Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury.
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2022-12
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Early hypotension after severe traumatic brain injury (sTBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors, commonly norepinephrine and phenylephrine, to support blood pressure after TBI. However, guidelines do not specify vasopressor type, resulting in variation in clinical practice. We describe early vasopressor utilization patterns in critically ill patients with TBI and examine the association between utilization of norepinephrine, compared to phenylephrine, with hospital mortality after sTBI.Methods
We conducted a retrospective cohort study of US hospitals participating in the Premier Healthcare Database between 2009 and 2018. We examined adult patients (>17 years of age) with a primary diagnosis of sTBI who were treated in an intensive care unit (ICU) after injury. The primary exposure was vasopressor choice (phenylephrine versus norepinephrine) within the first 2 days of hospital admission. The primary outcome was in-hospital mortality. Secondary outcomes examined included hospital length of stay (LOS) and ICU LOS. We conducted a post hoc subgroup analysis in all patients with intracranial pressure (ICP) monitor placement. Regression analysis was used to assess differences in outcomes between patients exposed to phenylephrine versus norepinephrine, with propensity matching to address selection bias due to the nonrandom allocation of treatment groups.Results
From 2009 to 2018, 24,718 (37.1%) of 66,610 sTBI patients received vasopressors within the first 2 days of hospitalization. Among these patients, 60.6% (n = 14,991) received only phenylephrine, 10.8% (n = 2668) received only norepinephrine, 3.5% (n = 877) received other vasopressors, and 25.0% (n = 6182) received multiple vasopressors. In that time period, the use of all vasopressors after sTBI increased. A moderate degree of variation in vasopressor choice was explained at the individual hospital level (23.1%). In propensity-matched analysis, the use of norepinephrine compared to phenylephrine was associated with an increased risk of in-hospital mortality (OR, 1.65; CI, 1.46-1.86; P < .0001).Conclusions
Early vasopressor utilization among critically ill patients with sTBI is common, increasing over the last decade, and varies across hospitals caring for TBI patients. Compared to phenylephrine, norepinephrine was associated with increased risk of in-hospital mortality in propensity-matched analysis. Given the wide variation in vasopressor utilization and possible differences in efficacy, our analysis suggests the need for randomized controlled trials to better inform vasopressor choice for patients with sTBI.Type
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Toro, Camilo, Tetsu Ohnuma, Jordan Komisarow, Monica S Vavilala, Daniel T Laskowitz, Michael L James, Joseph P Mathew, Adrian F Hernandez, et al. (2022). Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury. Anesthesia and analgesia, 135(6). pp. 1245–1252. 10.1213/ane.0000000000005949 Retrieved from https://hdl.handle.net/10161/33732.
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Scholars@Duke
Tetsu Ohnuma
Jordan Komisarow
Daniel Todd Laskowitz
Our laboratory uses molecular biology, cell culture, and animal modeling techniques to examine the CNS response to acute injury. In particular, our laboratory examines the role of microglial activation and the endogenous CNS inflammatory response in exacerbating secondary injury following acute brain insult. Much of the in vitro work in this laboratory is dedicated to elucidating cellular responses to injury with the ultimate goal of exploring new therapeutic interventions in the clinical setting of stroke, intracranial hemorrhage, and closed head injury.
In conjunction with the Multidisciplinary Neuroprotection Laboratories, we also focus on clinically relevant small animal models of acute CNS injury. For example, we have recently characterized murine models of closed head injury, subarachnoid hemorrhage, intracranial hemorrhage and perinatal hypoxia-ischemia, in addition to the standard rodent models of focal stroke and transient forebrain ischemia. Recently we have adapted several of these models from the rat to the mouse to take advantage of murine transgenic technology. The objective of these studies are two-fold: to gain better insight into the cellular responses and pathophysiology of acute brain injury, and to test novel therapeutic strategies for clinical translation. In both cell culture systems and animal models, our primary focus is on examining the role of oxidative stress and inflammatory mechanism in mediating brain injury following acute brain insult, and examining the neuroprotective effects of endogenous apolipoprotein E in the injured mammalian central nervous system.
Our laboratory is committed to translational research, and has several active clinical research protocols, which are designed to bring the research performed in the Multidisciplinary Research Laboratories to the clinical arena. These protocols are centered around patients following stroke and acute brain injury, and are primarily based out of the Emergency Room and Neurocritical Care Unit. For example, we are currently examining the role of inflammatory mediators for use as a point-of-care diagnostic marker following stroke, intracranial hemorrhage, and closed head injury. We have recently translated a novel apoE mimetic from the preclinical setting to a multi center Phase 2 trial evaluating efficacy in intracranial hemorrhage. We are also examining the functional role of different polymorphisms of of inflammatory cytokines in the setting of acute brain injury and neurological dysfunction following cardiopulmonary bypass.
Michael Lucas James
With a clinical background in neuroanesthesia and neurointensive care, I have a special interest in translational research in intracerebral hemorrhage and traumatic brain injury. I am fortunate to be part of a unique team of highly motivated and productive individuals who allow me to propel ideas from bench to bedside and the ability to reverse translate ideas from the bedside back to the bench.
Joseph P. Mathew
Current research interests include:
1. The relationship between white matter patency, functional connectivity (fMRI) and neurocognitive function following cardiac surgery.
2. The relationship between global and regional cortical beta-amyloid deposition and postoperative cognitive decline.
3. The effect of lidocaine infusion upon neurocognitive function following cardiac surgery.
4. The association between genotype and outcome after cardiac surgery.
5. Atrial fibrillation following cardiopulmonary bypass.
Adrian Felipe Hernandez
Benjamin Alan Goldstein
I study the meaningful use of Electronic Health Records data. My research interests sit at the intersection of biostatistics, biomedical informatics, machine learning and epidemiology. I collaborate with researchers both locally at Duke as well as nationally. I am interested in speaking with any students, methodologists or collaborators interested in EHR data.
Please find more information at: https://biostat.duke.edu/goldstein-lab
John Howard Sampson
Current research activities involve the immunotherapeutic targeting of a tumor-specific mutation in the epidermal growth factor receptor. Approaches used to target this tumor-specific epitope include unarmed and radiolabeled antibody therapy and cell mediated approaches using peptide vaccines and dendritic cells. Another area of interest involves drug delivery to brain tumors. Translational and clinical work is carried out in this area to formulate the relationship between various direct intratumoral infusion parameters and drug distribution within brain tumors and normal brain.
The Duke Brain Tumor Immunotherapy Program (BTIP) has an emphasis on translational research in Neuro-Oncology. There are two main areas of study. The first is novel mechanisms of delivery of large molecular weight molecules, such as monoclonal antibodies, throughout brain intersitial space using novel intracerebral infusion techniques developed by this laboratory. Studies exploring this technology are undertaken in both small and large laboratory animals and patients with brain tumors.
The other focus of the BTIP is translational immunotherapy. In this line of work, dendritic cell vaccination strategies and adoptive T-cell strategies have been developed to target novel and well-characterized tumor-specific antigens in patients with brain tumors. The BTIP integrates well with and works closely with the Preston Robert Tisch Brain Tumor Center at Duke. The BTIP is well funded and currently holds seven NIH grants, including a SPORE in Brain Cancer grant. There are a large number of investigators at various levels so that students will get exposure to various levels of research and mentorship.
Vijay Krishnamoorthy
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