Should modulation of p50 be a therapeutic target in the critically ill?

Methemoglobin (MetHb) is an oxidized form on hemoglobin, which is unable to bind oxygen and consequently carry it to the tissues. Normally present in small quantities (<1%) without detrimental effects, its elevation produces hypoxemia which can be profound and even lethal. Methemoglobinemia is an abnormal increase of MetHb (>3%) of total hemoglobin. It can be classified in two types: hereditary and acquired. Acquired form is caused by exogenous oxidizing agents, such as nitrites or certain medications, while hereditary types of disease are the result of genetic deficiency in cytochrome B5 reductase, an enzyme responsible for MetHb reduction to hemoglobin. Little data is available on the epidemiology of methemoglobinemia. In general population only sporadic cases are described, while some isolated ethnic populations have increased incidence, possibly inherited from a common ancestor. We present a case of congenital methemoglobinemia in which detection of MetHb was hampered by faulty initial blood gas spectrometry results. A short literature review is also included.

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“…Although very useful measurement in critically ill, P50 is unsuitable for neonates as a result of reference range absence. 9…”

Section: Discussionmentioning

confidence: 99%

Congenital Methemoglobinemia: Rare Presentation of Cyanosis in Newborns

Viršilas

Timukienė

Liubšys

2019

Clinics and Practice

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“…The formation of superoxide in the heme pocket is attributed to enhanced heme pocket flexibility. Greater flexibility facilitates the interactions of distal histidine and the transfer of electrons from Fe 2+ to bound oxygen, which destabilize the iron–oxygen bond, resulting in the release of superoxide radical into the heme pocket .…”

Section: Discussionmentioning

confidence: 99%

Study on Oxidation Stability and Oxygen Affinity of Hemoglobin During Storage

Zhang

et al. 2018

Artificial Organs

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The factors affecting hemoglobin (Hb) oxidation in its short- and long-term storage were investigated. Porcine Hb with different levels of oxygen saturation was stored at 25°C or 4°C for 40 days. The methemoglobin (metHb) content increased rapidly when Hb was at half saturation with oxygen at 4°C, increased gradually with the increase in Hb oxygenation or deoxygenation, and was almost unchanged when Hb was highly oxygenated or deoxygenated. The Hb oxidation was more intense when stored at 25°C. This indicated that highly oxygenated or deoxygenated Hb can be stored short term at 4°C. The accelerated test showed that metHb content was almost unchanged when Hb was highly deoxygenated and stored at 37°C for 7 days; however, the metHb content rapidly increased when Hb was highly oxygenated and stored at 37°C, which indicated that only highly deoxygenated Hb is suitable for long-term storage. Then, the long-term oxidation stability of highly deoxygenated Hb and polymerized hemoglobin was verified; the metHb content of both did not show significant changes at 4°C for 18 months. Moreover, the results in this work indicated that a temperature increasing from 20 to 40°C clearly increased the partial oxygen pressure (P50), which represents decreased oxygen affinity and is beneficial to deoxygenation. Furthermore, P50 was increased when the pH decreased from 9 to 7. Therefore, we concluded that the appropriate high temperature and neutral condition in vitro are conducive to reducing the oxygen affinity of Hb to achieve efficient deoxygenation, which could promote the development of hemoglobin-based oxygen carriers.

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“…Anemia of varying severity is very distributed in COVID-19 ( 2 , 7 , 8 , 53 ). P 50 often increases during anemia ( 54 – 57 ) due to a stimulated 2,3-BPG synthesis, which results from lowered venous O 2 saturation during tissue passage (reducing free BPG because of improved binding to Hb) or hyperventilation (increased pH). This effect is independent of the type of illness but decreased pH may cancel the P 50 change ( 32 , 58 ).…”

Section: The Effect Of Anemia In Covid-19mentioning

confidence: 99%

The oxygen dissociation curve of blood in COVID-19

Böning

Kuebler

Bloch

2021

American Journal of Physiology-Lung Cellular and Molecular Phys

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COVID-19 hinders oxygen transport to the consuming tissues by at least 2 mechanisms: In the injured lung saturation of hemoglobin is compromised, in the tissues an associated anemia reduces the volume of delivered oxygen. For the first problem increased hemoglobin oxygen affinity (left shift of the oxygen dissociation curve ODC) is of advantage, for the 2nd, however, the contrary is the case. Indeed a right shift of the ODC has been found in former studies for anemia caused by reduced cell production or hemolysis. This resulted from increased 2,3-biphosphglycerate (2,3-BPG) concentration. In 3 investigations in COVID-19, however, no change of hemoglobin affinity was detected in spite of probably high [2,3-BPG]. The most plausible cause for this finding is formation of methemoglobin, which increases the oxygen affinity and thus apparently compensates for the 2,3-BPG effect. But this "useful effect" is cancelled by the concomitant reduction of functional hemoglobin. In the largest study on COVID-19 even a clear left shift of the ODC was detected when calculated from measurements in fresh blood rather than after equilibration with gases outside the body. This additional „in vivo" left shift possibly results from various factors (e. g. concentration changes of Cl-, 2,3-BPG, ATP, lactate, nitrocompounds, glutathione, glutamate, because of time delay between blood sampling and end of equilibration, or enlarged distribution space including interstitial fluid and is useful for O2 uptake in the lungs. Under discussion for therapy are the affinity-increasing 5-hydroxymethyl-2-furfural (5-HMF), erythropoiesis stimulating substances like erythropoietin, and methylene blue against MetHb formation.

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Should modulation of p50 be a therapeutic target in the critically ill?

Cited by 29 publications

References 72 publications

Congenital Methemoglobinemia: Rare Presentation of Cyanosis in Newborns

Congenital Methemoglobinemia: Rare Presentation of Cyanosis in Newborns

Study on Oxidation Stability and Oxygen Affinity of Hemoglobin During Storage

The oxygen dissociation curve of blood in COVID-19

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