Guy Rosenthal

Brain tissue oxygen tension is more indicative of oxygen diffusion than oxygen delivery and metabolism in patients with traumatic brain injury

Objectives:Despite the growing clinical use of brain tissue oxygen monitoring, the specific determinants of low brain tissue oxygen tension (Pbto2) following severe traumatic brain injury (TBI) remain poorly defined. The objective of this study was to evaluate whether Pbto2 more closely reflects variables related to cerebral oxygen diffusion or reflects cerebral oxygen delivery and metabolism. Design:Prospective observational study. Setting:Level I trauma center. Patients:Fourteen TBI patients with advanced neuromonitoring underwent an oxygen challenge (increase in Fio2 to 1.0) to assess tissue oxygen reactivity, pressure challenge (increase in mean arterial pressure) to assess autoregulation, and CO2 challenge (hyperventilation) to assess cerebral vasoreactivity. Interventions:None. Measurements and Main Results:Pbto2 was measured directly with a parenchymal probe in the least-injured hemisphere. Local cerebral blood flow (CBF) was measured with a parenchymal thermal diffusion probe. Cerebral venous blood gases were drawn from a jugular bulb venous catheter. We performed 119 measurements of Pao2, arterial oxygen content (Cao2), jugular bulb venous oxygen tension (P&OV0413;o2), venous oxygen content (C&OV0413;o2), arteriovenous oxygen content difference (AVDO2), and local cerebral metabolic rate of oxygen (locCMRO2). In multivariable analysis adjusting for various variables of cerebral oxygen delivery and metabolism, the only statistically significant relationship was that between Pbto2 and the product of CBF and cerebral arteriovenous oxygen tension difference (AVTO2), suggesting a strong association between brain tissue oxygen tension and diffusion of dissolved plasma oxygen across the blood-brain barrier. Conclusions:Measurements of Pbto2 represent the product of CBF and the cerebral AVTO2 rather than a direct measurement of total oxygen delivery or cerebral oxygen metabolism. This improved understanding of the cerebral physiology of Pbto2 should enhance the clinical utility of brain tissue oxygen monitoring in patients with TBI.

Radiation-induced meningioma.

The long-term or delayed side effects of irradiation on neural tissue are now known to include the induction of new central nervous system neoplasms. However, during the first half of the 20th century, human neural tissue was generally considered relatively resistant to the carcinogenic and other ill effects of ionizing radiation. As a result, exposure to relatively high doses of x-rays from diagnostic examinations and therapeutic treatment was common. In the present article the authors review the literature relating to radiation-induced meningiomas (RIMs). Emphasis is placed on meningiomas resulting from childhood treatment for primary brain tumor or tinea capitis, exposure to dental x-rays, and exposure to atomic explosions in Hiroshima and Nagasaki. The incidence and natural history of RIMs following exposure to high- and low-dose radiation is presented, including latency, multiplicity, histopathological features, and recurrence rates. The authors review the typical presentation of patients with RIMs and discuss unique aspects of the surgical management of these tumors compared with sporadic meningioma, based on their clinical experience in treating these lesions.

Post-operative expansion of hemorrhagic contusions after unilateral decompressive hemicraniectomy in severe traumatic brain injury.

Decompressive hemicraniectomy is commonly performed in patients with traumatic brain injury (TBI) with diffuse brain swelling or refractory raised intracranial pressure. Expansion of hemorrhagic contusions in TBI patients is common, but its frequency following decompressive hemicraniectomy has not been well established. The aim of this retrospective study was to determine the rate of hemorrhagic contusion expansion following unilateral hemicraniectomy in severe TBI, to identify factors associated with contusion expansion, and to examine whether contusion expansion is associated with worsened clinical outcomes. Computed tomography (CT) scans of 40 consecutive patients with non-penetrating TBI who underwent decompressive hemicraniectomy were analyzed. Hemorrhagic contusion volumes were measured on initial, last pre-operative, and first post-operative CT scans. Mortality and 6-month Glasgow Outcome Scale (GOS) score were recorded. Hemorrhagic contusions of any size were present on the initial head CT scan in 48% of patients, but hemorrhagic contusions with a total volume of >5 cc were present in only 10%. New or expanded hemorrhagic contusions of >or=5 cc were observed after hemicraniectomy in 58% of patients. The mean volume of increased hemorrhage among these patients was 37.1+/-36.3 cc. The Rotterdam CT score on the initial head CT was strongly associated with the occurrence and the total volume of expanded hemorrhagic contusions following decompressive hemicraniectomy. Expanded hemorrhagic contusion volume greater than 20 cc after hemicraniectomy was strongly associated with mortality and poor 6-month GOS even after controlling for age and initial Glasgow Coma Scale (GCS) score. Expansion of hemorrhagic contusions is common after decompressive hemicraniectomy following severe TBI. The volume of hemorrhagic contusion expansion following hemicraniectomy is strongly associated with mortality and poor outcome. Severity of initial CT findings may predict the risk of contusion expansion following hemicraniectomy, thereby identifying a subgroup of patients who might benefit from therapies aimed at augmenting the coagulation system.

Characterizing the dose-response relationship between mannitol and intracranial pressure in traumatic brain injury patients using a high-frequency physiological data collection system.

Despite the widespread use of mannitol to treat elevated intracranial pressure (ICP), there is no consensus regarding the optimal dosage. The objective of this study was to retrospectively characterize the dose-response relationship between mannitol and ICP using data collected with a continuous high-frequency physiological data collection system. To this end, we measured ICP continuously in 28 patients with traumatic brain injury (TBI) who were given at least one dose of mannitol. Twenty TBI patients were given a total of 85 doses of 50 g of mannitol, and 18 patients were given 50 doses of 100 g. Some patients received both amounts. Cerebral perfusion pressure was maintained above 60 mm Hg. The average ICP was 22.0 +/- 10.6 mm Hg when mannitol was administered, fell immediately after dosing, and continued falling for approximately 30 min to 15.7 +/- 8.1 mm Hg across all patients. After 30 min, ICP was equal in the 100-g group (15.6 +/- 10.9) versus the 50-g group (15.7 +/- 6.3). However, at 100 min, ICP had increased in the 50-g group to nearly its initial value but was still lower in the 100-g group (18.6 +/- 7.6 vs. 14.2 +/- 6.7 mm Hg; p = 0.001). Osmotic agents such as mannitol have been used for decades to treat cerebral edema, but there has been no definitive quantitative information regarding the dosing of mannitol. In a large, retrospective study of high-frequency ICP data, we have quantitatively shown that mannitols effect on ICP is dose-dependent and that higher doses provide a more durable reduction in ICP.

Use of hemoglobin-based oxygen-carrying solution-201 to improve resuscitation parameters and prevent secondary brain injury in a swine model of traumatic brain injury and hemorrhage: laboratory investigation.

OBJECT Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)-201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study. METHODS Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 +/- 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration. RESULTS Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO(2)) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 +/- 374 mm(3)) or LR solution (1246 +/- 279 mm(3); p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B-positive cells/hpf was seen between HBOC-201 solution (61.5 +/- 14.7) and LR solution (48.9 +/- 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B-positive cells/hpf was seen in animals resuscitated with LR solution (42.8 +/- 28.3) compared with those resuscitated with HBOC-201 solution (5.6 +/- 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine. CONCLUSIONS The improved MAP, CPP, and PbtO(2) observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying-201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.

Measurement of cerebrospinal fluid oxygen partial pressure in humans using MRI.

Fluid‐attenuated inversion recovery (FLAIR) images obtained during the administration of supplemental oxygen demonstrate a hyperintense signal within the cerebrospinal fluid (CSF) that is likely caused by T1 changes induced by paramagnetic molecular oxygen. Previous studies demonstrated a linear relationship between the longitudinal relaxation rate (R1 = 1/T1) and oxygen content, which permits quantification of the CSF oxygen partial pressure (PcsfO2). In the current study, CSF T1 was measured at 1.5 T in the lateral ventricles, third ventricle, cortical sulci, and basilar cisterns of eight normal subjects breathing room air or 100% oxygen. Phantom studies performed with artificial CSF enabled absolute PcsfO2 quantitation. Regional PcsfO2 differences on room air were observed, from 65 ± 27 mmHg in the basilar cisterns to 130 ± 49 mmHg in the third ventricle. During 100% oxygen, PcsfO2 increases of 155 ± 45 and 124 ± 34 mmHg were measured in the basilar cisterns and cortical sulci, respectively, with no change observed in the lateral or third ventricles. PcsfO2 measurements in humans breathing room air or 100% oxygen using a T1 method are comparable to results from invasive human and animal studies. Similar approaches could be applied to noninvasively monitor oxygenation in many acellular, low‐protein body fluids. Magn Reson Med 54:113–121, 2005.

Polyetheretherketone implants for the repair of large cranial defects: a 3-center experience.

BACKGROUND Calvarial reconstruction of large cranial defects following decompressive surgery is challenging. Autologous bone cannot always be used due to infection, fragmentation, bone resorption, and other causes. Polyetheretherketone (PEEK) is a synthetic material that has many advantages in cranial-repair surgery, including strength, stiffness, durability, and inertness. OBJECTIVE To describe our experience with custom-made PEEK implants for the repair of large cranial defects in 3 institutions: San Francisco General Hospital, Hadassah-Hebrew University Hospital, and the National Neuroscience Institute, Singapore. METHODS A preoperative high-resolution computed tomography scan was obtained for each patient for design of the PEEK implant. Cranioplasty was performed via standard technique with the use of self-tapping titanium screws and miniplates. RESULTS Between 2006 and 2012, 66 cranioplasties with PEEK implants were performed in 65 patients (46 men, 19 women, mean age 35 ± 14 years) for repair of large cranial defects. There were 5 infections of implants and 1 wound breakdown requiring removal of the implant (infection and surgical removal rates of 7.6% and 9.1%, respectively). Two patients required drainage of postoperative hematoma (overall surgical complication rate, 12.7%). Nonsurgical complications in 5 patients included seizures, nonoperative collection, and cerebrospinal fluid rhinorrhea that resolved spontaneously. Overall median patient or family satisfaction with the cranioplasty and aesthetic result was good, 4 on a scale of 5. Temporal wasting was the main aesthetic concern. CONCLUSION Custom-designed PEEK implants are a good option for patients with large cranial defects. The rate of complications is comparable to other implants or autologous bone. Given the large size of these defects, the aesthetic results are good.

The new licox combined brain tissue oxygen and brain temperature monitor: Assessment of in vitro accuracy and clinical experience in severe traumatic brain injury

OBJECTIVE Monitoring of brain tissue oxygen tension is increasingly being used to monitor patients after severe traumatic brain injury and to guide therapies aimed at maintaining brain tissue oxygen tension above threshold levels. The new Licox PMO combined oxygen and temperature catheter (Integra LifeSciences, Plainsboro, NJ) combines measurements of oxygen tension and temperature in a single probe inserted through a bolt mechanism. In this study, we sought to evaluate the accuracy of the new Licox PMO probe under controlled laboratory conditions and to assess the accuracy of oxygen tension and temperature measurements and the new automated card calibration system. We also describe our clinical experience with the Licox PMO probe. METHODS Oxygen tension was measured in a 2-chambered apparatus at different oxygen tensions and temperatures. The new card calibration system was compared with a manually calibrated system. Rates of hematoma, infection, and dislodgement in our clinical experience were recorded. RESULTS The new Licox PMO probe accurately measures oxygen tension over a wide range of oxygen concentrations and physiological temperatures, but it does have a small tendency to underestimate oxygen tension (mean error, −3.8 ± 3.5%) that is more pronounced between the temperatures of 33 and 39°C. The thermistor of the PMO probe also has a tendency to underestimate temperature when compared with a resistance thermometer (mean error, −0.67 ± 0.22°C). The card calibration system was also found to introduce some variability in measurements of oxygen tension when compared with a manually calibrated system. Clinical experience with the new probe indicates good placement within the white matter using the improved bolt system and low rates of hematoma (2.9%), infection (0%), and dislodgement (5.9%). conclusion The new Licox PMO probe is accurate but has a small, consistent tendency to under-read oxygen tension that is more pronounced at higher temperatures. The probe tends to under-read temperature by 0.5 to 0.8°C across temperatures, suggesting that caution should be used when brain temperature is measured with the Licox PMO probe and used to guide temperature-directed treatment strategies. The Licox PMO probe improves upon previous models in allowing consistent and accurate placement in the white matter and obviating the need for placement of 2 separate probes to measure oxygen tension and temperature.

Assessment of a noninvasive cerebral oxygenation monitor in patients with severe traumatic brain injury.

OBJECT Development of a noninvasive monitor to assess cerebral oxygenation has long been a goal in neurocritical care. The authors evaluated the feasibility and utility of a noninvasive cerebral oxygenation monitor, the CerOx 3110, which uses near-infrared spectroscopy and ultrasound to measure regional cerebral tissue oxygenation in patients with severe traumatic brain injury (TBI), and compared measurements obtained using this device to those obtained using invasive cerebral monitoring. METHODS Patients with severe TBI admitted to the intensive care unit at Hadassah-Hebrew University Hospital requiring intracranial pressure (ICP) monitoring and advanced neuromonitoring were included in this study. The authors assessed 18 patients with severe TBI using the CerOx monitor and invasive advanced cerebral monitors. RESULTS The mean age of the patients was 45.3 ± 23.7 years and the median Glasgow Coma Scale score on admission was 5 (interquartile range 3-7). Eight patients underwent unilateral decompressive hemicraniectomy and 1 patient underwent craniotomy. Sixteen patients underwent insertion of a jugular bulb venous catheter, and 18 patients underwent insertion of a Licox brain tissue oxygen monitor. The authors found a strong correlation (r = 0.60, p < 0.001) between the jugular bulb venous saturation from the venous blood gas and the CerOx measure of regional cerebral tissue saturation on the side ipsilateral to the catheter. A multivariate analysis revealed that among the physiological parameters of mean arterial blood pressure, ICP, brain tissue oxygen tension, and CerOx measurements on the ipsilateral and contralateral sides, only ipsilateral CerOx measurements were significantly correlated to jugular bulb venous saturation (p < 0.001). CONCLUSIONS Measuring regional cerebral tissue oxygenation with the CerOx monitor in a noninvasive manner is feasible in patients with severe TBI in the neurointensive care unit. The correlation between the CerOx measurements and the jugular bulb venous measurements of oxygen saturation indicate that the CerOx may be able to provide an estimation of cerebral oxygenation status in a noninvasive manner.

The role of lung function in brain tissue oxygenation following traumatic brain injury

OBJECTIVE Previous studies have demonstrated that periods of low brain tissue oxygen tension (PbtO2) are associated with poor outcome after head trauma but have primarily focused on cerebral and hemodynamic factors as causes of low PbtO2. The purpose of this study was to investigate the influence of lung function on PbtO2 with an oxygen challenge (increase in fraction of inspired oxygen [FiO2] concentration to 1.0). METHODS This prospective observational cohort study was performed in the neurointensive care unit of the Level 1 trauma center at San Francisco General Hospital. Thirty-seven patients with severe traumatic brain injury (TBI) undergoing brain tissue oxygen monitoring as part of regular care underwent an oxygen challenge, consisting of an increase in FiO2 concentration from baseline to 1.0 for 20 minutes. Partial pressure of arterial oxygen (PaO2), PbtO2, and the ratio of PaO2 to FiO2 (the PF ratio) were determined before and after oxygen challenge. RESULTS Patients with higher PF ratios achieved greater PbtO2 during oxygen challenge than those with a low PF ratio because they achieved a higher PaO2 after an oxygen challenge. Lung function, specifically the PF ratio, is a major determinant of the maximal PbtO2 attained during an oxygen challenge. CONCLUSIONS Given that patients with TBI are at risk for pulmonary complications such as pneumonia, severe atelectasis, and adult respiratory distress syndrome, lung function must be considered when interpreting brain tissue oxygenation.