Reduced mortality rate in patients with severe traumatic brain injury treated with brain tissue oxygen monitoring

OBJECT: An intracranial pressure (ICP) monitor, from which cerebral perfusion pressure (CPP) is estimated, is recommended in the care of severe traumatic brain injury (TBI). Nevertheless, optimal ICP and CPP management may not always prevent cerebral ischemia, which adversely influences patient outcome. The authors therefore determined whether the addition of a brain tissue oxygen tension (PO2) monitor in the treatment of TBI was associated with an improved patient outcome. METHODS: Patients with severe TBI (Glasgow Coma Scale [GCS] score < 8) who had been admitted to a Level I trauma center were evaluated as part of a prospective observational database. Patients treated with ICP and brain tissue PO2 monitoring were compared with historical controls matched for age, pathological features, admission GCS score, and Injury Severity Score who had undergone ICP monitoring alone. Therapy in both patient groups was aimed at maintaining an ICP less than 20 mm Hg and a CPP greater than 60 mm Hg. Among patients whose brain tissue PO2 was monitored, oxygenation was maintained at levels greater than 25 mm Hg. Twenty-five patients with a mean age of 44 +/- 14 years were treated using an ICP monitor alone. Twenty-eight patients with a mean age of 38 +/- 18 years underwent brain tissue PO2-directed care. The mean daily ICP and CPP levels were similar in each group. The mortality rate in patients treated using conventional ICP and CPP management was 44%. Patients who also underwent brain tissue PO2 monitoring had a significantly reduced mortality rate of 25% (p < 0.05). CONCLUSIONS: The use of both ICP and brain tissue PO2 monitors and therapy directed at brain tissue PO2 is associated with reduced patient death following severe TBI.     

Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma

BACKGROUND: This study aimed to determine whether glial fibrillary acidic protein (GFAP) is released after traumatic brain injury (TBI), whether GFAP is related to brain injury severity and outcome after TBI, and whether GFAP is released after multiple trauma without TBI. METHODS: This prospective study enrolled 114 patients who had TBI with or without multiple trauma (n = 101) or multiple trauma without TBI (n = 13), as verified by computerized tomography. Daily GFAP measurement began at admission (<12 hours after trauma) and continued for the duration of intensive care (1-22 days). Documentation included categorization of computerized tomography according to Marshall classification, based on daily highest intracranial pressure (ICP), lowest cerebral perfusion pressure (CPP), lowest mean arterial pressure (MAP), and 3-month Glasgow Outcome Score (GOS). RESULTS: The GFAP concentration was lower for diffuse injury 2 than for diffuse injury 4 (p < 0.0005) or nonevacuated mass lesions larger than than 25 mL (p < 0.005), lower for a ICP less than 25 mm Hg than for a ICP of 25 mm Hg or more, lower for a CPP of 60 mm Hg or more than for a CPP of 60 mm Hg or less, lower for a MAP of 60 mm Hg or more than for a MAP less than 60 mm Hg (all p < 0.0005), and lower for a GOS of 1 or 2 than for a GOS of 3, 4 (p < 0.05), or 5 (p < 0.0005). After TBI, GFAP was higher in nonsurvivors (n = 39) than in survivors (n = 62) (p < 0.005). After multiple trauma without TBI, GFAP remained normal. CONCLUSIONS: The findings showed that GFAP is released after TBI, that GFAP is related to brain injury severity and outcome after TBI, and that GFAP is not released after multiple trauma without brain injury.     

Cerebral cortical oxygenation: a pilot study

BACKGROUND: Cerebral hypoxia (cerebral cortical oxygenation [Pbro2] < 20 mm Hg) monitored by direct measurement has been shown in animal and small clinical studies to be associated with poor outcome. We present our preliminary results observing Pbro2 in patients with traumatic brain injury (TBI). METHODS: A prospective observational cohort study was performed. Institutional review board approval was obtained. All patients with TBI who required measurement of intracranial pressure (ICP), cerebral perfusion pressure (CPP), and Pbro2 because of a Glasgow Coma Scale score < 8 were enrolled. Data sets (ICP, CPP, Pbro2, positive end-expiratory pressure (PEEP), Pao2, and Paco2) were recorded during routine manipulation. Episodes of cerebral hypoxia were compared with episodes without. Results are displayed as mean +/- SEM; t test, chi2, and Fisher's exact test were used to answer questions of interest. RESULTS: One hundred eighty-one data sets were abstracted from 20 patients. Thirty-five episodes of regional cerebral hypoxia were identified in 14 patients. Compared with episodes of acceptable cerebral oxygenation, episodes of cerebral hypoxia were noted to be associated with a significantly lower mean Pao2 (144 +/- 14 vs. 165 +/- 8; p < 0.01) and higher mean PEEP (8.8 +/- 0.7 vs. 7.1 +/- 0.3; p < 0.01). Mean ICP and CPP measurements were similar between groups. In a univariate analysis, cerebral hypoxic episodes were associated with Pao2 < or = 100 mm Hg (p < 0.01) and PEEP > 5 cm H2O (p < 0.01), but not ICP > 20 mm Hg, CPP < or = 65 mm Hg, or Pac2 < or = 35 mm Hg. CONCLUSION: Cerebral oxymetry is confirmed safe in the patient with multiple injuries with TBI. Occult cerebral hypoxia is present in the traumatic brain injured patient despite normal traditional measurements of cerebral perfusion. Further research is necessary to determine whether management protocols aimed at the prevention of cerebral cortical hypoxia will affect outcome.     

Cerebral hemodynamic responses to blood pressure manipulation in severely head-injured patients in the presence or absence of intracranial hypertension

The management of cerebral perfusion pressure (CPP) remains a controversial issue in the critical care of severely head-injured patients. Recently, it has been proposed that the state of cerebrovascular autoregulation should determine individual CPP targets. To find optimal perfusion pressure, we pharmacologically manipulated CPP in a range of 51 mm Hg (median; 25th-75th percentile, 48-53 mm Hg) to 108 mm Hg (102-112 mm Hg) on Days 0, 1, and 2 after severe head injury in 13 patients and studied the effects on intracranial pressure (ICP), autoregulation capacity, and brain tissue partial pressure of oxygen. Autoregulation was expressed as a static rate of regulation for 5-mm Hg CPP intervals based on middle cerebral artery flow velocity. When ICP was normal (26 occasions), there were no major changes in the measured variables when CPP was altered from a baseline level of 78 mm Hg (74-83 mm Hg), indicating that the brain was within autoregulation limits. Conversely, when intracranial hypertension was present (11 occasions), CPP reduction to less than 77 mm Hg (73-82 mm Hg) further increased ICP, decreased the static rate of regulation, and decreased brain tissue partial pressure of oxygen, whereas a CPP increase improved these variables, indicating that the brain was operating at the lower limit of autoregulation. We conclude that daily trial manipulation of arterial blood pressure over a wide range can provide information that may be used to optimize CPP management.     

Cerebral oxygenation following decompressive hemicraniectomy for the treatment of refractory intracranial hypertension

OBJECT: Medically intractable intracranial hypertension is a major cause of morbidity and mortality after severe brain injury. One potential treatment for intracranial hypertension is decompressive hemicraniectomy (DCH). Whether and when to use DCH, however, remain unclear. The authors therefore studied the effects of DCH on cerebral O2 to develop a better understanding of the effects of this treatment on the recovery from injury and disease. METHODS: The study focused on seven patients (mean age 30.6 +/- 9.7 years) admitted to the hospital after traumatic brain injury (five patients) or subarachnoid hemorrhage (two patients) as part of a prospective observational database at a Level I trauma center. At admission the Glasgow Coma Scale (GCS) score was 6 or less in all patients. Patients received continuous monitoring of intracranial pressure (ICP), cerebral perfusion pressure (CPP), blood pressure, and arterial O2 saturation. Cerebral oxygenation was measured using the commercially available Licox Brain Tissue Oxygen Monitoring System manufactured by Integra NeuroSciences. A DCH was performed when the patient's ICP remained elevated despite maximal medical management. CONCLUSIONS: All patients tolerated DCH without complications. Before the operation, the mean ICP was elevated in all patients (26 +/- 4 mm Hg), despite maximal medical management. After surgery, there was an immediate and sustained decrease in ICP (19 +/- 11 mm Hg) and an increase in CPP (81 +/- 17 mm Hg). Following DCH, cerebral oxygenation improved from a mean of 21.2 +/- 13.8 mm Hg to 45.5 +/- 25.4 mm Hg, a 114.8% increase. The change in brain tissue O2 and the change in ICP after DCH demonstrated only a modest relationship (r2 = 0.3). These results indicate that the use of DCH in the treatment of severe brain injury is associated with a significant improvement in brain O2.     

Prehospital HBOC-201 after traumatic brain injury and hemorrhagic shock in swine

BACKGROUND: Data are limited on the actions of hemoglobin based oxygen carriers (HBOCs) after traumatic brain injury (TBI). This study evaluates neurotoxicity, vasoactivity, cardiac toxicity, and inflammatory activity of HBOC-201 (Biopure, Cambridge, Mass.) resuscitation in a TBI model. METHODS: Swine received TBI and hemorrhage. After 30 minutes, resuscitation was initiated with 10 mL/kg normal saline (NS), followed by either HBOC-201 (6 mL/kg, n = 10) or NS control (n = 10). Supplemental NS was administered to both groups to maintain mean arterial pressure (MAP) >60 mm Hg until 60 minutes, and to maintain cerebral perfusion pressure (CPP) >70 mm Hg from 60 to 300 minutes. The control group received mannitol (1 g/kg) and blood (10 mL/kg) at 90 minutes and half (n = 5) received CPP directed phenylephrine (PE) therapy after 120 minutes. Serum cytokines were measured with ELISA and coagulation was evaluated with thromboelastography. Brains were harvested for neuropathology. RESULTS: With HBOC administration, MAP, CPP, and brain tissue PO2 were restored within 30 minutes and maintained until 300 minutes. Clot strength and fibrin formation were maintained and 9/10 successfully extubated. In contrast, with control, MAP and brain tissue PO2 did not correct until 120 minutes, after mannitol, transfusion and 40% more crystalloid. Furthermore, without PE, CPP did not reach target and 0/5 could be extubated. Lactate, heart rate, cardiac output, mixed venous oxygenation, muscle oxygenation, serum cytokines, and histology did not differ between groups. CONCLUSIONS: After TBI, a single HBOC-201 bolus with minimal supplements provided rapid resuscitation, while maintaining CPP and improving brain oxygenation, without causing cardiac dysfunction, coagulopathy, cytokine release, or brain structural changes.     

High intracranial pressure effects on cerebral cortical microvascular flow in rats

To manage patients with high intracranial pressure (ICP), clinicians need to know the critical cerebral perfusion pressure (CPP) required to maintain cerebral blood flow (CBF). Historically, the critical CPP obtained by decreasing mean arterial pressure (MAP) to lower CPP was 60?mm Hg, which fell to 30?mm Hg when CPP was reduced by increasing ICP. We examined whether this decrease in critical CPP was due to a pathological shift from capillary (CAP) to high-velocity microvessel flow or thoroughfare channel (TFC) shunt flow. Cortical microvessel red blood cell velocity and NADH fluorescence were measured by in vivo two-photon laser scanning microscopy in rats at CPP of 70, 50, and 30?mm Hg by increasing ICP or decreasing MAP. Water content was measured by wet/dry weight, and cortical perfusion by laser Doppler flux. Reduction of CPP by raising ICP increased TFC shunt flow from 30.4±2.3% to 51.2±5.2% (mean±SEM, p<0.001), NADH increased by 20.3±6.8% and 58.1±8.2% (p<0.01), and brain water content from 72.9±0.47% to 77.8±2.42% (p<0.01). Decreasing CPP by MAP decreased TFC shunt flow with a smaller rise in NADH and no edema. Doppler flux decreased less with increasing ICP than decreasing MAP. The decrease seen in the critical CPP with increased ICP is likely due to a redistribution of microvascular flow from capillary to microvascular shunt flow or TFC shunt flow, resulting in a pathologically elevated CBF associated with tissue hypoxia and brain edema, characteristic of non-nutritive shunt flow.     

Pressure reactivity as a guide in the treatment of cerebral perfusion pressure in patients with brain trauma

OBJECT: The aim of this study was to compare the effects of two different treatment protocols on physiological characteristics and outcome in patients with brain trauma. One protocol was primarily oriented toward reducing intracranial pressure (ICP), and the other primarily on maintaining cerebral perfusion pressure (CPP). METHODS: A series of 67 patients in Uppsala were treated according to a protocol aimed at keeping ICP less than 20 mm Hg and, as a secondary target, CPP at approximately 60 mm Hg. Another series of 64 patients in Edinburgh were treated according to a protocol aimed primarily at maintaining CPP greater than 70 mm Hg and, secondarily, ICP less than 25 mm Hg for the first 24 hours and 30 mm Hg subsequently. The ICP and CPP insults were assessed as the percentage of monitoring time that ICP was greater than or equal to 20 mm Hg and CPP less than 60 mm Hg, respectively. Pressure reactivity in each patient was assessed based on the slope of the regression line relating mean arterial blood pressure (MABP) to ICP. Outcome was analyzed at 6 months according to the Glasgow Outcome Scale (GOS). The prognostic value of secondary insults and pressure reactivity was determined using linear methods and a neural network. In patients treated according to the CPP-oriented protocol, even short durations of CPP insults were strong predictors of death. In patients treated according to the ICP-oriented protocol, even long durations of CPP insult-mostly in the range of 50 to 60 mm Hg--were significant predictors of favorable outcome (GOS Score 4 or 5). Among those who had undergone ICP-oriented treatment, pressure-passive patients (MABP/ICP slope > or = 0.13) had a better outcome. Among those who had undergone CPP-oriented treatment, the more pressure-active (MABP/ICP slope < 0.13) patients had a better outcome. CONCLUSION: Based on data from this study, the authors concluded that ICP-oriented therapy should be used in patients whose slope of the MABP/ICP regression line is at least 0.13, that is, in pressure-passive patients. If the slope is less than 0.13, then hypertensive CPP therapy is likely to produce a better outcome.     

Positive end-expiratory pressure alters intracranial and cerebral perfusion pressure in severe traumatic brain injury

BACKGROUND: Optimizing intracranial pressure (ICP) and cerebral perfusion pressure (CPP) is important in the management of severe traumatic brain injury (TBI). In trauma patients with TBI and respiratory dysfunction, positive end-expiratory pressure (PEEP) is often required to support oxygenation. Increases in PEEP may lead to reduced CPP. We hypothesized that increases in PEEP are associated with compromised hemodynamics and altered cerebral perfusion. METHODS: Twenty patients (mean Injury Severity Score of 28) with TBI (Glasgow Coma Scale score < 8) were examined. All required simultaneous ICP and hemodynamic monitoring. Data were categorized on the basis of PEEP levels. Variables included central venous pressure, pulmonary artery occlusion pressure, cardiac index, oxygen delivery, and oxygen consumption indices. Differences were assessed using Kruskal-Wallis analysis of variance. RESULTS: Data were expressed as mean +/- SE. As PEEP increased from 0 to 5, to 6 to 10 and 11 to 15 cm H O, ICP decreased from 14.7 +/- 0.2 to 13.6 +/- 0.2 and 13.1 +/- 0.3 mm Hg, respectively. Concurrently, CPP improved from 77.5 +/- 0.3 to 80.1 +/- 0.5 and 78.9 +/- 0.7 mm Hg. As central venous pressure (5.9 +/- 0.1, 8.3 +/- 0.2, and 12.0 +/- 0.3 mm Hg) and pulmonary artery occlusion pressure (8.3 +/- 0.2, 11.6 +/- 0.4, and 15.6 +/- 0.4 mm Hg) increased with rising levels of PEEP, cardiac index, oxygen delivery, and oxygen consumption indices remained unaffected. Overall mortality was 30%. CONCLUSION: In trauma patients with severe TBI, the strategy of increasing PEEP to optimize oxygenation is not associated with reduced cerebral perfusion or compromised oxygen transport.     

Relationship of cerebral perfusion pressure and survival in pediatric brain-injured patients

BACKGROUND: Adult brain injury studies recommend maintaining cerebral perfusion pressure (CPP) above 70 mm Hg. We evaluated CPP and outcome in brain-injured children. METHODS: We retrospectively reviewed the hospital courses of children at two Level I trauma centers who required insertion of intracranial pressure (ICP) monitors for management of traumatic brain injury. ICP, CPP, and mean arterial pressure were evaluated hourly, and means were calculated for the first 48 hours after injury. RESULTS: Of 188 brain-injured children, 118 had ICP monitors placed within 24 hours of injury. They suffered severe brain injury, with average admitting Glasgow Coma Scale scores of 6 +/- 3. Overall mortality rate was 28%. No patient with mean CPP less than 40 mm Hg survived. Among patients with mean CPP in deciles of 40 to 49, 50 to 59, 60 to 69, or 70 mm Hg, no significant difference in Glasgow Outcome Scale distribution existed. CONCLUSION: Low mean CPP was lethal. In children with survivable brain injury (mean CPP > 40 mm Hg), CPP did not stratify patients for risk of adverse outcome.     

Computed tomographic brain density measurement as a predictor of elevated intracranial pressure in blunt head trauma

There are no independent computed tomography (CT) findings predictive of elevated intracranial pressure (ICP). The purpose of this study was to evaluate brain density measurement on CT as a predictor of elevated ICP or decreased cerebral perfusion pressure (CPP). A prospectively collected database of patients with acute traumatic brain injury was used to identify patients who had a brain CT followed within 2 hours by ICP measurement. Blinded reviewers measured mean density in Hounsfield Units (HU) within a 100-mm2 elliptical region at four standardized positions. Brain density measurement was compared for patients with an ICP of 20 or greater versus less than 20 mm Hg and CPP of 70 or greater versus less than 70 mm Hg. During a 2-year period, 47 patients had ICP monitoring after brain CT. Average age was 40 +/- 18 years old; 93.6 per cent were male; mean Injury Severity Score was 25 +/- 10; and Glasgow Coma Scale was 6 +/- 4. There was no difference in brain density measurement for observer 1, ICP less than 20 (26.3 HU) versus ICP 20 or greater (27.4 HU, P = 0.545) or for CPP less than 70 (27.1 HU) versus CPP 70 or greater (26.2, P = 0.624). Similarly, there was no difference for observer 2, ICP less than 20 (26.8 HU) versus ICP 20 or greater (27.4, P = 0.753) and CPP less than 70 (27.6 HU) versus CPP 70 or greater (26.2, P = 0.436). CT-measured brain density does not correlate with elevated ICP or depressed CPP and cannot predict patients with traumatic brain injury who would benefit from invasive ICP monitoring.     

Building a better fluid for emergency resuscitation of traumatic brain injury

Hextend (HEX) is a colloid solution that is FDA-approved for volume expansion during surgery. ATL-146e is a novel adenosine A2A receptor agonist that has anti-inflammatory, neuroprotective, and coronary vasodilator properties. Three series of experiments were designed to evaluate the therapeutic potential of HEX+/-ATL-146e for emergency resuscitation from traumatic brain injury (TBI) + hemorrhagic hypotension. METHODS: In the first two studies in vivo, anesthetized, ventilated pigs (30-45 kg) received a fluid percussion TBI, 45% arterial hemorrhage, and 30 minutes shock period. In Series 1, resuscitation consisted of unlimited crystalloid (n = 8) or HEX (n = 8) to correct systolic arterial pressure >100 mm Hg and heart rate <100 bpm for the first 60 minutes ("emergency phase"), and then maintain cerebral perfusion pressure (CPP) > 70 mm Hg for 60-240 minutes. In Series 2 (n = 31), resuscitation consisted of a 1 L bolus of HEX + ATL-146e (10 ng/kg/min, n = 10) or HEX +placebo (n = 10) followed by crystalloid to the same endpoints. In Series 3 in vivo, the hemodynamic response evoked by 0, 10, 50, or 100 ng/kg/min ATL-146e was measured before or 60 minutes after HEX resuscitation from 45% hemorrhage. RESULTS: Following TBI+hemorrhage, there were 4/22 deaths in series 1 and 11/31 deaths in series 2. In those alive at 30 minutes, mean arterial pressure, cardiac index, mixed venous O2 saturation, and cerebral venous O2 saturation were all reduced by 40-60%, while heart rate and lactate were increased 2-5 fold. With no resuscitation (n = 2), there was minimal hemodynamic compensation and progressive acidosis. Upon resuscitation, these values corrected but intracranial pressure progressively rose from <5 mm Hg to 15-20 mm Hg. Series 1: With HEX (n = 8) versus crystalloid (n = 8), CPP was less labile, acid/base was maintained, and the fluid requirement was reduced by 60% (all p < 0.05) Series 2: With ATL-146e (n = 10) versus placebo (n = 10), stroke volume and cardiac output were improved by 40-60%, and the fluid requirement was reduced by 30% (all p < 0.05). Series 3: ATL-146e caused a dose-related increase (p < 0.05) in stroke volume after, but not before, hemorrhage. The effects on pre-load, afterload, and heart rate were similar before and after hemorrhage. CONCLUSIONS: HEX alone is a safe and efficacious low volume alternative to initial crystalloid resuscitation after TBI. An adenosine A2A agonist combined with 1 L of HEX safely and effectively counteracted a decrease in cardiac performance noted after TBI+hemorrhage without causing hypotension or bradycardia.     

Short-term moderate hypocapnia augments detection of optimal cerebral perfusion pressure

An autoregulation-oriented strategy has been proposed to guide neurocritical therapy toward the optimal cerebral perfusion pressure (CPPOPT). The influence of ventilation changes is, however, unclear. We sought to find out whether short-term moderate hypocapnia (HC) shifts the CPPOPT or affects its detection. Thirty patients with traumatic brain injury (TBI), who required sedation and mechanical ventilation, were studied during 20?min of normocapnia (5.1±0.4?kPa) and 30 min of moderate HC (4.4±3.0?kPa). Monitoring included bilateral transcranial Doppler of the middle cerebral arteries (MCA), invasive arterial blood pressure (ABP), and intracranial pressure (ICP). Mx -autoregulatory index provided a measure for the CPP responsiveness of MCA flow velocity. CPPOPT was assessed as the CPP at which autoregulation (Mx) was working with the maximal efficiency. During normocapnia, CPPOPT (left: 80.65±6.18; right: 79.11±5.84?mm Hg) was detectable in 12 of 30 patients. Moderate HC did not shift this CPPOPT but enabled its detection in another 17 patients (CPPOPT left: 83.94±14.82; right: 85.28±14.73?mm Hg). The detection of CPPOPT was achieved via significantly improved Mx-autoregulatory index and an increase of CPP mean. It appeared that short-term moderate HC augmented the detection of an optimum CPP, and may therefore usefully support CPP-guided therapy in patients with TBI.     

Changes in intracranial pressure, coagulation, and neurologic outcome after resuscitation from experimental traumatic brain injury with hetastarch

BACKGROUND: In a model of traumatic brain injury (TBI), 2 protocols compared changes in intracranial pressure (ICP), coagulation, and neurologic outcome after intravenous fluid (IVF) resuscitation with either Hextend (HEX, 6% hetastarch in lactated electrolyte injection) or standard of care, crystalloid plus mannitol (MAN). METHODS: In the nonsurvivor protocol, swine (n = 28) received a fluid percussion TBI and hemorrhage (27 +/- 3 mL/kg). At 30 minutes, resuscitation began with lactated Ringer's (LR) or HEX. After 60 minutes, MAN (1 g/kg) or placebo was given plus supplemental IVF to maintain cerebral perfusion pressure (CPP) > or = 70 mm Hg for 240 minutes. Swine in the survivor group (n = 15) also underwent TBI and hemorrhage, and resuscitation with HEX was compared to that of normal saline (NS)+MAN. Neurologic outcome and coagulation were evaluated for 72 hours. RESULTS: In the nonsurvivor protocol, HEX, LR+MAN, and HEX+MAN attenuated the time-related rise of ICP and prevented ICP >20 mm Hg versus LR alone (P < .05). HEX alone maintained CPP (relative to baseline) and decreased total IVF by 50% versus LR +/- MAN (P < .05). MAN had no additive effect with HEX. Coagulation, measured by thromboelastograph reaction time (R), was 11 +/- 1 and 9 +/- 1 minutes at baseline and after TBI (before randomization). At 240 minutes after HEX or LR+MAN, R was 6 +/- 1 or 7 +/- 2 minutes, which indicates a hypercoagulable state, but there was no difference between treatments. In the survivor protocol, ICP and CPP were similar with NS+MAN versus HEX, but IVF requirement was 161 +/- 20 versus 28 +/- 3 mL/kg (P < .05). Motor scores were higher on days 2 and 3 with HEX (P < .05). At 72 hours, R was 28 +/- 14 versus 26 +/- 6 minutes with NS+MAN versus HEX, which indicates a hypocoagulable state, but there was no difference between treatments. CONCLUSIONS: Hextend as the sole resuscitation fluid after severe TBI reduces fluid requirement, obviates the need for mannitol, improves neurologic outcome, and has no adverse effect on the coagulation profile relative to the crystalloid plus mannitol standard of care.     

Interaction between brain chemistry and physiology after traumatic brain injury: impact of autoregulation and microdialysis catheter location

Bedside monitoring of cerebral metabolism in traumatic brain injury (TBI) with microdialysis is gaining wider clinical acceptance. The objective of this study was to examine the relationship between the fundamental physiological neuromonitoring modalities intracranial pressure (ICP), cerebral perfusion pressure (CPP), brain tissue oxygen (P(bt)O(2)), and cerebrovascular pressure reactivity index (PRx), and cerebral chemistry assessed with microdialysis, with particular focus on the lactate/pyruvate (LP) ratio as a marker of energy metabolism. Prospectively collected observational neuromonitoring data from 97 patients with TBI, requiring neurointensive care management and invasive cerebral monitoring, were analyzed. A linear mixed model analysis was used to account for individual patient differences. Perilesional tissue chemistry exhibited a significant independent relationship with ICP, P(bt)O(2) and CPP thresholds, with increasing LP ratio in response to decrease in P(bt)O(2) and CPP, and increase in ICP. The relationship between CPP and chemistry depended upon the state of PRx. Within the studied physiological range, tissue chemistry only changed in response to increasing ICP or drop in P(bt)O(2)<1.33 kPa (10 mmHg). In agreement with previous studies, significantly higher levels of cerebral lactate (p<0.001), glycerol (p=0.013), LP ratio (p<0.001) and lactate/glucose (LG) ratio (p=0.003) were found in perilesional tissue, compared to "normal" brain tissue (Mann-Whitney test). These differences remained significant following adjustment for the influences of other important physiological parameters (ICP, CPP, P(bt)O(2), P(bt)CO(2), PRx, and brain temperature; mixed linear model), suggesting that they may reflect inherent tissue properties related to the initial injury. Despite inherent biochemical differences between less-injured brain and "perilesional" cerebral tissue, both tissue types exhibited relationships between established physiological variables and biochemistry. Decreases in perfusion and oxygenation were associated with deteriorating neurochemistry and these effects were more pronounced in perilesional tissue and when cerebrovascular reactivity was impaired.     

Cerebral perfusion pressure directed therapy following traumatic brain injury and hypotension in swine

There is a paucity of studies, clinical and experimental, attesting to the benefit of cerebral perfusion pressure (CPP) directed pressor therapy following traumatic brain injury (TBI). The current study evaluates this therapy in a swine model of TBI and hypotension. Forty-five anesthetized and ventilated swine received TBI followed by a 45% blood volume bleed. After 1 h, all animals were resuscitated with 0.9% sodium chloride equal to three times the shed blood volume. The experimental group (PHE) received phenylephrine to maintain CPP > 80 mm Hg; the control group (SAL) did not. Outcomes in the first phase (n = 33) of the study were as follows: cerebro-venous oxygen saturation (S(cv)O(2)), cerebro-vascular carbon dioxide reactivity (DeltaS(cv)O(2)), and brain structural damage (beta-amyloid precursor protein [betaAPP] immunoreactivity). In the second phase (n = 12) of the study, extravascular blood free water (EVBFW) was measured in the brain and lung. After resuscitation, intracranial and mean arterial pressures were >15 and >80 mm Hg, respectively, in both groups. CPP declined to 64 +/- 5 mm Hg in the SAL group, despite fluid supplements. CPP was maintained at >80 mm Hg with pressors in the PHE group. PHE animals maintained better S(cv)O(2) (p < 0.05 at 180, 210, 240, 270, and 300 min post-TBI). At baseline, 5% CO(2) evoked a 16 +/- 4% increase in S(cv)O(2), indicating cerebral vasodilatation and luxury perfusion. By 240 min, this response was absent in SAL animals and preserved in PHE animals (p < 0.05). Brain EVBFW was higher in SAL animals; however, lung EVBFW was higher in PHE animals. There was no difference in betaAPP immunoreactivity between the SAL and PHE groups (p > 0.05). In this swine model of TBI and hypotension, CPP directed pressor therapy improved brain oxygenation and maintained cerebro-vascular CO(2) reactivity. Brain edema was lower, but lung edema was greater, suggesting a higher propensity for pulmonary complications.     

The effect of nimodipine on cerebral oxygenation in patients with poor-grade subarachnoid hemorrhage

OBJECT: Nimodipine has been shown to improve neurological outcome after subarachnoid hemorrhage (SAH); the mechanism of this improvement, however, is uncertain. In addition, adverse systemic effects such as hypotension have been described. The authors investigated the effect of nimodipine on brain tissue PO2. METHODS: Patients in whom Hunt and Hess Grade IV or V SAH had occurred who underwent aneurysm occlusion and had stable blood pressure were prospectively evaluated using continuous brain tissue PO2 monitoring. Nimodipine (60 mg) was delivered through a nasogastric or Dobhoff tube every 4 hours. Data were obtained from 11 patients and measurements of brain tissue PO2, intracranial pressure (ICP), mean arterial blood pressure (MABP), and cerebral perfusion pressure (CPP) were recorded every 15 minutes. Nimodipine resulted in a significant reduction in brain tissue PO2 in seven (64%) of 11 patients. The baseline PO2 before nimodipine administration was 38.4+/-10.9 mm Hg. The baseline MABP and CPP were 90+/-20 and 84+/-19 mm Hg, respectively. The greatest reduction in brain tissue PO2 occurred 15 minutes after administration, when the mean pressure was 26.9+/-7.7 mm Hg (p < 0.05). The PO2 remained suppressed at 30 minutes (27.5+/-7.7 mm Hg [p < 0.05]) and at 60 minutes (29.7+/-11.1 mm Hg [p < 0.05]) after nimodipine administration but returned to baseline levels 2 hours later. In the seven patients in whom brain tissue PO2 decreased, other physiological variables such as arterial saturation, end-tidal CO2, heart rate, MABP, ICP, and CPP did not demonstrate any association with the nimodipine-induced reduction in PO2. In four patients PO2 remained stable and none of these patients had a significant increase in brain tissue PO2. CONCLUSIONS: Although nimodipine use is associated with improved outcome following SAH, in some patients it can temporarily reduce brain tissue PO2.     

Effects of cisatracurium on cerebral and cardiovascular hemodynamics in patients with severe brain injury

Background : For neuroanesthesia and neurocritical care the use of drugs that do not increase or preferentially decrease intracranial pressure (ICP) or change cerebral perfusion pressure (CPP) and cerebral blood flow (CBF) are preferred. The current study investigates the effects of a single rapid bolus dose of cisatracurium on cerebral blood flow velocity, ICP, CPP, mean arterial pressure (MAP) and heart rate (HR) in 24 mechanically ventilated patients with intracranial hypertension after severe brain trauma (Glasgow coma scale 6) under continuous sedation with sufentanil and midazolam.
Methods : Patients were randomly assigned to receive either 2XED95 (n=12) or 4XED95 (n=12) of cisatracurium as a rapid i.v. bolus injection. Before and after bolus administration mean cerebral blood flow velocity (BFV, cm/s) was measured in the middle cerebral artery using a 2–MHz transcranial Doppler sonography system, ICP (mm Hg) was measured using an extradural probe, and MAP (mm Hg) and HR (b/min) were measured during a study period of 20 min. Cerebral perfusion pressure (CPP=MAP–ICP) was also calculated.
Results : Our data show that a single bolus dose of up to 4 × ED95 cisatracurium caused no significant (P<0.05) changes in BFV, ICP, CPP, MAP and HR. Possible histamine-related events were not observed during the study.
Conclusions : The results from this study suggest that cisatracurium is a safe neuromuscular blocking agent for use in adult severe brain–injured patients with increased ICP under mild hyperventilation and continuous sedation.     

Intracranial pressure responses to PEEP in head-injured patients.

PEEP (positive end-expiratory pressure) was required in 12 head-injured patients in whom intracranial pressure (ICP) monitoring had been previously established. In six, ICP increased by 10 mm Hg or more as 4-8 cm H2O of PEEP were administered. In 10 patients the mean arterial pressure decreased during PEEP. Before PEEP, the mean cerebral perfusion pressure (CPP = BP-ICP) was above 50 mm Hg in all patients. The CPP was less than 50 mm Hg in six patients given PEEP. Neurological deterioration occurred in two patients during PEEP therapy. In head-injured patients, optimal titration of PEEP therapy should include ICP measurement and/or continuous evaluation of neurologic status.