Optimization of cerebral oxygenation based on regional cerebral oxygen saturation monitoring during carotid endarterectomy: a Phase III multicenter, double-blind randomized controlled trial.

BACKGROUND: Whether the optimization of cerebral oxygenation based on regional cerebral oxygen saturation (rSO2) monitoring reduces the occurrence of cerebral ischemic lesions is unknown. METHODS: This multicenter, randomized, controlled trial recruited adults admitted for scheduled carotid endarterectomy. Patients were randomized between the standard of care or optimization of cerebral oxygenation based on rSO2 monitoring using near-infrared spectroscopy. In the intervention group, in case of a decrease in rSO2 in the intervention, the following treatments were sequentially recommended: (1) increasing oxygenotherapy, (2) reducing the tidal volume, (3) legs up-raising, (4) performing a fluid challenge and (5) initiating vasopressor support. The primary endpoint was the number of new cerebral ischemic lesions detected using magnetic resonance imaging pre- and postoperatively. Secondary endpoints included new neurological deficits and mortality on day 120 after surgery. RESULTS: Among the 879 patients who were randomized, 665 (75.7%) were men. There was no statistically significant difference between groups for the mean number of new cerebral ischemic lesions per patient up to 3 days after surgery: 0.35 (±1.05) in the standard group vs. 0.58 (±2.83), in the NIRS group; mean difference, 0.23 [95% CI, -0.06 to 0.52]; estimate, 0.22 [95% CI, -0.06 to 0.50]. New neurological deficits up to day 120 after hospital discharge were not different between the groups: 15 (3,39%) in the standard group vs. 42 (5,49%) in the NIRS group; absolute difference, 2,10 [95% CI, -0,62 to 4,82]. There was no significant difference between groups for the median [IQR] hospital length of stay: 4.0 [4.0-6.0] in the standard group vs. 5.0 [4.0-6.0] in the NIRS group; mean difference, -0.11 [95% CI, -0.65 to 0.44]. The mortality rate on day 120 was not different between the standard group (0.68%) vs. the NIRS group (0.92%); absolute difference = 0.24% [95% CI, -0.94 to 1.41]. CONCLUSIONS: Among patients undergoing carotid endarterectomy, optimization of cerebral oxygenation based on rSO2 did not reduce the occurrence of cerebral ischemic lesions postoperatively compared with controlled hypertensive therapy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01415648.

Psychomotor retardation: What about the partial responders to magnetic transcranial stimulation in treatment resistant depression ?

OBJECTIVE: Psychomotor retardation is a core clinical component of Major Depressive Disorder responsible for disability and is known as a treatment response marker of biological treatments for depression. Our objective was to describe cognitive and motoric measures changes during a treatment by repetitive Transcranial Magnetic Stimulation (rTMS) within the THETAD-DEP trial for treatment-resistant depression (TRD), and compare those performances at the end of treatment and one month after between responders (>50% improvement on MADRS score), partial responders (25-50%) and non-reponders (no clinically relevant improvement). Our secondary aim was to investigate baseline psychomotor performances associated with non-response and response even partial. METHODS: Fifty-four patients with treatment-resistant unipolar depression and treated by either high frequency 10 Hz rTMS or iTBS for 4 weeks (20 sessions) underwent assessment including French Retardation Rating Scale for Depression (ERD), Verbal Fluency test, and Trail Making Test A. before, just after treatment and one month later. RESULTS: 20 patients were responders (R, 21 partial responders (PR) and 13 non-responders (NR). rTMS treatment improved psychomotor performances in the R and PR groups unlike NR patients whose psychomotor performance was not enhanced by treatment. At baseline, participants, later identified as partial responders, showed significantly higher performances than non-responders. CONCLUSION: Higher cognitivo-motor performances at baseline may be associated with clinical improvement after rTMS treatment. This work highlights the value of objective psychomotor testing for the identification of rTMS responders and partial responders, and thus may be useful for patient selection and protocol individualization such as treatment continuation for early partial responders.

Ketamine Compared With Morphine for Out-of-Hospital Analgesia for Patients With Traumatic Pain: A Randomized Clinical Trial.

Importance: Pain is a common out-of-hospital symptom among patients, and opioids are often prescribed. Research suggests that overprescribing for acute traumatic pain is still prevalent, even when limits restricting opioid prescriptions have been implemented. Ketamine hydrochloride is an alternative to opioids in adults with out-of-hospital traumatic pain. Objective: To assess the noninferiority of intravenous ketamine compared with intravenous morphine sulfate to provide pain relief in adults with out-of-hospital traumatic pain. Design, Setting, and Participants: The Intravenous Subdissociative-Dose Ketamine Versus Morphine for Prehospital Analgesia (KETAMORPH) study was a multicenter, single-blind, noninferiority randomized clinical trial comparing ketamine hydrochloride (20 mg, followed by 10 mg every 5 minutes) with morphine sulfate (2 or 3 mg every 5 minutes) in adult patients with out-of-hospital trauma and a verbal pain score equal to or greater than 5. Enrollment occurred from November 23, 2017, to November 26, 2022, in 11 French out-of-hospital emergency medical units. Interventions: Patients were randomly assigned to ketamine (n = 128) or morphine (n = 123). Main Outcomes and Measures: The primary outcome was the between-group difference in mean change in verbal rating scale pain scores measured from the time before administration of the study drug to 30 minutes later. A noninferiority margin of 1.3 was chosen. Results: A total of 251 patients were randomized (median age, 51 [IQR, 34-69] years; 111 women [44.9%] and 140 men [55.1%] among the 247 with data available) and were included in the intention-to-treat population. The mean pain score change was -3.7 (95% CI, -4.2 to -3.2) in the ketamine group compared with -3.8 (95% CI, -4.2 to -3.4) in the morphine group. The difference in mean pain score change was 0.1 (95% CI, -0.7 to 0.9) points. There were no clinically meaningful differences for vital signs between the 2 groups. The intravenous morphine group had 19 of 113 (16.8% [95% CI, 10.4%-25.0%]) adverse effects reported (most commonly nausea [12 of 113 (10.6%)]) compared with 49 of 120 (40.8% [95% CI, 32.0%-49.6%]) in the ketamine group (most commonly emergence phenomenon [24 of 120 (20.0%)]). No adverse events required intervention. Conclusions and Relevance: In the KETAMORPH study of patients with out-of-hospital traumatic pain, the use of intravenous ketamine compared with morphine showed noninferiority for pain reduction. In the ongoing opioid crisis, ketamine administered alone is an alternative to opioids in adults with out-of-hospital traumatic pain. Trial Registration: ClinicalTrials.gov Identifier: NCT03236805.

Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort.

BACKGROUND: Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy. METHODS: This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy. RESULTS: Among 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0-7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2-6] and 39 [30-48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3-4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3-4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1-4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU. CONCLUSION: ICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3-4 toxicities, and half of patients being alive and in complete remission at one year.