P Kirkpatrick

Cambridge University Hospitals NHS Foundation Trust, Cambridge, England, United Kingdom

Are you P Kirkpatrick?

Claim your profile

Publications (29)127.27 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Prevention of cerebral vasospasm is the target of modern drug therapy, candidates of which include statins. The results of phase 11 studies have shown promise in this arena. STASH is an international multicentre randomised controlled phase 111 trial designed to assess the effects of Simvastatin 40 mg on the long and short term outcome of patients who have suffered from an acute aneurysmal subarachnoid haemorrhage (SAH).
    Neurosurgery 08/2014; 61 Suppl 1:228. · 2.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The extent of hemodynamic disturbances following subarachnoid hemorrhage (SAH) varies. We aim to determine the prognostic implications of unilateral and bilateral autoregulatory failure on delayed cerebral ischemia (DCI) and outcome.
    Neurosurgery 08/2014; 61 Suppl 1:203. · 2.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cerebral vasospasm has traditionally been regarded as an important cause of delayed cerebral ischaemia (DCI) which occurs after aneurysmal subarachnoid haemorrhage, and often leads to cerebral infarction and poor neurological outcome. However, data from recent studies argue against a pure focus on vasospasm as the cause of delayed ischaemic complications. Findings that marked reduction in the incidence of vasospasm does not translate to a reduction in DCI, or better outcomes has intensified research into other possible mechanisms which may promote ischaemic complications. Early brain injury and cell death, blood-brain barrier disruption and initiation of an inflammatory cascade, microvascular spasm, microthrombosis, cortical spreading depolarisations and failure of cerebral autoregulation, have all been implicated in the pathophysiology of DCI. This review summarises the current knowledge about the mechanisms underlying the development of DCI. Furthermore, it aims to describe and categorise the known pharmacological treatment options with respect to the presumed mechanism of action and its role in DCI.
    Journal of neurology, neurosurgery, and psychiatry. 05/2014;
  • Source
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background The benefi t of statins in patients with acute aneurysmal subarachnoid haemorrhage is unclear. We aimed to determine whether simvastatin 40 mg could improve the long-term outcome in patients with this disorder. Methods In this international, multicentre, randomised, double-blind trial, we enrolled patients aged 18–65 years with confi rmatory evidence of an aneurysmal subarachnoid haemorrhage and presenting less than 96 h from ictus from 35 acute neurosurgical centres in nine countries. Patients were randomly allocated (1:1) to receive either simvastatin 40 mg or placebo once a day for up to 21 days. We used a computer-generated randomisation code to randomise patients in every centre by blocks of ten (fi ve simvastatin, fi ve placebo). Participants and investigators were masked to treatment assignment. The primary outcome was the distribution of modifi ed Rankin Scale (mRS) score obtained by questionnaire at 6 months. Analyses were done on the intention-to-treat population. This trial has been completed and is registered with Current Controlled Trials, number ISRCTN75948817. Findings Between Jan 6, 2007, and Feb 1, 2013, apart from the period between May 15, 2009, and Feb 8, 2011, when recruitment was on hold, 803 patients were randomly assigned to receive either simvastatin 40 mg (n=391) or placebo (n=412). All patients were included in the intention-to-treat population. 782 (97%) patients had outcome data recorded at 6 months, of whom 560 (72%) were classed as having a favourable outcome, mRS 0–2 (271 patients in the simvastatin group vs 289 in the placebo group). The primary ordinal analysis of the mRS, adjusted for age and World Federation of Neurological Surgeons grade on admission, gave a common odds ratio (OR) of 0∙97, 95% CI 0∙75–1∙25; p=0∙803. At 6 months, we recorded 37 (10%) deaths in the simvastatin group compared with 35 (9%) in the placebo group (log-rank p=0·592). 70 (18%) serious adverse events were reported in the simvastatin group compared with 74 (18%) in the placebo group. No suspected unexpected serious adverse reactions were reported. Interpretation The STASH trial did not detect any benefi t in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage. Despite demonstrating no safety concerns, we conclude that patients with subarachnoid haemorrhage should not be treated routinely with simvastatin during the acute stages.
    The Lancet Neurology 01/2014; · 23.92 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Backround The extent of hemodynamic disturbances following subarachnoid hemorrhage (SAH) varies. We aim to determine the prognostic implications of unilateral and bilateral autoregulatory failure on delayed cerebral ische-mia (DCI) and outcome. Methods Ninety-eight patients with aneurysmal SAH were recruited. Autoregulation was assessed using systolic flow index—Sxa. Interhemispheric difference in autoreg-ulation was calculated to assess the spatial distribution and symmetry of autoregulatory changes. Assessment of interhemispheric difference in autoregulation in combina-tion with overall autoregulation was used to measure the extent of autoregulatory impairment. Patients were dichotomized by the presence of DCI and 3-month mRS. Results Higher flow velocity and worse autoregulation (p < 0.0000001, 95 % CI 10.7–21.3 and p = 0.00001, 95 % CI 0.03–0.07 for difference in FV and Sxa, respec-tively) were found ipsilateral to the ischemic hemisphere or location of aneurysm (if no ischemia detected). DCI group had a higher interhemispheric difference of autoregulation than non-DCI group (p = 0.035, 95 % CI 0.003–0.08). 16/18 patients with unfavorable outcome vs. 17/72 with favorable outcome had overall poor autoregulation with low interhemispheric differences (p = 0.0013, v 2). Uni-lateral autoregulatory failure was seen on a median day 3, bilateral on day 4, and vasospasm was detected on day 6. Conclusions Unilateral autoregulation failure was seen in patients who developed DCI (worse ipsilateral to the ischemic hemisphere). Bilateral autoregulation failure was seen more frequently in patients with unfavorable outcome. Analysis of the temporal profile showed unilateral dysau-toregulation as the primary event predisposing to DCI, which in selected cases led to bilateral failure and unfa-vorable outcomes.
    Neurocritical Care 01/2014; · 3.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Human brain chemistry is incompletely understood and better methodologies are needed. Traumatic brain injury (TBI) causes metabolic perturbations, one result of which includes increased brain lactate levels. Attention has largely focussed on glycolysis, whereby glucose is converted to pyruvate and lactate, and is proposed to act as an energy source by feeding into neurons' tricarboxylic acid (TCA) cycle, generating ATP. Also reportedly upregulated by TBI is the pentose phosphate pathway (PPP) that does not generate ATP but produces various molecules that are putatively neuroprotective, antioxidant and reparative, in addition to lactate among the end products. We have developed a novel combination of (13)C-labelled cerebral microdialysis both to deliver (13)C-labelled substrates into brains of TBI patients and recover the (13)C-labelled metabolites, with high-resolution (13)C NMR analysis of the microdialysates. This methodology has enabled us to achieve the first direct demonstration in humans that the brain can utilise lactate via the TCA cycle. We are currently using this methodology to make the first direct comparison of glycolysis and the PPP in human brain. In this article, we consider the application of (13)C-labelled cerebral microdialysis for studying brain energy metabolism in patients. We set this methodology within the context of metabolic pathways in the brain, and (13)C research modalities addressing them.
    European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 12/2013; · 2.61 Impact Factor
  • J Nicholas P Higgins, Peter J Kirkpatrick
    British Journal of Neurosurgery 12/2013; 27(6):851. · 0.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background. Recent studies suggest more favourable recovery of oculomotor nerve palsy (ONP) caused by posterior communicating artery (PComA) aneurysms with microsurgical clipping compared to endovascular coiling. We describe a consecutive series of patients with ONP from PComA aneurysms treated by microsurgical clipping or endovascular coiling. Methods. We retrospectively reviewed medical records of all patients from 2005 to 2009 with complete or partial ONP from PComA aneurysms. Results. Twenty patients were identified, three with unruptured aneurysms. Two patients with ruptured aneurysms were unfit for treatment and therefore excluded. Of the 18 patients included (15 female), 9 underwent microsurgical clipping and 9 received endovascular coiling. Patients treated by surgical clipping were significantly younger compared to those treated by endovascular coiling (mean 52.3 vs. 67.9 years; p = 0.039). Five patients had incomplete ONP (3 clipped, 2 coiled) and thirteen had complete ONP. At 6 months, six of nine patients treated with clipping and five of nine patients treated with coiling had complete resolution of their ONP (p = 1.0); the remainder had partial improvement. There was no significant difference in duration of pre-treatment ONP, age, sex or status of aneurysm (ruptured or unruptured) between patients in the two groups or between those with full or partial recovery. However, all 5 patients with incomplete ONP at presentation recovered fully, compared with 6 of 13 patients who presented with complete ONP. Conclusions. We found no significant difference between clipping and coiling in the recovery of ONP due to PComA aneurysms. Patient who present with incomplete ONP are more likely to have a full recovery of ONP following either treatment modality than those who present with complete ONP.
    British Journal of Neurosurgery 11/2013; · 0.86 Impact Factor
  • Source
    Critical Care 01/2011; · 4.93 Impact Factor
  • The Lancet 01/2010; 375(9710):195-6. · 39.06 Impact Factor
  • J K Hollands, T Santarius, P J Kirkpatrick, J N Higgins
    [Show abstract] [Hide abstract]
    ABSTRACT: We report a case of a 34-year-old female with type IV Ehlers-Danlos syndrome diagnosed with a carotid cavernous fistula presenting with progressive proptosis. Endovascular embolization using balloons or coils carries a high risk of complications in this group of patients, owing to the extreme fragility of the blood vessels. Initial treatment was conservative until an intracerebral haemorrhage occurred. To avoid transfemoral angiography, the ipsilateral carotid arteries and the internal jugular vein were surgically exposed for insertion of two endovascular sheaths. The patient was transferred from theatre to the angiography suite and the sheaths were used for embolization access. The fistula was closed, with preservation of the carotid artery, using Guglielmi detachable coils deployed in the cavernous sinus from the arterial and venous sides. Rapid resolution of symptoms and signs followed, which was sustained at 6-month follow-up. This technique offers alternative access for endovascular treatment, which may reduce the high incidence of mortality associated with catheter angiography in this condition.
    Neuroradiology 08/2006; 48(7):491-4. · 2.70 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cerebrovascular vasomotor reactivity reflects changes in smooth muscle tone in the arterial wall in response to changes in transmural pressure or concentration of carbon dioxide in blood. We have investigated whether slow waves in ABP and ICP may be used to derive an index which reflects reactivity of vessels to changes in arterial blood pressure. A method for the continuous monitoring of the association between slow spontaneous waves in ICP and AP has been adopted in a group of 98 head injured patients. ABP, ICP and transcranial Doppler blood flow velocity (FV) in the middle cerebral artery was recorded daily (20 to 120 minutes time periods). A Pressure-Reactivity Index (PRx) was calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and ABP averaged over 5 seconds. A moving correlation coefficient between spontaneous fluctuations of mean FV and CPP (Mx), which was previously reported to describe cerebral blood flow autoregulation, was also calculated. In an additional 25 patients, PRx was calculated and recorded continuously along with mean ICP, ABP and parameters describing ICP waveform. A positive PRx correlated with high ICP (r = 0.366; p < 0.001), low admission GCS (r = 0.29; p < 0.01), and poor outcome at 6 months after injury (r = 0.48; p < 0.00001). During the first two days following injury, PRx was positive (p < 0.05) in patients with unfavourable outcome. The correlation between PRx and Mx (r = 0.63) was highly significant (p < 0.000001). Continuous recordings demonstrated that PRx was able to indicate individual thresholds of vascular reactivity for CPP, ICP, and ventilation parameters. Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.
    Acta neurochirurgica. Supplement 02/1998; 71:74-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to assess Near-infrared spectroscopy (NIRS) as a tool for testing CO2 reactivity in patients with carotid occlusive disease. One hundred sixty patients were examined (age range 44 to 85 years). Monitored parameters included transcranial Doppler flow velocity (FV), changes in concentration of oxy-(HbO2) and deoxy (Hb) haemoglobin, cutaneous Laser Doppler blood flow (LDF), endtidal CO2, ABP, and SaO2. Hypercapnia was induced using a 5% CO2 air mixture for inhalation. To estimate the skin flow contribution to NIRS during reactivity testing, the superficial temporal artery was compressed, and the NIRS changes in response to the fall in LDF recorded. FV and HbO2 derived reactivity values were related to the severity of the stenosis (p = 0.0001 and 0.021 respectively). The correlation between the two modalities was significant (r = 0.47, p < 0.000001). The average estimated skin contribution to NIRS changes was 16.5%. Reproducibility of HbO2-reactivity was similar but worse than FV reactivity (19.1% and 13.8% variation respectively). The clinical correlations improved when our method of correction for skin influence was used. NIRS shows potential as an alternative technique for testing CO2 reactivity in patients with carotid disease provided the conditions are carefully controlled and the contribution from extracranial tissue is taken into account.
    Acta neurochirurgica. Supplement 02/1998; 71:263-5.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cerebral haemodynamic responses to short and longlasting episodes of decreased cerebral perfusion pressure contain information about the state of autoregulation of cerebral blood flow. Mathematical simulation may help to elucidate which of the indices, that can be derived using transcranial Doppler ultrasonography and trends of intracranial pressure and blood pressure, are useful in clinical tests of autoregulatory reserve. Time dependent interactions between pressure, flow, and volume of cerebral blood and CSF were modelled using a set of non-linear differential equations. The model simulates changes in arterial blood inflow and storage, arteriolar and capillary blood flow controlled by cerebral autoregulation, venous blood storage and venous outflow modulated by changes in ICP, and CSF storage and reabsorption. The model was used to simulate patterns of blood flow during either short or longlasting decreases in cerebral perfusion pressure. These simulations can be considered as clinically equivalent to a short compression of the common carotid artery, systemic hypotension, and intracranial hypertension. Simulations were performed in autoregulating and non-autoregulating systems and compared with recordings obtained in patients. After brief compression of the common carotid artery, a subsequent transient hyperaemia can be interpreted as evidence of intact autoregulation. During longlasting sustained hypoperfusion, a gradual increase in the systolic value of the blood flow velocity waveform along with a decrease in the diastolic value is specific for an autoregulating cerebrovascular system. Modelling studies help to interpret both clinical and experimental cerebral haemodynamic phenomena and their dependence on the state of autoregulation.
    Journal of Neurology Neurosurgery &amp Psychiatry 01/1998; 63(6):721-31. · 4.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present a computing system for the recording and on-line analysis of analogue signals derived from bedside cerebrovascular monitors in different pathophysiological conditions. These include arterial blood pressure and oxygen saturation, end-tidal carbon dioxide concentration, cerebral blood flow velocities using transcranial Doppler ultrasonography, and concentration changes in cerebral oxy- and deoxyhaemoglobin from near infrared spectroscopy. Configuration and analysis adopts arithmetic expressions of different signal processing functions, various statistical properties for each signal, frequency spectrum analysis using fast Fourier transformation, and correlation/cross-correlation. The software offers off-line analysis of non-invasive tests of cerebrovascular reactivity. Several examples of clinical assessment of cerebrovascular reactivity are presented, including cerebral haemodynamic stress tests which employ carbon dioxide, acetazolamide, the breath holding test, leg cuff inflation and deflation, and transient carotid artery compression. Application within the experimental setting with induced haemorrhagic hypotension can also be used.
    International Journal of Clinical Monitoring and Computing 09/1997; 14(3):185-98.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cerebrovascular vasomotor reactivity reflects changes in smooth muscle tone in the arterial wall in response to changes in transmural pressure or the concentration of carbon dioxide in blood. We investigated whether slow waves in arterial blood pressure (ABP) and intracranial pressure (ICP) may be used to derive an index that reflects the reactivity of vessels to changes in ABP. A method for the continuous monitoring of the association between slow spontaneous waves in ICP and arterial pressure was adopted in a group of 82 patients with head injuries. ABP, ICP, and transcranial doppler blood flow velocity in the middle cerebral artery was recorded daily (20- to 120-min time periods). A Pressure-Reactivity Index (PRx) was calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and ABP averaged for a period of 5 seconds. A moving correlation coefficient (Mean Index) between spontaneous fluctuations of mean flow velocity and cerebral perfusion pressure, which was previously reported to describe cerebral blood flow autoregulation, was also calculated. A positive PRx correlated with high ICP (r = 0.366; P < 0.001), low admission Glasgow Coma Scale score (r = 0.29; P < 0.01), and poor outcome at 6 months after injury (r = 0.48; P < 0.00001). During the first 2 days after injury, PRx was positive (P < 0.05), although only in patients with unfavorable outcomes. The correlation between PRx and Mean index (r = 0.63) was highly significant (P < 0.000001). Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.
    Neurosurgery 08/1997; 41(1):11-7; discussion 17-9. · 2.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The transient hyperemic response test has been shown to provide an index of cerebral autoregulation in healthy individuals and in patients who have suffered a subarachnoid hemorrhage. In this study, the test was applied to patients who had received a severe head injury, and the value of the test was assessed by comparing its result with the individual's clinical condition (Glasgow Coma Scale [GCS] score), cerebral perfusion pressure (CPP), transcranial Doppler wave form-derived index for cerebral autoregulation (relationship between the CPP and the middle cerebral artery flow velocity), and outcome (Glasgow Outcome Scale [GOS] score). Forty-seven patients, aged 16 to 63 years, with head injuries were included in the study. Signals of intracranial pressure, arterial blood pressure, flow velocity, and cortical microcirculatory flux were digitized and recorded for a period of 30 minutes using special computer software. Two carotid compressions were performed at the beginning of each recording. The transient hyperemic response ratio (THRR: the ratio of the hyperemic flow velocity recorded after carotid release and the precompression baseline flow velocity) was calculated, as was the correlation coefficient Sx used to describe the relationship between slow fluctuations in the systolic flow velocity and CPP throughout the period of recording. No significant changes in CPP were found during compression. There was a significant correlation between the THRR and the Sx (r = 0.49, p < 0.0001). The hyperemic response proved to be lower in patients who exhibited a poor clinical grade at presentation (GCS scores < 6, p = 0.01) and lower in patients achieving a poor outcome (GOS scores of 3, 4, and 5, p = 0.003). Loss of postcompression hyperemia occurred when the CPP fell below 50 mm Hg. The carotid compression test provides a simple index of cerebral autoregulation that is relevant to the clinical condition and outcome of the severely head injured patient.
    Journal of Neurosurgery 05/1997; 86(5):773-8. · 3.15 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Near-infrared spectroscopy (NIRS) derives information about the concentrations of oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) from measurements of light attenuation caused by these chromosphores. The aim of this study was to assess NIRS as a tool for testing CO2 reactivity in patients with carotid artery disease. One hundred patients with symptomatic carotid occlusive disease were examined (age range, 44 to 83 years). The severity of stenosis ranged from 30% to 100% (median, 80%) on the ipsilateral side and 0% to 100% (median, 30%) on the contralateral side. Monitored parameters included transcranial Doppler flow velocity, changes in concentration of HbO2 and Hb, cutaneous laser-Doppler blood flow, endtidal CO2, arterial blood pressure, and arterial oxygen saturation. Hypercapnia was induced with the use of a 5% CO2/air mixture for inhalation. To estimate the contribution of skin flow to NIRS during reactivity testing, the superficial temporal artery was compressed, and the NIRS changes in response to the fall in laser-Doppler blood flow were recorded. Finally, reproducibility of reactivity testing was assessed in 10 patients who were subjected to repeated examinations over 3 days. Flow velocity- and HbO2-derived reactivity values were related to the severity of the stenosis (P = .0001 and P = .017, respectively). The correlation between the two reactivity modalities was significant (r = .49, P < .000001). The median estimated contribution of skin flow to NIRS changes was 15.8%. Another variable affecting HbO2 signal changes during the CO2 challenge was arterial blood pressure (P = .025). Reproducibility of HbO2 reactivity was similar to flow velocity reactivity (14.3% and 18.6% variation, respectively). NIRS shows potential as an alternative technique for testing CO2 reactivity in patients with carotid disease provided that conditions are carefully controlled. Marked changes in arterial blood pressure may render the NIRS reactivity indices unreliable, and the contribution from extracranial tissue must be taken into account when significant.
    Stroke 02/1997; 28(2):331-8. · 6.16 Impact Factor

Publication Stats

798 Citations
127.27 Total Impact Points

Institutions

  • 2014
    • Cambridge University Hospitals NHS Foundation Trust
      Cambridge, England, United Kingdom
  • 1994–2014
    • University of Cambridge
      • • Department of Clinical Neurosciences
      • • Neurosurgery Unit
      Cambridge, England, United Kingdom