Intravenous fluid administration should be considered as any other pharmacological prescription. There are three main indications: resuscitation, replacement, and maintenance. Moreover, the impact of fluid administration as drug diluent or to preserve catheter patency, i.e., fluid creep, should also be considered. As for antibiotics, intravenous fluid administration should follow the four Ds: drug, dosing, duration, de-escalation. Among crystalloids, balanced solutions limit acid-base alterations and chloride load and should be preferred, as this likely prevents renal dysfunction. Among colloids, albumin, the only available natural colloid, may have beneficial effects. The last decade has seen growing interest in the potential harms related to fluid overloading. In the perioperative setting, appropriate fluid management that maintains adequate organ perfusion while limiting fluid administration should represent the standard of care. Protocols including a restrictive continuous fluid administration alongside bolus administration to achieve hemodynamic targets have been proposed. A similar approach should be considered also for critically ill patients, in whom increased endothelial permeability makes this strategy more relevant. Active de-escalation protocols may be necessary in a later phase. The R.O.S.E. conceptual model (Resuscitation, Optimization, Stabilization, Evacuation) summarizes accurately a dynamic approach to fluid therapy, maximizing benefits and minimizing harms. Even in specific categories of critically ill patients, i.e., with trauma or burns, fluid therapy should be carefully applied, considering the importance of their specific aims; maintaining peripheral oxygen delivery, while avoiding the consequences of fluid overload.

Introduction: Severe coronavirus 2019 disease (CoViD-19) may lead to respiratory failure and mechanical ventilation. Therefore, ventilator associated pneumonia (VAP) may complicate the course of the disease. The aim of the current article was to investigate possible predictive factors for bacterial VAP on a retrospective manner, in a cohort of mechanically ventilated CoViD-19 patients. Additionally, determinant factors of lethality were analyzed. Methods: Medical records of patients hospitalized in the intensive care units (ICU) at the university hospital UZ Brussel during the epidemic were reviewed. VAP was defined following the National Healthcare Safety Network 2017 criteria. Univariate and multivariate logistic regressions analyses were performed. Results: Among the 39 patients included in the study, 54% were diagnosed with bacterial VAP. Case fatality rate was 44%, but 59% of the deceased patients had a do-not-resuscitate status. Multivariate logistic regression for prediction of VAP showed significant differences in duration of ICU hospitalization and in minimal lung compliance. Additional analyses were performed on CoViD-19 patients who were affected by bacterial respiratory superinfection. The responsible pathogens correspond to the commonly found bacteria in VAP. However, 71% of the isolated germs were multi-drug resistant and bacteraemia was reported in 38%. Multivariate analyses for prediction of lethality found significant difference in SOFA score. Conclusions: Mechanically ventilated CoViD-19 patients might frequently develop VAP. Longer ICU hospitalization was associated with pulmonary superinfection in the current cohort. Moreover, decreased minimal lung compliance was correlated to VAP and higher SOFA score at VAP diagnosis was associated with lethality.

A histological and morphometric analysis of human metacarpal and carpal anlagen between the 16th and 22nd embryonic weeks was carried out with the aim of studying the establishment of the respective anlage architecture. No differences in the pattern of growth were documented between the peripheral and central zones of the metacarpal epiphyses and those of the carpals. The regulation of longitudinal growth in long bone anlagen occurred in the transition zone between the epiphysis and the diaphysis (homologous to the metaphyseal growth plate cartilage in more advanced developmental stage of the bone). Comparative zonal analysis was conducted to assess the chondrocyte density, the mean chondrocyte lacunar area, the paired chondrocyte polarity in the orthogonal longitudinal and transverse planes, and the lacunar shape transformation in the metacarpal. In transition from epiphysis to diaphysis chondrocyte density decreased and mean lacunar area increased. No significant differences in the chondrocyte maturation cycle were observed between proximal/distal metacarpal epiphyses and the carpal anlagen. The number of paired chondrocyte oriented along the growth vector was significantly higher in both proximal/distal transition zones between epiphysis and diaphysis. Human metacarpals shared with experimental models (like mice and nonmammal tetrapods) an early common chondrocyte maturation cycle but with a different timing due to the slower embryonic and fetal developmental rate of human anlagen.

Background The non-invasive analysis of body fluid composition with bio-electrical impedance analysis (BIA) provides additional information allowing for more persona-lised therapy to improve outcomes. The aim of this study is to assess the prognostic value of fluid overload (FO) in the first week of intensive care unit (ICU) stay. Methods A retrospective, observational analysis of 101 ICU patients. Whole-body BIA measurements were performed, and FO was defined as a 5% increase in volume excess from baseline body weight. Results Baseline demographic data, including severity scores, were similar in both the fluid overload-positive (FO+, n = 49) patients and in patients without fluid overload (FO–, n = 52). Patients with FO+ had significantly higher cumulative fluid balance during their ICU stay compared to those without FO (8.8 ± 7.0 vs. 5.5 ± 5.4 litres; P = 0.009), VE (9.9 ± 6.5 vs. 1.5 ± 1.5 litres; P < 0.001), total body water (63.0 ± 9.5 vs. 52.8 ± 8.1%; P < 0.001), and extracellular water (27.0 ± 7.3 vs. 19.6 ± 3.7 litres; P < 0.001). The presence of 5%, 7.5%, and 10% fluid overload was directly associated with increased ICU mortality rates. The percentage fluid overload ( P = 0.039) was an independent predictor for hospital mortality. Conclusions A higher mortality rate in ICU-patients with FO was observed. FO is an independent prognostic factor because neither APACHE-II, SOFA, nor SAPS-II significantly differed on admission between survivors and non-survivors. Further research is needed to confirm these data prospectively and to evaluate whether BIA-guided deresuscitation in the subacute phase will improve mortality rates.

Background Neurological outcome and mortality of patients suffering from poor grade subarachnoid hemorrhage (SAH) may have changed over time. Several factors, including patients’ characteristics, the presence of hydrocephalus and intraparenchymal hematoma, might also contribute to this effect. The aim of this study was to assess the temporal changes in mortality and neurologic outcome in SAH patients and identify their predictors. Methods We performed a single center retrospective cohort study from 2004 to 2018. All non-traumatic SAH patients with poor grade on admission (WFNS score of 4 or 5) who remained at least 24 h in the hospital were included. Time course was analyzed into four groups according to the years of admission (2004–2007; 2008–2011; 2012–2015 and 2016–2018). Results A total of 353 patients were included in this study: 202 patients died (57 %) and 260 (74 %) had unfavorable neurological outcome (UO) at 3 months. Mortality tended to decrease in in 2008–2011 and 2016–2018 periods (HR 0.55 [0.34–0.89] and HR 0.33 [0.20–0.53], respectively, when compared to 2004–2007). The proportion of patients with UO remained high and did not vary significantly over time. Patients with WFNS 5 had higher mortality (68 % vs. 34 %, p = 0.001) and more frequent UO (83 % vs. 54 %, p = 0.001) than those with WFNS 4. In the multivariable analysis, WFNS 5 was independently associated with mortality (HR 2.12 [1.43–3.14]) and UO (OR 3.23 [1.67–6.25]). The presence of hydrocephalus was associated with a lower risk of mortality (HR 0.60 [0.43–0.84]). Conclusions Both hospital mortality and UO remained high in poor grade SAH patients. Patients with WFNS 5 on admission had worse prognosis than others; this should be taken into consideration for future clinical studies.

Background: General pathophysiological mechanisms regarding associations between fluid administration and intra-abdominal hypertension (IAH) are evident, but specific effects of type, amount, and timing of fluids are less clear. Objectives: This review aims to summarize current knowledge on associations between fluid administration and intra-abdominal pressure (IAP) and fluid management in patients at risk of intra-abdominal hypertension and abdominal compartment syndrome (ACS). Methods: We performed a structured literature search from 1950 until May 2021 to identify evidence of associations between fluid management and intra-abdominal pressure not limited to any specific study or patient population. Findings were summarized based on the following information: general concepts of fluid management, physiology of fluid movement in patients with intra-abdominal hypertension, and data on associations between fluid administration and IAH. Results: We identified three randomized controlled trials (RCTs), 38 prospective observational studies, 29 retrospective studies, 18 case reports in adults, two observational studies and 10 case reports in children, and three animal studies that addressed associations between fluid administration and IAH. Associations between fluid resuscitation and IAH were confirmed in most studies. Fluid resuscitation contributes to the development of IAH. However, patients with IAH receive more fluids to manage the effect of IAH on other organ systems, thereby causing a vicious cycle. Timing and approach to de-resuscitation are of utmost importance, but clear indicators to guide this decision-making process are lacking. In selected cases, only surgical decompression of the abdomen can stop deterioration and prevent further morbidity and mortality. Conclusions: Current evidence confirms an association between fluid resuscitation and secondary IAH, but optimal fluid management strategies for patients with IAH remain controversial.

What is passive leg raising (PLR)?Fluid therapy is often used as first line therapy in critically ill patients in shock. Among the methods currently available to detect preload responsiveness, the PLR test has been demonstrated to be reliable in many studies and a recent meta-analysis (1,2). According to Monnet and Teboul, five rules need to be taken into account, when performing a PLR (3). First, PLR should start from the semi-recumbent and not the supine position. Second, the PLR effects must be assessed by a direct measurement of cardiac output and not by the simple measurement of blood pressure. Third, the technique used to measure cardiac output during PLR must be able to detect short-term and transient changes since the PLR effects may vanish after 1 min. Fourth, cardiac output must be measured not only before and during PLR but also after PLR when the patient has been moved back to the semi-recumbent position, in order to check that it returns to baseline. Fifth, pain, cough, discomfort, and awakening could provoke adrenergic stimulation, resulting in erroneous interpretation of cardiac output changes. We would like to add a sixth rule: confounding factors and underlying conditions that may influence the PLR must be assessed before performing the test, these include increased intrathoracic pressure [high PEEP, presence of autoPEEP, thoracic compartment syndrome (e.g., tension pneumothorax)], cardiac tamponade, right ventricular infarction or failure and intra-abdominal hypertension Cite this article as: Minini A, Abraham P, Malbrain MLNG.Predicting fluid responsiveness with the passive leg raising test: don't be fooled by intra-abdominal hypertension! Ann Transl

There is a persistent debate on the optimal target temperature to use during cooling procedures in cardiac arrest survivors. A large randomized clinical trial (RCT) including more than 900 patients showed that targeted temperature management (TTM) at 33 °C had similar mortality and unfavorable neurological outcome (UO) rates as TTM at 36 °C in out-of-hospital cardiac arrest patients with any initial rhythm. Since then, several observational studies have been published on the effects of changes in target temperature (i.e., from 33 to 36 °C) on patients’ outcome. We performed a systematic literature search from 1 January 2014 to 4 December 2020 and identified nine retrospective studies (very low levels of certainty; high risk of bias), including 3799 patients, that evaluated TTM at 33 °C vs. TTM at 36 °C on the occurrence of UO (n = seven studies) and mortality (n = nine studies). TTM at 33 °C was associated with a lower risk of UO when studies assessing neurological outcome with the Cerebral Performance Categories were analyzed (OR 0.80 [95% CIs 0.65–0.99]; p = 0.04). No differences in mortality were observed within the two TTM strategies. These results suggest that an inappropriate translation of TTM protocols from large well-conducted randomized trials into clinical management may result in unexpected effects on patients’ outcome. As for all newly commercialized drugs, epidemiological studies and surveillance programs with an adequate follow-up on large databases are necessary to understand how RCTs are implemented into medical practice.