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Experimental Studies on Diagnostic and Therapeutic Aspects of Intraosseous Access
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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 [en]
Infusions, Intraosseous, Sepsis, Point-of-care Systems, Blood Coagulation, Antibiotics
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-321403ISBN: 978-91-554-9937-2 (print)OAI: oai:DiVA.org:uu-321403DiVA: diva2:1092955
Public defence
2017-09-01, Hedstrandsalen, Akademiska Sjukhuset, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2017-06-07 Created: 2017-05-04 Last updated: 2017-08-09
List of papers
1. Analysis of intraosseous samples using point of care technology: an experimental study in the anaesthetised pig
Open this publication in new window or tab >>Analysis of intraosseous samples using point of care technology: an experimental study in the anaesthetised pig
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2012 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 83, no 11, 1381-1385 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND:

Intraosseous access is an essential method in emergency medicine when other forms of vascular access are unavailable and there is an urgent need for fluid or drug therapy. A number of publications have discussed the suitability of using intraosseous access for laboratory testing. We aimed to further evaluate this issue and to study the accuracy and precision of intraosseous measurements.

METHODS:

Five healthy, anaesthetised pigs were instrumented with bilateral tibial intraosseous cannulae and an arterial catheter. Samples were collected hourly for 6h and analysed for blood gases, acid base status, haemoglobin and electrolytes using an I-Stat(®) point of care analyser.

RESULTS:

There was no clinically relevant difference between results from left and right intraosseous sites. The variability of the intraosseous sample values, measured as the coefficient of variance (CV), was maximally 11%, and smaller than for the arterial sample values for all variables except SO(2). For most variables, there seems to be some degree of systematic difference between intraosseous and arterial results. However, the direction of this difference seems to be predictable.

CONCLUSION:

Based on our findings in this animal model, cartridge based point of care instruments appear suitable for the analysis of intraosseous samples. The agreement between intraosseous and arterial analysis seems to be good enough for the method to be clinically useful. The precision, quantified in terms of CV, is at least as good for intraosseous as for arterial analysis. There is no clinically important difference between samples from left and right tibia, indicating a good reproducibility.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-181455 (URN)10.1016/j.resuscitation.2012.04.007 (DOI)000311793100023 ()22542768 (PubMedID)
Available from: 2012-09-24 Created: 2012-09-24 Last updated: 2017-05-08Bibliographically approved
2. Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig
Open this publication in new window or tab >>Analysis of intraosseous samples in endotoxemic shock: an experimental study in the anaesthetised pig
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2014 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 58, no 3, 337-344 p.Article in journal (Refereed) Published
Abstract [en]

Background

Intraosseous (IO) access is used in emergency situations to allow rapid initiation of treatment. IO access is also sometimes used for blood sampling, although data on accuracy of such sampling in critical illness are limited. There is also a potential risk that bone marrow fragments in IO samples may damage laboratory equipment. It is ethically questionable to perform a simultaneous comparison between IO and arterial/venous sampling in critically ill humans. We have, thus, studied the analytical performance of IO sampling in a porcine septic shock model using a cartridge-based analyser.

Methods

Eight pigs with endotoxin-induced septic shock were sampled hourly for 6 h, and analysed for blood gases, acid base status, haemoglobin, glucose and lactate using point of care instruments. Samples were taken from three IO cannulae (tibia bilaterally, one with infusion, and humerus), one arterial and one venous. An interaction test was used to assess changes in agreement between methods over time. Bland–Altman plots were constructed to study bias between methods.

Results

There were, to a varying extent, differences between IO and arterial/venous levels for all studied variables, but agreement did not change significantly during the experiment. A general finding was a large dispersion of differences between methods.

Conclusions

IO sample values should be treated with caution in this setting but may add useful information to the clinical picture. The tibia or humerus may be used for sampling. IO infusion decreases agreement, thus sampling during infusion should be avoided.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-220973 (URN)10.1111/aas.12274 (DOI)000331406500011 ()
Available from: 2014-03-25 Created: 2014-03-24 Last updated: 2017-05-08Bibliographically approved
3. Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock
Open this publication in new window or tab >>Intraosseous and intravenous administration of antibiotics yields comparable plasma concentrations during experimental septic shock
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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.

National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-240273 (URN)10.1111/aas.12454 (DOI)000349604000009 ()25557933 (PubMedID)
Available from: 2015-01-06 Created: 2015-01-06 Last updated: 2017-05-08Bibliographically approved
4. Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study
Open this publication in new window or tab >>Analysis of Thromboelastography, PT, APTT and Fibrinogen in Intraosseous and Venous Samples: An Experimental Study
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2016 (English)In: Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine, ISSN 1757-7241, E-ISSN 1757-7241, Vol. 24, 131Article in journal (Refereed) Published
Abstract [en]

Background:Laboratory analysis of coagulation is often important in emergencies. If vascular access is challenging,intraosseous catheterization may be necessary for treatment. We studied the analysis of coagulation parameters inintraosseous aspirate during stable conditions and after major haemorrhage in a porcine model.Methods:Ten anesthetized pigs received central venous and intraosseous catheters and samples were taken foranalysis of thromboelastography (TEG), prothrombin time (PT), activated partial thromboplastin time (APTT) andfibrinogen concentration. Analyses were repeated after removal of 50 % of the calculated blood volume andresuscitation with crystalloid. Intraosseous and venous values were compared.Results:Bleeding and resuscitation resulted in haemodilution and hypotension. Median TEG reaction time wasshorter in intraosseous than in venous samples before (1.6 vs 4.6 min) and after (1.6 vs 4.7 min) haemodilution.Median maximal amplitude was smaller in intraosseous samples at baseline (68.3 vs 76.4 mm). No major differenceswere demonstrated for the other TEG parameters. The intraosseous samples often coagulated in vitro, makinganalysis of PT, APTT and fibrinogen difficult. After haemodilution, TEG maximal amplitude andα-angle, andfibrinogen concentration, were decreased and PT increased.Discussion:The intraosseous samples were clinically hypercoagulable and the TEG demonstrated a shortenedreaction time. The reason for this may hypothetically be found in the composition of the IO aspirate or in thesampling technique. After 50 % haemorrhage and haemodilution, a clinically relevant decrease in fibrinogenconcentration and a lower TEG maximal amplitude were observed.Conclusions:Although the sample is small, these data indicate that intraosseous samples are hypercoagulable,which may limit their usefulness for coagulation studies. Major haemodilution only moderately affected the studied parameters.

Keyword
Blood coagulation; Haemorrhage; Infusions; Intraosseous; Thrombelastography
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-306587 (URN)10.1186/s13049-016-0318-0 (DOI)000386860300001 ()
Available from: 2016-10-29 Created: 2016-10-29 Last updated: 2017-05-08Bibliographically approved
5. Comparison of Intraosseous, Arterial and Venous Blood Sampling for Laboratory Analysis in Haemorrhagic Shock
Open this publication in new window or tab >>Comparison of Intraosseous, Arterial and Venous Blood Sampling for Laboratory Analysis in Haemorrhagic Shock
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Abstract

Introduction Intraosseous (IO) access is often indicated for administration of drugs and fluids in emergencies when venous access is challenging. There is no consensus regarding which laboratory analyses may be performed on IO aspirates, and research on hemodynamically unstable subjects is limited.

Methods 12 anaesthetised pigs were sampled from IO, venous and arterial accesses during stable circulation and after haemorrhage corresponding to 20% and 40% of the blood volume. Samples were analysed for blood gases and acid-base status, electrolytes, haematocrit, creatinine, glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), alkaline phosphatase (ALP) and creatine kinase (CK).

Results Average differences of blood gases and acid-base parameters, sodium, creatinine, haematocrit, ALT and γ-GT and between IO and venous samples were small at baseline and after haemorrhage while differences for lactate and glucose increased with hypovolaemia. Both IO-arterial and venoarterial differences in acid-base parameters increased with hypovolaemia. Dispersions of differences were often large.

Conclusions Average levels of blood gases, acid base parameters, haematocrit, creatinine and ALT, but not lactate and glucose, were similar in IO and venous samples in hypovolaemia. However, precision was limited, indicating that IO test results should be confirmed when other vascular access is established, and that analysis of IO samples should be limited to acute situations and not used for detailed diagnostics in this setting.

Keyword
Intraosseous access, shock
National Category
Anesthesiology and Intensive Care
Research subject
Anaesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-321402 (URN)
Available from: 2017-05-04 Created: 2017-05-04 Last updated: 2017-05-04

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