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Should I Monitor Brain Tissue PO₂?

Karl L. Kiening, Asita S. Sarrafzadeh, John F. Stover, and Andreas W. Unterberg

BRIEF ANSWER

Background

Importance of Posttraumatic Cerebral PbtO₂

Patients with severe traumatic brain injury (TBI) are at risk of developing inadequate cerebral perfusion pressure (CPP) and consequent secondary cerebral ischemic damage, most commonly because of intracranial hypertension or arterial hypotension. Low CPP, in turn, may compromise cerebral blood flow (CBF) and tissue oxygenation, potentially contributing to evolving structural and functional tissue damage and thus negatively affecting the final neurologic outcome. Consequently, maintenance of an adequate CPP, either by reducing elevated intracranial pressure (ICP) or increasing mean arterial blood pressure (MAP), is a widely accepted recommendation of the evidence-based Guidelines for the Management of Severe Traumatic Brain Injury produced by the Brain Trauma Foundation, the American Association of Neurological Surgeons (AANS), and the AANS/Congress of Neurological Surgeons (CNS) Section on Neurotrauma and Critical Care (class III data).¹

In healthy individuals, tissue oxygenation and cerebral perfusion show a critical and mutual interdependence (class II data).² The existence of a strict perfusion-dependent increase in tissue oxygenation in activated human cortex underlines the importance of oxidative metabolism for meeting activation-induced increases in energy demands. Consequently, any decrease in cerebral perfusion may impair oxygen supply and oxidative metabolism. As shown in clinical (class II data)^3,4 as well as experimental⁵ pathophysiologic studies, changes in PbtO₂ can be used to reliably monitor evolving disturbances of tissue metabolism. Because the mammalian brain is not equipped with sufficient oxygen and energy depots and because the activity of many key enzymes is regulated by PbtO₂ (class III data),⁶ tissue oxygenation must be maintained within physiologic limits to prevent additional cell damage.

Recent experience has taught us that local cerebral hypoxia may develop under conditions of normal ICP, CPP, and MAP, stressing the importance of targeted monitoring within the tissue of interest. Such episodes of local cerebral hypoxia may be caused by hyper-ventilation-induced hypocapnia (class II data),^3,7 by insufficient arterial oxygenation (class II data),³ or by a mismatch between oxygen delivery, that is, CBF, and cerebral metabolic rate of oxygen (CMRO₂) (class III data).8

Techniques for Monitoring Cerebral Oxygenation

Given the overriding importance of oxygen in maintaining energetic and ionic homeostasis and in preserving the integrity of cellular and subcellular function and structure, early detection of any decrease in cerebral oxygenation is likely to be necessary to guide adequate therapy. Real-time monitoring of cerebral oxygenation can be performed by tracking changes in jugular venous oxygen saturation (SjvO₂) via jugular bulb oximetry (class II data),⁹ which measures global cerebral oxygenation. Cerebral partial pressure of oxygen can also be measured with intraparenchymal oxygen sensors (class II data),¹⁰ which indicate local cerebral oxygenation.

Despite the strength of its scientific background (class II data),^9,11 SjvO₂ monitoring is not widely used because it can be cumbersome and because it is prone to artifact and to other potential problems with poor data quality (class II and III data).^12,13 On the other hand, monitoring of PbtO₂ has steadily increased in popularity because of its reliability and safety (class II data).¹⁴ Currently, two main PbtO₂ monitoring systems are commercially available: the Licox (Integra Neuroscience, Plainsboro, NJ) and the Neurotrend (Diametrics Medical, St. Paul, MN). The Neurotrend system is a multiparameter sensor that measures brain PCO₂, pH, and temperature in addition to PbtO₂. The Licox system measures only PbtO₂ (insertion of a separate temperature probe is usually performed as well).

Initially, both systems were based on the polarographic technique (modified “Cark-type” electrodes).¹⁵ In 1998, Neurotrend performed significant technical modifications and switched from a polarographic to a colorimetric method, utilizing optical fluorescence in combination with fiberoptics to measure changes in PbtO₂. In the latest Licox system design, the catheters are precalibrated and therefore suitable for immediate insertion, whereas in the Neurotrend system bedside calibration to a defined concentration of oxygen is necessary. Moreover, these systems cannot be compared because of differences in insertion depth, in accuracy of measurements at the zero point (Licox: 0.3 ± 0.3 mmHg; Neurotrend: 7.0 ± 1.4 mmHg) (class II data)¹⁶ and, in particular, differences in reported cerebral ischemic thresholds [Licox: 10 mmHg (class II data)¹⁷; Neurotrend: 19 mmHg (class II data)].¹⁸ In addition, the change in the type of PO₂ monitoring technology used in the Neurotrend catheter makes it difficult to perform a direct comparison of PbtO₂ data obtained with the old versus new Neurotrend sensors.

Where to Measure PbtO₂

Experimental studies have demonstrated that tissue oxygenation has a very heterogeneous distribution. The PbtO₂ value that is measured depends in part on the surrounding cell density and on the proximity of the inserted electrodes to blood vessels. The highest PbtO₂ levels are found close to penetrating vessels and in neuron-rich areas, for example, cortex and hippocampus, as opposed to white matter tracts that consist predominantly of axons (class III data).⁶

To date, no consensus has been reached as to the ideal placement of PbtO₂ monitors relative to different traumatic brain lesions; for example, focal/unilateral versus multiple/bilateral versus diffuse brain injury versus generalized edema. The PbtO₂ values that are measured in brain-injured patients are strongly influenced by the positioning of the catheter relative to cerebral contusions, with PbtO₂ values close to a lesion being significantly lower than those in areas in which a computed tomography scan reveals no injury (class II data).¹⁹

In clinical practice, parenchymal oxygen sensors are often placed in white matter that is contralateral to a focal lesion (“uninjured”). The assumption underlying this strategy is that a reduction in PbtO₂ in the uninjured hemisphere is indicative of widespread, global energetic perturbation caused by such events as a decrease in arterial oxygenation, an increase in ICP, impairment of cerebral perfusion, use of uncontrolled hyperventilation, or similar event. When bilateral lesions are present, those who use this approach prefer to monitor PbtO₂ in the hemisphere with the least injury. Some investigators, however, recommend the opposite approach. They suggest that it may be wiser to monitor PbtO₂ in the pericontusional zone, concentrating on the tissue that is at high risk of death (comparable to the penumbra in stroke).

A PubMed search was performed covering the period from 1996 (first clinical report on this topic10) to July 2002. Using the key word “brain tissue PO₂,” 141 references were generated, whereas the headings “cerebral oxygenation” and “head injury” resulted in 105 papers. After eliminating duplicates, experimental articles, nontrauma papers, non-PbtO₂ papers, reviews, and papers with purely technical issues, the 45 remaining papers dealt with clinical head injury and invasive monitoring of brain tissue PO₂ by one of the two fundamentally different monitoring systems described above.

In the following discussion, we focus on the Licox catheter, which is more commonly used and which provides a larger scientific background (30 articles) than the published papers that employed the Neurotrend catheter (n = 15). Only four papers compared both catheters.

As mentioned above, none of the Licox or Neurotrend papers contains data from a prospective, blinded, controlled, randomized study. Consequently, no class I evidence is available on which to base a “gold standard” recommendation. The clinical papers related to the Licox catheter (30 papers) deal with studies that employed prospective data collection and retrospective analyses, making them class II evidence at best. A further elimination of papers with only a small sample size (n ≤ 10), or in which PbtO₂ was not major parameter of interest, reduces the number to 24 eligible studies. These papers mainly focus on hypoxic thresholds (n = 3), clinical outcome (n = 8), hyperventilation therapy (n = 9), CPP therapy (n = 7), metabolic monitoring via microdialysis (n = 3), and hypothermia (n = 1) (some papers address more than one of these topics).

Critical PbtO₂ Thresholds and Neurologic Outcome

PbtO₂ monitoring has been validated in severe TBI patients by comparison to other established methods like SjvO₂ monitoring, in which a decrease in oxygen saturation to below 50% is indicative of cerebral ischemia. In one study, this critical threshold for jugular venous oxygen saturation was found to correspond to a PbtO₂ of 8.5 mmHg (class II data).¹³ Other clinical (class II data)³ and experimental²⁰ studies also suggest that the PbtO₂ threshold below which ischemic damage develops is 8 to 10 mmHg.