Pediatric Critical Care Medicine:
Chapter 13. Hyperventilation
Kochanek, Patrick M. MD, FCCM; Carney, Nancy PhD; Adelson, P. David MD, FACS, FAAP; Ashwal, Stephen MD; Bell, Michael J. MD; Bratton, Susan MD, MPH, FAAP; Carson, Susan MPH; Chesnut, Randall M. MD, FCCM, FACS; Ghajar, Jamshid MD, PhD, FACS; Goldstein, Brahm MD, FAAP, FCCM; Grant, Gerald A. MD; Kissoon, Niranjan MD, FAAP, FCCM; Peterson, Kimberly BSc; Selden, Nathan R. MD, PhD, FACS, FAAP; Tong, Karen A. MD; Tasker, Robert C. MBBS, MD, FRCP; Vavilala, Monica S. MD; Wainwright, Mark S. MD, PhD; Warden, Craig R. MD, MPH, FAAP, FACEP
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.
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Strength of Recommendations: Weak.
Quality of Evidence: Low, from one poor-quality study and one moderate-quality class III study.
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
Avoidance of prophylactic severe hyperventilation to a PaCO2 <30 mm Hg may be considered in the initial 48 hrs after injury.
If hyperventilation is used in the management of refractory intracranial hypertension, advanced neuromonitoring for evaluation of cerebral ischemia may be considered.
II. EVIDENCE TABLE (see Table 1)
Hyperventilation has been used in the management of severe pediatric traumatic brain injury (TBI) for the rapid reduction of ICP since the 1970s. This approach was based on the assumption that hyperemia was common after pediatric TBI. Hyperventilation therapy was thought to benefit the injured brain primarily through an increase in perfusion to ischemic brain regions and a decrease in ICP. More recent pediatric studies have shown that hyperemia is uncommon and also have raised concerns about the safety of hyperventilation therapy (1–6).
Research on the effect of hyperventilation in children has focused on assessment of cerebral physiological variables. The effect of hyperventilation therapy on outcome in infants and children with severe TBI has not been directly compared with other therapies such as hyperosmolar agents, barbiturates, hypothermia, or early decompressive craniectomy.
Hyperventilation reduces ICP by producing hypocapnia-induced cerebral vasoconstriction and a reduction in cerebral blood flow (CBF) and cerebral blood volume, resulting in a decrease in ICP. Recent clinical studies in mixed adult and pediatric populations have demonstrated that hyperventilation may decrease cerebral oxygenation and may induce brain ischemia (5, 7–9). In addition, after TBI, the CBF response to changes in PaCO2 can be unpredictable. A study by Stringer et al (10) studied regional CBF using xenon computed tomography and vascular reactivity before and after hyperventilation in 12 patients including three children with severe TBI. Hyperventilation-induced CBF reductions affected both injured and apparently intact areas of the brain. The ischemic threshold was defined as a CBF of 23 mL/100 g/min in gray matter and this occurred in four of 12 patients after hyperventilation. Changes in ICP, cerebral perfusion pressure, and mean arterial pressure were variable in these patients after hyperventilation. The level of hyperventilation used in this study was profound with end-tidal CO2 values of 20–26 mm Hg before and 8–19 mm Hg after hyperventilation. In addition to reducing CBF, prophylactic hypocarbia after TBI has been shown experimentally to reduce the buffering capacity of cerebrospinal fluid (CSF), an effect that may be as or more important than its effect on CBF (5).
Despite a prior recommendation in the 2003 guidelines against prophylactic hyperventilation, it remains a commonly used therapy in children (11–13). For example, >40% of the children in the recent Canadian multicentered trial of hypothermia in severe pediatric TBI had PaCO2 <30 mm Hg (12). Similarly, in the study by Curry et al (11), 50% of patients with severe TBI had severe hypocarbia (PaCO2 <30 mm Hg) by arterial blood gas in the first 48 hrs of admission. This finding parallels another recent report that mild hyperventilation was the most commonly used therapy, having been applied in >90% of patients in the data bank of >500 children with severe TBI from the United Kingdom and Ireland (14).
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 reference lists. Of 15 potentially relevant studies, one was added to the existing table and used as evidence for this topic.
V. SCIENTIFIC FOUNDATION
Two class III studies met the inclusion criteria for this topic and provide evidence to support the recommendations (11, 15). Neither represented a comparison of hyperventilation vs. normal ventilation or to any other therapy targeting control of ICP. Similarly, there were no reports in children specifically addressing the effects of varying levels of hyperventilation on ICP or outcome or studies of the transient application of hyperventilation in the setting of impending herniation or ICP crisis. Lastly, neither study had a standardized protocol to assess PaCO2, measuring it only intermittently.
One report described the effects of hyperventilation on CBF, brain physiology, and Glasgow Outcome Scale at 6 months (15). A study by Skippen et al (15) was carried out as a prospective nonrandomized, selected case series of 23 children (3 months to 16 yrs of age) with isolated severe TBI. CBF was measured by xenon computed tomography during PaCO2 adjustments to >35, 25–35, and <25 mm Hg. The ischemic threshold was defined as CBF <18 mL/100 g/min. However, the ischemic threshold in children is not defined and may vary with age. CO2 reactivity of CBF was also assessed. Management included CSF drainage and hyperosmolar therapy but not steroids or barbiturates. As PaCO2 was reduced with hyperventilation, CBF decreased in almost all patients despite decreased ICP and increased cerebral perfusion pressure. A relationship between the level of hypocarbia and frequency of cerebral ischemia was observed. The frequency of regional ischemia was 28.9% during normocapnia and increased to 59.4% and 73.1% for PaCO2 25–35 mm Hg and <25 mm Hg, respectively. However, no statistical analysis was done. Fifty-two percent had a good or moderate outcome, 43.5% were severely disabled or vegetative, and 4.3% died. Again, no analysis was conducted.
A second report examined the association between hypocarbia and outcome at hospital discharge in a large pediatric series of severe TBI victims who were all mechanically ventilated (11). A study by Curry et al (11) was carried out as a retrospective cohort study of 464 patients <15 yrs of age with an admission Glasgow Coma Scale score <9 and a head Abbreviated Injury Score ≥3 with a PaCO2 recorded in the first 48 hrs of admission for the years 2000–2005. The authors examined the incidence of severe hypocarbia (PaCO2 <30 mm Hg) and its relationship with neurologic outcome before (375 patients) and after (89 patients) the publication of the 2003 pediatric TBI guidelines (16). They found a nonsignificant change in the incidence of severe hypocarbia from 60% of patients before to 52% after (p = .19). Patients with one documented episode of severe hypocarbia, controlling for emergency department Glasgow Coma Scale score, lowest emergency department systolic blood pressure, Injury Severity Score, PaCO2 sampling frequency, and year of admission, had an adjusted odds ratio (95% confidence interval) for mortality of 1.44 (0.56–3.73) for one episode of severe hypocarbia, 4.18 (1.58–11.03) for two episodes, and 3.93 (1.61–9.62) for three or more episodes compared with patients with mild or no hypocarbia. These findings, although retrospective, show a strong association of severe hypocarbia with poor outcomes. However, there might be other contributors to hypocarbia such as marked reduction in metabolic rates or acidosis from systemic shock. Thus, the exact contribution of induced hyperventilation to poor outcome cannot be clearly defined from this study.
VI. INFORMATION FROM OTHER SOURCES
A. Indications From the Adult Guidelines
The most recent adult guidelines (17) had one level II recommendation: “prophylactic hyperventilation (PaCO2 of 25 mm Hg or less) is not recommended.” The authors also had several level III recommendations: 1) “hyperventilation is recommended as a temporizing measure for the reduction of elevated ICP”; 2) “hyperventilation should be avoided during the first 24 hrs after injury when CBF is often critically reduced”; and 3) “if hyperventilation is used, jugular venous oxygenation saturation or brain tissue oxygen tension measurements are recommended to monitor oxygen delivery.”
Despite a lack of published evidence supporting the use of hyperventilation in the management of pediatric patients with severe TBI, it continues to be used commonly worldwide. No randomized controlled trial has been carried out to study the impact of hyperventilation on any aspect of the management of severe TBI in children such as in the setting of refractory intracranial hypertension or herniation. The limited evidence, however, supports that prophylactic severe hyperventilation to a PaCO2 <30 mm Hg should be avoided in the initial 48 hrs after injury. Arguing against the use of prophylactic hyperventilation, published evidence discussed in this report indicates that the use of hyperventilation is associated with CBF reductions and that prolonged and or significant hypocarbia is associated with poor outcome in pediatric patients with severe TBI. As a result, advanced neuromonitoring for evaluation of cerebral ischemia may be considered if hyperventilation is to be used in the management of refractory intracranial hypertension.
VIII. KEY ISSUES FOR FUTURE INVESTIGATION
* In the setting of refractory intracranial hypertension or brain herniation, studies are needed to determine the efficacy of hyperventilation in comparison to other second-tier therapies.
* Studies are needed to determine the optimal monitoring technique in patients treated with hyperventilation, including assessments of markers of cerebral ischemia, such as CBF, brain tissue oxygen tension, jugular venous oxygenation saturation, transcranial Doppler, near-infrared spectroscopy, serum biomarkers of brain injury, or other advanced neuromonitoring.
* The effects of hyperventilation on long-term outcome should be addressed.
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10. Stringer WA, Hasso AN, Thompson JR, et al.: Hyperventilation-induced cerebral ischemia in patients with acute brain lesions: Demonstration by Xenon-enhanced CT. AJNR Am J Neuroradiol 1993; 14:475–484
11. Curry R, Hollingworth W, Ellenbogen RG, et al.: Incidence of hypo- and hypercarbia in severe traumatic brain injury before and after 2003 pediatric guidelines. Pediatr Crit Care Med 2008; 9:141–146
12. Hutchison JS, Ward RE, Lacroix J, et al.: Hypothermia therapy after traumatic brain injury in children. N Engl J Med 2008; 358:2447–2456
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15. Skippen P, Seear M, Poskitt K, et al.: Effect of hyperventilation on regional cerebral blood flow in head-injured children. Crit Care Med 1997; 25:1402–1409
16. 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 14. The role of temperature control following severe pediatric traumatic brain injury. Pediatr Crit Care Med 2003; 4:S53–S55
17. Bratton SL, Chestnut RM, Ghajar J, et al.: Guidelines for the management of severe traumatic brain injury. XIV. Hyperventilation. J Neurotrauma 2007; 24(Suppl 1):S87–S90
©2012The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
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