Shankar P. Gopinath

Jugular venous desaturation and outcome after head injury.

Early experience with continuous monitoring of jugular venous oxygen saturation (SjvO2) suggested that this technology might allow early identification of global cerebral ischaemia in patients with severe head injury. The purpose of the present study was to examine the relationship between episodes of jugular venous desaturation and neurological outcome. One hundred and sixteen severely head-injured patients had continuous monitoring of SjvO2 during days 1-5 after injury. Episodes of jugular venous desaturation (SjvO2 < 50% for more than 10 minutes) were prospectively identified, and the incidence of desaturation was correlated with neurological outcome: 77 episodes of desaturation occurred in 46 of the 116 patients; 27 had one episode and 19 had multiple episodes of desaturation. The causes of these episodes were systemic (n = 36), cerebral (n = 35), or both (n = 6). Most of the episodes were less than 1 hour in duration, and it is probable that many of them would not have been detected without continuous measurement of SjvO2. Episodes of desaturation were most common on day 1 after injury, and were twice as common in patients with a reduced cerebral blood flow as in patients with a normal or elevated cerebral blood flow. The occurrence of jugular venous desaturation was strongly associated with a poor neurological outcome. The percentage of patients with a poor neurological outcome was 90% with multiple episodes of desaturation and 74% in patients with one desaturation, compared to 55% in patients with no episodes of desaturation. When adjusted for all co-variates that were found to be significant, including age, Glasgow coma score, papillary reactivity, type of injury, lowest recorded cerebral perfusion pressure, and highest recorded temperature, the incidence of desaturation remained significantly associated with a poor outcome. Although a cause and effect relationship with outcome cannot be established in this study, the data suggest that monitoring SvO2 might allow early identification and therefore treatment of many types of secondary injury to the brain.

Relationship of brain tissue PO2 to outcome after severe head injury

OBJECTIVE To determine thresholds of brain tissue PO2 (PbtO2) that are critical for survival after severe head injury. DESIGN Prospective data collection. SETTING Neurosurgical intensive care unit of Ben Taub General Hospital, a comprehensive academic neurosurgical facility and Level I trauma center. PATIENTS Forty-three severely head-injured patients who were not obeying commands on presentation or whose condition deteriorated to this level shortly after admission. INTERVENTIONS Intracerebral placement of Licox (n=39) or Paratrend (n=4) PO2 probes during craniotomy or in the intensive care unit. MEASUREMENTS AND MAIN RESULTS PbtO2 monitoring continued for an average of 84.6+/-41.8 hrs. The probes were calibrated before insertion according to the manufacturers specifications. After removal, probes were tested in room air and in blood gas standard calibration solutions. PbtO2 data were analyzed by comparing the average time that PbtO2 was below the values of 20, 15, 10, 8, 6, 4, and 2 torr (2.7, 2.0, 1.3, 1.0, 0.8, 0.5, and 0.3 kPa, respectively) in patients who were living 3 mos after injury vs. those who died. A Tobit regression analysis using maximum likelihood methods was utilized. Both Licox and Paratrend probes functioned well in room air and in the Level I control. However, in the zero-oxygen solution, the Paratrend probes gave an average reading of 7.0+/-1.4 torr (0.9+/-0.2 kPa), compared with 0.3+/-0.3 torr (0.04+/-0.04 kPa) for the Licox probes. CONCLUSIONS Analysis of the PbtO2 monitoring data suggested that the likelihood of death increased with increasing duration of time at or below a PbtO2 of 15 torr (2.0 kPa) or with the occurrence of any PbtO2 values of < or =6 torr (< or =0.8 kPa).

Extracellular lactate and glucose alterations in the brain after head injury measured by microdialysis.

OBJECTIVE To study cerebral glucose and lactate metabolism in head-injured patients using microdialysis. DESIGN Prospective, nonrandomized, clinical study. SETTING Neurosurgical intensive care unit in a university-affiliated county hospital. PATIENTS One hundred twenty-six head-injured patients. INTERVENTIONS Cerebral cortical neurochemical monitoring using microdialysis coupled with systemic hemodynamic and oxygenation monitoring, measurement of cerebral perfusion pressure and intracranial pressure, and measurement of global cerebral oxygenation using jugular venous oxygen saturation in all 126 patients. In selected cases, cerebral blood flow was also measured using cortical thermodilution probes in 33 patients, and regional cerebral oxygenation was measured using PO2 probes in 65 patients. MEASUREMENTS AND MAIN RESULTS Elevated extracellular lactate, reduced glucose, and an elevated lactate/glucose ratio were observed with cerebral hypoxia and ischemia. Elevated lactate and an increased lactate/glucose ratio strongly correlated with death. Other more subtle alterations of lactate and glucose were seen early after injury that may reflect compensatory alterations in cerebral metabolism. CONCLUSIONS Clinical neurochemical monitoring of glucose and lactate levels in the extracellular space of the cerebral cortex is technically feasible and provides insight into the bioenergetic status of the brain. Increased lactate and decreased glucose, indicating accelerated glycolysis, commonly occurred with cerebral ischemia or hypoxia, and increased anaerobic glycolysis in this setting is associated with a poor outcome.

Effect of Erythropoietin and Transfusion Threshold on Neurological Recovery After Traumatic Brain Injury: A Randomized Clinical Trial

IMPORTANCE There is limited information about the effect of erythropoietin or a high hemoglobin transfusion threshold after a traumatic brain injury. OBJECTIVE To compare the effects of erythropoietin and 2 hemoglobin transfusion thresholds (7 and 10 g/dL) on neurological recovery after traumatic brain injury. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 200 patients (erythropoietin, n = 102; placebo, n = 98) with closed head injury who were unable to follow commands and were enrolled within 6 hours of injury at neurosurgical intensive care units in 2 US level I trauma centers between May 2006 and August 2012. The study used a factorial design to test whether erythropoietin would fail to improve favorable outcomes by 20% and whether a hemoglobin transfusion threshold of greater than 10 g/dL would increase favorable outcomes without increasing complications. Erythropoietin or placebo was initially dosed daily for 3 days and then weekly for 2 more weeks (n = 74) and then the 24- and 48-hour doses were stopped for the remainder of the patients (n = 126). There were 99 patients assigned to a hemoglobin transfusion threshold of 7 g/dL and 101 patients assigned to 10 g/dL. INTERVENTIONS Intravenous erythropoietin (500 IU/kg per dose) or saline. Transfusion threshold maintained with packed red blood cells. MAIN OUTCOMES AND MEASURES Glasgow Outcome Scale score dichotomized as favorable (good recovery and moderate disability) or unfavorable (severe disability, vegetative, or dead) at 6 months postinjury. RESULTS There was no interaction between erythropoietin and hemoglobin transfusion threshold. Compared with placebo (favorable outcome rate: 34/89 [38.2%; 95% CI, 28.1% to 49.1%]), both erythropoietin groups were futile (first dosing regimen: 17/35 [48.6%; 95% CI, 31.4% to 66.0%], P = .13; second dosing regimen: 17/57 [29.8%; 95% CI, 18.4% to 43.4%], P < .001). Favorable outcome rates were 37/87 (42.5%) for the hemoglobin transfusion threshold of 7 g/dL and 31/94 (33.0%) for 10 g/dL (95% CI for the difference, -0.06 to 0.25, P = .28). There was a higher incidence of thromboembolic events for the transfusion threshold of 10 g/dL (22/101 [21.8%] vs 8/99 [8.1%] for the threshold of 7 g/dL, odds ratio, 0.32 [95% CI, 0.12 to 0.79], P = .009). CONCLUSIONS AND RELEVANCE In patients with closed head injury, neither the administration of erythropoietin nor maintaining hemoglobin concentration of greater than 10 g/dL resulted in improved neurological outcome at 6 months. The transfusion threshold of 10 g/dL was associated with a higher incidence of adverse events. These findings do not support either approach in this setting. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00313716.

Brain temperature exceeds systemic temperature in head-injured patients

OBJECTIVE To identify the temperature differences in readings taken from the brain, jugular bulb, and core body in head-injured patients. DESIGN Prospective, observational study. SETTING Neurosurgical intensive care unit of a university-affiliated county hospital. PATIENTS Thirty patients with severe head injuries had measurements of brain and core body temperatures. Fourteen patients also had measurements of jugular venous blood at the level of the jugular bulb. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Brain temperature was increased an average of 2.0 degrees F (1.1 degrees C) over the core body temperature. In individual patients, the average brain temperature increase over the core body temperature ranged from -0.5 degrees to 3.8 degrees F (-0.30 degrees to 2.1 degrees C). Jugular vein and core body temperatures were similar. The difference in the brain and body temperatures increased when cerebral perfusion pressure decreased to between 20 and 50 mm Hg. The difference in the brain and body temperatures decreased in those patients treated with barbiturate coma. CONCLUSIONS Direct measurement of temperature in head-injured patients is a safe procedure. Temperatures in the brain are typically increased over the core body temperature and the jugular bulb temperatures. Jugular vein temperature measurement is not a good measurement of brain temperature since it reflects body, not brain temperature. These findings support the potential importance of monitoring brain temperature and the importance of controlling fever in severely head-injured patients since brain temperature may be higher than expected.

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.

Management of Intracranial Hypertension

Effective management of intracranial hypertension involves meticulous avoidance of factors that precipitate or aggravate increased intracranial pressure. When intracranial pressure becomes elevated, it is important to rule out new mass lesions that should be surgically evacuated. Medical management of increased intracranial pressure should include sedation, drainage of cerebrospinal fluid, and osmotherapy with either mannitol or hypertonic saline. For intracranial hypertension refractory to initial medical management, barbiturate coma, hypothermia, or decompressive craniectomy should be considered. Steroids are not indicated and may be harmful in the treatment of intracranial hypertension resulting from traumatic brain injury.

Cerebral oxygenation during warming after cardiopulmonary bypass

OBJECTIVES To evaluate jugular venous oxygen saturation (SjVO2), measured with a fiberoptic oximetry catheter, and brain tissue oxygen saturation, measured by near-infrared spectroscopy (NIRSO2), as monitors of cerebral oxygenation during cardiopulmonary bypass surgery. DESIGN Prospective, clinical study. SETTING Operating room of a Veterans Administration Hospital. PATIENTS Nineteen patients undergoing moderate hypothermic cardiopulmonary bypass surgery. INTERVENTIONS SjvO2 and NIRSO2 were monitored in the patients during the surgical procedure. MEASUREMENTS AND MAIN RESULTS Moderate hypothermic cardiopulmonary bypass surgery had two distinct cerebral hemodynamic phases. While the patients were hypothermic, SjvO2 averaged 80 +/- 7% and none of the patients had an increase in cerebral lactate production. During the rewarming period, however, reductions in SjvO2 to < 50% occurred in 16 (84%) patients and increased cerebral anaerobic metabolism developed in 11 (58%) patients. SjvO2 during rewarming was dependent on mean arterial pressure, with 60 mm Hg appearing to be a critical value. Two other factors appeared to also contribute to the jugular desaturation, a low hematocrit and a rapid warming time. The SjvO2 catheter had excellent performance during the surgery. The average difference between paired measurements of SjvO2 by the catheter and in blood samples was -0.4 +/- 4.25%, and the correlation between the two measurements was highly significant (r2 = .93; p < .001). The NIRSO2 trended with the SjvO2 in most patients (r2 = .63; p < .001). CONCLUSIONS The study confirms other studies showing that jugular venous desaturation can occur during rewarming after cardiopulmonary bypass surgery. Presently, SjvO2 appears to be a better monitor of cerebral oxygenation than NIRSO2. However, NIRSO2 has promise as a noninvasive monitor of cerebral oxygenation if future developments allow more quantitative measurements of oxygen saturation.

METABOLIC CHANGES IN THE BRAIN DURING TRANSIENT ISCHEMIA MEASURED WITH MICRODIALYSIS

Forty-four patients with severe head injury were monitored for episodes of cerebral ischemia using jugular venous oxygen saturation (sjvO2), brain tissue pO2 (ti-pO2), and a microdialysis probe. The concentration of lactate and glucose were measured in the microdialysate. A total of 10 episodes of global ischemia were observed. The characteristic pattern of a simultaneous decrease in sjvO2 and brain ti-pO2 with an increase in the concentration of lactate occurred in all 10 patients. In addition, 3 episodes of regional ischemia were observed. Although brain ti-pO2 decreased to very low values and the concentration of lactate increased in the microdialysate, sjvO2 remained unchanged. Brain ti-pO2 adds another dimension to our cerebral monitoring by allowing the detection of regional cerebral ischemia.

Brain tissue oxygen tension response to induced hyperoxia reduced in hypoperfused brain

OBJECTIVES Increasing PaO2 can increase brain tissue PO2 (PbtO2). Nevertheless, the small increase in arterial O2 content induced by hyperoxia does not increase O2 delivery much, especially when cerebral blood flow (CBF) is low, and the effectiveness of hyperoxia as a therapeutic intervention remains controversial. The purpose of this study was to examine the role of regional (r)CBF at the site of the PO2 probe in determining the response of PbtO2 to induced hyperoxia. METHODS The authors measured PaO2 and PbtO2 at baseline normoxic conditions and after increasing inspired O2 concentration to 100% on 111 occasions in 83 patients with severe traumatic brain injury in whom a stable xenon-enhanced computed tomography measurement of CBF was available. The O2 reactivity was calculated as the change in PbtO2 x 100/change in PaO2. RESULTS The O2 reactivity was significantly different (p < 0.001) at the 5 levels of rCBF (<10, 11-15, 16-20, 21-40, and > 40 ml/100 g/min). When rCBF was < 20 ml/100 g/min, the increase in PbtO2 induced by hyperoxia was very small compared with the increase that occurred when rCBF was > 20 ml/100 g/min. CONCLUSIONS Although the level of CBF is probably only one of the factors that determines the PbtO2 response to hyperoxia, it is apparent from these results that the areas of the brain that would most likely benefit from improved oxygenation are the areas that are the least likely to have increased PbtO2.