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Fraction of Inspired Oxygen
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Increasing the Fio2 is perhaps the simplest and quickest way to improve arterial oxygenation and should be done immediately in the setting of life-threatening hypoxia. Unfortunately, simply increasing Fio2 may be the least physiologic way to improve oxygenation from a pulmonary mechanics standpoint, and prolonged administration of high levels of oxygen has consequences.
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Lung tissue is exposed to the highest concentrations of oxygen in the body. In animal and human studies, high fractions of inspired oxygen can cause lung injury, ranging from mild subjective symptoms to diffuse alveolar damage histologically indistinguishable from ARDS.43,44 Exposure to elevated Fio2 can reduce lung volumes secondary to absorptive atelectasis, increase intrapulmonary right-to-left shunt, and directly injure pulmonary parenchyma. The onset and rate of development are likely directly related to level of oxygen administration as well as duration.
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Hypoxia is known to cause secondary brain injury, and the delivery of Fio2 1.0 has been shown to increase brain tissue oxygenation.45 Typically, the partial pressure of brain oxygen tension (Pbto2) measured by a brain tissue oxygen probe improves almost immediately when Fio2 is increased.45 The administration of high levels of oxygen should be cautioned against, however. Despite some studies demonstrating reduced lactate levels and reduced lactate-to-pyruvate ratios, other studies have not reproduced these findings, and no good clinical studies demonstrate benefit of normobaric hyperoxia.46,47,48,49 In addition, systemic hyperoxia has not been shown to improve cerebral metabolic rate or functional outcome.50 Given these negative findings, as well as the well-known toxicity of hyperoxia, administration of prolonged levels of increased Fio2 should be discouraged in favor of better ventilator management to maximize recruitment, PEEP effects, and the compliant portion of the PV curve. When Fio2 exceeds 0.60, the clinician should manipulate the ventilator settings to improve oxygenation.
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Positive End-Expiratory Pressure
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Positive end-expiratory pressure (PEEP) maintains airway pressure above atmospheric pressure throughout the respiratory cycle by pressurization of the ventilator circuit. A full review of the topic is beyond the scope of this chapter, as the published literature on PEEP is extensive. However, the clinician should be aware of the pathophysiology pertinent to PEEP setting, advantages and side effects, approaches to PEEP setting, and the use of PEEP in the neurologically injured patient.
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In patients with hypoxia due to atelectasis, alveolar edema, and/or volume loss (which causes most type I respiratory failure), PEEP serves to restore functional residual capacity (FRC), reduce intrapulmonary shunt, shift ventilation to a more compliant portion of the PV curve, and prevent end-expiratory volume loss (derecruitment).51 PEEP recruits previously nonaerated lung tissue and homogenizes regional distribution of tidal ventilation. The net effect on gas exchange reflects the balance between recruitment and overdistention. In the setting of obstructive physiology or expiratory flow limitation, PEEP serves less to improve oxygenation and more to improve patient-ventilator synchrony and triggering (discussed below).5,6,52
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PEEP is not without side effects. Given the heterogenous distribution of lung injury in acute lung injury (ALI)/ARDS, PEEP can overdistend more compliant lung units, contributing to VILI.53 If PEEP leads to overdistention, it can augment dead space, increase pulmonary vascular resistance, and cause right heart dysfunction. It can also decrease venous return and, in the setting of volume depletion, decrease cardiac output.
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The optimal way to set PEEP is widely debated and controversial, as is the optimal level of PEEP to use.34-36,54,55,56,57,58 The literature reveals that PEEP has been set to maximal compliance, a level just exceeding the lower inflection point on a PV curve, the lowest PEEP to achieve adequate oxygenation, or a PEEP-Fio2 combination table.34,56,59,60 There is no widely accepted method to enhance clinical outcome. Before implementing any PEEP-setting strategy, an assessment of the risks and benefits and, most important, the potential to recruit alveolar units should be ascertained. Patients with primary pulmonary disorders, such as pneumonia or pulmonary contusions, usually have lung units with much less recruitability compared to patients with an extrapulmonary etiology of hypoxia, such as sepsis.61 Villar et al set PEEP at 2 cm H2O above the lower inflection point and demonstrated a mortality decrease from 53.3% to 32%.56 Using higher PEEP, Ranieri demonstrated attenuation in cytokine response, suggesting decreased inflammatory signaling with higher PEEP.58 These studies were done with simultaneous decreases in tidal volumes, however. The ALVEOLI trial was done to determine the isolated benefit of higher levels of PEEP in patients with ARDS. Despite improvement in oxygenation, the higher PEEP group showed no improvement in clinically relevant outcomes.34 In two recently published trials, high PEEP was set based on a “lung open ventilation” protocol along with recruitment maneuvers and adjusted as high as possible to not exceed a PPL of 28 to 30 cm H2O. Both of these trials demonstrated improved oxygenation, but no mortality benefit.35,36 Another physiologically attractive alternative is PEEP setting under the guidance of an esophageal balloon. The balloon is placed similarly to a nasogastric tube and is used to estimate pleural pressure in order to calculate transpulmonary pressure. Recent data show an improvement in oxygenation and compliance, but again no improvement in clinically relevant outcomes.24 Data have shown wide variability with respect to lung recruitment and PEEP effect on lung recruitment. As such, individualizing PEEP setting is likely the most prudent approach.
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PEEP can be set with or without recruitment maneuvers, with the aim being to open collapsed alveoli that may need higher, sustained inflation pressures to open. Clinical characteristics, such as etiology of ALI, can help assess potential for recruitment, but likely the easiest way to assess potential for alveolar recruitment is with a recruitment maneuver. After recruitment, alveoli are more compliant and easier to keep open. Recruitment maneuvers have been applied as sustained inflation pressures (30-40 seconds at 35-50 cm H2O), as pressure-controlled breaths at increased PEEP levels, or as intermittent sighs.35,55,59,62,63,64,65 They are generally very effective at improving oxygenation; however, they should be followed by an incremental increase in PEEP, or the effects will only be transient. In general, recruitment maneuvers are safe and tolerated well, but should likely be limited to patients early in the course of lung injury (more recruitability) with bilateral lung disease and no evidence of hypovolemia.
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PEEP can adversely affect ICP and cerebral perfusion pressure (CPP), and PEEP setting in patients with neurologic injury has been a controversial topic.26,27 By increasing intrathoracic pressure, and therefore juxtacardiac pressure, right atrial pressure can increase. This can impede venous outflow from the brain and lead to elevated ICP. Also, if PEEP decreases cardiac output, this can lead to hypotension and reduced cerebral blood flow. These effects are usually less significant in patients with reduced lung compliance. Also, if PEEP leads to overdistention, as opposed to alveolar recruitment, an increase in dead space can lead to elevated Paco2 levels. Elevated ICP and reduced CPP have historically been viewed as (relative) contraindications to the use of increasing levels of PEEP. This has led to the observation of a lower threshold to simply increase the Fio2 to combat hypoxia in this patient population. Fortunately, the literature demonstrates that PEEP is well tolerated in patients with TBI.26,27,66,67 Early studies show that PEEP causes only modest, clinically insignificant changes in ICP.68,69,70,71 In fact, PEEP set lower than ICP typically does not result in an increase in ICP, and if PEEP achieves alveolar recruitment, it can reduce ICP. Even in the setting of normal lung compliance (and therefore greater transmission of pressure to the intravascular space), PEEP has been shown to not significantly increase ICP. Furthermore, if PEEP results in alveolar recruitment, brain oxygenation may improve as a result.72 Therefore, traumatic brain injury and elevated ICP should not be considered contraindications to PEEP setting in patients who need alveolar recruitment. The data and physiology dictate that the benefits likely outweigh the risks in the majority of patients.
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In summary, PEEP serves to improve alveolar recruitment, decrease shunt, and improve oxygenation, as well as improve triggering in the setting of expiratory flow limitation. It has predictable physiologic effects, but the net hemodynamic effect of PEEP is some combination of volume status, ventricular function, and alveolar recruitment versus overdistention. There are several approaches to PEEP setting, but there is no convincing evidence that one method is superior to another. In the setting of TBI and/or elevated ICP, most data show that PEEP is well tolerated, and therefore should be attempted when necessary. PEEP setting and improving respiratory system mechanics should be favored over increasing Fio2, as this approach has a higher risk versus benefit profile and is less physiologically sound management. When confronted with a neurologically injured patient with either hypoxemia or unacceptable levels of inspired oxygen, the approach given in Figure 36-4 can be used.
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Partial Pressure of Brain Tissue Oxygen Tension
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Cerebral monitoring has historically focused on ICP and CPP. However, with the knowledge that cerebral ischemia is associated with worse clinical outcomes, Pbto2 monitoring allows the clinician continuous monitoring of cerebral oxygenation.73 Despite an ongoing clinical debate regarding Pbto2 monitoring, data suggest worse outcomes associated with low Pbto2 levels.74 Systemic oxygenation, pulmonary function, and cerebral oxygenation are strongly linked, given the basic physiology of oxygen transport from the lungs to the brain.75 ALI is also an independent risk factor for cerebral hypoxia in the setting of TBI.76 Given these facts, the care of patients with severe TBI should consider brain-lung interactions and that maneuvers that safely increase systemic oxygenation will likely increase Pbto2 as well.
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If monitored, Pbto2 values of less than 15 mm Hg should be a concern. The first step in addressing persistently low Pbto2 values should be the assessment of the invasive monitoring probe, as it may reside in dead tissue. Similarly, catheter fidelity must be maintained and assessed. While the absolute cutoff point of acceptable Pbto2 is debatable, persistently low values have again been shown to be associated with worse outcomes.74 Different threshold values likely exist for different patients and conditions, and other clinical questions remain (such as what defines “acceptable” brain oxygenation). Mechanical ventilator strategies to increase Pbto2 parallel strategies to increase Pao2: manipulation of Fio2, PEEP setting, manipulation of the I-to-E ratio to increase mean airway pressure, advanced mechanical ventilation modes, and rescue therapies such as inhaled nitric oxide.
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Upon insertion and calibration of the EVD, ICP monitor, and brain tissue oxygen monitor, the patient's ICP is 35 mm Hg, CPP 55 mm Hg, and Pbto2 13 mm Hg. You institute standard medical therapy for elevated ICP with good results. To address the hypoxia and elevated airway pressures, you PEEP set (without using a recruitment maneuver). Also, citing the data from large ARDSNet trials that showed that low tidal volume ventilation was associated with Paco2 levels in the 40s, you figured you could decrease his tidal volume safely. You set tidal volume to 6 mL/kg based on ideal body weight (IBW). After some time, his ICP is 20 mm Hg, CPP is 60 mm Hg, Pbto2 is 19 mm Hg, and ABG is 7.29/48/80. Despite raising his PEEP to 15 cm H2O, his PPL is actually better now at 30 cm H2O (you must have improved compliance by recruiting collapsed alveoli) and his Fio2 is 0.60. Just as you begin to feel comfortable, you wonder if his lung injury will continue to worsen. As you walk through the unit, you see his PPL is now 42 H2O and his mean arterial pressure is falling, and you notice a large v wave on his central venous pressure (CVP) tracing, which reads 19 mm Hg. His ICP is creeping close to 30 mm Hg, and his Pbto2 is 13 mm Hg. You are concerned his lung injury and airway pressures are harming forward blood flow.