Microglia Promote Increased Pain Behavior through Enhanced Inflammation in the Spinal Cord during Repeated Social Defeat Stress.

Clinical studies indicate that psychosocial stress contributes to adverse chronic pain outcomes in patients, but it is unclear how this is initiated or amplified by stress. Repeated social defeat (RSD) is a mouse model of psychosocial stress that activates microglia, increases neuroinflammatory signaling, and augments pain and anxiety-like behaviors. We hypothesized that activated microglia within the spinal cord facilitate increased pain sensitivity following RSD. Here we show that mechanical allodynia in male mice was increased with exposure to RSD. This stress-induced behavior corresponded with increased mRNA expression of several inflammatory genes, including IL-1ß, TNF-α, CCL2, and TLR4 in the lumbar spinal cord. While there were several adhesion and chemokine-related genes increased in the lumbar spinal cord after RSD, there was no accumulation of monocytes or neutrophils. Notably, there was evidence of microglial activation selectively within the nociceptive neurocircuitry of the dorsal horn of the lumbar cord. Elimination of microglia using the colony stimulating factor 1 receptor antagonist PLX5622 from the brain and spinal cord prevented the development of mechanical allodynia in RSD-exposed mice. Microglial elimination also attenuated RSD-induced IL-1ß, CCR2, and TLR4 mRNA expression in the lumbar spinal cord. Together, RSD-induced allodynia was associated with microglia-mediated inflammation within the dorsal horn of the lumbar spinal cord.SIGNIFICANCE STATEMENT Mounting evidence indicates that psychological stress contributes to the onset and progression of adverse nociceptive conditions. We show here that repeated social defeat stress causes increased pain sensitivity due to inflammatory signaling within the nociceptive circuits of the spinal cord. Studies here mechanistically tested the role of microglia in the development of pain by stress. Pharmacological ablation of microglia prevented stress-induced pain sensitivity. These findings demonstrate that microglia are critical mediators in the induction of pain conditions by stress. Moreover, these studies provide a proof of principle that microglia can be targeted as a therapeutic strategy to mitigate adverse pain conditions.

Evaluating the Efficacy of Two Regional Pain Management Modalities in Autologous Breast Reconstruction.

At our institution, multimodal opiate-sparing pain management is the cornerstone of our enhanced recovery program for autologous breast reconstruction. The purpose of this study was to compare postoperative outcomes and pain control metrics following implementation of an enhanced recovery program with two different regional analgesia approaches. METHODS: This retrospective cohort study identified 145 women who underwent autologous breast reconstruction from 2015 to 2017. Three groups were included: historical control patients (n = 46) and enhanced recovery patients that received multimodal pain management including a postoperative transversalis abdominis plane block with either a continuous local anesthetic catheter (n = 60) or a single-shot of liposomal bupivacaine (n = 39). The primary outcome was pain scores in the first three postoperative days. Secondary outcomes were opioid consumption in oral morphine equivalents and length of stay. RESULTS: Postoperative pain scores were similar across all three groups until postoperative day 3. Length of stay was significantly shorter in both of the enhanced recovery cohorts (3.0 [3.0, 4.0]) compared with control patients (4.0 [4.0, 5.0], P < 0.001). Likewise, average total oral morphine equivalents consumption was significantly reduced in enhanced recovery patients (continuous catheter 215.9 (95% CI, 165.4-266.3); liposomal bupivacaine 211.0 (95% CI, 154.8-267.2); control 518.4 (95% CI 454.2-582.7), P < 0.001). Neither length of stay (P = 0.953), nor oral morphine equivalents consumption (P = 0.883) differed by type of regional analgesia. CONCLUSION: Compared with control patients, both approaches to regional transversalis abdominis plane block analgesia as part of an opiate-sparing enhanced recovery pain management strategy were successful, but neither superior to the other.

Neuroimmune Interactions in Pain and Stress: An Interdisciplinary Approach.

Mounting evidence indicates that disruptions in bidirectional communication pathways between the central nervous system (CNS) and peripheral immune system underlie the etiology of pathologic pain conditions. The purpose of this review is to focus on the cross-talk between these two systems in mediating nociceptive circuitry under various conditions, including nervous system disorders. Elevated and prolonged proinflammatory signaling in the CNS is argued to play a role in psychiatric illnesses and chronic pain states. Here we review current research on the dynamic interplay between altered nociceptive mechanisms, both peripheral and central, and physiological and behavioral changes associated with CNS disorders.

Survey of provider perceptions of enhanced recovery after surgery and perioperative surgical home protocols at a tertiary care hospital.

ABSTRACT: Enhanced recovery after surgery (ERAS) and perioperative surgical home (PSH) initiatives are widely utilized to improve quality of patient care. Despite their established benefits, implementation still has significant barriers. We developed a survey for perioperative clinicians to gather information on perception and knowledge of ERAS/PSH programs to guide future expansion of these programs at our institution. The survey included questions about familiarity with ERAS/PSH and perceived value, perceived barriers to protocol implementation, preferred learning methods and prioritization of various ERAS/PSH protocol elements into care delivery and provider education. Faculty surgeons and anesthesiologists, in addition to advanced practice nurses and postgraduate physician trainees in the Departments of Surgery and Anesthesiology were asked to complete the survey. Overall survey participation was 25% (223/888). About half of survey respondents had provided care to a patient on an ERAS/PSH protocol, and a majority felt at least somewhat knowledgeable about ERAS/PSH protocols. Perception of the value of ERAS/PSH was positive. Participants were enthusiastic about on-going learning, with multimodal pain management being the topic of most interest and learning by direct participation in care of protocol patients being the favored educational approach. A significant majority of participants felt that upcoming health providers should receive formal ERAS/PSH education as part of their training. Based on our survey results, we plan to explore teaching methods that successfully engage learners of all levels of clinical expertise and also overcome the major barriers to gaining knowledge about ERAS/PSH identified by study participants, most notably lack of time for busy clinicians.

Effect of Cognitive Prehabilitation on the Incidence of Postoperative Delirium Among Older Adults Undergoing Major Noncardiac Surgery: The Neurobics Randomized Clinical Trial.

Importance: Postoperative delirium in older adults is a common and costly complication after surgery. Cognitive reserve affects the risk of postoperative delirium, and thus preoperative augmentation of reserve as a preventive technique is of vital interest. Objective: To determine whether cognitive prehabilitation reduces the incidence of postoperative delirium among older adults. Design, Setting, and Participants: This was a prospective, single-blinded randomized clinical trial conducted from March 2015 to August 2019 at the Ohio State University Wexner Medical Center in Columbus. Patients 60 years and older undergoing major, noncardiac, nonneurological surgery under general anesthesia, with an expected hospital stay of at least 72 hours, were eligible for trial inclusion. Patients were excluded for preoperative cognitive dysfunction and active depression. Interventions: Participation in electronic, tablet-based preoperative cognitive exercise targeting memory, speed, attention, flexibility, and problem-solving functions. Main Outcomes and Measures: The primary outcome was incidence of delirium between postoperative day 0 to day 7 or discharge, as measured by a brief Confusion Assessment Method, Memorial Delirium Assessment Scale, or a structured medical record review. Secondary outcomes compared delirium characteristics between patients in the intervention and control groups. Results: Of the 699 patients approached for trial participation, 322 completed consent and 268 were randomized. Subsequently, 17 patients were excluded, leaving 251 patients in the primary outcome analysis. A total of 125 patients in the intervention group and 126 control patients were included in the final analysis (median [interquartile range] age, 67 [63-71] years; 163 women [64.9%]). Ninety-seven percent of the patients in the intervention group completed some brain exercise (median, 4.6 [interquartile range, 1.31-7.4] hours). The delirium rate among control participants was 23.0% (29 of 126). With intention-to-treat analysis, the delirium rate in the intervention group was 14.4% (18 of 125; P = .08). Post hoc analysis removed 4 patients who did not attempt any cognitive exercise from the intervention group, yielding a delirium rate of 13.2% (16 of 121; P = .04). Secondary analyses among patients with delirium showed no differences in postoperative delirium onset day or duration or total delirium-positive days across study groups. Conclusions and Relevance: The intervention lowered delirium risk in patients who were at least minimally compliant. The ideal activities, timing, and effective dosage for cognitive exercise-based interventions to decrease postoperative delirium risk and burden need further study. Trial Registration: ClinicalTrials.gov Identifier: NCT02230605.

Multimodal Prehabilitation Programs for Older Surgical Patients.

Despite advances in perioperative care, short-term and long-term postoperative complications are still experienced by many patients, which is of special relevance to the older adult population, considered to be high-risk surgical candidates because of less functional reserve and comorbidity burden. Through the implementation of prehabilitation programs, patients can be optimized to handle the physical and mental stress of surgery. Benefits have been described in a variety of surgical populations, but more studies targeting older surgical patients are needed. These studies should include standardized prehabilitation protocols and large sample sizes to avoid the limitations of the existing prehabilitation literature.

Development of a postoperative ileus risk assessment scale: identification of intraoperative opioid exposure as a significant predictor after spinal surgery.

OBJECTIVE: Postoperative ileus (POI) is associated with abdominal pain, nausea, vomiting, and delayed mobilization that in turn lead to diminished patient satisfaction, increased hospital length of stay (LOS), and increased healthcare costs. In this study, the authors developed a risk assessment scale to predict the likelihood of developing POI following spinal surgery. METHODS: The authors undertook a retrospective review of a prospectively maintained registry of consecutive patients who underwent arthrodesis/fusion surgeries between May 2013 and December 2017. They extracted clinical information, including cumulative intraoperative and postoperative opioid doses using standardized converted morphine milligram equivalent (MME) values. Univariate and multivariate analyses were performed and several categorical and continuous variables were evaluated in a binary logistic regression model built with backward elimination to assess for independent predictors. A points-based prediction model was developed and validated to determine the risk of POI. RESULTS: A total of 334 patients who underwent spinal fusion surgeries were included. Fifty-six patients (16.8%) developed POI, more frequently in those who underwent long-segment surgeries compared to short-segment surgeries (33.3% vs 10.4%; p < 0.001). POI was associated with an increased LOS when compared with patients who did not develop POI (8.0 ± 4.5 days vs 4.4 ± 2.4 days; p < 0.01). The incidences of liver disease (16% vs 3.7%; p = 0.01) and substance abuse history (12.0% vs 3.2%; p = 0.04) were higher in POI patients than non-POI patients undergoing short-segment surgeries. While the incidences of preoperative opioid intake (p = 0.23) and cumulative 24-hour (87.7 MME vs 73.2 MME; p = 0.08) and 72-hour (225.6 MME vs 221.4 MME; p = 0.87) postoperative opioid administration were not different, remifentanil (3059.3 µg vs 1821.5 µg; p < 0.01) and overall intraoperative opioid (326.7 MME vs 201.7 MME; p < 0.01) dosing were increased in the POI group. The authors derived a multivariate model based on the 5 most significant factors predictive of POI (number of surgical levels, intraoperative MME, liver disease, age, and history of substance abuse) and calculated relative POI risks using a derived 32-point system. CONCLUSIONS: Intraoperative opioid administration, incorporated in a comprehensive risk assessment scale, represents an early and potentially modifiable predictor of POI. These data indicate that potential preventive strategies, implemented as part of enhanced recovery after surgery protocols, could be instituted in the preoperative phase of care to reduce POI incidence.

Defining quality of recovery - What is important to patients?

Postoperative recovery is a complex process with several interrelated domains. Traditionally, the absence of negative physiological symptoms like nausea and pain, along with avoidance of major postoperative complications, has been the standard set by clinicians and hospitals for a satisfactory postoperative recovery. Nonetheless, evidence from recent studies reports these items to be the least important from the patient point of view. Effective communication, active involvement of the patient in their healthcare decisions, and empathy from healthcare providers are rated by patients as significant factors for their quality of recovery. Although challenging to study, the development of a multimodal, patient-centered approach to evaluate the postsurgical period is critical for a truly comprehensive assessment of recovery quality. This review provides an overview of our current understanding of how patient factors like satisfaction can be impacted by the Anesthesia Care Team and how overall quality of recovery is related to perioperative patient experiences.

Anesthetic considerations for renal transplant surgery in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome: a case report.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome is a progressive syndrome with variable involvement of multiple-organ systems. These patients require special consideration for preoperative optimization, intraoperative management, and postoperative care. The medical literature regarding perioperative management of these patients relies heavily on case reports. Here we present a novel experience providing care for a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome who underwent renal transplantation for focal segmental glomerulosclerosis and end-stage renal disease.

Anesthesia care for subcutaneous implantable cardioverter/defibrillator placement: a single-center experience.

BACKGROUND: The recently approved subcutaneous implantable cardioverter/defibrillator (S-ICD) uses a single extrathoracic subcutaneous lead to treat life-threatening ventricular arrhythmias, such as ventricular tachycardia and ventricular fibrillation. This is different from conventional transvenous ICDs, which are typically implanted under sedation. Currently, there are no reports regarding the anesthetic management of patients undergoing S-ICD implantation. STUDY OBJECTIVES: This study describes the anesthetic management and outcomes in patients undergoing S-ICD implantation and defibrillation threshold (DFT) testing. METHODS: The study population consists of 73 patients who underwent S-ICD implantation. General anesthesia (n = 69, 95%) or conscious/deep sedation (n = 4, 5%) was used for device implantation. MEASUREMENTS: Systolic blood pressure (SBP) and heart rate were recorded periprocedurally for S-ICD implantation and DFTs. Major adverse events were SBP <90 mm Hg refractory to vasopressor agents, significant bradycardia (heart rate <45 beats per minute) requiring pharmacologic intervention and, "severe" pain at the lead tunneling site and the S-ICD generator insertion site based on patient perception. INTERVENTIONS: Of the 73 patients, 39 had SBP <90 mm Hg (53%), and intermittent boluses of vasopressors and inotropes were administered with recovery of SBP. In 2 patients, SBP did not respond, and the patients required vasopressor infusion in the intensive care unit. MAIN RESULTS: Although the S-ICD procedure involved extensive tunneling and a mean of 2.5 ± 1.7 DFTs per patient, refractory hypotension was a major adverse event in only 2 patients. The mean baseline SBP was 132.5 ± 22.0 mm Hg, and the mean minimum SBP during the procedure was 97.3 ± 9.2 mm Hg (P < .01). There was also a mean 13-beats per minute decrease in heart rate (P < .01), but no pharmacologic intervention was required. Eight patients developed "severe" pain at the lead tunneling and generator insertion sites and were adequately managed with intravenous morphine. CONCLUSIONS: Among a heterogeneous population, anesthesiologists can safely manage patients undergoing S-ICD implantation and repeated DFTs without wide swings in SBP and with minimal intermittent pharmacologic support.

Perioperative Cognitive Protection-Cognitive Exercise and Cognitive Reserve (The Neurobics Trial): A Single-blind Randomized Trial.

PURPOSE: The Neurobics Trial is a single-blind, parallel-group, randomized, controlled trial. The main study objective is to compare effectiveness of preoperative cognitive exercise versus no intervention for lowering the incidence of postoperative delirium. Enrollment began March 2015 and is ongoing. METHODS: Eligible participants include patients older than 60 years of age scheduled for nonemergent, noncardiac, nonneurological surgery at our institution. Patients provide consent and are screened at our Outpatient Preoperative Assessment Clinic to rule out preexisting cognitive dysfunction, significant mental health disorders, and history of surgery requiring general anesthesia in the preceding 6 months. Participants meeting criteria are randomized to complete 1 hour daily of electronic tablet-based cognitive exercise for 10 days before surgery or no preoperative intervention. Compliance with the effective dose of 10 total hours of preoperative exercise is verified on return of the patient for surgery with time logs created by the software application and by patient self-reporting. After surgery, patients are evaluated for delirium in the postanesthesia recovery area, and then twice daily for the remainder of their hospitalization. Additionally, postoperative quality of recovery is assessed daily, along with pain scores and opiate use. More comprehensive cognitive assessments are completed just before discharge for baseline comparison, and quality of recovery is assessed via telephone interview 7, 30, and 90 days post-surgery. The primary outcome is the incidence of delirium during the postoperative hospitalization period. Randomization is computer generated, with allocation concealment in opaque envelopes. All postoperative assessments are completed by blinded study personnel. FINDINGS: The study is actively recruiting with 19 patients having provided consent to date, and a total of 264 patients is required for study completion; therefore, no data analysis is currently under way (www.clinicaltrials.gov; NCT02230605). IMPLICATIONS: To our knowledge, the Neurobics Trial is the first randomized, controlled study to investigate the effectiveness of a significant preoperative cognitive exercise regimen for the prevention of delirium after noncardiac, nonneurological surgery in elderly patients.