Respiratory failure: a physiologic approach Dr. Dennis Prabhu Dayal

Introduction Respiratory failure - failure of V/Q – N – 0.8 lung ventilation (V) lung perfusion (Q) or their coupling (V/Q) V/Q – N – 0.8 Mismatch – exchange of gaseous O2 and CO2 becomes inefficient >1 – too much ventilation or too little blood flow <1 – too little ventilation or too much blood flow

O2 vs CO2 Oxygen Carbon dioxide Hemoglobin dependent Alveoli with high V/Q cannot add extra O2 for alveoli with low V/Q PaO2 – N – 80-100 mm Hg Decreases with age and supine position Solubility Alveoli with high V/Q compensate well for alveoli with low V/Q PaCO2 – N – close to 40 mm Hg Unaffected by age or body position

Causes Low partial pressure of o2 (Pio2) Diffusion impairment Right-to-left shunt Low V/Q mismatch Hypoventilation High partial pressure of inspired co2

Right to left shunt V/Q uncoupled Cardiac (R-L) Pulmonary Vascular Small – Cirrhosis Large – hereditary hemorrhagic telengiectasias Pulmonary Parenchymal Alveolar consolidation or atelectasis prevents gases from reaching alveoli while blood flow continues through their capillary beds Pneumonia, ARDS Nonhypercapnic hypoxemic respiratory failure

Low V/Q mismatch Dominant pathophysiology in abnormalities of gaseous exchange Mild – moderate – Hypoxemic Severe – Hypoxemia + Hypercapnia CO2 – solubility, better ventilation from normal alveoli Not enough Normal – high V/Q alveoli For a patient breathing room air, V/Q mismatch never causes hypercapnia in the absence of hypoxemia

Hypoventilation Decreased minute ventilation with normal lungs Minute ventilation is reduced relative to the metabolic demand present for oxygen uptake and co2 production alveolar ventilation - abnormally low, resulting in decreased gas exchange between the external environment and the alveoli Gas exchange between the alveoli and the pulmonary capillary blood is not impeded

Hypoventilation Hypoventilation by definition causes both arterial hypoxemia and a raised arterial Pco2 The alveolar Pco2 can rise to the point that the partial pressure of o2 is significantly reduced Extrapulmonary causes of respiratory failure

Differential Diagnosis of Extrapulmonary Respiratory Failure Central nervous system - Respiratory center depression owing to overdose, primary alveolar hypoventilation, myxedema Peripheral nervous system - Spinal cord disease, amyotrophic lateral sclerosis, Guillain-Barre syndrome Respiratory muscles - Muscle fatigue, myasthenia gravis, polymyositis, hypophosphatemia Chest wall - Ankylosing spondylitis, flail chest, thoracoplasty Pleura - Restrictive pleuritis Upper airway obstruction - Tracheal stenosis, vocal cord tumor

Overlapping factors More than 1 mechanism A decrease in cardiac output may worsen hypoxemia primarily due to marked V/Q abnormalities, a large right- to-left shunt, or both Primary cause of hypercapnia + Shunt – worsening of hypercapnia In patients with an impaired capacity to clear co2, increases in production may gain clinical relevance Fever increases co2 production by 13% for each 1°C temperature elevation above normal Nutritional support with excessive total calories or proportionally high carbohydrate loads also increases co2 production

Analytical Tools Alveolar – arterial PO2 gradient to separate extrapulmonary and primary pulmonary disorders as long as patient is breathing room air (A-a) gradient = [FIO2x(pAtm - pH2O)] - (pCO2 / RespQuot) - paO2 Gradient between alveolus and capillary Extra pulmonary failure – N gradient Shunt or V/Q mismatch – gradient increases Evaluation of Hypercapnia Gradient > 20 – indicative of pulmonary dysfunction Measure the severity of gas exchange impairment Influenced by Age and FiO2

a/A PO2 Ratio Relatively unaffected by FiO2 a/A PO2 = 1- (A-a PO2)/PAO2 Normal on room air – 0.74 – 0.77 On 100% Oxygen – 0.80 – 0.82 Low <0.6 – shunt, V/Q mismatch <0.35 – weaning failure <0.15 – refractory hypoxemia

PaO2/FiO2 ratio When the Fio2 is above 0.21, the A-a gradient becomes a less accurate measure of the efficiency of gas exchange Pao2/Fio2ratio can be used to assess the severity of the gas exchange defect The normal value for Pao2/Fio2 is 300 to 500 A value of less than 300 is indicative of gas exchange derangement and a value below 200 is indicative of severe impairment Although the Pao2/Fio2 is felt to be a more reliable measure of degree of gas exchange impairment at higher Fio2s, it too has the potential to be unreliable, particularly in the presence of a large shunt or a low Fio2

100% Oxygen inhalation Low V/Q mismatch v/s shunt In areas of low V/Q mismatch, the alveolar Po2 is low. If 100% oxygen is delivered via a closed system, even a poorly ventilated alveolus in theory soon contains 100% oxygen diluted only by the partial pressures of water and co2. Thus, with low V/Q mismatch the Pao2 rises dramatically if the Fio2 is increased. In contrast, areas of shunt are never exposed to o2, and there is no response to an increase in Fio2. If the Pao2 with the patient breathing 100% o2 is greater than 500 mm Hg, then prior hypoxemia is largely due to V/Q mismatch . If the Po2 on 100% o2 is less than 350 mm Hg, then major shunting is present.

Nuclear Scanning Diagnosis of the etiology of shunt Technetium labelled macroaggregated albumin is a relatively large particle that does not pass through capillaries Differentiate shunt with normal vasculature from shunt due to abnormal vascular connections If vascular anatomy is normal, the technetium-labelled molecules of the nuclear scan are filtered by the pulmonary capillaries and remain in the lung In contrast, with abnormal connection (s) between the right and left heart vasculatures, significant amounts of technetium-labelled particles bypass pulmonary capillaries and are then filtered by systemic capillaries (e.g., brain and kidneys)

Contrast Echocardiography If the shunt is not pulmonary parenchymal, the final step in differentiation would be contrast echocardiography, Document right-to-left cardiac shunting if present immediate transit (within four cardiac cycles) to the left heart can be seen with intracardiac shunt. If there is no cardiac shunt or if contrast appears after five cardiac cycles, then the abnormal vascular connection is in the pulmonary circulation.

Respiratory Acid Base disorders Nature – Respiratory/ Metabolic, Simple/complicated Acuity Minutes to hours – acute Several days or longer – chronic Arterial [H+] = 24(PaCO2/HCO3-) ∆[H+]/∆PCO2 Respiratory acidosis 0.8 – acute, 0.3 – chronic , 0.3-0.8 – acute on chronic Respiratory alkalosis 0.8 – acute, 0.17 – chronic

Clinical approach Respiratory failure occurs when gas exchange becomes significantly impaired Analyse the ABG for the severity, type, and acuity of the gas exchange disturbance These factors and the expected duration of the process guide interventions Acute hypercapnia can be evaluated for reversible causes. If none is found, mechanical ventilatory support is needed

Clinical approach In an acute-on-chronic situation, the trend of the acidosis is most crucial in deciding whether mechanical ventilatory support is necessary If the ratio is consistent with an acute respiratory acidosis, the patient who fails to improve with treatment should receive ventilatory support Fear of causing increased hypercapnia should not be a deterrent to the use of supplemental oxygen in an acutely ill hypoxemic patient Start supplemental oxygen at a low dose and then to slowly increase the Fio2 until adequate oxygenation is achieved

Clinical approach Respiratory alkalosis is not itself a cause of respiratory failure unless the increased work of breathing cannot be sustained by the respiratory muscles. Management therefore depends on diagnosis of the underlying stimulus for hyperventilation and on treatment specific to that condition. When respiratory alkalosis continues to worsen in critically ill patients on mechanical ventilatory support, however, it may become necessary to treat the respiratory alkalosis directly. In such a setting, sedation with or without paralysis of skeletal muscles can be useful.

Clinical approach Hypoxemia that responds only minimally to large increases in Fio2 involves significant shunt Cardiac shunt or large pulmonary arteriovenous shunts may be amenable to invasive intervention. Diffuse pulmonary parenchymal shunt, as can occur in acute respiratory distress syndrome, may be amenable to positive end-expiratory pressure. In clinical scenarios in which reversal or amelioration of the underlying process may be possible within the short- term, noninvasive ventilation may provide a therapeutic bridge that allows avoidance of the possible disadvantages of intubation and mechanical ventilation

Conclusion The most clinically relevant physiologic mechanisms underlying all abnormalities of gas exchange low V/Q mismatch, hypoventilation, and shunt. A series of tools that can be used to analyse and differentiate these physiologic possibilities and define the acuity of a disorder. Analysis of the type and acuity of a process should lead to an attempt to define the responsible disease process(es) and to intervene specifically. The decision of when or whether to institute mechanical ventilatory support, especially with intubation, is not always clear from numbers alone; this decision involves the art as well as the science of medicine.

Suggested reading Irwin and Rippe's Intensive Care Medicine, 6th Edition The ICU book, Paul L. Marino, 4th Edition