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Biomedical subjects

L B Santamaria

Publications and source records attributed to L B Santamaria.

At least 19 recordsLinked to original sources
PubMed2006

Alzheimer's disease and anaesthesia: implications for the central cholinergic system.

Alzheimer's disease (AD) is associated with a loss of cholinergic neurons resulting in profound memory disturbances and irreversible impairment of cognitive function. The central cholinergic system is involved in the action of general anaesthetic agents. Anaesthetic modulation of cholinergic transmission has profound effects on brain function via a cascade of synaptic and postsynaptic events by binding both nicotinic and muscarinic receptors. During general anaesthesia, decrease in acetylcholine release and depression of cholinergic transmission facilitates the desirable effects of general anaesthetics, such as loss of consciousness, pain, voluntary movements and memory. From this point of view, patients with AD, characterized by a compromised neuronal transmission, represent particular cases in which the choice of anaesthesia drugs may have a negative effect on the postoperative outcome. A future challenge may be the identification of brain targets of general anaesthetics which do not expose patients to postoperative cognitive dysfunction, nor interfere with prognosis of brain degenerative disease.

Alzheimer Disease↗
PubMed2006

Cerebral haemodynamic changes during propofol-remifentanil or sevoflurane anaesthesia: transcranial Doppler study under bispectral index monitoring.

BACKGROUND: Sevoflurane or propofol-remifentanil-based anaesthetic regimens represent modern techniques for neurosurgical anaesthesia. Nevertheless, there are potential differences related to their activity on the cerebrovascular system. The magnitude of such difference is not completely known. METHODS: In total 40 patients, treated for spinal or maxillo-facial disorders, were randomly allocated to either i.v. propofol-remifentanil or inhalational sevoflurane anaesthesia. Transcranial Doppler was used to assess changes in cerebral blood flow velocity, carbon dioxide reactivity, cerebral autoregulation and the bispectral index to assess the depth of anaesthesia. RESULTS: Time-averaged mean flow velocity (MFV) was significantly reduced after induction of anaesthesia in both sevoflurane and propofol-remifentanil groups (P<0.001). At deeper levels of anaesthesia, MFV increased in the sevoflurane group, suggesting an uncoupling flow/metabolism, whereas it was further reduced in the propofol-remifentanil group (P<0.001). Indices of cerebral autoregulation were reduced in patients with high-dose sevoflurane whereas autoregulation was preserved in patients anaesthetized with propofol-remifentanil (P<0.001). Higher CO(2) concentrations impaired cerebral autoregulation in the sevoflurane group but not in patients anaesthetized with propofol-remifentanil. CONCLUSIONS: Propofol-remifentanil anaesthesia induced a dose-dependent low-flow state with preserved cerebral autoregulation, whereas sevoflurane at high doses provided a certain degree of luxury perfusion.

Adult↗
PubMed2006

The importance of predicting the prognosis in patients with hepatopulmonary syndrome: a simple scoring system.

Hepatopulmonary syndrome (HPS) is a pulmonary vascular disorder, complicating hepatic diseases, and is responsible for an increased morbidity and mortality among patients awaiting liver transplantation. Nowadays, it is recognized as an independent risk factor for death in this patient population. The severity of hypoxemia and the advanced stage of the liver dysfunction are determinants for the prognosis. Therefore, the possibility to be successful, thus improving survival, consists of addressing HPS at an earlier stage, giving more attention to moderate evidences of this pathology instead of the severe ones. On the basis of scientific evidence, we suggest a simple scoring system to predict prognosis among patients with HPS, founded on the integration of two main factors: the severity of hepatic disease, expressed as class of Child-Pugh, and the severity of the hypoxemia. This model of prognostic evaluation has the objective of estimating the additional risk of these patients, thereby avoiding a deleterious underestimate of risk and an arbitrariness of management.

Hepatopulmonary Syndrome↗
PubMed2006

Significance of hypoxemia screening in candidates for liver transplantation: our experience.

Hepatopulmonary syndrome (HPS) is recognized as one of the causes of hypoxemia in patients with chronic liver disease. This complication is responsible for increased mortality and increased perioperative risk in liver transplantation candidates. Recent data from the literature suggest extending the screening for HPS to all candidates for liver transplantation. The aim of this retrospective study was to evaluate the incidence of hypoxemia among a population of patients awaiting liver transplantation. Using pulse oximetry as a screening tool for hypoxemia, 39 of 198 patients (20%) were hypoxemic. The results of this study confirmed the importance of screening for hypoxemia among patients awaiting liver transplantation. In these patients, a more accurate evaluation of respiratory function should be performed to confirm or exclude the diagnosis of HPS.

Humans↗
PubMed2006

Effect of tramadol on Bispectral Index during intravenous anaesthesia with propofol and remifentanil.

The aim of this study was to investigate the effects of tramadol on the Bispectral Index (BIS) during total intravenous propofol-remifentanil anaesthesia. Forty-four adult ASA Physical status I-II patients, scheduled for elective general surgical procedures were included in a prospective observational randomized study. Doses for anaesthetics and opioids were adjusted to keep the BIS value at 50 +/- 5. After 20 minutes of stable anaesthesia, the subjects were randomly allocated to receive intravenous saline (control group) or tramadol 1.5 mg/kg (tramadol group). BIS values, mean arterial pressure, and heart rate were recorded every five minutes for 20 minutes. Mean BIS values after tramadol administration were not significantly different from those following saline, throughout the observation period (P > 0.05). There were no patients in whom BIS values were more than 60 or who presented explicit recall of events under anaesthesia. There were no significant changes in mean arterial pressure, SpO2, or heart rate (P > 0.05). The results indicate that the administration of tramadol during stable total intravenous anaesthesia with propofol-remifentanil does not affect BIS values. The clinical relevance is that tramadol can be safely administered pre- and intraoperatively as pre-emptive or preventive analgesia without modification of the depth of anaesthesia.

Aged↗
PubMed2005

Tramadol does not modify the Bispectral Index during anaesthesia with sevoflurane and remifentanil.

BACKGROUND: The aim of this study was to investigate the effects of tramadol administered with ketorolac on the Bispectral Index (BIS) during anaesthesia with sevoflurane and remifentanil. METHODS: Forty-six adult patients, ASA I-III, scheduled for elective minor surgical procedures were studied. Patients were premedicated with remifentanil infusion 0.4 microg kg(-1) min(-1) and anaesthesia was induced 4-5 min later with propofol 1.5 mg kg(-1) and maintained with air-oxygen (FI(O(2)) 0.4), remifentanil 0.1-0.15 microg kg(-1) min(-1) and sevoflurane, adjusted to keep the BIS between 40 and 50. After 20 min of stable anaesthesia, the subjects were allocated randomly to receive i.v. tramadol 1.5 mg kg(-1) and i.v. ketorolac 0.3 mg kg(-1) (tramadol group) or saline (control group). BIS values, mean arterial pressure, heart rate and end-tidal carbon dioxide were recorded every 5 min for 20 min. RESULTS: Mean BIS values after tramadol administration were not significantly different from those recorded in patients receiving saline throughout the period of observation. There were no patients who presented explicit recall of events under anaesthesia. No significant changes in mean arterial pressure, heart rate and end-tidal carbon dioxide were noted after tramadol injection. CONCLUSION: Tramadol, given with ketorolac to prevent postoperative pain, during anaesthesia maintained with sevoflurane and remifentanil at BIS between 40 and 50, does not modify the BIS value.

Adult↗
PubMed2005

Fatal exacerbation of peripheral neuropathy during lamivudine therapy: evidence for iatrogenic mitochondrial damage.

A 57-year-old man with mild neuropathy who was positive for hepatitis B and C viruses was treated with lamivudine 300 mg.day(-1). After 3 months he presented with dysphonia and progressive muscle weakness. Subsequently, he developed tetraparesis followed by acute respiratory failure requiring mechanical ventilation, which was complicated by sudden cardiac arrest. After lamivudine was stopped, the neuropathy improved and respiratory capacity improved. Unfortunately, the patient died suddenly in spite of haemodynamic, ventilatory and metabolic support. Electrophysiological studies showed evidence of a sensory-motor axonal neuropathy. Nerve biopsy, muscle biopsy, biochemistry and mitochondrial DNA molecular genetics suggested possible widespread iatrogenic mitochondrial damage. Mitochondrial DNA dysfunction could be a potential cause of the sudden cardiac arrest. Stopping lamivudine treatment sooner after the onset of peripheral neuropathy or its exacerbation is important as continued therapy could lead to acute respiratory failure requiring mechanical ventilation and intensive care unit admission.

Fatal Outcome↗
PubMed2004

Acute motor axonal polyneuropathy after a cisatracurium infusion and concomitant corticosteroid therapy.

A 40-yr-old male was admitted to the intensive care unit following blunt chest trauma. He had multiple rib fractures, bilateral pneumothoraces, and acute respiratory failure requiring mechanical ventilation. Sedation was achieved with midazolam and morphine, and later with propofol. The patient was paralysed with a continuous infusion of cisatracurium 1.42-5.75 micro g kg(-1) min(-1). Methylprednisolone 125 mg i.v. every 12 h was also started. After discontinuation of the cisatracurium infusion 7 days later, the patient manifested a flaccid quadriplegia with absence of deep-tendon reflexes. No sensory deficits were observed. Electromyography (EMG), repetitive nerve stimulation testing, and single fibre EMG (SFEMG) were performed at regular intervals after stopping cisatracurium. Clinical symptoms and electrophysiological examinations supported the diagnosis of acute motor axonal polyneuropathy related to concomitant administration of cisatracurium and corticosteroid therapy.

Acute Disease↗
PubMed2004

Hepatopulmonary syndrome: a concern for the anesthetist? Pre-operative evaluation of hypoxemic patients with liver disease.

Liver cirrhosis and other chronic hepatic diseases are followed in a subset of affected patients by gas exchange abnormalities resulting from a syndrome called hepatopulmonary syndrome (HPS). The structural basis of this clinical entity is an alteration of pulmonary vasculature resulting in abnormal vasodilatation and mismatching of ventilation and perfusion of the lung. Dilatation of the capillary bed near the gas exchange area is the most important factor implicated; it precludes O2 molecules diffusing to the centrum of the dilated vessels to oxygenate venous blood. Contrast (microbubbles) echocardiography and lung perfusion scan are, respectively, the screening tests with the highest sensitivity and specificity for HPS diagnosis. Because of the high morbidity and mortality of HPS, clinicians have been trying to understand the pathophysiology of pulmonary vasodilatation in the hope that the process can be reversed pharmacologically or surgically. An imbalance between production and clearance of vasoactive circulating substances has been implicated in the pathogenesis of HPS with glucagon and nitric oxide among the principal responsible factors. To date various molecules have been implicated for therapy but without definitive positive results. Liver transplantation remains the only real therapy for HPS, and resolution of gas exchange defects outlines the possible functional reversible nature of vascular abnormalities of this syndrome. The need to perform surgery under general anesthesia for hepatic and extrahepatic procedures in patients with HPS is followed by an increased peri-operative risk. The authors emphasize the role of pre-operative clinical evaluation for proper patient management during the peri-operative period.

Anesthesia↗
PubMed2002

Laudanosine, an atracurium and cisatracurium metabolite.

Laudanosine is a metabolite of the neuromuscular-blocking drugs atracurium and cisatracurium with potentially toxic systemic effects. It crosses the blood-brain barrier and may cause excitement and seizure activity. Its interest in recent years has increased because of the recognized interaction with gamma-aminobutyric acid, opioid and nicotinic acetylcholine receptors. It has been shown to produce analgesia in animals. In the cardiovascular system, high plasma concentrations produce hypotension and bradycardia. In hepatic failure, its elimination half-life is prolonged but only moderate accumulation occurs in adults, whereas in infants and children plasma concentration are greater. In patients undergoing liver transplantation, laudanosine concentrations are increased during preanhepatic, anhepatic and postanhepatic stages. Patients with renal failure have higher plasma concentrations and a longer mean elimination half-life. In pregnancy, laudanosine crosses the placental barrier. The mean transplacental transfer is 14% of maternal blood concentrations. Except for prolonged administration of atracurium in intensive care units, laudanosine accumulation and related toxicity seem unlikely to be achieved in clinical practice. When cisatracurium is used, plasma concentrations of laudanosine are lower. Further studies are needed, especially around the interactions with gamma-aminobutyric acid, opioid and nicotinic acetylcholine receptors.

Atracurium↗
PubMed2001

Oxidative stress causes nuclear factor-kappaB activation in acute hypovolemic hemorrhagic shock.

Nuclear Factor kappaB (NFkappaB) is an ubiquitous rapid response transcription factor involved in inflammatory reactions and exerts its action by expressing cytokines, chemokines, and cell adhesion molecules. We investigated the role of NF-kappaB in acute hypovolemic hemorrhagic (Hem) shock. Hem shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter over a period of 20 min (bleeding period) until mean arterial blood pressure (MAP) fell and stabilized within the range of 20-30 mmHg. Hemorrhagic shocked rats died in 26.3 +/- 2.1 min following the discontinuance of bleeding, experienced a marked hypotension (mean arterial blood pressure = 20-30 mmHg) and had enhanced plasma levels of Tumor Necrosis Factor-alpha (200 +/- 15 pg/ml, 20 min after the end of bleeding). Furthermore, aortas taken 20 min after bleeding from hemorrhagic shocked rats showed a marked hypo-reactivity to phenylephrine (PE; 1nM to 10 microM) compared with aortas harvested from sham shocked rats. Hem shocked rats also had increased levels of TNF-alpha mRNA in the liver (15-20 min after the end of bleeding) and enhanced plasma levels of 2,5-dihydroxybenzoic acid (2,5-DHBA; 6 +/- 2.2 microm), 2,3-dihydroxybenzoic acid (2,3-DHBA; 13 +/- 2.1 microm), both studied to evaluate OH(*) production. Electrophoretic mobility shift assay showed that liver NF-kappaB binding activity increased in the nucleus 10 min after the end of hemorrhage and remained elevated until the death of animals. Western blot analysis suggested that the levels of inhibitory IkappaBalpha protein in the cytoplasm became decreased at 5 min after the end of bleeding. IRFI-042, a vitamin E analogue (20 mg/kg intraperitoneally 2 min after the end of bleeding), inhibited the loss of IkappaBalpha protein from the cytoplasm and blunted the increase in NF-kappaB binding activity. Furthermore IRFI-042 increased survival time (117.8 +/- 6.51 min; p <.01) and survival rate (vehicle = 0% and IRFI-042 = 80%, at 120 min after the end of bleeding), reverted the marked hypotension, decreased liver mRNA for TNF-alpha, reduced plasma TNF-alpha (21 +/- 4.3 pg/ml), and restored to control values the hypo-reactivity to PE. Our results suggest that acute blood loss (50% of the estimated total blood volume over a period of 20 min) causes early activation of NF-kappaB, likely through an increased production of reactive oxygen species. This experiment indicates that NF-kappaB-triggered inflammatory cascade becomes early activated during acute hemorrhage even in the absence of resuscitation procedures.

Animals↗
PubMed2001

Nuclear factor-kappaB as a target of cyclosporin in acute hypovolemic hemorrhagic shock.

BACKGROUND: Cyclosporin is an immunosuppressive drug that blocks Nuclear Factor kappaB (NF-kappaB) activation. We investigated the role of NF-kappaB in acute hypovolemic hemorrhagic (Hem) shock and the effects of cyclosporin in this model of experimental shock. METHODS: Hem shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter over a period of 20 min (bleeding period) until mean arterial blood pressure (MAP) fell and stabilized within the range of 20-30 mmHg. Two minutes after bleeding cessation, animals received intravenously cyclosporin (1 mg kg(-1)) or its vehicle. Survival rate and survival time were evaluated for 120 min after bleeding was discontinued. Plasma TNF-alpha levels were investigated at different time points after bleeding cessation. Moreover we investigated levels of TNF-alpha mRNA in the liver, vascular reactivity, liver NF-kappaB binding activity and levels of the inhibitory protein IkappaBalpha in the cytoplasm. RESULTS: Hemorrhagic shocked rats died in 27+/-6 min following the cessation of bleeding, experienced a marked hypotension (mean arterial blood pressure=20-30 mmHg) and had enhanced plasma levels of Tumor Necrosis Factor-alpha (208+/-22 pg ml(-1), 20 min after the end of bleeding). Furthermore, aortas taken 20 min after bleeding from hemorrhagic shocked rats showed a marked hypo-reactivity to phenylephrine (PE: 1 nM-10 microM) compared with aortas harvested from sham shocked rats. Hem shocked rats also had increased levels of TNF-alpha mRNA in the liver (15-20 min after the end of bleeding). Electrophoretic mobility shift assay showed that liver NF-kappaB binding activity increased in the nucleus 10 min after the end of hemorrhage and remained elevated until the death of animals. Western blot analysis suggested that the levels of inhibitory protein IkappaBalpha in the cytoplasm decreased at 5 min after the end of bleeding. Cyclosporin inhibited the loss of IkappaBalpha protein from the cytoplasm and prevented NF-kappaB binding activity in the nucleus. Furthermore, cyclosporin increased survival time (118+/-7 min; P<0.01) and survival rate (vehicle=0% and cyclosporin=80%, at 120 min after the end of bleeding), reverted the marked hypotension, decreased liver mRNA for TNF-alpha, reduced plasma TNF-alpha (28+/-7 pg ml(-1)), and restored to control values the hypo-reactivity to PE. CONCLUSIONS: Our results suggest that acute blood loss (50% of the estimated total blood volume over a period of 20 min) causes early activation of NF-kappaB which triggers an inflammatory cascade leading to a fatal outcome. Cyclosporin blocks NF-kappaB activation and protects against hypovolemic hemorrhagic shock.

Animals↗