A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg^-1. This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg^-1) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.     

An inhibitory anti-factor IX antibody effectively reduces thrombus formation in a rat model of venous thrombosis

An inhibitory anti-factor IX/IXa antibody (BC2) has been investigated as an anti-thrombotic agent in a rat venous thrombosis model. The treatment of rats post-injury with a single bolus dose of BC2 (3 mg/kg, i.v.) resulted in an approximately 4 fold reduction in venous thrombus mass (P = 0.043). This efficacy was matched by a minimal (<2.5 fold) prolongation of the aPTT and had no effect on the prothrombin time (PT). Heparin by comparison, given as a bolus followed by continuous infusion, at doses comparable in efficacy at reducing thrombus formation, prolonged the aPTT >50 fold. These results demonstrate that the anti-factor IX/IXa antibody (BC2), when compared to heparin, can effectively reduce venous thrombosis with less disruptive consequences on blood clotting.     

Nosocomial respiratory syncytial virus infection in Canadian pediatric hospitals: a Pediatric Investigators Collaborative Network on Infections in Canada Study

OBJECTIVE: To determine nosocomial transmission of respiratory syncytial virus (RSV) in Canadian pediatric hospitals, outcomes associated with nosocomial disease, and infection control practices. DESIGN: A prospective cohort study in the 1992 to 1994 winter respiratory seasons. SETTING: Nine Canadian pediatric university-affiliated hospitals. PARTICIPANTS: Hospitalized children with symptoms of lower respiratory tract infection (at least one of cough, wheezing, dyspnea, tachypnea, and apnea) and RSV antigen identified in a nasopharyngeal aspirate. RESULTS: Of 1516 children, 91 (6%) had nosocomial RSV (NRSV), defined as symptoms of lower respiratory tract infection and RSV antigen beginning >72 hours after admission. The nosocomial ratio (NRSV/[com-munity-acquired RSV {CARSV})] + NRSV) varied by site from 2.8% to 13%. The median length of stay attributable to RSV for community-acquired illness was 5 days, but 10 days for nosocomial illness. Four children with NRSV (4. 4%) died within 2 weeks of infection, compared with 6 (0.42%) with CARSV (relative risk = 10.4, 95% confidence interval: 3.0, 36.4). All sites isolated RSV-positive patients in single rooms or cohorted them. In a multivariate model, no particular isolation policy was associated with decreased nosocomial ratio, but gowning to enter the room was associated with increased risk of RSV transmission (incidence rate ratio 2.81; confidence interval: 1.65, 4.77). CONCLUSIONS: RSV transmission risk in Canadian pediatric hospitals is generally low. Although use of barrier methods varies, all sites cohort or isolate RSV-positive patients in single rooms. Children with risk factors for severe disease who acquire infection nosocomially have prolonged stays and excess mortality.     

Reliability of the heparin management test for monitoring high levels of unfractionated heparin: in vitro findings in volunteers versus in vivo findings during cardiopulmonary bypass

BACKGROUND: The authors assessed the heparin management test in vitro in volunteers and in vivo during cardiopulmonary bypass. METHODS: In vitro, the heparin management test was analyzed for heparin levels between 0 and 6 IU/ml using variations in hematocrit, platelets, procoagulants, and storage time. The in vivostudies consisted of two groups: In group I (cardiopulmonary bypass /= 180 min, with aprotinin) included use (n = 10) and nonuse of coumadin (n = 10) and anticoagulation according to the automated heparin dose-response assay. Tests were performed in duplicate (whole blood, two heparin management test analyzers) and compared with anti-Xa activity (plasma). RESULTS: In vitro, the results of the heparin management test (n = 1,070) correlated well with heparin concentration (r2 = 0.98). Dilution and storage time did not affect the heparin management test; a hematocrit of 60% and reduced procoagulants (10%) prolonged clotting time. In vivo, the correlation (heparin management test vs. anti-Xa) was strong in group I (r2 = 0.97 [with aprotinin] and 0.96 [without aprotinin]; n = 960) and group II without coumadin (r2 = 0.89, n = 516). In group II with coumadin, the overall correlation was r2 = 0.87 and 0.79 (n = 484), although the range varied widely (0.57-0.94, between-analyzer differences 0-47%). CONCLUSIONS: The results of the heparin management test were influenced by hematocrit, plasma coagulation factors, and the heparin level, but not by use of aprotinin. The heparin management test provided reliable values in vitro in group I, and in group II without coumadin but was less reliable in group II with coumadin.     

Fear of aids: An assessment of knowledge and attitudes of medical,nursing, and medical technology students

The reluctance of students in health professions to care for AIDS patients is partially based on the perceived risk of transmission of HIV from patient contact. We hypothesize that fear of contagion is due to lack of knowledge and deep‐rooted attitudes and emotions existing even in areas of low HIV seroprevalence. We tested this hypothesis on medical, nursing, and medical technology students. Using a questionnaire that yielded four scales, results showed only 58% of students were knowledgeable, 81% were fearful of contagion, 57% were homophobic, and 8% had death anxiety. Lack of knowledge was correlated with fear of contagion (p < .05), whereas homophobia was weakly associated (p = .08). We conclude that this perceived risk of infection is a result of lack of knowledge, disbelief of the facts, and the interplay of personal values and emotions. Alternative educational methods are needed to increase students’ knowledge and to encourage students to examine their personal feelings and attitudes.     

Experimental investigation of the character of hypnosis

A backward masking paradigm was employed to test die hypothesis that high hypnotic susceptible Ss are able to process information at a faster rate than low susceptible Ss. The critical interstimulus interval was determined for 8 high and 8 low susceptible Ss. A t-test analysis of the critical interstimulus intervals showed a significant difference between high and low susceptible Ss with the high susceptible Ss showing a lower critical interstimulus interval. Mean critical interstimulus intervals for die high (76 milliseconds) and low (98 milliseconds) susceptible groups suggested that the high susceptible Ss were an average of 22 milliseconds faster at processing information. Results were interpreted as being consistent with, and providing support for attentional theories of hypnosis.     

Cognitive impairment in survivors of out-of-hospital cardiac arrest

Background

The huge importance of rapid provision of care, especially early defibrillation, for survival of out-of-hospital cardiac arrest (OHCA) is well known. This prospective cohort study investigated cognitive functioning of OHCA survivors in relation to the time-related elements of the resuscitation.

Methods

Fifty-seven consecutive survivors, from a cohort of 308 witnessed OHCA patients with ventricular fibrillation as the initial rhythm, underwent extensive neuropsychologic examination, including tests of memory, attention, and executive functioning, 6 months after the resuscitation. Time-related aspects of the resuscitation were collected on scene. Cognitive functioning was studied in relation to the administration of cardiopulmonary resuscitation (CPR) prior to ambulance arrival, and time from collapse to start of CPR, defibrillation, and return of spontaneous circulation (ROSC).

Results

Depending of the test, between 11% and 28% of survivors were cognitively impaired, while 58% scored unimpaired for all tests. Daily life activities were limited in 19% of the patients. Patients who received CPR prior to arrival of the ambulance showed a trend towards overall better cognitive functioning and significant better immediate memory and visuomotor tracking (P = .03 and P < .01). We found a weak correlation between the time to CPR, time to defibrillation, or time to ROSC and cognitive functioning.

Conclusions

The majority of survivors of OHCA with ventricular fibrillation as the initial rhythm are cognitively unimpaired. Long delays to ROSC are compatible with good cognitive outcome. Initiation and cessation of resuscitation efforts should not be based on the duration of circulatory arrest.