OBJECTIVE: Maneuvers assessing fluid responsiveness before an intravascular volume expansion may limit useless fluid administration, which in turn may improve outcomes.
OBJECTIVE: To describe maneuvers for assessing fluid responsiveness in mechanically ventilated patients.
BACKGROUND: The protocol was registered at PROSPERO: CRD42019146781.
UNASSIGNED: PubMed, EMBASE, CINAHL, SCOPUS, and Web of Science were search from inception to 08/08/2023.
METHODS: Prospective and intervention studies were selected.
METHODS: Data for each maneuver were reported individually and data from the five most employed maneuvers were aggregated. A traditional and a Bayesian meta-analysis approach were performed.
RESULTS: A total of 69 studies, encompassing 3185 fluid challenges and 2711 patients were analyzed. The prevalence of fluid responsiveness was 49.9%. Pulse pressure variation (PPV) was studied in 40 studies, mean threshold with 95% confidence intervals (95% CI) = 11.5 (10.5-12.4)%, and area under the receiver operating characteristics curve (AUC) with 95% CI was 0.87 (0.84-0.90). Stroke volume variation (SVV) was studied in 24 studies, mean threshold with 95% CI = 12.1 (10.9-13.3)%, and AUC with 95% CI was 0.87 (0.84-0.91). The plethysmographic variability index (PVI) was studied in 17 studies, mean threshold = 13.8 (12.3-15.3)%, and AUC was 0.88 (0.82-0.94). Central venous pressure (CVP) was studied in 12 studies, mean threshold with 95% CI = 9.0 (7.7-10.1) mmHg, and AUC with 95% CI was 0.77 (0.69-0.87). Inferior vena cava variation (∆IVC) was studied in 8 studies, mean threshold = 15.4 (13.3-17.6)%, and AUC with 95% CI was 0.83 (0.78-0.89).
CONCLUSIONS: Fluid responsiveness can be reliably assessed in adult patients under mechanical ventilation. Among the five maneuvers compared in predicting fluid responsiveness, PPV, SVV, and PVI were superior to CVP and ∆IVC. However, there is no data supporting any of the above mentioned as being the best maneuver. Additionally, other well-established tests, such as the passive leg raising test, end-expiratory occlusion test, and tidal volume challenge, are also reliable.

Body composition assessments using air displacement plethysmography (ADP, PEAPOD®) have been introduced into clinical practice at a few neonatal units. To allow accurate body composition assessments in term and preterm infants, a workflow for routine testing is needed. The aim of this study was to analyze the feasibility of weekly routine ADP testing. We analyzed (1) postnatal ages at first ADP assessment, (2) the number of weekly routine in-hospital assessments, and (3) the workload of body composition measurements using ADP in clinical practice on the basis of an retrospective analysis of our own clinical operating procedures. The retrospective analysis of weekly routine ADP testing proved feasible at Nuremberg Children\'s Hospital. The analysis of postnatal age at the first ADP test revealed differences across groups, with extremely preterm infants starting at a mean postmenstrual age of 36.6 weeks, very preterm infants starting at 34.2 weeks, and moderate to late preterm infants starting at 35.3 weeks. The mean number of tests before discharge was significantly greater in the extremely preterm group (n = 3.0) than in the very preterm (n = 2.4) and moderate to late preterm groups (n = 1.7). The workload of the procedure is reasonable, at 8-13 min per test cycle. The study proved that weekly routine ADP assessments in preterm infants are feasible. However, the initiation of routine testing in extremely preterm infants starts at a significantly greater postnatal age than in the more mature population. ADP assessments can be safely and easily integrated into clinical practice and may be valuable tools for providing additional information on nutritional status and infant growth. A standardized routine protocol allowing identical measurement conditions across healthcare institutions and a standardized interpretation tool for age-adapted body composition data, however, would improve comparability and usability.

BACKGROUND: Currently, there is conflicting information and guidance on the effective management of Alpha 1 Antitrypsin Deficiency (AATD). Establishing a consensus of assessment and disease management specific to AATD is important for achieving a standardized treatment pathway and for improving patient outcomes. Here, we aim to utilize the Delphi method to establish a European consensus for the assessment and management of patients with severe AATD.
METHODS: Two rounds of a Delphi survey were completed online by members of the European Alpha-1 Research Collaboration (EARCO). Respondents were asked to indicate their agreement with proposed statements for patients with no respiratory symptoms, stable respiratory disease, and worsening respiratory disease using a Likert scale of 1-7. Levels of agreement between respondents were calculated using a weighted average.
RESULTS: Round 1 of the Delphi survey was sent to 103 members of EARCO and 38/103 (36.9%) pulmonologists from across 15 countries completed all 109 questions. Round 2 was sent to all who completed Round 1 and 36/38 (94.7%) completed all 79 questions. Responses regarding spirometry, body plethysmography, high-resolution computed tomography, and the initiation of augmentation therapy showed little variability among physicians, but there was discordance among other aspects, such as the use of low-dose computed tomography in both a research setting and routine clinical care.
CONCLUSIONS: These results provide expert opinions for the assessment and monitoring of patients with severe AATD, which could be used to provide updated recommendations and standardized treatment pathways for patients across Europe.

The emergence of new synthetic opioids (NSOs) has added complexity to recreational opioid markets worldwide. While NSOs with diverse chemical structures have emerged, brorphine currently remains the only NSO with a piperidine benzimidazolone scaffold. However, the emergence of new generations of NSOs, including brorphine analogues, can be anticipated. This study explored the pharmaco-toxicological, opioid-like effect profile of brorphine alongside its non-brominated analogue (orphine) and three other halogenated analogues (fluorphine, chlorphine, iodorphine). In vitro, radioligand binding assays in rat brain tissue indicated that all analogues bind to the μ-opioid receptor (MOR) with nM affinity. While analogues with smaller-sized substituents showed the highest MOR affinity, further in vitro characterization via two cell-based (HEK 293T) MOR activation (β-arrestin 2 and mini-Gαi recruitment) assays indicated that chlorphine, brorphine, and iodorphine were generally the most active MOR agonists. None of the compounds showed significant in vitro biased agonism compared to hydromorphone. In vivo, we investigated the effects of intraperitoneal (IP) administration of the benzimidazolones (0.01-15 mg/kg) on mechanical and thermal antinociception in male CD-1 mice. Chlorphine and brorphine overall induced the highest levels of antinociception. Furthermore, the effects on respiratory changes induced by a fixed dose (15 mg/kg IP) of the compounds were investigated using non-invasive plethysmography. Fluorphine-, chlorphine-, and brorphine-induced respiratory depressant effects were the most pronounced. For some compounds, pretreatment with naloxone (6 mg/kg IP) could not reverse respiratory depression. Taken together, brorphine-like piperidine benzimidazolones are opioid agonists that have the potential to cause substantial harm to users should they emerge as NSOs.

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the methyl-CPG-binding protein 2 (Mecp2) gene. Frequent apneas and irregular breathing are prevalent in RTT, and also occur in rodent models of the disorder, including Mecp2Bird and Mecp2R168X mice. Sarizotan, a serotonin 5-HT1a and dopamine D2-like receptor agonist, reduces the incidence of apneas and irregular breathing in mouse models of RTT (Abdala et al., 2014). Targeting the 5HT1a receptor alone also improves respiration in RTT mice (Levitt et al., 2013). However, the contribution of D2-like receptors in correcting these respiratory disturbances remains untested. PAOPA, a dopamine D2-like receptor positive allosteric modulator, and quinpirole, a dopamine D2-like receptor orthosteric agonist, were used in conjunction with whole-body plethysmography to evaluate whether activation of D2-like receptors is sufficient to improve breathing disturbances in female heterozygous Mecp2Bird/+ and Mecp2R168X/+ mice. PAOPA did not significantly change apnea incidence or irregularity score in RTT mice. PAOPA also had no effect on the ventilatory response to hypercapnia (7 % CO2). In contrast, quinpirole reduced apnea incidence and irregularity scores and improved the hypercapnic ventilatory response in Mecp2R168X/+ and Mecp2Bird/+ mice, while also reducing respiratory rate. These results suggest that D2-like receptors could contribute to the positive effects of sarizotan in the correction of respiratory abnormalities in Rett syndrome. However, positive allosteric modulation of D2-like receptors alone was not sufficient to evoke these effects.

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UNASSIGNED: Sergi, TE, Roberts, BM, and Heileson, JL. What About Water? Implications for Body Composition Assessment in Military Personnel. J Strength Cond Res 38(9): e534-e540, 2024-Body composition standards ensure service members maintain physical fitness, wellness, and support mission readiness. Anthropometric techniques (i.e., height/mass, circumference-based \"tape test\") have been the primary screening and percent body fat (%BF) assessment method in military personnel for about 4 decades. Recently, the Army and Marine Corps have implemented more advanced body composition assessment methods, such as air displacement plethysmography (ADP), multifrequency bioelectrical impedance analysis (MF-BIA), and dual-energy x-ray absorptiometry (DXA), to serve as supplemental %BF assessment after failing the tape test. Although supplemental assessments are intended to improve on the accuracy and precision of the tape test, preassessment standardization, specifically regarding acute water ingestion (AWI), is lacking. Thus, the purpose of this narrative review was to (a) summarize the available literature regarding the influence of AWI on body composition estimates derived from ADP, MF-BIA, and DXA and (b) provide evidence-based recommendations for researchers and practitioners. Studies indicate that AWI increases %BF estimates with ADP (4 of 6 [4/6] observations) and MF-BIA (6/7), whereas AWI increases muscle mass (6/6) and likely decreases %BF (2/3) when obtained by DXA. In conclusion, ADP, MF-BIA, and DXA are susceptible to confounding from AWI, leading to inaccurate body composition estimates that may negatively affect the careers of military personnel. Based on the findings from this narrative review, military practitioners and researchers should (a) follow manufacturer guidelines for calorie intake [food and fluid] and exercise avoidance, (b) conduct urine-specific gravity testing [if possible], and (c) limit AWI to <250 ml before assessment.

For decades spirometry has been the benchmark test for capturing lung function in children but its recognized limitations required the development of other techniques. This article introduces novel techniques in lung function assessment for pediatric patients, including multiple breath washout, impulse oscillometry, structured light plethysmography, and electrical impedance tomography, and common themes in interpreting the results. Challenges include standardization, reference data, and clinical integration of these innovative tools. Further research is ongoing to optimize these tests for clinical use, especially in diverse populations and pediatric settings.

UNASSIGNED: Blood lactate is a marker of tissue hypoxia while capillary refill time (CRT) is a surrogate of tissue perfusion. Measuring these parameters is recommended for assessing circulatory status and guiding resuscitation. However, blood lactate is not widely available in African emergency departments. Additionally, CRT assessment faces challenges related to its precision and reproducibility. This study aims to evaluate the accuracy of visual CRT(V-CRT) compared to plethysmographic CRT (P-CRT) in predicting lactate levels among septic patients.
UNASSIGNED: This prospective observational study enrolled consecutive patients with sepsis or septic shock over a 6-month period from a tertiary hospital in Marrakech, Morroco. V-CRT and P-CRT were evaluated upon admission, and simultaneous measurements of arterial lactate levels were obtained. The precision of V-CRT and P-CRT in predicting arterial lactate was assessed using ROC curve analysis.
UNASSIGNED: Forty-three patients aged of 64±15 years, of whom 70 % were male, were included in the study. Of these, 23 patients (53 %) had sepsis, and 20 patients (47 %) experienced septic shock. Both V-CRT and P-CRT demonstrated statistically significant correlations with arterial lactate, with correlation coefficients of 0.529 (p < 0.0001) and 0.517 (p = 0.001), respectively. ROC curve analysis revealed that V-CRT exhibited satisfactory accuracy in predicting arterial lactate levels >2 mmol/l, with an area under the curve (AUC) of 0.8 (95 % CI=0.65 - 0.93; p < 0.0001). The prediction ability of P-CRT was lower than V-CRT with an AUC of 0.73 (95 % CI: 0.57-0.89; p = 0.043). The optimal thresholds were determined as 3.4 s for V-CRT (sensitivity = 90 %, specificity = 58 %) and 4.1 s for P-CRT (sensitivity = 85 %, specificity = 62 %).
UNASSIGNED: These findings suggest that the plethysmographic evaluation did not improve the accuracy of CRT for predicting lactate level. However, V-CRT may still serve as a viable surrogate for lactate in septic patients in low-income settings.

In the absence of appropriate medical care, exposure to organophosphorus nerve agents, such as VX, can lead to respiratory failure, and potentially death by asphyxiation. Despite the critical role of respiratory disturbances in organophosphorus-induced toxicity, the nature and underlying mechanisms of respiratory failure remain poorly understood. This study aimed to characterize respiratory alterations by determining their type and duration in mice exposed to a subcutaneous sublethal dose of VX. Respiratory ventilation in Swiss mice was monitored using dual-chamber plethysmography for up to 7 days post-exposure. Cholinesterase activity was assessed via spectrophotometry, and levels of inflammatory biomarkers were quantified using Luminex technology in blood and tissues involved in respiration (diaphragm, lung, and medulla oblongata). Additionally, a histological study was conducted on these tissues to ensure their structural integrity. Ventilatory alterations appeared 20-25 minutes after the injection of 0.9 LD50 VX and increased until the end of the recording, i.e., 40 minutes after intoxication. Concurrent with the occurrence of apnea, increased inspiratory and expiratory times resulted in a significant decrease in respiratory rate in exposed mice compared to controls. Ventilatory amplitude and, consequently, minute volume were reduced, while specific airway resistance significantly increased, indicating bronchoconstriction. These ventilatory effects persisted up to 24 or even 72 hours post-intoxication, resolving on the 7th day. They were correlated with a decrease in acetylcholinesterase activity in the diaphragm, which persisted for up to 72 hours, and with the triggering of an inflammatory reaction in the same tissue. No significant histologic lesions were observed in the examined tissues. The ventilatory alterations observed up to 72 hours post-VX exposure appear to result from a functional failure of the respiratory system rather than tissue damage. This comprehensive characterization contributes to a better understanding of the respiratory effects induced by VX exposure, which is crucial for developing specific medical countermeasures.