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Biomedical subjects

P J Kirkpatrick

Publications and source records attributed to P J Kirkpatrick.

At least 37 records · Page 2Linked to original sources
PubMed2002

Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography.

BACKGROUND: Atherosclerotic plaque rupture is usually a consequence of inflammatory cell activity within the plaque. Current imaging techniques provide anatomic data but no indication of plaque inflammation. The glucose analogue [18F]-fluorodeoxyglucose (18FDG) can be used to image inflammatory cell activity non-invasively by PET. In this study we tested whether 18FDG-PET imaging can identify inflammation within carotid artery atherosclerotic plaques. METHODS AND RESULTS: Eight patients with symptomatic carotid atherosclerosis were imaged using 18FDG-PET and co-registered CT. Symptomatic carotid plaques were visible in 18FDG-PET images acquired 3 hours post-18FDG injection. The estimated net 18FDG accumulation rate (plaque/integral plasma) in symptomatic lesions was 27% higher than in contralateral asymptomatic lesions. There was no measurable 18FDG uptake into normal carotid arteries. Autoradiography of excised plaques confirmed accumulation of deoxyglucose in macrophage-rich areas of the plaque. CONCLUSIONS: This study demonstrates that atherosclerotic plaque inflammation can be imaged with 18FDG-PET, and that symptomatic, unstable plaques accumulate more 18FDG than asymptomatic lesions.

Aged↗
PubMed2002

Multi-modal monitoring of acute brain injury.

OBJECTIVE: To review the scientific basis for and utility of the traditional cerebral monitors used currently in neurointensive care, together with research techniques that are soon likely to become used in managing severe head injury and subarachnoid haemorrhage. DESIGN AND CONTENT: Firstly, the pathophysiology of acute brain injury including cerebral haemodynamics, oxygen and metabolism and the role of secondary insults are discussed. Secondly, the importance of assessment of cerebrovascular autoregulation and reactivity is reviewed together with methods for its continuous non-invasive measurement using transcranial Doppler and intracranial pressure/arterial pressure recordings. Thirdly, the respective roles of jugular venous oxygen and brain tissue oxygen monitoring are analysed. Fourthly, the use of cerebral microdialysis is described, together with an overview of its utility. CONCLUSION: Cerebral multimodal monitoring can be helpful for the optimal management of acute brain injury and essential for future exploratory trials of neuroprotective drugs.

Acute Disease↗
PubMed2002

Effects of variation in cerebral haemodynamics during aneurysm surgery on brain tissue oxygen and metabolism.

OBJECTIVES: This study explores the sensitivities of multiparameter tissue gas sensors and microdialysis to variations in blood pressure, CSF drainage and to well-defined periods of ischaemia accompanying aneurysm surgery, and their predictive value for infarction. METHODS: A Neurotrend sensor [brain tissue partial pressure of oxygen (PBO2), carbon dioxide (PBCO2), brain pH (pHB) and temperature] and microdialysis catheter were inserted into the appropriate vascular territory prior to craniotomy. RESULTS: Baseline data showed a clear correlation between PBO2 and mean arterial pressure (MAP) below a threshold of 80 mmHg. PBO2 improved with CSF drainage in 20 out of 28 (Wilcoxon: P < 0.05) cases where data was available. In 26 patients the effects of temporary vascular clipping (TC) (mean duration 16 minutes) were assessed. 2 patients subsequently declared infarction in the region of the probes. PBO2 fell from a mean 3.2 (95% CI 2.4-4.1) kPa to a minimum of 1.5 (95% CI 1.0-2.0) kPa in the non-infarct group. There was a lower baseline PBO2 (mean 0.8 kPa) in the patients who infarcted. PBCO2 mirrored PBO2 changes, whereas pHB did not change significantly in either group. Microdialysis changes associated with decreased PBO2 included a delayed increase in lactate, a raised lactate/pyruvate ratio and more rarely an increased glutamate. These changes were seen in 11 patients but were not predictive of infarction. CONCLUSION: Hypotension during aneurysm surgery is associated with a low PBO2. Multiparameter sensors can be sensitive to acute ischaemia. Microdialysis shows potential in the detection of metabolic changes during tissue hypoxia.

Adult↗
PubMed2002

Clinical cerebral microdialysis--determining the true extracellular concentration.

Current monitoring of the cerebral extracellular chemistry of neurosurgical patients using microdialysis does not provide the true extracellular concentration because full equilibration across the membrane is not achieved. By varying the flow rate and extrapolating to zero flow, the relative recovery i.e. the concentration of the substance in the microdialysate as a proportion of the true concentration in the extracellular space may be calculated. The disadvantage of this method is that it depends on the underlying baseline chemistry being constant during measurements for the calculations, which is not the case in the changing environment of a neuro-intensive unit. We have therefore designed a modification of the extrapolation to zero flow method using an adjacent constant flow rate catheter to monitor the baseline. The results demonstrate that the relative recovery varies considerably with flow rate, and for the CMA70 10 mm membrane catheter, is approximately 70% at a rate of 0.3 microliter/min and 30% at a rate of 1.0 microliter/min for glucose, lactate, pyruvate and glutamate.

Biomarkers↗
PubMed2002

Extracellular lactate/pyruvate and glutamate changes in patients during per-operative episodes of cerebral ischaemia.

OBJECTIVE: Temporary Internal Carotid Artery (ICA) clipping necessary during aneurysm surgery was used as a model to investigate metabolic changes in the human brain during defined episodes of ischaemia. DESIGN: An observational study using intracerebral monitors: PBO2 (Neurotrend) and microdialysis (CMA, Sweden). SUBJECTS: 16 patients monitored during complex aneurysm surgery. OUTCOME MEASURES: Changes in extracellular concentrations of glucose, lactate, and glutamate and lactate/pyruvate ratio (L/P). RESULTS: Mean age was 55. 10 patients presented with subarachnoid haemorrhage and 6 with mass effect (4 giant). Temporary ICA occlusion was required for dissection (n = 9), intraoperative rupture (n = 5) or aneurysmal thrombectomy (n = 2). The mean total duration was 15 minutes (range 4-52 minutes). No infarcts developed in the monitored regions. Microdialysis was unsuccessful in 3 patients and Neurotrend in 1. Patients were grouped according to the degree and duration of fall in PBO2: minimal brief falls were not associated with microdialysis changes (n = 5). More pronounced falls were associated with increases in L/P (n = 4). Only prolonged occlusions averaging 42 minutes (n = 3) with PBO2 sustained below 1 kPa were associated with rises in glutamate. CONCLUSIONS: Brief temporary ICA occlusion caused an initial increased L/P. Glutamate increases were only seen after occlusion that was prolonged with PBO2 below 1.0 kPa.

Adult↗
PubMed2002

Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent.

AIMS: Promising pre-clinical results from laboratory studies of neuro-protective drugs for the treatment of patients with stroke and head injury have not been translated into benefit during clinical trials. The objective of the study was to assess the feasibility of administrating a potential neuro-protective drug (chlormethiazole) in conjunction with multimodality monitoring (including microdialysis) to patients with severe head injury in order to determine the effect of the agent on surrogate endpoints and penetration into the brain. METHODS: Multimodality monitoring including cerebral and peripheral microdialysis was applied to five head-injured patients on the neuro-intensive care unit. Chlormethiazole (0.8%) was administered as a rapid (10 ml min(-1)) intravenous loading infusion for 5 min followed by a slow (1 ml min(-1)) continuous infusion for 60 min. The following parameters were monitored: heart rate, mean arterial blood pressure, intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, continuous arterial oxygen partial pressure, arterial carbon dioxide partial pressure, arterial pH, arterial temperature, cerebral tissue oxygen pressure, cerebral tissue carbon dioxide pressure, cerebral pH, cerebral temperature, electroencephalograph (EEG), bi-spectral index, plasma glucose, plasma chlormethiazole, and cerebral and peripheral microdialysis assay for chlormethiazole, glucose, lactate, pyruvate and amino acids. RESULTS: Despite achieving adequate plasma concentrations, chlormethiazole was not detected in the peripheral or cerebral microdialysis samples. The drug was well tolerated and did not induce hypotension, hyperglycaemia or withdrawal seizures. The drug did not change the values of the physiological or chemical parameters including levels of GABA, lactate/pyruvate ratio and glutamate. The drug did, however, induce EEG changes, including burst suppression in two patients. CONCLUSIONS: Chlormethiazole can be safely given to ventilated patients with severe head injury. There was no evidence of hypotension or withdrawal seizures. Combining a pilot clinical study of a neuro-protective agent with multimodality monitoring is feasible and, despite the lack of effect on physiological and chemical parameters in this study, may be a useful adjunct to the development of neuro-protective drugs in the future. Further investigation of the capability of microdialysis in this setting is required. By investigating the effect of a drug on surrogate end-points, it may be possible to identify promising agents from small pilot clinical studies before embarking on large phase III clinical trials.

Adult↗
PubMed2002

How can we measure substrate, metabolite and neurotransmitter concentrations in the human brain?

Cerebral injury and disease is associated with fundamental derangements in metabolism, with changes in the concentration of important substrates (e.g. glucose), metabolites (e.g. lactate) and neurotransmitters (e.g. glutamate and y-aminobutyric acid) in addition to changes in oxygen utilization. The ability to measure these substances in the human brain is increasing our understanding of the pathophysiology of trauma, stroke, epilepsy and tumours. There are several techniques in clinical practice already in use and new methods are under evaluation. Such techniques include the use of cerebral probes (e.g. microdialysis. voltammetry and spectrophotometry) and functional imaging (e.g. positron emission tomography and magnetic resonance spectroscopy). This review describes these techniques in terms of their principles and clinical applications.

Brain↗
PubMed2002

Effect of hypothermia on brain tissue oxygenation in patients with severe head injury.

BACKGROUND: There is renewed interest in the use of induced hypothermia as a method of neuroprotection both intraoperatively and in the intensive care management of severe brain injury. In this study we have investigated the effects of hypothermia on brain tissue oxygenation in patients with severe head injury. METHODS: Thirty patients with severe head injury (Glasgow coma score <8) were monitored with a multimodal sensor inserted into the brain which measures tissue PO2, PCO2, pH and temperature in addition to routine monitoring. Patients were cooled to a minimum of 33 degrees C when clinically indicated. RESULTS: For all 30 patients brain and systemic temperature correlated well (r=0.96). Brain temperature was consistently higher than systemic temperature by 0.41 +/- 0.26 degrees C (confidence limits). Brain tissue PO2 decreased with hypothermia, with a significant reduction below 35 degrees C (P<0.05). CONCLUSIONS: These results emphasize the advantage of measuring brain temperature directly, and suggest that decreasing brain temperature below 35 degrees C may impair brain tissue oxygenation.

Adolescent↗
PubMed2002

Increases in GABA concentrations during cerebral ischaemia: a microdialysis study of extracellular amino acids.

OBJECTIVES: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably gamma-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. METHODS: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. RESULTS: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found (r=0.71, p<0.005). CONCLUSIONS: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.

Adolescent↗
PubMed2002

Timing of surgery for supratentorial aneurysmal subarachnoid haemorrhage: report of a prospective study.

OBJECTIVES: The debate on the timing of aneurysm surgery after subarachnoid haemorrhage (SAH) pivots on the balance of the temporal risk for fatal rebleeding versus the risk of surgical morbidity when operating early on an acutely injured brain. By following a strict management protocol for SAH, the hypothesis has been tested that in the modern arena of treatment for aneurysmal SAH the timing of surgery to secure supratentorial aneurysms does not affect surgical outcome. METHODS: Over a 6 year period, patients admitted with a diagnosis of SAH to a regional neurosurgical unit have been prospectively studied. All have been on a management protocol in which early transfer and resuscitation has been followed regardless of age and clinical condition. Angiographic investigation and surgery have been pursued in those who have been able to at least flex to pain. A total of 1168 patients (60.7% female, mean age 54.3) with proved SAH were received on median day 1 (86.4% arrived within 3 days) of the ictus. Of these, 784 (67.1%) showed aneurysms on angiography and were prepared for surgery. Those who received surgery for a supratentorial aneurysm within 21 days of the ictus were included in the final analysis (n=550). Patients with an initial negative angiogram, with posterior circulation aneurysms, or aneurysms treated by endovascular means, with aneurysms requiring emergency surgery for space occupying haematomas, with aneurysms which re-bled before surgery, and those who received very late surgery (after 21 days from ictus) were excluded. Surgical outcomes at hospital discharge and after 6 months were assessed using the Glasgow outcome score (GOS). Discharge destination and duration of stay in a neurosurgical ward were also documented. The influence of the timing of surgery (early group day 1-3 postictus, intermediate group day 4-10, or late group day 11-21) was analysed prospectively. RESULTS: 60.2% of cases fell into the early surgery group, 32.4% into the intermediate group, and 7.5% into the late operated group. Late surgery was due to delays in diagnosis, transfer, and logistic factors, but not clinical decision. The demographic characteristics, site of aneurysm, and clinical condition of the patients at the time of initial medical assessment were balanced in the three surgical timing groups. There was no significant difference in GOS between the surgical timing groups at 6 months (favourable GOS score 4 and 5: 83.2%, 80.5%, and 83.8% respectively; p=0.47, Kruskal-Wallis test). Outcome was favourable in 84% of patients under 65 years, and 70% in those over 65. The discharge destinations (home, referring hospital, nursing home, rehabilitation centre) showed no significant difference between surgical timing groups. There was no significant difference in mean time to discharge after admission to this hospital from the referring hospital (16.2, 16.2, and 14.6 days for early, intermediate, and late groups respectively; p=0.789, Analysis of variance (ANOVA)). As a result, there was reduction in the mean duration of total hospital inpatient stay in favour of the earliest operated patients (mean time 18.1, 22.0, and 28.3 days respectively; p=0.001. ANOVA showed that besides age, the only determinant of surgical outcome and duration of stay was presenting clinical grade (p<0.0005). CONCLUSION: The current management of patients presenting with SAH from anterior circulation aneurysms allows early surgery to be followed safely regardless of age. The only independent variables affecting outcome are age and clinical grade at presentation. The timing of surgery did not significantly affect surgical outcome, promoting a policy for early surgery that avoids the known risks of rebleeding and reduces inpatient stay.

Adolescent↗
PubMed2001

Timing of surgery for aneurysmal subarachnoid haemorrhage.

BACKGROUND: The timing of surgery to secure a ruptured aneurysm after a subarachnoid haemorrhage is an important issue. Early clipping of an aneurysm prevents rebleeding, a major cause of death after a subarachnoid haemorrhage. However, concerns about the possible deleterious effects of early surgery raise questions about the safety and efficacy of this approach. This review examines the randomised controlled evidence addressing the effect of surgery at different time intervals on the outcome after a subarachnoid haemorrhage. OBJECTIVES: To determine whether the timing of surgery after a subarachnoid haemorrhage significantly influences overall management outcome. SEARCH STRATEGY: We searched the Cochrane Stroke Review Group Trials Register and in addition searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register (CENTRAL/CCTR). Colleagues were contacted to identify further studies and unpublished trials. SELECTION CRITERIA: All completed, unconfounded, truly randomised trials comparing "best medical treatment plus early surgery" with "best medical treatment plus delayed surgery". DATA COLLECTION AND ANALYSIS: The authors selected trials for inclusion, or exclusion, according to the above criteria. An "intention to treat" analysis strategy was utilised. MAIN RESULTS: Only one randomised controlled trial addressing the timing of surgery after aneurysmal subarachnoid haemorrhage was identified. Patients undergoing early surgery tended to fare better than those undergoing late surgery (death or dependency at 3 months OR 0.37 95% CI 0.13,1.02). Patients undergoing surgery in the intermediate time period appeared to fare worse than those undergoing early surgery although confidence intervals were wide (death or dependency at 3 months OR 0.34 95% CI 0.12, 0.93). REVIEWER'S CONCLUSIONS: Based upon the limited randomised controlled evidence available, the timing of surgery was not a critical factor in determining outcome following a subarachnoid haemorrhage. Since the publication of the only randomised controlled study in 1989, techniques for the treatment of subarachnoid haemorrhage have progressed, questioning the validity of the conclusions in the modern era. Currently, most neurovascular surgeons elect to operate within 3 or 4 days of the bleed in good grade patients to minimise the chances of a devastating rebleed. However, the treatment of patients in poorer grades warrants further scrutiny in a randomised controlled trial.

Humans↗
PubMed2001

Bifrontal decompressive craniectomy in the management of posttraumatic intracranial hypertension.

Bifrontal decompressive craniectomy has been used on an ad hoc basis for the treatment of post-traumatic intracranial hypertension for more than thirty years. In this observational study we report the clinical outcome and physiological effects of the procedure in a series of 26 patients with refractory intracranial hypertension treated on a protocol driven basis. Bifrontal decompressive craniectomy was associated with significant reductions in mean ICP from 37.5 to 18.1 mmHg (p = 0.003). In addition, craniectomy reduced the amplitude of ICP waves (p < 0.02) and increased compensatory reserve (p < 0.05). A favourable outcome was achieved in 69% of patients; 8% were severely disabled and 23% died. We conclude that this study provides pathophysiological evidence that bifrontal decompressive craniectomy significantly reduces posttraumatic intracranial hypertension and improves pressure dynamics. Our results support the continued use of bifrontal decompressive craniectomy in selected patients after head injury.

Adolescent↗
PubMed2001

Carotid artery disease: should angioplasty be considered an alternative to open carotid surgery?

The importance of treating symptomatic high-grade stenosis of the carotid artery is now widely acknowledged. The criteria for nonmedical treatment is continually refined by taking into account the patient's symptoms, age, gender, family history, and treatment-related risk factors. Such refinements have realized importance because the small benefit of invasive treatment can be negated by treatment complications. Improvements in medical treatments such as novel antiplatelet agents, antioxidant, and statin therapy, will ensure that the gain from invasive methods will be further reduced. Surgical (open) carotid endarterectomy (CEA) is the gold standard treatment for high-risk lesions, because it achieves the crucial goal of excising the culprit atheroma, thus providing treatment durability. However, this treatment is highly dependent on surgical standards, and therefore, it may not be beneficial in all centers. In carotid angioplasty (CAP), the atheroma is distended with an endovascular balloon. Because the atheroma is not removed, but the pathologic process is altered, durability cannot be assumed and restenosis remains a significant possibility. In this article, the areas of concern for CEA and CAP will be compared and contrasted. I will address the standards of care used when treating patients with carotid artery disease, and discuss the procedure that should be followed when introducing new treatment options.

Angioplasty, Balloon↗