Adjuvant Analgesics in Acute Pain - Evaluation of Efficacy.

PURPOSE OF THE REVIEW: Acute postoperative pain impacts a significant number of patients and is associated with various complications, such as a higher occurrence of chronic postsurgical pain as well as increased morbidity and mortality. RECENT FINDINGS: Opioids are often used to manage severe pain, but they come with serious adverse effects, such as sedation, respiratory depression, postoperative nausea and vomiting, and impaired bowel function. Therefore, most enhanced recovery after surgery protocols promote multimodal analgesia, which includes adjuvant analgesics, to provide optimal pain control. In this article, we aim to offer a comprehensive review of the contemporary literature on adjuvant analgesics in the management of acute pain, especially in the perioperative setting. Adjuvant analgesics have proven efficacy in treating postoperative pain and reducing need for opioids. While ketamine is an established option for opioid-dependent patients, magnesium and α2-agonists have, in addition to their analgetic effect, the potential to attenuate hemodynamic responses, which make them especially useful in painful laparoscopic procedures. Furthermore, α2-agonists and dexamethasone can extend the analgesic effect of regional anesthesia techniques. However, findings for lidocaine remain inconclusive.

Nerve Blocks for Craniotomy.

PURPOSE OF REVIEW: Postcraniotomy headache (PCH) is a common adverse event and can lead to various complications and decreased quality of life. RECENT FINDINGS: To reduce postcraniotomy pain and associated complications, a multimodal pain therapy including analgesics, analgesic adjuncts, and regional anesthesia is essential. The use of opioids should be minimized to facilitate prompt postoperative neurosurgical assessment. Here, we provide an update on the latest evidence regarding the role of scalp nerve blocks in the pain management of patients undergoing craniotomy procedure. Nerve blocks are effective in alleviating postoperative pain after craniotomy. Scalp blocks contribute to lower pain levels and less opioid consumption in the first 48 h following surgery. Moreover, there is a significant decrease in patients suffering from PONV among patients who receive scalp block.

Characteristics and outcomes of men with erectile dysfunction as the presenting symptom due to a lactotroph adenoma.

PURPOSE: Erectile dysfunction (ED) is frequently underreported in men suffering from prolactinomas and can be challenging to manage. Both dopamine agonists (DAs) and transsphenoidal surgery (TSS) correct hyperprolactinemia and restore gonadal function. However, there is scarce data regarding their effectiveness in correcting ED over the long term. METHODS: This study is a retrospective single-center comparative cohort study analyzing men diagnosed with prolactinomas, both with and without confirmed erectile dysfunction (ED) at diagnosis. Independent risk factors for persistent ED over the long term were examined using multivariate logistic regression. RESULTS: Among the 39 men with lactotroph adenomas, ED was one of the presenting symptoms in 22 (56%). The mean age at diagnosis was 45 ± 12 years. Surgery was the primary treatment in 6 (27%) ED patients and 8 (47%) non-ED patients. After a mean follow-up of 74 ± 48 months, remission from hyperprolactinemia was achieved in the majority (76%) of men: 71% in the non-ED cohort and 81% in the ED group (p = 0.70), regardless of the primary treatment strategy (surgical 84% versus medical 72%, p = 0.46). Long-term remission of ED was noted in 16 (73%) patients. Interestingly, high baseline BMI levels emerged as potential risk factors for persistent ED over the long term (OR 1.4, 95%CI 1.0-1.9; p = 0.04), while neither the initial adenoma size nor the primary treatment strategy (i.e., TSS vs. DAs) reached statistical significance. CONCLUSIONS: Correcting hyperprolactinemia and its associated hypogonadism significantly improves ED in the majority of men with prolactinomas over the long term, regardless of the primary treatment strategy employed. In addition to addressing endocrine deficiencies, the early initiation of weight control programs may be considered for men with lactotroph adenomas and ED. Although our study suggests an association between BMI and the risk of persistent ED, further research is needed to establish any causal relationships.

Spinal anesthesia in ambulatory patients.

PURPOSE OF REVIEW: To assess current practice in the use of spinal anesthesia in major ambulatory surgery, highlighting its advantages over general anesthesia and identifying potential areas for improvement to facilitate a transition to a sustainable healthcare system. RECENT FINDINGS: Spinal anesthesia might be preferred in selected populations when compared to general anesthesia providing the highest standards of healthcare quality.The use of local anesthetics with short half-life has proven to be efficient in achieving high anesthesia success rates. Spinal anesthesia does not increase perioperative complications; instead, it has shown a reduction in postoperative nausea and vomiting, an improvement in patient comfort, and a favorable economic impact when compared to general anesthesia. SUMMARY: Spinal anesthesia is an appropriate method for anesthesia in ambulatory patients, offering advantages over general anesthesia in selected populations.The use of spinal anesthesia is expanding to meet surgical needs. Therefore, it is crucial to plan ahead and anticipate organizational failures in the ambulatory setting to maintain safety and efficiency during outpatient procedures and surgeries.

Advancements in Modern Treatment Approaches for Central Post-Stroke Pain: A Narrative Review.

PURPOSE OF REVIEW: Central post-stroke pain (CPSP) poses a multifaceted challenge in medical practice, necessitating a thorough and multidisciplinary approach for its diagnosis and treatment. This review examines current methods for addressing CPSP, highlighting both pharmacological and non-pharmacological therapies. It covers the mechanisms and clinical effectiveness of these treatments in managing CPSP and emphasizes the importance of personalized treatment plans, given the varied causes of CPSP. RECENT FINDINGS: Recent advancements have illuminated diverse treatment modalities for CPSP. Pharmacotherapy spans from conventional analgesics to anticonvulsants and antidepressants, tailored to mitigate the neuropathic characteristics of CPSP. Non-pharmacological interventions, including physical therapy and psychological strategies, are pivotal in managing CPSP's chronic nature. For cases resistant to standard treatments, advanced interventions such as nerve blocks and surgical procedures like deep brain stimulation (DBS) or motor cortex stimulation (MCS) are considered. Additionally, innovative technologies such as neuromodulation techniques and personalized medicine are emerging as promising avenues to enhance therapeutic outcomes and improve quality of life for individuals grappling with CPSP. SUMMARY: Modern approaches in managing CPSP require an interdisciplinary and patient-centric approach. Customizing treatment plans to address the specific etiology and symptoms of CPSP is crucial. Pharmacotherapy remains fundamental, encompassing medications such as anticonvulsants and antidepressants tailored to manage neuropathic pain. Integrating non-pharmacological interventions is crucial for providing comprehensive care. Additionally, investigating innovative technologies and personalized medicine presents promising opportunities to enhance treatment results and elevate the quality of life for those suffering from CPSP. Ultimately, an integrated approach that acknowledges the multifaceted nature of CPSP is essential for effective management and patient well-being.

Association of Indoleamine 2,3-Dioxygenase (IDO) Activity with Outcome after Cardiac Surgery in Adult Patients.

Indoleamine 2,3-deoxygenase (IDO) plays an important role in the catabolism of the amino acid tryptophan. Tryptophan and its metabolites are key immune modulators. Increased IDO activity has been observed in various diseases and is associated with worse clinical outcomes. However, comprehensive research regarding its role in cardiac surgery remains limited. Therefore, we aimed to investigate perioperative changes in IDO activity and pathway metabolites, along with their impact on clinical outcomes in adult patients undergoing cardiac surgery. As an observational cohort study conducted at the Inselspital in Bern from January to December 2019, we retrospectively analyzed the data of prospectively collected biobank samples of patients undergoing cardiac surgery with the use of cardiopulmonary bypass. IDO pathway metabolite analysis was conducted by mass spectrometry. Perioperative dynamics were descriptively assessed and associated with pre-defined clinical outcome measures (30-day mortality, 1-year mortality, incidence of stroke and myocardial infarction, and length of hospital stay) through a multi-step exploratory regression analysis. A cohort of 192 adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass were included (median age 67.0, IQR 60.0-73.0, 75.5% male). A significant perioperative decrease in the kynurenine/tryptophan (Kyn/Trp) ratio (-2.298, 95% CI -4.028 to -596, p = 0.009) and significant perioperative dynamics in the associated metabolites was observed. No association of perioperative changes in IDO activity and pathway metabolites with clinical outcomes was found. A significant decrease in the Kyn/Trp ratio among adult patients undergoing cardiac surgery indicates a perioperative downregulation of IDO, which stands in contrast to other pro-inflammatory conditions. Further studies are needed to investigate IDO in the setting of perioperative immunomodulation, which is a key driver of postoperative complications in cardiac surgery patients.

Levels of Circulating Ketone Bodies in Patients Undergoing Cardiac Surgery on Cardiopulmonary Bypass.

Ketone bodies (KBs) are energy-efficient substrates utilized by the heart depending on its metabolic demand and substrate availability. Levels of circulating KBs have been shown to be elevated in acute and chronic cardiovascular disease and are associated with severity of disease in patients with heart failure and functional outcome after myocardial infarction. To investigate whether this pattern similarly applies to patients undergoing cardiac surgery involving cardiopulmonary bypass (CPB), we analysed prospectively collected pre- and postoperative blood samples from 192 cardiac surgery patients and compared levels and perioperative changes in total KBs with Troponin T as a marker of myocardial cell injury. We explored the association of patient characteristics and comorbidities for each of the two biomarkers separately and comparatively. Median levels of KBs decreased significantly over the perioperative period and inversely correlated with changes observed for Troponin T. Associations of patient characteristics with ketone body perioperative course showed notable differences compared to Troponin T, possibly highlighting factors acting as a "driver" for the change in the respective biomarker. We found an inverse correlation between perioperative change in ketone body levels and changes in troponin, indicating a marked decrease in ketone body concentrations in patients exhibiting greater myocardial cell injury. Further investigations aimed at better understanding the role of KBs on perioperative changes are warranted.

A new model to analyze metaphyseal bone healing in mice.

BACKGROUND: Despite the increasing clinical problems with metaphyseal fractures, most experimental studies investigate the healing of diaphyseal fractures. Although the mouse would be the preferable species to study the molecular and genetic aspects of metaphyseal fracture healing, a murine model does not exist yet. Using a special locking plate system, we herein introduce a new model, which allows the analysis of metaphyseal bone healing in mice. METHODS: In 24 CD-1 mice the distal metaphysis of the femur was osteotomized. After stabilization with the locking plate, bone repair was analyzed radiologically, biomechanically, and histologically after 2 (n=12) and 5 wk (n=12). Additionally, the stiffness of the bone-implant construct was tested biomechanically ex vivo. RESULTS: The torsional stiffness of the bone-implant construct was low compared with nonfractured control femora (0.23 ± 0.1 Nmm/°versus 1.78 ± 0.15 Nmm/°, P<0.05). The cause of failure was a pullout of the distal screw. At 2 wk after stabilization, radiological analysis showed that most bones were partly bridged. At 5 wk, all bones showed radiological union. Accordingly, biomechanical analyses revealed a significantly higher torsional stiffness after 5 wk compared with that after 2 wk. Successful healing was indicated by a torsional stiffness of 90% of the contralateral control femora. Histological analyses showed new woven bone bridging the osteotomy without external callus formation and in absence of any cartilaginous tissue, indicating intramembranous healing. CONCLUSION: With the model introduced herein we report, for the first time, successful metaphyseal bone repair in mice. The model may be used to obtain deeper insights into the molecular mechanisms of metaphyseal fracture healing.

The influence of comorbidities on the treatment outcome in symptomatic lumbar spinal stenosis: A systematic review and meta-analysis.

BACKGROUND: Lumbar spinal stenosis (LSS) affects mainly elderly patients. To this day, it is unclear whether comorbidities influence treatment success. The aim of this systematic review and meta-analysis was to assess the impact of comorbidities on the treatment effectiveness in symptomatic LSS. METHODS: We conducted a systematic review and meta-analysis and reviewed prospective or retrospective studies from Medline, Embase, Cochrane Library and CINAHL from inception to May 2020, including adult patients with LSS undergoing surgical or conservative treatment. Main outcomes were satisfaction, functional and symptoms improvement, and adverse events (AE). Proportions of outcomes within two subgroups of a comorbidity were compared with risk ratio (RR) as summary measure. Availability of ≥3 studies for the same subgroup and outcome was required for meta-analysis. RESULTS: Of 72 publications, 51 studies, mostly assessing surgery, there was no evidence reported that patients with comorbidities were less satisfied compared to patients without comorbidities (RR 1.06, 95% confidence interval (CI) 0.77 to 1.45, I 2 94%), but they had an increased risk for AE (RR 1.46, 95% CI 1.06 to 2.01, I 2 72%). A limited number of studies found no influence of comorbidities on functional and symptoms improvement. Older age did not affect satisfaction, symptoms and functional improvement, and AE (age >80 years RR 1.22, 95% CI 0.98 to 1.52, I 2 60%). Diabetes was associated with more AE (RR 1.72, 95% CI 1.19 to 2.47, I 2 58%). CONCLUSION: In patients with LSS and comorbidities (in particular diabetes), a higher risk for AE should be considered in the treatment decision. Older age alone was not associated with an increased risk for AE, less functional and symptoms improvement, and less treatment satisfaction.

Comparison of healing process in open osteotomy model and open fracture model: Delayed healing of osteotomies after intramedullary screw fixation.

Murine osteotomy and fracture models have become the standard to study molecular mechanisms of bone healing. Because there is little information whether the healing of osteotomies differs from that of fractures, we herein studied in mice the healing of femur osteotomies compared to femur fractures. Twenty CD-1 mice underwent a standardized open femur osteotomy. Another 20 mice received a standardized open femur fracture. Stabilization was performed by an intramedullary screw. Bone healing was studied by micro-CT, biomechanical, histomorphometric and protein expression analyses. Osteotomies revealed a significantly lower biomechanical stiffness compared to fractures. Micro-CT showed a reduced bone/tissue volume within the callus of the osteotomies. Histomorphometric analyses demonstrated also a significantly lower amount of osseous tissue in the callus of osteotomies (26% and 88% after 2 and 5 weeks) compared to fractures (50% and 100%). This was associated with a delayed remodeling. Western blot analyses demonstrated comparable BMP-2 and BMP-4 expression, but higher levels of collagen-2, CYR61 and VEGF after osteotomy. Therefore, we conclude that open femur osteotomies in mice show a markedly delayed healing when stabilized less rigidly with an intramedullary screw. This should be considered when choosing a model for studying the mechanisms of bone healing in mice.