1388 SECTION XII Pediatric Critical Care Environmental Injury and Trauma can serve as an early warning monitor of the development of an unfavorable trend in cerebral perfusion It can also assess autor[.]
1388 S E C T I O N X I I Pediatric Critical Care: Environmental Injury and Trauma can serve as an early warning monitor of the development of an unfavorable trend in cerebral perfusion It can also assess autoregulation, identify vasospasm, and contribute to prognostic information.15,145 TCD measures velocity rather than flow and usually is applied to assess middle cerebral artery distribution However, the inability of TCD to acquire regional data limits its use in titrating care Some have suggested that TCD also can identify the presence of raised ICP, but results have been conflicting.146,147 ASL-MRI has been used for decades in preclinical investigations in TBI and is now used routinely in advanced neurocritical care in some centers.129,148 However, its use to assess CBF in pediatric TBI is only beginning to emerge.149 It is not a monitoring tool given its need for MRI However, it provides quantitative maps of CBF at a single point in time and can be used for dynamic studies such as assessment of CO2 reactivity or pressure autoregulation Its use is likely to increase as faster MRI techniques are developed Unfortunately, the stable xenon CT method that was used in a number of seminal studies of pediatric TBI (Fig 118.9) is not available for routine clinical use.25,150 Brady and associates72 have generated interest in continuous monitoring of blood pressure autoregulation of CBF with use of a PRx that is calculated as a linear correlation between ICP and blood pressure With use of this noninvasive adjunct to ICP monitoring, intact autoregulation was shown to be associated with survival in 21 children with severe TBI This method also may contribute to better definition of optimal CPP However, it fails to provide regional assessments—and, as the consistency of its bedside performance is unclear, it remains a research tool at this time.74 Monitoring Cerebral Metabolism Jugular venous saturation has been used to monitor cerebral oxygen delivery in adults, but limited data on the use of this technique in children are available.63,64 Studies in adults suggest that therapies such as barbiturates and hyperventilation can be titrated according to jugular venous saturation.151,152 Desaturations below the threshold value of 50% are associated with mortality in adults.153 However, jugular venous desaturation below this level was rarely the sole indication that urgent intervention was needed, and false desaturations occurred Nevertheless, this tool can assist in clinical decision-making, but some have questioned its ability to monitor regional effects Thus, it has not been commonly used in pediatric TBI.154 Several other modes to monitor cerebral metabolic rate may be helpful Near-infrared spectroscopy has been used to track the oxidative state of cytochromes in the brain Near-infrared spectroscopy has been used to assess cerebral metabolic status in hypoxemic-ischemic neonates155 and is beginning to be used in pediatric TBI.156 Although its role remains unclear, it may prove valuable as a trend monitor.157 Limitations with topographic resolution and the dominance of the superficial brain tissue in generating the signal are concerns Monitoring partial pressure of oxygen in brain tissue (PbtO2) with a microelectrode implanted in the parenchyma has now been given a level III recommendation in the severe pediatric TBI guidelines.13,158 Maintaining a threshold value greater than 10 mm Hg is recommended, although thresholds anywhere from 10 to 30 mm Hg have been recommended in various studies Stiefel and colleagues159 reported on the use of PbtO2 monitoring in children and suggested a threshold of 20 mm Hg Stippler and associates reported experience with PbtO2 monitoring in a series of children and found that a PbtO2 of 30 mm Hg was associated with the highest sensitivity/specificity for favorable 6-month neurologic outcome.160 We routinely use PbtO2 in children with TBI, targeting a threshold of 20 mm Hg Therapy is first targeted to optimize ICP and CPP However, in some cases, PbtO2 is less than 20 mm Hg despite control of ICP, and it is necessary to evaluate other potential factors that might be affecting brain oxygenation This could include inadvertent hyperventilation or a decline in partial pressure of arterial oxygen (Pao2) due to lung disease; if so, these issues should be addressed If there is no extracerebral complication affecting PbtO2, interventions such as increasing Fio2 or raising partial pressure of arterial carbon dioxide (Paco2) or MAP/CPP to improve CBF may increase PbtO2 The limitations of PbtO2 are its invasiveness and provision of only focal data Suggestions to integrate PbtO2 monitoring and ICP/ CPP-guided therapy are provided in the severe TBI algorithm.4 In adults, PbtO2 measurement has been coupled to cerebral microdialysis to provide metabolic data (i.e., glutamate levels).161,162 Finally, positron emission tomography (PET) has been used in adults with severe TBI (Fig 118.10).30 Although limited by long acquisition times and the risk of intrahospital transport of critically ill patients, the metabolic maps generated provide much insight, particularly into cerebral glucose utilization after TBI Diringer and coworkers163 used PET to provide insight into the effect of hyperventilation on CMRO2 in adults with severe TBI (see the section on hyperventilation) Both PET and advanced MRI, along with magnetic resonance spectroscopy, can provide insight into regional brain disturbances and the effect of therapy Treatment in the Pediatric Intensive Care Unit Once the initial resuscitation is completed and evacuable intracranial masses have been addressed, maintenance of physiologic stability and recognition and management of raised ICP are the priorities A flow diagram illustrating a general approach to firsttier treatments of the child with severe TBI is provided in the pediatric severe TBI algorithm (Fig 118.11).4 The injured brain has complex metabolic requirements that are poorly understood.164 Autoregulation of CBF may be disturbed, and metabolic demands may be either decreased or increased.22,64–66,73,165 It is clear, however, that evidence of neuronal death from cerebral ischemia is a common finding on autopsy in patients who die after severe TBI Control of ICP and maintenance of adequate CPP and PbtO2 may limit the risk of developing secondary ischemia The goals of management are to avoid secondary insults by optimizing ICP, CPP, PbtO2, and CBF, creating the best possible environment for brain recovery Intracranial Pressure and Cerebral Perfusion Pressure Thresholds Adult patients with severe TBI who have an ICP of 20 mm Hg have a poorer outcome than those without increased ICP.135,136,166 Despite the RCT showing similar outcomes for adults with severe TBI managed in Latin America with versus without ICP monitoring, a consensus-based interpretation of that study suggested that the results of the trial should not be generalized and that it should not change practice of those currently using ICP monitoring.141,142 A prospective cohort study155 also suggested better outcomes in adults monitored and treated with CHAPTER 118 Traumatic Brain Injury A Level Level Level B Level Level Level C Level Level Level • Fig 118.9 Time course of CBF measured by Xe-enhanced computed tomography (CT) images in a 2-month-old infant after severe traumatic brain injury from a motor vehicle accident Standard CT images (upper row) and Xe-enhanced cerebral blood flow (CBF) maps (lower row) are shown from studies performed on admission (A) and at days (B) and days (C) after injury Flow is severely reduced (black) on admission Some recovery of CBF is seen at days and days after injury CBF ranges from lowest (darkest image) to highest (brightest image) 1389 1390 S E C T I O N X I I Pediatric Critical Care: Environmental Injury and Trauma 140 0 PostOp PreOp CT mg/100g/min ml/100g/min XeCT fdg-PET • Fig 118.10 Computed tomography (CT) image (left) of an acute subdural hematoma with mass effect that was treated with surgical evacuation 18F-fluorodeoxyglucose positron emission tomographic (FDGPET) map (center) obtained days after surgery shows marked local increases in cerebral glucose utilization in the brain regions underlying the hematoma Stable Xe-enhanced CT cerebral blood flow (CBF) map (right) also obtained days after surgery shows increased CBF in the same region, indicating that the increase in glucose utilization is not the result of hypoperfusion This phenomenon, termed hyperglycolysis, likely represents increased glucose utilization by astrocytes coupled to glutamate uptake This highlights the complex regional metabolic demands of the traumatically injured brain (From Bergsneider M, Hovda DA, Shalmon E, et al Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study J Neurosurg 1997;86:241–251.) CSF drainage versus those without ICP monitoring Some studies suggest that optimal outcome is achieved when even lower levels of ICP (i.e., 15 mm Hg) are the target.167 However, the most recent adult TBI guidelines update recommended an ICP threshold of 22 mm Hg rather than 20 mm Hg.168 Although no pediatric study has prospectively compared ICP treatment thresholds and their effect on outcome using a specific treatment regimen, the pediatric literature provides clues on the optimal ICP treatment threshold Early studies, including a total of more than 230 cases of severe pediatric TBI, reported that poor outcome was associated with ICP 20 mm Hg.65,169–172 Chambers and associates173 used an ICP threshold of 15 mm Hg in 99 children with head injuries (0–13 years of age) in the United Kingdom However, it remains a key unanswered question regarding whether a lower ICP threshold is appropriate for infants in whom physiologic MAP is lower than in adults.174 As with ICP, no RCT has been conducted to define the optimal CPP for pediatric TBI, although its importance in patient management is recognized Reductions in CPP below specific threshold values are associated with poor outcome The first pediatric guidelines recommendation of 40 mm Hg was based on four studies that defined the CPP associated with poor outcome as between 40 and 65 mm Hg.172,175–177 Several publications have further clarified the issue of optimal CPP in children, suggesting the need for age-dependent thresholds Chambers and colleagues178 published an insightful study on this topic based on data from 235 children They suggested minimum CPP values of 53, 63, and 66 mm Hg for children between the ages of and years, and 10 years, and 11 and 16 years, respectively However, that study considered only the first hours of monitoring, and CPP and ICP were not addressed for patients younger than years of age In a follow-up study of 91 children, Chambers and colleagues173 used a pressure-time index to determine critical CPP thresholds of 48, 54, and 58 mm Hg in children aged to years, to 10 years, and 11 to 15 years, respectively Allen and coworkers179 assessed data from more than 2000 children in the New York State Brain Trauma Foundation database, suggesting CPP thresholds of more than 60 mm Hg in adults, 50 to 60 mm Hg in children to 17 years of age, and more than 40 mm Hg in infants and children to years of age These are reasonable recommendations until prospective trials of CPP-directed therapy in children are carried out In addition to the methods described later for control of ICP, titration of vasopressor or inotropic support may be necessary to achieve an appropriate level of CPP once adequate filling pressure and hemoglobin are confirmed In some situations, as with the development of neurogenic pulmonary edema, aggressive cardiovascular monitoring and optimal titration of cardiopulmonary support can be challenging and key determinants of outcome Finally, not only are the optimal ICP and CPP targets likely to be important, but how one achieves these target values may be equally important DiGennaro and colleagues180 suggested that norepinephrine was associated with the best CPP and ICP profiles compared with other pressors in pediatric TBI Baseline Care Accompanying the third edition of the pediatric TBI guidelines, the algorithm (see Fig 118.11) provides a more comprehensive overview of the approaches to first-tier therapy than in prior versions given the inclusion of consensus-based recommendations and expanded format This includes recommendations for “Baseline Care” in the PICU after insertion of the ICP monitor Those recommendations include (1) maintaining appropriate sedation and analgesia, (2) controlled mechanical ventilation maintaining adequate arterial oxygenation and ventilation (targeting Paco2 of CHAPTER 118 Traumatic Brain Injury 1391 TBI (GCS ≤ 8) Cranial CT Surgery as Indicated Insert ICP Monitor δ Based on CVP, urine output, BUN, serum creatinine, fluid balance, and exam Ψ The timing of instituting first tier therapies depends on many factors such as the level of ICP and the tempo of disease progression; interventions may need to be bypassed, repeated or initiated concurrently * ICP 20-25 for >5 min; more rapidly for ICP >25 mmHg ** Mannitol could be substituted # Monitor EEG Herniation Pathway Baseline Care CPP Pathway Maintain appropriate analgesia/sedation Continue mechanical ventilation; maintain adequate arterial oxygenation; PaCO2 ~35 mmHg Maintain normothermia (7 g/dL (minimum); higher levels may be optimal based on advanced monitoring Treat coagulopathy Elevate HOB 30° Phenytoin or Levetiracetam/Consider continuous EEG monitoring throughout the management course Begin nutrition as early as feasible and treat hypoglycemia Maintain CPP Appropriate for age Minim 40 mmHg PbrO2 Pathway Emergent Treatment: Hyperventilation titrate to reverse pupillary dilation FiO2 = 1.0 Bolus mannitol or hypertonic saline Open EVD to continuous drainage Emergency CT ↑ ICP Ψ* Yes Maintain CPP Appropriate for age Minim 40 mmHg No CSF drainage if ventriculostomy present ↓ CPP ↓PbrO2 ICP Pathway If signs and symptoms of herniation • Pupillary dilation • Hypertension/bradycardia • Extensor posturing Confirm appropriate intravascular volume status (CVP) δ Vasopressor infusion Bolus of hypertonic saline Raise FiO2 ↑ ICP Ψ* Yes No Bolus and/ or infusion of hypertonic saline** ↑ ICP Ψ* Yes No Additional analgesia/sedation ↑ ICP Ψ* Yes No Carefully wean or withdraw ICP, CPP and/or PbrO2 directed therapy To Surgery if Indicated Neurological examination may help guide weaning or withdrawal of therapy and/or extent of monitoring ↓PbrO2 Neuromuscular blockade # Vasopressor infusion Adjust PaCO2 Optimize Hgb ↓PbrO2 ↓ CPP ↑ ICP Ψ* Yes No Additional hypertonic saline/hyperosmolar therapy ↑ ICP Ψ* Yes No ϕ Note: When ICP-directed care is deemed to be refractory to first tier therapies depends on many factors such as the level of ICP, the tempo of disease progression and others ϕSecond Tier Therapy • Fig 118.11 Algorithm for use at the bedside to guide first-tier therapies to treat severe pediatric trau- matic brain injury (TBI).4 This evidence- and consensus-based document that accompanied the third edition of the guidelines includes baseline care (gray), an intracranial pressure (ICP) pathway (yellow), a herniation pathway (green), a cerebral perfusion pressure (CPP) pathway (orange), a brain tissue partial pressure of oxygen (PbtO2) pathway (purple), and surgical intervention (red) The caregiver should integrate all the available information and implement the evidence in the guidelines in the context of each patient’s unique response to therapies to craft the most optimal treatment regimen Although a linear approach in each pathway is provided, variations in tempo and timing during which therapies are implemented will vary from case to case In some cases, a single intervention for raised ICP may suffice, while in others, multiple simultaneous interventions may be required The blue box indicates the need for second-tier therapy (see Fig 118.12) BUN, Blood urea nitrogen; CSF, cerebrospinal fluid; CT, computed tomography; CVP, central venous pressure; EEG, electroencephalogram; EVD, external ventricular drain; Fio2, fraction of inspired oxygen concentration; GCS, Glasgow Coma Scale; Hgb, hemoglobin; HOB, head of bed; Paco2, partial pressure of arterial carbon dioxide; Pao2, partial pressure of arterial oxygen 1392 S E C T I O N X I I Pediatric Critical Care: Environmental Injury and Trauma ,35 mm Hg), (3) maintaining normothermia, (4) ensuring appropriate intravascular volume status, (5) maintaining a hemoglobin of greater than g/dL (minimum) although higher levels may be needed depending on advanced monitoring, (6) treating coagulopathy, (7) elevating the head of the bed 30 degrees, and (7) beginning nutritional support as early as is feasible Seizure prophylaxis is discussed later in this chapter.4 Details about the specific first-tier therapies and pathway for application for the treatment of intracranial hypertension follow, along with the progression to second-tier therapies Treatment of Intracranial Hypertension: First-Tier Therapies Ventricular Cerebrospinal Fluid Drainage Ventricular CSF drainage has been used to manage raised ICP in adults for more than 40 years CSF drainage for treatment of intracranial hypertension in children was shown to improve CBF in 1971.181 Fortune and colleagues182 compared the effect of CSF drainage and mannitol in adults after severe TBI and noted similar effects on CBF and ICP Use of CSF drainage was associated with a greater increase in jugular venous saturation than was mannitol therapy CSF can be drained intermittently or continuously, with threshold values for drainage determined on the basis of the clinical indication In a small retrospective, two-center comparison between continuous and intermittent CSF drainage approaches in children with severe TBI, Shore and coworkers183 reported that continuous drainage was associated with removal of a much greater amount of CSF, markedly reduced CSF levels of biochemical mediators, and lower ICP However, the efficacy of CSF drainage versus other treatments of raised ICP remains unclear, and larger studies are needed However, if continuous drainage is used, inserting a second parenchymal ICP monitor may be of value because continuous drainage limits the ability to continuously monitor ICP and spikes of intracranial hypertension could be missed.184 Given that effectiveness of ICP control with or without CSF diversion is one of the hypotheses of the ADAPT trial, data on this important question should be forthcoming A recent development in our understanding of CSF dynamics is the discovery of the glymphatic pathway—a perivascular pathway for clearance of macromolecules in brain interstitial fluid analogous to the lymphatic system outside of the CNS.185 Since increases in ICP actually facilitate glymphatic flux, it is unclear what impact CSF drainage has on this homeostatic pathway.186 Osmolar Therapy Based on the hypothesis that BBB permeability and increases in CBV play only limited roles in the development of cerebral swelling and that tissue osmolar load may be more important, particularly in contusion, osmolar therapies (e.g., hypertonic saline solution and mannitol) are logical The BBB is nearly impermeable to both mannitol and sodium Despite its ubiquitous use and studies supporting its use for the management of TBI in adults, mannitol has been subjected to limited study in pediatric TBI Even though mannitol is a cornerstone for management of intracranial hypertension in pediatric and adult TBI,3,4 it has not been subjected to controlled clinical trials compared with placebo, other osmolar agents, or other mechanism-based therapies in children Mannitol reduces ICP by two distinct mechanisms First, it produces a rapid reduction in ICP by reducing blood viscosity, with a resultant decrease in blood vessel diameter and CBV.187 This mechanism is dependent on intact viscosity autoregulation of CBF that is linked to blood pressure autoregulation of CBF The effect of mannitol administration on blood viscosity and CBV is transient (lasting ,75 minutes) The second mechanism by which mannitol administration reduces ICP is via an osmotic effect This effect develops more slowly (over 15–30 minutes) and results from movement of water from parenchyma into the circulation The effect persists between and hours and depends on an intact BBB Changes in serum osmolality reduce brain water only in relatively normal brain regions Mannitol may accumulate in injured brain regions and a reverse osmotic shift may occur, with fluid moving from the circulation to the parenchyma, possibly exacerbating intracranial hypertension After 48 hours of therapy in adults, mannitol levels in CSF increase and, in some cases, a reverse osmotic gradient can be seen, explaining the lack of effect of this therapy or the need for escalating doses after several days of use.66 It was suggested to measure CSF mannitol levels to guide therapy Others have suggested titration of mannitol to osmolar gap.188 Mannitol is excreted unchanged in urine; a risk for development of acute tubular necrosis and renal failure has been suggested with serum osmolarity greater than 320 mOsm in adults However, the literature supporting this finding dates from the late 1970s and early 1980s, an era when dehydration therapy in combination with mannitol use was common Hyperosmolar euvolemia is targeted with contemporary mannitol use High levels of serum osmolarity (365 mOsm) appear to be tolerated in children when induced with hypertonic saline solution, although renal impairment can be seen with these high osmolarity levels in children.189,190 Few data support the concomitant use of diuretics and mannitol to reduce ICP James191 performed a retrospective study of 60 patients (ages 1–73 years) treated with mannitol for increased ICP After bolus mannitol administration, ICP decreased after 116 of 119 doses The reduction in ICP in response to mannitol administration was dose dependent between 0.18 and 2.5 g/kg In contrast, Marshall and colleagues192 reported equivalence for doses between 0.25 and 1.00 g/kg in adults Despite a remarkable track record for controlling ICP in TBI, clinical studies of mannitol use in pediatric TBI are lacking One epidemiologic study suggested that mannitol use was associated with prolonged PICU length of stay but no survival advantage.193 Nevertheless, it remains a first-tier therapy in severe pediatric TBI Use of hypertonic saline for treatment of raised ICP was first described in 1919 but failed to gain clinical acceptance.194 Hypertonic saline has now advanced to become the first-choice tier I pharmacotherapy for the treatment of raised ICP with the strongest support—level II in the third edition of the guidelines.3 Penetration of sodium across the BBB is low Sodium has a reflection coefficient higher than that of mannitol and shares with mannitol both the favorable rheologic effects on CBV and osmolar gradient effects Hypertonic saline exhibits other theoretic benefits, such as restoration of cell resting membrane potential, stimulation of atrial natriuretic peptide release, inhibition of inflammation, and enhancement of cardiac performance Shein et al.195 carried out a comparison of bolus 3% saline (between and mL/kg administered over 10–20 minutes), fentanyl, pentobarbital, or mannitol on ICP and CPP in real-world use with over 300 doses in 16 children with ICP crises after severe TBI Hypertonic saline reduced ICP and improved CPP and was the only therapy of those tested that favorably affected CPP There was an insufficient number of patients who received mannitol to draw conclusions about that therapy However, this study, combined with prior reports, provided level II evidence for bolus 3% ... not the result of hypoperfusion This phenomenon, termed hyperglycolysis, likely represents increased glucose utilization by astrocytes coupled to glutamate uptake This highlights the complex regional... therapies to treat severe pediatric trau- matic brain injury (TBI).4 This evidence- and consensus-based document that accompanied the third edition of the guidelines includes baseline care (gray),... CPP and ICP profiles compared with other pressors in pediatric TBI Baseline Care Accompanying the third edition of the pediatric TBI guidelines, the algorithm (see Fig 118.11) provides a more comprehensive