January 2021

Synopsis: Persistent vasoplegia and hypotension requiring continuous infusion of vasoactive medications is a barrier to intensive care unit (ICU) discharge. Midodrine, an oral α1-adrenergic agonist, is frequently prescribed as an adjunct to facilitate discontinuation of intravenous (IV) vasopressors, despite extremely limited data from small observational studies.

The MIDAS study was a prospective, multicenter, randomized, double-blind, placebo-controlled trial designed to test the hypothesis that midodrine shortens the duration of IV vasopressor support. Eligible participants were hypotensive patients aged 18 or older who were admitted to an ICU (or setting in which vasopressor medications use was allowed) who required a single-agent intravenous vasopressor treatment (< 100 mcg/min phenylephrine, < 8 mcg/min norepinephrine, or < 50 mcg/min metaraminol) and were unable to be liberated from these from at least 24 hours after resuscitation and correction of treatable causes of hypotension and while maintaining blood pressure and end-organ perfusion goals.

Participants were randomized in a 1:1 ratio to receive 20 mg of midodrine or the placebo. Oral doses of midodrine or placebo were administered every 8 hours and vasoactive infusions were continued as needed. Study drugs were administered until ICU discharge or until any of the following occurred: worsening hypotension requiring high-dose vasopressors, epinephrine requirement, signs or symptoms of organ failure or hypoperfusion, adverse events related to midodrine, including serious allergic reactions, or death. 

The primary outcome they measured was length of time, in hours, from study drug initiation until discontinuation of intravenous vasopressors (vasopressor-free period of at least 24 hours). Secondary outcomes included time to ICU discharge readiness, ICU and hospital length of stay, and rates of ICU readmission during hospital stay. Adverse events, including hypertension, bradycardia, hemodynamically significant tachyarrhythmias, and new onset organ failure were recorded. 

The authors utilized a modified intention to treat approach for analysis. Overall, the study randomized 132 patients (Midodrine, N=66; Placebo, N=66). Median age was 68 years, 95% of patients were white, median BMI was 29, and 66% of patients were post-operative or surgical. Median time to vasopressor discontinuation was not significantly different between groups (Midodrine 23.5 hours (IQR 10-54) vs. Placebo 22.5 hours (IQR 10.4-40), p=0.62). For secondary outcomes, there was no statistically significant difference in ICU length of stay, hospital length of stay, time to ICU discharge readiness, or ICU readmission rates. In post hoc analysis, time to vasopressor discontinuation was shorter in the midodrine group for patients receiving epidural analgesia (incidence rate ratio 0.53, CI 0.28 to 0.99 p = 0.045). The overall rate of adverse events was similar between the two groups, but the midodrine group had a significantly increased risk of bradycardia compared to the placebo group (p=0.02).

Bottom line: The use of midodrine did not decrease the time to vasopressor discontinuation in the ICU, did not encourage faster ICU downgrade, and did not decrease hospital length of stay. It was associated with a higher rate of bradycardic events.

Synopsis: Although advances in trauma care have resulted in dramatic improvements in survival after injury, patients who are successfully discharged often face significant challenges as they attempt to reintegrate their lives. Recent studies have attempted to better quantify these obstacles through patient reported outcomes, including two from our institution that point out survivors often have worse physical and mental health as compared to the general population including difficulties with pain management, unemployment, substance abuse, and posttraumatic stress disorder (PTSD) (PMID’s 33223252 and 31746949). Work in cancer populations with comparable complicated outpatient needs have started to implement multidisciplinary clinics to address challenges and potentially improve long term outcomes. While some trauma centers have created integrated clinics, there remains a dearth of resources or guidance on how to best support trauma patients in the post-discharge period.

To address these unmet needs, a group from the New Jersey Trauma Center at University Hospital in Newark created the Center for Trauma Survivorship (CTS). The goal of this effort was to enhance discharge compliance, improve utilization of behavioral health services, and reduce unplanned hospitalizations. To better understand the needs of their patient population, the authors interviewed focus groups of injured patients and caregivers who were at least 1 year out from the initial event. Five themes emerged from these sessions that mirrored the literature including feelings of abandonment by the trauma center, need for mental health or addiction services, inadequate pain control, physical limitations, and objective challenges to daily living such as lack of transportation or financial hardship. Interestingly, patients who were discharged to a rehabilitation center felt more isolated from the trauma center than those discharged to home, citing wound care issues, difficulty accessing follow up appointments, and lack of support from what they felt to be a less sympathetic set of new care providers. 

The authors used the focus group findings to further tailor the Center for Trauma Survivorship to patient needs. The target population were adults aged 18-80 years old who were either admitted to the ICU for >2 days and/or had a New Injury Severity Score of >16. Patients were identified for inclusion during their hospitalization and scheduled for the CTS clinic instead of routine trauma clinic. At a minimum, a patient’s CTS team consisted of a dedicated nurse practitioner, social worker, and health care navigator. Patient navigators coordinated transportation including initiating scheduling transportation from rehabilitation centers or using Uber Health rides for patients in need of a ride coming from home. Appointments were made in proximity to standing subspecialty appointments as able. Patients were scheduled for an hour in order to provide ample time to discuss medication, pain management, long term goals, and needs for rehabilitation or other subspecialty providers. Patients were seen by a trauma physiatrist or trauma surgeon as needed. Patients were also screened for PTSD and depression. Those who screened positive and/or requested further support were connected with a behavioral health specialist as needed. All patients had 24/7 access to their CTS team via phone or email. 

As a result of these efforts, 107 of 137 patients identified for enrollment made it to the CTS clinic. This is a vast improvement over a 41% follow up rate for trauma clinics just one year prior. All CTS patients were seen by a dedicated nurse practitioner and 25% of patients were seen by a trauma surgeon for wound care or more complex surgical decisions. In addition, 80% of patients were seen by trauma physiatrist for issues with pain management or rehabilitation and 86% of patients who screened positive for PTSD or depression were seen by behavioral health specialists. Interestingly, these successes were associated with a decrease in ED utilization when compared to a similarly injured cohort of trauma patients from just a year prior. This included a reduction in avoidable ED visits and a decrease in the number of patients requiring multiple visits. Although additional work is needed to evaluate the long term outcomes of the CTS in terms of quality of life, return to work, behavioral health, and other patient reported outcomes, the authors illustrate that coordinated multidisciplinary care is a viable and likely cost effective tool in the effort to address the multi-faceted discharge needs of trauma survivors.  

Synopsis: Current guidelines recommend carotid endarterectomy (CEA) as first line treatment for asymptomatic patients with 60 to 99% internal carotid artery (ICA) stenosis, and symptomatic patients with 50% to 99% stenosis. However, CEA still poses a significant risk for postoperative cardiovascular complications especially in high risk patients, in addition to the risk of cranial nerve injuries associated with CEA. With the development of endovascular techniques, transfemoral carotid artery stenting (TFCAS) has been frequently used to treat carotid stenosis in high-risk frail patients. TFCAS has resulted in fewer postoperative cardiac complications as compared to CEA, however at the expense of increased risk of postoperative stroke owing to iatrogenic embolic events.

Transcarotid Revascularization with flow reversal (TCAR) by Silk Road Medical is a novel, less invasive hybrid approach for the treatment of carotid stenosis. It involves direct access to the common carotid artery (CCA) via a small incision at the base of the neck, CCA cannulation, reversal of ipsilateral cerebral blood flow using a powered filtering system that returns blood to the femoral vein while the carotid stent is deployed. TCAR has been proposed to have a lower risk of postoperative stroke compared to TFCAS secondary to embolic neuroprotection as a result of direct access of the carotid artery (and avoiding wire manipulation in the aortic arch) and ipsilateral cerebral flow reversal during TCAR. Initial studies on TCAR were promising but were preliminary and underpowered. 

“TransCarotid Revascularization with Dynamic Flow reversal versus Carotid Endarterectomy in the Vascular Quality Initiative Surveillance Project”, published in the Annals of Surgery in September 2020, is a retrospective propensity score-matched analysis of the vascular quality initiative (VQI) data that compared perioperative and 1-year cardiovascular outcomes between patients undergoing CEA vs TCAR in the United States and Canada between 2016 and 2019 for both asymptomatic and symptomatic carotid artery stenosis. There were 6,384 patients in each group (TCAR vs CEA after propensity score matching). There were no significant differences between TCAR and CEA in terms of in-hospital stroke/death (composite outcome) [TCAR: 1.6% vs CEA: 1.6%, P=0.945], stroke [TCAR: 1.4% vs CEA: 1.4%, P=0.881], or death [TCAR: 0.4% vs CEA: 0.3%, P=0.662]. Compared to CEA, TCAR patients had lower rates of in-hospital myocardial infarction (MI) [TCAR: 0.5% vs CEA: 0.9%, P=0.005], cranial nerve injury [TCAR: 0.4% vs CEA: 2.7%, P<0.001], and postprocedural hypertension [TCAR: 13% vs CEA 18.8%, P<0·001]. TCAR patients were less likely to stay in the hospital longer than one day [26.4% vs 30.1%, P<0.001]. The postoperative outcomes were similar (to the outcomes above) after stratifying by symptomatic status (symptomatic vs asymptomatic carotid stenosis). At one year, the incidence of ipsilateral stroke or death was similar between the 2 groups (TCAR: 5.7% vs CEA: 6.6%, P=0.44) 

This study showed that patients undergoing TCAR were not at any disadvantage with regards to perioperative stroke or death compared to traditional CEA. Moreover, TCAR was associated with lower rates of MI, cranial nerve injury and shorter length of stay. These promising outcomes suggest that TCAR could be a safe, less invasive option for carotid revascularization in patients at high-risk for CEA. Further studies, ideally randomized clinical trials with long-term follow up, are needed to validate the role of TCAR in treating carotid artery stenosis and stroke prevention.