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

Near-Infrared Spectroscopy can Monitor Dynamic Cerebral Autoregulation in Adults

Objective: To study the correlation between a dynamic index of cerebral autoregulation assessed with blood flow velocity (FV) using transcranial Doppler, and a tissue oxygenation index (TOI) recorded with near-infrared spectroscopy (NIRS). Methods: Twenty-three patients with sepsis, severe sepsis, or septic shock were monitored daily on up to four consecutive days. FV, TOI, and mean arterial blood pressure (ABP) were recorded for 60min every day. An index of autoregulation (Mx) was calculated as the moving correlation coefficient between 10-s averaged values of FV and ABP over moving 5min time-windows. The index Tox was evaluated as the correlation coefficient between TOI and ABP in the same way. The indices Mx and Tox, ABP and arterial partial pressure of CO2 were averaged for each patient. Results: Synchronized slow waves, presenting with periods from 20s to 2min, were seen in the TOI and FV of most patients, with a reasonable coherence between the signals in this bandwidth (coherence >0.5). The indices, Mx and Tox, demonstrated good correlation with each other (R=0.81; P<0.0001) in the whole group of patients. Both indices showed a significant (P<0.05) tendency to indicate weaker autoregulation in the state of vasodilatation associated with greater values of arterial partial pressure of CO2 or lower values of ABP. Conclusion: NIRS shows promise for the continuous assessment of cerebral autoregulation in adult

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

Sustained moderate reductions in arterial CO2 after brain trauma Time-course of cerebral blood flow velocity and intracranial pressure

Objective: In healthy volunteers cerebral blood flow starts to recover towards baseline within a few minutes of continued hyperventilation due to normalisation of perivascular pH. We investigated the time-course of changes in middle cerebral artery mean flow velocity (FVm) and intracranial pressure (ICP) in head-injured patients during sustained moderate reductions in arterial partial pressure of CO2 (PaCO2). Design: Observational study. Patients: Twenty-seven sedated, mechanically ventilated patients with severe head injury. Interventions: Measurements were made during and after routine determination of CO2-reactivity: an acute 20% increase in respiratory minute volume was followed by a 10-min stabilisation period and 50min of continued moderate hyperventilation at a constant PaCO2 (>3.5kPa). Measurements and results: FVm was monitored with transcranial Doppler, ICP was monitored with intraparenchymal probes. During the 50-min period with stable PaCO2 FVm increased in 36% of patients. All other patients showed a decline in FVm over the same time period. Overall FVm recovery was −0.03±0.14%·min-1. The time-course of ICP changes was significantly different from that of FVm, with ICP reaching its lowest value earlier than FVm (23±12 vs 37±20min; P = 0.001) and returning more rapidly towards baseline than FVm (0.23±0.23 vs −0.03±0.14%·min-1; P< 0.0001). Conclusions: Head-injured patients may adapt differently to hyperventilation than healthy volunteers. Potentially harmful reductions in cerebral blood flow may persist beyond the duration of useful ICP reductio

Succinylcholine versus rocuronium for rapid sequence intubation in intensive care: a prospective, randomized controlled trial

Succinylcholine and rocuronium are widely used to facilitate rapid sequence induction (RSI) intubation in intensive care. Concerns relate to the side effects of succinylcholine and to slower onset and inferior intubation conditions associated with rocuronium. So far, succinylcholine and rocuronium have not been compared in an adequately powered randomized trial in intensive care. Accordingly, the aim of the present study was to compare the incidence of hypoxemia after rocuronium or succinylcholine in critically ill patients requiring an emergent RSI

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