Effect of early vs. delayed extubation on functional outcome among patients with acute ischemic stroke treated with endovascular thrombectomy under general anesthesia: the prospective, randomized controlled EDESTROKE trial study protocol.

BACKGROUND: Recent meta-analyses and randomized studies have shown that among patients with acute ischemic stroke undergoing endovascular thrombectomy, general anesthesia with mechanical ventilation is associated with better functional status compared to local anesthesia and sedation, and they recommend its use. But once the procedure is completed, when is the optimal moment for extubation? Currently, there are no guidelines recommending the optimal moment for extubation. Prolonged mechanical ventilation time could potentially be linked to increased complications such as pneumonia or disturbances in cerebral blood flow due to the vasodilatation produced by most anesthetic drugs. However, premature extubation in a patient who has suffered a stroke could led to complications such as agitation, disorientation, abolished reflexes, sudden fluctuations in blood pressure, alterations in cerebral blood flow, respiratory distress, bronchial aspiration, and the need for reintubation. We therefore designed a randomized study hypothesizing that early compared with delayed extubation is associated with a better functional outcome 3 months after endovascular thrombectomy treatment under general anesthesia for acute ischemic stroke. METHODS: This investigator-initiated, single-center, prospective, parallel, evaluated blinded, superiority, randomized controlled trial will include 178 patients with a proximal occlusion of the anterior circulation treated with successful endovascular thrombectomy (TICI 2b-3) under general anesthesia. Patients will be randomly allocated to receive early (< 6 h) or delayed (6-12 h) extubation after the procedure. The primary outcome measure is functional independence (mRS of 0-2) at 90 days, measured with the modified Rankin Score (mRS), ranging from 0 (no symptoms) to 6 (death). DISCUSSION: This will be the first trial to compare the effect of mechanical ventilation duration (early vs delayed extubation) after satisfactory endovascular thrombectomy for acute ischemic stroke under general anesthesia. TRIAL REGISTRATION: The study protocol was approved April 11, 2023, by the by the Santiago-Lugo Research Ethics Committee (CEI-SL), number 2023/127, and was registered into the clinicaltrials.gov clinical trials registry with No. NCT05847309. Informed consent is required. Participant recruitment begins on April 18, 2023. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

Impact of Universal Use of the McGrath Videolaryngoscope as a Device for All Intubations in the Cardiac Operating Room. A Prospective Before-After VIDEOLAR-CAR Study.

OBJECTIVE: Tracheal intubation in cardiac surgery patients has a higher incidence of difficult laryngoscopic views compared with patients undergoing other types of surgery. The authors hypothesized that using the McGrath Mac videolaryngoscope as the first intubation option for cardiac surgery patients improves the percentage of patients with "easy intubation" compared with using a direct Macintosh laryngoscope. DESIGN: A prospective, observational, before-after study. SETTING: At a tertiary-care hospital. PARTICIPANTS: One thousand one hundred nine patients undergoing cardiac surgery. INTERVENTION: Consecutive patients undergoing cardiac surgery were intubated using, as the first option, a Macintosh laryngoscope (preinterventional phase) or a McGrath Mac videolaryngoscope (interventional phase). MEASUREMENTS AND MAIN RESULTS: The main objective was to assess whether the use of the McGrath videolaryngoscope, as the first intubation option, improves the percentage of patients with "easy intubation," defined as successful intubation on the first attempt, modified Cormack-Lehane grades of I or IIa, and the absence of the need for adjuvant airway devices. A total of 1,109 patients were included, 801 in the noninterventional phase and 308 in the interventional phase. The incidence of "easy intubation" was 93% in the interventional phase versus 78% in the noninterventional phase (p < 0.001). First-success-rate intubation was higher in the interventional phase (304/308; 98.7%) compared with the noninterventional phase (754/801, 94.1%; p = 0.005). Intubation in the interventional phase showed decreases in the incidence of difficult laryngoscopy (12/308 [3.9%] v 157/801 [19.6%]; p < 0.001), as well as moderate or difficult intubation (5/308 [1.6%] v 57/801 [7.1%]; p < 0.001). CONCLUSIONS: The use of the McGrath videolaryngoscope as the first intubation option for tracheal intubation in cardiac surgery improves the percentage of patients with "easy" intubation," increasing glottic view and first-success-rate intubation and decreasing the incidence of moderate or difficult intubation.

Videolaryngoscope versus conventional technique for insertion of a transesophageal echocardiography probe in intubated ICU patients (VIDLARECO trial): A randomized clinical trial.

BACKGROUND: Transesophageal echocardiogram probe insertion in intubated critically ill patients can be difficult, leading to complications, such as gastric bleeding or lesions in the oropharyngeal mucosa. We hypothesised that the use of a videolaryngoscope would facilitate the first attempt at insertion of the transesophageal echocardiogram probe and would decrease the incidence of complications compared to the conventional insertion technique. METHODS: In this clinical trial, patients were randomly assigned the insertion of a transesophageal echocardiogram probe using a videolaryngoscope or conventional technique. The primary outcome was the successful transesophageal echocardiogram probe insertion on the first attempt. The secondary outcomes included total success rate, number of insertion attempts, and incidence of pharyngeal complications. RESULTS: A total of 100 intubated critically ill patients were enrolled. The success rate of transesophageal echocardiogram probe insertion on the first attempt was higher in the videolaryngoscope group than in the conventional group (90% vs. 58%; absolute difference, 32%; 95% CI 16%-48%; p < 0.001). The overall success rate was higher in the videolaryngoscope group than in the conventional group (100% vs. 72%; absolute difference, 28%; 95% CI 16%-40%; p < 0.001). The incidence of pharyngeal mucosal injury was smaller in the videolaryngoscope group than in the conventional group (14% vs. 52%; absolute difference, 38%; 95% CI 21%-55%; p < 0.001). CONCLUSIONS: Our study showed that in intubated critically ill patients required transesophageal echocardiogram, the use of videolaryngoscope resulted in higher successful insertion on the first attempt with lower rate of complications when compared with the conventional insertion technique. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04980976.

Role of SHP2 (PTPN11) in glycoprotein VI-dependent thrombus formation: Improved platelet responsiveness by the allosteric drug SHP099 in Noonan syndrome patients.

INTRODUCTION: The protein tyrosine phosphatase SHP2 (PTPN11) is a negative regulator of glycoprotein VI (GPVI)-induced platelet signal under certain conditions. Clinical trials with derivatives of the allosteric drug SHP099, inhibiting SHP2, are ongoing as potential therapy for solid cancers. Gain-of-function mutations of the PTPN11 gene are observed in part of the patients with the Noonan syndrome, associated with a mild bleeding disorder. Assessment of the effects of SHP2 inhibition in platelets from controls and Noonan syndrome patients. MATERIALS AND METHODS: Washed human platelets were incubated with SHP099 and stimulated with collagen-related peptide (CRP) for stirred aggregation and flow cytometric measurements. Whole-blood microfluidics assays using a dosed collagen and tissue factor coating were performed to assess shear-dependent thrombus and fibrin formation. Effects on clot formation were evaluated by thromboelastometry. RESULTS: Pharmacological inhibition of SHP2 did not alter GPVI-dependent platelet aggregation under stirring, but it enhanced integrin αIIbß3 activation in response to CRP. Using whole-blood microfluidics, SHP099 increased the thrombus buildup on collagen surfaces. In the presence of tissue factor and coagulation, SHP099 increased thrombus size and reduced time to fibrin formation. Blood from PTPN11-mutated Noonan syndrome patients, with low platelet responsiveness, after ex vivo treatment with SHP099 showed a normalized platelet function. In thromboelastometry, SHP2 inhibition tended to increase tissue factor-induced blood clotting profiles with tranexamic acid, preventing fibrinolysis. CONCLUSION: Pharmacological inhibition of SHP2 by the allosteric drug SHP099 enhances GPVI-induced platelet activation under shear conditions with a potential to improve platelet functions of Noonan syndrome patients.

Effectiveness of Prone Positioning in Nonintubated Intensive Care Unit Patients With Moderate to Severe Acute Respiratory Distress Syndrome by Coronavirus Disease 2019.

BACKGROUND: In the treatment for severe acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID-19), the World Health Organization (WHO) recommends prone positioning (PP) during mechanical ventilation for periods of 12-16 h/d to potentially improve oxygenation and survival. In this prospective observational study, we evaluated the ability of long PP sessions to improve oxygenation in awake intensive care unit (ICU) patients with moderate or severe ARDS due to COVID-19. METHODS: The study was approved by the ethics committee of Galicia (code No. 2020-188), and all patients provided informed consent. In this case series, awake patients with moderate or severe ARDS by COVID-19 admitted to the ICU at University Hospital of Santiago from March 21 to April 5, 2020 were prospectively analyzed. Patients were instructed to remain in PP as long as possible until the patient felt too tired to maintain that position. Light sedation was administered with dexmedetomidine. The following information was collected: number and duration of PP sessions; tissue O2 saturation (StO2) and blood gases before, during, and following a PP session; need of mechanical ventilation; duration of ICU admission; and ICU outcome. Linear mixed-effects models (LMM) were fit to estimate changes from baseline with a random effect for patient. RESULTS: Seven patients with moderate or severe ARDS by COVID-19 were included. All patients received at least 1 PP session. A total of 16 PP sessions were performed in the 7 patients during the period study. The median duration of PP sessions was 10 hours. Dexmedetomidine was used in all PP sessions. Oxygenation increased in all 16 sessions performed in the 7 patients. The ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FIO2) significantly increased during PP (change from baseline 110 with 97.5% confidence interval [CI], 19-202) and, after PP, albeit not significantly (change from baseline 38 with 97.5% CI, -9.2 to 85) compared with previous supine position. Similarly, tissue oxygenation underwent a small improvement during PP (change from baseline 2.6% with 97.5% CI, 0.69-4.6) without significant changes after PP. Two patients required intubation. All patients were discharged from the ICU. CONCLUSIONS: We found that PP improved oxygenation in ICU patients with COVID-19 and moderate or severe ARDS. PP was relatively well tolerated in our patients and may be a simple strategy to improve oxygenation trying to reduce the number of patients in mechanical ventilation and the length of stay in the ICU, especially in COVID-19 pandemic.

Reintubation in the ICU following cardiac surgery: is it more difficult than first-time intubation in the operating room?: A prospective observational study.

BACKGROUND: After cardiac surgery, a patient's trachea is usually extubated; however, 2 to 13% of cardiac surgery patients require reintubation in the ICU. OBJECTIVE: The objective of this study was to compare the initial intubation in the cardiac operating room with reintubation (if required) in the ICU following cardiac surgery. DESIGN: A prospective, observational study. SETTING: Department of Anesthesiology and Intensive Care Medicine, Clinical Hospital of Santiago, Spain. PATIENTS: With approval of the local ethics committee, over a 44-month period, we prospectively enrolled all cardiac surgical patients who were intubated in the operating room using direct laryngoscopy, and who required reintubation later in the ICU. MAIN OUTCOME MEASURES: The primary endpoint was to compare first-time success rates for intubation in the operating room and ICU. Secondary endpoints were to compare the technical difficulties of intubation (modified Cormack-Lehane glottic view, operator-reported difficulty of intubation, need for support devices for direct laryngoscopy) and the incidence of complications. RESULTS: A total of 122 cardiac surgical patients required reintubation in the ICU. Reintubation was associated with a lower first-time success rate than in the operating room (88.5 vs. 97.6%, P = 0.0048). Reintubation in the ICU was associated with a higher incidence of Cormack-Lehane grades IIb, III or IV views (34.5 vs. 10.7%, P < 0.0001), a higher incidence of moderate or difficult intubation (17.2 vs. 6.5%, P = 0.0001) and a greater need for additional support during direct laryngoscopy (20.5 vs. 10.7%, P = 0.005). Complications were more common during reintubations in the ICU (39.3 vs. 5.7%, P < 0.0001). CONCLUSION: Compared with intubations in the operating room, reintubation of cardiac surgical patients in the ICU was associated with more technical difficulties and a higher incidence of complications. CLINICAL TRIAL NUMBER: Ethics committee of Galicia number 2015-012.

Postoperative costs associated with outcomes after cardiac surgery with extracorporeal circulation: role of antithrombin levels.

OBJECTIVE: To study the impact on postoperative costs of a patient's antithrombin levels associated with outcomes after cardiac surgery with extracorporeal circulation. DESIGN: An analytic decision model was designed to estimate costs and clinical outcomes after cardiac surgery in a typical patient with low antithrombin levels (<63.7%) compared with a patient with normal antithrombin levels (≥63.7%). The data used in the model were obtained from a literature review and subsequently validated by a panel of experts in cardiothoracic anesthesiology. SETTING: Multi-institutional (14 Spanish hospitals). PARTICIPANTS: Consultant anesthesiologists. MEASUREMENTS AND MAIN RESULTS: A sensitivity analysis of extreme scenarios was carried out to assess the impact of the major variables in the model results. The average cost per patient was €18,772 for a typical patient with low antithrombin levels and €13,881 for a typical patient with normal antithrombin levels. The difference in cost was due mainly to the longer hospital stay of a patient with low antithrombin levels compared with a patient with normal levels (13 v 10 days, respectively, representing a €4,596 higher cost) rather than to costs related to the management of postoperative complications (€215, mostly owing to transfusions). Sensitivity analysis showed a high variability range of approximately ±55% of the base case cost between the minimum and maximum scenarios, with the hospital stay contributing more significantly to the variation. CONCLUSIONS: Based on this analytic decision model, there could be a marked increase in the postoperative costs of patients with low antithrombin activity levels at the end of cardiac surgery, mainly ascribed to a longer hospitalization.