Nicoleta Stoicea

Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review

Introduction: The use of opioids has been increasing in operating room and intensive care unit to provide perioperative analgesia as well as stable hemodynamics. However, many authors have suggested that the use of opioids is associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) in experimental studies and clinical observations in dose and/or time dependent exposure even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management during anesthesia as well as in the intensive care units because of its rapid onset and offset. Objectives: Search of the available literature to assess remifentanil AOT and OIH based on available published data. Methods: We reviewed articles analyzing remifentanil AOT and OIH, and focused our literature search on evidence based information. Experimental and clinical studies were identified using electronic searches of Medline (PubMed, Ovid, Springer, and Elsevier, ClinicalKey). Results: Our results showed that the development of remifentanil AOT and OIH is a clinically significant phenomenon requiring further research. Discussions and Conclusions: AOT – defined as an increase in the required opioid dose to maintain adequate analgesia, and OIH – defined as decreased pain threshold after chronic opioid treatment, should be suspected with any unexplained pain report unassociated with the disease progression. The clinical significance of these findings was evaluated taking into account multiple methodological issues including the dose and duration of opioids administration, the different infusion mode, the co-administrated anesthetic drug’s effect, method assessing pain sensitivity, and the repetitive and potentially tissue damaging nature of the stimuli used to determine the threshold during opioid infusion. Future studies need to investigate the contribution of remifentanil induced hyperalgesia to chronic pain and the role of pharmacological modulation to reverse this process.

Opioid-induced hyperalgesia in chronic pain patients and the mitigating effects of gabapentin.

Chronic pain patients receiving opioid drugs are at risk for opioid-induced hyperalgesia (OIH), wherein opioid pain medication leads to a paradoxical pain state. OIH involves central sensitization of primary and secondary afferent neurons in the dorsal horn and dorsal root ganglion, similar to neuropathic pain. Gabapentin, a gamma-aminobutyric acid (GABA) analog anticonvulsant used to treat neuropathic pain, has been shown in animal models to reduce fentanyl hyperalgesia without compromising analgesic effect. Chronic pain patients have also exhibited lower opioid consumption and improved pain response when given gabapentin. However, few human studies investigating gabapentin use in OIH have been performed in recent years. In this review, we discuss the potential mechanisms that underlie OIH and provide a critical overview of interventional therapeutic strategies, especially the clinically-successful drug gabapentin, which may reduce OIH.

Remifentanil-acute opioid tolerance and opioid-induced hyperalgesia: a systematic review.

The use of opioids may seem to be a double-edged sword; they provide straight analgesic and antihyperalgesic effects initially, but subsequently are associated with the expression of acute opioid tolerance (AOT) and opioid-induced hyperalgesia (OIH) that have been reported in experimental studies and clinical observations. It has been suggested that opioids can induce an acute tolerance and hyperalgesia in dose- and/or time-dependent manners even when used within the clinically accepted doses. Recently, remifentanil has been used for pain management in clinical anesthesia and in the intensive care units because of its rapid onset and offset. We reviewed articles analyzing AOT and/or OIH by remifentanil and focused on the following issues: (1) evidence of remifentanil inducing AOT and/or OIH and (2) importance of AOT and/or OIH in considering the reduction of remifentanil dosage or adopting preventive modulations. Twenty-four experimental and clinical studies were identified using electronic searches of MEDLINE (PubMed, Ovid, Springer, and Elsevier). However, the development of AOT and OIH by remifentanil administration remains controversial. There is no sufficient evidence to support or refute the existence of OIH in humans.

The MiRNA Journey from Theory to Practice as a CNS Biomarker.

MicroRNAs (miRNAs), small nucleotide sequences that control gene transcription, have the potential to serve an expanded function as indicators in the diagnosis and progression of neurological disorders. Studies involving debilitating neurological diseases such as, Alzheimers disease, multiple sclerosis, traumatic brain injuries, Parkinsons disease and CNS tumors, already provide validation for their clinical diagnostic use. These small nucleotide sequences have several features, making them favorable candidates as biomarkers, including function in multiple tissues, stability in bodily fluids, a role in pathogenesis, and the ability to be detected early in the disease course. Cerebrospinal fluid, with its cell-free environment, collection process that minimizes tissue damage, and direct contact with the brain and spinal cord, is a promising source of miRNA in the diagnosis of many neurological disorders. Despite the advantages of miRNA analysis, current analytic technology is not yet affordable as a clinically viable diagnostic tool and requires standardization. The goal of this review is to explore the prospective use of CSF miRNA as a reliable and affordable biomarker for different neurological disorders.

Impact of Demographic, Socioeconomic, and Psychological Factors on Glycemic Self-Management in Adults with Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) is reported as one of the most complex chronic diseases worldwide. In the United States, Type 2 DM (T2DM) is the seventh leading cause of morbidity and mortality. Individuals with diabetes require lifelong personal care to reduce the possibility of developing long-term complications. A good knowledge of diabetes risk factors, including obesity, dyslipidemia, hypertension, family history of DM, and sedentary lifestyle, play an essential role in prevention and treatment. Also, sociodemographic, economic, psychological, and environmental factors are directly and indirectly associated with diabetes control and health outcomes. Our review intends to analyze the interaction between demographics, knowledge, environment, and other diabetes-related factors based on an extended literature search, and to provide insight for improving glycemic control and reducing the incidence of chronic complications.

Ketamine-Based Anesthetic Protocols and Evoked Potential Monitoring: A Risk/Benefit Overview

Since its discovery, ketamine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist related to phencyclidine, has been linked to multiple adverse reactions sometimes described as “out of body” and “near death experiences,” including emergence phenomena, delusions, hallucinations, delirium, and confusion. Due to these effects, ketamine has been withdrawn from mainstream anesthetic use in adult patients. Evoked potentials (EPs) are utilized to monitor neural pathways during surgery, detect intraoperative stress or damage, detect and define the level of neural lesions, and define abnormalities. Unfortunately, many of the volatile anesthetics commonly used during spinal and neurologic procedures suppress EP amplitude and monitoring. Ketamine has been found in several preclinical and clinical studies to actually increase EP amplitude and thus has been used as an analgesic adjunct in procedures where EP monitoring is critical. Once the gap in our knowledge of ketamines risks has been sufficiently addressed in animal models, informed clinical trials should be conducted in order to properly incorporate ketamine-based anesthetic regimens during EP-monitored neurosurgeries.

Delirium—biomarkers and genetic variance

Advancement in quality of health care has resulted in improved patient outcomes; however, knowledge of delirium as well as methods of treatment and its prevention are not well known. The prevalence of delirium in postoperative patients is associated with an increase in mortality, impaired recovery, and increased hospital costs (Chu et al., 2011). Complex syndromes, like delirium, are usually not associated with a single independent cause but instead with a number of different sources (van Munster et al., 2011). Delirium is defined by the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V) as a disturbance in attention and awareness according to several criteria (American Psychiatric Association, 2013). Biomarkers are biochemical or molecular traces related to the presence or severity of a disease (Chu et al., 2011). Biomarkers present before the onset of the disease can be used as a risk marker, the rise and fall of biomarkers during illness can be tracked as a disease marker, and remaining biomarkers can be seen as an end product of a disease (Chu et al., 2011). The aim of this paper is to identify biomarkers that may have a diagnostic and prognostic role in delirium.

Child-Witnessed Domestic Violence and its Adverse Effects on Brain Development: A Call for Societal Self-Examination and Awareness

There is substantial evidence indicating that children who witness domestic violence (DV) have psychosocial maladaptation that is associated with demonstrable changes in the anatomic and physiological make up of their central nervous system. Individuals with these changes do not function well in society and present communities with serious medical, sociological, and economic dilemmas. In this focused perspective, we discuss the psychosocially induced biological alterations (midbrain, cerebral cortex, limbic system, corpus callosum, cerebellum, and the hypothalamic, pituitary, and adrenal axis) that are related to maladaptation (especially post-traumatic stress disorder) in the context of child-witnessed DV, and provide evidence for these physical alterations to the brain. Herein, we hope to stimulate the necessary political discourse to encourage legal systems around the world to make the act of DV in the presence of a child, including a first time act, a stand-alone felony.

Alternative Therapies for the Prevention of Postoperative Nausea and Vomiting

Postoperative nausea and vomiting (PONV) is a complication affecting between 20 and 40% of all surgery patients, with high-risk patients experiencing rates of up to 80%. Recent studies and publications have shed light on the uses of alternative treatment for PONV through their modulation of endogenous opioid neuropeptides and neurokinin ligands. In addition to reducing PONV, hypnosis was reported to be useful in attenuating postoperative pain and anxiety, and contributing to hemodynamic stability. Music therapy has been utilized to deepen the sedation level and decrease patient anxiety, antiemetic and analgesic requirements, hospital length of stay, and fatigue. Isopropyl alcohol and peppermint oil aromatherapy have both been used to reduce postoperative nausea. With correct training in traditional Chinese healing techniques, acupuncture (APu) at the P6 acupoint has also been shown to be useful in preventing early PONV, postdischarge nausea and vomiting, and alleviating of pain. Electro-acupuncture (EAPu), as with APu, provided analgesic and antiemetic effects through release and modulation of opioid neuropeptides. These non-pharmacological modalities of treatment contribute to an overall patient wellbeing, assisting in physical and emotional healing.

Blood Genome-Wide Transcriptional Profiles Reflect Broad Molecular Impairments and Strong Blood-Brain Links in Alzheimer's Disease

To date, little is known regarding the etiology and disease mechanisms of Alzheimers disease (AD). There is a general urgency for novel approaches to advance AD research. In this study, we analyzed blood RNA from female patients with advanced AD and matched healthy controls using genome-wide gene expression microarrays. Our data showed significant alterations in 3,944 genes (≥2-fold, FDR ≤1%) in AD whole blood, including 2,932 genes that are involved in broad biological functions. Importantly, we observed abnormal transcripts of numerous tissue-specific genes in AD blood involving virtually all tissues, especially the brain. Of altered genes, 157 are known to be essential in neurological functions, such as neuronal plasticity, synaptic transmission and neurogenesis. More importantly, 205 dysregulated genes in AD blood have been linked to neurological disease, including AD/dementia and Parkinsons disease, and 43 are known to be the causative genes of 42 inherited mental retardation and neurodegenerative diseases. The detected transcriptional abnormalities also support robust inflammation, profound extracellular matrix impairments, broad metabolic dysfunction, aberrant oxidative stress, DNA damage, and cell death. While the mechanisms are currently unclear, this study demonstrates strong blood-brain correlations in AD. The blood transcriptional profiles reflect the complex neuropathological status in AD, including neuropathological changes and broad somatic impairments. The majority of genes altered in AD blood have not previously been linked to AD. We believe that blood genome-wide transcriptional profiling may provide a powerful and minimally invasive tool for the identification of novel targets beyond Aβ and tauopathy for AD research.