Novel Biodegradable 3D-Printed Analgesics-Eluting-Nanofibers Incorporated Nuss Bars for Therapy of Pectus Excavatum.

A novel hybrid biodegradable Nuss bar model was developed to surgically correct the pectus excavatum and reduce the associated pain during treatment. The scheme consisted of a three-dimensional (3D) printed biodegradable polylactide (PLA) Nuss bar as the surgical implant and electrospun polylactide-polyglycolide (PLGA) nanofibers loaded with lidocaine and ketorolac as the analgesic agents. The degradation rate and mechanical properties of the PLA Nuss bars were characterized after submersion in a buffered mixture for different time periods. In addition, the in vivo biocompatibility of the integrated PLA Nuss bars/analgesic-loaded PLGA nanofibers was assessed using a rabbit chest wall model. The outcomes of this work suggest that integration of PLA Nuss bar and PLGA/analgesic nanofibers could successfully enhance the results of pectus excavatum treatment in the animal model. The histological analysis also demonstrated good biocompatibility of the PLA Nuss bars with animal tissues. Eventually, the 3D printed biodegradable Nuss bars may have a potential role in pectus excavatum treatment in humans.

Wooden Chest syndrome: The atypical pharmacology of fentanyl overdose.

WHAT IS KNOWN AND OBJECTIVE: A large percentage of opioid overdose fatalities involve fentanyl or one of its legal or illegal analogs (F/FAs). Is there something about the pharmacology of these drugs that make them unusually dangerous in an overdose? COMMENT: Some of the reasons for the dangers of overdose of F/FAs is their high potency and low cost (that leads to wide distribution). But it is rarely asked if the basic pharmacology of F/FAs differ in some fundamental way from conventional opioids such as morphine and heroin. In addition to centrally mediated respiratory depression via opioid receptors, F/FAs cause rigidity in the key respiratory muscles of the chest, upper airway and diaphragm ("wooden chest syndrome," WCS) by a non-opioid mechanism. WHAT IS NEW AND CONCLUSION: WCS is an atypical pharmacology of F/FAs. Because of its rapid onset and non-opioid mechanism, WCS makes F/FA overdose particularly dangerous.

Overdoses due to fentanyl and its analogues (F/FAs) push naloxone to the limit.

WHAT IS KNOWN AND OBJECTIVE: Food and Drug Administration (FDA) risk evaluation and mitigation strategies (REMs) encourage emergency responders, paramedics, law enforcement agents, and even laypeople to be trained in the administration of naloxone with the intent of rescuing individuals from a known or suspected opioid overdose. COMMENT: Although naloxone is generally safe and effective at reversing respiratory depression caused by a conventional opioid such as morphine or heroin by competing with the opioid and displacing it from the µ-opioid receptor, questions increasingly are arising as to whether naloxone can adequately reverse opioid overdoses that may involve the potent opioids fentanyl and its analogues (F/FAs). In other words, as more and more opioid overdoses involve F/FAs, can naloxone keep up? WHAT IS NEW AND CONCLUSION: As a competitive antagonist at µ-opioid receptors, naloxone is often a life-saving agent in cases of overdose caused by conventional opioids, but it may not be versatile or powerful enough to combat the rising tide of overdoses due to fentanyl and its illicit analogues, or in cases of overdose involving combinations of opioids and non-opioids.

Antibacterial and antibiofilm effects of flufenamic acid against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are one of the most serious surgery complications, and their prevention is of utmost importance. Flufenamic acid is a non-steroid anti-inflammatory drug approved for clinical use to relieve inflammation and pain in rheumatoid arthritis patients. In this study, we explored the antibacterial efficacy of flufenamic acid and the mechanisms underlying this effect. By using minimal inhibitory concentration (MIC), time-kill, resistance induction assays, and the antibiotic synergy test, we demonstrated that flufenamic acid inhibited the growth of methicillin-resistant staphylococci and did not induce resistance when it was used at the MIC. Furthermore, flufenamic acid acted synergistically with the beta-lactam antibiotic oxacillin and did not show significant toxicity toward mammalian cells. The biofilm inhibition assay revealed that flufenamic acid could prevent biofilm formation on medical implants and destroy the ultrastructure of the bacterial cell wall. RNA sequencing and quantitative RT-PCR indicated that flufenamic acid inhibited the expression of genes associated with peptidoglycan biosynthesis, beta-lactam resistance, quorum sensing, and biofilm formation. Furthermore, flufenamic acid efficiently ameliorated a local infection caused by MRSA in mice. In conclusion, flufenamic acid may be a potent therapeutic compound against MRSA infections and a promising candidate for antimicrobial coating of implants and surgical devices.

Pamidronate in chronic non-bacterial osteomyelitis: a randomized, double-blinded, placebo-controlled pilot trial.

OBJECTIVE: This is the first randomized double-blinded, placebo-controlled pilot trial to investigate the efficacy of pamidronate in reducing radiological and clinical disease activity in chronic non-bacterial osteomyelitis (CNO). METHOD: Patients received pamidronate or placebo at baseline and weeks 12 and 24. Whole-body magnetic resonance imaging was performed at baseline and weeks 12 and 36, and computed tomography of the anterior chest wall (ACW) at baseline and week 36. Radiological disease activity was systematically scored in the ACW and spine. Patient-reported outcomes [visual analogue scale (VAS) pain, VAS global health, Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions (EQ-5D), and 36-item Short-Form Health Survey (SF-36)] and biomarkers of bone turnover and inflammation were assessed at baseline and weeks 1, 4, 12, 24, and 36. Data are expressed as median [interquartile range]. RESULTS: Fourteen patients were randomized and 12 were analysed. From baseline to week 36, the radiological disease activity score in the ACW decreased from 5 [4-7] to 2.5 [1-3] in the pamidronate group, but did not change in the placebo group (p = 0.04). From baseline to week 36, VAS pain and VAS global health tended to decrease more in the pamidronate than in the placebo group (p = 0.11, p = 0.08). Physical functioning (HAQ) and health-related quality of life (EQ-5D, SF-36) did not change. Biomarkers of bone turnover decreased only in the pamidronate group (p ≤ 0.02). CONCLUSION: Pamidronate may improve radiological and clinical disease activity in CNO. Methods to score radiological disease activity in adult CNO were suggested. Clinical Trials: NCT02594878.

Regional Anesthesia in Cardiac Surgery: An Overview of Fascial Plane Chest Wall Blocks.

Optimal analgesia is an integral part of enhanced recovery after surgery (ERAS) programs designed to improve patients' perioperative experience and outcomes. Regional anesthetic techniques in a form of various fascial plane chest wall blocks are an important adjunct to the optimal postoperative analgesia in cardiac surgery. The most common application of fascial plane chest wall blocks has been for minimally invasive cardiac surgical procedures. An abundance of case reports has been described in the anesthesia literature and reports appear promising, yet higher-level safety and efficacy evidence is lacking. Those providing anesthesia for minimally invasive cardiac procedures should become familiar with fascial plane anatomy and block techniques to be able to provide enhanced postsurgical analgesia and facilitate faster functional recovery and earlier discharge. The purpose of this review is to provide an overview of contemporary fascial plane chest wall blocks used for analgesia in cardiothoracic surgery. Specifically, we focus on relevant anatomic considerations and technical descriptions including pectoralis I and II, serratus anterior, pectointercostal fascial, transverse thoracic muscle, and erector spine plane blocks. In addition, we provide a summary of reported local anesthetic doses used for these blocks and a current state of the literature investigating their efficacy, duration, and comparisons with standard practices. Finally, we hope to stimulate further research with a focus on delineating mechanisms of action of novel emerging blocks, appropriate dosing regimens, and subsequent analysis of their effect on patient outcomes.

Wooden chest syndrome: Beware of opioid antagonists, not just agonists.

BACKGROUND: In a constantly increasing world of opioid addiction, naloxone has become a topic of great discussion and use. With seemingly minimal side effects, naloxone has become one of the most wellknown and widely used reversal agents for opioid intoxication. While more common effects of using naloxone include agitation, abdominal cramps, piloerection, diarrhea, nausea, and yawning, lesser known side effects involve muscle spasms, flushing, hyperreflexia in neonates, and seizures. This case study demonstrates a side effect of rigidity secondary to IV naloxone that has not previously been documented. CASE: A 56 year old man was brought in by EMS after being found unresponsive in a car with a bag of drugs beside him. He was given 0.5 mg naloxone IV by EMS and immediately brought to the hospital. On arrival, the pt was noted to have tight rigidity of his upper extremities, with severe flexion. This presentation was not noted before the delivery of naloxone by EMS. CONCLUSIONS: While this case highlights a patient with a rare side effect of naloxone, it reminds physicians that all medications come with a cost. Of course, ABCs remain the highest priority of resuscitation, however when administering a medication to reverse a drug overdose, it is important to keep in mind all possible consequences of said agent. Recognizing that complete muscle rigidity may remain a result of naloxone administration allows physicians to perhaps save patients from further medical workup.

Review of Procedures for Reconstruction of Soft Tissue Chest Wall Defects Following Advanced Breast Malignancies.

The purpose of this article is to review closure options for complex chest wounds in patients with locally advanced breast cancer. Experiences of the plastic and oncologic surgery teams at Moffitt Cancer Center were reviewed, and the literature researched for various surgical options of complex chest wound closure. Multiple treatment modalities exist for reconstruction of complex chest wall wounds with the external oblique and V-Y latissimus dorsi musculocutaneous advancement flaps serving as workhorses in reconstruction. Treatment of cancer has moved from simply a surgical solution to include other modalities such as hormonal therapy, chemotherapy, and radiation-the latter 2 having serious consequences for wound healing. A team approach and knowledge of available flap options are vital for closure of complex wounds in a timely manner. Appropriate planning can optimize the primary goal of the oncologic surgeon to remove the cancer and the plastic surgeon's objective to reconstruct the defect and achieve a closed, durable wound prior to chemotherapy and radiation. We present the experience at the Moffitt Cancer Center in reconstructing challenging chest defects and review the reconstructive ladder.

Aminophylline increases parasternal muscle action in awake canines.

The traditional theophylline bronchodilator, aminophylline, is still widely used, especially in the treatment of COPD. The effects of aminophylline on ventilation and action of the costal diaphragm have been previously defined, but other respiratory muscles - notably the chest wall, are not well determined. Therefore, we investigated the effects of aminophylline on the Parasternal intercostal, a key obligatory inspiratory muscle, examining muscle length, shortening and EMG. We studied 11 awake canines, chronically implanted with sonomicrometer crystals and fine-wire EMG electrodes in the parasternal muscle. Ventilatory parameters, muscle length (shortening), and moving average muscle EMG activity, were measured at baseline and with aminophylline, during resting and hypercapnic stimulated breathing. Experiments were carried out prior to administration of aminophylline (baseline), and 1.5 h after loading and ongoing infusion. Minute ventilation, tidal volume and respiratory frequency all increased significantly with aminophylline, both during resting breathing and at equivalent levels of hypercapnic stimulated breathing. Parasternal baseline muscle length was entirely unchanged with aminophylline. Parasternal shortening increased significantly with aminophylline while corresponding parasternal EMG activity remained constant, consistent with increased contractility. Thus, in awake, intact mammals, aminophylline, in the usual therapeutic range, elicits increased ventilation and increased contractility of all primary inspiratory respiratory muscles, including both chest wall and diaphragm.

The effect of two doses of fentanyl on chest wall rigidity at equipotent doses of isoflurane in dogs.

OBJECTIVE: To evaluate the effect of two doses of fentanyl upon chest wall rigidity of dogs anesthetized at equipotent doses of isoflurane [1.3 minimum alveolar concentration (MACISO) of each dose of fentanyl]. STUDY DESIGN: Prospective crossover randomized study. ANIMALS: A group of eight male Beagle dogs, approximately 1 year old and weighing 12.1 ± 1.6 kg (mean ± standard deviation). METHODS: The dogs were anesthetized with isoflurane and instrumented for the measurement of esophageal pressure (PESO), flow (V˙) and volume (V). Chest wall elastance (ECW) was estimated by multiple linear regression of the model. PESO(t) = V˙(t) × RCW + V(t) × ECW + EEPESO where t is time, RCW is chest wall resistance and EEPESO is end-expiratory PESO. Chest wall compliance (CCW) was calculated as 1/ECW and normalized to the body weight of each dog (mL cmH2O-1 kg-1). Anesthesia was maintained at 1.3 MACISO for at least 15 minutes and CCW recorded (CCW-ISO). The dogs were randomly assigned to the lower fentanyl dose [loading dose (33 µg kg-1) and infusion (0.2 µg kg-1 minute-1)] or the higher fentanyl dose [loading dose (102 µg kg-1) and infusion (0.8 µg kg-1 minute-1)]. After 60 minutes of fentanyl infusion, CCW was recorded for each dose (CCW-FENT). During fentanyl infusion, the dogs were maintained at equipotent doses of isoflurane (1.3 MACISO for each fentanyl dose). A two-way analysis of variance followed by a Bonferroni test was used to compare CCW-ISO and CCW-FENT in both treatments and CCW-FENT between treatments. A p value <0.05 was considered significant. RESULTS: Neither of the fentanyl doses decreased CCW and there was no difference in CCW-FENT between doses. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl at the studied doses did not result in chest wall rigidity in dogs anesthetized with equipotent doses of isoflurane (1.3 MACISO).

Evaluation of lung and chest wall mechanics during anaesthesia using the PEEP-step method.

BACKGROUND: Postoperative pulmonary complications are common. Between patients there are differences in lung and chest wall mechanics. Individualised mechanical ventilation based on measurement of transpulmonary pressures would be a step forward. A previously described method evaluates lung and chest wall mechanics from a change of ΔPEEP and calculation of change in end-expiratory lung volume (ΔEELV). The aim of the present study was to validate this PEEP-step method (PSM) during general anaesthesia by comparing it with the conventional method using oesophageal pressure (PES) measurements. METHODS: In 24 lung healthy subjects (BMI 18.5-32), three different sizes of PEEP steps were performed during general anaesthesia and ΔEELVs were calculated. Transpulmonary driving pressure (ΔPL) for a tidal volume equal to each ΔEELV was measured using PES measurements and compared to ΔPEEP with limits of agreement and intraclass correlation coefficients (ICC). ΔPL calculated with both methods was compared with a Bland-Altman plot. RESULTS: Mean differences between ΔPEEP and ΔPL were <0.15 cm H2O, 95% limits of agreements -2.1 to 2.0 cm H2O, ICC 0.6-0.83. Mean differences between ΔPL calculated by both methods were <0.2 cm H2O. Ratio of lung elastance and respiratory system elastance was 0.5-0.95. CONCLUSIONS: The large variation in mechanical properties among the lung healthy patients stresses the need for individualised ventilator settings based on measurements of lung and chest wall mechanics. The agreement between ΔPLs measured by the two methods during general anaesthesia suggests the use of the non-invasive PSM in this patient population. CLINICAL TRIAL REGISTRATION: NCT 02830516.

Continuous chest wall ropivacaine infusion for analgesia in children undergoing Nuss procedure: a comparison with thoracic epidural.

BACKGROUND: Pain following Nuss procedure is severe and its management is challenging. Many different pain treatment modalities are currently being used, but none of them have been found to be ideal. AIM: In this retrospective review, we compare our current multimodal approach, which involves continuous ropivacaine infusion through chest wall catheters (CWC), intravenous patient-controlled analgesia (IV-PCA), and adjunctive medications (gabapentin and clonidine), with the technique that we used in the past, the thoracic epidural catheter (TEC). METHODS: Following IRB approval, we performed a retrospective analysis of data on 32 patients who underwent the Nuss procedure at our institution. All children were divided into two groups: TEC group: 0.2% ropivacaine and hydromorphone 10 mcg·ml(-1) epidural infusion (n = 15) and CWC group (with IV-PCA and adjuncts [gabapentin + clonidine]): 0.2% ropivacaine infusion and hydromorphone PCA, oral gabapentin, and transdermal clonidine patch (n = 17). RESULTS: Both the groups were demographically similar. Average numeric pain scores were higher in the CWC group only on the day of surgery (mean ± sd: 3.79 ± 1.58 vs 2.68 ± 1.30; 95% CI: -2.16 to -0.05). Pain scores on postoperative day 1 (mean ± sd: 3.40 ± 1.59 vs 3.35 ± 1.32; 95% CI: -1.11 to 1.01), day 2 (mean± sd: 3.39 ± 1.79 vs 2.99 ± 1.06; 95% CI: -1.50 to 0.70), and on the day of discharge (DOD) (mean± sd: 3.25 ± 1.84 vs 3.99 ± 1.28; 95% CI: -0.42 to 1.89) were comparable between the groups. The CWC group needed fewer changes in the therapeutic regimen to maintain acceptable pain relief, had lower incidence of nausea and vomiting, had shorter anesthesia time, total OR time, and hospital length of stay. CONCLUSION: TEC provided better analgesia following the Nuss procedure only on the day of surgery. On the subsequent days until discharge, pain scores were comparable. However, CWC offered other advantages: it was less labor intensive and had fewer side effects, shorter OR time, and shorter hospital stay.

Serratus plane block: a novel ultrasound-guided thoracic wall nerve block.

We present a novel ultrasound-guided regional anaesthetic technique that may achieve complete paraesthesia of the hemithorax. This technique may be a viable alternative to current regional anaesthetic techniques such as thoracic paravertebral and central neuraxial blockade, which can be technically more challenging and have a higher potential side-effect profile. We performed the serratus block at two different levels in the midaxillary line on four female volunteers. We recorded the degree of paraesthesia obtained and performed fat-suppression magnetic resonance imaging and three-dimensional reconstructions of the spread of local anaesthetic in the serratus plane. All volunteers reported an effective block that provided long-lasting paraesthesia (750-840 min). There were no side-effects noted in this initial descriptive study. While these are preliminary findings, and must be confirmed in a clinical trial, they highlight the potential for the serratus plane block to provide analgesia following surgery on the thoracic wall. We suggest that this novel approach appears to be safe, effective, and easy to perform, and is associated with a low risk of side-effects.

Effects of propofol anaesthesia on thoraco-abdominal volume variations during spontaneous breathing and mechanical ventilation.

BACKGROUND: Anaesthesia based on inhalational agents has profound effects on chest wall configuration and breathing pattern. The effects of propofol are less well characterised. The aim of the current study was to evaluate the effects of propofol anaesthesia on chest wall motion during spontaneous breathing and positive pressure ventilation. METHODS: We studied 16 subjects undergoing elective surgery requiring general anaesthesia. Chest wall volumes were continuously monitored by opto-electronic plethysmography during quiet breathing (QB) in the conscious state, induction of anaesthesia, spontaneous breathing during anaesthesia (SB), pressure support ventilation (PSV) and pressure control ventilation (PCV) after muscle paralysis. RESULTS: The total chest wall volume decreased by 0.41 ± 0.08 l immediately after induction by equal reductions in the rib cage and abdominal volumes. An increase in the rib cage volume was then seen, resulting in total chest wall volumes 0.26 ± 0.09, 0.24 ± 0.10, 0.22 ± 0.10 l lower than baseline, during SB, PSV and PCV, respectively. During QB, rib cage volume displacement corresponded to 34.2 ± 5.3% of the tidal volume. During SB, PSV and PCV, this increased to 42.2 ± 4.9%, 48.2 ± 3.6% and 46.3 ± 3.2%, respectively, with a corresponding decrease in the abdominal contribution. Breathing was initiated by the rib cage muscles during SB. CONCLUSION: Propofol anaesthesia decreases end-expiratory chest wall volume, with a more pronounced effect on the diaphragm than on the rib cage muscles, which initiate breathing after apnoea.