A Phase I Study of Autologous Dendritic Cell Vaccine Pulsed with Allogeneic Stem-like Cell Line Lysate in Patients with Newly Diagnosed or Recurrent Glioblastoma.

PURPOSE: Glioblastoma (GBM) is a heterogeneous malignancy with multiple subpopulations of cancer cells present within any tumor. We present the results of a phase I clinical trial using an autologous dendritic cell (DC) vaccine pulsed with lysate derived from a GBM stem-like cell line. PATIENTS AND METHODS: Patients with newly diagnosed and recurrent GBM were enrolled as separate cohorts. Eligibility criteria included a qualifying surgical resection or minimal tumor size, ≤ 4-mg dexamethasone daily dose, and Karnofsky score ≥70. Vaccine treatment consisted of two phases: an induction phase with vaccine given weekly for 4 weeks, and a maintenance phase with vaccines administered every 8 weeks until depletion of supply or disease progression. Patients with newly diagnosed GBM also received standard-of-care radiation and temozolomide. The primary objective for this open-label, single-institution trial was to assess the safety and tolerability of the autologous DC vaccine. RESULTS: For the 11 patients with newly diagnosed GBM, median progression-free survival (PFS) was 8.75 months, and median overall survival was 20.36 months. For the 25 patients with recurrent GBM, median PFS was 3.23 months, 6-month PFS was 24%, and median survival was 11.97 months. A subset of patients developed a cytotoxic T-cell response as determined by an IFNγ ELISpot assay. CONCLUSIONS: In this trial, treatment of newly diagnosed and recurrent GBM with autologous DC vaccine pulsed with lysate derived from an allogeneic stem-like cell line was safe and well tolerated. Clinical outcomes add to the body of evidence suggesting that immunotherapy plays a role in the treatment of GBM.

Implementation of clinical practice changes by experienced anesthesiologists after simulation-based ultrasound-guided regional anesthesia training.

BACKGROUND: Anesthesiologists who have finished formal training and want to learn ultrasound-guided regional anesthesia (UGRA) commonly attend 1 day workshops. However, it is unclear whether participation actually changes clinical practice. We assessed change implementation after completion of a 1 day simulation-based UGRA workshop. METHODS: Practicing anesthesiologists who participated in a 1 day UGRA course from January 2012 through May 2014 were surveyed. The course consisted of clinical observation of UGRA procedures, didactic lectures, ultrasound scanning, hands-on perineural catheter placement, and mannequin simulation. The primary outcome was the average number of UGRA blocks per month reported at follow-up versus baseline. Secondary outcomes included preference for ultrasound as the nerve localization technique, ratings of UGRA teaching methods, and obstacles to performing UGRA. RESULTS: Survey data from 46 course participants (60% response rate) were included for analysis. Participants were (median [10th-90th percentile]) 50 (37-63) years old, had been in practice for 17 (5-30) years, and were surveyed 27 (10-34) months after their UGRA training. Participants reported performing 24 (4-90) blocks per month at follow-up compared to 10 (2-24) blocks at baseline (P < 0.001). Compared to baseline, more participants at follow-up preferred ultrasound for nerve localization. The major obstacle to implementing UGRA in clinical practice was time pressure. CONCLUSIONS: Participation in a 1 day simulation-based UGRA course may increase UGRA procedural volume by practicing anesthesiologists.

An ultrasound-guided fascia iliaca catheter technique does not impair ambulatory ability within a clinical pathway for total hip arthroplasty.

BACKGROUND: Both neuraxial and peripheral regional analgesic techniques offer postoperative analgesia for total hip arthroplasty (THA) patients. While no single technique is preferred, quadriceps muscle weakness from peripheral nerve blocks may impede rehabilitation. We designed this study to compare postoperative ambulation outcome in THA patients who were treated with a new ultrasound-guided fascia iliaca catheter (FIC) technique or intrathecal morphine (ITM). METHODS: We reviewed the electronic health records of a sequential series of primary unilateral THA patients who were part of a standardized clinical pathway; apart from differences in regional analgesic technique, all other aspects of the pathway were the same. Our primary outcome was total ambulation distance (meters) combined for postoperative days 1 and 2. Secondary outcomes included daily opioid consumption (morphine milligram equivalents) and analgesic-related side effects. We examined the association between the primary outcome and analgesic technique by performing crude and adjusted ordinary least-squares linear regression. A P value < 0.05 was considered statistically-significant. RESULTS: The study analyzed the records of 179 patients (fascia iliaca, n = 106; intrathecal, n = 73). The primary outcome (total ambulation distance) did not differ between the groups (P = 0.08). Body mass index (BMI) was the only factor (ß = -1.7 [95% CI -0.5 to -2.9], P < 0.01) associated with ambulation distance. Opioid consumption did not differ, while increased pruritus was seen in the intrathecal group (P < 0.01). CONCLUSIONS: BMI affects postoperative ambulation outcome after hip arthroplasty, whereas the type of regional analgesic technique used does not. An ultrasound-guided FIC technique offers similar analgesia with fewer side effects when compared with ITM.

Comparative-Effectiveness of Simulation-Based Deliberate Practice Versus Self-Guided Practice on Resident Anesthesiologists' Acquisition of Ultrasound-Guided Regional Anesthesia Skills.

BACKGROUND AND OBJECTIVES: Simulation-based education strategies to teach regional anesthesia have been described, but their efficacy largely has been assumed. We designed this study to determine whether residents trained using the simulation-based strategy of deliberate practice show greater improvement of ultrasound-guided regional anesthesia (UGRA) skills than residents trained using self-guided practice in simulation. METHODS: Anesthesiology residents new to UGRA were randomized to participate in either simulation-based deliberate practice (intervention) or self-guided practice (control). Participants were recorded and assessed while performing simulated peripheral nerve blocks at baseline, immediately after the experimental condition, and 3 months after enrollment. Subject performance was scored from video by 2 blinded reviewers using a composite tool. The amount of time each participant spent in deliberate or self-guided practice was recorded. RESULTS: Twenty-eight participants completed the study. Both groups showed within-group improvement from baseline scores immediately after the curriculum and 3 months following study enrollment. There was no difference between groups in changed composite scores immediately after the curriculum (P = 0.461) and 3 months following study enrollment (P = 0.927) from baseline. The average time in minutes that subjects spent in simulation practice was 6.8 minutes for the control group compared with 48.5 minutes for the intervention group (P < 0.001). CONCLUSIONS: In this comparative effectiveness study, there was no difference in acquisition and retention of skills in UGRA for novice residents taught by either simulation-based deliberate practice or self-guided practice. Both methods increased skill from baseline; however, self-guided practice required less time and faculty resources.

Can bedside patient-reported numbness predict postoperative ambulation ability for total knee arthroplasty patients with nerve block catheters?

BACKGROUND: Adductor canal catheters offer advantages over femoral nerve catheters for knee replacement patients because they produce less quadriceps muscle weakness; however, applying adductor canal catheters in bedside clinical practice remains challenging. There is currently no patient-reported outcome that accurately predicts patients' physical function after knee replacement. The present study evaluates the validity of a relatively new patient-reported outcome, i.e., a numbness score obtained using a numeric rating scale, and assesses its predictive value on postoperative ambulation. METHODS: We conducted a retrospective cohort study pooling data from two previously-published clinical trials using identical research methodologies. Both studies recruited patients undergoing knee replacement; one studied adductor canal catheters while the other studied femoral nerve catheters. Our primary outcome was patient-reported numbness scores on postoperative day 1. We also examined postoperative day 1 ambulation distance and its association with postoperative numbness using linear regression, adjusting for age, body mass index, and physical status. RESULTS: Data from 94 subjects were included (femoral subjects, n = 46; adductor canal subjects, n = 48). Adductor canal patients reported decreased numbness (median [10(th)-90(th) percentiles]) compared to femoral patients (0 [0-5] vs. 4 [0-10], P = 0.001). Adductor canal patients also ambulated seven times further on postoperative day 1 relative to femoral patients. There was a significant association between postoperative day 1 total ambulation distance and numbness (Beta = -2.6; 95% CI: -4.5, -0.8, P = 0.01) with R(2) = 0.1. CONCLUSIONS: Adductor canal catheters facilitate improved early ambulation and produce less patient-reported numbness after knee replacement, but the correlation between these two variables is weak.

Evaluation of a Standardized Program for Training Practicing Anesthesiologists in Ultrasound-Guided Regional Anesthesia Skills.

OBJECTIVES: Practicing anesthesiologists have generally not received formal training in ultrasound-guided perineural catheter insertion. We designed this study to determine the efficacy of a standardized teaching program in this population. METHODS: Anesthesiologists in practice for 10 years or more were recruited and enrolled to participate in a 1-day program: lectures and live-model ultrasound scanning (morning) and faculty-led iterative practice and mannequin-based simulation (afternoon). Participants were assessed and recorded while performing ultrasound-guided perineural catheter insertion at baseline, at midday (interval), and after the program (final). Videos were scored by 2 blinded reviewers using a composite tool and global rating scale. Participants were surveyed every 3 months for 1 year to report the number of procedures, efficacy of teaching methods, and implementation obstacles. RESULTS: Thirty-two participants were enrolled and completed the program; 31 of 32 (97%) completed the 1-year follow-up. Final scores [median (10th-90th percentiles)] were 21.5 (14.5-28.0) of 30 points compared to 14.0 (9.0-20.0) at interval (P < .001 versus final) and 12.0 (8.5-17.5) at baseline (P < .001 versus final), with no difference between interval and baseline. The global rating scale showed an identical pattern. Twelve of 26 participants without previous experience performed at least 1 perineural catheter insertion after training (P < .001). However, there were no differences in the monthly average number of procedures or complications after the course when compared to baseline. CONCLUSIONS: Practicing anesthesiologists without previous training in ultrasound-guided regional anesthesia can acquire perineural catheter insertion skills after a 1-day standardized course, but changing clinical practice remains a challenge.

Comparative effectiveness of infraclavicular and supraclavicular perineural catheters for ultrasound-guided through-the-catheter bolus anesthesia.

OBJECTIVES: Using a through-the-needle local anesthetic bolus technique, ultrasound-guided infraclavicular perineural catheters have been shown to provide greater analgesia compared to supraclavicular catheters. A through-the-catheter bolus technique, which arguably "tests" the anesthetic efficacy of the catheter before initiating an infusion, has been validated for infraclavicular catheters but not supraclavicular catheters. This study investigated the through-the-catheter bolus technique for supraclavicular catheters and tested the hypothesis that infraclavicular catheters provide faster onset of brachial plexus anesthesia. METHODS: Preoperatively, patients were randomly assigned to receive either a supraclavicular or an infraclavicular catheter using an ultrasound-guided nonstimulating catheter insertion technique with a mepivacaine bolus via the catheter and ropivacaine perineural infusion initiated postoperatively. The primary outcome was time to achieve complete sensory anesthesia in the ulnar and median nerve distributions. Secondary outcomes included procedural time, procedure-related pain and complications, and postoperative pain, opioid consumption, sleep disturbances, and motor weakness. RESULTS: Fifty patients were enrolled in the study; all but 2 perineural catheters were successfully placed per protocol. Twenty-one of 24 (88%) and 24 of 24 (100%) patients in the supraclavicular and infraclavicular groups, respectively, achieved complete sensory anesthesia by 30 minutes (P= .088). There was no difference in the time to achieve complete sensory anesthesia. Supraclavicular patients reported more sleep disturbances postoperatively, but there were no statistically significant differences in other outcomes. CONCLUSIONS: Both supraclavicular and infraclavicular perineural catheters using a through-the-catheter bolus technique provide effective brachial plexus anesthesia.

A retrospective comparative provider workload analysis for femoral nerve and adductor canal catheters following knee arthroplasty.

Adductor canal catheters preserve quadriceps strength better than femoral nerve catheters and may facilitate postoperative ambulation following total knee arthroplasty. However, the effect of this newer technique on provider workload, if any, is unknown. We conducted a retrospective provider workload analysis comparing these two catheter techniques; all other aspects of the clinical pathway remained the same. The primary outcome was number of interventions recorded per patient postoperatively. Secondary outcomes included infusion duration, ambulation distance, opioid consumption, and hospital length of stay. Adductor canal patients required a median (10-90th percentiles) of 0.0 (0.0-2.6) interventions compared to 1.0 (0.3-3.0) interventions for femoral patients (p < 0.001); 18/23 adductor canal patients (78 %) compared to 2/22 femoral patients (9 %) required no interventions (p < 0.001). Adductor canal catheter infusions lasted 2.0 (1.4-2.0) days compared to 1.5 (1.0-2.7) days in the femoral group (p = 0.016). Adductor canal patients ambulated further [mean (SD)] than femoral patients on postoperative day 1 [24.5 (21.7) vs. 11.9 (14.6) meters, respectively; p = 0.030] and day 2 [44.9 (26.3) vs. 22.0 (22.2) meters, respectively; p = 0.003]. Postoperative opioid consumption and length of stay were similar between groups. We conclude that adductor canal catheters offer both patient and provider benefits when compared to femoral nerve catheters.

Comparison of catheter tip migration using flexible and stimulating catheters inserted into the adductor canal in a cadaver model.

Use of adductor canal blocks and catheters for perioperative pain management following total knee arthroplasty is becoming increasingly common. However, the optimal equipment, timing of catheter insertion, and catheter dislodgement rate remain unknown. A previous study has suggested, but not proven, that non-tunneled stimulating catheters may be at increased risk for catheter migration and dislodgement after knee manipulation. We designed this follow-up study to directly compare tip migration of two catheter types after knee range of motion exercises. In a male unembalmed human cadaver, 30 catheter insertion trials were randomly assigned to one of two catheter types: flexible or stimulating. All catheters were inserted using an ultrasound-guided short-axis in-plane technique. Intraoperative knee manipulation similar to that performed during surgery was simulated by five sequential range of motion exercises. A blinded regional anesthesiologist performed caliper measurements on the ultrasound images before and after exercise. Changes in catheter tip to nerve distance (p = 0.547) and catheter length within the adductor canal (p = 0.498) were not different between groups. Therefore, catheter type may not affect the risk of catheter tip migration when placed prior to knee arthroplasty.

A randomized comparison of proximal and distal ultrasound-guided adductor canal catheter insertion sites for knee arthroplasty.

OBJECTIVES: Proximal and distal (mid-thigh) ultrasound-guided continuous adductor canal block techniques have been described but not yet compared, and infusion benefits or side effects may be determined by catheter location. We hypothesized that proximal placement will result in faster onset of saphenous nerve anesthesia, without additional motor block, compared to a distal technique. METHODS: Preoperatively, patients receiving an ultrasound-guided nonstimulating adductor canal catheter for knee arthroplasty were randomly assigned to either proximal or distal insertion. A local anesthetic bolus was administered via the catheter after successful placement. The primary outcome was the time to achieve complete sensory anesthesia in the saphenous nerve distribution. Secondary outcomes included procedural time, procedure-related pain and complications, postoperative pain, opioid consumption, and motor weakness. RESULTS: Proximal insertion (n = 23) took a median (10th-90th percentiles) of 12.0 (3.0-21.0) minutes versus 6.0 (3.0-21.0) minutes for distal insertion (n = 21; P= .106) to anesthetize the medial calf. Only 10 of 25 (40%) and 10 of 24 (42%) patients in the proximal and distal groups, respectively, developed anesthesia at both the medial calf and top of the patella (P= .978). Bolus-induced motor weakness occurred in 19 of 25 (76%) and 16 of 24 (67%) patients in the proximal and distal groups (P = .529). Ten of 24 patients (42%) in the distal group required intravenous morphine postoperatively, compared to 2 of 24 (8%) in the proximal group (P = .008), but there were no differences in other secondary outcomes. CONCLUSIONS: Continuous adductor canal blocks can be performed reliably at both proximal and distal locations. The proximal approach may offer minor analgesic and logistic advantages without an increase in motor block.

A randomized comparison of long-axis and short-axis imaging for in-plane ultrasound-guided popliteal-sciatic perineural catheter insertion.

PURPOSE: Ultrasound-guided long-axis in-plane sciatic perineural catheter insertion has been described but not validated. For the popliteal-sciatic nerve, we hypothesized that a long-axis in-plane technique, placing the catheter parallel and posterior to the nerve, results in faster onset of sensory anesthesia compared to a short-axis in-plane technique. METHODS: Preoperatively, patients receiving a popliteal-sciatic perineural catheter were randomly assigned to either the long-axis or short-axis technique. Mepivacaine 2% was administered via the catheter following insertion. The primary outcome was time to achieve complete sensory anesthesia. Secondary outcomes included procedural time, onset time of motor block, and pain on postoperative day 1. RESULTS: Fifty patients were enrolled. In the long-axis group (n = 25), all patients except 1 (4%) had successful catheter placement per protocol. Two patients (8%) in the long-axis group and 1 patient (4%) in the short-axis group (n = 25) did not achieve sensory anesthesia by 30 min and were withdrawn. Seventeen of 24 (71%) and 17 of 22 (77%) patients in the short-axis and long-axis groups, respectively, achieved the primary outcome of complete sensory anesthesia (p = 0.589). The short-axis group (n = 17) required a median (10th-90th ‰) of 18.0 (8.4-30.0) min compared to 18.0 (11.4-27.6) min for the long-axis group (n = 17, p = 0.208) to achieve complete sensory anesthesia. Procedural time was 6.5 (4.0-12.0) min for the short-axis and 9.5 (7.0-12.7) min for the long-axis (p < 0.001) group. There were no statistically significant differences in other secondary outcomes. CONCLUSION: Long-axis in-plane popliteal-sciatic perineural catheter insertion requires more time to perform compared to a short-axis in-plane technique without demonstrating any advantages.

Percutaneous tracheostomy at the bedside: 13 tips for improving safety and success.

We have developed a set of routines and practices in the course of performing a large series (n = 70) of percutaneous dilational tracheostomy (PDT). The 13 tips discussed in this review fall into 4 categories. System factors that facilitate training, patient safety, and avoidance of crises including the use of appropriate personnel, importance of timing, use of premedication, and the utility and content of a preprocedure briefing. Suggestions to prevent loss of the airway include tips on airway assessment, preparation of airway equipment, and use of exchange catheter techniques. Strategies to avoid and manage both microvascular and large-vessel bleeding are discussed. We also discuss the management of common postprocedure problems including tracheostomy tube obstruction, malposition requiring tube exchange or replacement, and air leak. The practical considerations for successful execution of PDT involve common sense, thorough planning, and structured approaches to prevent adverse effects if the procedure does not go as smoothly as expected. These strategies will aid anesthesiologists and intensivists in improving their comfort level, safety, and competence in performing this beside procedure.

Continuous adductor canal blocks are superior to continuous femoral nerve blocks in promoting early ambulation after TKA.

BACKGROUND: Femoral continuous peripheral nerve blocks (CPNBs) provide effective analgesia after TKA but have been associated with quadriceps weakness and delayed ambulation. A promising alternative is adductor canal CPNB that delivers a primarily sensory blockade; however, the differential effects of these two techniques on functional outcomes after TKA are not well established. QUESTIONS/PURPOSES: We determined whether, after TKA, patients with adductor canal CPNB versus patients with femoral CPNB demonstrated (1) greater total ambulation distance on Postoperative Day (POD) 1 and 2 and (2) decreased daily opioid consumption, pain scores, and hospital length of stay. METHODS: Between October 2011 and October 2012, 180 patients underwent primary TKA at our practice site, of whom 93% (n = 168) had CPNBs. In this sequential series, the first 102 patients had femoral CPNBs, and the next 66 had adductor canal CPNBs. The change resulted from a modification to our clinical pathway, which involved only a change to the block. An evaluator not involved in the patients' care reviewed their medical records to record the parameters noted above. RESULTS: Ambulation distances were higher in the adductor canal group than in the femoral group on POD 1 (median [10(th)-90(th) percentiles]: 37 m [0-90 m] versus 6 m [0-51 m]; p < 0.001) and POD 2 (60 m [0-120 m] versus 21 m [0-78 m]; p = 0.003). Adjusted linear regression confirmed the association between adductor canal catheter use and ambulation distance on POD 1 (B = 23; 95% CI = 14-33; p < 0.001) and POD 2 (B = 19; 95% CI = 5-33; p = 0.008). Pain scores, daily opioid consumption, and hospital length of stay were similar between groups. CONCLUSIONS: Adductor canal CPNB may promote greater early postoperative ambulation compared to femoral CPNB after TKA without a reduction in analgesia. Future randomized studies are needed to validate our major findings. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

A randomized comparison of long-and short-axis imaging for in-plane ultrasound-guided femoral perineural catheter insertion.

OBJECTIVES: Continuous femoral nerve blocks provide effective analgesia after knee arthroplasty, and infusion effects depend on reliable catheter location. Ultrasound-guided perineural catheter insertion using a short-axis in-plane technique has been validated, but the optimal catheter location relative to target nerve and placement orientation remain unknown. We hypothesized that a long-axis in-plane technique for femoral perineural catheter insertion results in faster onset of sensory anesthesia compared to a short-axis in-plane technique. METHODS: Preoperatively, patients receiving an ultrasound-guided nonstimulating femoral perineural catheter for knee surgery were randomly assigned to either the long-axis in-plane or short-axis in-plane technique. A local anesthetic was administered via the catheter after successful insertion. The primary outcome was the time to achieve complete sensory anesthesia. Secondary outcomes included the procedural time, the onset time of the motor block, pain and muscle weakness reported on postoperative day 1, and procedure-related complications. RESULTS: The short-axis group (n = 23) took a median (10th-90th percentiles) of 9.0 (6.0-20.4) minutes compared to 6.0 (3.0-14.4) minutes for the long-axis group (n = 23; P = .044) to achieve complete sensory anesthesia. Short-axis procedures took 5.0 (4.0-7.8) minutes to perform compared to 9.0 (7.0-14.8) minutes for long-axis procedures (P < .001). In the short-axis group, 19 of 23 (83%) achieved a complete motor block within the testing period compared to 18 of 23 (78%) in the long-axis group (P = .813); short-axis procedures took 12.0 (6.0-15.0) minutes versus 15.0 (5.1-27.9) minutes for long-axis procedures (P = .048). There were no statistically significant differences in other secondary outcomes. CONCLUSIONS: Long-axis in-plane femoral perineural catheters result in a slightly faster onset of sensory anesthesia, but placement takes longer to perform without other clinical advantages.