Performance of the MRI lesion pattern score in predicting neurological outcome after out of hospital cardiac arrest: a retrospective cohort analysis.

BACKGROUND: Despite advances in resuscitation practice, patient survival following cardiac arrest remains poor. The utilization of MRI in neurological outcome prognostication post-cardiac arrest is growing and various classifications has been proposed; however a consensus has yet to be established. MRI, though valuable, is resource-intensive, time-consuming, costly, and not universally available. This study aims to validate a MRI lesion pattern score in a cohort of out of hospital cardiac arrest patients at a tertiary referral hospital in Switzerland. METHODS: This cohort study spanned twelve months from February 2021 to January 2022, encompassing all unconscious patients aged ≥ 18 years who experienced out-of-hospital cardiac arrest of any cause and were admitted to the intensive care unit (ICU) at Inselspital, University Hospital Bern, Switzerland. We included patients who underwent the neuroprognostication process, assessing the performance and validation of a MRI scoring system. RESULTS: Over the twelve-month period, 137 patients were admitted to the ICU, with 52 entering the neuroprognostication process and 47 undergoing MRI analysis. Among the 35 MRIs indicating severe hypoxic brain injury, 33 patients (94%) experienced an unfavourable outcome (UO), while ten (83%) of the twelve patients with no or minimal MRI lesions had a favourable outcome. This yielded a sensitivity of 0.94 and specificity of 0.83 for predicting UO with the proposed MRI scoring system. The positive and negative likelihood ratios were 5.53 and 0.07, respectively, resulting in an accuracy of 91.49%. CONCLUSION: We demonstrated the effectiveness of the MLP scoring scheme in predicting neurological outcome in patients following cardiac arrest. However, to ensure a comprehensive neuroprognostication, MRI results need to be combined with other assessments. While neuroimaging is a promising objective tool for neuroprognostication, given the absence of sedation-related confounders-compared to electroencephalogram (EEG) and clinical examination-the current lack of a validated scoring system necessitates further studies. Incorporating standardized MRI techniques and grading systems is crucial for advancing the reliability of neuroimaging for neuroprognostication. TRIAL REGISTRATION: Registry of all Projects in Switzerland (RAPS) 2020-01761.

Bilateral phrenic nerve block to reduce hazardous respiratory drive in a mechanically ventilated patient with COVID-19-A case report.

Key Clinical Message: Forced inspiration during mechanical ventilation risks self-inflicted lung injury. However, controlling it with sedation or paralysis may cause polyneuropathy and myopathy. We tested bilateral phrenic nerve paralysis with local anesthetic in a patient, showing reduced inspiratory force. This offers an alternative to drug-induced muscle paralysis. Abstract: Mechanical ventilation, although a life-saving measure, can also pose a risk of causing lung injury known as "ventilator-induced lung injury" or VILI. Patients undergoing mechanical ventilation sometimes exhibit heightened inspiratory efforts, wherein the negative pressure generated by the respiratory muscles adds to the positive pressure generated by the ventilator. This combination of high pressures can lead to a syndrome similar to VILI, referred to as "patient self-inflicted lung injury" or P-SILI. Prevention of P-SILI requires the administration of deep sedation and muscle paralysis to the patients, but both these measures can have undesired effects on their health. In this case report, we demonstrate the effect of a bilateral phrenic nerve block aiming to reduce excessive inspiratory respiratory efforts in a patient suffering from COVID-19 pneumonitis.

Longitudinal analysis of caloric requirements in critically ill trauma patients: a retrospective cohort study.

PURPOSE: Nutrition is of paramount importance in critically ill trauma patients. However, adequate supply is difficult to achieve, as caloric requirements are unknown. This study investigated caloric requirements over time, based on indirect calorimetry, in critically ill trauma patients. METHODS: Retrospective cohort study at a tertiary trauma center including critically ill trauma patients who underwent indirect calorimetry 2012-2019. Caloric requirements were assessed as resting energy expenditure (REE) during the intensive care unit stay up to 28 days and analyzed in patient-clustered linear regression analysis. RESULTS: A total of 129 patients were included. Median REE per day was 2376 kcal. The caloric intake did not meet REE at any time with a median daily deficit of 1167 kcal. In univariable analysis, ISS was not significantly associated with REE over time (RC 0.03, p = 0.600). Multivariable analysis revealed a significant REE increase (RC 0.62, p < 0.001) and subsequent decrease (RC - 0.03, p < 0.001) over time. Age < 65 years (RC 2.07, p = 0.018), male sex (RC 4.38, p < 0.001), and BMI ≥ 35 kg/m2 (RC 6.94, p < 0.001) were identified as independent predictors for higher REE over time. Severe head trauma was associated with lower REE over time (RC - 2.10, p = 0.030). CONCLUSION: In critically ill trauma patients, caloric requirements significantly increased and subsequently decreased over time. Younger age, male sex and higher BMI were identified as independent predictors for higher caloric requirements, whereas severe head trauma was associated with lower caloric requirements over time. These results support the use of IC and will help to adjust nutritional support in critically ill trauma patients.

BET-inhibitor DYB-41 reduces pulmonary inflammation and local and systemic cytokine levels in LPS-induced acute respiratory distress syndrome: an experimental rodent study.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a form of respiratory failure stemming from various underlying conditions that ultimately lead to inflammation and lung fibrosis. Bromodomain and Extra-Terminal motif (BET) inhibitors are a class of medications that selectively bind to the bromodomains of BET motif proteins, effectively reducing inflammation. However, the use of BET inhibitors in ARDS treatment has not been previously investigated. In our study, we induced ARDS in rats using endotoxin and administered a BET inhibitor. We evaluated the outcomes by examining inflammation markers and lung histopathology. RESULTS: Nine animals received treatment, while 12 served as controls. In the lung tissue of treated animals, we observed a significant reduction in TNFα levels (549 [149-977] pg/mg vs. 3010 [396-5529] pg/mg; p = 0.009) and IL-1ß levels (447 [369-580] pg/mg vs. 662 [523-924] pg/mg; p = 0.012), although IL-6 and IL-10 levels showed no significant differences. In the blood, treated animals exhibited a reduced TNFα level (25 [25-424] pg/ml vs. 900 [285-1744] pg/ml, p = 0.016), but IL-1ß levels were significantly higher (1254 [435-2474] pg/ml vs. 384 [213-907] pg/ml, p = 0.049). No differences were observed in IL-6 and IL-10 levels. There were no significant variations in lung tissue levels of TGF-ß, SP-D, or RAGE. Histopathological analysis revealed substantial damage, with notably less perivascular edema (3 vs 2; p = 0.0046) and visually more inflammatory cells. However, two semi-quantitative histopathologic scoring systems did not indicate significant differences. CONCLUSIONS: These preliminary findings suggest a potential beneficial effect of BET inhibitors in the treatment of acute lung injury and ARDS. Further validation and replication of these results with a larger cohort of animals, in diverse models, and using different BET inhibitors are needed to explore their clinical implications.

Triggered Seizures for Ictal SPECT Imaging: A Case Series and Feasibility Study.

Ictal SPECT is an informative seizure imaging technique to tailor epilepsy surgery. However, capturing the onset of unpredictable seizures is a medical and logistic challenge. Here, we sought to image planned seizures triggered by direct stimulation of epileptic networks via stereotactic electroencephalography (sEEG) electrodes. Methods: In this case series of 3 adult participants with left temporal epilepsy, we identified and stimulated sEEG contacts able to trigger patient-typical seizures. We administered 99mTc-HMPAO within 12 s of ictal onset and acquired SPECT images within 40 min without any adverse events. Results: Ictal hyperperfusion maps partially overlapped concomitant sEEG seizure activity. In both participants known for periictal aphasia, SPECT imaging revealed hyperperfusion in the speech cortex lacking sEEG coverage. Conclusion: Triggering of seizures for ictal SPECT complements discrete sEEG sampling with spatially complete images of early seizure propagation. This readily implementable method revives interest in seizure imaging to guide resective epilepsy surgery.

Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm: A Meta-Analysis.

Importance: International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable. Objective: To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm. Data Sources: Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis. Study Selection: The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score. Data Extraction and Synthesis: Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation. Main Outcomes and Measures: The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5. Results: A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups. Conclusions and Relevance: In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.

Resuscitative endovascular balloon occlusion of the aorta in out-of-hospital cardiac arrest - A Delphi consensus study for uniform data collection.

Background: Evolving research on resuscitative endovascular balloon occlusion of the aorta (REBOA) as an adjunct treatment for out-of-hospital cardiac arrest mandates uniform recording and reporting of data. A consensus on which variables need to be collected may enable comparing and merging data from different studies. We aimed to establish a standard set of variables to be collected and reported in future REBOA studies in out-of-hospital cardiac arrest. Methods: A four-round stepwise Delphi consensus process first asked experts to propose without restraint variables for future REBOA research in out-of-hospital cardiac arrest. The experts then reviewed the variables on a 5-point Likert scale and ≥75% agreement was defined as consensus. First authors of published papers on REBOA in out-of-hospital cardiac arrest over the last five years were invited to join the expert panel. Results: The data were collected between May 2022 and December 2022. A total of 28 experts out of 34 primarily invited completed the Delphi process, which developed a set of 31 variables that might be considered as a supplement to the Utstein style reporting of research in out-of-hospital cardiac arrest. Conclusions: This Delphi consensus process suggested 31 variables that enable future uniform reporting of REBOA in out-of-hospital cardiac arrest.

Effects of immersive virtual reality on sensory overload in a random sample of critically ill patients.

Background: Sensory overload and sensory deprivation have both been associated with negative health outcomes in critically ill patients. While there is a lack of any clear treatment or prevention strategies, immersive virtual reality is a promising tool for addressing such problems, but which has not been repetitively tested in random samples. Therefore, this study aimed to determine how critically ill patients react to repeated sessions of immersive virtual reality. Methods: This exploratory study was conducted in the mixed medical-surgical intermediate care unit of the University Hospital of Bern (Inselspital). Participants (N = 45; 20 women, 25 men; age = 57.73 ± 15.92 years) received two immersive virtual reality sessions via a head-mounted display and noise-canceling headphones within 24 h during their stay in the unit. Each session lasted 30-min and showed a 360-degree nature landscape. Physiological data were collected as part of the participants' standard care, while environmental awareness, cybersickness, and general acceptance were assessed using a questionnaire designed by our team (1 = not at all, 10 = extremely). Results: During both virtual reality sessions, there was a significant negative linear relationship found between the heart rate and stimulation duration [first session: r(43) = -0.78, p < 0.001; second session: r(38) = -0.81, p < 0.001] and between the blood pressure and stimulation duration [first session: r(39) = -0.78, p < 0.001; second session: r(30) = -0.78, p < 0.001]. The participants had a high comfort score [median (interquartile range {IQR}) = 8 (7, 10); mean = 8.06 ± 2.31], did not report being unwell [median (IQR) = 1 (1, 1); mean = 1.11 ± 0.62], and were not aware of their real-world surroundings [median (IQR) = 1 (1, 5); mean = 2.99 ± 3.22]. Conclusion: The subjectively reported decrease in environmental awareness as well as the decrease in the heart rate and blood pressure over time highlights the ability of immersive virtual reality to help critically ill patients overcome sensory overload and sensory deprivation. Immersive virtual reality can successfully and repetitively be provided to a randomly selected sample of critically ill patients over a prolonged duration.

Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.

BACKGROUND AND AIMS: Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. METHODS: This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. RESULTS: Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790-0.828), 0.835 (95% CI 0.816-0.852) for the TTM-score, 0.820 (95% CI 0.800-0.839) for the CAHP-score and 0.770 (95% CI 0.748-0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. CONCLUSIONS: The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials.

The effect of sedation and time after cardiac arrest on coma outcome prognostication based on EEG power spectra.

Early prognostication of long-term outcome of comatose patients after cardiac arrest remains challenging. Electroencephalography-based power spectra after cardiac arrest have been shown to help with the identification of patients with favourable outcome during the first day of coma. Here, we aim at comparing the power spectra prognostic value during the first and second day after coma onset following cardiac arrest and to investigate the impact of sedation on prognostication. In this cohort observational study, we included comatose patients (N = 91) after cardiac arrest for whom resting-state electroencephalography was collected on the first and second day after cardiac arrest in four Swiss hospitals. We evaluated whether the average power spectra values at 4.6-15.2 Hz were predictive of patients' outcome based on the best cerebral performance category score at 3 months, with scores ranging from 1 to 5 and dichotomized as favourable (1-2) and unfavourable (3-5). We assessed the effect of sedation and its interaction with the electroencephalography-based power spectra on patient outcome prediction through a generalized linear mixed model. Power spectra values provided 100% positive predictive value (95% confidence intervals: 0.81-1.00) on the first day of coma, with correctly predicted 18 out of 45 favourable outcome patients. On the second day, power spectra values were not predictive of patients' outcome (positive predictive value: 0.46, 95% confidence intervals: 0.19-0.75). On the first day, we did not find evidence of any significant contribution of sedative infusion rates to the patient outcome prediction (P > 0.05). Comatose patients' outcome prediction based on electroencephalographic power spectra is higher on the first compared with the second day after cardiac arrest. Sedation does not appear to impact patient outcome prediction.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Association of Noninvasive Respiratory Support with Extubation Outcomes in Brain-injured Patients Receiving Mechanical Ventilation: A Secondary Analysis of the ENIO Prospective Observational Study.

Rationale: Noninvasive respiratory support using a high-flow nasal cannula (HFNC) or noninvasive positive pressure ventilation (NIPPV) can decrease the risk of reintubation in patients being liberated from mechanical ventilation, but effects in patients with acute brain injury (ABI) are unknown. Objectives: To evaluate the association between postextubation noninvasive respiratory support and reintubation in patients with ABI being liberated from mechanical ventilation. Methods: This was a secondary analysis of a prospective, observational study of mechanically ventilated patients with ABI (clinicaltrials.gov identifier NCT03400904). The primary endpoint was reintubation during ICU admission. We used mixed-effects logistic regression models with patient-level covariates and random intercepts for hospital and country to evaluate the association between prophylactic (i.e., planned) HFNC or NIPPV and reintubation. Measurements and Main Results: 1,115 patients were included from 62 hospitals and 19 countries, of whom 267 received HFNC or NIPPV following extubation (23.9%). Compared with conventional oxygen therapy, neither prophylactic HFNC nor NIPPV was associated with decreased odds of reintubation (respectively, odds ratios of 0.97 [95% confidence interval, 0.54-1.73] and 0.63 [0.30-1.32]). Findings remained consistent in sensitivity analyses accounting for alternate adjustment procedures, missing data, shorter time frames of the primary endpoint, and competing risks precluding reintubation. In a Bayesian analysis using skeptical and data-driven priors, the probabilities of reduced reintubation ranged from 17% to 34% for HFNC and from 46% to 74% for NIPPV. Conclusions: In a large cohort of brain-injured patients undergoing liberation from mechanical ventilation, prophylactic use of HFNC and NIPPV were not associated with reintubation. Prospective trials are needed to confirm treatment effects in this population. Primary study registered with www.clinicaltrials.gov (NCT03400904).

EFFECTS OF M101-AN EXTRACELLULAR HEMOGLOBIN-APPLIED DURING CARDIOPULMONARY RESUSCITATION: AN EXPERIMENTAL RODENT STUDY.

ABSTRACT: During and immediately after cardiac arrest, cerebral oxygen delivery is impaired mainly by microthrombi and cerebral vasoconstriction. This may narrow capillaries so much that it might impede the flow of red blood cells and thus oxygen transport. The aim of this proof-of-concept study was to evaluate the effect of M101, an extracellular hemoglobin-based oxygen carrier (Hemarina SA, Morlaix, France) derived from Arenicola marina , applied during cardiac arrest in a rodent model, on markers of brain inflammation, brain damage, and regional cerebral oxygen saturation. Twenty-seven Wistar rats subjected to 6 min of asystolic cardiac arrest were infused M101 (300 mg/kg) or placebo (NaCl 0.9%) concomitantly with start of cardiopulmonary resuscitation. Brain oxygenation and five biomarkers of inflammation and brain damage (from blood, cerebrospinal fluid, and homogenates from four brain regions) were measured 8 h after return of spontaneous circulation. In these 21 different measurements, M101-treated animals were not significantly different from controls except for phospho-tau only in single cerebellum regions ( P = 0.048; ANOVA of all brain regions: P = 0.004). Arterial blood pressure increased significantly only at 4 to 8 min after return of spontaneous circulation ( P < 0.001) and acidosis decreased ( P = 0.009). While M101 applied during cardiac arrest did not significantly change inflammation or brain oxygenation, the data suggest cerebral damage reduction due to hypoxic brain injury, measured by phospho-tau. Global burden of ischemia appeared reduced because acidosis was less severe. Whether postcardiac arrest infusion of M101 improves brain oxygenation is unknown and needs to be investigated.

Integral assessment of gas exchange during veno-arterial ECMO: accuracy and precision of a modified Fick principle in a porcine model.

Assessment of native cardiac output during extracorporeal circulation is challenging. We assessed a modified Fick principle under conditions such as dead space and shunt in 13 anesthetized swine undergoing centrally cannulated veno-arterial extracorporeal membrane oxygenation (V-A ECMO, 308 measurement periods) therapy. We assumed that the ratio of carbon dioxide elimination (V̇co2) or oxygen uptake (V̇o2) between the membrane and native lung corresponds to the ratio of respective blood flows. Unequal ventilation/perfusion (V̇/Q̇) ratios were corrected towards unity. Pulmonary blood flow was calculated and compared to an ultrasonic flow probe on the pulmonary artery with a bias of 99 mL/min (limits of agreement -542 to 741 mL/min) with blood content V̇o2 and no-shunt, no-dead space conditions, which showed good trending ability (least significant change from 82 to 129 mL). Shunt conditions led to underestimation of native pulmonary blood flow (bias -395, limits of agreement -1,290 to 500 mL/min). Bias and trending further depended on the gas (O2, CO2) and measurement approach (blood content vs. gas phase). Measurements in the gas phase increased the bias (253 [LoA -1,357 to 1,863 mL/min] for expired V̇o2 bias 482 [LoA -760 to 1,724 mL/min] for expired V̇co2) and could be improved by correction of V̇/Q̇ inequalities. Our results show that common assumptions of the Fick principle in two competing circulations give results with adequate accuracy and may offer a clinically applicable tool. Precision depends on specific conditions. This highlights the complexity of gas exchange in membrane lungs and may further deepen the understanding of V-A ECMO.

Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial.

BACKGROUND: Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes. METHODS: In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4-6 on modified Rankin scale). RESULTS: A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (p = 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84-1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80-1.26). CONCLUSIONS: Using a hospital's average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.

Extubation in neurocritical care patients: the ENIO international prospective study.

PURPOSE: Neurocritical care patients receive prolonged invasive mechanical ventilation (IMV), but there is poor specific information in this high-risk population about the liberation strategies of invasive mechanical ventilation. METHODS: ENIO (NCT03400904) is an international, prospective observational study, in 73 intensive care units (ICUs) in 18 countries from 2018 to 2020. Neurocritical care patients with a Glasgow Coma Score (GCS) ≤ 12, receiving IMV ≥ 24 h, undergoing extubation attempt or tracheostomy were included. The primary endpoint was extubation failure by day 5. An extubation success prediction score was created, with 2/3 of patients randomly allocated to the training cohort and 1/3 to the validation cohort. Secondary endpoints were the duration of IMV and in-ICU mortality. RESULTS: 1512 patients were included. Among the 1193 (78.9%) patients who underwent an extubation attempt, 231 (19.4%) failures were recorded. The score for successful extubation prediction retained 20 variables as independent predictors. The area under the curve (AUC) in the training cohort was 0.79 95% confidence interval (CI95) [0.71-0.87] and 0.71 CI95 [0.61-0.81] in the validation cohort. Patients with extubation failure displayed a longer IMV duration (14 [7-21] vs 6 [3-11] days) and a higher in-ICU mortality rate (8.7% vs 2.4%). Three hundred and nineteen (21.1%) patients underwent tracheostomy without extubation attempt. Patients with direct tracheostomy displayed a longer duration of IMV and higher in-ICU mortality than patients with an extubation attempt (success and failure). CONCLUSIONS: In neurocritical care patients, extubation failure is high and is associated with unfavourable outcomes. A score could predict extubation success in multiple settings. However, it will be mandatory to validate our findings in another prospective independent cohort.

Influence of temperature management at 33 °C versus normothermia on survival in patients with vasopressor support after out-of-hospital cardiac arrest: a post hoc analysis of the TTM-2 trial.

BACKGROUND: Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. METHODS: We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. RESULTS: The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78-1.39] in the no-, 1.22 [98.3% CI 0.97-1.53] in the moderate-, and 0.97 [98.3% CI 0.68-1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. CONCLUSIONS: In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308 , registered September 20, 2016.

Effects of brain tissue oxygen (PbtO2) guided management on patient outcomes following severe traumatic brain injury: A systematic review and meta-analysis.

Monitoring and optimisation of brain tissue oxygen tension (PbtO2) has been associated with improved neurological outcome and survival in observational studies of severe traumatic brain injury (TBI). We carried out a systematic review of randomized controlled trials to determine if PbtO2-guided management is associated with differential neurological outcomes, survival, and adverse events. Searches were carried out to 10 February 2022 in Medline (OvidSP), 11 February in EMBASE (OvidSP) and 8 February in Cochrane library. Randomized controlled trials comparing PbtO2 and ICP-guided management to ICP-guided management alone were included. The primary outcome was survival with favourable neurological outcome at 6-months post injury. Data were extracted by two independent authors and GRADE certainty of evidence assessed. There was no difference in the proportion of patients with favourable neurological outcomes with PbtO2-guided management (relative risk [RR] 1.42, 95% CI 0.97 to 2.08; p = 0.07; I2 = 0%, very low certainty evidence) but PbtO2-guided management was associated with reduced mortality (RR 0.54, 95% CI 0.31 to 0.93; p = 0.03; I2 = 42%; very low certainty evidence) and ICP (mean difference (MD) - 4.62, 95% CI - 8.27 to - 0.98; p = 0.01; I2 = 63%; very low certainty evidence). There was no significant difference in the risk of adverse respiratory or cardiovascular events. PbtO2-guided management in addition to ICP-based care was not significantly associated with increased favourable neurological outcomes, but was associated with increased survival and reduced ICP, with no difference in respiratory or cardiovascular adverse events. However, based on GRADE criteria, the certainty of evidence provided by this meta-analysis was consistently very low. MESH: Brain Ischemia; Intensive Care; Glasgow Outcome Scale; Randomized Controlled Trial; Craniocerebral Trauma.

Reversible global hypoperfusion in an adult patient with a mixed diabetic ketoacidosis/hyperglycemic hyperosmolar coma: A case report.

Diabetic ketoacidosis is a severe complication of diabetes mellitus. We report a case of global hypoperfusion in an elderly patient on CT, with complete resolution shown on early MRI follow-up. Metabolic causes have always to be included in the differential diagnosis of diffuse hypoperfusion in the appropriate clinical setting.