Hypoxic, anemic and cardiac hypoxemia: When does tissue hypoxia begin?

Abstract

In case of hypoxemia, the oxygen content is often still in the lower normal range, so that there is no hypoxia in the tissue. If the hypoxia-threshold is reached in the tissue in hypoxic, anemic and also cardiac-related hypoxemia, identical counterregulations occur in the cell metabolism, regardless of the cause of hypoxemia. In clinical practice, this pathophysiologic fact is sometimes ignored, although depending on the cause of hypoxemia, assessment and therapy vary widely. While restrictive and generally accepted rules are specified in the transfusion guidelines for anemic hypoxemia, in the case of hypoxic hypoxia, the indication for invasive ventilation is made very early. The clinical assessment and indication are limited to the parameters oxygen saturation, oxygen partial pressure and oxygenation index. During the corona pandemic, misinterpretations of pathophysiology have become evident and may have led to unnecessary intubations. However, there is no evidence for the treatment of hypoxic hypoxia with ventilation. This review addresses the pathophysiology of the different types of hypoxia focusing on the problems associated with intubation and ventilation in the intensive care unit.

Kernaussagen

• Für die suffiziente Behandlung von hypoxämischen Erkrankungen auf der Intensivstation ist eine Kenntnis der Pathophysiologie des Sauerstofftransportes unerlässlich.

• Eine Hypoxie auf zellulärer Ebene kann kardial, pulmonal oder anämisch bedingt sein. Die Folgen des Sauerstoffmangels auf zellulärer Ebene sind unabhängig von der Ursache die gleichen. Erst bei schwerer Hypoxämie tritt eine Hypoxie im Gewebe auf.

• Zumeist wird die kritische Hypoxieschwelle nicht unterschritten, sodass viele Maßnahmen zur Anhebung des sO₂ oder des Hämoglobinwerts unnötig sind und die Patienten nur zusätzlich belasten.

• Eine Intubation bei isolierter Hypoxämie kann fast immer vermieden werden. Nach den Literaturdaten und der eigenen klinischen Erfahrung ist als Richtwert ein caO₂ von 10mlO₂/dl Blut in den allermeisten Fällen unkritisch.

Take home messages

• Knowledge of the pathophysiology of oxygen transport is essential for the sufficient treatment of hypoxemic diseases in the intensive care unit.

• The consequences of hypoxia at the cellular level are the same regardless of the cause. Only when hypoxemia is severe, tissue hypoxia occurs.

• In most cases, the critical hypoxia threshold is not undercut, so many measures to raise sO₂ or Hb are unnecessary and only add to the patient’s burden.

• Intubation for isolated hypoxemia can almost always be avoided. According to the literature data and our own clinical experience, a caO₂ of 10mlO₂/dl blood is not critical in the vast majority of cases as a guideline value.

Keywords

Hypoxia - Hypoxemia - Oxygen Saturation - Oxygen Content - Oxygen Delivery - mechanical ventilation

Publication History

Article published online:
29 March 2023

• Literatur

• 1 World Health Organisation. Living guidance for clinical management of COVID-19. Accessed November 01, 2022 at: https://www.who.int/publications/i/item/WHO-2019-nCoV-clinical-2021–2
• 2 Voshaar T, Stais P, Köhler D. et al. Conservative management of COVID-19 associated hypoxaemia. ERJ Open Res 2021; 7: 00026-2021 DOI: 10.1183/23120541.00026-2021. (PMID: 33738306)
• 3 Roedl K, Jarczak D, Thasler L. et al. Mechanical ventilation and mortality among 223 critically ill patients with coronavirus disease 2019: A multicentric study in Germany. Aust Crit Care 2021; 34: 167-175 DOI: 10.1016/j.aucc.2020.10.009.
• 4 Gottlieb J, Capetian P, Hamsen U. et al. Sauerstoff in der Akuttherapie beim Erwachsenen. Accessed November 01, 2022 at: https://www.awmf.org/uploads/tx_szleitlinien/020-021l_S3_Sauerstoff-in-der-Akuttherapie-beim-Erwachsenen_2021-06.pdf
• 5 Bundesärztekammer. Querschnitts-Leitlinien zur Therapie mit Blutkomponenten und Plasmaderivaten. Accessed November 01, 2022 at: https://www.bundesaerztekammer.de/fileadmin/user_upload/_old-files/downloads/pdf-Ordner/MuE/Querschnitts-Leitlinien_BAEK_zur_Therapie_mit_Blutkomponenten_und_Plasmaderivaten-Gesamtnovelle_2020.pdf
• 6 Haidl P, Jany B, Geiseler J. et al. Leitlinie zur Langzeit-Sauerstofftherapie. Accessed December 01, 2022 at: https://www.awmf.org/uploads/tx_szleitlinien/020–002l_S2k_Langzeit_Sauerstofftherapie_2020–08.pdf
• 7 Banerjee D, Yee BJ, Piper AJ. et al. Obesity hypoventilation syndrome: hypoxemia during continuous positive airway pressure. Chest 2007; 131: 1678-1684 DOI: 10.1378/chest.06-2447.
• 8 Catterall JR, Douglas NJ, Calverley PM. et al. Transient hypoxemia during sleep in chronic obstructive pulmonary disease is not a sleep apnea syndrome. Am Rev Respir Dis 1983; 128: 24-29 DOI: 10.1164/arrd.1983.128.1.24.
• 9 Köhler D. CaO2-Wert zur Beurteilung der Sauerstoff-Organversorgung: Klinische Bedeutung des Sauerstoffgehaltes. Dtsch Arztebl 2005; 102: A 2026-2030
• 10 Dellweg D, Schmitten J, Kerl J. et al. Impact of hypobaric flight simulation on walking distance and oxygenation in COPD patients. Respir Physiol Neurobiol 2019; 260: 1-7 DOI: 10.1016/j.resp.2018.11.010. (PMID: 30476554)
• 11 Goodman M. Suffer and Survive: The Extreme Life of J.S. Haldane. New York; Simon & Schuster: 2007. 329f.
• 12 West JB. Acclimatization and tolerance to extreme altitude. J Wilderness Med 1993; 4: 17-26 DOI: 10.1580/0953-9859-4.1.17. (PMID: 11538296)
• 13 Grocott MP, Martin DS, Levett DZ. et al. Arterial blood gases and oxygen content in climbers on Mount Everest. N Engl J Med 2009; 360: 140-149 DOI: 10.1056/NEJMoa0801581. (PMID: 19129527)
• 14 Nielsen M, Smith H. Studies on the regulation of respiration in acute hypoxia; with a appendix on respiratory control during prolonged hypoxia. Acta Physiol Scand 1952; 24: 293-313 DOI: 10.1111/j.1748-1716.1952.tb00847.x. (PMID: 14933122)
• 15 Severinghaus JW, Naifeh KH. Accuracy of response of six pulse oximeters to profound hypoxia. Anesthesiol 1987; 67: 551-558 DOI: 10.1097/00000542-198710000-00017. (PMID: 3662082)
• 16 Jubran A, Tobin MJ. Effect of isocapnic hypoxia on variational activity of breathing. Am J Respir Crit Care Med 2000; 162: 1202-1209 DOI: 10.1164/ajrccm.162.4.9907003. (PMID: 11029318)
• 17 Tobin MJ, Laghi F, Jubran A. Why COVID-19 Silent Hypoxemia Is Baffling to Physicians. Am J Respir Crit Care Med 2020; 202: 356-360 DOI: 10.1164/rccm.202006-2157CP. (PMID: 32539537)
• 18 Medicom. COVID-19: Die ersten sechs Monate. Accessed November 01, 2022 at: https://medicom.cc/de/publikationen/intensiv-news/202004/entries/01-Erfahrungen-mit-COVID-19.php
• 19 Legrand M, Vallée F, Mateo J. et al. Influence of arterial dissolved oxygen level on venous oxygen saturation: don't forget the PaO2!. Shock 2014; 41: 510-513 DOI: 10.1097/SHK.0000000000000162. (PMID: 24667613)
• 20 Greif R, Akça O, Horn EP. et al. Outcomes Research Group. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. N Engl J Med 2000; 342: 161-167 DOI: 10.1056/NEJM200001203420303.
• 21 Zander R. Physiologie und klinischer Nutzen einer Hyperoxie [Physiology and clinical relevance of hyperoxygenation]. Anasthesiol Intensivmed Notfallmed Schmerzther 2005; 40: 616-23 DOI: 10.1055/s-2005-870471. (PMID: 16252228)
• 22 Sekhar K, Rao SC. John Scott Haldane: The father of oxygen therapy. Indian J Anaesthesiol 2014; 58: 350-352 DOI: 10.4103/0019-5049.135087. (PMID: 25024490)
• 23 Schumacker PT, Cain SM. The concept of a critical oxygen delivery. Intens Care Med 1987; 13: 223-229 DOI: 10.1007/BF00265110. (PMID: 3301969)
• 24 Wolff CB. Normal cardiac output, oxygen delivery and oxygen extraction. Adv Exp Med Biol 2007; 599: 169-182 DOI: 10.1007/978-0-387-71764-7_23. (PMID: 17727262)
• 25 Ba ZF, Wang P, Koo DJ. et al. Alterations in tissue oxygen consumption and extraction after trauma and hemorrhagic shock. Crit Care Med 2000; 28: 2837-2842 DOI: 10.1097/00003246-200008000-00026. (PMID: 10966259)
• 26 Cain SM. Appearance of excess lactate in anesthetized dogs during anemic and hypoxic hypoxia. Am J Physiol 1965; 209: 604-610 DOI: 10.1152/ajplegacy.1965.209.3.604. (PMID: 5837745)
• 27 Weiskopf RB, Viele MK, Feiner J. et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998; 279: 217-221 DOI: 10.1001/jama.279.3.217. (PMID: 9438742)
• 28 Weil JV, Byrne-Quinn E, Sodal IE. et al. Hypoxic ventilatory drive in normal man. J Clin Invest 1970; 49: 1061-1072 DOI: 10.1172/JCI106322. (PMID: 5422012)
• 29 Dominelli PB, Baker SE, Wiggins CC. et al. Dissociating the effects of oxygen pressure and content on the control of breathing and acute hypoxic response. J Appl Physiol 2019; 127: 1622-1631 DOI: 10.1152/japplphysiol.00569.2019. (PMID: 31647724)
• 30 Cilley RE, Scharenberg AM, Bongiorno PF. et al. Low oxygen delivery produced by anemia, hypoxia, and low cardiac output. J Surg Res 1991; 51: 425-433 DOI: 10.1016/0022-4804(91)90145-c. (PMID: 1758176)
• 31 Scholz H, Schurek HJ, Eckardt KU. et al. Role of erythropoietin in adaptation to hypoxia. Experientia 1990; 46: 1197-1201 DOI: 10.1007/BF01936936. (PMID: 2253723)
• 32 Schumacker PT, Samsel RW. Analysis of oxygen delivery and uptake relationships in the Krogh tissue model. J Appl Physiol 1989; 67: 1234-1244 DOI: 10.1152/jappl.1989.67.3.1234. (PMID: 2793716)
• 33 Scandurra FM, Gnaiger E. Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics. Adv Exp Med Biol 2010; 662: 7-25 DOI: 10.1007/978-1-4419-1241-1_2. (PMID: 20204766)
• 34 Chant C, Wilson G, Friedrich JO. Anemia, transfusion, and phlebotomy practices in critically ill patients with prolonged ICU length of stay: a cohort study. Crit Care 2006; 10: R140 DOI: 10.1186/cc5054. (PMID: 17002795)
• 35 Fowler AJ, Ahmad T, Phull MK. et al. Meta-analysis of the association between preoperative anaemia and mortality after surgery. Br J Surg 2015; 102: 1314-1324 DOI: 10.1002/bjs.9861.
• 36 Tobin MJ, Jubran A, Laghi F. PaO2 /FIO2 ratio: the mismeasure of oxygenation in COVID-19. Eur Respir J 2021; 57: 2100274 DOI: 10.1183/13993003.00274-2021.
• 37 Schönhofer B, Wenzel M, Geibel M. et al. Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease. Crit Care Med 1998; 26: 1824-1828 DOI: 10.1097/00003246-199811000-00022.
• 38 Schönhofer B, Böhrer H, Köhler D. Blood transfusion facilitating difficult weaning from the ventilator. Anaesthesia 1998; 53: 181-184 DOI: 10.1046/j.1365-2044.1998.00275.x. (PMID: 9534644)
• 39 Comellini V, Pacilli AMG, Nava S. Benefits of non-invasive ventilation in acute hypercapnic respiratory failure. Respirology 2019; 24: 308-317 DOI: 10.1111/resp.13469. (PMID: 30636373)
• 40 Agostoni A, Lotto A, Stabilini R. et al. Hemoglobin oxygen affinity in patients with low-output heart failure and cardiogenic shock after acute myocardial infaraction. Eur J Cardiol 1975; 3: 53-58
• 41 Ge RL, Simonson TS, Gordeuk V. et al. Metabolic aspects of high-altitude adaptation in Tibetans. Exp Physiol 2015; 100: 1247-1255 DOI: 10.1113/EP085292. (PMID: 26053282)
• 42 Horscroft JA, Kotwica AO, Laner V. et al. Metabolic basis to Sherpa altitude adaptation. Proc Natl Acad Sci U S A 2017; 114: 6382-6387 DOI: 10.1073/pnas.1700527114. (PMID: 28533386)
• 43 Köhler D. Wie viel Hypoxämie verträgt der Mensch?. Dtsch Med Wochenschr 2010; 135: 474-477 DOI: 10.1055/s-0030-1249192. (PMID: 20198547)
• 44 Simon LM, Robin ED, Phillips JR. et al. Enzymatic basis for bioenergetic differences of alveolar versus peritoneal macrophages and enzyme regulation by molecular O2. J Clin Invest 1977; 59: 443-448 DOI: 10.1172/JCI108658. (PMID: 190266)
• 45 Singer M, Young PJ, Laffey JG. et al. Dangers of hyperoxia. Crit Care 2021; 25: 440 DOI: 10.1186/s13054-021-03815-y. (PMID: 34924022)