Stein Silva

WAKEFULNESS AND LOSS OF AWARENESS: BRAIN AND BRAINSTEM INTERACTION IN THE VEGETATIVE STATE

Objective: The ascending reticular activating system (ARAS) modulates circadian wakefulness, which is preserved in a persistent vegetative state (PVS). Its metabolism is preserved. Impairment of metabolism in the polymodal associative cortices (i.e., precuneus) is characteristic of PVS where awareness is abolished. Because the interaction of these 2 structures allows conscious sensory perception, our hypothesis was that an impaired functional connectivity between them participates in the loss of conscious perception. Methods: 15O-radiolabeled water PET measurement of regional cerebral blood flow (rCBF) was performed at rest and during a proprioceptive stimulation. Ten patients in PVS and 10 controls were compared in a cross-sectional study. The functional connectivity from the primary sensorimotor cortex (S1M1) and the ARAS in both groups was also investigated. Results: Compared with controls, patients showed significantly less rCBF in posterior medial cortices (precuneus) and higher rCBF in ARAS at rest. During stimulation, bilateral Brodmann area 40 was less activated and not functionally correlated to S1M1 in PVS as it was in controls. Precuneus showed a lesser degree of deactivation in patients. Finally, ARAS whose activity was functionally correlated to that of the precuneus in controls was not in PVS. Conclusions: Global neuronal workspace theory predicts that damage to long-distance white matter tracts should impair access to conscious perception. During persistent vegetative state, we identified a hypermetabolism in the ascending reticular activating system (ARAS) and impaired functional connectivity between the ARAS and the precuneus. This result emphasizes the functional link between cortices and brainstem in the genesis of perceptual awareness and strengthens the hypothesis that consciousness is based on a widespread neural network.

Predicting preload responsiveness using simultaneous recordings of inferior and superior vena cavae diameters

IntroductionEchocardiographic indices based on respiratory variations of superior and inferior vena cavae diameters (ΔSVC and ΔIVC, respectively) have been proposed as predictors of fluid responsiveness in mechanically ventilated patients, but they have never been compared simultaneously in the same patient sample. The aim of this study was to compare the predictive value of these echocardiographic indices when concomitantly recorded in mechanically ventilated septic patients.MethodsSeptic shock patients requiring hemodynamic monitoring were prospectively enrolled over a 1-year period in a mixed medical surgical ICU of a university teaching hospital (Toulouse, France). All patients were mechanically ventilated. Predictive indices were obtained by transesophageal and transthoracic echocardiography and were calculated as follows: (Dmax - Dmin)/Dmax for ΔSVC and (Dmax - Dmin)/Dmin for ΔIVC, where Dmax and Dmin are the maximal and minimal diameters of SVC and IVC. Measurements were performed at baseline and after a 7-ml/kg volume expansion using a plasma expander. Patients were separated into responders (increase in cardiac index ≥15%) and nonresponders (increase in cardiac index <15%).ResultsAmong 44 included patients, 26 (59%) patients were responders (R). ΔSVC was significantly more accurate than ΔIVC in predicting fluid responsiveness. The areas under the receiver operating characteristic curves for ΔSVC and ΔIVC regarding assessment of fluid responsiveness were significantly different (0.74 (95% confidence interval (CI): 0.59 to 0.88) and 0.43 (95% CI: 0.25 to 0.61), respectively (P = 0.012)). No significant correlation between ΔSVC and ΔIVC was found (r = 0.005, P = 0.98). The best threshold values for discriminating R from NR was 29% for ΔSVC, with 54% sensitivity and 89% specificity, and 21% for ΔIVC, with 38% sensitivity and 61% specificity.ConclusionsΔSVC was better than ΔIVC in predicting fluid responsiveness in our cohort. It is worth noting that the sensitivity and specificity values of ΔSVC and ΔIVC for predicting fluid responsiveness were lower than those reported in the literature, highlighting the limits of using these indices in a heterogeneous sample of medical and surgical septic patients.

Comparison of esCCO and transthoracic echocardiography for non-invasive measurement of cardiac output intensive care

BACKGROUND The esCCO monitor (ECG- estimated Continuous Cardiac Output, Nihon Kohden(®)) is a new non-invasive tool for estimating cardiac output (CO). It derives CO from the pulse wave transit time (PWTT) estimated by the ECG and the plethysmographic wave. An initial calibration is needed to refine the relation linking pulse pressure (measured by arterial pressure cuff) to PWTT. To assess the accuracy and reliability of the esCCO system, we performed an analysis of agreement of CO values obtained by transthoracic echocardiography (TTE). METHODS Thirty-eight intensive care unit patients were prospectively included. CO was determined simultaneously using esCCO (CO(esCCO)) and TTE (CO(TTE)) as our reference method. RESULTS A total of 103 paired readings from 38 patients were collected. The correlation coefficient between CO(esCCO) and CO(TTE) was 0.61 (P<0.001). The Bland and Altman analysis corrected for repeated measures showed a bias of -1.6 litre min(-1) and limits of agreement from -4.7 to +1.5 litre min(-1), with a percentage error (2 sd/mean CO) of 49%. The correlation for CO changes was significant (R=0.63, P<0.001), but the concordance rate was poor (73%). Polar plot analysis showed an angular bias of -9° with radial limits of agreement from -54° to +36°. The bias appeared to correlate with systemic vascular resistance (R=-0.45, P<0.001). CONCLUSIONS In critically ill patients, the performance of the esCCO monitor was not clinically acceptable, and this monitor cannot be recommended in this setting. Moreover, the esCCO failed to trend CO data reliably.

Disruption of posteromedial large-scale neural communication predicts recovery from coma

Objective: We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks. Methods: We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 ± 2 days after withdrawal of sedation. Analysis of resting-state fMRI connectivity involved a hypothesis-driven, region of interest–based strategy. We assessed patient outcome after 3 months using the Coma Recovery Scale–Revised (CRS-R). Results: Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, globally notwithstanding etiology. The functional connectivity strength between PCC and medial prefrontal cortex (mPFC) was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury (Kruskal-Wallis test, p < 0.001; linear regression between CRS-R and PCC-mPFC activity coupling at rest, Spearman ρ = 0.93, p < 0.003). Conclusion: In both etiology groups (traumatic and anoxic), changes in the connectivity of PCC-centered, spontaneously synchronized, large-scale networks account for the loss of external and internal self-centered awareness observed during coma. Sparing of functional connectivity between PCC and mPFC may predict patient outcome, and further studies are needed to substantiate this potential prognosis biomarker.

The efficacy of skin temperature for block assessment after infraclavicular brachial plexus block.

BACKGROUND: Although it has been reported that an increase in skin temperature indicates block success with higher specificity and sensibility than skin sensitivity to pinprick and cold, the methodology previously used computer-assisted infrared thermography, a technique that is expensive and requires substantial personnel training. In this prospective observational study, we evaluated whether a simple infrared thermometer can reliably predict block effectiveness after infraclavicular brachial plexus blockade. METHODS: Thirty consecutive patients undergoing upper limb surgery under infraclavicular block were enrolled. From the end of the local anesthetic injection, skin temperature was measured in all four major nerve distribution areas, and the sensory block onset (using cold and pinprick with 0 = no sensation to 2 = normal) were evaluated every 5 min for 30 min. A successful block was defined as the absence of sensation to cold (swab soaked with alcohol) and pinprick (needle) with a score of “0” within 30 min after the injection in the 4 major nerve distribution areas (radial, ulnar, median and musculocutaneous). Skin temperature measurements were performed using a noncontact temperature probe. RESULTS: One-hundred-twenty nerves (30 patients, 4 nerves per patient) were anesthetized. Twenty-five patients had a successful block. Four patients required supplementation for block failure. General anesthesia was performed in one patient. Skin temperature variation was not different among different nerves. There was a statistically significant increase in cutaneous temperature after nerve block compared to the same skin area before the procedure (P < 0.0001 from T5 to T30). Average temperature variations in blocked versus unblocked nerves at the same time were significantly different (P < 0.05 at T5 then P < 0.0001 from T10 to T30). When temperature in a specific sensory territory increased 1°C or more, at 5 and 10 min, the specific nerve was blocked (the score was “0”). Thus, when temperature changes in all 4 nerves were noted at 5 and 10 min, the block was successful at 30 min. No change in temperature in the contralateral arm or in the core temperature was observed. CONCLUSION: Skin temperature assessment with an infrared thermometer is a reliable, simple and early indicator of a successful nerve block.

Impaired visual hand recognition in preoperative patients during brachial plexus anesthesia: importance of peripheral neural input for mental representation of the hand.

Background: Perceptual illusions described in healthy subjects undergoing regional anesthesia (RA) are probably related to short-term plastic brain changes. We addressed whether performance on an implicit mental rotation task reflects these RA-induced changes in body schema brain representations. Studying these changes in healthy volunteers may shed light on normal function and the central mechanisms of pain. Methods: Performance pattern was studied in upper limb–anesthetized subjects on a left/right hand judgment task, which is known to involve motor imagery processes relating to hand posture. Three conditions were used: control (i.e., absence of deafferentation), RA (i.e., deafferentation), and vision (i.e., deafferentated limb exposed to view). To limit potential bias such as order effect, the control state was recorded in a randomized manner. Results: All subjects described perceptual illusions of their anesthetized limb. They were slower and less accurate on the task during RA compared with control. Response patterns were similar in all conditions, suggesting sensitivity of performance to arm/hand biomechanical constraints. Vision was associated with an increase in the proportion of correct responses and a reduction of the response times in hand judgment and was accompanied by disappearance of the lateralization of the underlying mental representations, which was identified during RA. Conclusions: These results suggest the following: (1) the right/left judgment task involves mental simulation of hand movements, (2) underlying mental representations and their neural substrates are subject to acute alterations after RA, and (3) the proprioceptive deficit induced by RA is influenced by the subjects ability to see the anesthetized limb.

Doppler renal resistive index for early detection of acute kidney injury after major orthopaedic surgery: a prospective observational study.

BACKGROUND Postoperative acute kidney injury (AKI) is a cause of morbidity and mortality. Its diagnosis requires better markers than variations in diuresis or postoperative serum creatinine. OBJECTIVES The aim of this study was to evaluate the accuracy of Doppler renal resistive index for early detection of AKI after hip or knee arthroplasty. DESIGN A prospective observational study. SETTING A single-centre study in a university hospital. PATIENTS Fifty men and women older than 65 years, requiring hip or knee replacement with at least two perioperative AKI risk factors, including diabetes, arteritis, chronic heart or renal dysfunction, and prescription of angiotensin-converting enzyme (ACE) inhibitors. Exclusion criteria were poor abdominal echogenicity, arrhythmia, respiratory failure or agitation. INTERVENTION Renal resistive index was measured preoperatively and in the postanaesthesia care unit. RESULTS Sixteen patients presented with AKI in the postoperative period. Resistive index was increased in this group in both the preoperative [0.72 (0.69 to 0.73) vs. 0.66 (0.58 to 0.71); P = 0.01] and postoperative periods [0.75 (0.71 to 0.75) vs. 0.67 (0.62 to 0.72); P = 0.0001]. Resistive index evaluated by ROC curves and AUC to detect AKI was 0.862 [95% confidence interval (95% CI) 0.735 to 0.943]. The most accurate cut-off value was a postoperative resistive index of 0.705 (sensitivity = 94%, specificity = 71%, LR+ = 3.19 and LR– = 0.09). The grey area between 0.705 and 0.73, corresponding to the inconclusive zone, included 26% (13/50) of all the patients. CONCLUSION Postoperative resistive index appears to be effective for early detection of AKI after major orthopaedic surgery. Resistive index can be measured in the postoperative care unit in patients at risk of AKI. TRIAL REGISTRATION NUMBER 29-0512.

Practices of end-of-life decisions in 66 southern French ICUs 4 years after an official legal framework: A 1-day audit

OBJECTIVE Since the implementation of two French laws in 2002 and 2005 and the implementation of guidelines about End-of-Life (EoL) decisions, few studies concerning EoL practices in French intensive care units (ICUs) have been reported. This study was aimed at assessing compliance with recommendations and current legislation concerning EoL decisions. METHOD Prospective observational study based on 1-day audit conducted from January to May 2009 in 66 southern French ICUs. RESULTS Six hundred and twenty-five patients were included (median age: 63 [52-76] years, median SAPS II: 46 [34-58]). The written designation of a surrogate decision-maker was reported for 87 (15%) patients. Advance directives were completed for only 4% of patients. The EoL decision-making process consisted in a multidisciplinary approach for 99 (47%) patients and was recorded in the medical chart for 63 (64%) cases. Families were informed about medical decisions in 58% of cases. This proportion was higher (87%) if a decision to forego life-sustaining therapy was made. EoL decisions consisted of withholding treatments for 72 (94%) patients and withdrawal of treatments for 5 (6%) patients. In the multivariate stepwise logistic regression, four variables were independently associated with a decision to forego life support: preexisting dependence on others (P<0.0001), advance directives (P=0.01), age (P=0.008) and the SAPS 2 score (P=0.009). CONCLUSION The major finding of the present study is the existence of a gap between the widely approved EoL recommendations made by scientific societies and the daily practice of southern French ICUs. Even if EoL decisions are mostly shared with relatives, their written documentation in medical charts remains insufficient. Concerning EoL practices, the withdrawal of treatment remains an uncommon decision.

Combined Thoracic Ultrasound Assessment during a Successful Weaning Trial Predicts Postextubation Distress

Background: Recent studies suggest that isolated sonographic assessment of the respiratory, cardiac, or neuromuscular functions in mechanically ventilated patients may assist in identifying patients at risk of postextubation distress. The aim of the present study was to prospectively investigate the value of an integrated thoracic ultrasound evaluation, encompassing bedside respiratory, cardiac, and diaphragm sonographic data in predicting postextubation distress. Methods: Longitudinal ultrasound data from 136 patients who were extubated after passing a trial of pressure support ventilation were measured immediately after the start and at the end of this trial. In case of postextubation distress (31 of 136 patients), an additional combined ultrasound assessment was performed while the patient was still in acute respiratory failure. We applied machine-learning methods to improve the accuracy of the related predictive assessments. Results: Overall, integrated thoracic ultrasound models accurately predict postextubation distress when applied to thoracic ultrasound data immediately recorded before the start and at the end of the trial of pressure support ventilation (learning sample area under the curve: start, 0.921; end, 0.951; test sample area under the curve: start, 0.972; end, 0.920). Among integrated thoracic ultrasound data, the recognition of lung interstitial edema and the increased telediastolic left ventricular pressure were the most relevant predictive factors. In addition, the use of thoracic ultrasound appeared to be highly accurate in identifying the causes of postextubation distress. Conclusions: The decision to attempt extubation could be significantly assisted by an integrative, dynamic, and fully bedside ultrasonographic assessment of cardiac, lung, and diaphragm functions.

Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study

BACKGROUND Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome. METHODS This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954. FINDINGS Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91-0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9-91·6) and a positive predictive value of 100% (90·0-100), with 89·7% sensitivity (75·8-97·1) and 100% specificity (69·1-100) for the prediction of unfavourable outcome. INTERPRETATION In patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI. FUNDING French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.