50 doses, 95% CI: 0.02-0.98, p = 0.04). No statistically significant differences were detected in other outcomes. Conclusion: This meta-analysis suggests that TAP block provides greater duration of analgesia than caudal block after pediatric surgeries. TAP block was also associated with fewer rescue analgesic doses in the first 24 h without increased pain scores. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=380876, identifier: CRD42022380876.

Frailty: the perioperative and anesthesia challenges of an emerging pandemic.

Frailty is a complex and multisystem biological process characterized by reductions in physiological reserve. It is an increasingly common phenomena in the surgical population, and significantly impacts postoperative recovery. In this review, we will discuss the pathophysiology of frailty, as well as preoperative, intraoperative, and postoperative considerations for frailty care. We will also discuss the different models of postoperative care, including enhanced recovery pathways, as well as elective critical care admission. With discoveries of new effective interventions, and advances in healthcare information technology, optimized pathways could be developed to provide the best care possible that meets the challenges of perioperative frailty.

Anesthesia, the developing brain, and dexmedetomidine for neuroprotection.

Anesthesia-induced neurotoxicity is a set of unfavorable adverse effects on central or peripheral nervous systems associated with administration of anesthesia. Several animal model studies from the early 2000's, from rodents to non-human primates, have shown that general anesthetics cause neuroapoptosis and impairment in neurodevelopment. It has been difficult to translate this evidence to clinical practice. However, some studies suggest lasting behavioral effects in humans due to early anesthesia exposure. Dexmedetomidine is a sedative and analgesic with agonist activities on the alpha-2 (ɑ2) adrenoceptors as well as imidazoline type 2 (I2) receptors, allowing it to affect intracellular signaling and modulate cellular processes. In addition to being easily delivered, distributed, and eliminated from the body, dexmedetomidine stands out for its ability to offer neuroprotection against apoptosis, ischemia, and inflammation while preserving neuroplasticity, as demonstrated through many animal studies. This property puts dexmedetomidine in the unique position as an anesthetic that may circumvent the neurotoxicity potentially associated with anesthesia.

The Potential Effect of General Anesthetics in Cancer Surgery: Meta-Analysis of Postoperative Metastasis and Inflammatory Cytokines.

Metastasis or recurrence following curative surgery is the main indicator of tumor progress and is the main cause of patient death. For more than three decades, the potential for general anesthesia to affect cancer outcomes has been a subject of concern with considerable research interest. Here, we conducted this systematic review and meta-analysis to summarize the effect of inhalational anesthesia (IHNA) vs. propofol-based total intravenous anesthesia (TIVA) on metastasis and recurrence after cancer surgery from clinical and pre-clinical studies. The relative risk for metastasis/recurrence in TIVA is 0.61 (95% confidence interval (95% CI) 0.46 to 0.82, p = 0.0009) compared to IHNA. Inflammatory cytokines have been implicated in cancer metastasis following cancer surgery, thus we analyzed inflammatory cytokines levels after surgery under IHNA or TIVA. Based on pooled analysis, a lower IL-6 level was noticed in TIVA in comparison to IHNA (standardized mean difference (SMD) = 0.77, 95% CI = 0.097 to 1.44, I2 = 92%, p = 0.02) but not TNF-α or IL-10. Preclinical animal model studies show that inhalational anesthetics increase the risk of breast cancer metastasis compared to propofol. In conclusion, the current evidence suggests intravenous anesthetic propofol is associated with less metastasis/recurrence and lower postoperative IL-6 level over inhaled anesthetics in the oncological surgery. We urge more well-designed clinical and preclinical studies in this field.

Oliceridine for the Management of Moderate to Severe Acute Postoperative Pain: A Narrative Review.

Despite current advances in acute postoperative pain management, prevalence remains high. Inadequate treatment could lead to poor outcomes and even progression to chronic pain. Opioids have traditionally been the mainstay for treatment of moderate to severe acute pain. However, their use has been associated with opioid-related adverse events (ORAEs), such as respiratory depression, sedation, nausea, vomiting, pruritus, and decreased bowel motility. In addition, their liberal use has been implicated in the current opioid epidemic. As a result, there has been renewed interest in multimodal analgesia to target different mechanisms of action in order to achieve a synergistic effect and minimize opioid usage. Oliceridine is a novel mu-opioid receptor agonist that is part of a new class of biased ligands that selectively activate G-protein signaling and downregulate ß-arrestin recruitment. Since G-protein signaling has been associated with analgesia while ß-arrestin recruitment has been associated with ORAEs, there is potential for a wider therapeutic window. In this review, we will discuss the clinical evidence behind oliceridine and its potential role in acute postoperative pain management. We have systematically searched the PubMed database using the keywords oliceridine, olinvyk, and trv130. All articles identified were reviewed and evaluated, and all clinical trials were included.

Effectiveness of Thoracic Wall Blocks in Video-Assisted Thoracoscopic Surgery, a Network Meta-Analysis.

Introduction: Thoracic epidural analgesia (TEA) and thoracic paravertebral blocks (PVB) are well-established techniques for pain management in thoracotomy. Here, we examine the efficacy of various thoracic fascial plane blocks vs TEA and PVB for intraoperative and postoperative analgesia for video assisted thoracoscopy surgery (VATS) with network meta-analysis. Methods: A search for prospective randomized control studies using adult patients undergoing VATS with general anesthesia. The interventions of interest were any regional anesthesia techniques used for postoperative pain control after VATS. Primary outcomes of interest were 24-hour opioid requirement and 24-hour pain scores. A Bayesian network meta-analysis was conducted. Results: We identified 42 studies that fulfilled our inclusion criteria. For patients who underwent VATS, TEA (MD = -27MME, 95% CI = -46.2 to -9MME), ESP (MD = -20MME, 95% CI -33 to -7.9MME), PVB (MD = -15MME, 95% CI = -26 to -4.5MME) demonstrated significant opioid sparing efficacy, as well as reduction in cumulative 24-hour static pain scores. However, exclusion of one study due to high risk of bias revealed that TEA did not significantly reduce opioid consumption, nor did it reduce the incidence of PONV, pulmonary complications, or LOS when compared to ESP, SAP, PVB, ICN, or PECS blocks. Conclusion: Our findings suggest that TEA did not provide superior pain relief compared to ESP, SAP, PVB, ICN, or PECS blocks following VATS. Therefore, we propose ESP as a suitable intervention for the prevention of postoperative pain after VATS.

Utilization of Wearable Pedometer Devices in the Perioperative Period: A Qualitative Systematic Review.

Functional capacity assessment is important for perioperative risk stratification; however, there are currently limited options for objective and economical functional capacity evaluation. Pedometer functions are now widely available in mobile devices and offer a nonintrusive and objective approach to measuring patient activity level over time. Therefore, we conducted this systematic review to assess the value of pedometer readings in predicting perioperative outcomes. We systematically searched PubMed, EMBASE (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science Citation Index for studies, which assessed the correlation between perioperative (30 days before to 30 days after surgery) pedometer data and perioperative outcomes. We identified a total of 18 studies for inclusion. Seven of the studies recorded preoperative pedometer data, and 13 studies recorded postoperative pedometer data. Notably, 10 of the studies covered oncologic surgery patients. The included studies consistently reported that preoperative pedometer readings correlated with postoperative complication rates. In addition, in-hospital postoperative pedometer readings correlated with postdischarge complications and readmissions. Perioperative pedometer data demonstrated consistent and biologically plausible association with perioperative outcomes. Further studies are needed to validate the use of pedometer in the perioperative period and to identify the optimal approach for its use to potentially improve patient outcomes.

A novel long-acting local anesthetic - HTX-011 (ZYNRELEF™) for postoperative pain control.

INTRODUCTION: Pain following most surgical procedures is expected. However, the treatment and management of postoperative surgical pain have remained challenging. The use of opioid therapy has become increasingly controversial given the limited therapeutic window of these drugs, the adverse side effects, and the potential for abuse. A multimodal approach to the treatment of postoperative pain has been shown to improve pain outcomes after surgery and improve patient satisfaction. Here, we examine a new formulation of bupivacaine and meloxicam extended-release solution HTX-011 (ZYNRELEF®) and its efficacy in postoperative pain control. AREAS COVERED: HTX-011 exists as an extended-release polymer that controls the release of the active ingredients over 72 hours. A systematic approach was taken to review PubMed (Medline) for prospective and retrospective studies related to the use of HTX-011 for the management of postoperative pain. EXPERT OPINION: HTX-011 represents a new tool to help modulate postoperative pain. Although multimodal analgesia has been effective in managing postoperative pain, direct surgical infiltration with local anesthetics has had limited efficacy due to their short duration of action. The HTX-011 formulation provides a long-acting local anesthetic at the surgical site, which provides a longer period of analgesia while maintaining a favorable safety profile.

Rescue Treatment of Postoperative Nausea and Vomiting: A Systematic Review of Current Clinical Evidence.

Although prophylactic antiemetics are commonly used perioperatively, an estimated 30% of surgical patients still suffer from postoperative nausea and vomiting (PONV). Very few prospective trials have studied rescue treatment of PONV after failure of prophylaxis, providing limited evidence to support clinical management. In patients who have failed PONV prophylaxis, administering a rescue antiemetic from the same drug class has been reported to be ineffective. For many antiemetics currently used in PONV rescue, significant uncertainty remains around the effective dose range, speed of onset, duration of effect, safety, and overall risk-benefit ratio. As prompt, effective PONV rescue after failure of prophylaxis is important to optimize postoperative recovery and resource utilization, we conduct this systematic review to summarize the current evidence available on the topic.

Brain Prehabilitation for Oncologic Surgery.

PURPOSE OF REVIEW: This review aims to summarize the current research on postoperative cognitive complications, such as delirium and cognitive dysfunction. This includes discussion on preoperative preventive strategies, such as physical and nutritional prehabilitation as well as up-to-date information on neuroprehabilitation. RECENT FINDINGS: Current recommendations for prevention of postoperative delirium have focused on multicomponent interventions. The optimal composition of surgical prehabilitation programs targeting exercise and nutrition has not yet been established. The Neurobics Trial shows that cognitive prehabilitation improves cognitive reserve and may be a useful addition to multimodal surgical prehabilitation. Perioperative management of oncologic patients is often associated with a myriad of challenges, such as the management of tumor-related pathologies, adverse events from neoadjuvant therapy, and chronic metabolic and immunological changes associated with malignancy. In addition, oncologic patients are at increased risk of developing frailty, which adversely affects postoperative recovery and further cancer treatment. As a result, oncologic patients are at considerable risk of developing postoperative cognitive complications, such as delirium and cognitive dysfunction. In this review, we discuss the effect of prehabilitation on postoperative cognitive outcomes.

Framework, component, and implementation of enhanced recovery pathways.

The introduction of enhanced recovery pathways (ERPs) has led to a considerable paradigm shift towards evidence-based, multidisciplinary perioperative care. Such pathways are now widely implemented in a variety of surgical specialties, with largely positive results. In this narrative review, we summarize the principles, components and implementation of ERPs, focusing on recent developments in the field. We also discuss 'special cases' in ERPs, including: surgery in frail patients; emergency procedures; and patients with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2/COVID-19).

Potential Therapeutic Application of Local Anesthetics in Cancer Treatment.

Local anesthetics are voltage-gated sodium channel blockers primarily administered locally or to the innervating nerves for anesthetic or analgesic purposes. In vitro studies have found direct effects of local anesthetics on cancer cells, such as impact on cancer cell proliferation, apoptosis, migration, invasion, and chemosensitivity, by multiple mechanisms. So far, in vivo evidence regarding the effect of local anesthetics on cancer cell lines is relatively lacking. Local and regional anesthesia administration has been reported to reduce postoperative pain and opioid use in cancer treatment. Additionally, regional anesthesia may reduce the perioperative stress response. However, the clinical therapeutic application of local anesthetics in cancer remains exploratory. In this review, we will discuss the direct and indirect effects of local anesthetics on cancer cells, and discuss the current evidence related to the use of local anesthetics in the treatment of cancer.

Evaluating oliceridine as a treatment option for moderate to severe acute post-operative pain in adults.

INTRODUCTION: Despite the advances in regional anesthesia and non-opioid systemic analgesia, opioids remain the primary rescue analgesic for moderate to severe pain. However, the risks and side effects of opioid medications are well documented. Oliceridine is a novel opioid receptor agonist which is thought to have less risk of adverse events, such as postoperative nausea and vomiting (PONV) and respiratory depression. AREAS COVERED: In this review, the authors discuss the limitations of the current opioid and non-opioid analgesic options. They also review the pharmacokinetics of oliceridine, its analgesic efficacy, and risk of adverse events; and its added clinical value in managing moderate to severe pain. EXPERT OPINION: Despite the advances in regional anesthesia and multimodal systemic analgesia, opioid free analgesia is only feasible in selected procedures and patients. Oliceridine is effective in the management of moderate to severe pain and appears to be associated with lower risk of nausea and vomiting. The risk of sedation and respiratory depression associated with oliceridine will require further study. The availability of an opioid agonist with a better side effect profile could potentially change the current paradigm of opioid avoidance in postoperative pain management.

Silent Hypoxemia in Patients with COVID-19 Pneumonia: A Review.

During the coronavirus disease 2019 (COVID-19) pandemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, patients presented with COVID-19 pneumonia of varying severity. The phenomenon of severe hypoxemia without signs of respiratory distress is also known as silent or hidden hypoxemia. Although silent hypoxemia is not unique to pneumonia due to SARS-CoV-2 infection, this phenomenon is now recognized to be associated with severe COVID-19 pneumonia. Proper management of critically ill patients is the key to reducing mortality. Herein, we summarize the possible and rare factors contributing to silent hypoxemia in patients with COVID-19. Microvascular thrombosis causes dead space ventilation in the lungs, and the flow of pulmonary capillaries is reduced, which leads to an imbalance in the V/Q ratio. The dissociation curve of oxyhemoglobin shifts to the left and limits the release of oxygen to the tissue. SARS-CoV-2 interferes with the synthesis of hemoglobin and reduces the ability to carry oxygen. The accumulation of endogenous carbon monoxide and carboxyhemoglobin will reduce the total oxygen carrying capacity and interfere with pulse oxygen saturation readings. There are also some non-specific factors that cause the difference between pulse oximetry and oxygen partial pressure. We propose some potentially more effective clinical alternatives and recommendations for optimizing the clinical management processes of patients with COVID-19. This review aims to describe the prevalence of silent hypoxemia in COVID-19 pneumonia, to provide an update on what is known of the pathophysiology, and to highlight the importance of diagnosing silent hypoxemia in patients with COVID-19 pneumonia.