Pharmacokinetic and Pharmacodynamic Changes in the Elderly: Impact on Anesthetics.

Anesthesiologists are increasingly required to care for frail elderly patients. A detailed knowledge of the influence of age on the pharmacokinetics and dynamics of the anesthetic drugs is essential for optimal safety and care. For most of the anesthetic drugs, the elderly need lower doses to achieve the same plasma concentrations, and at any given plasma and effect-site concentration, they will have more profound clinical effects than younger patients. Caution is required, with close monitoring of clinical effects and active titration of dose administration to achieve the desired level of effect, ideally following the "start low, go slow" principle.

Postoperative neurocognitive disorders.

A decline in cognitive function is a frequent complication of major surgery. Postoperative cognitive impairments have generally been divided into short- (postoperative delirium) and long-term disturbances (postoperative cognitive dysfunction [POCD]). Long-term impairments are often subtle and overlooked. They need to be objectively assessed using neuropsychological tests to be diagnosed. Although POCD has been the subject of considerable research over the past decades, it remains uncertain why some patients do not return to preoperative levels of cognitive function. Surgery and anesthesia have both been implicated to play a role in POCD development, and certain patient-related factors, such as advanced age and low preoperative baseline cognitive function, have consistently been found to predict postoperative cognitive decline. This article will present an overview of POCD and its etiology and provide advice on possible strategies on its prevention.

Expanding the moral circle: farmed fish as objects of moral concern.

Until recently fish welfare attracted little attention, but international and national legislation and standards of fish welfare are now emerging and an overview of these developments is presented in this study. Whereas animal welfare legislation is based on public morality, animal ethics does not automatically accept public morality as normative and elaborates arguments regarding the way humans should treat animals (referred to as moral standards). In this study we present the most common animal ethics theories. For most of these, sentience is considered a demarcation line for moral concern: if an animal is sentient, then it should be included in the moral circle, i.e. receive moral consideration in its own right and some basic welfare should be ensured. As for fish, research has revealed that the sensory system of teleosts can detect noxious stimuli, and that some kind of phenomenal consciousness, allowing the fish to feel pain, seems to be present. This raises the ethical question as to how much evidence we need in order to act on such indications of fish sentience. A simple risk analysis shows that the probability that fishes can feel pain is not negligible and that if they do indeed experience pain the consequences in terms of the number of suffering individuals are great. We conclude that farmed fish should be given the benefit of the doubt and we should make efforts that their welfare needs are met as well as possible. Finally, the way forward is briefly discussed: efforts must be made to understand what fish welfare means in practical fish farming. This will involve the development of research and education, greater accountability and transparency, compliance with and control of policies, and quality assurance schemes.

Cortisol acts through central mechanisms to blunt counterregulatory responses to hypoglycemia in conscious rats.

Physiological levels of cortisol have been found to blunt neuroendocrine and metabolic responses to subsequent hypoglycemia in humans. The aim of this study was to determine whether cortisol acts directly on the brain to elicit this effect. A total of 41 conscious unrestrained Sprague-Dawley rats were studied during 2-day experiments. Day 1 consisted of two episodes of clamped 2-h hyperinsulinemic (30 pmol. kg(-1) x min(-1)) hypoglycemia (2.8 +/- 0.1 mmol/l; n = 12; ANTE HYPO), euglycemia (6.2 +/- 0.1 mmol/l; n = 12; ANTE EUG), or euglycemia (6.2 +/- 0.1 mmol/l) plus simultaneous intracerebroventricular (ICV) infusion of cortisol (25 microg/h; n = 9; ANTE EUG+Cort) or saline (24 microl/h; n = 8; ANTE EUG+Sal). For all groups, day 2 consisted of a 2-h hyperinsulinemic (30 pmol x kg(-1) x min(-1)) hypoglycemic (2.9 +/- 0.2 mmol/l) clamp. Plasma epinephrine and glucagon incremental area under the curve (Delta AUC) responses were significantly less in ANTE EUG+Cort and ANTE HYPO versus both ANTE EUG and ANTE EUG+Sal (P < 0.05). The Delta AUC responses of plasma norepinephrine were significantly lower in ANTE EUG+Cort versus both ANTE EUG and ANTE EUG+Sal (P < 0.05). Endogenous glucose production was significantly less in ANTE HYPO and ANTE EUG+Cort versus the other groups (P < 0.05). Lastly, the glucose infusion rate to maintain the desired hypoglycemia was significantly greater in ANTE EUG+Cort and ANTE HYPO versus the other two groups (P < 0.05). In summary, ICV infusion of cortisol significantly blunted norepinephrine, epinephrine, glucagon, and endogenous glucose production responses to next-day hypoglycemia. We conclude that cortisol can act directly on the central nervous system to blunt counterregulatory responses to subsequent hypoglycemia in the conscious rat.