Marek Czosnyka

Continuous assessment of the cerebral vasomotor reactivity in head injury.

OBJECTIVE 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. METHODS 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. RESULTS 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). CONCLUSION 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.

Monitoring and interpretation of intracranial pressure

Intracranial pressure (ICP) is derived from cerebral blood and cerebrospinal fluid (CSF) circulatory dynamics and can be affected in the course of many diseases of the central nervous system. Monitoring of ICP requires an invasive transducer, although some attempts have been made to measure it non-invasively. Because of its dynamic nature, instant CSF pressure measurement using the height of a fluid column via lumbar puncture may be misleading. An averaging over 30 minutes should be the minimum, with a period of overnight monitoring in conscious patients providing the optimal standard. Computer-aided recording with online waveform analysis of ICP is very helpful. Although there is no “Class I” evidence, ICP monitoring is useful, if not essential, in head injury, poor grade subarachnoid haemorrhage, stroke, intracerebral haematoma, meningitis, acute liver failure, hydrocephalus, benign intracranial hypertension, craniosynostosis etc. Information which can be derived from ICP and its waveforms includes cerebral perfusion pressure (CPP), regulation of cerebral blood flow and volume, CSF absorption capacity, brain compensatory reserve, and content of vasogenic events. Some of these parameters allow prediction of prognosis of survival following head injury and optimisation of “CPP-guided therapy”. In hydrocephalus CSF dynamic tests aid diagnosis and subsequent monitoring of shunt function.

Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury.

Objectives To define optimal cerebral perfusion pressure (CPPOPT) in individual head-injured patients using continuous monitoring of cerebrovascular pressure reactivity. To test the hypothesis that patients with poor outcome were managed at a cerebral perfusion pressure (CPP) differing more from their CPPOPT than were patients with good outcome. Design Retrospective analysis of prospectively collected data. Setting Neurosciences critical care unit of a university hospital. Patients A total of 114 head-injured patients admitted between January 1997 and August 2000 with continuous monitoring of mean arterial blood pressure (MAP) and intracranial pressure (ICP). Measurements and Main Results MAP, ICP, and CPP were continuously recorded and a pressure reactivity index (PRx) was calculated online. PRx is the moving correlation coefficient recorded over 4-min periods between averaged values (6-sec periods) of MAP and ICP representing cerebrovascular pressure reactivity. When cerebrovascular reactivity is intact, PRx has negative or zero values, otherwise PRx is positive. Outcome was assessed at 6 months using the Glasgow Outcome Scale. A total of 13,633 hrs of data were recorded. CPPOPT was defined as the CPP where PRx reaches its minimum value when plotted against CPP. Identification of CPPOPT was possible in 68 patients (60%). In 22 patients (27%), CPPOPT was not found because it presumably lay outside the studied range of CPP. Patients’ outcome correlated with the difference between CPP and CPPOPT for patients who were managed on average below CPPOPT (r = .53, p < .001) and for patients whose mean CPP was above CPPOPT (r = −.40, p < .05). Conclusions CPPOPT could be identified in a majority of patients. Patients with a mean CPP close to CPPOPT were more likely to have a favorable outcome than those whose mean CPP was more different from CPPOPT. We propose use of the criterion of minimal achievable PRx to guide future trials of CPP oriented treatment in head injured patients.

Monitoring of Cerebral Autoregulation in Head-Injured Patients

BACKGROUND AND PURPOSE Disturbed cerebral autoregulation has been reported to correlate with an unfavorable outcome after head injury. Using transcranial Doppler ultrasonography, we investigated whether hemodynamic responses to spontaneous variations of cerebral perfusion pressure (CPP) provide reliable information on cerebral autoregulatory reserve. METHODS We studied 82 patients with head injury daily. Waveforms of intracranial pressure (ICP), arterial pressure, and transcranial Doppler flow velocity (FV) were captured during 2-hour periods. Time-averaged mean FV (FVm) and the FV during cardiac systole (FVs) were resolved. The correlation coefficient indices between FVm and CPP (Mx) and between FVs and CPP (Sx) during spontaneous fluctuations of CPP were calculated during 3-minute epochs and averaged for each investigation. RESULTS Mx and Sx correlated with CPP (r = -.34, P = < .002; r = -.2, P = NS. respectively), with ICP (r = .46, P < .0001; r = .34, P < .003, respectively), with admission Glasgow Coma Scale score (r = -.34, P < .0025; r = -.38, P < .0008, respectively), and with outcome after head injury (r = .41, P < .0002; r = .48, P < .00009, respectively). In patients who died, cerebral autoregulation was severely disturbed during the first 2 days after injury. CONCLUSIONS Indices derived from spontaneous fluctuations of FV waveform and CPP describe cerebral vascular pressure reactivity. They correlate with outcome after head injury and therefore may be used to guide autoregulation-oriented intensive therapy.

Effects of Acute Treatment With Pravastatin on Cerebral Vasospasm, Autoregulation, and Delayed Ischemic Deficits After Aneurysmal Subarachnoid Hemorrhage: A Phase II Randomized Placebo-Controlled Trial

Background and Purpose— Statins may improve cerebral vasomotor reactivity through cholesterol-dependent and -independent mechanisms. A phase II randomized controlled trial was conducted to examine the hypothesis that acute pravastatin treatment could improve cerebrovascular autoregulation and reduce vasospasm-related complications after aneurysmal subarachnoid hemorrhage (SAH). Methods— A total of 80 aneurysmal SAH (aSAH) patients (18 to 84 years of age) within 72 hours from the ictus were randomized equally to receive either oral pravastatin (40 mg) or placebo daily for up to 14 days. Primary end points were the incidence, duration, and severity of cerebral vasospasm, and duration of impaired autoregulation estimated from transcranial Doppler ultrasonography. Secondary end points were the incidence of vasospasm-related delayed ischemic deficits (DIDs) and disability at discharge. Results— Prerandomization characteristics were balanced between the 2 groups. No treatment-related complication was observed. The incidences of vasospasm and severe vasospasm were reduced by 32% (P=0.006) and 42% (P=0.044), respectively, and the duration of severe vasospasm was shortened by 0.8 days (P=0.068) in the pravastatin group. These measurements were maximal on the ipsilateral side of ruptured aneurysms. The duration of impaired autoregulation was shortened bilaterally (P≤0.01), and the incidence of vasospasm-related DIDs and mortality were decreased by 83% (P<0.001) and 75% (P=0.037), respectively, in the pravastatin group. Conclusion— Acute treatment with pravastatin after aSAH is safe and ameliorates cerebral vasospasm, improves cerebral autoregulation, and reduces vasospasm-related DID. Unfavorable outcome at discharge was reduced primarily because of a reduction in overall mortality. This is the first demonstration of clinical benefits with immediate statin therapy for an acute cerebrovascular disorder.

Decompressive craniectomy in traumatic brain injury: the randomized multicenter RESCUEicp study (www.RESCUEicp.com)

The RESCUEicp (Randomized Evaluation of Surgery with Craniectomy for Uncontrollable Elevation of intracranial pressure) study has been established to determine whether decompressive craniectomy has a role in the management of patients with traumatic brain injury and raised intracranial pressure that does not respond to initial treatment measures. We describe the concept of decompressive craniectomy in traumatic brain injury and the rationale and protocol of the RESCUEicp study.

Continuous determination of optimal cerebral perfusion pressure in traumatic brain injury

Objectives: We have sought to develop an automated methodology for the continuous updating of optimal cerebral perfusion pressure (CPPopt) for patients after severe traumatic head injury, using continuous monitoring of cerebrovascular pressure reactivity. We then validated the CPPopt algorithm by determining the association between outcome and the deviation of actual CPP from CPPopt. Design: Retrospective analysis of prospectively collected data. Setting: Neurosciences critical care unit of a university hospital. Patients: A total of 327 traumatic head-injury patients admitted between 2003 and 2009 with continuous monitoring of arterial blood pressure and intracranial pressure. Measurements and Main Results: Arterial blood pressure, intracranial pressure, and CPP were continuously recorded, and pressure reactivity index was calculated online. Outcome was assessed at 6 months. An automated curve fitting method was applied to determine CPP at the minimum value for pressure reactivity index (CPPopt). A time trend of CPPopt was created using a moving 4-hr window, updated every minute. Identification of CPPopt was, on average, feasible during 55% of the whole recording period. Patient outcome correlated with the continuously updated difference between median CPP and CPPopt (chi-square = 45, p < .001; outcome dichotomized into fatal and nonfatal). Mortality was associated with relative “hypoperfusion” (CPP < CPPopt), severe disability with “hyperperfusion” (CPP > CPPopt), and favorable outcome was associated with smaller deviations of CPP from the individualized CPPopt. While deviations from global target CPP values of 60 mm Hg and 70 mm Hg were also related to outcome, these relationships were less robust. Conclusions: Real-time CPPopt could be identified during the recording time of majority of the patients. Patients with a median CPP close to CPPopt were more likely to have a favorable outcome than those in whom median CPP was widely different from CPPopt. Deviations from individualized CPPopt were more predictive of outcome than deviations from a common target CPP. CPP management to optimize cerebrovascular pressure reactivity should be the subject of future clinical trial in severe traumatic head-injury patients.

Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients

Secondary insults can adversely influence outcome following severe traumatic brain injury. Monitoring of cerebral extracellular chemistry with microdialysis has the potential for early detection of metabolic derangements associated with such events. The objective of this study was to determine the relationship between the fundamental biochemical markers and neurological outcome in a large cohort of patients with traumatic brain injury. Prospectively collected observational neuromonitoring data from 223 patients were analysed. Monitoring modalities included digitally recorded intracranial pressure, cerebral perfusion pressure, cerebrovascular pressure reactivity index and microdialysis markers glucose, lactate, pyruvate, glutamate, glycerol and the lactate/pyruvate ratio. Outcome was assessed using the Glasgow Outcome Scale at 6 months post-injury. Patient-averaged values of parameters were used in statistical analysis, which included univariate non-parametric methods and multivariate logistic regression. Monitoring with microdialysis commenced on median (interquartile range) Day 1 (1-2) from injury and median (interquartile range) duration of monitoring was 4 (2-7) days. Averaged over the total monitoring period levels of glutamate (P = 0.048), lactate/pyruvate ratio (P = 0.044), intracranial pressure (P = 0.006) and cerebrovascular pressure reactivity index (P = 0.01) were significantly higher in patients who died. During the initial 72 h of monitoring, median glycerol levels were also higher in the mortality group (P = 0.014) and median lactate/pyruvate ratio (P = 0.026) and lactate (P = 0.033) levels were significantly lower in patients with favourable outcome. In a multivariate logistic regression model (P < 0.0001), which employed data averaged over the whole monitoring period, significant independent positive predictors of mortality were glucose (P = 0.024), lactate/pyruvate ratio (P = 0.016), intracranial pressure (P = 0.029), cerebrovascular pressure reactivity index (P = 0.036) and age (P = 0.003), while pyruvate was a significant independent negative predictor of mortality (P = 0.004). The results of this study suggest that extracellular metabolic markers are independently associated with outcome following traumatic brain injury. Whether treatment-related improvement in biochemistry translates into better outcome remains to be established.

Impact of Intracranial Pressure and Cerebral Perfusion Pressure on Severe Disability and Mortality After Head Injury

ObjectiveTo investigate the relationships between intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome after traumatic brain injury.Material and MethodsA retrospective analysis of prospectively recorded data from 429 patients after head injury requiring intensive treatment on the Neuroscience Intensive Annex and the Neuro Critical Care Unit, Cambridge, UK.ICP, CPP, and arterial blood pressure (ABP) were continuously recorded. Mean values of pressures were compared to outcome assessed at 6 months after injury (using the Glasgow Outcome Scale).ResultsThe mortality rate was greater in those having mean ICP greater than 20 mmHg (17% below versus 47% above; p<0.00001). The mortality rate was dramatically increased for CPP below 55 mmHg (81% below versus 23% above; p<0.0001). For values of CPP greater than 95 mmHg, favorable outcome was less frequent (50% below versus 28% above; p<0.033). The rate of severe disability showed the tendency to increase with CPP (r=0.87; p=0.02), suggesting that a higher CPP does not help in achieving favorable outcomes.ICP was greater in those who died in comparison to those who survived (27±19 mmHg versus 16±6 mmHg; p<0.10–7), and CPP was lower (68±21 versus 76±10 mmHg; p<0.0002). There was no difference between mean ICP and CPP in good/moderate and severe disability outcome groups.ConclusionHigh ICP is strongly associated with fatal outcome. Excessive CPP seems to reduce the probability of achieving a favorable outcome following head trauma.

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.