Management of perioperative bleeding risk in patients on antithrombotic medications undergoing cardiac surgery-a systematic review.

Background: Antithrombotic drugs increase the risk of bleeding, especially in patients who need urgent surgery without an adequate wash-out period. This review aims to evaluate perioperative bleeding complications in patients on dual antiplatelet therapy (DAPT) or direct-acting oral anticoagulants (DOACs) undergoing high-bleeding risk cardiovascular surgery and to present currently available potential solutions to mitigate antithrombotic therapy-related bleeding complications. Methods: As a first step, we searched for relevant articles, over the last 10 years, in Medline (PubMed) and abstracted clinical information based on pre-defined criteria for bleeding complications. In the next step, an additional search evaluating potential solutions to mitigate bleeding complications was performed. The literature screening and selection process followed the principles derived from the PRISMA statement. Results: From all reviewed studies, a total of 19 articles could be included evaluating the risk for bleeding in cardiac surgery related to DAPT or DOACs and 10 papers evaluating antithrombotic drug reversal or removal in the setting of cardiovascular surgery. Reported bleeding rates ranged between 18% and 41%. The variability of the reported data is remarkable. Idarucizumab is reported to provide optimal perioperative hemostasis in up to 93% of patients. It has been observed that andexanet alfa causes unresponsiveness to the anticoagulant effects of heparin. Antithrombotic removal by intraoperative hemoadsorption is found to be associated with a significant decrease in re-thoracotomy rate, overall procedure duration, administered transfusion volumes, chest-tube drainage, and length of hospitalization. Discussion: Bleeding complications in patients treated with DAPT or DOACs in cardiac surgery are high. New costly reversal agents are available but have not been sufficiently tested in the cardio-surgical setting so far. Interestingly, bleeding-related complications seem to be effectively reduced by applying innovative intraoperative hemoadsorption techniques. Expected results from the ongoing trials should provide better insights concerning the efficacy and safety of several potential solutions. Currently, the variability of reports and the deficit of high-quality studies in this specific setting represent the major limitation for the unbiased conclusion of this review.

Hemoadsorption Treatment with CytoSorb® in Probable Hemophagocytic Lymphohistiocytosis: A Role as Adjunctive Therapy?

Acute hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease, with an annual incidence of 1 : 800,000 people. The disease is characterized by a cytokine storm, with concomitant macrophage and natural killer (NK) cell activation; death can occur from multiple organ failure or complications such as bleeding diathesis. Therefore, HLH treatment remains a challenging one. We hereby present a case of a 76-year-old man with severe HLH in whom hemoadsorption was successfully applied. Due to the failure of the immunomodulatory therapy , continuous venovenous hemodiafiltration therapy with the CytoSorb® adsorber was successfully applied for 48 hours. Upon therapy discontinuation, the biological and clinical condition reverted, unfortunately evolving towards the patient's death.

The Potential Role of Extracorporeal Cytokine Removal in Hemodynamic Stabilization in Hyperinflammatory Shock.

Hemodynamic instability due to dysregulated host response is a life-threatening condition requiring vasopressors and vital organ support. Hemoadsorption with Cytosorb has proven to be effective in reducing cytokines and possibly in attenuating the devastating effects of the cytokine storm originating from the immune over-response to the initial insult. We reviewed the PubMed database to assess evidence of the impact of Cytosorb on norepinephrine needs in the critically ill. We further analyzed those studies including data on control cohorts in a comparative pooled analysis, defining a treatment effect as the standardized mean differences in relative reductions in vasopressor dosage at 24 h. The literature search returned 33 eligible studies. We found evidence of a significant reduction in norepinephrine requirement after treatment: median before, 0.55 (IQR: 0.39-0.90); after, 0.09 (0.00-0.25) µg/kg/min, p < 0.001. The pooled effect size at 24 h was large, though characterized by high heterogeneity. In light of the importance of a quick resolution of hemodynamic instability in the critically ill, further research is encouraged to enrich knowledge on the potentials of the therapy.

Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects.

OBJECTIVE: To assess the potential of dexmedetomidine for targeted sedation in complex Intensive Care (ICU) patients for >24 h. DESIGN: Prospective, open label, clinical trial. SETTING: Tertiary general ICU. PATIENTS: Twenty critically ill patients, mean APACHE II 23(+/-9). INTERVENTIONS: A continuous infusion of dexmedetomidine, median infusion time 71.5 (35-168) h, starting at 0.4 microg.kg.h without a loading dose and adjusted (0.2-0.7 microg.kg.h) to a target Ramsay Sedation Score (RSS) of 2-4. Rescue midazolam and/or morphine/fentanyl were given as clinically indicated. MEASUREMENTS AND RESULTS: Haemodynamic parameters and RSSs were collected until 24 h after cessation. An RSS 2-5 was achieved in 1,147 (83%) of observations with a reduction in RSS of 6 from 13% in the first 6 h to 3% between 18 h and 24 h. Sixteen patients needed minimal or no additional midazolam, median 4 mg/day (0.5-10) and ten required minimal or no additional analgesia, median 2 mg/day (0.5-4.5), 55 microg/day (14-63) of morphine/fentanyl. RESULTS: A 16% reduction in mean systolic blood pressure (SBP) and 21% reduction in heart rate (HR) occurred over the first 4 h followed by minimal (+/- 10%) changes throughout the infusion. A rise in SBP was observed in two patients. After abrupt cessation, SBP and HR monitored for 24 h rose by 7% and 11%, respectively. CONCLUSIONS: Dexmedetomidine was an effective sedative and analgesic sparing drug in critically ill patients when used without a loading dose for longer than 24 h with predictable falls in blood pressure and HR. There was no evidence of cardiovascular rebound 24 h after abrupt cessation of infusion.

Memories of intensive care and experiences of survivors of a critical illness: an interview study.

Recovery from a critical illness can be a complex and protracted process. It is known that for some, health-related quality of life (HRQOL) does not return to pre-illness levels for many months, and in some disease processes this may be longer. This study was undertaken as part of a larger project examining the pain and health status of survivors of a critical illness. The aims of the qualitative aspect of the study were to examine the participants' memories of intensive care and hospitalisation at 6 months post-discharge, and to explore the impact of the critical illness experience on their recovery. Purposive sampling was used to enable rich descriptions of the experience of recovery from those patients best able to articulate their experiences. Three common themes were found with our six participants: recollections, responses, and comfort/discomfort. Recovery from their critical illness continued to affect the participants and carers, some profoundly so. Better integration of services and continued support is required for survivors of a critical illness up to and beyond 6 months.

The use of activated protein C (drotrecogin alfa (activated)) in the treatment of severe sepsis.

Advances in intensive care have allowed many critically ill patients to survive their initial insult. These patients may later demonstrate multiple organ dysfunction and failure, the genesis of which appears to be the body's reaction to critical illness, manifested by an imbalance and failure of inflammatory and immune system homeostasis. The manifestation of multiple organ dysfunction in the critically ill has been termed multiple organ dysfunction syndrome (MODS). MODS mortality is high and remains a leading cause of death in intensive care units (ICUs). The understanding of the pathophysiology of severe sepsis and MODS has moved from a focus on inflammation to include an understanding of the associated anti-inflammatory responses. Loss of homeostasis can manifest as malignant inflammation or immune paralysis. Increased emphasis is emerging on the role of loss of immune homeostasis and disordered coagulation as a cause of organ injury and dysfunction. Treatment of severe sepsis is based upon aggressive resuscitation, source control and support for failing organs. Novel therapies directed at the modifying the inflammatory response have, up to now, not proven beneficial. However, a new agent, drotrecogin alfa (activated) has been shown, in a phase III randomised controlled trial, to be of benefit in the treatment of severe sepsis. This new agent affects both the inflammatory and coagulation dimensions of severe sepsis. The developing concepts of the pathophysiology of sepsis and the emergence of a new therapy increases the complexity of the already complex demands of providing nursing care for the patient with severe sepsis and MODS. This article reviews pathophysiological processes in sepsis, reviews clinical data on activated protein C and illustrates the utility of this therapy in a case study.

The effect of chronic pain on health related quality of life amongst intensive care survivors.

Intensive care unit (ICU) survivors report reductions in health-related quality of life (HR-QOL), whilst chronic pain is common in the general population. However, it is unknown whether there are associations between the experience of ICU and the incidence of chronic pain. A questionnaire--Pain Scale, Pain Self-Efficacy Questionnaire (PSEQ), Centre of Epidemiology Study Depression Scale (CES-D Scale) and the Short Form Health Survey (SF-36)--was sent to 99 consenting patients who had been in the ICU for >48 hours. Sixty-six and 52 questionnaires were returned at 1 and 6 months respectively. There was a general limitation in activities of daily living; younger ages (36-65 years) experienced a decease in work performance and other physical activities. Bodily pain increased, general health diminished, and engagements in social activities were severely affected. There was a decline in mental health for those 36-65 years of age. HR-QOL improved over time; 28% experienced chronic pain and had longer hospital length of stay (LOS), tended to have longer ICU LOS and were ventilated for longer. Those with chronic pain had significant reductions in physical function, bodily pain, general health and vitality. Ventilator hours and hospital LOS were associated with risk of chronic pain (OR 1.09, p=0.033 and OR 1.27, p=0.046). HR-QOL in ICU survivors declined, although there was a general improvement from 1-6 months. This decline in HR-QOL affected younger people (less than 65 years) more than older people. Chronic pain is a significant issue post ICU and is associated with poorer HR-QOL.