Evaluating residual anti-Xa levels following discontinuation of treatment-dose enoxaparin in patients presenting for elective surgery: a prospective observational trial.

INTRODUCTION: Prior studies have demonstrated that patients presenting for elective surgery may have higher-than-expected residual anti-Xa level activity at or beyond 24 hours following their last treatment dose of enoxaparin. Given that 24 hours of abstinence is currently recommended by both European and American societies before the performance of neuraxial or deep anesthetic/analgesic procedures, determining the actual timeframe at which residual anti-Xa level activity reliably falls below 0.2 IU/mL, the lower limit of the target range for thromboprophylaxis, is critical. METHODS: This was a prospective observational trial. Consenting patients on treatment-dose enoxaparin were randomized to either a 24-hour group (last dose at 07:00 the day prior to surgery) or a 36-hour group (last dose at 19:00 2 days prior to surgery). On arrival for surgery, blood samples were obtained to assess residual anti-Xa level activity and renal function. The primary outcome was residual anti-Xa level activity following the last treatment dose of enoxaparin. Incorporating all patients, linear regression modeling was performed to predict the timepoint at which the level of anti-Xa activity reliably fell below 0.2 IU/mL. RESULTS: 103 patients were analyzed. Time from the last dose at which residual anti-Xa activity fell below 0.2 IU/mL, based on the upper bound of the 95% CI, was 31.5 hours. No correlation overall between age, renal function, or sex was found. CONCLUSION: Residual levels of anti-Xa activity do not reliably fall below 0.2 IU/mL 24 hours following discontinuation of treatment-dose enoxaparin. Therefore, current time-based guidelines are not conservative enough. Routine anti-Xa testing should be strongly considered, or current time-based guidelines should be reassessed. TRIAL REGISTRATION NUMBER: NCT03296033.

Opioid abuse and perioperative care: a new medical disease.

PURPOSE OF REVIEW: This review article aims to describe the perioperative clinical implications of opioid use or opioid use disorder (OUD) and to provide recommendations related to analgesia, anesthesia, and postoperative care for patients with this 'new medical disease'. RECENT FINDINGS: Evidence suggest that 1 in 4 surgical patients will be using opioids preoperatively. Management of these patients, or those with OUD, can be challenging given their opioid tolerance, hyperalgesia, decreased pain tolerance, and increased pain sensitivity. Therefore, an individualized plan that considers how to manage OUD treatment medications, the risk of relapse, multimodal analgesia, and postoperative monitoring requirements is highly important. Fortunately, recent publications provide both insight and guidance on these topics. Postoperatively, persistent opioid utilization appears higher in patients currently using opioids and even for those with a prior history. Although numerous other adverse outcomes are also associated with opioid use or abuse, some may be modifiable with cessation. SUMMARY: A coordinated, evidence-based, multidisciplinary team approach is critical when caring for patients with OUD to ensure safety, provide adequate analgesia, and reduce the risk of relapse. Enhanced postoperative monitoring, multimodal analgesia, and a plan for preoperative opioid management may help to modify the risks of adverse postoperative outcomes.

Surface Landmarks in the Lateral Decubitus Position Are Unreliable for Thoracic Epidural Catheter Placement: A Case Series.

Thoracic epidurals remain the optimal method for providing postoperative analgesia after complex open abdominal and thoracic surgeries. However, they can be challenging to both place and maintain, as evidenced by a failure rate that exceeds 30%.1 Proper identification of the epidural space and accurate placement of the catheter are critical in order to deliver effective postoperative analgesia and avoid failure.2,3 This case series investigated the difficulty in correctly identifying the proper vertebral level for thoracic epidural catheter procedures when performed in the lateral decubitus position.

Cancer immune control dynamics: a clinical data driven model of systemic immunity in patients with metastatic melanoma.

BACKGROUND: Recent clinical advances in cancer immuno-therapeutics underscore the need for improved understanding of the complex relationship between cancer and the multiple, multi-functional, inter-dependent, cellular and humoral mediators/regulators of the human immune system. This interdisciplinary effort exploits engineering analysis methods utilized to investigate anomalous physical system behaviors to explore immune system behaviors. Cancer Immune Control Dynamics (CICD), a systems analysis approach, attempts to identify differences between systemic immune homeostasis of 27 healthy volunteers versus 14 patients with metastatic malignant melanoma based on daily serial measurements of conventional peripheral blood biomarkers (15 cell subsets, 35 cytokines). The modeling strategy applies engineering control theory to analyze an individual's immune system based on the biomarkers' dynamic non-linear oscillatory behaviors. The reverse engineering analysis uses a Singular Value Decomposition (SVD) algorithm to solve the inverse problem and identify a solution profile of the active biomarker relationships. Herein, 28,605 biologically possible biomarker interactions are modeled by a set of matrix equations creating a system interaction model. CICD quantifies the model with a participant's biomarker data then computationally solves it to measure each relationship's activity allowing a visualization of the individual's current state of immunity. RESULTS: CICD results provide initial evidence that this model-based analysis is consistent with identified roles of biomarkers in systemic immunity of cancer patients versus that of healthy volunteers. The mathematical computations alone identified a plausible network of immune cells, including T cells, natural killer (NK) cells, monocytes, and dendritic cells (DC) with cytokines MCP-1 [CXCL2], IP-10 [CXCL10], and IL-8 that play a role in sustaining the state of immunity in advanced cancer. CONCLUSIONS: With CICD modeling capabilities, the complexity of the immune system is mathematically quantified through thousands of possible interactions between multiple biomarkers. Therefore, the overall state of an individual's immune system regardless of clinical status, is modeled as reflected in their blood samples. It is anticipated that CICD-based capabilities will provide tools to specifically address cancer and treatment modulated (immune checkpoint inhibitors) parameters of human immunity, revealing clinically relevant biological interactions.

Ilioinguinal/Iliohypogastric versus quadratus lumborum nerve blockade for elective open inguinal herniorrhaphy: a prospective, randomized, double-blinded, equivalency trial.

BACKGROUND: Open inguinal herniorrhaphy (OIH) is a commonly performed surgical procedure with expected postoperative pain. Historically, an option for regional analgesia has been an ilioinguinal and iliohypogastric nerve block (IINB). More recently, the transmuscular quadratus lumborum block (QLB) has been used as an analgesic technique for a variety of abdominal and truncal surgical procedures. Given our own institutional experiences with the performance of QLB combined with the body of literature supporting the proximal blockade of the ilioinguinal and iliohypogastric nerves via this approach, we compared the analgesia provided by an IINB to a QLB. We hypothesized that the two blocks would provide equivalent analgesia, as defined by a difference of less than±2 points on the pain scale (0-10 numeric rating scale (NRS)), for patients undergoing OIH. METHODS: Sixty patients scheduled for elective outpatient OIH under general anesthesia were randomized to preoperatively receive either an IINB or a transmuscular QLB with 0.25% bupivacaine/epinephrine/clonidine for postoperative analgesia. The primary endpoint was movement NRS pain scores at 8 hours. Secondary outcomes included resting NRS pain scores at 8 and 24 hours, movement NRS pain scores at 24 hours, incidence of opioid related side effects (nausea, vomiting, pruritus), time-to-first oral opioid analgesic, and total opioid consumption at 24 hours. RESULTS: Fifty-nine patients were analyzed per an intention-to-treat approach (one patient was excluded because the surgical procedure was canceled). Movement pain scores at 8 hours were equivalent (IINB 5.10±3.02 vs QLB 5.03±3.01 (mean NRS±SD); two one-sided test mean difference (90% CI), 0.07 (-1.24 to 1.38), p ≤0.01). There were no differences between groups for any of the secondary endpoints. CONCLUSION: An IINB and a transmuscular QLB are equivalent with regards to their ability to provide postoperative analgesia after OIH.

Analgesic Benefit of Pectoral Nerve Block II Blockade for Open Subpectoral Biceps Tenodesis: A Randomized, Prospective, Double-Blinded, Controlled Trial.

BACKGROUND: Axillary pain is common after arthroscopic shoulder surgery with an open subpectoral biceps tenodesis. We hypothesized that adding a pectoral nerve block II (Pecs II) to an interscalene block (ISB) would improve postoperative analgesia in this surgical population. METHODS: Forty patients were enrolled in this prospective, randomized, observer and patient-blinded, single-institution trial. All 40 patients received a single-injection ISB with 20 mL of 0.25% bupivacaine with 1:400,000 epinephrine and 1:600,000 clonidine. The intervention arm (ISB + Pecs II) consisted of 20 patients who also received a Pecs II block using 30 mL of 0.25% bupivacaine with 1:400,000 epinephrine and 1:600,000 clonidine. The 20 control group patients (ISB) received a sham Pecs II block. The primary outcome was postoperative pain scores at 6 hours using the numeric rating scale (NRS; range, 0-10) and was analyzed using the Mann-Whitney U test. Secondary outcomes included the presence of axillary pain at 6 hours, the need for postanesthesia care unit (PACU) opioids, PACU length of stay (LOS) (minutes), NRS pain scores at 24 hours, cumulative opioid usage postdischarge through 24 hours, the presence of nausea or vomiting during the first 24 hours, and Pecs II block duration (in hours, based on time to onset of axillary pain). Data were analyzed using a modified intention-to-treat (ITT) methodology. RESULTS: Pain scores (NRS, 0-10) at 6 hours differed significantly between groups: ISB 3.0 (0.25-5.0) (1.7-4.3) versus ISB + Pecs II 0.0 (0-2.0) (0.0-1.1) (median [IQR] [95% CI]); P = .026. Hodges-Lehmann estimator of the difference was 2.0 (95% CI, 0.0-4.0). Fewer patients in the ISB + Pecs II group reported axillary pain at 6 hours and fewer required opioids in the PACU. There were no differences in any of the remaining secondary outcomes. CONCLUSIONS: The addition of a Pecs II block to an ISB for patients undergoing arthroscopic shoulder surgery with an open subpectoral biceps tenodesis significantly improved postoperative analgesia and reduced the need for opioids in the PACU.

Preprocedural checklist for regional anesthesia: impact on the incidence of wrong site nerve blockade (an 8-year perspective).

BACKGROUND: The term "Wrong-Site Surgery (WSS)" is commonly associated with surgical procedures; however, The Joint Commission (TJC) considers any invasive procedure, not just a surgical procedure, performed on the wrong side, at the wrong site, or on the wrong patient to be a WSS. For anesthesia providers, this means that a wrong-site nerve block (WSNB) also constitutes a WSS and would be considered a sentinel event by TJC. In an attempt to combat WSNB, the American Society of Regional Anesthesia and Pain Medicine published guidelines in 2014 recommending the use of a preprocedural checklist before performing regional blocks. The effectiveness of such a checklist, however, to reduce the occurrence of WSNB has not yet been demonstrated. We hypothesized that the introduction of a preprocedural checklist specific for regional anesthesia would be associated with a lower rate of WSNB procedures. METHODS: A retrospective review was performed to compare the incidence of WSNB 2 years before, to 6 years after the implementation of a preprocedural checklist specific to regional anesthesia. RESULTS: Prior to checklist implementation, 4 WSNB events occurred during 10 123 procedures (3.95 per 10 000 (95% CI 1.26 to 9.53). Following implementation, WSNB events occurred during 35 890 procedures (0 per 10 000 (95% CI 0 to 0.84)); p=0.0023. CONCLUSIONS: Implementation of a regional anesthesia specific preprocedural checklist was associated with a significantly lower incidence of WSNB procedures. While prospective controlled studies would be required to demonstrate causation, this study suggests that for regional anesthesia procedures, a preprocedural checklist may positively impact patient safety.

Single-Injection Adductor Canal Block With Multiple Adjuvants Provides Equivalent Analgesia When Compared With Continuous Adductor Canal Blockade for Primary Total Knee Arthroplasty: A Double-Blinded, Randomized, Controlled, Equivalency Trial.

BACKGROUND: Peripheral nerve blockade is used to provide analgesia for patients undergoing total knee arthroplasty. This study compared a single-injection adductor canal block (SACB) with adjuvants to continuous adductor canal blockade (CACB). The hypothesis was that the 2 groups would have equivalent analgesia at 30 hours after neural blockade. METHODS: This was a double-blinded, randomized, controlled, equivalency trial. Sixty patients were randomized to either the SACB group (20 mL of 0.25% bupivacaine, 1.67 mcg/mL of clonidine, 2 mg of dexamethasone, 150 mcg of buprenorphine, and 2.5 mcg/mL of epinephrine) or the CACB group (20 mL 0.25% of bupivacaine injection with 2.5 mcg/mL of epinephrine followed by an 8 mL/h infusion of 0.125% bupivacaine continued through postoperative day 2). The primary outcome was movement pain scores at 30 hours using the numeric rating scale (NRS). The secondary outcomes included serial postoperative NRS pain scores (rest and movement every 6 hours), opioid consumption, time to first opioid administration, ability to straight leg raise, patient satisfaction, length of stay, and the incidence of nausea/vomiting. RESULTS: An intention-to-treat analysis included 59 patients. The NRS pain scores with movement were equivalent at 30 hours (SACB 5.5 ± 2.8 vs CACB 5.7 ± 2.9 [mean NRS ± standard deviation]; mean difference 0.2 [-1.5 to 1.0 {90% confidence interval}]). All NRS pain scores were equivalent until 42 hours (rest) and 48 hours (rest and movement) with the CACB group having lower pain scores. Other secondary outcomes were not statistically different. CONCLUSION: An SACB provides equivalent analgesia for up to 36 hours after block placement when compared with a CACB for patients undergoing total knee arthroplasty, though a CACB was favored at 42 hours and beyond.

Perineural dexamethasone successfully prolongs adductor canal block when assessed by objective pinprick sensory testing: A prospective, randomized, dose-dependent, placebo-controlled equivalency trial.

STUDY OBJECTIVE: To determine whether perineural dexamethasone prolongs peripheral nerve blockade (PNB) when measured objectively; and to determine if a 1 mg and 4 mg dose provide equivalent PNB prolongation compared to PNB without dexamethasone. SETTING: Multiple studies have reported that perineural dexamethasone added to local anesthetics (LA) can prolong PNB. However, these studies have relied on subjective end-points to quantify PNB duration. The optimal dose remains unknown. We hypothesized that 1 mg of perineural dexamethasone would be equivalent in prolonging an adductor canal block (ACB) when compared to 4 mg of dexamethasone, and that both doses would be superior to an ACB performed without dexamethasone. DESIGN: This was a prospective, randomized, double-blind, placebo-controlled equivalency trial involving 85 patients undergoing a unicompartmental knee arthroplasty. INTERVENTIONS: All patients received an ACB with 20 ml of 0.25% bupivacaine with 1:400,000 epinephrine. Twelve patients had 0 mg of dexamethasone (placebo) added to the LA mixture; 36 patients had 1 mg of dexamethasone in the LA; and 37 patients had 4 mg of dexamethasone in the LA. MEASUREMENTS: The primary outcome was block duration determined by serial neurologic pinprick examinations. Secondary outcomes included time to first analgesic, serial pain scores, and cumulative opioid consumption. MAIN RESULTS: The 1 mg (31.8 ±â€¯10.5 h) and 4 mg (37.9 ±â€¯10 h) groups were not equivalent, TOST [Mean difference (95% CI); 6.1 (-10.5, -2.3)]. Also, the 4 mg group was superior to the 1 mg group (p-value = 0.035), and the placebo group (29.7 ±â€¯6.8 h, p-value = 0.011). There were no differences in opioid consumption or time to analgesic request; however, some pain scores were significantly lower in the dexamethasone groups when compared to placebo. CONCLUSION: Dexamethasone 4 mg, but not 1 mg, prolonged the duration of an ACB when measured by serial neurologic pinprick exams. CLINICAL TRIAL REGISTRATION: NCT02462148.

Placement of Stimulating Epidural Catheter for a Patient With Large Scapular Sarcoma: A Case Report.

We report the use of continuous electrical stimulation to assist with the preoperative placement of a thoracic epidural which was used to provide postoperative analgesia in a patient undergoing excision of a large scapular sarcoma. The size of the sarcoma and the surrounding area required to maintain a sterile surgical field necessitated that the epidural catheter be inserted several vertebral interspaces caudal to the level of desired catheter tip termination. The use of electrical stimulation allowed for sequential intercostal muscle stimulation during threading, which enabled the placement of the catheter tip at the appropriate spinal level to optimize analgesia.

Residual Enoxaparin Activity, Anti-Xa Levels, and Concerns About the American Society of Regional Anesthesia and Pain Medicine Anticoagulation Guidelines.

Currently, the American Society of Regional Anesthesia and Pain Medicine (ASRA) anticoagulation guidelines recommend that before the performance of a neuraxial procedure a minimum of 24 hours should elapse following a treatment dose of enoxaparin (1 mg/kg twice daily or 1.5 mg/kg once daily). The guidelines have since their inception also consistently recommended against the routine use of anti-Xa level monitoring for patients receiving enoxaparin. However, we noted in our clinical practice that anti-Xa levels were frequently still elevated despite patients meeting the time-based recommendation for treatment dose enoxaparin. To further investigate the possibility that residual anticoagulant activity may persist longer than 24 hours after a treatment dose of enoxaparin, we assessed anti-Xa level activity in patients presenting for elective surgery. Despite nearly universal compliance with ASRA's anticoagulation guidelines (1 sample was drawn at 23.25 hours), anti-Xa activity was found to be elevated in 11 of 19 patients. While 10 patients had an anti-Xa level within the peak prophylactic range (0.2-0.5 IU/mL), 1 patient's level was found to still be in the peak therapeutic range (0.5-1.0 IU/mL). These findings suggest that significant anticoagulant activity may persist longer than previously appreciated after the last treatment dose of enoxaparin and that the current time-based ASRA recommendation may not be conservative enough. Further research is needed to delineate the level of anti-Xa activity below which it is likely safe to proceed with a neuraxial procedure, but it may be time to reconsider the utility of anti-Xa level monitoring when it is available.

Epidural Blood Patch Using Manometry for Sinking Skin Flap Syndrome.

We describe here a 55-year-old male patient with a medical history significant for chronic back pain and substance abuse with cocaine who sustained a traumatic subarachnoid hemorrhage after a fall from a roof while acutely intoxicated on cocaine requiring decompressive hemicraniectomy and cranioplasty that was complicated by an epidural abscess requiring a repeat craniectomy. He was diagnosed with sinking skin flap syndrome consistent with altered mental status and a sunken skin flap with increased midline shift. Despite treatment with Trendelenburg positioning and appropriate fluid management, the patient continued to decline, and an epidural blood patch was requested for treatment. After placement of the epidural blood patch using manometry in the epidural space, the patient's neurologic status improved allowing him to ultimately receive a cranioplasty. The patient is now able to perform several of his activities of daily living and communicate effectively.

Burst and principal components analyses of MEA data for 16 chemicals describe at least three effects classes.

Microelectrode arrays (MEAs) can be used to detect drug and chemical induced changes in neuronal network function and have been used for neurotoxicity screening. As a proof-of-concept, the current study assessed the utility of analytical "fingerprinting" using principal components analysis (PCA) and chemical class prediction using support vector machines (SVMs) to classify chemical effects based on MEA data from 16 chemicals. Spontaneous firing rate in primary cortical cultures was increased by bicuculline (BIC), lindane (LND), RDX and picrotoxin (PTX); not changed by nicotine (NIC), acetaminophen (ACE), and glyphosate (GLY); and decreased by muscimol (MUS), verapamil (VER), fipronil (FIP), fluoxetine (FLU), chlorpyrifos oxon (CPO), domoic acid (DA), deltamethrin (DELT) and dimethyl phthalate (DMP). PCA was performed on mean firing rate, bursting parameters and synchrony data for concentrations above each chemical's EC50 for mean firing rate. The first three principal components accounted for 67.5, 19.7, and 6.9% of the data variability and were used to identify separation between chemical classes visually through spatial proximity. In the PCA, there was clear separation of GABAA antagonists BIC, LND, and RDX from other chemicals. For the SVM prediction model, the experiments were classified into the three chemical classes of increasing, decreasing or no change in activity with a mean accuracy of 83.8% under a radial kernel with 10-fold cross-validation. The separation of different chemical classes through PCA and high prediction accuracy in SVM of a small dataset indicates that MEA data may be useful for separating chemicals into effects classes using these or other related approaches.

Binding energies for alkane molecules on a carbon surface from gas-solid chromatography and molecular mechanics.

Gas-solid chromatography was used to determine B(2s) (gas-solid virial coefficient) values for 12 alkanes (10 branched and 2 cyclic) interacting with a carbon powder (Carbopack B, Supelco). B(2s) values were determined by multiple size variant injections within the temperature range of 393 to 623 K with each alkane measured at 5 or 6 different temperatures. The temperature variations of the gas-solid virial coefficients were used to find the experimental adsorption energy or binding energy values (E( *)) for each alkane. A molecular mechanics based, rough-surface model was used to calculate the molecule-surface binding energy (E(cal)( *)) using augmented MM2 parameters. The surface model consisted of three parallel graphene layers with each layer containing 127 interconnected benzene rings and two separated nanostructures each containing 17 benzene rings arranged in a linear strip. As the parallel nanostructures are moved closer together, the surface roughness increases and molecule-surface interactions are enhanced. A comparison of the experimental and calculated binding energies showed excellent agreement with an average difference of 3.8%. Linear regressions of E( *) versus E(cal)( *) for the current data set and a combined current and prior alkane data set both gave excellent correlations. For the combined data set with 18 linear, branched and cyclic alkanes; a linear regression of E( *)=0.9848E(cal)( *) and r(2)=0.976 was obtained. The results indicate that alkane-surface binding energies may be calculated from MM2 parameters for some gas-solid systems.