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.

Raising the Bar: Multimodal Analgesia with Transdermal Lidocaine for Nuss Repair of Pectus Excavatum Decreases Length of Stay and Opioid Use.

INTRO: Pain management for minimally invasive (Nuss) repair of pectus excavatum (PE) is challenging, particularly as the judicious use of opioids has become a patient safety priority. Multi-modal pain management protocols are increasingly used, but there is limited experience using transdermal lidocaine patches (TLP) in this patient population. METHODS: Pediatric anesthesiologists and surgeons in a children's hospital within a hospital designed a multi-modal perioperative pain management protocol for patients undergoing Nuss repair of PE (IRB00068901). The protocol included use of TLP in addition to other adjuncts such as methadone, gabapentin, and NSAIDS. Following initiation of the protocol charts were reviewed retrospectively, comparing outcomes before and after implementation of the protocol. RESULTS: Forty-nine patients underwent a Nuss procedure between 2013 and 2022, 15 prior to initiation of the protocol and 34 after. Patient demographics and operative length were similar between the two groups. Average length of stay decreased from 4.7 to 3.3 days and reported opioid use at the time of the first outpatient post-op visit dropped from 60% to 24% (p < 0.05). Morphine milligram equivalents (MME) usage was decreased following implementation during hospital admission, at discharge, and at first post-operative visit (464 vs. 169, 1288 vs. 218, and 214 vs. 56, respectfully, p < 0.05). There were no ED visits or readmissions <30 days related to post-operative pain. CONCLUSION: Post-operative opioid usage and hospital length of stay were decreased after initiation of the protocol. Transdermal lidocaine patches may be a helpful adjunct to minimize narcotic requirements after repair of pectus excavatum. LEVEL OF EVIDENCE: Level II.

Comparison of Femoral Nerve Catheter, Adductor Canal Catheter, and Periarticular Liposomal Bupivacaine Infiltration for Postoperative Analgesia After Primary Total Knee Arthroplasty.

BACKGROUND: Peripheral nerve catheters are used to provide analgesia after total knee arthroplasty (TKA) and have been shown to decrease pain and opioid use, to facilitate participation with physical therapy (PT), and to hasten discharge. More recently, pericapsular infiltration using liposomal bupivacaine (LB) has been employed as an alternative analgesic approach. METHODS: This retrospective study compared outcomes for three analgesic approaches: femoral nerve catheter (FNC), adductor canal catheter (ACC), and intraoperative LB infiltration. The primary outcome was numeric rating scale (NRS) pain scores at 24 hours. Secondary outcomes included pain scores at 12, 36, and 48 hours, time-to-first opioid, cumulative opioid use, distance walked, and time-to-discharge. RESULTS: Pain scores at 24 hours were significantly lower in both the ACC and FNC cohorts when compared to the LB cohort (3.1 versus 4.6 [P = .017] and 2.4 versus 4.6 [P < .0001]). The ACC and FNC groups did not differ significantly at that timepoint (P = .27). Similar comparisons were found at 12 and 36 hours, while at 48 hours the FNC group was superior. Time to first opioid and opioid consumption favored the ACC and FNC groups. Walking distance favored the ACC group. Both the ACC and LB groups had a faster time-to-discharge than the FNC group. CONCLUSION: Both ACCs and FNCs provided superior analgesia at 24 hours compared to LB, while being equivalent to each other. Pain scores at 12 hours and 36 hours as well as opioid consumption through 48 hours mirrored this finding. Although various differences were found between groups in terms of time-to-first analgesic, walking distance and time-to-discharge, the ACC approach appeared to optimally balance analgesia, ambulation, and time-to-discharge.

A randomized comparison of loss of resistance versus loss of resistance plus electrical stimulation: effect on success of thoracic epidural placement.

BACKGROUND: Loss of resistance (LOR) for epidural catheter placement has been utilized for almost a century. LOR is a subjective endpoint associated with a high failure rate. Nerve stimulation (NS) has been described as an objective method for confirming placement of an epidural catheter. We hypothesized that the addition of NS to LOR would improve the success of epidural catheter placement. METHODS: One-hundred patients were randomized to thoracic epidural analgesia (TEA) utilizing LOR-alone or loss of resistance plus nerve stimulation (LOR + NS). The primary endpoint was rate of success, defined as loss of sensation following test dose. Secondary endpoints included performance time. An intention-to-treat analysis was planned, but a per-protocol analysis was performed to investigate the success rate when stimulation was achieved. RESULTS: In the intention-to-treat analysis there was no difference in success rates (90% vs 82% [LOR + NS vs LOR-alone]; P = 0.39). The procedural time increased in the LOR + NS group (33.9 ± 12.8 vs 24.0 ± 8.0 min; P < 0.001). The per-protocol analysis found a statistically higher success rate for the LOR + NS group compared to the LOR-alone group (98% vs. 82%; P = 0.017) when only patients in whom stimulation was achieved were included. CONCLUSIONS: Addition of NS technique did not statistically improve the success rate for epidural placement when analyzed in an intention-to-treat format and was associated with a longer procedural time. In a per-protocol analysis a statistically higher success rate for patients in whom stimulation was obtained highlights the potential benefit of adding NS to LOR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03087604 on 3/22/2017; Institutional Review Board Wake Forest School of Medicine IRB00039522, Food and Drug Administration Investigational Device Exemption: G160273.

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.

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.

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.

An Evaluation of Ultrasound-Guided Adductor Canal Blockade for Postoperative Analgesia After Medial Unicondylar Knee Arthroplasty.

BACKGROUND: Unicondylar knee arthroplasty (UKA) is a commonly performed procedure with significant expected postoperative pain. Peripheral nerve blocks are 1 analgesic option, but some approaches may decrease quadriceps motor strength and interfere with early ambulation. In this study, we compared the analgesia provided by an adductor canal block (ACB) and a psoas compartment block (PCB) after UKA. We hypothesized that the ACB would provide equivalent analgesia, defined as a difference of <2 points on the pain scale (0-10 numeric rating scale [NRS]), at rest and with movement 6 hours after block placement. METHODS: One hundred fifty patients undergoing medial UKA were randomly assigned to receive either an ACB or a PCB with 0.25% bupivacaine, 5 µg/mL epinephrine, and 1.67 µg/mL clonidine. All patients received multimodal analgesics, sham blockade at the alternate site, and a posterior capsule injection during surgery. Patients and observers were blinded to treatment groups. The primary end points were NRS pain scores with rest and movement at 6 hours. Secondary end points included quadriceps muscle strength at 6 hours (0-5 [5 being full strength]; Medical Research Council scale) as well as NRS pain scores, opioid consumption, and opioid-related side effects over 24 hours. RESULTS: One hundred forty-seven patients were analyzed. Pain scores were equivalent at 6 hours with rest (ACB 1.0 ± 2 vs PCB 1.1 ± 2.2 [mean NRS ± SD]; 95% confidence interval of mean difference, -0.8 to 0.6; P < 0.0001) and with movement (ACB 1.6 ± 2.6 vs PCB 1.5 ± 2.8; 95% confidence interval of mean difference, -0.8 to 0.9; P < 0.0001). In addition, pain scores at rest and with movement at 12, 18, and 24 hours were equivalent. Quadriceps motor strength was significantly increased in the ACB group (Medical Research Council scale score, 4.0 ± 1.1 vs 2.5 ± 1.3 [mean ± SD]; P < 0.0001). No significant differences were found between groups for time to first analgesic or for cumulative opioid consumption at 6, 12, 18, or 24 hours. Other than an increase in the incidence of pruritus in the ACB group at 6 hours, there were no differences in opioid-related side effects. CONCLUSIONS: An ACB provides equivalent analgesia after medial UKA when compared with a PCB. In addition, the ACB caused significantly less motor weakness. An ACB should be considered for postoperative analgesia after medial UKA.

Characterization of a unique aspartate-rich protein of the SET/TAF-family in the human malaria parasite, Plasmodium falciparum, which inhibits protein phosphatase 2A.

A search for physiological inhibitors of protein phosphatases led to the identification of a Plasmodium falciparum (Pf) cDNA that had the potential to code for an aspartate-rich protein and hence named ARP. The PfARP was virtually identical to its Plasmodium berghei counterpart in gene structure and protein sequence. The PfARP coding sequence contained two introns, and the predicted protein contained 269 amino acid residues. Its primary structure showed significant similarity to eukaryotic proteins of the SET and TAF-family that included two inhibitors of mammalian serine/threonine protein phosphatase 2A (PP2A), namely I1(PP2A) and I2(PP2A). Like the SET and TAF proteins, it had an extremely acidic tail. The cDNA was confirmed by recombinant expression in bacteria. Native parasitic ARP was purified and was found to be highly thermostable. PfARP specifically inhibited the parasitic PP2A at nanomolar concentrations, with no effect on PP1, PP2B, PP5, or PPJ. Expression of PfARP in HeLa cells led to elevated phosphorylation of c-Jun, and activation of transcription factors AP1 and NF-kappa B. These functional properties are also characteristic of the SET/TAF-family proteins. The ARP mRNA and protein were detectable in all the erythrocytic asexual stages of the parasite, and the protein was located mainly in the parasitic cytoplasm. Thus, PfARP is a unique cytoplasmic member of the SET/TAF-family and a candidate physiological regulator of the Plasmodium PP2A.