Brief Assessment of Patient Phenotype to Explain Variability in Postsurgical Pain and Opioid Consumption after Cesarean Delivery: Performance of a Novel Brief Questionnaire Compared to Long Questionnaires.

BACKGROUND: Understanding factors that explain why some women experience greater postoperative pain and consume more opioids after cesarean delivery is crucial to building an evidence base for personalized prevention. Comprehensive psychosocial assessment with validated questionnaires in the preoperative period can be time-consuming. A three-item questionnaire has shown promise as a simpler tool to be integrated into clinical practice, but its brevity may limit the ability to explain heterogeneity in psychosocial pain modulators among individuals. This study compared the explanatory ability of three models: (1) the 3-item questionnaire, (2) a 58-item questionnaire (long) including validated questionnaires (e.g., Brief Pain Inventory, Patient Reported Outcome Measurement Information System [PROMIS]) plus the 3-item questionnaire, and (3) a novel 19-item questionnaire (brief) assessing several psychosocial factors plus the 3-item questionnaire. Additionally, this study explored the utility of adding a pragmatic quantitative sensory test to models. METHODS: In this prospective, observational study, 545 women undergoing cesarean delivery completed questionnaires presurgery. Pain during local anesthetic skin wheal before spinal placement served as a pragmatic quantitative sensory test. Postoperatively, pain and opioid consumption were assessed. Linear regression analysis assessed model fit and the association of model items with pain and opioid consumption during the 48 h after surgery. RESULTS: A modest amount of variability was explained by each of the three models for postoperative pain and opioid consumption. Both the brief and long questionnaire models performed better than the three-item questionnaire but were themselves statistically indistinguishable. Items that were independently associated with pain and opioid consumption included anticipated postsurgical pain medication requirement, surgical anxiety, poor sleep, pre-existing pain, and catastrophic thinking about pain. The quantitative sensory test was itself independently associated with pain across models but only modestly improved models for postoperative pain. CONCLUSIONS: The brief questionnaire may be more clinically feasible than longer validated questionnaires, while still performing better and integrating a more comprehensive psychosocial assessment than the three-item questionnaire.

Labor Analgesia Initiation With Dural Puncture Epidural Versus Conventional Epidural Techniques: A Randomized Biased-Coin Sequential Allocation Trial to Determine the Effective Dose for 90% of Patients of Bupivacaine.

BACKGROUND: The dural puncture epidural (DPE) technique has a faster onset, better sacral spread, and improved bilateral coverage when compared to the conventional epidural (EPL) technique. Whether these qualities translate into a lower bupivacaine dose to provide initial analgesia is unknown. We sought to determine the effective dose of bupivacaine to achieve initial (first 30 minutes) labor analgesia in 90% of patients (ED90) with the DPE and EPL techniques, using a biased-coin, sequential allocation method. METHODS: A total of 100 women of mixed parity with term, singleton gestation at ≤5 cm dilation with no major comorbidities were randomized to receive a DPE or an EPL technique. An experienced anesthesiologist performed these techniques and administered an allocated dose of plain bupivacaine diluted with isotonic sterile 0.9% saline to a total volume of 20 mL via the EPL catheter. Bupivacaine doses for each subject were determined by the response of the previous subject, using a biased-coin sequential allocation method, with success defined by a numeric rating scale (NRS) < 3 at 30 minutes. Outcome assessments were performed by an investigator blinded to the technique and bupivacaine dose. Sensory and motor blockade and maternal or fetal side effects were recorded every 5 minutes for the first 30 minutes. The ED90 of bupivacaine with each technique was estimated using centered isotonic regression. RESULTS: A total of 95 women were included in the final analysis. The ED90 of bupivacaine was estimated at 29.30 mg (90% confidence interval [CI], 28.55-31.56) with a DPE technique and 45.25 mg (90% CI, 42.80-52.03) with an EPL technique. CONCLUSIONS: Using a biased-coin, sequential allocation method, the DPE technique requires less bupivacaine to achieve effective initial analgesia (ED90) when compared to the EPL technique.

External Validation of a Multivariable Prediction Model for Placenta Accreta Spectrum.

BACKGROUND: Placenta accreta spectrum (PAS) is a disorder of abnormal placentation associated with severe postpartum hemorrhage, maternal morbidity, and mortality. Predelivery prediction of this condition is important to determine appropriate delivery location and multidisciplinary planning for operative management. This study aimed to validate a prediction model for PAS developed by Weiniger et al in 2 cohorts who delivered at 2 different United States tertiary centers. METHODS: Cohort A (Brigham and Women's Hospital; N = 253) included patients with risk factors (prior cesarean delivery and placenta previa) and/or ultrasound features of PAS presenting to a tertiary-care hospital. Cohort B (Columbia University Irving Medical Center; N = 99) consisted of patients referred to a tertiary-care hospital specifically because of ultrasound features of PAS. Using the outcome variable of surgical and/or pathological diagnosis of PAS, discrimination (via c-statistic), calibration (via intercept, slope, and flexible calibration curve), and clinical usefulness (via decision curve analysis) were determined. RESULTS: The model c-statistics in cohorts A and B were 0.728 (95% confidence interval [CI], 0.662-0.794) and 0.866 (95% CI, 0.754-0.977) signifying acceptable and excellent discrimination, respectively. The calibration intercept (0.537 [95% CI, 0.154-0.980] for cohort A and 3.001 [95% CI, 1.899- 4.335] for B), slopes (0.342 [95% CI, 0.170-0.532] for cohort A and 0.604 [95% CI, -0.166 to 1.221] for B), and flexible calibration curves in each cohort indicated that the model underestimated true PAS risks on average and that there was evidence of overfitting in both validation cohorts. The use of the model compared to a treat-all strategy by decision curve analysis showed a greater net benefit of the model at a threshold probability of >0.25 in cohort A. However, no net benefit of the model over the treat-all strategy was seen in cohort B at any threshold probability. CONCLUSIONS: The performance of the Weiniger model is variable based on the case-mix of the population with regard to PAS clinical risk factors and ultrasound features, highlighting the importance of spectrum bias when applying this PAS prediction model to distinct populations. The model showed benefit for predicting PAS in populations with substantial case-mix heterogeneity at threshold probability of >25%.

Thrombosis-Related Loss of Arterial Lines in the First Wave of COVID-19 and Non-COVID-19 Intensive Care Unit Patients.

BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) can present with severe respiratory distress requiring intensive care unit (ICU)-level care. Such care often requires placement of an arterial line for monitoring of pulmonary disease progression, hemodynamics, and laboratory tests. During the first wave of the COVID-19 pandemic in March 2020, experienced physicians anecdotally reported multiple attempts, decreased insertion durations, and greater need for replacement of arterial lines in patients with COVID-19 due to persistent thrombosis. Because invasive procedures in patients with COVID-19 may increase the risk for caregiver infection, better defining difficulties in maintaining arterial lines in COVID-19 patients is important. We sought to explore the association between COVID-19 infection and arterial line thrombosis in critically ill patients. METHODS: In this primary exploratory analysis, a multivariable Fine-Gray subdistribution hazard model was used to retrospectively estimate the association between critically ill COVID-19 (versus sepsis/acute respiratory distress syndrome [ARDS]) patients and the risk of arterial line removal for thrombosis (with arterial line removal for any other reason treated as a competing risk). As a sensitivity analysis, we compared the number of arterial line clots per 1000 arterial line days between critically ill COVID-19 and sepsis/ARDS patients using multivariable negative binomial regression. RESULTS: We retrospectively identified 119 patients and 200 arterial line insertions in patients with COVID-19 and 54 patients and 68 arterial line insertions with non-COVID ARDS. Using a Fine-Gray subdistribution hazard model, we found the adjusted subdistribution hazard ratio (95% confidence interval [CI]) for arterial line clot to be 2.18 (1.06-4.46) for arterial lines placed in COVID-19 patients versus non-COVID-19 sepsis/ARDS patients ( P = .034). Patients with COVID-19 had 36.3 arterial line clots per 1000 arterial line days compared to 19.1 arterial line clots per 1000 arterial line days in patients without COVID-19 (adjusted incidence rate ratio [IRR] [95% CI], 1.78 [0.94-3.39]; P = .078). CONCLUSIONS: Our study suggests that arterial line complications due to thrombosis are more likely in COVID-19 patients and supports the need for further research on the association between COVID-19 and arterial line dysfunction requiring replacement.

Frequency and Risk Factors for Difficult Intubation in Women Undergoing General Anesthesia for Cesarean Delivery: A Multicenter Retrospective Cohort Analysis.

BACKGROUND: Estimates for the incidence of difficult intubation in the obstetric population vary widely, although previous studies reporting rates of difficult intubation in obstetrics are older and limited by smaller samples. The goals of this study were to provide a contemporary estimate of the frequency of difficult and failed intubation in women undergoing general anesthesia for cesarean delivery and to elucidate risk factors for difficult intubation in women undergoing general anesthesia for cesarean delivery. METHODS: This is a multicenter, retrospective cohort study utilizing the Multicenter Perioperative Outcomes Group database. The study population included women aged 15 to 44 yr undergoing general anesthesia for cesarean delivery between 2004 and 2019 at 1 of 45 medical centers. Coprimary outcomes included the frequencies of difficult and failed intubation. Difficult intubation was defined as Cormack-Lehane view of 3 or greater, three or more intubation attempts, rescue fiberoptic intubation, rescue supraglottic airway, or surgical airway. Failed intubation was defined as any attempt at intubation without successful endotracheal tube placement. The rates of difficult and failed intubation were assessed. Several patient demographic, anatomical, and obstetric factors were evaluated for potential associations with difficult intubation. RESULTS: This study identified 14,748 cases of cesarean delivery performed under general anesthesia. There were 295 cases of difficult intubation, with a frequency of 1:49 (95% CI, 1:55 to 1:44; n = 14,531). There were 18 cases of failed intubation, with a frequency of 1:808 (95% CI, 1:1,276 to 1:511; n = 14,537). Factors with the highest point estimates for the odds of difficult intubation included increased body mass index, Mallampati score III or IV, small hyoid-to-mentum distance, limited jaw protrusion, limited mouth opening, and cervical spine limitations. CONCLUSIONS: In this large, multicenter, contemporary study of more than 14,000 general anesthetics for cesarean delivery, an overall risk of difficult intubation of 1:49 and a risk of failed intubation of 1:808 were observed. Most risk factors for difficult intubation were nonobstetric in nature. These data demonstrate that difficult intubation in obstetrics remains an ongoing concern.

Tranexamic acid administered during cesarean delivery in high-risk patients: maternal pharmacokinetics, pharmacodynamics, and coagulation status.

BACKGROUND: Tranexamic acid is frequently administered for postpartum hemorrhage. The World Health Organization recommends 1 g intravenous dosing, repeated once after 30 minutes for ongoing bleeding. Understanding the pharmacokinetics and pharmacodynamics of tranexamic acid in patients at high risk of postpartum hemorrhage may enable dosage tailoring for optimal antifibrinolysis with minimal adverse events, such as thrombosis or renal cortical necrosis. OBJECTIVE: This study aimed to report tranexamic acid pharmacokinetics and pharmacodynamics after 1 g intravenous dosing during cesarean delivery in patients at risk of hemorrhage. The primary endpoint was tranexamic acid plasma concentration of >10 µg/mL, known to inhibit 80% of fibrinolysis. In addition, the correlation between patient demographics and rotational thromboelastometry coagulation changes were analyzed. STUDY DESIGN: In this prospective study, 20 women aged 18 to 50 years, ≥23 weeks of gestation undergoing cesarean delivery with at least 1 major (placenta previa, suspected placenta accreta spectrum, or active bleeding) or 2 minor (≥2 previous cesarean deliveries, previous postpartum hemorrhage, chorioamnionitis, polyhydramnios, macrosomia, obesity, or suspected placental abruption) risk factors for postpartum hemorrhage were recruited. The exclusion criteria were allergy to tranexamic acid, inherited thrombophilia, previous or current thrombosis, seizure history, renal or liver dysfunction, anticoagulation, or category III fetal heart tracing. Tranexamic acid 1 g was administered after umbilical cord clamping. Blood samples were drawn at 3, 7, 15, and 30 minutes and then at 30-minute intervals up to 5 hours. Plasma concentrations were evaluated as mean (standard error). Serial rotational thromboelastometry was performed and correlated with tranexamic acid plasma concentrations. RESULTS: The median age of participants was 37.5 years (interquartile range, 35.0-39.5), and the median body mass index was 28.6 kg/m2 (interquartile range, 24.9-35.0). The median blood loss (estimated or quantitative) was 1500 mL (interquartile range, 898.5-2076.0). Of note, 9 of 20 (45%) received a transfusion of packed red blood cells. The mean peak tranexamic acid plasma concentration at 3 minutes was 59.8±4.7 µg/mL. All patients had a plasma concentration >10 µg/mL for 1 hour after infusion. Plasma concentration was >10 µg/mL in more than half of the patients at 3 hours and fell <10 µg/mL in all patients at 5 hours. There was a moderate negative correlation between body mass index and the plasma concentration area under the curve (r=-0.49; 95% confidence interval, -0.77 to -0.07; P=.026). Rotational thromboelastometry EXTEM maximum clot firmness had a weak positive correlation with longitudinal plasma concentration (r=0.32; 95% confidence interval, 0.21-0.46; P<.001). EXTEM maximum clot lysis was 0% after infusion in 18 patients (90%), and no patient in the study demonstrated a maximum lysis of >15% at any interval from 3 minutes to 5 hours. There was no significant correlation between EXTEM clot lysis at 30 minutes and longitudinal tranexamic acid plasma concentrations (r=0.10; 95% confidence interval, -0.20 to 0.19; P=.252). CONCLUSION: After standard 1 g intravenous dosing of tranexamic acid during cesarean delivery in patients at high risk of hemorrhage, a plasma concentration of ≥10 µg/mL was sustained for at least 60 minutes. Plasma tranexamic acid levels correlated inversely with body mass index. The concurrent use of rotational thromboelastometry may demonstrate tranexamic acid's impact on clot firmness but not a hyperfibrinolysis-derived trigger for therapy.

Inconsistent Methodology as a Barrier to Meaningful Research Outputs From Studies of Atrial Fibrillation After Cardiac Surgery.

Atrial fibrillation after cardiac surgery (AFACS) is a serious postoperative complication. There is significant research interest in this field but also relevant heterogeneity in reported AFACS definitions and approaches used for its identification. Few data exist on the extent of this variation in clinical studies. The authors reviewed the literature since 2001 and included manuscripts reporting outcomes of AFACS in adults. They excluded smaller studies and studies in which patients did not undergo a sternotomy. The documented protocol in each manuscript was analyzed according to six different categories to determine how AFACS was defined, which techniques were used to identify it, and the inclusion and/or exclusion criteria. They also noted when a category was not described in the documented protocol. The authors identified 302 studies, of which 92 were included. Sixty-two percent of studies were randomized controlled trials. There was significant heterogeneity in the manuscripts, including the exclusion of patients with preoperative AF, the definition and duration of AF needed to meet the primary endpoint, the type of screening approach (continuous, episodic, or opportunistic), the duration of monitoring during the study period in days, the diagnosis with predefined electrocardiogram criteria, and the requirement for independent confirmation by study investigators. Furthermore, the definitions of these criteria frequently were not described. Consistent reporting standards for AFACS research are needed to advance scientific progress in the field. The authors here propose pragmatic standards for trial design and reporting standards. These include adequate sample size estimation, a clear definition of the AFACS endpoints, and a protocol for AFACS detection.

Prediction of Persistent Pain Severity and Impact 12 Months After Breast Surgery Using Comprehensive Preoperative Assessment of Biopsychosocial Pain Modulators.

BACKGROUND: Persistent post-mastectomy pain (PPMP) is a significant negative outcome occurring after breast surgery, and understanding which individual women are most at risk is essential to targeting of preventive efforts. The biopsychosocial model of pain suggests that factors from many domains may importantly modulate pain processing and predict the progression to pain persistence. METHODS: This prospective longitudinal observational cohort study used detailed and comprehensive psychosocial and psychophysical assessment to characterize individual pain-processing phenotypes in 259 women preoperatively. Pain severity and functional impact then were longitudinally assessed using both validated surgery-specific and general pain questionnaires to survey patients who underwent lumpectomy, mastectomy, or mastectomy with reconstruction in the first postsurgical year. An agnostic, multivariable modeling strategy identified consistent predictors of several pain outcomes at 12 months. RESULTS: The preoperative characteristics most consistently associated with PPMP outcomes were preexisting surgical area pain, less education, increased somatization, and baseline sleep disturbance, with axillary dissection emerging as the only consistent surgical variable to predict worse pain. Greater pain catastrophizing, negative affect, younger age, higher body mass index (BMI), and chemotherapy also were independently predictive of pain impact, but not severity. Sensory disturbance in the surgical area was predicted by a slightly different subset of factors, including higher preoperative temporal summation of pain. CONCLUSIONS: This comprehensive approach assessing consistent predictors of pain severity, functional impact, and sensory disturbance may inform personalized prevention of PPMP and also may allow stratification and enrichment in future preventive studies of women at higher risk of this outcome, including pharmacologic and behavioral interventions and regional anesthesia.

Patient characteristics associated with SARS-CoV-2 infection in parturients admitted for labour and delivery in Massachusetts during the spring 2020 surge: A prospective cohort study.

BACKGROUND: While studies from large cities affected by coronavirus disease 2019 (COVID-19) have reported on the prevalence of SARS-CoV-2 in the context of universal testing during admission for delivery, the patient demographic, social and clinical factors associated with SARS-CoV-2 infection in pregnant women are not fully understood. OBJECTIVE: To evaluate the epidemiological factors associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in women admitted for labour and delivery, in the context of universal screening at four Boston-area hospitals. METHODS: In this prospective cohort study, we reviewed the health records of all women admitted for labour and delivery at four hospitals from the largest health system in Massachusetts between 19 April 2020 and 27 June 2020. We calculated the risk of SARS-CoV-2 infection, including asymptomatic infection. We calculated associations between SARS-CoV-2 infection and demographic and clinical characteristics. RESULTS: A total of 93 patients (3.2%, 95% confidence interval 2.5, 3.8) tested positive for SARS-CoV-2 infection on admission for labour and delivery out of 2945 patients included in the analysis; 80 (86.0%) of the patients who tested positive were asymptomatic at the time of testing. Factors associated with SARS-CoV-2 infection included the following: younger age, obesity, African American or Hispanic race/ethnicity, residence in heavily affected communities (as measured in cases reported per capita), presence of a household member with known SARS-CoV-2 infection, non-health care essential worker occupation and MassHealth or Medicaid insurance compared to commercial insurance. 93.8% of patients testing positive for SARS-CoV-2 on admission had one or more identifiable factors associated with disease acquisition. CONCLUSIONS: In this large sample of deliveries during the height of the surge in infections during the spring of 2020, SARS-CoV-2 infection was largely concentrated in patients with distinct demographic characteristics, those largely from disadvantaged communities. Racial disparities seen in pregnancy persist with respect to SARS-CoV-2 infection.

Risk of Postdural Puncture Headache in Adolescents and Adults.

BACKGROUND: Spinal anesthesia is known to have numerous benefits, including reductions in nausea and opioid consumption; however, postdural puncture headache (PDPH) remains a significant risk associated with this technique. The literature specifically examining this complication in adolescents is scarce. Our primary objective was therefore (1) to estimate the incidence of PDPH with a 27G pencil-point needle in patients between the ages of 12 and 19 undergoing ambulatory lower extremity procedures and (2) to compare it to the incidence in adults aged 20-45 years. METHODS: After institutional review board (IRB) approval, patients aged 12-45 years undergoing ambulatory lower extremity surgery were approached. Patients undergoing the procedure under combined spinal-epidural (CSE) or spinal anesthesia with a 27G pencil-point needle were eligible for enrollment. Patients were consented before surgery and received a survey via e-mail on postoperative day (POD) 4 inquiring about the presence of a headache. Each headache was described by the participant and assessed for severity, time of onset, duration, location, and whether it was of a postural nature. All patients reporting a postural headache were contacted by a physician author to confirm a diagnosis of PDPH using the International Headache Society diagnostic criteria. RESULTS: A total of 656 patients were included in the analysis. Overall, 3.4% of patients developed PDPH. The percentage developing PDPH was 4.9% (3.0-7.8) among those aged 12-19 years and 1.8% (0.8-3.9) in the 20- to 45-year-old group. After adjusting for covariates, the age group between 12 and 19 years was associated with an almost 3-fold increase in the odds (2.8 [95% confidence interval {CI}, 1.1-7.3]) for the development of PDPH compared to that in the 20-45 age group. One patient in the adult group required an epidural blood patch. CONCLUSIONS: The overall incidence for the development of PDPH in ambulatory patients <45 years of age is low. However, the odds for developing PDPH is significantly higher in teenagers compared to those aged 20-45 years. This increase was not associated with an increase in the need for an epidural blood patch. Providers may incorporate these data in their consent process and have a higher index of suspicion for PDPH in teenagers who report headaches after neuraxial anesthesia.

Introduction of a Novel System for Quantitating Blood Loss After Vaginal Delivery: A Retrospective Interrupted Time Series Analysis With Concurrent Control Group.

BACKGROUND: Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. While volumetric and gravimetric blood loss measurement techniques have been shown to increase PPH detection compared to visual estimation of blood loss (vBL), a combination of these methods has not been evaluated. The primary aim of this study was to compare the change in odds of PPH detection after vaginal delivery (VD; the intervention series) versus cesarean delivery (CD; the control series) before versus after implementation of a device (Triton L&D, Gauss Surgical, Inc, Los Altos, CA) that combines gravimetric and volumetric estimation of blood loss (tBL). METHODS: After institutional review board (IRB) approval, patients were identified who had a VD or CD at our institution 3 months before and 3 months after the implementation of a tBL device for VD. The levels and trends in odds of PPH detection (the primary outcome, defined as blood loss ≥500 mL for VD and ≥1000 mL for CD) were compared within and between delivery methods before and after implementation of the device. Secondary outcomes were blood loss ≥1000 mL, total blood loss, secondary uterotonic use, and a composite outcome related to PPH management (transfusion, vasopressor administration, and/or surgical procedures). A post hoc subgroup analysis compared nadir hematocrit, hematocrit reduction ≥10%, and difference between vBL or tBL and calculated blood loss (cBL) between VDs before and after introduction of the device. All outcome comparisons were performed using segmented regression with inverse probability of treatment weighting. RESULTS: The weighted odds ratio (wOR) of PPH detection post- versus preimplementation of the device was 2.74 (95% confidence interval [CI], 1.39-5.41; P = .004) for VDs versus 1.43 (95% CI, 0.72-2.85; P = .304) for CDs (P for interaction .190). No difference was detected in the secondary outcomes for VDs between time periods. In the subgroup of VD patients who had postdelivery hematocrits measured, the mean difference between vBL or tBL and cBL was smaller in the tBL (mean ± standard deviation [SD]: -237 ± 522 mL) versus vBL group (-600 ± 596 mL; weighted difference in means [95% CI]: 349 mL [13-684]; P = .042). CONCLUSIONS: In this interrupted time series analysis, the odds of PPH detection after VD increased after implementation of the tBL device. However, a statistical difference was not detected between the increase in PPH detection post- versus preimplementation of the device in VDs versus CDs.

What Pain Levels Do TSA Patients Experience When Given a Long-acting Nerve Block and Multimodal Analgesia?

BACKGROUND: The pain experience for total shoulder arthroplasty (TSA) patients in the first 2 weeks after surgery has not been well described. Many approaches to pain management have been used, with none emerging as clearly superior; it is important that any approach minimizes postoperative opioid use. QUESTIONS/PURPOSES: (1) With a long-acting nerve block and comprehensive multimodal analgesia, what are the pain levels after TSA from day of surgery until postoperative day (POD) 14? (2) How many opioids do TSA patients take from the day of surgery until POD 14? (3) What are the PainOUT responses at POD 1 and POD 14, focusing on side effects from opioids usage? METHODS: From January 27, 2017 to December 6, 2017, 154 TSA patients were identified as potentially eligible for this prospective, institutional review board-approved observational study. Of those, 46 patients (30%) were excluded (either because they were deemed not appropriate for the study, research staff were not available, patients were not eligible, or they declined to participate), and another six (4%) had incomplete followup data and could not be studied, leaving 102 patients (66%) for analysis here. Median preoperative pain with movement was 7 (interquartile range [IQR], 5-9) and 13 of 102 patients used preoperative opioids. All patients received a single-injection bupivacaine interscalene block with adjuvant clonidine, dexamethasone, and buprenorphine. Multimodal analgesia included acetaminophen, NSAIDs, and opioids. The primary outcome was the Numerical Rating Scale (NRS) pain score with movement on POD 14. The NRS pain score ranges from 0 (no pain) to 10 (worst pain possible). Secondary outcomes included NRS pain scores at rest and with movement (day of surgery, and PODs 1, 3, 7 and 14), daily analgesic use from day of surgery to POD 14 (both oral and intravenous), Opioid-Related Symptom Distress Scale (which assesses 12 symptoms ranging from 0 to 4, with 4 being the most distressing; the composite score is the mean of the 12 symptom-specific scores) on POD 1, and the PainOut questionnaire on POD 1 and POD 14. The PainOut questionnaire includes questions rating nausea, drowsiness, itching from 0 (none) to 10 (severe), as well as rating difficulty staying asleep from 0 (does not interfere) to 10 (completely interferes). RESULTS: The median NRS pain scores with movement were 2 (IQR, 0-5) on POD 1, 5 (IQR, 3-6) on POD 3, and the pain score was 3 (IQR, 1-5) on POD 14. Median total opioid use (converted to oral morphine equivalents) was 16 mg (4-50 mg) for the first 24 hours, 30 mg (8-63 mg) for the third, and 0 mg (0-20 mg) by the eighth 24-hour period, while the most frequent number of activations of the intravenous patient-controlled analgesia device was 0. Median PainOut scores on POD 1 and POD 14 for sleep interference, nausea, drowsiness and itching were 0, and the median composite Opioid-Related Symptom Distress Scale score on day 1 was 0.3 (IQR, 0.1-0.5). CONCLUSIONS: Clinicians using this protocol, which combines a long-acting, single-injection nerve block with multimodal analgesia, can inform TSA patients that their postoperative pain will likely be less than their preoperative pain, and that on average they will stop using opioids after 7 days. Future research could investigate what the individual components of this protocol contribute. Larger cohort studies or registries would document the incidence of rare complications. Randomized controlled trials could directly compare analgesic effectiveness and cost-benefits for this protocol versus alternative strategies, such as perineural catheters or liposomal bupivacaine. Perhaps most importantly, future studies could seek ways to further reduce peak pain and opioid usage on POD 2 and POD 3. LEVEL OF EVIDENCE: Level IV, therapeutic study.

Pyrimethamine significantly lowers cerebrospinal fluid Cu/Zn superoxide dismutase in amyotrophic lateral sclerosis patients with SOD1 mutations.

OBJECTIVE: Cu/Zn superoxide dismutase (SOD1) reduction prolongs survival in SOD1-transgenic animal models. Pyrimethamine produces dose-dependent SOD1 reduction in cell culture systems. A previous phase 1 trial showed pyrimethamine lowers SOD1 levels in leukocytes in patients with SOD1 mutations. This study investigated whether pyrimethamine lowered SOD1 levels in the cerebrospinal fluid (CSF) in patients carrying SOD1 mutations linked to familial amyotrophic lateral sclerosis (fALS/SOD1). METHODS: A multicenter (5 sites), open-label, 9-month-duration, dose-ranging study was undertaken to determine the safety and efficacy of pyrimethamine to lower SOD1 levels in the CSF in fALS/SOD1. All participants underwent 3 lumbar punctures, blood draw, clinical assessment of strength, motor function, quality of life, and adverse effect assessments. SOD1 levels were measured in erythrocytes and CSF. Pyrimethamine was measured in plasma and CSF. Appel ALS score, ALS Functional Rating Scale-Revised, and McGill Quality of Life Single-Item Scale were measured at screening, visit 6, and visit 9. RESULTS: We enrolled 32 patients; 24 completed 6 visits (18 weeks), and 21 completed all study visits. A linear mixed effects model showed a significant reduction in CSF SOD1 at visit 6 (p < 0.001) with a mean reduction of 13.5% (95% confidence interval [CI] = 8.4-18.5) and at visit 9 (p < 0.001) with a mean reduction of 10.5% (95% CI = 5.2-15.8). INTERPRETATION: Pyrimethamine is safe and well tolerated in ALS. Pyrimethamine is capable of producing a significant reduction in total CSF SOD1 protein content in patients with ALS caused by different SOD1 mutations. Further long-term studies are warranted to assess clinical efficacy. Ann Neurol 2017;81:837-848.

Readiness for Discharge After Foot and Ankle Surgery Using Peripheral Nerve Blocks: A Randomized Controlled Trial Comparing Spinal and General Anesthesia as Supplements to Nerve Blocks.

BACKGROUND: Neuraxial anesthesia is often viewed as superior to general anesthesia but may delay discharge. Comparisons do not typically use multimodal analgesics and nerve blockade. Combining nerve blockade with general anesthesia may reduce pain, opioid consumption, and nausea. We hypothesized that general anesthesia (with nerve blocks) would lead to earlier readiness for discharge, compared to spinal anesthesia (with nerve blocks). METHODS: All patients underwent ambulatory foot and ankle surgery, with a predicted case duration of 1-3 hours. All patients received popliteal and adductor canal nerve blocks using bupivacaine and dexamethasone. No intraoperative opioids were administered. All patients received ondansetron, dexamethasone, ketamine, and ketorolac. Patients, data collectors, and the data analyst were not informed of group assignment. Patients were randomized to spinal or general anesthesia with concealed allocation. Spinal anesthesia was performed with mepivacaine and accompanied with propofol sedation. After general anesthesia was induced with propofol, a laryngeal mask airway was inserted, followed by sevoflurane and propofol. Time until ready for discharge, the primary outcome, was compared between groups after adjusting for age and surgery time using multivariable unconditional quantile regression. Secondary outcomes compared at multiple timepoints were adjusted for multiple comparisons using the Holm-Bonferroni step-down procedure. RESULTS: General anesthesia patients were ready for discharge at a median of 39 minutes earlier (95% confidence interval, 2-75; P = .038) versus spinal anesthesia patients. Patients in both groups met readiness criteria for discharge substantially before actual discharge. Pain scores at rest were higher among general anesthesia patients 1 hour after leaving the operating room (adjusted difference in means, 2.1 [95% confidence interval, 1.0-3.2]; P < .001). Other secondary outcomes (including opioid use, opioid side effects, nausea, headache, sore throat, and back pain) were not different. CONCLUSIONS: General anesthesia was associated with earlier readiness for discharge, but the difference may not be clinically significant and did not lead to earlier actual discharge. Most secondary outcomes were not different between groups. The choice of spinal or general anesthesia as an adjunct to peripheral nerve blockade can reflect patient, clinician, and institutional preferences.

Diagnosis of Intraabdominal Fluid Extravasation After Hip Arthroscopy With Point-of-Care Ultrasonography Can Identify Patients at an Increased Risk for Postoperative Pain.

BACKGROUND: Intraabdominal fluid extravasation (IAFE) after hip arthroscopy has historically been diagnosed in catastrophic circumstances with abdominal compartment syndrome requiring diuresis or surgical decompression. A previous retrospective study found the prevalence of symptomatic IAFE requiring diuresis or decompression to be 0.16%, with risk factors including surgical procedure and high pump pressures. IAFE can be diagnosed rapidly by using point-of-care ultrasound (POCUS) via the Focused Assessment With Sonography for Trauma (FAST) examination, which is a well-established means to detect free fluid with high specificity and sensitivity. In this study, we used POCUS to determine the incidence of IAFE in patients undergoing hip arthroscopy. We predicted a higher incidence and that patients with IAFE would have symptoms of peritoneal irritation such as pain and nausea. METHODS: One hundred patients undergoing ambulatory hip arthroscopy were prospectively enrolled. A FAST examination was performed after induction by a trained anesthesiologist to exclude the preoperative presence of intraperitoneal fluid. Postoperatively, the same anesthesiologist repeated the FAST examination, and patients with new fluid in the abdominal or pelvic peritoneum were diagnosed with IAFE. Patients were followed up in the postanesthesia care unit (PACU) for 6 hours assessing pain, antiemetic and opioid use, and length of stay. RESULTS: Sixteen of 100 patients were found to have IAFE (16.0%; 99% confidence interval [CI], 8.4-28.1). These patients had, on average, a greater increase in pain score from their baseline assessment throughout their entire PACU stay (adjusted difference in means [99% CI]: 2.1 points [0.4-3.9]; P = .002). Patients with IAFE used more opioids, but this difference did not meet statistical significance (adjusted difference in means [99% CI]: 7.8 mg oral morphine equivalents [-2.8 to 18.3]; P = .053). There were no differences in postoperative nausea interventions or length of stay. CONCLUSIONS: Our incidence of IAFE was 16%, showing that IAFE occurs quite commonly in hip arthroscopy. Patients with IAFE had a greater increase in pain scores from baseline throughout the PACU stay. None of our patients required interventions. These findings suggest that even a small amount of new fluid in the peritoneum may be associated with a worse postoperative experience. This study brings awareness to a common yet potentially life-threatening complication of hip arthroscopy and highlights a unique and meaningful way that anesthesiologists in the perioperative setting can use POCUS to rapidly identify and guide management of these patients. Further studies with a larger sample size are needed to identify surgical and patient risk factors.

Anterior Inferior Iliac Spine Morphology and Outcomes of Hip Arthroscopy in Soccer Athletes: A Comparison to Nonkicking Athletes.

PURPOSE: To describe the anterior inferior iliac spine (AIIS) morphology and clinical outcomes following arthroscopic surgical decompression in a group of high-level soccer athletes presenting with symptomatic hip impingement when compared with a control group of nonkicking athletes. METHODS: From 2009 to 2012, we retrospectively reviewed our prospective hip registry for soccer athletes who underwent arthroscopic treatment for femoroacetabular impingement (FAI) with 2-year follow-up, comparing with a control group of nonkicking athletes. Demographics were collected and radiographic studies (plain radiograph and computed tomographic scan) reviewed for several parameters, including AIIS morphology. Patient-reported outcome scores, including modified Harris Hip Score (mHHS), Hip Outcome Score-Activities of Daily Living (HOS-ADL) and Sport-Specific Subscale (HOS-SSS), and International Hip Outcome Tool-33 (iHOT-33), were administered preoperatively, at 6 months, and at 1, 2, and 3 years postoperatively. RESULTS: Twenty-six soccer players (34 hips) and 87 nonkicking athletes (115) hips were identified. Demographics, including age (19.2 ± 4.1 vs 20.1 ± 3.8 years) and gender distribution (53.8% vs 51.7% male), were similar between the soccer and nonkicking athletes (P = .288, .849). Eighty-four percent of soccer players demonstrated some abnormality of the AIIS extending to (type II, 52%) or below the anterior acetabular rim (type III, 32%), compared with 52% nonkicking athletes (P < .001). At a mean follow-up of 35 months (range, 24-57 months) there was significant improvement in all outcome scores in both groups from pre- to postoperation (P < .001). There was no evidence of differences in outcome scores between groups (mHSS: 89 ± 14.6 vs 88.2 ± 14.4, P = .804; HOS-ADL: 94.1 ± 9.1 vs 92.2 ± 11.1, P = .431; HOS-SSS: 86 ± 17.1 vs 81.3 ± 24.3, P = .362) with the exception of iHOT-33 (81.7 ± 19 vs 70.3 ± 23.6, P = .027). CONCLUSIONS: High-level soccer players have a significantly higher rate of subspine impingement compared with nonkicking athletes. There should be a high index of suspicion when treating soccer players for FAI, where appropriate recognition and treatment of subspine impingement can yield excellent clinical results. LEVEL OF EVIDENCE: Level III, retrospective case-control study.

Functional Outcomes and Cam Recurrence After Arthroscopic Treatment of Femoroacetabular Impingement in Adolescents.

PURPOSE: To compare the functional outcomes after arthroscopic treatment of femoroacetabular impingement (FAI) in adolescent patients and non-adolescent patients, and to report on the rate of cam recurrence within 2 years after femoral osteoplasty in a limited sample of the adolescent group. METHODS: From 2010 to 2014, patients younger than 18 years with symptomatic FAI (alpha angle >50°) who underwent hip arthroscopy with minimum 2-year follow-up or reoperation were identified. A group of non-adolescent patients with identical inclusion criteria, except age of 18 years or older, was also identified for comparison. In addition, a separate group of adolescent patients with 2-year postoperative radiographs was reviewed for cam recurrence. Demographic data, operative data, and radiographic and clinical outcomes (modified Harris Hip Score [mHHS], Hip Outcome Score-Activities of Daily Living [HOS-ADL], Hip Outcome Score-Sport-Specific Subscale [HOS-SSS], and International Hip Outcome Tool 33 [iHOT-33] score) were collected. RESULTS: We identified 34 adolescent patients (38 hips) with an average age of 16 years (range, 13-17 years). The mean clinical follow-up period was 36.1 ± 11.6 months (range, 24.1-71.7 months) and 29.6 ± 2.4 months (range, 27.9-31.3 months) without and with reoperation, respectively. A control group of 296 non-adolescent patients (306 hips), with a mean age of 31 years (range, 18-59 years), was identified as our non-adolescent group. The mean clinical follow-up period was 34.1 ± 11 months (range, 24.0-77.4 months) and 15.1 ± 9.1 months (range, 3.6-34.6 months) without and with reoperation, respectively. Significant improvement was noted in adolescents in the changes in outcome scores (mHHS, 22.2 [95% confidence interval (CI), 15.4-29.0]; HOS-ADL, 18.6 [95% CI, 11.9-25.2]; HOS-SSS, 33.5 [95% CI, 24.5-42.5]; and iHOT-33 score, 30.5 [95% CI, 21.8-39.2]; P < .001). Similar improvements were observed in non-adolescents (mHHS, 21.0 [95% CI, 19.0-23.0]; HOS-ADL, 16.6 [95% CI, 14.6-18.6]; HOS-SSS, 30.1 [95% CI, 26.6-33.6]; and iHOT-33 score, 34.9 [95% CI, 31.5-38.3]; P < .001). There was no evidence of a difference in follow-up survey scores between groups (P > .203). Revision surgery was required in 2 adolescent hips (5.3% [95% CI, 1.5%-17.3%]) and 19 non-adolescent hips (6.2% [95% CI, 4.0%-9.5%]). Minimum 2-year radiographs were available for review in 24 adolescent patients (30 hips). The alpha angle (mean ± standard deviation) was reduced from 55.4° ± 12.1° preoperatively to 38.7° ± 4.9° at 6 weeks postoperatively (mean difference, -16.4° [95% CI, -19.8° to -12.9°]; P < .001). At 2 years, the alpha angle remained at 39.2° ± 11.2°, which did not differ from 6-week measurements (mean difference, 0.5° [95% CI, -2.9° to 3.9°]; P = .784). There were no cases of cam recurrence (0% [95% CI, 0%-11.4%]). CONCLUSIONS: Significant improvement in clinical outcomes can be anticipated after arthroscopic treatment of FAI in adolescents. From a limited sample of our adolescent population, the risk of cam recurrence appears low; however, further follow-up is needed to ensure this does not represent a biased sample of the initial population. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Perineural dexamethasone with subsartorial saphenous nerve blocks in ACL reconstruction.

PURPOSE: Subsartorial saphenous nerve blockade (SSNB) is an effective analgesic alternative to femoral nerve blockade after anterior cruciate ligament (ACL) reconstruction with bone-tendon-bone (BTB) autograft. It was hypothesized that dexamethasone in a SSNB will prolong analgesia, improve pain and satisfaction, and reduce postoperative opioid requirements and side effects. METHODS: One hundred ninety-five patients undergoing ACL reconstruction with BTB autograft (ages 16-65) were enrolled. Subjects received SSNB with 13 ml of 0.5 % bupivacaine (control group), 1 mg preservative-free dexamethasone +0.5 % bupivacaine (treatment group I), or 4 mg preservative-free dexamethasone +0.5 % bupivacaine (treatment group II). Subjects received identical perioperative management. On postoperative days 1 and 2, subjects reported perceived block duration, pain scores, satisfaction, opioid use, and side effects. Cox-proportional hazards modelling was used to compare block duration, adjusting for body mass index, age, sex, tourniquet time, American Society of Anesthesiologists classification, and intravenous dexamethasone dose. RESULTS: Patient-perceived block duration was significantly increased in treatment group I [hazard ratio (95 % confidence interval [CI]) 0.48 (0.31-0.75); P = 0.001] and treatment group II (hazard ratio (95 % CI): 0.52 (0.33-0.81); P = 0.004) compared to control. The block was extended from a median (95 % CI) of 33.1 (28.4-37.3) to 41.2 (32.4-50.9) and 46.5 (35.8-48.9) hours, respectively. Additionally, patients in treatment group II reported increased time that block provided pain relief, higher patient satisfaction, lower pain scores at rest, and decreased drowsiness and confusion. CONCLUSION: The addition of 1 and 4 mg of dexamethasone to the block injectate significantly increased SSNB duration by 8-13 h compared to control. LEVEL OF EVIDENCE: Therapeutic study, level 1.