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Hematopoietic stem cell transplantation (SCT) is a therapeutic option for patients with bone marrow failure, certain malignancies and inborn errors of metabolism. Complications requiring intensive care are frequent, and intensivists need to be familiar with the transplantation process and the disorders that are unique to these patients. The transplant process involves the use of high dose chemotherapy or radiation, followed by intravenous infusion of stem cells matched with the recipient at the human leukocyte antigen (HLA) loci. Full recovery of a normal immune system can take a year or more, so following transplantation, patients are exquisitely susceptible to infections. Moreover, complications such as graft versus host disease, idiopathic pneumonia syndrome, sinusoidal obstruction syndrome and transplant associated thrombotic microangiopathy are common in the first hundred days after stem cell infusion. Respiratory failure is a common presentation necessitating intensive care admission and may be due to infectious or non-infectious causes. Mechanical ventilation may be needed along with broad spectrum anti-microbial coverage; corticosteroids are commonly used if graft versus host disease is present. Acute graft versus host disease is most frequent in children receiving grafts from unrelated donors and results in significant morbidity. Increased immunosuppression is the cornerstone of therapy for graft versus host disease, and protection of the children from infection is essential to survival. Sinusoidal obstruction syndrome and transplant associated thrombotic microangiopathy may lead to multiple organ failure with limited therapeutic options, but both disorders can resolve with good supportive care during the period of organ failure. Outcomes for patients who develop multiple organ failure following SCT remain poor despite aggressive supportive care, however, children with failure of a single organ can do well. Integrated multi-disciplinary care between intensivists and transplant physicians, and other specialists such as nephrologists and pulmonologists leads to improved outcomes.

The purpose of this study is to determine the effect of clonidine on cardiac norepinephrine spillover utilizing an isolated rat heart preparation with attached cardiac sympathetic nerves. Following a 20-minute stabilization period, the sympathetic ganglion for each heart preparation was electrically stimulated with 10V and 2 Hz for 30 seconds (S1: 60 pulses). Heart rate, left ventricular developed pressure, and coronary perfusion pressure was allowed to return to baseline and the perfusate was randomly switched to Krebs buffer containing one of two treatments: placebo or clonidine (1 microM). After 10 minutes of treatment, the sympathetic ganglion was again electrically stimulated with 10V and 2 Hz for 30 seconds (S2: 60 pulses). The perfusate exiting the heart before, during, and after each electrical stimulation was collected for the determination of cardiac norepinephrine spillover. Clonidine administration significantly reduced cardiac norepinephrine spillover by approximately 50% (P < 0.05) and was associated with a 36% reduction in heart rate (P < 0.05). These findings provide evidence that clonidine can directly suppress NE spillover from cardiac sympathetic nerve terminals. Thus, suppression of cardiac NE by clonidine may be due to stimulation of presynaptic alpha2-adrenergic receptors or imidazoline subtype I receptors located on cardiac sympathetic nerve terminals. Results from our study demonstrate a reduction in cardiac NE spillover by clonidine and provide additional evidence that it can directly suppress peripheral sympathetic activity in that our results were obtained utilizing an isolated perfused heart preparation with attached cardiac sympathetic nerves devoid of any CNS input.