Studio sperimentale di fase IV monocentrico randomizzato in doppio cieco di confronto tra ketamina e remifentanil per l'analgosedazione di pazienti ventilati invasivamente in terapia intensiva

Although in the literature there are many studies comparing the efficacy of different regimens of analgo-sedation in the Intensive Care Unit (ICU), more studies are needed to directly compare ketamine versus remifentanil in terms of its ability to effectively sedate and control pain in mechanically ventilated critically-ill patients. Remifentanil, which belongs to the opioid family of drugs, is routinely used in continuous infusion in the operating room (OR) and ICU. Ketamine, a NMDA-receptor antagonist, is used more often in the OR to provide pain relief while its use is not widespread in the ICU setting as remifentanil. Ketamine is mainly given as a bolus injection, while there are no data focusing on ketamine in continuous infusion/Targeted Controlled Infusion (TCI).It does not belong to the opioid family of drugs and thus does not act mainly on the mu-receptors, its action is free of many undesired effects that are typical of prolonged opioid administration, such as: cardiovascular depression, intestinal paralysis, nausea, pruritus, tolerance and withdrawal syndromes. Moreover ketamine may have a role in decreasing the incidence of delirium and depression after long periods of ICU stay. These are the reasons why we would like to investigate the effectiveness of ketamine in continuous infusion to provide at least the same quality level of analgosedation as another routinely used analgo-sedative drug - remifentanil - in mechanically ventilated critically ill patients. We expect ketamine not to be inferior to remifentanil in providing adequate sedation and analgesia. At the same time, we hope to show a decreased incidence of cardiovascular depression with a subsequent reduced need for use of cathecolamines, lower rates of intestinal paralysis, nausea, pruritus, tolerance, withdrawal syndromes, delirium and depression in patients treated with ketamine in comparison to patients treated with remifentanil. To avoid adverse emergence reactions such as psychomotor agitation and visual and tactile disturbances when ketamine or remifentanil are discontinued in our protocol we made sure that the administration of both drugs is simultaneous with that of propofol in continuous infusion at any time

A Persistent Left-Sided Superior Vena Cava With Agenesis of the Right Superior Vena Cava in a Patient Who Underwent Liver Transplantation: A Case Report

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Veno-Venous ECMO: An Alternative Strategy for Acute Respiratory Failure After High-Voltage Electrocution. The Utility of Point-of-Care Tests

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Narrow band imaging in the intra-operative definition of resection margins in oral cavity and oropharyngeal cancer

Objectives: In oncological surgery, a three-dimensional resection 1.5\u20132 cm from the gross tumour edge is currently considered appropriate, and the status of resection margins is the most reliable indicator of radicality. Awareness of \u2018\u2018field cancerization\u2019\u2019 calls for a re-evaluation of the benchmarks of tumour resection; however, its identification is not simple because the dysplastic areas may be far from the main lesion and difficult to recognize macroscopically. New technologies such as narrow band imaging (NBI) could improve the detection of neoplastic and pre-neoplastic areas, ensuring more precise resections. The main purpose of this study was to investigate the value of NBI in detecting pre-cancerous areas and/or cancer around the tumour bulk intra-operatively, to achieve adequate resection of the tumour. Materials and Methods: The resection margins of 8 oral cavity and 8 oropharyngeal cancers were first drawn by macroscopic evaluation and then re-defined using NBI. Resections were performed following the NBI-drawing if extemporaneous histological examinations of the NBI-defined enlargements were positive for dysplasia or cancer. The number of clear margins was evaluated. Results: Resections margins were free of tumour or dysplasia at extemporaneous examination; on definitive histology, two patients had a margin positive for cancer and dysplasia, respectively. Among the NBI-defined enlargements, 25% were positive for dysplasia and 75% for cancer. The sensitivity, specificity, positive and negative predictive values were 100%, 88.9%, 100% and 87.5%, respectively. Conclusion: The method we propose could be useful for obtaining free surgical margins and reducing the potential development of tumour foci resulting from incomplete resection

Topical Steroids in Rhinosinusitis and Intraoperative Bleeding: More Harm Than Good?

The aim of this study was to assess whether the chronic preoperative administration of intranasal corticosteroids (INCs) in chronic rhinosinusitis with/without nasal polyposis (CRSwNP/CRSsNP, respectively) could significantly influence bleeding during functional endoscopic sinus surgery (FESS). We prospectively enrolled 109 patients (56 CRSwNP and 53 CRSsNP) candidate for FESS who underwent clinical evaluation and anamnestic data collection. They were allocated to 2 groups depending on whether or not they were chronic INC users, as declared at their first medical evaluation: chronic "INC users" represented the treated group, while "INC nonusers" formed the control group. Lund-Mackay and American Society of Anesthesiology (ASA) scores, blood loss expressed both in milliliters and using the Boezaart scale, operation time in minutes, pre- and postoperative 22-item Sino Nasal Outcome Scores (SNOT-22) were collected. Each sample underwent histopathological evaluation. The results showed that anamnestic information, Lund-Mackay, and SNOT-22 scores were similar between the 2 groups ( P > .05). The average blood loss expressed in milliliters and operative time were slightly, but not significantly, higher in the INC user group, while the Boezaart scores proved significantly higher in the INC users ( P = .038). No differences emerged between CRSwNP and CRSsNP within each group in terms of bleeding. The pathologist described common features in the majority (78%) of INC group samples: ectatic venules embedded in a fibrous stroma and hypertrophy of the arterial muscular layer. In our experience, despite the presence of NP, chronic preoperative administration of INCs was associated with increased intraoperative bleeding according the Boezaart scale although objective recordings of blood loss were not statistically different between the INC users and nonusers

Frozen sections and complete resection in oral cancer surgery

OBJECTIVES: Although the reliability of frozen sections for the intraoperative assessment of complete tumour excision has been established, the best location for collection and the impact of the type of sampling are still debated. We retrospectively investigated the reliability of frozen sections when collected from the surgical bed as tissue strips representative of the whole superficial margin and as a bowl of tissue underlying the resection site for deep margin, and the possibility of relying on frozen section negativity to consider resections complete. MATERIALS AND METHODS: Frozen section reliability was calculated by comparing histology before and after formalin embedding and then categorised by sampling type, in 182 patients undergoing transoral resection of oral cancer. RESULTS: Comparing frozen and permanent histology, sensitivity, specificity and accuracy were 69%, 98% and 96%, respectively; categorisation by sampling type failed to produce statistically significant differences. Based on frozen section negativity after formalin embedding, complete resections were obtained in 91.7% of patients with multiple-strip and bowl frozen sections. CONCLUSION: Frozen sections collected as tissue strips and bowl are as reliable as point sampling in the intraoperative guidance of surgical resections. They effectively provide for margin enlargement, thereby increasing the surgeon's confidence that negative margins are clear

Outcomes of COVID-19 patients intubated after failure of non-invasive ventilation: a multicenter observational study

The efficacy of non-invasive ventilation (NIV) in acute respiratory failure secondary to SARS-CoV-2 infection remains controversial. Current literature mainly examined efficacy, safety and potential predictors of NIV failure provided out of the intensive care unit (ICU). On the contrary, the outcomes of ICU patients, intubated after NIV failure, remain to be explored. The aims of the present study are: (1) investigating in-hospital mortality in coronavirus disease 2019 (COVID-19) ICU patients receiving endotracheal intubation after NIV failure and (2) assessing whether the length of NIV application affects patient survival. This observational multicenter study included all consecutive COVID-19 adult patients, admitted into the twenty-five ICUs of the COVID-19 VENETO ICU network (February-April 2020), who underwent endotracheal intubation after NIV failure. Among the 704 patients admitted to ICU during the study period, 280 (40%) presented the inclusion criteria and were enrolled. The median age was 69 [60-76] years; 219 patients (78%) were male. In-hospital mortality was 43%. Only the length of NIV application before ICU admission (OR 2.03 (95% CI 1.06-4.98), p = 0.03) and age (OR 1.18 (95% CI 1.04-1.33), p < 0.01) were identified as independent risk factors of in-hospital mortality; whilst the length of NIV after ICU admission did not affect patient outcome. In-hospital mortality of ICU patients intubated after NIV failure was 43%. Days on NIV before ICU admission and age were assessed to be potential risk factors of greater in-hospital mortality

Erector Spinae Plane Block and Chronic Pain: An Updated Review and Possible Future Directions

: Chronic pain is a common, pervasive, and often disabling medical condition that affects millions of people worldwide. According to the Global Burden of Disease survey, painful chronic conditions are causing the largest numbers of years lived with disability worldwide. In America, more than one in five adults experiences chronic pain. Erector spinae plane block is a novel regional anesthesia technique used to provide analgesia with multiple possible uses and a relatively low learning curve and complication rate. Here, we review the erector spinae plane block rationale, mechanism of action and possible complications, and discuss its potential use for chronic pain with possible future directions for research

Static compliance and driving pressure are associated with ICU mortality in intubated COVID-19 ARDS

Background Pathophysiological features of coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) were indicated to be somewhat different from those described in nonCOVID-19 ARDS, because of relatively preserved compliance of the respiratory system despite marked hypoxemia. We aim ascertaining whether respiratory system static compliance (Crs), driving pressure (DP), and tidal volume normalized for ideal body weight (VT/kg IBW) at the 1st day of controlled mechanical ventilation are associated with intensive care unit (ICU) mortality in COVID-19 ARDS. Methods Observational multicenter cohort study. All consecutive COVID-19 adult patients admitted to 25 ICUs belonging to the COVID-19 VENETO ICU network (February 28th-April 28th, 2020), who received controlled mechanical ventilation, were screened. Only patients fulfilling ARDS criteria and with complete records of Crs, DP and VT/kg IBW within the 1st day of controlled mechanical ventilation were included. Crs, DP and VT/kg IBW were collected in sedated, paralyzed and supine patients. Results A total of 704 COVID-19 patients were screened and 241 enrolled. Seventy-one patients (29%) died in ICU. The logistic regression analysis showed that: (1) Crs was not linearly associated with ICU mortality (p value for nonlinearity = 0.01), with a greater risk of death for values < 48 ml/cmH(2)O; (2) the association between DP and ICU mortality was linear (p value for nonlinearity = 0.68), and increasing DP from 10 to 14 cmH(2)O caused significant higher odds of in-ICU death (OR 1.45, 95% CI 1.06-1.99); (3) VT/kg IBW was not associated with a significant increase of the risk of death (OR 0.92, 95% CI 0.55-1.52). Multivariable analysis confirmed these findings. Conclusions Crs < 48 ml/cmH(2)O was associated with ICU mortality, while DP was linearly associated with mortality. DP should be kept as low as possible, even in the case of relatively preserved Crs, irrespective of VT/kg IBW, to reduce the risk of death

Studio sperimentale di fase IV monocentrico randomizzato in doppio cieco di confronto tra ketamina e remifentanil per l'analgosedazione di pazienti ventilati invasivamente in terapia intensiva

Although in the literature there are many studies comparing the efficacy of different regimens of analgo-sedation in the Intensive Care Unit (ICU), more studies are needed to directly compare ketamine versus remifentanil in terms of its ability to effectively sedate and control pain in mechanically ventilated critically-ill patients. Remifentanil, which belongs to the opioid family of drugs, is routinely used in continuous infusion in the operating room (OR) and ICU. Ketamine, a NMDA-receptor antagonist, is used more often in the OR to provide pain relief while its use is not widespread in the ICU setting as remifentanil. Ketamine is mainly given as a bolus injection, while there are no data focusing on ketamine in continuous infusion/Targeted Controlled Infusion (TCI).It does not belong to the opioid family of drugs and thus does not act mainly on the mu-receptors, its action is free of many undesired effects that are typical of prolonged opioid administration, such as: cardiovascular depression, intestinal paralysis, nausea, pruritus, tolerance and withdrawal syndromes. Moreover ketamine may have a role in decreasing the incidence of delirium and depression after long periods of ICU stay. These are the reasons why we would like to investigate the effectiveness of ketamine in continuous infusion to provide at least the same quality level of analgosedation as another routinely used analgo-sedative drug - remifentanil - in mechanically ventilated critically ill patients. We expect ketamine not to be inferior to remifentanil in providing adequate sedation and analgesia. At the same time, we hope to show a decreased incidence of cardiovascular depression with a subsequent reduced need for use of cathecolamines, lower rates of intestinal paralysis, nausea, pruritus, tolerance, withdrawal syndromes, delirium and depression in patients treated with ketamine in comparison to patients treated with remifentanil. To avoid adverse emergence reactions such as psychomotor agitation and visual and tactile disturbances when ketamine or remifentanil are discontinued in our protocol we made sure that the administration of both drugs is simultaneous with that of propofol in continuous infusion at any time.Sebbene in letteratura ci siano molti studi di confronto tra l'efficacia di differenti regimi analgosedativi in ambito intensivistico e durante procedure chirurgiche in parte complesse, al momento non c'è alcun lavoro focalizzato sul paragone diretto tra ketamina e remifentanil, somministrate in infusione continua e in associazione a propofol, in termini di abilità  nel garantire un'efficace sedazione e controllo del dolore in pazienti critici, ricoverati in TI e ventilati meccanicamente per più di 24h. Quando la ketamina viene utilizzata in ICU, la somministrazione è in genere a boli e nulli sono i lavori basati sul suo impiego a "lungo-termine" in associazione a propofol. Alcuni studi preliminari hanno dimostrato che la ketamina gioca anche un ruolo importante nella riduzione dell'incidenza di delirio e depressione dopo lunghi periodi di ricovero in ambito ospedaliero, o se somministrata prima dell'inizio di un intervento di chirurgia maggiore negli adulti, soprattutto di età > 65 anni, e durante chirurgia pediatrica. Abbiamo proposto quindi uno studio clinico sperimentale, monocentrico, randomizzato, basato sull'arruolamento di pazienti ricoverati in ISTAR 1 e 2, due rianimazioni polivalenti (direttore: Prof. C. Ori) dell'Azienda Ospedaliera di Padova. L'attività di ricerca si è basa su un confronto diretto tra due protocolli analgo-sedativi differenti (ketamina+propofol in infusione continua vs remifentanil+propofol) in pazienti critici ventilati meccanicamente per un periodo massimo di 7 giorni e minimo di 36 ore. Nello specifico gli obiettivi di studio sono stati di indagare ed approfondire: - l'abilità del farmaco in infusione continua di raggiungere e mantenere un valore target di RASS tra -2 and 0 durante i primi 7 gg (valore atteso: stesso livello di efficacia di ketamina vs remifentanil o di non inferiorità); - l'incidenza di delirio nei 7 gg e a lungo termine (valore atteso: superiorità di ketamina); - monitoraggio comfort o sofferenza del paziente durante ventilazione meccanica (tramite Critical Care Pain Observational Tool, CCPOT) - incidenza di delirium a breve termine (nei primi 3 gg dopo l'estubazione) (ICU-Confusion Assessment Method, ICU-CAM) - incidenza di deficit cognitivo/delirium alla dimissione dalla TI (Mini Mental Status Exam-test, MMSE) - incidenza di tolleranza/iperalgesia durante i primi 7 gg o sindrome astinenziale - incidenza di depressione cardiovascolare durante i primi 7 gg - durata della ventilazione meccanica - durata della degenza in ICU e mortalità in ICU - tollerabilità della NE ed effetti avversi durante l'analgosedazione - incidenza depressione a 3mesi (Hospital Anxiety Depression Scale,HADS). I pazienti arruolati in questi anni di dottorato, rappresentanti il campione preliminare di uno studio assai più complesso e con una numerosità campionaria presunta molto superiore, sono stati 50 (33M e 17F) così suddivisi: - 23 (46%) pazienti arruolati nel braccio ketamina+propofol - 27 (54%) nel braccio remifentanil+propofol. A sua volta ciascun paziente è stato poi distinto in MEDICO, CHIRURGICO, TRAUMA, USTIONATO. Dall'analisi dei dati preliminari, è emerso che l'infusione continua di ketamina rappresenta una valida alternativa ai più comuni protocolli analgosedativi utilizzati nelle rianimazioni di tutto il mondo. La ketamina sembra avere capacità di mantenere un RASS target tra 0 e -2 (nei pazienti critici) sovrapponibile a remifentanil, con probabilità di eventi avversi pressoché identiche (circa 13% in entrambi i gruppi). Idem per quanto riguarda i dati che riguardano il dolore e il comfort paziente-ventilazione (valutazione realizzata tramite CCPOT). Buoni risultati sono stati ottenuti dall'uso dell'antagonista-NMDA nei pazienti con iniziale sostegno inotropo. Minor utilizzo di catecolamine ed instabilità emodinamica nei pazienti chirurgici, traumatizzati ed ustionati se trattati con ketamina vs remifentanil. Dati ancora incompleti sulle eventuali differenze di canalizzazione o tollerabilità alla nutrizione enterale tra i due protocolli. Per quanto riguarda i risultati sull'incidenza di delirium nei primi 3 giorni dopo l'estubazione, trend a favore dei pazienti trattati con ketamina (34% vs 44%) ma necessario approfondimento delle eventuali correlazioni con storia clinica, gravità, età, deficit cognitivo alla dimissione (MMSE) ed incidenza di ansia/depressione a lungo termine (HADS). Nello specifico per quanto riguarda il riscontro di delirium a breve termine, cioè entro i primi 3 giorni dopo l'estubazione, e alla dimissione dalla TI, ben 4 pazienti sono risultati positivi ad entrambi i test (2 per ketamina e 2 per remifentanil) ed avevano più di 65 anni. Per concludere tale risultato lascia presupporre una possibile correlazione tra insorgenza di delirium, età e declino cognitivo/funzionale nell'adulto