Ari Ercole

Modelling the impact of an influenza A/H1N1 pandemic on critical care demand from early pathogenicity data: the case for sentinel reporting

Projected critical care demand for pandemic influenza H1N1 in England was estimated in this study. The effect of varying hospital admission rates under statistical uncertainty was examined. Early in a pandemic, uncertainty in epidemiological parameters leads to a wide range of credible scenarios, with projected demand ranging from insignificant to overwhelming. However, even small changes to input assumptions make the major incident scenario increasingly likely. Before any cases are admitted to hospital, 95% confidence limit on admission rates led to a range in predicted peak critical care bed occupancy of between 0% and 37% of total critical care bed capacity, half of these cases requiring ventilatory support. For hospital admission rates above 0.25%, critical care bed availability would be exceeded. Further, only 10% of critical care beds in England are in specialist paediatric units, but best estimates suggest that 30% of patients requiring critical care will be children. Paediatric intensive care facilities are likely to be quickly exhausted and suggest that older children should be managed in adult critical care units to allow resource optimisation. Crucially this study highlights the need for sentinel reporting and real‐time modelling to guide rational decision making.

Severe traumatic brain injury: targeted management in the intensive care unit

Severe traumatic brain injury (TBI) is currently managed in the intensive care unit with a combined medical-surgical approach. Treatment aims to prevent additional brain damage and to optimise conditions for brain recovery. TBI is typically considered and treated as one pathological entity, although in fact it is a syndrome comprising a range of lesions that can require different therapies and physiological goals. Owing to advances in monitoring and imaging, there is now the potential to identify specific mechanisms of brain damage and to better target treatment to individuals or subsets of patients. Targeted treatment is especially relevant for elderly people-who now represent an increasing proportion of patients with TBI-as preinjury comorbidities and their therapies demand tailored management strategies. Progress in monitoring and in understanding pathophysiological mechanisms of TBI could change current management in the intensive care unit, enabling targeted interventions that could ultimately improve outcomes.

Serial sampling of serum protein biomarkers for monitoring human traumatic brain injury dynamics: A systematic review

Background The proteins S100B, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and neurofilament light (NF-L) have been serially sampled in serum of patients suffering from traumatic brain injury (TBI) in order to assess injury severity and tissue fate. We review the current literature of serum level dynamics of these proteins following TBI and used the term “effective half-life” (t1/2) in order to describe the “fall” rate in serum. Materials and methods Through searches on EMBASE, Medline, and Scopus, we looked for articles where these proteins had been serially sampled in serum in human TBI. We excluded animal studies, studies with only one presented sample and studies without neuroradiological examinations. Results Following screening (10,389 papers), n = 122 papers were included. The proteins S100B (n = 66) and NSE (n = 27) were the two most frequent biomarkers that were serially sampled. For S100B in severe TBI, a majority of studies indicate a t1/2 of about 24 h, even if very early sampling in these patients reveals rapid decreases (1–2 h) though possibly of non-cerebral origin. In contrast, the t1/2 for NSE is comparably longer, ranging from 48 to 72 h in severe TBI cases. The protein GFAP (n = 18) appears to have t1/2 of about 24–48 h in severe TBI. The protein UCH-L1 (n = 9) presents a t1/2 around 7 h in mild TBI and about 10 h in severe. Frequent sampling of these proteins revealed different trajectories with persisting high serum levels, or secondary peaks, in patients with unfavorable outcome or in patients developing secondary detrimental events. Finally, NF-L (n = 2) only increased in the few studies available, suggesting a serum availability of >10 days. To date, automated assays are available for S100B and NSE making them faster and more practical to use. Conclusion Serial sampling of brain-specific proteins in serum reveals different temporal trajectories that should be acknowledged. Proteins with shorter serum availability, like S100B, may be superior to proteins such as NF-L in detection of secondary harmful events when monitoring patients with TBI.

Multifractal analysis of hemodynamic behavior: intraoperative instability and its pharmacological manipulation.

Background:Physiologic instability is a common clinical problem in the critically ill. Many natural feedback systems are nonlinear, and seemingly random fluctuations may result from the amplification of external perturbations or even arise de novo as a consequence of their underlying dynamics. Characterization of the underlying nonlinear state may be of clinical importance, providing a technique to monitor complex physiology in real-time, guiding patient care and improving outcomes. Methods:We employ the wavelet modulus maxima technique to characterize the multifractal properties of heart rate and mean arterial pressure physiology retrospectively for four patients during open abdominal aortic aneurysm repair. We calculated point-estimates for the dominant Hölder exponent (hmHR, hmMAP) and multifractal spectrum width-at-half-height for both heart rate and mean arterial pressure signals. We investigated how these parameters changed with the administration of an intravenous vasoconstrictor and examined how this varied with atropine pretreatment. Results:Hypotensive patients showed lower values of hmMAP, consistent with a more highly fluctuating and complex behavior. Treatment with a vasoconstrictor led to a transient increase in hmMAP, revealing the appearance of longer-range correlations, but did not impact hmHR. On the other hand, prior treatment with atropine had no effect on hmMAP behavior but did tend to increase hmHR. Conclusions:Hypotension leads to a reduction in dominant Hölder exponents for mean arterial pressure, demonstrating an increasing signal complexity consistent with the activation of important homeokinetic processes. Conversely, pharmacological interventions may also alter the underlying dynamics. Pharmacological restoration of homeostasis leads to system decomplexification, suggesting that homeokinetic mechanisms are derecruited as homeostasis is restored.

Modelling the impact of pandemic influenza A(H1N1) on UK paediatric intensive care demand

Background: Each winter seasonal respiratory virus infections account for large variations in unplanned admission to UK paediatric intensive care units (PICU). The emergence of pandemic influenza A(H1N1) has been associated with a notable predominance in children and may be expected to have a significant impact on PICU provision. Aims: To derive conservative projections for PICU demand from current data and examine the effect of regional variations in bed provision. Methods and Results: PICU demand was estimated with the FluSurge 2.0 model using age-stratified data for the UK population and recently published conservative estimates for epidemiological parameters. The data suggest that a significant proportion of current total capacity may be required at the peak of the pandemic. Variation in per capita critical care provision across the UK leads to a wide range in potential impact at a regional level. Conclusions: Contingency measures for children needing paediatric intensive care are needed to absorb the likely increase in activity expected due to pandemic influenza this winter. Because of variations in provision by region, the role of paediatric retrieval services will be especially important.

Critical care management of traumatic brain injury

Traumatic brain injury (TBI) is a growing global problem, which is responsible for a substantial burden of disability and death, and which generates substantial healthcare costs. High-quality intensive care can save lives and improve the quality of outcome. TBI is extremely heterogeneous in terms of clinical presentation, pathophysiology, and outcome. Current approaches to the critical care management of TBI are not underpinned by high-quality evidence, and many of the current therapies in use have not shown benefit in randomized control trials. However, observational studies have informed the development of authoritative international guidelines, and the use of multimodality monitoring may facilitate rational approaches to optimizing acute physiology, allowing clinicians to optimize the balance between benefit and risk from these interventions in individual patients. Such approaches, along with the emerging impact of advanced neuroimaging, genomics, and protein biomarkers, could lead to the development of precision medicine approaches to the intensive care management of TBI.

Evaluation of the self-inflating bag-valve-mask and non-rebreather mask as preoxygenation devices in volunteers

Objective To evaluate and compare the effectiveness and tolerability of preoxygenation with the self-inflating bag-valve-mask (BVM) and non-rebreather mask (NRM) as are used before emergency anaesthesia. Design Device performance evaluation. Setting Experimental study. Participants 12 male and 12 female healthy volunteers (age range 24–47) with no history of clinically significant respiratory disease. Interventions End-expiration oxygen measurements (FEO2) after 3 min of preoxygenation with BVM (without mechanical assistance) and NRM devices. Mask pressures were measured and subjective difficulty of breathing was also assessed with a visual analogue score (VAS). Primary and secondary outcome measures The final FEO2 achieved was 58.0% (SD 7.3%) for the NRM compared to 53.1% (SD 13.4%) for the BVM (p=0.072). Preoxygenation was associated with small increases in FECO2 that were greater for the BVM (0.50%; 95% CI 0.48 to 0.52) than the NRM (0.29%; 95% CI 0.31 to 0.28); this difference was statistically significant (p=0.028). Both devices were well tolerated on VAS assessment of difficulty of breathing although this was higher for the BVM than the NRM (median VAS 1.85/10 compared to 1.1/10; p=0.041). Inspiratory and expiratory mask pressures were higher for the BVM. Conclusions In healthy volunteers, the NRM performs comparably to the BVM in terms of the degree of denitrogenation achieved although neither performed well. Although it was well tolerated, the BVM was subjectively more difficult to breathe through and was associated with greater mask pressures and a small increase in FECO2 consistent with hypoventilation or rebreathing. Our results suggest that preoxygenation with the NRM may be a preferable approach in spontaneously breathing patients.

Variation in monitoring and treatment policies for intracranial hypertension in traumatic brain injury: a survey in 66 neurotrauma centers participating in the CENTER-TBI study

BackgroundNo definitive evidence exists on how intracranial hypertension should be treated in patients with traumatic brain injury (TBI). It is therefore likely that centers and practitioners individually balance potential benefits and risks of different intracranial pressure (ICP) management strategies, resulting in practice variation. The aim of this study was to examine variation in monitoring and treatment policies for intracranial hypertension in patients with TBI.MethodsA 29-item survey on ICP monitoring and treatment was developed on the basis of literature and expert opinion, and it was pilot-tested in 16 centers. The questionnaire was sent to 68 neurotrauma centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study.ResultsThe survey was completed by 66 centers (97% response rate). Centers were mainly academic hospitals (n = 60, 91%) and designated level I trauma centers (n = 44, 67%). The Brain Trauma Foundation guidelines were used in 49 (74%) centers. Approximately 90% of the participants (n = 58) indicated placing an ICP monitor in patients with severe TBI and computed tomographic abnormalities. There was no consensus on other indications or on peri-insertion precautions. We found wide variation in the use of first- and second-tier treatments for elevated ICP. Approximately half of the centers were classified as using a relatively aggressive approach to ICP monitoring and treatment (n = 32, 48%), whereas the others were considered more conservative (n = 34, 52%).ConclusionsSubstantial variation was found regarding monitoring and treatment policies in patients with TBI and intracranial hypertension. The results of this survey indicate a lack of consensus between European neurotrauma centers and provide an opportunity and necessity for comparative effectiveness research.

Label-free monitoring of tissue biochemistry following traumatic brain injury using Raman spectroscopy

Acute tissue biochemical response to traumatic brain injury is revealed using Raman spectroscopy.

Enhanced Visualization of Optimal Cerebral Perfusion Pressure Over Time to Support Clinical Decision Making

Objective:Cerebrovascular reactivity can provide a continuously updated individualized target for management of cerebral perfusion pressure, termed optimal cerebral perfusion pressure. The objective of this project was to find a way of improving the optimal cerebral perfusion pressure methodology by introducing a new visualization method. Data Sources:Four severe traumatic brain injury patients with intracranial pressure monitoring. Data Extraction:Data were collected and pre-processed using ICM+ software. Data Synthesis:Sequential optimal cerebral perfusion pressure curves were used to create a color-coded maps of autoregulation - cerebral perfusion pressure relationship evolution over time. Conclusions:The visualization method addresses some of the main drawbacks of the original methodology and might bring the potential for its clinical application closer.