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Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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2015 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 59, no 3, 346-353 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: We aimed to investigate whether comparable antibiotic concentrations could be reached with intraosseous and intravenous administration during septic shock.

METHODS: In this randomized, prospective experimental study conducted at an animal research laboratory at the University Hospital of Uppsala, eight anesthetized pigs, weighing 21.2 to 29.1 kg (mean: 25.2 ± 2.3 kg), received endotoxin infusion at 4 μg/kg/h for 6 h. At the onset of clinical shock, alternatively after 3 h of endotoxemia, they received 75 mg/kg of cefotaxime and 7 mg/kg of gentamicin either in a proximal tibial intraosseous catheter or in a peripheral intravenous catheter. Mixed venous samples were taken after 5, 15, 30, 60, 120 and 180 min and analyzed for antibiotic concentrations.

RESULTS: For both antibiotics, plasma concentrations after intraosseous and intravenous administration followed similar curves throughout the observation period, and peak concentrations were comparable. Mean concentration area under the curve (AUC mg × h/l) for cefotaxime was 108.1 ± 19.5 after intraosseous and 116.5 ± 11.1 after intravenous administration; ratio 0.93, (95% CI 0.71-1.19). Mean AUC for gentamicin was 28.1 ± 6.8 for intraosseous and 32.2 ± 3.5 for intravenous administration; ratio 0.87 (95% CI 0.62-1.19).

CONCLUSIONS: In this porcine septic shock model, intraosseous and intravenous administration of gentamicin and cefotaxime yielded comparable concentrations. In an emergency, intraosseous administration of these antibiotics may be considered in severe infections when venous access is difficult.

Place, publisher, year, edition, pages
2015. Vol. 59, no 3, 346-353 p.
National Category
Anesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-240273DOI: 10.1111/aas.12454ISI: 000349604000009PubMedID: 25557933OAI: oai:DiVA.org:uu-240273DiVA: diva2:776099
Available from: 2015-01-06 Created: 2015-01-06 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Experimental Studies on Diagnostic and Therapeutic Aspects of Intraosseous Access
Open this publication in new window or tab >>Experimental Studies on Diagnostic and Therapeutic Aspects of Intraosseous Access
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Reliable access to the circulation is paramount in most medical and surgical emergencies. When venous access cannot be expediently established, intraosseous (IO) access is indicated. This method has a high success rate even in relatively inexperienced hands and there is considerable clinical experience of IO administration of drugs and fluids. There is however limited evidence on the use of IO samples for laboratory analysis. Also, uptake of drugs during shock has not been extensively studied. Further, there have been concerns that analysis of IO samples may damage laboratory equipment. We have studied, in a porcine model, the use of IO samples for point of care analysis of blood gases, acid base parameters and blood chemistries in stable circulation, in experimental septic shock, and in hypovolemia after major hemorrhage, comparing IO samples with arterial and venous samples, and comparing IO samples from different sites. We have also studied coagulation assays on IO samples in stable circulation and after major hemorrhage. Furthermore, we have compared IO and intravenous administration of antibiotics in experimental sepsis.

Average differences between IO and arterial/venous samples varied between the studied analytes. During stable circulation, average IO levels of blood gases, acid-base parameters, hemoglobin/hematocrit and several blood chemistries approximated venous levels relatively well. Differences in acid-base and blood gas parameters, and lactate, were more pronounced in hypovolemia, as well as in sepsis. The dispersion of the differences was often relatively large, indicating limited precision. Average differences between two intraosseous sites were small.

Intraosseous samples were clinically hypercoagulable with a strong tendency to clot in vitro, and thromboelastography demonstrated shortened reaction times compared with venous samples. Major bleeding and hemodilution moderately affected the studied coagulation parameters.

In endotoxemic animals with circulatory instability, concentrations of cefotaxime and gentamicin in samples from the pulmonary artery were comparable at 5 minutes after intraosseous and intravenous administration, and during a 3 hour observation period.

In summary, agreement between analytes in intraosseous and conventional blood samples was variable and often unpredictable, especially during circulatory compromise. Intraosseous samples clinically appeared hypercoagulable, and thromboelastography confirmed this. High and comparable concentrations of cefotaxime and gentamicin were found after intraosseous and intravenous administration of equivalent doses, suggesting that uptake is acceptable during septic instability.  

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 55 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1337
Keyword
Infusions, Intraosseous, Sepsis, Point-of-care Systems, Blood Coagulation, Antibiotics
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-321403 (URN)978-91-554-9937-2 (ISBN)
Public defence
2017-09-01, Hedstrandsalen, Akademiska Sjukhuset, Uppsala, 13:00 (Swedish)
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Supervisors
Available from: 2017-06-07 Created: 2017-05-04 Last updated: 2017-08-09

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Strandberg, GunnarLarsson, AndersLipcsey, MiklosEriksson, Mats

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