If you wish to respond to a paper or other item already published in the BJA, please go to the abstract/full text version of that item and click on the link "E-Letters: Submit a response to the article".
Electronic Letters to:
|
|
E-letters: Electronic letters published:
-
![[Read E-letter]](/icons/misc/sectionDOWN.gif)
Permissive Hypoxemia in ARDS – Is There a Place for a New Strategy?
- Mohamad Abdelsalam Abdelkader (29 December 2004)
|
|
|||
|
Mohamad Abdelsalam Abdelkader
Send letter to journal:
|
The acute respiratory distress syndrome (ARDS) was first described in 1967, when Ashbaugh and colleagues reported 12 patients with acute respiratory distress, cyanosis refractory to oxygen therapy, decreased lung compliance and diffuse pulmonary infiltrates on the chest radiograph (1). In 1994, new definition was recommended by the American-European Consensus Conference that has been widely accepted by clinicians and research workers. Acute lung injury (ALI) is defined as a syndrome of acute and persistent lung inflammation with increased vascular permeability. It is characterized by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) of 300 or less, regardless of the level of PEEP, bilateral pulmonary infiltrates on the chest radiograph and the absence of clinical evidence of elevated left atrial pressure or if measured, the pulmonary capillary wedge pressure (PCWP) of 18 mm Hg or less. The definition of ARDS is exactly the same except that the hypoxemia is more severe with a PaO2 to FiO2 ratio of 200 or less, regardless of the level of PEEP (2). Mechanical ventilation is a life-saving therapy that has become the mainstay of management of patients with ARDS. Traditionally, the adverse consequences of mechanical ventilation include hypotension from reduced venous return and barotrauma with pneumothorax, pneumomediastinum and rarely air embolism. More recently, various studies have shown less obvious and perhaps more dangerous types of ventilator-induced lung injury, including volutrauma, atelectrauma and biotrauma (3). Volutrauma is a more subtle type of lung injury that can occur secondary to alveolar overdistension when large tidal volumes and/or excessive PEEP are used. The term volutrauma indicates that it is the lung volume rather than the airway pressure that causes this type of lung injury (4). Cyclical atelectasis or atelectrauma refers to the damage that can occur when the lungs become atelectatic during expiration and re-expanded on inspiration, particularly when low levels of PEEP are applied (5). Biotrauma is characterized by the release of inflammatory mediators from the injured lungs into the systemic circulation. These mediators can promote further lung injury and contribute to the development of multi-organ failure, particularly during traditional tidal volume ventilation (10 to 15 mL/Kg of ideal body weight) (6). The concept of biotrauma may explain why the mortality of ARDS remains high (about 50 percent), despite the great advances in mechanical ventilation, as most patients die of multi-organ failure rather than respiratory failure (7). For most patients with ARDS, high levels of FiO2 and PEEP are required to achieve satisfactory arterial oxygenation. Unfortunately, both of these treatments have potential adverse effects that must be carefully considered in individual patients. A spectrum of lung injury, ranging from mild tracheobronchitis to diffuse alveolar damage which is histologically indistinguishable from ARDS, may result from high concentrations of inspired oxygen (8). In general, an FiO2 of 0.6 or less is usually considered to be safe. However, the diseased lungs, in ARDS, may be more susceptible to oxygen toxicity at a relatively low FiO2 (9). Permissive hypoxemia indicates that arterial oxygen saturation below 90 percent can be accepted, as long as there is no evidence of tissue hypoxia. We can therefore, avoid the application of high FiO2 and/or excessive PEEP that can induce pulmonary oxygen toxicity, barotrauma, volutrauma and contribute to multi-organ failure. It must be emphasised that even safe levels of FiO2 (equal to or less than 0.6) can cause oxygen toxicity and promote further lung injury, that can be difficult to diagnose in the clinical setting of ARDS. Permissive hypoxemia illustrates the importance of tissue oxygenation rather than arterial oxygen saturation as a goal of therapy of patients with ARDS. On the contrary, conventional ventilatory strategies for patients with ARDS focus on maintaining adequate arterial oxygenation (SaO2 around 90 percent) assuming that lower levels of SaO2 would compromise tissue oxygenation and lead to tissue hypoxia. However, the relationship between arterial oxygen saturation and oxygen delivery is not always parallel as it is not only the saturation of hemoglobin, but also hemoglobin affinity that determines the amount of oxygen released to the tissues. Hemoglobin affinity for oxygen changes according to variations in pH, partial pressure of arterial carbon dioxide (PaCO2), temperature and red-cell 2,3-diphosphoglycerate (2,3 DPG). In patients with acidosis or hypercapnia, hemoglobin affinity is decreased and oxygen dissociation curve is shifted to the right, facilitating the release of oxygen to the tissues (10). Therefore, SaO2 may be relatively low, in spite of improved oxygen delivery to the tissues, raising a concern about arterial oxygen saturation as an indicator of tissue oxygenation. As a result of the widely used lung- protective ventilation, many patients with ARDS are now prone to develop hypercapnia and respiratory acidosis (permissive hypercapnia), that can promote oxygen delivery and improve tissue oxygenation, regardless of the relatively low arterial oxygen saturation. During permissive hypercapnia, the relatively low SaO2 for a given PaO2 may lead to unnecessary increase in FiO2 and/or PEEP that can be particularly deleterious to patients with ARDS. Permissive hypoxemia therefore, has the theoretical advantage of reducing the risk of pulmonary oxygen toxicity, barotrauma, alveolar overdistension and multi-organ failure without necessarily compromising tissue oxygenation, especially in the adequately sedated and paralysed patients. Arterial hypoxemia may compromise oxygen delivery and lead to tissue hypoxia, especially when accompanied by decreased cardiac output, low hemoglobin concentration or increased metabolic demands of the body. However, to what extent is tissue hypoxia implicated in the pathogenesis of multi-organ failure and death in patients with ARDS? Surprisingly, tissue hypoxia probably contributes only a little to the pathogenesis of multi-organ failure. The release of inflammatory mediators into the systemic circulation, as a result of alveolar overdistension may contribute to the development of multi-organ failure and death in ARDS patients (6). The concept of biotrauma, rather than tissue hypoxia may explain why multi-organ failure, rather than hypoxemia is the major cause of death of ARDS. In the absence of tissue hypoxia, permissive hypoxemia may be more safe than increasing the FiO2 and/or PEEP, which can induce pulmonary oxygen toxicity, alveolar overdistension and multi-organ failure, in spite of maintaining adequate arterial oxygenation. I may therefore, hypothesize that maintaining the SaO2 at 90 percent or more through the application of relatively high FiO2 or PEEP can be more dangerous than permissive hypoxemia, as long as it has not resulted in significant tissue hypoxia. Tissue oxygenation reflects the balance between oxygen delivery (DO2) and oxygen consumption (VO2). Tissue hypoxia can develop if there is a decrease in DO2, as in shock, hypoxemia or severe anemia or increase in VO2, as a result of increased metabolic demands of the body (11). Tissue oxygenation is not determined by arterial oxygen saturation alone, other factors include cardiac output, hemoglobin concentration, oxygen affinity of hemoglobin and oxygen demand of the body. It must be emphasised that the body can remarkably tolerate hypoxemia by a compensatory increase in blood flow and oxygen extraction ratio (12). I may therefore, speculate that permissive hypoxemia is not necessarily accompanied by significant tissue hypoxia, particularly if the other parameters of oxygen delivery, such as cardiac output and hemoglobin concentration are normalized and oxygen consumption is minimized by the appropriate use of sedation, analgesia and muscle paralysis. Because of the sigmoid shape of oxygen dissociation curve, once the PaO2 has reached 60 mm Hg, further decrease in PaO2, will result in dramatic fall in arterial oxygen saturation. When the PaO2 is allowed to decrease below 60 mm Hg, as in permissive hypoxemia, the dissociation curve becomes very steep reflecting the low oxygen affinity of hemoglobin that enhances the release of oxygen to the tissues, in spite of the low arterial oxygen saturation. Permissive hypoxemia may therefore, favour oxygen unloading at the tissues by reducing hemoglobin affinity for oxygen. At a PaO2 of 60 mm Hg, the dissociation curve is almost flat indicating that further increase in PaO2 will have little effect on arterial oxygen saturation (13). Hence, a PaO2 of 60 mm Hg or SaO2 of 90 percent has been considered as an index of adequate arterial oxygenation in most ventilatory strategies of ARDS. However, lower levels of PaO2 or SaO2 may not necessarily lead to significant tissue hypoxia, because of the decrease in oxygen affinity of hemoglobin that favours peripheral oxygen unloading, increase in oxygen extraction and reduction in metabolic demand and oxygen consumption in the ventilated, sedated and paralyzed patients. Mild pulmonary hypertension is frequently seen in patients with ARDS. In some patients, acute cor pulmonale and right ventricular dysfunction can develop (14). Inhaled nitric oxide is a potent pulmonary vasodilator, that can be used in some patients with refractory hypoxemia or severe pulmonary hypertension, without causing systemic vasodilatation (15). During permissive hypoxemia, especially when relatively low levels of PaO2 are allowed, continuous hemodynamic monitoring of pulmonary artery pressure, with Swan-Ganz catheter is important to detect clinically significant pulmonary hypertension that may require treatment with inhaled nitric oxide or prostacyclin. Cardiac index greater than 4.5 liters per minute per square meter of body surface area is commonly referred to as supra-normal cardiac output. I may hypothesize that oxygen delivery can be maintained within normal or near- normal value by augmenting cardiac output to compensate for the low arterial oxygen saturation. Maintaining supra-normal cardiac output can therefore, reduce tissue hypoxia during permissive hypoxemia and may be a useful alternative to increasing FiO2 or PEEP, particularly when relatively unsafe levels have been reached. DO2 = 1.34 x Hb x SaO2 x Qt According to the previous equation, oxygen delivery (DO2) can be maintained, at least theoretically by supra-normal cardiac output (Qt) if arterial oxygen saturation is relatively low. Inotropic agents, such as dobutamine or milrinone can be used to increase cardiac output to supra- normal levels with only minimal increase in oxygen consumption. Volume expansion, with crystalloids or colloids and vasodilator agents, such as nitroprusside and nitrates can also be used. As previously mentioned, arterial oxygen content is determined mainly by arterial oxygen saturation and hemoglobin concentration, as the amount of oxygen dissolved in plasma is minimal. Arterial oxygen content is reduced during permissive hypoxemia as a result of the low arterial oxygen saturation. In such circumstances, hemoglobin concentration would be particularly important in determining arterial oxygen content and oxygen delivery. However, what might be the optimal hemoglobin concentration during permissive hypoxemia? Hébert and his colleagues in the Canadian Critical Care Trials Group demonstrated that a restrictive strategy of red -cell transfusion, in which hemoglobin concentration is maintained at 7 to 9 g per deciliter, is at least as effective as and possibly superior to a liberal transfusion strategy, in which hemoglobin concentration is maintained at 10 to12 g per deciliter (16). However, oxygen delivery and oxygen consumption were not calculated or measured in this trial, making it difficult to evaluate the usefulness of restrictive transfusion strategy in critically ill patients with hypoxemia, a clinical situation in which arterial oxygen content and oxygen delivery are reduced. Thus, it may not be appropriate to use a hemoglobin level of less than 7 g per deciliter as a threshold for red-cell transfusion to patients with ARDS, especially if there is evidence of tissue hypoxia. Maintaining hemoglobin concentration at 9 to10 g per deciliter may therefore, be advisable during permissive hypoxemia to avoid further reduction in arterial oxygen content and oxygen delivery. Clinical and biochemical assessment of tissue hypoxia is important to all patients during permissive hypoxemia. Whole-body oxygen consumption can be measured in ventilated patients by modern gas exchange monitors. Alternatively, VO2 can be calculated as a function of the cardiac output and arteriovenous oxygen content difference. VO2 = Qt x 1.34 x Hb x (SaO2 - SvO2) However, oxygen consumption derived from this equation is less accurate than that measured by calorimetry (17). Global assessment of tissue hypoxia also includes mixed venous oxygen saturation, which can be measured either intermittently by withdrawing blood from a pulmonary arterial line or continuously by fiberoptic pulmonary artery catheter (18). SvO2 is probably the best single indicator of the adequacy of whole- body oxygen transport since it represents the amount of oxygen left in systemic venous blood after passing through the tissues (19). A decrease in SvO2 can be caused by a decrease in cardiac output, arterial oxygen saturation or hemoglobin concentration and/or an increase in oxygen demand. However, a normal value of SvO2 does not rule out regional tissue hypoxia that can result from extensive redistribution of blood flow, especially in septic shock. Regional tissue hypoxia is often difficult to detect by global indices of tissue hypoxia, such as SvO2 or arterial blood lactate (20, 21). In patients with ARDS and sepsis, the same limitation of SvO2 for the detection of regional tissue hypoxia is still present, whether permissive hypoxemia is used or not. However, in the context of permissive hypoxemia, it may be more appropriate to use oxygen extraction ratio rather than SvO2 as an index of global tissue hypoxia, since the initially low SaO2 may further reduce SvO2 without necessarily indicating increased oxygen extraction and tissue hypoxia. O2 ER = (SaO2 - SvO2) / SaO2 Increased production of lactate is one of the most common abnormalities in patients with tissue hypoxia. However, lactic acidosis is not specific for tissue hypoxia and blood lactate may increase in several clinical situations, including sepsis, without other evidence of tissue hypoxia. Other parameters of regional tissue hypoxia include measurement of gastric mucosal pH and cerebral oxygen extraction ratio. The adequacy of cerebral oxygenation can be evaluated invasively, by calculating cerebral oxygen extraction ratio or non-invasively by infrared and near-infrared spectroscopy (22). Cerebral O2 ER = SaO2 - SvjO2 / SaO2 where SvjO2 is the oxygen saturation of internal jugular venous blood. In selected patients with coronary artery disease, myocardial oxygenation can be evaluated by measuring myocardial blood lactate, oxygen extraction ratio and regional pH during transvenous catheterization of the coronary sinus that drains most of the cardiac veins and opens into the right atrium. Non-invasive assessment of myocardial oxygenation can be performed with electrocardiography, to detect ST segment -T wave changes and echocardiography for evaluating the left ventricular function and regional wall motion. Renal function should also be closely monitored with urine output, BUN and creatinine. In conclusion, permissive hypoxemia is a hypothetical ventilatory strategy that focuses on maintaining adequate tissue oxygenation rather than arterial oxygen saturation. During permissive hypoxemia, relatively low SaO2 (as low as 85 or 80 percent) may be accepted, without necessarily increasing the FiO2 or PEEP, as long as there is no evidence of significant tissue hypoxia. Permissive hypoxemia can therefore, reduce the incidence of pulmonary oxygen toxicity, alveolar overdistension, multi-organ failure and death in patients with ARDS. In addition, I may hypothesize that oxygen delivery can be maintained within normal or near-normal value by augmenting cardiac output and minimizing oxygen demand of the body, thereby reducing the risk of tissue hypoxia. Finally, permissive hypoxemia remains hypothetical until evaluating its impact on mortality and morbidity of patients with ARDS. References 1. Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress syndrome in adults. Lancet 1967;2:319-323. 2. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relative outcomes and clinical trial coordination. Am J Respir Crit Care Med 1994;149:818- 824. 3. Parker JC, Hernandez LA, Peevy KJ. Mechanisms of ventilator-induced lung injury. Crit Care Med 1993;21:131. 4. Dreyfuss D, Saumon G. barotrauma is volutrauma, which volume is the one responsible? [editorial]. Intensive Care Med 1992;18:139. 5. Lachmann B. Open up the lung and keep the lung open [editorial; comment]. Intensive Care Med 1992;18;319. 6. Ranieri VM, Suter PM, Tortorella C, et al. Effects of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA 1999;282:54-61. 7. Montgomry A.B.M.A, Stager CJ, Caricco and Hudson LD. Causes of mortality in patients with the adult respiratory distress syndrome. Am Rev Respir Dis 1985;132:485. 8. Davis WB, Rennard SI, Bitterman PD, Crystal RG. Pulmonary oxygen toxicity. Early reversible changes in human alveolar structures induced by hyperoxia. N Engl J Med 1983;309:878. 9. Witschi HR, Haschek WM, Klein-Szanto AJ, et al. Potentiation of diffuse lung damage by oxygen. Am Rev Respir Dis 1981;123:98-103. 10. Connie CW, Hsia MD. Respiratory Function of Hemoglobin. N Engl J Med 1998;338:239. 11. Guyton AC, Hall JE. Transport of Oxygen and Carbon Dioxide in the Blood and Body Fluids. Textbook of Medical Physiology, 2000.p.463-473. 12. Hochachka PW. Defence strategies against hypoxia and hypothermia. Science 1986;231:234. 13. Rob Law, Bukwirwa H. The physiology of Oxygen Delivery. Update in Anaesthesia 1999;10:3. 14. Steltzer H, Kraft P, Fridich P, et al. Right ventricular function and oxygen transport patterns in patients with acute respiratory distress syndrome. Anaesthesia 1994;49:1039. 15. Roy G, Brower MD, Loraraine B, et al. Treatment of ARDS. Chest 2001;120:1347. 16. He'bert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999;340:409-417. 17. Takala J, Keinanen O, Vaisanen P, Kari A. Measurement of gas exchange in intensive care : laboratory and clinical validation of a new device. Crit Care Med 1989; 17:1041. 18. Armaganidis A, Dhainaut JF, Billard JL, Klouche K, Mira JP, et al. Accuracy assessment of three fiberoptic pulmonary artery catheters for SvO2 monitoring. Intensive Care Med 1994;20:484. 19. Weissman C, Kemper M. The oxygen uptake-oxygen delivery relationship during ICU interventions. Chest 1991;99:430. 20. Third European Consensus Conference in Intensive Care. 1996. Paris 7-8 December, 1995. Tissue hypoxia: how to detect, how to correct, how to prevent? Reanimation Urgencies, 5, 161, 320. 21. Ruokonen E, Takala J, Kari A, et al. Regional blood flow and oxygen transport in septic shock. Crit Care Med 1993;21:1296. 22. Mancini DM, Bolinger L, Li K, et al. Validation of near-infrared spectroscopy in humans. J Appl Physiol 1994;77:2740. Conflict of Interest:None declared |
|||