Online correlation of spontaneous arterial and intracranial pressure fluctuations in patients with diffuse severe head injury

Determination of relevant clinical monitoring parameters for helping guide the intensive care therapy in patients with severe head injury, is one of the most demanding issues in neurotrauma research. New insights into cerebral autoregulation and metabolism have revealed that a rigid cerebral perfusion pressure (CPP) regimen might not be suitable for all severe head injured patients. We thus developed an online analysis technique to monitor the correlation (AI rho) between the spontaneous fluctuations of the mean arterial blood pressure (MABP) and the intracranial pressure (ICP). In addition, brain tissue oxygen (PtiO2) and metabolic microdialysate measures including glucose and lactate were registered. We found that in patients with good outcome, the AI rho values were significantly lower as compared with patients with poor outcome. Accordingly, microdialysate glucose and lactate were significantly higher in the good outcome group. We conclude that online determination of AI rho offers a valuable additional and technically easily performable tool for guidance of therapy in patients with severe head injury.

Clinical trials in head injury

Secondary brain damage, following severe head injury is considered to be a major cause for bad outcome. Impressive reductions of the extent of brain damage in experimental studies have raised high expectations for cerebral neuroprotective treatment, in the clinic. Therefore multiple compounds were and are being evaluated in trials. In this review we discuss the pathomechanisms of traumatic brain damage, based upon their clinical importance. The role of hypothermia, mannitol, barbiturates, steroids, free radical scavengers, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and potassium channel blockers, will be discussed. The importance of a uniform strategic approach for evaluation of potentially interesting new compounds in clinical trials, to ameliorate outcome in patients with severe head injury, is proposed. To achieve this goal, two nonprofit organizations were founded: the European Brain Injury Consortium (EBIC) and the American Brain Injury Consortium (ABIC). Their aim lies in conducting better clinical trials, which incorporate lessons learned from previous trials, such that the succession of negative, or incomplete studies, as performed in previous years, will cease.

Investigating the Contribution of Personality and Neurological Disruption to Postinjury Outcome in Athletes with Mild Head Injury

Despite the increase in research regarding mild head injury (MHI), relatively little has investigated whether, or the extent to which, premorbid factors (i.e., personality traits) influence, or otherwise account for, outcomes post-MHI. The current study examined the extent to which postinjury outcome after MHI is analogous to the outcome post-moderate or- severe traumatic brain injury (by comparing the current results to previous literature pertaining to individuals with more severe brain injuries) and whether these changes in function and behaviour are solely, or primarily, due to the injury, or reflect, and are possibly a consequence of, one’s preinjury status. In a quasi-experimental, test-retest design, physiological indices, cognitive abilities, and personality characteristics of university students were measured. Since the incidence of MHI is elevated in high-risk activities (including high-risk sports, compared to other etiologies of MHI; see Laker, 2011) and it has been found that high-risk athletes present with unique, risk-taking behaviours (in terms of personality; similar to what has been observed post-MHI) compared to low-risk and non-athletes. Seventy-seven individuals (42% with a history of MHI) of various athletic statuses (non-athletes, low-risk athletes, and high-risk athletes) were recruited. Consistent with earlier studies (e.g., Baker & Good, 2014), it was found that individuals with a history of MHI displayed decreased physiological arousal (i.e., electrodermal activation) and, also, endorsed elevated levels of sensation seeking and physical/reactive aggression compared to individuals without a history of MHI. These traits were directly associated with decreased physiological arousal. Moreover, athletic status did not account for this pattern of performance, since low- and high-risk athletes did not differ in terms of personality characteristics. It was concluded that changes in behaviour post-MHI are associated, at least in part, with the neurological and physiological compromise of the injury itself (i.e., physiological underarousal and possible subtle OFC dysfunction) above and beyond influences of premorbid characteristics.

High level of extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

OBJECT: Disturbed ionic and neurotransmitter homeostasis are now recognized as probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brain injury (TBI). Evidence obtained in animal models indicates that posttraumatic neuronal excitation by excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with measurements of intracranial pressure (ICP), patient outcome, and levels of dialysate glutamate and lactate, and cerebral blood flow (CBF) to determine the role of ischemia in this posttraumatic ion dysfunction. METHODS: Eighty-five patients with severe TBI (Glasgow Coma Scale Score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed using flame photometry, and dialysate glutamate and dialysate lactate levels were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients, respectively. Cerebral blood flow studies (stable xenon computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, dialysate potassium values were increased (dialysate potassium > 1.8 mM) for 3 hours or more. A mean amount of dialysate potassium greater than 2 mM throughout the entire monitoring period was associated with ICP above 30 mm Hg and fatal outcome, as were progressively rising levels of dialysate potassium. The presence of dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate (p < 0.0001) levels. Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). CONCLUSIONS: Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase in dialysate potassium, together with dialysate glutamate and lactate, supports the concept that glutamate induces ionic flux and consequently increases ICP, which the authors speculate may be due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered vasoreactivity in cerebral blood vessels caused by higher levels of potassium after trauma. Additional studies in which potassium-sensitive microelectrodes are used are needed to validate these ionic events more clearly.

Cerebral oxygenation in patients after severe head injury: monitoring and effects of arterial hyperoxia on cerebral blood flow, metabolism and intracranial pressure

Early impaired cerebral blood flow (CBF) after severe head injury (SHI) leads to poor brain tissue oxygen delivery and lactate accumulation. The purpose of this investigation was to elucidate the relationship between CBF, local dialysate lactate (lact(md)) and dialysate glucose (gluc(md)), and brain tissue oxygen levels (PtiO2) under arterial normoxia. The effect of increased brain tissue oxygenation due to high fractions of inspired oxygen (FiO2) on lact(md) and CBF was explored. A total of 47 patients with SHI were enrolled in this studies (Glasgow Coma Score [GCS] < 8). CBF was first assessed in 40 patients at one time point in the first 96 hours (27 +/- 28 hours) after SHI using stable xenon computed tomography (Xe-CT) (30% inspired xenon [FiXe] and 35% FiO2). In a second study, sequential double CBF measurements were performed in 7 patients with 35% FiO2 and 60% FiO2, respectively, with an interval of 30 minutes. In a subsequent study, 14 patients underwent normobaric hyperoxia by increasing FiO2 from 35 +/- 5% to 60% and then 100% over a period of 6 hours. This was done to test the effect of normobaric hyperoxia on lact(md) and brain gluc(md), as measured by local microdialysis. Changes in PtiO2 in response to changes in FiO2 were analyzed by calculating the oxygen reactivity. Oxygen reactivity was then related to the 3-month outcome data. The levels of lact(md) and gluc(md) under hyperoxia were compared with the baseline levels, measured at 35% FiO2. Under normoxic conditions, there was a significant correlation between CBF and PtiO2 (R = 0.7; P < .001). In the sequential double CBF study, however, FiO2 was inversely correlated with CBF (P < .05). In the 14 patients undergoing the 6-hour 100% FiO2 challenge, the mean PtiO2 levels increased to 353 (87% compared with baseline), although the mean lact(md) levels decreased by 38 +/- 16% (P < .05). The PtiO2 response to 100% FiO2 (oxygen reactivity) was inversely correlated with outcome (P < .01). Monitoring PtiO2 after SHI provides valuable information about cerebral oxygenation and substrate delivery. Increasing arterial oxygen tension (PaO2) effectively increased PtiO2, and brain lact(md) was reduced by the same maneuver.

High extracellular potassium and its correlates after severe head injury: relationship to high intracranial pressure

Disturbed ionic and neurotransmitter homeostasis are now recognized to be probably the most important mechanisms contributing to the development of secondary brain swelling after traumatic brian injury (TBI). Evidence obtained from animal models indicates that posttraumatic neuronal excitation via excitatory amino acids leads to an increase in extracellular potassium, probably due to ion channel activation. The purpose of this study was therefore to measure dialysate potassium in severely head injured patients and to correlate these results with intracranial pressure (ICP), outcome, and also with the levels of dialysate glutamate, lactate, and cerebral blood flow (CBF) so as to determine the role of ischemia in this posttraumatic ionic dysfunction. Eighty-five patients with severe TBI (Glasgow Coma Scale score < 8) were treated according to an intensive ICP management-focused protocol. All patients underwent intracerebral microdialyis. Dialysate potassium levels were analyzed by flame photometry, as were dialysate glutamate and dialysate lactate levels, which were measured using high-performance liquid chromatography and an enzyme-linked amperometric method in 72 and 84 patients respectively. Cerebral blood flow studies (stable Xenon--computerized tomography scanning) were performed in 59 patients. In approximately 20% of the patients, potassium values were increased (dialysate potassium > 1.8 mmol). Mean dialysate potassium (> 2 mmol) was associated with ICP above 30 mm Hg and fatal outcome. Dialysate potassium correlated positively with dialysate glutamate (p < 0.0001) and lactate levels (p < 0.0001). Dialysate potassium was significantly inversely correlated with reduced CBF (p = 0.019). Dialysate potassium was increased after TBI in 20% of measurements. High levels of dialysate potassium were associated with increased ICP and poor outcome. The simultaneous increase of potassium, together with dialysate glutamate and lactate, supports the hypothesis that glutamate induces ionic flux and consequently increases ICP due to astrocytic swelling. Reduced CBF was also significantly correlated with increased levels of dialysate potassium. This may be due to either cell swelling or altered potassium reactivity in cerebral blood vessels after trauma.

Increased inspired oxygen concentration as a factor in improved brain tissue oxygenation and tissue lactate levels after severe human head injury

OBJECT: Early impairment of cerebral blood flow in patients with severe head injury correlates with poor brain tissue O2 delivery and may be an important cause of ischemic brain damage. The purpose of this study was to measure cerebral tissue PO2, lactate, and glucose in patients after severe head injury to determine the effect of increased tissue O2 achieved by increasing the fraction of inspired oxygen (FiO2). METHODS: In addition to standard monitoring of intracranial pressure and cerebral perfusion pressure, the authors continuously measured brain tissue PO2, PCO2, pH, and temperature in 22 patients with severe head injury. Microdialysis was performed to analyze lactate and glucose levels. In one cohort of 12 patients, the PaO2 was increased to 441+/-88 mm Hg over a period of 6 hours by raising the FiO2 from 35+/-5% to 100% in two stages. The results were analyzed and compared with the findings in a control cohort of 12 patients who received standard respiratory therapy (mean PaO2 136.4+/-22.1 mm Hg). The mean brain PO2 levels increased in the O2-treated patients up to 359+/-39% of the baseline level during the 6-hour FiO2 enhancement period, whereas the mean dialysate lactate levels decreased by 40% (p < 0.05). During this O2 enhancement period, glucose levels in brain tissue demonstrated a heterogeneous course. None of the monitored parameters in the control cohort showed significant variations during the entire observation period. CONCLUSIONS: Markedly elevated lactate levels in brain tissue are common after severe head injury. Increasing PaO2 to higher levels than necessary to saturate hemoglobin, as performed in the O2-treated cohort, appears to improve the O2 supply in brain tissue. During the early period after severe head injury, increased lactate levels in brain tissue were reduced by increasing FiO2. This may imply a shift to aerobic metabolism.

rCBF in hemorrhagic, non-hemorrhagic and mixed contusions after severe head injury and its effect on perilesional cerebral blood flow

Intracerebral contusions can lead to regional ischemia caused by extensive release of excitotoxic aminoacids leading to increased cytotoxic brain edema and raised intracranial pressure. rCBF measurements might provide further information about the risk of ischemia within and around contusions. Therefore, the aim of the presented study was to compare the intra- and perilesional rCBF of hemorrhagic, non-hemorrhagic and mixed intracerebral contusions. In 44 patients, 60 stable Xenon-enhanced CT CBF-studies were performed (EtCO2 30 +/- 4 mmHg SD), initially 29 hours (39 studies) and subsequent 95 hours after injury (21 studies). All lesions were classified according to localization and lesion type using CT/MRI scans. The rCBF was calculated within and 1-cm adjacent to each lesion in CT-isodens brain. The rCBF within all contusions (n = 100) of 29 +/- 11 ml/100 g/min was significantly lower (p < 0.0001, Mann-Whitney U) compared to perilesional rCBF of 44 +/- 12 ml/100 g/min and intra/perilesional correlation was 0.4 (p < 0.0005). Hemorrhagic contusions showed an intra/perilesional rCBF of 31 +/- 11/44 +/- 13 ml/100 g/min (p < 0.005), non-hemorrhagic contusions 35 +/- 13/46 +/- 10 ml/100 g/min (p < 0.01). rCBF in mixed contusions (25 +/- 9/44 +/- 12 ml/100 g/min, p < 0.0001) was significantly lower compared to hemorrhagic and non-hemorrhagic contusions (p < 0.02). Intracontusional rCBF is significantly reduced to 29 +/- 11 ml/100 g/min but reduced below ischemic levels of 18 ml/100 g/min in only 16% of all contusions. Perilesional CBF in CT normal appearing brain closed to contusions is not critically reduced. Further differentiation of contusions demonstrates significantly lower rCBF in mixed contusions (defined by both hyper- and hypodense areas in the CT-scan) compared to hemorrhagic and non-hemorrhagic contusions. Mixed contusions may evolve from hemorrhagic contusions with secondary increased perilesional cytotoxic brain edema leading to reduced cerebral blood flow and altered brain metabolism. Therefore, the treatment of ICP might be individually modified by the measurement of intra- and pericontusional cerebral blood.

The social consequences of mild head injury and executive dysfunction /

Mild head injury (MHI) is a serious cause of neurological impairment as is evident by the substantial percentage (15%) of individuals who remain symptomatic at least 1-year following "mild" head trauma. However, there is a paucity of research investigating the social consequences following a MHI. The first objective of this study was to examine whether measures of executive functioning were predictive of specific forms of antisocial behaviour, such as reactive aggression, impulsive antisocial behaviour, behavioural disinhibition, and deficits in social awareness after controlling for the variance accounted for by sex differences. The second objective was to investigate whether a history of MHI was predictive of these same social consequences after controlling for both sex differences and executive functioning. Ninety university students participated in neuropsychological testing and filled out self-report questionnaires. Fifty-two percent of the sample self-reported experiencing a MHI. As expected, men were more reactively aggressive and antisocial than women. Furthermore, executive dysfunction predicted reactive aggression and impulsive antisocial behaviour after controlling for sex differences. Finally, as expected, MHI status predicted reactive aggression, impulsive antisocial behaviour, and behavioural disinhibition after controlling for sex and executive fimctioning. MHI status and executive functioning did not predict social awareness or sensitivity to reward or punishment. These results suggest that incurring a MHI has serious social consequences that mirror the neurobehavioural profile following severe cases of brain injury. Therefore, the social sequelae after MHI imply a continuum of behavioural deficits between MHI and more severe forms of brain injury.

The Influence of Arousal on Moral Decision-making for Individuals with and without Mild Head Injury

Recent research has shown that University students with a history of self-reported mild head injury (MHI) are more willing to endorse moral transgressions associated with personal, relative to impersonal, dilemmas (Chiappetta & Good, 2008). However, the terms 'personal' and 'impersonal' in these dilemmas have functionally confounded the 'intentionality' of the transgression with the 'personal impact' or 'outcome' of the transgression. In this study we used a modified version of these moral dilemmas to investigate decision-making and sympathetic nervous system responsivity. Forty-eight University students (24 with MHI, 24 with no-MHI) read 24 scenarios depicting moral dilemmas varying as a function of 'intentionality' of the act (deliberate or unintentional) and its 'outcome' (physical harm, no physical harm, non-moral) and were required to rate their willingness to engage in the act. Physiological indices of arousal (e.g., heart rate - HR) were recorded throughout. Additionally, participants completed several neurocognitive tests. Results indicated significantly lowered HR activity at baseline, prior to, and during (but not after) making a decision for each type of dilemma for participants with MHI compared to their non-injured cohort. Further, they were more likely than their cohort to authorize personal injuries that were deliberately induced. MHI history was also associated with better performance on tasks of cognitive flexibility and attention; while students' complaints of postconcussive symptoms and their social problem solving abilities did not differ as a function of MHI history. The results provide subtle support for the hypothesis that both emotional and cognitive information guide moral decision making in ambiguous and emotionally distressing situations. Persons with even a MHI have diminished physiological arousal that may reflect disruption to the neural pathways of the VMPFC/OFC similar to those with more severe injuries.

Intraoperative blood loss and blood transfusion requirements in patients undergoing orthognathic surgery

Procedures for the surgical correction of dentofacial deformities may produce important complications, whether due to the potential for vascular injury or to prolonged surgery, both of which may lead to severe blood loss. Fluid replacement with crystalloid, colloid, or even blood products may be required. The aim of this study was to assess blood loss and transfusion requirements in 45 patients (18 males and 27 females; mean age 29.29 years, range 16-52 years) undergoing orthognathic surgery, assigned to one of two groups according to procedure type-rapid maxillary expansion or double-jaw orthognathic surgery. Preoperative hemoglobin and hematocrit levels and intraoperative blood loss were measured. There was a substantial individual variation in pre- and postoperative hemoglobin values (10.3-17 and 8.8-15.4 g/dL, respectively; p < 0.05). Mean hematocrit values were 41.53 % preoperatively (range 31.3-50.0 %) and 36.56 % postoperatively (range 25-43.8 %) (p < 0.05). Mean blood loss was 274.60 mL (range 45-855 mL). Only two patients required blood transfusion. Although blood loss and transfusion requirements were minimal in the present study, surgical teams should monitor the duration of surgery and follow meticulous protocols to minimize the risks.

Blood transfusion in cardiac surgery is a risk factor for increased hospital length of stay in adult patients

Abstract Background Allogeneic red blood cell (RBC) transfusion has been proposed as a negative indicator of quality in cardiac surgery. Hospital length of stay (LOS) may be a surrogate of poor outcome in transfused patients. Methods Data from 502 patients included in Transfusion Requirements After Cardiac Surgery (TRACS) study were analyzed to assess the relationship between RBC transfusion and hospital LOS in patients undergoing cardiac surgery and enrolled in the TRACS study. Results According to the status of RBC transfusion, patients were categorized into the following three groups: 1) 199 patients (40%) who did not receive RBC, 2) 241 patients (48%) who received 3 RBC units or fewer (low transfusion requirement group), and 3) 62 patients (12%) who received more than 3 RBC units (high transfusion requirement group). In a multivariable Cox proportional hazards model, the following factors were predictive of a prolonged hospital length of stay: age higher than 65 years, EuroSCORE, valvular surgery, combined procedure, LVEF lower than 40% and RBC transfusion of > 3 units. Conclusion RBC transfusion is an independent risk factor for increased LOS in patients undergoing cardiac surgery. This finding highlights the adequacy of a restrictive transfusion therapy in patients undergoing cardiac surgery. Trial registration Clinicaltrials.gov identifier: http://NCT01021631.

Neurological outcome, working capacity and prognostic factors of patients with SCIWORA

STUDY DESIGN: Retrospective case review. OBJECTIVES: In the present study, the neurological outcome, retirement and prognostic factors of patients with spinal cord injury without radiographic abnormality (SCIWORA) were evaluated. SETTING: Swiss national work accident insurance database. METHODS: The medical histories of 32 patients who were insured by the Swiss Accident Insurance Fund (SUVA) and had SCIWORA between 1995 and 2004 were evaluated thoroughly. Moreover, all available magnetic resonance imaging (MRI) scans were evaluated. RESULTS: At the last follow-up, none of the patients had complete spinal cord injury, only 4 patients had severe deficits and 12 patients had normal motor and sensory function in the neurological examination. However, only 7 out of 32 patients had returned to full-time work and 10 out of 32 patients were fully retired. Both the presence of spinal cord change (ρ=0.51) and higher maximum spinal cord compression (ρ=0.57) in MRI scan correlated with the likelihood for retirement; older age (ρ=0.38) and physical load of work (ρ=0.4) correlated with retirement to a lesser extent. CONCLUSION: Although the neurological outcome of SCIWORA is mostly good, the retirement rate is high. Presence of spinal cord change and severity of cord compression are the best predictors for the degree of retirement.

Normobaric hyperoxia--induced improvement in cerebral metabolism and reduction in intracranial pressure in patients with severe head injury: a prospective historical cohort-matched study

OBJECT: The effect of normobaric hyperoxia (fraction of inspired O2 [FIO2] concentration 100%) in the treatment of patients with traumatic brain injury (TBI) remains controversial. The aim of this study was to investigate the effects of normobaric hyperoxia on five cerebral metabolic indices, which have putative prognostic significance following TBI in humans. METHODS: At two independent neurointensive care units, the authors performed a prospective study of 52 patients with severe TBI who were treated for 24 hours with 100% FIO2, starting within 6 hours of admission. Data for these patients were compared with data for a cohort of 112 patients who were treated in the past; patients in the historical control group matched the patients in our study according to their Glasgow Coma Scale scores after resuscitation and their intracranial pressure within the first 8 hours after admission. Patients were monitored with the aid of intracerebral microdialysis and tissue O2 probes. Normobaric hyperoxia treatment resulted in a significant improvement in biochemical markers in the brain compared with the baseline measures for patients treated in our study (patients acting as their own controls) and also compared with findings from the historical control group. In the dialysate the glucose levels increased (369.02 +/- 20.1 micromol/L in the control group and 466.9 +/- 20.39 micromol/L in the 100% O2 group, p = 0.001), whereas the glutamate and lactate levels significantly decreased (p < 0.005). There were also reductions in the lactate/glucose and lactate/pyruvate ratios. Intracranial pressure in the treatment group was reduced significantly both during and after hyperoxia treatment compared with the control groups (15.03 +/- 0.8 mm Hg in the control group and 12.13 +/- 0.75 mm Hg in the 100% O2 group, p < 0.005) with no changes in cerebral perfusion pressure. Outcomes of the patients in the treatment group improved. CONCLUSIONS: The results of the study support the hypothesis that normobaric hyperoxia in patients with severe TBI improves the indices of brain oxidative metabolism. Based on these data further mechanistic studies and a prospective randomized controlled trial are warranted.