Advances in technology have provided us with an array of monitors that may be used in the intensive care unit (ICU) to monitor patients with acute brain injury (Fig. 1). It is, however, particularly important when considering this topic, to remember that the brain will not function without the support of other body systems, e.g., the cardiovascular and respiratory systems. Proper discussion must therefore start with the basic principles of management and monitoring of the acutely ill patient.

Objective: To ascertain if norepinephrine can be used as part of the cerebral perfusion pressure (CPP) management to increase arterial blood pressure (MAP) without causing cerebral hyperemia after severe head injury (HI).¶Design: Prospective, interventional study.¶Setting: Intensive care unit in a university hospital.¶Patients: Twelve severely HI patients; median Glasgow Coma Scale was 6 (range 3–8).¶Interventions: CPP management ( = 70 mmHg). Pressure autoregulation (assessed by norepinephrine infusion) was defined intact if %CPP/%CVR ≤ 2.¶Results: Cerebral blood flow (CBF: Xe133 inhalation technique), jugular bulb oxygen saturation (SjO2) and transcranial Doppler (TCD) were recorded during the test. Norepinephrine increased CPP by 33 % ( ± 4). Autoregulation was found to be intact in ten patients and defective in two. In the ten patients with preserved autoregulation, CBF decreased from 31 ± 3 to 28 ± 3 ml/100 g/min; in the two patients with impaired autoregulation CBF increased respectively from 16 to 35 and from 21 to 70 ml/100 g/min. SjO2 did not change significantly from baseline. TCD remained within the normal range.¶Conclusions: During CPP management norepinephrine can be used to increase MAP without potentiating hyperemia if pressure autoregulation is preserved. The assessment of pressure autoregulation should be considered as a guide for arterial pressure-oriented therapy after HI.

Objective: To quantify central neuronal damage in patients with acute traumatic brain injury (TBI), to determine if brain tissue ischaemia was present using lactate as a marker, and to describe methods of delivering intensive anaesthetic care within a magnetic resonance scanner. Design: Patients underwent T2 weighted magnetic resonance and spectroscopic imaging (SI) early after TBI. Setting: A tertiary referral centre for neurosurgery and neurointensive care in Scotland. Subjects: Eight adults with TBI imaged 4-26 days (mean 13) after injury. Findings were compared to six healthy volunteer control subjects. Measurements and results: A significant reduction of N-acetyl aspartate (NAA- a neurone specific amino acid) was found in areas of brain with obvious lesions on T2 weighted imaging (p<0.001), and in areas where there were no obvious T2 lesions (p<0.02) compared with volunteer control spectra. We found no evidence of lactate. Conclusions: SI may be useful in assessing the extent of neuronal injury which compliments CT and MRI information. Traumatic brain injury affects all age groups and the associated morbidity has devastating consequences, SI may therefore assist clinicians in the management of these patients in the future. As demand for MR imaging of intensive care patients increases, clinicians will require to continue to develop safe working practices and maintain intensive care monitoring and therapies during these investigations.

Neuron specific enolase (NSE) and protein S-100 have previously been described as markers of brain injury. We aimed to discover whether concentrations of either were raised in arterial and jugular venous serum after traumatic brain injury, and whether serum profiles were related to injury severity and neurological outcome. We recruited 22 patients with a traumatic brain injury who were admitted to the intensive care unit. Paired arterial and jugular venous blood samples were taken on admission, and at 24, 48 and 96 hrs after injury. Samples were analysed for NSE and S-100 by RIA. Concentrations of both NSE and S-100 were increased above controls--mean NSE concentration was highest on admission, whilst mean S-100 peaked at 24 hours after injury. There was a small, but significant difference between jugular venous and arterial concentrations of S-100 (p = 0.022). High NSE and S-100 concentrations were significantly related to poor neurological outcome (p = 0.004 and p < 0.001 respectively). Both serum NSE and S-100 may be of some value in helping to predict outcome after a traumatic brain injury.

Neuroanaesthesia Society of Great Britain and Ireland: ABSTRACTS FROM THE ANNUAL MEETING OF THE NEUROANESTHESIA SOCIETY OF GREAT BRITAIN AND IRELAND: PDF Only

Adhesion molecules control the migration of leukocytes into tissue after injury.This may result in further cellular damage. We hypothesized that altered serum concentrations of soluble intercellular adhesion molecule (sICAM)-1 and soluble L-selectin (sL-selectin) after traumatic brain injury would correlate with injury severity and neurological outcome. We investigated serum concentrations of sICAM-1 and sL-selectin in 22 patients with traumatic brain injury admitted to the intensive care unit. The Glasgow Coma Scale (GCS) score and Injury Severity Score were recorded. Paired arterial and jugular venous blood samples were taken on admission and 24, 48, and 96 h after injury. Mean systemic and jugular venous concentrations of sICAM-1 were normal on admission but became significantly increased by 96 h (P = 0.018). sL-selectin concentrations of injured patients were markedly below those of controls at all time points (P < 0.001). There were no significant differences between jugular venous and arterial concentrations of either sICAM-1 or sL-selectin. Serum sICAM-1 was significantly related to neurological outcome (P < 0.001) and to the GCS score (P < 0.001). These changes in adhesion molecule expression after acute brain injury may be important in the pathophysiology of secondary injury. The highly significant relationship between serum sICAM-1 and neurological outcome suggests that the inflammatory response to injury may be detrimental. Drugs that antagonize the actions of the adhesion molecules may have a role in therapy after traumatic brain injury. Implications: This observational study shows that there is a strong association between soluble intercellular adhesion molecule-1 in serum and poor neurological outcome after traumatic brain injury. This suggests that inflammation after brain injury may worsen the prognosis and that therapies directed against this inflammation may prove useful. (Anesth Analg 1998;86:759-65)

Once thought to be relatively shielded from the immunological and inflammatory processes which occur in the tissues of other body systems after acute injury, the brain participates actively in these processes. As a result of trauma, haemorrhage or ischaemia, injury to the brain releases mediators such as the cytokines which activate inflammation and cause further secondary brain injury. Intensive care physicians can do little to alleviate the gravity of the primary injury, but by understanding the mechanisms responsible for secondary injury, and how these mechanisms may, in future, be altered by drug therapy, they may be able to improve patient management and outcome. A primary brain injury stimulates the cells of the central nervous system (CNS) to produce a variety of mediators. Laboratory and human studies have shown that there are at least three important cytokines which are released both by microglia and astrocytes after injury: interleukin-1 (IL-1), tumour necrosis factor (TNF) and interleukin-6 (IL-6). 67 68 82 These proteins function as intercellular communication molecules and stimulate the reparative process which is termed gliosis. Gliosis, however, results in further production and release of cytokines by hypertrophied astrocytes and microglial cells, in addition to mediators released by cells of the peripheral immune system, such as polymorphonuclear cells (PMN), which migrate across a “leaky” blood– brain barrier. The net result may therefore be further damage to brain tissue. The first part of this review focuses on the parts played by these cytokines. Leucocyte adhesion molecules, which are expressed on the surface of leucocytes and endothelial cells, control the migration of leucocytes into tissue. The expression of these molecules after brain injury is linked closely to cytokine production. They mediate toxicity in two ways: by causing leucocyte plugging of micro-vessels and by facilitating the release of toxic oxygen-derived free radicals by PMN which migrate into brain tissue as a result of adhesion molecule activity. The second part of this review focuses on the parts played by the adhesion molecules, intercellular adhesion molecule (ICAM)-1, E-selectin, L-selectin, P-selectin and the integrins in brain injury, and on the evidence linking the cytokines to adhesion molecule upregulation. Finally, we shall discuss if anti-cytokine or anti-adhesion molecule therapy may improve outcome after acute brain injury. (Br. J. Anaesth. 1998; 80: 77–84)

Adhesion molecules have an important role in leukocyte migration into tissue after injury. We hypothesised that changes in ICAM-1 and L-selectin expression after traumatic brain injury would result in altered serum concentrations of these molecules, which would be related to injury severity and outcome. We investigated arterial and jugular venous concentrations of ICAM-1 and L-selectin in 22 patients. The Glasgow Coma Score and Injury Severity Score were recorded. Paired arterial and jugular venous blood samples were taken at designated times after brain injury: on admission, at 24 hours, 48 hours and 96 hours. Glasgow Outcome Scores at 6 months were obtained. Mean serum concentrations of ICAM-1 were normal on admission, but became significantly increased by 96 hours (p = 0.018). Mean L-selectin concentrations were markedly below controls at all time points (p 0.001). There were no significant differences between jugular venous and arterial concentrations of either ICAM-1 or L-selectin. Serum ICAM-1 was significantly related to neurological outcome (p < 0.001) and to the Glasgow Coma Score (p < 0.001). These changes in adhesion molecule expression may be important in the pathophysiology of secondary injury. The highly significant relationship between serum ICAM-1 and neurological outcome suggests that drugs which antagonize adhesion molecule activity may improve outcome after traumatic brain injury.

Few data exist regarding the management of severe head injury in non-neurosurgical centres within the UK. We aimed to discover the number of intensive care units admitting head injury patients, the number of patients admitted annually, and the monitoring and treatment methods followed. Questionnaires were sent to the senior nurse and consultant in 263 intensive care units within non-neurosurgical hospitals. The response rate was 78.8%, with at least one response received from 93.2% of hospitals. The severely head injured were routinely admitted in 56.7% of units. Approximately 2100 patients are admitted annually, a mean of 15 per unit. Intracranial pressure monitoring is routine in only 9% of units and 7% are without 24-h facilities for CT, a cause for concern. More encouragingly, 63% of hospitals have access to rehabilitation facilities. Distribution of guidelines to all intensive care units participating in the care of head injury may improve management and outcome.

The leucocyte adhesion molecules control adhesion of leucocytes to the cerebrovascular endothelium and their subsequent migration into brain tissue. We have shown that concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and soluble L-selectin (sL-selectin) are increased and decreased, respectively, after acute injury to the brain [1]. We hypothesized that these changes would be related to injury type, severity and neurological outcome. We studied 32 patients (22 with traumatic brain injury (TBI) and 10 with spontaneous subarachnoid haemorrhage) admitted to the intensive care unit. Data collected on admission included the Glasgow Coma Score (GCS) and Injury Severity Score (ISS - in TBI). Injury type was classified as focal or diffuse in patients with TBI from the initial CT scan by a single neuroradiologist. Arterial blood samples were taken at designated times after brain injury: on admission, at 24 h, 48 h and 96 h. Analysis of serum for sL-selectin and sICAM-1 was performed by ELISA. A total of 110 samples were analysed in duplicate for each adhesion molecule. Glasgow Outcome Scores (GOS) at 6 months after injury were obtained from information supplied by the patients' general practitioners. The GOS refer to the following: 1 - dead, 2 - vegetative, 3 - severely disabled, 4 - moderate recovery, 5 - good recovery [2]. Median time from primary insult to admission sample was 8 h 30 min (range 2-14 h). Controlling for time (two-way ANOVA with interaction factor), in all patients, there was no significant relation between sL-selectin concentrations and outcome (P=0.053). However, there was a highly significant relation between sICAM-1 and outcome when the maximum number of time points were considered (P<0.001). sICAM-1 concentrations were significantly related to outcome in the traumatic brain injury group, but not in the smaller subarachnoid haemorrhage group (P=0.001 and P=0.272, respectively). When only the concentrations on admission and at 24 h were considered in the traumatic brain injury group, there remained a significant relation with outcome (P=0.014). There was a significant negative correlation between sICAM-1 and GCS (r=−0.382, P<0.001), but no correlation between sICAM-1 and ISS in the TBI group. There was no relation between either sICAM-1 or sL-selectin and injury type, and no relation between sL-selectin and either GCS or ISS. The relation between sICAM-1 and outcome could not be explained by the additional presence of extracranial injuries. This is the first study to examine serial changes in adhesion molecule concentrations and their relation to outcome after acute brain injury. We have shown that there is a highly significant relation between arterial concentrations of sICAM-1 and neurological outcome, and between sICAM-1 and severity of brain injury. These are new and important findings, as rather than merely being a marker of injury, ICAM-1 is an active mediator in the ongoing inflammaory process which results in secondary brain injury. By antagonizing the actions of ICAM-1, it may be possible to limit inflammatory secondary damage and improve outcome in this patient population.

After acute brain injury there may be increased intracranial production of cytokines, with activation of inflammatory cascades. We have sought to determine if a transcranial cytokine gradient was demonstrable in paired sera of 32 patients requiring intensive care after acute brain injury. The difference between concentrations of IL-1 beta, IL-6, IL-8 and TNF alpha in jugular venous and arterial serum was measured on admission, and at 24, 48 and 96 h after the primary injury. There were no differences in IL-1 beta, IL-8 or TNF alpha, but median gradients of 6.7 and 11.5 pg ml-1 for IL-6 were demonstrated in the traumatic brain injury (n = 22) and subarachnoid haemorrhage (n = 10) groups, respectively (normal values in serum < 4.7 pg ml-1; P < 0.001 both groups). This suggests that there is significant production of IL-6 by intracranial cells after acute brain injury. Therapy directed towards combatting the negative effects of IL-6 may potentially benefit patients who have sustained an acute brain injury.

Assessment of cerebral oxygenation using near-infrared spectroscopy in intensive care is increasing. We compared the ability of the Invos 3100 and the Critikon 2020 monitors to produce stable and consistent readings of regional cerebral oxygen saturation in resting volunteers. Failure to obtain any stable reading with the Critikon occurred in eight out of 18 subjects (44.4%) and with the Invos in three out of 15 subjects (20%). The Critikon showed a significantly higher failure rate in male subjects (p = 0.0011). Differences in recorded values of cerebral oxygen saturation (Critikon-Invos) ranged from -4.7% to 12.6% and were significantly related to the average saturation level (p < 0.0001). The within-monitor variability was significantly higher for the Invos (p = 0.0124). Neither monitor is able to give stable and consistent readings over time, particularly in male subjects. The unacceptably high failure rate of the recently introduced Critikon 2020 will limit or prevent its clinical use.