A Prehospital Acute Stroke Trial has Only Modest Impact on Enrollment in Concurrent, Post-arrival-Recruiting Stroke Trials.

BACKGROUND: Because "time is brain," acute stroke trials are migrating to the prehospital setting. The impact upon enrollment in post-arrival trials of earlier recruitment in a prehospital trial requires delineation. METHODS: We analyzed all patients recruited into acute and prevention stroke trials during an 8-year period when an academic medical center (AMC) was participating in a prehospital treatment trial - the NIH Field Administration of Stroke Treatment - Magnesium (FAST-MAG) study. RESULTS: During the study period, in addition to FAST-MAG, the AMC participated in 33 post-arrival stroke trials: 27 for acute cerebral ischemia, one for intracerebral hemorrhage, and 5 secondary prevention trials. Throughout the study period, the AMC was recruiting for at least 3 concurrent post-arrival acute trials. Among 199 patients enrolled in acute stroke trials, 98 (49%) were in FAST-MAG and 101 (51%) in concurrent, post-arrival acute trials. Among FAST-MAG patients, 67% were not eligible for any concurrent acute, post-arrival trial. Of 134 patients eligible for post-arrival acute trials, 101 (76%) were enrolled in post-arrival trials and 32 (24%) in FAST-MAG. Leading reasons FAST-MAG patients were ineligible for post-arrival acute trials were: NIHSS too low (23.4%), intracranial hemorrhage (17.9%), IV tPA used in standard management (9.0%), NIHSS too high (7.1%), and age too high (5.2%). CONCLUSIONS: A prehospital hyperacute stroke trial with wide entry criteria reduced only modestly, by one-fourth, enrollment into concurrently active, post-arrival stroke trials. Simultaneous performance of prehospital and post-arrival acute and secondary prevention stroke trials in research networks is feasible.

AAN position statement: The COVID-19 pandemic and the ethical duties of the neurologist.

Patients, clinicians, and hospitals have undergone monumental changes during the coronavirus disease 2019 (COVID-19) pandemic. This crisis has forced us to consider the obligations that we neurologists have to our individual patients as well as the greater community. By returning to our fundamental understanding of these duties, we can ensure that we are providing the most ethically appropriate contingency and crisis care possible. We recommend specific adaptations to both the inpatient and outpatient settings, as well as changes to medical and trainee education. Furthermore, we explore the daunting but potentially necessary implementation of scare resource allocation protocols. As the pandemic evolves, we will need to adapt continuously to these rapidly changing circumstances and consider both national and regional standards and variation.

Systematic review and meta-analysis of intravascular temperature management vs. surface cooling in comatose patients resuscitated from cardiac arrest.

OBJECTIVE: To systematically review the effectiveness and safety of intravascular temperature management (IVTM) vs. surface cooling methods (SCM) for induced hypothermia (IH). METHODS: Systematic review and meta-analysis. English-language PubMed, Embase and the Cochrane Database of Systematic Reviews were searched on May 27, 2019. The quality of included observational studies was graded using the Newcastle-Ottawa Quality Assessment tool. The quality of included randomized trials was evaluated using the Cochrane Collaboration's risk of bias tool. Random effects modeling was used to calculate risk differences for each outcome. Statistical heterogeneity and publication bias were assessed using standard methods. ELIGIBILITY: Observational or randomized studies comparing survival and/or neurologic outcomes in adults aged 18 years or greater resuscitated from out-of-hospital cardiac arrest receiving IH via IVTM vs. SCM were eligible for inclusion. RESULTS: In total, 12 studies met inclusion criteria. These enrolled 1573 patients who received IVTM; and 4008 who received SCM. Survival was 55.0% in the IVTM group and 51.2% in the SCM group [pooled risk difference 2% (95% CI -1%, 5%)]. Good neurological outcome was achieved in 40.9% in the IVTM and 29.5% in the surface group [pooled risk difference 5% (95% CI 2%, 8%)]. There was a 6% (95% CI 11%, 2%) lower risk of arrhythmia with use of IVTM and 15% (95% CI 22%, 7%) decreased risk of overcooling with use of IVTM vs. SCM. There was no significant difference in other evaluated adverse events between groups. CONCLUSIONS: IVTM was associated with improved neurological outcomes vs. SCM among survivors resuscitated following cardiac arrest. These results may have implications for care of patients in the emergency department and intensive care settings after resuscitation from cardiac arrest.

Fluid therapy in neurointensive care patients: ESICM consensus and clinical practice recommendations.

OBJECTIVE: To report the ESICM consensus and clinical practice recommendations on fluid therapy in neurointensive care patients. DESIGN: A consensus committee comprising 22 international experts met in October 2016 during ESICM LIVES2016. Teleconferences and electronic-based discussions between the members of the committee subsequently served to discuss and develop the consensus process. METHODS: Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles generated. The consensus focused on three main topics: (1) general fluid resuscitation and maintenance in neurointensive care patients, (2) hyperosmolar fluids for intracranial pressure control, (3) fluid management in delayed cerebral ischemia after subarachnoid haemorrhage. After an extensive literature search, the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system were applied to assess the quality of evidence (from high to very low), to formulate treatment recommendations as strong or weak, and to issue best practice statements when applicable. A modified Delphi process based on the integration of evidence provided by the literature and expert opinions-using a sequential approach to avoid biases and misinterpretations-was used to generate the final consensus statement. RESULTS: The final consensus comprises a total of 32 statements, including 13 strong recommendations and 17 weak recommendations. No recommendations were provided for two statements. CONCLUSIONS: We present a consensus statement and clinical practice recommendations on fluid therapy for neurointensive care patients.

Emergency research: using exception from informed consent, evaluation of community consultations.

BACKGROUND: In 1996, the U.S. Food and Drug Administration approved regulations authorizing an exception from informed consent (EFIC) for research conducted in emergency settings when obtaining prospective informed consent is not possible due to the potential subject's critical illness or injury. The regulations require that investigators conduct community consultation (CC) efforts before initiating a study and require that institutional review boards review the results of CC prior to approving a study. However, little is known about how communities view EFIC research or the CC process. OBJECTIVES: The objective was to assess the views of CC meeting attendees regarding the CC process, their understanding and views of EFIC research relating to the specific research trial under discussion, and their level of trust in physician-investigators. METHODS: Following CC meetings at two study sites (San Francisco and Atlanta) for the Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), an active comparison, randomized trial of prehospital treatment for status epilepticus, the authors administered a pair of surveys to participants. One survey focused on CC experiences (CC survey) and trust in physician-investigators; the second assessed participants' understanding of EFIC and the RAMPART clinical trial design (EFIC survey). RESULTS: A total of 317 individuals participated in one of the two most popular types of CC meetings (group meetings and focus group sessions) at both sites. A total of 189 participants (59%) completed the CC survey and trust questions, and 297 (92%) completed the EFIC survey. Of those who completed the CC survey, 173 of 189 (92%) were very satisfied with the meeting, and 174 of 189 (92%) felt that they learned a lot about research at the meeting. A total of 169 of 189 participants (88%) felt that researchers heard the community's concerns, while only 106 of 189 (56%) said researchers would be willing to make changes to the study based on their concerns. Of those who completed the EFIC survey, 261 of 297 (88%) supported the study, 207 of 297 (70%) said they would agree to participate in the study, and 203 of 297 (68%) reported that they would agree to consent a loved one into the study. On a recently validated scale measuring trust in physician-investigators, participants at both sites seemed to have higher levels of trust in physician-investigators than the validation study population. CONCLUSIONS: Overall, members of these two communities expressed satisfaction with the CC session and had relatively high levels of support for the study and trust in physician-investigators.

Continuous muscle tissue oxygenation in critically injured patients: a prospective observational study.

BACKGROUND: Despite normalization of vital signs, critically injured patients may remain in a state of occult underresuscitation that sets the stage for sepsis, organ failure, and death. A continuous, sensitive, and accurate measure of resuscitation after injury remains elusive. METHODS: In this pilot study, we evaluated the ability of two continuous measures of peripheral tissue oxygenation in their ability to detect hypoperfusion: the Licox polarographic tissue oxygen monitor (PmO2) and the InSpectra near-infrared spectrometer (StO2). We hypothesized that deltoid muscle tissue oxygenation measurements could detect patients in "occult shock" who are at increased risk for post-injury complications. The study was designed to (1) define values for PmO2 and StO2 in patients who by all standard measures appeared to be clinically resuscitated; (2) evaluate the relationship between PmO2, StO2 and other physiologic variables including mean arterial pressure (MAP), lactate and base deficit (BD); and (3) examine the relationship between early low tissue oxygen values and the subsequent development of infections and organ dysfunction. Licox probes were inserted into the deltoid muscle of critically injured patients after initial surgical and radiologic interventions, and transcutaneous StO2 monitors were applied over the same muscle bed. PmO2, StO2, and standard physiologic data were collected continuously using a multimodal bioinformatics system. RESULTS: Twenty-eight critically injured patients were enrolled in this study at admission to the intensive care unit (ICU). For patients who appeared to be well resuscitated (defined as MAP > or = 70 mm Hg, heart rate [HR] < or = 110 bpm, BD > or = -2, and partial pressure of arterial oxygen (PaO2) = 80 and 150 mm Hg), the mean PmO2 was 34 +/- 11 mm Hg and StO2 was 63 +/- 27%. There was a strong relationship between PmO2 and BD (p < 0.001) but no significant relationship between StO2 and BD. The relationship between PmO2 and StO2 was weak but statistically significant. Early low values of both PmO2 and StO2 identified patients at risk for infectious complications or multiple organ failure (MOF). In patients who were well resuscitated by standard continuous parameters (HR and MAP), low PmO2 during the first 24 hours after admission (PmO2 < or = 25 for at least 2 hours) was strongly associated with the development of infectious complications (Odds Ratio = 16.5, 95% CI 1.49 to 183, p = 0.02). CONCLUSIONS: PmO2 is a responsive, reliable and continuous monitor of changes in base deficit. Initial low values for either PmO2 or StO2 were associated with post-injury complications. PmO2 monitoring may be useful in identifying patients in the state of occult underresuscitation who remain at risk for developing infection and MOF.

Clinical implementation of the ARDS network protocol is associated with reduced hospital mortality compared with historical controls.

OBJECTIVE: To assess the impact of implementing a low tidal volume ventilation strategy on hospital mortality for patients with acute lung injury or acute respiratory distress syndrome. DESIGN: Retrospective, uncontrolled study. SETTING: Adult medical-surgical and trauma intensive care units at a major inner city, university-affiliated hospital. PATIENTS: A total of 292 patients with acute lung injury or acute respiratory distress syndrome. INTERVENTIONS: Between the years 2000 and 2003, 200 prospectively identified patients with acute lung injury/acute respiratory distress syndrome were managed by the ARDS Network low tidal volume protocol. A historical control group of 92 acute respiratory distress syndrome patients managed by routine practice from 1998 to 1999 was used for comparison. MEASUREMENTS AND MAIN RESULTS: Patients managed with the ARDS Network protocol had a lower hospital mortality compared with historical controls (32% vs. 51%, respectively; p = .004). Multivariate logistic regression estimated an odds ratio of 0.32 (95% CI, 0.17-0.59; p = .0003) for mortality risk with use of the ARDS Network protocol. Protocol-managed patients had a lower tidal volume (6.2 +/- 1.1 vs. 9.8 +/- 1.5 mL/kg; p < .0001) and plateau pressure (27.5 +/- 6.4 vs. 33.8 +/- 8.9 cm H2O; p < .0001) than historical controls. CONCLUSION: Adoption of the ARDS Network protocol for routine ventilator management of acute lung injury/acute respiratory distress syndrome patients was associated with a lower mortality compared with recent historical controls.