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Objectives: We sought to characterize 1) the difference in the diffusion gradient of cellular oxygen delivery and 2) the presence of diffusion limitation physiology in hypoxic-ischemic brain injury patients with brain hypoxia, as defined by parenchymal brain tissue oxygen tension less than 20 mm Hg versus normoxia (brain tissue oxygen tension > 20 mm Hg)., Design: Post hoc subanalysis of a prospective study in hypoxic-ischemic brain injury patients dichotomized into those with brain hypoxia versus normoxia., Setting: Quaternary ICU., Patients: Fourteen adult hypoxic-ischemic brain injury patients after cardiac arrest., Interventions: Patients underwent monitoring with brain oxygen tension, intracranial pressure, cerebral perfusion pressure, mean arterial pressure, and jugular venous bulb oxygen saturation. Data were recorded in real time at 300Hz into the ICM+ monitoring software (Cambridge University Enterprises, Cambridge, United Kingdom). Simultaneous arterial and jugular venous bulb blood gas samples were recorded prospectively., Measurements and Main Results: Both the normoxia and hypoxia groups consisted of seven patients. In the normoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen tension, and cerebral perfusion pressure were 29 mm Hg (SD, 9), 45 mm Hg (SD, 9), and 80 mm Hg (SD, 7), respectively. In the hypoxia group, the mean brain tissue oxygen tension, jugular venous bulb oxygen to brain tissue oxygen tension gradient, and cerebral perfusion pressure were 14 mm Hg (SD, 4), 53 mm Hg (SD, 8), and 72 mm Hg (SD, 6), respectively. There were significant differences in the jugular venous bulb oxygen tension-brain oxygen tension gradient (16 mm Hg [sd, 6] vs 39 mm Hg SD, 11]; p < 0.001) and in the relationship of jugular venous bulb oxygen tension-brain oxygen tension gradient to cerebral perfusion pressure (p = 0.004) when comparing normoxia to hypoxia. Each 1 mm Hg increase in cerebral perfusion pressure led to a decrease in the jugular venous bulb oxygen tension-brain oxygen tension gradient by 0.36 mm Hg (95% CI, -0.54 to 0.18; p < 0.001) in the normoxia group, but no such relation was demonstrable in the hypoxia group., Conclusions: In hypoxic-ischemic brain injury patients with brain hypoxia, there is an elevation in the jugular venous bulb oxygen tension-brain oxygen tension gradient, which is not modulated by changes in cerebral perfusion pressure.

Purpose: There is conflicting evidence regarding the influence of intensive care unit (ICU) occupancy at the time of admission on important patient outcomes such as mortality. The objective of this analysis was to characterize the association between ICU occupancy at the time of ICU admission and subsequent mortality., Methods: This single-centre, retrospective cohort study included all patients admitted to the ICU at the Vancouver General Hospital between 4 January 2010 and 8 October 2017. Intensive care unit occupancy was defined as the number of ICU bed hours utilized in a day divided by the total amount of ICU bed hours available for that day. We constructed mixed-effects logistic regression models controlling for relevant covariates to assess the impact of admission occupancy quintiles on total inpatient (ICU and ward) and early (72-hr) ICU mortality., Results: This analysis included 10,365 ICU admissions by 8,562 unique patients. Compared with ICU admissions in the median occupancy quintile, admissions in the highest and second highest occupancy quintile were associated with a significant increase in the odds of inpatient mortality (highest: odds ratio [OR], 1.33; 95% confidence interval [CI], 1.12 to 1.59; P value < 0.001; second highest: OR, 1.21; 95% CI, 1.02 to 1.44; P value < 0.03). No association between admission occupancy and 72-hr ICU mortality was observed., Conclusions: Admission to the ICU on days of high occupancy was associated with increased inpatient mortality, but not with increased 72-hr ICU mortality. Capacity strain on the ICU may result in significant negative consequences for patients, but further research is needed to fully characterize the complex effects of capacity strain.

Introduction: In hypoxic ischemic brain injury (HIBI), increased intracranial pressure (ICP) can ensue from cerebral edema stemming from cytotoxic and vasogenic mechanisms. Downstream sequelae of restricted cerebral blood flow lead to neurologic braindeath. There is limited data characterizing the temporal trends and patterns of ICP and compliance in human HIBI patients., Methods: Patients underwent invasive ICP monitoring with a parenchymal probe (Camino) and were managed with a tier-based management algorithm for elevated ICP. Data pertaining to mean arterial pressure (MAP), ICP, brain tissue oxygenation (PbtO 2 ), end tidal carbon dioxide (ETCO 2 ), core body temperature and RAP (moving correlation coefficient between mean ICP and its mean pulse amplitude) as a measure of intracranial compliance were recorded in the ICM + software. Data pertaining to ICP lowering interventions was also collected., Results: Ten patients were included with a median age of 47 (range 20-71) and seven were male (7/10). The mean ICP was 14 mmHg (SD 11) and time of ICP> 20 mmHg was 22% (range 0-100). The mean MAP, ETCO 2 and temperature were 89 mmHg (SD 13), 31 mmHg (SD 7), 35.7 °C (SD 0.9), respectively. The mean RAP was 0.58 (SD 0.34) and time of RAP > 0.4 was 78% (range 57-97). There were no significant relationships between ETCO 2 and temperature with ICP., Conclusions: In our cohort, HIBI was characterized by normal ICP but with limited intracranial compliance. However, significant in between patient heterogeneity exists with respect to temporal patterns of intracranial pressure - volume relationships in HIBI., Trial Registration: clinicaltrials.gov (NCT03609333)., (Crown Copyright © 2019. Published by Elsevier B.V. All rights reserved.)

Objectives: In patients at risk of hypoxic ischemic brain injury following cardiac arrest, we sought to: 1) characterize brain oxygenation and determine the prevalence of brain hypoxia, 2) characterize autoregulation using the pressure reactivity index and identify the optimal mean arterial pressure, and 3) assess the relationship between optimal mean arterial pressure and brain tissue oxygenation., Design: Prospective interventional study., Setting: Quaternary ICU., Patients: Adult patients with return of spontaneous circulation greater than 10 minutes and a postresuscitation Glasgow Coma Scale score under 9 within 72 hours of cardiac arrest., Interventions: All patients underwent multimodal neuromonitoring which included: 1) brain tissue oxygenation, 2) intracranial pressure, 3) jugular venous continuous oximetry, 4) regional saturation of oxygen using near-infrared spectroscopy, and 5) pressure reactivity index-based determination of optimal mean arterial pressure, lower and upper limit of autoregulation. We additionally collected mean arterial pressure, end-tidal CO2, and temperature. All data were captured at 300 Hz using ICM+ (Cambridge Enterprise, Cambridge, United Kingdom) brain monitoring software., Measurements and Main Results: Ten patients (7 males) were included with a median age 47 (range 20-71) and return to spontaneous circulation 22 minutes (12-36 min). The median duration of monitoring was 47 hours (15-88 hr), and median duration from cardiac arrest to inclusion was 15 hours (6-44 hr). The mean brain tissue oxygenation was 23 mm Hg (SD 8 mm Hg), and the mean percentage of time with a brain tissue oxygenation below 20 mm Hg was 38% (6-100%). The mean pressure reactivity index was 0.23 (0.27), and the percentage of time with a pressure reactivity index greater than 0.3 was 50% (12-91%). The mean optimal mean arterial pressure, lower and upper of autoregulation were 89 mm Hg (11), 82 mm Hg (8), and 96 mm Hg (9), respectively. There was marked between-patient variability in the relationship between mean arterial pressure and indices of brain oxygenation. As the patients' actual mean arterial pressure approached optimal mean arterial pressure, brain tissue oxygenation increased (p < 0.001). This positive relationship did not persist when the actual mean arterial pressure was above optimal mean arterial pressure., Conclusions: Episodes of brain hypoxia in hypoxic ischemic brain injury are frequent, and perfusion within proximity of optimal mean arterial pressure is associated with increased brain tissue oxygenation. Pressure reactivity index can yield optimal mean arterial pressure, lower and upper limit of autoregulation in patients following cardiac arrest.

Aim: Increased intracranial pressure (ICP) in hypoxic ischaemic brain injury (HIBI) can cause secondary ischaemic brain injury and culminate in brain death. Invasive ICP monitoring is limited by associated risks in HIBI patients. We sought to evaluate the agreement between invasive ICP measurements and non-invasive estimators of ICP (nICP) in HIBI patients., Methods: Eligible consecutive adult (age>18) cardiac arrest patients with HIBI were included as part of a single centre prospective interventional study. Invasive ICP monitoring and nICP measurements were undertaken using: a) transcranial Doppler ultrasonography (TCD), b) optic nerve sheet diameter ultrasound (ONSD) and c) jugular venous bulb pressure (JVP). Multiple measurements applied in linear mixed-effects models were considered to obtain the correlation coefficient between ICP and nICP as well as their predictive abilities to detect intracranial hypertension (ICP≥20mm Hg)., Results: Eleven patients were included (median age of 47 [range 20-71], 8 males and 3 females). There was a linear relationship between ICP and nICP with ONSD (R=0.53 [p<0.0001]), JVP (R=0.38 [p<0.001]) and TCD (R=0.30 [p<0.01]). The ability to predict intracranial hypertension was highest for ONSD and TCD (area under the receiver operating curve (AUC)=0.96 [95% CI: 0.90-1.00] and AUC=0.91 [95% CI: 0.83-1.00], respectively). JVP presented the weakest prediction ability (AUC=0.75 [95% CI: 0.56-0.94])., Conclusions: ONSD and TCD methods demonstrated agreement with invasively-monitored ICP, suggesting their potential roles in the detection of intracranial hypertension in HIBI after cardiac arrest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Sedation in the intensive care unit (ICU) is challenging, as both over- and under-sedation are detrimental. Current methods of assessment, such as the Richmond Agitation Sedation Scale (RASS), are measured intermittently and rely on patients' behavioral response to stimulation, which may interrupt sleep/rest. A non-stimulating method for continuous sedation monitoring may be beneficial and allow more frequent assessment. Processed electroencephalography (EEG) monitors have not been routinely adopted in the ICU. The aim of this observational study was to assess the feasibility of using the NeuroSENSE™ monitor for EEG-based continuous sedation assessment. With ethical approval, ICU patients on continuous propofol sedation were recruited. Depth-of-hypnosis index (WAV CNS ) values were obtained from the NeuroSENSE. Bedside nurses, blinded to the NeuroSENSE, performed regular RASS assessments and maintained the sedation regimen as per standard of care. Participants were monitored throughout the duration of their propofol infusion, up to 24 h. Fifteen patients, with median [interquartile range] age of 57 [52-62.5] years were each monitored for a duration of 9.0 [5.7-20.1] h. Valid WAV CNS values were obtained for 89% [66-99] of monitoring time and were widely distributed within and between individuals, with 6% [1-31] spent < 40 (very deep), and 3% [1-15] spent > 90 (awake). Significant EEG suppression was detected in 3/15 (20%) participants. Observed RASS matched RASS goals in 36/89 (40%) assessments. The WAV CNS variability, and incidence of EEG suppression, highlight the limitations of using RASS as a standalone sedation measure, and suggests potential benefit of adjunct continuous brain monitoring.

Purpose: Although recruitment maneuvers have been advocated as part of a lung protective ventilation strategy, their effects on cerebral physiology during elective neurosurgery are unknown. Our objectives were to determine the effects of an alveolar recruitment maneuver on subdural pressure (SDP), brain relaxation score (BRS), and cerebral perfusion pressure among patients undergoing supratentorial tumour resection., Methods: In this prospective crossover study, patients scheduled for resection of a supratentorial brain tumour were randomized to undergo either a recruitment maneuver (30 cm of water for 30 sec) or a "sham" maneuver (5 cm of water for 30 sec), followed by the alternative intervention after a 90-sec equilibration period. Subdural pressure was measured through a dural perforation following opening of the cranium. Subdural pressure and mean arterial pressure (MAP) were recorded continuously. The blinded neurosurgeon provided a BRS at baseline and at the end of each intervention. During each treatment, the changes in SDP, BRS, and MAP were compared., Results: Twenty-one patients underwent the study procedure. The increase in SDP was higher during the recruitment maneuver than during the sham maneuver (difference, 3.9 mmHg; 95% confidence interval [CI], 2.2 to 5.6; P < 0.001). Mean arterial pressure decreased further in the recruitment maneuver than in the sham maneuver (difference, -9.0 mmHg; 95% CI, -12.5 to -5.6; P < 0.001). Cerebral perfusion pressure decreased 14 mmHg (95% CI, 4 to 24) during the recruitment maneuver. The BRS did not change with either maneuver., Conclusion: Our results suggest that recruitment maneuvers increase subdural pressure and reduce cerebral perfusion pressure, although the clinical importance of these findings is thus far unknown. This trial was registered with ClinicalTrials.gov, NCT02093117.

Aim: To examine the relationship between daily mean hemoglobin concentration and neurological outcome in hypoxic ischemic brain injury (HIBI) following cardiac arrest., Methods: We conducted a single center retrospective observational study using a database of HIBI patients between March 2009 and December 2014. We included all adults admitted to the intensive care unit following an in-hospital or out-of-hospital cardiac arrest. The primary outcome was neurological outcome measured by the Cerebral Performance Category (CPC) at hospital discharge. Multivariable logistic regression was used to analyze the association of mean hemoglobin concentration over 48h and 7 days after the onset of HIBI and discharge CPC. Favorable and unfavorable neurological outcome was dichotomized for a discharge CPC 1-2 vs 3-5, respectively., Results: 118 patients were included in the analysis. Patients with a favorable neurological outcome had higher mean 7-day hemoglobin (115g/L vs 107g/L; p=0.05) compared to those with unfavorable outcome. Multivariate logistic regression controlling for age, time to return of spontaneous circulation and blood transfusion demonstrated that lower mean 48-h hemoglobin concentration was associated with unfavorable outcome (OR 0.69 per 10 unit change in Hgb, 95% CI 0.54-0.88, p<0.01). A repeated analysis using mean Hgb for the first 7 days yielded similar results for unfavorable outcome (OR 0.75 per 10 unit change in Hgb, 95% CI 0.57-0.97, p=0.03)., Conclusions: Lower mean hemoglobin concentration in the first 48h and 7 days following HIBI is associated with a higher odds of unfavorable outcome at hospital discharge. Further study to examine this association is warranted., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Prospectively assess cerebral autoregulation and optimal mean arterial pressure (MAPOPT) using the dynamic relationship between MAP and regional saturation of oxygen (rSO2) using near-infrared spectroscopy., Methods: Feasibility study of twenty patients admitted to the intensive care unit following a cardiac arrest. All patients underwent continuous rSO2 monitoring using the INVOS(®) cerebral oximeter. ICM+(®) brain monitoring software calculates the cerebral oximetry index (COx) in real-time which is a moving Pearson correlation coefficient between 30 consecutive, 10-s averaged values of MAP and correspond rSO2 signals. When rSO2 increases with increasing MAP (COx ≥0.3), cerebral autoregulation is dysfunctional. Conversely, when rSO2 remains constant or decreases with increasing MAP (COx <0.3), autoregulation is preserved. ICM+(®) fits a U-shaped curve through the COx values plotted vs. MAP. The MAPOPT is nadir of this curve., Results: The median age was 59 years (IQR 54-67) and 7 of 20 were female. The cardiac arrest was caused by myocardial infarction in 12 (60%) patients. Nineteen arrests were witnessed and return of spontaneous circulation occurred in a median of 15.5min (IQR 8-33). Patients underwent a median of 30h (IQR 23-46) of monitoring. COx curves and MAPOPT were generated in all patients. The mean overall MAP and MAPOPT were 76mmHg (SD 10) and 76mmHg (SD 7), respectively. MAP was outside of 5mmHg from MAPOPT in 50% (SD 15) of the time. Out of the 7672 5-min averaged COx measurements, 1182 (15%) were at 0.3 or above, indicating absence of autoregulation. Multivariable polynomial fractional regression demonstrated an increase in COx with increasing temperature (P=0.008)., Conclusions: We demonstrated the feasibility to determine a MAPOPT using cerebral oximetry in patients after cardiac arrest., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The purpose of the study is to compare outcomes in patients who had severe hypoxemic respiratory failure (Pao2/fraction of inspired oxygen <100) who received early veno-venous extracorporeal membrane oxygenation (ECMO) as an adjunct to mechanical ventilation, to those in patients who received conventional mechanical ventilation alone., Materials and Methods: This is a multicenter, retrospective unmatched and matched cohort study of patients admitted between April 2006 and December 2013. Generalized logistic mixed-effects models and Cox proportional hazards models were used to determine the association between treatment with ECMO that was started within 3 days of intensive care unit (ICU) admission and ICU and hospital mortality and length of stay, respectively., Results: A total of 2440 patients who had severe hypoxemic respiratory failure due to various etiologies were included, 46 who received early veno-venous ECMO and 2394 unmatched and 398 matched controls who received conventional ventilation alone. Compared to matched controls, ECMO was associated with a lower odds of ICU (odds ratio [95% confidence interval], 0.30 [0.13-0.67]) and inhospital death (odds ratio 0.30 [0.14-0.67]). In addition, ECMO was associated with longer times to discharge from ICU and hospital (hazard ratio, 0.42 [0.37-0.47] and 0.53 [0.38-0.73], respectively)., Conclusions: In this observational study, use of early ECMO compared to conventional mechanical ventilation alone in patients who had severe hypoxemic respiratory failure was associated with a lower risk of mortality and a longer length of stay., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: Hypertonic saline (HTS) is used to control intracranial pressure (ICP) in patients with traumatic brain injury (TBI); however, in prior studies, the resultant hypernatremia has been associated with increased mortality. We aimed to study the effect of HTS on ICP and mortality in patients with severe TBI., Methods: We performed a retrospective cohort study of 231 patients with severe TBI (Glasgow Coma Scale [GCS] ≤ 8) admitted to two neurotrauma units from 2006-2012. We recorded daily HTS, ICP, and serum sodium (Na) concentration. We used Cox proportional regression modelling for hospital mortality and incorporated the following time-dependent variables: use of HTS, hypernatremia, and desmopressin administration., Results: The mean [standard deviation (SD)] age of patients was 34 (17) and the median (interquartile range [IQR]) GCS was 6 [3-8]. Hypertonic saline was administered as a continuous infusion in 124 of 231 (54%) patients over 788 of 2,968 (27%) patient-days. Hypernatremia (Na > 145 mmol·L(-1)) developed in 151 of 231 (65%) patients over 717 of 2,968 (24%) patients-days. In patients who developed hypernatremia, the median [IQR] Na was 146 [142-147] mmol·L(-1). Overall hospital mortality was 26% (59 of 231 patients). After adjusting for baseline covariates, neither HTS (hazard ratio [HR], 1.07; 95% confidence interval [CI], 0.56 to 2.05; P = 0.84) nor hypernatremia (HR, 1.31; 95% CI, 0.68 to 2.55; P = 0.42) was associated with hospital mortality. There was no effect modification by either HTS or hypernatremia on each another. Patients who received HTS observed a significant decrease in ICP during their ICU stay compared with those who did not receive HTS (4 mmHg; 95% CI, 2 to 6; P < 0.001 vs 2 mmHg; 95% CI, -1 to 5; P = 0.14)., Conclusions: Hypertonic saline and hypernatremia are not associated with hospital mortality in patients with severe TBI.

Objective: The optimal surgical management of acute traumatic subdural hematoma (ASDH) is controversial; both craniectomy and craniotomy are performed. The purpose of this study was to determine the current management of ASDH in the United States., Methods: This retrospective cohort study used the Nationwide Inpatient Sample from the years 2006-2011 to examine patients with a primary diagnosis of ASDH. All patients ≥18 years old with a primary diagnosis of ASDH were included in the analysis. Patients with procedure codes for craniectomy and craniotomy were isolated from the database. Propensity score matching based on logistic regression was used to match craniotomy to craniectomy in a 1:1 fashion., Results: There were 47,911,414 hospitalizations analyzed. Of 60,435 patients with ASDH identified, 1763 underwent craniotomy and 177 underwent craniectomy. The average age of patients who underwent craniectomy was 49.5 years (SD 20.8) compared with an average age of 68.9 years (SD 17.1) of patients who underwent craniotomy (P < 0.0001). Hospital mortality was significantly higher in patients who underwent craniectomy (35.0% vs. 10.9%, P < 0.0001). Patients who underwent craniectomy had longer hospital stays compared with patients who underwent craniotomy (median duration 14.3 days [interquartile range 25] for craniectomy vs. 10.9 days [interquartile range 9] for craniotomy, P < 0.0001). Patients who underwent craniectomy were also more likely to be discharged to a skilled nursing or rehabilitation facility (79.1% vs. 63.9%, P = 0.0011)., Conclusions: Craniotomy is the preferred surgical technique for management of ASDH in the United States, being performed 10 times more frequently than craniectomy. Craniectomy was associated with significantly higher in-hospital mortality after propensity score matched analysis., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Multimodal neuromonitoring in the management of traumatic brain injury (TBI) enables clinicians to make individualized management decisions to prevent secondary ischemic brain injury. Traditionally, neuromonitoring in TBI patients has consisted of a combination of clinical examination, neuroimaging and intracranial pressure monitoring. Unfortunately, each of these modalities has its limitations and although pragmatic, this simplistic approach has failed to demonstrate improved outcomes, likely owing to an inability to consider the underlying heterogeneity of various injury patterns. As neurocritical care has evolved, so has our understanding of underlying disease pathophysiology and patient specific considerations. Recent additions to the multimodal neuromonitoring platform include measures of cerebrovascular autoregulation, brain tissue oxygenation, microdialysis and continuous electroencephalography. The implementation of neurocritical care teams to manage patients with advanced brain injury has led to improved outcomes. Herein, we present a narrative review of the recent advances in multimodal neuromonitoring and highlight the utility of dedicated neurocritical care., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Hypoxic ischaemic brain injury (HIBI) is a major cause of disability after cardiac arrest. HIBI leads to impaired cerebral autoregulation such that adequate cerebral perfusion becomes critically dependent on blood pressure. However, the optimal blood pressure after cardiac arrest remains unclear. Therefore, we conducted a systematic review to investigate the association between blood pressure and neurologic outcome patients after cardiac arrest., Methods: We systematically searched MEDLINE, EMBASE, conference abstracts and article references to identify randomized and observational studies investigating the relationship between blood pressure and neurologic outcome. We included studies that reported adjusted point estimates for the relationship between blood pressure and neurologic status in adult patients after cardiac arrest., Results: We included 9 studies with a total of 13,150 patients. Three studies included only patients with an out-of-hospital cardiac arrest. There was marked between-study heterogeneity with respect to blood pressure definition (MAP vs. systolic), exposure duration and modelling (dichotomous vs. continuous). All studies examined either mortality or neurological status as an outcome. Seven of nine studies demonstrated that higher blood pressure was associated with improved outcomes either by an association between higher MAP and good neurologic outcome or the presence of hypotension and increased odds of mortality., Conclusions: The included studies suggest improved neurologic outcomes are associated with higher blood pressures in patients after cardiac arrest. This study highlights a need for further research to define the optimal management of blood pressure in this population., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

New Findings: What is the central question of this study? Does the induction of a model of lung injury affect the expiratory time constant (τE) in terms of either total duration or morphology? Does ventilation with gases of different densities alter the duration or morphology of τE either before or after injury? What is the main finding and its importance? The use of sulfur hexafluoride in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both nitrogen and helium mixtures. Sulfur hexafluoride mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with nitrogen and helium mixtures. Acute lung injury is characterized by regional heterogeneity of lung resistance and elastance that may lead to regional heterogeneity of expiratory time constants (τE). We hypothesized that increasing airflow resistance by using inhaled sulfur hexafluoride (SF6) would lengthen time constants and decrease their heterogeneity in an experimental model of lung injury when compared with nitrogen or helium mixtures. To overcome the limitations of a single-compartment model, we employed a multisegment model of expiratory gas flow. An experimental model of lung injury was created using intratracheal injection of sodium polyacrylate in anaesthetized and mechanically ventilated female Yorkshire-cross pigs (n = 7). The animals were ventilated with 50% O2 and the remaining 50% as nitrogen (N2), helium (He) or sulfur hexafluoride (SF6). Values for τE decreased with injury and were more variable after injury than before (P < 0.001). Values for τE increased throughout expiration both before and after injury, and the rate of increase in τE was lessened by SF6 (P < 0.001 when compared with N2 both before and after injury). Altering the inhaled gas density did not affect indices of oxygenation, dead space or shunt. The use of SF6 in ventilating gas mixtures lengthens total expiratory time constants before and after lung injury compared with both N2 and He mixtures. Importantly, SF6 mixtures also decrease the difference and variability of τE between fast- and slow-emptying compartments before and after injury when compared with N2 and He mixtures., (© 2015 The Authors. Experimental Physiology © 2015 The Physiological Society.)

Background: Red blood cell (RBC) transfusion is associated with inconsistent changes in brain tissue oxygenation (PbO2). Previous studies have failed to consider alterations in cerebral autoregulation. Our objective was to investigate the effect of RBC transfusion on cerebral autoregulation, as measured by pressure reactivity index (PRx)., Methods: Retrospective analysis of 28 severe traumatic brain injury (TBI) patients from a prospective registry between 2007 and 2014. We recorded hemoglobin (Hb) concentration, intracranial pressure, PbO2, cerebral perfusion pressure, PRx, and cerebral lactate/pyruvate ratio for 6 h before and after RBC transfusion. We also recorded body temperature, PaO2, PCO2, pH, and fraction of inspired oxygen. Subgroups of normoxia (PbO2 >20 mmHg) and hypoxia (PbO2 <20 mmHg) prior to transfusion were defined a priori., Results: The median age was 36 years [interquartile range (IQR) 27-49], 32% were female. The median admission Glasgow Coma score was 5 (IQR 4-9) and injury severity score was 16 (IQR 9-21). Overall, mean Hb concentration [80 g/L (SD 7) to 89 g/L (SD 8), p < 0.001] and PbO2 increased [23.5 mmHg (SD 8) to 25.0 mmHg (SD 9), p = 0.033] following transfusion. PRx increased post-transfusion [0.028 (SD 0.29) to 0.11 (SD 0.24), p = 0.034], indicating worsening cerebrovascular pressure reactivity. In patients with mean PbO2 >20 mmHg pre-transfusion (n = 20), the PRx increased significantly [-0.052 (SD 0.24) to 0.079 (SD 0.22), p = 0.007] but did not change in patients with PbO2 <20 mmHg: PRx [0.22 (SD 0.34) to 0.18 (SD 0.30), p = 0.36]., Conclusion: RBC transfusion in severe TBI patients results in worsening PRx, indicating impaired cerebral autoregulation.

Purpose: There is conflicting data on the relationship between anemia and outcomes in patients with traumatic brain injuries (TBI). The objective of this study was to determine if the proportion of time and area under the hemoglobin-time curve of ≥90 g/L are independently associated with 6-month functional outcomes., Methods: Retrospective cohort study of 116 patients with a severe TBI who underwent invasive neuromonitoring between June 2006 and December 2013. Hemoglobin area (HAI) and time (HTI) indices were calculated by dividing the total area, or time, under the hemoglobin-time curve at 90 g/L or above by the total duration of monitoring. Multivariable log-binomial regression was used to model the association between HAI or HTI and 6 month favorable neurologic outcome (Glasgow Outcome Score 4 or 5)., Results: Patients had a mean age of 38 years (SD 16) with a median admission Glasgow Coma Scale of 6 (IQR 4-7). There were 1523 hemoglobin measurements and 523 monitoring days. Patients had a hemoglobin ≥90 g/L for a median of 70 % (IQR 37-100) of the time. Each 10 g/L increase in HAI (RR 1.23, 95 %CI 1.04-1.44, P = 0.011), and 10 % increase in HTI (1.10, 95 %CI 1.04-1.16, P < 0.001) were associated with improved neurologic outcome. Thirty-one patients (27 %) received a transfusion with the median pre-transfusion hemoglobin being 81 g/L (IQR 76-87)., Conclusions: In patients with severe TBI, increased area under the curve and percentage of time that the hemoglobin concentration was ≥90 g/L, were associated with improved neurologic outcomes.

Purpose: The aims of this study are to assess adherence to the Brain Trauma Foundation (BTF) cerebral perfusion pressure (CPP) guidelines and to determine if adherence is associated with mortality in patients who have a severe traumatic brain injury., Materials and Methods: Retrospective cohort study of 127 patients admitted to one intensive care unit between 2006 and 2012. Adherence to BTF guidelines was measured as the time that the CPP was within 50 to 70 mm Hg divided by the total time of CPP monitoring (CPP time index)., Results: The percentage of time that the CPP was within the recommended range was 31.6% (SD, 22.2); CPP was greater than 70 mm Hg for 63.9% (SD, 26.2) of the time and less than 50 mm Hg for 4.5% of the time (SD, 16.3). After adjustment for covariates, CPP time index (between 50 and 70 mm Hg) was not associated with hospital mortality (odds ratio [OR], 1.2; 95% confidence interval [CI], 0.98-1.6; P= .079). The time indices for CPP ≥70 and <50 mm Hg were associated with decreased (OR, 0.66; 95%CI, 0.52-0.82; P< .0001) and increased (OR, 9.9; 95% CI, 1.4-69.6; P= .021) mortality, respectively., Conclusion: Cerebral perfusion pressure was greater than 70 mm Hg for most of the time. This level of CPP was associated with decreased hospital mortality., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: Increased intracranial pressure (ICP) is associated with worse outcomes following traumatic brain injury (TBI). Studies have confirmed that ICP is correlated with optic nerve sheath diameter (ONSD) on ultrasound. The aim of our study was to assess the independent relationship between ONSD measured using CT and mortality in a population of patients admitted with severe TBI., Methods: We conducted a retrospective cohort study of patients with a TBI requiring ICP monitoring admitted to the ICU between April 2006 and May 2012 to two neurotrauma centers. ONSD was independently measured by two physicians blinded to patient outcomes. Multivariable logistic regression modeling was used to assess an association between ONSD and hospital mortality., Results: A total of 220 patients were included in the analysis. Overall, the cohort had a mean age of 35 (SD 17) years and 171 of 220 (79 %) were male. The median admission GCS was 6 (IQR 3-8). Intra-class correlation coefficient between raters for ONSD measurements was 0.92 (95 % CI 0.90-0.94, P < 0.0001). On multivariable analysis, each 1 mm increase in ONSD was associated with a twofold increase in hospital mortality (OR 2.0, 95 % CI 1.2-3.2, P = 0.007). Using linear regression, ONSD was independently associated with increased ICP in the first 48 h after admission (β = 4.4, 95 % CI 2.5-6.3, P < 0.0001)., Conclusions: In patients with TBI, ONSD measured on CT scanning was independently associated with ICP and mortality.

Purpose: Assess the relationship between optic nerve sheath diameter (ONSD) measured on bedside portable computed tomography (CT) scans and simultaneously measured intracranial pressure (ICP) in patients with severe traumatic brain injury., Methods: Retrospective cohort study of 57 patients admitted between 2009 and 2013. Linear and logistic regression were used to model the correlation and discrimination between ONSD and ICP or intracranial hypertension, respectively., Results: The cohort had a mean age of 40 years (SD 16) and a median admission Glasgow coma score of 7 (IQR 4-10). The between-rater agreement by intraclass coefficient was 0.89 (95 % CI 0.83-0.93, P < 0.001). The mean ONSD was 6.7 mm (SD 0.75) and the mean ICP during CT was 21.3 mmHg (SD 8.4). Using linear regression, there was a strong correlation between ICP and ONSD (r = 0.74, P < 0.001). ONSD had an area under the curve to discriminate elevated ICP (≥20 mmHg vs. <20 mmHg) of 0.83 (95 % CI 0.73-0.94). Using a cutoff of 6.0 mm, ONSD had a sensitivity of 97 %, specificity of 42 %, positive predictive value of 67 %, and a negative predictive value of 92 %. Comparing linear regression models, ONSD was a much stronger predictor of ICP (R(2) of 0.56) compared to other CT features (R(2) of 0.21)., Conclusions: Simultaneous measurement of ONSD on CT and ICP were strongly correlated and ONSD was discriminative for intracranial hypertension. ONSD was much more predictive of ICP than other CT features. There was excellent agreement between raters in measuring ONSD.

Objective: To define the incidence and perioperative risk factors of acute kidney injury (AKI) within 72 hours after lung transplantation and clarify the relationship between postoperative AKI and outcome in patients undergoing lung transplantation., Design: A retrospective observational study., Setting: A tertiary care academic center., Participants: Fifty-four patients who underwent lung transplantation between January 2006 and March 2010., Interventions: None., Measurements and Main Results: After excluding 4 patients who died or required additional surgery during the first 72 hours after transplantation, 50 patients were included in the final analysis. Data were extracted from medical charts and electronic health record information system. Risk, injury, failure, loss, endstage (RIFLE) renal disease creatinine criteria were used for the diagnosis of AKI. AKI developed in 27 patients (54%) within 72 hours after transplantation. The incidence of AKI after double-lung transplantation was 87% compared to 40% following single-lung transplantation. The percentage of patients with intraoperative hypoxemia (SpO2<90%) was significantly different between the groups (AKI, 59%; Non-AKI, 22%). Volume of hydroxyethyl starch was significantly higher in AKI patients (912±507 mL) than non-AKI patients (535±338 mL). Baseline estimated glomerular filtration rate (eGFR) was significantly higher in AKI patients (99±27 mL/min/1.73 m2) than non-AKI patients (77±20 mL/min/1.73 m2)., Conclusions: AKI based on the RIFLE criteria following lung transplantation is common. Patients who developed AKI were more likely to have an episode of intraoperative hypoxemia and undergo a double-lung transplantation. Contrary to other published studies, patients with a higher preoperative eGFR were more likely to develop AKI in the authors' cohort., (© 2013 Elsevier Inc. All rights reserved.)

Introduction: The critical care management of traumatic brain injury focuses on preventing secondary ischemic injury. Cerebral oxygen delivery is dependent upon the cerebral perfusion pressure and the oxygen content of blood, which is principally determined by hemoglobin. Despite its importance to the cerebral oxygen delivery, the precise hemoglobin concentration to provide adequate oxygen delivery to injured neuronal tissue in TBI patients is controversial with limited evidence to provide transfusion thresholds., Methods: We conducted a retrospective cohort study of severe TBI patients, investigating the association between mean 7-day hemoglobin concentration and hospital mortality. Demographic, physiologic, intensive care interventions, clinical outcomes and daily hemoglobin concentrations were recorded for all patients. Patients were all cared for at a tertiary, level 1 trauma center in a mixed medical and surgical intensive unit. Patients were divided into quartiles based on their mean 7-day hemoglobin concentration: < 90 g/L, 90 - 99 g/L, 100 - 109 g/L and > 110 g/L. Multivariable log-binomial regression was used to model the association between mean daily hemoglobin concentration and hospital mortality., Results: Two hundred seventy-three patients with traumatic brain injury were identified and 169 were included in the analysis based on inclusion/exclusion criteria. Of these, 77% of the patients were male, with a mean age of 38 (SD 17) years and a median best GCS of 6 (IQR 5 - 7). One hundred fifteen patients (68%) received a red blood cell (RBC) transfusion. In RBCs administered in the ICU, the median pre-transfusion hemoglobin was 79 g/L (IQR 73 - 85). Thirty-seven patients (22%) died in hospital. Multivariable analysis revealed that mean 7-day hemoglobin concentration < 90 g/L was independently associated with an increased risk of hospital mortality (RR 3.1, 95% CI 1.5 - 6.3, p = 0.03). Other variables associated with increased mortality on multivariable regression were insertion of external ventricular drain, age and decreased GCS. Red blood cell transfusion was not associated with mortality following multivariable adjustment., Conclusions: A mean 7-day hemoglobin concentration of < 90g/L is associated with increased hospital mortality in patients with severe traumatic brain injury.

Measurement of regional blood flow to the respiratory muscles has traditionally been invasive. The blood flow index (BFI), a minimally invasive method using indocyanine green dye (ICG) and near infrared spectroscopy, allows assessment of within subject changes in regional blood flow. This study assessed regional BFI to the vastus lateralis muscle (QBFI) and the superficial respiratory muscles in the seventh intercostal space (RMBFI). Eight healthy subjects cycled continuously at incrementally more difficulty stages to exhaustion. In our subjects, QBFI declined between 83% and 100% of maximal exertion (p=0.002) and no statistically significant changes in RMBFI were seen despite steadily increasing ventilatory workloads. Post hoc pairwise comparisons demonstrated that QBFI at 83% work (0.015μmoless(-1)±0.005) was significantly higher than at maximum work output (0.011μmoless(-1)±0.004, p=0.007). There were no other significant differences of QBFI between maximum work output and different levels of work. The current study suggests that respiratory and locomotor muscle blood flow during sub-maximal and maximal exertion is unable to match increasing workloads., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Purpose: Although 4% albumin is associated with increased mortality in patients with traumatic brain injury (TBI), evidence concerning the safety of synthetic colloids is lacking. We aimed to determine if there is an association between synthetic colloids and mortality in patients with severe TBI., Materials and Methods: A retrospective cohort study of patients with severe TBI was conducted. Data were collected on all intravenous fluids administered during the first 14 days of admission. Multivariable Cox proportional hazards regression was used to model the association between daily cumulative pentastarch quintiles and mortality., Results: Patients receiving pentastarch had higher Acute Physiology and Chronic Health II scores (23.9 vs 21.6, P < .01), frequency of craniotomy (42.5% vs 21.6%, P = .02), longer duration of intensive care unit stay (12 vs 4 days, P < .01), and mechanical ventilation (10 vs 3 days, P < .01). On unadjusted Cox regression, patients in the highest quintile of cumulative pentastarch administration had a higher rate of mortality compared with those receiving no colloid (hazard ratio, 3.8; 95% confidence interval, 1.2-12.4; P = .03). However, this relationship did not persist in the final multivariable model (hazard ratio 1.0; 95% confidence interval, 0.25-4.1; P = .98)., Conclusion: There was no association between cumulative exposure to pentastarch and mortality in patients with severe TBI., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: Cardiogenic shock is associated with poor clinical outcomes. Extracorporeal life support is used in most centers for short-term circulatory support. Alternatively, the Impella LP 5.0 and right direct (RD) microaxial ventricular assist device (Abiomed, Danvers, Mass) can provide isolated left and right ventricular support, respectively., Methods: A retrospective, single center review was performed on all patients receiving circulatory assistance with either extracorporeal life support or Impella ventricular assist device. All Impella LP 5.0 were inserted via the femoral artery, while the RD system required sternotomy., Results: Twenty-nine patients received ventricular assist device support (Impella LP 5.0; n = 24; and Impella RD; n = 5), whereas 32 patients were placed on extracorporeal life support. The baseline characteristics of patients with cardiogenic shock, assisted by Impella or extracorporeal life support, were similar, but the etiology of cardiogenic shock was distributed differently in the 2 groups (P = .008). Forty-one percent of the Impella patients and 47% of the extracorporeal life support patients were weaned from support. The 30-day mortality (44% in the extracorporeal life support vs 38% in the Impella group) and proportion of patients discharged home (41% in the extracorporeal life support vs 59% in the Impella group) were not statistically different between the 2 groups. Arterial thrombosis was less frequent in the Impella group (3.4% vs 18.8%; P = .04). Blood product transfusions were less frequent in the Impella group (P < .001)., Conclusions: Both extracorporeal life support and axial flow pumps provided adequate support in patients with various etiologies of cardiogenic shock. Axial-flow pump may be an optimal type of support for patients with univentricular failure, whereas extracorporeal life support could be reserved for patients with biventricular failure or combined respiratory and circulatory failure., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Near-infrared spectroscopy (NIRS) in combination with indocyanine green (ICG) dye has recently been used to measure respiratory muscle blood flow (RMBF) in humans. This method is based on the Fick principle and is determined by measuring ICG in the respiratory muscles using transcutaneous NIRS in relation to the [ICG] in arterial blood as measured using photodensitometry. This method is invasive since it requires arterial cannulation, repeated blood withdrawals, and reinfusions. A less invasive alternative is to calculate a relative measure of blood flow known as the blood flow index (BFI), which is based solely on the NIRS ICG curve, thus negating the need for arterial cannulation. Accordingly, the purpose of this study was to determine whether BFI can be used to measure RMBF at rest and during voluntary isocapnic hyperpnea at 25, 40, 55, and 70% of maximal voluntary ventilation in seven healthy humans. BFI was calculated as the change in maximal [ICG] divided by the rise time of the NIRS-derived ICG curve. Intercostal and sternocleidomastoid muscle BFI were correlated with simultaneously measured work of breathing and electromyography (EMG) data from the same muscles. BFI showed strong relationships with the work of breathing and EMG for both respiratory muscles. The coefficients of determination (R(2)) comparing BFI vs. the work of breathing for the intercostal and sternocleidomastoid muscles were 0.887 (P < 0.001) and 0.863 (P < 0.001), respectively, whereas the R(2) for BFI vs. EMG for the intercostal and sternocleidomastoid muscles were 0.879 (P < 0.001) and 0.930 (P < 0.001), respectively. These data suggest that the BFI closely reflects RMBF in conscious humans across a wide range of ventilations and provides a less invasive and less technically demanding alternative to measuring RMBF.

Purpose: The aim of the study was to evaluate if early achievement of physiologic goals of resuscitation in critically ill septic patients admitted from the ward may prevent acute kidney injury (AKI)., Materials and Methods: Patients admitted to the intensive care unit (ICU) with a diagnosis of sepsis were retrospectively identified. Mean arterial pressure greater than 65 mm Hg, central venous pressure greater than 8 mm Hg, and central venous oxygenation greater than 70% achieved within 6 hours after ICU consultation at the ward was considered early achievement. Acute kidney injury was defined by the RIFLE criteria., Results: Of 85 patients, 29% achieved all goals within 6 hours, 42% had late or no achievement of goals, and 28% had incomplete documentation of goals. Of these, 52% developed AKI. Patients who eventually developed AKI had a significantly higher creatinine level at ICU consultation before resuscitation. Delay in achievement of goals results in a 3.4% creatinine level rise per hour in multivariate analysis (P = .03). The development of AKI was significantly influenced by delayed achievement of physiologic goals on the ICU (P = .02)., Conclusions: Although most of AKI occurred before ICU consultation, early physiologic resuscitation and achievement of hemodynamic goals on the ICU is associated with a decrease in development of AKI of septic patients admitted from the ward., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Arthur Guyton's concepts of the determinative role of right heart filling in cardiac output continue to be controversial. This paper reviews his seminal experiments in detail and clarifies the often confusing concepts underpinning his model. One primary criticism of Guyton's model is that the parameters describing venous return had not been measured in a functioning cardiovascular system in humans. Thus, concerns have been expressed in regard to the ability of Guyton's simplistic model, with few parameters, to model the complex human circulation. Further concerns have been raised in regard to the artificial experimental preparations that Guyton used. Recently reported measurements in humans support Guyton's theoretical and animal work.

Aquaporins are a family of transmembrane proteins that selectively allow the passage of water through the plasma membrane. Their importance is highlighted by their ubiquitous presence from bacteria to mammals. In humans, they are found throughout the body and recent work has highlighted their function within the brain. They are intimately involved in the production of cerebrospinal fluid and the control of water movement at the blood-brain barrier. Aquaporin levels are up-regulated in animal models of trauma, stroke and water intoxication as well as around human malignant brain tumors. They have thus been implicated in the formation of brain edema. Knockout mice, without the aquaporin gene, appear to have reduced brain edema compared to their wild type brethren in models of brain edema. Currently, the clinical treatment of brain edema is limited. Increased knowledge of the aquaporins may open new targeted therapies for brain edema.

Background: Calcium pyrophosphate dihydrate deposition in the cervical spine is infrequently symptomatic. This is especially true at the craniocervical junction and upper cervical spine., Case Report: A 70-year-old previously healthy woman presented with a progressive cervical myelopathy of four months duration., Results: Examination revealed sensorimotor findings consistent with an upper cervical myelopathy. Radiological studies (plain radiographs, computed tomography, and magnetic resonance imaging) revealed C1-2 instability, and a well-defined extradural 3 cm x 1 cm retro-odontoid mass causing spinal cord compression. Transoral resection of the mass was performed followed by posterior C1-2 stabilization. Histological examination of the mass confirmed calcium pyrophosphate dihydrate deposition. Follow-up examination showed marked clinical and radiological improvement., Conclusion: Although uncommon, calcium pyrophosphate dihydrate deposition disease should be considered in the differential diagnosis of extradural mass lesions in the region of the odontoid.