Critical Care

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ISSN / EISSN : 1364-8535 / 1364-8535
Published by: Springer Nature (10.1186)
Total articles ≅ 15,345
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, Peter Hoffmann, Daniel Schwarzkopf, Christian Scheer, Friedhelm Bach, Marcus Komann, Herwig Gerlach, Manfred Weiss, Matthias Lindner, Hendrik Rüddel, et al.
Published: 21 October 2021
Critical Care, Volume 25, pp 1-10;

Background Fever and hypothermia have been observed in septic patients. Their influence on prognosis is subject to ongoing debates. Methods We did a secondary analysis of a large clinical dataset from a quality improvement trial. A binary logistic regression model was calculated to assess the association of the thermal response with outcome and a multinomial regression model to assess factors associated with fever or hypothermia. Results With 6542 analyzable cases we observed a bimodal temperature response characterized by fever or hypothermia, normothermia was rare. Hypothermia and high fever were both associated with higher lactate values. Hypothermia was associated with higher mortality, but this association was reduced after adjustment for other risk factors. Age, community-acquired sepsis, lower BMI and lower outside temperatures were associated with hypothermia while bacteremia and higher procalcitonin values were associated with high fever. Conclusions Septic patients show either a hypothermic or a fever response. Whether hypothermia is a maladaptive response, as indicated by the higher mortality in hypothermic patients, or an adaptive response in patients with limited metabolic reserves under colder environmental conditions, remains an open question. Trial registration The original trial whose dataset was analyzed was registered at (NCT01187134) on August 23, 2010, the first patient was included on July 1, 2011.
, Napplika Kongpolprom
Published: 19 October 2021
Critical Care, Volume 25, pp 1-9;

Background Timing of swallows in relation to respiratory phases is associated with aspiration events. Oxygen therapy possibly affects the timing of swallows, which may alter airway protective mechanisms. Objectives To compare the coordination between swallowing and respiration during water infusion in post-extubation patients using high flow nasal oxygen (HFNO) with the coordination in those using low flow nasal oxygen (LFNO). Methods We conducted a randomized controlled crossover study in post-extubation patients. The patients extubated within 48 h were randomly assigned to two groups, namely, HFNO and LFNO. The eligible patients in each group received either HFNO with fraction of inspired oxygen (FiO2) 0.35, flow 50 L per minute (LPM), and temperature 34 °C or LFNO 5 LPM for 5 min. The coordination between swallowing and respiration was observed during continuous infusion of 10-ml water one minute three times. Respiratory phases and swallowing were monitored using electrocardiogram (EKG)-derived respiratory signals and submental electromyography (EMG), respectively. The swallowing frequency and timing of swallows in relation to respiratory phases were recorded. The coordination between swallowing and respiration was classified into 4 patterns, namely I, E, I-E, and E-I swallows. (I; inspiration and E; expiration) Subsequently, after a 5-min washout period, the patients were switched to the other type of oxygen therapy using the same procedure. The Wilcoxon Signed-Rank Test was used for statistical analysis. Results A total of 22 patients with a mean age of 56 years were enrolled in the study. The major indication for invasive mechanical ventilation was pneumonia with a median duration of endotracheal intubation of 2.5 days. The median total swallowing numbers (three minutes) were 18.5 times in the HFNO period and 21 times in the LFNO period (p = NS). The most common swallowing pattern was E-swallow. The patients using HFNO had higher numbers of E-swallow pattern (74.3% in HFNO vs 67.6% in LFNO; p = 0.048) and lower numbers of I-swallow pattern (14.3% in HFNO vs 23.1% in LFNO; p = 0.044). The numbers of other swallowing patterns were not different between the 2 groups. Conclusions Compared with LFNO, HFNO significantly increased the E-swallow and decreased the I-swallow in post-extubation patients. The findings indicated that HFNO might reduce a risk of aspiration during the post-extubation period. Clinical trial No.: Thai clinical trial TCTR20200206004 Registered February 4, 2020. URL:
, Ohoud Aljuhani, Abdulrahman I. Al Shaya, Abdullah Kharbosh, Raed Kensara, Alhomaidi Al Guwairy, Aisha Alharbi, Rahmah Algarni, Shmeylan Al Harbi, Ramesh Vishwakarma, et al.
Published: 18 October 2021
Critical Care, Volume 25, pp 1-8;

Background Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The role of zinc in critically ill patients with COVID-19 remains unclear. This study aims to evaluate the efficacy and safety of zinc sulfate as adjunctive therapy in critically ill patients with COVID-19. Methods Patients aged ≥ 18 years with COVID-19 who were admitted to the intensive care unit (ICU) in two tertiary hospitals in Saudi Arabia were retrospectively assessed for zinc use from March 1, 2020 until March 31, 2021. After propensity score matching (1:1 ratio) based on the selected criteria, we assessed the association of zinc used as adjunctive therapy with the 30-day mortality. Secondary outcomes included the in-hospital mortality, ventilator free days, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. Results A total of 164 patients were included, 82 patients received zinc. Patients who received zinc sulfate as adjunctive therapy have a lower 30-day mortality (HR 0.52, CI 0.29, 0.92; p = 0.03). On the other hand, the in-hospital mortality was not statistically significant between the two groups (HR 0.64, CI 0.37–1.10; p = 0.11). Zinc sulfate use was associated with a lower odds of acute kidney injury development during ICU stay (OR 0.46 CI 0.19–1.06; p = 0.07); however, it did not reach statistical significance. Conclusion The use of zinc sulfate as an additional treatment in critically ill COVID-19 patients may improve survival. Furthermore, zinc supplementation may have a protective effect on the kidneys.
Published: 18 October 2021
Critical Care, Volume 25, pp 1-9;

Purpose Intensive care unit (ICU) survivors have reduced physical function likely due to skeletal muscle wasting and weakness acquired during critical illness. However, the contribution of pre-morbid muscle mass has not been elucidated. We aimed to examine the association between pre-ICU muscle mass and ICU admission risk. Secondary outcomes include the relationship between muscle mass and ICU outcomes. Methods ICU admissions between June 1, 1998, and February 1, 2019, were identified among participants of Geelong Osteoporosis Study (GOS), a population-based cohort study. Cox proportional hazard regression models estimated hazard ratios (HR) for ICU admission across T-score strata and continuous values of DXA-derived lean mass measures of skeletal mass index (SMI, lean mass/body mass %) and appendicular lean mass corrected for height (ALM/h2, kg/m2). Multivariable regression was used to determine the relationship between lean mass and ICU outcomes. Results One hundred and eighty-six of 3126 participants enrolled in GOS were admitted to the ICU during the follow-up period. In adjusted models, lean mass was not predictive of ICU admission (SMI: HR 0.99 95%CI 0.97–1.01, p = 0.32; ALM/h2: HR 1.11 95%CI 0.94–1.31, p = 0.23), while greater appendicular lean mass was related to reduced 28-day mortality (ALM/h2 adjOR: 0.25, 95%CI 0.10–0.63, p = 0.003, SMI adjOR: 0.91, 95%CI 0.82–1.02, p = 0.09). Conclusion Lean mass was not associated with ICU admission in this population-based cohort study; however, greater appendicular lean mass was associated with reduced mortality. This suggests pre-ICU muscle status may not predict development of critical illness but is associated with better survival after critical illness occurs.
, Andrew F. Shorr, Matteo Bassetti, Jean-Francois Timsit, Scott T. Micek, Andrew P. Michelson, Jose Garnacho-Montero
Published: 15 October 2021
Critical Care, Volume 25, pp 1-10;

Severe or life threatening infections are common among patients in the intensive care unit (ICU). Most infections in the ICU are bacterial or fungal in origin and require antimicrobial therapy for clinical resolution. Antibiotics are the cornerstone of therapy for infected critically ill patients. However, antibiotics are often not optimally administered resulting in less favorable patient outcomes including greater mortality. The timing of antibiotics in patients with life threatening infections including sepsis and septic shock is now recognized as one of the most important determinants of survival for this population. Individuals who have a delay in the administration of antibiotic therapy for serious infections can have a doubling or more in their mortality. Additionally, the timing of an appropriate antibiotic regimen, one that is active against the offending pathogens based on in vitro susceptibility, also influences survival. Thus not only is early empiric antibiotic administration important but the selection of those agents is crucial as well. The duration of antibiotic infusions, especially for β-lactams, can also influence antibiotic efficacy by increasing antimicrobial drug exposure for the offending pathogen. However, due to mounting antibiotic resistance, aggressive antimicrobial de-escalation based on microbiology results is necessary to counterbalance the pressures of early broad-spectrum antibiotic therapy. In this review, we examine time related variables impacting antibiotic optimization as it relates to the treatment of life threatening infections in the ICU. In addition to highlighting the importance of antibiotic timing in the ICU we hope to provide an approach to antimicrobials that also minimizes the unnecessary use of these agents. Such approaches will increasingly be linked to advances in molecular microbiology testing and artificial intelligence/machine learning. Such advances should help identify patients needing empiric antibiotic therapy at an earlier time point as well as the specific antibiotics required in order to avoid unnecessary administration of broad-spectrum antibiotics.
Yuean Zhao, Faming Jiang, He Yu, Ye Wang, Zhen Wang, Peng Sun, Zhong Ni, Weiya Wang, Lili Jiang, Junping Fan, et al.
Published: 14 October 2021
Critical Care, Volume 25, pp 1-10;

Background Examinations based on lung tissue specimen can play a significant role in the diagnosis for critically ill and intubated patients with lung infiltration. However, severe complications including tension pneumothorax and intrabronchial hemorrhage limit the application of needle biopsy. Methods A refined needle biopsy technique, named bronchus-blocked ultrasound-guided percutaneous transthoracic needle biopsy (BUS-PTNB), was performed on four intubated patients between August 2020 and April 2021. BUS-PTNB was done at bedside, following an EPUBNOW (evaluation, preparation, ultrasound location, bronchus blocking, needle biopsy, observation, and withdrawal of blocker) workflow. Parameters including procedure feasibility, sample acquisition, perioperative conditions, and complications were observed. Tissue specimens were sent to pathological examinations and microbial tests. Results Adequate specimens were successfully obtained from four patients. Diagnosis and treatment were correspondingly refined based on pathological and microbial tests. Intrabronchial hemorrhage occurred in patient 1 but was stopped by endobronchial blocker. Mild pneumothorax happened in patient 4 due to little air leakage, and closed thoracic drainage was placed. During the procedure, peripheral capillary hemoglobin oxygen saturation (SPO2), blood pressure, and heart rate of patient 4 fluctuated but recovered quickly. Vital signs were stable for patient 1–3. Conclusions BUS-PTNB provides a promising, practical and feasible method in acquiring tissue specimen for critically ill patients under intratracheal intubation. It may facilitate the pathological diagnosis or other tissue-based tests for intubated patients and improve clinical outcomes.
Mairi Ziaka, Aristomenis Exadaktylos
Published: 13 October 2021
Critical Care, Volume 25, pp 1-10;

During the last decade, experimental and clinical studies have demonstrated that isolated acute brain injury (ABI) may cause severe dysfunction of peripheral extracranial organs and systems. Of all potential target organs and systems, the lung appears to be the most vulnerable to damage after brain injury (BI). The pathophysiology of these brain–lung interactions are complex and involve neurogenic pulmonary oedema, inflammation, neurodegeneration, neurotransmitters, immune suppression and dysfunction of the autonomic system. The systemic effects of inflammatory mediators in patients with BI create a systemic inflammatory environment that makes extracranial organs vulnerable to secondary procedures that enhance inflammation, such as mechanical ventilation (MV), surgery and infections. Indeed, previous studies have shown that in the presence of a systemic inflammatory environment, specific neurointensive care interventions—such as MV—may significantly contribute to the development of lung injury, regardless of the underlying mechanisms. Although current knowledge supports protective ventilation in patients with BI, it must be born in mind that ABI-related lung injury has distinct mechanisms that involve complex interactions between the brain and lungs. In this context, the role of extracerebral pathophysiology, especially in the lungs, has often been overlooked, as most physicians focus on intracranial injury and cerebral dysfunction. The present review aims to fill this gap by describing the pathophysiology of complications due to lung injuries in patients with a single ABI, and discusses the possible impact of MV in neurocritical care patients with normal lungs.
Yang Jiao, Ti Zhang, Chengmi Zhang, Haiying Ji, Xingyu Tong, Ran Xia, Wei Wang, Zhengliang Ma, Xueyin Shi
Published: 12 October 2021
Critical Care, Volume 25, pp 1-15;

Background Polymorphonuclear neutrophils (PMNs) play an important role in sepsis-related acute lung injury (ALI). Accumulating evidence suggests PMN-derived exosomes as a new subcellular entity acting as a fundamental link between PMN-driven inflammation and tissue damage. However, the role of PMN-derived exosomes in sepsis-related ALI and the underlying mechanisms remains unclear. Methods Tumor necrosis factor-α (TNF-α), a key regulator of innate immunity in sepsis-related ALI, was used to stimulate PMNs from healthy C57BL/6J mice in vitro. Exosomes isolated from the supernatant were injected to C57BL/6J wild-type mice intraperitoneally (i.p.) and then examined for lung inflammation, macrophage (Mϕ) polarization and pyroptosis. In vitro co-culture system was applied where the mouse Raw264.7 macrophages or bone marrow-derived macrophages (BMDMs) were co-cultured with PMN-derived exosomes to further confirm the results of in vivo animal study and explore the potential mechanisms involved. Results Exosomes released by TNF-α-stimulated PMNs (TNF-Exo) promoted M1 macrophage activation after in vivo i.p. injection or in vitro co-culture. In addition, TNF-Exo primed macrophage for pyroptosis by upregulating NOD-like receptor 3 (NLRP3) inflammasome expression through nuclear factor κB (NF-κB) signaling pathway. Mechanistic studies demonstrated that miR-30d-5p mediated the function of TNF-Exo by targeting suppressor of cytokine signaling (SOCS-1) and sirtuin 1 (SIRT1) in macrophages. Furthermore, intravenous administration of miR-30d-5p inhibitors significantly decreased TNF-Exo or cecal ligation and puncture (CLP)-induced M1 macrophage activation and macrophage death in the lung, as well as the histological lesions. Conclusions The present study demonstrated that exosomal miR-30d-5p from PMNs contributed to sepsis-related ALI by inducing M1 macrophage polarization and priming macrophage pyroptosis through activating NF-κB signaling. These findings suggest a novel mechanism of PMN-Mϕ interaction in sepsis-related ALI, which may provide new therapeutic strategies in sepsis patients.
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