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.

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.

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 .).

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.

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.

Emerging strategies for the treatment of patients with acute hepatic failure.

PURPOSE OF REVIEW: The objective of this article is to review the latest developments related to the treatment of patients with acute liver failure (ALF). RECENT FINDINGS: As the treatment of ALF has evolved, there is an increasing recognition regarding the risk of intracranial hypertension related to advanced hepatic encephalopathy. Therefore, there is an enhanced emphasis on neuromonitoring and therapies targeting intracranial hypertension. Also, new evidence implicates systemic proinflammatory cytokines as an etiology for the development of multiorgan system dysfunction in ALF; the recent finding of a survival benefit in ALF with high-volume plasmapheresis further supports this theory. SUMMARY: Advances in the critical care management of ALF have translated to a substantial decrease in mortality related to this disease process. The extrapolation of therapies from general neurocritical care to the treatment of ALF-induced intracranial hypertension has resulted in improved neurologic outcomes. In addition, recognition of the systemic inflammatory response and multiorgan dysfunction in ALF has guided current treatment recommendations, and will provide avenues for future research endeavors. With respect to extracorporeal liver support systems, further randomized studies are required to assess their efficacy in ALF, with attention to nonsurvival end points such as bridging to liver transplantation.

"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.

Current management of acute liver failure.

PURPOSE OF REVIEW: Acute liver failure (ALF) is a rare but life-threatening systemic disorder. Survival rates with or without emergency liver transplantation (ELT) are increasing. The benefit of ELT in some cases has been questioned and the potential for survival with medical management alone is changing our approach to the management of this disease. RECENT FINDINGS: Survival rates for all causes of ALF are increasing because of improvements in the care of the critically ill patient. A multifactorial approach involving support of respiratory, circulatory and renal function together with measures to avoid intracranial hypertension, metabolic disequilibrium and sepsis are required. For those who do not respond to these measures or specific antidotes, the selection methods for those likely to benefit from transplantation remain imperfect and novel methods based on the prediction of hepatic regeneration are required. For patients with ALF secondary to acetaminophen overdose, some experts believe a randomized controlled trial is required to find those most likely to benefit from ELT. SUMMARY: ALF remains a life-threatening condition with a high mortality rate requiring prompt support of multiorgan failure. Historical listing criteria for ELT are being questioned and improvement in medical management offers the option of continued improvements in transplant-free survival.

Update on acute liver failure.

PURPOSE OF REVIEW: Although advances in critical care management and liver transplantation have improved survival in acute liver failure (ALF), mortality remains significant. An evidence base to support management has been lacking, due to the condition's rarity, severity and heterogeneity. The purpose of this review is to critically appraise the latest evidence, updating clinicians on the current understanding of the best management. RECENT FINDINGS: Transplant-free survival in acetaminophen-related ALF has improved considerably, such that reconsidering thresholds for transplant is required, perhaps utilizing biomarkers of liver regeneration. Autoimmune hepatitis-related ALF may be too advanced to permit rescue with corticosteroids, which could be deleterious in the sickest patients. Acute kidney injury is commoner in ALF than previously suspected. Intracranial pressure monitoring does not appear to alter mortality. Despite altered traditional indices of coagulation, new thrombin generation assays suggest a rebalanced coagulation in liver failure. Antimicrobial prophylaxis may not be required in all patients. Liver support systems remain controversial and require further evaluation. SUMMARY: Traditional dogma in ALF management is questioned: transplant thresholds for acetaminophen overdose, steroid use in autoimmune ALF, routine antimicrobial prophylaxis, the coagulopathy of liver disease, the value of intracranial pressure monitoring and extracorporeal liver support.

Long-term outcome of severe herpes simplex encephalitis: a population-based observational study.

INTRODUCTION: Herpes simplex encephalitis (HSE) is a rare disease with a poor prognosis. No recent evaluation of hospital incidence, acute mortality and morbidity is available. In particular, decompressive craniectomy has rarely been proposed in cases of life-threatening HSE with temporal herniation, in the absence of evidence. This study aimed to assess the hospital incidence and mortality of HSE, and to evaluate the characteristics, management, the potential value of decompressive craniectomy and the outcome of patients with HSE admitted to intensive care units (ICUs). METHODS: Epidemiological study: we used the hospital medical and administrative discharge database to identify hospital stays, deaths and ICU admissions relating to HSE in 39 hospitals, from 2010 to 2013. Retrospective monocentric cohort: all patients with HSE admitted to the ICU of the university hospital during the study were included. The use of decompressive craniectomy and long-term outcome were analyzed. The initial brain images were analyzed blind to outcome. RESULTS: The hospital incidence of HSE was 1.2/100,000 inhabitants per year, 32 % of the patients were admitted to ICUs and 17 % were mechanically ventilated. Hospital mortality was 5.5 % overall, but was as high as 11.9 % in ICUs. In the monocentric cohort, 87 % of the patients were still alive after one year but half of them had moderate to severe disability. Three patients had a high intracranial pressure (ICP) with brain herniation and eventually underwent decompressive hemicraniectomy. The one-year outcome of these patients did not seem to be different from that of the other patients. It was not possible to predict brain herniation reliably from the initial brain images. CONCLUSIONS: HSE appears to be more frequent than historically reported. The high incidence we observed probably reflects improvements in diagnostic performance (routine use of PCR). Mortality during the acute phase and long-term disability appear to be stable. High ICP and brain herniation are rare, but must be monitored carefully, as initial brain imaging is not useful for identifying high-risk patients. Decompressive craniectomy may be a useful salvage procedure in cases of intractable high ICP.

Application of lumbar drainage in vasospasm after spontaneous subarachnoid hemorrhage and prevention of late cerebral infarction.

Cerebral vasospasm, especially delayed cerebral ischemia following subarachnoid hemorrhage (SAH) is the most important complication that effects mortality and morbidity of patients with intracranial aneurysms. The presence of cerebral vasospasm has been correlated with an increase in mortality in the first 2 weeks after SAH. Despite clinical studies and research, the etiopathogenesis of cerebral vasospasm is not understood exactly and there is not yet an effective therapy. The aim of our study was to investigate the effect of application of lumber drainage on vasospasm and delayed cerebral infarction following SAH and to examine the incidence of complications. Patient groups were determined by retrospective screening of 70 patients who underwent a surgical operation at the Osmangazi University Medical Faculty Department of Neurosurgery between 2009 and 2013 after a diagnosis of ruptured aneurysmal SAH. After the application of lumbar drainage, the complications and mortality after aneurysm surgery was significantly decreased and correlated with the amount of hemorrhagic cerebrospinal fluid drainage.

Randomized controlled trial comparing cerebral perfusion pressure-targeted therapy versus intracranial pressure-targeted therapy for raised intracranial pressure due to acute CNS infections in children.

OBJECTIVE: In children with acute CNS infection, management of raised intracranial pressure improves mortality and neuromorbidity. We compared cerebral perfusion pressure-targeted approach with the conventional intracranial pressure-targeted approach to treat raised intracranial pressure in these children. DESIGN: Prospective open-label randomized controlled trial. SETTING: PICU in a tertiary care academic institute. PATIENTS: Hundred ten children (1-12 yr) with acute CNS infections having raised intracranial pressure and a modified Glasgow Coma Scale score less than or equal to 8 were enrolled. INTERVENTIONS: Patients were randomized to receive either cerebral perfusion pressure-targeted therapy (n = 55) (maintaining cerebral perfusion pressure ≥ 60 mm Hg, using normal saline bolus and vasoactive therapy-dopamine, and if needed noradrenaline) or intracranial pressure-targeted therapy (n = 55) (maintaining intracranial pressure < 20 mm Hg using osmotherapy while ensuring normal blood pressure). The primary outcome was mortality up to 90 days after discharge from PICU. Secondary outcome was modified Glasgow Coma Scale score at 72 hours after enrollment, length of PICU stay, duration of mechanical ventilation, and hearing deficit and functional neurodisability at discharge and 90-day follow-up. MEASUREMENTS AND MAIN RESULTS: A 90-day mortality in intracranial pressure group (38.2%) was significantly higher than cerebral perfusion pressure group (18.2%; relative risk = 2.1; 95% CI, 1.09-4.04; p = 0.020). The cerebral perfusion pressure group in comparison with intracranial pressure group had significantly higher median (interquartile range) modified Glasgow Coma Scale score at 72 hours (10 [8-11] vs 7 [4-9], p < 0.001), shorter length of PICU stay (13 d [10.8-15.2 d] vs. 18 d [14.5-21.5 d], p = 0.002) and mechanical ventilation (7.5 d [5.4-9.6 d] vs. 11.5 d [9.5-13.5 d], p = 0.003), lower prevalence of hearing deficit (8.9% vs 37.1%; relative risk = 0.69; 95% CI, 0.53-0.90; p = 0.005), and neurodisability at discharge from PICU (53.3% vs. 82.9%; relative risk = 0.37; 95% CI, 0.17-0.81; p = 0.005) and 90 days after discharge (37.8% vs. 70.6%; relative risk = 0.47; 95% CI, 0.27-0.83; p = 0.004). CONCLUSION: Cerebral perfusion pressure-targeted therapy, which relied on more frequent use of vasopressors and lesser use of hyperventilation and osmotherapy, was superior to intracranial pressure-targeted therapy for management of raised intracranial pressure in children with acute CNS infection in reducing mortality and morbidity.

Outcomes and complications of intracranial pressure monitoring in acute liver failure: a retrospective cohort study.

OBJECTIVE: To determine if intracranial pressure monitor placement in patients with acute liver failure is associated with significant clinical outcomes. DESIGN: Retrospective multicenter cohort study. SETTING: Academic liver transplant centers comprising the U.S. Acute Liver Failure Study Group. PATIENTS: Adult critically ill patients with acute liver failure presenting with grade III/IV hepatic encephalopathy (n = 629) prospectively enrolled between March 2004 and August 2011. INTERVENTION: Intracranial pressure monitored (n = 140) versus nonmonitored controls (n = 489). MEASUREMENTS AND MAIN RESULTS: Intracranial pressure monitored patients were younger than controls (35 vs 43 yr, p < 0.001) and more likely to be on renal replacement therapy (52% vs 38%, p = 0.003). Of 87 intracranial pressure monitored patients with detailed information, 44 (51%) had evidence of intracranial hypertension (intracranial pressure > 25 mm Hg) and overall 21-day mortality was higher in patients with intracranial hypertension (43% vs 23%, p = 0.05). During the first 7 days, intracranial pressure monitored patients received more intracranial hypertension-directed therapies (mannitol, 56% vs 21%; hypertonic saline, 14% vs 7%; hypothermia, 24% vs 10%; p < 0.03 for each). Forty-one percent of intracranial pressure monitored patients received liver transplant (vs 18% controls; p < 0.001). Overall 21-day mortality was similar (intracranial pressure monitored 33% vs controls 38%, p = 0.24). Where data were available, hemorrhagic complications were rare in intracranial pressure monitored patients (4 of 56 [7%]; three died). When stratifying by acetaminophen status and adjusting for confounders, intracranial pressure monitor placement did not impact 21-day mortality in acetaminophen patients (p = 0.89). However, intracranial pressure monitor was associated with increased 21-day mortality in nonacetaminophen patients (odds ratio, ~ 3.04; p = 0.014). CONCLUSIONS: In intracranial pressure monitored patients with acute liver failure, intracranial hypertension is commonly observed. The use of intracranial pressure monitor in acetaminophen acute liver failure did not confer a significant 21-day mortality benefit, whereas in nonacetaminophen acute liver failure, it may be associated with worse outcomes. Hemorrhagic complications from intracranial pressure monitor placement were uncommon and cannot account for mortality trends. Although our results cannot conclusively confirm or refute the utility of intracranial pressure monitoring in patients with acute liver failure, patient selection and ancillary assessments of cerebral blood flow likely have a significant role. Prospective studies would be required to conclusively account for confounding by illness severity and transplant.

Economic evaluation of decompressive craniectomy versus barbiturate coma for refractory intracranial hypertension following traumatic brain injury.

OBJECTIVES: Decompressive craniectomy and barbiturate coma are often used as second-tier strategies when intracranial hypertension following severe traumatic brain injury is refractory to first-line treatments. Uncertainty surrounds the decision to choose either treatment option. We investigated which strategy is more economically attractive in this context. DESIGN: We performed a cost-utility analysis. A Markov Monte Carlo microsimulation model with a life-long time horizon was created to compare quality-adjusted survival and cost of the two treatment strategies, from the perspective of healthcare payer. Model parameters were estimated from the literature. Two-dimensional simulation was used to incorporate parameter uncertainty into the model. Value of information analysis was conducted to identify major drivers of decision uncertainty and focus future research. SETTING: Trauma centers in the United States. SUBJECTS: Base case was a population of patients (mean age = 25 yr) who developed refractory intracranial hypertension following traumatic brain injury. INTERVENTIONS: We compared two treatment strategies: decompressive craniectomy and barbiturate coma. MEASUREMENTS AND MAIN RESULTS: Decompressive craniectomy was associated with an average gain of 1.5 quality-adjusted life years relative to barbiturate coma, with an incremental cost-effectiveness ratio of $9,565/quality-adjusted life year gained. Decompressive craniectomy resulted in a greater quality-adjusted life expectancy 86% of the time and was more cost-effective than barbiturate coma in 78% of cases if our willingness-to-pay threshold is $50,000/quality-adjusted life year and 82% of cases at a threshold of $100,000/quality-adjusted life year. At older age, decompressive craniectomy continued to increase survival but at higher cost (incremental cost-effectiveness ratio = $197,906/quality-adjusted life year at mean age = 85 yr). CONCLUSIONS: Based on available evidence, decompressive craniectomy for the treatment of refractory intracranial hypertension following traumatic brain injury provides better value in terms of costs and health gains than barbiturate coma. However, decompressive craniectomy might be less economically attractive for older patients. Further research, particularly on natural history of severe traumatic brain injury patients, is needed to make more informed treatment decisions.

Neurocritical care: why does it make a difference?

PURPOSE OF REVIEW: The care of critically ill brain-injured patients is complex and requires careful balancing of cerebral and systemic treatment priorities. A growing number of studies have reported improved outcomes when patients are admitted to dedicated neurocritical care units (NCCUs). The reasons for this observation have not been definitively clarified. RECENT FINDINGS: When recently published articles are combined with older literature, there have been more than 40 000 patients assessed in observational studies that compare neurological and general ICUs. Although results are heterogeneous, admission to NCCUs is associated with lower mortality and a greater chance of favorable recovery. These findings are remarkable considering that there are few interventions in neurocritical care that have been demonstrated to be efficacious in randomized trials. Whether the relationship is causal is still being elucidated but potential explanations include higher patient volume and, in turn, greater clinician experience; more emphasis on and adherence to protocols to avoid secondary brain injury; practice differences related to prognostication and withdrawal of life-sustaining interventions; and differences in the use and interpretation of neuroimaging and neuromonitoring data. SUMMARY: Neurocritical care is an evolving field that is associated with improvements in outcomes over the past decade. Further research is required to determine how monitoring and treatment protocols can be optimized.

Effect of prolonged therapeutic hypothermia on intracranial pressure, organ function, and hospital outcomes among patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: Global cerebral edema (GCE) with subsequent refractory intracranial hypertension complicates some cases of aneurysmal subarachnoid hemorrhage (aSAH), and typically is associated with poorer outcome. Treatment options for refractory intracranial pressure (ICP) cases are limited to decompressive hemicraniectomy (DHC) and targeted temperature management (TTM) with induced hypothermia (32-34 °C). No outcomes comparison between patients treated with either or both forms of refractory ICP therapy exists, and data on the effect of prolonged hypothermia on ICP and organ function among patients with aSAH are limited. METHODS: This is a retrospective study of aSAH patients who underwent DHC and/or prolonged hypothermia (greater than 48 h) for refractory ICP (i.e., ICP >20 mmHg after osmotherapy) in the intensive care unit of a single, tertiary-care academic center. RESULTS: Nineteen individuals with aSAH underwent TTM with or without DHC; sixteen patients underwent DHC alone. The patients in TTM group were younger (median age 44 years) than the DHC without TTM population (median age 60 years). TTM was started on median day 2 with a median duration of 7 days. There were no significant group differences in survival to discharge (59 % vs. 69 %) or in the mean modified Rankin score on follow-up (3.6 vs. 3.7), despite the TTM group having longer hospital length of stay (24 vs. 19 days, p = 0.03), longer duration of mechanical ventilation (20 vs. 9 days, p = 0.04), a higher cumulative fluid balance (12.8 vs. 5.1 L, p = 0.01), and higher APACHEII scores. The median maximal ICP decreased from 23.5 to 21 mmHg within 24 h of hypothermia initiation. There were no significant differences in other markers of end-organ function (respiratory, hematologic, renal, liver, and cardiac), infection rate, or adverse events between groups. CONCLUSIONS: Use of prolonged TTM among aSAH patients with GCE and refractory ICP elevations is associated with a longer duration of mechanical ventilation but is not different in terms of neurological outcomes measured by modified Rankin score or organ function outcomes compared to patients who received DHC alone.