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Neuraxial drug administration, i.e., the injection of drugs into the epidural or intrathecal space to produce anesthesia or analgesia, is a technique developed more than 120 years ago. Today, it still is widely used in daily practice in anesthesiology and in acute and chronic pain therapy. A multitude of different drugs have been introduced for neuraxial injection, only a part of which have obtained official approval for that indication. A broad understanding of the pharmacology of those agents is essential to the clinician to utilize them in a safe and efficient manner. In the present narrative review, we summarize current knowledge on neuraxial anatomy relevant to clinical practice, including pediatric anatomy. Then, we delineate the general pharmacology of neuraxial drug administration, with particular attention to specific aspects of epidural and intrathecal pharmacokinetics and pharmacodynamics. Furthermore, we describe the most common clinical indications for neuraxial drug administration, including the perioperative setting, obstetrics, and chronic pain. Then, we discuss possible neurotoxic effects of neuraxial drugs, and moreover, we detail the specific properties of the most commonly used neuraxial drugs that are relevant to clinicians who employ epidural or intrathecal drug administration, in order to ensure adequate treatment and patient safety in these techniques. Finally, we give a brief overview on new developments in neuraxial drug therapy.

Background: Respiratory motion presents a challenge in radiotherapy of thoracic and upper abdominal tumors. Techniques to account for respiratory motion include tracking. Using magnetic resonance imaging (MRI) guided radiotherapy systems, tumors can be tracked continuously. Using conventional linear accelerators, tracking of lung tumors is possible by determining tumor motion on kilo voltage (kV) imaging. But tracking of abdominal tumors with kV imaging is hampered by limited contrast. Therefore, surrogates for the tumor are used. One of the possible surrogates is the diaphragm. However, there is no universal method for establishing the error when using a surrogate and there are particular challenges in establishing such errors during free breathing (FB). Prolonged breath-holding might address these challenges. Purpose: The aim of this study was to quantify the error when using the right hemidiaphragm top (RHT) as surrogate for abdominal organ motion during prolonged breath-holds (PBH) for possible application in radiation treatments. Methods: Fifteen healthy volunteers were trained to perform PBHs in two subsequent MRI sessions (PBH-MRI1 and PBH-MRI2). From each MRI acquisition, we selected seven images (dynamics) to determine organ displacement during PBH by using deformable image registration (DIR). On the first dynamic, the RHT, right and left hemidiaphragm, liver, spleen and right and left kidney were segmented. We used the deformation vector fields (DVF), generated by DIR, to determine the displacement of each organ between two dynamics in inferior-superior (IS), anterior-posterior (AP), left-right (LR) direction and we calculated the 3D vector magnitude (|d|). The displacements of the RHT, both hemidiaphragms and the abdominal organs were compared using a linear fit to determine the correlation (R2 of the fit) and the displacement ratio (DR, slope of the fit) between displacements of the RHT and each organ. We quantified the median difference between the DRs of PBH-MRI1 and PBH-MRI2 for each organ. Additionally, we estimated organ displacement in the second PBH by applying the DR from the first PBH to the displacement of the RHT measured during the second PBH. We compared the estimated organ displacement to the measured organ displacement during the second PBH. The difference between the two values was defined as the estimation error of using the RHT as a surrogate and assuming a constant DR over MRI sessions. Results: The linear relationships were confirmed by the high R2 values of the linear fit between the displacements of the RHT and the abdominal organs (R2 > 0.96) in the IS and AP direction and |d|, and high to moderate correlations in the LR direction (0.93 > R2 > 0.64). The median DR difference between PBH-MRI1 and PBH-MRI2 varied between 0.13 and 0.31 for all organs. The median estimation error of the RHT as a surrogate varied between 0.4 and 0.8 mm/min for all organs. Conclusion: The RHT could serve as an accurate surrogate for abdominal organ motion during radiation treatments, for example, in tracking, provided the error of the RHT as motion surrogate is taken into account in the margins. Trial registration: The study was registered in the Netherlands Trial Register (NL7603).

Neonatal surgery and concomitant anesthesia coincide with a timeframe of rapid brain development. The speed and complexity of early brain development superimposed on immature regulatory mechanisms that include incomplete cerebral autoregulation, insufficient free radical scavenging and an immature immune response puts the brain at risk. Brain injury may have long-term consequences for multiple functional domains including cognition, learning skills, and behavior. Neurodevelopmental follow-up studies have noted mild-to-moderate deficits in children who underwent major neonatal surgery and related anesthesia. The present review evaluates neonatal surgery against the background of neurobiological processes that unfold at a pace unparalleled by any other period of human brain development. First, a structured summary of early brain development is provided in order to establish theoretical groundwork. Next, literature on brain injury and neurodevelopmental outcome after neonatal surgery is discussed. Special attention is given to recent findings of structural brain damage reported after neonatal surgery. Notably, high-quality imaging data acquired before surgery are currently lacking. Third, mechanisms of injury are interrogated taking the perspective of early brain development into account. We propose a novel disease model that constitutes a triad of inflammation, vascular immaturity, and neurotoxicity of prolonged exposure to anesthetic drugs. With each of these components exacerbating the other, this amalgam incites the perfect storm, resulting in brain injury. When examining the brain, it seems intuitive to distinguish between neonates (i.e.

Background and objectives: documentation is important for quality improvement, education, and research. There is currently a lack of recommendations regarding key aspects of documentation in regional anesthesia. The aim of this study was to establish recommendations for documentation in regional anesthesia. Methods: following the formation of the executive committee and a directed literature review, a long list of potential documentation components was created. A modified Delphi process was then employed to achieve consensus amongst a group of international experts in regional anesthesia. This consisted of 2 rounds of anonymous electronic voting and a final virtual round table discussion with live polling on items not yet excluded or accepted from previous rounds. Progression or exclusion of potential components through the rounds was based on the achievement of strong consensus. Strong consensus was defined as >= 75% agreement and weak consensus as 50%-74% agreement. Results: seventy-seven collaborators participated in both rounds 1 and 2, while 50 collaborators took part in round 3. In total, experts voted on 83 items and achieved a strong consensus on 51 items, weak consensus on 3 and rejected 29. Conclusion: by means of a modified Delphi process, we have established expert consensus on documentation in regional anesthesia., European Society of Regional Anaesthesia and Pain Therapy (ESRA); ASRA Pain Medicine

Objective Uncorrected metabolic alkalosis in infantile hypertrophic pyloric stenosis (IHPS) could lead to perioperative apnea. However, the precise incidence of preoperative respiratory problems and the association with metabolic alkalosis are unknown. Therefore, we aimed to determine the incidence of preoperative respiratory problems in IHPS and to assess the association with metabolic alkalosis. Methods We retrospectively reviewed all patients diagnosed with IHPS during 2007–2017. Respiratory problems were classified as present or absent. With multivariate logistic regression we analyzed the association between bicarbonate and respiratory problems, corrected for gestational age and birth weight. Results We included 459 infants, of whom 23 developed preoperative respiratory problems (5.0%). Infants with preoperative respiratory problems were more often female (43.5% vs. 13.3% p = 0.001) and had significantly higher median serum levels of bicarbonate (32.0 mmol/L vs. 30.0 mmol/L), base excess (6.5 mmol/L vs. 5.3 mmol/L) and pCO2 (6.4 kPa vs. 5.9 kPa), compared to infants without respiratory problems. Multivariate analysis of serum bicarbonate and presence of respiratory problems showed an OR of 2.18 per 10 mmol/L (95% CI 1.21–4.71) (p = 0.009). The optimal bicarbonate cutoff point was 25.7 mmol/L (sensitivity 100%, specificity 13.4%). Conclusion IHPS with metabolic alkalosis potentially results in preoperative respiratory problems. A lower bicarbonate target before surgery might be recommended and respiratory monitoring should be considered. Level of evidence Level IV.

Background: Infantile hypertrophic pyloric stenosis (IHPS) leads to excessive vomiting and metabolic alkalosis, which may subsequently cause apnea. Although it is generally assumed that metabolic derangements should be corrected prior to surgery to prevent apnea, the exact incidence of perioperative apneas in infants with IHPS and the association with metabolic alkalosis are unknown. We performed this systematic review to assess the incidence of apnea in infants with IHPS and to verify the possible association between apnea and metabolic alkalosis. Methods: We searched MEDLINE, Embase, and Cochrane library to identify studies regarding infants with metabolic alkalosis, respiratory problems, and hypertrophic pyloric stenosis. We conducted a descriptive synthesis of the findings of the included studies. Results: Thirteen studies were included for analysis. Six studies described preoperative apnea, three studies described postoperative apnea, and four studies described both. All studies were of low quality or had other research questions. We found an incidence of 27% of preoperative and 0.2%-16% of postoperative apnea, respectively. None of the studies examined the association between apnea and metabolic alkalosis in infants with IHPS. Conclusions: Infants with IHPS may have a risk to develop perioperative apnea. However, the incidence rates should be interpreted with caution because of the low quality and quantity of the studies. Therefore, further studies are required to determine the incidence of perioperative apnea in infants with IHPS. The precise underlying mechanism of apnea in these infants is still unknown, and the role of metabolic alkalosis should be further evaluated.

Background Normalization of metabolic alkalosis is an important pillar in the treatment of infantile hypertrophic pyloric stenosis (IHPS) because uncorrected metabolic alkalosis may lead to perioperative respiratory events. However, the evidence on the incidence of respiratory events is limited. We aimed to study the incidence of peroperative hypoxemia and postoperative respiratory events in infants undergoing pyloromyotomy and the potential role of metabolic alkalosis. Materials and Methods We retrospectively reviewed all patients undergoing pyloromyotomy between 2007 and 2017. All infants received intravenous fluids preoperatively to correct metabolic abnormalities close to normal. We assessed the incidence of perioperative hypoxemia (defined as oxygen saturation [SpO2] 1min) and postoperative respiratory events. Additionally, the incidence of difficult intubations was evaluated. We performed a multivariate logistic regression analysis to evaluate the association between admission or preoperative serum pH values, bicarbonate or chloride, and peri- and postoperative hypoxemia or respiratory events. Results Of 406 included infants, 208 (51%) developed 1 or more episodes of hypoxemia during the perioperative period, of whom 130 (32%) experienced it during induction, 43 (11%) intraoperatively, and 112 (28%) during emergence. About 7.5% of the infants had a difficult intubation and 17 required more than 3 attempts by a pediatric anesthesiologist. Three patients developed respiratory insufficiency and 95 postoperative respiratory events were noticed. We did not find a clinically meaningful association between laboratory values reflecting metabolic alkalosis and respiratory events. Conclusions IHPS frequently leads to peri- and postoperative hypoxemia or respiratory events and high incidence of difficult tracheal intubations. Preoperative pH, bicarbonate, and chloride were bad predictors of respiratory events.

Background The incidence of metachronous contralateral inguinal hernia (MCIH) is high in infants with an inguinal hernia (5–30%), with the highest risk in infants aged 6 months or younger. MCIH is associated with the risk of incarceration and necessitates a second operation. This might be avoided by contralateral exploration during primary surgery. However, contralateral exploration may be unnecessary, leads to additional operating time and costs and may result in additional complications of surgery and anaesthesia. Thus, there is no consensus whether contralateral exploration should be performed routinely. Methods The Hernia-Exploration-oR-Not-In-Infants-Analysis (HERNIIA) study is a multicentre randomised controlled trial with an economic evaluation alongside to study the (cost-)effectiveness of contralateral exploration during unilateral hernia repair. Infants aged 6 months or younger who need to undergo primary unilateral hernia repair will be randomised to contralateral exploration or no contralateral exploration (n = 378 patients). Primary endpoint is the proportion of infants that need to undergo a second operation related to inguinal hernia within 1 year after primary repair. Secondary endpoints include (a) total duration of operation(s) (including anaesthesia time) and hospital admission(s); (b) complications of anaesthesia and surgery; and (c) participants’ health-related quality of life and distress and anxiety of their families, all assessed within 1 year after primary hernia repair. Statistical testing will be performed two-sided with α = .05 and according to the intention-to-treat principle. Logistic regression analysis will be performed adjusted for centre and possible confounders. The economic evaluation will be performed from a societal perspective and all relevant costs will be measured, valued and analysed. Discussion This study evaluates the effectiveness and cost-effectiveness of contralateral surgical exploration during unilateral inguinal hernia repair in children younger than 6 months with a unilateral inguinal hernia. Trial registration ClinicalTrials.govNCT03623893. Registered on August 9, 2018 Netherlands Trial Register NL7194. Registered on July 24, 2018 Central Committee on Research Involving Human Subjects (CCMO) NL59817.029.18. Registered on July 3, 2018

Introduction: Epidural analgesia is a popular approach to postoperative and labor pain. Neurotoxicity and drug-specific systemic side effects can occur after epidural administration. As an increasing number of epidural drugs are studied and clinically applied, drug efficacy and safety evaluation are crucial. Areas covered: In this narrative review, the authors provide a thorough overview on the safety of the most widely used epidural drugs, focusing on potential neurotoxicity, side effects, and complications in the adult, non-pregnant population. A combined text and MeSH heading search strategy was used to identify relevant publications. Expert opinion: The search for the ideal epidural medication has resulted in a surplus of drug combinations with extensive heterogeneity amongst studies, while the value of investigating these is not always evident. Epidural drugs pose a potential threat of neurotoxicity and other side effects. Consequently, we should pursue safe epidural drug administration to patients and refrain from drugs with minimal proven benefit. Also, studies should compare epidural with systemic application. Because why use a drug epidurally, which can be safely used systemically? Future research should focus on providing solid evidence regarding efficacy of epidural analgesia compared to new and already existing modalities and optimizing presently used medicinal regimens.

Background and objectivesLearning epidural anesthesia traditionally involves bedside teaching. Visualization aids or a simulator can help in acquiring motor skills, increasing patient safety and steepening the learning curve. We evaluated the face and construct validity of the TU-Delft Epidural Simulator and the effect of needle visualization.MethodsSixty-eight anesthesiologists, anesthesia residents, and final-year medical students tested the epidural simulator. Participants performed six epidural simulations with and six without needle visualization. We tested face validity on a Likert scale questionnaire. We collected data with the simulator software (spinal taps, dura contacts, bone contacts, attempts, and time) and tested for correlation with the performer’s experience (construct validity). A visualization aid was tested in a randomized crossover design.ResultsFace validity as rated by the participants was above average, with a mean of 3.7 (2.0–4.8) on a 5-point scale. Construct validity was indicated by significantly more spinal taps (0.4 [0–4) vs 0.07 [0–2], p=0.04) and more dura contacts (0.58 [0–6] vs 0.37 [0–3], p=0.002) by the inexperienced group compared with the expert group. The visualization aid improved performance by reducing the number of bone contacts and the number of attempts, and by decreasing the procedure time. Prior visualization training reduced the total procedure time from 279 s (69–574) to 180 s (53–605) (p=0.01) for the “blind” procedure.ConclusionsThe TU-Delft Epidural Simulator is a useful tool for teaching motor skills during epidural needle placement. Prior use of a visualization tool improves performance even without visual support during consequent simulations.

IntroductionPectus excavatum repair is associated with substantial postoperative pain, despite the use of epidural analgesia and other analgesic regimens. Perioperative recorded music interventions have been shown to alleviate pain and anxiety in adults, but evidence for children and adolescents is still lacking. This study protocol describes a randomised controlled trial that evaluates the effects of recorded music interventions on postoperative pain relief in children and adolescents after pectus excavatum repair.MethodsA multicentre randomised controlled trial was set up comparing the effects of perioperative recorded music interventions in addition to standard care with those of standard care only in patients undergoing a Nuss procedure for pectus excavatum repair. One hundred and seventy subjects (12–18 years of age) will be included in three centres in the Netherlands. Patient inclusion has started in November 2018, and is ongoing. The primary outcome is self-reported perceived pain measured on the visual analogue scale. Secondary outcomes are anxiety level, analgesics consumption, vital parameters such as heart rate, blood pressure and respiratory rate, length of hospital stay, postoperative complications, quality of life and cost-effectiveness.Ethics and disseminationThis study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Centre Rotterdam, The Netherlands, has approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations.Trial registration numberNL6863

BackgroundEpidural catheters are frequently colonized by gram-positive bacteria. Although the incidence of associated epidural infections is low, their consequences can be devastating. We investigated bacterial growth on epidural catheters by quantitative bacterial culture and scanning electron microscopy (SEM) in order to explore the patterns of epidural catheter colonization.Methods28 patients undergoing major abdominal surgery with thoracic epidurals (treatment ≥72 hours) were studied. Before the removal of the catheter, the skin surrounding the insertion site was swabbed. The entire catheter was divided into extracorporeal, subcutaneous, and tip segments. Skin swabs and catheter segments were quantitatively cultured, bacterial species were identified, and SEM was performed on four selected catheters.Results27 of 28 catheters were included. The percentages of positive cultures were: skin swab 29.6%, extracorporeal segments 11.1%, subcutaneous segments 14.8%, and tip segments 33.3%. One patient was diagnosed with a catheter-associated infection.Staphylococcus epidermidiswas cultured from the skin and the catheter extracorporeal, subcutaneous, and tip segments. SEM of this catheter showed bacteria-like and intraluminal host cell-like structures. SEM of two other catheters showed intraluminal fibrin networks in their tip segments.ConclusionsWe present the first SEM pictures of an epidural catheter with a bacterial infection. Bacterial growth developed from the skin to the tip of this catheter, indicating the skin as a primary source of infection. By SEM, catheters with low levels of bacterial growth demonstrated an intraluminal fibrous network which possibly plays a role in catheter obstruction.

Introduction: In the Emergency Department, regional anesthesia is increasingly used in elderly patients with hip fractures. An example is a Fascia Iliaca Compartment Block (FICB). Traditionally, this block is administered below the inguinal ligament. There is no Emergency Department data regarding effectivity of an alternative, more cranial approach above the inguinal ligament. The objective was to determine analgesic effects of an ultrasound-guided supra-inguinal FICB in hip fracture patients in the Emergency Department. Methods: This case series included all Emergency Department hip fracture patients who were treated with a supra-inguinal FICB during a period of 10 months. All data were recorded prospectively. Primary study outcome was decrease in Numerical Rating Scale (NRS) pain scores 60 min after the FICB. Secondary outcomes included the proportion of patients achieving 1.5 NRS points decrease at 60 min; NRS differences at 30 and 120 min compared to baseline; need for additional analgesia and occurrence of adverse events. Results: A total of 22 patients were included in the study. At 60 min median NRS pain scores decreased from 6.0 to 3.0 (p < 0.001). Of all patients, a total of 59% achieved a decrease in 1.5 NRS points after 60 min. Median pain scores at 30 and 120 min were 4.0 (Interquartile Range (IQR) 2.0–5.0) and 2.5 (IQR 0.8–3.0). Seven patients (31.8%) required additional opioid analgesia after the FICB. No adverse events were recorded. Conclusion: An ultrasound-guided supra-inguinal FICB decreases NRS pain scores in hip fracture patients both clinically relevant and statistically significantly after 60 min. Clinical trial registration: The study was registered in the ISRCTN database (ISRCTN74920258).

Background and aims Epidural catheters are frequently colonized by gram positive bacteria. the incidence of epidural infections is low, but their consequences can be devastating. We investigated the pattern of bacterial colonization of epidural catheters. Epidural catheters of patients showing signs of local infection were investigated by scanning electron microscopy (SEM) in order to delineate mechanism of catheter infection. Methods 28 patients receiving thoracic epidural analgesia for more than 72 hours were studied. All received antibiotic prophylaxis after catheter placement (cefazolin, metronidazole). Skin swabs and catheter segments were cultured after catheter removal. Bacteria were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry. SEM of culture positive catheters was performed. Results 27 of 28 catheters could be investigated. Colonization percentages were: skin swab in 22%, extracorporeal segments in 11% and subcutaneous segments in 3.7%. Cultures revealed Staphylococcus epidermidis, Staphylococcus simulans, Propionibacterium acnes, and Micrococcus luteus. In one patient, a clinically relevant infection was recorded, caused by S. epidermidis. Bacteria were cultured from extracorporeal and subcutaneous segments and the tip of this catheter. SEM displayed host cell-like structures on inner catheter surface and an intraluminal fibrin network which formatted around a catheter hole. Conclusions Epidural catheter colonization seems to spread from the skin segments to the deeper parts of the catheter, resembling the pattern of colonization of central venous catheters. the inner surface of the catheter tip is invaded by probably immune cells and fibrin fibers forming a microfilm-like structure.

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects. These include effects on the peripheral nervous system and CNS, where lidocaine acts via silencing ectopic discharges, suppression of inflammatory processes, and modulation of inhibitory and excitatory neurotransmission. We highlight promising objectives for future research to further unravel these antinociceptive mechanisms, which subsequently may facilitate the development of new analgesic strategies and therapies for acute and chronic pain.

Dexamethasone is commonly applied during arthroplasty to control post-operative nausea and vomiting (PONV). However, conflicting views of orthopaedic surgeons and anaesthesiologists regarding the use of dexamethasone raise questions about risks of impaired wound healing and surgical site infections (SSI). The aim of this systematic review is to determine the level of evidence for the safety of a peri-operative single low dose of dexamethasone in hip and knee arthroplasty. We systematically reviewed literature in PubMed, EMBASE and Cochrane databases and cited references in articles found in the initial search from 1980 to 2013 based on predefined inclusion criteria. The review was completed with a ‘pro’ and ‘con’ discussion. After identifying 11 studies out of 104, only eight studies met the inclusion criteria. In total, 1335 patients were studied without any incidence of SSI. Causes of SSI are multifactorial. Therefore, 27 205 patients would be required (power = 90%, alpha = 0.05) to provide substantiated conclusions on safety of a single low dose of dexamethasone. Positively, many studies demonstrated showed convincing effects of low-dose dexamethasone on prevention of PONV and dose-dependent effects on post-operative pain and quality of recovery. Dexamethasone induces hyperglycaemia, but none of the studies demonstrated a concomitant SSI. Conversely, animal studies showed that high dose dexamethasone inhibits wound healing. A team approach of anaesthesiologists and orthopaedic surgeons is mandatory in order to balance the risk–benefit ratio of peri-operatively applied steroids for individual arthroplasty patients. We did not find evidence that a single low dose of dexamethasone contributes to SSI or wound healing impairment from the current studies. Cite this article: Wegener JT, Kraal T, Stevens MF, Hollman MW, Kerkhoffs GMMJ, Haverkamp D. Low-dose dexamethasone during arthroplasty: what do we know about the risks? EFORT Open Rev 2016;1:303-309. DOI: 10.1302/2058-5241.1.000039.

A patient suffered massive subcutaneous emphysema and bilateral tension pneumothoraces after receiving supplemental oxygen through an airway exchange catheter (AEC). Complications of AEC placement include misplacement, direct injury to the larynx, bronchi or lung, barotrauma related to oxygen supplementation, and a loss of airway. We review these complications and discuss the specific risks of supplementing oxygen using an AEC. We suggest measures to limit pressure from the oxygen source and warn against advancing an AEC too far into the tracheobronchial tree.

The COVID-19 pandemic poses great challenges for healthcare workers around the world, including perioperative specialists. Previously, we provided a first overview of available literature on SARS-CoV-2 and COVID-19, relevant for anaesthetists and intensivists. In the current review, we provide an update of this topic, after a literature search current through May 2020. We discuss the evidence on perioperative risk for COVID-19 patients presenting for surgery, the risk of transmission of SARS-CoV-2 in the operating room, and the current literature on laboratory diagnostics. Furthermore, cardiovascular and nervous system involvement in COVID-19 are discussed, as well as considerations in diabetic patients. Lastly, the latest evidence on pharmacological treatment is summarised.

Background Although an emergency surgical airway is recommended in the guidelines for a paediatric cannot intubate, cannot oxygenate (CICO), there is currently no evidence regarding the best technique for this procedure. Objective To review the available literature on the paediatric emergency surgical airway to give recommendations for establishing a best practice for this procedure. Design Systematic review: Considering the nature of the original studies, a meta-analysis was not possible. Data sources MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Google Scholar and LILACS databases. Eligibility criteria Studies addressing the paediatric emergency surgical airway and reporting the following outcomes: time to tracheal access, success rate, complications and perceived ease of use of the technique were included. Data were reported using a Strengths, Weaknesses, Opportunities and Threats analysis. Strengths and Weaknesses describe the intrinsic (dis)advantages of the techniques. The opportunities and threats describe the (dis)advantage of the techniques in the setting of a paediatric CICO scenario. Results Five studies described four techniques: catheter over needle, wire-guided, cannula or scalpel technique. Mean time for placement of a definitive airway was 44 s for catheter over needle, 67.3 s for the cannula and 108.7 s for the scalpel technique. No time was reported for the wire-guided technique. Success rates were 43 (10/23), 100 (16/16), 56 (87/154) and 88% (51/58), respectively. Complication rates were 34 (3/10), 69 (11/16), 36 (55/151) and 38% (18/48), respectively. Analysis shows: catheter over needle, quick but with a high failure rate; wire-guided, high success rate but high complication rate; cannula, less complications but high failure rate; scalpel, high success rate but longer procedural time. The available data are limited and heterogeneous in terms of reported studies; thus, these results need to be interpreted with caution. Conclusion The absence of best practice evidence necessitates further studies to provide a clear advice on best practice management for the paediatric emergency surgical airway in the CICO scenario.

Background Contemporary axillary brachial plexus block is performed by separate injections targeting radial, median, ulnar and musculocutaneous nerve. These nerves are arranged around the axillary artery, making ultrasound visualisation sometimes challenging. In particular, the radial nerve can be difficult to localise deep to the artery. Objectives The primary aim of this study was to investigate which arm position optimises the visibility of the radial nerve. Secondary aims were the visibility and position of the other nerves during varying arm positions. Design A prospective observational study. Setting University teaching hospital, November 2012. Participants Twenty volunteers, recruited by an advertisement on the Department's bulletin board. Inclusion criterion age more than 18 years. Exclusion criteria refusal of ultrasound examination, restricted shoulder movement, local infection, BMI greater than 30 kg m⁻². Intervention One anaesthesiologist performed bilateral ultrasound examinations of the axillary brachial plexus on 20 volunteers. Each arm was placed in different positions [shoulder (S) 90° or 180° abduction, elbow (E) 0° or 90° extension] and scans were performed proximally in the axilla, and additionally 5 cm distally to this point [proximal (P) vs. distal (D)], resulting in eight different scans stored for off-line analysis performed by two blinded anaesthesiologists. Main outcome measures For radial, median, ulnar and musculocutaneous nerve, visibility was assessed on a six-point visibility scale. Distances and angles of the nerves relative to the axillary artery and distances relative to the skin were measured. Results No significant differences between arm positions were found in the visibility score of radial (P = 0.359) and musculocutaneous nerves (P = 0.073). Visibility of the median nerve was improved in positions S90°/E0°/D and S180°/E0°/P (P = 0.02). The ulnar nerve was more visible in position S180°/E 0°/P and D (P = 0.007). The greatest distance between artery and radial nerve was 7.4 ± 4.7 mm at an angle of 120 ± 14° in position S180°/E 0°/D. Conclusion The visibility of the radial nerve was not improved by varying positions of the arm. S180°/E0° provided the best overall visibility and accessibility of nerves. Trial registration https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm Identifier: NL42116.018.12.

The neuropathy of type II diabetes mellitus (DM) is increasing in prevalence worldwide. We aimed to test the hypothesis that in a rodent model of type II DM, neuropathy would lead to increased neurotoxicity and block duration after lidocaine-induced sciatic nerve block when compared with control animals. Experiments were carried out in Zucker diabetic fatty rats aged 10 weeks (early diabetic) or 18 weeks (late diabetic, with or without insulin 3 units per day), and age-matched healthy controls. Left sciatic nerve block was performed using 0.2 ml lidocaine 2%. Nerve conduction velocity (NCV) and F-wave latency were used to quantify nerve function before, and 1 week after nerve block, after which sciatic nerves were used for neurohistopathology. Early diabetic animals did not show increased signs of nerve dysfunction after nerve block. In late diabetic animals without insulin vs control animals, NCV was 34.8 (5.0) vs 41.1 (4.1) ms s(-1) (P

Body temperature homeostasis is accurately regulated by complex feedback-driven neuronal mechanisms, which involve a multitude of thermoregulatory pathways. Thus, core temperature is constantly maintained within a narrow range. As one of the most effective regulatory systems skin temperature is dependent on skin blood flow. Skin blood flow in turn is highly dependent on sympathetic activity. Regional anaesthesia leads to blockade not only of somatosensory and motor nerve fibres but also of sympathetic fibres. As a consequence, vasoconstrictor tonic activity is abrogated and a vasodilation leads to an increase in skin blood flow and temperature. The aim of this review was to summarize the general physiology of thermoregulation and skin temperature as well as the alterations during regional anaesthesia. The main focus was the usefulness of measuring skin temperature as an indicator of regional anaesthesia success. According to the available literature, assessment of skin temperature can indeed serve to predict success of regional anaesthesia. Hence, it is important to realize that relevant and reliable temperature increase is only seen in the most distal body parts, ie fingers and toes. More proximally, temperature changes are frequently small and inconsistent, which means that assessment of block levels is not possible by temperature measurement. Furthermore, relevant skin temperature increases will only be observed in patients, which are initially vasoconstricted. In conclusion, measurement of skin temperature represents a reliable and feasible diagnostic tool to assess and predict the success or failure of regional anaesthesia procedures, especially in patients in which sensory testing is impossible.

Postoperative epidural analgesia often needs rate readjustment using top-ups. Patient-controlled epidural analgesia (PCEA) is said to reduce the requirement of epidural top-ups when compared to continuous epidural analgesia (CEA). We compared CEA and PCEA in major thoracic and abdominal surgery, in a cohort study. The primary endpoint was the required number of epidural top-ups. Secondary endpoints were pain scores, side effects and workload differences. We analysed 199 patients with CEA and 187 with PCEA. Both groups had similar pain scores. The total number of top-ups was 75 in 57 patients (CEA) versus 20 top-ups in 18 patients (PCEA). (p = 0.0001) Sedation tended to occur more frequently in patients with CEA versus PCEA, 5.5% vs 1.6% (p = 0.05). Implementation of PCEA led to a decreased number of top-ups, fewer side-effects and decreased use of the postoperative care unit.

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31 127 anaesthetic procedures in 30 874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0–5·5) with an incidence of respiratory critical events of 3·1% (2·9–3·3). Cardiovascular instability occurred in 1·9% (1·7–2·1), with an immediate poor outcome in 5·4% (3·7–7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10 000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86–0·90; p

Background Cerebral air emboli occur as a complication of invasive medical procedures. The sensitivity of cerebral monitoring methods for the detection of air emboli is not known. This study investigates the utility of electroencephalography and non-invasively measured cerebral oxygen saturation in the detection of intracerebrovascular air. New method In 12 pigs oxygen saturation was continuously measured using transcranial near-infrared spectroscopy and oxygen tension was continuously measured using intraparenchymal probes. Additionally, quantitative electroencephalography and microdialysis were performed. Doses of 0.2, 0.4, 0.8, and 1.6 ml of air were injected into the cerebral arterial vasculature through a catheter. Results Oxygen saturation and electroencephalography both reacted almost instantaneously on the air emboli, but were less sensitive than the intraparenchymal oxygen tension. There was reasonable correlation (ρ ranging from 0.417 to 0.898) between oxygen saturation, oxygen tension, electroencephalography and microdialysis values. Comparison with existing methods Our study is the first to demonstrate the effects of cerebral air emboli using multimodal monitoring, specifically on oxygen saturation as measured using near-infrared spectroscopy. Conclusions Our results show that non-invasively measured oxygen saturation and quantitative electroencephalography can detect the local effects of air emboli on cerebral oxygenation, but with reduced sensitivity as compared to intraparenchymal oxygen tension. Prospective human studies using multimodal monitoring incorporating electroencephalography and oxygen saturation should be performed.

Background Signalling of several G-protein-coupled receptors of the Gq/11 family is time-dependently inhibited by local anaesthetics (LAs). Since LA-induced modulation of muscarinic m1 and m3 receptor function may explain their beneficial effects in clinical practice, such as decreased postoperative cognitive dysfunction or less bronchoconstriction, we studied how prolonged exposure affects muscarinic signalling (Wang D, Wu X, Li J, Xiao F, Liu X, Meng M. The effect of lidocaine on early postoperative cognitive dysfunction after coronary artery bypass surgery. Anesth Analg 2002; 95 : 1134–41; Groeben H, Silvanus MT, Beste M, Peters J. Combined lidocaine and salbutamol inhalation for airway anesthesia markedly protects against reflex bronchoconstriction. Chest 2000; 118 : 509–15). Methods A two-electrode voltage clamp was used to assess the effects of lidocaine or its permanently charged analogue QX314 on recombinantly expressed m1 and m3 receptors in Xenopus oocytes. Antisense knock-down of functional Gαq-protein and inhibition of protein kinase C (PKC) served to define mechanisms and sites of action. Results Lidocaine affected muscarinic signalling in a biphasic way: an initial decrease in methylcholine bromide-elicited m1 and m3 responses after 30 min, followed by a significant increase in muscarinic responses after 8 h. Intracellularly injected QX314 time-dependently inhibited muscarinic signalling, but had no effect in Gαq-depleted oocytes. PKC-antagonism enhanced m1 and m3 signalling, but completely abolished the LA-induced increase in muscarinic responses, unmasking an underlying time-dependent inhibition of m1 and m3 responses after 8 h. Conclusions Lidocaine modulates muscarinic m1 and m3 receptors in a time- and Gαq-dependent manner, but this is masked by enhanced PKC activity. The biphasic time course may be due to interactions of LAs with an extracellular receptor domain, modulated by PKC activity. Prolonged exposure to LAs may not benefit pulmonary function, but may positively affect postoperative cognitive function.

Background and Objectives Local anesthetics (LAs) are widely known for inhibition of voltage-gated sodium channels underlying their antiarrhythmic and antinociceptive effects. However, LAs have significant immunomodulatory properties and were shown to affect human neutrophil functions independent of sodium-channel blockade. Previous studies suggest a highly selective interaction between LAs and the α-subunit of G protein–coupled receptors of the Gq/G11 family as underlying mechanism. Providing a detailed structure function analysis, this study aimed to determine the active parts within the LA molecule responsible for the effects on human neutrophil priming. Methods Human neutrophils were incubated with structurally different LAs for 60 minutes, followed by priming and activation using either platelet-activating factor or lysophosphatidic acid and N-formyl-methionyl-L-leucyl-L-phenylalanine. Superoxide anion generation was determined, using the cytochrome c reduction assay. Results Differences in priming inhibition of human neutrophils between LAs were smaller than expected, although significant. Ester-linked LAs blocked priming responses more effectively than did amide LAs. Furthermore, the inhibitory potency of LAs on priming decreased with an increase of their respective octanol-buffer coefficient, and inhibition did not correlate with sodium-channel–blocking potency. Charge was not crucially required for priming inhibition, yet it played a role in effect size. Conclusions Local anesthetics significantly attenuated Gαq-protein–mediated neutrophil priming. The most potent inhibition was achieved by ester compounds, inversely correlated with their octanol-buffer coefficient, and enhanced by permanent charges within the LA molecule. No correlation to their potency of blocking sodium channels was found.

Background and Objectives Use of ultrasound-guided regional anesthesia (UGRA) requires considerable training. An embedded electronic tutorial as an element of an ultrasound machine may help to identify sonoanatomy for novices. Therefore, we investigated whether an electronic tutorial could improve accuracy or speed of performance in identifying anatomical structures. Methods Thirty-five novices in UGRA participated in a workshop on brachial plexus sonoanatomy. Following a lecture and training in handling of ultrasound machines and hand-eye coordination, participants were randomized in either group S, using a standard ultrasound machine, or group T, using the same type of machine with an onboard electronic tutorial. Each participant had to identify 27 anatomical structures from the brachial plexus of a volunteer. A correctly identified structure scored 1 point. An experienced observer noted scores and time required. Scores ± SD (in %) and times ± SD (in seconds) were compared between groups by analyses of independent-samples t test and analysis of variance. Influence of anesthesia experience was determined by multivariate analyses. Results Group T scored significantly higher (16.8 ± 3.6 [62%] vs 13.4 ± 4.4 [50%], P = 0.018), whereas time required was longer (1053 ± 244 vs 740 ± 244 seconds, P = 0.001). Multivariate analysis revealed that experience had no influence on scores or time required. Examination of structures took more time in the beginning than at the end in group T. Conclusions An electronic tutorial can help novices in UGRA identify anatomical structures. A significant increase in correct identifications was gained at the expense of significantly longer time required for this process. Increased time required may partly be related to unfamiliarity with the tutorial.

Background and Objectives This is a follow-up to determine long-term outcomes after total knee arthroplasty (TKA) in patients enrolled in a previous randomized trial that found reduced postoperative pain after addition of sciatic nerve block to continuous femoral nerve block for TKA. Methods Physical function after TKA was evaluated at 3 and 12 months in patients (n = 89) receiving continuous femoral nerve block alone (group F), combined with a single-injection (group Fs) or continuous sciatic nerve block (group FCS) after TKA, until the second postoperative day. Physical function, stiffness, and pain were measured by using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Oxford Knee Score 12-item knee questionnaires, and visual analog scale at rest and during mobilization before TKA and 3 and 12 months afterward. Post hoc, a median split on poor functioning (WOMAC) was analyzed. Results Western Ontario and McMaster Universities Osteoarthritis Index, Oxford Knee Score 12-item knee, and visual analog scale scores improved significantly in all patients, without any differences among groups. Median (range) WOMAC at 3 months were in group F, 83 (20–97); group Fs, 72 (25–99); and group, FCS 76 (28–100) and at 12 months 87 (35–98), 77 (43–100), and 89 (35–100), respectively. Conclusions No differences were detected in the secondary outcomes we examined. Thus, improved postoperative outcome did not translate into improved functional outcome or long-term pain.

This review summarizes current knowledge concerning incidence, risk factors, and mechanisms of perioperative nerve injury, with focus on local anesthetic-induced neurotoxicity. Perioperative nerve injury is a complex phenomenon and can be caused by a number of clinical factors. Anesthetic risk factors for perioperative nerve injury include regional block technique, patient risk factors, and local anesthetic-induced neurotoxicity. Surgery can lead to nerve damage by use of tourniquets or by direct mechanical stress on nerves, such as traction, transection, compression, contusion, ischemia, and stretching. Current literature suggests that the majority of perioperative nerve injuries are unrelated to regional anesthesia. Besides the blockade of sodium channels which is responsible for the anesthetic effect, systemic local anesthetics can have a positive influence on the inflammatory response and the hemostatic system in the perioperative period. However, next to these beneficial effects, local anesthetics exhibit time and dose-dependent toxicity to a variety of tissues, including nerves. There is equivocal experimental evidence that the toxicity varies among local anesthetics. Even though the precise order of events during local anesthetic-induced neurotoxicity is not clear, possible cellular mechanisms have been identified. These include the intrinsic caspase-pathway, PI3K-pathway, and MAPK-pathways. Further research will need to determine whether these pathways are non-specifically activated by local anesthetics, or whether there is a single common precipitating factor.

UNLABELLED The reamer-irrigator-aspirator (RIA) is a device that has recently been developed to retrieve bone graft from the medullary canal of the femur and the tibia. As for most new surgical procedures, complications arise as part of the learning curve and/or imperfections in the design or technique. To increase awareness of potential complications and to prevent unnecessary harm to the patient, new complications need to be reported. We present case reports of 2 patients who developed severe intraoperative cardiac events presumably caused by excessive and rapid blood loss during RIA bone graft harvesting. This complication has not been described before. Increased awareness of excessive blood loss and subsequent cardiac events during an RIA procedure is warranted. LEVEL OF EVIDENCE Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Objective: Cerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other invasive procedures. We used a swine model of CAGE to determine if quantitative electroencephalography (qEEG) is a useful tool in diagnosis and prognostication of CAGE. Methods: 0.05 ml/kg of air was injected into the ascending pharyngeal artery in 16 pigs. Intracranial pressure, lactate in brain microdialysate and brain oxygen tension were measured during 4 h after embolization. The qEEG parameters mean amplitude (MAMP), alpha-delta ratio (ADR), spectral edge frequency (SEF90), spatial brain symmetry index (sBSI) and temporal brain symmetry index (tBSI) were calculated. Results: MAMP and tBSI but not ADR, SEF90 and sBSI correlate with intracranial pressure, brain lactate and brain oxygen tension after 4 h. Early levels of MAMP and tBSI can predict intracranial pressure, brain lactate and brain oxygen tension after 4 h. Conclusions: MAMP and tBSI are sensitive for cerebral injury and can predict outcome in a swine model of CAGE. Significance: This study provides evidence for the utility of qEEG for diagnosis and prognosis in CAGE. Further studies are necessary to investigate the use of this method in patients. (C) 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved

Background and objectives Local neurotoxicity of local anaesthetics is a well known phenomenon which is determined by lipophilicity. Recent reports have indicated the relevance of local anaesthetic-induced cytotoxicity also in nonneuronal tissues. This study re-evaluates the role of lipophilicity in local anaesthetic cytotoxicity in nonneuronal cells. In addition, the toxicities of pipecoloxylidine S(-) enantiomers were investigated. Methods Local anaesthetic-induced cytotoxicity was investigated in vitro in T-lymphoma cells (Jurkat). Cells were incubated with each of eight different local anaesthetics, two esters and six amides. Annexin V-fluorescein isothiocyanate and 7-aminoactinomycin D double staining followed by flow cytometry were used to investigate the fraction of early apoptotic cells as well as the overall cell death. The concentrations leading to 50% cell death (LC(50)) were calculated and compared. In a second step, we compared the toxicities of S(-) bupivacaine and the racemate as well as R(R) and S(-) ropivacaine. Results Concentration-dependent cytotoxicity was observed for all investigated local anaesthetics. Apoptosis was seen at low concentrations, whereas necrosis was observed at higher concentrations. LC(50) values of the different local anaesthetics yielded the following decreasing order of toxicity: tetracaine, bupivacaine, ropivacaine, prilocaine, procaine, lidocaine, articaine and mepivacaine. Toxicity correlated with octanol/buffer partition coefficients, but was independent of the ester or amide linkage. There was no effect of stereoisomerism on apoptosis and necrosis. Conclusion Moderate correlations for cytotoxicity with lipophilicity and clinical potency of local anaesthetics can be found in nonneuronal cells that are less than those reported previously with neuronal cells. Structural factors such as ester or amide linkage or stereospecificity do not have any influence on cytotoxicity. Although S(-) enantiomers may be advantageous with regard to systemic toxicity, they have no advantage in respect of local cytotoxicity in vitro. Eur J Anaesthesiol 2012;29:35-41 Published online 19 October 2011

Background: Neurotoxic properties of local anesthetics can rarely lead to irreversible neuronal damage as in cauda equina syndrome. Clinically, local anesthetics are often combined with adjuvants to improve or prolong the anesthetic effect, whereas the impact of such adjuvants on lidocaine-induced apoptosis is unclear. Therefore, we investigated the influence of different adjuvants on the neurotoxicity of lidocaine. Methods: Human neuroblastoma cells and primary rat astrocytes were incubated for 24 hrs with lidocaine at a toxic concentration alone and in combination with morphine, sufentanil, clonidine, epinephrine, neostigmine, ketamine, and midazolam. Subsequently, the rates of cell death and early apoptosis were measured by flow cytometry in neuroblastoma cells, whereas astrocyte viability was analyzed by mitochondrial activity assay. In addition, isobolograms were calculated to describe the additive effects of lidocaine with ketamine or midazolam, respectively. Results: Coadministration of lidocaine with sufentanil, clonidine, epinephrine, and neostigmine did not alter the rates of cell death compared with cells treated with lidocaine alone. Morphine improved the viability of astrocytes only at concentrations beyond those occurring clinically. In contrast, coincubation of lidocaine with ketamine or midazolam led to significantly increased rates of cell death. The combined toxicity of ketamine and lidocaine was additive, whereas the combined toxicity of midazolam and lidocaine was subadditive. Conclusions: Sufentanil, clonidine, epinephrine, and neostigmine do not influence the neurotoxicity of lidocaine in vitro. Morphine may have some cytoprotective effect at concentrations greater than those seen intrathecally in humans. In contrast, ketamine and midazolam increase the neurotoxicity of lidocaine in vitro, presumably by additive induction of mitochondrial apoptosis.

Cerebral arterial gas embolism is a risk in diving and occurs as a complication in surgery and interventional radiology. Swine models for cerebral arterial gas embolism have been used in the past. However, injection of air into the main artery feeding the pig brain - the ascending pharyngeal artery - might be complicated by the presence of the carotid rete, an arteriolar network at the base of the brain. On the other hand, anastomoses between external and internal carotid territories are present in the pig. In order to determine the most appropriate vessel for air injection, we performed experiments in which air was injected into either the ascending pharyngeal artery or the external carotid artery. We injected 0.25 ml/kg of room air selectively into the ascending pharyngeal artery or the external carotid artery of 35-40 kg Landrace pigs (n = 8). We assessed the effect on cerebral metabolism by measuring intracranial pressure, brain oxygen tension and brain glucose and lactate concentrations using cerebral microdialysis. Intracranial pressure and brain oxygen tension changed significantly in both groups, but did not differ between groups. Brain lactate increased significantly more in pigs in which air was injected into the ascending pharyngeal artery. Intracranial pressure, brain oxygen tension and brain lactate correlated after injection of air into the ascending pharyngeal artery, but not after injection into the external carotid artery. Our model is suitable for investigation of cerebral arterial gas embolism. The ascending pharyngeal artery is the most appropriate vessel for air injection. (C) 2010 Elsevier B.V. All rights reserved

Background Local anaesthetics are known to induce apoptosis in clinically relevant concentrations. Hitherto, it is unknown what determines the apoptotic potency of local anaesthetics. Therefore, we compared apoptosis induction by local anaesthetics related to their physicochemical properties in human neuronal cells. Methods Neuroblastoma cells (SHEP) were incubated with eight local anaesthetics, two of the ester and six of the amide types. At least, five concentrations of each local anaesthetic were evaluated. After incubation for 24 h, rates of cells in early apoptotic stages and overall cell death were evaluated by annexin V and 7-amino-actinomycin D double staining by flow cytometry. The concentrations that led to half-maximal neurotoxic effects (LD50) were calculated and compared for all local anaesthetics. Results All local anaesthetics were neurotoxic in a concentration-dependent manner. All drugs induced similar rates of early apoptotic cell formation at low concentrations, whereas at high concentrations, late apoptotic or necrotic cell death predominated. Comparison of LD50 values of the different local anaesthetics resulted in the following order of apoptotic potency from high to low toxicity: tetracaine>bupivacaine>prilocaine=mepivacaine=ropivacaine>lidocaine>procaine=articaine. The toxicity correlated with octanol/buffer coefficients and also with experimental potency of the local anaesthetic, but was unrelated to the structure (ester or amide type). Conclusions All commonly used local anaesthetics induce neuronal apoptosis in clinically used concentrations. The neurotoxicity correlates with lipid solubility and thus with the conduction blocking potency of the local anaesthetic, but is independent of the chemical class (ester/amide).

Background and Objectives: In neuraxial anesthesia, increase of skin temperature is an early sign of successful block. Yet, during peripheral nerve block of the lower extremity, increase in skin temperature is a highly sensitive, but late sign of a successful block. We hypothesized that after interscalene brachial plexus block, a rise in skin temperature follows impairment of sensation during successful nerve block and occurs only distally, as observed in the lower extremity. Methods: in the present study, we prospectively evaluated the changes in skin temperature after interscalene brachial plexus blockade in 45 patients scheduled for elective shoulder surgery. We assessed pinprick and cold sensation as well as skin temperature at sites of the skin innervated by the median, ulnar, radial, axillary and musculocutaneous nerve. Results: At the skin areas innervated by the axillary and musculocutaneous nerve, skin temperature did not increase after successful block. At the distal sites, innervated by the median, ulnar, and radial nerve, skin temperature increased significantly (1.9-2.1 degrees C within 30 min) after successful block while it did not after failed nerve block or on the contralateral side. in these areas attenuation of skin sensation preceded a measurable rise in skin temperature ( >= 1 degrees C) in 56.3% of nerve blocks, occurred at the same time in 35.2%, and in 8.5% the temperature rise occurred first. Conclusions: Assessment of skin temperature cannot predict the success of an interscalene brachial plexus block of the axillary and musculocutaneous nerve. Distally, the increase of skin temperature has a high sensitivity and specificity but occurs later than the loss of sensory and motor functions. Therefore, the measurement of skin temperature during interscalene blockade is of limited clinical value

Background: Local anesthetics, especially lidocaine, can lead to persistent cauda equina syndrome after spinal anesthesia. Recently, lidocaine has been reported to trigger apoptosis, although the underlying mechanisms remain unknown. To elucidate the pathway of lidocaine-induced apoptosis, the authors used genetically modified cells with overexpression or deficiencies of key regulators of apoptosis. Methods: Human Jurkat T-lymphoma cells overexpressing the antiapoptotic protein B-cell lymphoma 2 as well as cells deficient of caspase 9, caspase 8, or Fas-associated protein with death domain were exposed to lidocaine and compared with parental cells. The authors evaluated cell viability, mitochondrial alterations, cytochrome c release, caspase activation, and early apoptosis. Apoptosis was in addition investigated in neuroblastoma cells. Results: In Jurkat cells, lidocaine reduced viability, associated with a loss of the mitochondrial membrane potential. At low concentrations (3–6 mm) of lidocaine, caspase 3 was activated and release of cytochrome c was detected, whereas at higher concentrations (10 mm), no caspase activation was found. Apoptosis by lidocaine was strongly reduced by B-cell lymphoma-2 protein overexpression or caspase-9 deficiency, whereas cells lacking the death receptor pathway components caspase 8 and Fas-associated protein with death domain were not protected and displayed similar apoptotic alterations as the parental cells. Lidocaine also induced apoptotic caspase activation in neuroblastoma cells. Conclusions: Apoptosis is triggered by concentrations of lidocaine occurring intrathecally after spinal anesthesia, whereas higher concentrations induce necrosis. The data indicate that death receptors are not involved in lidocaine-induced apoptosis. In contrast, the observation that B-cell lymphoma-2 protein overexpression or the lack of caspase 9 abolished apoptosis clearly implicates the intrinsic mitochondrial death pathway in lidocaine-induced apoptosis.

OBJECTIVE: Inflammatory cytokines as well as nitric oxide (NO) play a key role in the pathogenesis of persistent and exaggerated pain states. To document this, we investigated whether a range of cytokines and NO were detectable in the plasma of chronic pain patients and whether cytokine and NO levels correlated with pain severity. METHODS: Plasma samples of 94 chronic pain patients and 6 healthy volunteers were obtained. Average pain intensity during the last 24 h was assessed on a 11-point numeric rating scale and patients were distributed to three groups: light, moderate and severe pain. The concentrations of TNF-alpha, GM-CSF, interleukin (IL)-1beta, IL-6, IL-8, interferon (IFN)-gamma, IL-2, IL-4, IL-5, IL-10 and nitrate/nitrite were determined. RESULTS: Patients with light pain demonstrated significantly increased levels of IL-6 compared to controls. In the severe pain group IL-6 and nitrate/nitrite were significantly increased. Serum concentrations of IL-1beta, TNF-alpha, IL-2 and IL-4 were increased but as we adjusted the level of significance at p = 0.0045, most cytokine plasma levels failed to reach statistical significance. CONCLUSIONS: Pro-inflammatory cytokines (IL-1beta, IL-2, IL-6, IFN-gamma, TNF-alpha) in the plasma correlate with increasing pain intensity. Chronic pain patients show a significant increase in plasma levels of NO in comparison to healthy controls

BACKGROUND AND OBJECTIVES: Skin-temperature increase is a reliable but late indicator of success during regional-anesthesia techniques. The goal of this study is to determine the distribution of skin-temperature changes during different regional techniques. Does skin temperature increase in the whole area innervated by the blocked neural structures or only in certain regions within this area with the capability to react preferentially to sympathetic block (i.e., vessel-rich skin)? Although onset time may vary between different regional-anesthetic techniques, we hypothesized that the distribution of skin warming is equal. METHODS: Skin temperature was assessed continuously by infrared thermography in 24 patients who received either combined femoral-nerve and sciatic-nerve block, epidural anesthesia, or spinal anesthesia. RESULTS: Apart from differences in time of onset, no differential spatial distribution of skin-temperature changes could be detected. The earliest and greatest rise of skin temperature occurred at the great toe (10.6 degrees C +/- 0.4 degrees C), became smaller proximally, and was negligible above the ankles, irrespective of the type and extent of block. Video-thermography revealed that cold blood flows through subcutaneous veins immediately after onset of sympathetic block and initially decreases skin temperature (0.6 degrees C +/- 0.3 degrees C) during onset of spinal anesthesia. CONCLUSION: Irrespective of the applied regional-anesthetic technique, skin-temperature changes are more pronounced distally. Thermography prevents false measurements of skin temperature above subcutaneous veins and displays flow of cold blood as the mechanism of initial skin-temperature drop after regional anesthesia. Measurements of skin-temperature increase cannot be used to evaluate the extent of analgesia or sympathetic block