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Abstract Despite interesting and unique pharmacological properties, levosimendan has not proven a clear superiority to placebo in the patient populations that have been enrolled in the various recent multicenter randomized controlled trials. However, the pharmacodynamic effects of levosimendan are still considered potentially very useful in a number of specific situations. Patients with decompensated heart failure requiring inotropic support and receiving beta-blockers represent the most widely accepted indication. Repeated infusions of levosimendan are increasingly used to facilitate weaning from dobutamine and avoid prolonged hospitalizations in patients with end-stage heart failure, awaiting heart transplantation or left ventricular assist device implantation. New trials are under way to confirm or refute the potential usefulness of levosimendan to facilitate weaning from veno-arterial ECMO, to treat cardiogenic shock due to left or right ventricular failure because the current evidence is mostly retrospective and requires confirmation with better-designed studies. Takotsubo syndrome may represent an ideal target for this non-adrenergic inotrope, but this statement also relies on expert opinion. There is no benefit from levosimendan in patients with septic shock. The two large trials evaluating the prophylactic administration of levosimendan (pharmacological preconditioning) in cardiac surgical patients with poor left ventricular ejection fraction could not show a significant reduction in their composite endpoints reflecting low cardiac output syndrome with respect to placebo. However, the subgroup of those who underwent isolated CABG appeared to have a reduction in mortality. A new study will be required to confirm this exploratory finding. Levosimendan remains a potentially useful inodilator agent in a number of specific situations due to its unique pharmacological properties. More studies are needed to provide a higher level of proof regarding these indications.

Abstract Background The Extracorporeal Life Support Organization (ELSO) Maastricht Treaty for Nomenclature in Extracorporeal Life Support (ECLS) established consensus nomenclature and abbreviations for ECLS to ensure accurate, concise communication. Methods We build on this consensus nomenclature by layering a framework of precise and efficient abbreviations for cannula configuration that describe flow direction, number of cannulae used, any additional ECLS-related catheters, and cannulation sites. This work is a consensus of international representatives of the ELSO, including those from the North American, Latin American, European, South and West Asian, and Asian-Pacific chapters of ELSO. Results The classification increases in descriptive capability by introducing a third (cannula tip position) and fourth (cannula dimension) level to those provided in the previous consensus on ECLS cannulation configuration nomenclature. This expansion offers the simplest level needed to convey cannulation information yet allows for more details when required. Conclusions A complete nomenclature for ECLS cannulation configurations accommodating future revisions was developed to facilitate ability to compare practices and results, to promote efficient communication, and to improve quality of registry data.

Abstract Background Drowning is a cause of significant global mortality. The mechanism of injury involves inhalation of water, lung injury and hypoxia. This systematic review addressed the following question: In drowning patients with lung injury, what is the evidence from primary studies regarding treatment strategies and subsequent patient outcomes? Methods The search strategy utilised PRISMA guidelines. Databases searched were MEDLINE, EMBASE, CINAHL, Web of Science and SCOPUS. There were no restrictions on publication date or age of participants. Quality of evidence was evaluated using GRADE methodology. Results Forty-one papers were included. The quality of evidence was very low. Seventeen papers addressed the lung injury of drowning in their research question and 24 had less specific research questions, however included relevant outcome data. There were 21 studies regarding extra-corporeal life support, 14 papers covering the theme of ventilation strategies, 14 addressed antibiotic use, seven papers addressed steroid use and five studies investigating diuretic use. There were no clinical trials. One retrospective comparison of therapeutic strategies was found. There was insufficient evidence to make recommendations as to best practice when supplemental oxygen alone is insufficient. Mechanical ventilation is associated with barotrauma in drowning patients, but the evidence predates the practice of lung protective ventilation. There was insufficient evidence to make recommendations regarding adjuvant therapies. Conclusions Treating the lung injury of drowning has a limited evidentiary basis. There is an urgent need for comparative studies of therapeutic strategies in drowning.

Abstract Background Intensive care units (ICUs) face financial, bed management, and staffing constraints. Detailed data covering all aspects of patients’ journeys into and through intensive care are now collected and stored in electronic health records: machine learning has been used to analyse such data in order to provide decision support to clinicians. Methods Systematic review of the applications of machine learning to routinely collected ICU data. Web of Science and MEDLINE databases were searched to identify candidate articles: those on image processing were excluded. The study aim, the type of machine learning used, the size of dataset analysed, whether and how the model was validated, and measures of predictive accuracy were extracted. Results Of 2450 papers identified, 258 fulfilled eligibility criteria. The most common study aims were predicting complications (77 papers [29.8% of studies]), predicting mortality (70 [27.1%]), improving prognostic models (43 [16.7%]), and classifying sub-populations (29 [11.2%]). Median sample size was 488 (IQR 108–4099): 41 studies analysed data on > 10,000 patients. Analyses focused on 169 (65.5%) papers that used machine learning to predict complications, mortality, length of stay, or improvement of health. Predictions were validated in 161 (95.2%) of these studies: the area under the ROC curve (AUC) was reported by 97 (60.2%) but only 10 (6.2%) validated predictions using independent data. The median AUC was 0.83 in studies of 1000–10,000 patients, rising to 0.94 in studies of > 100,000 patients. The most common machine learning methods were neural networks (72 studies [42.6%]), support vector machines (40 [23.7%]), and classification/decision trees (34 [20.1%]). Since 2015 (125 studies [48.4%]), the most common methods were support vector machines (37 studies [29.6%]) and random forests (29 [23.2%]). Conclusions The rate of publication of studies using machine learning to analyse routinely collected ICU data is increasing rapidly. The sample sizes used in many published studies are too small to exploit the potential of these methods. Methodological and reporting guidelines are needed, particularly with regard to the choice of method and validation of predictions, to increase confidence in reported findings and aid in translating findings towards routine use in clinical practice.

Abstract Background The timely integration of palliative care is important for patients suffering from various advanced diseases with limited prognosis. While a German S-3-guideline on palliative care exists for patients with incurable cancer, a recommendation for non-oncological patients and especially for integration of palliative care into intensive care medicine is missing to date. Method Ten German medical societies worked on recommendations on palliative care aspects in intensive care in a consensus process from 2018 to 2023. Results Based on the german consensus paper, the palliative care aspects of the respective medical disciplines concerning intensive care are addressed. The recommendations partly refer to general situations, but also to specific aspects or diseases, such as geriatric issues, heart or lung diseases, encephalopathies and delirium, terminal renal diseases, oncological diseases and palliative emergencies in intensive care medicine. Measures such as non-invasive ventilation for symptom control and compassionate weaning are also included. Conclusion The timely integration of palliative care into intensive care medicine aims to improve quality of life and symptom control and also takes into acccount the often urgently needed support for patients’ highly stressed relatives.

Abstract COVID-19 patients with acute hypoxemic respiratory failure (AHRF) benefit from high flow nasal cannula (HFNC) oxygen therapy. However, delays in initiating invasive ventilation after HFNC failure are associated with poorer outcomes. The respiratory oxygenation (ROX) index, combining SpO2/FiO2 and respiratory rate, can predict HFNC failure. This meta-analysis evaluated the optimal ROX index cut-offs in predicting HFNC failure among COVID-19 patients at different measurement timings and clinical settings. Three databases were searched for eligible papers. From each study, we reconstructed the confusion matrices at different cut-offs, fitted linear mixed models to estimate the ROX index distribution function, and derived the area under the summary receiver operator characteristic curve (sAUC) and optimal cut-offs to predict HFNC failure. 24 studies containing 4790 patients were included. Overall sAUC was 0.771 (95% CI: 0.666–0.847) (optimal cut-off: 5.23, sensitivity: 0.732, specificity: 0.690). The cut-off values to achieve 80%, 90% sensitivity, 80%, 90% specificity were 5.70, 6.69, 4.45, 3.37, respectively. We stratified the analysis by ROX measurement time and estimated optimal cut-offs and cut-offs to achieve 80% sensitivity and specificity. For 2–6 h and 6–12 h post-HFNC initiation, we propose the use of 80% specific cut-offs to rule in HFNC failure of 6.07 to rule out HFNC failure. Our analysis confirms the overall utility of the ROX index in risk stratification of COVID-19 patients with AHRF receiving HFNC and provides potentially useful cut-offs for different times from HFNC initiation.

Abstract Critical illness is a continuum, but patient care is often fragmented. Value-based critical care focuses on the overall health of the patient, not on an episode of care. The “ICU without borders” model incorporates a concept where members of the critical care team are involved in the management of patients from the onset of critical illness until recovery and beyond. In this paper, we summarise the potential benefits and challenges to patients, families, staff and the wider healthcare system and list some essential requirements, including a tight governance framework, advanced technologies, investment and trust. We also argue that “ICU without borders” should be viewed as a bi-directional model, allowing extended visiting hours, giving patients and families direct access to experienced critical care staff and offering mutual aid when needed.

Abstract Use of extracorporeal membrane oxygenation (ECMO) in cardiopulmonary resuscitation, termed eCPR, offers the prospect of improving survival with good neurological function after cardiac arrest. After death, ECMO can also be used for enhanced preservation of abdominal and thoracic organs, designated normothermic regional perfusion (NRP), before organ recovery for transplantation. To optimize resuscitation and transplantation outcomes, healthcare networks in Portugal and Italy have developed cardiac arrest protocols that integrate use of eCPR with NRP. Similar dissemination of eCPR and its integration with NRP in the USA raise novel ethical issues due to a non-nationalized health system and an opt-in framework for organ donation, as well as other legal and cultural factors. Nonetheless, eCPR investigations are ongoing, and both eCPR and NRP are selectively employed in clinical practice. This paper delineates the most pressing relevant ethical considerations and proposes recommendations for implementation of protocols that aim to promote public trust and reduce conflicts of interest. Transparent policies should rely on protocols that separate lifesaving from organ preservation considerations; robust, centralized eCPR data to inform equitable and evidence-based allocations; uniform practices concerning clinical decision-making and resource utilization; and partnership with community stakeholders, allowing patients to make decisions about emergency care that align with their values. Proactively addressing these ethical and logistical challenges could enable eCPR dissemination and integration with NRP protocols in the USA, with the potential to maximize lives saved through both improved resuscitation with good neurological outcomes and increased organ donation opportunities when resuscitation is unsuccessful or not in accordance with individuals’ wishes.

Abstract This paper discusses the use of Artificial Intelligence Chatbot in scientific writing. ChatGPT is a type of chatbot, developed by OpenAI, that uses the Generative Pre-trained Transformer (GPT) language model to understand and respond to natural language inputs. AI chatbot and ChatGPT in particular appear to be useful tools in scientific writing, assisting researchers and scientists in organizing material, generating an initial draft and/or in proofreading. There is no publication in the field of critical care medicine prepared using this approach; however, this will be a possibility in the next future. ChatGPT work should not be used as a replacement for human judgment and the output should always be reviewed by experts before being used in any critical decision-making or application. Moreover, several ethical issues arise about using these tools, such as the risk of plagiarism and inaccuracies, as well as a potential imbalance in its accessibility between high- and low-income countries, if the software becomes paying. For this reason, a consensus on how to regulate the use of chatbots in scientific writing will soon be required.

Abstract Background Several biomarkers have been proposed to predict the occurrence of acute kidney injury (AKI); however, their efficacy varies between different trials. The aim of this study was to compare the predictive performance of different candidate biomarkers for AKI. Methods In this systematic review, we searched PubMed, Medline, Embase, and the Cochrane Library for papers published up to August 15, 2022. We selected all studies of adults (> 18 years) that reported the predictive performance of damage biomarkers (neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP)), inflammatory biomarker (interleukin-18 (IL-18)), and stress biomarker (tissue inhibitor of metalloproteinases-2 × insulin-like growth factor-binding protein-7 (TIMP-2 × IGFBP-7)) for the occurrence of AKI. We performed pairwise meta-analyses to calculate odds ratios (ORs) and 95% confidence intervals (CIs) individually. Hierarchical summary receiver operating characteristic curves (HSROCs) were used to summarize the pooled test performance, and the Grading of Recommendations, Assessment, Development and Evaluations criteria were used to appraise the quality of evidence. Results We identified 242 published relevant studies from 1,803 screened abstracts, of which 110 studies with 38,725 patients were included in this meta-analysis. Urinary NGAL/creatinine (diagnostic odds ratio [DOR] 16.2, 95% CI 10.1–25.9), urinary NGAL (DOR 13.8, 95% CI 10.2–18.8), and serum NGAL (DOR 12.6, 95% CI 9.3–17.3) had the best diagnostic accuracy for the risk of AKI. In subgroup analyses, urinary NGAL, urinary NGAL/creatinine, and serum NGAL had better diagnostic accuracy for AKI than urinary IL-18 in non-critically ill patients. However, all of the biomarkers had similar diagnostic accuracy in critically ill patients. In the setting of medical and non-sepsis patients, urinary NGAL had better predictive performance than urinary IL-18, urinary L-FABP, and urinary TIMP-2 × IGFBP-7: 0.3. In the surgical patients, urinary NGAL/creatinine and urinary KIM-1 had the best diagnostic accuracy. The HSROC values of urinary NGAL/creatinine, urinary NGAL, and serum NGAL were 91.4%, 85.2%, and 84.7%, respectively. Conclusions Biomarkers containing NGAL had the best predictive accuracy for the occurrence of AKI, regardless of whether or not the values were adjusted by urinary creatinine, and especially in medically treated patients. However, the predictive performance of urinary NGAL was limited in surgical patients, and urinary NGAL/creatinine seemed to be the most accurate biomarkers in these patients. All of the biomarkers had similar predictive performance in critically ill patients. Trial registration CRD42020207883 , October 06, 2020.

Abstract Early haemorrhage control and minimizing the time to definitive care have long been the cornerstones of therapy for patients exsanguinating from non-compressible haemorrhage (NCH) after penetrating injuries, as only basic treatment could be provided on scene. However, more recently, advanced on-scene treatments such as the transfusion of blood products, resuscitative thoracotomy (RT) and resuscitative endovascular balloon occlusion of the aorta (REBOA) have become available in a small number of pre-hospital critical care teams. Although these advanced techniques are included in the current traumatic cardiac arrest algorithm of the European Resuscitation Council (ERC), published in 2021, clear guidance on the practical application of these techniques in the pre-hospital setting is scarce. This paper provides a scoping review on how these advanced techniques can be incorporated into practice for the resuscitation of patients exsanguinating from NCH after penetrating injuries, based on available literature and the collective experience of several helicopter emergency medical services (HEMS) across Europe who have introduced these advanced resuscitation interventions into routine practice. Graphical Abstract

Abstract Background New-onset atrial fibrillation (NOAF) in patients treated on an intensive care unit (ICU) is common and associated with significant morbidity and mortality. We undertook a systematic scoping review to summarise comparative evidence to inform NOAF management for patients admitted to ICU. Methods We searched MEDLINE, EMBASE, CINAHL, Web of Science, OpenGrey, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, ISRCTN, ClinicalTrials.gov, EU Clinical Trials register, additional WHO ICTRP trial databases, and NIHR Clinical Trials Gateway in March 2019. We included studies evaluating treatment or prevention strategies for NOAF or acute anticoagulation in general medical, surgical or mixed adult ICUs. We extracted study details, population characteristics, intervention and comparator(s), methods addressing confounding, results, and recommendations for future research onto study-specific forms. Results Of 3,651 citations, 42 articles were eligible: 25 primary studies, 12 review articles and 5 surveys/opinion papers. Definitions of NOAF varied between NOAF lasting 30 s to NOAF lasting > 24 h. Only one comparative study investigated effects of anticoagulation. Evidence from small RCTs suggests calcium channel blockers (CCBs) result in slower rhythm control than beta blockers (1 study), and more cardiovascular instability than amiodarone (1 study). Evidence from 4 non-randomised studies suggests beta blocker and amiodarone therapy may be equivalent in respect to rhythm control. Beta blockers may be associated with improved survival compared to amiodarone, CCBs, and digoxin, though supporting evidence is subject to confounding. Currently, the limited evidence does not support therapeutic anticoagulation during ICU admission. Conclusions From the limited evidence available beta blockers or amiodarone may be superior to CCBs as first line therapy in undifferentiated patients in ICU. The little evidence available does not support therapeutic anticoagulation for NOAF whilst patients are critically ill. Consensus definitions for NOAF, rate and rhythm control are needed.

Abstract Background Disrupted vital-sign circadian rhythms in the intensive care unit (ICU) are associated with complications such as immune system disruption, delirium and increased patient mortality. However, the prevalence and extent of this disruption is not well understood. Tools for its detection are currently limited. Methods This paper evaluated and compared vital-sign circadian rhythms in systolic blood pressure, heart rate, respiratory rate and temperature. Comparisons were made between the cohort of patients who recovered from the ICU and those who did not, across three large, publicly available clinical databases. This comparison included a qualitative assessment of rhythm profiles, as well as quantitative metrics such as peak–nadir excursions and correlation to a demographically matched ‘recovered’ profile. Results Circadian rhythms were present at the cohort level in all vital signs throughout an ICU stay. Peak–nadir excursions and correlation to a ‘recovered’ profile were typically greater throughout an ICU stay in the cohort of patients who recovered, compared to the cohort of patients who did not. Conclusions These results suggest that vital-sign circadian rhythms are typically present at the cohort level throughout an ICU stay and that quantitative assessment of these rhythms may provide information of prognostic use in the ICU.

Abstract Medications used for supportive care or prophylaxis constitute a significant portion of drug utilization in the intensive care unit. Evidence-based guidelines are available for many aspects of supportive care but drug doses listed are typically for patients with normal body habitus and not morbid obesity. Failure to account for the pharmacokinetic changes that occur with obesity can lead to an incorrect dose and treatment failure or toxicity. This paper is intended to help clinicians design initial dosing regimens in critically ill obese patients for medications commonly used for hemodynamic support or prophylaxis. A detailed literature search of medications used for supportive care or prophylaxis listed in practice guidelines was conducted with an emphasis on obesity, pharmacokinetics and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided. For medications used for hemodynamic support, a similar strategy can be used as in non-obese patients. Similarly, medications for stress ulcer prophylaxis do not need to be adjusted. Anticoagulants for venous thromboembolism prophylaxis, on the other hand, require an individualized approach where higher doses are necessary.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Practice guidelines provide clear evidence-based recommendations for the use of drug therapy to manage pain, agitation, and delirium associated with critical illness. Dosing recommendations however are often based on strategies used in patients with normal body habitus. Recommendations specific to critically ill patients with extreme obesity are lacking. Nonetheless, clinicians must craft dosing regimens for this population. This paper is intended to help clinicians design initial dosing regimens for medications commonly used in the management of pain, agitation, and delirium in critically ill patients with extreme obesity. A detailed literature search was conducted with an emphasis on obesity, pharmacokinetics, and dosing. Relevant manuscripts were reviewed and strategies for dosing are provided.

Abstract Mass critical care caused by the severe acute respiratory syndrome corona virus 2 pandemic poses an extreme challenge to hospitals. The primary goal of hospital disaster preparedness and response is to maintain conventional or contingency care for as long as possible. Crisis care must be delayed as long as possible by appropriate measures. Increasing the intensive care unit (ICU) capacities is essential. In order to adjust surge capacity, the reduction of planned, elective patient care is an adequate response. However, this involves numerous problems that must be solved with a sense of proportion. This paper summarises preparedness and response measures recommended to acute care hospitals.

Abstract In order to assess the significance of drug/substance levels measured in intensive care medicine and clinical and forensic toxicology as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. We revisited and expanded our 2012 compilation of therapeutic and toxic plasma concentration ranges as well as half-lives of now more than 1100 drugs and other xenobiotics. Data have been abstracted from original papers, text books, and previous compilations and have been completed with data collected in our own forensic and clinical toxicology laboratories. We compiled the data presented in the table and the corresponding annotations over the past 30+ years. A previous compilation was completely double-checked, revised, and updated, if necessary. In addition, more than 200 substances, especially drugs who have been introduced since 2012 to the market as well as illegal drugs and other xenobiotics which became known to cause intoxications were added. We carefully referenced all data. Moreover, the annotations providing details were updated and revised, when necessary. For more than 1100 drugs and other xenobiotics, therapeutic (“normal”) and, if data was available, toxic, and comatose-fatal plasma/blood concentrations as well as elimination half-lives were compiled in a table. In case of intoxications, the blood concentration of the substance and/or metabolite better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment and monitoring of acute and chronic intoxications as well as to support forensic and clinical expert opinions.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Patients admitted to the intensive care unit (ICU) often require invasive mechanical ventilation. Ventilator-associated lower respiratory tract infections (VA-LRTI), either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP), are the most common complication among this patient cohort. VAT and VAP are currently diagnosed and treated as separate entities, viewed as binary disease elements despite an inherent subjectivity in distinguishing them clinically. This paper describes a new approach to pulmonary infections in critically ill patients. Our conjecture is that the host-pathogen interaction during mechanical ventilation determines a local compartmentalized or systemic de-compartmentalized response, based on host immunity and inflammation, and the pathogenic potential of the infecting organism. This compartmentalized or de-compartmentalized response establishes disease severity along a continuum of colonization, VAT or VAP. This change in approach is underpinned by the dissemination hypothesis, which acknowledges the role of immune and inflammatory systems in determining host response to pathogenic organisms in the lower respiratory tract. Those with intact immune and inflammatory pathways may limit infection to a compartmentalized VAT, while immunosuppressed mechanically ventilated patients are at greater risk of a de-compartmentalized VAP. Taking this model from the realm of theory to the bedside will require a greater understanding of inflammatory and immune pathways, and the development of novel disease-specific biomarkers and diagnostic techniques. Advances will lead to early initiation of optimal bespoke antimicrobial therapy, where the intensity and duration of therapy are tailored to clinical, immune and biomarker response. This approach will benefit towards a personalized treatment.

Abstract This paper discusses the physiological and technological concepts that might form the future of critical care medicine. Initially, we discuss the need for a personalized approach and introduce the concept of personalized physiological medicine (PPM), including (1) assessment of frailty and physiological reserve, (2) continuous assessment of organ function, (3) assessment of the microcirculation and parenchymal cells, and (4) integration of organ and cell function for continuous therapeutic feedback control. To understand the cellular basis of organ failure, we discuss the processes that lead to cell death, including necrosis, necroptosis, autophagy, mitophagy, and cellular senescence. In vivo technology is used to monitor these processes. To this end, we discuss new materials for developing in vivo biosensors and drug delivery systems. Such in vivo biosensors will define the diagnostic platform of the future ICU in vivo interacting with theragnostic drugs. In addition to pharmacological therapeutic options, placement and control of artificial organs to support or replace failing organs will be central in the ICU in vivo of the future. Remote monitoring and control of these biosensors and artificial organs will be made using adaptive physiological mathematical modeling of the critically ill patient. The current state of these developments is discussed.

Abstract The rationale for the provision of nitrogen from proteins given via the enteral route or from intravenous amino acids is to boost the synthesis of muscle proteins, and thereby to limit the severity of intensive care unit-acquired weakness by the prevention of muscle loss. However, the optimal timing for supplemental nitrogen provision is a matter of debate and controversy. Indeed, consistent data from retrospective studies support an association between high early protein intakes and better outcomes, while recent post-hoc findings from prospective studies raise safety concerns. This pro–con paper details the arguments of both sides and highlights the need for large-scale prospective studies assessing the safety and efficacy of different levels of protein intake in combination with physical activity and summarizes the currently recruiting clinical trials.

An amendment to this paper has been published and can be accessed via the original article.

Abstract Background Circulatory shock is a common syndrome with a high mortality and limited therapeutic options. Despite its discovery and use in clinical and experimental settings more than a half-century ago, angiotensin II (Ang II) has only been recently evaluated as a vasopressor in distributive shock. We examined existing literature for associations between Ang II and the resolution of circulatory shock. Methods We searched PubMed, MEDLINE, Ovid, and Embase to identify all English literature accounts of intravenous Ang II in humans for the treatment of shock (systolic blood pressure [SBP] ≤ 90 mmHg or a mean arterial pressure [MAP] ≤ 65 mmHg), and hand-searched the references of extracted papers for further studies meeting inclusion criteria. Of 3743 articles identified, 24 studies including 353 patients met inclusion criteria. Complete data existed for 276 patients. Extracted data included study type, publication year, demographics, type of shock, dosing of Ang II or other vasoactive medications, and changes in BP, lactate, and urine output. BP effects were grouped according to type of shock, with additional analyses completed for patients with absent blood pressure. Shock was distributive (n = 225), cardiogenic (n = 38), or from other causes (n = 90). Blood pressure as absent in 18 patients. Results For the 276 patients with complete data, MAP rose by 23.4% from 63.3 mmHg to 78.1 mmHg in response to Ang II (dose range: 15 ng/kg/min to 60 mcg/min). SBP rose by 125.2% from 56.9 mmHg to 128.2 mmHg (dose range: 0.2 mcg/min to a 1500 mcg bolus). A total of 271 patients with complete data were determined to exhibit a BP effect which was directly associated with Ang II. Subgroups (patients with cardiogenic, septic, and other types of shock) exhibited similar increases in BP. In patients with absent BP, deemed to be cardiac arrest, return of spontaneous circulation (ROSC) was achieved, and BP increased by an average of 107.3 mmHg in 11 of 18 patients. The remaining seven patients with cardiac arrest did not respond. Conclusions Intravenous Ang II is associated with increased BP in patients with cardiogenic, distributive, and unclassified shock. A role may exist for Ang II in restoring circulation in cardiac arrest.

Abstract With imprecise definitions, inexact measurement tools, and flawed study execution, our clinical science often lags behind bedside experience and simply documents what appear to be the apparent faults or validity of ongoing practices. These impressions are later confirmed, modified, or overturned by the results of the next trial. On the other hand, insights that stem from the intuitions of experienced clinicians, scientists and educators—while often neglected—help place current thinking into proper perspective and occasionally point the way toward formulating novel hypotheses that direct future research. Both streams of information and opinion contribute to progress. In this paper we present a wide-ranging set of unproven ‘out of the mainstream’ ideas of our FCCM faculty, each with a defensible rationale and holding clear implications for altering bedside management. Each proposition was designed deliberately to be provocative so as to raise awareness, stimulate new thinking and initiate lively dialog.

Abstract This paper introduces the concept of personalized physiological medicine that is specifically directed at the needs of the critically ill patient. This differs from the conventional view of personalized medicine, characterized by biomarkers and gene profiling, instead focusing on time-variant changes in the pathophysiology and regulation of various organ systems and their cellular and subcellular constituents. I propose that personalized physiological medicine is composed of four pillars relevant to the critically ill patient. Pillar 1 is defined by the frailty and fitness of the patient and their physiological reserve to cope with the stress of critical illness and therapy. Pillar 2 involves monitoring of the key physiological variables of the different organ systems and their response to disease and therapy. Pillar 3 concerns the evaluation of the success of resuscitation by assessment of the hemodynamic coherence between the systemic and microcirculation and parenchyma of the organ systems. Finally, pillar 4 is defined by the integration of the physiological and clinical data into a time-learning adaptive model of the patient to provide feedback about the function of organ systems and to guide and assess the response to disease and therapy. I discuss each pillar and describe the challenges to research and development that will allow the realization of personalized physiological medicine to be practiced at the bedside for critically ill patients.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

Abstract The concept of net ultrafiltration (UFNET) mentioned in the paper by Murugan et al. in a recent issue of Critical Care does not equate to the real UFNET in patients with renal replacement therapy initiation. Furthermore, the baseline blood pressure among the groups had a statistically significant difference. Both of these two factors may affect the final results. Thus, we should be cautious interpreting the conclusions.