A clinically significant incidence of bleeding in critically ill children receiving therapeutic doses of unfractionated heparin: a prospective cohort study

Unfractionated heparin (UFH) is frequently prescribed for children for the prevention and treatment of thrombosis; however, its safety and efficacy have not been assessed. The aim of this single center, prospective cohort study was to determine the incidence of major bleeding and recurrent thrombosis in children receiving UFH. Major bleeding was defined a priori as: central nervous system or retroperitoneal bleeding, bleeding resulting in UFH being stopped or overt bleeding causing a drop in hemoglobin >20 g/dL in less than 24 h. Major bleeding events occurred in 9/38 children (24%, 95% CI 11-40%) and 2/38 (5%, 95% CI 0-18%) developed thrombosis. In conclusion, there is clinically significant bleeding in children receiving UFH.     

Lack of agreement between thermodilution and fick cardiac output in critically ill patients

STUDY OBJECTIVE:s: Individual comparison of cardiac output via intermittent thermodilution and Fick technique over a wide range of cardiac outputs. DESIGN: Prospective clinical investigation. SETTING: Multidisciplinary ICUs of two teaching hospitals in Vancouver, British Columbia. PARTICIPANTS: Eighteen critically ill patients who had pulmonary and systemic arterial catheters and in whom active support was being withdrawn. INTERVENTIONS: Measurement of thermodilution cardiac output and calculation of Fick cardiac output while support was withdrawn. Active support was withdrawn in a three-step process: removal of vasopressors followed by decrease in fraction of inspired oxygen to 0.21, and finally removal of mechanical ventilation. MEASUREMENTS AND RESULTS: Simultaneous Fick and thermodilution cardiac outputs were obtained over a wide range. Fick calculated cardiac outputs were obtained using the Fick equation with oxygen uptake (O(2)) being measured with indirect calorimetry. O(2) determinations were made using five measurements over 5 min, with the mean being used for subsequent analysis. Thermodilution cardiac outputs were determined by the mean of five measurements, with the first being discarded. Coefficient of variation was calculated for the O(2) and thermodilution cardiac outputs. One hundred thirty-six simultaneous cardiac outputs were obtained in 18 patients with a mean APACHE (acute physiology and chronic health evaluation) II score of 25.5. The range of cardiac outputs was 1.39 to 16.95 L/min. Linear regression analysis found a good correlation of the data sets, with an R of 0.85. Bias and precision calculations found a bias of - 0.17 L/min with the upper and lower limits of agreement being 2.96 L/min and - 3.30 L/min, respectively. In patients with high cardiac outputs (> 7 L/min), the bias was - 1.90 with the limits of agreement being 1.87 L/min and - 5.67 L/min. The coefficient of variation for O(2) was 4.6% and for thermodilution cardiac output was 7.75%. CONCLUSIONS: There was good consistency of each of the measurements with a low coefficient of variation. The bias for the whole group was small, but the limits of agreement extended into a clinically relevant area, resulting in a lack of agreement. In patients with high cardiac outputs, the Fick tended to consistently produce higher cardiac outputs compared to thermodilution, suggesting a systematic error.     

Low-molecular-weight heparin versus unfractionated heparin in the treatment of patients with acute pulmonary thromboembolism

BACKGROUND: Low-molecular-weight heparin (LMWH) appears to be as effective as unfractionated heparin (UFH) for both treatment and prophylaxis of deep vein thrombosis (DVT), but limited data are available for its use in acute pulmonary thromboembolism (PTE). OBJECTIVE: To determine whether enoxaparin, a LMWH, was clinically as efficient and safe as UFH in patients with a diagnosis of acute PTE. MATERIAL AND METHODS: After exclusion of those with massive forms, 59 patients with acute PTE were randomly assigned to either subcutaneous enoxaparin given twice daily (1 mg/kg/dose) or adjusted dose intravenous UFH. Oral anticoagulant treatment was begun on the second day and was given for at least 6 months. We compared the treatment regimens at day 8 and day 90 with respect to a combined end point of major bleeding, recurrent venous thromboembolism (VTE), and death. RESULTS: In the first 8 days of treatment, 1 of 30 patients assigned to receive UFH (3.3%) reached one of the end points (recurrence), as compared with none of 29 patients assigned to enoxaparin. Statistically this difference was not significant (p = 0.508). By day 90, 3 patients assigned to UFH (10%) had symptomatic recurrent VTE, as compared with 1 patient assigned to enoxaparin (3.4%). There was neither major bleeding nor death in the study groups. There was an absolute difference of 6.4 percentage points between the two treatment groups, but the difference was statistically not significant (p = 0.318). CONCLUSION: Initial subcutaneous treatment with enoxaparin appeared to be as effective and safe as UFH in acute PTE.     

Hemostasis and thrombosis in critically ill children

Patients in the pediatric intensive care unit (PICU) often suffer from a variety of pathophysiologic conditions that are associated with abnormal hemostasis. Bleeding is a major complication of any surgery or trauma, thus patients with inherited or acquired coagulopathies or those experiencing massive trauma or undergoing major (especially cardiac) operations present a special challenge to the ICU experts as well as to the hematologist. Awareness of thromboembolic events in the pediatric population has been increasing in the past few years mainly due to improvement in diagnostic tools, advances in new therapy and procedures, together with an increased index of suspicion. Young infants are at greater risk for either bleeding or thromboembolic events, due to lower concentration of vitamin K-dependent procoagulant clotting factors, reduced thrombin potential, and altered fibrinolytic pathway with low levels of the coagulation inhibitors. The combination of infection, hypotension, acidosis, and release of activated substances, such as tumor necrosis factor, is common after severe trauma or in seriously ill ICU patients and often leads to disseminated intravascular coagulation, which may be complicated either by bleeding or thrombosis. The conditions, risk factors, and therapeutic options available for critically ill PICU patients are discussed in this review.     

A regional cohort study of the treatment of critically ill children with bronchiolitis

Objective: To describe the treatment practices in critically ill children with RSV bronchiolitis across four regional PICUs in the northeastern United States, and to determine the factors associated with increased ICU length of stay in this population. Methods: We conducted a retrospective cohort study of children who were admitted with RSV bronchiolitis between July 2009 and July 2011 to the PICUs of Connecticut Children's Medical Center, Yale-New Haven Children's Hospital, Maria Fareri Children's Hospital, and Baystate Children's Hospital. Data were collected regarding clinical characteristics and intensive care course among these hospitals. Results: During the study period, 323 children were admitted to one of the four ICUs with RSV bronchiolitis. Despite similar mortality risk scores among ICUs, there was considerable variation in the use of therapies, particularly intubation and mechanical ventilation, in which there was greater than a 3.5-fold increased risk of intubation between sites with the highest and lowest frequency of intubation (odds ratio: 3.8; 95% confidence interval: 2.2–6.4). Albuterol was the most commonly used respiratory treatment, followed by chest physiotherapy, high-flow nasal cannula, and hypertonic saline. Longer stays in the ICU were associated with more frequent use of therapies, specifically invasive mechanical ventilation, inhaled corticosteroids, intrapulmonary percussive ventilation, and chest physiotherapy. Conclusions: Even within a close geographic region, there is significant variation in the treatment provided to critically ill children with RSV bronchiolitis. None of these treatments were associated with shorter durations of hospitalization in this population and some, such as mechanical ventilation, were associated with longer ICU lengths of stay.     

Subcutaneous unfractionated heparin compared with low-molecular-weight heparin for the initial treatment of venous thromboembolism

PURPOSE OF REVIEW: Low-molecular-weight heparin is the preferred choice for the initial treatment of acute, uncomplicated venous thromboembolism. In this context, unfractionated heparin is as safe and effective as low-molecular-weight heparin but requires strict laboratory monitoring. Twice-daily subcutaneous unfractionated heparin is more effective than, and as safe as, intravenous unfractionated heparin and may simplify patient treatment in or out of the hospital, being possibly cost saving, especially if it is used in weight-based, fixed, unadjusted doses. The present review focuses on the relative values of low-molecular-weight heparin and subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism. RECENT FINDINGS: The major advantages of low-molecular-weight heparin over unfractionated heparin seem to be ease of administration and cost savings associated with home therapy or early hospital discharge; however, many patients with venous thromboembolism are still admitted to the hospital for treatment, and unfractionated heparin is extensively used to this purpose, especially in the United States. Subcutaneous unfractionated heparin, adjusted according to activated partial thromboplastin time algorithms, is as safe and effective as low-molecular-weight heparin for the treatment of venous thromboembolism, allows for quick mobilization and early discharge of suitable patients, and represents a cost-effective strategy. Fixed-dose unfractionated heparin, like low-molecular-weight heparin, may be used for the home treatment of deep vein thrombosis. SUMMARY: Subcutaneous unfractionated heparin, targeted on activated partial thromboplastin time results or in fixed doses, may be used in or out of the hospital for the treatment of venous thromboembolism, being possibly cost effective; however, these findings need confirmation through appropriate, large-sample, randomized clinical trials.     

Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant Staphylococcus aureus pneumonia

BackgroundVancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend giving an initial loading dose (LD) of 25–30 mg/kg to rapidly increase the serum concentration. However, high-quality evidence for the clinical benefit of LD is lacking. Herein, we aim to examine the association between vancomycin LD and clinical outcome.MethodsA retrospective cohort study was conducted on adult patients treated for MRSA pneumonia with vancomycin in medical intensive care units from April 2016 to August 2018. MRSA pneumonia was defined by the Centers for Disease Control and National Healthcare Safety Network definition. The primary outcome was the clinical cure of pneumonia. Secondary outcome measures included time to pharmacokinetic (PK) target attainment, microbiological cure, acute kidney injury, and all-cause mortality.ResultsA total of 81 patients were included; of these 22 (27.2%) received LD. The mean initial dose was significantly higher in the LD group. Clinical cure was similar in both groups (68.2% vs. 66.1% in the LD and non-LD groups, respectively; P=0.860). No significant difference was observed in the microbiological cure, all-cause mortality, and incidence of acute kidney injury. Furthermore, no difference was observed in terms of time to PK target attainment (69.2 vs. 63.4 h in the LD and non-LD groups, respectively; P=0.624). Vancomycin minimum inhibitory concentration of <2 mg/L was identified as an independent predictive factor for clinical cure in multivariable analysis, whereas vancomycin LD was not.ConclusionsInitial LD is not associated with better clinical outcome or rapid pharmacological target attainment in critically ill patients with MRSA pneumonia. Further studies are warranted to provide better evidence for this widely recommended practice.     

Point of care coagulation tests in critically ill patients

Point of care assays for various analytes have been established in critical care, including blood gas analysis, glucose, electrolytes, and markers for cardiac ischemia. Coagulation assays can also be adapted to the critical care environment by using whole blood as sample material and instruments optimized for point of care analysis. Available assays include the conventional coagulation assays, such as prothrombin time and activated partial thromboplastin time, fibrinogen, assays for monitoring of anticoagulant drugs, global coagulation assays based on thrombelastography and viscosimetry, platelet function assays, and D-dimer assays. The main problem in point of care coagulation diagnostics is quality control. Point of care coagulation assays help in rapidly establishing a diagnosis, clarifying causes of bleeding, and monitoring therapy. Thrombelastography and similar assays extend the scope of coagulation diagnostics by visualizing the process of clot formation and extending the observation period to provide an estimate of clot stability versus mechanical and proteolytic attack.     

小型猪冠状动脉再狭窄模型中普通肝素用量的探讨

目的:评价低、中度肝素化在小型猪冠状动脉再狭窄模型中的应用效果,探讨该模型合理的普通肝素用量。方法:根据普通肝素用量将24只健康小型猪随机分为低度肝素化组(100U/kg)和中度肝素化组(150U/kg)。分别测定基础活化凝血时间(activating clotting time,ACT)值和静脉注射肝素后不同时间点ACT值。比较2组的抗凝效果,术后压迫止血情况及术中、术后24h的安全性。结果:中度肝素化组和低度肝素化组在静脉推注普通肝素后5minACT达到峰值〔(315.1±50.85)svs(276.2±59.38)s,P=0.110〕,20min时2组均维持较高ACT值,但中度肝素化组明显高于低度肝素化组〔(284.8±45.14)svs(206.3±32.44)s,P=0.003〕。60min时中度肝素化组仍维持较高的ACT值(193.9±21.87)s,而低度肝素化组ACT值明显回落(132.2±13.30)s,与前者相比差异有统计学意义(P0.001)。中度肝素化组术后徒手压迫止血时间显著长于低度肝素化组有〔(17.3±2.06)minvs(13.5±2.94)min,P=0.006〕。总体手术平均时间为(13.2±2.34)min。2组术中和术后24h均未发生冠状动脉事件。结论:在小型猪冠状动脉再狭窄模型中,若手术时间控制在20min内,则低度肝素化(100U/kg)既可保证手术的安全性又可缩短压迫止血时间。     

危重患者血栓弹力图与常规凝血指标的对比研究

目的探讨血栓弹力图(TEG)与常规凝血指标在重症监护病房(ICU)危重患者应用中的共性与差异。方法回顾分析2014年8月至2017年5月苏州市立医院本部ICU危重患者(86例)血栓弹力图的R值、K值、α-angle、最大振幅(MA),以及常规凝血指标中的凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、血小板计数(PLT),计算中位数,进行Fisher精确概率检验及Kappa一致性分析。结果与正常参考范围相比,PT和APTT的中位数值增高,PLT的中位数值降低,而FIB和TEG的各参数的中位数值均在正常范围内。Fisher精确概率检验结果表明,R值与PT和APTT,K值与APTT、FIB和PLT,α-angle与PT、APIT、FIB和PLT,以及MA与FIB和PLT间的检验差异均具有统计学意义(P0.05)。Kappa分析结果显示,常规凝血指标与TEG参数的一致性均较弱。结论 ICU内TEG与常规凝血检查结果一致性弱,两种方法不能相互替代。     

Dead space ventilation in critically ill children with lung injury

STUDY OBJECTIVE: In children with acute lung injury, there is an increase in minute ventilation (E) and inefficient gas exchange due to a high level of physiologic dead space ventilation (VD/VT). Mechanical ventilation with positive end-expiratory pressure, when used in critically ill patients to correct hypoxemia, may contribute to increased VD/VT. The purpose of this study was to measure metabolic parameters and VD/VT in critically ill children. DESIGN: A cross-sectional study. SETTING: Pediatric ICU of a university hospital. PATIENTS: A total of 45 mechanically intubated children (mean age, 5.5 years). INTERVENTIONS: Indirect calorimetry was used to measure metabolic parameters. VD/VT parameters were calculated using the modified Bohr-Enghoff equation. ARDS was defined based on criteria by The American-European Consensus Conference. Measurements and results: The group mean (+/- SD) ventilatory equivalent for oxygen (VeqO(2)) and ventilatory equivalent for carbon dioxide (VeqCO(2)) were 2.9 +/- 1 and 3.3 +/- 1 L per 100 mL, respectively. The group mean VD/VT was 0.48 +/- 0.2. When compared to non-ARDS patients (33 patients), the patients with ARDS (12 patients) had a significantly higher VeqO(2) (3.3 +/- 1 vs 2.8 +/- 1 L per 100 mL, respectively; p < 0.05), a significantly higher VeqCO(2) (3.7 +/- 1 L/100 vs 3.1 +/- 1 L per 100 mL, respectively; p < 0.05), and a significantly higher VD/VT (0.62 +/- 0.14 vs 0.43 +/- 0.15, respectively; p < 0.0005). CONCLUSIONS: Critically ill children with ARDS have increased VD/VT. Increased VD/VT was the main cause of the excess of E demand in these patients. Increased metabolic demands, as shown by the VeqO(2), VeqCO(2), and ventilatory support, are the major determinants of E requirements in children with ARDS.     

A case of pulmonary thromboembolism after interruption of treatment with unfractionated heparin

Pulmonary embolism is a quite frequent event (incidence 1/10000/year), and blood stasis, endothelial lesions and coagulation disorders are predisposable factors. Elective treatment is heparin, but the use of this medication is associated with a possible ipercoagulative rebound effect. The case presented is a patient with unstable angina treated with heparin infusion, who developed pulmonary embolism after discontinuation of heparin treatment; the patient didn't present a genetic coagulopathy. Others risk factors have been analyzed and it was observed that discontinuation of heparin infusion could have a predominant role in the development of thrombosis. A MedLine research on the rebound effect of heparin and how to reduce it has been carried out.