Rescue treatment with terlipressin in children with refractory septic shock: a clinical study

INTRODUCTION Refractory septic shock has dismal prognosis despite aggressive therapy. The purpose of the present study is to report the effects of terlipressin (TP) as a rescue treatment in children with catecholamine refractory hypotensive septic shock. METHODS We prospectively registered the children with severe septic shock and hypotension resistant to standard intensive care, including a high dose of catecholamines, who received compassionate therapy with TP in nine pediatric intensive care units in Spain, over a 12-month period. The TP dose was 0.02 mg/kg every four hours. RESULTS Sixteen children (age range, 1 month-13 years) were included. The cause of sepsis was meningococcal in eight cases, Staphylococcus aureus in two cases, and unknown in six cases. At inclusion the median (range) Pediatric Logistic Organ Dysfunction score was 23.5 (12-52) and the median (range) Pediatric Risk of Mortality score was 24.5 (16-43). All children had been treated with a combination of at least two catecholamines at high dose rates. TP treatment induced a rapid and sustained improvement in the mean arterial blood pressure that allowed reduction of the catecholamine infusion rate after one hour in 14 out of 16 patients. The mean (range) arterial blood pressure 30 minutes after TP administration increased from 50.5 (37-93) to 77 (42-100) mmHg (P < 0.05). The noradrenaline infusion rate 24 hours after TP treatment decreased from 2 (1-4) to 1 (0-2.5) microg/kg/min (P < 0.05). Seven patients survived to the sepsis episode. The causes of death were refractory shock in three cases, withdrawal of therapy in two cases, refractory arrhythmia in three cases, and multiorgan failure in one case. Four of the survivors had sequelae: major amputations (lower limbs and hands) in one case, minor amputations (finger) in two cases, and minor neurological deficit in one case. CONCLUSION TP is an effective vasopressor agent that could be an alternative or complementary therapy in children with refractory vasodilatory septic shock. The addition of TP to high doses of catecholamines, however, can induce excessive vasoconstriction. Additional studies are needed to define the safety profile and the clinical effectiveness of TP in children with septic shock.

Thin healthy women have a similar low bone mass to women with anorexia nervosa.

An association between anorexia nerviosa (AN) and low bone mass has been demonstrated. Bone loss associated with AN involves hormonal and nutritional impairments, though their exact contribution is not clearly established. We compared bone mass in AN patients with women of similar weight with no criteria for AN, and a third group of healthy, normal-weight, age-matched women. The study included forty-eight patients with AN, twenty-two healthy eumenorrhoeic women with low weight (LW group; BMI < 18.5 kg/m2) and twenty healthy women with BMI >18.5 kg/m2 (control group), all of similar age. We measured lean body mass, percentage fat mass, total bone mineral content (BMC) and bone mineral density in lumbar spine (BMD LS) and in total (tBMD). We measured anthropometric parameters, leptin and growth hormone. The control group had greater tBMD and BMD LS than the other groups, with no differences between the AN and LW groups. No differences were found in tBMD, BMD LS and total BMC between the restrictive (n 25) and binge-purge type (n 23) in AN patients. In AN, minimum weight (P = 0.002) and percentage fat mass (P = 0.02) explained BMD LS variation (r2 0.48) and minimum weight (r2 0.42; P = 0.002) for tBMD in stepwise regression analyses. In the LW group, BMI explained BMD LS (r2 0.72; P = 0.01) and tBMD (r2 0.57; P = 0.04). We concluded that patients with AN had similar BMD to healthy thin women. Anthropometric parameters could contribute more significantly than oestrogen deficiency in the achievement of peak bone mass in AN patients.

Prospective phase II trial of extended treatment with rituximab in patients with B-cell post-transplant lymphoproliferative disease.

BACKGROUND AND OBJECTIVES The elective treatment of patients with post-transplant lymphoproliferative disorders is controversial. The purpose of this trial was to evaluate the efficacy of treatment with extended doses of rituximab adapted to the response in patients with post-transplant lymphoproliferative disorders after solid organ transplantation. DESIGN AND METHODS This was a prospective, multicenter, phase II trial. Patients were treated with reduction of immunosuppression and four weekly infusions of rituximab. Those patients who did not achieve complete remission (CR) received a second course of four rituximab infusions. The primary end-point of the study was the CR rate. RESULTS Thirty-eight patients were assesable. One episode of grade 4 neutropenia was the only severe adverse event observed. After the first course of rituximab, 13 (34.2%) patients achieved CR, 8 patients did not respond, and 17 patients achieved partial remission. Among those 17 patients, 12 could be treated with a second course of rituximab, and 10 (83.3%) achieved CR, yielding an intention-to-treat CR rate of 60.5%. Eight patients excluded from the trial because of absence of CR were treated with rituximab combined with chemotherapy, and six (75%) achieved CR. Event-free survival was 42% and overall survival was 47% at 27.5 months. Fourteen patients died, ten of progression of their post-transplant lymphoproliferative disorder. INTERPRETATION AND CONCLUSIONS These results confirm that extended treatment with rituximab can obtain a high rate of CR in patients with post-transplant lymphoproliferative disorders after solid organ transplantation without increasing toxicity, and should be recommended as initial therapy for these patients.