Changing the stroke network during pandemic scenarios does not affect the management of patients with a positive Cincinnati prehospital stroke scale.

INTRODUCTION: Time plays a crucial role in the management of stroke, and changing the prehospital emergency network, altering the HUB and spoke relationship in pandemic scenarios, might have an impact on time to fibrinolysis or thrombectomy. The aim of this study was to evaluate the time-dependent stroke emergency network in Lombardy region (Italy) by comparing 2019 with 2020 and early 2021. Three parameters were investigated: (i) time of arrival of the first vehicle at the scene, (ii) overall duration of missions, and (iii) number of patients transported by emergency vehicles. METHODS: Data analysis process conducted using the SAS-AREU portal (SAS Institute, USA). RESULTS: The number of patients with a positive CPSS was similar among the different pandemic waves. Mission duration increased from a mean time (SD) of 52.9 (16.1) min in 2019 to 64.1 (19.7) in 2020 and 55.0 (16.8) in 2021. Time to first vehicle on scene increased to 15.7 (8.4) min in 2020 and 16.0 (7.0) in 2021 compared to 2019, 13.6 (7.2) (P < 0.05). The number of hospital with available stroke units decreased from 46 in 2019 to 10 during the first pandemic wave. CONCLUSIONS: The pandemic forced changes in the clinical mission of many hospitals by reducing the number of stroke units. Despite this, the organization of the emergency system allowed to identify strategic hospitals and thus avoid excessive transport time. The result was an adequate time for fibrinolysis/thrombectomy, in agreement with the guidelines. Coordinated management in emergency situations makes it possible to maintain service quality standards, despite the unfavorable scenario.

Baroreflex dynamics during the rest to exercise transient in acute normobaric hypoxia in humans.

PURPOSE: We hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A1) due to lower vagal activity in H than N. METHODS: Ten participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O2 = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method. RESULTS: Upon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg-1 at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg-1 (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg-1 at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg-1 (p < 0.01 vs. rest). CO-A1 was 2.96 ± 1.51 and 2.31 ± 0.94 l min-1 in N and H, respectively (p = 0.06). HR-A1 was 7.7 ± 4.6 and 7.1 ± 5.9 min-1 in N and H, respectively (p = 0.81). CONCLUSION: The immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive.

Effectiveness of Cardiopulmonary Resuscitation at the Workplace.

BACKGROUND: Out-of-Hospital Cardiac Arrest (OHCA) is a medical emergency whose chances of survival can be increased by rapid Cardiopulmonary Resuscitation (CPR) and early use of Public Access Defibrillators (PAD). Basic Life Support (BLS) training became mandatory in Italy to spread knowledge of resuscitation maneuvers in the workplace. Basic Life Support (BLS) training became mandatory according to the DL 81/2008 law. To improve the level of cardioprotection in the workplace, the national law DL 116/2021 increased the number of places required to be provided with PADs. The study highlights the possibility of a Return to spontaneous circulation in OHCA in the workplace. METHODS: A multivariate logistic regression model was fitted to the data to extrapolate associations between ROSC and the dependent variables. The associations' robustness was evaluated through sensitivity analysis. RESULTS: The chance to receive CPR (OR 2.3; 95% CI:1.8-2.9), PAD (OR 7.2; 95% CI:4.9 - 10.7), and achieve Return to spontaneous circulation (ROSC) (crude OR 2.2; 95% CI:1.7-3.0, adjusted OR 1.6; 95% CI:1.2-2.2) is higher in the workplace compared to all other places. CONCLUSION: The workplace could be considered cardioprotective, although further research is necessary to understand the causes of missed CPRs and identify the best places to increase BLS and defibrillation training to help policymakers implement correct programming on the activation of PAD projects.

Cardiopulmonary resuscitation missed by bystanders: Collateral damage of coronavirus disease 2019.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic changed the time-dependent cardiac arrest network. This study aims to understand whether the rescue standards of cardiopulmonary resuscitation (CPR) and out-of-hospital cardiac arrest (OHCA) were handled differently during pandemic compared to the previous year. METHODS: Data for the years 2019 and 2020 were provided by the records of the Lombardy office of the Regional Agency for Emergency and Urgency. We analysed where the cardiac arrest occurred, when CPR started and whether the bystanders used public access to defibrillation (PAD). RESULTS: During 2020, there was a reduction in CPRs performed by bystanders (odds ratio [OR] = 0.936 [95% confidence interval (CI95% ) 0.882-0.993], p = .029) and in the return of spontaneous circulation (ROSC) (OR = 0.621 [CI95% 0.563-0.685], p < .0001), while there was no significant reduction in the use of PAD. Analysing only March, the period of the first wave in Lombardy, the comparison shows a reduction in bystanders CPRs (OR = 0.727 [CI95% 0.602-0.877], p = .0008), use of PAD (OR = 0.441 [CI95% 0.272-0.716], p = .0009) and in ROSC (OR = 0.179 [CI95% 0.124-0.257], p < .0001). These phenomena could be influenced by the different settings in which the OHCAs occurred; in fact, those that occurred in public places with a mandatory PAD were strongly reduced (OR = 0.49 [CI95% , 0.44-0.55], p < .0001). CONCLUSIONS: COVID-19 had a profound impact on the time-dependant OHCA network. During the first pandemic wave, CPR and PAD used by bystanders decreased. The different contexts in which OHCAs occurred may partially explain these differences.

A century of exercise physiology: key concepts on coupling respiratory oxygen flow to muscle energy demand during exercise.

After a short historical account, and a discussion of Hill and Meyerhof's theory of the energetics of muscular exercise, we analyse steady-state rest and exercise as the condition wherein coupling of respiration to metabolism is most perfect. The quantitative relationships show that the homeostatic equilibrium, centred around arterial pH of 7.4 and arterial carbon dioxide partial pressure of 40 mmHg, is attained when the ratio of alveolar ventilation to carbon dioxide flow ([Formula: see text]) is - 21.6. Several combinations, exploited during exercise, of pertinent respiratory variables are compatible with this equilibrium, allowing adjustment of oxygen flow to oxygen demand without its alteration. During exercise transients, the balance is broken, but the coupling of respiration to metabolism is preserved when, as during moderate exercise, the respiratory system responds faster than the metabolic pathways. At higher exercise intensities, early blood lactate accumulation suggests that the coupling of respiration to metabolism is transiently broken, to be re-established when, at steady state, blood lactate stabilizes at higher levels than resting. In the severe exercise domain, coupling cannot be re-established, so that anaerobic lactic metabolism also contributes to sustain energy demand, lactate concentration goes up and arterial pH falls continuously. The [Formula: see text] decreases below - 21.6, because of ensuing hyperventilation, while lactate keeps being accumulated, so that exercise is rapidly interrupted. The most extreme rupture of the homeostatic equilibrium occurs during breath-holding, because oxygen flow from ambient air to mitochondria is interrupted. No coupling at all is possible between respiration and metabolism in this case.

Dynamics of cardiovascular and baroreflex readjustments during a light-to-moderate exercise transient in humans.

PURPOSE: We hypothesised that, during a light-to-moderate exercise transient, compared to an equivalent rest-to-exercise transient, (1) a further baroreflex sensitivity (BRS) decrease would be slower, (2) no rapid heart rate (HR) response would occur, and (3) the rapid cardiac output (CO) response would have a smaller amplitude (A1). Hence, we analysed the dynamics of arterial baroreflexes and the HR and CO kinetics during rest-to-50 W (0-50 W) and 50-to-100 W (50-100 W) exercise transients. METHODS: 10 subjects performed three 0-50 W and three 50-100 W on a cycle ergometer. We recorded arterial blood pressure profiles (photo-plethysmography) and R-to-R interval (RRi, electrocardiography). The former were analysed to obtain beat-by-beat mean arterial pressure (MAP) and stroke volume (SV). CO was calculated as SV times HR. BRS was measured by modified sequence method. RESULTS: During 0-50 W, MAP transiently fell (- 9.0 ± 5.7 mmHg, p < 0.01) and BRS passed from 15.0 ± 3.7 at rest to 7.3 ± 2.4 ms mmHg-1 at 50 W (p < 0.01) promptly (first BRS sequence: 8.1 ± 4.6 ms mmHg-1, p < 0.01 vs. rest). During 50-100 W, MAP did not fall and BRS passed from 7.2 ± 2.6 at 50 W to 3.3 ± 1.3 ms mmHg-1 at 100 W (p < 0.01) slowly (first BRS sequence: 5.3 ± 3.1 ms mmHg-1, p = 0.07 vs. 50 W). A1 for HR was 9.2 ± 6.0 and 6.0 ± 4.5 min-1 in 0-50 W and 50-100 W, respectively (p = 0.19). The corresponding A1 for CO were 2.80 ± 1.54 and 0.91 ± 0.55 l∙min-1 (p < 0.01). CONCLUSION: During 50-100 W, with respect to 0-50 W, BRS decreased more slowly, in absence of a prompt pressure decrease. BRS decrease and rapid HR response in 50-100 W were unexpected and ascribed to possible persistence of some vagal tone at 50 W.

Effects of the Level and Duration of Mobilization Therapy in the Surgical ICU on the Loss of the Ability to Live Independently: An International Prospective Cohort Study.

OBJECTIVES: It is unclear whether early mobilization in the surgical ICU helps improve patients' functional recovery to a level that enables independent living. We assessed dose of mobilization (level + duration). We tested the research hypotheses that dose of mobilization predicts adverse discharge and that both duration of mobilization and maximum mobilization level predict adverse discharge. DESIGN: International, prospective cohort study. SETTING: Study conducted in five surgical ICUs at four different institutions. PATIENTS: One hundred fifty patients who were functionally independent before admission (Barthel Index ≥ 70) and who were expected to stay in the ICU for greater than or equal to 72 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mobilization was quantified daily, and treatments from all healthcare providers were included. We developed and used the Mobilization Quantification Score that quantifies both level and duration of mobilization. We assessed the association between the dose of mobilization (level + duration; exposure) and adverse discharge disposition (loss of the ability to live independently; primary outcome). There was wide variability in the dose of mobilization across centers and patients, which could not be explained by patients' comorbidity or disease severity. Dose of mobilization was associated with reduced risk of adverse discharge (adjusted odds ratio, 0.21; 95%CI, 0.09-0.50; p < 0.001). Both level and duration explained variance of adverse discharge (adjusted odds ratio, 0.28; 95% CI, 0.12-0.65; p = 0.003; adjusted odds ratio, 0.14; 95% CI, 0.06-0.36; p < 0.001, respectively). Duration compared with the level of mobilization tended to explain more variance in adverse discharge (area under the curve duration 0.73; 95% CI, 0.64-0.82; area under the curve mobilization level 0.68; 95% CI, 0.58-0.77; p = 0.10). CONCLUSIONS: We observed wide variability in dose of mobilization treatment applied, which could not be explained by patients' comorbidity or disease severity. High dose of mobilization is an independent predictor of patients' ability to live independently after discharge. Duration of mobilization sessions should be taken into account in future quality improvement and research projects.

A closed-loop approach to the study of the baroreflex dynamics during posture changes at rest and at exercise in humans.

We hypothesized that during rapid uptilting at rest, due to vagal withdrawal, arterial baroreflex sensitivity (BRS) may decrease promptly and precede the operating point (OP) resetting, whereas different kinetics are expected during exercise steady state, due to lower vagal activity than at rest. To test this, eleven subjects were rapidly (<2 s) tilted from supine (S) to upright (U) and vice versa every 3 min, at rest and during steady-state 50 W pedaling. Mean arterial pressure (MAP) was measured by finger cuff (Portapres) and R-to-R interval (RRi) by electrocardiography. BRS was computed with the sequence method both during steady and unsteady states. At rest, BRS was 35.1 ms·mmHg-1 (SD = 17.1) in S and 16.7 ms·mmHg-1 (SD = 6.4) in U (P < 0.01), RRi was 901 ms (SD = 118) in S and 749 ms (SD = 98) in U (P < 0.01), and MAP was 76 mmHg (SD = 11) in S and 83 mmHg (SD = 8) in U (P < 0.01). During uptilt, BRS decreased promptly [first BRS sequence was 19.7 ms·mmHg-1 (SD = 5.0)] and was followed by an OP resetting (MAP increase without changes in RRi). At exercise, BRS and OP did not differ between supine and upright positions [BRS was 7.7 ms·mmHg-1 (SD = 3.0) and 7.7 ms·mmHg-1 (SD = 3.5), MAP was 85 mmHg (SD = 13) and 88 mmHg (SD = 10), and RRi was 622 ms (SD = 61) and 600 ms (SD = 70), respectively]. The results support the tested hypothesis. The prompt BRS decrease during uptilt at rest may be ascribed to a vagal withdrawal, similarly to what occurs at exercise onset. The OP resetting may be due to a slower control mechanism, possibly an increase in sympathetic activity.

The Lombardy Emergency Medical System Faced with COVID-19: The Impact of Out-of-Hospital Outbreak.

OBJECTIVE: The Lombardy region was among the areas most affected by COVID-19 infection worldwide; the Lombardy Emergency Medical System (EMS) responded immediately to this emergency. We analyzed several critical aspects to understand what occurred in that region. METHODS: This retrospective study compares the events managed by the dispatch center and the characteristics of the patients transported to the hospital -age, sex, SpO2, deaths- managed by the EMS in Brescia and Bergamo provinces between March-April 2020 and March-April 2019. Ambulances' waiting time at the hospitals before discharging patients and the patients' severity at emergency department admission were also analyzed. RESULTS: EMS managed 37,340 events in March-April 2020, +51.5% versus 2019. "Breathing" or "Infective" events reported to the dispatch center increased more than ten-fold (OR 25.1, p < 0.0001) in March 2020 and two-fold in April 2020 compared to 2019 (OR 3, p < 0.0001). Deaths increased +246% (OR 1.7, p < 0.0001), and patients not transported to hospital +481% (OR 2.9, p < 0.0001) in March 2020 compared to 2019. In some hospitals, ambulances waited more than one hour before discharging the patients, and the emergency departments doubled the admission of critically ill patients. Transported patients for "Breathing" or "Infective" events were primarily males (OR 1.5, p < 0.0001). The patients had lower SpO2 in 2020 than in 2019 and they were younger. CONCLUSIONS: The Lombardy region experienced an unexpected outbreak in an extremely short timeframe and in a limited area. The EMS coped with this pandemic, covering an extremely higher number of requests, with a ten-fold increase in the number of events managed.

Vagal blockade suppresses the phase I heart rate response but not the phase I cardiac output response at exercise onset in humans.

PURPOSE: We tested the vagal withdrawal concept for heart rate (HR) and cardiac output (CO) kinetics upon moderate exercise onset, by analysing the effects of vagal blockade on cardiovascular kinetics in humans. We hypothesized that, under atropine, the φ1 amplitude (A1) for HR would reduce to nil, whereas the A1 for CO would still be positive, due to the sudden increase in stroke volume (SV) at exercise onset. METHODS: On nine young non-smoking men, during 0-80 W exercise transients of 5-min duration on the cycle ergometer, preceded by 5-min rest, we continuously recorded HR, CO, SV and oxygen uptake ([Formula: see text]O2) upright and supine, in control condition and after full vagal blockade with atropine. Kinetics were analysed with the double exponential model, wherein we computed the amplitudes (A) and time constants (τ) of phase 1 (φ1) and phase 2 (φ2). RESULTS: In atropine versus control, A1 for HR was strongly reduced and fell to 0 bpm in seven out of nine subjects for HR was practically suppressed by atropine in them. The A1 for CO was lower in atropine, but not reduced to nil. Thus, SV only determined A1 for CO in atropine. A2 did not differ between control and atropine. No effect on τ1 and τ2 was found. These patterns were independent of posture. CONCLUSION: The results are fully compatible with the tested hypothesis. They provide the first direct demonstration that vagal blockade, while suppressing HR φ1, did not affect φ1 of CO.

Baroreflex responses during dry resting and exercise apnoeas in air and pure oxygen.

PURPOSE: We analysed the characteristics of arterial baroreflexes during the first phase of apnoea (φ1). METHODS: 12 divers performed rest and exercise (30 W) apnoeas (air and oxygen). We measured beat-by-beat R-to-R interval (RRi) and mean arterial pressure (MAP). Mean RRi and MAP values defined the operating point (OP) before (PRE-ss) and in the second phase (φ2) of apnoea. Baroreflex sensitivity (BRS, ms·mmHg-1) was calculated with the sequence method. RESULTS: In PRE-ss, BRS was (median [IQR]): at rest, 20.3 [10.0-28.6] in air and 18.8 [13.8-25.2] in O2; at exercise 9.2[8.4-13.2] in air and 10.1[8.4-13.6] in O2. In φ1, during MAP decrease, BRS was lower than in PRE-ss at rest (6.6 [5.3-11.4] in air and 7.7 [4.9-14.3] in O2, p < 0.05). At exercise, BRS in φ1 was 6.4 [3.9-13.1] in air and 6.7 [4.1-9.5] in O2. After attainment of minimum MAP (MAPmin), baroreflex resetting started. After attainment of minimum RRi, baroreflex sequences reappeared. In φ2, BRS at rest was 12.1 [9.6-16.2] in air, 12.9 [9.2-15.8] in O2. At exercise (no φ2 in air), it was 7.9 [5.4-10.7] in O2. In φ2, OP acts at higher MAP values. CONCLUSION: In apnoea φ1, there is a sudden correction of MAP fall via baroreflex. The lower BRS in the earliest φ1 suggests a possible parasympathetic mechanism underpinning this reduction. After MAPmin, baroreflex resets, displacing its OP at higher MAP level; thus, resetting may not be due to central command. After resetting, restoration of BRS suggests re-establishment of vagal drive.

Breath holding as an example of extreme hypoventilation: experimental testing of a new model describing alveolar gas pathways.

NEW FINDINGS: What is the central question of this study? We modelled the alveolar pathway during breath holding on the hypothesis that it follows a hypoventilation loop on the O2 -CO2 diagram. What is the main finding and its importance? Validation of the model was possible within the range of alveolar gas compositions compatible with consciousness. Within this range, the experimental data were compatible with the proposed model. The model and its characteristics might allow predictions of alveolar gas composition whenever the alveolar ventilation goes to zero; for example, static and dynamic breath holding at the surface or during ventilation/intubation failure in anaesthesia. ABSTRACT: According to the hypothesis that alveolar partial pressures of O2 and CO2 during breath holding (BH) should vary following a hypoventilation loop, we modelled the alveolar gas pathways during BH on the O2 -CO2 diagram and tested it experimentally during ambient air and pure oxygen breathing. In air, the model was constructed using the inspired and alveolar partial pressures of O2 ( PIO2 and PAO2 , respectively) and CO2 ( PICO2 and PACO2 , respectively) and the steady-state values of the pre-BH respiratory exchange ratio (RER). In pure oxygen, the model respected the constraint of PACO2=-PAO2+PIO2 . To test this, 12 subjects performed several BHs of increasing duration and one maximal BH at rest and during exercise (30 W cycling supine), while breathing air or pure oxygen. We measured gas flows, PAO2 and PACO2 before and at the end of all BHs. Measured data were fitted through the model. In air, PIO2  = 150 ± 1 mmHg and PICO2  = 0.3 ± 0.0 mmHg, both at rest and at 30 W. Before BH, steady-state RER was 0.83 ± 0.16 at rest and 0.77 ± 0.14 at 30 W; PAO2  = 107 ± 7 mmHg at rest and 102 ± 8 mmHg at 30 W; and PACO2  = 36 ± 4 mmHg at rest and 38 ± 3 mmHg at 30 W. By model fitting, we computed the RER during the early phase of BH: 0.10 [95% confidence interval (95% CI) = 0.08-0.12] at rest and 0.13 (95% CI = 0.11-0.15) at 30 W. In oxygen, model fitting provided PIO2 : 692 (95% CI = 688-696) mmHg at rest and 693 (95% CI = 689-698) mmHg at 30 W. The experimental data are compatible with the proposed model, within its physiological range.

Impact of a posttraumatic cerebral infarction on outcome in patients with TBI: the Italian multicenter cohort INCEPT study.

BACKGROUND: Post-traumatic cerebral infarction (PTCI) is common after traumatic brain injury (TBI). It is unclear what the occurrence of a PTCI is, how it impacts the long-term outcome, and whether it adds incremental prognostic value to established outcome predictors. METHODS: This was a prospective multicenter cohort study of moderate and severe TBI patients. The primary objective was to evaluate if PTCI was an independent risk factor for the 6-month outcome assessed with the Glasgow Outcome Scale (GOS). We also assessed the PTCI occurrence and if it adds incremental value to the International Mission for Prognosis and Clinical Trial design in TBI (IMPACT) core and extended models. RESULTS: We enrolled 143 patients, of whom 47 (32.9%) developed a PTCI. In the multiple ordered logistic regression, PTCI was retained in both the core and extended IMPACT models as an independent predictor of the GOS. The predictive performances increased significantly when PTCI was added to the IMPACT core model (AUC = 0.73, 95% C.I. 0.66-0.82; increased to AUC = 0.79, 95% CI 0.71-0.83, p = 0.0007) and extended model (AUC = 0.74, 95% C.I. 0.65-0.81 increased to AUC = 0.80, 95% C.I. 0.69-0.85; p = 0.00008). Patients with PTCI showed higher ICU mortality and 6-month mortality, whereas hospital mortality did not differ between the two groups. CONCLUSIONS: PTCI is a common complication in patients suffering from a moderate or severe TBI and is an independent risk factor for long-term disability. The addition of PTCI to the IMPACT core and extended predictive models significantly increased their performance in predicting the GOS. TRIAL REGISTRATION: The present study was registered in ClinicalTrial.gov with the ID number NCT02430324.

Determination of Imminent Brain Death Using the Full Outline of Unresponsiveness Score and the Glasgow Coma Scale: A Prospective, Multicenter, Pilot Feasibility Study.

PURPOSE: To evaluate the accuracy of the imminent brain death (IBD) diagnosis in predicting brain death (BD) by daily assessment of the Full Outline of Unresponsiveness (FOUR) score and the Glasgow Coma Scale (GCS) with the assessment of brain stem reflexes. MATERIALS AND METHODS: Prospective multicenter pilot study carried out in 5 adult Italian intensive care units (ICUs). Imminent brain death was established when the FOUR score was 0 (IBD-FOUR) or the GCS score was 3 and at least 3 among pupillary light, corneal, pharyngeal, carinal, oculovestibular, and trigeminal reflexes were absent (IBD-GCS). RESULTS: A total of 219 neurologic evaluations were performed in 40 patients with deep coma at ICU admission (median GCS 3). Twenty-six had a diagnosis of IBD-FOUR, 27 of IBD-GCS, 14 were declared BD, and 9 were organ donors. The mean interval between IBD diagnosis and BD was 1.7 days (standard deviation [SD] 2.0 days) using IBD-FOUR and 2.0 days (SD 1.96 days) using IBD-GCS. Both FOUR and GCS had 100% sensitivity and low specificity (FOUR: 53.8%; GCS: 50.0%) in predicting BD. CONCLUSIONS: Daily IBD evaluation in the ICU is feasible using FOUR and GCS with the assessment of brain stem reflexes. Both scales had 100% sensitivity in predicting IBD, but FOUR may be preferable since it incorporates the pupillary, corneal, and cough reflexes and spontaneous breathing that are easily assessed in the ICU.

The IN-PANCIA Study: Clinical Evaluation of Gastrointestinal Dysfunction and Failure, Multiple Organ Failure, and Levels of Citrulline in Critically Ill Patients.

PURPOSE: Gastrointestinal dysfunction and failure (GID and GIF) in critically ill patients are a common, relevant, and underestimated complications in ICU patients. The aims of this study were (1) to determine plasmatic levels of citrulline, glutamine, and arginine as markers of GID/GIF in critically ill patients with or without GID/GIF with or without multiple organ failure (MOF) and (2) to assess the role of intra-abdominal hypertension in these patient groups. MATERIALS AND METHODS: This is a 1-year, monocentric (Italian hospital), prospective observational study. Inclusion criteria were adult patients with GID/GIF, with or without MOF. The GIF score was daily evaluated in 39 critically ill patients. Amino acids were measured at the time of GID or GIF. RESULTS: We enrolled 39 patients. Nine patients developed GID and 7 GIF; 6 of patients with GID/GIF developed MOF. Citrulline was lower (P < .001) in patients with GID/GIF (11.3 [4.4] µmol/L), compared to patients without GID/GIF (22.4 [6.8] µmol/L); likewise, glutamine was lower in patients with GID/GIF, whereas arginine was nonstatistically different between the 2 groups. Intra-abdominal pressure was higher in patients affected by MOF (13.0 [2.2] mm Hg) than in patients with GIF/GID without MOF (9.6 [2.6] mm Hg) and compared to patients without GID/GIF (7.2 [2.1] mm Hg). CONCLUSIONS: Both GID and GIF in critically ill patients are associated with low levels of citrulline and glutamine, which could be considered as markers of small bowel dysfunction. The higher the GIF score, the lower the citrulline levels. Patients affected by MOF had higher levels of intra-abdominal pressure.

Effect of Lower Body Negative Pressure on Phase I Cardiovascular Responses at Exercise Onset.

We hypothesised that vagal withdrawal and increased venous return interact in determining the rapid cardiac output (CO) response (phase I) at exercise onset. We used lower body negative pressure (LBNP) to increase blood distribution to the heart by muscle pump action and reduce resting vagal activity. We expected a larger increase in stroke volume (SV) and smaller for heart rate (HR) at progressively stronger LBNP levels, therefore CO response would remain unchanged. To this aim ten young, healthy males performed a 50 W exercise in supine position at 0 (Control), -15, -30 and -45 mmHg LBNP exposure. On single beat basis, we measured HR, SV, and CO. Oxygen uptake was measured breath-by-breath. Phase I response amplitudes were obtained applying an exponential model. LBNP increased SV response amplitude threefold from Control to -45 mmHg. HR response amplitude tended to decrease and prevented changes in CO response. The rapid response of CO explained that of oxygen uptake. The rapid SV kinetics at exercise onset is compatible with an increased venous return, whereas the vagal withdrawal conjecture cannot be dismissed for HR. The rapid CO response may indeed be the result of two independent yet parallel mechanisms, one acting on SV, the other on HR.

Experimental validation of the 3-parameter critical power model in cycling.

PURPOSE: The three-parameter model of critical power (3-p) implies that in the severe exercise intensity domain time to exhaustion (Tlim) decreases hyperbolically with power output starting from the power asymptote (critical power, wcr) and reaching 0 s at a finite power limit (w0) thanks to a negative time asymptote (k). We aimed to validate 3-p for short Tlim and to test the hypothesis that w0 represents the maximal instantaneous muscular power. METHODS: Ten subjects performed an incremental test and nine constant-power trials to exhaustion on an electronically braked cycle ergometer. All trials were fitted to 3-p by means of non-linear regression, and those with Tlim greater than 2 min also to the 2-parameter model (2-p), obtained constraining k to 0 s. Five vertical squat jumps on a force platform were also performed to determine the single-leg (i.e., halved) maximal instantaneous power. RESULTS: Tlim ranged from 26 ± 4 s to 15.7 ± 4.9 min. In 3-p, with respect to 2-p, wcr was identical (177 ± 26 W), while curvature constant W' was higher (17.0 ± 4.3 vs 15.9 ± 4.2 kJ, p < 0.01). 3-p-derived w0 was lower than single-leg maximal instantaneous power (1184 ± 265 vs 1554 ± 235 W, p < 0.01). CONCLUSIONS: 3-p is a good descriptor of the work capacity above wcr up to Tlim as short as 20 s. However, since there is a discrepancy between estimated w0 and measured maximal instantaneous power, a modification of the model has been proposed.

Daptomycin Plasma and CSF Levels in Patients with Healthcare-Associated Meningitis.

BACKGROUND: There are currently few data concerning the cerebrospinal fluid (CSF) penetration of daptomycin in patients with healthcare-associated meningitis. This study aims (1) to better characterize the pharmacokinetics of daptomycin in humans during a 7-day intravenous (IV) therapy course, and (2) to study the penetration of daptomycin in the CSF after IV infusion at the dose of 10 mg/kg. RESULTS: In this prospective observational study, we enrolled nine patients with an implanted external ventricular drainage and a diagnosis of a healthcare-associated meningitis. Daptomycin was administered at 10 mg/kg for a maximum of 7 days. The pharmacokinetic of daptomycin was studied using a two-compartment population/pharmacokinetic (POP/PK) model and by means of a nonlinear mixed effects modeling approach. A large inter-individual variability in plasma area under the curve (Range: 574.7-1366.3 h mg/L), paralleled by high-peak plasma concentration (Cmax) (all values > 60 mg/L), was noted. The inter-individual variability of CSF-AUC although significant (range: 1.17-6.81 h mg/L) was narrower than previously reported and with a late occurrence of CSF-Cmax (range: 6.04-9.54 h). The terminal half-life between plasma and CSF was similar. tmax values in CSF did not show a high inter-individual variability, and the fluctuations of predicted CSF concentrations were minimal. The mean value for daptomycin penetration obtained from our model was 0.45%. CONCLUSIONS: Our POP/PK model was able to describe the pharmacokinetics of daptomycin in both plasma and CSF, showing that daptomycin (up to 7 days at 10 mg/kg) has minimal penetration into central nervous system. Furthermore, the observed variability of AUC, tmax and predicted concentration in CSF was lower than what previously reported in the literature. Based on the present findings, it is unlikely that daptomycin could reach CSF concentrations high enough to have clinical efficacy; this should be tested in future studies.

Worldwide Survey of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Drugs, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Empowerment" (ABCDEF) Bundle.

OBJECTIVES: To assess the knowledge and use of the Assessment, prevention, and management of pain; spontaneous awakening and breathing trials; Choice of analgesia and sedation; Delirium assessment; Early mobility and exercise; and Family engagement and empowerment (ABCDEF) bundle to implement the Pain, Agitation, Delirium guidelines. DESIGN: Worldwide online survey. SETTING: Intensive care. INTERVENTION: A cross-sectional online survey using the Delphi method was administered to intensivists worldwide, to assess the knowledge and use of all aspects of the ABCDEF bundle. MEASUREMENT AND MAIN RESULTS: There were 1,521 respondents from 47 countries, 57% had implemented the ABCDEF bundle, with varying degrees of compliance across continents. Most of the respondents (83%) used a scale to evaluate pain. Spontaneous awakening trials and spontaneous breathing trials are performed in 66% and 67% of the responder ICUs, respectively. Sedation scale was used in 89% of ICUs. Delirium monitoring was implemented in 70% of ICUs, but only 42% used a validated delirium tool. Likewise, early mobilization was "prescribed" by most, but 69% had no mobility team and 79% used no formal mobility scale. Only 36% of the respondents assessed ICU-acquired weakness. Family members were actively involved in 67% of ICUs; however, only 33% used dedicated staff to support families and only 35% reported that their unit was open 24 hr/d for family visits. CONCLUSIONS: The current implementation of the ABCDEF bundle varies across individual components and regions. We identified specific targets for quality improvement and adoption of the ABCDEF bundle. Our data reflect a significant but incomplete shift toward patient- and family-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines.