Strength of Recommendations:Weak.
Quality of Evidence: Low, from Class III studies, or Class II studies with contradictory findings.

Adult

1. Hypotensive patients should be treated with isotonic fluids.
2. Hypertonic resuscitation is a treatment option for TBI patients with a Glasgow Coma Scale Score (GCS) < 8.

Pediatrics

1. For the pediatric TBI patient, hypotension should be treated with isotonic solutions.

Hemorrhage following trauma decreases cardiac preload. When compensatory mechanisms are overwhelmed, this hypovolemia leads to decreased peripheral perfusion and oxygen delivery. Fluid therapy is used to replete preload, supporting cardiovascular function and peripheral oxygen delivery. This is particularly important in patients with TBI, as decreased cerebral perfusion can increase the extent of primary neurological injury. Specifically, hypotension has been shown to produce significant secondary brain injury and substantially worsen outcome.

In adults, hypotension is defined as a systolic blood pressure (SBP) < 90 mmHg. In children, hypotension is defined as SBP less than the 5th percentile for age or by clinical signs of shock. Usual values are:

To date, crystalloid fluid has been used most often to augment cardiac preload, maintain cardiac output, and support peripheral oxygen delivery in trauma patients. The recommendation for adults is to rapidly infuse two liters of Ringer's lactate or normal saline as the initial fluid bolus.1 In children, fluid resuscitation is indicated for clinical signs of decreased perfusion even when an adequate blood pressure reading is obtained.

The goal of prehospital fluid resuscitation is to support oxygen delivery and optimize cerebral hemodynamics. Crystalloid fluid is most often used, although other options such as hyperoncotic and hypertonic fluids as well as hemoglobin substitutes have been used. If hypotension does occur, blood pressure and oxygen delivery should be promptly restored to avoid secondary brain injury. Ideally, this infusion should be accomplished without causing secondary blood loss or hemodilution.

For this update 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 15 potentially relevant publications, 1 was added to the existing table and used as evidence for this question. For pediatric studies, of 23 potentially relevant publications, no new studies were included (see Evidence Tables).

Adult

A. Hypotensive patients should be treated with isotonic fluids.

Foundation. The deleterious effects of hypotension in both adult and pediatric patients with TBI have been documented. Early hypotension has been shown to be a statistically significant and independent factor associated with worsening outcome from TBI.3,5,9,20 From the report on prediction of outcome from TBI,2 hypotension was one of the five factors found to have a 70% or greater positive predictive value for mortality. Despite the solid evidence of the negative influence of early hypotension on outcome from TBI in adults, there is much less evidence that reducing or preventing this secondary insult improves outcome.

Because the underlying cause of hypotension in these patients is almost always blood and/or fluid losses, intravascular volume repletion is the most effective way of restoring blood pressure. In contrast, data indicate that early restoration of blood pressure in patients with penetrating torso trauma worsens outcome. The relationship between these data and outcome in patients with TBI is unknown.

Specific evidence indicating that pre-hospital protocols prevent or minimize hypotensive insults and improve outcome is minimal. Despite the use of multivariate analysis to control for confounding variables, the possibility remains that some, most, or all secondary insults occurring during the pre-hospital period that are associated with poor recovery are simply manifestations of the severity of injury and not treatable entities.

B. Hypertonic resuscitation is a treatment option for TBI patients with a Glasgow Coma Scale Score (GCS) < 8.

Foundation. Isotonic crystalloid solution is the fluid most often used in the prehospital resuscitation of TBI patients. However, little data have been published to support its use.

Wade reviewed a set of studies containing data for patients with TBI who received hypertonic saline.19 Survival to discharge was 38% for patients treated with hypertonic saline and 27% for standard therapy (p =0.08). When logistic regression analysis was performed comparing hypertonic with isotonic fluids, the odds ratio was 1.92 for 24-hour survival and 2.12 for survival to discharge (p = 0.048).

Vassar et al. published four randomized, doubleblind trials of hypertonic saline.15,16,17,18 In the first, comparing two groups of TBI patients receiving either hypertonic or normal saline, no differences in outcome were found.16 Additionally, intracranial bleeding did not increase with either therapy. In a later study comparing hypertonic saline with Ringer's lactate in 166 patients, (32% with severe TBI)logistic regression analysis showed the hypertonic saline group to have improved survival.17 A third study of 258 patients (10% with severe TBI) compared hypertonic saline with hypertonic saline and dextran.18 In patients with a GCS less than 8 or with severe anatomic cerebral damage, survival with either fluid was greater than predicted by the Trauma Related Injury Severity Score (TRISS). In 1993, Vassar published a multi-center trial of 194 patients, 74% had severe TBI.15 Although there was no overall effect on survival, patients in the hypertonic saline group with an initial GCS < 8 had better survival.

More recently, Cooper et al. reported a randomized double blind trial of hypertonic saline or standard fluid therapy in 229 patients with severe TBI and hypotension.4 Multi-trauma patients were included but patients with comorbid conditions, peripheral edema or close proximity to the hospital were excluded. Following an initial fluid bolus of 250 mL, patients received standard resuscitation, both in the field and in the hospital. There were no differences in outcomes between the two groups.

Pediatrics

A. For the pediatric TBI patient, hypotension should be treated with isotonic solutions.

Foundation. The negative impact of hypotension with or without hypoxia and hypercarbia in patients with severe TBI has been demonstrated repeatedly in studies of mixed adult and pediatric populations.2,3,5,14 In these studies, hypoxia, hypercarbia, and hypotension were all commonly observed.

In a prospective study of 200 children, Mayer10 found that mortality was 55% in the presence of hypoxia, hypercarbia or hypotension and only 7.7% without any of these factors present (p < 0.01). In a prospective cohort study by Ong12 in Kuala Lumpur, the presence of hypotension increased the probability of a poor outcome. In the setting of abusive TBI, Johnson6 found that apnea was present in the majority of patients and 50% were also hypotensive. It was concluded that cerebral hypoxia and/or ischemia was more strongly associated with poor outcome than mechanism of injury.

Pigula et al13 analyzed the influence of hypotension on mortality from severe TBI (GCS ≤ 8) in two prospectively collected pediatric (age ≤16 years) databases. The participating centers were well developed pediatric trauma centers. They reported an 18% incidence of hypotension (defined as either a systolic blood pressure (SBP) ≤ 90 mmHg or a SBP less than the fifth percentile for age) on arrival to the emergency department. Amortality rate of 61% was observed with hypotension on admission versus 22% among patients without hypotension. When hypotension was combined with hypoxia, the mortality rate was 85%. Hypotension was a statistically significant predictor of outcome with a PPV of 61% for mortality. Early hypotension negated the improvement in survival from severe TBI that is generally afforded by youth.

Kokosa et al.7 performed a retrospective chart review of all pediatric patients admitted to a single Level I trauma center over a 5 year period. Limiting the patient population to children with non-penetrating TBI with post-resuscitation age-adjusted GCS scores between 6-8 (n = 72), they indexed secondary insults occurring during transport to the emergency department up through the first 24 hours in the ICU. Hypotension was defined as five or more minutes at or below the fifth percentile for age according to the Task Force on Blood Pressure Control in Children.1 The majority of hypotensive episodes occurred during resuscitation in the ED(39%) and the PICU(37%). Patients with residual moderate and severe disability had experienced significantly more hypotensive episodes than those with good outcomes.

Michaud11 found that hypotension in the field and emergency department was significantly related to mortality in children. In a data bank study from four centers,8 Levin found that outcome was poorest in patients 0-4 year olds, which was the group that demonstrated high rates of hypotension (32%).

In a prospective series of 6,908 adults and 1906 children less than 15 years of age at 41 centers, Luerssen et al.9 found that hypotension was significantly associated with higher mortality in children. They reported a greater deleterious effect of hypotension in children than adults. Notably, children with severe hypertension had the lowest mortality rate.

Studies of fluid resuscitation in the prehospital setting are needed. Few data exist to guide endpoints of therapy. The current concern that raising blood pressure may increase secondary blood loss after certain types of trauma, thus worsening cerebral hemodynamics, needs to be validated in humans. Additional investigation to determine the most effective fluid for resuscitation, and the role of "newer" fluid regimens including various hypertonic solutions, mannitol, and synthetic colloids needs to be performed.

There is a lack of studies in children that assess whether prehospital protocols directed at minimizing or preventing hypotension actually improve outcome from TBI. This issue may be approached using large, prospectively collected observational databases that allow analysis of blood pressure and volume status while controlling for confounding variables. It has been suggested that supranormal blood pressuresmaybe acceptable or even associated with improved outcome in children with severe TBI.20 Further investigation in this area is needed.

The following specific questions need to be studied in the prehospital arena for both adults and children:

1. What is the optimal target blood pressure for resuscitation in patients with either isolated TBI or those with multiple injuries including TBI?
2. Is mean arterial blood pressure a better endpoint than systolic blood pressure?
3. Is there a subgroup of brain injured patients in whom a lower volume of resuscitation fluid should be used?
4. What is the ideal resuscitation fluid in the prehospital setting?
5. Is there a role for large particle colloids in the prehospital setting?
6. What is the role of hemoglobin substitutes in the prehospital setting?
7. Can noninvasive field technology identify and help titrate therapy in the prehospital setting of patients with severe TBI?