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Haydn Hoffman, Karl Abi-Aad, Katherine M. Bunch, Timothy Beutler, Fadar O. Otite, and Lawrence S. Chin

OBJECTIVE

Brain tissue oxygen monitoring combined with intracranial pressure (ICP) monitoring in patients with severe traumatic brain injury (sTBI) may confer better outcomes than ICP monitoring alone. The authors sought to investigate this using a national database.

METHODS

The National Trauma Data Bank from 2013 to 2017 was queried to identify patients with sTBI who had an external ventricular drain or intraparenchymal ICP monitor placed. Patients were stratified according to the placement of an intraparenchymal brain tissue oxygen tension (PbtO2) monitor, and a 2:1 propensity score matching pair was used to compare outcomes in patients with and those without PbtO2 monitoring. Sensitivity analyses were performed using the entire cohort, and each model was adjusted for age, sex, Glasgow Coma Scale score, Injury Severity Score, presence of hypotension, insurance, race, and hospital teaching status. The primary outcome of interest was in-hospital mortality, and secondary outcomes included ICU length of stay (LOS) and overall LOS.

RESULTS

A total of 3421 patients with sTBI who underwent ICP monitoring were identified. Of these, 155 (4.5%) patients had a PbtO2 monitor placed. Among the propensity score–matched patients, mortality occurred in 35.4% of patients without oxygen monitoring and 23.4% of patients with oxygen monitoring (OR 0.53, 95% CI 0.33–0.85; p = 0.007). The unfavorable discharge rates were 56.3% and 47.4%, respectively, in patients with and those without oxygen monitoring (OR 1.41, 95% CI 0.87–2.30; p = 0.168). There was no difference in overall LOS, but patients with PbtO2 monitoring had a significantly longer ICU LOS and duration of mechanical ventilation. In the sensitivity analysis, PbtO2 monitoring was associated with decreased odds of mortality (OR 0.56, 95% CI 0.37–0.84) but higher odds of unfavorable discharge (OR 1.59, 95% CI 1.06–2.40).

CONCLUSIONS

When combined with ICP monitoring, PbtO2 monitoring was associated with lower inpatient mortality for patients with sTBI. This supports the findings of the recent Brain Oxygen Optimization in Severe Traumatic Brain Injury phase 2 (BOOST 2) trial and highlights the importance of the ongoing BOOST3 trial.

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Josef Pleticha, Timothy P. Maus, Jodie A. Christner, Michael P. Marsh, Kendall H. Lee, W. Michael Hooten, and Andreas S. Beutler

Dorsal root ganglia (DRG) are critical anatomical structures involved in nociception. Intraganglionic (IG) drug delivery is therefore an important route of administration for novel analgesic therapies. Although IG injection in large animal models is highly desirable for preclinical biodistribution and toxicology studies of new drugs, no method to deliver pharmaceutical agents into the DRG has been reported in any large species. The present study describes a minimally invasive technique of IG agent delivery in domestic swine, one of the most common large animal models. The technique utilizes CT guidance for DRG targeting and a custom-made injection assembly for convectionenhanced delivery (CED) of therapeutic agents directly into DRG parenchyma. The DRG were initially visualized by CT myelography to determine the optimal access route to the DRG. The subsequent IG injection consisted of 3 steps. First, a commercially available guide needle was advanced to a position dorsolateral to the DRG, and the dural root sleeve was punctured, leaving the guide needle contiguous with, but not penetrating, the DRG. Second, the custom-made stepped stylet was inserted through the guide needle into the DRG parenchyma. Third, the stepped stylet was replaced by the custom-made stepped needle, which was used for the IG CED. Initial dye injections performed in pig cadavers confirmed the accuracy of DRG targeting under CT guidance. Intraganglionic administration of adeno-associated virus in vivo resulted in a unilateral transduction of the injected DRG, with 33.5% DRG neurons transduced. Transgene expression was also found in the dorsal root entry zones at the corresponding spinal levels. The results thereby confirm the efficacy of CED by the stepped needle and a selectivity of DRG targeting. Imaging-based modeling of the procedure in humans suggests that IG CED may be translatable to the clinical setting.