Fink, Tobias

Ganse, Bergita

Knobe, Matthias

Koch, Laura

Laschke, Matthias W.

Meiser, Andreas

Menger, Michael D.

Orth, Marcel

Pastor, Torsten

Pohlemann, Tim

Volk, Thomas

English

Acronym

Koch et al. Critical Care          (2023) 27:367  https://doi.org/10.1186/s13054-023-04657-6CORRESPONDENCE Open Access© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecom-mons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Critical CareLower oxygen saturation with higher rates of norepinephrine in bone fractures of polytrauma patients: a pilot studyLaura Koch1, Marcel Orth2, Tobias Fink3, Andreas Meiser3, Thomas Volk3, Michael D. Menger4, Matthias W. Laschke4, Torsten Pastor5, Matthias Knobe6,7,8, Tim Pohlemann2 and Bergita Ganse1,2* Keywords Multiple trauma, Catecholamines, Noradrenaline, Non-union, Fracture healing, Microcirculation, Perfusion, O2C, Injury, Mean arterial pressureTrial registration: The study is registered in the German Clinical Trials Register (DRKS00031942)Hypoxia is a risk factor for non-union and appears to be one of the causes of the higher incidence of non-union in patients with multiple injuries [1]. Norepineph-rine (NE) decreased bone perfusion in animal studies [2]. While the intramedullary bone-marrow pressure usually correlates with the systemic blood pressure, the contrary was observed under NE treatment: the systemic blood pressure increased, and simultaneously, the intramedul-lary bone-marrow pressure dropped [2]. This effect was independent of the systemic blood pressure and is prob-ably caused by α-receptor-transmitted vasoconstriction of the nutrient vessels. Patients in a more severe state receive NE to increase their systemic blood pressure. The target systolic blood pressure, according to current guidelines, is 80–90 mmHg [3]. NE is currently the most frequently used and recommended catecholamine for polytraumatized patients in intensive care units [3, 4]. In human patients, the effect of i.v.-NE administration on the blood perfusion in fractures and the correlation with the systemic arterial blood pressure have not yet been investigated. We hypothesized lower oxygen saturation  (SO2) in the fracture gap with higher doses of NE, inde-pendent of MAP.In a pilot trial, we used the laser-Doppler device ‘Oxy-gen to see’ (O2C, LEA Medizintechnik, Winchesterstr. 2, D-35394 Gießen, Germany) to measure  SO2, haemo-globin (Hb), and blood flow (BF) in 3, 10, and 14/16 mm depth in four tibial and clavicle fractures of three patients with multiple injuries who received NE. The O2C oper-ates with a laser (wavelength 820 nm) and a detector in the white-light spectrum range (wavelength 500–800 nm) [5]. Probes were covered in single-use ‘Ultracover for TEE Endocavity Probe Cover’ (ECOLAB, Microtek Med-ical B.V., Hekkehorst 24, 7207 NL-Zutphen, The Neth-erlands), 25 × 11 × 1000  mm, made of polyurethane. The non-invasive probe was fixed on the skin with black kine-siology tape to avoid measurement error by the ambient light and to standardize the contact pressure. In each of the fractures, multiple measurements were conducted throughout the time course of treatment with varying NE *Correspondence:Bergita Gansebergita.ganse@uks.eu1 Werner Siemens-Endowed Chair for Innovative Implant Development (Fracture Healing), Departments and Institutes of Surgery, Saarland University, Homburg, Germany2 Department of Trauma, Hand and Reconstructive Surgery, Departments and Institutes of Surgery, Saarland University, Homburg, Germany3 Department of Anaesthesiology, Intensive Care and Pain Therapy, Saarland University, Homburg, Germany4 Institute for Clinical and Experimental Surgery, Saarland University, Homburg, Germany5 Department of Orthopaedic and Trauma Surgery, Lucerne Cantonal Hospital, Lucerne, Switzerland6 Department of Orthopaedic and Trauma Surgery, Westmuensterland Hospital, Ahaus, Germany7 Medical Faculty, University of Zurich, Zurich, Switzerland8 Medical Faculty, RWTH University Aachen, Aachen, GermanyPage 2 of 3Koch et al. Critical Care          (2023) 27:367 rates. During each measurement, three recordings of 10 s each were taken in slightly different spots over each frac-ture gap and averaged. MAP was measured by an arterial probe as part of regular patient monitoring and recorded for each measurement. Of note, the present study was purely observational and did not interfere with the NE administration rate. NE was administered through injec-tion pumps solely operated by the intensive care unit staff independent of the study. Multiple linear regression sta-tistics were conducted with forced entry for each of the perfusion parameters and each depth separate as the dependent variable. The relationships of each of these parameters with the NE rate and the MAP as independ-ent variables were explored.Three male patients with three tibial fractures and a clavicle fracture were included (age 57.3 ± 33.1  years, weight 77.7 ± 6.8  kg, height 177.7 ± 4.0  cm, BMI 24.7 ± 3.1  kg/cm2). A total of 125 measurements were taken, all within the first week after fracture. Signifi-cantly higher NE rates were associated with lower  SO2 in 10 mm (p = 0.018) and 14/16 mm depth (p = 0.006) of fractures (Fig.  1A–C). Significant correlations between the MAP and  SO2 were found in 3 (p = 0.007) and 10 mm depth (p = 0.030) (Fig. 1D–F). Higher NE administration rates and lower MAP were associated with lower  SO2. Hb and BF in the fracture gap were neither affected by the NE rate nor the MAP. In 10 mm depth, up to 16.2% (adjusted  R2) of the variability of  SO2 could be explained by NE and MAP. In 3 mm, up to 14.7% of the variability could be explained by MAP alone, and in 14/16 mm, up to 13.5% by NE alone. Thus, only NE and not MAP had an effect on  SO2 in 14/16 mm depth inside the fractures.Fig. 1 Relationships of the NE rate (A–C) and the MAP (D–F) with the measured  SO2 values. P values from the multiple linear regression analysis are shown only, if significantPage 3 of 3Koch et al. Critical Care          (2023) 27:367  The present pilot study is the first to measure fracture perfusion in patients with NE. The presented findings need to be confirmed in larger cohorts. The reported data indicate an association of NE administration rates with decreases in bone fracture oxygenation that may be caused by the NE, but could also be related to other mechanisms associated with the more severe state of the patients that require NE treatment. As lower  SO2 in frac-tures may lead to delayed bone healing and non-union, it might be of interest to study the effects of alterna-tive drugs for blood pressure elevation on bone perfu-sion that do not show a vasoconstrictive effect on bone. Among the catecholamines, dobutamine mainly has an effect on β1 receptors, but shows almost no α-receptor-mediated vasoconstriction. If it can be confirmed that NE decreases bone blood supply, NE might be used to decrease blood loss from fractures. Laser-Doppler-based devices and other instruments should be validated for perfusion measurements and  SO2-monitoring in bone fractures of patients.AbbreviationsBF  Blood flowHb  Haemoglobini.v.  IntravenousMAP  Mean arterial pressuremmHg  Millimetre of mercuryNE  NorepinephrineO2C  Oxygen to see (device)SO2  Oxygen saturationAcknowledgementsNot applicable.Author contributionsLK conducted the measurements. MO, TPO, TF, AM and TV provided the patients and patient access. LK, MDM, MWL, TPA, and MK helped with data interpretation. TPO acquired the funding. BG contributed the study idea and conceptualization, obtained IRB approval, analysed the data, made the figure, and drafted the manuscript. All authors have interpreted and discussed the results, revised the manuscript, and agreed to its publication in its present form.FundingThe Werner Siemens Foundation (project Smart Implants) funded this work. The funding body did not have a role in the design of the study and collec-tion, analysis, and interpretation of data and in writing the manuscript.Availability of data and materialsThe data set obtained in the current study is available from the corresponding author on reasonable request.DeclarationsEthics approval and consent to participateEthical approval was obtained from the IRB of Saarland Medical Board (Ärztekammer des Saarlandes, Germany, application number 127/22). Written informed consent was conducted according to the Declaration of Helsinki prior to the start of measurements.Consent for publicationAll authors have consented to the publication of the present manuscript.Competing interestsTP is president and board member of the AO Foundation, Switzerland, and extended board member of the German Society of Orthopaedic Trauma Surgery (DGU), the German Society of Orthopaedic Surgery and Traumatology (DGOU), and the German Society of Surgery (DGCH). TP is also the speaker of the medical advisory board of the German Ministry of Defence. The remain-ing authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Received: 16 September 2023   Accepted: 19 September 2023References 1. Hildebrand F, van Griensven M, Huber-Lang M, Flohe SB, Andruszkow H, Marzi I, Pape HC. Trauma research network of the German society of trauma, DGU. Is there an impact of concomitant injuries and timing of fixation of major fractures on fracture healing? A focused review of clinical and experimental evidence. J Orthop Trauma. 2016;30(3):104–12. https:// doi. org/ 10. 1097/ BOT. 00000 00000 000489. 2. Stein AH Jr, Morgan HC, Porras RF. The effect of pressor and depressor drugs on intramedullary bone-marrow pressure. J Bone Jt Surg Am. 1958;40(5):1103–10. 3. Rossaint R, Afshari A, Bouillon B, Cerny V, Cimpoesu D, Curry N, Duranteau J, Filipescu D, Grottke O, Grønlykke L, Harrois A, Hunt BJ, Kaserer A, Komadina R, Madsen MH, Maegele M, Mora L, Riddez L, Romero CS, Samama CM, Vincent JL, Wiberg S, Spahn DR. The European guide-line on management of major bleeding and coagulopathy following trauma: sixth edition. Crit Care. 2023;27(1):80. https:// doi. org/ 10. 1186/ s13054- 023- 04327-7. 4. Gauss T, Gayat E, Harrois A, Raux M, Follin A, Daban JL, Cook F, Hamada S. TraumaBase Group; Prehospital Traumabase Group Ile de France, SAMU=Service d’Aide Médicale Urgente. Effect of early use of noradrena-line on in-hospital mortality in haemorrhagic shock after major trauma: a propensity-score analysis. Br J Anaesth. 2018;120(6):1237–44. https:// doi. org/ 10. 1016/j. bja. 2018. 02. 032. 5. Forst T, Hohberg C, Tarakci E, Forst S, Kann P, Pfutzner A. Reliability of lightguide spectrophotometry (O2C) for the investigation of skin tissue microvascular blood flow and tissue oxygen supply in diabetic and nondiabetic subjects. J Diab Sci Technol. 2008;2:1151–6. https:// doi. org/ 10. 1177/ 19322 96808 00200 625.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in pub-lished maps and institutional affiliations.

Lower oxygen saturation with higher rates of norepinephrine in bone fractures of polytrauma patients: a pilot study

Universaar

https://publikationen.sulb.uni-saarland.de/bitstream/20.500.11880/37064/1/s13054-023-04657-6.pdf

Lower oxygen saturation with higher rates of norepinephrine in bone fractures of polytrauma patients: a pilot study

Abstract

Similar works

Full text

Available Versions

Acronym

Universaar