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Neurocritical Care Jun 2020Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding...
BACKGROUND
Acute treatment of cerebral edema and elevated intracranial pressure is a common issue in patients with neurological injury. Practical recommendations regarding selection and monitoring of therapies for initial management of cerebral edema for optimal efficacy and safety are generally lacking. This guideline evaluates the role of hyperosmolar agents (mannitol, HTS), corticosteroids, and selected non-pharmacologic therapies in the acute treatment of cerebral edema. Clinicians must be able to select appropriate therapies for initial cerebral edema management based on available evidence while balancing efficacy and safety.
METHODS
The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacy to create a panel in 2017. The group generated 16 clinical questions related to initial management of cerebral edema in various neurological insults using the PICO format. A research librarian executed a comprehensive literature search through July 2018. The panel screened the identified articles for inclusion related to each specific PICO question and abstracted necessary information for pertinent publications. The panel used GRADE methodology to categorize the quality of evidence as high, moderate, low, or very low based on their confidence that the findings of each publication approximate the true effect of the therapy.
RESULTS
The panel generated recommendations regarding initial management of cerebral edema in neurocritical care patients with subarachnoid hemorrhage, traumatic brain injury, acute ischemic stroke, intracerebral hemorrhage, bacterial meningitis, and hepatic encephalopathy.
CONCLUSION
The available evidence suggests hyperosmolar therapy may be helpful in reducing ICP elevations or cerebral edema in patients with SAH, TBI, AIS, ICH, and HE, although neurological outcomes do not appear to be affected. Corticosteroids appear to be helpful in reducing cerebral edema in patients with bacterial meningitis, but not ICH. Differences in therapeutic response and safety may exist between HTS and mannitol. The use of these agents in these critical clinical situations merits close monitoring for adverse effects. There is a dire need for high-quality research to better inform clinicians of the best options for individualized care of patients with cerebral edema.
Topics: Brain Edema; Brain Injuries, Traumatic; Cerebral Hemorrhage; Cerebrospinal Fluid Shunts; Critical Care; Diuretics, Osmotic; Emergency Medical Services; Glucocorticoids; Hepatic Encephalopathy; Humans; Intracranial Hypertension; Ischemic Stroke; Mannitol; Meningitis, Bacterial; Patient Positioning; Saline Solution, Hypertonic; Societies, Medical; Subarachnoid Hemorrhage
PubMed: 32227294
DOI: 10.1007/s12028-020-00959-7 -
Journal of Anesthesia Oct 2020Intracranial hypertension (IH) is a clinical condition commonly encountered in the intensive care unit, which requires immediate treatment. The maintenance of normal... (Review)
Review
Intracranial hypertension (IH) is a clinical condition commonly encountered in the intensive care unit, which requires immediate treatment. The maintenance of normal intracranial pressure (ICP) and cerebral perfusion pressure in order to prevent secondary brain injury (SBI) is the central focus of management. SBI can be detected through clinical examination and invasive and non-invasive ICP monitoring. Progress in monitoring and understanding the pathophysiological mechanisms of IH allows the implementation of targeted interventions in order to improve the outcome of these patients. Initially, general prophylactic measures such as patient's head elevation, fever control, adequate analgesia and sedation depth should be applied immediately to all patients with suspected IH. Based on specific indications and conditions, surgical resection of mass lesions and cerebrospinal fluid drainage should be considered as an initial treatment for lowering ICP. Hyperosmolar therapy (mannitol or hypertonic saline) represents the cornerstone of medical treatment of acute IH while hyperventilation should be limited to emergency management of life-threatening raised ICP. Therapeutic hypothermia could have a possible benefit on outcome. To control elevated ICP refractory to maximum standard medical and surgical treatment, at first, high-dose barbiturate administration and then decompressive craniectomy as a last step are recommended with unclear and probable benefit on outcomes, respectively. The therapeutic strategy should be based on a staircase approach and be individualized for each patient. Since most therapeutic interventions have an uncertain effect on neurological outcome and mortality, future research should focus on both studying the long-term benefits of current strategies and developing new ones.
Topics: Brain Injuries; Humans; Intensive Care Units; Intracranial Hypertension; Intracranial Pressure; Mannitol; Saline Solution, Hypertonic
PubMed: 32440802
DOI: 10.1007/s00540-020-02795-7 -
Medicine Aug 2020To compare the effects of 3% hypertonic saline solution and 20% mannitol solution on intracranial hypertension. (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
To compare the effects of 3% hypertonic saline solution and 20% mannitol solution on intracranial hypertension.
METHODS
WAN-FANGDATA, CNKI, and CQVIP databases were searched, and relevant literatures of randomized controlled trials comparing 3% hypertonic saline solution with mannitol in reducing intracranial hypertension from 2010 to October 2019 were collected. Meta-analysis was performed using RevMan software.
RESULTS
As a result, 10 articles that met the inclusion criteria were finally included. A total of 544 patients were enrolled in the study, 270 in the hypertonic saline group and 274 in the mannitol group. There was no significant difference in the decrease of intracranial pressure and the onset time of drug between the 2 groups after intervention (all P > .05). There was a statistically significant difference between the hypertonic saline group and the mannitol group in terms of duration of effect in reducing intracranial pressure (95% confidence interval: 0.64-1.05, Z = 8.09, P < .00001) and cerebral perfusion pressure after intervention (95% confidence interval: 0.15-0.92, Z = 2.72, P = .007).
CONCLUSION
Both 3% hypertonic saline and mannitol can effectively reduce intracranial pressure, but 3% hypertonic saline has a more sustained effect on intracranial pressure and can effectively increase cerebral perfusion pressure.
Topics: Brain Injuries, Traumatic; Diuretics, Osmotic; Humans; Intracranial Hypertension; Intracranial Pressure; Mannitol; Saline Solution, Hypertonic
PubMed: 32871879
DOI: 10.1097/MD.0000000000021655 -
Journal of Intensive Care Medicine Jul 2023Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet its initial detection remains difficult... (Review)
Review
Acutely elevated intracranial pressure (ICP) may have devastating effects on patient mortality and neurologic outcomes, yet its initial detection remains difficult because of the variety of manifestations that it can cause disease states it is associated with. Several treatment guidelines exist for specific disease processes such as trauma or ischemic stroke, but their recommendations may not apply to other causes. In the acute setting, management decisions must often be made before the underlying cause is known. In this review, we present an organized, evidence-based approach to the recognition and management of patients with suspected or confirmed elevated ICP in the first minutes to hours of resuscitation. We explore the utility of invasive and noninvasive methods of diagnosis, including history, physical examination, imaging, and ICP monitors. We synthesize various guidelines and expert recommendations and identify core management principles including noninvasive maneuvers, neuroprotective intubation and ventilation strategies, and pharmacologic therapies such as ketamine, lidocaine, corticosteroids, and the hyperosmolar agents mannitol and hypertonic saline. Although an in-depth discussion of the definitive management of each etiology is beyond the scope of this review, our goal is to provide an empirical approach to these time-sensitive, critical presentations in their initial stages.
Topics: Humans; Mannitol; Intracranial Hypertension; Brain Injuries, Traumatic; Brain Injuries; Saline Solution, Hypertonic; Intracranial Pressure
PubMed: 36802976
DOI: 10.1177/08850666231156589 -
Frontiers in Endocrinology 2022In standard 52-week phase III clinical trials, once weekly lonapegsomatropin, somatrogon and somapacitan have been found to yield non-inferior height velocities and... (Review)
Review
In standard 52-week phase III clinical trials, once weekly lonapegsomatropin, somatrogon and somapacitan have been found to yield non-inferior height velocities and similar safety profiles to daily GH (DGH) in children with pediatric growth hormone deficiency (PGHD). Lonapegsomatropin, a long-acting GH therapy (LAGH), was approved by the United States Food and Drug Administration (FDA) in August 2021 for the treatment of PGHD and has also been approved in other regions of the world. Somatrogon was approved for the treatment of PGHD beginning in some regions beginning in late 2021. Somapacitan was approved by the FDA for the treatment of Adult GHD in August 2020. The phase III clinical trial of somapacitan for the treatment of PGHD has been completed and demonstrated non-inferiority of somapacitan to DGH. New LAGH products may improve patient adherence, quality of life and clinical outcomes, particularly in patients with poor adherence to daily GH injections in the future. With the availability of new LAGH products, clinicians will need to identify the best candidates for LAGH therapy and understand how to monitor and adjust therapy. Long-term surveillance studies are needed to demonstrate adherence, efficacy, cost-effectiveness and safety of LAGH preparations and to understand how the non-physiological pharmacokinetic and pharmacodynamic profiles following administration of each LAGH product relate to short- and long-term safety and efficacy of LAGH therapy.
Topics: Adult; Child; Dwarfism, Pituitary; Growth Hormone; Histidine; Human Growth Hormone; Humans; Mannitol; Phenol; Quality of Life; United States
PubMed: 36072938
DOI: 10.3389/fendo.2022.980979 -
Neurosurgery Feb 2020Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect... (Comparative Study)
Comparative Study
Hypertonic Saline is Superior to Mannitol for the Combined Effect on Intracranial Pressure and Cerebral Perfusion Pressure Burdens in Patients With Severe Traumatic Brain Injury.
BACKGROUND
Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect on the cerebral perfusion pressure (CPP) and ICP has not been studied rigorously.
OBJECTIVE
To determine the difference in effects of HTS and mannitol on the combined burden of high ICP and low CPP in patients with severe TBI.
METHODS
We performed a case-control study using prospectively collected data from the New York State TBI-trac® database (Brain Trauma Foundation, New York, New York). Patients who received only 1 hyperosmotic agent, either mannitol or HTS for raised ICP, were included. Patients in the 2 groups were matched (1:1 and 1:2) for factors associated with 2-wk mortality: age, Glasgow Coma Scale score, pupillary reactivity, hypotension, abnormal computed tomography scans, and craniotomy. Primary endpoint was the combined burden of ICPhigh (> 25 mm Hg) and CPPlow (< 60 mm Hg).
RESULTS
There were 25 matched pairs for 1:1 comparison and 24 HTS patients matched to 48 mannitol patients in 1:2 comparisons. Cumulative median osmolar doses in the 2 groups were similar. In patients treated with HTS compared to mannitol, total number of days (0.6 ± 0.8 vs 2.4 ± 2.3 d, P < .01), percentage of days with (8.8 ± 10.6 vs 28.1 ± 26.9%, P < .01), and the total duration of ICPhigh + CPPlow (11.12 ± 14.11 vs 30.56 ± 31.89 h, P = .01) were significantly lower. These results were replicated in the 1:2 match comparisons.
CONCLUSION
HTS bolus therapy appears to be superior to mannitol in reduction of the combined burden of intracranial hypertension and associated hypoperfusion in severe TBI patients.
Topics: Adolescent; Adult; Brain Injuries, Traumatic; Case-Control Studies; Cerebrovascular Circulation; Diuretics, Osmotic; Female; Glasgow Coma Scale; Humans; Intracranial Hypertension; Intracranial Pressure; Male; Mannitol; Middle Aged; Prospective Studies; Saline Solution, Hypertonic; Treatment Outcome; Young Adult
PubMed: 30877299
DOI: 10.1093/neuros/nyz046 -
Journal of Neurotrauma Jul 2023Increased intracranial pressure (ICP) is one of the most important modifiable and immediate threats to critically ill patients suffering from traumatic brain injury...
Increased intracranial pressure (ICP) is one of the most important modifiable and immediate threats to critically ill patients suffering from traumatic brain injury (TBI). Two hyperosmolar agents (HOAs), mannitol and hypertonic saline (HTS), are routinely used in clinical practice to treat increased ICP. We aimed to assess whether a preference for mannitol, HTS, or their combined use translated into differences in outcome. The Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study is a prospective multi-center cohort study. For this study, patients with TBI, admitted to the intensive care unit (ICU), treated with mannitol and/or HTS, and aged ≥16 years were included. Patients and centers were differentiated based on treatment preference with mannitol and/or HTS based on structured, data-driven criteria such as first administered HOA in the ICU. We assessed influence of center and patient characteristics in the choice of agent using adjusted multi-variate models. Further, we assessed the influence of HOA preference on outcome using adjusted ordinal and logistic regression models, and instrumental variable analyses. In total, 2056 patients were assessed. Of these, 502 (24%) patients received mannitol and/or HTS in the ICU. The first received HOA was HTS for 287 (57%) patients, mannitol for 149 (30%) patients, or both mannitol and HTS on the same day for 66 (13%) patients. Two unreactive pupils were more common in patients receiving both (13, 21%), compared with patients receiving HTS (40, 14%) or mannitol (22, 16%). Center, rather than patient characteristics, was independently associated with the preferred choice of HOA (-value <0.05). ICU mortality and 6-month outcome were similar between patients preferably treated with mannitol compared with HTS (odds ratio [OR] = 1.0, confidence interval [CI] = 0.4-2.2; OR = 0.9, CI = 0.5-1.6, respectively). Patients who received both also had a similar ICU mortality and 6-month outcome compared with patients receiving HTS (OR = 1.8, CI = 0.7-5.0; OR = 0.6, CI = 0.3-1.7, respectively). We found between-center variability regarding HOA preference. Moreover, we found that center is a more important driver of the choice of HOA than patient characteristics. However, our study indicates that this variability is an acceptable practice given absence of differences in outcomes associated with a specific HOA.
Topics: Humans; Mannitol; Cohort Studies; Prospective Studies; Brain Injuries, Traumatic; Saline Solution, Hypertonic; Intracranial Hypertension; Intracranial Pressure
PubMed: 37014076
DOI: 10.1089/neu.2022.0465 -
JAMA Network Open Mar 2022Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited...
IMPORTANCE
Hyperosmolar agents are cornerstone therapies for pediatric severe traumatic brain injury. Guideline recommendations for 3% hypertonic saline (HTS) are based on limited numbers of patients, and no study to date has supported a recommendation for mannitol.
OBJECTIVES
To characterize current use of hyperosmolar agents in pediatric severe traumatic brain injury and assess whether HTS or mannitol is associated with greater decreases in intracranial pressure (ICP) and/or increases in cerebral perfusion pressure (CPP).
DESIGN, SETTING, AND PARTICIPANTS
In this comparative effectiveness research study, 1018 children were screened and 18 were excluded; 787 children received some form of hyperosmolar therapy during the ICP-directed phase of care, with 521 receiving a bolus. Three of these children were excluded because they had received only bolus administration of both HTS and mannitol in the same hour, leaving 518 children (at 44 clinical sites in 8 countries) for analysis. The study was conducted from February 1, 2014, to September 31, 2017, with follow-up for 1 week after injury. Final analysis was performed July 20, 2021.
INTERVENTIONS
Boluses of HTS and mannitol were administered.
MAIN OUTCOMES AND MEASURES
Data on ICP and CPP were collected before and after medication administration. Statistical methods included linear mixed models and corrections for potential confounding variables to compare the 2 treatments.
RESULTS
A total of 518 children (mean [SD] age, 7.6 [5.4] years; 336 [64.9%] male; 274 [52.9%] White) were included. Participants' mean (SD) Glasgow Coma Scale score was 5.2 (1.8). Bolus HTS was observed to decrease ICP and increase CPP (mean [SD] ICP, 1.03 [6.77] mm Hg; P < .001; mean [SD] CPP, 1.25 [12.47] mm Hg; P < .001), whereas mannitol was observed to increase CPP (mean [SD] CPP, 1.20 [11.43] mm Hg; P = .009). In the primary outcome, HTS was associated with a greater reduction in ICP compared with mannitol (unadjusted β, -0.85; 95% CI, -1.53 to -0.19), but no association was seen after adjustments (adjusted β, -0.53; 95% CI, -1.32 to 0.25; P = .18). No differences in CPP were observed. When ICP was greater than 20 mm Hg, greater than 25 mm Hg, or greater than 30 mm Hg, HTS outperformed mannitol for each threshold in observed ICP reduction (>20 mm Hg: unadjusted β, -2.51; 95% CI, -3.86 to -1.15, P < .001; >25 mm Hg: unadjusted β, -3.88; 95% CI, -5.69 to -2.06, P < .001; >30 mm Hg: unadjusted β, -4.07; 95% CI, -6.35 to -1.79, P < .001), with results remaining significant for ICP greater than 25 mm Hg in adjusted analysis.
CONCLUSIONS AND RELEVANCE
In this comparative effectiveness research study, bolus HTS was associated with lower ICP and higher CPP, whereas mannitol was associated only with higher CPP. After adjustment for confounders, both therapies showed no association with ICP and CPP. During ICP crises, HTS was associated with better performance than mannitol.
Topics: Brain Injuries, Traumatic; Child; Female; Humans; Intracranial Hypertension; Intracranial Pressure; Male; Mannitol; Saline Solution, Hypertonic
PubMed: 35267036
DOI: 10.1001/jamanetworkopen.2022.0891 -
Medicine Sep 2020Mannitol and hypertonic saline (HTS) are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their efficacy on the ICP... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Mannitol and hypertonic saline (HTS) are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their efficacy on the ICP has not been evaluated rigorously.
OBJECTIVE
To evaluate the efficacy of repeated bolus dosing of HTS and mannitol in similar osmotic burdens to treat intracranial hypertension (ICH) in patients with severe TBI.
METHODS
The authors used an alternating treatment protocol to evaluate the efficacy of HTS with that of mannitol given for ICH episodes in patients treated for severe TBI at their hospital during 2017 to 2019. Doses of similar osmotic burdens (20% mannitol, 2 ml/kg, or 10% HTS, 0.63 ml/kg, administered as a bolus via a central venous catheter, infused over 15 minutes) were given alternately to the individual patient with severe TBI during ICH episodes. The choice of osmotic agents for the treatment of the initial ICH episode was determined on a randomized basis; osmotic agents were alternated for every subsequent ICH episode in each individual patient. intracranial pressure (ICP), mean arterial pressure (MAP), and cerebral perfusion pressure (CPP) were continuously monitored between the beginning of each osmotherapy and the return of ICP to 20 mm Hg. The duration of the effect of ICP reduction (between the beginning of osmotherapy and the return of ICP to 20 mm Hg), the maximum reduction of ICP and its time was recorded after each dose. Serum sodium and plasma osmolality were measured before, 0.5 hours and 3 hours after each dose. Adverse effects such as central pontine myelinolysis (CPM), severe fluctuations of serum sodium and plasma osmolality were assessed to evaluate the safety of repeated dosing of HTS and mannitol.
RESULTS
Eighty three patients with severe TBI were assessed, including 437 ICH episodes, receiving 236 doses of HTS and 221 doses of mannitol totally. There was no significant difference between equimolar HTS and mannitol boluses on the magnitude of ICP reduction, the duration of effect, and the time to lowest ICP achieved (P > .05). The proportion of efficacious boluses was higher for HTS than for mannitol (P = .016), as was the increase in serum sodium (P = .038). The serum osmolality increased immediately after osmotherapy with a significant difference (P = .017). No cases of CPM were detected.
CONCLUSION
Repeat bolus dosing of 10% HTS and 20% mannitol appears to be significantly and similarly effective for treating ICH in patients with severe TBI. The proportion of efficacious doses of HTS on ICP reduction may be higher than mannitol.
Topics: Adult; Brain Injuries, Traumatic; Cerebrovascular Circulation; Diuretics, Osmotic; Female; Humans; Intracranial Hypertension; Intracranial Pressure; Male; Mannitol; Middle Aged; Saline Solution, Hypertonic; Trauma Severity Indices
PubMed: 32957318
DOI: 10.1097/MD.0000000000022004