Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock

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Abstract

Background

Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient’s own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock.

Methods

A model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30–40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA.

Results

Each treatment restored haemodynamic and tissue oxygen delivery parameters equivalently ( p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L ( p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels ( p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation ( p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery ( p = 0.012) but delayed peripheral perfusion ( p = 0.034).

Conclusions

Crystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.

Supplementary Information

The online version contains supplementary material available at 10.1186/s40635-022-00439-6.

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Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.

Rafael Lozano, Mohsen Naghavi, Kyle Foreman … (2013)

Reliable and timely information on the leading causes of death in populations, and how these are changing, is a crucial input into health policy debates. In the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010), we aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex. We attempted to identify all available data on causes of death for 187 countries from 1980 to 2010 from vital registration, verbal autopsy, mortality surveillance, censuses, surveys, hospitals, police records, and mortuaries. We assessed data quality for completeness, diagnostic accuracy, missing data, stochastic variations, and probable causes of death. We applied six different modelling strategies to estimate cause-specific mortality trends depending on the strength of the data. For 133 causes and three special aggregates we used the Cause of Death Ensemble model (CODEm) approach, which uses four families of statistical models testing a large set of different models using different permutations of covariates. Model ensembles were developed from these component models. We assessed model performance with rigorous out-of-sample testing of prediction error and the validity of 95% UIs. For 13 causes with low observed numbers of deaths, we developed negative binomial models with plausible covariates. For 27 causes for which death is rare, we modelled the higher level cause in the cause hierarchy of the GBD 2010 and then allocated deaths across component causes proportionately, estimated from all available data in the database. For selected causes (African trypanosomiasis, congenital syphilis, whooping cough, measles, typhoid and parathyroid, leishmaniasis, acute hepatitis E, and HIV/AIDS), we used natural history models based on information on incidence, prevalence, and case-fatality. We separately estimated cause fractions by aetiology for diarrhoea, lower respiratory infections, and meningitis, as well as disaggregations by subcause for chronic kidney disease, maternal disorders, cirrhosis, and liver cancer. For deaths due to collective violence and natural disasters, we used mortality shock regressions. For every cause, we estimated 95% UIs that captured both parameter estimation uncertainty and uncertainty due to model specification where CODEm was used. We constrained cause-specific fractions within every age-sex group to sum to total mortality based on draws from the uncertainty distributions. In 2010, there were 52·8 million deaths globally. At the most aggregate level, communicable, maternal, neonatal, and nutritional causes were 24·9% of deaths worldwide in 2010, down from 15·9 million (34·1%) of 46·5 million in 1990. This decrease was largely due to decreases in mortality from diarrhoeal disease (from 2·5 to 1·4 million), lower respiratory infections (from 3·4 to 2·8 million), neonatal disorders (from 3·1 to 2·2 million), measles (from 0·63 to 0·13 million), and tetanus (from 0·27 to 0·06 million). Deaths from HIV/AIDS increased from 0·30 million in 1990 to 1·5 million in 2010, reaching a peak of 1·7 million in 2006. Malaria mortality also rose by an estimated 19·9% since 1990 to 1·17 million deaths in 2010. Tuberculosis killed 1·2 million people in 2010. Deaths from non-communicable diseases rose by just under 8 million between 1990 and 2010, accounting for two of every three deaths (34·5 million) worldwide by 2010. 8 million people died from cancer in 2010, 38% more than two decades ago; of these, 1·5 million (19%) were from trachea, bronchus, and lung cancer. Ischaemic heart disease and stroke collectively killed 12·9 million people in 2010, or one in four deaths worldwide, compared with one in five in 1990; 1·3 million deaths were due to diabetes, twice as many as in 1990. The fraction of global deaths due to injuries (5·1 million deaths) was marginally higher in 2010 (9·6%) compared with two decades earlier (8·8%). This was driven by a 46% rise in deaths worldwide due to road traffic accidents (1·3 million in 2010) and a rise in deaths from falls. Ischaemic heart disease, stroke, chronic obstructive pulmonary disease (COPD), lower respiratory infections, lung cancer, and HIV/AIDS were the leading causes of death in 2010. Ischaemic heart disease, lower respiratory infections, stroke, diarrhoeal disease, malaria, and HIV/AIDS were the leading causes of years of life lost due to premature mortality (YLLs) in 2010, similar to what was estimated for 1990, except for HIV/AIDS and preterm birth complications. YLLs from lower respiratory infections and diarrhoea decreased by 45-54% since 1990; ischaemic heart disease and stroke YLLs increased by 17-28%. Regional variations in leading causes of death were substantial. Communicable, maternal, neonatal, and nutritional causes still accounted for 76% of premature mortality in sub-Saharan Africa in 2010. Age standardised death rates from some key disorders rose (HIV/AIDS, Alzheimer's disease, diabetes mellitus, and chronic kidney disease in particular), but for most diseases, death rates fell in the past two decades; including major vascular diseases, COPD, most forms of cancer, liver cirrhosis, and maternal disorders. For other conditions, notably malaria, prostate cancer, and injuries, little change was noted. Population growth, increased average age of the world's population, and largely decreasing age-specific, sex-specific, and cause-specific death rates combine to drive a broad shift from communicable, maternal, neonatal, and nutritional causes towards non-communicable diseases. Nevertheless, communicable, maternal, neonatal, and nutritional causes remain the dominant causes of YLLs in sub-Saharan Africa. Overlaid on this general pattern of the epidemiological transition, marked regional variation exists in many causes, such as interpersonal violence, suicide, liver cancer, diabetes, cirrhosis, Chagas disease, African trypanosomiasis, melanoma, and others. Regional heterogeneity highlights the importance of sound epidemiological assessments of the causes of death on a regular basis. Bill & Melinda Gates Foundation. Copyright © 2012 Elsevier Ltd. All rights reserved.

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The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

Donat R. Spahn, Bertil Bouillon, Vladimir Cerny … (2019)

Background Severe traumatic injury continues to present challenges to healthcare systems around the world, and post-traumatic bleeding remains a leading cause of potentially preventable death among injured patients. Now in its fifth edition, this document aims to provide guidance on the management of major bleeding and coagulopathy following traumatic injury and encourages adaptation of the guiding principles described here to individual institutional circumstances and resources. Methods The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma was founded in 2004, and the current author group included representatives of six relevant European professional societies. The group applied a structured, evidence-based consensus approach to address scientific queries that served as the basis for each recommendation and supporting rationale. Expert opinion and current clinical practice were also considered, particularly in areas in which randomised clinical trials have not or cannot be performed. Existing recommendations were re-examined and revised based on scientific evidence that has emerged since the previous edition and observed shifts in clinical practice. New recommendations were formulated to reflect current clinical concerns and areas in which new research data have been generated. Results Advances in our understanding of the pathophysiology of post-traumatic coagulopathy have supported improved management strategies, including evidence that early, individualised goal-directed treatment improves the outcome of severely injured patients. The overall organisation of the current guideline has been designed to reflect the clinical decision-making process along the patient pathway in an approximate temporal sequence. Recommendations are grouped behind the rationale for key decision points, which are patient- or problem-oriented rather than related to specific treatment modalities. While these recommendations provide guidance for the diagnosis and treatment of major bleeding and coagulopathy, emerging evidence supports the author group’s belief that the greatest outcome improvement can be achieved through education and the establishment of and adherence to local clinical management algorithms. Conclusions A multidisciplinary approach and adherence to evidence-based guidance are key to improving patient outcomes. If incorporated into local practice, these clinical practice guidelines have the potential to ensure a uniform standard of care across Europe and beyond and better outcomes for the severely bleeding trauma patient. Electronic supplementary material The online version of this article (10.1186/s13054-019-2347-3) contains supplementary material, which is available to authorized users.

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Clinical practice guideline: red blood cell transfusion in adult trauma and critical care.

Fred A Luchette, Vivian W. Chiu, Andrew L Corwin … (2009)

To develop a clinical practice guideline for red blood cell transfusion in adult trauma and critical care. Meetings, teleconferences and electronic-based communication to achieve grading of the published evidence, discussion and consensus among the entire committee members. This practice management guideline was developed by a joint taskforce of EAST (Eastern Association for Surgery of Trauma) and the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM). We performed a comprehensive literature review of the topic and graded the evidence using scientific assessment methods employed by the Canadian and U.S. Preventive Task Force (Grading of Evidence, Class I, II, III; Grading of Recommendations, Level I, II, III). A list of guideline recommendations was compiled by the members of the guidelines committees for the two societies. Following an extensive review process by external reviewers, the final guideline manuscript was reviewed and approved by the EAST Board of Directors, the Board of Regents of the ACCM and the Council of SCCM. Key recommendations are listed by category, including (A) Indications for RBC transfusion in the general critically ill patient; (B) RBC transfusion in sepsis; (C) RBC transfusion in patients at risk for or with acute lung injury and acute respiratory distress syndrome; (D) RBC transfusion in patients with neurologic injury and diseases; (E) RBC transfusion risks; (F) Alternatives to RBC transfusion; and (G) Strategies to reduce RBC transfusion. Evidence-based recommendations regarding the use of RBC transfusion in adult trauma and critical care will provide important information to critical care practitioners.

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Author and article information

Contributors

Wayne B. Dyer:

ORCID: http://orcid.org/0000-0003-3193-2559

wdyer@redcrossblood.org.au

Journal

Journal ID (nlm-ta): Intensive Care Med Exp

Journal ID (iso-abbrev): Intensive Care Med Exp

Title: Intensive Care Medicine Experimental

Publisher: Springer International Publishing (Cham )

ISSN (Electronic): 2197-425X

Publication date (Electronic): 4 April 2022

Publication date PMC-release: 4 April 2022

Publication date Collection: December 2022

Volume: 10

Electronic Location Identifier: 12

Affiliations

[1 ]GRID grid.420118.e, ISNI 0000 0000 8831 6915, Australian Red Cross Lifeblood, ; Sydney, Australia

[2 ]GRID grid.420118.e, ISNI 0000 0000 8831 6915, Australian Red Cross Lifeblood, ; Brisbane, Australia

[3 ]GRID grid.415184.d, ISNI 0000 0004 0614 0266, Critical Care Research Group, , The Prince Charles Hospital, ; Brisbane, Australia

[4 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, Faculty of Medicine, , The University of Queensland, ; Brisbane, Australia

[5 ]GRID grid.1024.7, ISNI 0000000089150953, Faculty of Health, , Queensland University of Technology, ; Brisbane, Australia

[6 ]GRID grid.410567.1, Cardiovascular Research Institute, ; Basel, Switzerland

[7 ]GRID grid.117476.2, ISNI 0000 0004 1936 7611, Faculty of Health, , University of Technology, ; Sydney, Australia

[8 ]GRID grid.1024.7, ISNI 0000000089150953, Medical Engineering Research Facility, , Queensland University of Technology, ; Brisbane, Australia

[9 ]GRID grid.10403.36, ISNI 0000000091771775, Institut d’Investigacions Biomèdiques August Pi i Sunyer, ; Barcelona, Spain

Author information

Wayne B. Dyer http://orcid.org/0000-0003-3193-2559

Article

Publisher ID: 439

DOI: 10.1186/s40635-022-00439-6

PMC ID: 8980119

PubMed ID: 35377109

SO-VID: 3fe1bab3-8961-4ed2-9395-0a8a4935e6be

License:

Open AccessThis 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/.

History

Date received : 17 January 2022

Date accepted : 20 March 2022

Funding

Funded by: National Blood Authority

Award ID: ID316

Award Recipient : John F. Fraser

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Keywords: haemorrhagic shock,patient blood management,tissue oxygen delivery,oxygen debt,microcirculation,haemodilution,transfusion thresholds

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Keywords: haemorrhagic shock, patient blood management, tissue oxygen delivery, oxygen debt, microcirculation, haemodilution, transfusion thresholds

Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock

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Most cited references 53

Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010.

The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition

Clinical practice guideline: red blood cell transfusion in adult trauma and critical care.

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