Clinical significance of thrombocytopenia in patients with septic shock: An observational retrospective study

PurposeWhether thrombocytopenia in critically ill patients accounts for a bystander of severity or drives specific complications is unclear. We addressed the effect of thrombocytopenia on septic shock, with emphasis on intensive care unit (ICU)-acquired bleeding, infections and thrombotic complications.Materials and methodsA retrospective (2008–2019) single-center study of patients with septic shock. Thrombocytopenia was assessed over the first seven days and was defined as severe (nadir <50 G/L), mild (nadir 50–150 G/L) and relative (30% decrease with nadir >150 G/L). Outcomes were ICU mortality and ICU-acquired complications defined by severe bleeding, infections and thrombotic events during the ICU stay.ResultsThe study comprised 1024 patients. Severe, mild and relative thrombocytopenia occurred in 33%, 40% and 9% of patients. The in-ICU mortality rate was 27%, independently associated with severe thrombocytopenia. ICU-acquired infections, hemorrhagic and thrombotic complications occurred in 27.5%, 13.3% and 11.6% of patients, respectively. Patients with severe, mild or relative thrombocytopenia exhibited higher incidences of bleeding events (20.3%, 15.3% and 14.4% vs. 3.6% in non-thrombocytopenic, p < 0.001), infections (35.2%, 21.9% and 33.3% vs. 23.1% in non-thrombocytopenic, p < 0.001) and thrombotic events (14.6%, 10.8% and 17.8% vs. 7.8% in non-thrombocytopenic, p = 0.03). Only severe thrombocytopenia remained independently associated with increased risk of bleeding.ConclusionsSevere thrombocytopenia was independently associated with ICU mortality and increased risk of bleeding, but not with infectious and thrombotic events.     

Recovery after AKI: Effects on outcomes over 15 years

PurposeTo examine the effect of kidney recovery on mortality, dialysis and kidney transplantation up to 15 years after AKI.Materials and methodsWe studied 29,726 survivors of critical illness and compared these outcomes stratified by AKI and recovery status at hospital discharge. Kidney recovery was defined as a return of serum creatinine to ≤150% of baseline without dialysis prior to hospital discharge.ResultsOverall AKI occurred in 59.2% in which two thirds developed stage 2–3 AKI. Recovery rate of AKI at hospital discharge was 80.8%. Patients who did not recover experienced the worst 15-year mortality compared to those who recovered and those without AKI (57.8% vs 45.2% vs 30.3%, p < 0.001). This pattern was also found in subgroups of patients with suspected sepsis-associated (57.1% vs 47.9% vs 36.5%, p < 0.001) and cardiac surgery-associated AKI (60.1% vs 41.8% vs 25.9%, p < 0.001). The rates of dialysis and transplantation at 15 years were low and not associated with recovery status.ConclusionsRecovery of AKI in critically ill patients at hospital discharge had an effect on long-term mortality for up to 15 years. These results have implications for acute care, follow-up and choice of endpoints for clinical trials.     

Physiological and clinical effects of different infusion rates of intravenous fluids for volume expansion: A scoping review

PurposeTo assess the physiological and clinical effects of different rates of intravenous fluids for volume expansion of critically ill and perioperative patients.MethodsWe searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for studies comparing intravenous infusion rates both in animals and studies involving healthy subjects, critically ill, and perioperative care patients of all ages.ResultsSeven animal studies, eleven clinical studies and three studies including healthy volunteers were identified. Slower infusion led to lower mortality in two studies, lower blood loss in one study, better or more sustained expansion of plasma volume and less edema in three studies, but slower restoration of blood pressure in one study. Three healthy volunteer studies suggested more effective plasma expansion with slower infusion, whereas one trial with postoperative patients did not show plasma volume differences between different infusion rates. One randomized trial found increased mortality with faster infusion in septic children, whereas a randomized trial found no significant differences in critically ill adults.ConclusionsIn this scoping review, most studies showed that slower intravenous infusion rates result in a more efficient intravascular expansion, with a longer effect, and less edema than faster rates. Effects on clinical outcomes were inconsistent.     

Safety,tolerability, pharmacokinetics,and efficacy of kukoamine B in patients with sepsis: A randomized phase IIa trial

PurposeTo evaluate the safety, tolerability, pharmacokinetics, and efficacy of kukoamine B (KB), an alkaloid compound with high affinity for both lipopolysaccharide (LPS) and oligodeoxynucle-otides containing CpG motifs (CpG DNA), in patients with sepsis-induced organ failure.Materials and methodsThis was a multicenter, randomized, double-blind, placebo-controlled phase IIa trial. Patients with sepsis-induced organ failure were randomized to receive either KB (0.06, 0.12, or 0.24 mg/kg) or placebo, every 8 h for 7 days. Primary endpoint was safety, and secondary endpoints included pharmacokinetic (PK) parameters, changes in inflammatory mediators' level, and prognostic parameters.ResultsOf 44 patients enrolled, adverse events occurred in 28 patients [n = 20, 66.7% (KB pooled); n = 8, 57.1% (placebo)], while treatment emergent adverse events were reported in 14 patients [n = 10, 33.3% (KB pooled); n = 4, 28.6% (placebo)]. Seven patients died at 28-day follow-up [n = 4, 13.3% (KB pooled); n = 3, 21.4% (placebo)], none was related to study drug. PK parameters suggested dose-dependent drug exposure and no drug accumulation. KB did not affect clinical outcomes such as ΔSOFA score, vasopressor-free days or ventilator-free days.ConclusionsIn patients with sepsis-induced organ failure, KB was safe and well tolerated. Further investigation is warranted.Trial registrationhttp://ClinicalTrials.gov, NCT03237728.     

The SERVE-HF safety notice in clinical practice – experiences of a tertiary sleep center

BackgroundIn May 2015, the results of the SERVE-HF trial – addressing adaptive servoventilation (ASV) in chronic congestive heart failure (CHF) patients with central sleep apnea (CSA) – prompted a field safety notice. It was recommended to identify CHF patients treated with ASV and to advise the discontinuation of the treatment. We aimed to analyze the identification process and effect of ASV discontinuation on affected patients.Methods126 patients treated with ASV on May 13th, 2015 at our institution were retrospectively analyzed. Treatment decisions, effect of ASV discontinuation and clinical course were followed for a year. Patients on ASV with CHF were compared to those without CHF.ResultsThe risk criteria of the safety notice were fulfilled by 10.3% of patients (13/126). Additional echocardiographies were performed in 38%. ASV was discontinued in 93% of patients without adverse events (emergency hospitalization in n = 1). CSA reappeared immediately. Day- or nighttime symptoms were reported by 61%. Symptomatic patients were started on alternative treatments. CHF and non-CHF patients differed in cardiac function and type of SDB. CHF patients had shorter overall treatment duration. Compliance to ASV was similar in both groups with a median usage of 412 min (269; 495)/night in the CHF group and 414.5 min (347; 480) in the non-CHF group.ConclusionIdentification of patients “at risk” is feasible but outcome of discontinuation of ASV cannot be evaluated based on these data. ASV withdrawal in patients with stable chronic CHF and CSA leads to an immediate return of sleep disordered breathing. Symptomatic patients may ask for alternative treatment options.     

Genex椎体成形在胸腰椎爆裂性骨折治疗中的意义

目的：探讨Genex椎体成形与椎弓根钉系统复位固定胸腰椎爆裂性骨折的方法与疗效。方法：自2007年2月至2009年10月,应用Genex人工骨椎体成形与椎弓根钉系统复位固定胸腰椎爆裂性骨折38例,其中男25例,女13例;平均年龄42岁（30～68岁）。致伤原因：车祸伤9例,压砸伤7例,坠落伤21例,其他伤1例。骨折类型按Denis分类：A型6例,B型22例,C型7例,D型3例。神经功能损害按（ASIA）标准分级：A级4例,B级7例,C级10例,D级6例,E级11例。术后通过X线片、CT检查以及（ASIA）神经功能评定标准评价手术疗效。结果：38例均获随访,时间6～34个月,平均16.5个月。术后1周X线检查：脊柱序列恢复正常,术后椎体前缘高度恢复（98.50±2.17）%,椎体后缘高度恢复（98.87±1.82）%,Cobb角降（1.63±2.15）°,椎管狭窄率恢复（1.45±3.47）%。术后6个月X线片显示椎体高度、Cobb角恢复无丢失,椎体骨组织密度接近正常。CT扫描发现椎体内骨缺损完全消失,骨缺损区已为正常骨组织。术后神经功能均有1～2级的恢复。结论：Genex人工骨作为植骨材料进行椎体成形术,生物相容性好,骨诱导能力强,椎体高度及Cobb角丢失少,近期效果满意。     

Etomidate as an induction agent for endotracheal intubation in critically ill patients: A meta-analysis of randomized trials

PurposeWe performed a meta-analysis of randomized controlled trials to evaluate if etomidate impacted mortality in critically ill adults when compared with other induction agents.Materials and methodsWe searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials which compared etomidate with any other induction agent in critically ill adult patients undergoing endotracheal intubation. The primary outcome was mortality at the main timepoint defined by the study. We conducted a fixed-effects meta-analysis for the risk ratio. Using that risk ratio and 95% confidence interval, we then estimated the probability of any harm (RR > 1) and the number needed to harm ≤100 (RR ≥ 1.05).ResultsWe included 11 randomized trials comprising 2704 patients. We found that etomidate increased mortality (319/1359 [23%] vs. 267/1345 [20%]; risk ratio (RR) = 1.16; 95% confidence interval (CI), 1.01–1.33; P = 0.03; I² = 0%; number needed to harm = 31). The probabilities of any increase and a 1% increase (NNH ≤100) in mortality were 98.1% and 92.1%, respectively.ConclusionsThis meta-analysis found a high probability that etomidate increases mortality when used as an induction agent in critically ill patients with a number needed to harm of 31.