Accuracy of injection pressure measurement at peripheral nerves using high-resolution 40 MHz ultrasound in an anesthetized porcine model.

BACKGROUND: Fluid injection pressure measurement is promoted as a marker of needle tip position that discriminates between tissue layers. However, clinical ultrasound has insufficient resolution to identify the exact position of the needle tip. Our primary objective was to use 40 MHz ultrasound in anesthetized pigs in order to precisely locate the tip of the needle and measure opening injection pressure in muscle, at epineurium and in subepineurium. METHODS: We surgically exposed the axillae of four anesthetized pigs. Two operators placed a 40 MHz ultrasound transducer over the pectoral muscle and imaged axillary, median and radial nerves. Injections (0.5 mL) were randomized to in-plane and out-of-plane needle trajectories and flow rates of 1, 6 and 12 mL/min. RESULTS: We identified 541 fascicles in 23 nerves. The ratio of fascicle area to nerve area remained constant at ~0.30 for all nerves. Axillary nerves were smaller than median and radial nerves, difference in diameter (95% CI) 1.61 (0.87 to 2.36) mm, p<0.001 and 1.59 (0.82 to 2.36) mm, p=0.001, respectively. Axillary nerves had less fascicles per nerve than median nerves, difference 7.63 (2.43 to 12.83) and radial nerves, difference 9.02 (3.64 to 14.40). We visualized the circumneurium and injection within the subcircumneural compartment. Intraneural injection increased nerve area (SD) from 5.7 (2.2) mm2 to 13.7 (5.5) mm2, difference 8.0 (5.4-10.6) mm2, p<0.001. Mean injection pressure was greater in subepineurium compared with muscle, geometric ratio 2.29 (1.30 to 4.10), p<0.001; and greater on epineurium compared with muscle, geometric ratio 1.73 (1.03 to 3.00), p=0.01. Twenty-two out of 23 injections in muscle, 14 out of 23 injections at epineurium and 11 out of 22 injections in subepineurium were <138 kPa (20 psi). CONCLUSION: Needle tip position was not discernible using pressure monitoring. The circumneurium and subcircumneural injection compartment were observed but not intrafascicular injection.

Recommendations for anatomical structures to identify on ultrasound for the performance of intermediate and advanced blocks in ultrasound-guided regional anesthesia.

Recent recommendations describe a set of core anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia (UGRA). This project aimed to generate consensus recommendations for core structures to identify during the performance of intermediate and advanced blocks. An initial longlist of structures was refined by an international panel of key opinion leaders in UGRA over a three-round Delphi process. All rounds were conducted virtually and anonymously. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for "block view" (which visualizes the block site and is maintained for needle insertion/injection). A "strong recommendation" was made if ≥75% of participants rated any structure as "definitely include" in any round. A "weak recommendation" was made if >50% of participants rated it as "definitely include" or "probably include" for all rounds, but the criterion for strong recommendation was never met. Structures which did not meet either criterion were excluded. Forty-one participants were invited and 40 accepted; 38 completed all three rounds. Participants considered the ultrasound scanning for 19 peripheral nerve blocks across all three rounds. Two hundred and seventy-four structures were reviewed for both orientation scanning and block view; a "strong recommendation" was made for 60 structures on orientation scanning and 44 on the block view. A "weak recommendation" was made for 107 and 62 structures, respectively. These recommendations are intended to help standardize teaching and research in UGRA and support widespread and consistent practice.

Traumatic needle damage to nerves during regional anesthesia: presentation of a novel mechanotransduction hypothesis.

Despite advances in needle positioning techniques, nerve damage still occurs after regional anesthesia. Recognized causes include local anesthetic toxicity, subperineural injection, high subepineural fluid injection pressures and subepineural hematoma after forceful needle--nerve contact.We hypothesize that subperineural injection is still possible, but less likely to be the cause of nerve damage because needle penetration of fascicles and mechanical damage is difficult to achieve. High-resolution (75 µm) 40 MHz micro-ultrasound images of pig axillae show short-bevelled 22 g, 0.7 mm wide block needles that are three times larger than the average fascicle. Fascicular bundles are extremely difficult to puncture because they spin away on needle contact. Histology from fresh cadavers after supposed intrafascicular injection shows fluid spread within perineurium and intrafascicular perineural septae, but no breach of endoneurium or axons.We propose that mechanotransduction, the cellular changes that occur in response to force, contributes to nerve damage. Piezo ion channel proteins transduce force into electrical activity by rapid entry of cations into cells. Excessive Ca2+ influx into cells has the potential to inhibit nerve regeneration. Cellular changes include regulation of gene expression. The forces associated with purposeful needle insertion are generally unknown. Our experiments in the soft embalmed Thiel cadaver showed a lognormal range of forces between 0.6 N and 16.8 N on epineural penetration.We hypothesize that forceful needle injury may cause nerve damage by activation of Piezo receptors and release of intracellular Ca2.

Needle insertion forces and fluid injection pressures during targeting of nerves in a soft embalmed cadaver model.

PURPOSE: Forceful needle-nerve contact and high subepineural pressures and are recognised causes of nerve damage. Pressure and force measurements are necessary to inform the mechanisms of nerve injury, build virtual simulator environments and provide operator feedback during simulation training. However, the range of pressures and forces encountered at tissue layers during targeted needle insertion and fluid injection are not known. METHODS: We built a needle that recorded in-line pressure during fluid injection and continuously measured force at the needle tip. Two anaesthetists were randomised to insert a 21 g block needle at 48 nerve sites on both sides of 3 soft embalmed Thiel cadavers. Our objective was to measure pressure and force during the course of targeted nerve injection at epimysium, in perineural tissue, on epineurium and during subepineural injection. At each interface, we infused a 0.5 ml bolus of embalming solution at a rate of 12 ml min-1 and recorded the pressure response. Force was measured continuously in the background throughout the procedure. RESULTS: Pressure was greater at epineurium and within subepineurium than perineural tissue, geometric ratio (95% CI) 4.7 (3.0-7.3) kPa and 3.8 (2.5-5.7) kPa, respectively, both P < 0.0001. Force on nerve contact and on nerve penetration was greater than force in perineural tissue, geometric ratios (95% CI) 3.0 (1.9-4.7) N and 3.6 (2.2-7.5) N, respectively, both P < 0.0001. On nerve contact, 1 in 6 insertions were ≥ 5 N CONCLUSIONS: Despite valid infusion pressures, anaesthetists exerted excessive force on nerves.

International consensus on anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia.

There is no universally agreed set of anatomical structures that must be identified on ultrasound for the performance of ultrasound-guided regional anesthesia (UGRA) techniques. This study aimed to produce standardized recommendations for core (minimum) structures to identify during seven basic blocks. An international consensus was sought through a modified Delphi process. A long-list of anatomical structures was refined through serial review by key opinion leaders in UGRA. All rounds were conducted remotely and anonymously to facilitate equal contribution of each participant. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for the "block view" (which visualizes the block site and is maintained for needle insertion/injection). Strong recommendations for inclusion were made if ≥75% of participants rated a structure as "definitely include" in any round. Weak recommendations were made if >50% of participants rated a structure as "definitely include" or "probably include" for all rounds (but the criterion for "strong recommendation" was never met). Thirty-six participants (94.7%) completed all rounds. 128 structures were reviewed; a "strong recommendation" is made for 35 structures on orientation scanning and 28 for the block view. A "weak recommendation" is made for 36 and 20 structures, respectively. This study provides recommendations on the core (minimum) set of anatomical structures to identify during ultrasound scanning for seven basic blocks in UGRA. They are intended to support consistent practice, empower non-experts using basic UGRA techniques, and standardize teaching and research.

Validation of the soft-embalmed Thiel cadaver as a high-fidelity simulator of pressure during targeted nerve injection.

INTRODUCTION: Although administration of regional anesthesia nerve blocks has increased during the COVID-19 pandemic, training opportunities in regional anesthesia have reduced. Simulation training may enhance skills, but simulators must be accurate enough for trainees to engage in a realistic way-for example, detection of excessive injection pressure. The soft-embalmed Thiel cadaver is a life-like, durable simulator that is used for dedicated practice and mastery learning training in regional anesthesia. We hypothesized that injection opening pressure in perineural tissue, at epineurium and in subepineurium were similar to opening pressures measured in experimental animals, fresh frozen cadavers, glycol soft-fix cadavers and patients. METHODS: We systematically reviewed historical data, then conducted three validation studies delivering a 0.5 mL hydrolocation bolus of embalming fluid and recording injection pressure. First, we delivered the bolus at 12 mL/min at epimysium, perineural tissue, epineurium and in subepineurium at 48 peripheral nerve sites on three cadavers. Second, we delivered the bolus at using three infusion rates: 1 mL/min, 6 mL/min and 12 mL/min on epineurium at 70 peripheral nerve sites on five cadavers. Third, we repeated three injections (12 mL/min) at 24 epineural sites over the median and sciatic nerves of three cadavers. RESULTS: Mean (95%) injection pressure was greater at epineurium compared with subepineurium (geometric ratio 1.2 (95% CI: 0.9 to 1.6)), p=0.04, and perineural tissue (geometric ratio 5.1 (95% CI: 3.7 to 7.0)), p<0.0001. Mean (95%) injection pressure was greater at 12 mL/min compared with 1 mL/min (geometric ratio 1.6 (95% CI: 1.2 to 2.1), p=0.005). Pressure measurements were similar in study 3 (p>0.05 for all comparisons). DISCUSSION: We conclude that the soft-embalmed Thiel cadaver is a realistic simulator of injection opening pressure.

Polybrominated Diphenyl Ethers in Human Follicular Fluid Dysregulate Mural and Cumulus Granulosa Cell Gene Expression.

Polybrominated diphenyl ethers (PBDEs), a major class of flame retardants incorporated into numerous consumer products, leach out into dust resulting in widespread exposure. There is evidence from in vitro and in vivo animal studies that PBDEs affect ovarian granulosa cell function and follicular development, yet human studies of their association with female infertility are inconclusive. Here, we tested the hypothesis that exposure to the PBDEs in follicular fluid is associated with dysregulation of gene expression in the mural and cumulus granulosa cells collected from women undergoing in vitro fertilization by intracytoplasmic sperm injection. The median concentration of the ∑ 10PBDEs detected in the follicular fluid samples (n = 37) was 15.04 pg/g wet weight. RNA microarray analyses revealed that many genes were differentially expressed in mural and cumulus granulosa cells. Highest vs lowest quartile exposure to the Σ 10PBDEs or to 2 predominant PBDE congeners, BDE-47 or BDE-153, was associated with significant effects on gene expression in both cell types. Mural granulosa cells were generally more sensitive to PBDE exposure compared to cumulus cells. Overall, gene expression changes associated with BDE-47 exposure were similar to those for ∑ 10PBDEs but distinct from those associated with BDE-153 exposure. Interestingly, exposure to BDE-47 and ∑ 10PBDEs activated the expression of genes in pathways that are important in innate immunity and inflammation. To the best of our knowledge, this is the first demonstration that exposure to these environmental chemicals is associated with the dysregulation of pathways that play an essential role in ovulation.

Ultrasound detection of iatrogenic injury during peribulbar eye block: a cadaveric study.

BACKGROUND: Ophthalmic eye blocks, such as retrobulbar, peribulbar and sub-Tenon's, are traditionally conducted "blind". Complications are rare but potentially devastating. Life-threatening complications include brain stem anesthesia and local anesthetic toxicity, whereas sight-threatening complications include globe perforation, optic nerve damage and ocular muscle damage. Ultrasound permits a view of orbital structures and can be used to guide needle placement. The ultrasound appearances of unintended local anesthetic injection into vital orbital structures have not been documented. This study aimed to record the ultrasound appearances of unintended injection locations. METHODS: The spherical shape of the eyeballs of three soft-fix Thiel embalmed human cadavers were restored using glycerol. Iatrogenic injury in peribulbar block was then simulated through injection of printers' ink mixed with Thiel embalming fluid. Ultrasound was used to guide the needles and the tips were redirected to lie within the globe, lateral rectus and optic nerve. Ultrasound images were recorded during injection. The orbital cavities were then dissected via a superior approach to record the location and extent of injectate spread. RESULTS: Real-time globe rupture, ocular muscle injection and optic nerve injection were visible using ultrasound. Characteristic appearances were identified in each case. Dissection confirmed needle and injection placement. CONCLUSIONS: The ultrasound appearance of block complications is important to document and should be an integral part of regional anesthesia training. This study is the first to provide such images for ophthalmic nerve blocks. It offers ophthalmic anesthetists and ophthalmologists the potential to diagnose severe complications rapidly and accurately with a potential impact on patient safety.

Validity and reliability of metrics for translation of regional anaesthesia performance from cadavers to patients.

BACKGROUND: Our goal is to develop metrics that quantify the translation of performance from cadavers to patients. Our primary objective was to develop steps and error checklists from a Delphi questionnaire. Our second objective was to show that our test scores were valid and reliable. METHODS: Sixteen UK experts identified 15 steps conducive to good performance and 15 errors to be avoided during interscalene block on the soft-embalmed cadaver and patients. Thereafter, six experts and six novices were trained, and then tested. Training consisted of psychometric assessment, an anatomy tutorial, volunteer scanning, and ultrasound-guided needle insertion on a pork phantom and on a soft-embalmed cadaver. For testing, participants conducted a single interscalene block on a dedicated soft-embalmed cadaver whilst wearing eye tracking glasses. RESULTS: We developed a 15-step checklist and a 15-error checklist. The internal consistency of our steps measures were 0.83 (95% confidence interval [CI]: 0.78-0.89) and 0.90 (95% CI: 0.87-0.93) for our error measures. The experts completed more steps (mean difference: 3.2 [95% CI: 1.5-4.8]; P<0.001), had less errors (mean difference: 4.9 [95% CI: 3.5-6.3]; P<0.001), had better global rating scores (mean difference: 6.8 [95% CI: 3.6-10.0]; P<0.001), and more eye-gaze fixations (median of differences: 128 [95% CI: 0-288]; P=0.048). Fixation count correlated negatively with steps (r=-0.60; P=0.04) and with errors (r=0.64; P=0.03). CONCLUSIONS: Our tests to quantify ultrasound-guided interscalene nerve block training and performance were valid and reliable.

Dioxins/furans and PCBs in Canadian human milk: 2008-2011.

Human milk was collected between 2008 and 2011 as part of the Maternal - Infant Research on Environmental Chemicals (MIREC) study that was initiated to establish Canadian national estimates of maternal and infant exposure to a broad suite of environmental contaminants (e.g., persistent organic pollutants [POPs], trace elements, phthalates, etc.). Among the 1017 human milk samples collected, 298 were analysed for polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and polychlorinated biphenyls (PCBs). World Health Organization (WHO) toxic equivalency concentrations (WHO TEQ2005) for PCDD/F+dioxin-like (DL) PCB ranged from 2.2pg TEQ2005 g-1 lipid to 27pg TEQ2005 g-1 lipid. The relative contribution of PCDDs to the overall WHO TEQ2005 (PCDD/F+DL PCB) has decreased from earlier investigations into POP levels in Canadian human milk. Significantly higher PCB concentrations were observed in milk from women born in Europe relative to those born in Canada (p<0.001), in contrast to results for the PCDD/Fs (p=0.496). Age was found to significantly impact milk ∑PCB concentrations (p=0.018), with elevated concentrations observed in milk from women >30years relative to those <30years of age. While this trend was also observed for the PCDD/Fs, this relationship was impacted by parity. WHO TEQ2005 concentrations were significantly higher in milk from primiparous women (p=0.019) and those >30years relative to those <30years of age (p<0.001). No significant differences were associated with education level or pre-pregnancy body mass index. PCB and PCDD/F concentrations have continued to decline in Canadian human milk since the last sampling of human milk was performed.

Hair as a biomarker of systemic exposure to polybrominated diphenyl ethers.

The efficacy of using hair as a biomarker for exposure to polybrominated diphenyl ether (PBDE) flame retardants was assessed in humans and an animal model. Paired human hair and serum samples were obtained from adult men and women (n = 50). In parallel, hair, serum, liver, and fat were collected from adult male Sprague-Dawley rats exposed to increasing doses of the PBDE mixture found in house dust for 70 days via the diet. All samples were analyzed by GC-MS for eight common PBDEs: BDE-28, -47, -99, -100, -153, -154, -183, and -209. Paired human hair and serum samples had five congeners (BDE-28, -47, -99, -100, and -154) with significant individual correlations (0.345-0.566). In rat samples, BDE-28 and BDE-183 were frequently below the level of detection. Significant correlations were observed for BDE-47, -99, -100, -153, -154, and -209 in rat hair, serum, liver, and fat across doses, with r values ranging from 0.803 to 0.988; weaker correlations were observed between hair and other tissues when data from the lowest dose group or for BDE-209 were analyzed. Thus, human and rat hair PBDE measurements correlate strongly with those in alternative matrices, validating the use of hair as a noninvasive biomarker of long-term PBDE exposure.

Brominated flame retardant concentrations in sera from the Canadian Health Measures Survey (CHMS) from 2007 to 2009.

Pooling of surplus serum from individual samples, collected between 2007 and 2009 during Cycle 1 of the Canadian Health Measures Survey (CHMS), was performed to develop a national baseline estimate of brominated flame retardants in Canadians. Serum samples were categorized by sex and distributed by five age groups ranging from 6 to 79years. Nearly 5000 (4583) serum samples were used to form 59 composite pools. Serum pools were created to ensure a high detection frequency of these analytes in serum because low volume samples had previously resulted in non-detectable concentrations. The analytes of interest in these serum pools included 23 polybrominated diphenyl ethers (PBDEs) and three hexabromocyclododecane (HBCD) isomers (α-, ß- and γ-HBCD). PBDEs were observed in all samples tested and total PBDE concentrations ranged from 27ngg(-1) lipid to 130ngg(-1) lipid (geometric mean [GM] 46ngg(-1) lipid). ∑PBDE concentrations were significantly elevated in samples representing the 6-11year old age group (GM 65ngg(-1) lipid) relative to ages above 40years, although no difference in concentration was observed between the sexes. PBDE concentrations in Canadian sera from the general population were higher than reported in Europe and Asia, but a little lower than observed in the US. PBDE 47 was the greatest contributor to ∑PBDE concentrations and the GM concentration for this congener was 22ngg(-1) lipid. The other dominant contributors to ∑PBDE concentrations were in descending order: 153 [GM 9.4ngg(-1) lipid]>99 [GM 4.6ngg(-1) lipid]≅100 [GM 4.1ngg(-1) lipid]>209 [GM 1.1ngg(-1) lipid] and 183 [GM 0.42ngg(-1) lipid]. ∑HBCD was detected in all samples analysed, although most samples were observed at concentrations <1ngg(-1) lipid, similar to global concentrations. α-HBCD was the dominant contributor to ∑HBCD concentrations in Canadians although ß- and γ-HBCD were detected in 23% and 35% of the samples, respectively. No differences in ∑HBCD concentration were associated with age or sex. This dataset represents the first national data describing HBCD isomers and some PBDEs (e.g., 183, 209) in Canadians.

Acute and chronic neuropathic pain in the hospital setting: use of screening tools.

OBJECTIVES: Chronic neuropathic pain (NP) is a well-known phenomenon, whereas acute neuropathic pain is increasingly recognized. Both are potentially difficult for a nonspecialist to diagnose. The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and DN4 scales are screening tools developed to identify chronic NP. We aimed to evaluate and compare their performance in 2 different populations: outpatients with chronic pain, and inpatients with acute postoperative pain. METHODS: Consecutive outpatients attending the Lothian Chronic Pain Service completed the LANSS and DN4. Experienced clinicians independently classified each patient's pain as NP, mixed, or non-NP. In the acute setting, patients undergoing elective general or orthopedic surgery were assessed postoperatively using the LANSS and DN4. RESULTS: Of 67 patients with chronic pain, consultants identified 17 (25.4%) patients with NP, 17 (25.4%) with mixed pain, and 33 (49%) with non-NP. The LANSS performed better than the DN4 in identification (positive predictive value 0.87 compared with 0.57). In the acute setting, the LANSS identified 5 of 165 patients (3%) as experiencing NP and the DN4 identified 7 of 165 (4.2%). DISCUSSION: Although the LANSS performed better than the DN4 in the chronic population, both tools performed less well than published literature, demonstrating the importance of evaluating screening tools in the proposed patient population. There may be potential for using these questionnaires to identify acute NP.

The impact of production type and region on polychlorinated biphenyl (PCB), polychlorinated dibenzo-p-dioxin and dibenzofuran (PCDD/F) concentrations in Canadian chicken egg yolks.

Chicken eggs from five different production types (conventional, omega-3 enriched, free range, organic and free run) were collected, when available, from three regions (west, central and east) of Canada to determine persistent organic pollutant (POP) concentrations. Total polychlorinated biphenyl (PCB) concentrations (∑37 congeners) in yolks from the eggs ranged from 0.162 ng g(-1) lipid to 24.8 ng g(-1) lipid (median 1.25 ng g(-1) lipid) while the concentration of the sum of the 6 indicator PCBs ranged from 0.100 ng g(-1) lipid to 9.33 ng g(-1) lipid (median 0.495 ng g(-1) lipid). Total polychlorinated dibenzo-p-dioxin/dibenzofuran (PCDD/F) concentrations ranged from 2.37 pg g(-1) lipid to 382 pg g(-1) lipid (median 9.53 pg g(-1) lipid). The 2005 WHO toxic equivalency (TEQ) ranged from 0.089 pg TEQ(PCDD/F+dioxin-like[DL]-PCB) g(-1) lipid to 12.8 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid (median 0.342 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid). PCB and PCDD/F concentrations were significantly different (p<0.001) in egg yolks from different regions of collection. In contrast to observations in Europe, PCB and PCDD/F concentrations in Canadian egg yolks were not impacted solely by the production type (e.g., conventional, free range, organic, etc.) used to maintain the laying chickens. Additionally, only one Canadian free range yolk from western Canada (12.8 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid) exceeded the European toxic equivalent concentration limits for eggs (5 pg TEQ(PCDD/F+DL-PCB) g(-1) lipid). This differs from observations in Europe where free range/home produced eggs frequently have higher POP concentrations than eggs from other production types. Median PCB dietary intake estimates based on consumption of eggs were less than 10 ng d(-1) while median PCDD/F intakes were less than 45 pg d(-1).

PCDD/F and PCB concentrations in sera from the Canadian Health Measures Survey (CHMS) from 2007 to 2009.

In order to establish a national baseline estimate of the concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and polychlorinated biphenyls (PCBs) in Canadians, pooling of individual human sera was performed to ensure that a high frequency of detectable concentrations of analytes would be achieved. Nearly 5000 (4583) sera samples from Cycle 1 of the Canadian Health Measures Survey (CHMS) collected between 2007 and 2009 were used to form 59 composite pools of approximately 25 mL each. Pools were categorized by sex and age with participants ranging from 6 to 79 years. The pooled samples were analysed for 17 PCDD/Fs and 36 PCB congeners, and from these data, total toxic equivalent concentrations (TEQ(2005 PCDD/F+Dioxin-like [DL]-PCB)) were estimated. The average 2,3,7,8 tetrachlorodibenzodioxin (TCDD) concentration was <1 pg g⁻¹ on a lipid extractable basis. The average total TEQ(2005 PCDD/F+DL-PCB) was 11 pg TEQ g⁻¹ lipid and average ΣPCB concentrations were about 100 ng g⁻¹ lipid. Sex did not affect the concentrations, while PCB and PCDD/F concentrations were positively correlated with age (p<0.001). It appeared in some cases that the age group 6-11 years had higher concentrations of these persistent organic pollutants (POPs) than the concentrations observed in 12-19 year olds, however, the results were not statistically significant based on pair-wise comparisons. Concentration levels and patterns observed in this study of Canadians were similar to those reported in the US and European populations.