Acta Clin Belg
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Neonatal drug dosing needs to be based on the physiological characteristics of the newborn and the pharmacokinetic parameters of the drug. Size-related changes can in part be modelled based on allometry and relates to the observation that metabolic rate relates to weight by a kg 0.75 trend. Until adult metabolic activity has been reached, ontogeny, i.e. isoenzyme-specific maturation and maturation of renal clearance also contributes to drug metabolism, making isoenzyme-specific documentation of maturation necessary. ⋯ While the first is mainly hepatic, the second route is mainly renal. Both hepatic metabolism and renal clearance display maturation in early life although other covariables (e.g. polymorphisms, co-administration of drugs, first pass metabolism, disease characteristics) further contribute to the interindividual variability in drug disposition. Documentation of these maturational processes based on in vivo 'case' studies is of value since these drug-specific observations can subsequently be extrapolated to other drugs which are either already being prescribed or even considered for use in neonates by the introduction of these observations in 'generic physiologically-based pharmacokinetic' models.
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Acute kidney injury (AKI) is a common and serious complication in the intensive care setting. It seldom occurs in isolation, but is mostly part of a multiple organ dysfunction syndrome. The pathogenesis is frequently multifactorial, with sepsis contributing to 50% of the cases. ⋯ Treatment of established AKI is largely supportive. The optimal modality for renal replacement therapy in critically-ill patients still remains a matter of debate). The majority of survivors recover renal function.
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Patients with sepsis often receive large amounts of fluids and the presence of capillary leak, trauma or bleeding results in ongoing fluid resuscitation. This increases interstitial and intestinal edema and finally leads to intra-abdominal hypertension (IAH), which in turn impedes lymphatic drainage. Patients with IAH often develop secondary respiratory failure needing mechanical ventilation with high intrathoracic pressure or PEEP that might further alter lymphatic drainage. This review will try to convince the reader of the importance of the lymphatics in septic patients with IAH. ⋯ Although often overlooked the role of lymphatic flow is complex but very important to determine not only the fluid balance in the lung but also in the peripheral organs. Different pathologies and treatments can markedly influence the pathophysiology of the lymphatics with dramatic effects on endorgan function.
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Gastrointestinal failure (GIF) has been postulated as the motor of multiple organ dysfunction syndrome (MODS) but is not commonly included among other organ failures in scoring systems identifying MODS. ⋯ There is no consensus on definition of GIF and different medical specialties have different approaches. Development of a proper definition of GIF is warranted.
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Acute kidney injury (AKI) is a serious complication in critically-ill patients and portends a high mortality. The incidence of AKI continues to increase and is often underestimated. The intriguing question to both the intensivists and nephrologists is whether the kidney is an innocent bystander in the process of multi-organ systems failure or whether the kidney is initiating various complex metabolic and humoral pathways affecting distant organs contributing to the overall mortality. ⋯ Volume overload and acid-base derangements typical of renal dysfunction have serious consequences in the duration and weaning of mechanical ventilation. Recent animal studies suggest that acutely ischaemic kidneys may induce both functional and transcriptional changes in the lung, independent of uraemia. In this review, we have attempted to discuss various physiological derangements and their clinical effects, in the setting of AKI.