The Impact of Regional Anesthesia in Masking Acute Compartment Syndrome after Limb Trauma.

Regional anesthesia has shown to be successful in controlling major pain in trauma patients. However, the possibility of masking acute compartment syndrome (ACS) after peripheral nerve blocks for limb injuries is still controversially discussed. Therefore, we aimed to summarize the current literature regarding this topic to shed light on the impact of peripheral regional anesthesia on the diagnosis of ACS in trauma patients. We searched Pubmed, Google Scholar and the Cochrane Library for literature following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines. The analysis of these reports was included in the context of the current literature concerning this topic. We found no (randomized) studies, and only six case reports dealing with the impact of peripheral nerve blocks and ACS in patients after a limb trauma met our criteria and were included in our review. Only one reported a delay in the diagnosis of ACS. In most of the cases (5 of 6), the breakthrough pain, despite the nerve block, proved to be a good indicator of a developing ACS. However, despite some narrative articles about the topic including some recommendations about the possibly safe use of regional anesthesia techniques for limb trauma, there is still no international consensus and only one national guideline focusing on the possibly safe use of peripheral nerve blocks in trauma patients at risk of ACS. After reviewing the respective literature, we consider that intra-articular analgesia, sensory blocks, fascial plane blocks and low-concentration continuous peripheral nerve blocks are effective for analgesia and a low-risk analgesia tool for trauma and postsurgical patients at risk of ACS due to the fact that they do not lead to a dense block. Finally, we summarized suggestions based on the results of the literature for the different regional anesthesia modalities in these patients in a table to facilitate the use of these techniques.

Surgical opioid-avoidance protocol: a postoperative pharmacological multimodal analgesic intervention in diverse patient populations.

INTRODUCTION: This study evaluated the effect of a surgical opioid-avoidance protocol (SOAP) on postoperative pain scores. The primary goal was to demonstrate that the SOAP was as effective as the pre-existing non-SOAP (without opioid restriction) protocol by measuring postoperative pain in a diverse, opioid-naive patient population undergoing inpatient surgery across multiple surgical services. METHODS: This prospective cohort study was divided into SOAP and non-SOAP groups based on surgery date. The non-SOAP group had no opioid restrictions (n=382), while the SOAP group (n=449) used a rigorous, opioid-avoidance order set with patient and staff education regarding multimodal analgesia. A non-inferiority analysis assessed the SOAP impact on postoperative pain scores. RESULTS: Postoperative pain scores in the SOAP group compared with the non-SOAP group were non-inferior (95% CI: -0.58, 0.10; non-inferiority margin=-1). The SOAP group consumed fewer postoperative opioids (median=0.67 (IQR=15) vs 8.17 morphine milliequivalents (MMEs) (IQR=40.33); p<0.01) and had fewer discharge prescription opioids (median=0 (IQR=60) vs 86.4 MMEs (IQR=140.4); p<0.01). DISCUSSION: The SOAP was as effective as the non-SOAP group in postoperative pain scores across a diverse patient population and associated with lower postoperative opioid consumption and discharge prescription opioids.

Acute Extremity Compartment Syndrome and (Regional): Anesthesia: The Monster Under the Bed.

Acute compartment syndrome (ACS) is a potential orthopedic emergency that leads, without prompt diagnosis and immediate treatment with surgical fasciotomy, to permanent disability. The role of regional anesthesia (RA) for analgesia in patients at risk for ACS remains unjustifiably controversial. This critical review aims to improve the perception of the published literature to answer the question, whether RA techniques actually delay or may even help to hasten the diagnosis of ACS. According to literature, peripheral RA alone does not delay ACS diagnosis and surgical treatment. Only in 4 clinical cases, epidural analgesia was associated with delayed ACS diagnosis.

Impact of Local Anesthetics on Cancer Behavior and Outcome during the Perioperative Period: A Review.

There is a growing interest regarding the impact of the perioperative period and the application of anesthetic drugs on the recurrence of cancer metastases. Among them, the use of amide-type local anesthetics seems promising since in vitro studies and animal models have shown their potential to inhibit the Intercellular Adhesion Molecule 1 (ICAM-1) expression and Src activity, which are clearly implicated in the process of inflammation and cancer metastases. This review emphasizes the potential of amide-type local anesthetics in this context.

Inadvertent Placement of an Infraclavicular Catheter in the Interscalene Region With an Unusual Complication: A Case Report.

An infraclavicular catheter is a very efficient technique to provide excellent perioperative anesthesia/analgesia for upper limb surgery. However, complications can occur and are dependent on the technique used. We report the inadvertent placement of an infraclavicular catheter in the interscalene region when an ultrasound-guided infraclavicular catheter was threaded cranially. We proposed some strategies to avoid the occurrence of complications when performing this block.

Low PEEP Mechanical Ventilation and PaO2/FiO2 Ratio Evolution in COVID-19 Patients.

Invasive mechanical ventilation (IMV) is the standard treatment in critically ill COVID-19 patients with acute severe respiratory distress syndrome (ARDS). When IMV setting is extremely aggressive, especially through the application of high positive-end-expiratory respiration (PEEP) values, lung damage can occur. Until today, in COVID-19 patients, two types of ARDS were identified (L- and H-type); for the L-type, a lower PEEP strategy was supposed to be preferred, but data are still missing. The aim of this study was to evaluate if a clinical management with lower PEEP values in critically ill L-type COVID-19 patients was safe and efficient in comparison to usual standard of care. A retrospective analysis was conducted on consecutive patients with COVID-19 ARDS admitted to the ICU and treated with IMV. Patients were treated with a lower PEEP strategy adapted to BMI: PEEP 10 cmH2O if BMI < 30 kg m-2, PEEP 12 cmH2O if BMI 30-50 kg m-2, PEEP 15 cmH2O if BMI > 50 kg m-2. Primary endpoint was the PaO2/FiO2 ratio evolution during the first 3 IMV days; secondary endpoints were to analyze ICU length of stay (LOS) and IMV length. From March 2 to January 15, 2021, 79 patients underwent IMV. Average applied PEEP was 11 ± 2.9 cmH2O for BMI < 30 kg m-2 and 16 ± 3.18 cmH2O for BMI > 30 kg m-2. During the first 24 h of IMV, patients' PaO2/FiO2 ratio presented an improvement (p<0.001; CI 99%) that continued daily up to 72 h (p<0.001; CI 99%). Median ICU LOS was 15 days (10-28); median duration of IMV was 12 days (8-26). The ICU mortality rate was 31.6%. Lower PEEP strategy treatment in L-type COVID-19 ARDS resulted in a PaO2/FiO2 ratio persistent daily improvement during the first 72 h of IMV. A lower PEEP strategy could be beneficial in the first phase of ARDS in critically ill COVID-19 patients.

Peripheral nerve block anesthesia/analgesia for patients undergoing primary hip and knee arthroplasty: recommendations from the International Consensus on Anesthesia-Related Outcomes after Surgery (ICAROS) group based on a systematic review and meta-analysis of current literature.

BACKGROUND: Evidence-based international expert consensus regarding the impact of peripheral nerve block (PNB) use in total hip/knee arthroplasty surgery. METHODS: A systematic review and meta-analysis: randomized controlled and observational studies investigating the impact of PNB utilization on major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, thromboembolic, neurologic, infectious, and bleeding complications.Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, were queried from 1946 to August 4, 2020.The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess evidence quality and for the development of recommendations. RESULTS: Analysis of 122 studies revealed that PNB use (compared with no use) was associated with lower ORs for (OR with 95% CIs) for numerous complications (total hip and knee arthroplasties (THA/TKA), respectively): cognitive dysfunction (OR 0.30, 95% CI 0.17 to 0.53/OR 0.52, 95% CI 0.34 to 0.80), respiratory failure (OR 0.36, 95% CI 0.17 to 0.74/OR 0.37, 95% CI 0.18 to 0.75), cardiac complications (OR 0.84, 95% CI 0.76 to 0.93/OR 0.83, 95% CI 0.79 to 0.86), surgical site infections (OR 0.55 95% CI 0.47 to 0.64/OR 0.86 95% CI 0.80 to 0.91), thromboembolism (OR 0.74, 95% CI 0.58 to 0.96/OR 0.90, 95% CI 0.84 to 0.96) and blood transfusion (OR 0.84, 95% CI 0.83 to 0.86/OR 0.91, 95% CI 0.90 to 0.92). CONCLUSIONS: Based on the current body of evidence, the consensus group recommends PNB use in THA/TKA for improved outcomes. RECOMMENDATION: PNB use is recommended for patients undergoing THA and TKA except when contraindications preclude their use. Furthermore, the alignment of provider skills and practice location resources needs to be ensured. Evidence level: moderate; recommendation: strong.

Inflammation reduces osteoblast cytotoxicity induced by diclofenac: An in vitro study.

BACKGROUND: Diclofenac and other NSAIDs are routinely used in the postoperative period. Their effect on fracture healing remains unclear and controversial. OBJECTIVE: The primary outcome was to assess the potential cytotoxicity of clinically relevant concentrations of diclofenac on human osteoblasts. DESIGN: Laboratory in vitro study. SETTING: Institute of Physiology, Zurich, Center for Integrative Human Physiology, University of Zurich. MATERIALS: Monolayers of human osteoblasts. INTERVENTIONS: Exposure of human osteoblast monolayers to several concentrations of diclofenac, for different periods of time, with and without an artificially induced inflammatory process. MAIN OUTCOME MEASURES: Cell count, cell viability, cell proliferation and apoptosis. RESULTS: A concentration-mediated, time and exposure dependent cytotoxic effect of diclofenac-mediated apoptosis was observed. Stimulated inflammatory conditions seemed to reduce toxic effects. CONCLUSION: Cytotoxic effects of diclofenac are exposure, time and concentration dependent. Simulating aspects of inflammatory conditions seems to increase resistance to diclofenac cytotoxicity, especially in the presence of higher concentration and longer exposure time.

The relationship between postoperative opioid consumption and the incidence of hypoxemic events following total hip arthroplasty: a post hoc analysis.

Background: Postoperative opioid analgesia may cause respiratory depression. We assessed whether following total hip arthroplasty, placebo-adjusted reductions in morphine consumption at 48 hours with parecoxib (47.0%), propacetamol (35.1%) or parecoxib plus propacetamol (67.9%) translated into a reduction in hypoxemic events. Methods: This was a post hoc analysis of a randomized, placebo-controlled, noninferiority study. Patients were randomly assigned to receive intravenous parecoxib (40 mg twice daily), propacetamol (2 g 4 times daily), parecoxib plus propacetamol (40 mg twice daily + 2 g 4 times daily) or placebo. Dose, date and time of morphine administration via patient-controlled analgesia were monitored throughout the study. In patients not receiving supplemental oxygen, peripheral blood oxygenation was assessed continuously for 48 hours after surgery. Hypoxemia was defined as peripheral oxygen saturation less than 90%. The times and oximeter readings of hypoxemic events were recorded. Pearson correlation coefficient was used to assess for correlations between cumulative morphine consumption at 48 hours and mean number of hypoxemic events. Results: A significantly smaller proportion of patients who received the combined treatment with parecoxib and propacetamol had hypoxemia versus placebo (2.8% v. 13.2%, p < 0.05), and the mean number of hypoxemic events was significantly smaller for parecoxib (0.12), propacetamol (0.06) and parecoxib plus propacetamol (0.03) versus placebo (0.36; all p < 0.05). There was no correlation between the reduction in cumulative morphine consumption at 48 hours and the mean number of hypoxemic events in any treatment group (all p > 0.1). Conclusion: Following total hip arthroplasty, a greater than 70% reduction in morphine consumption may be necessary to translate into a corresponding reduction in hypoxemic events.

Contexte: L'utilisation d'analgésiques opioïdes en période postopératoire peut provoquer une dépression respiratoire. Nous avons voulu déterminer si, après une arthroplastie totale de la hanche, une réduction de la consommation de morphine à 48 heures par l'administration de parécoxib (47,0 %), de propacétamol (35,1 %) ou d'une combinaison des deux (67,9 %) ­ avec ajustement selon un groupe placebo ­ se traduirait par une réduction du nombre d'épisodes d'hypoxémie. Méthodes: Nous avons effectué une analyse post hoc d'une étude randomisée de non-infériorité avec témoins sous placebo. Après une répartition aléatoire, chaque patient a reçu par intraveineuse du parécoxib (40 mg 2 fois par jour), du propacétamol (2 g 4 fois par jour), une combinaison de parécoxib et de propacétamol (40 mg 2 fois par jour + 2 g 4 fois par jour) ou un placebo. Tout au long de l'étude, la dose, la date et le moment de l'administration de morphine contrôlée par le patient ont été notés. Chez les patients qui ne recevaient pas d'oxygène d'appoint, la saturation périphérique en oxygène a été surveillée de manière continue pendant les 48 heures suivant l'opération. L'hypoxémie a été définie comme une saturation inférieure à 90 %. Le moment et les données d'oxymétrie ont été notés pour chaque épisode d'hypoxémie. Le coefficient de corrélation de Pearson a été utilisé pour évaluer la présence de corrélations entre la consommation cumulative de morphine durant les premières 48 heures et le nombre moyen d'épisodes d'hypoxémie. Résultats: Une proportion significativement plus faible de patients ayant reçu le traitement combiné de parécoxib et de propacétamol ont connu des épisodes d'hypoxémie, comparativement aux patients qui avaient reçu le placebo (2,8 % c. 13,2 %, p < 0,05), et le nombre moyen d'épisodes d'hypoxémie était significativement plus faible dans le groupe ayant reçu du parécoxib (0,12), du propacétamol (0,06) ou une combinaison de parécoxib et de propacétamol (0,03), par rapport au groupe placebo (0,36, p < 0,05 pour tous). Aucune corrélation n'a été observée entre la réduction de la quantité totale de morphine consommée à 48 heures et le nombre moyen d'épisodes d'hypoxémie pour tous les groupes (p > 0,1 pour tous). Conclusion: Après une arthroplastie totale de la hanche, une réduction de la consommation de morphine de plus de 70 % pourrait être nécessaire pour obtenir une réduction correspondante du nombre d'épisodes d'hypoxémie.

NOACs in Anesthesiology.

BACKGROUND: Due to increasing use of new oral anticoagulants (NOACs), clinicians are faced more and more frequently with clinical issues related to these drugs. OBJECTIVE: The objective of this publication is to make practical suggestions for the perioperative management of NOACs as well as for their handling in overdoses and bleedings. RECOMMENDATIONS: In elective surgery and creatinine clearance ≥ 50 ml/min, a NOAC should be discontinued 24-36 h before the intervention, and even earlier in case of reduced kidney function. In emergency interventions that cannot be delayed, the management is dependent on the NOAC plasma levels. With levels ≤ 30 ng/ml, surgery can be performed. With levels >30 ng/ml, reversal agents should be considered. In low bleeding risk surgery, NOACs can be re-started 24 h after the intervention, which is prolonged to 48-72 h after surgery with high bleeding risk. In case of NOAC overdose and minor bleedings, temporary discontinuation and supportive care are usually sufficient to control the situation. In severe or life-threatening bleedings, nonspecific and specific reversal agents should be considered.

Anaesthetic care of patients undergoing primary hip and knee arthroplasty: consensus recommendations from the International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) based on a systematic review and meta-analysis.

BACKGROUND: Evidence-based international expert consensus regarding anaesthetic practice in hip/knee arthroplasty surgery is needed for improved healthcare outcomes. METHODS: The International Consensus on Anaesthesia-Related Outcomes after Surgery group (ICAROS) systematic review, including randomised controlled and observational studies comparing neuraxial to general anaesthesia regarding major complications, including mortality, cardiac, pulmonary, gastrointestinal, renal, genitourinary, thromboembolic, neurological, infectious, and bleeding complications. Medline, PubMed, Embase, and Cochrane Library including Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, NHS Economic Evaluation Database, from 1946 to May 17, 2018 were queried. Meta-analysis and Grading of Recommendations Assessment, Development and Evaluation approach was utilised to assess evidence quality and to develop recommendations. RESULTS: The analysis of 94 studies revealed that neuraxial anaesthesia was associated with lower odds or no difference in virtually all reported complications, except for urinary retention. Excerpt of complications for neuraxial vs general anaesthesia in hip/knee arthroplasty, respectively: mortality odds ratio (OR): 0.67, 95% confidence interval (CI): 0.57-0.80/OR: 0.83, 95% CI: 0.60-1.15; pulmonary OR: 0.65, 95% CI: 0.52-0.80/OR: 0.69, 95% CI: 0.58-0.81; acute renal failure OR: 0.69, 95% CI: 0.59-0.81/OR: 0.73, 95% CI: 0.65-0.82; deep venous thrombosis OR: 0.52, 95% CI: 0.42-0.65/OR: 0.77, 95% CI: 0.64-0.93; infections OR: 0.73, 95% CI: 0.67-0.79/OR: 0.80, 95% CI: 0.76-0.85; and blood transfusion OR: 0.85, 95% CI: 0.82-0.89/OR: 0.84, 95% CI: 0.82-0.87. CONCLUSIONS: Recommendation: primary neuraxial anaesthesia is preferred for knee arthroplasty, given several positive postoperative outcome benefits; evidence level: low, weak recommendation. RECOMMENDATION: neuraxial anaesthesia is recommended for hip arthroplasty given associated outcome benefits; evidence level: moderate-low, strong recommendation. Based on current evidence, the consensus group recommends neuraxial over general anaesthesia for hip/knee arthroplasty. TRIAL REGISTRY NUMBER: PROSPERO CRD42018099935.

Dendrimer-Based Platform for Effective Capture of Tumor Cells after TGFß1-Induced Epithelial-Mesenchymal Transition.

Detection of circulating tumor cells (CTCs) relying on their expression of epithelial cell markers, such as epithelial cell adhesion molecule (EpCAM), has been commonly used. However, this approach unlikely captures CTCs that have undergone the process of epithelial-mesenchymal transition (EMT). In this study, we have induced EMT of in vitro prostate (PCa) and breast cancer (BCa) cell lines by treatment of transforming growth factor ß 1 (TGFß1), a pleiotropic cytokine with transition-regulating activities. We found that the TGFß1-treated, post-EMT cells exhibited up to a 45% reduction in binding affinity to antibodies against EpCAM (aEpCAM). To overcome this limitation, we designed our capture platform that integrates a unique combination of biomimetic cell rolling, dendrimer-mediated multivalent binding, and antibody cocktails of aEpCAM/aEGFR/aHER-2. Our capture surfaces resulted in up to 98% capture efficiency of post-EMT cells from mixtures of TGFß1-treated and untreated cancer cells spiked in culture media and human blood. In a clinical pilot study, our CTC device was also able to capture rare CTCs from PCa patients with significantly enhanced capture sensitivity and purity compared to the control surface with aEpCAM only, demonstrating its potential to provide a reliable detection solution for CTCs regardless of their EMT status.

Persistent postdischarge pain and chronic postoperative pain after breast cancer surgery under general anesthesia and single-shot paravertebral block: incidence, characteristics and impact on quality of life and healthcare costs.

Introduction: Breast surgery is associated with persistent postsurgical pain; usually related to poorly treated acute pain. Paravertebral block has been successfully employed in analgesic protocols for breast surgery; its impact on postdischarge pain (PDP) has not been investigated. The aim of this study was to assess characteristics of PDP after breast surgery, the development of chronic postoperative pain (CPP) and its impact on health care costs. Methods: We conducted a retrospective, observational study on a continuous cohort of adult female patients undergoing local breast cancer surgery under combined anesthesia. All patients were interviewed 6 months after hospital discharge. The survey was specifically conceived to assess incidence, features and duration of PDP. The overall cost of additional healthcare resources consumed with a specific relationship to persistent PDP was estimated. Results: A database of 244 patients was preliminarily analyzed. Of these, 188 were included in the following statistical analysis; 123 patients (65.2%) reported significant PDP, with a median intensity on NRS of 6 (IQR=2), more frequently described as burning and associated with paresthesia and/or hyperalgesia (87 patients, 46%). One hundred and six patients (56.5%) reported this pain as interfering with their normal daily activities, work and sleep. In 26.8% of cases (50 patients) symptoms lasted more than 1 month and in 28 patients (15.0%) pain became chronic. The majority of patients self-treated their pain with non-steroideal anti-inflammatory drugs, but in 50 patients (26.8%) this therapy was reported as ineffective. This additional consumption of healthcare resources led to a significant economical impact. Conclusion: PDP and CPP seem to be common complications after breast cancer surgery, even if a combined anesthesia technique with a thoracic paravertebral block is performed, leading to severe consequences on patients' quality of life and increasing consumption of healthcare resources after discharge. Trial number: NCT03618459 (www.clinicaltrials.gov).

How Anesthetic, Analgesic and Other Non-Surgical Techniques During Cancer Surgery Might Affect Postoperative Oncologic Outcomes: A Summary of Current State of Evidence.

The question of whether anesthetic, analgesic or other perioperative intervention during cancer resection surgery might influence long-term oncologic outcomes has generated much attention over the past 13 years. A wealth of experimental and observational clinical data have been published, but the results of prospective, randomized clinical trials are awaited. The European Union supports a pan-European network of researchers, clinicians and industry partners engaged in this question (COST Action 15204: Euro-Periscope). In this narrative review, members of the Euro-Periscope network briefly summarize the current state of evidence pertaining to the potential effects of the most commonly deployed anesthetic and analgesic techniques and other non-surgical interventions during cancer resection surgery on tumor recurrence or metastasis.

Early Recognition of a Transient Ischemic Attack Utilizing Cerebral Oxygenation Monitoring During Shoulder Surgery in the Beach Chair Position: A Case Report.

Shoulder surgery in the beach chair position is routinely performed, and central neurological events are rare but potentially devastating. We present a patient with transient neurological deficits after a sudden blood pressure drop with a simultaneous decrease of regional cerebral saturation values registered by cerebral oximetry. We reviewed published cases and proposed possible strategies to prevent the occurrence of similar complications in this context.

Impact of perioperative pain management on cancer recurrence: an ASRA/ESRA special article.

Cancer causes considerable suffering and 80% of advanced cancer patients experience moderate to severe pain. Surgical tumor excision remains a cornerstone of primary cancer treatment, but is also recognized as one of the greatest risk factors for metastatic spread. The perioperative period, characterized by the surgical stress response, pharmacologic-induced angiogenesis, and immunomodulation results in a physiologic environment that supports tumor spread and distant reimplantation.In the perioperative period, anesthesiologists may have a brief and uniquewindow of opportunity to modulate the unwanted consequences of the stressresponse on the immune system and minimize residual disease. This reviewdiscusses the current research on analgesic therapies and their impact ondisease progression, followed by an evidence-based evaluation of perioperativepain interventions and medications.

The beach chair position for shoulder surgery in intravenous general anesthesia and controlled hypotension: Impact on cerebral oxygenation, cerebral blood flow and neurobehavioral outcome.

STUDY OBJECTIVES: The aim of this study was to assess the impact of intravenous general anesthesia and controlled hypotension on cerebral saturation (rScO2), cerebral blood flow measured as middle cerebral artery blood flow velocity (Vmax MCA) and neurobehavioral outcome in patients scheduled for shoulder surgery in beach chair position. DESIGN: Prospective, assessor-blinded observational study. SETTING: University hospital, shoulder surgery operating room. PATIENTS: Forty ASA I-II patients scheduled for shoulder surgery in beach chair position and controlled hypotension. INTERVENTIONS: Neurological and neurobehavioral tests were performed prior and the day after surgery. The baseline data for near-infrared spectroscopy, bispectral index, cerebral blood flow, PaCO2 and invasive blood pressure (radial artery) were taken prior anesthesia and after anesthesia induction, after beach chair positioning and all 20 min after surgery start until discharge of the patient. MEASUREMENTS: Neurological and neurobehavioral tests, cerebral saturation (rScO2) using near-infrared spectroscopy, BIS, cerebral blood flow using Doppler of the middle cerebral artery (Vmax MCA), PaCO2 and invasive blood pressure assessed at heart and at the external acoustic meatus level. MAIN RESULTS: The incidence of cerebral desaturation events (CDEs) was 25%. The blood pressure drop 5 min after beach chair position measured at the acoustic meatus level in the CDE group was higher compared to patients without CDEs (p = 0.009) as was the rScO2 (p = 0.039) and the Vmax MCA (p = 0.002). There were no neurological deficits but patients with CDEs showed a greater negative impact on neurobehavioral tests 24 h after surgery compared to patients without CDEs (p = 0.001). CONCLUSIONS: In ASA I-II patients intravenous general anesthesia and controlled hypotension in the beach chair position affects cerebral blood flow and cerebral oxygenation with impact on the neurobehavioral outcome.

Does spinal chloroprocaine pharmacokinetic profile actually translate into a clinical advantage in terms of clinical outcomes when compared to low-dose spinal bupivacaine? A systematic review and meta-analysis.

STUDY OBJECTIVE: Spinal anesthesia is well suited for day-care surgery, however a persisting motor block after surgery can delay discharge. Among the new drugs available, chloroprocaine has been associated with a short onset time, and motor block duration and a quicker discharge. However, it is not clear if those outcomes are clinically significantly superior compared to those associated with the use of low-dose hyperbaric bupivacaine. DESIGN: Aim of the study was to determine if spinal 2-chloroprocaine was superior to low-dose spinal bupivacaine regarding the following outcomes: onset time, block duration, time to ambulation and time to discharge. PATIENTS/INTERVENTIONS: We performed a systematic literature search of the last 30 years using PubMed Embase and the Cochrane Controlled Trials Register. We included only blinded, prospective trials comparing chloroprocaine with a low dose of bupivacaine for spinal anesthesia. Low dose bupivacaine was defined as a dose of 10 mg or less. Outcomes of interest were time to motor block regression (primary outcome), time to ambulation and time to discharge (secondary outcomes), as indirect indicators of a complete recovery after spinal anesthesia. MAIN RESULTS: Compared to a low dose bupivacaine, spinal 2-chloroprocaine was associated with significantly faster motor and sensory block regression (pMD = -57 min-140.3 min; P = 0.015 and <0.001 respectively), a significantly shorter time to ambulation and an earlier discharge (pMD = -84.6 min; P < 0.001 and pMD = -88.6 min and <0.001 respectively). Onset time did not differ between the two drugs (pMD = -1.1 min; P = 0.118). CONCLUSIONS: Spinal 2-chloroprocaine has a shorter motor block duration, a significantly quicker time to ambulation and time to discharge compared to low dose hyperbaric bupivacaine and may be advantageous when spinal anesthesia is performed for day case surgery.

New local anesthetics.

Local anesthetics are used for performing various regional anesthesia techniques to provide intraoperative anesthesia and analgesia, as well as for the treatment of acute and chronic pain. Older medications such as lidocaine and bupivacaine as well as newer ones such as mepivacaine and ropivacaine are being used successfully for decades. Routes of administration include neuraxial, perineural, intravenous, various infiltrative approaches, topical, and transdermal. There are new innovations with the use of older local anesthetics in a novel manner, in addition to the development and use of new formulations. This chapter seeks to summarize the pharmacokinetics of local anesthetics and address the role of newer local anesthetics, as well as clinical implications, safety profiles, and the future of local anesthetic research. Finally, some clinical pearls are highlighted.

The effect of nonsteroidal anti-inflammatory drugs on bone healing in humans: A qualitative, systematic review.

STUDY OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in postoperative pain management. While an increasing number of in vitro and animal studies point toward an inhibitory effect of NSAIDs on bone healing process, the few existing retro- and prospective clinical studies present conflicting data. DESIGN: The aim of this qualitative, systematic review was to investigate the impact of perioperative use of NSAIDs in humans on postoperative fracture/spinal fusion healing compared to other used analgesics measured as fracture nonunion with radiological control. PATIENTS/INTERVENTIONS: We performed a systematic literature search of the last 38 years using PubMed Embase and the Cochrane Controlled Trials Register including retro- and prospective clinical, human trials assessing the effect of NSAIDs on postoperative fracture/spinal fusion healing when used for perioperative pain management with a radiological follow up to assess eventual nonunion. Due to different study designs, drugs, dosages/exposition times and different methods to assess fracture nonunion, these studies were not pooled for a meta-analysis. A descriptive summary of all studies, level of evidence, study quality and study bias assessment using different scores were used. MAIN RESULTS: Three prospective randomized controlled studies and thirteen retrospective cohort human studies were identified for a total of 12'895 patients. The overall study quality was low according to Jadad and Oxford Levels of Evidence scores. CONCLUSIONS: Published results of human trials did not show strong evidence that NDAIDs for pain therapy after fracture osteosynthesis or spinal fusion lead to an increased nonunion rate. Reviewed studies present such conflicting data, that no clinical recommendation can be made regarding the appropriate use of NSAIDs in this context. Considering laboratory data of animal, human tissue research and recommendation of clinical reviews, a short perioperative exposition to NSAIDs is most likely not deleterious. However, randomized, controlled studies are warranted to support or refute this hypothesis.