Ilaria Alice Crippa

Optimizing sedation in patients with acute brain injury

Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear. In patients with ABI, sedation has ‘general’ indications (control of anxiety, pain, discomfort, agitation, facilitation of mechanical ventilation) and ‘neuro-specific’ indications (reduction of cerebral metabolic demand, improved brain tolerance to ischaemia). Sedation also is an essential therapeutic component of intracranial pressure therapy, targeted temperature management and seizure control. Given the lack of large trials which have evaluated clinically relevant endpoints, sedative selection depends on the effect of each agent on cerebral and systemic haemodynamics. Titration and withdrawal of sedation in the NICU setting has to be balanced between the risk that interrupting sedation might exacerbate brain injury (e.g. intracranial pressure elevation) and the potential benefits of enhanced neurological function and reduced complications. In this review, we provide a concise summary of cerebral physiologic effects of sedatives and analgesics, the advantages/disadvantages of each agent, the comparative effects of standard sedatives (propofol and midazolam) and the emerging role of alternative drugs (ketamine). We suggest a pragmatic approach for the use of sedation-analgesia in the NICU, focusing on some practical aspects, including optimal titration and management of sedation withdrawal according to ABI severity.

Six-Month Outcome of Immunocompromised Patients with Severe Acute Respiratory Distress Syndrome Rescued by Extracorporeal Membrane Oxygenation. An International Multicenter Retrospective Study

OBJECTIVES To report outcomes of immunocompromised patients treated with extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) and to identify their pre-ECMO predictors of 6-month mortality and main ECMO-related complications. METHODS Retrospective multicenter study in 10 international intensive care units (ICUs) with high ECMO-case volumes. Immunocompromised patients, defined as having hematological malignancies, active solid tumor, solid-organ transplant, acquired immunodeficiency syndrome, or long-term or high-dose corticosteroid or immunosuppressant use, and severe ECMO-treated ARDS from 2008 to 2015 were included Measurements and Main Results: We collected demographics, clinical, ECMO-related complications, ICU- and 6-month-outcome data for 203 patients (median APACHE II 28 [25th ;75th percentile, 20;33]; age 51 [38;59] years, PaO2/FiO2 60 [50;82] mmHg before ECMO) who fulfilled our inclusion criteria. Six-month survival was only 30%, with a respective median ECMO duration and ICU stay of 8 [5;14] and 25 [16;50] days. Patients with hematological malignancies had significantly poorer outcomes than others (log-rank P=0.02). Multivariate analyses retained <30 days between immunodeficiency diagnosis and ECMO cannulation as being associated with lower 6-month mortality (odds ratio 0.32 (95% confidence interval 0.16-0.66); P=0.002), and lower platelet count, higher PCO2, age and driving pressure as independent pre-ECMO predictors of 6-month mortality. CONCLUSION Recently diagnosed immunodeficiency is associated with a much better prognosis in ECMO-treated severe ARDS. However, low 6-month survival of our large cohort of immunocompromised patients supports restricting ECMO to patients with realistic oncological/therapeutic prognoses, acceptable functional status and few pre-ECMO mortality-risk factors.Rationale: Because encouraging rates for hospital and long‐term survival of immunocompromised patients in ICUs have been described, these patients are more likely to receive invasive therapies, like extracorporeal membrane oxygenation (ECMO). Objectives: To report outcomes of immunocompromised patients treated with ECMO for severe acute respiratory distress syndrome (ARDS) and to identify their pre‐ECMO predictors of 6‐month mortality and main ECMO‐related complications. Methods: Retrospective multicenter study in 10 international ICUs with high volumes of ECMO cases. Immunocompromised patients, defined as having hematological malignancies, active solid tumor, solid‐organ transplant, acquired immunodeficiency syndrome, or long‐term or high‐dose corticosteroid or immunosuppressant use, and severe ECMO‐treated ARDS, from 2008 to 2015 were included. Measurements and Main Results: We collected demographics, clinical data, ECMO‐related complications, and ICU‐ and 6 month‐outcome data for 203 patients (median Acute Physiology and Chronic Health Evaluation II score, 28 [25th‐75th percentile, 20‐33]; age, 51 [38‐59] yr; PaO2/FiO2, 60 [50‐82] mm Hg before ECMO) who fulfilled our inclusion criteria. Six‐month survival was only 30%, with a respective median ECMO duration and ICU stay of 8 (5‐14) and 25 (16‐50) days. Patients with hematological malignancies had significantly poorer outcomes than others (log‐rank P = 0.02). ECMO‐related major bleeding, cannula infection, and ventilator‐associated pneumonia were frequent (36%, 10%, and 50%, respectively). Multivariate analyses retained fewer than 30 days between immunodeficiency diagnosis and ECMO cannulation as being associated with lower 6‐month mortality (odds ratio, 0.32 [95% confidence interval, 0.16‐0.66]; P = 0.002), and lower platelet count, higher Pco2, age, and driving pressure as independent pre‐ECMO predictors of 6‐month mortality. Conclusions: Recently diagnosed immunodeficiency is associated with a much better prognosis in ECMO‐treated severe ARDS. However, low 6‐month survival of our large cohort of immunocompromised patients supports restricting ECMO to patients with realistic oncological/therapeutic prognoses, acceptable functional status, and few pre‐ECMO mortality‐risk factors.

Normobaric hyperoxia after stroke: a word of caution

Oxygen is one of the most abundant elements in the universe and is essential for life as it is the main component of water and is involved in mitochondrial respiration. In the medical setting, oxygen therapy was introduced during surgical procedures almost a century ago and is now widely used in hospitalized patients or in emergency medicine for different medical conditions. Oxygen therapy is the first-line intervention in acute hypoxemia. Indeed, up to 85% of intensive care unit (ICU) patients who are not treated with mechanical ventilation receive supplementary oxygen via different interfaces, including nasal cannulas and facial masks [1]. Nevertheless, target values for arterial oxygen tension (PaO2) or hemoglobin saturations (SaO2) should not be ‘as high as possible,’ which has long been considered optimal. Excessive oxygen therapy may expose patients to high PaO2 levels, which are associated with potential harm.

Neuroprotective strategies and neuroprognostication after cardiac arrest

Neurocognitive disturbances are common among survivors of cardiac arrest (CA). Although initial management of CA, including bystander cardiopulmonary resuscitation, optimal chest compression, and early defibrillation, has been implemented continuously over the last years, few therapeutic interventions are available to minimize or attenuate the extent of brain injury occurring after the return of spontaneous circulation. In this review, we discuss several promising drugs that could provide some potential benefits for neurological recovery after CA. Most of these drugs have been investigated exclusively in experimental CA models and only limited clinical data are available. Further research, which also considers combined neuroprotective strategies that target multiple pathways involved in the pathophysiology of postanoxic brain injury, is certainly needed to demonstrate the effectiveness of these interventions in this setting. Moreover, the evaluation of neurological prognosis of comatose patients after CA remains an important challenge that requires the accurate use of several tools. As most patients with CA are currently treated with targeted temperature management (TTM), combined with sedative drug therapy, especially during the hypothermic phase, the reliability of neurological examination in evaluating these patients is delayed to 72-96 h after admission. Thus, additional tests, including electrophysiological examinations, brain imaging and biomarkers, have been largely implemented to evaluate earlier the extent of brain damage in these patients.