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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.

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Christos Lazaridis, Stacia M. DeSantis, Peter Smielewski, David K. Menon, Peter Hutchinson, John D. Pickard, and Marek Czosnyka

Object

Based on continuous monitoring of the pressure reactivity index (PRx), the authors defined individualized intracranial pressure (ICP) thresholds by graphing the relationship between ICP and PRx. These investigators hypothesized that an “ICP dose” based on individually assessed ICP thresholds would correlate more closely with the 6-month outcome when compared with ICP doses derived by the recommended universal thresholds of 20 and 25 mm Hg.

Methods

This study was a retrospective analysis of prospectively collected data from 327 patients with severe traumatic brain injury.

Results

Individualized thresholds were visually identified from graphs of PRx versus ICP; PRx > 0.2 was the cutoff. Intracranial pressure doses were then computed as the cumulative area under the curve above the defined thresholds in graphing ICP versus time. The term “Dose 20” (D20) was used to refer to an ICP threshold of 20 mm Hg; the markers D25 and DPRx were calculated similarly. Separate logistic regression models were fit with death as the outcome and each dose as the predictor, both alone and adjusted for covariates. The discriminative ability of each dose for mortality was assessed by receiver operating characteristic AUC analysis in which 5-fold cross-validation was used. A clearly identifiable PRx-based threshold was possible in 224 patients (68%). The DPRx (AUC 0.81, 95% CI 0.74–0.87) was found to have the highest area under the curve (AUC) over both D20 (0.75, 95% CI 0.68–0.81) and D25 (0.77, 95% CI 0.70–0.83); in the cross-validation model, DPRx remained the best discriminator of mortality (DPRx: AUC 0.77 [95% CI 0.68–0.89]; D20: 0.72 [95% CI 0.66–0.81]; and D25: 0.65 [95% CI 0.56–0.73]).

Conclusions

The authors explored the importance of different ICP thresholds for outcome by calculating patient-specific ICP doses based on the continuous monitoring of cerebrovascular pressure reactivity. They found that these individualized doses of intracranial hypertension were stronger predictors of death than doses derived from the universal thresholds of 20 and 25 mm Hg. The PRx could offer a method that can be directed toward individualizing the ICP threshold.

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Magdalena Hiler, Marek Czosnyka, Peter Hutchinson, Marcella Balestreri, Peter Smielewski, Basil Matta, and John D. Pickard

Object

The authors explored the relationship between computerized tomography (CT) scan findings and intracranial pressure (ICP) measurements obtained in the first 24 hours of monitoring to identify parameters predicting outcome in patients with severe traumatic brain injury (TBI).

Methods

Intracranial pressure, mean arterial blood pressure, cerebral perfusion pressure (CPP), and pressure reactivity index were measured continuously in 126 patients with severe TBI who were admitted to a neuroscience critical care unit. Mean values in the initial 24 hours of monitoring and in the total period of monitoring were compared with types of injury categorized on the basis of the initial CT scan according to the classification of Marshall, et al., and with Glasgow Outcome Scale scores.

The initial CT scan classification correlated significantly but weakly with ICP measured during the first 24 hours of monitoring (p = 0.036) but not with mean ICP over the total time of intensive care. Both midline shift and the ratio of frontal horn diameter to internal diameter correlated with ICP in the first 24 hours (p < 0.007) and with ICP over the total monitoring period (p < 0.03). Outcome score correlated with initial CT scan findings (p = 0.018), ICP over the total monitoring period (p < 0.0023), pressure reactivity over the total monitoring period (p < 0.0002), and pressure reactivity in the first 24 hours (p < 0.0001) but not with ICP in the first 24 hours. Patients with disturbed pressure reactivity in the first 24 hours after injury had a significantly higher mortality rate than patients with intact pressure reactivity (28.6% compared with 9.5%; p < 0.001).

Conclusions

Patients with severe TBI who have early loss of autoregulation have a worse prognosis. Mean ICP values in patients with diffuse TBI cannot be predicted by using the Marshall CT scan classification.

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Andrea Lavinio, Sally Harding, Floor Van Der Boogaard, Marek Czosnyka, Peter Smielewski, Hugh K. Richards, John D. Pickard, and Zofia H. Czosnyka

Object

Exposing patients with ventricular shunts to magnetic fields and MR imaging procedures poses a significant risk of unintentional changes in shunt settings. Shunt valves can also generate considerable imaging artifacts. The purpose of this study was to determine the magnetic field safety and MR imaging compatibility of 5 adjustable models of hydrocephalus shunts.

Methods

The Codman Hakim (regular and with SiphonGuard), Miethke ProGAV, Medtronic Strata, Sophysa Sophy and Polaris programmable valves were tested in a low-intensity magnetic field, and then translational attraction (TA), magnetic torque (MT), and volume of artifacts on T1-weighted spin echo (SE) and gradient echo (GE) pulse sequences in a 3-T MR imaging unit were measured.

Results

The ProGAV and Polaris valves were immune to unintentional reprogramming by magnetic fields up to 3 T. Other valves randomly changed settings, starting from the intensity of field: Sophy valve 24 mT, Strata valve 30 mT, and both Codman Hakim programmable valves from 42 mT. Shunt performances in the 3-T MR imaging unit are reported in the order of compatibility: 1) Codman Hakim regular, TA = 0.005 N, MT = 0.000 Nm, GE = 30 cm3, SE = 2 cm3; 2) Miethke ProGAV, TA = 0.001 N, MT = 1.4 × 10−3 Nm, GE = 231 cm3, SE = 13 cm3; 3) Codman Hakim with SiphonGuard, TA = 0.005 N, MT = 2.3 × 10−3 Nm, GE = 233 cm3, SE = 19 cm3; 4) Medtronic Strata, TA = 0.27 N, MT = 18.0 × 10−3 Nm, GE = 484 cm3, SE = 86 cm3; 5) Sophysa Sophy, TA = 0.82 N, MT = 38.9 × 10−3 Nm, GE = 758 cm3, SE = 72 cm3; and 6) Sophysa Polaris, TA = 0.80 N, MT = 39.6 × 10−3 Nm, GE = 954 cm3, SE = 100 cm3.

Conclusions

All valves, with the exception of the Polaris and ProGAV models, are prone to unintentional reprogramming when exposed to heterogeneous magnetic fields stronger than 40 mT. All tested valves can be considered safe for 3-T MR imaging. All valves generated a distortion of the MR image, especially the GE sequences.

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Georgios V. Varsos, Angelos G. Kolias, Peter Smielewski, Ken M. Brady, Vassilis G. Varsos, Peter J. Hutchinson, John D. Pickard, and Marek Czosnyka

OBJECT

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).

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.

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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

Object

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.

Methods

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.

Results

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.

Conclusions

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.