The role of acetaminophen against free hemoglobin effects in septic febrile patient, assessed by the analysis of microcirculation, tissue perfusion, and endotelial damage markers: a perspective observational study Lara Pantaleoni Abstract Sepsis was defined as a clinical syndrome determined by a deregulated immune response induced by an infectious insult. Epidemiologically, it is a relevant phenomenon, which has 1.4 millon of cases in the European Union each year, and which is caracterised by high mortality. Among the physiopatologic factors which this clinical condition is based on, microcirculatory disfuncion, associated to severe oxidative stress, represents a fundamental part. The presence of free circulating hemoglobin was linked to an increase of oxidative stress in sepsis, which could be considered responsible for a further worsening of the microcirculation of the septic patients, but also of their clinical situation. The purpose of the study “Free circulating hemoglobin and microcirculation after adminstration of acetaminophen in septic febrile patient”, developed according to the previous works, has been to assess if the antioxidant action of paracetamol can reduce oxidative stress caused by free circulating hemoglobin during sepsis, and therefore if it can improve microcirculation. The study, lasted from July 2017 until August 2018, took place upon the Anaesthesia and General, Respiratory and Major Trauma Resuscitation Clinic of the University Hospital of Ancona, and it involved 50 patients with diagnosis of sepsis and with detectable levels of free hemoglobin. The main objective was the assessment of an improvement of the microcirculatory parameter Perfused Vessel Density for small vessels (PVDs) after standardised administration of paracetamol according to clinical indication. Among the secondary objectives, there were the improvement of post hypoxic tissue reactivity with NIRS tecnology (Near Infra Red Spectroscopy) and the analysis of the trend of endothelial damage markers, both assessed before and after drug administration. The statistically relevant results showed that the main objective was satisfied, as the secondary one regarding NIRS analysis. Laboratoristic analysis showed apparently conflicting results, partly non statistically relevant, which require future further investigations. The observed improvement of the microcirculation, as the increase of post hypoxic tissue reactivity observed at the NIRS test after paracetamol administration, didn’t seem only caused by the drug’s vasodilatatory action , because there wasn't registered a statisticallly significant increase of individual parameters of Total Vessel Density (TVD). This result led to the hypothesis that the antioxidant action of acetaminophen can have a role in this effect. This result was likely to confirm the hypothesis which the study was based on, which suggested that the improvement of microcirculation, assessed in presence of sepsis and of detectable levels of free hemoglobin, could be linked to the acetaminophen action against oxidative stress caused by free hemoglobin. This seemed to confirm previous researches. Future further researches on this theory are anyway adviced.
Ruolo del paracetamolo contro gli effetti dell’emoglobina libera nel paziente settico febbrile, indagato mediante analisi del microcircolo, della perfusione tissutale e dei marcatori di danno endoteliale: studio prospettico osservazionale Lara Pantaleoni Abstract La sepsi è stata definita come una sindrome clinica determinata da una risposta immunitaria deregolata scatenata da un insulto infettivo, nonché come un fenomeno epidemiologicamente rilevante (1,4 milioni di casi all’anno nell’Unione Europea) e caratterizzato da elevata mortalità. Tra i fattori fisiopatologici che appartengono a tale quadro clinico, la disfunzione del microcircolo, associata ad una situazione di importante stress ossidativo, rappresenta una componente fondamentale. La presenza di emoglobina libera circolante è stata correlata ad un aumento dello stress ossidativo in corso di sepsi, che potrebbe essere responsabile di un ulteriore peggioramento del quadro microcircolatorio del paziente settico e dunque anche della sua condizione clinica. Il proposito dello studio “Emoglobina libera circolante e microcircolo dopo somministrazione di paracetamolo nel paziente settico febbrile”, elaborato anche sulla base dei risultati di precedenti lavori, è stato quello di indagare se il potere antiossidante del paracetamolo sia in grado di ridurre lo stress ossidativo causato dall’emoglobina libera circolante in corso di sepsi, e quindi di determinare un miglioramento del microcircolo. Lo studio si è svolto tra luglio 2017 ed agosto 2018 presso la Clinica di Anestesia e Rianimazione Generale, Respiratoria e del Trauma Maggiore dell’Azienda Ospedaliero-Universitaria Ospedali Riuniti di Ancona, ed ha coinvolto 50 pazienti con sepsi e con livelli di emoglobina libera rilevabili. L’obiettivo primario consisteva nella rilevazione di un miglioramento del parametro microcircolatoro Perfused Vessel Density for small vessels (PVDs) dopo somministrazione standardizzata di paracetamolo su indicazione clinica. Tra gli obiettivi secondari, vi erano il miglioramento della reattività tissutale post-ipossica, indagato mediante tecnica NIRS (Near-InfraRed Spectroscopy) e l’analisi dell’andamento dei marcatori di danno endoteliale, entrambi indagati prima e dopo la somministrazione del farmaco. I risultati statisticamente significativi ottenuti indicano che l’obiettivo primario è stato soddisfatto, come analogamente quello secondario relativo all’analisi con NIRS. L’analisi di laboratorio ha mostrato esiti in parte apparentemente discordanti, in parte non statisticamente significativi, che dovrebbero essere ulteriormente indagati in futuro Il miglioramento del microcircolo riscontrato, concorde con l’aumento della reattività tissutale post ipossica constatato al test con NIRS dopo somministrazione di paracetamolo, non sembra essere solamente imputabile all’azione vasodilatatoria del farmaco, poiché non è emerso un incremento statisticamente significativo dei parametri indicativi di densità vascolare totale (TVD, Total Vessel Density for total and small vessels), ma è ipotizzabile che l’azione antiossidante del paracetamolo abbia un ruolo in questo effetto. Tale esito sembra dunque confermare l’ipotesi alla base dello studio, secondo la quale il miglioramento microcircolatorio individuato in presenza di sepsi e di livelli rilevabili di emoglobina libera circolante sia attribuibile all’azione del paracetamolo contro lo stress ossidativo causato dall’emoglobina libera. Ciò appare inoltre in linea con i risultati delle ricerche precedenti. Si auspicano tuttavia future ricerche di conferma o approfondimento nei confronti di tale teoria.
Ruolo del paracetamolo contro gli effetti dell’emoglobina libera nel paziente settico febbrile, indagato mediante analisi del microcircolo, della perfusione tissutale e dei marcatori di danno endoteliale: studio prospettico osservazionale
PANTALEONI, LARA
2019/2020
Abstract
The role of acetaminophen against free hemoglobin effects in septic febrile patient, assessed by the analysis of microcirculation, tissue perfusion, and endotelial damage markers: a perspective observational study Lara Pantaleoni Abstract Sepsis was defined as a clinical syndrome determined by a deregulated immune response induced by an infectious insult. Epidemiologically, it is a relevant phenomenon, which has 1.4 millon of cases in the European Union each year, and which is caracterised by high mortality. Among the physiopatologic factors which this clinical condition is based on, microcirculatory disfuncion, associated to severe oxidative stress, represents a fundamental part. The presence of free circulating hemoglobin was linked to an increase of oxidative stress in sepsis, which could be considered responsible for a further worsening of the microcirculation of the septic patients, but also of their clinical situation. The purpose of the study “Free circulating hemoglobin and microcirculation after adminstration of acetaminophen in septic febrile patient”, developed according to the previous works, has been to assess if the antioxidant action of paracetamol can reduce oxidative stress caused by free circulating hemoglobin during sepsis, and therefore if it can improve microcirculation. The study, lasted from July 2017 until August 2018, took place upon the Anaesthesia and General, Respiratory and Major Trauma Resuscitation Clinic of the University Hospital of Ancona, and it involved 50 patients with diagnosis of sepsis and with detectable levels of free hemoglobin. The main objective was the assessment of an improvement of the microcirculatory parameter Perfused Vessel Density for small vessels (PVDs) after standardised administration of paracetamol according to clinical indication. Among the secondary objectives, there were the improvement of post hypoxic tissue reactivity with NIRS tecnology (Near Infra Red Spectroscopy) and the analysis of the trend of endothelial damage markers, both assessed before and after drug administration. The statistically relevant results showed that the main objective was satisfied, as the secondary one regarding NIRS analysis. Laboratoristic analysis showed apparently conflicting results, partly non statistically relevant, which require future further investigations. The observed improvement of the microcirculation, as the increase of post hypoxic tissue reactivity observed at the NIRS test after paracetamol administration, didn’t seem only caused by the drug’s vasodilatatory action , because there wasn't registered a statisticallly significant increase of individual parameters of Total Vessel Density (TVD). This result led to the hypothesis that the antioxidant action of acetaminophen can have a role in this effect. This result was likely to confirm the hypothesis which the study was based on, which suggested that the improvement of microcirculation, assessed in presence of sepsis and of detectable levels of free hemoglobin, could be linked to the acetaminophen action against oxidative stress caused by free hemoglobin. This seemed to confirm previous researches. Future further researches on this theory are anyway adviced.File | Dimensione | Formato | |
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Ruolo del paracetamolo contro gli effetti dell’emoglobina libera nel paziente settico febbrile, indagato mediante analisi del microcircolo.pdf
embargo fino al 21/06/2026
Descrizione: Ruolo del paracetamolo contro gli effetti dell’emoglobina libera nel paziente settico febbrile, indagato mediante analisi del microcircolo,
della perfusione tissutale e dei marcatori di danno endoteliale: studio prospettico osservazionale
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1.69 MB | Adobe PDF |
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https://hdl.handle.net/20.500.12075/2072