Critical Care Bulletin - April 2023

 

Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis

by Silei Sun, Daosheng Wang, Danfeng Dong, Lili Xu, Mengqi Xie, Yihui Wang, Tongtian Ni, Weisong Jiang, Xiaojuan Zhu, Ning Ning, Qian Sun, Shuyuan Zhao, Mengjiao Li, Peili Chen, Meiling Yu, Jian Li.

Critical Care volume 27, Article number: 127 (2023) Published: 28 March 2023

Background

The gut microbiome plays a pivotal role in the progression of sepsis. However, the specific mechanism of gut microbiota and its metabolites involved in the process of sepsis remains elusive, which limits its translational application.

Method

In this study, we used a combination of the microbiome and untargeted metabolomics to analyze stool samples from patients with sepsis enrolled at admission, then microbiota, metabolites, and potential signaling pathways that might play important roles in disease outcome were screened out. Finally, the above results were validated by the microbiome and transcriptomics analysis in an animal model of sepsis.

Results

Patients with sepsis showed destruction of symbiotic flora and elevated abundance of Enterococcus, which were validated in animal experiments. Additionally, patients with a high burden of Bacteroides, especially B. vulgatus, had higher Acute Physiology and Chronic Health Evaluation II scores and longer stays in the intensive care unit. The intestinal transcriptome in CLP rats illustrated that Enterococcus and Bacteroides had divergent profiles of correlation with differentially expressed genes, indicating distinctly different roles for these bacteria in sepsis. Furthermore, patients with sepsis exhibited disturbances in gut amino acid metabolism compared with healthy controls; namely, tryptophan metabolism was tightly related to an altered microbiota and the severity of sepsis.

Conclusion

Alterations in microbial and metabolic features in the gut corresponded with the progression of sepsis. Our findings may help to predict the clinical outcome of patients in the early stage of sepsis and provide a translational basis for exploring new therapies.

 

High-level burnout in physicians and nurses working in adult ICUs: a systematic review and meta-analysis

Intensive Care Medicine (2023) Published: 27 March 2023

Purpose

The prevalence of burnout in intensive care unit (ICU) professionals is difficult to establish due to the variety of survey instruments used, the heterogeneity of the targeted population, the design of the studies, and the differences among countries regarding ICU organization.

Methods

We performed a systematic review and meta-analysis examining the prevalence of high-level burnout in physicians and nurses working in adult ICUs, including only studies that use the Maslach Burnout Inventory (MBI) as a tool to evaluate burnout and involving at least 3 different ICUs.

Results

Twenty-five studies with a combined population of 20,723 healthcare workers from adult ICUs satisfied the inclusion criteria. Combining 18 studies including 8187 ICU physicians, 3660 of them reported a high level of burnout (prevalence 0.41, range 0.15–0.71, 95% CI [0.33; 0.5], I2 97.6%, 95% CI [96.9%; 98.1%]). The heterogeneity can be at least in part explained by the definition of burnout used and the response rate as confirmed by the multivariable metaregression done. In contrast, there was no significant difference regarding other factors such as the study period (before or during the coronavirus disease 2019 (COVID-19) pandemic), the income of the countries, or the Healthcare Access and Quality (HAQ) index. Combining 20 studies including 12,536 ICU nurses, 6232 of nurses were reporting burnout (prevalence 0.44, range 0.14–0.74, [95% CI 0.34; 0.55], I2 98.6% 95% CI [98.4%; 98.9%]). The prevalence of high-level burnout in ICU nurses for studies performed during the COVID-19 pandemic was higher than that reported for studies performed before the COVID-19 pandemic (0.61 [95% CI, 0.46; 0.75] and 0.37 [95% CI, 0.26; 0.49] respectively, p = 0.003). As for physicians, the heterogeneity is at least in part explained by the definition used for burnout using the MBI but not by the number of participants. When compared, the prevalence of high-level burnout was not different between ICU physicians and ICU nurses. However, the proportion of ICU nurses with a high level of emotional exhaustion was higher than for ICU physicians (0.42 [95% CI, 0.37; 0.48] and 0.28 [0.2; 0.39], respectively, p = 0.022).

Conclusion

According to this meta-analysis, the prevalence of high-level burnout is higher than 40% in all ICU professionals. However, there is a great heterogeneity in the results. To evaluate and to compare preventive and therapeutic strategies, there is the need to use a consensual definition of burnout when using the MBI instrument.

 

Comparison of clinical outcomes between aggressive and non-aggressive intravenous hydration for acute pancreatitis: a systematic review and meta-analysis

by Xiu-Wei Li, Chien-Ho Wang, Jhih-Wei Dai, Shu-Han Tsao, Po-Hsi Wang, Cheng-Chen Tai, Rong-Nan Chien, Shih-Chieh Shao and Edward Chia-Cheng Lai 

Critical Care volume 27, Article number: 122 (2023) Published: 22 March 2023

Background

Current practice guidelines for optimal infusion rates during early intravenous hydration in patients with acute pancreatitis (AP) remain inconsistent. This systematic review and meta-analysis aimed to compare treatment outcomes between aggressive and non-aggressive intravenous hydration in severe and non-severe AP.

Methods

This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We systematically searched PubMed, Embase and Cochrane Library for randomized controlled trials (RCTs) on November 23, 2022, and hand-searched the reference lists of included RCTs, relevant review articles and clinical guidelines. We included RCTs that compared clinical outcomes from aggressive and non-aggressive intravenous hydration in AP. Meta-analysis was performed using a random-effects model for participants with severe AP and non-severe AP. Our primary outcome was all-cause mortality, and several secondary outcomes included fluid-related complications, clinical improvement and APACHE II scores within 48 h.

Results

We included a total of 9 RCTs with 953 participants. The meta-analysis indicated that, compared to non-aggressive intravenous hydration, aggressive intravenous hydration significantly increased mortality risk in severe AP (pooled RR: 2.45, 95% CI: 1.37, 4.40), while the result in non-severe AP was inconclusive (pooled RR: 2.26, 95% CI: 0.54, 9.44). However, aggressive intravenous hydration significantly increased fluid-related complication risk in both severe (pooled RR: 2.22, 95% CI 1.36, 3.63) and non-severe AP (pooled RR: 3.25, 95% CI: 1.53, 6.93). The meta-analysis indicated worse APACHE II scores (pooled mean difference: 3.31, 95% CI: 1.79, 4.84) in severe AP, and no increased likelihood of clinical improvement (pooled RR:1.20, 95% CI: 0.63, 2.29) in non-severe AP. Sensitivity analyses including only RCTs with goal-directed fluid therapy after initial fluid resuscitation therapy yielded consistent results.

Conclusions

Aggressive intravenous hydration increased the mortality risk in severe AP, and fluid-related complication risk in both severe and non-severe AP. More conservative intravenous fluid resuscitation protocols for AP are suggested.

 A structured diagnostic algorithm for patients with ARDS

by Lieuwe Durk Jacobus Bos, Harm Jan de Grooth and Pieter Roel Tuinman 

Critical Care volume 27, Article number: 94 (2023) Published: 21 March 2023

Abstract

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2023. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901.

 

Mechanical power of ventilation and driving pressure: two undervalued parameters for pre extracorporeal membrane oxygenation ventilation and during daily management?

by K. Hoppe, E. Khan, P. Meybohm and T. Riese 

Critical Care volume 27, Article number: 111 (2023) Published: 14 March 2023

Abstract

The current ARDS guidelines highly recommend lung protective ventilation which include plateau pressure (Pplat < 30 cm H2O), positive end expiratory pressure (PEEP > 5 cm H2O) and tidal volume (Vt of 6 ml/kg) of predicted body weight. In contrast, the ELSO guidelines suggest the evaluation of an indication of veno-venous extracorporeal membrane oxygenation (ECMO) due to hypoxemic or hypercapnic respiratory failure or as bridge to lung transplantation. Finally, these recommendations remain a wide range of scope of interpretation. However, particularly patients with moderate-severe to severe ARDS might benefit from strict adherence to lung protective ventilation strategies. Subsequently, we discuss whether extended physiological ventilation parameter analysis might be relevant for indication of ECMO support and can be implemented during the daily routine evaluation of ARDS patients. Particularly, this viewpoint focus on driving pressure and mechanical power.

 

Comparison of the Diagnostic Accuracies of Monocyte Distribution Width, Procalcitonin, and C-Reactive Protein for Sepsis: A Systematic Review and Meta-Analysis

by Huang, Yu-Hsuan; Chen, Ching-Jung; Shao, Shih-Chieh; Li, Chih‑Huang; Hsiao, Chien-Han; Niu, Kuang-Yu; Yen, Chieh-Ching 

Critical Care Medicine ():10.1097/CCM.0000000000005820, March 06, 2023.

Objectives: 

We performed a systemic review and meta‐analysis to evaluate the diagnostic accuracy of monocyte distribution width (MDW) and to compare with procalcitonin and C‐reactive protein (CRP), in adult patients with sepsis.

Data Sources: 

A systematic literature search was performed in PubMed, Embase, and the Cochrane Library to identify all relevant diagnostic accuracy studies published before October 1, 2022.

Study Selection: 

Original articles reporting the diagnostic accuracy of MDW for sepsis detection with the Sepsis-2 or Sepsis-3 criteria were included.

Data Extraction: 

Study data were abstracted by two independent reviewers using a standardized data extraction form.

Data Synthesis: 

Eighteen studies were included in the meta‐analysis. The pooled sensitivity and specificity of MDW were 84% (95% CI [79–88%]) and 68% (95% CI [60–75%]). The estimated diagnostic odds ratio and the area under the summary receiver operating characteristic curve (SROC) were 11.11 (95% CI [7.36–16.77]) and 0.85 (95% CI [0.81–0.89]). Significant heterogeneity was observed among the included studies. Eight studies compared the diagnostic accuracies of MDW and procalcitonin, and five studies compared the diagnostic accuracies of MDW and CRP. For MDW versus procalcitonin, the area under the SROC was similar (0.88, CI = 0.84–0.93 vs 0.82, CI = 0.76–0.88). For MDW versus CRP, the area under the SROC was similar (0.88, CI = 0.83–0.93 vs 0.86, CI = 0.78–0.95).

Conclusions: 

The results of the meta-analysis indicate that MDW is a reliable diagnostic biomarker for sepsis as procalcitonin and CRP. Further studies investigating the combination of MDW and other biomarkers are advisable to increase the accuracy in sepsis detection.

 

The outcome of IV vitamin C therapy in patients with sepsis or septic shock: a meta-analysis of randomized controlled trials

by Baofang Liang, Jianwei Su, Hanquan Shao, Huiying Chen and Baocheng Xie 

Critical Care volume 27, Article number: 109 (2023) Published: 13 March 2023

Background

To update a meta-analysis of randomized controlled trials (RCTs) and further explore the outcome of IV vitamin C (IVVC) administration in sepsis or septic shock patients.

Methods

This study is a meta-analysis of RCTs. The RCTs of vitamin C therapy in sepsis or septic shock were searched in PubMed, EMBASE and Clinical Trials.gov from inception to January 16, 2023. We registered the protocol with PROSPERO (CRD42022354875). The primary outcome was delta Sequential Organ Failure Assessment (SOFA) score at 72–96 h. Two reviewers independently assessed RCTs according to eligibility criteria: (1) study type: RCT; (2) patient population: patients ≥ 18 years with sepsis or septic shock; (3) intervention: IVVC at any doses as monotherapy or combined with thiamine or and hydrocortisone compared with standard of care, no intervention or placebo (defined as control group); (4) the RCT described short-term mortality or SOFA score. Then, two authors independently extracted related information from RCTs.

Results

Eighteen RCTs (n = 3364 patients) were identified in this meta-analysis. There were significant effects in the delta SOFA score from baseline to 72–96 h (MD, − 0.62; 95% CI, − 1.00 to − 0.25; p = 0.001) and the duration of vasopressor use (MD, − 15.07; 95% CI, − 21.59 to − 8.55; p < 0.00001) with IVVC therapy. Treatment with IVVC was not shown to improve short-term mortality (OR, 0.89; 95% CI, 0.77 to 1.04; p = 0.14); nevertheless, dose at 25–100 mg/kg/d subgroup associated with a significant reduction in short-term mortality (OR, 0.80; 95% CI, 0.65 to 0.97; p = 0.03). An increase adverse event was observed in IVVC therapy (OR, 1.98; 95% CI, 1.06 to 3.68; p = 0.03).

Conclusion

In this meta-analysis, IVVC in sepsis or septic shock patients significantly improved delta SOFA score and reduced the duration of vasopressor use, whereas it was not associated with reduction in short-term mortality and had higher adverse events.

 

Right ventricle-specific therapies in acute respiratory distress syndrome: a scoping review

by Simran Ganeriwal, Gabriele Alves dos Anjos, Mary Schleicher, Maxwell A. Hockstein, Adriano R. Tonelli, Abhijit Duggal and Matthew T. Siuba 

Critical Care volume 27, Article number: 104 (2023) Published: 12 March 2023

Objective

To summarize knowledge and identify gaps in evidence regarding treatment of right ventricular dysfunction (RVD) in acute respiratory distress syndrome (ARDS).

Data sources

We conducted a comprehensive search of MEDLINE, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials.

Study selection

Studies were included if they reported effects of treatments on right ventricular function, whether or not the intent was to modify right ventricular function.

Data extraction

Data extraction was performed independently and in duplicate by two authors. Data items included the study design, patient population, type of intervention, comparison group, and RV-specific outcomes.

Data synthesis

Of 1,430 studies screened, 51 studies reporting on 1,526 patients were included. By frequency, the included studies examined the following interventions: ventilator settings (29.4%), inhaled medications (33.3%), extracorporeal life support (13.7%), intravenous or oral medications (13.7%), and prone positioning (9.8%). The majority of the studies were non-randomized experimental studies (53%), with the next most common being case reports (16%). Only 5.9% of studies were RCTs. In total, 27% of studies were conducted with the goal of modifying RV function.

Conclusions

Given the prevalence of RVD in ARDS and its association with mortality, the dearth of research on this topic is concerning. This review highlights the need for prospective trials aimed at treating RV dysfunction in ARDS.

 

Embracing complexity in sepsis

by Alex R. Schuurman, Peter M. A. Sloot, W. Joost Wiersinga and Tom van der Poll 

Critical Care volume 27, Article number: 102 (2023) Published: 11 March 2023

Abstract

Sepsis involves the dynamic interplay between a pathogen, the host response, the failure of organ systems, medical interventions and a myriad of other factors. This together results in a complex, dynamic and dysregulated state that has remained ungovernable thus far. While it is generally accepted that sepsis is very complex indeed, the concepts, approaches and methods that are necessary to understand this complexity remain underappreciated. In this perspective we view sepsis through the lens of complexity theory. We describe the concepts that support viewing sepsis as a state of a highly complex, non-linear and spatio-dynamic system. We argue that methods from the field of complex systems are pivotal for a fuller understanding of sepsis, and we highlight the progress that has been made over the last decades in this respect. Still, despite these considerable advancements, methods like computational modelling and network-based analyses continue to fly under the general scientific radar. We discuss what barriers contribute to this disconnect, and what we can do to embrace complexity with regards to measurements, research approaches and clinical applications. Specifically, we advocate a focus on longitudinal, more continuous biological data collection in sepsis. Understanding the complexity of sepsis will require a huge multidisciplinary effort, in which computational approaches derived from complex systems science must be supported by, and integrated with, biological data. Such integration could finetune computational models, guide validation experiments, and identify key pathways that could be targeted to modulate the system to the benefit of the host. We offer an example for immunological predictive modelling, which may inform agile trials that could be adjusted throughout the trajectory of disease. Overall, we argue that we should expand our current mental frameworks of sepsis, and embrace nonlinear, system-based thinking in order to move the field forward.

 

Hemorrhage, Disseminated Intravascular Coagulopathy, and Thrombosis Complications Among Critically Ill Patients with COVID-19: An International COVID-19 Critical Care Consortium Study

Critical Care Medicine ():e005798, February 28, 2023.

Objectives: To determine the prevalence and outcomes associated with hemorrhage, disseminated intravascular coagulopathy, and thrombosis (HECTOR) complications in ICU patients with COVID-19.

Design: Prospective, observational study.

Setting: Two hundred twenty-nine ICUs across 32 countries.

Patients: Adult patients (≥ 16 yr) admitted to participating ICUs for severe COVID-19 from January 1, 2020, to December 31, 2021.

Interventions: None.

Measurements and Main Results: HECTOR complications occurred in 1,732 of 11,969 study eligible patients (14%). Acute thrombosis occurred in 1,249 patients (10%), including 712 (57%) with pulmonary embolism, 413 (33%) with myocardial ischemia, 93 (7.4%) with deep vein thrombosis, and 49 (3.9%) with ischemic strokes. Hemorrhagic complications were reported in 579 patients (4.8%), including 276 (48%) with gastrointestinal hemorrhage, 83 (14%) with hemorrhagic stroke, 77 (13%) with pulmonary hemorrhage, and 68 (12%) with hemorrhage associated with extracorporeal membrane oxygenation (ECMO) cannula site. Disseminated intravascular coagulation occurred in 11 patients (0.09%). Univariate analysis showed that diabetes, cardiac and kidney diseases, and ECMO use were risk factors for HECTOR. Among survivors, ICU stay was longer (median days 19 vs 12; p < 0.001) for patients with versus without HECTOR, but the hazard of ICU mortality was similar (hazard ratio [HR] 1.01; 95% CI 0.92–1.12; p = 0.784) overall, although this hazard was identified when non-ECMO patients were considered (HR 1.13; 95% CI 1.02–1.25; p = 0.015). Hemorrhagic complications were associated with an increased hazard of ICU mortality compared to patients without HECTOR complications (HR 1.26; 95% CI 1.09–1.45; p = 0.002), whereas thrombosis complications were associated with reduced hazard (HR 0.88; 95% CI 0.79–0.99, p = 0.03).

Conclusions: HECTOR events are frequent complications of severe COVID-19 in ICU patients. Patients receiving ECMO are at particular risk of hemorrhagic complications. Hemorrhagic, but not thrombotic complications, are associated with increased ICU mortality.

 

Hyperoxemia after reperfusion in cardiac arrest patients: a potential dose–response association with 30-day survival

by Akil Awad, Per Nordberg, Martin Jonsson, Robin Hofmann, Mattias Ringh, Jacob Hollenberg, Jens Olson and Eva Joelsson-Alm 

Critical Care volume 27, Article number: 86 (2023) Published: 06 March 2023

Background

Hyperoxemia may aggravate reperfusion brain injury after cardiac arrest. The aim of this study was to study the associations between different levels of hyperoxemia in the reperfusion period after cardiac arrest and 30-day survival.

Methods

Nationwide observational study using data from four compulsory Swedish registries. Adult in- and out-of-hospital cardiac arrest patients admitted to an ICU, requiring mechanical ventilation, between January 2010 and March 2021, were included. The partial oxygen pressure (PaO2) was collected in a standardized way at ICU admission (± one hour) according to the simplified acute physiology score 3 reflecting the time interval with oxygen treatment from return of spontaneous circulation to ICU admission. Subsequently, patients were divided into groups based on the registered PaO2 at ICU admission. Hyperoxemia was categorized into mild (13.4–20 kPa), moderate (20.1–30 kPa) severe (30.1–40 kPa) and extreme (> 40 kPa), and normoxemia as PaO2 8–13.3 kPa. Hypoxemia was defined as PaO2 < 8 kPa. Primary outcome was 30-day survival and relative risks (RR) were estimated by multivariable modified Poisson regression.

Results

In total, 9735 patients were included of which 4344 (44.6%) were hyperoxemic at ICU admission. Among these, 2217 were classified as mild, 1091 as moderate, 507 as severe, and 529 as extreme hyperoxemia. Normoxemia was present in 4366 (44.8%) patients and 1025 (10.5%) had hypoxemia. Compared to the normoxemia group, the adjusted RR for 30-day survival in the whole hyperoxemia group was 0.87 (95% CI 0.82–0.91). The corresponding results for the different hyperoxemia subgroups were; mild 0.91 (95% CI 0.85–0.97), moderate 0.88 (95% CI 0.82–0.95), severe 0.79 (95% CI 0.7–0.89), and extreme 0.68 (95% CI 0.58–0.79). Adjusted 30-day survival for the hypoxemia compared to normoxemia group was 0.83 (95% CI 0.74–0.92). Similar associations were seen in both out-of-hospital and in-hospital cardiac arrests.

Conclusion

In this nationwide observational study comprising both in- and out-of-hospital cardiac arrest patients, hyperoxemia at ICU admission was associated with lower 30-day survival.

 

Improving vasopressor use in cardiac arrest

by Gavin D. Perkins and Keith Couper 

Critical Care volume 27, Article number: 81 (2023) Published: 02 March 2023

Abstract

The Chain of Survival highlights the effectiveness of early recognition of cardiac arrest and call for help, early cardiopulmonary resuscitation and early defibrillation. Most patients, however, remain in cardiac arrest despite these interventions. Drug treatments, particularly the use of vasopressors, have been included in resuscitation algorithms since their inception. This narrative review describes the current evidence base for vasopressors and reports that adrenaline (1 mg) is highly effective at achieving return of spontaneous circulation (number needed to treat 4) but is less effective on long-term outcomes (survival to 30 days, number needed to treat 111) with uncertain effects on survival with a favourable neurological outcome. Randomised trials evaluating vasopressin, either as an alternative to or in addition to adrenaline, and high-dose adrenaline have failed to find evidence of improved long-term outcomes. There is a need for future trials to evaluate the interaction between steroids and vasopressin. Evidence for other vasopressors (e.g. noradrenaline, phenylephedrine) is insufficient to support or refute their use. The use of intravenous calcium chloride as a routine intervention in out of hospital cardiac arrest is not associated with benefit and may cause harm. The optimal route for vascular access between peripheral intravenous versus intraosseous routes is currently the subject of two large randomised trials. Intracardiac, endobronchial, and intramuscular routes are not recommended. Central venous administration should be limited to patients where an existing central venous catheter is in situ and patent.

 

The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition

by Rolf Rossaint, Arash Afshari, Bertil Bouillon, Vladimir Cerny, Diana Cimpoesu, Nicola Curry, Jacques Duranteau, Daniela Filipescu, Oliver Grottke, Lars Grønlykke, Anatole Harrois, Beverley J. Hunt, Alexander Kaserer, Radko Komadina, Mikkel Herold Madsen, Marc Maegele

Critical Care volume 27, Article number: 80 (2023) Published: 01 March 2023

Background

Severe trauma represents a major global public health burden and the management of post-traumatic bleeding continues to challenge healthcare systems around the world. Post-traumatic bleeding and associated traumatic coagulopathy remain leading causes of potentially preventable multiorgan failure and death if not diagnosed and managed in an appropriate and timely manner. This sixth edition of the European guideline on the management of major bleeding and coagulopathy following traumatic injury aims to advise clinicians who care for the bleeding trauma patient during the initial diagnostic and therapeutic phases of patient management.

Methods

The pan-European, multidisciplinary Task Force for Advanced Bleeding Care in Trauma included representatives from six European professional societies and convened to assess and update the previous version of this guideline using a structured, evidence-based consensus approach. Structured literature searches covered the period since the last edition of the guideline, but considered evidence cited previously. The format of this edition has been adjusted to reflect the trend towards concise guideline documents that cite only the highest-quality studies and most relevant literature rather than attempting to provide a comprehensive literature review to accompany each recommendation.

Results

This guideline comprises 39 clinical practice recommendations that follow an approximate temporal path for management of the bleeding trauma patient, with recommendations grouped behind key decision points. While approximately one-third of patients who have experienced severe trauma arrive in hospital in a coagulopathic state, a systematic diagnostic and therapeutic approach has been shown to reduce the number of preventable deaths attributable to traumatic injury.

Conclusion

A multidisciplinary approach and adherence to evidence-based guidelines are pillars of best practice in the management of severely injured trauma patients. Further improvement in outcomes will be achieved by optimising and standardising trauma care in line with the available evidence across Europe and beyond.