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.

The role of fibrinogen and fibrinogen concentrate in cardiac surgery: an international consensus statement from the Haemostasis and Transfusion Scientific Subcommittee of the European Association of Cardiothoracic Anaesthesiology.

To date, data regarding the efficacy and safety of administering fibrinogen concentrate in cardiac surgery are limited. Studies are limited by their low sample size and large heterogeneity with regard to the patient population, by the timing of fibrinogen concentrate administration, and by the definition of transfusion trigger and target levels. Assessment of fibrinogen activity using viscoelastic point-of-care testing shortly before or after weaning from cardiopulmonary bypass in patients and procedures with a high risk of bleeding appears to be a rational strategy. In contrast, the use of Clauss fibrinogen test for determination of plasma fibrinogen level can no longer be recommended without restrictions due to its long turnaround time, high inter-assay variability and interference with high heparin levels and fibrin degradation products. Administration of fibrinogen concentrate for maintaining physiological fibrinogen activity in the case of microvascular post-cardiopulmonary bypass bleeding appears to be indicated. The available evidence does not suggest aiming for supranormal levels, however. Use of cryoprecipitate as an alternative to fibrinogen concentrate might be considered to increase plasma fibrinogen levels. Although conclusive evidence is lacking, fibrinogen concentrate does not seem to increase adverse outcomes (i.e., thromboembolic events). Large prospective multi-centre studies are needed to better define the optimal perioperative monitoring tool, transfusion trigger and target levels for fibrinogen replacement in cardiac surgery.

Ruptured popliteal artery aneurysm.

BACKGROUND: Popliteal artery aneurysms (PAAs) are generally complicated by thrombosis and distal embolization, whereas rupture is rare. The aim of this study was to describe the clinical characteristics and outcome in a cohort of patients who had surgery for ruptured PAA (rPAA). METHODS: Operations for rPAA were identified from the Swedish Vascular Registry, Swedvasc, 1987-2012. Medical records and imaging were reviewed. Comparison was made with patients treated for PAA without rupture. RESULTS: Forty-five patients with rPAA were identified. The proportion with rupture among those operated on for PAA was 2·5 per cent. Patients with rPAA were 8 years older (77·7 versus 69·7 years; P < 0·001), had more lung and heart disease (P = 0·003 and P = 0·019 respectively), and a larger mean popliteal aneurysm diameter (63·7 versus 30·9 mm; P < 0·001) than patients with PAA treated for other indications. At time of surgery, 22 of 45 patients were already receiving anticoagulants, seven for concomitant deep venous thrombosis (DVT) in the affected leg. There was extensive swelling of the whole leg in 20 patients. In 27 patients, the initial diagnosis was DVT or a Baker's cyst. All patients underwent surgery, all but three by the open method. There were four amputations, all performed within 1 week of surgery. One year after surgery, 26 of the 45 patients were alive. Among these, the reconstructions were patent in 20 of 22 patients. CONCLUSION: The diagnosis of rPAA is difficult, and often delayed. The condition affects old patients, who often are on anticoagulation treatment and have large aneurysms. The immediate surgical results are acceptable, but the condition is associated with a high risk of death within the first year after surgery.

Differences in regional cerebral oximetry during cardiac surgery for patients with or without postoperative cerebral ischaemic lesions evaluated by magnetic resonance imaging.

BACKGROUND: Near infrared spectroscopy (NIRS) is widely used to monitor regional cerebral tissue oxygenation (rScO2). We compared rScO2 values during cardiac surgery in patients with or without new cerebral ischaemic lesions on diffusion weighted magnetic resonance imaging (DWI). We hypothesised patients with new cerebral lesions would have impaired tissue oxygenation reflected in their rScO2 values. METHODS: NIRS and DWI data were collected in 152 elective cardiac surgery patients. Absolute rScO2 values, duration of desaturation below thresholds (baseline, 10%, and 20%), and accumulated cerebral desaturation load were compared between patients with or without new cerebral lesions on DWI. Primary outcome was time below 10% from rScO2 baseline. RESULTS: The time below 10% from rScO2 baseline was significantly longer for patients with new cerebral lesions than for patients without [median (inter-quartile range): 11.0 (0.4; 37.5) min vs 1.8 inter-quartile range: (0.05; 20.9) min, P=0.02]. Furthermore, they had a higher accumulated desaturation load below baseline (P=0.02) and 10% below baseline (P=0.02). Finally, their absolute minimum rScO2 value was significantly lower (P=0.01). However, the frequency of patients with desaturation below 10% and 20% was comparable between patients with and without new cerebral lesions. Receiver-operating characteristic curve analysis did not identify a clear-cut critical threshold among the investigated rScO2 variables. CONCLUSIONS: Use of NIRS identified significant group differences in rScO2 values between patients with or without new ischaemic lesions. However, a critical threshold could not be identified because of a high variation in NIRS values across both groups. CLINICAL TRIAL REGISTRATION: NCT 02185885.

Five-year outcomes following a randomized trial of femorofemoral and femoropopliteal bypass grafting with heparin-bonded or standard polytetrafluoroethylene grafts.

BACKGROUND: Cohort studies suggest superior long-term patency of luminal heparin-bonded polytetrafluoroethylene (Hb-PTFE) bypass grafts compared with standard PTFE grafts. The aim of this study was to compare the outcomes of Hb-PTFE grafts with those of standard PTFE grafts 5 years after a randomized trial. METHODS: Patients with intermittent claudication or critical limb ischaemia requiring femorofemoral or femoropopliteal bypass grafting were randomized in a clinical trial of Hb-PTFE versus standard PTFE in 11 Scandinavian centres between 2005 and 2009. Patients were followed up for 5 years with clinical assessment and surveillance Duplex ultrasound imaging. The primary endpoint of this study was primary patency. Secondary endpoints included major amputation and mortality. RESULTS: Overall, 569 patients were enrolled in the randomized trial. Some 552 had follow-up data available for analysis of the primary outcome. Use of Hb-PTFE significantly improved patency by 37 per cent at 2 years, but 5 years after randomization there was no difference in primary patency (adjusted hazard ratio (HR) 0·95, 95 per cent c.i. 0·71 to 1·28; P = 0·748). In patients with critical limb ischaemia the use of Hb-PTFE reduced the 5-year risk of loss of primary patency by 37 per cent (HR 0·63, 0·40 to 0·99; P = 0·049). CONCLUSION: In this study there was no difference in primary graft patency between Hb-PTFE and standard PTFE grafts. Patients receiving Hb-PTFE grafts for critical limb ischaemia were more likely to have a patent graft at 5 years than those with standard PTFE grafts.

Systematic review of the association of venous oxygenation and outcome in adult hospitalized patients.

BACKGROUND: Adequate tissue oxygenation is necessary to maintain organ function. Low venous oxygen saturation may reflect impaired tissue oxygenation, and may be used as a predictive tool and a therapeutic target to improve the care of critically ill patients. We therefore conducted a systematic review of the existing literature reflecting these aspects. METHODS: We searched electronic databases in January 2016 for relevant studies on venous oxygen saturation for treatment guidance and patient outcome. We sub-grouped results based on patient groups and setting. RESULTS: The search resulted in 5590 papers of which 42 studies were deemed relevant. The majority of the studies in cardiac and abdominal surgery patients showed associations between low venous oxygen saturation and increased mortality and morbidity, in particular increased length of intensive care. However, the cut-off level for low venous oxygen saturation varied between < 55 and 70% and all studies had high risk of bias. In patients with septic shock, recent randomized trials showed no benefit of early resuscitation guided by venous oxygen saturation. CONCLUSION: Low venous oxygen saturation may be associated with increased mortality, morbidity and length of intensive care in patients following cardiac or abdominal surgery. However, the wide range of cut-off levels and low quality of evidence hampers the clinical application. In patients with septic shock, the present evidence does not support goal-directed therapy using venous oxygen saturation during early resuscitation.

Treatment of Popliteal Aneurysm by Open and Endovascular Surgery: A Contemporary Study of 592 Procedures in Sweden.

BACKGROUND: Popliteal aneurysm (PA) is traditionally treated by open repair (OR). Endovascular repair (ER) has become more common. The aim was to describe time trends and compare results (OR/ER). METHODS: The Swedish vascular registry, Swedvasc, has a specific PA module. Data were collected (2008-2012) and supplemented with a specific protocol (response rate 99.1%). Data were compared with previously published data (1994-2002) from the same database. RESULTS: The number of operations for PA was 15.7/million person-years (8.3 during 1994-2001). Of 592 interventions for PA (499 patients), 174 (29.4%) were treated for acute ischaemia, 13 (2.2%) for rupture, 105 (17.7%) for other symptoms, and 300 (50.7%) were asymptomatic (31.5% were treated for acute ischaemia, 1994-2002, p = .58). There were no differences in background characteristics between OR and ER in the acute ischaemia group. The symptomatic and asymptomatic groups treated with ER were older (p = .006, p < .001). ER increased 3.6 fold (4.7% 1994-2002, 16.7% 2008-2012, p = .0001). Of those treated for acute ischaemia, a stent graft was used in 27 (16.4%). Secondary patency after ER was 70.4% at 30 days and 47.6% at 1 year, versus 93.1% and 86.8% after OR (p = .001, <.001). The amputation rate at 30 days was 14.8% after ER, 3.7% after OR (p = .022), and 17.4% and 6.8% at 1 year (p = .098). A stent graft was used in 18.3% for asymptomatic PA. Secondary patency after ER was 94.5% at 30 days and 83.7% at 1 year, compared with 98.8% and 93.5% after OR (p = .043 and 0.026). OR was performed with vein graft in 87.6% (395/451), with better primary and secondary patency at 1 year than prosthetic grafts (p = .002 and <.001), and with a posterior approach in 20.8% (121/581). CONCLUSIONS: The number of operations for PA doubled while the indications remained similar. ER patency was inferior to OR, especially after treatment for acute ischaemia, and the amputation risk tended to be higher, despite similar pre-operative characteristics.

Paediatric ECMO at low-volume paediatric cardiac centres in the Nordic countries.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a life-saving resource-intensive technology for patients with respiratory and/or circulatory failure. We aimed to evaluate outcome data from three Nordic paediatric centres comparing with data from the International Registry of the Extracorporeal Life Support Organization (ELSO) and selected high-volume single-centre studies. METHODS: One-hundred nineteen patients < 19 years from 2002 to 2012 were enrolled. Data on demographics and outcome were collected using a standardised registration form. Outcome data were compared with the ELSO registry and high-volume single-centre studies. RESULTS: Demographics, indications and diagnosis were similar to the ELSO register. Survival after ECMO was similar to outcome data from the ELSO register, apart from paediatric cardiac ECMO, where a significantly better survival to discharge was seen in the Nordic centres (68% vs. 49%; P = 0.03). Comparison with high-volume centres in the period after 2005 demonstrated a significantly better survival after cardiac ECMO in a single high-volume centre study, whereas four studies had significantly lower survival after cardiac ECMO. No significant difference was seen in children receiving respiratory ECMO in the Nordic centres and high-volume centres. CONCLUSIONS: Survival after ECMO in three low-volume Nordic centres demonstrated comparable outcome data with ELSO data and data from high-volume centres. We believe regular quality assurance surveys, as the present study, should be performed in order to maintain excellent therapy within the individual ECMO centres.

Vitamin A supplementation and BCG vaccination at birth may affect atopy in childhood: long-term follow-up of a randomized controlled trial.

BACKGROUND: Recent evidence suggests that immunogenic interventions such as vaccines and micronutrients may affect atopic sensitization and atopic disease. We aimed to determine whether neonatal BCG vaccination, vitamin A supplementation and other vaccinations affect atopy in childhood. METHODS: In Guinea-Bissau, low-birthweight infants were randomized to early (intervention) or delayed (usual policy) BCG. A subgroup was also randomly assigned vitamin A supplementation or placebo in a two-by-two factorial design. Participants were followed up at age 3-9 years. The main outcome was atopy defined as skin prick test reaction ≥3 mm. Secondary outcomes were symptoms of eczema, asthma and food allergy. RESULTS: Two hundred eighty-one children had valid skin prick tests performed, and 14% (39/281) were atopic. There was no significant difference in atopy between the early and delayed BCG groups (OR, 0.71; 95% CI, 0.34-1.47). Atopy was significantly reduced in children who had responded to BCG with a scar (OR, 0.42; 0.19-0.94). Vitamin A supplementation was associated with increased atopy (OR, 2.88; 1.26-6.58), especially in those who received simultaneous BCG (5.99; 1.99-18.1, P = 0.09 for interaction between vitamin A supplementation and BCG). Early vs delayed BCG was not associated with symptoms of atopic disease, but vitamin A supplementation increased odds of wheeze within the past 12 months (OR, 2.45; 1.20-4.96). CONCLUSIONS: There were no statistically significant effects of early vs delayed BCG on atopy or symptoms of atopic disease. Having a BCG scar was associated with reduced atopy, whereas neonatal vitamin A supplementation was associated with increased atopy. STUDY REGISTRATION: Clinicaltrials.gov NCT 01420705.

Metabolic effects of three different inotropic strategies in the newborn piglet myocardium.

INTRODUCTION: Neonates undergoing congenital heart surgery frequently need post-operative inotropic support. Knowledge about the effect of inotropes on myocardial metabolism in the newborn heart is limited, and the choice of inotropic therapy is based mainly on evidence from studies in adults. The aim of this study was to compare the effect of three inotropic strategies on the myocardial metabolism in a neonatal pig model. METHODS: Newborn piglets were randomised to intravenous infusions with: adrenaline and milrinone; dopamine and milrinone; dobutamine in haemodynamically equivalent doses; or isotonic saline, through 3 h. Microdialysis catheters were inserted in the myocardium of the left and right ventricle, and concentrations of lactate, pyruvate, glycerol, and glucose were measured in the microdialysate. In myocardial biopsies, tissue lactate and intracellular glycogen concentrations were determined, and arterial blood samples were analysed for lactate and glucose. RESULTS: No statistically significant differences were observed in haemodynamics between the three interventions. Metabolic variables demonstrated a consistent increase in lactate concentration in blood, myocardial dialysate, and biopsies in milrinone-adrenaline-treated animals. The lactate concentration remained stable in all other groups in all samples. The myocardial lactate/pyruvate ratio did not increase and was not significantly different between groups. CONCLUSION: Milrinone and adrenaline induced significantly higher lactate levels in neonatal piglets. The increase was not caused by myocardial ischaemia, but rather due to a beta-stimulation-induced glycolysis.

Lactate levels predict mortality and need for peritoneal dialysis in children undergoing congenital heart surgery.

BACKGROUND: The purpose of this study was to investigate whether an initial post-operative lactate level is a predictor of mortality, need for peritoneal dialysis (PD), duration of intubation or length of stay (LOS) in the intensive care unit (ICU) in children undergoing cardiac surgery. METHOD: A retrospective, observational follow-up study was conducted in 206 children undergoing cardiac surgery from 2006 to 2007. Multivariate logistics regression analyses were performed to determine whether the lactate level was an independent risk factor. The lactate concentration at arrival in the ICU, outcome and risk factors (patient demographics, surgical complexity, duration of cardiopulmonary bypass and inotropic score) were obtained from the electronic patient data management program and medical records. RESULT: The median (interquartile range) lactate level was 1.9 mmol/l (1.3-2.7) in children immediately after cardiac surgery and a mortality of 3.9%. Eight percent of the children had a lactate level higher than 4.5 mmol/l. An increased lactate level ≥4.5 mmol/l resulted in an odds ratio (95% confidence intervals) of 8.4 (1.5-46.1) for mortality and an odds ratio of 16.9 (2.7-106.8) for PD after adjusting for Risk Adjustment for Congenital Heart Surgery 1. Because of the low number of deaths, limited confounder analysis was performed. Duration of intubation and LOS in the ICU were not associated with the initial lactate level when adjusting for confounders. CONCLUSION: The initial post-operative lactate level was a predictor of mortality and need for PD in children undergoing surgery for congenital heart disease.

The Scandinavian Propaten(®) trial - 1-year patency of PTFE vascular prostheses with heparin-bonded luminal surfaces compared to ordinary pure PTFE vascular prostheses - a randomised clinical controlled multi-centre trial.

OBJECTIVE: To compare 1-year potencies' of heparin-bonded PTFE [(Hb-PTFE) (Propaten(®))] grafts with those of ordinary polytetraflouroethylene (PTFE) grafts in a blinded, randomised, clinically controlled, multi-centre study. MATERIALS AND METHODS: Eleven Scandinavian centres enrolled 569 patients with chronic functional or critical lower limb ischaemia who were scheduled to undergo femoro-femoral bypass or femoro-poplitaeal bypass. The patients were randomised 1:1 stratified by centre. Patency was assessed by duplex ultrasound scanning. A total of 546 patients (96%) completed the study with adequate follow-up. RESULTS: Perioperative bleeding was, on average, 370 ml with PTFE grafts and 399 ml with Heparin-bonded PTFE grafts (p = 0.32). Overall, primary patency after 1 year was 86.4% for Hb-PTFE grafts and 79.9% for PTFE grafts (OR = 0.627, 95% CI: 0.398; 0.989, p = 0.043). Secondary patency was 88% in Hb-PTFE grafts and 81% in PTFE grafts (OR = 0.569 (0.353; 0.917, p = 0.020)). Subgroup analyses revealed that significant reduction in risk (50%) was observed when Hb-PTFE was used for femoro-poplitaeal bypass (OR = 0.515 (0.281; 0.944, p = 0.030)), and a significant reduction in risk (50%) was observed with Hb-PTFE in cases with critical ischaemia (OR = 0.490 (0.249; 0.962, p = 0.036)). CONCLUSION: The Hb-PTFE graft significantly reduced the overall risk of primary graft failure by 37%. Risk reduction was 50% in femoro-poplitaeal bypass cases and in cases with critical ischaemia.

Urgent reversal of vitamin K antagonist therapy.

In the developed world, an increasing number of patients receive therapy with vitamin K antagonists (VKA). This group of patients poses an additional challenge in the perioperative management of emergency surgery and trauma. The present review offers a detailed description of some treatment options for reversal of VKA therapy. Optimal treatment of the anticoagulated patient requires a well-balanced intervention securing a reduced risk of haemorrhagic surgical complications as well as optimal anticoagulation post-operatively without exposing the patient to an increased risk of thromboembolic complications. The following factors must be considered in VKA-treated patients scheduled for emergency surgery: (1) the indication for VKA therapy, including the risk of thromboembolic events when the International normalized ratio (INR) is reduced, (2) type of surgery, including the risk of haemorrhagic complications and (3) the pharmacodynamic/-kinetic profile of the therapy used to revert the VKA therapy. Therapeutic options for acute reversal of VKA therapy include: vitamin K, fresh frozen plasma (FFP), prothrombin complex concentrate (PCC) and perhaps activated recombinant factor VII. PCC is a relatively new drug in some European countries and clinical experience is limited compared with the use of FFP. Reversal of VKA anticoagulation with PCC is faster and more efficient compared with FFP, but there are currently no randomized studies demonstrating an improved clinical outcome.

Simultaneous administration of vitamin A and DTP vaccine modulates the immune response in a murine cerebral malaria model.

The World Health Organisation recommends vitamin A supplementation (VAS) to children aged 6 months to 5 years in low-income countries, and for logistic reasons, this has been linked to routine childhood immunizations. Observational studies suggest that VAS given with diphtheria-tetanus-pertussis (DTP) vaccine may increase mortality from non-targeted diseases. We investigated the non-targeted effect of pretreatment with VAS and DTP vaccine in a murine model of experimental cerebral malaria. Our a priori hypothesis was that VAS/DTP would aggravate the infection. We found that the effect of VAS and DTP depended on pathogenesis; VAS/DTP tended to increase parasitaemia and significantly depressed cytokine responses in mice, which developed cerebral malaria, but this was not seen in mice dying of anaemia. The divergent effect according to pathogenesis may help elucidate why VAS has divergent effects on different diseases in humans. Our results support the hypothesis that immunological effects of VAS/DTP may have detrimental implications for disease outcomes.

Epidemiological studies of the non-specific effects of vaccines: II--methodological issues in the design and analysis of cohort studies.

We review sources of bias which can affect non-randomized cohort studies of non-specific effects of vaccines on child mortality. Using examples from the literature on non-specific effects, we describe different sources of selection and information bias, and, where possible, outline analysis strategies to mitigate or eliminate such biases.

Popliteal artery aneurysm: epidemiology and modern management.

PAA is a predominantly male disease, more than 90% of affected patients are men. Risk factors for amputation are poor run-off, use of a synthetic graft, emergency treatment and high age. The frequency of amputation decreased over time in Sweden, which was associated with increased use of preoperative thrombolysis and fasciotomy. Thrombolysis can transform an emergent into an elective situation, and often improves out-flow. The risk of late amputation is low. Operation with a Posterior approach is associated with lower risk of late expansion, and is considered first choice of treatment when a short by-pass is sufficient. Multiple aneurysm disease is common among patients with PAA, in particular among those with bilateral PAA. All patients, irrespective of age, should be included in a life-long surveillance program. Normal arterial segments should be re-examined after three years.

Risk of new aneurysms after surgery for popliteal artery aneurysm.

BACKGROUND: The risk of developing a new aneurysm after surgery for popliteal artery aneruysm (PAA) is not well known. The aim was to study this risk in a cohort of patients. METHODS: A total of 571 patients who had primary operation for PAA (717 legs) between 1987 and 2002 were identified from the Swedish Vascular Registry (Swedvasc). Of these, 190 patients were re-examined by ultrasonography after a median of 7 (range 2.9-18.7) years. RESULTS: The number of patients with at least one aneurysm in addition to the PAA was 108 (56.8 per cent) at the index operation and 131 (68.0 per cent) at re-examination. The overall number of aneurysms increased by 41.8 per cent, from 244 to 346. Among the 82 patients who had an isolated PAA at the index operation, 23 developed a new aneurysm; these patients tended to be older (P = 0.004). Bilateral PAA at the index operation was associated with a later development of abdominal aortic aneurysm (P = 0.004). Age (P = 0.004) and hypertension (P = 0.012) at the time of the index operation were associated with multianeurysm disease at any time. Six (4.3 per cent) of 138 legs treated by venous bypass grafts had developed a graft aneurysm by the time of re-examination. No normal arterial segment developed an aneurysm that required surgery within 3 years. CONCLUSION: The development of new aneurysms was common in patients with a PAA; lifelong surveillance may be warranted.

Junctional ectopic tachycardia after surgery for congenital heart disease in children.

OBJECTIVE: To determine incidence, predictors and outcome [intensive care unit (ICU) mortality and length of stay (LOS)] after postoperative junctional ectopic tachycardia (JET) in an unselected paediatric population. DESIGN: Patients with JET (n=89) were compared with non-JET controls (n=178) in a nested case-control study. SETTING: Tertiary ICU at Skejby Sygehus, Aarhus University Hospital, Denmark. PATIENTS: The patient records of all children (n=874) who underwent corrective cardiac surgery on cardio-pulmonary bypass (CPB) between 1998 and 2005 were reviewed for postoperative JET. METHODS AND RESULTS: The association between JET and its potential predictors was examined with multivariate conditional regression analyses. The overall incidence of JET was 10.2%. CPB duration>90 min [adjusted odds ratio (OR) 2.6; 95% confidence interval (CI) 1.1-6.5], high inotropic requirements (adjusted OR 2.6; CI 1.2-5.9) and high postoperative levels of creatine kinase (CK)-MB (adjusted OR 3.1; CI 1.3-7.1) were associated with an increased risk of JET. ICU mortality was higher for patients with JET (13.5%; CI 7.2-22.4%) than for controls (1.7%; CI 0.3-4.8%), and LOS in ICU was 3 times higher in JET patients (median 2 vs. 7 days, p<0.001). CONCLUSIONS: JET occurred in approximately 10% of children following cardiac surgery and was associated with higher mortality and longer ICU stay. Risk factors included high inotropic requirements after surgery and extensive myocardial injury in terms of high CK-MB values and longer CPB duration.

No adverse events after simultaneous administration of 50 000 IU vitamin A and Bacille Calmette-Guerin vaccination to normal-birth-weight newborns in Guinea-Bissau.

OBJECTIVE: To determine whether the combined intervention of 50 000 IU vitamin A administered together with Bacille Calmette-Guerin (BCG) vaccination at birth was associated with adverse events, in particular bulging fontanels and adverse reactions to BCG. SUBJECTS/METHODS: From an ongoing trial, 2145 infants randomized to 50 000 IU vitamin A or placebo with BCG vaccination were recruited. Adverse events were monitored in two different ways: (A) daily clinical examinations by a medical doctor during the first 3 days post supplementation; (B) weekly interviews by a trained assistant during the first month post supplementation. RESULTS: In part A, 1271 infants were enrolled, in part B 2078. Vitamin A supplementation (VAS) was associated with a relative risk (RR) of bulging fontanels of 1.16 (95% confidence interval (CI)=0.82-1.65). The rate of health care contacts and various symptoms during the first month were comparable between the groups. VAS was associated with larger peak local reactions to BCG vaccination in boys, but not in girls (P-value for test of interaction between VAS and sex=0.02). CONCLUSION: 50 000 IU vitamin A with BCG was not associated with adverse events. The observed sex-differential effect of VAS on local reaction to BCG is in line with other observations of sex-differential effects of VAS.