Brain dysfunction in sepsis: what can we learn from cerebral perfusion studies?

Investigations on the relationship between sepsis, brain dysfunction, and cerebral perfusion are methodologically very difficult to perform. It is important to interpret the results of such studies in view of our limited ability to diagnose and quantify brain dysfunction and to consider our limited understanding of the mechanisms that lead to or are associated with brain dysfunction in sepsis

Number of comorbidities and their impact on perioperative outcome and costs - a single centre cohort study

AIMS OF THE STUDY Multimorbidity is a growing global health problem, resulting in an increased perioperative risk for surgical patients. Data on both the prevalence of multimorbidity and its impact on perioperative outcome are limited. The American Society of Anesthesiologists (ASA) classification uses only the single most severe systemic disease to define the ASA class and ignores multimorbidity. This study aimed to assess the number and type of all anaesthesia-relevant comorbidities and to analyse their impact on outcome and hospital costs. METHODS This cohort study is nested in the ClassIntra® validation study and includes only patients enrolled at the University Hospital of Basel. Approximately 30 patients per surgical discipline undergoing any type of in-hospital surgery were followed up until hospital discharge to record all intra- and postoperative adverse events. In addition, the type and severity of all perioperatively relevant comorbidities were extracted from the electronic medical record according to a predefined list. The primary endpoint was the number of all anaesthesia-relevant comorbidities by ASA class. Using structural equation models, the direct and indirect effects of comorbidities on costs were estimated after adjustment for the ASA class and further relevant confounders and mediators. RESULTS Of 320 enrolled patients, 27 were ASA I (8%), 150 ASA II (47%), 116 ASA III (36%) and 27 ASA IV (8%). The median number of comorbidities per patient was 5 (range 0-18), this number significantly increasing with higher ASA class: 1 comorbidity (95% CI 0.0-2.0) in ASA I, 4 comorbidities (3.8-4.2) in ASA II, 9 (8.1-9.9) in ASA III and 12 (10-14) in ASA IV patients. Independent of ASA class, each additional comorbidity increased hospital costs by EUR 1,198 (95% CI 288-2108) with almost identical proportions of direct and indirect effects. The number of anaesthesia-relevant comorbidities also increased postoperative complications and postoperative length of hospital stay. CONCLUSIONS Multimorbidity in perioperative patients is highly prevalent and has a relevant impact on hospital costs, independent of the ASA class. Incorporating multimorbidity into the ASA classification might be warranted to improve its predictive ability and support adequate reimbursement

Independent External Validation of a Preoperative Prediction Model for Delirium After Cardiac Surgery: A Prospective Observational Cohort Study

Objective: This investigation provided independent external validation of an existing preoperative risk prediction model. Design: A prospective observational cohort study of patients undergoing cardiac surgery covering the period between April 16, 2018 and January 18, 2022. Setting: Two academic hospitals in Switzerland. Participants: Adult patients (≥60 years of age) who underwent elective cardiac surgery, including coronary artery bypass graft, mitral or aortic valve replacement or repair, and combined procedures. Interventions: None. Measurements and main results: The primary outcome measure was the incidence of postoperative delirium (POD) in the intensive or intermediate care unit, diagnosed using the Intensive Care Delirium Screening Checklist. The prediction model contained 4 preoperative risk factors to which the following points were assigned: Mini-Mental State Examination (MMSE) score ≤23 received 2 points; MMSE 24-27, Geriatric Depression Scale (GDS) >4, prior stroke and/or transient ischemic attack (TIA), and abnormal serum albumin (≤3.5 or ≥4.5 g/dL) received 1 point each. The missing data were handled using multiple imputation. In total, 348 patients were included in the study. Sixty patients (17.4%) developed POD. For point levels in the prediction model of 0, 1, 2, and ≥3, the cumulative incidence of POD was 12.6%, 22.8%, 25.8%, and 35%, respectively. The validation resulted in a pooled area under the receiver operating characteristics curve of 0.60 (median CI, 0.525-0.679). Conclusions: The evaluated predictive model for delirium after cardiac surgery in this patient cohort showed only poor discriminative capacity but fair calibration. Keywords: External validation; cardiac surgery; delirium; predictio

Cerebral perfusion in sepsis-associated delirium

INTRODUCTION: The pathophysiology of sepsis-associated delirium is not completely understood and the data on cerebral perfusion in sepsis are conflicting. We tested the hypothesis that cerebral perfusion and selected serum markers of inflammation and delirium differ in septic patients with and without sepsis-associated delirium. METHODS: We investigated 23 adult patients with sepsis, severe sepsis, or septic shock with an extracranial focus of infection and no history of intracranial pathology. Patients were investigated after stabilisation within 48 hours after admission to the intensive care unit. Sepsis-associated delirium was diagnosed using the confusion assessment method for the intensive care unit. Mean arterial pressure (MAP), blood flow velocity (FV) in the middle cerebral artery using transcranial Doppler, and cerebral tissue oxygenation using near-infrared spectroscopy were monitored for 1 hour. An index of cerebrovascular autoregulation was calculated from MAP and FV data. C-reactive protein (CRP), interleukin-6 (IL-6), S-100beta, and cortisol were measured during each data acquisition. RESULTS: Data from 16 patients, of whom 12 had sepsis-associated delirium, were analysed. There were no significant correlations or associations between MAP, cerebral blood FV, or tissue oxygenation and sepsis-associated delirium. However, we found a significant association between sepsis-associated delirium and disturbed autoregulation (P = 0.015). IL-6 did not differ between patients with and without sepsis-associated delirium, but we found a significant association between elevated CRP (P = 0.008), S-100beta (P = 0.029), and cortisol (P = 0.011) and sepsis-associated delirium. Elevated CRP was significantly correlated with disturbed autoregulation (Spearman rho = 0.62, P = 0.010). CONCLUSION: In this small group of patients, cerebral perfusion assessed with transcranial Doppler and near-infrared spectroscopy did not differ between patients with and without sepsis-associated delirium. However, the state of autoregulation differed between the two groups. This may be due to inflammation impeding cerebrovascular endothelial function. Further investigations defining the role of S-100beta and cortisol in the diagnosis of sepsis-associated delirium are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT00410111

Conversion between the Montreal Cognitive Assessment and the Mini-Mental Status Examination.

BACKGROUND Early and accurate detection of cognitive changes using simple tools is essential for an appropriate referral to a more detailed neurocognitive assessment and for the implementation of therapeutic strategies. The Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are two commonly used psychometric tests for cognitive screening. Both tests have different strengths and weaknesses. Preferences regarding test selection may therefore differ among clinicians. The aim of this retrospective observational cohort study was to define corresponding scores for the MMSE and the MoCA. METHODS We examined the relationship between the cognitive screening tests in 803 German-speaking Memory Clinic outpatients, encompassing a wide range of neurocognitive disorders. We produced a conversion table using the equipercentile equating method with log-linear smoothing. In addition, we conducted a systematic review of existing MMSE-MoCA conversions to create a table allowing for the conversion of MoCA scores into MMSE scores and vice versa using the weighted mean method. RESULTS The Memory Clinic sample showed that the prediction of MMSE to MoCA was overall less accurate compared to the conversion from MoCA to MMSE. The 19 studies included after thorough literature search showed that MoCA scores were consistently lower than MMSE scores. Eleven of 19 conversion studies had addressed the conversion of the MoCA to the MMSE, while two studies converted MMSE to MoCA scores. Another six studies applied bi-directional conversions. We provide an easy-to-use table covering the entire range of scores and taking into account all currently existing conversion formulas. CONCLUSION The comprehensive MMSE-MoCA conversion table enables a direct comparison of cognitive test scores at screening examinations and over the course of disease in patients with neurocognitive disorders

Influence of mild-moderate hypocapnia on intracranial pressure slow waves activity in TBI

Funder: University of CambridgeAbstract: Background: In traumatic brain injury (TBI) the patterns of intracranial pressure (ICP) waveforms may reflect pathological processes that ultimately lead to unfavorable outcome. In particular, ICP slow waves (sw) (0.005–0.05 Hz) magnitude and complexity have been shown to have positive association with favorable outcome. Mild-moderate hypocapnia is currently used for short periods to treat critical elevations in ICP. Our goals were to assess changes in the ICP sw activity occurring following sudden onset of mild-moderate hypocapnia and to examine the relationship between changes in ICP sw activity and other physiological variables during the hypocapnic challenge. Methods: ICP, arterial blood pressure (ABP), and bilateral middle cerebral artery blood flow velocity (FV), were prospectively collected in 29 adult severe TBI patients requiring ICP monitoring and mechanical ventilation in whom a minute volume ventilation increase (15–20% increase in respiratory minute volume) was performed as part of a clinical CO2-reactivity test. The time series were first treated using FFT filter (pass-band set to 0.005–0.05 Hz). Power spectral density analysis was performed. We calculated the following: mean value, standard deviation, variance and coefficient of variation in the time domain; total power and frequency centroid in the frequency domain; cerebrospinal compliance (Ci) and compensatory reserve index (RAP). Results: Hypocapnia led to a decrease in power and increase in frequency centroid and entropy of slow waves in ICP and FV (not ABP). In a multiple linear regression model, RAP at the baseline was the strongest predictor for the decrease in the power of ICP slow waves (p < 0.001). Conclusion: In severe TBI patients, a sudden mild-moderate hypocapnia induces a decrease in mean ICP and FV, but also in slow waves power of both signals. At the same time, it increases their higher frequency content and their morphological complexity. The difference in power of the ICP slow waves between the baseline and the hypocapnia period depends on the baseline cerebrospinal compensatory reserve as measured by RAP

Targeted temperature control following traumatic brain injury:ESICM/NACCS best practice consensus recommendations

Aims and scope: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. Methods: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. Results: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0–37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. Conclusions: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.</p

Targeted temperature control following traumatic brain injury:ESICM/NACCS best practice consensus recommendations

Aims and scope: The aim of this panel was to develop consensus recommendations on targeted temperature control (TTC) in patients with severe traumatic brain injury (TBI) and in patients with moderate TBI who deteriorate and require admission to the intensive care unit for intracranial pressure (ICP) management. Methods: A group of 18 international neuro-intensive care experts in the acute management of TBI participated in a modified Delphi process. An online anonymised survey based on a systematic literature review was completed ahead of the meeting, before the group convened to explore the level of consensus on TTC following TBI. Outputs from the meeting were combined into a further anonymous online survey round to finalise recommendations. Thresholds of ≥ 16 out of 18 panel members in agreement (≥ 88%) for strong consensus and ≥ 14 out of 18 (≥ 78%) for moderate consensus were prospectively set for all statements. Results: Strong consensus was reached on TTC being essential for high-quality TBI care. It was recommended that temperature should be monitored continuously, and that fever should be promptly identified and managed in patients perceived to be at risk of secondary brain injury. Controlled normothermia (36.0–37.5 °C) was strongly recommended as a therapeutic option to be considered in tier 1 and 2 of the Seattle International Severe Traumatic Brain Injury Consensus Conference ICP management protocol. Temperature control targets should be individualised based on the perceived risk of secondary brain injury and fever aetiology. Conclusions: Based on a modified Delphi expert consensus process, this report aims to inform on best practices for TTC delivery for patients following TBI, and to highlight areas of need for further research to improve clinical guidelines in this setting.</p

Cardiovascular imaging following perioperative myocardial infarction/injury

Patients developing perioperative myocardial infarction/injury (PMI) have a high mortality. PMI work-up and therapy remain poorly defined. This prospective multicenter study included high-risk patients undergoing major non-cardiac surgery within a systematic PMI screening and clinical response program. The frequency of cardiovascular imaging during PMI work-up and its yield for possible type 1 myocardial infarction (T1MI) was assessed. Automated PMI detection triggered evaluation by the treating physician/cardiologist, who determined selection/timing of cardiovascular imaging. T1M1 was considered with the presence of a new wall motion abnormality within 30 days in transthoracic echocardiography (TTE), a new scar or ischemia within 90 days in myocardial perfusion imaging (MPI), and Ambrose-Type II or complex lesions within 7 days of PMI in coronary angiography (CA). In patients with PMI, 21% (268/1269) underwent at least one cardiac imaging modality. TTE was used in 13% (163/1269), MPI in 3% (37/1269), and CA in 5% (68/1269). Cardiology consultation was associated with higher use of cardiovascular imaging (27% versus 13%). Signs indicative of T1MI were found in 8% of TTE, 46% of MPI, and 63% of CA. Most patients with PMI did not undergo any cardiovascular imaging within their PMI work-up. If performed, MPI and CA showed high yield for signs indicative of T1MI.Trial registration: https://clinicaltrials.gov/ct2/show/NCT02573532

Development of a quality indicator set to measure and improve quality of ICU care for patients with traumatic brain injury.

BACKGROUND: We aimed to develop a set of quality indicators for patients with traumatic brain injury (TBI) in intensive care units (ICUs) across Europe and to explore barriers and facilitators for implementation of these quality indicators. METHODS: A preliminary list of 66 quality indicators was developed, based on current guidelines, existing practice variation, and clinical expertise in TBI management at the ICU. Eight TBI experts of the Advisory Committee preselected the quality indicators during a first Delphi round. A larger Europe-wide expert panel was recruited for the next two Delphi rounds. Quality indicator definitions were evaluated on four criteria: validity (better performance on the indicator reflects better processes of care and leads to better patient outcome), feasibility (data are available or easy to obtain), discriminability (variability in clinical practice), and actionability (professionals can act based on the indicator). Experts scored indicators on a 5-point Likert scale delivered by an electronic survey tool. RESULTS: The expert panel consisted of 50 experts from 18 countries across Europe, mostly intensivists (N = 24, 48%) and neurosurgeons (N = 7, 14%). Experts agreed on a final set of 42 indicators to assess quality of ICU care: 17 structure indicators, 16 process indicators, and 9 outcome indicators. Experts are motivated to implement this finally proposed set (N = 49, 98%) and indicated routine measurement in registries (N = 41, 82%), benchmarking (N = 42, 84%), and quality improvement programs (N = 41, 82%) as future steps. Administrative burden was indicated as the most important barrier for implementation of the indicator set (N = 48, 98%). CONCLUSIONS: This Delphi consensus study gives insight in which quality indicators have the potential to improve quality of TBI care at European ICUs. The proposed quality indicator set is recommended to be used across Europe for registry purposes to gain insight in current ICU practices and outcomes of patients with TBI. This indicator set may become an important tool to support benchmarking and quality improvement programs for patients with TBI in the future