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Biomedical subjects

P J Kirkpatrick

Publications and source records attributed to P J Kirkpatrick.

At least 91 records · Page 5Linked to original sources

Non-invasive measurement of cerebral blood volume in volunteers.

Invasive techniques are used for conventional measurements of cerebral blood volume and there is a need for methods which are more readily applicable clinically. We studied 13 healthy volunteers using near infrared spectroscopy and transcranial Doppler sonography. Middle cerebral artery flow velocity (vmca) and changes in cerebral oxygenated haemoglobin (HbO2), deoxygenated Hb (Hb), HbO2 - Hb (Hbdiff) [corrected] and HbO2 + Hb (total haemoglobin; Hbt) were measured at baseline and during graded reduction in arterial oxygen saturation (Spo2) to 85% at hypo-, normo- and hypercapnia. Cerebral blood volume (CBV) values, calculated from regression lines of Hbdiff/SpO2 and HbO2/SpO2 were 5.38 and 4.03 ml 100 g-1 for the two methods, respectively. CBV varied directly with FE'CO2, with mean CBV reactivities of 1.25 and 1.06 ml 100 g-1 kPa-1, respectively. Changes in Hbt were not systematically related to changes in FE'CO2. An increase in vmca and reciprocal decrease in estimated cerebrovascular resistance were observed when oxygen saturation decreased to less than 90-93%. These results suggest that cerebral haemodynamics in individual subjects may be monitored non-invasively providing the methodology is modified to account for hypoxic vasodilatation.

Adult↗

Internal and external carotid contributions to near-infrared spectroscopy during carotid endarterectomy.

BACKGROUND AND PURPOSE: The internal carotid (ICA) and external carotid (ECA) contributions to changing concentrations of oxyhemoglobin (Hbo2) and deoxyhemoglobin (Hb) during carotid endarterectomy were assessed with the use of near-infrared spectroscopy (NIRS). METHODS: NIRS optodes were placed on the forehead with an interoptode distance of 6 cm, and laser-Doppler flowmetry (LDF) was used to monitor the change in skin blood flow between the optodes. Hb, Hbo2, LDF, arterial blood pressure, and middle cerebral artery flow velocity were recorded continuously. The ECA was clamped 2 minutes before the ICA was clamped. Suitable multimodal recordings were achieved in 44 patients. RESULTS: When the ECA was clamped, 76% of patients showed a fall in Hbo2 and 65% an increase in Hb. When corrected for changes in arterial blood pressure, an accompanying fall in cutaneous LDF predicted the fall in Hbo2 with high sensitivity (100%) and specificity (100%). Among those with no NIRS changes during ECA clamping, 56% had severe ECA stenosis or occlusion; none of these showed an accompanying fall in LDF. In contrast, when the ICA was clamped, substantial additional changes in NIRS occurred in 55% of cases, all of which were associated with a fall in flow velocity, but none with a change in LDF. Patients with a constant flow velocity after ICA clamping also showed no change in NIRS. CONCLUSIONS: Both the ECA and ICA vascular territories contribute to NIRS changes during carotid endarterectomy. The external carotid contribution to NIRS can be monitored with cutaneous LDF.

Aged↗

A feedback-controlled pump produces stable hypotension in anaesthetised rabbits.

A method is described for the reliable production of controlled hypotension in experimental animals. Reduction in arterial blood pressure was obtained in rabbits by withdrawing arterial blood using a computer-driven pump operating within a feedback control system. Arterial blood pressure, blood flow velocity in the basilar artery (measured using transcranial Doppler), and anterior cortical microcirculation (measured using laser Doppler) were monitored. The aim of the experiments was to compare stability of hypotension produced using arterial blood pressure or basilar flow velocity as feedback control variables. Basilar artery flow velocity provided the most stable profound hypotension and during reinfusion when animals were not autoregulating. However, arterial blood pressure provided the most accurate stepwise control in autoregulating animals.

Anesthesia↗

Early effects of mannitol in patients with head injuries assessed using bedside multimodality monitoring.

OBJECTIVE: We have employed bedside multimodality methods to assess the influence of a slow (20 min) bolus of hypertonic mannitol on cerebral hemodynamics in comatose patients with head injuries. METHODS: Middle cerebral artery flow velocities (FV) and cortical microcirculatory flows were measured in comatose patients with head injuries after the administration of 200 ml of 20% mannitol. A comparison was made with the effects of an identical bolus of isotonic saline. Fourteen patients with diffuse head injuries and with raised intracranial pressure were selected, and mannitol infusion studies were conducted when clinically indicated (n = 23). Using transcranial doppler and laser doppler flowmetry (LDF), indices of estimated cerebrovascular resistance (eCVR) were calculated for the macro- (eCVR-FV) and micro- (eCVR-LDF) circulation. RESULTS: During mannitol infusion, a significant rise in cerebral perfusion pressure was detected (+10%, P = 0.03) as a result of a fall in intracranial pressure (-21%, P = 0.001). Increases in both FV (+13%, P < 0.001) and LDF (+14%, P = 0.002) occurred only after the administration of mannitol and persisted beyond completion of infusion. The effect on FV and LDF decayed exponentially, with a time constant of 34.0 and 38.0 minutes, respectively, and was independent of the pressure autoregulatory status. There was a tendency for eCVR-FV and eCVR-LDF to decrease. No significant effects resulted from the administration of saline. CONCLUSION: Bedside multimodality monitoring may provide a useful means for assessing the effects of therapy in the comatose patient. The mechanisms by which mannitol reduces intracranial pressure in patients with head injuries are discussed.

Blood Flow Velocity↗

An audit of aneurysmal subarachnoid haemorrhage: earlier resuscitation and surgery reduces inpatient stay and deaths from rebleeding.

OBJECTIVE: To audit the outcome in patients with subarachnoid haemorrhage (SAH) after a change in management strategy. METHODS: A retrospective analysis of patients with aneurysmal subarachnoid haemorrhage over a 20 month period (phase 1) was followed by a prospective analysis of patients presenting during the next 20 months (phase 2) in which a protocol driven management regime of immediate intravenous fluid resuscitation and earlier surgery was pursued. Patients in this phase were grouped into those receiving early (within four days of subarachnoid haemorrhage) and late (after four days of subarachnoid haemorrhage) surgery. In phase 1, 75 out of a total of 92 patients underwent surgery on (median) day 12. From phase 2, 109 patients out of a total of 129 underwent surgery on (median) day 4, 58 of which had their surgery within 4 days of the subarachnoid haemorrhage. Patients in each phase/group were well matched for demographic features, site of aneurysm, and severity of subarachnoid haemorrhage. RESULTS: The surgical morbidity and mortality were no different in the two phases (P < 0.92; chi2 test). The management outcomes in the two phases of the study were also no different (P < 0.52). However, there was a significant reduction in the rebleed rate in patients undergoing surgery within four days of the subarachnoid haemorrhage in phase 2 (P < 0.0001) with an associated trend towards reduced incidence of postoperative ischaemia (P = 0.06) and mortality (P = 0.11). Operating earlier in phase 2 of the trial resulted in a lower total hospital inpatient stay of 15.8 (95% CI 13.1-18.5) days for survivors compared with 25.7 (95% CI 21.6-29.8) days in the late group (P < 0.00001; t test). CONCLUSIONS: surgical morbidity and mortality seemed independent of the timing of aneurysm surgery. Early surgery within four days was associated with a highly significant reduction in rebleed rate, and in the duration of total hospital inpatient stay.

Adult↗

Plasma antioxidant consumption associated with ischemia/reperfusion during carotid endarterectomy.

BACKGROUND AND PURPOSE: Thirteen patients undergoing carotid endarterectomy were studied to correlate changes in jugular bulb venous oxygen saturation (SjO2) with indices of free radical production during cerebral ischemia/reperfusion. Levels of oxidant species were also monitored in arterial samples to determine any change across the cerebral circulation. METHODS: Blood was sampled from a venous catheter inserted in the ipsilateral jugular bulb and from an arterial catheter. Co-oximetry measurements were made to determine jugular bulb venous oxygenation saturation. To monitor changes in oxidant stress, a colorimetric assay was used to determine plasma antioxidant potential, and electron paramagnetic resonance spectroscopy was used to quantify free radical-spin trap adducts formed in a blood sample treated with the spin trap alpha-tert-butyl phenyl nitrone (PBN). RESULTS: SjO2 decreased significantly from 68 +/- 11% to 61 +/- 10% (P < .05) during clamping of the internal carotid artery and returned to baseline (65 +/- 11%) when the carotid clamp was removed. Jugular venous plasma antioxidant potential decreased significantly from 32.76 +/- 5.42% inhibition to 28.02 +/- 6.77% inhibition (P < .05). There was no concomitant change in arterial plasma antioxidant potential values, indicating a decrease in antioxidant capacity across the cerebral circulation. However, analysis of spin trap-free radical adducts did not provide conclusive evidence for free radical production. CONCLUSIONS: These results provide supportive evidence for oxidant production during cerebral ischemia/reperfusion in a clinical setting.

Aged↗

Cortisol, dehydroepiandrosterone (DHEA), and DHEA sulfate in the cerebrospinal fluid of man: relation to blood levels and the effects of age.

The relation between blood and cerebrospinal fluid (CSF) concentrations of cortisol, dehydroepiandrosterone (DHEA), and its sulfate (DHEAS) was measured in 62 subjects aged 3-85 yr old, fitted with ventriculo-peritoneal or lumbar-peritoneal shunts for a variety of diagnoses. There were 36 males and 36 females. Forty-eight subjects were not taking exogenous corticosteroids; the other 14 were receiving either systemic or local steroids. A single sample of blood and CSF was taken from each subject within 10 min for measurement of cortisol, DHEA, and DHEAS. The proportional levels of cortisol (5.8%) and DHEA (5.4%) in the CSF compared with those in the blood were similar in subjects not taking steroids. However, CSF DHEAS levels were only 0.15% of those in the blood. Because DHEAS blood levels were so much greater than DHEA, DHEAS in the CSF was still higher than DHEA despite the reduced penetration of the sulfated steroid. The blood/CSF ratios were similar in subjects taking steroids. There were significant correlations in steroid-free subjects between blood and CSF levels for DHEA (r = 0.65) and DHEAS (r = 0.88) but not for cortisol (r = 0.26). Steroid treatment significantly lowered blood cortisol, DHEA and DHEAS, and CSF DHEA, but not CSF cortisol or DHEAS compared with an age- and sex-matched sample of steroid-free subjects. In steroid-free adults (18 yr and over; n = 37), blood cortisol showed no age-related change. However, CSF cortisol was markedly raised in a proportion of steroid-free subjects over the age of 60 yr. Levels of corticoid-binding globulin in plasma did not alter with age. As expected, there were significant age-related decrements in both blood DHEA and DHEAS. CSF DHEA (r = 0.42) and CSF DHEAS (r = 0.39) were significantly negatively correlated with age. In steroid-free juveniles (n = 11) there were no age-related changes in either blood or CSF cortisol, but significant increases with age in DHEA and DHEAS in both blood and CSF. Calculation of the cortisol/DHEA and cortisol/ DHEAS molar ratios in the CSF showed both to be raised in the very young (3-8 yr) and the elderly (60 yr and over) by a factor of 4-5 compared with young adults aged 18-39. There were no sex differences in any of the parameters measured. These findings show that the relation between levels in the blood and CSF differ for each of these three neuroactive steroids. The brain is exposed to relatively high levels of DHEA and DHEAS during later childhood and early adulthood but to relatively or absolutely high levels of cortisol during infancy and older age. In view of the known antiglucocorticoid action of DHEA and DHEAS, and the direct action of these steroids on membrane-bound transmitter events (such as gamma-aminobutyric acidA receptors), these changes may have important implications for age-related alterations in brain function.

Adolescent↗

Multimodal monitoring and assessment of cerebral haemodynamic reserve after severe head injury.

This article contains an overview of selected clinical techniques employed for neurointensive care monitoring and testing of cerebral autoregulation of patients following severe head injury. Multiple modalities are used for monitoring of cerebral haemodynamic reserve, including intracranial pressure, cerebral perfusion pressure (CPP), blood flow velocity (FV) in the middle cerebral artery (MCA), jugular bulb oxygen saturation, laser-Doppler cortical flowmetry, near infrared spectroscopy of cerebral cortex, tissue oxygenation, and microdialysis. Large volumes of information demand specialised computer support for sensible interpretation and filtration of artifacts. Methods of testing of cerebral autoregulatory reserve based on transcranial Doppler ultrasonography are reviewed. Repetitive or continuous assessment is important in practice as autoregulatory reserve may fluctuate in time. Static and dynamic rates of autoregulation show sensitivity to carbon dioxide-induced vasodilatation, but fail to correlate with outcome following head injury. The carotid artery compression test, useful for assessment of patients after subarachnoid haemorrhage, has yet to prove its usefulness in head injury. Continuous waveform analysis of MCA FV and CPP correlates with coma score after resuscitation and outcome and hence may be considered as a robust method for the assessment of autoregulation in ventilated head trauma patients.

Cerebrovascular Circulation↗

Estimation of laser-Doppler flux biological zero using basilar artery flow velocity in the rabbit.

Laser-Doppler flowmetry has potential for continuous cerebral blood flow (CBF) measurement in man and experimental animals. However, laser-Doppler flux (LDFx) measured when perfusion is absent (the biological zero, 0biol) does not necessarily coincide with the instrument's electrical zero. To evaluate laser-Doppler flowmetry further we have compared LDFx in rabbits with continuous measurement of the maximum flow velocity (FVx) in the basilar artery using Doppler ultrasonography. Arterial blood pressure (ABP), FVx, and LDFx were measured continuously in anesthetized New Zealand White rabbits. ABP was altered by controlled hemorrhage with subsequent reinfusion. 0biol was estimated from regression analysis of FVx vs. LDFx and compared with 0biol obtained after death. There was a strong linear relationship between LDFx and FVx (r = 0.94). The absolute difference between estimated 0biol and true 0biol was 5.24% of control prehemorrhage LDFx. Variations in 0biol (range 4-409) suggest that percent changes in LDFx must be related to 0biol if results between individual animals are to be compared.

Animals↗

An observational study of near-infrared spectroscopy during carotid endarterectomy.

Near-infrared spectroscopy was used to monitor changes in the cerebral oxygenation state in 13 patients during carotid endarterectomy. Variations in the levels of the chromophores (oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and oxidized cytochrome (CytO2)), and the total hemoglobin content (tHb) were compared with changes in middle cerebral artery flow velocity measured using transcranial Doppler ultrasonography. Of eight patients who showed a fall in flow velocity on application of the internal carotid artery cross-clamp, seven demonstrated a rapid and closely correlated fall in HbO2 signal, and an increase in Hb. Levels of CytO2 and tHb remained unchanged. During endarterectomy, recovery of the HbO2 and Hb levels toward preclamp baseline values occurred in three of these patients. Intraoperative shunts accelerated recovery of HbO2 and Hb signals in two of three individuals. Release of the internal carotid cross-clamp resulted in a rapid increase in HbO2 and decrease in Hb signal in those patients in whom spontaneous recovery had not occurred; in five instances, a hyperemia evolved with raised flow velocity and HbO2 to above baseline values. Cross-clamping and subsequent reperfusion of the external carotid artery had no effect on any parameter measured. The authors conclude that near-infrared spectroscopy can register changes in cerebral oxygenation during carotid endarterectomy without significant contamination from extracranial tissues.

Adult↗

Near-infrared spectroscopy use in patients with head injury.

A multimodality recording system was used in 14 ventilated patients with closed head injury to assess the potential use of near-infrared spectroscopy (NIRS) in the neurointensive care unit. Signals of intracranial pressure, cerebral perfusion pressure, peripheral oxygen saturation, jugular venous saturation, and NIRS-derived changes in the chromophores of oxy- and deoxyhemoglobin were digitized and recorded. After a review of 886 hours of continuous monitoring, 376 hours were considered free from artifact and were entered for final analysis. In nine of the patients 38 events were recorded that demonstrated clear changes in cerebral perfusion pressure accompanied by hemodynamic changes in middle cerebral artery flow velocity (transcranial Doppler) and cortical perfusion (laser Doppler flowmetry). Near-infrared spectroscopy showed correlated changes in 37 events (97%) whereas jugular venous saturation monitoring registered only 20 (53%). There was associated peripheral oxygen desaturation in eight cases (21%), intracranial hypertension in 10 (26%), and cerebral hyperemia in eight (21%). The remaining 12 events (32%) appeared to be complex changes of uncertain origin. Iatrogenic factors were identified as causative in 14 cases (37%). The potential application of NIRS in adults and the importance of using multiple parameter recording systems in the interpretation of cerebral events are discussed.

Adolescent↗

Digital imaging of umbelliferone clearance: a method for repeated measurements of cerebral cortical blood flow with high temporal and spatial resolution.

We have developed a procedure for digital imaging of the exposed cerebral cortex during elution of a fluorescent dye. This avoids disturbing the cortex and has provided a method for the repeated estimation of regional CBF (rCBF) with a high topographical resolution. Under varying conditions of MABP and arterial blood gases, grey-level images of the exposed cortex irradiated with ultraviolet light (340 or 370 nm) were digitised (8 bits) at 15-s intervals after the injection of 1-2 ml of saturated umbelliferone solution into the lingual or external carotid artery of anaesthetised cats and rabbits. Specifically designed software allowed (a) regions of interest (ROIs) in the exposed cortex to be defined that were automatically applied to the sequence of images in a selected clearance and (b) solution of the initial slope equation for rCBF from the decay in grey-level fluorescence by exponential regression. Separate software that solved the equation at the level of a single pixel allowed a pseudocolour map of cortical rCBF to be generated. The factors affecting the resolution of this technique have been identified and quantified. Thus consistent and reproducible results were obtained provided that the fluorescence enhancement exceeded 20 grey levels and the r2 coefficient for regression was 90% or above. Mean rCBF values of 99.5 [95% confidence interval (CI), 89.4-110] ml 100 g-1 min-1 were obtained for rabbits (N = 12; mean MABP = 75.2; mean PaCO2 = 32.9; PaO2 = 111.8; pH 7.38) and 65.1 (95% CI, 55.1-75.1) ml 100 g-1 min-1 for cats (N = 8; mean MABP = 92.8; PaCO2 = 31.5; PaO2 = 114.6, pH 7.40).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Continuous monitoring of cortical perfusion by laser Doppler flowmetry in ventilated patients with head injury.

A method for monitoring cortical perfusion by laser Doppler flowmetry (LDF) in the neurointensive care unit is described. Out of 22 patients with head injuries, reliable and long term recordings were obtained in 16. Laser Doppler flowmetry registered changes in cortical microcirculatory flow in response to spontaneous waves of raised intracranial pressure, and to therapeutic manoeuvres that altered the cerebral perfusion pressure. Comparisons of variations in flux signal with cerebral perfusion pressure provided an indication of the autoregulatory state of the cortical microcirculation, and analysis of raw LDF data demonstrated an autoregulatory breakpoint of cerebral perfusion pressure of 58 mm Hg, below which cortical perfusion failed. Although middle cerebral artery flow velocities were generally tightly coupled with LDF signal changes, episodes of uncoupling were seen. The potential uses and limitations of LDF in the neurointensive care setting are discussed.

Adult↗

Trigeminal nerve section for chronic migrainous neuralgia.

We report a series of 14 patients who underwent partial or complete trigeminal nerve root section for chronic unremitting migrainous neuralgia. They had all suffered attacks with severe pain for over 18 months without remission (mean duration 5.5 years). Symptoms were refractory to extended medical intervention and had caused prolonged disruption of lifestyle. The sensory root was completely divided in two cases with complete relief of pain (mean follow-up period 5.6 years). In the other 12 patients, 50-90% of the superomedial portion of the sensory root was divided. Of these, five received no further surgery, and experienced complete (n = 2), near complete (n = 2), or incomplete (n = 1) relief of neuralgia (mean follow-up 5.5 years). The remaining seven patients in the partially divided group were not relieved of pain after operation (n = 5) or suffered early recurrence of pain (n = 2). They showed incomplete sensory loss in the first trigeminal division (V1) and had a second operation to extend the nerve division. V1 anaesthesia was established in all cases after the second procedure, and as a result, four are currently completely free of pain and one has near complete relief of pain. The remaining two patients are still experiencing severe neuralgia (mean follow up 4.1 years). Twelve out of 14 patients (85.7%) receiving surgery for chronic migrainous neuralgia experienced adequate pain relief and are able to follow a normal life (mean follow up 5.6 years). Corneal abrasion was the commonest long-term complication, occurring in three cases (28.5%) and progressing to chronic keratitis in one. We conclude that total trigeminal nerve root section is an effective treatment for patients suffering from chronic migrainous neuralgia and can be safely offered as a primary surgical treatment.

Adult↗