Elevation of Systemic Oxygen Delivery in the Treatment of Critically Ill Patients

Hayes, Michelle; Timmins, Andrew C.; Yau, E.H.S.; Palazzo, M. G. A.; Hinds, C. J.; Watson, David

doi:10.1056/nejm199406163302404

Cited by 1,377 publications

(514 citation statements)

References 20 publications

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“…However, VO 2 only rose in response to increases in O 2 delivery in a subset of patients. When the increased oxygen delivery did not increase VO 2 mortality was extremely high 3. These studies suggest that cytopathic hypoxia (decreased oxygen extraction despite adequate oxygen delivery), rather than decreased oxygen delivery, is a central problem in many critically ill patients 4.…”

Section: Introductionmentioning

confidence: 94%

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Looking for CO ₂ : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

Berg

Donnino

Callaway

2018

JAHA

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Section: Introductionmentioning

confidence: 94%

“…Whether from impaired oxygen delivery or cytopathic hypoxia, lower VO 2 is associated with increased mortality in sepsis2, 3 and after cardiac arrest 5, 6. The details of exactly how cardiac arrest and resuscitation alter cellular metabolism remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Looking for CO ₂ : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

Berg

Donnino

Callaway

2018

JAHA

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“…Interventional studies attempting to increase oxygen delivery to supra‐normal levels have indeed not shown beneficial effects on outcomes, and in some cases even the opposite 4. Notably, not all patients and organs are predicted to tolerate relative reductions in blood flow: The renal medulla seems particularly prone to hypoxic injury, especially in patients with pre‐existing capillary flow disturbances.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

“…Apparently, MOF is not the result of insufficient blood supply to individual organs, and attempts to improve outcome by increasing oxygen delivery have yielded conflicting results 4. In the kidney, acute renal failure (ARF) in sepsis is associated with marked reductions of glomerular filtration rate and urine output.…”

mentioning

confidence: 99%

Microcirculatory dysfunction and tissue oxygenation in critical illness

Østergaard

Granfeldt

Secher

et al. 2015

Acta Anaesthesiol Scand

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Severe sepsis is defined by organ failure, often of the kidneys, heart, and brain. It has been proposed that inadequate delivery of oxygen, or insufficient extraction of oxygen in tissue, may explain organ failure. Despite adequate maintenance of systemic oxygen delivery in septic patients, their morbidity and mortality remain high.The assumption that tissue oxygenation can be preserved by maintaining its blood supply follows from physiological models that only apply to tissue with uniformly perfused capillaries. In sepsis, the microcirculation is profoundly disturbed, and the blood supply of individual organs may therefore no longer reflect their access to oxygen.We review how capillary flow patterns affect oxygen extraction efficacy in tissue, and how the regulation of tissue blood flow must be adjusted to meet the metabolic needs of the tissue as capillary flows become disturbed as observed in critical illness. Using the brain, heart, and kidney as examples, we discuss whether disturbed capillary flow patterns might explain the apparent mismatch between organ blood flow and organ function in sepsis. Finally, we discuss diagnostic means of detecting capillary flow disturbance in animal models and in critically ill patients, and address therapeutic strategies that might improve tissue oxygenation by modifying capillary flow patterns.

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“…Current strategies to increase oxygen delivery may be beneficial in the earliest phases of resuscitation, but this approach may be less effective, or even harmful, in later stages if mitochondrial oxidative phosphorylation is impaired (8). Currently, there is no practical method available to measure mitochondrial dysfunction within vital organs at the bedside.…”

Section: Introductionmentioning

confidence: 99%

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Karamercan¹,

Weiss²,

Villarroel

et al. 2013

Shock

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INTRODUCTION Although mitochondrial dysfunction is thought to contribute to the development of post-traumatic organ failure, current techniques to assess mitochondrial function in tissues are invasive and clinically impractical. We hypothesized that mitochondrial function in peripheral blood mononuclear cells (PBMCs) would reflect cellular respiration in other organs during hemorrhagic shock and resuscitation (HS&R). METHODS Using a fixed pressure HS model, Long Evan’s rats were bled to a mean arterial pressure (MAP) of 40 mmHg. When blood pressure could no longer be sustained without intermittent fluid infusion (Decompensated HS), Lactated Ringer’s (LR) was incrementally infused to maintain the MAP at 40 mmHg until 40% of the shed blood volume was returned (Severe HS). Animals were then resuscitated with 4X total shed volume in LR over 60 minutes (Resuscitation). Control animals underwent the same surgical procedures, but were not hemorrhaged. Animals were randomized to Control (n=6), Decompensated HS (n=6), Severe HS (n=6) or Resuscitation (n=6) groups. Kidney, liver, and heart tissues as well as PBMC’s were harvested from animals in each group to measure mitochondrial oxygen consumption using high resolution respirometry. Flow cytometry was used to assess mitochondrial membrane potential (Ψm) in PBMCs. One-way ANOVA and Pearson correlations were performed. RESULTS Mitochondrial oxygen consumption decreased in all tissues, including PBMC’s, following Decompensated HS, Severe HS, and Resuscitation. However, the degree of impairment varied significantly across tissues during HS&R. Of the tissues investigated, PBMC mitochondrial oxygen consumption and Ψm provided the closest correlation to kidney mitochondrial function during HS (complex I: r =0.65; complex II: r=0.65; complex IV: r=0.52; p<0.05). This association, however, disappeared with resuscitation. A weaker association between PBMC and heart mitochondrial function was observed but no association was noted between PBMC and liver mitochondrial function. CONCLUSION All tissues including PBMC’s demonstrated significant mitochondrial dysfunction following HS&R. Although PBMC and kidney mitochondrial function correlated well during hemorrhagic shock, the variability in mitochondrial response across tissues over the spectrum of hemorrhagic shock and resuscitation limits the usefulness of using PBMC’s as a proxy for tissue-specific cellular respiration.

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Elevation of Systemic Oxygen Delivery in the Treatment of Critically Ill Patients

Cited by 1,377 publications

References 20 publications

Looking for CO ₂ : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

Looking for CO ₂ : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

Microcirculatory dysfunction and tissue oxygenation in critical illness

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

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Elevation of Systemic Oxygen Delivery in the Treatment of Critically Ill Patients

Cited by 1,377 publications

References 20 publications

Looking for CO 2 : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

Looking for CO 2 : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

Microcirculatory dysfunction and tissue oxygenation in critical illness

Can Peripheral Blood Mononuclear Cells Be Used as a Proxy for Mitochondrial Dysfunction in Vital Organs During Hemorrhagic Shock and Resuscitation?

Contact Info

Product

Resources

About

Looking for CO ₂ : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest

Looking for CO ₂ : Exploring the Novel Finding of Low Respiratory Quotient After Cardiac Arrest