Antonio Abramo

Morphological evidence that xenon neuroprotects against N-methyl-DL-aspartic acid-induced damage in the rat arcuate nucleus: a time-dependent study.

Abstract:  The hyperactivation of glutamate receptors, especially those of the N‐methyl‐d‐aspartate subtype (NMDA), can induce excess calcium entry into cells, leading to neuronal death. Since the anesthetic gas xenon behaves as an NMDA antagonist, the present article investigated, by distinct morphological approaches and after different times, the possible neuroprotectant effects of this gas in a model of neuronal damage induced by N‐methyl‐dl‐aspartic acid (NMA) on rat arcuate nucleus. Rats were assigned to the following groups: controls; xenon exposure; NMA treatment; or xenon exposure + NMA treatment. Animals were placed in an experimental cage and after 10 min a mixture of xenon (or nitrogen) 70% and oxygen 30% was delivered. After 3 h, 1, 2, 5, or 7 days from gas exposure, rats were euthanized and the whole brain was removed and processed for either transmission electron microscopy or light microscopy. In the arcuate nucleus from NMA‐treated animals only 40–60% of cell population survived in all times with several degenerating neurons giving the typical appearance of a “bulls eye.” At ultrastructural level, chromatin margination, nuclear shrinkage, mitochondria with matrix dilution, dilated endoplasmic cisternae, and electrondense cytoplasm were detected. Xenon alone did not induce changes, but reduced of about 50% NMA‐induced cell loss as well as degenerating neurons, with the maximal neuroprotection at 7 days. These results confirm that in the rat arcuate nucleus NMA can induce a severe neuronal damage that is already marked after 3 h. Xenon significantly reduced the neuronal damage at all times and can be then regarded as a promising neuroprotectant agent.

Xenon induces transcription of ADNP in neonatal rat brain

Xenon and other inhalational agents induce cell and organ protection through different and only partially elucidated molecular mechanisms. Anesthesia induced or pharmacologic preconditioning is a recognized mechanism of cell protection. In this study we explored the gene transcription of activity-dependent neuroprotective protein (ADNP) in neonatal rat brain as consequence to xenon exposure, comparing the noble gas to nitrogen. Seven-day-old Sprague Dawley rats were exposed for 120 min to 75% xenon and 25% oxygen or control condition consisting of 75% nitrogen and 25% oxygen (Air). ADNP was found to be differentially expressed by SSH, validated by Relative Real-Time PCR (RT-PCR) and confirmed by western blot and immunohistochemistry. The differential expression of ADNP in the rat neonatal brain may account for the preconditioning and neuroprotective effects exerted by gas xenon.

Rapid Reversal of Severe Lactic Acidosis After Thiamine Administration in Critically Ill Adults A Report of 3 Cases

BACKGROUND Thiamine plays a critical role in energy metabolism. Critically ill patients may have thiamine deficiency and increased mortality due to potentially irreversible consequences. The aim of this study was to show the impact of thiamine deficiency in a series of patients and the rapid response to thiamine replacement, showing the changes in clinical and metabolic conditions over time. METHODS We described 3 cases of hospitalized patients who had received parenteral nutrition (PN) without vitamin supplementation. All the patients were admitted to the ICU between 2010 and 2011 with a severe form of lactic acidosis, an unstable circulatory state, and a different neurological disorder (a lethargic state, a severe form of impaired near-coma consciousness, and Wernicke encephalopathy). RESULTS Intravenous (IV) administration of thiamine was associated with a rapid and marked restoration of acid-base balance, hemodynamic stability and the disappearance of neurological disturbances, and normalization of the clinical and biochemical conditions of all the patients within the following hours. CONCLUSIONS The 3 cases demonstrated the rapidity of the reversal of severe thiamine deficiency, achieved by appropriate replacement in different hospitalized patients. The regression of clinical and biochemical disorders requires a prompt diagnosis and treatment based on the IV administration of thiamine and magnesium sulfate. In hospitalized patients at risk, thiamine deficiency is prevented by the integration of thiamine supplementation into PN and other forms of nutrition support.

Xenon Anesthesia Improves Respiratory Gas Exchanges in Morbidly Obese Patients

Background. Xenon-in-oxygen is a high density gas mixture and may improve PaO2/FiO2 ratio in morbidly obese patients uniforming distribution of ventilation during anesthesia. Methods. We compared xenon versus sevoflurane anesthesia in twenty adult morbidly obese patients (BMI > 35) candidate for roux-en-Y laparoscopic gastric bypass and assessed PaO2/FiO2 ratio at baseline, at 15 min from induction of anaesthesia and every 60 min during surgery. Differences in intraoperative and postoperative data including heart rate, systolic and diastolic pressure, oxygen saturation, plateau pressure, eyes opening and extubation time, Aldrete score on arrival to the PACU were compared by the Mann-Whitney test and were considered as secondary aims. Moreover the occurrence of side effects and postoperative analgesic demand were assessed. Results. In xenon group PaO2-FiO2 ratio was significantly higher after 60 min and 120 min from induction of anesthesia; heart rate and overall remifentanil consumption were lower; the eyes opening time and the extubation time were shorter; morphine consumption at 72 hours was lower; postoperative nausea was more common. Conclusions. Xenon anesthesia improved PaO2/FiO2 ratio and maintained its distinctive rapid recovery times and cardiovascular stability. A reduction of opioid consumption during and after surgery and an increased incidence of PONV were also observed in xenon group.

Evaluation of a preoperative pain score in response to pressure as a marker of postoperative pain and drugs consumption in surgical thyroidectomy.

Introdution:The success and effectiveness of a day surgery model are essentially related to a good postoperative course with a rapid recovery. Adequate management of analgesia during the hospital stay and after discharge becomes mandatory in reducing postoperative patient discomfort, and in facilitating discharge to home. Background:The aim of this study was to identify the efficacy of preoperative visual analog scale (VAS) score in predicting postoperative pain and analgesic drugs consumption. The hypothesis of a significant relation between preoperative pain and postoperative pain tolerance thresholds was tested using Spearman rank-order correlations, applied to patients scheduled for thyroidectomy in a Day Surgery Unit. Methods:Patients scheduled for total thyroidectomy underwent a preoperative pain test to assess the VAS value after a fixed stimulus (inflation of a sphygmomanometer with a pressure of 250 mm Hg). To estimate the power of the VAS in prediction of the postoperative analgesic requests, we divided the patients into 3 groups according to the preoperative VAS values (A group, including all patients with preoperative VAS⩽3; B group including patients with preoperative VAS>3⩽6; C group with preoperative VAS>6).Then we correlated preoperative results with postoperative VAS values and postoperative analgesic drug consumption, analyzing the correlation between the sensitivity and the specificity of the VAS test for a range of different cutoff values. Results:Thirty-two patients were included. A group (10 patients) showed a medium postoperative VAS<4, and required less analgesics than other groups (ketorolac, 51 mg). B group (10 patients) and C group (12 patients) showed higher postoperative VAS value and required more analgesic drug (B, 80 mg; C, 90 mg+1 g acetaminophen). Using the receiver operating characteristic or relative operating characteristic examination and calculating the underlying area , we could measure the discriminating ability of the test and found that the best VAS score cutoff was 3. Conclusion:The use of a preoperative test to assess individual pain threshold may be predictive for postoperative pain and analgesic request. The mathematical and statistical model used in this study confirms that a difference in the value of VAS of 3 shall be mathematically eligible for analgesia treatment.

Xenon-related Analgesia: A New Target for Pain Treatment.

The noble gas xenon has been known for >50 years in the field of anesthesia with an emerging series of favorable features; several clinical and preclinical studies performed over the last years reveal a renewed interest because they substantially agree on attributing relevant analgesic properties to xenon. The main mechanism of action is the inhibition of N-methyl-D-aspartate receptors of glutamate; it involves the blocking of painful stimuli transmissions from peripheral tissues to the brain and it also avoids the development of pain hypersensitivity. Therefore, this mechanism is responsible for the inhibition of pain transmission at spinal and supraspinal levels, as well as the cortical level. In all these levels of pain pathways, as the development of hyperalgesia is possible, xenon efficacy can also be based on the blocking of these processes. Several forms of pain share such mechanisms in their maintenance, and xenon can be successfully used at low dosages, which have no effects on vital parameters. The literature shows that analgesic features could also emerge outside the field of anesthesia; thus, this could permit xenon to have a larger usage according to local availability.