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INTRODUCTION: The International Neuromodulation Society convened a multispecialty group of physicians and scientists based on expertise with international representation to establish evidence-based guidance on intrathecal drug delivery in treating chronic pain. This Polyanalgesic Consensus Conference (PACC)® project, created more than two decades ago, intends to provide evidence-based guidance for important safety and efficacy issues surrounding intrathecal drug delivery and its impact on the practice of neuromodulation. MATERIALS AND METHODS: Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from 2017 (when PACC® last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on the strength of evidence or consensus when evidence is scant. RESULTS: The PACC® examined the published literature and established evidence- and consensus-based recommendations to guide best practices. Additional guidance will occur as new evidence is developed in future iterations of this process. CONCLUSIONS: The PACC® recommends best practices regarding intrathecal drug delivery to improve safety and efficacy. The evidence- and consensus-based recommendations should be used as a guide to assist decision-making when clinically appropriate.

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BACKGROUND: Poor pain control during the postoperative period has negative implications for recovery, and is a critical risk factor for development of persistent postsurgical pain. The aim of this scoping review is to identify gaps in healthcare delivery that patients undergoing inpatient noncardiac surgeries experience in pain management while recovering at home. METHODS: Searches were conducted by a medical librarian in PubMed, MEDLINE, EMBASE, EBSCO CINAHL, Web of Science, and Cochrane Database of Systematic Reviews for articles published between 2016 and 2022. Inclusion criteria were adults (≥18 yr), English language, inpatient noncardiac surgery, and included at least one gap in care for acute and/or persistent pain management after surgery within the first 3 months of recovery at home. Two reviewers independently screened articles for inclusion and extracted data. Quotations from each article related to gaps in care were synthesised using thematic analysis. RESULTS: There were 4794 results from databases and grey literature, of which 38 articles met inclusion criteria. From these, 23 gaps were extracted, encompassing all six domains of healthcare delivery (capacity, organisational structure, finances, patients, care processes and infrastructure, and culture). Identified gaps were synthesised into five overarching themes: education (22 studies), provision of continuity of care (21 studies), individualised management (10 studies), support for specific populations (11 studies), and research and knowledge translation (10 studies). CONCLUSIONS: This scoping review identified health delivery gaps during a critical period in postoperative pain management. These gaps represent potential targets for quality improvement and future research to improve perioperative care and longer-term patient-centred outcomes. SCOPING REVIEW PROTOCOL: Open Science Framework (https://osf.io/cq5m6/).

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BACKGROUND: This meta-analysis aimed to evaluate the body of evidence investigating the post-operative use of non-opioid analgesic drugs and techniques in endocrine neck surgeries. Adequate pain control is crucial for successful recovery after thyroid and parathyroid surgery. Effective postoperative pain control can shorten hospital stay, improve postoperative outcomes, decrease morbidity and improve the overall patient experience. Traditionally, opioids have been the mainstay of postoperative analgesia after thyroid and parathyroid surgeries. However, the use of opioids has been linked to an increased incidence of postoperative complications. METHODS: A comprehensive systematic literature review via Medline, Embase, Web of Science and Cochrane Central Register for Controlled Trials from inception until December 26th, 2020 was conducted, followed by meta-analysis. Abstract and full-text screening, data extraction and quality assessment were independently conducted by 2 investigators. Odds ratios (OR), mean differences (MD) and 95% confidence intervals were calculated using RevMan 5.3. RESULTS: Sixty-five randomized control trials were identified from 486 unique publications. Pooled MD and 95% confidence interval for pain scores were higher for the control group at 24 h postoperatively both at rest (-0.65 [-0.92, -0.37]) and with swallowing (-0.77 [-1.37, -0.16]). These differences were statistically significant. The pooled MD and confidence interval for postoperative analgesic requirements was lower in the intervention group (-1.38 [-1.86, -0.90]). The incidence of PONV had a pooled OR of 0.67 [0.48, 0.94]. CONCLUSION: Non-opioid analgesia was superior to the control group for pain control in patients undergoing thyroid and parathyroid operations with no significant difference in complications.

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BACKGROUND: In an attempt to aggregate observations from clinical trials, several meta-analyses have been published examining the effectiveness of systemic, non-opioid, pharmacological interventions to reduce the incidence of chronic postsurgical pain. OBJECTIVE: To inform the design and reporting of future studies, the purpose of our study was to examine the quality of these meta-analyses. EVIDENCE REVIEW: We conducted an electronic literature search in Embase, MEDLINE, and the Cochrane Database of Systematic Reviews. Published meta-analyses, from the years 2010 to 2020, examining the effect of perioperative, systemic, non-opioid pharmacological treatments on the incidence of chronic postsurgical pain in adult patients were identified. Data extraction focused on methodological details. Meta-analysis quality was assessed using the A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2) critical appraisal tool. FINDINGS: Our search yielded 17 published studies conducting 58 meta-analyses for gabapentinoids (gabapentin and pregabalin), ketamine, lidocaine, non-steroidal anti-inflammatory drugs, and mexiletine. According to AMSTAR 2, 88.2% of studies (or 15/17) were low or critically low in quality. The most common critical element missing was an analysis of publication bias. Trends indicated an improvement in quality over time and association with journal impact factor. CONCLUSIONS: With few individual trials adequately powered to detect treatment effects, meta-analyses play a crucial role in informing the perioperative management of chronic postsurgical pain. In light of this inherent value and despite a number of attempts, high-quality meta-analyses are still needed. PROSPERO REGISTRATION NUMBER: CRD42021230941.

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The management of neuropathic pain, defined as pain as a result of a lesion or disease in the somatosensory nervous system, continues to be researched and explored. As conventional methods demonstrate limited long-term efficacy, there is a significant need to discover therapies that offer both longitudinal and sustained management of this highly prevalent disease, which can be offered through interventional therapies. Tricyclic antidepressants (TCAs), gabapentinoids, lidocaine, serotonin norepinephrine reuptake inhibitors (SNRIs), and capsaicin have been shown to be the most efficacious pharmacologic agents for neuropathic pain relief. With respect to infusion therapies, the use of intravenous (IV) ketamine could be useful for complex regional pain syndrome, fibromyalgia, and traumatic spinal cord injury. Interventional approaches such as lumbar epidurals are a reasonable treatment choice for up to 3 months of pain relief for patients who failed to respond to conservative treatment, with a "B" strength of recommendation and moderate certainty. Neuroablative procedures like pulsed radiofrequency ablation work by delivering electrical field and heat bursts to targeted nerves or tissues without permanently damaging these structures, and have been recently explored for neuropathic pain relief. Alternatively, neuromodulation therapy is now recommended as the fourth line treatment of neuropathic pain after failed pharmacological therapy but prior to low dose opioids. Finally, the intrathecal delivery of various pharmacologic agents, such as quinoxaline-based kappa-opioid receptor agonists, can be utilized for neuropathic pain relief. In this review article, we aim to highlight advances and novel methods of interventional management of neuropathic pain.

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OBJECTIVE: To compare the efficacy and safety of patient-controlled analgesia (PCA) to epidural analgesia in adults undergoing open hepatic resection. BACKGROUND: Effective pain management in patients undergoing open hepatic resection is often achieved with epidural analgesia. However, associated risks have prompted investigation of alternative analgesic methods in this patient population. METHODS: A comprehensive systematic literature review via Medline, Embase, and the Cochrane databases from inception until December 2, 2017 was conducted, followed by meta-analysis. Abstract and full-text screening, data extraction, and quality assessment were conducted by 2 investigators. Odds ratios (OR), mean differences (MD), and 95% confidence intervals were calculated using RevMan 5.3. RESULTS: Four randomized controlled trials with 278 patients were identified. All studies compared the use of PCA to epidural, with differing regimens. Pooled MD and 95% confidence interval for pain score were higher for PCA at rest 24 hours postoperatively (0.59 [0.30, 0.88]), and with movement at 48 hours postoperatively (0.95 [0.31, 1.60]. Pooled MD for hospital length of stay was 1.23 days (-2.72, 5.19). Pooled OR was 0.68 (0.36, 1.3) and 0.24 (0.04, 1.36) for overall and analgesia-related complications, respectively. Need for blood transfusion had a pooled OR of 1.14 (0.31, 4.18). CONCLUSIONS: Epidural analgesia was observed to be superior to PCA for pain control in patients undergoing open hepatic resection, with no significant difference in hospital length of stay, complications, or transfusion requirements. Thus, epidural analgesia should be the preferred method for the management of postoperative pain in this patient population.

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PURPOSE: Epidural and spinal needle insertions, as well as facet joint denervation and injections are widely performed procedures on the lumbar spine for delivering anesthesia and analgesia. Ultrasound (US)-based approaches have gained popularity for accurate needle placement, as they use a non-ionizing, inexpensive and accessible modality for guiding these procedures. However, due to the inherent difficulties in interpreting spinal US, they yet to become the clinical standard-of-care. METHODS: A novel statistical shape [Formula: see text] pose [Formula: see text] scale (s [Formula: see text] p [Formula: see text] s) model of the lumbar spine is jointly registered to preoperative magnetic resonance (MR) and US images. An instance of the model is created for each modality. The shape and scale model parameters are jointly computed, while the pose parameters are estimated separately for each modality. RESULTS: The proposed method is successfully applied to nine pairs of preoperative clinical MR volumes and their corresponding US images. The results are assessed using the target registration error (TRE) metric in both MR and US domains. The s [Formula: see text] p [Formula: see text] s model in the proposed joint registration framework results in a mean TRE of 2.62 and 4.20 mm for MR and US images, respectively, on different landmarks. CONCLUSION: The joint framework benefits from the complementary features in both modalities, leading to significantly smaller TREs compared to a model-to-US registration approach. The s [Formula: see text] p [Formula: see text] s model also outperforms our previous shape [Formula: see text] pose model of the lumbar spine, as separating scale from pose allows to better capture pose and guarantees equally-sized vertebrae in both modalities. Furthermore, the simultaneous visualization of the patient-specific models on the MR and US domains makes it possible for clinicians to better evaluate the local registration accuracy.

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Spinal needle injections are guided by fluoroscopy or palpation, resulting in radiation exposure and/or multiple needle re-insertions. Consequently, guiding these procedures with live ultrasound has become more popular, but images are still challenging to interpret. We introduce a guidance system based on augmentation of ultrasound images with a patient-specific 3-D surface model of the lumbar spine. We assessed the feasibility of the system in a study on 12 patients. The system could accurately provide augmentations of the epidural space and the facet joint for all subjects. Following conventional, fluoroscopy-guided needle placement, augmentation accuracy was determined according to the electromagnetically tracked final position of the needle. In 9 of 12 cases, the accuracy was considered sufficient for successfully delivering anesthesia. The unsuccessful cases can be attributed to errors in the electromagnetic tracking reference, which can be avoided by a setup reducing the influence of the metal C-arm.

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PURPOSE: Facet joint injections and epidural needle insertions are widely used for spine anesthesia. Accurate needle placement is important for effective therapy delivery and avoiding complications arising from damage of soft tissue and nerves. Needle guidance is usually performed by fluoroscopy or palpation, resulting in radiation exposure and multiple needle re-insertions. Several ultrasound (US)-based approaches have been proposed but have not found wide acceptance in clinical routine. This is mainly due to difficulties in interpretation of the complex spinal anatomy in US, which leads to clinicians' lack of confidence in relying only on information derived from US for needle guidance. METHODS: We introduce a multimodal joint registration technique that takes advantage of easy-to-interpret preprocedure computed topography (CT) scans of the lumbar spine to concurrently register a shape+pose model to the intraprocedure 3D US. Common shape coefficients are assumed between two modalities, while pose coefficients are specific to each modality. RESULTS: The joint method was evaluated on patient data consisting of ten pairs of US and CT scans of the lumbar spine. It was successfully applied in all cases and yielded an RMS shape error of 2.1 mm compared to the CT ground truth. The joint registration technique was compared to a previously proposed method of statistical model to US registration Rasoulian et al. (Information processing in computer-assisted interventions. Springer, Berlin, pp 51-60, 2013). The joint framework improved registration accuracy to US in 7 out of 17 visible vertebrae, belonging to four patients. In the remaining cases, the two methods were equally accurate. CONCLUSION: The joint registration allows visualization and augmentation of important anatomy in both the US and CT domain and improves the registration accuracy in both modalities. Observing the patient-specific model in the CT domain allows the clinicians to assess the local registration accuracy qualitatively, which is likely to increase their confidence in using the US model for deriving needle guidance decisions.

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BACKGROUND AND OBJECTIVES: The establishment at our center of a dedicated regional anesthesia service in 2008-2009 has resulted in a marked increase in single-shot brachial plexus blocks (sBPBs) for ambulatory wrist fracture surgery. Despite the documented benefits of regional over general anesthesia (GA), there has been a perceived increase among sBPB patients in postoperative return rates for pain at our institution. We conducted a retrospective quality improvement project to examine this. METHODS: After exemption from human ethics board review, we sought to identify and contact all wrist fracture surgery patients treated at our center between 2003 and 2012. Our primary outcome was the incidence of unplanned physician visits (office/clinic or emergency department) for pain in the first 48 hours after surgery. Other main outcomes included the incidence of seeking any form of medical attention for pain and self-reporting of severe pain in the first 48 hours. RESULTS: Of 1008 identified patients, 419 could be contacted; 195 qualified for analysis. The incidence of unplanned physician visits in the first 48 hours was 12% (13 of 118) among sBPB patients versus 4% (3 of 77) in GA patients (odds ratio [OR], 3.1; 95% confidence interval [95% CI], 0.8-11.1; P = 0.11). More sBPB versus GA patients sought any form of medical attention for pain (20% vs 5%; OR, 4.7; 95% CI, 1.4-10.9; P = 0.003). Similarly, more sBPB patients reported severe postoperative pain (41% vs 10%; OR, 5.9; 95% CI, 2.6-13.4; P < 0.0001). CONCLUSIONS: Patients who received sBPBs for ambulatory wrist fracture surgery had a higher rate of unplanned health care resource utilization caused by pain after hospital discharge than those undergoing GA. These findings warrant confirmation in a prospective trial and emphasize the need for a defined postdischarge analgesic pathway as well as the potential merits of perineural home catheters.

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PURPOSE: Spinal needle injections are widely applied to alleviate back pain and for anesthesia. Current treatment is performed either blindly with palpation or using fluoroscopy or computed tomography (CT). Both fluoroscopy and CT guidance expose patients to ionizing radiation. Ultrasound (US) guidance for spinal needle procedures is becoming more prevalent as an alternative. It is challenging to use US as the sole imaging modality for intraoperative guidance of spine needle injections due to the acoustic shadows created by the bony structures of the vertebra that limit visibility of the target areas for injection. We propose registration of CT and the US images to augment anatomical visualization for the clinician during spinal interventions guided by US. METHODS: The proposed method involves automatic global and multi-vertebrae registration to find the closest alignment between CT and US data. This is performed by maximizing the similarity between the two modalities using voxel intensity information as well as features extracted from the input volumes. In our method, the lumbar spine is first globally aligned between the CT and US data using intensity-based registration followed by point-based registration. To account for possible curvature change of the spine between the CT and US volumes, a multi-vertebrae registration step is also performed. Springs are used to constrain the movement of the individually transformed vertebrae to ensure the optimal alignment is a pose of the lumbar spine that is physically possible. RESULTS: Evaluation of the algorithm is performed on 10 clinical patient datasets. The registration approach was able to align CT and US datasets from initial misalignments of up to 25 mm, with a mean TRE of 1.37 mm. These results suggest that the proposed approach has the potential to offer a sufficiently accurate registration between clinical CT and US data.

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PURPOSE: Facet joint injections of analgesic agents are widely used to treat patients with lower back pain. The current standard-of-care for guiding the injection is fluoroscopy, which exposes the patient and physician to significant radiation. As an alternative, several ultrasound guidance systems have been proposed, but have not become the standard-of-care, mainly because of the difficulty in image interpretation by the anesthesiologist unfamiliar with the complex spinal sonography. METHODS: We introduce an ultrasound-based navigation system that allows for live 2D ultrasound images augmented with a patient-specific statistical model of the spine and relating this information to the position of the tracked injection needle. The model registration accuracy is assessed on ultrasound data obtained from nine subjects who had prior CT images as the gold standard for the statistical model. The clinical validity of our method is evaluated on four subjects (of an ongoing in vivo study) which underwent facet joint injections. RESULTS: The statistical model could be registered to the bone structures in the ultrasound volume with an average RMS accuracy of 2.3±0.4 mm. The shape of the individual vertebrae could be estimated from the US volume with an average RMS surface distance error of 1.5±0.4 mm. The facet joints could be identified by the statistical model with an average accuracy of 5.1 ± 1.5 mm. CONCLUSIONS: The results of this initial feasibility assessment suggest that this ultrasound-based system is capable of providing information sufficient to guide facet joint injections. Further clinical studies are warranted.

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PURPOSE: Epidural needle insertions and facet joint injections play an important role in spine anaesthesia. The main challenge of safe needle insertion is the deep location of the target, resulting in a narrow and small insertion channel close to sensitive anatomy. Recent approaches utilizing ultrasound (US) as a low-cost and widely available guiding modality are promising but have yet to become routinely used in clinical practice due to the difficulty in interpreting US images, their limited view of the internal anatomy of the spine, and/or inclusion of cost-intensive tracking hardware which impacts the clinical workflow. METHODS: We propose a novel guidance system for spine anaesthesia. An efficient implementation allows us to continuously align and overlay a statistical model of the lumbar spine on the live 3D US stream without making use of additional tracking hardware. The system is evaluated in vivo on 12 volunteers. RESULTS: The in vivo study showed that the anatomical features of the epidural space and the facet joints could be continuously located, at a volume rate of 0.5 Hz, within an accuracy of 3 and 7 mm, respectively. CONCLUSIONS: A novel guidance system for spine anaesthesia has been presented which augments a live 3D US stream with detailed anatomical information of the spine. Results from an in vivo study indicate that the proposed system has potential for assisting the physician in quickly finding the target structure and planning a safe insertion trajectory in the spine.

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PURPOSE: The objective of this review is to evaluate the literature on medications associated with delirium after cardiac surgery and potential prophylactic agents for preventing it. SOURCE: Articles were searched in MEDLINE, Cumulative Index to Nursing and Allied Health, and EMBASE with the MeSH headings: delirium, cardiac surgical procedures, and risk factors, and the keywords: delirium, cardiac surgery, risk factors, and drugs. Principle inclusion criteria include having patient samples receiving cardiac procedures on cardiopulmonary bypass, and using DSM-IV-TR criteria or a standardized tool for the diagnosis of delirium. PRINCIPAL FINDINGS: Fifteen studies were reviewed. Two single drugs (intraoperative fentanyl and ketamine), and two classes of drugs (preoperative antipsychotics and postoperative inotropes) were identified in the literature as being independently associated with delirium after cardiac surgery. Another seven classes of drugs (preoperative antihypertensives, anticholinergics, antidepressants, benzodiazepines, opioids, and statins, and postoperative opioids) and three single drugs (intraoperative diazepam, and postoperative dexmedetomidine and rivastigmine) have mixed findings. One drug (risperidone) has been shown to prevent delirium when taken immediately upon awakening from cardiac surgery. None of these findings was replicated in the studies reviewed. CONCLUSION: These studies have shown that drugs taken perioperatively by cardiac surgery patients need to be considered in delirium risk management strategies. While medications with direct neurological actions are clearly important, this review has shown that specific cardiovascular drugs may also require attention. Future studies that are methodologically consistent are required to further validate these findings and improve their utility.

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PURPOSE: Our centre recently implemented a new ambulatory care model featuring two alternate regional anesthesia "swing" operating rooms (RA-SRs) managed by a single anesthesiologist. We hypothesized that this model would be associated with decreased turnover times and improved recovery profiles when compared with a traditional model with a single operating room using general anesthesia. METHODS: We conducted a retrospective cohort study of 164 patients scheduled for hand and wrist surgery who were treated in the RA-SRs under brachial plexus blockade, and we compared the findings with a matched historical control group of patients who underwent general anesthesia in a single operating room (GA-OR). The primary endpoint was room turnover time. Secondary endpoints included home discharge time, postoperative interventions for nausea and pain, and number of cases possible per eight-hour day. RESULTS: Patients in the RA-SR group had faster turnover times than patients in the GA-OR group (median [interquartile range]: 15 min [8-22] vs 54 min [49-61], respectively) as well as faster home discharge times (28 min [20-46] vs 156 min [118-215], respectively) (P < 0.0001). In the RA-SR group, postoperative antiemetics were used in 3/164 patients (2%) vs 28/164 (17%) in the GA-OR group (P < 0.0001), and opioids were used in 1/164 (0.6%) vs 132/164 (80%), respectively (P < 0.0001). The median number of daily cases possible in the RA-SR group was 56% greater than in the GA-OR group (8.4 [7.5-9.4] vs 5.4 [5.1-5.8], respectively; P < 0.0001). CONCLUSION: Compared with a traditional model using general anesthesia in a single operating room, the implementation of a model using regional anesthesia with two swing operating rooms was associated with reduced room turnover times, improved recovery profiles, and a higher case throughput.

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Animals prenatally exposed to ethanol (E) exhibit behavioral alterations in a wide variety of stressful or challenging tasks. The hypothalamic peptide corticotropin-releasing factor (CRF) is known to play a crucial role in integrating an organism's behavioral responses to environmental stressors or challenges. Previous research indicates that E animals exhibit increased hypothalamic-pituitary-adrenal (HPA) reactivity, including increased hypothalamic CRF expression under both basal and stress conditions. However, the possible role of CRF in mediating the behavioral changes observed in E animals remains to be determined. The current study investigated the hypothesis that E animals may be differentially sensitive to the effects of CRF on behavior in the elevated plus-maze, a task widely used to assess anxiety-like behavior in rodents. Sprague-Dawley offspring from prenatal E, pair-fed (PF), and ad lib-fed control (C) groups were tested at 60-90 days of age. Thirty minutes prior to a 5 min test on the elevated plus-maze, animals received an icv infusion of vehicle (VEH) or CRF (males: 0.75 microg or 1.5 microg ; females: 1.0 microg or 2.0 microg ). Under VEH conditions, E males showed greater activity (more total arm entries) than PF and C males and both E males and E and PF females showed less anxiety-like behavior (more open arm entries) than their PF and/or C counterparts. As expected, CRF treatment resulted in fewer open arm, closed arm and total arm entries, and total rears in both males and females in all prenatal groups, and increased time in the closed arms in males compared to that in their VEH-treated counterparts. Importantly, the effects of CRF were most pronounced in E animals. That is, when normalized for prenatal group differences following VEH treatment, CRF-treated E males showed fewer total arm entries and total rears than PF and C males, and CRF-treated E and PF females showed fewer open arm entries than C females. These results support and extend previous findings demonstrating that E animals show altered behavior in aversive or stressful situations. While some effects of CRF in females may be mediated partially by nutritional effects of ethanol, the data overall suggest that the behavioral alterations observed in E animals may be due, at least in part, to increased sensitivity to CRF.

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The effects of hydrostatic pressure upon (1) a segmented poly (ester urethane), (2) a hydrolytically degraded sample of the same polymer, and (3) models for the polyurethane and polyester segments in this polymer have been studied by Fourier transform infrared spectroscopy using high-pressure diamond anvil cells (DACs). The pressure responses of the vibrational frequencies of specific functional groups of the poly (ester urethane) in the 0-100-kbar range are compared with data for individual segment models and the partially degraded sample. The results indicated that the polymer is highly stable in this pressure regime, with no measurable degradation or phase changes. Differences in the pressure dependency of specific infrared bands between the poly (ester urethane) sample and the partially degraded sample are slight and consistent with changes in hydrogen-bonding interactions and shorter chain lengths in the degraded sample.

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