Liver function test abnormalities after traumatic brain injury: is hepato-biliary ultrasound a sensitive diagnostic tool?

BACKGROUND: This study was to evaluate the usefulness of hepato-biliary ultrasound (HBUS) for the investigation of isolated liver function tests (LFTs) abnormalities. METHODS: We retrospectively reviewed HBUS reports in traumatic brain injury (TBI) patients admitted to our tertiary neuro-critical care unit (NCCU; January 2005-June 2011). We included patients receiving an HBUS for isolated LFTs derangement, excluding pre-existing hepato-biliary diseases or trauma. We assessed the temporal profile of alanine aminotransferase (ALT), bilirubin (Bil), and alkaline phosphatase (ALP). RESULTS: Of 511 patients, 58 received an HBUS. Of these, 47 were investigated for isolated LFTs derangement; HBUS always failed to identify a cause for these abnormalities. The HBUS was performed on day 18 (range 6-51) with the following mean values: 246 IU litre(-1) [ALT, 95% confidence interval (CI) 183-308], 24 µmol litre(-1) (Bil, 95% CI 8-40), and 329 IU litre(-1) (ALP, 95% CI 267-390); only ALT (72, 95% CI 36-107) and ALP (73, 95% CI 65-81) were deranged from admission values (both P<0.01). At NCCU discharge, both ALT (160, 95% CI 118-202) and ALP (300, 95% CI 240-360) were higher than at admission (P<0.01). Compared with HBUS-day value, only ALT improved by NCCU discharge (P<0.05), while both were recovering by hospital discharge (ALT 83, 95% CI 59-107; ALP 216, 95% CI 181-251; P<0.01). At hospital discharge, ALP remained higher than at admission (P<0.01). CONCLUSIONS: In TBI patients, HBUS did not appear sensitive in detecting causes for isolated LFT abnormalities. Both ALT and ALP worsened and gradually recovered. Their abnormalities did not prevent NCCU discharge. ALP recovered more slowly than ALT. TBI and its complications, critical illness, and pharmacological strategies may explain the LFTs derangement.

Cerebrovascular reactivity during hypothermia and rewarming.

BACKGROUND: Experimental evidence from a murine model of traumatic brain injury (TBI) suggests that hypothermia followed by fast rewarming may damage cerebral microcirculation. The effects of hypothermia and subsequent rewarming on cerebral vasoreactivity in human TBI are unknown. METHODS: This is a retrospective analysis of data acquired during a prospective, observational neuromonitoring and imaging data collection project. Brain temperature, intracranial pressure (ICP), and cerebrovascular pressure reactivity index (PRx) were continuously monitored. RESULTS: Twenty-four TBI patients with refractory intracranial hypertension were cooled from 36.0 (0.9) to 34.2 (0.5) degrees C [mean (sd), P < 0.0001] in 3.9 (3.7) h. Induction of hypothermia [average duration 40 (45) h] significantly reduced ICP from 23.1 (3.6) to 18.3 (4.8) mm Hg (P < 0.05). Hypothermia did not impair cerebral vasoreactivity as average PRx changed non-significantly from 0.00 (0.21) to -0.01 (0.21). Slow rewarming up to 37.0 degrees C [rate of rewarming, 0.2 (0.2) degrees C h(-1)] did not increase ICP [18.6 (6.2) mm Hg] or PRx [0.06 (0.18)]. However, in 17 (70.1%) out of 24 patients, rewarming exceeded the brain temperature threshold of 37 degrees C. In these patients, the average brain temperature was allowed to increase to 37.8 (0.3) degrees C (P < 0.0001), ICP remained stable at 18.3 (8.0) mm Hg (P = 0.74), but average PRx increased to 0.32 (0.24) (P < 0.0001), indicating significant derangement in cerebrovascular reactivity. After rewarming, PRx correlated independently with brain temperature (R = 0.53; P < 0.05) and brain tissue O2 (R = 0.66; P < 0.01). CONCLUSIONS: After moderate hypothermia, rewarming exceeding the 37 degrees C threshold is associated with a significant increase in average PRx, indicating temperature-dependent hyperaemic derangement of cerebrovascular reactivity.

Incidence of adrenal insufficiency after severe traumatic brain injury varies according to definition used: clinical implications.

BACKGROUND: Adrenal insufficiency impacts on the haemodynamic management of patients in intensive care. Very little is known about the incidence of adrenal insufficiency in the first 10 days after traumatic brain injury. METHODS: We retrospectively reviewed the charts of 113 traumatic brain injury patients within 10 days of their injury. They all had a high-dose corticotropin stimulation test performed because of haemodynamic instability. Blood cortisol concentrations were measured at baseline, 30 and 60 min after the administration of high-dose corticotropin. The incidence of adrenal insufficiency was determined according to various definitions used in the literature. RESULTS: The baseline cortisol concentration was <414 nmol litre(-1) (15 microg dl(-1)) in 78% of patients and <690 nmol litre(-1) (25 microg dl(-1)) in all patients. The cortisol concentration did not rise above 500 nmol litre(-1) (18 microg dl(-1)) at 30 and 60 min in 49 and 22% of patients, respectively. The cortisol concentration did not rise by 250 nmol litre(-1) (9 microg dl(-1)) at 30 and 60 min in 48 and 25% of patients respectively. Primary adrenal insufficiency defined by an abnormal baseline cortisol concentration and an abnormal response to the high-dose corticotropin stimulation test was present in 13-28% of patients according to the cut-off values used. CONCLUSIONS: The incidence of adrenal insufficiency varies from 25 to 100% in the first 10 days after traumatic brain injury. The range of incidences reported illustrates the need for standardization of the definition of adrenal insufficiency. This has a direct impact on treatment. Sampling at 60 min after the high-dose corticotropin stimulation test seems to correlate better with the maximum secreting capacity of the adrenal glands.

The health economics of blood use in cerebrovascular aneurysm surgery: the experience of a UK centre.

BACKGROUND AND OBJECTIVE: Surgical treatment of patients presenting with subarachnoid haemorrhage secondary to a leaking cerebrovascular aneurysm involves coiling or clipping. Traditionally all patients undergoing this procedure are cross-matched routinely. With ever-increasing strains on the health budget and transfusion services in particular, as well as the real, albeit low risk of transfusion transmitted disease, we propose that a simple 'group and save', coupled with a reliable 'fast-issue' blood transfusion service should replace this outdated concept. METHOD: To assess this assumption, we carried out a retrospective analysis of 103 patients who underwent clipping or coiling during January to December 2001 in our Neurosurgical Unit. RESULTS: All patients but one had been cross-matched (99%). However, only 33 patients (32%) eventually required a blood transfusion. In real terms, this meant a total of 294 units of blood that had been cross-matched routinely, in our series of 103 patients, were not used. Had these patients only been 'group and saved' and a system of 'fast-issue' been adopted, assuming that none of the patients had abnormal antibodies, the blood transfusion department would have made a saving of 4815.72 pounds sterling for this group of patients. CONCLUSION: We conclude that advances in surgical technique have made routine cross-matching of blood in cerebral aneurysm surgery unnecessary.

Acute and chronic pain following craniotomy: a review.

Postoperative pain is an important clinical problem that has received increasing attention in recent years. However, pain following craniotomy has been a comparatively neglected topic; this review seeks to redress this imbalance. A brief overview of the anatomy of the skull and its linings is given, with particular reference to innervation. The various approaches for craniotomies are classified, with their association with acute and long-term effects on analgesic requirements. A comprehensive search of the literature was undertaken to ascertain the incidence of acute pain post craniotomy and current thoughts on pharmacological management, touching briefly on pre-emptive treatment. Also discussed is the much neglected but nevertheless real incidence of chronic pain following craniotomy and its underlying pathogenesis, prevention and treatment.

Cerebral blood flow augmentation in patients with severe subarachnoid haemorrhage.

Following aneurysmal subarachnoid haemorrhage (SAH), cerebral blood flow (CBF) may be reduced, resulting in poor outcome due to cerebral ischaemia and subsequent stroke. Hypertonic saline (HS) is known to be effective in reducing intracranial pressure (ICP). We have previously shown a 20-50% increase in CBF in ischaemic regions after intravenous infusion of HS. This study aims to determine the effect of HS on CBF augmentation, substrate delivery and metabolism. Continuous monitoring of arterial blood pressure (ABP), ICP, cerebral perfusion pressure (CPP), brain tissue oxygen (PbO2), middle cerebral artery flow velocity (FV), and microdialysis was performed in 14 poor grade SAH patients. Patients were given an infusion of 23.5% HS, and quantified xenon computerised tomography scanning (XeCT) was carried out before and after the infusion in 9 patients. The results showed a significant increase in ABP, CPP, FV and PbO2, and a significant decrease in ICP (p < 0.05). Nine patients showed a decrease in lactate-pyruvate ratio at 60 minutes following HS infusion. These results show that HS safely and effectively augments CBF in patients with poor grade SAH and significantly improves cerebral oxygenation. An improvement in cerebral metabolic status in terms of lactate-pyruvate ratio is also associated with HS infusion.

Integrated approaches to academic anaesthesia - the Cambridge experience.

There is mounting concern about the pressures experienced by University Departments of Anaesthesia, which, if lost, could threaten undergraduate peri-operative medicine teaching, development of critical appraisal skills among anaesthetists, and the future of coherent research programs. We have addressed these problems by establishing a foundation course in scientific methods and research techniques (the Cambridge SMART Course), complemented by competitive, fully funded, 12-month academic trainee attachments. Research conducted during academic attachments has been published and used to underpin substantive grant applications allowing work towards higher degrees. Following the attachment, a flexible scheme ensures safe reintroduction to clinical training. Research at consultant level is facilitated by encouraging applications for Clinician Scientist Fellowships, and by ensuring that the University Department champions, legitimises and validates the allocation of research time within the new consultant contract. We believe that these are important steps in safeguarding research and teaching in anaesthesia, critical care and peri-operative medicine.

Continuous assessment of cerebral autoregulation: clinical and laboratory experience.

The method for the continuous assessment of cerebral autoregulation using slow waves of MCA blood flow velocity (FV) and cerebral perfusion pressure (CPP) or arterial pressure (ABP) has been introduced seven years ago. We intend to review its clinical applications in various scenarios. Moving correlation coefficient (3-6 min window), named Mx, is calculated between low-pass filtered (0.05 Hz) signals of FV and CPP or ABP (when ICP is not measured directly). Data from ventilated 243 head injuries and 15 patients after poor grade subarachnoid haemorrhage, 38 patients with Carotid Artery stenosis, 35 patients with hydrocephalus and fourteen healthy volunteers is presented. Good agreement between the leg-cuff test and Mx has been confirmed in healthy volunteers (r = 0.81). Mx also correlated significantly with the static rate of autoregulation and transient hyperaemic response test. Autoregulation was disturbed (p < 0.021) by vasospasm after SAH and worse in patients with hydrocephalus in whom CSF circulation was normal (p < 0.02). In head injury, Mx indicated disturbed autoregulation with low CPP (< 55 mmHg) and too high CPP (> 95 mmHg). Mx strongly discriminated between patients with favourable and unfavourable outcome (p < 0.00002). This method can be used in many clinical scenarios for continuous monitoring of cerebral autoregulation, predicting outcome and optimising treatment strategies.

Management of comatose head-injured patients: are we getting any better?

This re-survey of neurosurgical centres was conducted to determine whether the publication of management guidelines has resulted in changes in the intensive care management of severely head-injured patients (defined as Glasgow Coma Score < 9) in the UK and Ireland. Results were compared with data collected from a similar survey conducted 2 years earlier. Almost 75% of centres monitor intracranial pressure in the majority of patients and 80% now set a target cerebral perfusion pressure of > 70 mmHg. The use of prolonged hyperventilation (> 12 h) is declining and the target PaCO2 is now most commonly > 4 kPa. More centres maintain core temperature < 36.5 degrees C. Although wide variations in the management of severely head-injured patients still exist, we found evidence of practice changing to comply with published guidelines.

Preliminary experience of the estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography.

OBJECTIVE: The direct calculation of cerebral perfusion pressure (CPP) as the difference between mean arterial pressure and intracranial pressure (ICP) produces a number which does not always adequately describe conditions for brain perfusion. A non-invasive method of CPP measurement has previously been reported based on waveform analysis of blood flow velocity measured in the middle cerebral artery (MCA) by transcranial Doppler. This study describes the results of clinical tests of the prototype bilateral transcranial Doppler based apparatus for non-invasive CPP measurement (nCPP). METHODS: Twenty five consecutive, paralysed, sedated, and ventilated patients with head injury were studied. Intracranial pressure (ICP) and arterial blood pressure (ABP) were monitored continuously. The left and right MCAs were insonated daily (108 measurements) using a purpose built transcranial Doppler monitor (Neuro Q(TM), Deltex Ltd, Chichester, UK) with software capable of the non-invasive estimation of CPP. Time averaged values of mean and diastolic flow velocities (FVm, FVd) and ABP were calculated. nCPP was then computed as: ABPxFVd/FVm+14. RESULTS: The absolute difference between real CPP and nCPP (daily averages) was less than 10 mm Hg in 89% of measurements and less than 13 mm Hg in 92% of measurements. The 95% confidence range for predictors was no wider than +/-12 mm Hg (n=25) for the CPP, varying from 70 to 95 mm Hg. The absolute value of side to side differences in nCPP was significantly greater (p<0.05) when CT based evidence of brain swelling was present and was also positively correlated (p<0.05) with mean ICP. CONCLUSION: The device is of potential benefit for intermittent or continuous monitoring of brain perfusion pressure in situations where the direct measurement is not available or its reliability is in question.

Effects of isoflurane, sevoflurane and propofol anaesthesia on jugular venous oxygen saturation in patients undergoing coronary artery bypass surgery.

We investigated the effect of sevoflurane, isoflurane and propofol on jugular venous bulb oxygen saturation (SjO2) in 21 patients undergoing coronary artery bypass graft surgery (CABG) during and after normothermic cardiopulmonary bypass (CPB). Patients received a standardized anaesthetic consisting of fentanyl, midazolam and were then randomly allocated to receive either isoflurane, sevoflurane or propofol for maintenance. SjO2 values were significantly lower than baseline 1 h after CPB in the propofol but not the isoflurane or the sevoflurane groups. Furthermore, SjO2 values were significantly higher during CPB in the isoflurane group (P = 0.0081) and significantly lower 6 h after CPB in the sevoflurane group (P = 0.0447) when compared to the propofol group. We conclude that jugular venous desaturation during and after normothermic CPB is more likely during propofol anaesthesia.

Sevoflurane and anesthesia for neurosurgery: a review.

This review assesses the extent to which sevoflurane fulfills the requirements of the ideal inhalational agent for use in neuroanesthetic practice. Sevoflurane's pharmacokinetic profile is outlined. Data from animal and human studies are used to discuss its effects on cerebral hemodynamics, central nervous system monitoring, and cardiovascular parameters. Where possible, sevoflurane is compared with isoflurane, currently considered the inhalational agent of choice in neuroanesthesia. Sevoflurane's potential for toxicity is reviewed.

Propofol anesthesia for craniotomy: a double-blind comparison of remifentanil, alfentanil, and fentanyl.

For patients undergoing craniotomy, it is desirable to have stable and easily controllable hemodynamics during intense surgical stimulation. However, rapid postoperative recovery is essential to assess neurologic function. Remifentanil, an ultra-short-acting mu-opioid receptor agonist, may be the ideal agent to confer the above characteristics. In this prospective randomized study, we compared the hemodynamic stability, recovery characteristics, and the dose of propofol required for maintaining anesthesia supplemented with an infusion of remifentanil, alfentanil, or fentanyl in 34 patients scheduled for supratentorial craniotomy. With routine monitors in place, anesthesia was induced with propofol (2-3 mg/kg), atracurium (0.5 mg/kg), and either remifentanil (1 microg/kg), alfentanil (10 microg/kg), or fentanyl (2 micro/kg). The lungs were ventilated with O2/air to mild hypocapnia. Anesthesia was maintained with infusions of propofol (50-100 microg/kg/min) and either remifentanil (0.2 microg/kg/min), alfentanil (20 microg/kg/h), or fentanyl (2 microg/kg/h). There were no significant differences among the groups in the dose of propofol maintenance required, heart rate, or mean arterial pressure. However, the time to eye opening (minutes) was significantly shorter in the remifentanil compared to the alfentanil group (6+/-3; 21+/-14; P = 0.0027) but not the fentanyl group (15+/-9). We conclude that remifentanil is an appropriate opioid to use in combination with propofol during anesthesia for supratentorial craniotomy.

Non-invasive cerebral perfusion pressure (nCPP): evaluation of the monitoring methodology in head injured patients.

The method of direct calculation of cerebral perfusion pressure (CPP) as the difference between mean arterial pressure and intracranial pressure (ICP) produces a number, which not always adequately expresses brain perfusion. We investigated an alternative non-invasive method, based on waveform analysis of Transcranial Doppler blood flow velocity in Middle Cerebral Arteries (MCA). 25 consecutive head injured patients, paralysed, sedated and ventilated were studied. Intracranial pressure (ICP) arterial blood pressure (ABP) were monitored continuously. The left and right MCAs were insonated daily (116 measurements) using a purpose-built transcranial Doppler monitor (Deltex Ltd, Chichester, U.K.) with software capable of the non-invasive estimation of CPP. Time averaged values of ABP, mean and diastolic flow velocities (FVm, FVd) were calculated and CPPe was computed as: ABP*FVd/FVm + 14. An absolute difference between real CPP and CPPe was less than 10 mm Hg in 82% of measurements and less than 13 mm Hg in 90% of measurements. The method demonstrated a high potential to detect both short-term and long-term changes in CPP. The method is of potential benefit for the intermittent measurement and continuous monitoring of changes in brain perfusion pressure in situations where the direct measurement of CPP is not available or its reliability is in question.

Continuous assessment of cerebral autoregulation--clinical verification of the method in head injured patients.

Previously, using transcranial Doppler ultrasonography, we investigated whether the hemodynamic response to spontaneous variations in cerebral perfusion pressure (CPP) provides reliable information about cerebral autoregulatory reserve. In the present study we have verified this method in 166 patients after head trauma. Waveforms of intracranial pressure (ICP), arterial pressure and transcranial Doppler flow velocity (FV) were captured daily over 0.5-2.0 hour periods. Time-averaged mean flow velocity (FV) and CPP were resolved. The correlation coefficient indices between FV and CPP (Mx) were calculated over 3 minutes epochs, and averaged for each investigation. An index of CBF (flow velocity diastolic to mean ratio) was calculated independently for each investigation. Mx depended on CPP (p < 0.0001) increasing to positive values when CPP decreased below 60 mm Hg. This threshold coincided with an averaged breakpoint for autoregulation, expressed by the index of CBF. Mx depended on outcome following head injury stronger than the Glasgow Coma Score on admission (ANOVA, F values 18 and 15 respectively; N = 166). In patients who died, cerebral autoregulation was disturbed during the first two days following injury. These results indicate an important role for the continuous monitoring of autoregulation following head trauma.

Direct cerebral vasodilatory effects of sevoflurane and isoflurane.

BACKGROUND: The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram. METHODS: Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 micro/g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels. RESULTS: Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4+/-3 and 17+/-3% at 0.5 and 1.5 MAC sevoflurane; 19+/-3 and 72+/-9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P<0.05). All patients required phenylephrine (100-300 microg) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia. CONCLUSIONS: In common with other volatile anesthetic agents, sevoflurane has an intrinsic dose-dependent cerebral vasodilatory effect. However, this effect is less than that of isoflurane.

Critical closing pressure in cerebrovascular circulation.

OBJECTIVE: Cerebral critical closing pressure (CCP) has been defined as an arterial pressure threshold below which arterial vessels collapse. Hypothetically this is equal to intracranial pressure (ICP) plus the contribution from the active tone of cerebral arterial smooth muscle. The correlation of CCP with ICP, cerebral autoregulation, and other clinical and haemodynamic modalities in patients with head injury was evaluated. METHOD: intracranial pressure, arterial blood pressure (ABP) and middle cerebral artery blood flow velocity were recorded daily in ventilated patients. Waveforms were processed to calculate CCP, the transcranial Doppler-derived cerebral autoregulation index (Mx), mean arterial pressure (ABP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). RESULTS: Critical closing pressure reflected the time related changes in ICP during plateau and B waves. Overall correlation between CCP and ICP was mild but significant (R=0.41; p<0.0002). The mean difference between ABP and CCP correlated with CPP (R=0.57, 95% confidence interval (95% CI) for prediction 25 mm Hg). The difference between CCP and ICP, described previously as proportional to arterial wall tension, correlated with the index of cerebral autoregulation Mx (p<0.0002) and CPP (p<0.0001). However, by contrast with the Mx index, CCP-ICP was not significantly correlated with outcome after head injury. CONCLUSION: Critical closing pressure, although sensitive to variations in ICP and CPP, cannot be used as an accurate estimator of these modalities with acceptable confidence intervals. The difference CCP-ICP significantly correlates with cerebral autoregulation, but it lacks the power to predict outcome after head injury.

Dynamic cerebral autoregulation during sevoflurane anesthesia: a comparison with isoflurane.

UNLABELLED: We investigated dynamic cerebral pressure autoregulation awake and during 1.5 minimum alveolar anesthetic concentration (MAC) sevoflurane or isoflurane anesthesia in 16 patients undergoing nonintracranial neurosurgical procedures. All patients received a standardized anesthetic, and their lungs were ventilated with 1.5 MAC volatile anesthetic in 100% oxygen to normocapnia. Routine monitors included electrocardiogram, pulse oximetry, end-tidal capnography, and continuous noninvasive blood pressure. In addition, middle cerebral artery blood velocity (Vmca) was measured continuously using transcranial Doppler ultrasonography. Dynamic cerebral autoregulation was tested by inducing a rapid transient decrease in mean arterial pressure by deflation of large thigh cuffs, which were placed around both thighs and inflated to 100 mm Hg above systolic pressure. The Vmca response to the decrease in blood pressure was fitted to a series of curves to determine the rate of dynamic cerebral autoregulation (dRoR). Awake dRoR values were similar in the isoflurane and sevoflurane groups, 32 +/- 2%/s and 29 +/- 2%/s, respectively. dRoR decreased to 5 +/- 1%/s during isoflurane anesthesia but to only 24 +/- 2%/s during sevoflurane anesthesia. We conclude that dynamic cerebral autoregulation is better preserved during sevoflurane than isoflurane anesthesia in humans. IMPLICATIONS: We investigated the effect of sevoflurane and isoflurane on dynamic cerebral pressure autoregulation using transcranial Doppler ultrasonography. At 1.5 minimum alveolar anesthetic concentration, dynamic autoregulation was better preserved during sevoflurane than isoflurane anesthesia.