Intraneural injection of a test dose of local anesthetic in peripheral nerves - does it induce histological changes in nerve tissue?

BACKGROUND & OBJECTIVES: Most anesthesiologists use the injection of a test dose of local anesthetic in order to evaluate the final needle tip position. Thus, the intraneural injection of a full dose can be avoided. The aim of this study was to analyze whether an intraneural injection of a test dose of bupivacaine could trigger histological changes. METHODS: Intraneural injections under direct vision were performed in 40 brachial plexus nerves in seven anesthetized pigs. Tibial nerves served as positive and negative controls. Two milliliter of bupivacaine 0.5% was injected in three nerves on the left brachial plexus. For control of local anesthetic's toxicity Ringer's solution was applied intraneurally on the right side. After maintaining 48 h of general anesthesia, the nerves were resected. The specimens were processed for histological examination and assessed for inflammation (hematoxylin and eosin stain, CD68-immunohistochemistry) and myelin damage (Kluver-Barrera stain). The degree of nerve injury was rated on a scale from 0 (no injury) to 4 (severe injury). RESULTS: Statistical analysis showed no significant differences between the bupivacaine group [median (interquartile range) 1 (1-1.5)] and the Ringer's solution group [1 (0.5-2) P = 0.772]. Mild myelin alteration was found in 12.5% of all specimens following intraneural injection, irrespective of the applied substance. CONCLUSIONS: "In our experimental study, intraneural injection of 2 ml of bupivacaine or Ringer's solution showed comparable mild inflammation. Nevertheless, inflammation can only be prevented by strictly avoiding nerve perforation followed by intraneural injection, as mechanical nerve perforation is a key factor for evolving inflammation.

Relevance of dihydropyrimidine-dehydrogenase and thymidylate-synthase in patients with pancreatic neuroendocrine neoplasms treated with 5-FU-based chemotherapy.

BACKGROUND: Chemotherapy with 5-FU and Streptozotocin (STZ) is recommended as first-line treatment in patients with metastatic pancreatic neuroendocrine neoplasms (PNEN). However, data about biomarkers involved in the 5-FU metabolism to predict response are still limited. OBJECTIVES: Evaluation of clinicopathological features and potential predictive and prognostic markers of patients with PNEN treated with 5-FU based regimens. PATIENTS AND METHODS: We retrospectively analyzed 41 patients with PNEN who were treated at the University Hospital Marburg between 2000 and 2013. Dihydropyrimidine-Dehydrogenase (DPD) and Thymidylate-Synthase (TS) expression was correlated with treatment response in 19 patients who had available tumour tissue and response data. The median overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. RESULTS: The median PFS in patients receiving 5-FU/STZ was 17 months with a median OS of 50 months. Objective response rate (ORR) and disease control rate (DCR) were 32% and 73%, respectively. Biochemical response (p = 0.005) and high DPD expression (p = 0.018) were predictive markers of response to 5-FU-based chemotherapy. Univariate analysis identified Ki-67 > 10%, no biochemical response, positive 5-HIAA levels and TS deficiency as independent risk factors for shorter PFS. Moreover, performance status (PS) ≥1 was an independent risk factors for impaired OS. CONCLUSIONS: DPD expression and biochemical response represent promising predictive biomarkers for response to 5-FU based chemotherapy. Moreover, Ki-67, PS and TS are independent prognostic markers of OS and PFS in patients with PNEN.

[A 59-year-old patient with recurrent flushes and bland hepatic cyst]. / 59-jähriger Patient mit rezidivierendem Erröten bei blander Leberzyste.

A 59-year-old patient was admitted to hospital with recurrent flush symptoms and pathologically elevated 5-hydroxyindoleacetic acid (5-HIAA) levels in urine. A known cystic lesion of the liver which had been followed for years by ultrasound examinations and was regarded as a bland hepatic cyst was identified as a metastasis of a neuroendocrine neoplasm of the ileum. In two sequential surgical interventions the primary tumor with mesenteric lymph node metastases as well as the cystic liver metastasis could be resected. After surgical treatment an R1 situation at the mesenteric site and suspicious para-aortic lymph nodes remained. The long established treatment of factor-V Leiden mutation by anticoagulation with phenprocoumon was supplemented by deep subcutaneous injection of lanreotide autogel every 4 weeks. Currently, there is no evidence for progressive disease and the patient is without clinical signs of a carcinoid syndrome.

Dual guidance improves needle tip placement for peripheral nerve blocks in a porcine model.

BACKGROUND: The objective of the study was to evaluate whether the use of ultrasound (US) together with nerve stimulation (USNST) provides a better needle tip position for performing peripheral regional anaesthesia than the use of US or nerve stimulation (NST) alone. METHODS: Needle placements were applied at the brachial plexus and sciatic nerves in 32 anaesthetised pigs. Following needle placement near the target nerve, using either the USNST or the US or NST, a volume of 0.3 ml synthetic resin was injected mimicking a 'test-dose' injection. The primary outcome was the incidence of close needle-to-nerve placement assessed by injectate localisation in direct contact with the nerve epineurium. Secondary endpoints were the incidences of intraneural injection and haematoma formation in direct contact with the target nerve. RESULTS: A total of 611 punctures were performed. The evaluation for the criterion 'close needle placement' revealed significant differences in favour of the USNST group (98.5%) compared with the NST (90.1%) and the US group (81.6%) (P = 0.001). Significant differences were observed regarding 'intraneural needle placement' between the groups as well (USNST, 0.5%; US, 4%; NST, 2.5%; P = 0.034). The incidence of haematoma formation was significantly higher in the NST group (10.8%) than in the US group (2.5%) and in the USNST group (1.5%) (P = 0.001). CONCLUSION: These findings suggest that the USNST approach combines the benefits of the US and the NST techniques in terms of a higher rate of close needle tip placements and a lower incidence of haematoma formation.

Histological Consequences of Needle-Nerve Contact following Nerve Stimulation in a Pig Model.

Background. Nerve stimulation can facilitate correct needle placement in peripheral regional anesthesia. The aim of this study was to determine whether the high threshold current is associated with reduced nerve injury due to fewer needle-nerve contacts compared with low current. Methods. In anaesthetized pigs, thirty-two nerves of the brachial plexus underwent needle placement at low (0.2 mA) or high current (1.0 mA). The occurrence of needle-nerve contact was recorded. After 48 hours, the nerves were analyzed for occurrence of histological changes. Nerve injury was scored ranging from 0 (no injury) to 4 (severe injury). Results. The frequency of needle-nerve contact was 94% at low compared to 6% at high current. The score was significantly higher at low (median [interquartile range] 2.0 [1.0-2.0]) compared to high current (0.0 [0.0-1.0] P = .001). Conclusions. Inflammatory responses were directly related to needle-nerve contacts. Hence, posttraumatic inflammation may be diminished using higher current for nerve localization.

Nerve perforation with pencil point or short bevelled needles: histological outcome.

BACKGROUND: In the case of needle nerve contact during peripheral blocks, pencil point needles are considered less traumatic compared with bevelled needles. However, there are not enough data to prove this notion. Therefore, the aim of this study was to challenge the hypothesis that nerve perforation with short bevelled needles is associated with major nerve damage compared with pencil point needles. METHODS: In five anaesthetised pigs, the brachial plexus was exposed bilaterally. Up to eight nerves underwent needle nerve perforation using a pencil point needles cannula or an short bevelled needle. After 48 h, the nerves were resected. The specimens were processed for visual examination and the detection of inflammatory cells (haematoxylin-eosin, i.e. CD68-immunohistochemistry to detect macrophages), myelin damage (Kluver-Barrera staining) and intraneural haematoma. The grade of nerve injury was characterised by an objective score ranging from 0 (no injury) to 4 (severe injury). RESULTS: Fifty nerves were examined. According to the injury score applied, there was no significant difference between the pencil point needles [median (inter-quartile range) 2.0 (2.0-2.0)] and the short bevelled-needle group [median 2.0 (2.0-2.0) P=0.23]. No myelin damage was observed. Signs of post-traumatic inflammation were equally distributed among both groups. CONCLUSIONS: In the present study, the magnitude of nerve injury after needle nerve perforation was not related to one of the applied needle types. Post-traumatic inflammation rather than structural damage of nerve tissue is the only notable sign of nerve injury after needle nerve perforation with either needle type. However, neither the pencil point- nor the short bevelled needle can be designated a less traumatic device.

Systematic evaluation of the highest current threshold for regional anaesthesia in a porcine model.

BACKGROUND: The purpose of this study was to determine systematically the highest minimal stimulation current threshold for regional anaesthesia in pigs. METHODS: In an established pig model for regional anaesthesia, needle placements applying electric nerve stimulation were performed. The primary outcome was the frequency of close needle to nerve placements as assessed by resin injects and subsequent anatomical evaluation. Following a statistical model (continual reassessment method), the applied output currents were selected to limit the necessary number of punctures, while providing guidance towards the highest output current range. RESULTS: Altogether 186 punctures were performed in 11 pigs. Within the range of 0.3-1.4 mA, no distant needle to nerve placement was found. In the range of 1.5-4.1 mA, 43 distant needle to nerve placements occurred. The range of 1.2-1.4 mA was the highest interval that resulted in a close needle to nerve placement rate of > or =95%. CONCLUSIONS: In the range of 0.3-1.4 mA, all resin deposition was found to be adjacent to nerve epineurium. The application of minimal current intensities up to 1.4 mA does not obviously lead to a reduction of epineural injectate contacts in pigs. These findings suggest that stimulation current thresholds up to 1.4 mA result in equivalent needle tip localisation in pigs.

Nerve injury by needle nerve perforation in regional anaesthesia: does size matter?

BACKGROUND: In regional anaesthesia, there is a risk of direct nerve injury. The purpose of this study was to determine whether the diameter of the applied needle is associated with the magnitude of nerve injury after needle nerve perforation. METHODS: In five anaesthetized pigs, the brachial plexus were exposed bilaterally. Up to eight nerves underwent needle nerve perforation using a 24 G pencil-point cannula (small diameter) or a 19 G pencil-point needle (large diameter). After 48 h, the nerves were resected during anaesthesia. The specimens were processed for visual examination and the detection of inflammatory cells, myelin damage and intraneural haematoma. The grade of nerve injury was scored ranging from 0 (no injury) to 4 (severe injury). RESULTS: Forty-eight nerves were examined. The applied injury score was significantly lower in the small-diameter group [median (inter-quartile range) 2.0 (2.0-2.0)] compared with the large-diameter group [3.5 (3.0-4.0) P<0.01]. Myelin damage and intraneural haematoma occurred predominantly in the large-diameter group. Signs of post-traumatic regional inflammation were comparable among both groups. CONCLUSIONS: The severity of nerve injury after needle nerve perforation was related to the diameter of the applied cannula. However, no such difference exists for regional inflammation. Functional consequences of these findings need to be determined. Currently, small-diameter cannulae may be advisable for peripheral nerve blocks to minimize the risk of nerve injury in the case of nerve perforation.

High or low current threshold for nerve stimulation for regional anaesthesia.

BACKGROUND: The purpose of this study was to determine whether the application of high stimulation current thresholds (SCT) leads to a distant needle to nerve proximity (NNP) compared with low SCT during nerve localization for regional anaesthesia in pigs. METHODS: A minimal motor response to the stimulation of femoral or brachial plexus nerves in 16 anaesthetized pigs was triggered either by a minimal SCT of a low (0.01-0.3 mA) or a high (0.8-1.0 mA) current in a random order. After eliciting a motor response with a predetermined SCT, synthetic resin was injected via the needle. After postmortem dissection of the injection site, the localization of the resin deposition was determined verifying the final position of the needle tip. Depending on the proximity of resin deposition to the nerve epineurium, the needle tip placement was considered either as a close or a distant NNP. RESULTS: A total of 235 punctures were performed. Ninety-one punctures were carried out with low SCT and 92 with a high SCT. Fifty-two punctures served as a control (1.8-2.0 mA). All injectates following both high or low SCT were considered 'close needle tip to nerve placement', whereas 27 of 52 injectates of the control group appeared distant to nerve epineurium. CONCLUSION: Regardless of the applied SCT, i.e. high or low, all resin deposition was found adjacent to nerve epineurium. These findings suggest that high and low SCT result in equivalent needle tip localization in pigs.