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Use of hypertonic saline (3% NaCl) in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric head injured patients
Abstract
Background: Hyperosmolar therapy is widely used to treat traumatic intracranial hypertension, with mannitol as the mainstay of therapy. Its adverse effects on hemodynamics and renal function, as well as the "rebound̊ rise in intracranial pressure (ICP) observed after withdrawal or with prolonged use make it a less-than-optimal agent. Hypertonic saline has recently been introduced as a new hyperosmolar treatment for intracranial hypertension and cerebral edema in critical care units. Methods: The data for this descriptive study was collected prospectively. Subjects were entered as part of a compassionate use protocol after failing conventional therapy and barbiturate coma for control of elevated intracranial pressure. Parental consent was obtained for all subjects. Ten children (3 months to 12 years) with seven head injuries (Glasgow Coma Score 3-7) were entered into the study. Inclusion criteria included persistently elevated ICP > 20mmHg despite aggressive treatment tiling head elevation, paralysis and hyperventilation (pCo2 30-35mmHg), mannitol (serum osmolarities 315-320 mOsm/l), external ventricular drainage (4patients), and thiopental sodium. A continuous infusion of 3% saline on a "sliding scale" was used to achieve a target serum sodium level, which was adjusted to maintain ICP less, than 20 mmHg once the conventional therapy and barbiturate coma as outlined above failed to control intracranial hypertension. Serum sodium, osmolarity, ICP, MAP, CPP, and pCO2 were recorded as 6-hour intervals. If the patient had external ventricular drainage (4 patients), total daily CSF drainage was recorded. The total number of ICP "spikes" (>20 mmHg) were recorded for each 6 hour interval. Data was analyzed using chi square analysis and multivariate linear regression. Results: A significant decrease in ICP from pretrial baseline (mean 24 mmHg ± 5) was observed at 12 hours (mean 15 mmHg ±5) (p < 0.01) and 24 hours (mean11 mmHg ±6) (p < 0.01). A significant decrease in the number of ICP spikes per 6-hour period from pretrial baseline (mean 3 ICP spikes per 6 hour) was observed by Trial Day #2 (mean 1 ICP spike per 6 hour) (p < 0.01). Average protocol duration was 16 days. Mean serum sodium was 162 mEq/l ± 7 (range 140-187 mEq / l) and mean serum osmolarity was 347 mOsm/l ± 24 (range 315-407 mMol / l). Renal failure developed in two patients during episodes of sepsis and systemic inflammatory response syndrome (SIRS); both patients recovered full renal function before discharge from the hospital. Mean serum creatinine in eight patients who did not develop renal failure was 0.63±0.23 (mean±SD). Nine patients (90%) survived with average Glasgow outcome score of 4. Conclusion: Hypertonic saline appears to be promising adjunctive therapy to the treatment of traumatic intracranial hypertension. Hypernatremia and hyperosmolarity are safely tolerated in brain injured pediatric patients. Controlled trials are needed prior to recommendation of widespread use.
... One of the widely used strategies to reduce intracranial pressure (ICP) and maintain adequate CBF in pediatric neurotrauma includes osmotic therapy with mannitol (0.25- 1 gm/kg) and 3% saline (0.1-1 mL/kg/hr) [3,6]. Although the use of 3% saline has been well described in pediatric TBI patients789, the use of 23.4% saline in children with severe TBI has not. Two cases of severe TBI in children with intracranial hypertension, in whom multiple boluses of 23.4% saline were administered to effectively lower ICP, are presented. ...
... The possible adverse effects from the use of 3% or 23.4% saline mostly occur as a consequence of the acute hyperosmolar state. These include renal failure and early renal insufficiency [8,17], acute heart failure, and pulmonary edema from rapid volume expansion, and theoretical worsening of cerebral edema or " reverse osmosis " phenomenon with a disrupted blood brain barrier. Furthermore, prolonged use of hypertonic saline may allow the cerebral homeostatic mechanism to equilibrate the osmotic gradient, resulting in hypothetical rebound edema and intracranial hypertension if hypertonic saline is discontinued abruptly. ...
The safety and efficacy of osmotic therapy with mannitol and 3% saline in the pediatric head-injured population has been widely reported; the use of 23.4% saline in children for the treatment of refractory intracranial hypertension has not. The clinical and physiologic responses of multiple 23.4% saline boluses in two children with severe traumatic brain injury (TBI) are presented. No complications were associated with the use of 23.4% saline in either patient.
... Importantly, the mechanisms underlying the pathogenesis that lead to such disabilities are still incompletely understood [15,16]. Therefore, while the post-TBI central nervous system (CNS) illnesses have a high prevalence [17]; few, if any, treatments are available to deter and prevent the pathological progression thought to lead to chronic neurological diseases and conditions [18][19][20][21]. Thus, a better understanding of the molecular mechanisms underlying TBI and neurological diseases is crucial to uncover the potential link between these conditions to enable development of effective diagnostic and treatment strategies which could reduce the incidence of post-TBI neurological complications. ...
Traumatic brain injury is among the most common causes of death and disability in youth and young adults. In addition to the acute risk of morbidity with moderate to severe injuries, traumatic brain injury is associated with a number of chronic neurological and neuropsychiatric sequelae including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. However, despite the high incidence of traumatic brain injuries and the established clinical correlation with neurodegeneration, the causative factors linking these processes have not yet been fully elucidated. Apart from removal from activity, few, if any prophylactic treatments against post-traumatic brain injury neurodegeneration exist. Therefore, it is imperative to understand the pathophysiological mechanisms of traumatic brain injury and neurodegeneration in order to identify potential factors that initiate neurodegenerative processes. Oxidative stress, neuroinflammation, and glutamatergic excitotoxicity have previously b
... [6] The use of infusions of 3% HS (Na+ = 514 mEq/L) and sustained hypernatremia and hyperosmolality is safely tolerated in pediatric patients with traumatic brain injury. [7] However, malignant edema formation late in the course of intracerebral hemorrhage after prolonged administration of HS may occur possibly due to a rebound phenomenon of hyperosmolar therapy. [8] Other recognized adverse effects of supra‑physiologic hyperosmolality include renal failure, pulmonary edema, or central pontine demyelination. ...
A previously healthy 1-year-old child with a traumatic acute subdural hemorrhage received 10 times higher dose of hypertonic saline inadvertently immediately before surgery. This case report describes deviations in fluid management needed to alleviate salt toxicity and its adverse effects during surgery under anesthesia perioperatively. The child made an uneventful recovery with no evident residual damage at follow-up. © 2017 Journal of Pediatric Neurosciences | Published by Wolters Kluwer - Medknow.
... Specifically, no patients suffered from severe hypernatremia during the whole period of infusion. According to previous studies, continuous infusion of 3% HS in traumatic brain injury patients decreased ICP but induced severe hypernatremia, which reached 180 mmol/L, resulting in neurological complications and renal failure [25,26] . Continuous furosemide infusion leads to a marked decrease in Na+ reabsorption from the thick ascending limb of the renal medulla, resulting in the low incidence of hypernatremia observed in our study. ...
Background:
Elevated intracranial pressure is one of the most common problems in patients with diverse intracranial disorders, leading to increased morbidity and mortality. Effective management for increased intracranial pressure is based mainly on surgical and medical techniques with hyperosmolar therapy as one of the core medical treatments. The study aimed to explore the effects of continuous micro-pump infusions of 3% hypertonic saline combined with furosemide on intracranial pressure control.
Material and methods:
We analyzed data on 56 eligible participants with intracranial pressure >20 mmHg from March 2013 to July 2014. The target was to increase and maintain plasma sodium to a level between 145 and 155 mmol/L and osmolarity to a level of 310 to 320 mOsmol/kg.
Results:
Plasma sodium levels significantly increased from 138±5 mmol/L at admission to 151±3 mmol/L at 24 h (P<0.01). Osmolarity increased from 282±11 mOsmol/kg at baseline to 311±8 mOsmol/kg at 24 h (P<0.01). Intracranial pressure significantly decreased from 32±7 mmHg to 15±6 mmHg at 24 h (P<0.01). There was a significant improvement in CPP (P<0.01). Moreover, central venous pressure, mean arterial pressure, and Glasgow Coma Scale slightly increased. However, these changes were not statistically significant.
Conclusions:
Continuous infusion of 3% hypertonic saline + furosemide is effective and safe for intracranial pressure control.
... Administration of HTS or mannitol increases serum sodium concentration or osmolality and decreases ICP and brain water content in noninjured brain areas, as shown in human and animal studies. [11][12][13] The principal mechanism underlying these effects is the induction of a water shift from brain tissues to the intravascular space by the hyperosmolarity of HTS and mannitol because ...
The aim of the study was to compare the effect of mannitol (M) and hypertonic saline (HTS) on brain relaxation and electrolyte balance.
Prospective, randomized, double-blind study.
A total of 114 patients with American Society of Anesthesiologists status II and III, scheduled to undergo craniotomy for supratentorial brain tumor resection were enrolled. Patients received 5 ml/kg 20% mannitol (n = 56) or 3% HTS (n = 58) at the start of scalp incision. Hemodynamics, fluid balance and electrolytes, were measured at 0, 15, 30, and 60 min and 6 h after infusion. Intensive Care Unit (ICU) stay between the two groups was also recorded. The surgeon assessed brain relaxation on a four-point scale (1 = Relaxed, 2 = Satisfactory, 3 = Firm, 4 = Bulging). Appropriate statistical tests were used for comparison; P < 0.05 was considered significant.
Brain relaxation conditions in the HTS group (relaxed/satisfactory/firm/bulging, n = 28/20/5/3) were better than those observed in the M group (relaxed/satisfactory/firm/bulging, n = 17/21/11/9). The levels of serum sodium were higher in the HTS group (P < 0.001). The average urine output was higher in the M group (5.50 ± 0.75 L) than in the HTS group (4.38 ± 0.72 L) (P < 0.005). There was no significant difference in fluid input, ICU stay, and hospital days between the two groups.
We concluded that HTS provided better brain relaxation than mannitol during elective supratentorial brain tumor surgery, without affecting ICU and hospital stay.
... Alternative interpretations of our results are that PMN-independent mechanisms play important roles in damaging brain tissue or that altered responses of circulating PMNs may not directly reflect the responses of PMNs in the cerebral space after TBI. Hypertonic fluid therapy is widely used to treat TBI patients because of clinical evidence that it reduces intracranial pressure, edema formation, and morbidity after head injuries [47,48]. In previous studies, HS therapy was employed for prolonged periods after the admission of patients to the ICU. ...
Activation of polymorphonuclear neutrophils (PMN) is thought to contribute to traumatic brain injury (TBI). Because hypertonic fluids can inhibit PMN activation, we studied whether hypertonic fluid resuscitation can reduce PMN activation in TBI patients.
Trauma patients with severe TBI were resuscitated with 250 ml of either 7.5% hypertonic saline (HS; n=22), HS + 6% dextran-70 (HSD; n=22), or 0.9% normal saline (NS; n=39) and blood samples were collected on hospital admission and 12 and 24 h after resuscitation. PMN activation (CD11b, CD62L, CD64) and degranulation (CD63, CD66b, CD35) markers and oxidative-burst activity as well as spontaneous PMN apoptosis were measured by flow cytometry.
Relative to healthy controls, TBI patients showed increased PMN activation and decreased apoptosis of PMN. In the HS group, but not in the HSD group, markers of PMN adhesion (CD11b, CD64) and degranulation (CD35, CD66b) were significantly lower than in the NS group. These effects were particularly pronounced 12 h after resuscitation. Treatment with HS and HSD inhibited PMN oxidative burst responses compared to NS-treated patients. HS alone partially restored apoptosis. Despite these differences, the groups did not differ in clinical outcome parameters such as mortality and Extended Glasgow Outcome Scale.
This study demonstrates that pre-hospital resuscitation with HS can partially restore normal PMN activity and the apoptotic behavior or PMNs, while resuscitation with HSD was largely ineffective. Although the results are intriguing, additional research will be required to translate these effects of HS into treatment strategies that improve clinical outcome in TBI patients.
... 76 Despite some conflicting evidence in animal models with regard to improved perfusion pressure but worsened oxygen delivery because of hemodilution caused by using hypertonic solutions, 77-79 there is much clinical evidence that HS or HS in combination with colloids is the fluid of choice for head trauma patients. 56,60,69,72,80 Clinical Recommendations-Prehospital Use. 67 The following protocols were all designed for the use of HSD (Rescueflow®). ...
... Treatment with HTS is commonly used in the NICU not only for management of elevated ICP and cerebral edema but also to maintain normo-natremia after SAH which is commonly due to CSW. Use of HTS in the past has been identified as a risk factor for development of AKI [18, 19]. On the contrary, recent studies from neurocritical care units around the US suggest use of HTS to be safe in neurologically ill patients [20, 21]. ...
Background and purpose:
The use of iodinated contrast-enhanced imaging studies is increasing in acute cerebrovascular diseases, especially in subarachnoid hemorrhage (SAH). In SAH, such studies are essential for both diagnosis and treatment of the cause and sequela of hemorrhage. These patients are often subjected to multiple contrast studies such as computed tomographic angiography, computed tomographic perfusion, and cerebral angiography. They are also predisposed to intravascular volume depletion as a part of the disease process from cerebral salt wasting (CSW) and as a result of multiple contrast exposure can develop contrast-induced nephropathy (CIN). Data regarding CIN in this population are scarce. We aimed to examine the incidence of CIN in SAH and identify potential associative risk factors.
Methods:
We analyzed data from a prospectively collected patient database of patients with SAH admitted to the neurocritical intensive care unit in a single center over a period of 1 year. CIN was defined as an increase in serum creatinine by >1.5 times or >0.3 mg/dl greater than the admission value, or urine output <0.5 ml/kg/h during one 6-h block.
Results:
In this cohort of 75 patients with SAH who had undergone at least one contrast study, the mean age was 57.3 ± 15.6 years and 70.7% were women. Four percent developed CIN which resolved within 72 h and none required renal replacement therapy or dialysis. Patients older than 75 years (20%, p < 0.05), those with borderline renal function (14.3%, p = 0.26), diabetics (11.1%, p = 0.32), and those with lower recommended "maximum contrast dose" volume (33.3%, p = 0.12) had a trend toward development of CIN, although most were not statistically significant. Twenty-seven patients (36 %) were on 3% hypertonic saline (HTS) for CSW during the contrasted study but none developed CIN.
Conclusions:
The incidence of CIN in SAH patients is comparable to previously published reports on non-neurological cohorts. No definite association was noted with any predisposing factors postulated to be responsible for CIN, except for advanced age. Concurrent use of 3% HTS was not associated with CIN in this population.
... Of interest, this group demonstrated improved outcomes based on trauma scores and found no adverse events despite extreme hyperosmolarity (serum Na > 180 meq/l in some cases). Khanna and colleagues reported the use of continuous hypertonic saline solution in ten children and found that institution of this therapy resulted in decreased ICP spikes with improved CPP [35]. Finally, in a double-blind, crossover study comparing 3% saline to normal saline for intracranial hypertension, Fisher and colleagues found a 25% decrease in ICP after 3% saline and no change in the normal saline group [36]. ...
Traumatic brain injury is a leading killer of children and is a major public health problem around the world. Using general principles of neurocritical care, various treatment strategies have been developed to attempt to restore homeostasis to the brain and allow brain healing, including mechanical factors, cerebrospinal fluid diversion, hyperventilation, hyperosmolar therapies, barbiturates and hypothermia. Careful application of these therapies, normally in a step-wise fashion as intracranial injuries evolve, is necessary in order to attain maximal neurological outcome for these children. It is hopeful that new therapies, such as early hypothermia or others currently in preclinical trials, will ultimately improve outcome and quality of life for children after traumatic brain injury.
p>Intracranial hypertension is a major cause of morbidity and mortality in critically ill patients. Great deal of research has been done with the goal to improve patient outcome, but the challenges are enormous. From basic managementlike sedation and analgesia, to higher tier therapies, there are mixed evidences, some indicating these interventions to be beneficial and some to be equivocal, but the paucity of high-quality trials limits strong recommendations. This review will try to analyze the extensive literature regarding management of raised intracranial pressure, with particular focus on recent advances and will also try to shed some light on future directions.
Bangladesh Crit Care J March 2017; 5(1): 53-62</p
OBJECTIVE
Mannitol is the standard of care for patients with increased intracranial pressure (ICP), but multiple administrations of mannitol risk renal toxicity and fluid accumulation in the brain parenchyma with consequent worsening of cerebral edema. This preliminary study assessed the safety and efficacy of small-volume injections of 23.4% sodium chloride solution for the treatment of intracranial hypertension in patients with traumatic brain injury who became tolerant to mannitol.
METHODS
We retrospectively reviewed the charts of 13 adult patients with traumatic brain injury who received mannitol and 23.4% sodium chloride independently for the treatment of intracranial hypertension at San Francisco General Hospital between January and October 2003. Charts were reviewed to determine ICP, cerebral perfusion pressure, mean arterial pressure, serum sodium values, and serum osmolarity before and after treatment with 23.4% sodium chloride and mannitol. Complications were noted.
RESULTS
The mean reductions in ICP after treatment were significant for both mannitol (P<0.001) and hypertonic saline (P<0.001); there were no significant differences between reductions in ICP when comparing the two agents (P = 0.174). The ICP reduction observed for hypertonic saline was durable, and its mean duration of effect (96 min) was significantly longer than that of mannitol treatment (59 min) (P = 0.016). No complications were associated with treatment with hypertonic saline.
CONCLUSION
This study suggests that 23.4% hypertonic saline is a safe and effective treatment for elevated ICP in patients after traumatic brain injury. These results warrant a rigorous evaluation of its efficacy as compared to mannitol in a prospective randomized controlled trial.
The term ‘brain relaxation’ is routinely used to describe the size and firmness of the brain tissue during craniotomy. The
status of brain relaxation is an important aspect of neuroanaesthesia practice and is relevant to the operating conditions,
retraction injury, and likely patient outcomes. Brain relaxation is determined by the relationship between the volume of the
intracranial contents and the capacity of the intracranial space (i.e. a content–space relationship). It is a concept related
to, but distinct from, intracranial pressure. The evaluation of brain relaxation should be standardized to facilitate clinical
communication and research collaboration. Both advantageous and disadvantageous effects of the various interventions for brain
relaxation should be taken into account in patient care. The outcomes that matter the most to patients should be emphasized
in defining, evaluating, and managing brain relaxation. To date, brain relaxation has not been reviewed specifically, and
the aim of this manuscript is to discuss the current approaches to the definition, evaluation, and management of brain relaxation,
knowledge gaps, and targets for future research.
Survival and neurological outcomes in children with traumatic brain injury (TBI) remain poor, despite the great effort toward improving outcomes in such patients. No single anesthetic protocol is suitable for all children with TBI undergoing surgical procedures. Although propofol offers advantages in terms of cerebral blood volume, a larger dose is required in children, increasing the risk of propofol infusion syndrome. Intracranial pressure monitoring should be considered when managing children with TBI. Hyperventilation (PCO2 of <25 mmHg) may cause cerebral ischemia. Temperature management is also very important, and hypothermia (32–33 °C) followed by rapid rewarming (0.5 °C every 2 h) is not recommended. Notably, hyperthermia in the early phase of TBI may cause poor neurological outcomes. Hemodynamic parameters are also critical, and the cerebral perfusion pressure should be >40 mmHg. Hypertonic saline may be used to avoid hyponatremia, which may cause brain edema and intracranial hypertension. Adequate postoperative sedation is required in the intensive care unit. Several pharmacological therapies have been developed to improve outcomes in children with TBI. Corticosteroid administration, however, is not recommended. Phenytoin may be used to prevent posttraumatic seizures. Barbiturates can be used to reduce intracranial pressure. Cerebrospinal fluid drainage may also effectively reduce intracranial pressure.
Objectives:
Traumatic brain injury contributes to morbidity in children and boys is disproportionately represented. Cerebral autoregulation is impaired after traumatic brain injury, contributing to poor outcome. Cerebral perfusion pressure is often normalized by the use of vasopressors to increase mean arterial pressure. In prior studies, we observed that phenylephrine prevented impairment of autoregulation in female but exacerbated in male piglets after fluid percussion injury. In contrast, dopamine prevented impairment of autoregulation in both sexes after fluid percussion injury, suggesting that pressor choice impacts outcome. The extracellular signal-regulated kinase isoform of mitogen-activated protein kinase produces hemodynamic impairment after fluid percussion injury, but the role of the cytokine interleukin-6 is unknown. We investigated whether norepinephrine sex-dependently protects autoregulation and limits histopathology after fluid percussion injury and the role of extracellular signal-regulated kinase and interleukin-6 in that outcome.
Design:
Prospective, randomized animal study.
Setting:
University laboratory.
Subjects:
Newborn (1-5 d old) pigs.
Interventions:
Cerebral perfusion pressure, cerebral blood flow, and pial artery diameter were determined before and after fluid percussion injury in piglets equipped with a closed cranial window and post-treated with norepinephrine. Cerebrospinal fluid extracellular-signal-regulated kinase mitogen-activated protein kinase was determined by enzyme-linked immunosorbent assay.
Measurements and main results:
Norepinephrine does not protect autoregulation or prevent reduction in cerebral blood flow in male but fully protects autoregulation in female piglets after fluid percussion injury. Papaverine-induced dilation was unchanged by fluid percussion injury and norepinephrine. Norepinephrine increased extracellular signal-regulated kinase mitogen-activated protein kinase up-regulation in male but blocked such up-regulation in female piglets after fluid percussion injury. Norepinephrine aggravated interleukin-6 upregulation in males in an extracellular signal-regulated kinase mitogen-activated protein kinase-dependent mechanism but blocked interleukin-6 up-regulation in females after fluid percussion injury. Norepinephrine augments loss of neurons in CA1 and CA3 hippocampus of male piglets after fluid percussion injury in an extracellular signal-regulated kinase mitogen-activated protein kinase-dependent and interleukin-6-dependent manner but prevents loss of neurons in females after fluid percussion injury.
Conclusion:
Norepinephrine protects autoregulation and limits hippocampal neuronal cell necrosis via modulation of extracellular signal-regulated kinase mitogen-activated protein kinase and interleukin-6 after fluid percussion injury in a sex-dependent manner.
The management of infants and children with conditions of the brain and spinal cord can be challenging, and optimal management requires a thorough understanding of the developmental stages, age related physiological changes, and the pathophysiological processes that occur with these conditions. Patients with neurological conditions often undergo neurosurgical procedures and encounter clinicians from a variety of specialties. The perioperative period, is therefore, an important therapeutic window and clinicians who manage these patients during this period can provide patients with the opportunity to achieve full neurological recovery before, during, and after neurosurgery. For the preoperative period, pediatricians and emergency physicians are able to diagnose urgent/emergent neurosurgical conditions, prepare patients neurosurgery and prevent clinical deterioration from neurological conditions until definitive therapy such as neurosurgery can be provided. During surgery, anesthesiologists aim to provide optimal brain physiological conditions and optimal anesthetic and hemodynamic care during complex neurosurgical procedures. During the postoperative period, intensivists are responsible for anticipating and preventing postoperative consequences, and for helping patients achieve full neurological recovery. This chapter provides information on the neurological issues that should be considered during the perioperative period in the care of children undergoing neurosurgery.
The purpose of this meta-analysis was to compare the effectiveness of mannitol and hypertonic saline for reducing intracranial pressure (ICP) after traumatic brain injury (TBI).
PubMed, Cochrane, Embase, and ISI Web of Knowledge databases were searched until July 3, 2014 using the terms intracranial hypertension, mannitol, and hypertonic saline. Randomized controlled trials and 2-arm prospective studies in which elevated ICP was present after TBI treated with mannitol or hypertonic saline were included. The primary outcome was the change of ICP from baseline to termination of the infusion, while the secondary outcomes were change from baseline to 30, 60, and 120 minutes after terminating the infusion and change of osmolarity from baseline to termination.
A total 7 studies with 169 patients were included. The mean age of patients receiving mannitol ranged from 30.8 to 47 years, and for patients receiving hypertonic saline ranged from 35 to 47 years. A pooled difference in means = −1.69 (95% confidence interval [CI]: −2.95 to −0.44, P = 0.008) indicated that hypertonic saline reduced ICP more effectively than mannitol when compared from the baseline value to the last measurement after treatment. At 30 minutes after intervention, there was no difference in the mean ICP change between the groups, whereas at 60 minutes after intervention (pooled difference in means = −2.58, 95% CI: −4.37 to −0.80, P = .005) and 120 min after intervention (pooled difference in means = −4.04, 95% CI: −6.75 to −1.32, P = .004) hypertonic saline resulted in a significantly greater decrease in ICP. The pooled difference in means = 1.84 (95% CI: −1.64 to 5.31, P = .301) indicated no difference in serum osmolarity between patients treated with hypertonic saline or mannitol.
Hypertonic saline is more effective than mannitol for reducing ICP in cases of TBI.
Hyponatremia is a well known occurrence in traumatic and non traumatic brain injury which is known to complicate the management, affect the prognosis and increase hospital length of stay. Hypertonic saline is one of the drugs among the clinician’s armamentarium in order to combat this complication. However its use is marked with many controversies and myths due to lack of robust evidence and non uniformity of trial protocols. In this review the author attempts to review the use of hypertonic saline in brain injury touching on practical use, indications, limitations and goes on to suggest a practical protocol for hypertonic saline in brain injury with raised intracranial pressure. Data Sources: MEDLINE, MICROMEDEX, The Cochrane database of Systematic Reviews from 1967 through May 2012.Bangladesh Crit Care J March 2015; 3 (1): 22-26
Raised intracranial pressure (ICP, > 20 mm Hg) is often seen in children with acute brain injury of various
etiologies and often complicates the clinical picture and management; it may progress into herniation
syndrome and death. The volume of intracranial compartments is tightly regulated, and cerebral blood
flow (CBF) is kept constant despite fluctuations in systemic blood pressure by ‘cerebral autoregulation’.
Symptoms and signs of raised ICP are neither sufficiently sensitive nor specific; hence identifying patients
at risk of developing raised ICP is a crucial for preventing seonday brain injury. Persistent elevation of
ICP above 20 mm Hg for greater than 5 minutes in a patient who is not being stimulated should be
treated immediately. Immediate goal of management is to prevent/reverse herniation and to maintain
good cerebral perfusion pressure. The therapeutic measures include stabilization of airway, breathing and
circulation, along with neutral neck position, head end elevation by 30°, adequate sedation and analgesia,
minimal stimulation, and hyperosmolar therapy (mannitol or 3% saline). Short-term hyperventilation,
to achieve PCO2≈30 mm Hg, using bag ventilation can be resorted to if impending herniation is
suspected. CPP targeted therapy (targeting CPP ≥ 60 mm Hg) is associated with better clinical outcome.
Decompressive craniotomy may improve the outcome in raised ICP unresponsive to medical treatment.
However, indiscriminate use of this surgery is not advised as the procedure and subsequent cranioplasty
are associated with a number of complications
The prompt diagnosis and initial management of pediatric traumatic brain injury poses many challenges to the emergency department (ED) physician. In this review, we aim to appraise the literature on specific management issues faced in the ED, specifically: indications for neuroimaging, choice of sedatives, applicability of hyperventilation, utility of hyperosmolar agents, prophylactic anti-epileptics, and effect of hypothermia in traumatic brain injury. A comprehensive literature search of PubMed and Embase was performed in each specific area of focus corresponding to the relevant questions. The majority of the head injured patients presenting to the ED are mild and can be observed. Clinical prediction rules assist the ED physician in deciding if neuroimaging is warranted. In cases of major head injury, prompt airway control and careful use of sedation are necessary to minimize the chance of hypoxia, while avoiding hyperventilation. Hyperosmolar agents should be started in these cases and normothermia maintained. The majority of the evidence is derived from adult studies, and most treatment modalities are still controversial. Recent multicenter trials have highlighted the need to establish common platforms for further collaboration.
Increased intracranial pressure (ICP) is associated with worse outcome after traumatic brain injury (TBI). The current guidelines and management strategies are aimed at maintaining adequate cerebral perfusion pressure and treating elevated ICP. Despite controversies, ICP monitoring is important particularly after severe TBI to guide treatment and in developed countries is accepted as a standard of care. We provide a narrative review of the recent evidence for the use of ICP monitoring and management of ICP in pediatric TBI.
Traumatic brain injury and intracranial hypertension often require treatment to optimize patient outcome. There are a variety of complex medical conditions that can preclude standard approaches to the treatment of intracranial hypertension. We describe a case where a novel approach using continuous dialysis with trisodium citrate was used to optimize the outcome of a young male with acute renal failure and ARDS in the setting of acute traumatic brain injury.
© 2014 Marshfield Clinic.
Traumatic brain injury is a major public health problem both in developed economies and developing countries contribute to a substantial number of deaths and cases of permanent disability. This translates into a societal cost of billions of USD per year for medical care and lost productivity. Traumatic brain injury (TBI) has been called a silent epidemic. In developing countries the incidence of TBI is high and rapidly increasing. TBI has not attracted the attention of policy makers and researchers for decades until war injuries in Iraq and Afghanistan and also sports injuries affected large number of young adults. The World Health Organization predicts that TBI and road traffic accidents will be the third greatest cause of disease and injury worldwide by 2020. TBI is a heterogeneous condition in terms of etiology, severity, and outcome. TBI occurs mainly due to vehicle accidents, sudden falls and hits to brain; this includes both primary and subsequent secondary injuries. The severity of a TBI may range from "mild," i.e., a brief change in mental status or consciousness to "severe," i.e., an extended period of unconsciousness or amnesia after the injury. Currently, no effective TBI therapy exists, with patients treated through a combination of surgery, rehabilitation and pharmacological agents managing post-trauma conditions such as depression. Despite the availability of evidence-based guidelines for the management of head-injured patients, considerable variations in care remain. Continuous attempts have been made worldwide to discover the best possible treatment, but an effective treatment method is not yet available. Evidence-based intensive care management strategies improves outcome. The most definite benefits in terms of survival after TBI come from admission to a specialist neurosurgical centre, with goal-targeted therapy and intensive care services. Early detection and objective characterization of abnormalities in TBI are important objectives of modern neuroimaging. Improved treatment will come through understanding the physical changes in the brain that occur at the microscopic and molecular levels when the brain is subject to trauma. Novel achievements in neuroprotection are now expected from developing antiapoptotic agents, from more potent antioxidants, cholinergic agents, alpha blockers, from researching various physiological substances, advances in molecular medicine including stem cell and gene therapy. A more analytical approach to understanding the complex array of factors that influence the incidence, severity, and outcome of TBI is essential. Appropriate targeting of prevention and improving outcome requires a detailed understanding of incidence, causes of injury, treatment approaches and outcome results. Improved patient outcomes will depend on organised trauma response systems, particularly to prevent the potentially reversible effects of secondary brain injury strategies.
Oxidative stress processes play an important role in the pathogenesis of secondary brain injury after traumatic brain injury (TBI). Hypertonic saline (HTS) has advantages as being preferred osmotic agent, but few studies investigated oxidant and antioxidant effects of HTS in TBI. This study was designed to compare two different regimens of HTS 5% with mannitol on TBI-induced oxidative stress.
Thirty-three adult patients with TBI were recruited and have randomly received one of the three protocols: 125 cc of HTS 5% every 6 h as bolus, 500 cc of HTS 5%as infusion for 24 h or 1 g/kg mannitol of 20% as a bolus, repeated with a dose of 0.25-0.5 g/kg every 6 h based on patient's response for 3 days. Serum total antioxidant power (TAP), reactive oxygen species (ROS) and nitric oxide (NO) were measured at baseline and daily for 3 days.
Initial serum ROS and NO levels in patients were higher than control(6.86± [3.2] vs. 1.57± [0.5] picoM, P = 0.001, 14.6± [1.6] vs. 7.8± [3.9] mM, P = 0.001, respectively). Levels of ROS have decreased for all patients, but reduction was significantly after HTS infusion and mannitol (3. 08 [±3.1] to 1.07 [±1.6], P = 0.001, 5.6 [±3.4] to 2.5 [±1.8], P = 0.003 respectively). During study, NO levels significantly decreased in HTS infusion but significantly increased in mannitol. TAP Levels had decreased in all patients during study especially in mannitol (P = 0.004).
Hypertonic saline 5% has significant effects on the oxidant responses compared to mannitol following TBI that makes HTS as a perfect therapeutic intervention for reducing unfavorable outcomes in TBI patients.
A rat model of middle cerebral artery permanent occlusion was established using the modified Longa method. Successfully established model animals were treated by blood-letting puncture at twelve Jing-Well points of the hand, and/or by injecting mannitol into the caudal vein twice daily. Brain tissue was collected at 24, 48 and 72 hours after modeling, and blood was collected through the retinal vein before Evans blue was injected, approximately 1 hour prior to harvesting of brain tissue. Results showed that Evans blue leakage into brain tissue and serum nitric oxide synthase activity were significantly increased in model rats. Treatment with blood-letting punctures at twelve Jing-Well points of the hand and/or injection of mannitol into the caudal vein reduced the amount of Evans blue leakage into the brain tissue and serum nitric oxide synthase activity to varying degrees. There was no significant difference between single treatment and combined treatment. Experimental findings indicate that blood-letting punctures at twelve Jing-Well points of the hand can decrease blood-brain barrier permeability and serum nitric oxide synthase activity in rats following middle cerebral artery occlusion, and its effect is similar to that of mannitol injection alone and Jing-Well points plus mannitol injection.
Traumatic Brain Injury (TBI) is one of the foremost causes of mortality secondary to trauma. Poorer outcomes are associated with secondary insults, after the initial brain injury occurred. The management goal of TBI is to prevent or minimise the effects of secondary brain injuries. The primary objective of this systematic review/meta-analysis was to assess the effects of Hypertonic Saline (HTS) compared to Standard Fluid Therapy (SFT) in the treatment and resuscitation of TBI patients. We searched CENTRAL, MEDLINE (from 1966), EBSCOhost, Scopus, ScienceDirect, Proquest Medical Library and EMBASE (from 1980) in May 2010 and updated searches in February 2011. Data were assessed and extracted by two independent authors. Risk ratios (RR) with a 95% confidence interval (CI) were used as the effect measure. The review included three RCTs (1184 participants) of which two were of high to moderate quality (1005 participants). HTS was not found to be associated with a reduction in mortality (3 RCTs, 1184 participants, RR 0.91, 95%CI 0.76 to 1.09) and morbidity in TBI patients. No significant improvement in haemodynamical stability was found whereas insufficient data were available to indicate a reduction in the intracranial pressure (ICP). In the HTS group, cerebral perfusion pressure (CPP) (MD 3.83 mmHg, 95%CI 1.08 to 6.57) and serum sodium level (MD 8 mEq/L, 95%CI 7.47 to 8.53) were higher. Existing studies show no indication that HTS, in comparison to SFT, reduces mortality or morbidity after the occurrence of TBI. Against this backdrop, some uncertainties still exist in terms of the use of different concentrations and volumes of HTS, the timing of administration as well as the benefit in specific injury profiles. As a result, formulating conclusive recommendations is complex. © 2014 Production and hosting by Elsevier on behalf of African Federation for Emergency Medicine.
Purpose: To clarify the appropriate concentration and dose of
hypertonic saline solution (HSS) for preventing delayed neuronal
death in the hippocampal CA1 subfield after transient forebrain
ischemia in gerbils.
Methods: Thirty gerbils were randomly assigned to five groups:
physiological saline solution (PSS) group, ischemia/reperfusion treated with PSS 2 mL·kg–1; 5% HSS group, treated with 5% HSS 2
mL·kg–1; 7.5% HSS group, treated with 7.5% HSS 2 mL·kg–1; 10%
HSS group, treated with 10% HSS 2 mL·kg–1; 20% HSS group,
treated with 20% HSS 2 mL·kg–1. Transient forebrain ischemia was
induced by occluding the bilateral common carotid arteries for four
minutes. Five days later, histopathological changes in the hippocampal
area were examined, and the degenerative ratio of the pyramidal
cells were measured according to the following formula: (number of
degenerative pyramidal cells/total number of pyramidal cells per 1
mm of hippocampal CA1 subfield) × 100.
Results: In PSS and 20% groups, neuronal cell damage was
observed five days after ischemia. In the other three groups, these
changes were not observed. The degenerative ratios of pyramidal
cells were as follows; PSS group: 91.6 ± 5.6%, 5% HSS group:
7.2 ± 1.6%, 7.5% group: 8.3 ± 1.4%, 10% HSS group: 6.2 ±1.1%, 20% HSS group: 85.8 ± 8.7% (P < 0.05; PSS and 20%HSS vs three other groups).
Conclusion: This study demonstrates that 5, 7.5 or 10% HSS 2mL·kg–1 may prevent delayed neuronal death in the hippocampal CA1 subfield after cerebral ischemia/reperfusion in gerbils.
Safe upper limits for therapeutic hypernatremia in the treatment of intracranial hypertension have not been well established. We investigated complications associated with hypernatremia in children who were treated with prolonged infusions of hypertonic saline.
Retrospective chart analysis.
PICU in university-affiliated children's hospital.
All children from 2004 to 2009 requiring intracranial pressure monitoring (external ventricular drain or fiberoptic intraparenchymal monitor) for at least 4 days who were treated with hypertonic saline infusion for elevated intracranial pressure and did not meet exclusion criteria.
Continuous hypertonic saline infusion on a sliding scale was used to achieve target sodium levels that would keep intracranial pressure less than 20 mm Hg once the conventional therapies failed.
Eighty-eight children met inclusion criteria. Etiologies of elevated intracranial pressure included trauma (n = 48), ischemic or hemorrhagic stroke (n = 20), infection (n = 8), acute disseminated encephalomyelitis (n = 5), neoplasm (n = 2), and others (n = 5). The mean peak serum sodium was 171.3 mEq/L (range, 150-202). The mean Glasgow Outcome Score was 2.8 (± 1.1) at time of discharge from the hospital. Overall mortality was 15.9%. Children with sustained (> 72 hr) serum sodium levels above 170 mEq/L had a significantly higher occurrence of thrombocytopenia (p < 0.001), renal failure (p < 0.001), neutropenia (p = 0.006), and acute respiratory distress syndrome (p = 0.029) after controlling for variables of age, gender, Pediatric Risk of Mortality score, duration of barbiturate-induced coma, duration of intracranial pressure monitoring, vasopressor requirements, and underlying pathology. Children with sustained serum sodium levels greater than 165 mEq/L had a significantly higher prevalence of anemia (p < 0.001).
Children treated by continuous hypertonic saline infusion for intracranial hypertension whose serum sodium levels exceeded certain thresholds experienced significantly more events of acute renal failure, thrombocytopenia, neutropenia, anemia, and acute respiratory distress syndrome than those whose sodium level was maintained below these thresholds.
Cerebral edema develops in response to and as a result of a variety of neurologic insults such as ischemic stroke, traumatic brain injury, and tumor. It deforms brain tissue, resulting in localized mass effect and increase in intracranial pressure (ICP) that are associated with a high rate of morbidity and mortality. When administered in bolus form, hyperosmolar agents such as mannitol and hypertonic saline have been shown to reduce total brain water content and decrease ICP, and are currently the mainstays of pharmacological treatment. However, surprisingly, little is known about the increasingly common clinical practice of inducing a state of sustained hypernatremia. Herein, we review the available studies employing sustained hyperosmolar therapy to induce hypernatremia for the prevention and/or treatment of cerebral edema. Insufficient evidence exists to recommend pharmacologic induction of hypernatremia as a treatment for cerebral edema. The strategy of vigilant avoidance of hyponatremia is currently a safer, potentially more efficacious paradigm.
Hypertonic saline (HS) is a promising fluid resuscitation therapy with the potential to reduce lung injury caused by severe trauma. The experimental evidence that HS has hemodynamic, anti-inflammatory, immunological, and neuroprotective properties and that it attenuates post-traumatic lung injury and multiple organ dysfunction syndrome (MODS) is undeniable. Laboratory evidence continues to accumulate to suggest that administration of HS affects cells, organs, and the neuro-humoral response to trauma, which affects both the innate and adaptive immunity. In contrast to the experimental findings, no clinical study to date has demonstrated that resuscitation of trauma patients with HS significantly reduces lung injury and MODS. Two recent clinical trials have confirmed that HS exerts similar hemodynamic, anti-inflammatory, and immunological effects as in experimental models. While it is possible that in humans such effects do not result in attenuation of post-traumatic lung injury and MODS, another explanation could be that no clinical study to date was powered to identify such clinical outcomes. An ongoing large, multicenter, randomized clinical trial across the USA and Canada is the first that is powered to determine whether resuscitation with a single dose of HS reduces post-traumatic lung dysfunction and consequently should become part of the resuscitation of severely traumatized patients.
Severe traumatic brain injury in children continues to pose significant challenges for the intensive care team. This paper reviews the current evidence base for the treatment strategies recommended and highlights the differences between paediatric and adult traumatic brain injury. The paediatric intensive care nurse has a key role to play in paediatric traumatic brain injury, but to contribute effectively to the multidisciplinary team must have a good understanding of the medical and surgical management strategies
Hypertonic saline (HS) solutions are increasingly used for reduction of elevated intracranial pressure in head-injured children and adults. Advantages over other hypertonic solutions such as mannitol were demonstrated in experimental and clinical studies with respect to intracranial pressure reduction, improvement of cerebral perfusion pressure, and cerebral oxygenation. However, there remains considerable uncertainty about the indications for the use of HS, the appropriate administration protocol, and the potential risks of using HS. The rationale of this article is to bring a systematic order into the currently available results and to help develop a protocol for the indication and application of HS solutions in adults and children with severe brain injury. Furthermore, fields of necessary future research are outlined.
Objective: To describe the optimal anesthetic management of patients with brain injury, with emphasis on the support of oxygen delivery to the brain, and the effects of anesthetic agents on cerebral perfusion.
Data sources: Clinical and experimental studies from both the human and veterinary neuroanesthesia literature.
Summary: The management of patients following primary traumatic brain injury (TBI) significantly impacts outcome. Outcome can be improved by strategies that improve oxygen delivery to the brain and prevent cerebral ischemia. Anesthetic agents have widely variable effects on the blood supply to the brain and, therefore, choice of anesthetic agent can influence neurological outcome. Although in the past, anesthetic agents have been selected for their neuroprotective properties, it is increasingly being recognized that the support of cerebral perfusion during anesthesia contributes more significantly to a positive outcome for these patients. Support of cardiorespiratory function is, therefore, highly important when anesthetizing patients with TBI.
Conclusion: Choice of anesthetic agent is determined by the extent of brain injury and intracranial pressure (ICP) elevation. Factors that should be considered when anesthetizing head trauma patients include the effects of anesthetic agents on the cardiac and respiratory systems, their effects on cerebral blood flow (CBF), ICP, and possible neuroprotective benefits offered by certain agents.
TBI and its sequelae remain a major healthcare issue throughout the world. With an improved understanding of the pathophysiology of TBI, refinements of monitoring technology, and ongoing research to determine optimal care, the prognosis of TBI continues to improve. In 2003, the Society of Critical Care Medicine published guidelines for the acute management of severe TBI in infants, children, and adolescents. As pediatric anesthesiologists are frequently involved in the perioperative management of such patients including their stabilization in the emergency department, familiarity with these guidelines is necessary to limit preventable secondary damage related to physiologic disturbances. This manuscript reviews the current evidence-based medicine regarding the care of pediatric patients with TBI as it relates to the perioperative care of such patients. The issues reviewed include those related to initial stabilization, airway management, intra-operative mechanical ventilation, hemodynamic support, administration of blood and blood products, positioning, and choice of anesthetic technique. The literature is reviewed regarding fluid management, glucose control, hyperosmolar therapy, therapeutic hypothermia, and corticosteroids. Whenever possible, management recommendations are provided.
In 1998, the Guidelines Committee on the Management of Severe Head Injury was established by the Japan Society of Neurotraumatology, and performed a critical review of national and international studies published over the past 10 years. The guidelines were first published in 2000 based on the results of this literature review and the Committee consensus, and the 2nd revised edition was published in 2006. This English version of the 2nd edition of the guidelines is intended to promote its concepts and use worldwide.
Description of a continuous hypertonic saline solution (HSS) infusion using a dose-adaptation of natremia in traumatic brain injured (TBI) patients with refractory intracranial hypertension (ICH).
We performed a single-center retrospective study in a surgical intensive care unit of a tertiary hospital. Fifty consecutive TBI patients with refractory ICH treated with continuous HSS infusion adapted to a target of natremia. In brief, a physician set a target of natremia adapted to the evolution of intracranial pressure (ICP). Flow of NaCl 20% was a priori calculated according to natriuresis, and the current and target natremia that were assessed every 4 hours.
The HSS infusion was initiated for a duration of 7 (5 to 10) (8 ± 4) days. ICP decreased from 29 (26 to 34) (31 ± 9) mm Hg at H0 to 20 (15 to 26) (21 ± 8) mm Hg at H1 (P < 0.05). Cerebral perfusion pressure increased from 61 (50 to 70) (61 ± 13) mm Hg at H0 up to 67 (60 to 79) (69 ± 12) mm Hg at H1 (P < 0.05). No rebound of ICH was reported after stopping continuous HSS infusion. Natremia increased from 140 (138 to 143) (140 ± 4) at H0 up to 144 (141 to 148) (144 ± 4) mmol/L at H4 (P < 0.05). Plasma osmolarity increased from 275 (268 to 281) (279 ± 17) mmol/L at H0 up to 290 (284 to 307) (297 ± 17) mmol/L at H24 (P < 0.05). The main side effect observed was an increase in chloremia from 111 (107 to 119) (113 ± 8) mmol/L at H0 up to 121 (117 to 124) (121 ± 6) mmol/L at H24 (P < 0.05). Neither acute kidney injury nor pontine myelinolysis was recorded.
Continuous HSS infusion adapted to close biologic monitoring enables long-lasting control of natremia in TBI patients along with a decreased ICP without any rebound on infusion discontinuation.
Currently, mannitol is the recommended first choice for a hyperosmolar agent for use in patients with elevated intracranial pressure (ICP). Some authors have argued that hypertonic saline (HTS) might be a more effective agent; however, there is no consensus as to appropriate indications for use, the best concentration, and the best method of delivery. To answer these questions better, the authors performed a review of the literature regarding the use of HTS for ICP reduction.
A PubMed search was performed to locate all papers pertaining to HTS use. This search was then narrowed to locate only those clinical studies relating to the use of HTS for ICP reduction.
A total of 36 articles were selected for review. Ten were prospective randomized controlled trials (RCTs), 1 was prospective and nonrandomized, 15 were prospective observational trials, and 10 were retrospective trials. The authors did not distinguish between retrospective observational studies and retrospective comparison trials. Prospective studies were considered observational if the effects of a treatment were evaluated over time but not compared with another treatment.
The available data are limited by low patient numbers, limited RCTs, and inconsistent methods between studies. However, a greater part of the data suggest that HTS given as either a bolus or continuous infusion can be more effective than mannitol in reducing episodes of elevated ICP. A meta-analysis of 8 prospective RCTs showed a higher rate of treatment failure or insufficiency with mannitol or normal saline versus HTS.
To describe patterns of use for mannitol and hypertonic saline in children with traumatic brain injury, to evaluate any potential associations between hypertonic saline and mannitol use and patient demographic, injury, and treatment hospital characteristics, and to determine whether the 2003 guidelines for severe pediatric traumatic brain injury impacted clinical practice regarding osmolar therapy.
Retrospective cohort study.
Pediatric Health Information System database, January, 2001 to December, 2008.
Children (age <18 yrs) with traumatic brain injury and head/neck Abbreviated Injury Scale score ≥ 3 who received mechanical ventilation and intensive care.
: None.
The primary outcome was hospital billing for parenteral hypertonic saline and mannitol use, by day of service. Overall, 33% (2,069 of 6,238) of the patients received hypertonic saline, and 40% (2,500 of 6,238) received mannitol. Of the 1,854 patients who received hypertonic saline or mannitol for ≥ 2 days in the first week of therapy, 29% did not have intracranial pressure monitoring. After adjustment for hospital-level variation, primary insurance payer, and overall injury severity, use of both drugs was independently associated with older patient age, intracranial hemorrhage (other than epidural), skull fracture, and higher head/neck injury severity. Hypertonic saline use increased and mannitol use decreased with publication of the 2003 guidelines, and these trends continued through 2008.
Hypertonic saline and mannitol are used less in infants than in older children. The patient-level and hospital-level variation in osmolar therapy use and the substantial amount of sustained osmolar therapy without intracranial pressure monitoring suggest opportunities to improve the quality of pediatric traumatic brain injury care. With limited high-quality evidence available, published expert guidelines appear to significantly impact clinical practice in this area.
Pediatric acute liver failure is often accompanied by hepatic encephalopathy, cerebral edema, and raised intracranial pressure. Elevated intracranial pressure can be managed more effectively with intracranial monitoring, but acute-liver-failure-associated coagulopathy is often considered a contraindication for invasive monitoring due to risk for intracranial bleeding. We reviewed our experience with use of early intracranial pressure monitoring in acute liver failure in children listed for liver transplantation.
Retrospective review of all intubated pediatric acute liver failure patients with grade III and grade IV encephalopathy requiring intracranial pressure monitoring and evaluated for potential liver transplant who were identified from an institutional liver transplant patient database from 1999 to 2009.
None.
A total of 14 patients were identified who met the inclusion criteria. Their ages ranged from 7 months to 20 yrs. Diagnoses of acute liver failure were infectious (three), drug-induced (seven), autoimmune hepatitis (two), and indeterminate (two). Grade III and IV encephalopathy was seen in ten (71%) and four (29%) patients, respectively. Computed tomography scans before intracranial pressure monitor placement showed cerebral edema in five (35.7%) patients. Before intracranial pressure monitor placement, fresh frozen plasma, vitamin K, and activated recombinant factor VIIa were given to all 14 patients, with significant improvement in coagulopathy (p < .04). The initial intracranial pressure ranged from 5 to 50 cm H2O; the intracranial pressure was significantly higher in patients with cerebral edema by computed tomography (p < .05). Eleven of 14 (78%) patients received hypertonic saline, and three (22%) received mannitol for elevated intracranial pressure. Eight of 14 (56%) monitored patients were managed to liver transplant, with 100% surviving neurologically intact. Four of 14 (28%) patients had spontaneous recovery without liver transplant. Two of 14 (14%) patients died due to multiple organ failure before transplant. One patient had a small 9-mm intracranial hemorrhage but survived after receiving a liver transplant. No patient developed intracranial infection.
In our series of patients, intracranial pressure monitoring had a low complication rate and was associated with a high survival rate despite severe hepatic encephalopathy and cerebral edema in the setting of pediatric acute liver failure. In our experience, monitoring of intracranial pressure allowed interventions to treat increased intracranial pressure and provided additional information regarding central nervous system injury before liver transplant. Further study is warranted to confirm if monitoring allows more directed intracranial pressure therapy and improves survival in pediatric acute liver failure.
Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP) at present. In this connection, 10% hypertonic saline (HS) alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol.
Adult male Sprague-Dawley (SD) rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO) and treated with a continuous intravenous infusion of 10% HS, 20% mannitol or D-[1-3H(N)]-mannitol. Brain water content (BWC) as analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats decreased more significantly after 10% HS treatment compared with 20% mannitol. Concentration of serum Na+ and plasma crystal osmotic pressure of the 10% HS group at 2, 6, 12 and 18 h following permanent MCAO increased significantly when compared with 20% mannitol treated group. Moreover, there was negative correlation between the BWC of the ipsilateral ischemic hemisphere and concentration of serum Na+, plasma crystal osmotic pressure and difference value of concentration of serum Na+ and concentration of brain Na+ in ipsilateral ischemic hemisphere in the 10% HS group at the various time points after MCAO. A remarkable finding was the progressive accumulation of mannitol in the ischemic brain tissue.
We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.
The purpose of this study was to explore a novel treatment involving removal of free water from ventricular cerebrospinal fluid (CSF) for the reduction of cerebra]l edema. The hypothesis is that removal of free water from the CSF will increase the osmolarity of the CSF, which will favor movement of tissue-bound water into the ventricles, where the water can be removed. Reductive ventricular osmotherapy (RVOT) was tested in a flowing solution of artificial CSF (aCSF) with two end-points: (1) the effect of RVOT on osmolarity of the CSF, and (2) the effect of RVOT on water content of ex vivo cerebral tissue. RVOT catheters are made up of membranes permeable only to water vapor. When a sweep gas is drawn through the catheter, free water in the form of water vapor is removed from the solution. With RVOT treatment, aCSF osmolarity increased from a baseline osmolarity of 318.8 ± 0.8 mOsm/L to 339.0 ± 3.3 mOsm/L (mean ± standard deviation) within 2 h. After 10 h of treatment, aCSF osmolarity approached an asymptote at 344.0 ± 4.2 mOsm/L, which was significantly greater than control aCSF osmolarity (p <0.001 by t-test, n = 8). Water content at the end of 6 h of circulating aCSF exposure was 6.4 ± 0.9 g H₂O (g dry wt)⁻¹ in controls, compared to 6.1 ± 0.7 g H₂O (g dry wt)⁻ after 6 h of RVOT treatment of aCSF (p = 0.02, n = 24). The results support the potential of RVOT as a treatment for cerebral edema and intracranial hypertension.
To compare the efficacy and side effects of 3% hypertonic saline and mannitol in the management of raised intracranial pressure in children.
Prospective randomized study.
Pediatric intensive care unit (PICU) in a tertiary care hospital.
200 patients with raised intracranial pressure.
Patients were randomized into two statistically comparable groups; Group A (n = 98) was treated with mannitol while Group B (n = 100) was treated with 3% hypertonic saline. Group C (n = 2) included those members of Group A in whom serum osmolality ≥320 mosmol/kg and were then treated with 3% hypertonic saline. Both Drugs were given at a loading dose of 5 ml/kg stat followed by 2 ml/kg in every 6 h(both have same osmolarity) for two days in their respective groups. Besides monitoring, blood pressure (NIBP), mean arterial pressure (pre and post 30 min of drug), serum sodium, chloride and osmolality were measured. Intracranial pressure was assessed indirectly by measuring mean arterial ressure "MAP". Student paired 't' test was applied.
Decrease in MAP was highly significant (P<0.001) at 0 h in males 0,6 h in females, and moderately significant at 12,36 h in females and significant(P<0.05) at 6,24,42 h in males of Group B. Decrease in coma hours was a highly significant finding (P<0.001) in Group B. In Group B, serum sodium and chloride increased significantly but remained within acceptable limits. There was no difference in osmolality and mortality (fisher Z).
Mannitol has several side effects, 3% hypertonic saline is a safe and effective alternative in managing cerebral edema.
Hypertonic fluids restore cerebral perfusion with reduced cerebral edema and modulate inflammatory response to reduce subsequent neuronal injury and thus have potential benefit in resuscitation of patients with traumatic brain injury (TBI).
To determine whether out-of-hospital administration of hypertonic fluids improves neurologic outcome following severe TBI.
Multicenter, double-blind, randomized, placebo-controlled clinical trial involving 114 North American emergency medical services agencies within the Resuscitation Outcomes Consortium, conducted between May 2006 and May 2009 among patients 15 years or older with blunt trauma and a prehospital Glasgow Coma Scale score of 8 or less who did not meet criteria for hypovolemic shock. Planned enrollment was 2122 patients.
A single 250-mL bolus of 7.5% saline/6% dextran 70 (hypertonic saline/dextran), 7.5% saline (hypertonic saline), or 0.9% saline (normal saline) initiated in the out-of-hospital setting.
Six-month neurologic outcome based on the Extended Glasgow Outcome Scale (GOSE) (dichotomized as >4 or ≤4).
The study was terminated by the data and safety monitoring board after randomization of 1331 patients, having met prespecified futility criteria. Among the 1282 patients enrolled, 6-month outcomes data were available for 1087 (85%). Baseline characteristics of the groups were equivalent. There was no difference in 6-month neurologic outcome among groups with regard to proportions of patients with severe TBI (GOSE ≤4) (hypertonic saline/dextran vs normal saline: 53.7% vs 51.5%; difference, 2.2% [95% CI, -4.5% to 9.0%]; hypertonic saline vs normal saline: 54.3% vs 51.5%; difference, 2.9% [95% CI, -4.0% to 9.7%]; P = .67). There were no statistically significant differences in distribution of GOSE category or Disability Rating Score by treatment group. Survival at 28 days was 74.3% with hypertonic saline/dextran, 75.7% with hypertonic saline, and 75.1% with normal saline (P = .88).
Among patients with severe TBI not in hypovolemic shock, initial resuscitation with either hypertonic saline or hypertonic saline/dextran, compared with normal saline, did not result in superior 6-month neurologic outcome or survival.
clinicaltrials.gov Identifier: NCT00316004.
Traumatic brain injury contributes to morbidity and mortality in children and boys are disproportionately represented. Hypotension is common and worsens outcome after traumatic brain injury. Extracellular signal-related kinase mitogen-activated protein kinase is upregulated and reduces cerebral blood flow after fluid percussion brain injury in piglets. We hypothesized that increased cerebral perfusion pressure through phenylephrine sex dependently reduces impairment of cerebral autoregulation during hypotension after fluid percussion brain injury through modulation of extracellular signal-related kinase mitogen-activated protein kinase.
Prospective, randomized animal study.
University laboratory.
Newborn (1- to 5-day-old) pigs.
Cerebral blood flow, pial artery diameter, intracranial pressure, and autoregulatory index were determined before and after fluid percussion brain injury in untreated, preinjury, and postinjury phenylephrine (1 microg/kg/min intravenously) treated male and female pigs during normotension and hemorrhagic hypotension. Cerebrospinal fluid extracellular signal-related kinase mitogen-activated protein kinase was determined by enzyme-linked immunosorbent assay.
Reductions in pial artery diameter, cerebral blood flow, cerebral perfusion pressure, and elevated intracranial pressure after fluid percussion brain injury were greater in males, which were blunted by phenylephrine pre- or postfluid percussion brain injury. During hypotension and fluid percussion brain injury, pial artery dilation was impaired more in males. Phenylephrine decreased impairment of hypotensive pial artery dilation after fluid percussion brain injury in females, but paradoxically caused vasoconstriction after fluid percussion brain injury in males. Papaverine-induced pial artery vasodilation was unchanged by fluid percussion brain injury and phenylephrine. Cerebral blood flow, cerebral perfusion pressure, and autoregulatory index decreased markedly during hypotension and fluid percussion brain injury in males but less in females. Phenylephrine prevented reductions in cerebral blood flow, cerebral perfusion pressure, and autoregulatory index during hypotension in females but increased reductions in males. Cerebrospinal fluid extracellular signal-related kinase mitogen-activated protein kinase was increased more in males than females after fluid percussion brain injury. Phenylephrine blunted extracellular signal-related kinase mitogen-activated protein kinase upregulation in females but increased extracellular signal-related kinase mitogen-activated protein kinase upregulation in males after fluid percussion brain injury.
These data indicate that elevation of cerebral perfusion pressure with phenylephrine sex dependently prevents impairment of cerebral autoregulation during hypotension after fluid percussion brain injury through modulation of extracellular signal-related kinase mitogen-activated protein kinase. These data suggest the potential role for sex-dependent mechanisms in cerebral autoregulation after pediatric traumatic brain injury.
To review current information regarding the pathophysiology associated with traumatic brain injury (TBI), and to outline appropriate patient assessment, diagnostic, and therapeutic options.
TBI in veterinary patients can occur subsequent to trauma induced by motor vehicle accidents, falls, and crush injuries. Primary brain injury occurs at the time of initial impact as a result of direct mechanical damage. Secondary brain injury occurs in the minutes to days following the trauma as a result of systemic extracranial events and intracranial changes.
The initial diagnosis is often made based on history and physical examination. Assessment should focus on the cardiovascular and respiratory systems followed by a complete neurologic examination. Advanced imaging may be indicated in a patient that fails to respond to appropriate medical therapy.
Primary brain injury is beyond the control of the veterinarian. Therefore, treatment should focus on minimizing the incidence or impact of secondary brain injury. Because of a lack of prospective or retrospective clinical data, treatment recommendations for veterinary TBI patients are primarily based on human and experimental studies and personal experience. Therapeutic guidelines have been developed that center on maintaining adequate cerebral perfusion.
Severe head trauma is associated with high mortality in humans and animals. However, dogs and cats have a remarkable ability to compensate for loss of cerebral tissue. It is therefore important not to reach hasty prognostic conclusions based on initial appearance. Many pets go on to have a functional outcome and recover from injury.
Raised intracranial pressure (ICP) is known to complicate both traumatic and non-traumatic encephalopathies. It impairs cerebral perfusion and may cause death due to global ischaemia and intracranial herniation. Osmotic agents are widely used to control ICP. In children, guidelines for their use are mainly guided by adult studies. We conducted this review to determine the current evidence of the effectiveness of osmotic agents and their effect on resolution of coma and outcome in children with acute encephalopathy.
We searched several databases for published and unpublished studies in English and French languages, between January 1966 and March 2009. We considered studies on the use of osmotic agents in children aged between 0 and 16 years with acute encephalopathies. We examined reduction in intracranial pressure, time to resolution of coma, and occurrence of neurological sequelae and death.
We identified four randomized controlled trials, three prospective studies, two retrospective studies and one case report. Hypertonic saline (HS) achieved greater reduction in intracranial pressure (ICP) compared to mannitol and other fluids; normal saline or ringer's lactate. This effect was sustained for longer when it was given as continuous infusion. Boluses of glycerol and mannitol achieved transient reduction in ICP. Oral glycerol was associated with lower mortality and neurological sequelae when compared to placebo in children with acute bacterial meningitis. HS was associated with lower mortality when compared to mannitol in children with non-traumatic encephalopathies.
HS appears to achieve a greater reduction in ICP than other osmotic agents. Oral glycerol seems to improve outcome among children with acute bacterial meningitis. A sustained reduction in ICP is desirable and could be achieved by modifying the modes and rates of administration of these osmotic agents, but these factors need further investigation.
To review the research literature on pharmacological interventions used in the acute phase of acquired brain injury (ABI) to manage ICP and improve neural recovery.
A literature search of multiple databases (CINAHL, EMBASE, MEDLINE and PSYCHINFO) and hand searched articles covering the years 1980-2008 was performed. Peer reviewed articles were assessed for methodological quality using the PEDro scoring system for randomized controlled trials (RCTs) and the Downs and Black tool for RCTs and non-randomized trials. Levels of evidence were assigned and recommendations were made.
In total, 11 pharmacological interventions used in the acute management of ABI were evaluated. These included propofol, barbiturates, opioids, midazolam, mannitol, hypertonic saline, corticosteroids, progesterone, bradykinin antagonists, dimethyl sulphoxide and cannabinoids. Of these interventions, corticosteroids were found to be contraindicated and cannabinoids were reported as ineffective. The other nine interventions demonstrated some benefit for treatment of acute ABI. However, rarely did these benefits result in improved long-term patient outcomes.
Substantial research has been devoted to evaluating the use of pharmacological interventions in the acute management of ABI. However, much of this research has focused on the application of individual interventions in small single-site trials. Future research will need to establish larger patient samples to evaluate the benefits of combined interventions within specific patient populations.