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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.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).During 2020, there was a reduction in CPRs performed by bystanders (odds ratio [OR] = 0.936 [95% confidence interval (CICOVID-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.

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 ($${\dot{V}}_{A}/{\dot{V}}_{R}{CO}_{2}$$ V ˙ A / V ˙ R CO 2 ) 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 $${\dot{V}}_{A}/{\dot{V}}_{R}{CO}_{2}$$ V ˙ A / V ˙ R CO 2 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.

Objectives: During the coronavirus disease 2019 pandemic, emergency medical services (EMSs) were among the most affected; in fact, there were delays in rescue and changes in time-dependent disease networks. The aim of the study is to understand the impact of COVID-19 on the time-dependent trauma network in the Lombardy region. Methods: A retrospective analysis on major trauma was performed by analysing all records saved in the EmMa database from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Age, gender, time to first emergency vehicle on scene and mission duration were collected. Results: In 2020, compared to 2019, there was a reduction in major trauma diagnoses in March and April, during the first lockdown, OR 0.59 (95% CI 0.49–0.70; p < 0.0001), and a reduction in road accidents and accidents at work, while injuries related to falls from height and violent events increased. There was no significant increase in the number of deaths in the prehospital setting, OR 1.09 (95% CI 0.73–1.30; p = 0.325). Conclusions: The COVID-19 pandemic has changed the epidemiology of major trauma, but in the Lombardy region there was no significant change in mortality in the out-of-hospital setting.

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 ($$ \dot{V} $$ V ˙ 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.

Background:During the COVID-19 pandemic, a total lockdown was enforced all over Italy starting on March 9, 2020. This resulted in the shrinking of economic activities. In addition, all formal occupational security-training courses were halted, among them the 81/08 law lectures and Basic Life Support-Defibrillation (BLS-D) laypersons training courses. The aim of this study was to evaluate the impact of the pandemic on BLS-D laypersons training courses in the Lombardy region.Methods:BLS-D training courses records for the Lombardy region were analyzed. The analysis was conducted from 2016 to 2020 as part of the Hippo project.Results:In the period between 2017 and 2019, BLS-D trained laypersons kept increasing, moving from 53500 trained individuals up to 74700. In 2020, a stark reduction was observed with only 22160 individuals trained. Formal courses were not halted completely during 2020. Still, in the months available for training, the number of individuals enrolled showed a sharp 50% reduction.Conclusions:Laypersons training courses for emergency management are a fundamental component of primary prevention practice. The 81/08 and 158/12 Italian laws have decreed this practice mandatory in the workplace. Following the enforcement of the lockdown and the subsequent interruption of emergency management courses, efforts will be necessary to re-establish and guarantee the high quality training of the pre-pandemic period.

Eighth of March 2020, the Italian government introduced a national lockdown to counter the exponential increase in the number of COVID-19 cases; this decision avoided putting a strain on the health system. During the lockdown all non-essential services were stopped and a "stay at home" order was imposed. The purpose is to evaluate the impact of COVID-19 lockdown on Emergency Department (ED) visits due to work-related traumas in the Lombardy region. We performed a retrospective analysis on trauma admissions to the ED registered through the regional portal (EUOL), from 1st January 2019 to 31st December 2019 and from 1st January 2020 to 31st December 2020. The number of ED admissions for traumatic injury and work-related traumas dropped by 32% between 2019 and 2020. A remarkable reduction of work-related traumas was recorded during the two pandemic waves, from March to June and in October and November. The percentage of patient in critical condition in ED slightly raised. These results are probably a consequence of the unprecedented measures imposed by the Italian government to cope with the spread of COVID-19, with important implications for work contexts. This analysis should be considered to optimise the organisation of the emergency system in other critical scenarios. We speculate that the different epidemiology of occupational injuries during the lockdown period is a consequence of smart-working policies that can be held responsible for the drastic reduction of work-related traumas.

Introduction Measuring physiological parameters at depth is an emergent challenge for athletic training, diver's safety and biomedical research. Recent advances in wearable sensor technology made this challenge affordable; however, its impact on breath-hold diving has never been comprehensively discussed. Methods We performed a systematic review of the literature in order to assess what types of sensors are available or suitable for human breath-hold diving, within the two-fold perspective of safety and athletic performance. Results In the 52 studies identified, sensed physiological variables were: electrocardiogram, body temperature, blood pressure, peripheral oxygen saturation, interstitial glucose concentration, impedance cardiography, heart rate, body segment inertia and orientation. Conclusions Limits and potential of each technology are separately reviewed. Inertial sensor technology and transmission pulse oximetry could produce the greatest impact on breath-hold diving performances in the future.

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 −1 at 50 W (p −1, p −1 at 100 W (p −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 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.

Background The Lombardy region has been one of the Italian regions most affected by the COVID-19 pandemic in 2020, with 22.7% of total Italian cases and 33.9% of total deaths. The emergency healthcare system was under deep stress throughout the period under consideration due to the admission of COVID-19 patients to the Emergency Department (ED) and had to be thoroughly reorganized. Methods We performed a retrospective descriptive analysis of patients admitted into the ED recorded in the Lombardy online regional portal called EUOL. We compared the data registered in the EUOL with the patients admitted to the EDs from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Results The number of admissions to the ED decreased by 32.5% in 2020 compared to 2019, reaching the lowest number in March and April. However, the percentage of patients hospitalised after ED significantly increased in 2020 compared to 2019 (OR 1.47, p < 0.0001), reflecting the management of patients with a more severe clinical condition. Indeed, the number of patients classified as red or yellow codes at hospital admission was significantly higher in 2020 than in 2019 (p < 0.0001). Moreover, more patients arrived at the ED by ambulance in 2020 (21.7% in 2020 versus 15.1% in 2019. OR 1.56, p < 0.0001), with more than 35% of patients transported by ambulance in March and April 2020. Conclusions Our results showed, on the one hand, inappropriate visits to the EDs by non-emergency and low complex cases in 2019 before the pandemic and, on the other hand, they also highlighted that patients in critical condition were reluctant to visit the ED due to the fear of getting infected. This analysis showed that EMS played a crucial role in the overall public health impact of the COVID-19 pandemic, increasing the percentage of patients transported to the hospital with a severe clinical condition, reorganizing and allocating resources to the areas that were most affected during the pandemic. Key messages This is a descriptive analysis of the public health impact of the COVID-19 pandemic on the admission to Emergency Departments in 2020. Our results underline the need to monitor the pandemic’s evolution in order to reorganize the hospitals that admitted the COVID-19 patients.

Background The Lombardy region has been the Italian region most affected by the coronavirus disease 2019 (COVID-19) pandemic in 2020. The emergency healthcare system was under deep stress throughout the past year due to the admission of COVID-19 patients to the emergency department (ED) and had to be thoroughly reorganized. Methods We performed a retrospective descriptive analysis of patients admitted into the ED recorded in the Lombardy online regional portal called EUOL (Emergenza e Urgenza OnLine). We compared the data registered in the EUOL with the patients admitted to the EDs from 1 January 2019 to 31 December 2019 and from 1 January 2020 to 31 December 2020. Results The number of admissions to the ED decreased by 32.5% in 2020 compared with 2019, reaching the lowest number in March and April. However, the percentage of patients hospitalized after ED significantly increased in 2020 compared with 2019 (P Conclusions This analysis showed the importance of monitoring the pandemic’s evolution in order to treat more critically ill patients, despite a lower number of patients.

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 (−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 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.This retrospective study compares the events managed by the dispatch center and the characteristics of the patients transported to the hospital -age, sex, SpOEMS 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 SpOThe 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.

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, ẇcr) and reaching 0 s at a finite power limit (ẇ0) thanks to a negative time asymptote (k). We aimed to validate 3-p for short Tlim and to test the hypothesis that ẇ0 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, ẇcr 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 ẇ0 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 ẇcr up to Tlim as short as 20 s. However, since there is a discrepancy between estimated ẇ0 and measured maximal instantaneous power, a modification of the model has been proposed.

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.

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 ( P I O 2 and P A O 2 , respectively) and CO2 ( P IC O 2 and P AC O 2 , respectively) and the steady-state values of the pre-BH respiratory exchange ratio (RER). In pure oxygen, the model respected the constraint of P AC O 2 = - P A O 2 + P I O 2 . 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, P A O 2 and P AC O 2 before and at the end of all BHs. Measured data were fitted through the model. In air, P I O 2 = 150 ± 1 mmHg and P IC O 2 = 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; P A O 2 = 107 ± 7 mmHg at rest and 102 ± 8 mmHg at 30 W; and P AC O 2 = 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 P I O 2 : 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.

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 2. 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.

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.

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.

Intensive care unit–acquired weakness (ICU-AW) is the most common neuromuscular impairment in critically ill patients. We discuss critical aspects of ICU-AW that have not been completely defined or that are still under discussion. Critical illness polyneuropathy, myopathy, and muscle atrophy contribute in various proportions to ICU-AW. Diagnosis of ICU-AW is clinical and is based on Medical Research Council sum score and handgrip dynamometry for limb weakness and recognition of a patient’s ventilator dependency or difficult weaning from artificial ventilation for diaphragmatic weakness (DW). ICU-AW can be caused by a critical illness polyneuropathy, a critical illness myopathy, or muscle disuse atrophy, alone or in combination. Its diagnosis requires both clinical assessment of muscle strength and complete electrophysiological evaluation of peripheral nerves and muscles. The peroneal nerve test (PENT) is a quick simplified electrophysiological test with high sensitivity and good specificity that can be used instead of complete electrophysiological evaluation as a screening test in non-cooperative patients. DW, assessed by bilateral phrenic nerve magnetic stimulation or diaphragm ultrasound, can be an isolated event without concurrent limb muscle involvement. Therefore, it remains uncertain whether DW and limb weakness are different manifestations of the same syndrome or are two distinct entities. Delirium is often associated with ICU-AW but a clear correlation between these two entities requires further studies. Artificial nutrition may have an impact on ICU-AW, but no study has assessed the impact of nutrition on ICU-AW as the primary outcome. Early mobilization improves activity limitation at hospital discharge if it is started early in the ICU, but beneficial long-term effects are not established. Determinants of ICU-AW can be many and can interact with each other. Therefore, future studies assessing early mobilization should consider a holistic patient approach with consideration of all components that may lead to muscle weakness.

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. 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%. 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.

Background: Post-traumatic cerebral infarction (PTCI) is common in patients dying after a 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 admitted to nine Italian intensive care units (ICUs). 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. Findings: We enrolled 143 patients; 47 (32·9%) developed a PTCI for a total of 94. The mean (SD) onset time of a PTCI was 6·2 (11·4). 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 a PTCI showed higher ICU mortality (10 patients [21·3%] vs one patient [1·0%], p

To check whether the evolution of alveolar pressures of O2 (PAO2) and CO2 (PACO2) explains the cardiovascular responses to apnoea, eight divers performed resting apnoeas of increasing duration in air and in O2. We measured heart rate (fH), arterial pressure (AP), and peripheral resistances (TPR) beat-by-beat, PAO2 and PACO2 at the end of each apnoea. The three phases of the cardiovascular response to apnoea were observed. In O2, TPR increase (9 ± 4 mmHg min l−1) and fH decrease (-11 ± 8 bpm) were lower than in air (15 ± 5 mmHg min l−1 and -28 ± 13 bpm, respectively). At end of maximal apnoeas in air, PAO2 and PACO2 were 50 ± 9 and 48 ± 5 mmHg, respectively; corresponding values in O2 were 653 ± 8 mmHg and 55 ± 5 mmHg. At end of phase II, PAO2 and PACO2 in air were 90 ± 13 mmHg and 42 ± 4 mmHg respectively; corresponding values in O2 were 669 ± 7 mmHg and 47 ± 6 mmHg. The PACO2 increase may trigger the AP rise in phase III.

The baroreflex system is a complex mechanism for short-term regulation of arterial blood pressure, involving the heart rate (HR), the heart contractility and the vascular tone in its efferent branches. The study of arterial baroreflexes relies on two different experimental approaches. On one hand, the closed-loop approach analyses the mutual relationship between HR and arterial blood pressure, both in steady state and in dynamic conditions. This article is protected by copyright. All rights reserved.

INTRODUCTION The carbon monoxide (CO) rebreathing method used for the determination of haemoglobin mass (Hbmass ) is associated with blood sample analysis (in this study: Radiometer ABL800). As an alternative hereto the aim of the present study was to evaluate the use of a portable and non-invasive CO pulse oximeter (Rad-57). METHOD With simultaneous determination of CO in the circulation by ABL800 (%HbCO) and Rad-57 (SpCO), Hbmass and blood volume (BV) were determined in duplicates in 24 volunteers. Percentage of typical errors (%TE) within methods and linear correlations between the two procedures were computed. RESULTS Hbmass (Rad-57 = 798 ± 230 g; ABL800 = 781 ± 192 g) and BV (Rad-57 = 5700 ± 1373 ml; ABL800 = 5581 ± 1096 ml) were similar between methods. However, the %TE for Hbmass was higher (P 905 g and BV > 6193 ml. CONCLUSION Assessment of SpCO by Rad-57 resulted in considerably less precise determinations of Hbmass and BV, especially for high values. Thus, non-invasive assessment of Hbmass and BV cannot be recommended for scientific purposes, but may nonetheless be useful in clinical settings.

If, as postulated, the end of the steady state phase (φ2) of cardiovascular responses to apnoea corresponds to the physiological breaking point, then we may hypothesize that φ2 should become visible if exercise apnoeas are performed in pure oxygen. We tested this hypothesis on 9 professional divers by means of continuous recording of blood pressure (BP), heart rate (fH), stroke volume (QS), and arterial oxygen saturation (SpO2) during dry maximal exercising apnoeas in ambient air and in oxygen. Apnoeas lasted 45.0 ± 16.9 s in air and 77.0 ± 28.9 s in oxygen (p

Cardiovascular responses during resting apnoea include three phases: (1) a dynamic phase of rapid changes, lasting at most 30 s; (2) a subsequent steady phase; and (3) a further dynamic phase, with a continuous decrease in heart rate (HR) and an increase in blood pressure. The interpretation was that the end of the steady phase corresponds to the physiological apnoea breaking point. This being so, during exercise apnoeas, the steady phase would be shorter, and the rate of cardiovascular changes in the subsequent unsteady phase would be faster than at rest. To test these hypotheses, we measured beat-by-beat systolic (SBP), diastolic, and mean blood pressures (MBP), HR, and stroke volume (SV) in six divers during dry resting (duration 239.4 ± 51.6 s) and exercise (30 W on cycle ergometer, duration 88.2 ± 20.9 s) maximal apnoeas, and we computed cardiac output ( $$\dot{Q}$$ ) and total peripheral resistance (TPR). Compared to control, at the beginning of resting (R1) and exercising (E1) apnoeas, SBP and MBP decreased and HR increased. SV and $$\dot{Q}$$ fell, so that TPR remained unchanged. At rest, HR, SV, $$\dot{Q}$$ , and SBP were stable during the subsequent phase; this steady phase was missing in exercise apnoeas. Subsequently, at rest (R3) and at exercise (E2), HR decreased and SBP increased continuously. SV returned to control values. Since $$\dot{Q}$$ remained unchanged, TPR grew. The lack of steady phase during exercise apnoeas suggests that the conditions determining R3 were already attained at the end of E1. This being so, E2 would correspond to R3.

A new analysis of the relationship between cardiac output (Q˙) and oxygen consumption V˙O2 is presented (Q˙-V˙O2 diagram). Data from different sources in the literature have been used for validation in three conditions: exercise and rest in normoxia, and exercise in hypoxia. The effects of changes in arterial oxygen concentration CaO2 on Q˙ are discussed, as well as the effects of predominant sympathetic or vagal stimulation. Differences appear depending on whether CaO2 is varied by means of changes in blood haemoglobin concentration or changes in arterial oxygen saturation. The present Q˙-V˙O2 diagram allows comprehensive description of oxygen transport in exercising humans; it expands applicability of the historical Q˙-V˙O2 relationship to include CaO2 variations; it opens new pathways for understanding underlying mechanisms; it allows computation of Q˙ from CaO2 and V˙O2 measurements, when Q˙ cannot be measured.

Background Untimely diagnosis of intracranial hypertension may lead to delays in therapy and worsening of outcome. Transcranial Doppler (TCD) detects variations in cerebral blood flow velocity which may correlate with intracranial pressure (ICP). We investigated if intracranial hypertension can be accurately excluded through use of TCD. Method This was a multicenter prospective pilot study in patients with acute brain injury requiring invasive ICP (ICPi) monitoring. ICP estimated with TCD (ICPtcd) was compared with ICPi in three separate time frames: immediately before ICPi placement, immediately after ICPi placement, and 3 hours following ICPi positioning. Sensitivity and specificity, and concordance correlation coefficient between ICPi and ICPtcd were calculated. Receiver operating curve (ROC) and the area under the curve (AUC) analyses were estimated after measurement averaging over time. Results A total of 38 patients were enrolled, and of these 12 (31.6%) had at least one episode of intracranial hypertension. One hundred fourteen paired measurements of ICPi and ICPtcd were gathered for analysis. With dichotomized ICPi (≤20 mmHg vs >20 mmHg), the sensitivity of ICPtcd was 100%; all measurements with high ICPi (>20 mmHg) also had a high ICPtcd values. Bland-Altman plot showed an overestimation of 6.2 mmHg (95% CI 5.08–7.30 mmHg) for ICPtcd compared to ICPi. AUC was 96.0% (95% CI 89.8–100%) and the estimated best threshold was at ICPi of 24.8 mmHg corresponding to a sensitivity 100% and a specificity of 91.2%. Conclusions This study provides preliminary evidence that ICPtcd may accurately exclude intracranial hypertension in patients with acute brain injury. Future studies with adequate power are needed to confirm this result.

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-andfamily-centered ICU care in accordance with the Pain, Agitation, Delirium guidelines

Introduction We tested the hypothesis that the alveolar gas composition at the transition between the steady phase II (φ2) and the dynamic phase III (φ3) of the cardiovascular response to apnoea may lay on the physiological breaking point curve (Lin et al., 1974). Methods Twelve elite divers performed maximal and φ2-interrupted apnoeas, in air and pure oxygen. We recorded beat-by-beat arterial blood pressure and heart rate; we measured alveolar oxygen and carbon dioxide pressures (P A O 2 and P A CO 2 , respectively) before and after apnoeas; we calculated the P A CO 2 difference between the end and the beginning of apnoeas (ΔP A CO 2 ). Results Cardiovascular responses to apnoea were similar compared to previous studies. P A O 2 and P A CO 2 at the end of φ2-interrupted apnoeas, corresponded to those reported at the physiological breaking point . For maximal apnoeas, P A CO 2 was less than reported by Lin et al. (1974). ΔP A CO 2 was higher in oxygen than in air. Conclusions The transition between φ2 and φ3 corresponds indeed to the physiological breaking point . We attribute this transition to ΔP A CO 2 , rather than the absolute P A CO 2 values, both in air and oxygen apnoeas.

We tested the linear critical power ( $$\dot{w}_{\text{cr}}$$ ) model for discrete incremental ramp exercise implying recovery intervals at the end of each step. Seven subjects performed incremental (power increment 25 W) stepwise ramps to subject’s exhaustion, with recovery intervals at the end of each step. Ramps’ slopes (S) were 0.83, 0.42, 0.28, 0.21, and 0.08 W s−1; recovery durations (t r) were 0 (continuous stepwise ramps), 60, and 180 s (discontinuous stepwise ramps). We determined the energy store component (W′), the peak power ( $$\dot{w}_{\text{peak}}$$ ), and $$\dot{w}_{\text{cr}}$$ . When t r = 0 s, $$\dot{w}_{\text{cr}}$$ and W′ were 187 ± 26 W and 14.5 ± 5.8 kJ, respectively. When t r = 60 or 180 s, the model for ramp exercise provided inconsistent $$\dot{w}_{\text{cr}}$$ values. A more general model, implying a quadratic $$\dot{w}_{\text{peak}}$$ versus $$\sqrt S$$ relationship, was developed. This model yielded, for t r = 60 s, $$\dot{w}_{\text{cr}}$$ = 189 ± 48 W and W′ = 18.6 ± 17.8 kJ, and for t r = 180 s, $$\dot{w}_{\text{cr}}$$ = 190 ± 34 W, and W′ = 16.4 ± 16.7 kJ. These $$\dot{w}_{\text{cr}}$$ and W′ did not differ from the corresponding values for t r = 0 s. Nevertheless, the overall amount of energy sustaining work above $$\dot{w}_{\text{cr}}$$ , due to energy store reconstitution during recovery intervals, was higher the longer t r, whence higher $$\dot{w}_{\text{peak}}$$ values. The linear $$\dot{w}_{\text{cr}}$$ model for ramp exercise represents a particular case (for t r = 0 s) of a more general model, accounting for energy resynthesis following oxygen deficit payment during recovery.

PURPOSE: The dynamics of the postulated phenomenon of exercise baroreflex resetting is poorly understood, but can be investigated using closed-loop procedures. To shed light on some mechanisms and temporal relationships participating in the resetting process, we studied the time course of the relationship between the R-R interval (RRi) and arterial pressure with a closed-loop approach. METHODS: On ten young volunteers at rest and during light exercise in supine and upright position, we continuously determined, on single-beat basis, RRi (electrocardiography), and arterial pressure (non-invasive finger pressure cuff). From pulse pressure profiles, we determined cardiac output (CO) by Modelflow, computed mean arterial pressure (MAP), and calculated total peripheral resistance (TPR). RESULTS: At exercise start, RRi was lower than in quiet rest. As exercise started, MAP fell to a minimum (MAPm) of 72.8 ± 9.6 mmHg upright and 73.9 ± 6.2 supine, while RRi dropped. The initial RRi versus MAP relationship was linear, with flatter slope than resting baroreflex sensitivity, in both postures. TPR fell and CO increased. After MAPm, RRi and MAP varied in opposite direction toward exercise steady state, with further CO increase. CONCLUSION: These results suggest that, initially, the MAP fall was corrected by a RRi reduction along a baroreflex curve, with lower sensitivity than at rest, but eventually in the same pressure range as at rest. After attainment of MAPm, a second phase started, where the postulated baroreflex resetting might have occurred. In conclusion, the change in baroreflex sensitivity and the resetting process are distinct phenomena, under different control systems.

Intensive care unit (ICU)–acquired weakness is one of the most frequent complications after ICU admission. The resulting sequelae may occur even years after discharge from the ICU; unfortunately, there are scanty data about effectively treatment that can counteract the muscle deconditioning. Neuromuscular electrical stimulation (NMES), widely used for several purposes, aims to maintain muscle trophism and function in critically ill patients. NMES may also be used as a diagnostic tool that can provide important information on the muscle state. This chapter provides the basic concepts, physiological mechanisms of NMES, and the latest evidence in the treatment of sepsis and acute respiratory failure, proposing an algorithm, and focusing on the proper execution of this physical therapy.

We hypothesized that the third dynamic phase (ϕ3) of the cardiovascular response to apnoea requires attainment of the physiological breaking point, so that the duration of the second steady phase (ϕ2) of the classical cardiovascular response to apnoea, though appearing in both air and oxygen, is longer in oxygen.Nineteen divers performed maximal apnoeas in air and oxygen. We measured beat-by-beat arterial pressure, heart rate (fH), stroke volume (SV), cardiac output (Q˙).The fH, SV and Q˙ changes during apnoea followed the same patterns in oxygen as in air. Duration of steady ϕ2 was 105 ± 37 and 185 ± 36 s, in air and oxygen (p0.05), respectively. At end of apnoea, arterial oxygen saturation was 1.00 ± 0.00 in oxygen and 0.75 ± 0.10 in air.The results support the tested hypothesis. Lack of hypoxaemia during oxygen apnoeas suggests that, if chemoreflexes determine ϕ3, the increase in CO2 stores might play a central role in eliciting their activation.

A new analysis of the relationship between cardiac output (Q˙) and oxygen consumption V˙O2 is presented (Q˙-V˙O2 diagram). Data from different sources in the literature have been used for validation in three conditions: exercise and rest in normoxia, and exercise in hypoxia. The effects of changes in arterial oxygen concentration CaO2 on Q˙ are discussed, as well as the effects of predominant sympathetic or vagal stimulation. Differences appear depending on whether CaO2 is varied by means of changes in blood haemoglobin concentration or changes in arterial oxygen saturation. The present Q˙-V˙O2 diagram allows comprehensive description of oxygen transport in exercising humans; it expands applicability of the historical Q˙-V˙O2 relationship to include CaO2 variations; it opens new pathways for understanding underlying mechanisms; it allows computation of Q˙ from CaO2 and V˙O2 measurements, when Q˙ cannot be measured.