The Spiegelberg Compliance Device (Spiegelberg KG, Hamburg, Germany) has been available for the automated measurement and calculation of minute by minute intracranial compliance. Widespread practical use has been somewhat limited by the instability of values; especially at low intracranial pressures. We looked at two aspects of a methodology in an attempt to increase the value of the Spiegelberg device in the clinical setting. Firstly, we discussed the difference in representing measured values as elastance (dp/dv) instead of compliance (dv/dp); and secondly we proposed the use of an averaging algorithm called the Exponentially Weighted Moving Average (ewma), which could be applied as a flexible method to follow trends and rapid changes in the elastance (or compliance). Clinical data from sixteen patients were gathered and statistical analysis was focused on three particular aspects, the coefficient of variation which indicates the variability of data values, the correlation between the elastance (or compliance) time series and the underlying ICP signal and the percentage of outliers greater than 2.5 standard deviations from the mean. Our results showed that expressing elastance (dp/dv) instead of compliance (dv/dp) yielded fewer outliers and had a better correlation to ICP, and the ewma method had a better correlation to ICP than the Spiegelberg method.

The Spiegelberg automated compliance device offers practical benefits over the standard manual injection techniques for assessing volume-pressure status. Currently, however, the system relies on the insertion of an intraventricular catheter. If automated continuous measurement of intraparenchymal compliance could be achieved, then this would be a further practical advance. Automated measurements of compliance using a prototype intraparenchymal probe were assessed in comparison with the current intraventricular probe in a sheep model of diffusely raised ICP. The results show poor correlation between intraventricular compliance (IVC) and intraparenchymal compliance (IPC) at low levels of cerebral perfusion pressure (CPP). The IPC response to decreasing CPP beyond probable levels of blood flow autoregulation suggest that IPC is more dependent on local tissue perfusion factors, rather than overall physical compliance. Further evaluation of compliance in the intraparenchymal compartment versus intraventricular compliance will be needed before adaptation of the automated system for clinical application.

Deciding upon shunting in patients with hydrocephalus with pos­sibly related symptomatology, is difficult. The Spiegelberg automated device allows continuous measurements of intracranial compliance. We aimed to evaluate the added information that this new technology can provide, in addition to standard continuous ICP monitoring. Thirty-three patients with hydrocephalus were continuously monitored for ICP and compliance. Patients with abnormal ICP or compliance profiles were selected for shunting. Thirteen patients underwent ventriculo-peritoneal shunting on this basis, with 12 obtaining benefit and one dying as a complication of shunt-related sepsis. The 13 patients undergoing shunting had abnormalities in either intracranial pressure or compliance or both. Only 1 patient had normal ICP, but abnormal compliance and so the true complementary role of continuous compliance measurements cannot be determined. It is proposed that further recruitment be on a larger multi-centre basis. Determination of benefit is required, particularly as a possible time lag of abnormal ICP abnormal compliance over appearing during monitoring can be demonstrated.

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.

The goal of this study was to compare the Spiegelberg intraventricular intracranial pressure (ICP)/intracranial compliance monitoring device, which features an air-pouch balloon catheter, with existing gold-standard methods of measuring ICP and intracranial compliance. A Spiegelberg intraventricular catheter, a standard intraventricular catheter, and a Codman intraparenchymal ICP microsensor were placed in five sheep, which previously had been given anesthetic and paralytic agents, to allow comparative measurement of ICP at incremental levels (range 5-50 mm Hg). Intracranial pressure measured using the Spiegelberg intraventricular air-pouch balloon catheter displayed a linear correlation with ICP measured using the standard intraventricular fluid-filled catheter (r2 = 0.9846, p < 0.001; average bias -0.74 mm Hg), as well as with ICP measured using the Codman intraparenchymal strain-gauge sensor (r2 = 0.9778, p < 0.001; average bias 0.01 mm Hg). Automated measurements of intraventricular compliance obtained using the Spiegelberg compliance device were compared with compliance measurements that were made using the gold-standard manual cerebrospinal fluid bolus injection technique at ICPs ranging from 5 to 50 mm Hg, and a linear correlation was demonstrated between the two methods (r2 = 0.7752, p < 0.001; average bias -0.019 ml/mm Hg). The Spiegelberg air-pouch ICP/compliance monitor provides ICP and compliance data that are very similar to those obtained using both gold-standard methods and an intraparenchymal ICP monitor over a range of pathophysiological ICPs. The automated closed Spiegelberg system offers practical advantages for the measurement of intraventricular compliance. Assessment of the clinical utility and robustness of the Spiegelberg system, together with the development of an intraparenchymal device, would enhance the clinical utility of automated compliance measurement and expand the range of its applications.

Little is known about the incidence of secondary insults, particularly cerebral perfusion pressure insults, in children. The objectives of this study were to assess the duration of CPP insults at three different thresholds in children and to relate CPP insults to outcome. Eighteen children (age < 16, median & mean 8 years) admitted to the Neurointensive Care Unit who had ICP, MAP and CPP continuously monitored were studied. Using the Edinburgh secondary insult analysis program, data was scanned for CPP insults at three different thresholds: CPP < 70 mmHg, < 60 mmHg and < 50 mmHg. Outcome was assessed using the Glasgow Outcome Scale. Thirty percent of the time CPP was between 60 and 70 mmHg, 21% of the time CPP was between 50 and 60 mmHg and 8% of the time the CPP was less than 50 mmHg. Compared with adults, there was more than twice the incidence of CPP insults in all threshold groups. BP remained relatively stable above 70 mmHg across all three CPP threshold groups. However, ICP increased slightly on average from about 13-->17 mmHg when CPP decreased from the < 70 to < 60 mmHg group (p < 0.001). There was a marked increase in ICP to greater than 30 mmHg on average in the CPP < 50 mmHg group (p < 0.001). CPP insults less than 70, 60 and 50 mmHg do occur commonly in children, a larger dataset and possibly longer term follow up measures will be needed to identify potentially treatable physiological factors most effecting the outcome of children.

Objective: To investigate the role of the endothelin system in pressure autoregulation of cerebral blood flow (CBF) in rats.Design: We tested pressure autoregulation by increasing cerebral perfusion pressure (CPP; mean arterial pressure–intracranial pressure) with norepinephrine (0.08 μg · kg−1· min−1 for 30 min) twice in ten anesthetized normocapnic rats. The first test was performed without (control test) and the second test after administration of the combined endothelin ETA/B receptor antagonist, bosentan, i. v. (30 mg/kg; drug test). CBF was measured by the hydrogen clearance technique.Results: During the control test, norepinephrine infusion increased CPP by 21 ± 2 (23 ± 2 %) mmHg (mean ± SEM; p < 0.001) and CBF by 3.6 ± 3.1 (6 ± 8 %) ml/100 g/min (p = 0.5, Fig. 1); during the drug test, norepinephrine infusion increased CPP by 18 ± 1 (20 ± 2 %) mmHg (p < 0.001) and CBF by 15.8 ± 4.1 (46 ± 13 %) ml/100 g/min (p = 0.004). Mean arterial pressure was not affected by bosentan infusion (p = 0.2). PaC02 levels were stable during the tests (40.2 ± 1.4 mmHg).Conclusions: The endothelin system is involved in cerebral pressure autoregulation in a rodent model in vivo. The role of this system under pathophysiologic conditions such as subarachnoid hemorrhage, where basal vascular tone and its regulation may be altered, remains to be defined.

OBJECTIVE: To study the changes of brain TXA(2) and PGI(2) levels in a new rodent model of impact acceleration diffuse brain injury with hypotention and hypoxia and the effect of diaspirin cross linked hemoglobin solution (DCLHb) on brain TXA(2) and PGI(2) levels. METHODS: Thirty-two male SD rats were randomized into sham, head injury alone, head injury with secondary insults and injury with insults followed by DCLHb administration groups. Animals were physiologically monitored throughout the experiment and the prostanoids were measured via radioimmunoassay (RIA). RESULTS: There were no changes in TXB(2) and 6-keto-PGF1alpha (stable metabolites of TXA(2) and PGI(2)) levels in injury alone group while TXB(2) level in secondary insults group elevated significantly and both TXB(2) and 6-keto-PGF1alpha levels in injury with insults followed by DCLHb administration augmented significantly in comparison with the corresponding value of sham at 4 h postimpact. CONCLUSIONS: The only increase in TXA(2) level in secondary insults rats suggests that there may be both thrombotic episodes and vasoconstriction leading to focal increase in micro-circulatory resistance which contributes to a decreased focal cerebral blood flow (CBF). And it is hypothesed that DCLHb may exert its protective properties through increasing PGI(2) production in injured brain by affecting CBF and cerebral perfusion pressure (CPP).

Continuous transcranial Doppler ultrasonography of the middle cerebral artery (TCD-MCA) has been proposed as a method of identifying the lower cerebral autoregulatory threshold. This study investigated the relationship between continuous TCD-MCA and cerebral blood flow (CBF) in sheep. Arterial blood pressure, intracranial pressure, CBF and left TCD-MCA were measured in 12 anaesthetized and ventilated merino sheep. Cerebral perfusion pressure (CPP) was reduced by haemorrhagic hypotension. Measurements were recorded continuously and breakpoint thresholds calculated by an analysis of variance. The TCD-MCA systolic velocity breakpoint (50 +/- 1.5 mmHg) did not significantly differ from the lower limit of autoregulation, identified by the CBF breakpoint (50 +/- 1.8 mmHg). The TCD-MCA diastolic velocity breakpoint occurred at a significantly higher level of CPP (64 +/- 2 mmHg) (P < 0.01). The relationship between TCD-MCA flow velocity and CBF thresholds has been described. Early divergence of flow velocity may represent a compensatory mechanism to maintain CBF.

Diaspirin cross-linked haemoglobin (DCLHb) is a new oxygen carrying blood substitute with vasoactive properties. Vasoactive properties may be mediated via high affinity binding of nitric oxide by the haem moiety. Using a rodent model of head injury combined with ischaemia, we studied the effects of DCLHb on cerebral blood flow (CBF) and intracranial pressure (ICP). Twenty anaesthetized rats were allocated randomly to receive treatment with DCLHb 400 mg kg-1 i.v. or placebo (oncotically matched plasma protein substitute 4.5% i.v.). To produce diffusely increased ICP, after a severe weight drop injury, all animals underwent a 30-min period of bilateral carotid ligation combined with a period of induced hypotension. After reperfusion, DCLHb or placebo was infused and the animals instrumented for measurement of intraventricular ICP and CBF in the region of the sensorimotor cortex using the hydrogen clearance technique. Mean arterial pressure (MAP), ICP, cerebral perfusion pressure (CPP) (CPP = MAP - ICP) and CBF were measured 4 h after injury in all animals. DCLHb significantly reduced ICP from mean 13 (SEM 2) to 3 (1) mm Hg (P < 0.001), increased CPP from 52 (8) to 95 (6) mm Hg (P < 0.001) and increased CBF from 21 (2) to 29 (2) ml 100 g-1 min-1 (P = 0.032). We conclude that DCLHb improved CPP without a reduction in CBF in a rodent model of post-traumatic brain swelling.

The strain-gauge Codman MicroSensor intracranial pressure (ICP) transducer has shown consistently good laboratory performance. To assess the practical performance of the system in patients following acute brain injury, 10 patients were fitted with a MicroSensor and a second ICP monitor. In five cases this was a fibre-optic transducer and in five cases an intraventricular fluid-filled device. Paired ICP values were recorded every 5 min. ICP values ranged from 0 to 31 mmHg. Altman-Bland plots showed that individual readings could differ by as much as 9 mmHg. Further analysis showed that much of this disagreement could be explained by a constant offset on each occasion. Comparison traces of ICP in individual patients show high agreement in timing and size of changes. The unexplained constant offset leads to uncertainty about the true ICP. Treatment decisions are often based upon absolute levels of ICP and patient care may therefore differ depending upon the monitor used.

Alfentanil is reported to increase intracranial pressure (ICP) after neurotrauma. A direct cerebral vasodilator effect has been postulated. We studied 17 Sprague-Dawley rats allocated to one of three groups. Animals were anaesthetized and their lungs ventilated, and arterial pressure, ICP and/or regional cerebral blood flow (CBF) measurements were undertaken. Group 1 (n = 6) received a severe closed head injury while group 2 (n = 5) received no injury. ICP and mean arterial pressure (MAP) were measured before, during and after rapid infusion of alfentanil 250, 500 and 750 micrograms kg-1. CBF was measured by hydrogen clearance before rapid infusions and at 30-min intervals after starting a subsequent slow infusion of alfentanil 500 micrograms kg-1 h-1. Group 3 (n = 6) underwent CBF measurement only, for comparison with those of groups 1 and 2. They received an injury but no alfentanil. ICP or MAP values did not differ significantly between groups 1 and 2. Rapid i.v. doses of alfentanil produced increases in ICP and reductions in MAP. ICP changes were consistent with a drug effect (P < 0.001) but were small. Reductions in MAP were significant (P < 0.05) and preceded changes in ICP. CBF values were similar and unaffected by slow alfentanil infusion in groups 1 and 2, and did not differ significantly between groups 1 and 3. We conclude that alfentanil did not appear to exert a direct effect on the cerebral circulation. Changes in ICP after rapid infusion were secondary to reductions in SAP. Slow infusion did not cause such changes.

Since the publication by Marmarou of a new rodent model of head injury, an increasing number of centres are adopting the model for use in a variety of paradigms. We report on two simple methods we have applied which allows us to monitor weight drop velocity and foam stiffness, both of which are critical factors for producing repeatable closed head injury with this model. We hope the application of these methods will assist in the standardisation of this model between centres.

Primary traumatic brain damage may be compounded by secondary pathophysiological insults that can occur soon after trauma, during transfer to hospital or subsequent treatment of the head-injured patient. The aim of this prospective study was to quantify the burden of a wide range of secondary insults occurring after head injury and to relate these to 12-month outcome. In 124 adult head-injured patients studied during intensive care using a computerized data collection system, < or = 14 clinically indicated physiological variables were measured minute-by-minute. Verified values falling outside threshold limits for > or = 5 min, as defined by the Edinburgh University Secondary Insult Grading scheme, were analysed by insult grade and duration. A greater incidence of secondary insults was detected than previous studies have indicated. Insults were found in 91% of patients and occurred in all severities of head trauma, at all ages, and at every level of Injury Severity Score (ISS). The cumulative durations were much greater than previously recorded although 85% of the total time was at the least severe grade. Short duration insults were common. In 71 patients, in whom 8 insults could be assessed (intracranial pressure, arterial hypo- and hypertension, cerebral perfusion pressure, hypoxemia, pyrexia, brady- and tachycardia), outcome at 12 months was analysed using logistic regression to determine the relative influence of age, admission Glasgow Coma Sumscore, ISS, pupil response on admission, and insult duration on both mortality and morbidity. The most significant predictors of mortality in this patient set were durations of hypotensive (p = .0064), pyrexic (p = .0137), and hypoxemic (p = .0244) insults. When good versus poor outcome was considered, hypotensive insults (p = .0118) and pupil response on admission (p = .0226) were significant.

Previous studies have suggested that only a small proportion (< 15%) of comatose head-injured patients whose initial computerized tomography (CT) scan was normal or did not show a mass lesion, midline shift, or abnormal basal cisterns develop intracranial hypertension. The aim of the present study was to re-examine this finding against a background of more intensive monitoring and data acquisition. Eight severely head-injured patients with a Glasgow Coma Scale score of 8 or less, whose admission CT scan did not show a mass lesion, midline shift, or effaced basal cisterns, underwent minute-to-minute recordings of arterial blood pressure, intracranial pressure (ICP), and cerebral perfusion pressure (CPP) derived from blood pressure minus ICP. Intracranial hypertension (ICP > or = 20 mm Hg lasting longer than 5 minutes) was recorded in seven of the eight patients; in five cases the rise was pronounced in terms of both magnitude (ICP > or = 30 mm Hg) and duration. Reduced CPP (< or = 60 mm Hg lasting longer than 5 minutes) was recorded in five patients. Severely head-injured (comatose) patients whose initial CT scan is normal or does not show a mass lesion, midline shift, or abnormal cisterns nevertheless remain at substantial risk of developing significant secondary cerebral insults due to elevated ICP and reduced CPP. The authors recommend continuous ICP and blood pressure monitoring with derivation of CPP in all comatose head-injured patients.

A group of 74 patients with head injury (54 severe, 17 moderate and 3 minor) had continuous monitoring of both arterial and intracranial pressure with computer-based registration of these pressures, cerebral perfusion pressure and other vairables. In 60 patients cerebral perfusion pressure CPP fell below 60 mm Hg for periods of 5 minutes or longer. The distribution over time of these reductions in CPP during up to 12 days of monitoring was studied, and each episode of reduced CPP was attributed to a fall in arterial pressure, an increase in intracranial pressure, or both. Two clusters of reduced CPP were found, one during the first 24 hours of monitoring, when reduced CPP was mainly caused by a reduction in arterial pressure, and the other at 5 or 6 days after injury, when reduced CPP was due mainly to an increase in intracranial pressure.