Intracranial hypertension in patients with aneurysmal subarachnoid hemorrhage: a systematic review and meta-analysis.

Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating and life-threatening condition with high mortality and morbidity. Even though there is an association with intracranial pressure (ICP) raise and aSAH, there is a lack of recommendations regarding the indications for ICP monitoring in patients with aSAH. Defining what patients are at a higher risk to develop intracranial hypertension and its role in the functional outcome and mortality in patients with aSAH will be the purpose of the following systematic review and meta-analysis. The primary endpoint is to determine the prevalence and impact on mortality of ICP in patients with aSAH. Secondary endpoints aim to describe the variables related to the development of ICP and the relationship between traumatic and aneurysmal etiology of intracranial hypertension. PubMed, Embase, Central Cochrane Registry of Controlled Trials, and research meeting abstracts were searched up to August 2019 for studies that performed ICP monitoring, assessed the prevalence of intracranial hypertension and the mortality, in adults. Newcastle Ottawa scale (NOS) was used to assess study quality. The statistical analysis was performed using the Mantel-Haenszel methodology for the prevalence and mortality of intracranial hypertension for reasons with a randomized effect analysis model. Heterogeneity was assessed by I2. A total of 110 bibliographic citations were identified, 20 were considered potentially eligible, and after a review of the full text, 12 studies were considered eligible and 5 met the inclusion criteria for this review. One study obtained 7 points in the NOS, another obtained 6 points, and the rest obtained 5 points. Five studies were chosen for the final analysis, involving 793 patients. The rate of intracranial hypertension secondary to aSAH was 70.69% (95% CI 56.79-82.84%) showing high heterogeneity (I2 = 92.48%, p = < 0.0001). The results of the meta-analysis of mortality rate associated with intracranial hypertension after aSAH found a total of four studies, which involved 385 patients. The mortality rate was 30.3% (95% CI: 14.79-48.57%). Heterogeneity was statistically significant (I2 = 90.36%; p value for heterogeneity < 0.001). We found that in several studies, they reported that a high degree of clinical severity scale (Hunt and Hess or WNFS) and tomographic (Fisher) were significantly correlated with the increase in ICP above 20 mmHg (P < 0.05). The interpretation of the results could be underestimated for the design heterogeneity of the included studies. New protocols establishing the indications for ICP monitoring in aSAH are needed. Given the high heterogeneity of the studies included, we cannot provide clinical recommendations regarding this issue.

Hyperosmolar Treatment for Patients at Risk for Increased Intracranial Pressure: A Single-Center Cohort Study.

Treatment with osmoactive agents such as mannitol or hypertonic saline (HTS) solutions is widely used to manage or prevent the increase of intracranial pressure (ICP) in central nervous system (CNS) disorders. We sought to evaluate the variability and mean plasma concentrations of the water and electrolyte balance parameters in critically ill patients treated with osmotic therapy and their influence on mortality. This cohort study covered patients hospitalized in an intensive care unit (ICU) from January 2017 to June 2019 with presumed increased ICP or considered to be at risk of it, treated with 15% mannitol (G1, n = 27), a combination of 15% mannitol and 10% hypertonic saline (HTS) (G2, n = 33) or 10% HTS only (G3, n = 13). Coefficients of variation (Cv) and arithmetic means (mean) were calculated for the parameters reflecting the water and electrolyte balance, i.e., sodium (NaCv/NaMean), chloride (ClCv/ClMean) and osmolality (mOsmCv/mOsmMean). In-hospital mortality was also analyzed. The study group comprised 73 individuals (36 men, 49%). Mortality was 67% (n = 49). Median NaCv (G1: p = 0.002, G3: p = 0.03), ClCv (G1: p = 0.02, G3: p = 0.04) and mOsmCv (G1: p = 0.001, G3: p = 0.02) were higher in deceased patients. NaMean (p = 0.004), ClMean (p = 0.04), mOsmMean (p = 0.003) were higher in deceased patients in G3. In G1: NaCv (AUC = 0.929, p < 0.0001), ClCv (AUC = 0.817, p = 0.0005), mOsmCv (AUC = 0.937, p < 0.0001) and in G3: NaMean (AUC = 0.976, p < 0.001), mOsmCv (AUC = 0.881, p = 0.002), mOsmMean (AUC = 1.00, p < 0.001) were the best predictors of mortality. The overall mortality prediction for combined G1+G2+G3 was very good, with AUC = 0.886 (p = 0.0002). The mortality of critically ill patients treated with osmotic agents is high. Electrolyte disequilibrium is the independent predictor of mortality regardless of the treatment method used. Variations of plasma sodium, chloride and osmolality are the most deleterious factors regardless of the absolute values of these parameters.

Controlling Blood Pressure Under Transcranial Doppler Guidance after Endovascular Treatment in Patients with Acute Ischemic Stroke.

OBJECTIVE: This study aimed to control blood pressure (BP) under transcranial Doppler (TCD) guidance in patients with anterior circulation acute ischemic stroke after endovascular treatment (EVT) to reduce the incidence of early neurological deterioration (END) and improve neurological prognosis. METHODS: This prospective randomized controlled study included 95 patients who were randomly divided into a TCD-guided BP control (TBC) group and a non-TCD-guided BP control (NBC) group. The patients were monitored by TCD within 72 h after EVT. In the TBC group, BP decreased, BP increased, or intracranial pressure decreased when TCD showed blood flow acceleration, deceleration, or intracranial hypertension respectively. The BP of the NBC group was controlled according to the guidelines. The incidence of END and the prognosis was compared between the 2 groups. RESULTS: TCD identified 18 patients with blood flow acceleration, but the prognosis of the 2 groups was not significantly different. TCD identified 23 patients with blood flow deceleration, and the poor prognosis rate at discharge was lower in the TBC group than in the NBC group (45.5 vs. 91.7%, p = 0.027). TCD identified 34 patients with intracranial hypertension, and the 3-month mortality rate of the TBC group was lower than that of the NBC group (0 vs. 36.8%, p = 0.011). The incidence rates of END and 3-month mortality in the TBC group were lower than those in the NBC group (13.8 vs. 37.5%, p = 0.036; 0 vs. 25.0%, p = 0.012) when TCD parameters were abnormal. Multivariable logistic regression analysis showed that the TBC group (adjusted OR 0.267, 95% CI 0.074-0.955; p = 0.042) was an independent protective factor against the incidence of END when TCD parameters were abnormal. CONCLUSION: These findings indicated that TCD-guided BP and intracranial pressure control improved the prognosis of patients with blood flow deceleration and intracranial hypertension.

Comparison of Outcomes of Severe Traumatic Brain Injury in 36,929 Patients Treated with or without Intracranial Pressure Monitoring in a Mature Trauma System.

BACKGROUND: Severe traumatic brain injury (TBI) remains a major cause of morbidity and mortality with mortality rates reaching 35%. Intracranial pressure (ICP) monitoring is used to prevent secondary brain injury and death. However, while the association of elevated ICP and worsened outcomes is accepted, routine ICP monitoring has been questioned after the publication of several studies including the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure trial. We examined whether severe TBI patients in the trauma system of Pennsylvania fared better with or without ICP monitoring. METHODS: We conducted a statewide retrospective analysis and included all TBI patients >18 years with an admission Glasgow Coma Scale (GCS) <9 from January 2000 through December 2017. The primary outcome was mortality. Secondary outcomes examined were intensive care unit length of stay (LOS) and discharge functional independence measure (FIM). RESULTS: A total of 36,929 patients matched our inclusion criteria and were included in the analysis. Of those, 6025 (16.3%) had ICP monitor placement. Mean ICU LOS was significantly higher in ICP-monitored patients (13.1 ± 11.6 days vs. 6.0 ± 10.8 days, P < 0.0001). Increasing age was a significant predictor of death (P < 0.0001). Mean FIM scores at discharge were significantly higher in patients without an ICP monitor (16.21 ± 4.91 vs. 9.53 ± 5.07, P < 0.0001). When controlling for injury severity score, GCS, age, and craniotomy, ICP monitoring conferred a hazard ratio of 0.85 (χ2 = 32.63, P < 0.0001), a 25% reduction of in-hospital mortality compared with non-ICP-monitored patients. CONCLUSION: We found that ICP-monitored patients had a lower risk of in-hospital mortality. Our findings support the use of ICP monitors in eligible patients.

Why Do Patients with Poor-Grade Subarachnoid Hemorrhage Die?

BACKGROUND: Poor-grade subarachnoid hemorrhage (SAH) has been associated with a high case fatality, either in the acute phase or in the later stages. The exact causes of death in these patients are unknown. METHODS: We performed a retrospective study of all consecutive patients with SAH with World Federation of Neurosurgical Societies grade IV or V on admission from 2009 to 2013 at 2 tertiary referral centers in Amsterdam, the Netherlands, and Toronto, Ontario, Canada, who had died during their hospital stay. RESULTS: Of 357 patients, 152 (43%) had died. Of these 152 patients, 87 (24%) had not undergone aneurysm treatment. The median interval to death was 3 days (interquartile range, 1-12 days) after initial hemorrhage. The major cause of death in both centers was withdrawal of life support (107 patients [71%]; 74 of 94 [79%] in Amsterdam and 33 of 58 [58%] in Toronto; P < 0.01), followed by brain death in 23 (15%; 16 of 58 [28%] in Amsterdam vs. 7 of 94 [7%] in Toronto; P < 0.01). The remaining causes of death represented <15%. CONCLUSIONS: The decision to withdraw life support was the major reason for death of patients with poor-grade SAH for an overwhelming majority of the patients. The exact reasons for withdrawal of life support, other than cultural and referral differences, were undetermined. Insight into the reasons of death should be prospectively studied to improve the care and clinical outcomes of patients with poor-grade SAH.

Management of moderate and severe traumatic brain injury.

Traumatic brain injury (TBI) is a common disorder with high morbidity and mortality, accounting for one in every three deaths due to injury. Older adults are especially vulnerable. They have the highest rates of TBI-related hospitalization and death. There are about 2.5 to 6.5 million US citizens living with TBI-related disabilities. The cost of care is very high. Aside from prevention, little can be done for the initial primary injury of neurotrauma. The tissue damage incurred directly from the inciting event, for example, a blow to the head or bullet penetration, is largely complete by the time medical care can be instituted. However, this event will give rise to secondary injury, which consists of a cascade of changes on a cellular and molecular level, including cellular swelling, loss of membrane gradients, influx of immune and inflammatory mediators, excitotoxic transmitter release, and changes in calcium dynamics. Clinicians can intercede with interventions to improve outcome in the mitigating secondary injury. The fundamental concepts in critical care management of moderate and severe TBI focus on alleviating intracranial pressure and avoiding hypotension and hypoxia. In addition to these important considerations, mechanical ventilation, appropriate transfusion of blood products, management of paroxysmal sympathetic hyperactivity, using nutrition as a therapy, and, of course, venous thromboembolism and seizure prevention are all essential in the management of moderate to severe TBI patients. These concepts will be reviewed using the recent 2016 Brain Trauma Foundation Guidelines to discuss best practices and identify future research priorities.

Impact of intracranial hypertension on the short-term prognosis in dogs undergoing brain tumor surgery.

The present study used data from anesthetic records to analyze variables of intracranial pressure (ICP) during brain tumor surgery or in the early postoperative period as prognostic indicators in dogs. Data from 17 dogs which were scheduled to undergo elective craniotomy for brain tumor surgery from 2009 to 2012 were included. Of these, five (29.4%) died during 14 days after the surgery because of respiratory failure following pneumonia (n=2), euthanasia due to difficulty in treatment of status epilepticus (n=1), tumor-bed hematoma (n=1), and unknown reason (n=1). In the 12 surviving dogs, neurological signs were improved or resolved at discharge. All dogs were administered midazolam and droperidol-fentanyl as premedication. General anesthesia was induced using propofol maintained on isoflurane and oxygen. Direct ICP was obtained via a Codman Microsensor strain gauge transducer. ICP hypertension (>13 mmHg) measured after 15 min of recovery from the moment after discontinuation of anesthesia by turning off the vaporizer dial was associated with poor prognosis (odds ratio, 20.00; 95% confidence interval, 1.39-287.60, P=0.028). This suggests that intracranial pressure influences the postoperative mortality rate in dogs undergoing brain tumor surgery.

Intracranial Pressure Trajectories: A Novel Approach to Informing Severe Traumatic Brain Injury Phenotypes.

OBJECTIVES: Intracranial pressure in traumatic brain injury is dynamic and influenced by factors like injury patterns, treatments, and genetics. Existing studies use time invariant summary intracranial pressure measures thus potentially losing critical information about temporal trends. We identified longitudinal intracranial pressure trajectories in severe traumatic brain injury and evaluated whether they predicted outcome. We further interrogated the model to explore whether ABCC8 polymorphisms (a known cerebraledema regulator) differed across trajectory groups. DESIGN: Prospective observational cohort. SETTING: Single-center academic medical center. PATIENTS: Four-hundred four severe traumatic brain injury patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We used group-based trajectory modeling to identify hourly intracranial pressure trajectories in days 0-5 post traumatic brain injury incorporating risk factor adjustment (age, sex, Glasgow Coma Scale 6score, craniectomy, primary hemorrhage pattern). We compared 6-month outcomes (Glasgow Outcome Scale, Disability Rating Scale, mortality) and ABCC8 tag-single-nucleotide polymorphisms associated with cerebral edema (rs2237982, rs7105832) across groups. Regression models determined whether trajectory groups predicted outcome. A six trajectory group model best fit the data, identifying cohorts differing in initial intracranial pressure, evolution, and number/proportion of spikes greater than 20 mm Hg. There were pattern differences in age, hemorrhage type, and craniectomy rates. ABCC8 polymorphisms differed across groups. GOS (p = 0.006), Disability Rating Scale (p = 0.001), mortality (p < 0.0001), and rs2237982 (p = 0.035) differed across groups. Unfavorable outcomes were surprisingly predicted by both low intracranial pressure trajectories and sustained intracranial hypertension. Intracranial pressure variability differed across groups (p < 0.001) and may reflect preserved/impaired intracranial elastance/compliance. CONCLUSIONS: We employed a novel approach investigating longitudinal/dynamic intracranial pressure patterns in traumatic brain injury. In a risk adjusted model, six groups were identified and predicted outcomes. If validated, trajectory modeling may be a first step toward developing a new, granular approach for intracranial pressure phenotyping in conjunction with other phenotyping tools like biomarkers and neuroimaging. This may be particularly relevant in light of changing traumatic brain injury demographics toward the elderly.

Long-term outcome following decompressive craniectomy: an inconvenient truth?

PURPOSE OF REVIEW: There is little doubt that decompressive craniectomy can reduce mortality following malignant middle cerebral infarction or severe traumatic brain injury. However, the concern has always been that the reduction in mortality comes at the cost of an increase in the number of survivors with severe neurological disability. RECENT FINDINGS: There has been a number of large multicentre randomized trials investigating surgical efficacy of the procedure. These trials have clearly demonstrated a survival benefit in those patients randomized to surgical decompression. However, it is only possible to demonstrate an improvement in outcome if the definition of favourable is changed such that it includes patients with either a modified Rankin score of 4 or upper severe disability. Without this recategorization, the results of these trials have confirmed the 'Inconvenient truth' that surgery reduces mortality at the expense of survival with severe disability. SUMMARY: Given these results, the time may have come for a nuanced examination of the value society places on an individual life, and the acceptability or otherwise of performing a procedure that converts death into survival with severe disability.

Intracranial Pressure Soon After Hemicraniectomy in Malignant Middle Cerebral Artery Infarction.

BACKGROUND: Decompressive hemicraniectomy reduces secondary brain injury related to brain edema and increased intracranial pressure (ICP) in patients with malignant middle cerebral artery infarction (MMI). However, a substantial proportion of patients still die despite hemicraniectomy due to refractory brain swelling. OBJECTIVE: We aim to investigate whether ICP measured immediately after hemicraniectomy may indicate decompression effects and predict survival in patients with MMI. METHODS: We included 25 patients with MMI who underwent ICP monitoring and brain computed tomography within the first hour of hemicraniectomy. Midline shifts were measured as radiological surrogates of decompression. The Glasgow Coma Scale and pupillary enlargements during the first day after hemicraniectomy were assessed as clinical surrogates of decompression. Long-term survival status at 6 months was used as the final outcome. We analyzed the relationships between early ICP and findings of midline shift, Glasgow Coma Scale, pupillary enlargement, and survival. RESULTS: Initial ICP was correlated with mean ICP ( P < .001) and maximal ICP ( P < .001) during the first postoperative day. Intracranial pressure was associated with midline shifts ( P = .009), lower Glasgow Coma Scale scores ( P = .025), and the pupillary enlargement ( P = .015). Sixteen (64.0%) patients survived at 6 months. In a Cox proportional hazard model, elevated ICP was associated with mortality at 6 months (hazard ratio: 1.13; 95% confidence interval: 1.03-1.24; P = .008). CONCLUSION: Increase in ICP soon after hemicraniectomy was associated with midline shift, poor neurological status, and mortality in patients with MMI. Measurements of ICP soon after hemicraniectomy may permit earlier interventions as well as more refined clinical assessments.

[Experience of shunting surgery in treatment for meningeal carcinomatosis].

OBJECTIVE: To evaluate the value of shunting surgery in the treatment for patients with meningeal carcinomatosis.
 Methods: The therapeutic process of shunting surgery was analyzed in 5 meningeal carcinomatosis patients.
 Results: The intracranial pressure could effectively be controlled, and the associated symptoms could be relieved. No complications associated with shunting surgery were found during the hospitalization and follow-up. One patient, who did not receive the surgery, died in 2 months later.
 Conclusion: Shunting surgery can effectively relieve the intracranial pressure caused by meningeal carcinomatosis, decrease the mortality and morbidity caused by intractable intracranial hypertension in these patients, and improve their live quality.

Perioperative Risk Assessment of Patients with Gliomatosis Cerebri.

BACKGROUND: Gliomatosis cerebri is a rare diffusely infiltrating malignant glial neoplasm. Presenting symptoms include seizures, neurologic deficits, and frequently symptoms related to increased intracranial pressure (ICP). Surgical intervention, including brain biopsy, may induce worsening of these neurologic symptoms. We reviewed our database to identify prognostic and risk factors for perioperative deterioration specifically associated with elevated ICP. METHODS: Between 2006 and 2014, 78 patients were treated for gliomatosis cerebri. Ten patients required perioperative emergent treatment for elevated ICP. The clinical course and outcome of these 10 patients (study group) were characterized and compared with the remaining 68 patients. RESULTS: The study group patients developed life-threatening symptoms of increased ICP and required urgent decompressive craniectomy (n = 5 urgent decompressive craniectomy after biopsy, n = 2 urgent decompressive craniectomy on admission) or aggressive medical therapy (n = 3). Demographic and clinical variables were similar in both groups. In patients with severe symptoms of increased ICP, enhancing tumor volume was significantly greater than in asymptomatic patients. Radiologic evidence of obliteration of the basal cisterns and herniation was more common in symptomatic patients. The proliferation index in the biopsy specimens of tumors was also significantly higher in patients with symptomatic ICP elevation. CONCLUSIONS: Clinical symptoms and radiologic appearance suggestive of elevated ICP at presentation, volume of contrast enhancement, and high Ki-67 proliferation index may predict the need for aggressive rapid treatment to control ICP in a small but significant subset of patients with GC. Further studies are needed to clarify the biologic basis for the unusual clinical course in these tumors.

Effectiveness of 7.5% hypertonic saline in children with severe traumatic brain injury.

PURPOSE: Hyperosmolar therapies aim at controlling increased intracranial pressure (ICP) in patients with traumatic brain injury (TBI). The aim of this study was to evaluate the effect of 7.5% hypertonic saline (HTS) on ICP and cerebral perfusion pressure (CPP) in children with severe TBI. MATERIALS AND METHODS: Medical records of patients 14 years or younger with severe TBI, admitted in the pediatric intensive care unit of "Aghia Sophia" Children's Hospital, Athens, Greece, during 2009 to 2015, and received HTS apart from mannitol were retrospectively reviewed. The ICP and CPP pre-HTS and 30, 60, and 120 minutes post-HTS infusion were evaluated. Furthermore, the presence of adverse effects, the long-term neurological outcome, and survival were recorded. RESULTS: Twenty-nine patients requiring in total 136 HTS infusions were analyzed. The ICP was significantly reduced and CPP elevated at 30, 60, and 120 minutes postinfusion; and furthermore, postadministration ICP and CPP were predominantly within acceptable limits. No significant adverse effects were recorded and most of the patients survived, however, one third had severe neurological impairment at 6 months postinjury. CONCLUSIONS: In our study, 7.5% HTS infusion as a second-tier osmotic therapy was associated with significant reduction of ICP and increase of CPP in children with severe TBI.

Age-related injury patterns in Spanish trauma ICU patients. Results from the RETRAUCI.

BACKGROUND: Injury patterns may differ in trauma patients when age is considered. This information is relevant in the management of trauma patients and for planning preventive measures. METHODS: We included in the study all patients admitted for traumatic disease in the participating ICUs from November 23rd, 2012 to July 31st, 2015 with complete records. Data on epidemiology, injury patterns, severity scores, acute management, resources utilisation and outcome were recorded and compared in the following groups of age: ≤55years (young adults), 56-65 years (adults), 66-75 years (elderly), >75years (very elderly). Quantitative data were reported as median (Interquartile Range (IQR) 25-75) and categorical data as number and percentage. Comparison between groups of age with quantitative variables was performed using the analysis of variance (ANOVA) test. Differences between groups with categorical variables were compared using the chi-square test. A value of p<0.05 was considered significant. RESULTS: We included 2700 patients (78.9% male). Median age was 46 (31-62) years. Blunt trauma was present in 93.7% of the patients. Median RTS was 7.55 (5.97-7.84). Median ISS was 20 (13-26). High-energy trauma secondary to motor-vehicle accident with rhabdomyolysis and drugs abuse showed an inverse linear association with ageing, whilst pedestrian falls with isolated brain injury, being run-over and pre-injury antiplatelets or anticoagulant treatment increased with age (in all cases p<0.001). Multiple injuries were more common in young adults (p<0.001). Acute kidney injury prevalence was higher in elderly and very elderly patients (p<0.001). ICU Mortality increased with age in spite of similar severity scores in all groups (p<0.001). The main cause of death in all groups was intracranial hypertension. CONCLUSIONS: Different injury patterns exist in relation with ageing in trauma ICU patients. Adult patients were more likely to present high-energy trauma with significant injuries in different areas whilst elderly patients were prone to low-energy falls, complicated by antiplatelets or anticoagulants use, resulting in severe brain injury and increased mortality.

Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension.

BACKGROUND: The effect of decompressive craniectomy on clinical outcomes in patients with refractory traumatic intracranial hypertension remains unclear. METHODS: From 2004 through 2014, we randomly assigned 408 patients, 10 to 65 years of age, with traumatic brain injury and refractory elevated intracranial pressure (>25 mm Hg) to undergo decompressive craniectomy or receive ongoing medical care. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOS-E) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 6 months. The primary-outcome measure was analyzed with an ordinal method based on the proportional-odds model. If the model was rejected, that would indicate a significant difference in the GOS-E distribution, and results would be reported descriptively. RESULTS: The GOS-E distribution differed between the two groups (P<0.001). The proportional-odds assumption was rejected, and therefore results are reported descriptively. At 6 months, the GOS-E distributions were as follows: death, 26.9% among 201 patients in the surgical group versus 48.9% among 188 patients in the medical group; vegetative state, 8.5% versus 2.1%; lower severe disability (dependent on others for care), 21.9% versus 14.4%; upper severe disability (independent at home), 15.4% versus 8.0%; moderate disability, 23.4% versus 19.7%; and good recovery, 4.0% versus 6.9%. At 12 months, the GOS-E distributions were as follows: death, 30.4% among 194 surgical patients versus 52.0% among 179 medical patients; vegetative state, 6.2% versus 1.7%; lower severe disability, 18.0% versus 14.0%; upper severe disability, 13.4% versus 3.9%; moderate disability, 22.2% versus 20.1%; and good recovery, 9.8% versus 8.4%. Surgical patients had fewer hours than medical patients with intracranial pressure above 25 mm Hg after randomization (median, 5.0 vs. 17.0 hours; P<0.001) but had a higher rate of adverse events (16.3% vs. 9.2%, P=0.03). CONCLUSIONS: At 6 months, decompressive craniectomy in patients with traumatic brain injury and refractory intracranial hypertension resulted in lower mortality and higher rates of vegetative state, lower severe disability, and upper severe disability than medical care. The rates of moderate disability and good recovery were similar in the two groups. (Funded by the Medical Research Council and others; RESCUEicp Current Controlled Trials number, ISRCTN66202560 .).

"Solid Red Line": An Observational Study on Death from Refractory Intracranial Hypertension.

The index of cerebrovascular pressure reactivity (PRx) correlates independently with outcome after traumatic brain injury (TBI). However, as an index plotted in the time domain, PRx is rather noisy. To "organise" PRx and make its interpretation easier, the colour coding of values, with green when PRx <0 and red when PRx> 0.3, has been introduced as a horizontal colour bar on the ICM+ screen. In rare cases of death from refractory intracranial hypertension, an increase in intracranial pressure (ICP) is commonly preceded by values of PRx >0.3, showing a "solid red line".Twenty patients after TBI and one after traumatic subarachnoid haemorrhage (SAH) from six centres in Europe and Australia have been studied. All of them died in a scenario of refractory intracranial hypertension. In the majority of cases the initial ICP was below 20 mmHg and finally increased to values well above 60 mmHg, resulting in cerebral perfusion pressure less than 20 mmHg. In three cases initial ICP was elevated at the start of monitoring. A solid red line was observed in all cases preceding an increase in ICP above 25 mmHg by minutes to hours and in two cases by 2 and 3 days, respectively. If a solid red line is observed over a prolonged period, it should be considered as an indicator of deep cerebrovascular deterioration.

Patient-Specific Thresholds and Doses of Intracranial Hypertension in Severe Traumatic Brain Injury.

Based on continuous monitoring of the pressure reactivity index (PRx), we defined individualized intracranial pressure (ICP) thresholds by graphing the relationship between ICP and PRx. We hypothesized that an "ICP dose" based on individually assessed ICP thresholds might correlate more closely with 6-month outcome compared with ICP doses derived from the recommended universal thresholds of 20 and 25 mmHg. Data from 327 patients with severe traumatic brain injury (TBI) were analyzed. ICP doses were 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. The discriminative ability of each dose with regard to mortality was assessed by receiver operating characteristics analysis using fivefold cross-validation (CV). DPRx was found to be the best discriminator of mortality, despite the fact that D20 was twice as large as DPRx. Individualized doses of intracranial hypertension were stronger predictors of mortality than doses derived from the universal thresholds of 20 and 25 mm Hg. The PRx could offer a method of individualizing the ICP threshold.

Intracranial Pressure Increases During Rewarming Period After Mild Therapeutic Hypothermia in Postcardiac Arrest Patients.

Elevation of intracranial pressure (ICP) may worsen brain injury and neurological outcome. Studies on the use of therapeutic hypothermia (TH) for traumatic brain injury suggests that rapid rewarming from TH is associated with elevated ICP and poorer outcomes. However, few studies describe the time course of ICP changes during TH/rewarming after cardiac arrest (CA). In this study, we observed the changes in ICP during mild TH and rewarming after CA. Secondarily, we examined whether ICP is related to outcome. We studied comatose patients resuscitated from CA, who were treated with TH and who had ICP monitored. Target core temperature was 34°C for 24 h and target rewarming rate was 0.25°C/h. ICP and cerebral perfusion pressure (CPP) were monitored during the period. Outcome was rated as cerebral performance category. In nine patients, ICP increased during TH and rewarming (6.0 [4.0-9.0] mmHg to 16.0 [12.0-26.0] mmHg, p = 0.008). CPP did not change during the period (83.3 [80.1-91.0] mmHg to 74.3 [52.0-87.3] mmHg). Higher ICP was associated with worse outcomes (p = 0.009). All the cases with ICP >25 mmHg or CPP <40 mmHg died. Major ICP increment was observed during the rewarming period, although, some increase of ICP occurred even during the mild TH. ICP increment was higher in patients with worse outcomes.

Intracranial pressure and outcome in critically ill patients with aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND: Evidences supporting the use of intracranial pressure (ICP) monitoring after aneurysmal subarachnoid hemorrhage (aSAH) are limited. The aim of our paper was to examine whether elevated intracranial pressure and ICP-derived variables predict mortality and functional outcomes after aSAH. EVIDENCE ACQUISITION: A systematic review of the literature was performed through PubMed and Cochrane databases up to June 2015. Population was restricted to aSAH patients requiring admission to the intensive care unit. ICP was included in the analysis as absolute value as well as variables derived from ICP monitoring (pressure reactivity index, ICP pulse wave amplitude, ICP-arterial blood pressure wave amplitude correlation and ICP variability). Outcomes included mortality, neurological recovery and delayed cerebral ischemia (DCI). Quality of evidence was rated using the GRADE system. EVIDENCE SYNTHESIS: Twenty-six studies were examined. Due to heterogeneity in qualifying studies, a meta-analysis could not be generated. We found a correlation between elevated ICP and mortality. However, ICP absolute values were not independent predictors of long-term functional outcomes (low quality of evidence). A variable relationship between elevated ICP and DCI was found (very low quality of evidence). ICP-derived variables had higher accuracy than ICP absolute values in predicting functional outcomes (moderate quality of evidence). CONCLUSIONS: Elevated ICP was associated with higher mortality however absolute ICP values per se were not independent predictors of functional recovery. Variables derived from ICP monitoring are more accurate than ICP absolute values in predicting outcome. Given the absence of good quality data, additional large studies may help to better define the prognostic value of ICP after aSAH.

An equiosmolar study on early intracranial physiology and long term outcome in severe traumatic brain injury comparing mannitol and hypertonic saline.

The impact of hypertonic saline (HTS) on long term control of intracranial hypertension (ICH) is yet to be established. The current prospective randomized controlled study was carried out in 38 patients with severe traumatic brain injury (TBI). Over 450 episodes of refractory ICH were treated with equiosmolar boluses of 20% mannitol in 20 patients and 3.0% HTS in 18 subjects. Intracranial pressure (ICP) was monitored for 6days. ICP and cerebral perfusion pressure (CPP) were comparable between the groups. The mannitol group had a progressive increase in the ICP over the study period (p=0.01). A similar increase was not seen in the HTS group (p=0.1). The percentage time for which the ICP remained below a threshold of 20 mmHg on day6 was higher in the HTS group (63% versus 49%; p=0.3). The duration of inotrope requirement in the HTS group was less compared to the mannitol group (p=0.06). The slope of fall in ICP in response to a bolus dose at a given baseline value of ICP was higher with HTS compared to mannitol (p=0.0001). In-hospital mortality tended to be lower in the HTS group (3 versus 10; p=0.07) while mortality at 6 months was not different between the groups (6 versus 10; p=0.41). Dichotomized Glasgow Outcome Scale scores at 6months were comparable between the groups (p=0.21). To conclude, immediate physiological advantages seen with HTS over mannitol did not translate into long term benefit on ICP/CPP control or mortality of patients with TBI.