Anaphylaxis in pregnancy: a population-based multinational European study.

Anaphylaxis in pregnancy is a rare but severe complication for both mother and infant. Population-based data on anaphylaxis in pregnancy are lacking from mainland European countries. This multinational study presents the incidence, causative agents, management and maternal and infant outcomes of anaphylaxis in pregnancy. This descriptive multinational study used a combination of retrospective (Finnish medical registries) and prospective population-based studies (UK, France, Belgium and the Netherlands) to identify cases of anaphylaxis. Sixty-five cases were identified among 4,446,120 maternities (1.5 per 100,000 maternities; 95%CI 1.1-1.9). The incidence did not vary between countries. Approximately three-quarters of reactions occurred at the time of delivery. The most common causes were antibiotics in 27 women (43%), and anaesthetic agents in 11 women (17%; including neuromuscular blocking drugs, 7), which varied between countries. Anaphylaxis had very poor outcomes for one in seven mothers and one in seven babies; the maternal case fatality rate was 3.2% (95%CI 0.4-11.0) and the neonatal encephalopathy rate was 14.3% (95%CI 4.8-30.3). Across Europe, anaphylaxis related to pregnancy is rare despite having a multitude of causative agents and different antibiotic prophylaxis protocols.

The Belgian Obstetric Surveillance System to monitor severe maternal morbidity.

BACKGROUND: In 2011 the Belgian Obstetric Surveillance System (B.OSS) was set up to monitor severe maternal morbidity in Belgium. AIM: The aim of B.OSS is to get an accurate picture of the obstetric complications under investigation and secondly, to improve the quality and safety of obstetric care in Belgium by practical recommendations based on the results. METHODOLOGY: Data are obtained through prospective active collection of cases by a monthly call according to the principle of nothing-to-report, along with data collection forms that confirm the diagnosis and gather detailed information. Data-collection occurs web-based since August 2013 through www.b-oss.be. RESULTS: B.OSS achieves excellent participation rates and response rates. The results of the first registration round are gradually brought out by means of scientific publications and presentations, biennial reports, newsletters and the website. The international comparison of results within the International Network of Obstetric Survey Systems (INOSS) gives important added value. No alternative mandatory data sources are appropriate to check for underreporting. CONCLUSIONS: B.OSS is successful in monitoring severe maternal morbidity thanks to the willingness of the Belgian OB-GYNs. The results of the first studies suggest the need to develop nationally adopted guidelines. Furthermore, the results invite to critically evaluate the current organisation of obstetric health care in Belgium. B.OSS aims to monitor the impact on patient safety in future surveys, when guidelines and recommendations are put into practice.

Nationwide population-based cohort study of uterine rupture in Belgium: results from the Belgian Obstetric Surveillance System.

OBJECTIVES: We aimed to assess the prevalence of uterine rupture in Belgium and to evaluate risk factors, management and outcomes for mother and child. DESIGN: Nationwide population-based prospective cohort study. SETTING: Emergency obstetric care. Participation of 97% of maternity units covering 98.6% of the deliveries in Belgium. PARTICIPANTS: All women with uterine rupture in Belgium between January 2012 and December 2013. 8 women were excluded because data collection forms were not returned. RESULTS: Data on 90 cases of confirmed uterine rupture were obtained, of which 73 had a previous Caesarean section (CS), representing an estimated prevalence of 3.6 (95% CI 2.9 to 4.4) per 10 000 deliveries overall and of 27 (95% CI 21 to 33) and 0.7 (95% CI 0.4 to 1.2) per 10 000 deliveries in women with and without previous CS, respectively. Rupture occurred during trial of labour after caesarean section (TOLAC) in 57 women (81.4%, 95% CI 68% to 88%), with a high rate of augmented (38.5%) and induced (29.8%) labour. All patients who underwent induction of labour had an unfavourable cervix at start of induction (Bishop Score ≤7 in 100%). Other uterine surgery was reported in the history of 22 cases (24%, 95% CI 17% to 34%), including 1 case of myomectomy, 3 cases of salpingectomy and 2 cases of hysteroscopic resection of a uterine septum. 14 cases ruptured in the absence of labour (15.6%, 95% CI 9.5% to 24.7%). No mothers died; 8 required hysterectomy (8.9%, 95% CI 4.6% to 16.6%). There were 10 perinatal deaths (perinatal mortality rate 117/1000 births, 95% CI 60 to 203) and perinatal asphyxia was observed in 29 infants (34.5%, 95% CI 25.2% to 45.1%). CONCLUSIONS: The prevalence of uterine rupture in Belgium is similar to that in other Western countries. There is scope for improvement through the implementation of nationally adopted guidelines on TOLAC, to prevent use of unsafe procedures, and thereby reduce avoidable morbidity and mortality.

Adult liver transplantation and steroid-azathioprine withdrawal in cyclosporine (Sandimmun)-based immunosuppression - 5 year results of a prospective study.

New immunosuppressants are said to be superior to cyclosporine due to their higher incidence of steroid sparing and to the reduced incidence of side-effects. From May 1992 to February 1995, 79 adults underwent primary liver transplantation using cyclosporine A (Sandimmun)-based triple drug immunosuppression. Nine patients who died early after liver transplantation due to reasons unrelated to immunological problems were excluded from this analysis. The long-term outcome of the remaining 70 patients was prospectively studied in relation to steroid and azathioprine withdrawal. They were re-evaluated 6-monthly in relation to liver and kidney function; cholesterolemia, infection, de novo diabetes mellitus and arterial hypertension, malignancy, ophthalmological and osteomuscular diseases. In case of rejection occurring during or after steroid tapering, patients were switched, by protocol, to tacrolimus therapy. Median follow-up was 81 months (range 60-96). Forty-four patients (62.8 %) were biopsied 5 years after transplant; 20 patients (28.6 %) were biopsied at a median follow-up of 32 months (range 7.8-47). Six patients (8.6 %) who refused biopsies more than 1 year after liver transplantation had normal liver values throughout the whole follow-up period. Five-year actual patient and graft survivals were 75 % and 65.8 %, respectively, for the whole group (n = 79) and 85.7 % and 74.3 % for the studied group (n = 70). Steroids could be withdrawn in all but two patients (97.1 %) at a median time of 7 months (range 3-42). Steroids were restarted in six patients (8.6 %) for extrahepatic reasons. Freedom from steroids was thus observed in 62 patients (88.6 %). Seven patients (10 %) had rejection after steroid tapering; six were switched to tacrolimus. Two patients (2.9 %) needed retransplantation because of acute and chronic rejection whilst still being on full immunosuppression. In total, three patients (4.3 %) had histological signs of chronic rejection during follow-up. At 5 years post-transplant, 66.6 % and 13.3 % of the 60 patients at risk were on cyclosporine and tacrolimus monotherapy, respectively; 93.3 % were steroid-free. Mean creatinine and cholesterol levels were 1.56 +/- 1.3 mg/dl and 193.5 +/- 56.6 mg/dl; incidences of de novo arterial hypertension, insulin dependent diabetes mellitus were 26.6 % and 13.3 %. Two patients (2.8 %) developed post-transplant lymphoproliferative disease, two (2.8 %) had skin cancer. Cyclosporine-based immunosuppression allows safe steroid withdrawal in most patients and cyclosporine monotherapy can be achieved in two-thirds without compromising graft and patient survival. Results of new immunosuppressive strategies should be approached with caution, especially when considering steroid sparing and the incidence of side-effects.

Pharmacokinetics of tacrolimus (FK506) in paediatric liver transplant recipients.

The pharmacokinetics of intravenous and oral tacrolimus was assessed in paediatric liver transplant patients at two centers in Europe. Sixteen patients, age 0.7 to 13 years, participated in the study; 12 patients were evaluable for intravenous pharmacokinetics, and 16 for oral. Intravenous tacrolimus was given as a continuous 24 h infusion (mean 0.037+/-0.013 mg/kg/day), and oral tacrolimus was given in 2 doses per day (mean 0.152+/-0.015 mg/kg). Whole blood samples for the intravenous pharmacokinetic profile were taken before initiation of the first infusion, 4, 8, 12 and 24 h post-infusion, and every 24 h thereafter until intravenous administration was discontinued. During the 12 h wash-out period between intravenous and oral administration, samples were taken every 3 h. Samples for the oral pharmacokinetic profile were taken immediately before the first oral dose and 0.5, 0.75, 1, 2, 2.5, 3, 4, 6, 8, 10 and 12 h post-administration. Non-compartmental procedures were used to characterise the pharmacokinetic parameters. Mean estimates for clearance and terminal half-life were 2.3+/-1.2 ml/min/kg and 11.5+/-3.8 h, respectively, following intravenous tacrolimus. The mean bioavailability of oral tacrolimus was 25+/-20%. A strong correlation was observed between AUC and trough whole blood levels of tacrolimus (r=0.90). The clearance was approximately 2-fold higher than that previously observed in adults; this could explain the higher dosage requirements in children.

Cavocaval liver transplantation without venovenous bypass and without temporary portocaval shunting: the ideal technique for adult liver grafting?

The influence of the implantation technique on the outcome was studied prospectively in a series of 116 consecutive adult patients undergoing primary liver transplantation during the period January 1991-June 1994. Thirty-eight patients (32.8%; group 1) underwent classical orthotopic liver transplantation (OLT) with replacement of the recipient's inferior vena cava (R-IVC) and with venovenous bypass (VVB). Thirty-nine patients (33.56%) had a piggy-back OLT with preservation of the R-IVC (group 2); bypass was used in 17 of them (43.6%) because of poor hemodynamic tolerance of R-IVC occlusion. Thirty-nine patients (33.6%) had OLT without VVB and with side-to-side cavocaval anastomosis (group 3). The three techniques were performed irrespective of the anatomical situation and of the status of the recipient at the time of transplantation. The following parameters were assessed in all patients: implantation time, blood product use, morbidity (e.g., hemorrhagic, thoracic, gastrointestinal, neurological, and renal complications), and outcome. Thirty-one patients underwent detailed intraoperative hemodynamic assessment. The early (< 3 months) post-transplant mortality of 10.3% (12/116 patients) was unrelated to the implantation technique. Group 3 had a significantly shorter mean implantation time, a reduced need for intraoperative blood products, and a lower rate of reoperation due to intra-abdominal bleeding. After excluding two immediate perioperative deaths and eight patients requiring early retransplantation because of primary nonfunction, the frequency of immediate extubation was significantly higher in group 3. Detailed hemodynamic assessment did not show a difference between 6 group 1 patients and 17 group 3 patients, indicating that partial lateral clamping of the IVC fulfills the function of venous bypass. Similar results were obtained in 6 group 2 patients who did not have IVC occlusion. Cavocaval OLT has become our preferred method of liver implantation. It allows the transplantation to be performed without VVB, regardless of the anatomical situation and of the condition of the patient at the time of transplantation. Moreover, it avoids all of the potential complications and costs of VVB.

Adult liver transplantation and abnormalities of splanchnic veins: experience in 53 patients.

The aim of this study was to analyze the influence of technical problems resulting from splanchnic venous anomalies on the outcome of orthotopic liver transplantation. From February 1984 until December 1995, 53 (16.3%) of 326 adults underwent consecutive transplantations whilst having acquired anomalies of the splanchnic veins. These consisted of portal vein thrombosis (n = 32, 9.8%), thrombosis with inflammatory venous changes (phlebitis; n = 6, 1.8%) and alterations related to portal hypertension surgery (n = 15, 4.6%). Because of major changes in surgical technique, i.e., eversion instead of blind venous thrombectomy, immediate superior mesenteric vein approach in cases of extended thrombosis, and piggyback implantation with preservation instead of removal of the inferior vena cava, patients were divided into two groups: those who underwent transplantation during the period February 1984 to December 1990 (group 1) and those transplanted between January 1991 and December 1995 (group 2). Surgical procedures to overcome the anomalies consisted of venous thrombectomy (n = 26), implantation of the donor portal vein at the splenomesenteric confluence (n = 5) or onto a splenic (n = 1) or ileal varix (n = 1), interposition of a free iliac venous graft between recipient superior mesenteric vein and donor portal vein (n = 9), and interruption of surgical portosystemic shunt (n = 13). All patients had a complete follow-up. The 1- and 5-year actuarial patient survival rates were similar in patients with (n = 53) and without (n = 273) splanchnic venous abnormalities (75.5% vs 78.1% and 64.3% vs 66.9%, respectively). Early (< 3 months) post-transplant mortality was 24.5% (13/53 patients). Mortality was highest in the portal vein thrombophlebitis group (5/6, 83.3%), followed by the portal hypertension surgery group (5/15, 33.3%) and the portal vein thrombosis group (3/32, 9.4%). Technical modifications significantly reduced mortality in group 2 (10.3%, 3/29 vs 41.7%, 10/24 patients in group 1; P < 0.05) as well as the need for re-exploration for bleeding (13.8%, 4/29 patients in group 2 vs 15/24, 62.5% in group 1; P < 0.01). Mortality directly related to bleeding was also significantly lowered (1/29, 3.4% in group 2 vs 9/ 24, 37.5% in group 1; P < 0.01). We conclude that liver transplantation can be safely performed in the presence of splanchnic vein thrombosis and previous portal hypertension surgery.

Clinical pharmacokinetics of Neoral in pediatric recipients of primary liver transplants.

Pediatric liver transplant recipients constitute a population characterized by a particularly unpredictable and poor bioavailability of cyclosporin (CyA). Even though several adult studies show that the new oral formulation of CyA, Neoral (NEO), produces better bioavailability and blood level predictability, few data describe its pharmacokinetics in children. We performed a complete analysis of the pharmacokinetics of NEO in ten small children after primary liver transplantation. Three pharmacokinetic profiles were set up with data obtained from tests taken during i.v. administration of CyA, after the first oral NEO dose, and after the last NEO dose before discharge from the hospital. The mean half-lives obtained were 8.1, 7.7, and 6.9 h, respectively, and the bioavailabilities were 22% and 21% for the first and last NEO doses. A large interpatient variability was observed. This was due, in part, to episodes of diarrhea that interfered with the pharmacokinetic evaluation and, in part, to the variability of post-transplant hepatic function. There was a good correlation between CyA trough levels and their related AUCs for both NEO profiles (r = 0.93 and r = 0.74, respectively). We conclude that, even though the pediatric OLT population remains more unpredictable than that of adults, NEO has a relatively rapid half-life and a remarkably improved bioavailability.