In critical care units, pupil examination is an important clinical parameter for patient monitoring. Current practice is to use a penlight to observe the pupillary light reflex. The result seems to ...be a subjective measurement, with low precision and reproducibility. Several quantitative pupillometer devices are now available, although their use is primarily restricted to the research setting. To assess whether adoption of these technologies would benefit the clinic, we compared automated quantitative pupillometry with the standard clinical pupillary examination currently used for brain-injured patients.
In order to determine inter-observer agreement of the device, we performed repetitive measurements in 200 healthy volunteers ranging in age from 21 to 58 years, providing a total of 400 paired (alternative right eye, left eye) measurements under a wide variety of ambient light condition with NeuroLight Algiscan pupillometer. During another period, we conducted a prospective, observational, double-blinded study in two neurocritical care units. Patients admitted to these units after an acute brain injury were included. Initially, nursing staff measured pupil size, anisocoria and pupillary light reflex. A blinded physician subsequently performed measurement using an automated pupillometer.
In 200 healthy volunteers, intra-class correlation coefficient for maximum resting pupil size was 0.95 (IC: 0.93-0.97) and for minimum pupil size after light stimulation 0.87 (0.83-0.89). We found only 3-pupil asymmetry (≥ 1 mm) in these volunteers (1.5% of the population) with a clear pupil asymmetry during clinical inspection. The mean pupil light reactivity was 40 ± 7%. In 59 patients, 406 pupillary measurements were prospectively performed. Concordance between measurements for pupil size collected using the pupillometer, versus subjective assessment, was poor (Spearmen's rho = 0.75, IC: 0.70-0.79; P < 0.001). Nursing staff failed to diagnose half of the cases (15/30) of anisocoria detected using the pupillometer device. A global rate of discordance of 18% (72/406) was found between the two techniques when assessing the pupillary light reflex. For measurements with small pupils (diameters <2 mm) the error rate was 39% (24/61).
Standard practice in pupillary monitoring yields inaccurate data. Automated quantitative pupillometry is a more reliable method with which to collect pupillary measurements at the bedside.
BACKGROUND:In the Protective Ventilation in Cardiac Surgery (PROVECS) randomized, controlled trial, an open-lung ventilation strategy did not improve postoperative respiratory outcomes after on-pump ...cardiac surgery. In this prespecified subanalysis, the authors aimed to assess the regional distribution of ventilation and plasma biomarkers of lung epithelial and endothelial injury produced by that strategy.
METHODS:Perioperative open-lung ventilation consisted of recruitment maneuvers, positive end-expiratory pressure (PEEP) = 8 cm H2O, and low-tidal volume ventilation including during cardiopulmonary bypass. Control ventilation strategy was a low-PEEP (2 cm H2O) low-tidal volume approach. Electrical impedance tomography was used serially throughout the perioperative period (n = 56) to compute the dorsal fraction of ventilation (defined as the ratio of dorsal tidal impedance variation to global tidal impedance variation). Lung injury was assessed serially using biomarkers of epithelial (soluble form of the receptor for advanced glycation end-products, sRAGE) and endothelial (angiopoietin-2) lung injury (n = 30).
RESULTS:Eighty-six patients (age = 64 ± 12 yr; EuroSCORE II = 1.65 ± 1.57%) undergoing elective on-pump cardiac surgery were studied. Induction of general anesthesia was associated with ventral redistribution of tidal volumes and higher dorsal fraction of ventilation in the open-lung than the control strategy (0.38 ± 0.07 vs. 0.30 ± 0.10; P = 0.004). No effect of the open-lung strategy on the dorsal fraction of ventilation was noted at the end of surgery after median sternotomy closure (open-lung = 0.37 ± 0.09 vs. control = 0.34 ± 0.11; P = 0.743) or in extubated patients at postoperative day 2 (open-lung = 0.63 ± 0.18 vs. control = 0.59 ± 0.11; P > 0.999). Open-lung ventilation was associated with increased intraoperative plasma sRAGE (7,677 ± 3,097 pg/ml vs. 6,125 ± 1,400 pg/ml; P = 0.037) and had no effect on angiopoietin-2 (P > 0.999).
CONCLUSIONS:In cardiac surgery patients, open-lung ventilation provided larger dorsal lung ventilation early during surgery without a maintained benefit as compared with controls at the end of surgery and postoperative day 2 and was associated with higher intraoperative plasma concentration of sRAGE suggesting lung overdistension.
Dynamic action of anesthetic agents was compared at cortical and subcortical levels during induction of anesthesia. Unconsciousness involved the cortical brain but suppression of movement in response ...to noxious stimuli was mediated through subcortical structures.
Twenty-five patients with Parkinson disease, previously implanted with a deep-brain stimulation electrode, were enrolled during the implantation of the definitive pulse generator. During induction of anesthesia with propofol (n = 13) or sevoflurane (n = 12) alone, cortical (EEG) and subcortical (ESCoG) electrogenesis were obtained, respectively, from a frontal montage (F3-C3) and through the deep-brain electrode (p0-p3). In EEG and ESCoG spectral analysis, spectral edge (90%) frequency, median power frequency, and nonlinear analysis dimensional activation calculations were determined.
Sevoflurane and propofol decreased EEG and ESCoG activity in a dose-related fashion. EEG values decreased dramatically at loss of consciousness, whereas there was little change in ESCoG values. Quantitative parameters derived from EEG but not from ESCoG were able to predict consciousness versus unconsciousness. Conversely, quantitative parameters derived from ESCoG but not from EEG were able to predict movement in response to laryngoscopy.
These data suggest that in humans, unconsciousness mainly involves the cortical brain, but that suppression of movement in response to noxious stimuli is mediated through the effect of anesthetic agents on subcortical structures.
Several lipid metabolites in cerebrospinal fluid are correlated with poor outcomes in aneurysmal subarachnoid haemorrhage. Most of these metabolites bind to ubiquitous thromboxane-prostaglandin (TP) ...receptors, causing vasoconstriction and inflammation. Here, we evaluated terutroban (TBN), a specific TP receptor antagonist, for the prevention of post-haemorrhage blood-brain barrier disruption, neuronal apoptosis and delayed cerebral hypoperfusion.
The rat double subarachnoid haemorrhage model was produced by twice injecting (days 1 and 2) autologous blood into the cisterna magna. Seventy-eight male Sprague-Dawley rats were assigned to experimental groups. Rats exposed to subarachnoid haemorrhage were allocated to no treatment (SAH group) or TBN treatment by gastric gavage during the first 5 days after haemorrhage (SAH+TBN group). Control rats received artificial cerebrospinal fluid injections (CSF group). Sham-operated rats with or without TBN administration were also studied. Body weight and Garcia neurological scores were assessed on day 2 and day 5. We used nanoscale single-photon emission computed tomography (nanoSPECT) to measure brain uptake of three radiolabelled agents:
Technetium-diethylenetriaminepentacetate (
Tc-DTPA), which indicated blood-brain barrier permeability on day 3,
Technetium-annexin V-128 (
Tc-Anx-V128), which indicated apoptosis on day 4, and
Technetium-hexamethylpropyleneamineoxime (
Tc-HMPAO), which indicated cerebral perfusion on day 5. Basilar artery narrowing was verified histologically, and cerebral TP receptor agonists were quantified.
Tc-DTPA uptake unveiled blood-brain barrier disruption in the SAH group. TBN mitigated this disruption in the brainstem area.
Tc-Anx-V128 uptake was increased in the SAH group and TBN diminished this effect in the cerebellum.
Tc-HMPAO uptake revealed a global decreased perfusion on day 5 in the SAH group that was significantly counteracted by TBN. TBN also mitigated basilar artery vasoconstriction, neurological deficits (on day 2), body weight loss (on day 5) and cerebral production of vasoconstrictors such as Thromboxane B2 and Prostaglandin F2α.
Based on in vivo nanoscale imaging, we demonstrated that TBN protected against blood-brain barrier disruption, exerted an anti-apoptotic effect and improved cerebral perfusion. Thus, TP receptor antagonists showed promising results in treating post-haemorrhage neurovascular events.
Purpose
To evaluate whether a perioperative open-lung ventilation strategy prevents postoperative pulmonary complications after elective on-pump cardiac surgery.
Methods
In a pragmatic, randomized, ...multicenter, controlled trial, we assigned patients planned for on-pump cardiac surgery to either a conventional ventilation strategy with no ventilation during cardiopulmonary bypass (CPB) and lower perioperative positive end-expiratory pressure (PEEP) levels (2 cm H
2
O) or an open-lung ventilation strategy that included maintaining ventilation during CPB along with perioperative recruitment maneuvers and higher PEEP levels (8 cm H
2
O). All study patients were ventilated with low-tidal volumes before and after CPB (6 to 8 ml/kg of predicted body weight). The primary end point was a composite of pulmonary complications occurring within the first 7 postoperative days.
Results
Among 493 randomized patients, 488 completed the study (mean age, 65.7 years; 360 (73.7%) men; 230 (47.1%) underwent isolated valve surgery). Postoperative pulmonary complications occurred in 133 of 243 patients (54.7%) assigned to open-lung ventilation and in 145 of 245 patients (59.2%) assigned to conventional ventilation (
p
= 0.32). Open-lung ventilation did not significantly reduce the use of high-flow nasal oxygenotherapy (8.6% vs 9.4%;
p
= 0.77), non-invasive ventilation (13.2% vs 15.5%;
p
= 0.46) or new invasive mechanical ventilation (0.8% vs 2.4%,
p
= 0.28). Mean alive ICU-free days at postoperative day 7 was 4.4 ± 1.3 days in the open-lung group vs 4.3 ± 1.3 days in the conventional group (mean difference, 0.1 ± 0.1 day,
p
= 0.51). Extra-pulmonary complications and adverse events did not significantly differ between groups.
Conclusions
A perioperative open-lung ventilation including ventilation during CPB does not reduce the incidence of postoperative pulmonary complications as compared with usual care. This finding does not support the use of such a strategy in patients undergoing on-pump cardiac surgery.
Trial registration
Clinicaltrials.gov Identifier: NCT 02866578.
https://clinicaltrials.gov/ct2/show/NCT02866578
Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) is a major cause of complications and death. Here, we set out to identify high-performance predictive biomarkers of ...DCI and its underlying metabolic disruptions using metabolomics and lipidomics approaches. This single-center prospective observational study enrolled 61 consecutive patients with severe aSAH; among them, 22 experienced a DCI. Nine patients without aSAH were included as validation controls. Blood and cerebrospinal fluid (CSF) were sampled within the first 24 h after admission. We identified a panel of 20 metabolites that, together, showed high predictive performance for DCI. This panel of metabolites included lactate, cotinine, salicylate, 6 phosphatidylcholines, and 4 sphingomyelins. The interplay of the metabolome and the lipidome found between CSF and plasma in our patients underscores that aSAH and its associated DCI complications can extend beyond cerebral implications, with a peripheral dimension as well. As an illustration, early biological disruptions that might explain the subsequent DCI found systemic hypoxia driven mainly by higher blood lactate, arginine, and proline metabolism likely associated with vascular NO and disrupted ceramide/sphingolipid metabolism. We conclude that targeting early peripheral hypoxia preceding DCI could provide an interesting strategy for the prevention of vascular dysfunction.
Background and objectives
Pneumococcal meningitis is a devastating disease that requires adequate meningeal antibiotic penetration to limit the mortality. Despite a large usage in this indication, ...data about CSF concentration of cefotaxime during pneumococcal meningitis in adults are scarce. Therefore, we aimed to describe the CSF concentration obtained after high-dose cefotaxime administration in adult patients treated for Streptococcus pneumoniae meningitis.
Patients and methods
In this multicentre, observational, retrospective study, cases of adult patients with S. pneumoniae meningitis hospitalized between January 2013 and October 2019 for whom cefotaxime concentration was measured in CSF were reviewed.
Results
Cefotaxime concentration was analysed in 44 CSF samples collected among 31 patients. Median (IQR) age was 61 years (52–69). Dexamethasone was administered in 27 subjects. Median (IQR) cefotaxime daily dosage was 15 g (12–19), corresponding to 200 mg/kg (150–280). CSF samples were collected approximately 5 days after cefotaxime initiation. Median (IQR, range) cefotaxime CSF concentration was 10.3 mg/L (4.8–19.3, 1.2–43.4). Median (range) MIC for Streptococcus pneumoniae was 0.25 mg/L (0.008–1) (n = 22). The median (IQR, range) CSF/MIC ratio was 38 (12–146, 4–1844). Twenty-five CSF concentrations (81%) were above 10 times the MIC. Cefotaxime was discontinued in two patients for toxicity. In-hospital mortality rate was 29%.
Conclusions
Adult patients with pneumococcal meningitis treated with a high dose of cefotaxime (200 mg/kg/day) had elevated CSF concentrations with satisfying pharmacokinetics/pharmacodynamics parameters and tolerability profile. This study brings reassuring pharmacological data regarding the use of high-dose cefotaxime monotherapy for treating pneumococcal meningitis with susceptible strains to cefotaxime.
In the Protective Ventilation in Cardiac Surgery (PROVECS) randomized, controlled trial, an open-lung ventilation strategy did not improve postoperative respiratory outcomes after on-pump cardiac ...surgery. In this prespecified subanalysis, the authors aimed to assess the regional distribution of ventilation and plasma biomarkers of lung epithelial and endothelial injury produced by that strategy.
Perioperative open-lung ventilation consisted of recruitment maneuvers, positive end-expiratory pressure (PEEP) = 8 cm H2O, and low-tidal volume ventilation including during cardiopulmonary bypass. Control ventilation strategy was a low-PEEP (2 cm H2O) low-tidal volume approach. Electrical impedance tomography was used serially throughout the perioperative period (n = 56) to compute the dorsal fraction of ventilation (defined as the ratio of dorsal tidal impedance variation to global tidal impedance variation). Lung injury was assessed serially using biomarkers of epithelial (soluble form of the receptor for advanced glycation end-products, sRAGE) and endothelial (angiopoietin-2) lung injury (n = 30).
Eighty-six patients (age = 64 ± 12 yr; EuroSCORE II = 1.65 ± 1.57%) undergoing elective on-pump cardiac surgery were studied. Induction of general anesthesia was associated with ventral redistribution of tidal volumes and higher dorsal fraction of ventilation in the open-lung than the control strategy (0.38 ± 0.07 vs. 0.30 ± 0.10; P = 0.004). No effect of the open-lung strategy on the dorsal fraction of ventilation was noted at the end of surgery after median sternotomy closure (open-lung = 0.37 ± 0.09 vs. control = 0.34 ± 0.11; P = 0.743) or in extubated patients at postoperative day 2 (open-lung = 0.63 ± 0.18 vs. control = 0.59 ± 0.11; P > 0.999). Open-lung ventilation was associated with increased intraoperative plasma sRAGE (7,677 ± 3,097 pg/ml vs. 6,125 ± 1,400 pg/ml; P = 0.037) and had no effect on angiopoietin-2 (P > 0.999).
In cardiac surgery patients, open-lung ventilation provided larger dorsal lung ventilation early during surgery without a maintained benefit as compared with controls at the end of surgery and postoperative day 2 and was associated with higher intraoperative plasma concentration of sRAGE suggesting lung overdistension.
BACKGROUNDMany aspects of the perioperative management of aneurysmal subarachnoid haemorrhage (SAH) remain controversial. It would be useful to assess differences in the treatment of SAH in Europe to ...identify areas for improvement.
OBJECTIVETo determine the clinical practice of physicians treating SAH and to evaluate any discrepancy between practice and published evidence.
DESIGNAn electronic survey.
PARTICIPANTSPhysicians identified through each national society of neuroanaesthesiology and neurocritical care.
INTERVENTIONSA 31-item online questionnaire was distributed by the ENIG group. Questions were designed to investigate anaesthetic management of SAH and diagnostic and treatment approaches to cerebral vasospasm. The survey was available from early October to the end of November 2012.
RESULTSCompleted surveys were received from 268 respondents, of whom 81% replied that aneurysm treatment was conducted early (within 24 h). Sixty-five percent of centres treated more than 60% of SAH by coiling, 19% had high-volume clipping (>60% of aneurysms clipped) and 16% used both methods equally. No clear threshold for arterial blood pressure target was identified during coiling, temporary clipping or in patients without vasospasm after the aneurysm had been secured. Almost all respondents used nimodipine (97%); 21% also used statins and 20% used magnesium for prevention of vasospasm. A quarter of respondents used intra-arterial vasodilators alone, 5% used cerebral angioplasty alone and 48% used both endovascular methods to treat symptomatic vasospasm. In high-volume clipping treatment centres, 58% of respondents used endovascular methods to manage vasospasm compared with 86% at high-volume coiling treatment centres (P < 0.001). The most commonly used intra-arterial vasodilator was nimodipine (82%), but milrinone was used by 23% and papaverine by 19%. More respondents (44%) selected ‘triple-H’ therapy over hypertension alone (30%) to treat vasospasm.
CONCLUSIONWe found striking variability in the practice patterns of European physicians involved in early treatment of SAH. Significant differences were noted among countries and between high and low-volume coiling centres.
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