Refractory Shock Research Articles

Application of Adsorptive Blood Purification Techniques during Cardiopulmonary Bypass in Cardiac Surgery.

By reason of surgical demand, the majority of cardiovascular procedures still depend on the use of cardiopulmonary bypass (CPB). Due to the nonphysiological state of CPB, it can cause complex and unpredictable inflammatory response, which may lead to significant morbidity and mortality. Unfortunately, the pharmacological and mechanical strategies that currently exist do not offer significant advantages in controlling inflammatory response and improving patient outcomes. The best strategy to reduce inflammation in CPB is still uncertain. In recent years, adsorptive blood purification techniques (BPTs) have emerged, among which CytoSorb is the latest representative device. Currently, the primary application area of adsorptive BPTs is in the control and treatment of systemic hyperinflammatory states, such as refractory septic shock patients. However, the evidences on efficacy and safety of adsorptive BPTs application during CPB surgery are still inconclusive, so we summarize the relevant evidences here and suggest future potential research areas.

Septic shock with Chlamydia abortus infection

A 65-year-old man presented with an acute onset of fever (39·8°C), dizziness, and headache without evident predisposition. A CT scan showed left upper lobe pneumonia and he received imipenem–cilastatin (2 g every 8 h), but his symptoms did not improve. However, on day 3 of admission, he rapidly developed refractory hypoxaemia, respiratory failure, and septic shock. He then presented to the Department of Critical Care Medicine at Guangdong Provincial People's Hospital (Guangzhou, China). The severity of hypoxia and multiple organ dysfunction syndrome did not match the pulmonary imaging changes from day 4 to day 9 (figure).

Vasopressors and Risk of Acute Mesenteric Ischemia: A Worldwide Pharmacovigilance Analysis and Comprehensive Literature Review.

Vasodilatory shock, such as septic shock, requires personalized management which include adequate fluid therapy and vasopressor treatments. While these potent drugs are numerous, they all aim to counterbalance the vasodilatory effects of a systemic inflammatory response syndrome. Their specific receptors include α- and β-adrenergic receptors, arginine-vasopressin receptors, angiotensin II receptors and dopamine receptors. Consequently, these may be associated with severe adverse effects, including acute mesenteric ischemia (AMI). As the risk of AMI depends on drug class, we aimed to review the evidence of plausible associations by performing a worldwide pharmacovigilance analysis based on the World Health Organization database, VigiBase®. Among 24 million reports, 104 AMI events were reported, and disproportionality analyses yielded significant association with all vasopressors, to the exception of selepressin. Furthermore, in a comprehensive literature review, we detailed mechanistic phenomena which may enhance vasopressor selection, in the course of treating vasodilatory shock.

Indication of Resuscitative Endovascular Balloon Occlusion of the Aorta in Trauma Patients

In trauma bays, resuscitation as a bridge to definitive hemorrhage control to avoid cardiac arrest is challenging.Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a resuscitation procedure for refractory hemorrhagicshock. The REBOA procedure itself is simple compared to other endovascular procedures, such as angioembolizationor stent graft placement. However, adequate REBOA implementation requires a complete understanding ofits potential risks and simulation training. We should be aware that REBOA is not a hemostatic device, but a bridge todefinitive hemorrhage control; furthermore, it is not a magical device that can improve the critical situation in traumaresuscitation. For appropriate use, we herein describe the indication of REBOA in trauma resuscitation based onexisting evidence.

Novel Use of Seraph-100™ Blood Purification Therapy in Heat Stroke.

The Seraph-100™ is a purification filter that blunts cytokine storm, providing a more favorable environment to establish immune homeostasis. We present a novel case of compassionate use of Seraph filter in a young, healthy active duty service member with heat injury-induced massive inflammatory response. The patient is a previously healthy 26-year-old male with altered mental status, tachycardia, fever to 40.3 °C, and hypotension after losing consciousness during a 4-mile run. He had a history of one heat injury in college and took no medications or supplements. Initial workup demonstrated hemoconcentration, leukocytosis, and hyperkalemia. He was intubated, received isotonic crystalloid fluid, and was admitted to the intensive care unit. The patient developed vasopressor-resistant shock and multiorgan failure with rhabdomyolysis requiring continuous renal replacement therapy. The addition of the Seraph resulted in improved hemodynamic stability, decreased inflammatory markers, and improved organ function. Approximately 1 week after the final Seraph treatment, the patient had an abrupt massive lower gastrointestinal bleed and was transitioned to comfort care by family. We present the novel use of Seraph in the setting of multiorgan failure and hyperinflammatory state due to heat injury. The patient's vasopressor refractory distributive shock was believed to be secondary to heat stroke-induced massive inflammatory response, leading to a trial of Seraph therapy. This case demonstrates that the Seraph filter has the potential to improve hemodynamic instability and reduce cytokine storm in nonsepsis patients.

Bispectral index and suppression ratio after cardiac arrest: are they useful as bedside tools for rational treatment escalation plans?

Introduction and objectivesMyocardial dysfunction contributes to early mortality (24-72 hours) among survivors of a cardiac arrest (CA). The benefits of mechanical support in refractory shock should be balanced against the patient's potential for neurological recovery. To date, these early treatment decisions have been taken based on limited information leading mainly to undertreatment. Therefore, there is a need for early, reliable, accessible, and simple tools that offer information on the possibilities of neurological improvement. MethodsWe collected data from bispectral index (BIS) and suppression ratio (SR) monitoring of adult comatose survivors of CA managed with targeted temperature management (TTM). Neurological status was assessed according to the Cerebral Performance Category (CPC) scale. ResultsWe included 340 patients. At the first full neurological evaluation, 211 patients (62.1%) achieved good outcome or CPC 1-2. Mean BIS values were significantly higher and median SR lower in patients with CPC 1-2. An average BIS> 26 during first 12 hours of TTM predicted good outcome with 89.5% sensitivity and 75.8% specificity (AUC of 0.869), while average SR values> 24 during the first 12 hours of TTM predicted poor outcome (CPC 3-5) with 91.5% sensitivity and 81.8% specificity (AUC, 0.906). Hourly BIS and SR values exhibited good predictive performance (AUC> 0.85), as soon as hour 2 for SR and hour 4 for BIS. ConclusionsBIS/SR are associated with patients’ potential for neurological recovery after CA. This finding could help to create awareness of the possibility of a better outcome in patients who might otherwise be wrongly considered as nonviable and to establish personalized treatment escalation plans.

Clinical and biochemical endpoints and predictors of response to plasma exchange in septic shock: results from a randomized controlled trial

BackgroundRecently, a randomized controlled trial (RCT) demonstrated rapid but individually variable hemodynamic improvement with therapeutic plasma exchange (TPE) in patients with septic shock. Prediction of clinical efficacy in specific sepsis treatments is fundamental for individualized sepsis therapy.MethodsIn the original RCT, patients with septic shock of < 24 h duration and norepinephrine (NE) requirement ≥ 0.4 μg/kg/min received standard of care (SOC) or SOC + one single TPE. Here, we report all clinical and biological endpoints of this study. Multivariate mixed-effects modeling of NE reduction was performed to investigate characteristics that could be associated with clinical response to TPE.ResultsA continuous effect of TPE on the reduction in NE doses over the initial 24 h was observed (SOC group: estimated NE dose reduction of 0.005 µg/kg/min per hour; TPE group: 0.018 µg/kg/min per hour, p = 0.004). Similarly, under TPE, serum lactate levels, continuously decreased over the initial 24 h in the TPE group, whereas lactate levels increased under SOC (p = 0.001). A reduction in biomarkers and disease mediators (such as PCT (p = 0.037), vWF:Ag (p < 0.001), Angpt-2 (p = 0.009), sTie-2 (p = 0.005)) along with a repletion of exhausted protective factors (such as AT-III (p = 0.026), Protein C (p = 0.012), ADAMTS-13 (p = 0.008)) could be observed in the TPE but not in the SOC group. In a multivariate mixed effects model, increasing baseline lactate levels led to greater NE dose reduction effects with TPE as opposed to SOC (p = 0.004).ConclusionsAdjunctive TPE is associated with the removal of injurious mediators and repletion of consumed protective factors altogether leading to preserved hemodynamic stabilization in refractory septic shock. We identified that baseline lactate concentration as a potential response predictor might guide future designing of large RCTs that will further evaluate TPE with regard to hard endpoints.Trial registration Retrospectively registered 18th January 2020 at clinicaltrials.gov (Identifier: NCT04231994).

Epidemiology and outcomes of septic shock in children with complex chronic conditions in a developing country PICU

ObjectiveTo investigate the role of Complex Chronic Conditions (CCCs) on the outcomes of pediatric patients with refractory septic shock, as well as the accuracy of PELOD-2 and Vasoactive Inotropic Score (VIS) to predict mortality in this specific population. MethodsThis is a single-center, retrospective cohort study. All patients diagnosed with septic shock requiring vasoactive drugs admitted to a 13-bed PICU in southern Brazil, between January 2016 and July 2018, were included. Clinical and demographic characteristics, presence of CCCs and VIS, and PELOD-2 scores were accessed by reviewing electronic medical records. The main outcome was considered PICU mortality. Results218 patients with septic shock requiring vasoactive drugs were identified in the 30-month period and 72% of them had at least one CCC. Overall mortality was 22%. Comparing to patients without previous comorbidities, those with CCCs had a higher mortality (26.7% vs 9.8%; OR = 3.4 [1.3–8.4]) and longer hospital length of stay (29.3 vs 14.8; OR 2.39 [1.1- 5.3]). Among the subgroups of CCCs, “Malignancy” was particularly associated with mortality (OR = 2.3 [1.0–5.1]). VIS and PELOD-2 scores in 24 and 48 hours were associated with mortality and a PELOD-2 in 48 hours > 8 had the best performance in predicting mortality in patients with CCC (AUROC = 0.89). ConclusionPatients with CCCs accounted for the majority of those admitted to the PICU with septic shock and related to poor outcomes. The high prevalence of hospitalizations, use of resources, and significant mortality determine that patients with CCCs should be considered a priority in the healthcare system.

Predictors of Requirement of Inotrope Among Patients With Early Sepsis: Special Reference to Microcirculatory Parameters

IntroductionThe management of septic shock and refractory septic shock is essential in preventing sepsis-related death. The handheld vital microscope is a new modality of investigation for sepsis for microcirculatory assessment. This study aimed to identify predictors of inotrope requirements among patients with early sepsis and impending septic shock with particular reference to sublingual microcirculation assessment parameters.MethodologyWe conducted an observational cross-sectional hospital-based study in central India. The formal sample size was calculated to be 52 patients using a convenient sampling technique. The study was initiated with ethics approval (IHEC-LOP/2019/ MD0090) with consent from the patients. We used the MicroScan (MicroVision Medical, Netherlands) Video Microscope System (No.16A00102) to obtain sidestream dark-field imaging along with the AVA 4.3C software (MicroVision Medical).ResultsOf 51 cases, 60.8% were women, and 39.2% were men, and the study population had a mean age of 41.0 ± 14.9 years. Patients were recruited from medical wards (64.7%) and emergency departments (35.3%). The most common site of infection was gastrointestinal (33.3%), followed by respiratory infections (25.5%) and genitourinary infections (11.8%). The quick sequential organ failure assessment score was 2.0 ± 0.1. Eight patients required inotropes, and six patients died. High respiratory rates and lactate levels were important predictors of inotrope requirements in patients with early sepsis. Sublingual microcirculatory parameters at baseline did not significantly affect the requirement of inotropes consequently.ConclusionsSublingual microscopy is a suggested tool for the management of sepsis. However, without clearly defined cut-off values, handheld vital microscopy could not predict fluid responsiveness among patients with early sepsis. Also, it would be difficult to incorporate this technology into regular practice without equipment upgrades and image acquisition software.

Association Between the Acidemia, Lactic Acidosis, and Shock Severity With Outcomes in Patients With Cardiogenic Shock.

BackgroundLactic acidosis is associated with mortality in patients with cardiogenic shock (CS). Elevated lactate levels and systemic acidemia (low blood pH) have both been proposed as drivers of death. We, therefore, analyzed the association of both high lactate concentrations and low blood pH with 30‐day mortality in patients with CS.Methods and ResultsThis was a 2‐center historical cohort study of unselected patients with CS with available data for admission lactate level or blood pH. CS severity was graded using the Society for Cardiovascular Angiography and Intervention (SCAI) shock classification. All‐cause survival at 30 days was analyzed using Kaplan‐Meier curves and Cox proportional‐hazards analysis. There were 1814 patients with CS (mean age, 67.3 years; 68.5% men); 51.8% had myocardial infarction and 53.0% had cardiac arrest. The distribution of SCAI shock stages was B, 10.8%; C, 30.7%; D, 38.1%; and E, 18.7%. In both cohorts, higher lactate or lower pH predicted a higher risk of adjusted 30‐day mortality. Patients with a lactate ≥5 mmol/L or pH <7.2 were at increased risk of adjusted 30‐day mortality; patients with both lactate ≥5 mmol/L and pH <7.2 had the highest risk of adjusted 30‐day mortality. Patients in SCAI shock stages C, D, and E had higher 30‐day mortality in each SCAI shock stage if they had lactate ≥5 mmol/L or pH <7.2, particularly if they met both criteria.ConclusionsHigher lactate and lower pH predict mortality in patients with cardiogenic shock beyond standard measures of shock severity. Severe lactic acidosis may serve as a risk modifier for the SCAI shock classification. Definitions of refractory or hemometabolic shock should include high lactate levels and low blood pH.

Time-dependent prognostic value of bispectral index and suppression ratio during targeted temperature management: an early triage tool for treatment escalation plans

Abstract Funding Acknowledgements Type of funding sources: None. Background Post-cardiac arrest myocardial dysfunction contributes to morbidity in survivors of cardiac arrest (CA) and, in case of refractory shock, some patients will benefit from aggressive mechanical support. In this scenario, a non-invasive, reliable and real-time estimation of potential neurological recovery is required to establish personalized treatment escalation plans. Methods We prospectively collected data of bispectral index (BIS) and suppression ratio (SR) monitoring of adult comatose survivors of CA consecutively admitted to an acute cardiac care unit and managed with targeted temperature management (TTM). Neurological status was assessed according to the Cerebral Performance Category (CPC) scale. Results We included 340 patients, 72.1% had an initial shockable rhythm, 72 (21.2%) were females and their mean age was 61.7 ± 14.3 years. Throughout 3-month follow-up, 210 patients (61.8%) achieved a CPC of 1-2 and 130 (38.2%) a CPC of 3-5. Mean BIS values were significantly higher and median SR lower in patients with CPC 1-2 (Figure 1). An average BIS value &amp;gt;26 during first 12 hours of TTM predicted good outcome with 89.3% sensitivity and 75.2% specificity (AUC of 0.86), while average SR values &amp;gt;24 during first 12 hours of TTM predicted poor outcome (CPC 3-5) with 83.6% of sensitivity and 91.8% of specificity (AUC of 0.92). Hourly BIS and SR values exhibited a good predictive performance (AUC &amp;gt; 0.85), starting as soon as hour 2 for SR and 4 for BIS. Conclusions BIS and SR real-time monitoring correlates with patient´s potential of neurological recovery after CA. This finding could help establish personalized treatment escalation plans that reduce consequences of inappropriate interventions, economic costs and uncertainty burden of the patient´s family.

Clinical Profile and Outcome of Hospitalized Confirmed Cases of Omicron Variant of SARS-CoV-2 Among Children in Pune, India.

BackgroundThe Omicron variant of SARS-CoV-2 infection was seen to be more infectious but less severe in children than adults with reduced hospitalization rates. There is a paucity of data on hospitalized children with confirmed Omicron variant.ObjectiveWe describe demographic, epidemiologic, clinical, radiological, laboratory features and outcomes of children with confirmed Omicron variant of SARS-CoV-2 infection admitted to a tertiary care teaching hospital in Pune, India.MethodologyChildren who tested positive for SARS-CoV-2 - Omicron variant and were admitted between 1st December 2021 and 28th February 2022 were included in the study.ResultsOut of a total of 37 Covid-positive children admitted during the study period, 16 underwent genome sequencing of which 14 were confirmed to be Omicron variant and two were Delta variant. The age range was one month to 12 years and seven (50%) were male. Common presenting features were fever (n=13, 93%), cough (n=7, 50%), seizures (n=7, 50%) and coryza (n=5, 36%). Comorbidities noted were epilepsy (n=3, 21%) and one each with Thalassemia Major, suspected inborn error of metabolism (IEM), operated anorectal malformation with hypospadias, chronic suppurative otitis media with complications (mastoiditis and facial nerve palsy), neonatal cholestasis and intracranial bleed with dural venous sinus thrombosis. Malnutrition was noted in 42%, pallor in 10 cases (71%). Severe anaemia (n=10, 71%), elevated ferritin (n=6, 43%), positive C-Reactive Protein (n=4, 28%) and deranged D-dimer (n=11, 78%) were noted. The Neutrophil to Lymphocyte ratio (NLR) was >3.3 in five (36%) children. Four (28%) had evidence of pneumonia on the chest radiograph. Oxygen therapy was needed in nine (64%) while two children (14%) required mechanical ventilation. There were two deaths (14%) in children with multiorgan dysfunction and refractory shock. Intravenous immunoglobulin and methylprednisolone were administered to one patient respectively (14%). The median hospital stay was 10 days (Interquartile range = 8).ConclusionHospitalized children with Omicron variant of SARS-CoV-2 who have underlying comorbidities may have severe presentations needing ICU care. Mortality rates are low with appropriate ICU care.

Peripheral Vasoactive Administration in Critically Ill Children With Shock: A Single-Center Retrospective Cohort Study.

Management of fluid refractory pediatric shock requires prompt administration of vasoactive agents. Although delivery of vasoactive therapy is generally provided via a central venous catheter, their placement can delay drug administration and is associated with complications. We characterize peripheral vasoactive administration in a cohort of critically ill children with shock, evaluate progression to central venous catheter placement, and describe complications associated with extravasation. Retrospective cohort study. Single-center, quaternary PICU (January 2010 to December 2015). Children (31 d to 18 yr) who received epinephrine, norepinephrine, or dopamine. None. We compared patients based on the initial site of vasoactive infusion: peripheral venous access (PVA) or central venous access (CVA) and, within the PVA group, compared patients based on subsequent placement of a central catheter for vasoactive infusion. We also characterized peripheral extravasations. We evaluated 756 patients: 231 (30.6%) PVA and 525 (69.4%) CVA patients. PVA patients were older, had lower illness severity, and more frequently had vasoactive therapy initiated at night compared with CVA patients. In PVA patients, 124 (53.7%) had a central catheter placed after a median of 140 minutes (interquartile range, 65-247 min) of peripheral treatment. Patients who avoided central catheter placement had lower illness severity. Of the 93 patients with septic shock, 44 (47.3%) did not have a central catheter placed. Extravasations occurred in four of 231 (1.7% [95% CI, 0.03-3.4]) PVA patients, exclusively in the hand. Three patients received pharmacologic intervention, and none had long-term disabilities. In our experience, peripheral venous catheters can be used for vasoactive administration. In our series, the upper limit of the 95% CI for extravasation is approximately 1-in-30, meaning that this route may be an appropriate option while evaluating the need for central access, particularly in patients with low illness severity.

Enteral nutrition in critically ill patients under vasoactive drug therapy: The NUTRIVAD study.

Enteral nutrition (EN) in critically ill patients requiring vasoactive drug (VAD) support is controversial. This study assesses the tolerability and safety of EN in such patients. This prospective observational study was conducted in 23 intensive care units (ICUs) over 30 months. Inclusion criteria were a need for VADs and/or mechanic circulatory support (MCS) over a minimum of 48 h, a need for ≥48 h of mechanical ventilation, an estimated life expectancy >72 h, and ≥72 h of ICU stay. Patients with refractory shock were excluded. EN was performed according to established protocols during which descriptive, daily hemodynamic and efficacy, and safety data were collected. An independent research group conducted the statistical analysis. Of 200 patients included, 30 (15%) required MCS and 145 (73%) met early multiorgan dysfunction criteria. Mortality was 24%. Patients needed a mean dose of norepinephrine in the first 48 h of 0.71 mcg/kg/min (95% CI, 0.63-0.8) targeting a mean arterial pressure of 68 mm Hg (95% CI, 67-70) during the first 48 h. EN was started 34 h (95% CI, 31-37) after ICU admission. Mean energy and protein delivered by EN/patient/day were 1159 kcal (95% CI, 1098-1220) and 55.6 g (95% CI, 52.4-58.7), respectively. Daily energy balance during EN/patient/day was -432 (95% CI, -496 to -368). One hundred and fifty-four (77%) patients experienced EN-related complications. However, severe complications, such as mesenteric ischemia, were recorded in only one (0.5%) patient. EN in these patients seems feasible, safe, and unrelated to serious complications. Reaching the energy target only through EN is difficult.

Methylene blue versus vasopressin analog for refractory septic shock in the preterm neonate: A randomized controlled trial.

Refractory septic shock in neonates is still associated with high mortality, necessitating an alternative therapy, despite all currently available treatments. This study aims to assess the vasopressor effect of methylene blue (MB) in comparison to terlipressin (TP) as adjuvant therapy for refractory septic shock in the preterm neonate. A double-blinded randomized controlled trial was conducted in the Neonatal Intensive Care Units at Ain Shams University, Egypt. Thirty preterm neonates with refractory septic shock were randomized to receive either MB or TP as an adjuvant to conventional therapy. Both MB and TP were administered as an intravenous loading dose followed by continuous intravenous infusion. The hemodynamic variables, functional echocardiographic variables, and oxidant stress marker were assessed over a 24 h period together with the side effects of MB. MB causes significant improvement in mean arterial blood pressure with a significant decrease of the norepinephrine requirements (1.15±0.21μm/kg/min at baseline vs. 0.55±0.15μm/kg/min at 24 h). MB infusion causes an increase of the pulmonary pressure (44.73±8.53 mmHg at baseline vs. 47.27±7.91 mmHg after 24 h) without affecting the cardiac output. Serum malonaldehyde decreased from 5.45±1.30 nmol/mL at baseline to 4.40±0.90 nmol/mL at 24 h in the MB group. Administration of MB to preterm infants with refractory septic shock showed rapid increases in systemic vascular resistance and arterial blood pressure with minimal side effects.

Critical Illness-Related Corticosteroid Insufficiency (CIRCI) among Patients with Refractory Shock at a Tertiary Hospital: A Look into Clinical Practices and Patient Outcomes

Introduction. A significant number of critically ill patients, as high as 60% among patients with septic shock, suffer from critical illness-related corticosteroid insufficiency (CIRCI), which refers to an inadequate corticosteroid response to the level of stress.&#x0D; Objectives. This study aimed to determine the strategies employed in managing patients with critical illness-related corticosteroid insufficiency and the outcomes of these patients at a tertiary hospital.&#x0D; Methods. This was a single-center, mixed-methods study which consisted of a review of charts of patients 19 years old and above admitted for shock or developed refractory hypotension from January 2017-December 2019, and key informant interviews and focus group discussion among clinicians who have experience in managing CIRCI.&#x0D; Results. A total number of 362 patient charts reviewed showed a relatively low rate of initiation of corticosteroids for patients with refractory shock, at just 28.57% of the entire population. After corticosteroids were initiated, patients were in shock for a median of just one day and the median blood pressure improved to 100/60 mm Hg. In this cohort, patients who were started on steroids had more severe illness, as measured by the Mortality Probability Model (MPM) score, which had a median of 43.65% for the group on steroids and just 25.0% for the non-steroid group (p ≤ 0.0001). Patients who were started on steroids had a statistically significant longer median days on a ventilator, 5 days vs. 3 days for the non-steroid group (p = 0.0297); longer median length of intensive care unit (ICU) stay, 8 days vs. 5 days for the non-steroid group (p = 0.0410), and a higher morbidity and mortality rate. The need for steroids, the presence of septic shock, and a higher MPM score were significant predictors of mortality.&#x0D; Discussions among clinicians revealed significant variability in practices in the management of CIRCI.&#x0D; Conclusion. The presence of clinical features of CIRCI is a poor prognostic factor. Timely recognition, work-up, and interventions to address CIRCI are paramount in critical care.

Slow It Down: A Case Report Of Microangiopathic Hemolytic Anemia In A Heartmate III Patient

<h3>Introduction</h3> Incidence of hemolysis in left ventricular assist devices (LVADs) is reported from 13-18%, but with HeartMate 3 (HM3) LVAD has been decreased to <1%. Typically, hemolysis is associated with LVAD thrombosis with subsequent decreased survival rate at 1 year (38.9% vs. 89.3%). We present a case of microangiopathic hemolytic anemia (MAHA), not related to pump thrombosis in a recent implanted HM3 LVAD patient which resolved by decreasing LVAD speed. <h3>Case Report</h3> A 44 year-old man with status post LVAD HM3 4 months prior complicated with right ventricular (RV) failure, pulmonary hypertension and CKD Stage III was admitted for mixed vasodilatory and cardiogenic shock. Patient required dual inotropes, vasopressors and temporary renal replacement therapy in an effort to stabilize him and continue his evaluation for heart and kidney transplant. Meanwhile, patient developed acute, severe thrombocytopenia (platelet count of 26K) and mild anemia. Disseminated intravascular coagulation was unlikely (normal fibrinogen level). Heparin-induced thrombosis (HIT) antibody testing was non-reactive. No active sepsis. There were no power spikes or suspected LVAD thrombosis (Table 1). Intrinsic bone marrow disease was thought to be unlikely. LDH was elevated and haptoglobin level undetectable (Table 2), blood smear showed schistocytes, raising suspicious for MAHA, therefore LVAD speed was decreased to 5100 RPM to diminish red blood cell (RBC) fragmentation and maintained in systemic unfractionated heparin infusion. This resulted in recovery of platelets and hemolysis parameters (Table 2). Ultimately, patient underwent dual organ transplantation without complications. <h3>Conclusions</h3> Per our knowledge, this is the first case reported of MAHA in a LVAD HM3 patient, not related to pump thrombosis that resolves with decrease in LVAD speed. MAHA is caused by mechanical injury of RBCs. The effective treatment in this scenario was to decrease the speed of the LVAD, hypothetically to decrease excessive shear in circulation. Further research should be done to delineate efficacy of reducing LVAD speed in these patients.

To Summarize and Analyze the Epidemiological Characteristics and Prognostic Risk Factors of Patients with Pelvic Fracture Complicated with Perineal Injury.

This study is aimed at summarizing and analyzing the epidemiological characteristics and prognostic risk factors of patients with a pelvic fracture with perineal injury. The clinical data of 153 patients with pelvic fracture with perineal injury treated in our hospital from January 2012 to June 2021 were analyzed retrospectively. The data of sex, age, injury mechanism, pelvic fracture type, shock index (SI), perineal wound depth, concomitant injury, total hospital stay, and death were collected by the electronic medical record system. Among the 153 patients, there were 94 males and 59 females, with an average age of (43.2 ± 16.8) years. The cases were mainly concentrated into two age groups: 20–29 years old and 50–59 years old. In a year, pelvic fractures were mainly concentrated in 1–2 months and 11–12 months. In terms of injury time, there were mainly two periods of time in a day: 10 : 00～12 : 00 and 15 : 00～18 : 00. The MOTS-RTS scores of the patients in the undead group and the dead group were (7.12 ± 1.52), (2.69 ± 0.96), ISS scores were (27.36 ± 15.84), (61.32 ± 7.08), GCS scores were (12.84 ± 3.69), (4.13 ± 1.25), APACH II scores were (12.87 ± 8.84), (32.41 ± 6.98), and SOFA scores were (6.68 ± 5.87), (17.12 ± 3.12). The MOTS-RTS and GCS scores of the nondeath group were significantly higher, while the ISS score, APACH II score, SOFA score, and shock index were significantly lower. The overall mortality rate of 153 patients was 13.7%. The average area of perineal trauma in undead and dead patients was (54.5 ± 113.52) cm2 and (262.63 ± 300.84) cm2, respectively. The average depth of perineal trauma was (9.63 ± 7.22) cm and (16.23 ± 10.13) cm, respectively. The larger the area of perineal injury and the deeper the depth of perineal trauma, the worse their prognosis. Cox multivariate analysis showed that complications, MOTS-RTS score, ISS score, GCS score, perineal trauma area, and perineal trauma depth were independent risk factors affecting the prognosis of patients with pelvic fracture with perineal injury. Most of the patients with pelvic fracture complicated with perineal injury are 20–29 years old and 50–59 years old. The more serious the perineal injury is, the higher the mortality is. The main causes of death are refractory hemorrhagic shock and infection.

Terlipressin for refractory septic shock: a study protocol of a single center, placebo-controlled double-blind phase III RCT (The TERESEP study).

Introduction: In septic shock, vasopressin is a standard treatment that increases blood pressure by vasopressin receptor activation. Vasopressin can reduce catecholamine dose requirement and reduce cardiac arrhythmia in septic shock. Terlipressin is specific vasopressin 1 receptor that may replace vasopressin for septic shock treatment.The TERESEP trial evaluates the benefit of terlipressin add-on catecholamine versus catecholamine only treatment for septic shock. Methods and analysis: This single-center randomized controlled clinical trial is enrolling hospitalized intensive care patients with septic shock with norepinephrine doses of more than 0.2 microgram/kilogram/min or norepinephrine combine with epinephrine. Patient randomized for terlipressin combined with catecholamine or placebo combined with catecholamine. The primary endpoint is successful of shock treatment within 6 hours define as the rate of mean arterial blood pressure more than 65 mmHg achievement with catecholamine requirement dose less than 0.2 mcg/kg/min. The secondary outcomes include mean blood pressure, 28 days mortality, hospital mortality, intensive care unit range of stay, rate of urine output achievement, lactate clearance, accumulative catecholamine dose, cardiac arrhythmia, 28 days alive without any organ support. The main analysis will use intension to treat approach. Ethic and dissemination: The Ethics Committee has approved this study of Siriraj hospital, Mahidol University (COA No. SI 049/2020). The trial result will be disseminated through the presentation at medical publication. Authorship will consider and grant using the policy of Mahidol University. Trial registrations: ClinicalTrials.govNCT04339868. Registered on April 9,2020.

Hemophagocytic lymphohistiocytosis: a rare disease unveiling the diagnosis of EBV-related large B cell lymphoma in a patient with HIV

BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rare disease resulting from the overactivation of the immune system due to under regulation of cytotoxic lymphocytes, macrophages and natural killer (NK) cells. HLH is associated with malignancies, infections, autoimmune disorders and rarely AIDS and is rapidly fatal.Case presentationThis case report identified a 53 year old male with acquired immunodeficiency syndrome (AIDS) who presented with neutropenic fever of unknown origin. He had two previous hospitalizations prior to the hospitalization diagnosing HLH. The first led to a diagnosis of drug fevers in the setting of treatment for thrombotic thrombocytopenic purpura and subsequent hospitalization led to empiric treatment of hospital acquired pneumonia after workup for intermittent fevers was negative. He was discharged but readmitted 10 days after for recurrence of neutropenic fevers. During this final hospitalization, he was found to have elevated liver enzymes, ferritin, triglycerides and soluble IL-2 receptor with persistent fevers, new splenomegaly and bicytopenia meeting the 2004 HLH criteria. Bone marrow biopsy confirmed the diagnosis of HLH as well as EBV associated large B-cell lymphoma. The patient improved on treatment with steroids, rituximab, tocilizumab, and chemotherapy but ultimately passed away due to refractory septic shock from multi-drug resistant Klebsiella pneumoniae.ConclusionThis novel case highlights a patient diagnosed with HLH in the setting of several risk factors for the disease, including AIDS, B-cell lymphoma and EBV. Additionally, this case highlights the importance of early consideration of HLH in the setting of neutropenic fever without clear infectious etiology and search for malignancy associated reasons for HLH especially in immunocompromised patients.