Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians.

BACKGROUND: Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. AIM: To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. METHODS: A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. RESULTS: Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. CONCLUSION: The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Brain tissue PO2: correlation with cerebral blood flow.

This investigation analyzed 22 xenon CT cerebral blood flow (CBF) studies from 18 severely head-injured patients (Glasgow motor score < 6) who underwent xenon CT scanning while brain tissue oxygen tension (PbtO2) was being monitored. CBF was determined both in a localized region of interest around the actual or estimated location of the tip of the PbtO2 probe and in the entire corresponding CT slice. Linear regression analysis was used to examine the relationship between these CBF measurements and PbtO2 values recorded immediately prior to the xenon CT CBF study. PbtO2 varied linearly with both regional CBF (rCBF) and global CBF measurements, but the average global CBF value was significantly higher than the average rCBF value. Very low values were significantly less common for global CBF than for rCBF. Further investigation is necessary to determine how probe placement near contused areas vs. in normal tissue affects our understanding of the relationship between rCBF, global CBF, PbtO2, and cerebral oxygen consumption.

Microdialysate nitrate/nitrite levels following severe head injury.

Nitric oxide (NO) has important regulatory functions within the central nervous system. The purpose of this study was to measure the concentration of nitric oxide in the brain after severe traumatic brain injury. NO is oxidized in vivo to nitrate and nitrite. Measurement of these products gives an index of NO production. Laboratory studies have shown a good correlation between NO measured directly with an electrode, and indirectly by microdialysis nitrate/nitrite. Using chemiluminescence method we measured nitrate/nitrite levels in 2024 microdialysate samples obtained from 24 patients during the first five days following severe head injury. We used CMA 70 probe (AB Microdialysis, Sweden) perfused by normal saline at a rate of 2 microliters/min. The median values of nitrate/nitrite for the whole group were highest on day 1 and gradually decreased over the 5 day monitoring period (day 1-19.2 mumol/l, day 5-12.7 mumol/l). Average values were lowest in the patients that died of their injury (14.3 mumol/l), and highest in patients who recovered by 3 months after injury with a moderate or severe disability (25.8 mumol/l or 31.9 mumol/l). In addition, there was a strong interaction between the severity of neurological injury and the change in dialysate nitrate/nitrite over time. The results suggest that nitric oxide may have a role in secondary injury mechanisms, but that this role is complex and varies as the injury evolves over time.

Measurement of the nitric oxide metabolites nitrate and nitrite in the human brain by microdialysis.

To examine the feasibility of measuring the nitric oxide (NO) metabolites nitrate and nitrite in microdialysate samples from the human brain, microdialysis probes were placed in normal appearing cerebral cortex of severely head injured patients in the Neurosurgical Intensive Care Unit at Ben Taub General Hospital. Nitrate/nitrite analysis was performed using NO chemiluminescence. Low micromolar levels of NO metabolites were consistently and easily detected. These levels seen are comparable to levels reported in CSF but tissue tortuosity and probe recovery considerations suggest that the absolute concentrations at the probe site are probably ten fold higher. Microdialysis with measurement of nitric oxide metabolites is technically feasible and may provide valuable insights into both normal neurochemistry and neurochemical derangements in disease.

Comparison of microdialysate arginine and glutamate levels in severely head-injured patient.

L-arginine concentrations in the brain are of interest following TBI because L-arginine is the immediate precursor of nitric oxide (NO). In addition, in vitro studies suggest that glutamate, which is a mediator of secondary injury after TBI, may stimulate release of arginine from glial cells. This study examines arginine concentrations in brain tissue using the microdialysis technique after human TBI. From 78 TBI patients, a total of 1739 microdialysate samples were collected using a CMA-70 probe perfused with normal saline at 2 microliters/min and concentrations of amino acids in microdialysate were determined. Amino acid concentrations for each patient were averaged for 8-hour periods during the first 3 days after injury, and daily for postinjury days 4 and 5. Following an initial rapid decrease in arginine, the dialysate arginine concentrations were low on days 1-3 and then increased over the days 4-5 after injury. In contrast, the microdialysate glutamate levels decreased slowly over the first 48 hours after TBI and thereafter remained low. Thirty-five episodes of jugular venous desaturation (SjvO2 < 50%) occurred during monitoring. Arginine and glutamate levels simultaneously doubled during desaturation and decreased as the clinical episode resolved. The low concentrations of arginine during the first 3 days after TBI may indicate that substrate unavailability could contribute to the decreased NO concentrations that have been observed after TBI. The simultaneous increase in glutamate and arginine during ischemic events is consistent with experimental data which has observed that glutamate induces release of arginine.

Adult respiratory distress syndrome: a complication of induced hypertension after severe head injury.

OBJECT: The factors involved in the development of adult respiratory distress syndrome (ARDS) after severe head injury were studied. The presence of ARDS complicates the treatment of patients with severe head injury, both because hypoxia causes additional injury to the brain and because therapies that are used to protect the lungs and improve oxygenation in patients with ARDS can reduce cerebral blood flow (CBF) and increase intracranial pressure (ICP). In a recent randomized trial of two head-injury management strategies (ICP-targeted and CBF-targeted), a fivefold increase in the incidence of ARDS was observed in the CBF-targeted group. METHODS: Injury severity, physiological data, and treatment data in 18 patients in whom ARDS had developed were compared with the remaining 171 patients in the randomized trial in whom it had not developed. Logistic regression analysis was used to study the interaction of the factors that were related to the development of ARDS. In the final exact logistic regression model, several factors were found to be significantly associated with an increased risk of ARDS: administration of epinephrine (5.7-fold increased risk), administration of dopamine in a larger than median dose (10.8-fold increased risk), and a history of drug abuse (3.1-fold increased risk). CONCLUSIONS: Although this clinical trial was not designed to study the association of management strategy and the occurrence of ARDS, the data strongly indicated that induced hypertension in this high-risk group of patients is associated with the development of symptomatic ARDS.

Subarachnoid-pleural fistula treated with noninvasive positive-pressure ventilation. Case report.

The authors describe the case of a 24-year-old man who underwent an L-1 corpectomy for spinal decompression and stabilization following an injury that caused an L-1 burst fracture. Postoperatively, an accumulation of spinal fluid developed in the pleural space, which was refractory to 1 week of thoracostomy tube drainage and lumbar cerebrospinal fluid (CSF) diversion. The authors then initiated a regimen of positive-pressure ventilation in which a bi-level positive airway pressure (PAP) mask was used. After 5 days, the CSF collection in the pleural space resolved. Use of a bi-level PAP mask represents a safe, noninvasive method of reducing the negative intrathoracic pressure that promotes CSF leakage into the pleural cavity and may be a useful adjunct in the treatment of subarachnoid-pleural fistula.

How well do neurosurgeons care for trauma patients? A survey of the membership of the American Association for the Surgery of Trauma.

OBJECTIVE: To quantify the trauma community's perceptions about neurosurgeons' involvement in trauma. METHODS: Mail survey of the membership of the American Association for the Surgery of Trauma. RESULTS: The response rate was 33.6% (280 of 833 mailings). Eighty-four percent of respondents practiced in an academic setting, and 51% reported that neurosurgery residents were available in their hospitals at night and on weekends. Approximately 60% reported that neurosurgeons were in charge of the care of adults with isolated head injuries (HIs) who had been operated on. A similar percentage thought that neurosurgeons should be in charge of such patients' care. Only 31.5% indicated that neurosurgeons were in charge if no operation had been performed (P < 0.001 versus patients who had been operated on), but 42.1% thought that neurosurgeons should be in charge of patients who had not been operated on (P < 0.001 versus neurosurgeons who actually were in charge of such patients). The same question was asked with regard to adults with both HIs and systemic injuries and with regard to children with HIs with and without systemic injuries. In general, the actuality of a leadership role for neurosurgeons depended on whether a craniotomy had been performed, and it was believed that more neurosurgeons should be in charge than actually were in charge of patients with HIs. Reluctance to insert intracranial pressure monitors was the most commonly reported problem (44.8% of respondents) with regard to neurosurgeons' care of patients with HIs. All problems were reported to be significantly more common when in-house neurosurgery residents were not available. More than 40% of respondents indicated that non-neurosurgeons should be allowed to insert intracranial pressure monitors, and 14% thought that non-neurosurgeons should be allowed to perform trauma craniotomies. These opinions were strongly associated with the reporting of problems in neurosurgeons' performance in these areas (P < 0.001 and P = 0.001, respectively). CONCLUSION: Neurosurgeons frequently yield responsibility for managing patients with HIs to other specialists, but more frequent leadership of neurosurgeons in this area would be welcome. Reported problems with neurosurgical care of trauma patients may be related to a lack of immediate availability of neurosurgeons, such as the absence of in-house neurosurgery residents at night. Failure of neurosurgeons to address perceived deficiencies in their care of trauma patients may lead to serious erosion of the central role of neurosurgeons in managing patients with HIs.

Management of cerebral perfusion pressure.

The management of cerebral perfusion pressure is among the most controversial treatment issues. Cerebral perfusion pressure (CPP) is normally expressed as the difference between mean arterial blood pressure and intracranial pressure and has two important physiological roles in the patient with severe head injury. First, CPP represents the pressure gradient acting across the cerebrovascular bed and hence is an important factor in the regulation of cerebral blood flow. Second, CPP contributes to the hydrostatic pressure within the intracerebral vessels, and therefore is one of the factors that determines edema formation in the injured brain. The border between adequate and inadequate CPP should be assessed individually and continuously, as it may fluctuate in time. The treatment plan that includes rapid identification of intracranial hemorrhage, rapid evacuation of extra-axial blood, treatment of intracranial hypertension, and promotion of cerebral and systemic perfusion is likely to provide the best outcome for all patients.

Midline shift after severe head injury: pathophysiologic implications.

OBJECTIVE: To investigate the mechanism of the adverse effect of midline shift after severe traumatic brain injury. METHODS: This study compared averaged cerebral metabolic parameters of patients with midline shift > 5 mm (S) on initial computerized tomography scan to those of patients with shift < or = 5 mm (NS). The effect of an acute subdural hematoma (SDH) was determined by separating patients into those with and those without SDH and then re-examining the effect of shift in these subgroups. RESULTS: Four hundred fifty-four patients were studied. Cerebral metabolic rate of oxygen (CMRO2, in mL/100 g per min) was always lower with shift: 1.74 for SDH-S versus 2.21 for SDH-NS (p < 0.001), and 1.80 for non-SDH-S versus 2.24 for non-SDH-NS (p < 0.001). No other major effects of shift were seen in SDH patients. Among non-SDH patients, shift was associated with higher intracranial pressure (ICP): 23.1 mm Hg versus 16.3 mm Hg (p < 0.001). Other differences between shift and nonshift patients in the non-SDH group were due at least in part to interventions to treat the elevated ICP. CONCLUSION: Midline shift after severe traumatic brain injury is associated with reduced CMRo2, regardless of whether or not SDH is present. The deleterious effects of subdural blood may be related more to the mass effect of large SDHs than to the biochemical abnormalities caused by small amounts of blood in the subdural space.

Similarities between civilian gunshot wounds to the head and nongunshot head injuries.

BACKGROUND: This investigation compared the cerebral pathophysiologic status of gunshot wounds to the head (GSWH) with that of severe head injury of other causes (non-GSWH). METHODS: Data were collected prospectively from 71 GSWH and 541 non-GSWH patients. The two groups had similar demographic characteristics and injury severities. Cerebral metabolic parameters for each patient were averaged for the entire period of monitoring. These per-patient averages were compared between GSWH and non-GSWH groups. RESULTS: Median intracranial pressure was 21.4 mm Hg in GSWH patients vs. 16.7 mm Hg in non-GSWH patients (p < 0.001). Mean arterial pressures were similar, but the higher intracranial pressure in GSWH patients produced a lower median cerebral perfusion pressure. Cerebral blood flow, cerebrovascular resistance, cerebral metabolic rate of oxygen, average jugular venous oxygen saturation, and number of jugular venous desaturations did not differ significantly between the groups. Three-month outcome was death in 43% of GSWH patients and 32% of non-GSWH patients, persistent vegetative state or severe disability in 33% and 32%, respectively, and moderate disability or good recovery in 24% and 36%, respectively. These outcomes were not significantly different (p = 0.11). CONCLUSION: GSWH patients suffer global cerebral metabolic disturbances that are at least as severe as those seen in non-GSWH patients with injuries of comparable severity. This selected population of GSWH patients may enjoy outcomes comparable to those of non-GSWH patients if they are treated by the same aggressive protocols.

Extracellular glutamate and aspartate in head injured patients.

Eighty-six patients in coma from a severe head injury underwent monitoring of extracellular concentrations of glutamate and aspartate by a microdialysis technique during the first few days after injury. The median value for glutamate was 7.4 microM (interquartile range 3.6-18.8 microM). The median value for aspartate was 2.4 microM (interquartile range 1.1-5.0 microM). Average values for the dialysate concentrations of glutamate and aspartate, were closely related to outcome (p < .001 and p = .002, respectively). Patients who died of their head injury had significantly higher dialysate glutamate and aspartate concentrations compared to patients who recovered to a Glasgow Outcome Score of good recovery or moderate disability. Dialysate glutamate and aspartate levels were also significantly related to type of injury (p = .008 and p = .004, respectively). The highest values were found in patients with gunshot wounds, followed by patients with evacuated and unevacuated mass lesions. Patients with diffuse injuries had the lowest values of glutamate and aspartate. These results suggest that excitatory amino acids may play a role in the evolution of injury to the brain after trauma.

Global and regional techniques for monitoring cerebral oxidative metabolism after severe traumatic brain injury.

The disturbance of normal mechanisms of oxygen delivery and metabolism is a hallmark of severe traumatic brain injury (TBI). In the past, investigations into the status of cerebral oxygen metabolism depended on changes in the differences in oxygen content between arterial and jugular venous blood. The development of jugular venous oximetry permitted continuous monitoring of jugular venous oxygen saturation, thereby overcoming earlier limitations caused by intermittent sampling. Neuromonitoring techniques that utilize only jugular vein sampling provide information only about global cerebral metabolism, but direct measurement of brain tissue oxygen tension via intraparenchymal probes makes possible the assessment of regional cerebral oxygen metabolism. Regional and global neuromonitoring techniques are not competitive or mutually exclusive. Rather, they are best regarded as complementary, with each providing valuable information that has a direct bearing on patient outcomes. The authors review the currently available techniques used in the monitoring of cerebral oxidative metabolism in patients who have sustained severe TBI.

Comparison of jugular venous oxygen saturation and brain tissue Po2 as monitors of cerebral ischemia after head injury.

OBJECTIVE: To compare the characteristics of jugular venous oxygen saturation (Sjvo2) and brain tissue Po2 (Pbto2) as monitors for cerebral ischemia after severe head injury. Sjvo2 has been useful as a monitor for cerebral ischemia, but it is limited by its inability to identify regional cerebral ischemia. Pbto2 may be superior to Sjvo2 for this purpose, because oxygenation in localized areas of the brain can be monitored. DESIGN: Sjvo2 and Pbto2 were successfully monitored in 58 patients with severe head injury. The changes in Sjvo2 and Pbto2 were compared during ischemic episodes. SETTING: Neurosurgical intensive care unit of a level I trauma center. MEASUREMENTS AND MAIN RESULTS: During the monitoring period, which averaged 90 hrs/patient, there were 54 episodes during which Sjvo2 decreased to <50% and/or Pbto2 decreased to <8 torr. Two of these episodes were caused by an infarction in the area of the Po2 probe, leaving 52 episodes of global hypoxia/ischemia that were identified by one of the two monitors. The sensitivities of the two monitors for detecting ischemia, using the thresholds of 50% and 8 torr for Sjvo2 and Pbto2, respectively, were similar. The Sjvo2 catheter detected 69.7% of the episodes and the Pbto2 catheter detected 63.5% of the episodes. In most of the remaining episodes, both probes reflected a decrease in oxygenation, but not to levels below the defined thresholds. The major differences in the two measures of oxygenation included the following: a) Sjvo2 more consistently reflected a reduction in oxygenation during hyperventilation; b) Pbto2 was affected more by changes in arterial Po2; and c) during severe global ischemia, Pbto2 decreased to 0 and remained at 0, whereas Sjvo2 initially decreased but then increased again as cerebral blood flow ceased, and the only blood in the jugular bulb was of extracerebral origin. CONCLUSIONS: The two monitors provide complimentary information, and neither monitor alone identifies all episodes of ischemia. The best strategy for using these monitors is to take advantage of the unique features of each monitor. Sjvo2 should be used as a monitor of global oxygenation; but Pbto2 should be used as a monitor of local oxygenation, ideally with the catheter placed in an area of the brain that is vulnerable to ischemia but that may be salvageable with appropriate treatment.

Prevention of secondary ischemic insults after severe head injury.

OBJECTIVE: The purpose of this study was to compare the effects of two acute-care management strategies on the frequency of jugular venous desaturation and refractory intracranial hypertension and on long-term neurologic outcome in patients with severe head injury. DESIGN: Randomized clinical trial. SETTING: Level I trauma hospital. PATIENTS: One hundred eighty-nine adults admitted in coma because of severe head injury. INTERVENTIONS: Patients were assigned to either cerebral blood flow (CBF)-targeted or intracranial pressure (ICP)-targeted management protocols during randomly assigned time blocks. In the CBF-targeted protocol, cerebral perfusion pressure was kept at >70 mm Hg and PaCO2 was kept at approximately 35 torr (4.67 kPa). In the ICP-targeted protocol, cerebral perfusion pressure was kept at >50 mm Hg and hyperventilation to a PaCO2 of 25-30 torr (3.33-4.00 kPa) was used to treat intracranial hypertension. MEASUREMENTS AND MAIN RESULTS: The CBF-targeted protocol reduced the frequency of jugular desaturation from 50.6% to 30% (p = .006). Even when the frequency of jugular desaturation was adjusted for all confounding factors that were significant, the risk of cerebral ischemia was 2.4-fold greater with the ICP-targeted protocol. Despite the reduction in secondary ischemic insults, there was no difference in neurologic outcome. Failure to alter long-term neurologic outcome was probably attributable to two major factors. A low jugular venous oxygen saturation was treated in both groups, minimizing the injury that occurred in the ICP-targeted group. The beneficial effects of the CBF-targeted protocol may have been offset by a five-fold increase in the frequency of adult respiratory distress syndrome. CONCLUSIONS: Secondary ischemic insults caused by systemic factors after severe head injury can be prevented with a targeted management protocol. However, potential adverse effects of this management strategy may offset these beneficial effects.

Cerebral hemodynamic effects of pentobarbital coma in head-injured patients.

The purpose of this study was to examine the changes in cerebral hemodynamics of head-injured patients undergoing barbiturate treatment of refractory intracranial hypertension. Cerebral blood flow (CBF) and metabolism variables were measured in 67 severely head-injured patients at the following times: before the loading dose of pentobarbital; after the loading dose of pentobarbital (average pentobarbital level 28.1+/-8.3 microg/mL); and 3 days later, when the peak pentobarbital level averaged 42.5+/-17.2 microg/mL. Intracranial pressure (ICP) and mean arterial blood pressure (MAP) were decreased by the loading dose of pentobarbital by an average of 12 and 9 mm Hg, respectively. Cerebral perfusion pressure (CPP) was unchanged when the entire group was analyzed together. CBF, cerebral oxygen consumption (CMR(O)2), and arteriovenous oxygen difference (AVD(O)2) were significantly decreased after the loading dose of pentobarbital, by 20%, 31%, and 11%, respectively. The average cerebrovascular resistance (CVR) was increased by 20%. The change in CMR(O)2 with the loading dose of pentobarbital was closely related to the pretreatment value (n = 67, r2 = 0.65, p < .001). Thirty (45%) of the patients had a "good ICP response," with a reduction in ICP from 34+/-9 to 15+/-5 mm Hg after the initial loading dose of pentobarbital. Twenty-seven (40%) of the patients had a "partial ICP response," with ICP decreasing but still remaining above 20 mm Hg after the loading dose of pentobarbital. In the remaining 10 patients, ICP did not change or even increased after pentobarbital. In the 30 patients with a good ICP response, pretreatment CMR(O)2 and AVD(O)2 were greater before administration of pentobarbital, and CMR(O)2 and AVD(O)2 decreased more with the loading dose of pentobarbital, than in the patients with partial or no ICP response. The outcome was significantly better in the patients with a good or partial ICP response to pentobarbital, with 21% of these patients having a good recovery or moderate disability at 3 months after injury, compared with 100% persistent vegetative state or death in the nonresponders. In summary, barbiturate coma can be a useful treatment modality for acutely reducing ICP in selected patients. Patients with overwhelmingly severe injuries are not likely to benefit, partly because their CMR(O)2 is already markedly reduced by the injury and partly because their outcome is already predetermined by the injury. Patients with systemic hypotension are not likely to have a good response because hypotension limits the amount of barbiturates that can be given.