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.

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.

Modern Approaches to the Treatment of Acute Facial Pain.

PURPOSE OF REVIEW: Acute facial pain presents a complex challenge in medical practice, requiring a comprehensive and interdisciplinary approach to its management. This narrative review explores the contemporary landscape of treating acute facial pain, delving into pharmacological, non-pharmacological, and advanced interventions. The significance of tailored treatment strategies, rooted in the diverse etiologies of facial pain, such as dental infections, trigeminal neuralgia, temporomandibular joint disorders, sinusitis, or neurological conditions like migraines or cluster headaches, is underscored. We particularly emphasize recent advances in treating trigeminal neuralgia, elucidating current treatment concepts in managing this particular acute facial pain. RECENT FINDINGS: Recent research sheds light on various treatment modalities for acute facial pain. Pharmacotherapy ranges from traditional NSAIDs and analgesics to anticonvulsants and antidepressants. Non-pharmacological interventions, including physical therapy and psychological approaches, play pivotal roles. Advanced interventions, such as nerve blocks and surgical procedures, are considered in cases of treatment resistance. Moreover, we explore innovative technologies like neuromodulation techniques and personalized medicine, offering promising avenues for optimizing treatment outcomes in acute facial pain management. Modern management of acute facial pain requires a nuanced and patient-centric approach. Tailoring treatment strategies to the individual's underlying condition is paramount. While pharmacotherapy remains a cornerstone, the integration of non-pharmacological interventions is essential for comprehensive care. Advanced interventions should be reserved for cases where conservative measures prove inadequate. Furthermore, leveraging innovative technologies and personalized medicine holds promise for enhancing treatment efficacy. Ultimately, a holistic approach that considers the diverse needs of patients is crucial for effectively addressing acute facial pain.

Morbidities and mortality among hospitalized patients with hypopituitarism: Prevalence, causes and management.

Hypopituitarism is a highly heterogeneous multisystem disorder that can have a major impact on long-term morbidity and mortality, but even more so during acute medical conditions requiring hospitalization. Recent studies suggest a significant in-hospital burden with prolonged length of stay, increased rate of intensive care unit (ICU) admission, and initiation of mechanical ventilation - all of which may lead to an increased risk of in-hospital mortality. On the one hand, patients with hypopituitarism are often burdened by metabolic complications, including obesity, hypertension, dyslipidemia, and hyperglycemia, which alone, or in combination, are known to significantly alter relevant physiological mechanisms, including metabolism, innate and adaptive immune responses, coagulation, and wound healing, thereby contributing to adverse in-hospital outcomes. On the other hand, depending on the extent and the number of pituitary hormone deficiencies, early recognition of hormone deficiencies and appropriate management and replacement strategy within a well-organized multidisciplinary team are even stronger determinants of short-term outcomes during acute hospitalization in this vulnerable patient population. This review aims to provide an up-to-date summary of recent advances in pathophysiologic understanding, clinical implications, and recommendations for optimized multidisciplinary management of hospitalized patients with hypopituitarism.

Pseudomeningocele Mimicking Sciatica.

We report on an elderly woman with sciatica due to disc herniation, experiencing complete pain resolution following surgery. Four weeks later, she developed refractory, excruciating pain with foot palsy, prompting a lumbar magnetic resonance imaging that revealed no recurrent disc herniation. Upon exploration, intermittent nerve entrapment through the dural tear and pseudomeningocele was identified. Following dural repair and nerve repositioning, the postoperative course and long-term outcome were uneventful.In contrast to recurrent disc herniation, sciatica resulting from nerve entrapment by a pseudomeningocele is exceedingly rare. Its differential diagnosis is crucial in cases with seemingly unspectacular magnetic resonance imaging findings, as paralysis can occur in symptomatic patients. The radiological presence of a postoperative pseudomeningocele could be overlooked, and the cause of sciatica might become apparent solely during surgical exploration.

Age and Stroke Severity Matter Most for Clinical Outcome in Acute Arteriosclerotic Tandem Lesions.

Background: Tandem lesions (TLs) cause up to 15-30% of all acute ischemic strokes (AISs). Endovascular treatment (EVT) is regarded as the first-line treatment; however, uncertainties remain with respect to the treatment and predictive outcome parameters. Here, we aimed to identify the clinical and demographic factors associated with functional short- and long-term outcomes in AIS patients with arteriosclerotic TLs undergoing EVT. Methods: This was a retrospective, mono-centric cohort study of 116 consecutive AIS patients with arteriosclerotic TLs who were endovascularly treated at a stroke center, with analysis of the relevant demographic, procedural, and imaging data. Results: A total of 116 patients were included in this study, with a median age of 72 years (IQR 63-80), 31% of whom were female (n = 36). The median NIHSS on admission was 14 (IQR 7-19), with a median ASPECT score of 9 (IQR 8-10) and median NASCET score of 99% (IQR 88-100%). A total of 52% of the patients received intravenous thrombolysis. In 77% (n = 89) of the patients, an antegrade EVT approach was used, with a good recanalization (mTICI2b3) achieved in 83% of patients (n = 96). Symptomatic intracerebral hemorrhage occurred in 12.7% (n = 15) of patients. A favorable outcome (mRS0-2) and mortality at 3 months were obtained for 40% (n = 47) and 28% of patients (n = 32), respectively. Age and NIHSS on admission were strongly associated with outcome parameters. Diabetes mellitus and previous neurological disorders were independently associated with long-term mortality (median 11 months, IQR 0-42). Conclusions: Younger age, lower stroke severity, and good recanalization were found to be independently associated with a favorable outcome. In contrast, older age, higher stroke severity, previous neurological disorders, and diabetes were correlated with mortality. The endovascular treatment of acute arteriosclerotic tandem lesions is feasible and relatively safe.

Cannabinoids for Acute Pain Management: Approaches and Rationale.

PURPOSE OF THE REVIEW: Acute pain management remains a challenge and postoperative pain is often undermanaged despite many available treatment options, also including cannabinoids. RECENT FINDINGS: In the light of the opioid epidemic, there has been growing interest in alternative care bundles for pain management, including cannabinoids as potential treatment to decrease opioid prescribing. Despite the lack of solid evidence on the efficacy of cannabinoids, their use among patients with pain, including those using opioids, is currently increasing. This use is supported by data suggesting that cannabinoids could potentially contribute to a better pain management and to a reduction in opioid doses while maintaining effective analgesia with minimum side effects. The scientific basis for supporting the use of cannabis is extensive, although it does not necessarily translate into relevant clinical outcomes. The use of cannabinoids in acute pain did not always consistently show statistically significant results in improving acute pain. Large randomized, controlled trials evaluating diverse cannabis extracts are needed in different clinical pain populations to determine safety and efficacy.

The diagnostic yield of inferior petrosal sinus sampling in Cushing syndrome in the era of ovine CRH shortage.

PURPOSE: The ovine corticotropin-releasing hormone (oCRH) stimulation test has been routinely used in the diagnostic work-up of ACTH-dependent Cushing syndrome (CS). With oCRH currently being out-of-stock in Europe, we aimed at evaluating the diagnostic performance of inferior petrosal sinus sampling (IPSS) without oCRH stimulation. METHODS: We compared the values of 40 patients with ACTH-dependent CS and negative MRI findings in whom ACTH was measured before and after oCRH stimulation. RESULTS: The ratio of central-to-peripheral ACTH measurement (IPS:P) before the combined 3, 5, and 10 min of oCRH stimulation yielded diminished sensitivity (85% vs. 97%), alongside markedly decreased specificity (57% vs. 71%), as well as reduced positive and negative predictive values (90% vs. 94% and 44% vs. 83%), respectively. CONCLUSIONS: With the current drug shortages in Europe, ACTH measurements without oCRH stimulation in IPSS cannot be recommended. Thus, we call for desmopressin or the commercially available human CRH as a potential alternative in the confirmation of ACTH excess by IPSS in equivocal MRI findings.

Gender-specific prolactin thresholds to determine prolactinoma size: a novel Bayesian approach and its clinical utility.

Background: In clinical practice, the size of adenomas is crucial for guiding prolactinoma patients towards the most suitable initial treatment. Consequently, establishing guidelines for serum prolactin level thresholds to assess prolactinoma size is essential. However, the potential impact of gender differences in prolactin levels on estimating adenoma size (micro- vs. macroadenoma) is not yet fully comprehended. Objective: To introduce a novel statistical method for deriving gender-specific prolactin thresholds to discriminate between micro- and macroadenomas and to assess their clinical utility. Methods: We present a novel, multilevel Bayesian logistic regression approach to compute observationally constrained gender-specific prolactin thresholds in a large cohort of prolactinoma patients (N = 133) with respect to dichotomized adenoma size. The robustness of the approach is examined with an ensemble machine learning approach (a so-called super learner), where the observed differences in prolactin and adenoma size between female and male patients are preserved and the initial sample size is artificially increased tenfold. Results: The framework results in a global prolactin threshold of 239.4 µg/L (95% credible interval: 44.0-451.2 µg/L) to discriminate between micro- and macroadenomas. We find evidence of gender-specific prolactin thresholds of 211.6 µg/L (95% credible interval: 29.0-426.2 µg/L) for women and 1,046.1 µg/L (95% credible interval: 582.2-2,325.9 µg/L) for men. Global (that is, gender-independent) thresholds result in a high sensitivity (0.97) and low specificity (0.57) when evaluated among men as most prolactin values are above the global threshold. Applying male-specific thresholds results in a slightly different scenario, with a high specificity (0.99) and moderate sensitivity (0.74). The male-dependent prolactin threshold shows large uncertainty and features some dependency on the choice of priors, in particular for small sample sizes. The augmented datasets demonstrate that future, larger cohorts are likely able to reduce the uncertainty range of the prolactin thresholds. Conclusions: The proposed framework represents a significant advancement in patient-centered care for treating prolactinoma patients by introducing gender-specific thresholds. These thresholds enable tailored treatment strategies by distinguishing between micro- and macroadenomas based on gender. Specifically, in men, a negative diagnosis using a universal prolactin threshold can effectively rule out a macroadenoma, while a positive diagnosis using a male-specific prolactin threshold can indicate its presence. However, the clinical utility of a female-specific prolactin threshold in our cohort is limited. This framework can be easily adapted to various biomedical settings with two subgroups having imbalanced average biomarkers and outcomes of interest. Using machine learning techniques to expand the dataset while preserving significant observed imbalances presents a valuable method for assessing the reliability of gender-specific threshold estimates. However, external cohorts are necessary to thoroughly validate our thresholds.

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.

Safety and functional outcome analysis of ventriculoperitoneal shunt placement for hydrocephalus within the critical phase of possible delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

Shunt-dependent hydrocephalus (HC) is a common sequela following aneurysmal subarachnoid hemorrhage (aSAH). However, there is still poor evidence regarding the optimal timing of ventriculoperitoneal shunt (VPS) placement, particularly in the context of early aSAH-associated complications such as delayed cerebral ischemia (DCI). The purpose of this study was to compare the impact of early (< 21 days after aSAH) versus late (≥ 21 days after aSAH) VPS placement on the functional clinical outcome. We retrospectively analyzed data from 82 patients with VPS placement after aSAH enrolled in our institutional database between 2011 and 2021. We compared two groups, early VPS placement (< 21 days after aSAH) versus late VPS placement (≥ 21 days after aSAH) in terms of demographics, SAH grading, radiological parameters, externalized cerebrospinal fluid diversions, DCI, VPS variables, and functional outcome. We identified 53 patients with early and 29 patients with late VPS implantation. Baseline variables, such as the modified Rankin Scale (mRS), the World Federation of Neurological Surgeons Scale, the Glasgow Coma Scale, and Fisher grade were not significantly different between the groups. Postoperatively, the mRS (p = 0.0037), the Glasgow Outcome Scale (p = 0.0037), and the extended Glasgow Outcome Scale (p = 0.0032) showed significantly better functional results in patients with early cerebrospinal fluid diversion. The rate of DCI did not differ significantly between the groups (p = 0.53). There was no difference in the rate of VPS placement associated complications (p = 0.44) or overall mortality (p = 0.39). Early shunt implantation, within 21 days after aSAH and therefore during the timeframe of possible DCI, might not be harmful in patients developing HC after aSAH.

Topographic distribution of inflammation factors in a healing aneurysm.

BACKGROUND: Healing of intracranial aneurysms following endovascular treatment relies on the organization of early thrombus into mature scar tissue and neointima formation. Activation and deactivation of the inflammation cascade plays an important role in this process. In addition to timely evolution, its topographic distribution is hypothesized to be crucial for successful aneurysm healing. METHODS: Decellularized saccular sidewall aneurysms were created in Lewis rats and coiled. At follow-up (after 3 days (n = 16); 7 days (n = 19); 21 days (n = 8)), aneurysms were harvested and assessed for healing status. In situ hybridization was performed for soluble inflammatory markers (IL6, MMP2, MMP9, TNF-α, FGF23, VEGF), and immunohistochemical analysis to visualize inflammatory cells (CD45, CD3, CD20, CD31, CD163, HLA-DR). These markers were specifically documented for five regions of interest: aneurysm neck, dome, neointima, thrombus, and adjacent vessel wall. RESULTS: Coiled aneurysms showed enhanced patterns of thrombus organization and neointima formation, whereas those without treatment demonstrated heterogeneous patterns of thrombosis, thrombus recanalization, and aneurysm growth (p = 0.02). In coiled aneurysms, inflammation markers tended to accumulate inside the thrombus and in the neointima (p < 0.001). Endothelial cells accumulated directly in the neointima (p < 0.0001), and their presence was associated with complete aneurysm healing. CONCLUSION: The presence of proinflammatory cells plays a crucial role in aneurysm remodeling after coiling. Whereas thrombus organization is hallmarked by a pronounced intra-thrombotic inflammatory reaction, neointima maturation is characterized by direct invasion of endothelial cells. Knowledge concerning topographic distribution of regenerative inflammatory processes may pave the way for future treatment modalities which enhance aneurysm healing after endovascular therapy.

Anatomical distribution and clinical significance of middle cerebral artery M2 segment vessel occlusions and its cortical branches in acute ischaemic stroke patients.

Background: Characterisation of anatomical distribution and the clinical impact of middle cerebral artery M2 (MCA-M2) segment occlusion and its subsequent cortical branches (CBs) in acute ischaemic stroke patients (AIS). Methods: Retrospective, monocentric study analysing radiological and clinical data of AIS patients with MCA-M2 segment occlusion with regard to the anatomic distribution of MCA-M2 occlusion and its subsequent CB. Results: A total of 203 patients (median age 77 (IQR 66-83) years, 112 women) were included. There was an equal distribution of right-sided versus left-sided MCA-M2 vessel occlusions (right: n=97; left: n=106), as well as with a median number of affected MCA-M2 CBs of 4 (IQR, 3-6) and a median National Institute of Health Stroke Scale score (NIHSS) on admission of 9 (3-15). For both hemispheres, CBs of the inferior trunks were significantly more affected than the superior trunks. Endovascular treatment (EVT, n=94) was associated with a significant better outcome compared with patients with medical management alone (p=0.027). Conclusion: In acute MCA-M2 segment occlusions, inferior trunks are significantly more affected compared with the superior trunks. The subsequent CBs of the paracentral region of both hemispheres are more commonly involved. In eloquent vascular territories, EVT was more often performed.

Acute Pain and Development of Opioid Use Disorder: Patient Risk Factors.

PURPOSE OF REVIEW: Pharmacological therapy for acute pain carries the risk of opioid misuse, with opioid use disorder (OUD) reaching epidemic proportions worldwide in recent years. This narrative review covers the latest research on patient risk factors for opioid misuse in the treatment of acute pain. In particular, we emphasize newer findings and evidence-based strategies to reduce the prevalence of OUD. RECENT FINDINGS: This narrative review captures a subset of recent advances in the field targeting the literature on patients' risk factors for OUD in the treatment for acute pain. Besides well-recognized risk factors such as younger age, male sex, lower socioeconomic status, White race, psychiatric comorbidities, and prior substance use, additional challenges such as COVID-19 further aggravated the opioid crisis due to associated stress, unemployment, loneliness, or depression. To reduce OUD, providers should evaluate both the individual patient's risk factors and preferences for adequate timing and dosing of opioid prescriptions. Short-term prescription should be considered and patients at-risk closely monitored. The integration of non-opioid analgesics and regional anesthesia to create multimodal, personalized analgesic plans is important. In the management of acute pain, routine prescription of long-acting opioids should be avoided, with implementation of a close monitoring and cessation plan.

Meditation as an Adjunct to the Management of Acute Pain.

PURPOSE OF REVIEW: We aim to present current understanding and evidence for meditation, mostly referring to mindfulness meditation, for the management of acute pain and potential opportunities of incorporating it into the acute pain service practice. RECENT FINDINGS: There is conflicting evidence concerning meditation as a remedy in acute pain. While some studies have found a bigger impact of meditation on the emotional response to a painful stimulus than on the reduction in actual pain intensities, functional Magnet Resonance Imaging has enabled the identification of various brain areas involved in meditation-induced pain relief. Potential benefits of meditation in acute pain treatment include changes in neurocognitive processes. Practice and Experience are necessary to induce pain modulation. In the treatment of acute pain, evidence is emerging only recently. Meditative techniques represent a promising approach for acute pain in various settings.