This study indicates that dyssynchronization of the melatonin secretion rhythm is common in critically ill and mechanically ventilated patients. It could be hypothesized that an impairment of the melatonin rhythm may play a role in the development of sleep disturbances and delirium in intensive care patients, and that melatonin supply could reduce the incidence of these phenomena.

Intensive care unit syndrome/delirium is associated with anemia, drug therapy and duration of ventilation treatment.

Apart from the effects of nitric oxide on central hemodynamics in this model, the scintigraphic findings indicate an in vivo effect of nitric oxide on the accumulation of platelets and neutrophils in the lungs, probably due to inhibition of the adhesion and/or aggregation of these cells.

Activation and accumulation of polymorphonuclear leukocytes (PMNs, neutrophils) in the lungs is considered an important mechanism in the pathogenesis of pulmonary dysfunction in association with sepsis. It probably constitutes only part of a general cellular response; and a corresponding reaction has been implicated in other organs during sepsis (e.g., the liver). In this experiment a model was developed that allows study of the dynamic PMN reaction in the lungs and visceral organs during early abdominal sepsis. The animals were divided into two groups. In the septic group (n = 8) a bacterial challenge was attempted through the intraperitoneal administration of Escherichia coli (1 x 10(11)/kg). Five animals served as controls. All animals in the septic group developed bacteremia, leukopenia, and a hypodynamic circulatory response. PMNs were selectively labeled with 111In-oxine. The activity over the organs was followed dynamically with a gamma camera. The animals subjected to peritonitis exhibited a significant increase in 111In-oxine activity (i.e., neutrophil trapping) in the lungs, compared to the controls at 40 minutes and onward during the observation period. A similar picture was seen over the liver and abdomen, with significance after 70 minutes. The findings in this study indicate that accumulation of PMNs is an early phenomenon not only in the lungs but also in the liver during the development of sepsis. The present model offers possibilities for further studies of the cellular reactions during sepsis.

The feasibility of administering drugs in a wide size range by passive diffusion through a standardized skin mini-erosion was demonstrated; the rate of absorption decreased with increasing molecular weight. The small area of the erosion restricts and controls the concentration driven diffusion of drug into the circulation. As a consequence of the favorable findings, three placebo-controlled clinical studies using Morphine cellpatch for postoperative pain relief are currently underway.