From Critical Care Medicine (PMK, MJB), University of Pittsburgh School of Medicine, Pittsburgh, PA; Department of Medical Informatics and Clinical Epidemiology (NC, SC, KP), Oregon Health & Science University, Portland, OR; Barrow Neurological Institute at Phoenix Children's Hospital (PDA), and Pediatric Neurosurgery/ Children' Neurosciences (PDA), Phoenix, AZ; Division of Child Neurology, Department of Pediatrics (SA) and Section of Neuroradiology (KAT), Loma Linda University School of Medicine, Loma Linda, CA; Pediatric Critical Care Medicine (SB), University of Utah School of Medicine, Salt Lake City, UT; Department of Neurological Surgery (NRS), Oregon Health & Science University, Portland, OR; Orthopedics and Sports Medicine (RMC), University of Washington School of Medicine, Seattle, WA; Neurological Surgery (JG), Weill Cornell Medical College; President of the Brain Trauma Foundation (JG), New York, NY; Translational Science (BG), Ikaria, Inc., Clinton, NJ; Pediatrics (BG), University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ; Surgery and Pediatrics (GAG), Duke University School of Medicine, Durham, NC; Pediatrics and Emergency Medicine (NK), British Columbia's Children's Hospital, University of British Columbia, Vancouver, BC; Neurocritical Care (RCT), Children's Hospital Boston; Neurology and Anesthesia (RCT), Harvard Medical School, Boston, MA; Anesthesiology and Pediatrics (MSV), University of Washington School of Medicine, Seattle, WA; Molecular Pharmacology and Biological Chemistry (MSW), Northwestern University Feinberg School of Medicine, Chicago, IL; Emergency Medicine and Pediatrics (CRW), and Pediatric Emergency Services (CRW), Oregon Health & Science University/Doernbercher Children's Hospital, Portland, OR.
Funding provided by the Brain Trauma Foundation and partial funding from the Charles Maddock Foundation.
The authors have not disclosed any potential conflicts of interest.
For information regarding this article, E-mail: firstname.lastname@example.org
Strength of Recommendations: Weak.
Quality of Evidence: Low, from poor and moderate-quality class III studies.
A. Level I
There are insufficient data to support a level I recommendation for this topic.
B. Level II
There are insufficient data to support a level II recommendation for this topic.
C. Level III
Use of intracranial pressure (ICP) monitoring may be considered in infants and children with severe traumatic brain injury (TBI).
II. EVIDENCE TABLE (see Table 1)
Secondary injury to the brain after severe TBI occurs, in part, as a result of reduced perfusion of surviving neural tissue, resulting in reduced oxygen and metabolite delivery and reduced clearance of metabolic waste and toxins. Secondary injury also occurs as the result of cerebral herniation syndromes, resulting in focal ischemic injury and brain stem compression along with other mechanisms. Intracranial hypertension represents a key pathophysiological variable in each of these secondary injury mechanisms (1–3).
Since the late 1970s, significant improvements in both survival and functional outcome after severe TBI have been achieved using intensive care management protocols that center on the measurement of ICP and medical and surgical treatment of intracranial hypertension (4). A study by Tilford and colleagues (5) demonstrated that an intensive care unit with higher incidence of ICP monitoring in severely brain-injured children, plus certain medical interventions, had a trend toward lower mortality than two other pediatric intensive care units. Similarly, a study by Tilford and colleagues (4) demonstrated improved outcomes after severe TBI in an era during which the overall rates of ICP monitoring in these patients increased. Attempts to evaluate the independent benefit of direct ICP measurement to improve outcomes, per se, are confounded by the numerous therapeutic interventions that have been simultaneously introduced and have not been subjected individually to controlled trials. These confounders include protocol-driven prehospital care, tracheal intubation and oxygenation, aggressive treatment of systemic hypotension and hypovolemia, osmolar treatment of cerebral edema, rapid cranial computed tomography (CT) imaging to detect mass lesions, improved enteral and parenteral nutrition, among others.
Several studies demonstrate an association between intracranial hypertension and/or systemic hypotension and poor outcome after severe TBI (6–8). It is less clear, however, whether intracranial hypertension or reduced cerebral perfusion secondary to intracranial hypertension is the primary mechanism of secondary injury. Cerebral perfusion pressure (equals mean arterial pressure minus ICP) is the simplest correlate of global cerebral perfusion (9–12). The relative value of ICP monitoring as a means of evaluating and manipulating cerebral perfusion pressure, vs. avoidance of cerebral herniation events, is also unclear (13).
The lack of controlled trials on ICP monitoring limited the strength of the recommendations contained in the first edition of the Guidelines for the Management of Severe TBI in Children (14). This dearth of strong evidence is associated with mixed adoption of guidelines-directed management in the United States and abroad (15–17). In a 2007 survey of U.S. neurosurgeons and nonneurosurgeons caring for such patients, Dean et al (15) found approximately 60% agreement and conformity with guidelines recommendations. In the United Kingdom, only 59% of children presenting with severe TBI underwent ICP monitoring with only half of clinical units caring for such children using monitoring technology (16, 17). The use of monitoring in children <2 yrs of age with severe TBI may be even less likely. A study by Keenan et al (18) observed use of ICP monitoring in only 33% of patients in this young age group at multiple centers in the state of North Carolina. There is also significant variability in the incidence of using various interventions for the treatment of intracranial hypertension at different centers (5).
For this update, MEDLINE was searched from 1996 through 2010 (Appendix B for search strategy), and results were supplemented with literature recommended by peers or identified from references lists. Of 36 potentially relevant studies, seven studies were added to the existing table and used as evidence for this topic.
V. SCIENTIFIC FOUNDATION
Two moderate and 14 poor-quality class III studies met the inclusion criteria for this topic and provide evidence to support the recommendation (9, 19–33).
Are Children With Severe TBI at Risk of Intracranial Hypertension?
A number of small studies demonstrate a high incidence of intracranial hypertension in children with severe TBI (20, 21, 23, 24, 26, 28, 31, 33). Some of these studies identify in preliminary fashion other clinical factors that, in combination with severe TBI in a child, are indicative of a high incidence of intracranial hypertension. In these patients, “diffuse cerebral swelling” on CT scan is 75% specific for the presence of intracranial hypertension (26). In a study of 56 severely brain-injured patients (39 of whom had severe TBI), 32% of children had an initial ICP measurement >20 mm Hg but 50% had ICP maximum >20 mm Hg at some point during their intensive care course (20). Intracranial hypertension (ICP >20 mm Hg) may also be significantly more prevalent in children with severe TBI who do not demonstrate spontaneous motor function (80%) than those who do (20%) (21).
These studies suggest that children presenting with severe TBI are at notable risk of intracranial hypertension. No specific markers have been identified that reliably determine the presence or absence of intracranial hypertension without monitoring in this population.
Are ICP Data Useful in Managing Pediatric Severe TBI?
Fifteen studies involving 857 pediatric patients demonstrated an association between intracranial hypertension (generally >20 mm Hg) and poor neurologic outcome or death (9, 19–28, 30–33).
One small study of 48 patients failed to demonstrate a clear association between intracranial hypertension and poor outcome (29). Specifically, a study by Grinkeviciute et al reported similar mean ICP in children with good and poor outcome. In their study, however, children with higher peak ICP were immediately and successfully treated with decompressive craniectomy.
These studies suggest that ICP is an important prognostic variable. It also plays a strong role both independently and as a component of cerebral perfusion pressure in directing the management of pediatric patients with severe TBI.
Does ICP Monitoring and Treatment Improve Outcome?
Two studies of combined treatment strategies also suggest that improved clinical outcomes are associated with successful control of intracranial hypertension (19, 30). A prospective observational study of 100 children with severe TBI treated with varying combinations of hyperventilation, diuretics, cerebrospinal fluid drainage, sedation, pharmacologic paralysis, and barbiturates reported that children whose intracranial hypertension was successfully lowered had better 1-yr outcomes than children whose intracranial hypertension was uncontrollable (but worse than those without intracranial hypertension) (19). A retrospective review of a prospectively acquired TBI database showed that reduced survival and worsened outcome in children with severe TBI were associated with intracranial hypertension refractory to treatment rather than peak ICP per se (30). In this study, successful control of intracranial hypertension, irrespective of treatment modality (osmolar therapy, cerebrospinal fluid drainage, decompression, etc.), was deemed to be important.
Although they represent only class III evidence for long-term outcome related to ICP monitoring and are only correlative, these studies support the association of successful ICP monitor-based management of intracranial hypertension with improved survival and neurologic outcome.
VI. INFORMATION FROM OTHER SOURCES
A. Indications From the Adult Guidelines
The adult guidelines offer the following recommendation.
* Level II: ICP should be monitored in all salvageable patients with a severe TBI (Glasgow Coma Scale score of 3–8 after resuscitation) and an abnormal CT scan. An abnormal CT scan of the head is one that reveals hematomas, contusions, swelling, herniation, or compressed basal cisterns.
* Level III: ICP monitoring is indicated in patients with severe TBI with a normal CT scan if two or more of the following features are noted at admission: age >40 yrs, unilateral or bilateral motor posturing, or systolic blood pressure <90 mm Hg.
What Patients Are at High Risk of ICP Elevation?
Patients with severe TBI (Glasgow Coma Scale ≤8) are at high risk for intracranial hypertension (8, 34). The combination of severe TBI and an abnormal head CT scan suggests a high likelihood (53% to 63%) of raised ICP (34). However, even with a normal admission CT scan, intracranial hypertension may be present (35, 36). Data collected predominantly in adult patients suggest that detection and treatment of intracranial hypertension may protect cerebral perfusion pressure, avoid cerebral herniation, and improve neurologic outcome (8, 11, 34, 37–39).
In certain conscious patients with CT findings suggesting risk of neurologic deterioration (hematomas, contusions, swelling, herniation, or compressed basal cisterns), however, monitoring may be considered based on the opinion of the treating physician (35, 38). Inability to perform serial neurologic examinations, because of pharmacologic sedation or anesthesia, may also influence a clinician's decision to monitor ICP in an individual patient (40, 41).
How Does ICP Data Influence Patient Management?
ICP data allow the management of severe TBI by objective criteria. This is particularly important because many, perhaps all, medical and surgical measures for the treatment of intracranial hypertension have significant potential adverse consequences (2, 7, 42). Thus, ICP monitoring allows the judicious use of interventions such as hyperosmolar therapy, sedatives, neuromuscular blockade, barbiturates, ventilator management, etc., with a defined end point that is correlated with clinical outcome. This may avoid potentially harmful, overly aggressive treatment.
Does ICP Monitoring Improve Outcome?
In adults, intensive management protocols for severe TBI, including ICP monitoring, have been associated with lowered mortality rates as compared with historical controls or centers in other countries not using monitoring techniques (8, 43–45). A study by Eisenberg et al (46) reported that improved ICP control was associated with improved outcome in severely head-injured patients with medically intractable intracranial hypertension. Finally, in a small, single-institution study of patients triaged according to the attending neurosurgery call schedule, mortality was over four times higher in nonmonitored than in monitored patients with severe TBI (47).
B. Information Not Included as Evidence
Various class III studies have demonstrated improved outcomes, vs. historical controls, in the era of ICP monitor-directed intensive therapy of patients with severe TBI (11, 35, 43, 48, 49). Two specific ICP monitor-directed therapies effective in treating acute intracranial hypertension have been associated with improved survival and clinical outcomes after severe TBI in children. As indicated in the evidence table, a study by Bruce et al (1) reported that aggressive therapy with hyperventilation and/or barbiturates to treat intracranial hypertension in 85 children with severe TBI resulted in 87.5% good outcomes and only 9% mortality. Not included as evidence, Peterson et al (50) performed a retrospective study of severe TBI in 68 infants and children, which showed that effective treatment of refractory intracranial hypertension using continuous infusion of hypertonic (3%) saline resulted in a mortality rate (15%) lower than expected as a result of trauma severity score (40%). There were only three deaths in this study (4%) resulting from uncontrolled intracranial hypertension.
Four lines of evidence support the use of ICP monitoring in children with severe TBI: a frequently reported high incidence of intracranial hypertension in children with severe TBI, a widely reported association of intracranial hypertension and poor neurologic outcome, the concordance of protocol-based intracranial hypertension therapy and best-reported clinical outcomes, and improved outcomes associated with successful ICP-lowering therapies. Evidence reviewed in the adult guidelines mirrors that for pediatric patients, further suggesting that ICP monitoring is of clinical benefit in patients with severe TBI.
Intracranial hypertension is both difficult to diagnose and is associated with poor neurologic outcomes and death in infants and young children. Intracranial hypertension may be present in children with open fontanelles and sutures (18). ICP monitoring is of significant use in these patient populations.
The presence of intracranial hypertension can also be influenced by the type of pathology on CT such as diffuse injury or specific etiologies such as traumatic sinus thrombosis.
By contrast, ICP monitoring is not routinely indicated in children with mild or moderate TBI. Treating physicians may, however, in some circumstances, choose to use ICP monitoring in conscious children who are at relative risk for neurologic deterioration as a result of the presence of traumatic mass lesions or in whom serial neurologic examination is precluded by sedation, neuromuscular blockade, or anesthesia.
VIII. KEY ISSUES FOR FUTURE INVESTIGATION
* Studies of specific subpopulations of pediatric patients with TBI in whom ICP monitoring is indicated; in particular, in the categories of infants and young children with abusive head trauma and/or infants with open fontanelles and sutures.
* Studies of the incidence of intracranial hypertension based on clinical and radiologic parameters in children of different ages and injury mechanisms.
* Focused multivariate analyses of children with intracranial hypertension to predict those who respond better to specific ICP-lowering therapies.
* Careful monitoring of the impact of adoption of ICP monitoring-directed protocols by hospitals and health systems should be undertaken to provide further evaluation of the impact of these measures on outcome as well as system performance variables.
* Studies are also needed to determine whether the type of ICP monitor (e.g., ventricular, parenchyma) or approach to monitoring (e.g., continuous or intermittent with cerebrospinal fluid drainage) influences outcome.
1. Bruce DA, Alavi A, Bilaniuk L, et al.: Diffuse cerebral swelling following head injuries in children: The syndrome of ‘malignant brain edema.’ J Neurosurg 1981; 54:170–178
2. Muizelaar JP, Marmarou A, DeSalles AA, et al.: Cerebral blood flow and metabolism in severely head-injured children. Part 1: Relationship with GCS score, outcome, ICP, and PVI. J Neurosurg 1989; 71:63–71
3. Sharples PM, Stuart AG, Matthews DS, et al.: Cerebral blood flow and metabolism in children with severe head injury. Part 1: Relation to age, Glasgow Coma Score, outcome, intracranial pressure, and time after injury. J Neurol Neurosurg Psychiatry 1995; 58:145–152
4. Tilford JM, Aitken ME, Anand KJ, et al.: Hospitalizations for critically ill children with traumatic brain injuries: A longitudinal analysis. Crit Care Med 2005; 33:2074–2081
5. Tilford JM, Simpson PM, Yeh TS, et al.: Variation in therapy and outcome for pediatric head trauma patients. Crit Care Med 2001; 29:1056–1061
6. Schoon P, Benito Mori L, Orlandi G, et al.: Incidence of intracranial hypertension related to jugular bulb oxygen saturation disturbances in severe traumatic brain injury patients. Acta Neurochir Suppl 2002; 81:285–287
7. Chesnut RM, Marshall LF, Klauber MR, et al.: The role of secondary brain injury in determining outcome from severe head injury. J Trauma 1993; 34:216–222
8. Marmarou A, Anderson R, Ward J, et al.: Impact of ICP instability and hypotension on outcome in patients with severe head trauma. J Neurosurg 1991; 75:S59–S66
9. Chambers IR, Treadwell L, Mendelow AD: Determination of threshold levels of cerebral perfusion pressure and intracranial pressure in severe head injury by using receiver-operating characteristic curves: An observational study in 291 patients. J Neurosurg 2001; 94:412–416
10. Chambers IR, Treadwell L, Mendelow AD: The cause and incidence of secondary insults in severely head-injured adults and children. Br J Neurosurg 2000; 14:424–431
11. Miller JD, Butterworth JF, Gudeman SK, et al.: Further experience in the management of severe head injury. J Neurosurg 1981; 54:289–299
12. Rosner MJ, Daughton S: Cerebral perfusion pressure management in head injury. J Trauma 1990; 30:933–940; discussion 940–941
13. Prabhakaran P, Reddy AT, Oakes WJ, et al.: A pilot trial comparing cerebral perfusion pressure-targeted therapy to intracranial pressure-targeted therapy in children with severe traumatic brain injury. J Neurosurg 2004; 100:454–459
14. Adelson PD, Bratton SL, Carney NA, et al.: Guidelines for the acute medical management of severe traumatic brain injury in infants, children, and adolescents. Chapter 5. Indications for intracranial pressure monitoring in pediatric patients with severe traumatic brain injury. Pediatr Crit Care Med 2003; 4:S19–S24
15. Dean NP, Boslaugh S, Adelson PD, et al.: Physician agreement with evidence-based recommendations for the treatment of severe traumatic brain injury in children. J Neurosurg 2007; 107:387–391
16. Morris KP, Forsyth RJ, Parslow RC, et al.: Intracranial pressure complicating severe traumatic brain injury in children: monitoring and management. Intensive Care Med 2006; 32:1606–1612
17. Segal S, Gallagher AC, Shefler AG, et al.: Survey of the use of intracranial pressure monitoring in children in the United Kingdom. Intensive Care Med 2001; 27:236–239
18. Keenan HT, Nocera M, Bratton SL: Frequency of intracranial pressure monitoring in infants and young toddlers with traumatic brain injury. Pediatr Crit Care Med 2005; 6:537–541
19. Alberico AM, Ward JD, Choi SC, et al.: Outcome after severe head injury. Relationship to mass lesions, diffuse injury, and ICP course in pediatric and adult patients. J Neurosurg 1987; 67:648–656
20. Barzilay Z, Augarten A, Sagy M, et al.: Variables affecting outcome from severe brain injury in children. Intensive Care Med 1988; 14:417–421
21. Bruce DA, Raphaely RC, Goldberg AI, et al.: Pathophysiology, treatment and outcome following severe head injury in children. Childs Brain 1979; 5:174–191
22. Downard C, Hulka F, Mullins RJ, et al.: Relationship of cerebral perfusion pressure and survival in pediatric brain-injured patients. J Trauma 2000; 49:654–658; discussion 658–659
23. Esparza J, M-Portillo J, Sarabia M, et al.: Outcome in children with severe head injuries. Childs Nerv Syst 1985; 1:109–114
24. Kasoff SS, Lansen TA, Holder D, et al.: Aggressive physiologic monitoring of pediatric head trauma patients with elevated intracranial pressure. Pediatr Neurosci 1988; 14:241–249
25. Michaud LJ, Rivara FP, Grady MS, et al.: Predictors of survival and severity of disability after severe brain injury in children. Neurosurgery 1992; 31:254–264
26. Shapiro K, Marmarou A: Clinical applications of the pressure–volume index in treatment of pediatric head injuries. J Neurosurg 1982; 56:819–825
27. Adelson PD, Ragheb J, Kanev P, et al.: Phase II clinical trial of moderate hypothermia after severe traumatic brain injury in children. Neurosurgery 2005; 56:740–754; discussion 740–754
28. Cruz J, Nakayama P, Imamura JH, et al.: Cerebral extraction of oxygen and intracranial hypertension in severe, acute, pediatric brain trauma: Preliminary novel management strategies. Neurosurgery 2002; 50:774–779; discussion 779–780
29. Grinkeviciute DE, Kevalas R, Matukevicius A, et al.: Significance of intracranial pressure and cerebral perfusion pressure in severe pediatric traumatic brain injury. Medicina (Kaunas, Lithuania) 2008; 44:119–125
30. Jagannathan J, Okonkwo DO, Yeoh HK, et al.: Long-term outcomes and prognostic factors in pediatric patients with severe traumatic brain injury and elevated intracranial pressure. J Neurosurg Pediatr 2008; 2:240–249
31. Pfenninger J, Santi A: Severe traumatic brain injury in children—Are the results improving? Swiss Med Wkly 2002; 132:116–120
32. Wahlstrom MR, Olivecrona M, Koskinen LO, et al.: Severe traumatic brain injury in pediatric patients: Treatment and outcome using an intracranial pressure targeted therapy—The Lund concept. Intensive Care Med 2005; 31:832–839
33. White JR, Farukhi Z, Bull C, et al.: Predictors of outcome in severely head-injured children. Crit Care Med 2001; 29:534–540
34. Narayan RK, Kishore PR, Becker DP, et al.: Intracranial pressure: To monitor or not to monitor? A review of our experience with severe head injury. J Neurosurg 1982; 56:650–659
35. Marshall L, Gautille T, Klauber M: The outcome of severe closed head injury. J Neurosurg 1991; 75:S28–S36
36. O'Sullivan MG, Statham PF, Jones PA, et al.: Role of intracranial pressure monitoring in severely head-injured patients without signs of intracranial hypertension on initial computerized tomography. J Neurosurg 1994; 80:46–50
37. Eisenberg HM, Gary HE Jr, Aldrich EF, et al.: Initial CT findings in 753 patients with severe head injury. A report from the NIH Traumatic Coma Data Bank. J Neurosurg 1990; 73:688–698
38. Levin HS, Eisenberg HM, Gary HE, et al.: Intracranial hypertension in relation to memory functioning during the first year after severe head injury. Neurosurgery 1991; 28:196–199; discussion 200
39. Gopinath S, Constant C, Robertson C: Critical thresholds for physiological parameters in patients with severe head injury. Congress of Neurological Surgeons, Vancouver, BC, Canada, 1993
40. Humphreys RP, Hendrick EB, Hoffman HJ: The head-injured child who ‘talks and dies.’ A report of 4 cases. Childs Nerv Syst 1990; 6:139–142
41. Lobato RD, Rivas JJ, Gomez PA, et al.: Head-injured patients who talk and deteriorate into coma. Analysis of 211 cases studied with computerized tomography. J Neurosurg 1991; 75:256–261
42. Kaufmann AM, Cardoso ER: Aggravation of vasogenic cerebral edema by multiple-dose mannitol. J Neurosurg 1992; 77:584–589
43. Becker DP, Miller JD, Ward JD, et al.: The outcome from severe head injury with early diagnosis and intensive management. J Neurosurg 1977; 47:491–502
44. Colohan AR, Alves WM, Gross CR, et al.: Head injury mortality in two centers with different emergency medical services and intensive care. J Neurosurg 1989; 71:202–207
45. Jennett B, Teasdale G, Galbraith S, et al.: Severe head injuries in three countries. J Neurol Neurosurg Psychiatry 1977; 40:291–298
46. Eisenberg HM, Frankowski RF, Contant CF, et al.: High-dose barbiturate control of elevated intracranial pressure in patients with severe head injury. J Neurosurg 1988; 69:15–23
47. Ghajar J, Hariri R, Patterson R: Improved outcome from traumatic coma using only ventricular CSF drainage for ICP control. Adv Neurosurg 1993; 21:173–177
48. Patel HC, Menon DK, Tebbs S, et al.: Specialist neurocritical care and outcome from head injury. Intensive Care Med 2002; 28:547–553
49. Ritter AM, Muizelaar JP, Barnes T, et al.: Brain stem blood flow, pupillary response, and outcome in patients with severe head injuries. Neurosurgery 1999; 44:941–948
50. Peterson B, Khanna S, Fisher B, et al.: Prolonged hypernatremia controls elevated intracranial pressure in head-injured pediatric patients. Crit Care Med 2000; 28:1136–1143