Background And ObjectivesNociceptin/Orphanin FQ (N/OFQ) is a non-classical endogenous opioid peptide that modulates immune function in vitro. Its importance in inflammation and human sepsis is unknown. The objectives of this study were to determine the relationship between N/OFQ, transcripts for its precursor (pre-pro-N/OFQ [ppNOC]) and receptor (NOP), inflammatory markers and clinical outcomes in patients undergoing cardiopulmonary bypass and with sepsis.MethodsA prospective observational cohort study of 82 patients admitted to Intensive Care (ICU) with sepsis and 40 patients undergoing cardiac surgery under cardiopulmonary bypass (as a model of systemic inflammation). Sixty three healthy volunteers, matched by age and sex to the patients with sepsis were also studied. Clinical and laboratory details were recorded. Polymorph ppNOC and NOP receptor mRNA were determined using quantitative PCR. Plasma N/OFQ was determined using ELISA and cytokines (TNF- α, IL-8, IL-10) measured using radioimmunoassay. Data from patients undergoing cardiac surgery were recorded before, 3 and 24 hours after cardiopulmonary bypass. ICU patients with sepsis were assessed on Days 1 and 2 of ICU admission, and after clinical recovery.Main ResultsPlasma N/OFQ concentrations increased (p<0.0001) on Days 1 and 2 of ICU admission with sepsis compared to matched recovery samples. Polymorph ppNOC (p= 0.019) and NOP mRNA (p<0.0001) decreased compared to healthy volunteers. TNF-α, IL-8 and IL-10 concentrations increased on Day 1 compared to matched recovery samples and volunteers (p<0.0001). Similar changes (increased plasma N/OFQ, [p=0.0058], decreased ppNOC [p<0.0001], increased IL-8 and IL-10 concentrations [both p<0.0001]) occurred after cardiac surgery but these were comparatively lower and of shorter duration.ConclusionsThe N/OFQ system is modulated in ICU patients with sepsis with similar but reduced changes after cardiac surgery under cardiopulmonary bypass. Further studies are required to clarify the role of the N/OFQ system in inflammation and sepsis, and the mechanisms involved.

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Antihypertensive drugs are used commonly in anaesthesia and intensive care medicine. Patients might require antihypertensive drugs before surgery for the treatment of essential hypertension, pre-eclampsia or, occasionally for conditions such as phaeochromocytoma; during surgery as part of a deliberate hypotensive anaesthetic technique; or to reduce postoperative cardiovascular complications. Here, we discuss the physiology of blood pressure control, the pharmacology of antihypertensive drugs, current guidelines, and practical applications of antihypertensive therapy.Keywords antihypertensive agents; autonomic nervous system; blood pressure; hypertension; renin-angiotensin system; vasomotor system Introduction Arterial pressure is modulated by the interaction among vessel tone, blood volume, and cardiac function, which are regulated by local and nervous mechanisms. Local mechanisms include metabolites that influence vascular tone and blood flow within tissues. Nervous mechanisms control the distribution of blood throughout the body, as well as coordination of cardiac output, heart rate, and contractility. The autonomic nervous system (ANS) is controlled by centres in the spinal cord, brainstem and hypothalamus, which are influenced by higher centres. The renin-angiotensin system (RAS) affects vascular tone and excretion of sodium and water in response to changes in circulating volume and arterial pressure. Blood pressure can be manipulated by drugs acting at several of these sites (Figure 1).

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