Current pharmaceutical design
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Perioperative cerebral damage can result in various clinical sequela ranging from minor neurocognitive deficits to catastrophic neurological morbidity with permanent impairment and death. The goal of neuroprotective treatments is to reduce the clinical effects of cerebral damage through two major mechanisms: increased tolerance of neurological tissue to ischemia and changes in intra-cellular responses to energy supply deprivation. In this review, we present the clinical evidence of intravenous anesthetics on perioperative neuroprotection, and we also provide a critical perspective for future studies. ⋯ Current evidence, while inconclusive, suggest that intravenous anesthetics may be both neuroprotective and neurotoxic in the perioperative period. A critical analysis on data recorded from randomized control trials (RCTs) is essential in identifying patients who may benefit or be harmed by a particular anesthetic. RCTs will also contribute to defining methodologies for future studies on the neuroprotective effects of intravenous anesthetics.
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Remifentanil is a selective mu-opioid receptor agonist characterized by a rapid onset and ultrashort predictable duration of action providing intense analgesia without prolonged respiratory depression. Remifentanil has been implicated in the causation of intraoperative bradyarrhythmias and asystole both in adults and in pediatric patients. Electrophysiological studies in humans and animals show that remifentanil provokes a dose-dependent depressor effect on sinus and AV node function, manifested by a significant prolongation of sinus node recovery time, sino-atrial conduction time and Wenckebach cycle length. These electrophysiologic effects of remifentanil suggest that it should be used with attention in vulnerable patients with predisposition to bradiarritmias during anesthesia.
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Tissue injury secondary to surgical lesion produces profound changes in endocrine-metabolic function and defence mechanisms in the patient (inflammatory, immunological), leading to an increase in catabolism, immunosuppression and postoperative morbidity. The best anaesthetic and surgical technique should be capable of modulating this response, especially in major surgery, where it can be most harmful and increase patient morbidity. Many of the changes that maintain homeostasis are controlled by the hypothalamicpituitary- adrenal axis. ⋯ The aim of this review is to present clinical evidence on perioperative stress modulation with different anesthetics. We also describe a different point of view in immunomodulation with the intraoperative management of haemodynamic responses with inhalational bolus of sevoflurane or with remifentanil intravenous bolus. The effects of sevoflurane used as an inhalational bolus to counteract patients' intraoperative haemodynamic responses modulates the immune response the same than opioid remifentanil.
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Since several clinical data have suggested that the incidence of neurological deficit after aortic surgery has not changed appreciably over the last 50 years, anesthesiologists as well as vascular surgeons have attempted to resolve this clinically important issue by employing various strategies to prevent ischemic spinal cord injury. With respect to inhalational anesthetics, it is thought that isoflurane as well as sevoflurane preconditioning might provide neuroprotective effects against spinal ischemia via activation of TWIK-related K channels-1 or the potassium ATP channel. Glutamate receptor antagonists, including ketamine, could also potentially provide some neuroprotection against spinal ischemia. ⋯ Inhaled nitric oxide (iNO) therapy (40-80ppm), a common treatment for pulmonary hypertension, has been reported to prevent ischemic brain injury in animal studies by selective dilation of collateral arterioles. The vasodilating effects of iNO on the central nervous system might enhance the "collateral network" in the spinal cord during aortic cross-clamp, potentially protecting the spinal cord. In conclusion, some anesthetics, especially inhalational anesthetics, may provide neuroprotective effects against spinal cord ischemia, but administration of neuraxial opioid after spinal cord ischemia might exacerbate neurological dysfunction.
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A spinal cord injury leads to disturbances of sensory and motor signals due to the damage to white matter and myelinated fiber tracts. Moreover, the damage to gray matter causes segmental loss of interneurons of dorsal horn and motoneurons and restricts the therapeutic options. Neuroprotective strategies have the potential to improve the neurological outcome of patients. ⋯ This review includes consideration of: 1) basic concepts of the pathophysiological mechanisms following spinal cord injury and 2) anesthetics and analgesics displaying neuroprotective potential. In particular, we review the application of isoflurane as an inhalational neuroprotectant and discuss evidence for the neuroprotection provided by barbiturates. In addition, 3) recent advances in stem cell biology, neural injury and repair, and progress toward the development of neuroprotective and regenerative interventions are the basis for increased optimism.