Continuous intraoperative neuromonitoring of the recurrent laryngeal nerve during lung operations.

Background: The recurrent laryngeal nerve (RLN), especially on the left side, is particularly vulnerable during lung operations. Therefore, continuous intraoperative neuromonitoring (cIONM) would be desirable. With the use of a double-lumen tube (DLT) for single-lung ventilation, there is some uncertainty where the recording electrode should be positioned. The aim of this study was to assess the feasibility of this technique and to predict the ideal position of a single recording electrode. Methods: Patients scheduled to undergo left thoracotomy due to pulmonary pathologies, two adhesive electrodes were affixed consecutively above the proximal cuff of the DLT prior to intubation for a precise location of the recording from the vocal cords. Following thoracotomy, the vagus nerve alongside the aortic arch was exposed. A continuous stimulation probe (Saxophone® electrode, Dr. Langer Medical, Waldkirch, Germany) was placed around the nerve. The signals of the respective electrode were recorded and analyzed with regard to previously defined limits of positive signaling. Results: Strong signals with an amplitude of at least 165 µV were recorded in 18 of 20 patients. In these patients 100% of the signals were recorded via the distally located electrode. An additional signal was recorded via the proximal electrode in four patients. cIONM was found to be a safe and reproducible technique. Conclusions: The described technique enables the use of cIONM of the RLN throughout the entire course of the surgical procedure.

Changes in the degree of substitution of HES in vivo and their influence on methods for determining HES concentrations in plasma.

OBJECTIVE: The degree of substitution (DS) of HES describes the average proportion of substituted glucose molecules in a starch molecule. Although no quantitative studies of the in vivo behavior of the DS have been conducted so far, most pharmacokinetic studies to date have measured HES concentrations using the enzymatic method. This method assumes that at any point in time after an infusion, the DS in a serum remains constant and is identical to the DS in the infused solution. In the present study, we examined the changes in the DS of HES 130/0.42 in vivo in an animal model and compared two methods of measuring HES concentrations in plasma (the enzymatic and the o-Toluidine method). METHODOLOGY: We randomized 22 pigs into 2 groups. After induction of anesthesia, the pigs received 500 ml or 1000 ml of HES 130/0.42 (Tetraspan®). The DS was measured directly after the infusion, then after 30, 60, 120 and 240 minutes. In determining the DS, the hydroxyethyl starch was extracted from the plasma and hydrolyzed with hydrochloric acid to form non-substituted glucose and hydroxyethyl glucose. Subsequently, the concentration of free unsubstituted glucose was determined enzymatically and the total concentration of all (i.e., substituted and unsubstituted) glucose molecules was determined using the o-Toluidine method. From this, the concentration of the substituted glucose (hydroxyethyl glucose) and the DS could be calculated. In addition, the HES concentration was measured first in vitro and then in vivo at any point after the infusion by both the enzymatic method and the o-Toluidine method. RESULTS: The DS increased significantly directly after the infusion from 0.42 to 0.53 (for 500ml) or to 0.50 (for 1000ml); 4 hours later this had further increased to 0.55 and 0.54, respectively (p <0.0001). The HES concentration in vitro showed no significant difference (p = 0.17) when determined with the enzymatic and the o-Toluidine method. In contrast, the serum concentrations in vivo displayed significant differences (p<0.0001) between the two measurement methods. Immediately after the infusion of 500ml HES, the concentration measured with the o-Toluidine method was 31% higher than the one measured with the enzymatic method; 4 hours later, this discrepancy was still at 25%. For 1000 ml HES, the differences amounted to 16% and 25%, respectively. CONCLUSION: The DS of HES in vivo increases significantly over time. As a result, an HES concentration measured with the enzymatic method in vivo will be significantly lower than the same concentration determined with the o-Toluidine method. In future pharmacokinetic studies, HES concentrations should be measured using a method that takes into account changes in the DS in vivo.

Urolithiasis in Germany: Trends from the National DRG Database.

INTRODUCTION: Urolithiasis is a common disease leading to a high socioeconomic burden due to treatment costs and sickness leave. The aim of this study was to evaluate recent trends in the incidence of urolithiasis in Germany and in the use of therapeutic interventions. METHODS: Treatment data for all in-patient hospital episodes for urolithiasis between 2005 and 2016 were extracted from the national DRG statistics at DESTATIS and analysed with regard to the corresponding procedures according to the OPS code. RESULTS: Incidence for urolithiasis was stable at around 120,000 cases per year during the observation period with a male:female ratio of 2:1. Rising numbers were noted for patients >80 years. Nevertheless, the number of coded procedures rose significantly with a marked disproportionate transition from extracorporeal shock wave lithotripsy towards ureterorenoscopy. Percutaneous nephrolithotomy was performed more frequently on a smaller scale. DISCUSSION/CONCLUSION: While the global incidence of urolithiasis is still rising, Germany, as other Western countries, has reached a plateau. There is a remarkable trend towards invasive treatment of even asymptomatic kidney stones. Besides the effects on individual patients with increased risk for complications, this results in a higher monetary burden to the health care system and society.

Videolaryngoscopy versus direct laryngoscopy for double-lumen endotracheal tube intubation in thoracic surgery - a randomised controlled clinical trial.

BACKGROUND: Double-lumen tube (DLT) intubation is necessary for thoracic surgery and other operations with the need for lung separation. However, DLT insertion is complex and might result in airway trauma. A new videolaryngoscopy (GVL) with a thin blade might improve the intubation time and reduce complexity as well as iatrogenic airway complications compared to conventional direct laryngoscopy (DL) for DLT intubation. METHODS: A randomised, controlled trial was conducted in 70 patients undergoing elective thoracic surgery using DLT for lung separation. Primary endpoint was time to successful intubation. The secondary endpoints of this study were number of intubation attempts, the assessment of difficulty, any complications during DLT intubation and the incidence of objective trauma of the oropharynx and supraglottic space and intubation-related subjective symptoms. RESULTS: 65 patients were included (DL group [n  =  31], GVL group [n  =  34]). Median intubation time (25th-75th percentiles) in GVL group was 93 s (63-160) versus 74 (58-94) in DL group [p = 0.044]. GVL resulted in significantly improved visualisation of the larynx (Cormack and Lehane grade of 1 in GVL group was 97% vs. 74% in DL Group [p = 0.008]). Endoscopic examinations revealed significant differences in GVL group compared to DL group showing less red-blooded vocal cord [p = 0.004], vocal cord haematoma [p = 0.022] and vocal cord haemorrhage [p = 0.002]. No significant differences regarding the postoperative subjective symptoms of airway were found. CONCLUSIONS: Videolaryngoscopy using the GlideScope®-Titanium shortly prolongs DLT intubation duration compared to direct laryngoscopy but improves the view. Objective intubation trauma but not subjective complaints are reduced. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020978, retrospectively registered on 09. March 2020.

Side Effect Rates of Opioids in Equianalgesic Doses via Intravenous Patient-Controlled Analgesia: A Systematic Review and Network Meta-analysis.

BACKGROUND: Side effects of opioids used for the treatment of acute pain frequently limit their analgesic quality. Many studies have compared opioid side effects in patient-controlled analgesia (PCA), but it remains unclear whether there are specific side effect profiles that can be exploited when choosing an opioid for a patient. In this review, we wanted to determine the risk ratios (RRs) for the most common side effects when using different opioids for intravenous PCA in equianalgesic doses and rank the substances accordingly. METHODS: A search of MEDLINE, EMBASE, the Cochrane Library (CENTRAL), and Web of Science identified 63 randomized controlled trials comparing opioids under equianalgesic conditions. Inclusion criteria were comparable pain stimulus between groups, equal coanalgesic treatment, and comparable resulting pain scores. Quality of studies was assessed using the Cochrane risk of bias tool with 6 items. Frequentistic network meta-analysis was conducted with morphine as the comparator. This method not only summarizes all estimated effects from direct comparisons of different interventions but also allows for indirect comparisons between interventions that can be linked via the common comparator, in which case the indirect evidence can be used to enhance the precision of the direct comparisons. Primary end points of this study were RRs for nausea and vomiting, pruritus, and events of sedation, as well as mean differences for scores of sedation. Events of respiratory depression were counted. Secondary end point was patient satisfaction (mean difference). The study protocol was registered at PROSPERO (CRD42017062355). RESULTS: Sixteen opioid interventions were compared in the largest network (nausea and vomiting outcome) and 7 opioid interventions in the smallest network (sedation events outcome). Most interventions did not differ from morphine on the primary outcomes (side effects), with some exceptions. Buprenorphine had a significantly higher RR of nausea and vomiting, whereas fentanyl had a lower RR of nausea and vomiting. Nalbuphine, butorphanol, methadone, and pethidine/meperidine had a lower risk of pruritus. Respiratory depression was rare (22 of 2452 patients). Pethidine/meperidine, fentanyl, and oxymorphone caused significantly lower sedation scores. Tramadol caused significantly lower satisfaction scores, whereas oxycodone, alfentanil, remifentanil, fentanyl, and pethidine/meperidine caused significantly higher satisfaction scores. CONCLUSIONS: The opiate chosen for treatment most likely has little effect on the incidence of pruritus and nausea/vomiting, although considerable differences exist in terms of better and worse opioids in the presented rankings. Larger differences between drugs were observed with regard to sedation and patient satisfaction, and choosing the appropriate opioid may help to improve PCA in this regard.

Prednisolone as preservation additive prevents from ischemia reperfusion injury in a rat model of orthotopic lung transplantation.

The lung is, more than other solid organs, susceptible for ischemia reperfusion injury after orthotopic transplantation. Corticosteroids are known to potently suppress pro-inflammatory processes when given in the post-operative setting or during rejection episodes. Whereas their use has been approved for these clinical indications, there is no study investigating its potential as a preservation additive in preventing vascular damage already in the phase of ischemia. To investigate these effects we performed orthotopic lung transplantations (LTX) in the rat. Prednisolone was either added to the perfusion solution for lung preservation or omitted and rats were followed for 48 hours after LTX. Prednisolone preconditioning significantly increased survival and diminished reperfusion edema. Hypoxia induced vasoactive cytokines such as VEGF were reduced. Markers of leukocyte invasiveness like matrix metalloprotease (MMP)-2, or common pro-inflammatory molecules like the CXCR4 receptor or the chemokine (C-C motif) ligand (CCL)-2 were downregulated by prednisolone. Neutrophil recruitment to the grafts was only increased in Perfadex treated lungs. Together with this, prednisolone treated animals displayed significantly reduced lung protein levels of neutrophil chemoattractants like CINC-1, CINC-2α/ß and LIX and upregulated tissue inhibitor of matrix metalloproteinase (TIMP)-1. Interestingly, lung macrophage invasion was increased in both, Perfadex and prednisolone treated grafts, as measured by MMP-12 or RM4. Markers of anti-inflammatory macrophage transdifferentiation like MRC-1, IL-13, IL-4 and CD163, significantly correlated with prednisolone treatment. These observations lead to the conclusion that prednisolone as an additive to the perfusion solution protects from hypoxia triggered danger signals already in the phase of ischemia and thus reduces graft edema in the phase of reperfusion. Additionally, prednisolone preconditioning might also lead to macrophage polarization as a beneficial long-term effect.

Ionic Stabilization of the Polythiophene-Oxygen Charge-Transfer Complex.

A substantial reduction in the rate of irreversible polymer photo-oxidation was observed through the ionic stabilization of the polymer-O2 charge-transfer complex (CTC) in amorphous polythiophene thin films. Through the incorporation of anionic functionality containing mobile cations, it was found that CTC stability increases with increasing cation charge density. This results in an increased rate of electron transfer to molecular oxygen relative to photosensitization and reaction of 1O2, leading to a reduction in the overall rate of polymer degradation. UV-vis and FTIR spectroscopy were utilized to determine the identity of intermediate and irreversible photodegradation products as well as the effect of ion identity on the dominant photo-oxidation mechanism. As polymer-O2 CTCs are common in the photo-oxidation of many conjugated polymers, these results have significant implications for the ongoing effort to produce commercially viable organic electronic and photonic devices.