A 16-year-old man with leptospirosis and atypical disseminated intravascular coagulation: a case report.

BACKGROUND: Leptospirosis is known for its pulmonary form characterized by intra-alveolar hemorrhage, exhibiting a high mortality rate. Management by venous-venous extracorporeal membrane oxygenation has been reported in a small number of cases. CASE PRESENTATION: We report herein the case of a 16-year-old Caucasian male who was admitted with rapidly deteriorating respiratory and digestive complaints. He developed severe acute respiratory distress syndrome secondary to disseminated intravascular coagulation and intra-alveolar hemorrhage, requiring initiation of venous-venous extracorporeal membrane oxygenation. Initial infectious and immunological assessments were inconclusive, but repeat serology on the tenth day of admission confirmed a diagnosis of leptospirosis. The patient received multiple transfusions, and upon favorable response to treatment with corticosteroids and antibiotics, he was successfully weaned off venous-venous extracorporeal membrane oxygenation, which was discontinued after 12 days. CONCLUSION: Leptospirosis is a rare cause of severe acute respiratory failure following pulmonary hemorrhage. It is typically diagnosed by serology, with detectable IgM antibodies 5-7 days after the onset of symptoms. We report that early support with respiratory extracorporeal membrane oxygenation favors timely clearance of endobronchial clotting, parenchymal recovery, and prevention of ventilator-induced lung injury. Major hypofibrinogenemia, which did not seem to worsen during extracorporeal membrane oxygenation application, was managed by repeated transfusions. Further studies investigating the pathogenesis of this coagulopathy are required to further optimize the management of this rare and severe complication.

Cerebro-spinal fluid glucose and lactate concentrations changes in response to therapies in patIents with primary brain injury: the START-TRIP study.

INTRODUCTION: Altered levels of cerebrospinal fluid (CSF) glucose and lactate concentrations are associated with poor outcomes in acute brain injury patients. However, no data on changes in such metabolites consequently to therapeutic interventions are available. The aim of the study was to assess CSF glucose-to-lactate ratio (CGLR) changes related to therapies aimed at reducing intracranial pressure (ICP). METHODS: A multicentric prospective cohort study was conducted in 12 intensive care units (ICUs) from September 2017 to March 2022. Adult (> 18 years) patients admitted after an acute brain injury were included if an external ventricular drain (EVD) for intracranial pressure (ICP) monitoring was inserted within 24 h of admission. During the first 48-72 h from admission, CGLR was measured before and 2 h after any intervention aiming to reduce ICP ("intervention"). Patients with normal ICP were also sampled at the same time points and served as the "control" group. RESULTS: A total of 219 patients were included. In the intervention group (n = 115, 53%), ICP significantly decreased and CPP increased. After 2 h from the intervention, CGLR rose in both the intervention and control groups, although the magnitude was higher in the intervention than in the control group (20.2% vs 1.6%; p = 0.001). In a linear regression model adjusted for several confounders, therapies to manage ICP were independently associated with changes in CGLR. There was a weak inverse correlation between changes in ICP and CGRL in the intervention group. CONCLUSIONS: In this study, CGLR significantly changed over time, regardless of the study group. However, these effects were more significant in those patients receiving interventions to reduce ICP.

Early Prediction of High-Flow Oxygen Therapy Failure in COVID-19 Acute Hypoxemic Respiratory Failure: A Retrospective Study of Scores and Thresholds.

Background High-flow oxygen therapy (HFOT) has been widely used as an effective alternative to invasive mechanical ventilation (IMV) in some critically ill patients with COVID-19 pneumonia. This study aimed to compare different tools, including the respiratory rate and oxygenation (ROX) index, to predict HFOT failure in this setting. Methodology This single-center retrospective observational study was conducted from September to December 2020 and assessed COVID-19 patients who required HFOT as the first treatment at admission; HFOT failure was defined as IMV use. Prognostic scoring tools were as follows: the Sequential Organ Failure Assessment (SOFA), Acute Physiology And Chronic Health Evaluation (APACHE) II, and Simplified Acute Physiology Score (SAPS) III scores; C-reactive protein; lung consolidation percentage on chest CT; mean partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FiO2) ratio; and ROX index and modified ROX index, calculated using PaO2 instead of blood oxygen saturation, within the first 24 hours after admission to the intensive care unit (ICU). These scores were analyzed using a multivariate Cox proportional hazard model; optimal cutoffs were computed using the R system for statistical computing. Results The study enrolled 52 patients, 31 (60%) of whom experienced HFOT failure. The best predictors of HFOT failure measured 24 hours after HFOT initiation were as follows: PaO2/FiO2 (threshold 123.6, sensitivity 87%, specificity 81%, hazard ratio [HR] 7.76, and 95% confidence interval [CI] 2.39-17.1); ROX index (threshold 5.63, sensitivity 68%, specificity 95%, HR 6.18, and 95% CI 2.54-13.4); and modified ROX index (threshold 4.94, sensitivity 81%, specificity 90%, HR 8.16, and 95% CI 3.16-21.5) (P < 0.001 for all). Conclusions Early assessment of the ROX index, modified ROX index, and PaO2/FiO2 ratio can adequately predict, with high accuracy, HFOT failure in COVID-19 patients. Because thresholds remain debated and are still not sufficiently validated, we advocate using them with caution for clinical decision-making in this context.

Reduced anticoagulation targets in extracorporeal life support (RATE): study protocol for a randomized controlled trial.

BACKGROUND: Although life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT). However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome. METHODS: We will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2-2.5 times baseline aPTT, 1.5-2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months. DISCUSSION: We hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO. TRIAL REGISTRATION: ClinicalTrials.gov NCT04536272 . Registered on 2 September 2020. Netherlands Trial Register NL7969.

How should dexmedetomidine and clonidine be prescribed in the critical care setting? / Como a dexmedetomidina e a clonidina devem ser prescritas no ambiente de terapia intensiva?

Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.

O manejo cardíaco, ventilatório e renal no ambiente de terapia intensiva tem melhorado nas últimas décadas. Cognição e sedação representam dois dos últimos desafios a vencer. Como a sedação convencional não é ideal, e a sedação evocada por agonistas adrenérgicos alfa-2 (sedação "cooperativa" com dexmedetomidina, clonidina ou guanfacina) representa uma alternativa valiosa, este artigo abrange três tópicos práticos para os quais há lacunas na medicina baseada em evidência. O primeiro deles é a mudança de sedação convencional para sedação cooperativa ("mudança"): a resposta curta consiste em retirada abrupta de sedação convencional, implantação imediata de infusão de um agonista alfa-2 e uso de "sedação de resgate" (bolos de midazolam) ou "sedação agressiva" (haloperidol em bolos) para estabilizar a sedação cooperativa. O segundo tópico é a mudança de sedação convencional para sedação cooperativa em pacientes instáveis (por exemplo: delirium tremens refratário, choque séptico, síndrome do desconforto respiratório agudo etc.), pois, para evitar a hipotensão e a bradicardia provocadas por desativadores simpáticos, a resposta curta é manter o volume sistólico por administração de volume, vasopressores e inotrópicos. Por fim, para evitar essas mudanças e dificuldades associadas, os agonistas alfa-2 podem ser sedativos de primeira linha. A resposta curta é administrar agonistas alfa-2 lentamente desde a admissão ou intubação endotraqueal, até estabilização da sedação cooperativa. Dessa forma, conclui-se que os agonistas alfa-2 são, ao mesmo tempo, agentes desativadores simpáticos e sedativos, bem como a desativação simpática implica na manutenção do volume sistólico e na avaliação persistente da volemia. A medicina baseada em evidência deve documentar esta proposta.

Como a dexmedetomidina e a clonidina devem ser prescritas no ambiente de terapia intensiva? / How should dexmedetomidine and clonidine be prescribed in the critical care setting?

RESUMO O manejo cardíaco, ventilatório e renal no ambiente de terapia intensiva tem melhorado nas últimas décadas. Cognição e sedação representam dois dos últimos desafios a vencer. Como a sedação convencional não é ideal, e a sedação evocada por agonistas adrenérgicos alfa-2 (sedação "cooperativa" com dexmedetomidina, clonidina ou guanfacina) representa uma alternativa valiosa, este artigo abrange três tópicos práticos para os quais há lacunas na medicina baseada em evidência. O primeiro deles é a mudança de sedação convencional para sedação cooperativa ("mudança"): a resposta curta consiste em retirada abrupta de sedação convencional, implantação imediata de infusão de um agonista alfa-2 e uso de "sedação de resgate" (bolos de midazolam) ou "sedação agressiva" (haloperidol em bolos) para estabilizar a sedação cooperativa. O segundo tópico é a mudança de sedação convencional para sedação cooperativa em pacientes instáveis (por exemplo: delirium tremens refratário, choque séptico, síndrome do desconforto respiratório agudo etc.), pois, para evitar a hipotensão e a bradicardia provocadas por desativadores simpáticos, a resposta curta é manter o volume sistólico por administração de volume, vasopressores e inotrópicos. Por fim, para evitar essas mudanças e dificuldades associadas, os agonistas alfa-2 podem ser sedativos de primeira linha. A resposta curta é administrar agonistas alfa-2 lentamente desde a admissão ou intubação endotraqueal, até estabilização da sedação cooperativa. Dessa forma, conclui-se que os agonistas alfa-2 são, ao mesmo tempo, agentes desativadores simpáticos e sedativos, bem como a desativação simpática implica na manutenção do volume sistólico e na avaliação persistente da volemia. A medicina baseada em evidência deve documentar esta proposta.

ABSTRACT Cardiac, ventilatory and kidney management in the critical care setting has been optimized over the past decades. Cognition and sedation represent one of the last remaning challenges. As conventional sedation is suboptimal and as the sedation evoked by alpha-2 adrenergic agonists ("cooperative" sedation with dexmedetomidine, clonidine or guanfacine) represents a valuable alternative, this manuscript covers three practical topics for which evidence-based medicine is lacking: a) Switching from conventional to cooperative sedation ("switching"): the short answer is the abrupt withdrawal of conventional sedation, immediate implementation of alpha-2 agonist infusion and the use of "rescue sedation" (midazolam bolus[es]) or "breakthrough sedation" (haloperidol bolus[es]) to stabilize cooperative sedation. b) Switching from conventional to cooperative sedation in unstable patients (e.g., refractory delirium tremens, septic shock, acute respiratory distress syndrome, etc.): to avoid hypotension and bradycardia evoked by sympathetic deactivation, the short answer is to maintain the stroke volume through volume loading, vasopressors and inotropes. c) To avoid these switches and associated difficulties, alpha-2 agonists may be considered first-line sedatives. The short answer is to administer alpha-2 agonists slowly from admission or endotracheal intubation up to stabilized cooperative sedation. The "take home" message is as follows: a) alpha-2 agonists are jointly sympathetic deactivators and sedative agents; b) sympathetic deactivation implies maintaining the stroke volume and iterative assessment of volemia. Evidence-based medicine should document our propositions.

Pleth variability index and fluid management practices: a multicenter service evaluation.

OBJECTIVES: The introduction of a new technology has the potential to modify clinical practices, especially if easy to use, reliable and non-invasive. This observational before/after multicenter service evaluation compares fluid management practices during surgery (with fluids volumes as primary outcome), and clinical outcomes (secondary outcomes) before and after the introduction of the Pleth Variability Index (PVI), a non-invasive fluid responsiveness monitoring. RESULTS: In five centers, 23 anesthesiologists participated during a 2-years period. Eighty-eight procedures were included. Median fluid volumes infused during surgery were similar before and after PVI introduction (respectively, 1000 ml [interquartile range 25-75 [750-1700] and 1000 ml [750-2000]). The follow-up was complete for 60 from these and outcomes were similar. No detectable change in the fluid management was observed after the introduction of a new technology in low to moderate risk surgery. These results suggest that the introduction of a new technology should be associated with an implementation strategy if it is intended to be associated with changes in clinical practice.

What Can We Learn from Sarcopenia with Curarisation in the Context of Cancer Surgery? A Review of the Literature.

INTRODUCTION: The monitoring of the curarisation is a unique opportunity to investigate the function of the neuromuscular junction (NMJ) during cancer surgery, especially in frailty-induced and age-related sarcopenia. METHOD: We conducted a comprehensive literature review in PubMed, without any limit of time related to frailty, sarcopenia, age and response to neuromuscular blockers in the context of cancer surgery. RESULTS: Several modifications appear with age: changes in cardiac output, a decrease in muscle mass and increase in body fat, the deterioration in renal and hepatic function, the plasma clearance and the volume of distribution in elderly are smaller. These changes can be exacerbated in cancer patients. We also find modifications of the NMJ: dysfunctional mitochondria, modifications in the innervation of muscle fibers and motor units, uncoupling of the excitation-contraction of muscle fibers, inflammation. Neuromuscular blocking agents (NMBAs) compete with acetylcholine and prevent it from fixing itself on its receptor. Many publications reported guidelines for using NMBAs in the elderly, based on studies comparing old people with young people. No one screened frailty before, and thus, no studies compared frail elderly and non-frail elderly undergoing cancer surgery. CONCLUSION: Despite many studies about curarisation in the specific populations, and many arguments for a potential interest for investigation, no studies investigated specifically the response to NMBAs in regard of the frailty-induced and age-related sarcopenia.

Pulmonary lobectomy in two multitrauma patients under extracorporeal circulation placed preoperatively in an intensive care unit: A case report.

The clinical course of our two patients highlights the feasibility of using venovenous extracorporeal membrane oxygenation (ECMO) with heparin for multitraumatic patients needing thoracic surgery. Further research is required to determine if surgery can be performed with totally heparin-free vv-ECMO. All ICU teams should become familiar with this technique.

Cancer surgery induces inflammation, immunosuppression and neo-angiogenesis, but is it influenced by analgesics?

Surgery remains a main part of the treatment of most solid tumors. Paradoxically, rapid disease progression may be a consequence of surgery in patients presenting with a dysregulated inflammatory response, and increased angiogenesis consequent to a suppressed antitumoral immune response. Physicians taking care of cancer patients should be aware of the important findings that indicate that analgesic techniques could play a role in these phenomena.