John D. Pickard and Alonso Pena
Marek Czosnyka, Peter Smielewski, Ivan Timofeev, Andrea Lavinio, Eric Guazzo, Peter Hutchinson, and John D. Pickard
✓Many doctors involved in the critical care of head-injured patients understand intracranial pressure (ICP) as a number, characterizing the state of the brain pressure–volume relationships. However, the dynamics of ICP, its waveform, and secondarily derived indices portray useful information about brain homeostasis. There is circumstantial evidence that this information can be used to modify and optimize patients' treatment. Secondary variables, such as pulse amplitude and the magnitude of slow waves, index of compensatory reserve, and pressure–reactivity index (PRx), look promising in clinical practice. The optimal cerebral perfusion pressure (CPP) derived using the PRx is a new concept that may help to avoid excessive use of vasopressors in CPP-oriented therapy. However, the use of secondary ICP indices remains to be confirmed in clinical trials.
Ming-Yuan Tseng, Marek Czosnyka, Hugh Richards, John D. Pickard, and Peter J. Kirkpatrick
The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs). In the current study, they test the hypothesis that these effects are associated with improvement in indices describing autoregulation of cerebral blood flow.
In this double-blind study, 80 patients between the ages of 18 and 84 years who had aneurysmal SAH were randomized equally to receive either 40 mg of oral pravastatin or placebo once daily for up to 14 days (medication was started 1.8 ± 1.3 days after ictus). Autoregulation was measured using a daily transient hyperemic response test (THRT) on transcranial Doppler ultrasonography (800 measurements in 80 patients), and data were compared between the pravastatin and placebo groups and between patients with or without vasospasm, DINDs, or unfavorable outcome. Measurement of autoregulation also was performed using the pressure-reactivity index, a moving correlation coefficient between mean arterial and intracranial pressures (Days 0–5, 132 measurements in 32 patients).
There was no difference in baseline autoregulation indices between the trial groups. The members of the pravastatin group not only had a shorter duration of impaired autoregulation but also had stronger transient hyperemic response ratios (THRRs) bilaterally. A negative correlation existed between the mean flow velocity in the middle cerebral artery and THRRs. Onset of DINDs occurred when bilateral autoregulation failed. On Days 3, 4, and 5, the pressure-reactivity index correlated significantly with ipsilateral impaired autoregulation.
The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation. A routine and daily assessment of cerebral autoregulation by using the THRT may help identify patients at high risk of DINDs.
Afroditi Despina Lalou, Marek Czosnyka, Joseph Donnelly, John D. Pickard, FMedSci, Eva Nabbanja, Nicole C. Keong, Matthew Garnett, and Zofia H. Czosnyka
Normal pressure hydrocephalus is not simply the result of a disturbance in CSF circulation, but often includes cardiovascular comorbidity and abnormalities within the cerebral mantle. In this study, the authors have examined the relationship between the global autoregulation pressure reactivity index (PRx), the profile of disturbed CSF circulation and pressure-volume compensation, and their possible effects on outcome after surgery.
The authors studied a cohort of 131 patients in whom a clinical suspicion of normal pressure hydrocephalus was investigated. Parameters describing CSF compensation and circulation were calculated during the CSF infusion test, and PRx was calculated from CSF pressure and mean arterial blood pressure (MAP) recordings. A simple scale was used to mark the patients’ outcome 6 months after surgery (improvement, temporary improvement, and no improvement).
The PRx was negatively correlated with resistance to CSF outflow (R = −0.18; p = 0.044); patients with normal CSF circulation tended to have worse autoregulation. The correlation for patients who were surgically treated (n = 83) was R = −0.28; p = 0.01, and it was stronger in patients who experienced sustained improvement after surgery (n = 48, R = −0.43; p = 0.002). In patients who did not improve, the correlation was not significantly different from zero (n = 19, R = −0.07; p = 0.97). There was a trend toward higher values for PRx in nonresponders than in responders (0.16 ± 0.04 vs 0.09 ± 0.02, respectively; p = 0.061), associated with higher MAP values (107.2 ± 8.2 in nonresponders vs 89.5 ± 3.5 in responders; p = 0.195). The product of MAP × (1 + PRx), which was proposed as a measure of combined arterial hypertension and deranged autoregulation, showed a significant association with outcome (greater value in nonresponders; p = 0.013).
Autoregulation proves to associate with CSF circulation and appears strongest in shunt responders. Outcome following CSF diversion is possibly most favorable when CSF outflow resistance is increased and global cerebral autoregulation is intact, in combination with arterial normotension.
Nicole C. H. Keong, Alonso Pena, Stephen J. Price, Marek Czosnyka, Zofia Czosnyka, and John D. Pickard
The pathophysiology of NPH continues to provoke debate. Although guidelines and best-practice recommendations are well established, there remains a lack of consensus about the role of individual imaging modalities in characterizing specific features of the condition and predicting the success of CSF shunting. Variability of clinical presentation and imperfect responsiveness to shunting are obstacles to the application of novel imaging techniques. Few studies have sought to interpret imaging findings in the context of theories of NPH pathogenesis. In this paper, the authors discuss the major streams of thought for the evolution of NPH and the relevance of key imaging studies contributing to the understanding of the pathophysiology of this complex condition.
Marek Czosnyka, Zofia Czosnyka, Nicole Keong, Andreas Lavinio, Piotr Smielewski, Shahan Momjian, Eric A. Schmidt, Gianpaolo Petrella, Brian Owler, and John D. Pickard
Apart from its mean value, the pulse waveform of intracranial pressure (ICP) is an essential element of pressure recording. The authors reviewed their experience with the measurement and interpretation of ICP pulse amplitude by referring to a database of recordings in hydrocephalic patients.
The database contained computerized pressure recordings from 2100 infusion studies (either lumbar or intraventricular) or overnight ICP monitoring sessions in patients suffering from hydrocephalus of various types (both communicating and noncommunicating), origins, and stages of management (shunt or no shunt). Amplitude was calculated from ICP waveforms by using a spectral analysis methodology.
The appearance of a pulse waveform amplitude is positive evidence of a technically correct recording of ICP and helps to distinguish between postural and vasogenic variations in ICP. Pulse amplitude is significantly correlated with the amplitude of cerebral blood flow velocity (R = 0.4, p = 0.012) as assessed using Doppler ultrasonography. Amplitude is positively correlated with a mean ICP (R = 0.21 in idiopathic normal-pressure hydrocephalus [NPH]; number of cases 131; p < 0.01) and resistance to cerebrospinal fluid outflow (R = 0.22) but does not seem to be correlated with cerebrospinal elasticity, dilation of ventricles, or severity of hydrocephalus (NPH score). Amplitude increases slightly with age (R = 0.39, p < 0.01; number of cases 46). A positive association between pulse amplitude and increased ICP during an infusion study is helpful in distinguishing between hydrocephalus and predominant brain atrophy. A large amplitude is associated with a good outcome after shunting (positive predictive power 0.9), whereas a low amplitude has no predictive power in outcome prognostication (0.5). Pulse amplitude is reduced by a properly functioning shunt.
Proper recording, detection, and interpretation of ICP pulse waveforms provide clinically useful information about patients suffering from hydrocephalus.
Christian Zweifel, Andrea Lavinio, Luzius A. Steiner, Danila Radolovich, Peter Smielewski, Ivan Timofeev, Magdalena Hiler, Marcella Balestreri, Peter J. Kirkpatrick, John D. Pickard, Peter Hutchinson, and Marek Czosnyka
Cerebrovascular pressure reactivity is the ability of cerebral vessels to respond to changes in transmural pressure. A cerebrovascular pressure reactivity index (PRx) can be determined as the moving correlation coefficient between mean intracranial pressure (ICP) and mean arterial blood pressure.
The authors analyzed a database consisting of 398 patients with head injuries who underwent continuous monitoring of cerebrovascular pressure reactivity. In 298 patients, the PRx was compared with a transcranial Doppler ultrasonography assessment of cerebrovascular autoregulation (the mean index [Mx]), in 17 patients with the PET–assessed static rate of autoregulation, and in 22 patients with the cerebral metabolic rate for O2. Patient outcome was assessed 6 months after injury.
There was a positive and significant association between the PRx and Mx (R2 = 0.36, p < 0.001) and with the static rate of autoregulation (R2 = 0.31, p = 0.02). A PRx > 0.35 was associated with a high mortality rate (> 50%). The PRx showed significant deterioration in refractory intracranial hypertension, was correlated with outcome, and was able to differentiate patients with good outcome, moderate disability, severe disability, and death. The graph of PRx compared with cerebral perfusion pressure (CPP) indicated a U–shaped curve, suggesting that too low and too high CPP was associated with a disturbance in pressure reactivity. Such an optimal CPP was confirmed in individual cases and a greater difference between current and optimal CPP was associated with worse outcome (for patients who, on average, were treated below optimal CPP [R2 = 0.53, p < 0.001] and for patients whose mean CPP was above optimal CPP [R2 = −0.40, p < 0.05]). Following decompressive craniectomy, pressure reactivity initially worsened (median −0.03 [interquartile range −0.13 to 0.06] to 0.14 [interquartile range 0.12–0.22]; p < 0.01) and improved in the later postoperative course. After therapeutic hypothermia, in 17 (70.8%) of 24 patients in whom rewarming exceeded the brain temperature threshold of 37°C, ICP remained stable, but the average PRx increased to 0.32 (p < 0.0001), indicating significant derangement in cerebrovascular reactivity.
The PRx is a secondary index derived from changes in ICP and arterial blood pressure and can be used as a surrogate marker of cerebrovascular impairment. In view of an autoregulation–guided CPP therapy, a continuous determination of a PRx is feasible, but its value has to be evaluated in a prospective controlled trial.
Georgios V. Varsos, Angelos G. Kolias, Peter Smielewski, Ken M. Brady, Vassilis G. Varsos, Peter J. Hutchinson, John D. Pickard, and Marek Czosnyka
Cerebral blood flow is associated with cerebral perfusion pressure (CPP), which is clinically monitored through arterial blood pressure (ABP) and invasive measurements of intracranial pressure (ICP). Based on critical closing pressure (CrCP), the authors introduce a novel method for a noninvasive estimator of CPP (eCPP).
Data from 280 head-injured patients with ABP, ICP, and transcranial Doppler ultrasonography measurements were retrospectively examined. CrCP was calculated with a noninvasive version of the cerebrovascular impedance method. The eCPP was refined with a predictive regression model of CrCP-based estimation of ICP from known ICP using data from 232 patients, and validated with data from the remaining 48 patients.
Cohort analysis showed eCPP to be correlated with measured CPP (R = 0.851, p < 0.001), with a mean ± SD difference of 4.02 ± 6.01 mm Hg, and 83.3% of the cases with an estimation error below 10 mm Hg. eCPP accurately predicted low CPP (< 70 mm Hg) with an area under the curve of 0.913 (95% CI 0.883–0.944). When each recording session of a patient was assessed individually, eCPP could predict CPP with a 95% CI of the SD for estimating CPP between multiple recording sessions of 1.89–5.01 mm Hg.
Overall, CrCP-based eCPP was strongly correlated with invasive CPP, with sensitivity and specificity for detection of low CPP that show promise for clinical use.