Moderate-dose sedation and analgesia during targeted temperature management after cardiac arrest.

BACKGROUND: Sedation and analgesia regimens during targeted temperature management (TTM), after cardiac arrest varies widely, are poorly described in the literature and may have a negative impact on outcome. Since implementing TTM in 2005, we have used moderate-dose sedation and describe our experience with this approach. METHODS: In this retrospective review, we included patients treated with TTM for cardiac arrest at our institution for 2008-2012. Patients received TTM if they did not follow verbal commands following cardiac arrest, regardless of place of arrest or rhythm. Utstein-compatible data were prospectively entered into the International Cardiac Arrest Registry, supplemented by review of nursing, pharmacy, and physical therapy records. We report analgesic and sedative medications and doses during the 24 h of active TTM at 33 °C, resource utilization, and important clinical events. RESULTS: 166 patients treated with TTM after in- and out-of-hospital cardiac arrest with complete data were included. Overall survival was 42 %, median time to following commands was 3 h after rewarming (-6, 14), time to spontaneous breathing trial was 19 h (5-35), time to extubation was 28 h (9-60), and 59 % of survivors were discharged directly home at 13 (10-20) days. The incidence of seizure was 6 %, septic shock 4 %, and pneumonia 32 %. Four survivors required tracheostomy at 8, 8, 12, and 16 days. CONCLUSIONS: A moderate-dose sedation and analgesia regimen was well tolerated and effective during therapeutic hypothermia after cardiac arrest and is an effective alternative to very deep sedation. We recommend more complete description of sedation and analgesia protocols in future studies, including expanded outcome reporting to include variables affected by sedation therapy. Further study is required to define which sedation approach for TTM may be best

Continuous surface EMG power reflects the metabolic cost of shivering during targeted temperature management after cardiac arrest.

AIM: Shivering may interfere with targeted temperature management (TTM) after cardiac arrest, contributing to secondary brain injury. Early identification of shivering is challenging with existing tools. We hypothesized that shivering detected by continuous surface sEMG monitoring would be validated with calorimetry and detected earlier than by intermittent clinical observation. METHODS: This prospective observational study enrolled a convenience sample of comatose adult cardiac arrest patients treated with TTM at 33 °C. Clinical shivering was monitored hourly using the Bedside Shivering Assessment Scale (BSAS) by bedside nurses who administered intermittent neuromuscular blockade (NMB) when BSAS ≥ 1. The research team monitored independently for shivering with BSAS every 15 min during continuous blinded monitoring of oxygen consumption (VO RESULTS: Among 18 patients, clinical shivering was detected 23 times in 14 patients. Hierarchical models to predict a shiver event determined by the VO CONCLUSIONS: Shivering was detected by sEMG power earlier than by clinical assessment with BSAS, with similar accuracy compared to the indirect calorimetry gold standard. Continuous sEMG monitoring appears useful for clinical assessment and research for shivering during TTM

Feasibility of bispectral index monitoring to guide early post-resuscitation cardiac arrest triage.

INTRODUCTION: Triage after resuscitation from cardiac arrest is hindered by reliable early estimation of brain injury. We evaluated the performance of a triage model based on early bispectral index (BIS) findings and cardiac risk classes. METHODS: Retrospective evaluation of serial patients resuscitated from cardiac arrest, unable to follow commands, and undergoing hypothermia. Patients were assigned to a cardiac risk group: STEMI, VT/VF shock, VT/VF no shock, or PEA/asystole, and to a neurological dysfunction group, based on the BIS score following first neuromuscular blockade (BISi), and classified as BISi\u3e20, BISi 10-20, or BISi RESULTS: BISi in 171 patients was measured at 267(±177)min after resuscitation and 35(±1.7)°C. BISi82% neurological-cause and 91% overall mortality, BISi 10-20 35% neurological and 55% overall mortality, and BISi\u3e20 12% neurological and 36% overall mortality. 33 patients presented with STEMI, 15 VT/VF-shock, 41 VT/VF-no shock, and 80 PEA/asystole. Among BISi\u3e20 patients, 75% with STEMI underwent urgent cardiac catheterization (cath) and 94% had good outcome. When BISi\u3e20 with VT/VF and shock, urgent cath was infrequent (33%), and 4 deaths (44%) were uniformly of circulatory etiology. Of 56 VT/VF patients without STEMI, 24 were BISi\u3e20 but did not undergo urgent cath - 5(20.8%) of these had circulatory-etiology death. Circulatory-etiology death also occurred in 26.5% BIS\u3e20 patients with PEA/asystole. When BISi CONCLUSIONS: Neurocardiac triage based on very early processed EEG (BIS) is feasible, and may identify patients appropriate for individualized post-resuscitation care. This and other triage models warrant further study

Number of circulating CD 73-expressing lymphocytes correlates with survival after cardiac arrest.

Background Patients resuscitated from cardiac arrest ( CA ) have highly variable neurological, circulatory, and systemic ischemia-reperfusion injuries. After the initial hypoxic-ischemic insult, a cascade of immune and inflammatory responses develops and is often fatal. The role of the immune response in pathophysiological characteristics and recovery is not well understood. We studied immune cell activity and its association with outcomes in a cohort of CA survivors. Methods and Results After informed consent, we collected blood samples at intervals over a week after resuscitation from CA . We examined the expression of CD 39 and CD 73 (alias 5\u27-nucleotidase), production of tumor necrosis factor-α, generation of reactive oxygen species, and secretion of vascular endothelial growth factor by circulating myeloid and lymphoid cells, in comparison to cells obtained from control subjects before coronary artery bypass grafting surgery. The number of circulating total and CD 73-expressing lymphocytes correlated with survival after CA . Incubation of immune cells, obtained from post- CA subjects, with AMP , a substrate for CD 73, resulted in inhibition of tumor necrosis factor-α production and generation of reactive oxygen species. This effect was blocked by adenosine 5\u27-(α, β-methylene) diphosphate, a specific inhibitor of CD 73 and ZM 241385, an A2 adenosine receptor antagonist. We also found that AMP -dependent activation of CD 73 induces production of vascular endothelial growth factor. Conclusions CD 73-expressing lymphocytes mediate cellular protection from inflammation after CA through inhibition of proinflammatory activation of myeloid cells and promotion of vascular endothelial growth factor secretion. The contribution of CD 73 lymphocytes in the regulation of acute inflammation and tissue injury after CA warrants further study

Inadequacy of Headache Management After Subarachnoid Hemorrhage.

BACKGROUND: Headache profoundly affects management of spontaneous subarachnoid hemorrhage but is poorly characterized. OBJECTIVE: To characterize headache after spontaneous subarachnoid hemorrhage. METHODS: Medical records of patients with Hunt and Hess grades I-III subarachnoid hemorrhage admitted from 2011 to 2013 were reviewed. Demographics, clinical and radiographic features, medications, and pain scores were recorded through day 14 after hemorrhage. Headache pain was characterized on the basis of a numeric rating scale and analgesic use. Severe headache was defined as 2 or more days with maximum pain scores of 8 or greater or need for 3 or more different analgesics for 2 or more days. Univariate and multivariable models were used to analyze factors associated with severe headache. RESULTS: Of the 77 patients in the sample, 57% were women; median age was 57 years. Severe headache (73% overall) was associated nonlinearly with Hunt and Hess grade: grade I, 58%; grade II, 88%; and grade III, 56% (P = .01), and with Hijdra score: score 0-10, 56%; score 11-20, 86%; score 21-30, 76% (P = .03). By univariate analysis, patients with low Hijdra scores were less likely to have severe headache (27% vs 57%; P = .02). In a multivariable model, younger age and higher Hijdra score tended to be associated with severe headache. CONCLUSIONS: Headache after spontaneous subarachnoid hemorrhage was often severe, necessitating multiple opioid and nonopioid analgesics. Many patients reported persistent headache and inadequate pain control

Chemokine dynamics and the inflammatory response after cardiac injury

Problem/Background: The initial ischemic insult of a cardiac arrest (CA) episode triggers the inflammatory response, resulting in neurological, circulatory, and systemic ischemia-reperfusion injuries that are frequently fatal. More than 500,000 Americans suffer cardiac arrest annually, and despite improved cardiopulmonary resuscitation, post-resuscitation therapy, and cardiovascular systems of care, outcomes remain poor. Understanding molecular mechanisms contributing to survival after CA may lead to identification of therapeutic targets and improvement of outcomes. Chemotactic cytokines (chemokines) are secreted soluble or membrane-bound proteins that signal through G-protein coupled receptors to stimulate immune cell migration to the site of injury, acting as the first mobilizers of the inflammatory response. To our knowledge chemokine expression and function in cardiac arrest has not been examined. We measured levels of circulating chemokines in CA subjects as well as in Coronary Artery Bypass Graft (CABG) subjects before surgery. Approach: Study subjects admitted to intensive care after a CA episode and treated with therapeutic temperature management underwent phlebotomy at 6, 12, 24, 48, and 72 hours, and 7 days after return of spontaneous circulation (ROSC). Control subjects underwent CABG surgery with phlebotomy at pre-op, surgery, 4-8 hours, 24 hours, and 4 days postop. Blood samples were processed within 4 to 6 hours of collection. Platelets free plasma (PFP) was obtained from venous blood via consecutive centrifugations and stored at -800C. CCL2, CCL4, and CCL23 protein levels were determined using Human CCL2, CCL4, and CCL23 DuoSet ELISA (R&D Systems/biotechne) kits. Data analysis was performed with GraphPad Prism. Results: Each chemokine demonstrated unique dynamics in the context of cardiac arrest. Our results revealed large inter-individual variability, in accord with other analyte testing in this study group. All three chemokines were found at significantly elevated levels 24 hours post-ROSC as compared to control. CCL23 (MPIF-1, myeloid progenitor inhibitory factor-1), emerged as a protein of interest. This chemokine exhibits a specific time-dependent pattern associated with increased circulating levels at 24 to 48 hours post-ROSC. In our cohort, CCL23 levels are statistically significantly different between non-survivors (n=19) and survivors (n=23) at 48 hours post-ROSC, with non-survivor median CCL23 levels twice that seen in survivors. We also observed positive correlation between the number of white blood cells (WBCs) and CCL23 levels at 48 hours post-ROSC. Conclusion: Chemokine dynamics may provide insight into potential targets for treatment after cardiac arrest with focus on the inflammatory response in the first two days after injury. The current study provides an important contribution to our understanding of the role of chemokines and the inflammatory response after cardiac arrest. Further investigation into the expression locations and mechanisms of action of chemokines is warranted

Ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arresT (PROTECT): study protocol for a randomized, placebo-controlled trial

BACKGROUND: Pneumonia is the most common infection after out-of-hospital cardiac arrest (OHCA) occurring in up to 65% of patients who remain comatose after return of spontaneous circulation. Preventing infection after OHCA may (1) reduce exposure to broad-spectrum antibiotics, (2) prevent hemodynamic derangements due to local and systemic inflammation, and (3) prevent infection-associated morbidity and mortality. METHODS: The ceftriaxone to PRevent pneumOnia and inflammaTion aftEr Cardiac arrest (PROTECT) trial is a randomized, placebo-controlled, single-center, quadruple-blind (patient, treatment team, research team, outcome assessors), non-commercial, superiority trial to be conducted at Maine Medical Center in Portland, Maine, USA. Ceftriaxone 2 g intravenously every 12 h for 3 days will be compared with matching placebo. The primary efficacy outcome is incidence of early-onset pneumonia occurring \u3c 4 days after mechanical ventilation initiation. Concurrently, T cell-mediated inflammation bacterial resistomes will be examined. Safety outcomes include incidence of type-one immediate-type hypersensitivity reactions, gallbladder injury, and Clostridioides difficile-associated diarrhea. The trial will enroll 120 subjects over approximately 3 to 4 years. DISCUSSION: The PROTECT trial is novel in its (1) inclusion of OHCA survivors regardless of initial heart rhythm, (2) use of a low-risk antibiotic available in the USA that has not previously been tested after OHCA, (3) inclusion of anti-inflammatory effects of ceftriaxone as a novel mechanism for improved clinical outcomes, and (4) complete metagenomic assessment of bacterial resistomes pre- and post-ceftriaxone prophylaxis. The long-term goal is to develop a definitive phase III trial powered for mortality or functional outcome. TRIAL REGISTRATION: ClinicalTrials.gov NCT04999592 . Registered on August 10, 2021