Factors that may improve outcomes of early traumatic brain injury care: prospective multicenter study in Austria

The Austrian Ministry of Health and the Austrian Worker’s Compensation Board (AUVA) decided to fund the project, managed by the International Neurotrauma Research Organization (INRO). In 10/2008 all Austrian hospitals that treat patients with severe TBI were invited to participate in the study. 15 centers completed both data collection phases. One of them had very few patients in the second phase due to personnel issues. Therefore in final analyses we included 14 centers that participated in both phases and included patients according the inclusion criteria.

In Austria, out of approximately 120 hospitals treating any kind of traumatic brain injury (TBI) 30 hospitals treat more than 10 patients with severe TBI annually. According to patient load, hospitals participating in our study belong to this latter group.

In 11/2008, representatives from participating centers met in Vienna and founded the “Austrian Working Group on Improvement of Early TBI Care” (Working Group). The Working Group discussed and modified the study protocol prepared by INRO, and decided on a strategy for data collection. The Working Group made the following decisions used as inclusion criteria for the study:

The study was approved by the ethical committees of all participating centers.

Between 5/2009 and 4/2010 a total of 408 patients were enrolled by 14 participating centers. In each center one or more persons (local study manager) were in charge of patient enrollment. Information was collected on patient folders containing paper forms (mostly multiple-choice check-boxes, some fields for numbers, dates and times) for demographic and trauma data, prehospital status and treatment, trauma room status and treatment, computed tomography (CT) findings, data on surgical procedures, intensive care unit (ICU) status and treatment, and hospital outcome. Copies of relevant records (prehospital, trauma room, and anesthesia records, first laboratory results, DVDs with CT scan data) were included in these folders. Prehospital data were collected from Emergency Medical Services (EMS) protocols; any missing information was obtained from EMS by the local study managers and transcribed into study patients’ files. Each patient or a close relative gave written informed consent to agree to the follow-up.

The patient folders were collected at regular intervals by the project manager (AB) from the local study managers who were responsible for data collection. The data were then entered into an online database, created by INRO for this project. The database consisted of electronic transcript of patient folders used for data collection, separate sheets on Patient & Trauma data, Trauma Room data, CT & Operation data, Intensive Care Unit data, Outcome data. The online database was used for continuous data storage. In most cases data were entered on site, and missing data were obtained directly from the local study managers. In some cases data were entered in the INRO office, and missing data were obtained via phone call or e-mail. The DVDs with CT scan data were viewed by an intensive care specialist (WM), a radiologist, and a trauma surgeon (JL); judgement differences (e.g., with regard to the predominant injury) were resolved by a conference. All data collection forms were checked for completeness, and the local study managers were asked to provide missing information, if available. All information was checked for inconsistencies and/or implausible values; obvious errors were corrected. Six months after trauma the Extended Glasgow Outcome Scale (GOSE) score was obtained by phone interviews with patients and/or relatives and/or caregivers; this information was then entered into the database [17]. Ratings for the GOSE range from 1 to 8 (Dead to Upper Good Recovery). The 6-month outcome was dichotomized into unfavorable (GOSE score 1-6) and favorable (GOSE score 7–8) outcome groups.

Demographic data of patients from Phase 1 versus Phase 2 are given in Table 1. The two groups were similar; there were no significant differences regarding mean age, male: female ratio, and mechanisms of trauma.

Severity of trauma, CT scan findings, and expected outcomes are given in Table 2. The initial GCS was significantly higher in Phase 2 patients; the median, however, indicated that in both groups most patients had severe TBI. The ISS was also significantly higher in Phase 2 patients. The proportion of patients with prehospital hypotension and/or hypoxia was similar in both groups. Phase 2 sample had a significantly lower rate of patients with normal pupillary reflex. Regarding CT scan findings compressed or closed basal cisterns as well as greater midline shift were seen significantly more frequently in Phase 2 patients. The predominant type of brain lesion was not significantly different between the 2 groups. Phase 2 patients had higher trauma severity, worse CT findings, and worse pupillary reactivity. Expected mortality rates and the expected rates of unfavorable outcome were similar in both groups.

The treatment options that had been recommended based on association with improved outcomes are listed in Table 3. All of them were used more frequently during Phase 2. Direct transportation to the participating centers occurred significantly more frequently (87 vs. 78 %). Regarding time intervals, in Phase 2 significantly more patients reached the hospital within 60 min after EMS arrival (61 vs. 41 %), had their first CT scan within 60 min after hospital arrival (74 vs. 66 %), and – if required – had neurosurgical operations started within 120 min of hospital arrival (36 vs. 32 %). Prehospital monitoring (pulse oximetry, blood pressure monitoring, and capnography) was used more frequently in Phase 2. Prehospital ventilation was improved, as fewer patients were hyperventilated and more patients had optimal ventilation. Regarding prehospital fluid resuscitation Ringer’s lactate solutions as well as colloids (mainly hydroxy ethyl starch) were used less frequently, while Ringer’s and other balanced electrolyte solutions were used more frequently. Prehospital infusion volumes were not significantly different: 700 (SD 698 ml) in Phase 1 vs. 800 (SD 737 ml) in Phase 2, and were given on average within the time frame of EMS care (50 ± 25) minutes. Within in-hospital treatment in Phase 2 thrombelastometry (TEM) was used more frequently (in 40 % vs. 24 %), and corticosteroids were given significantly less frequently: 2 of the 3 cases that received corticosteroids during Phase 2 had concomitant spinal cord injuries, and the corticosteroids were used due to that.

During Phase 2 neurosurgical procedures were required more frequently (67 % vs. 59 %), ICP was monitored more often (in 60 % vs. 51 %), but for shorter periods (8 [IQR 5–14] vs. 9 days [IQR 5–13]), and the duration of ventilation was longer (10 days [IQR 3–18] vs. 8 [IQR 2–15]). No significant differences between Phase 2 and Phase 1 were observed regarding rates of prehospital intubation (62 % vs. 60 %), of prehospital management by helicopter crews (48 % vs. 46 %), and of therapeutic hypothermia (14 % vs. 21 %).

Outcomes were significantly better in Phase 2 (Table 4). Hospital mortality was 22 % in Phase 2 vs. 29 % in Phase 1, and the rate of patients with unfavorable outcome was 32 % in Phase 2 vs. 38 % in Phase 1.

Comparison of expected and observed outcomes is presented in Table 5. There were significantly more unexpected survivors as well as patients with unexpected favorable outcomes.

Table 6 presents the results of multivariable analysis of factors influencing the outcome of patients. For the logistic regression model the variables that had significant influence on the outcome in univariate analysis were used. Patients in Phase 2 had significantly higher odds of ICU survival (OR 2.92, CI95%: 1.35–6.31) and hospital survival (OR 3.01, 1.41–6.38) and higher odds of favorable outcome (OR 3.14, 1.72–5.73). These findings have been adjusted for age, indicators of severity and treatment, and for “center effect” (by including the treatment center as one of the independent variables in the model).

To the best of our knowledge this is the first project that tried to identify the most important treatment options, summarized these in a short document, and began implementing them. The results demonstrated that outcomes of patients with TBI can be improved if the recommended treatment options are used more frequently. Predicted mortality and predicted rate of unfavorable outcome were identical in both phases. There were no other differences in treatment options (e.g., increased use of tranexamic acid etc.). Thus, we believe the significantly better outcomes observed in Phase 2 were probably due to the achieved improvements in early TBI care.

The impact of time factors after TBI seems to be well known; yet there is conflicting evidence, whether duration (“golden hour”) or quality of emergency care has more influence on the outcome of TBI patients [20]. Some studies suggest that direct transport to an appropriate center is associated with improved outcomes [21]. The importance of in-hospital time factors has been shown in other studies, too [22, 23]. Our project successfully significantly reduced rates of secondary transfers and significantly increased proportion of those patients who got to the hospital within 60 min from EMS arrival. Regarding the time intervals hospital admission – ‘first CT in less than 60 min after admission’ and ‘from hospital admission to operation room in less than 120 min’ the project was less successful; the improvements were statistically not significant.

The use of capnography in patients who need prehospital intubation has been shown to reduce the rate of hyperventilation [24]. It has also been shown that end-tidal CO₂ correlates well with ventilation in patients with isolated TBI [25]. However, the same study showed that end-tidal pCO₂ shows poor correlation to ventilation in patients with major trauma and shock. This is due to the fact that end-tidal pCO₂ may be related to pulmonary perfusion rather than to ventilation in these states. Therefore, the target range of end-tidal pCO₂ has to be chosen according to the status of the trauma patient. Our recommendations included a target range of 30–35 mmHg (corresponding to an arterial pCO₂ of 35–40 mmHg in patients with normal perfusion). Our data show that the use of capnography reduced the rate of hyperventilation. This part of the project was implemented successfully.

Fluid resuscitation is an important option in patients with TBI. Resuscitation with isotonic crystalloids is considered standard care. It has been shown that resuscitation using albumin is associated with worse outcomes in TBI patients [26], and that hypertonic saline is not superior to normal saline [27] in hypotensive patients with TBI. Our recommendations were to avoid hypotonic crystalloids (e.g., Ringer’s lactate), use isotonic crystalloids, and to add colloids and/or hypertonic saline in hypotensive patients. These recommendations were followed in the majority of patients.

The recommendation to use TEM as early as possible to optimize coagulation in all patients >60 years and/or on anticoagulants is a new aspect. This recommendation was based on the finding that during Phase 1, patients who had had TEM in the Trauma Room had higher hospital survival (51 % vs. 38 %) and a higher rate of favorable outcome (40 % vs. 28 %). A number of recent studies suggest that the use of TEM to guide coagulation management may be beneficial after multiple trauma [28, 29] as well as after TBI [30]. The significant increase in early use of TEM during Phase 2 may have contributed to the better outcomes of the Phase 2 patients.

The recommendation not to use steroids was made because during the first Phase 15 patients received corticosteroids; the mortality of these patients was significantly higher (15 % vs. 0 %) – thus, the use of corticosteroids more than doubled the odds for mortality. The recommendations not to use corticosteroids was one of the few “standards” in the 1996 BTF guidelines [12], and is still a “Level 1” recommendation in the 2007 version. The CRASH trial [31] has shown that use of corticosteroids is associated with increased mortality. It is unclear why corticosteroids were used so frequently during Phase 1; only 1/15 patients had a concomitant spinal cord injury.

Regarding epidemiology, >70 % of the patients were male; this is the typical male: female ratio for moderate and severe TBI [32]. The mean age was rather high; almost one third of the patients were > 65 years old. This mirrors a clear trend during the last decades: a high rate of geriatric TBI has been observed in other European studies, too [9]. Thus, traffic accidents were a leading cause of injury, but same-level falls (i.e., the typical mechanism of TBI in geriatric patients) were the cause of accident in almost one third of all cases.

It is important to address the study limitations. The hospital selection may have introduced bias as the treatment centers participated in our study based on their own decision upon the invitation.

Despite the thorough monitoring we were not able to prevent missing data in the prehospital setting and outcome follow-up. Loss to follow-up is prominent mainly in Phase 1 with 44 % of unknown outcome. The main reason was the absence of contact information and that was better taken care of in Phase 2.

In conclusion, in a study done in 14 Austrian centers we have identified prehospital and early hospital treatment options that were potentially associated with better outcomes. Based on these results, recommendations were drafted and implemented with the support of participating hospitals and EMS. These recommendations dealt with time factors, monitoring and treatment options. We were able to demonstrate that these recommendations led to reduction of time delays and improved quality of care, both pre- and in-hospital in Phase 2 of our study. Patients treated in participating treatment centers after the implementation of recommended changes had three-fold chance of survival and favorable long-term outcome.

Thus, improvement in early TBI care was followed by a significant improvement in patient outcomes.