Strength of Recommendations:Weak.
Quality of Evidence: Low, primarily from Class III studies and indirect evidence.

Adult

1. Mild or prophylactic hyperventilation (PaCO₂ < 35 mmHg) should be avoided. Hyperventilation therapy titrated to clinical effect may be necessary for brief periods in cases of cerebral herniation or acute neurologic deterioration.3
2. Patients should be assessed frequently for clinical signs of cerebral herniation. The clinical signs of cerebral herniation include dilated and unreactive pupils, asymmetric pupils, a motor exam that identifies either extensor posturing or no response, or progressive neurologic deterioration (decrease in the Glasgow Coma Scale [GCS] Score of more than 2 points from the patient's prior best score in patients with an initial GCS < 9).
3. In patients who are normoventilated, well oxygenated, and normotensive - and still have signs of cerebral herniation - hyperventilation should be used as a temporizing measure, and discontinued when clinical signs of herniation resolve.

Hyperventilation is administered as:

• 20 breaths per minute in an adult
• 25 breaths per minute in a child
• 30 breaths per minute in an infant less than 1 year old

The goal of hyperventilation is EtCO₂ of 30-35 mmHg. Capnography is the preferred method for monitoring ventilation.

Neuronal injury may result from the initial trauma (primary injury) or as the result of indirect mechanisms (secondary injury), such as hypoxemia, hypotension, and cerebral edema. Injury may also occur as the result of associated conditions that caused the trauma, such as hypoglycemia or drug toxicity. The goal of resuscitation in TBI is to preserve cerebral perfusion and to minimize neuronal injury. As discussed in other sections of these guidelines, hypotension and hypoxemia are associated with poor outcomes in patients with TBI, thus systemic resuscitation is the highest priority in prehospital management.

Management of patients with TBI is directed at maintaining cerebral perfusion. Signs of cerebral herniation include dilated or unreactive pupil(s), asymmetric pupils, extensor posturing, or progressive neurologic deterioration (decrease in the GCS score of more than 2 points from the patient's prior best score in patients with an initial GCS less than 9).31

Hyperventilation is beneficial in the immediate management of patients demonstrating signs of cerebral herniation, but it is not recommended as a prophylactic measure.6 Mannitol is effective in reducing intracranial pressure (ICP) and is recommended for control of increased ICP. A number of pharmacologic agents have been investigated in an attempt to prevent the secondary injury associated with TBI, but none have proven efficacious.23

For this topic Medline was searched from 1996 through July 2006 using the search strategy for this question (see Appendix B), and results were supplemented with literature recommended by peers or identified from reference lists. For adult studies, of 69 potentially relevant publications, 6 were used as evidence for this topic. For pediatric studies, of 48 potentially relevant publications, no studies were used as evidence for this topic (see Evidence Table).

Adult and Pediatrics

1. Mild or prophylactic hyperventilation (PaCO₂ < 35 mmHg) should be avoided. Hyperventilation therapy titrated to clinical effect may be necessary for brief periods in cases of cerebral herniation or acute neurologic deterioration.
2. Patients should be assessed frequently for clinical signs of cerebral herniation. The clinical signs of cerebral herniation include dilated and unreactive pupils, asymmetric pupils, a motor exam that identifies either extensor posturing or no response, or progressive neurologic deterioration (decrease in the Glasgow Coma Scale [GCS] Score of more than 2 points from the patient's prior best score in patients with an initial GCS < 9).
3. In patients who are normoventilated, well oxygenated, and normotensive - and still have signs of cerebral herniation - hyperventilation should be used as a temporizing measure, and discontinued when clinical signs of herniation resolve. Hyperventilation is administered as:
   • 20 breaths per minute in an adult
   • 25 breaths per minute in a child
   • 30 breaths per minute in an infant less than 1 year old

The goal of hyperventilation is EtCO₂ of 30-35 mmHg. Capnography is the preferred method for monitoring ventilation.

Foundation. Hyperventilation in the acute setting reduces ICP by causing cerebral vasoconstriction with a subsequent reduction in cerebral blood flow.28 Hyperventilation has been shown to reduce ICP in many patients with cerebral edema.22 There is evidence that hyperventilation also reduces cerebral blood flow, a deleterious effect.28 Class II data indicate that patients chronically hyperventilated in the inhospital setting have worse outcomes at 3 and 6 months but equivalent outcomes at one year.24

It appears that in some patients with progressive cerebral edema, hyperventilation can temporize impending herniation. In patients who have objective evidence of herniation, the benefits of hyperventilation in delaying that process outweigh the potential detrimental effects. The key to hyperventilation therapy, therefore, becomes the ability to identify those patients at risk for herniation and to avoid hyperventilation in those not at risk; that is, to carefully avoid the routine hyperventilation of all TBI patients and especially those not at risk for herniation. Unfortunately, unintentional hyperventilation appears to be common in the prehospital environment from a variety of causes.21 Even the use of capnography can not assure the avoidance of inadvertent hyperventilation.4-7,9,13,17,18,20,29,30,35

A recent study demonstrated a relationship between field intubation and poor outcomes.10 The authors investigated the association between hyperventilation and increased morbidity; post hoc analysis indicated a relationship between lower PaCO₂ upon arrival in the emergency department and poorer outcomes.9,11 These data, however, are retrospective and use emergency department blood gas measurements as a surrogate assessment of field ventilation.

In the hospital setting, intracranial pressure (ICP) is used as a guide for the use of hyperventilation. Since this is not available in the prehospital phase, clinical criteria must substitute to identify those patients at risk. Consequently, hyperventilation is reserved as a temporizing measure for those patients with severe TBI who show signs of cerebral herniation (defined above).

Although not specifically supported by TBI outcome data, current best practice would appear to be to assure adequate oxygenation as described elsewhere in this document, and per American Heart Association Cardiopulmonary Resuscitation ventilation protocols. For patients who demonstrate or develop signs of cerebral herniation, hyperventilation should be instituted, as determined by ventilatory rate; that is 20 bpm in an adult, 25 bpm in a child, and 30 bpm in an infant less than one year old.2

Hyperosmolar Therapies. Mannitol has long been accepted as an effective tool for reducing intracranial pressure.3,15,19,33,36 Numerous mechanistic laboratory studies support this conclusion. However, there is no evidence to support its use in the prehospital setting. In addition, its impact on outcome has not been demonstrated in a Class I trial that tests mannitol against placebo. Schwartz et al. conducted a study comparing mannitol to pentobarbital which failed to demonstrate the superiority of pentobarbital and which demonstrated better outcomes and maintenance of CPP in the mannitol group.33

Hypertonic saline offers an attractive alternative to mannitol as a brain targeted hyperosmotic therapy. Its ability to reduce elevated ICP has been demonstrated with studies in the ICU and in the operating room.12,16,25,26 Hypertonic saline is a low volume resuscitation fluid. While the qualities that make it useful as a low volume resuscitation fluid and as a brain targeted therapy are related, this discussion will be limited to its role as a brain targeted therapy.

There is no consensus on what is meant by "hypertonic saline". Concentrations of 3%, 7.2%, 7.5%, 10% and 23.4% have all been used. There is no consensus on the optimum concentration for reduction of ICP.12,16,25,37 Hypertonic saline is dosed in different ways. In some studies, it is given as an infusion, the goal of which is to elevate serum sodium to 155-160 mEq/L, although some investigators have gone as high as 180 mEq/L. This elevated serum sodium is thought to help stabilize ICP and reduce the therapeutic intensity required to prevent elevated ICP.26,27 This modality would not be used in the prehospital environment.

Multiple animal studies and several human studies have demonstrated that hypertonic saline, as a bolus, can reduce ICP in a monitored environment such as the operating room or ICU where ICP monitoring is present.14,35,37 Comparison of these studies is difficult since they do not use the same concentrations or protocols. Unlike mannitol, no study has demonstrated an effect of hypertonic saline on clinical indicators of herniation, such as pupillary widening or posturing.

One Class II study evaluated the impact of prehospital hypertonic saline on neurological outcome.8 Hypertonic saline did not demonstrate any advantage over normal saline on neurological outcome when given as a prehospital resuscitation fluid. Similarly, a Class III study comparing 1.6% saline to lactated Ringer's found no difference in outcomes between groups, but baseline differences and other flaws limit the findings of this study.36 The current literature therefore does not support the use of hypertonic saline as a braintargeted therapy in the prehospital environment. This conclusion, however, does not extend to its use as a resuscitation fluid, a topic covered elsewhere in these guidelines.

Pediatrics - Additional Considerations

As stated in the Guidelines for the Acute Medical Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents,1 the effect of hyperventilation on long-term outcome has not been addressed in pediatric TBI. We used their recommendations relevant to prehospital care, which were based upon indirect evidence from adult studies.

Further data on the impact of the prehospital use of hypertonic saline on TBI outcome is needed. Cognitive recovery as a separate endpoint from blood pressure resuscitation needs to be investigated.

The use of capnography in managing prehospital hyperventilation needs to be better defined. Current extrapolations from inhospital and operating room settings are inaccurate and misleading. Independent prehospital data on the use and limitations of capnography is needed. Evidence-based capnography thresholds need to be developed.

Better prehospital methods are needed for assessing which patients are at risk for herniation or in need of high level TBI interventions.

The role of mannitol in herniation should be investigated.