Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

Objective: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. Setting: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. Patients: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. Interventions: Endotracheal Intubation Adverse Events. Main variables of interests: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. Results: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. Conclusion: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. Clinical Trial registration: www.clinicaltrials.gov identifier: NCT04909476.

Objetivo: Pocos estudios han informado las implicaciones y los eventos adversos de realizar una intubación endotraqueal para pacientes críticos con COVID-19 ingresados ​​en unidades de cuidados intensivos. El objetivo del presente estudio fue determinar los eventos adversos relacionados con la intubación traqueal en pacientes con COVID-19, definidos como la aparición de inestabilidad hemodinámica, hipoxemia severa y paro cardíaco. Ámbito: Hospitales médicos de atención terciaria, estudio de doble centro realizado en el norte de Italia desde noviembre de 2020 hasta mayo de 2021. Pacientes: Pacientes adultos con prueba PCR SARS-CoV-2 positiva, ingresados por insuficiencia respiratoria y necesidad de manejo avanzado de vías aéreas invasivas. Intervenciones: Eventos adversos de la intubación endotraqueal. Principales variables de interés: El punto final primario fue determinar la ocurrencia de al menos 1 de los siguientes eventos dentro de los 30 minutos posteriores al inicio del procedimiento de intubación y describir los tipos de eventos adversos periintubación mayores. : hipoxemia severa definida como una saturación de oxígeno medida por pulsioximetría <80%; inestabilidad hemodinámica definida como PAS 65 mmHg registrada al menos una vez o PAS < 90 mmHg durante 30 minutos, nuevo requerimiento o aumento de vasopresores, bolo de líquidos > 15 mL/kg para mantener la presión arterial objetivo; paro cardiaco. Resultados: Entre 142 pacientes, el 73,94% experimentó al menos un evento periintubación adverso importante. El evento predominante fue la inestabilidad cardiovascular, observada en el 65,49% de todos los pacientes sometidos a intubación de urgencia, seguido de la hipoxemia severa (43,54%). El 2,82% de los pacientes tuvo un paro cardíaco. Conclusión: En este estudio de prácticas de intubación en pacientes críticos con COVID-19, los eventos adversos periintubación mayores fueron frecuentes. Registro de ensayos clínicos: www.clinicaltrials.gov identificador: NCT04909476.

A Delphi consensus statement of the Neuropathic Pain Special Interest Group of the Italian Neurological Society on pharmacoresistant neuropathic pain.

To improve patient care and help clinical research, the Neuropathic Pain Special Interest Group of the Italian Neurological Society appointed a task force to elaborate a consensus statement on pharmacoresistant neuropathic pain. The task force included 19 experts in neuropathic pain. These experts participated in a Delphi survey consisting of three consecutive rounds of questions and a face-to-face meeting, designed to achieve a consensus definition of pharmacoresistant neuropathic pain. In the three rounds of questions, the participants identified and described the main distinguishing features of pharmacoresistance. In the face-to-face meeting the participants discussed the clinical features determining pharmacoresistance. They finally agreed that neuropathic pain is pharmacoresistant when "the patient does not reach the 50% reduction of pain or an improvement of at least 2 points in the Patient Global Impression of Change, having used all drug classes indicated as first, second, or third line in the most recent and widely agreed international guidelines, for at least 1 month after titration to the highest tolerable dose." Our consensus statement might be useful for identifying eligible patients for invasive treatments, and selecting patients in pharmacological trials, thus improving patient care and helping clinical research.

Interference of confounding factors on the use of (1,3)-beta-D-glucan in the diagnosis of invasive candidiasis in the intensive care unit.

Invasive fungal infections (IFIs) are an increasing problem in intensive care units (ICUs), and conventional diagnostic methods are not always reliable or timely enough to deliver appropriate antimicrobial therapy. The dosage of fungal antigens in serum is a promising diagnostic technique, but several confounding factors, such as treatment with immunoglobulins (Ig), albumin, or antifungals, could interfere with the correct interpretation of the (1,3)-beta-D-glucan (BG) assay. This study assessed the reliability of the BG assay and the influence of timing and dosage of major confounding factors on circulating levels of IFI biomarkers. 267 ICU patients who underwent a BG assay were retrospectively studied. The timing and dosage of albumin, use of azole treatment, and infusions of intravenous IgG, red blood cells, concentrated platelets, and frozen plasma were analyzed to find possible correlations with the BG results. The sensitivity and specificity of the BG assay were calculated. The BG test in serum showed high sensitivity (82.9 %) but low specificity (56.7 %). The optimal cut-off for the test was 95.9 pg/mL. The mean BG level in proven invasive candidiasis was around 400 pg/mL. The only factor that was found to significantly confound (p < 0.05) the diagnostic performance of the BG assay was the administration of more than 30 g of albumin within 2 days prior to BG testing. The BG assay remains a useful diagnostic test in ICU patients and the levels of BG are useful in evaluating the positive predictive value of this biomarker. The only confounding factor in our study was the use of albumin.

Airways management in SARS-COV-2 acute respiratory failure: A prospective observational multi-center study.

OBJECTIVE: Few studies have reported the implications and adverse events of performing endotracheal intubation for critically ill COVID-19 patients admitted to intensive care units. The aim of the present study was to determine the adverse events related to tracheal intubation in COVID-19 patients, defined as the onset of hemodynamic instability, severe hypoxemia, and cardiac arrest. SETTING: Tertiary care medical hospitals, dual-centre study performed in Northern Italy from November 2020 to May 2021. PATIENTS: Adult patients with positive SARS-CoV-2 PCR test, admitted for respiratory failure and need of advanced invasive airways management. INTERVENTIONS: Endotracheal Intubation Adverse Events. MAIN VARIABLES OF INTERESTS: The primary endpoint was to determine the occurrence of at least 1 of the following events within 30 minutes from the start of the intubation procedure and to describe the types of major adverse peri-intubation events: severe hypoxemia defined as an oxygen saturation as measured by pulse-oximetry <80%; hemodynamic instability defined as a SBP 65 mmHg recoded at least once or SBP < 90 mmHg for 30 minutes, a new requirement or increase of vasopressors, fluid bolus >15 mL/kg to maintain the target blood pressure; cardiac arrest. RESULTS: Among 142 patients, 73.94% experienced at least one major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 65.49% of all patients undergoing emergency intubation, followed by severe hypoxemia (43.54%). 2.82% of the patients had a cardiac arrest. CONCLUSION: In this study of intubation practices in critically ill patients with COVID-19, major adverse peri-intubation events were frequent. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov identifier: NCT04909476.

Changing the paradigm in postherpetic neuralgia treatment: lidocaine 700 mg medicated plaster.

OBJECTIVE: Chronic pain is currently considered a disease state with biopsychosocial consequences and a negative impact on patients' quality of life (QoL). Pain from postherpetic neuralgia (PHN) can persist for months or years and is a prototypical example of chronic pain. We analyzed PHN as a model of chronic pain, including its effects on QoL and clinical aspects. We explored treatment options, focusing on the topical treatment with lidocaine 700 mg medicated plaster (LMP) and how this impacts PHN management. MATERIALS AND METHODS: This article is a narrative review of published studies. Preclinical and clinical studies were retrieved from literature through a search performed in PubMed/MEDLINE. RESULTS: To choose the appropriate treatment for chronic pains, such as PHN, not only efficacy but also tolerability, manageability, practicality, and compliance are important factors, especially in the long term. It is also important to set treatment expectations with the patients as total suppression of pain may be unrealistic, and a balance needs to be found between pain control and the minimization of adverse events. In this respect, LMP may be the best currently available treatment: it is easy to use, has low systemic absorption and thus a low risk for pharmacological interactions. Therefore, treatments can be personalized, and concomitant medications can be added, if needed. Recent data from a real-world study support this view by showing that LMP has superior effectiveness in reducing pain and improving the QoL compared to other commonly used systemic treatments and confirming its good tolerability profile that is mainly characterized by localized skin reactions. CONCLUSIONS: LMP is one of the best currently available treatment options for PHN patients balancing good efficacy with an excellent tolerability profile and can therefore be considered for use as a first-line treatment for PHN.

Acute nephrotoxicity of NSAID from the foetus to the adult.

NSAIDs are generally considered to be safe and well tolerated, but, even with the advent of selective COX-2 inhibitors, nephrotoxicity remains a concern. An impaired renal perfusion caused by the inhibition of prostaglandin synthesis is claimed like the more frequent cause of an acute renal failure due to NSAIDs, while a chronic interstitial nephritis or an analgesic nephropathy are believed the causes of a chronic renal failure. The real incidence of renal side effects of NSAIDs is still unclear and it differs between the age of the patients and the reports present in the literature. The occurrence of renal side effects following prenatal exposure to NSAIDs seems to be rare considering the large number of pregnant woman treated with indomethacin or other prostaglandin inhibitors. NSAID-related nephrotoxicity remains an important clinical problem in the newborns, in whom the functionally immature kidney may exert a significant effect on the disposition of the drugs. Instead, nephrotoxicity is a rare event in children and the risk is lower than adults. In healthy adult patients the incidence of renal adverse effects is very low, less than 1%. The risk increased with age. The elderly are at higher risk, and it is correlated at the presence of pretreatment renal disease, hypovolemia due to use of diuretics, diabetes, congestive heart failure or alteration of NSAID pharmacokinetics.

Sufentanil Sublingual Tablet System: from rationale of use to clinical practice.

The control of post-operative pain in Italy and other western countries is still suboptimal. In recent years, the Sufentanil Sublingual Tablet System (SSTS; Zalviso; AcelRx Pharmaceuticals, Redwood City, CA, USA), which is designed for patient-controlled analgesia (PCA), has entered clinical practice. SSTS enables patients to manage moderate-to-severe acute pain during the first 72 postoperative hours directly in the hospital setting. However, the role of SSTS within the current framework of options for the management of post-operative pain needs to be better established. This paper presents the position on the use of SSTS of a multidisciplinary group of Italian Experts and provides protocols for the use of this device.

The role of neurolytic celiac plexus block in the treatment of pancreatic cancer pain.

Pancreatic carcinoma, an important leading cause of cancer death, has increased steadily in incidence and still has a poor prognosis. Pain is one of the most frequent symptoms, affecting more than 75% of patients. It is often present in the early stages of disease and may be severe and difficult to treat. Abdominal viscera, including pancreas, liver, gallbladder, adrenal, kidney, and the gastrointestinal tract from the level of the gastroesophageal junction to the splenic flexure of the colon are innervated, at least in part, via the celiac plexus. Thus, painful tumors in these viscera may have pain relieved through the use of a neurolytic celiac plexus block (NCPB). Although some investigators questioned the role and the efficacy of NCPB in the treatment of upper abdominal cancer pain, most of them have suggested that it may represent the optimal treatment, especially for pancreatic cancer pain. In this report we have reviewed the techniques, results, and complications of NCPB for the treatment of pancreatic cancer pain.

Retrogasserian glycerol injection: a retrospective study of 112 patients.

From 1984 to 1989, 112 patients with typical drug-refractory trigeminal neuralgia were treated by retrogasserian glycerol injection. The present study assesses results and complications after a mean follow-up period of 3.5 years (range 0.1-5.5 years). One hundred and three of 112 patients (91.9%) showed complete pain relief 1 month postoperatively, and at the end of follow-up 80 patients (71.4%) were still enjoying complete pain relief (recurrence rate 20.5%). Abnormal facial sensations were noted in 49 patients, the most common complication being mild hypoesthesia (32% of patients), while paresthesia occurred in 19% of cases and dysesthesia in 3%. The corneal reflex was absent in 3% of patients and reduced in 5%. None of the patients developed anesthesia dolorosa, permanent masseter weakness, neuroparalytic keratitis, or diplopia.

Percutaneous controlled thermocoagulation in the treatment of trigeminal neuralgia.

This study reviews the results and complications of 162 percutaneous thermocoagulations of the gasserian ganglion in 124 patients with typical idiopathic trigeminal neuralgia. The mean duration of follow-up observation was 3.7 years (range, 1-6 years). One hundred eighteen of 124 patients continued to show complete pain relief 1 month after the operation, and at the end of follow-up observation, 83 of 124 patients (67%) continued to enjoy complete pain relief (recurrence rate, 28.2%). Anesthesia dolorosa occurred in 3% of cases, dysesthesia in 3%, and paresthesia in 17%; neuroparalytic keratitis with permanent reduction of visual acuity was observed in 2% of cases, permanent diplopia in 1%, permanent hearing deficit in 3%, and permanent impairment of mastication in 3%. We compare thermocoagulation with other surgical procedures (microvascular decompression, glycerol injection, and percutaneous decompression) used in the treatment of trigeminal neuralgia.

Day surgery: the value of monitored anesthesia care and intraoperative monitoring.

Recently an increasing percentage of patients is receiving care and surgical procedures in Day Surgery (DS), undergoing local or loco-regional anesthesia techniques, to which many patients appear to be rather reluctant and show fear and anxiety. The anesthesiologist can resolve this problem administering i.v. hypnotic and analgesic drugs and adjusting their level to patient's needs and type of surgery. They increase the patient's compliance to DS care and contribute to its diffusion. Nowadays, commonly used drugs permit quick changes of anesthesia depth with a fast and safe recovery but these require an appropriate monitoring in order to prevent and rapidly detect the onset of complications. In this study we analyze the peculiarity of Monitored Anesthesia Care and the appropriate intraoperative monitoring especially regarding the use of pulse oximetry.

[The pre-emptive analgesia in the treatment of postoperative pain]. / La pre-emptive analgesia nel trattamento del dolore post-operatorio.

The term "pre-emptive analgesia" implies the hypothesis that an analgesic treatment, given before nociceptive stimuli reach the Central Nervous System, could prevent or reduce the subsequent pain. The rational basis of this phenomenon, giving rise to much interest in the last years, comes from the finding that noxious stimuli cause wind-up and receptive fields expansion phenomena in the dorsal horn neurons of the spinal cord leading to hyperalgesia. Recently, many clinical trials to verify the existence of a pre-emptive effect regarding the management of postoperative pain by the administration of non steroidal antiinflammatory drugs (NSAIDs), local anesthetics and opioids have been conducted. As regards NSAIDs to date no study demonstrated a pre-emptive effect. Conflicting results emerged from trials employing local anesthetics, opioids or associations of the three classes of drugs. Thus, the "pre-emptive analgesia" represents a very important phenomenon for the basic research, but further trials must investigate its clinical impact.

[Intravenous patient-controlled analgesia (PCA) in the treatment of postoperative pain: rationale and clinical application]. / Patient-Controlled Analgesia (PCA) endovenosa nel trattamento del dolore post-operatorio: razionale ed applicazione clinica.

The clinical use of the patient-controlled analgesia (PCA) represents a further improvement in the treatment of post-operative pain. In this way in success due to inadequate protocols, unpredictability of the drug absorption and variability of the response to one drug or to the same pain patterns between patients can be avoided. This technique allows the patient himself to control the pain without depending upon nurses or physicians for the administration of analgesic drugs. Although the PCA is in use since several years, there are still some unresolved problems which are considered in this paper.

[The neuroendocrine and metabolic response to surgical stress]. / La risposta neuro-endocrina e metabolica allo stress chirurgico.

Surgical stress and post-operative pain evoke complex neuroendocrine and tissue responses aiming at defence from injury and recovery of body integrity. Such a reaction appears to be a real "hormonal storm" which is mainly induced by Sympathetic Nervous System and sympatho-adrenomedullary and hypothalamic-pituitary-adrenal systems activation and, in the periphery, by the release of inflammatory mediators at the site of injury. These substances by means of complex regulatory mechanisms and reciprocal interactions induce significant cardiovascular, metabolic, inflammatory and immunologic changes. However, this response may became excessive and contribute to an increase in postoperative morbidity and mortality. Since pain is a major factor in neuroendocrine response triggered by surgical injury every effort must be made to achieve effective intra and post-operative pain control.

[Postoperative pain in pediatric patients]. / Il dolore post-operatorio nel paziente pediatrico.

Surgery is an unpleasant experience which is always related to a period of pain. In the pediatric patient this results in an important effective and metabolic-neuroendocrine manifestation. After a short review of the methods recently used to evaluate pain-qualitatively as well as quantitatively, we focused on the different techniques and drugs which can be used by the anesthesiologist to achieve an adequate control of the pain symptoms. The aim is to provide devices which can be used for different groups of age in order to guarantee the maximum efficacy in pain control with the least side effect and invasiveness.

[Treatment of postoperative pain by balanced spinal analgesia]. / Il trattamento del dolore post-operatorio mediante analgesia spinale bilanciata.

Postoperative pain relief has the aim to provide patient subjective comfort, to inhibit neuroendocrine and metabolic responses to surgical injury and to enhance restoration of function by allowing the patient to breathe, cough, move more easily and to begin enteral nutrition. Opioid analgesics, independently from the route of administration, are unable to provide all this. In addition to spinal opioids other drugs, such as local anesthetics, alpha 2-agonists and cholinergic drugs, may produce an antinociceptive effect when administered by spinal route. All these drugs may be administered in combination between them, realising the so called "balanced spinal analgesia". The aim of this study is to analyse the available methods for the evaluation of pharmacological interactions, the types of interaction among different spinal antinociceptive drugs and the role of balanced spinal analgesia in the treatment of postoperative pain. Analysis of the presented data shows that the spinal synergism between opioids-local anesthetics and opioids-alpha 2-agonists can be useful in the treatment of postoperative pain, because these drug combinations are able to provide a satisfactory pain control at low doses with a reduction of the adverse effects. Furthermore, the combined use of opioids-local anesthetics proved to be effective also in abolishing postoperative incident pain and in inhibiting neuroendocrine and metabolic responses to surgical injury. Especially in high risk patients this is related to a better outcome. Finally, even if the synergism between cholinergic drugs with opioids or a2-agonists have been proved, at the moment their use in man by spinal route in the treatment of postoperative pain is not advisable.

[Treatment of pain in advanced-stage intra-abdominal neoplasms]. / Il trattamento del dolore nelle neoplasie endoaddominali in fase avanzata.

Different types of pain are present in far advanced intra-abdominal cancer, sometimes in the same site too. An accurate semeiological analysis of pain is important because different types of pain often differently respond to the available therapeutical tools. In this paper the results and the complications of the most important methods of pain management in far advanced intra-abdominal cancer are examined. Analysis of the data reveals that the association of more methods, pharmacological and non, should be a rule rather than the exception.

[Hemodynamic and metabolic impairment during hepatectomy: effect of continuous dobutamine infusion]. / Alterazioni emodinamiche e metaboliche in corso di intervento di emiepatectomia: effetto dell'infusione continua di dobutamina.

Following surgical liver resection haemodynamic and metabolic impairment, potentially responsible for post-operative hepatic failure may occur. In this prospective, randomized study such impairments and the effect on them of continuous peri-operative infusion of dobutamine were examined. Twelve patients, scheduled for hepatectomy, were divided in two groups: Group I was treated with an infusion of dobutamine 6 micrograms/kg/min from 10 minutes before the induction of anaesthesia till the fifth postoperative hour; Group II was considered as the control group. The main haemodynamic parameters, gastric pHi and serum lactate level were examined. No significant differences were detected in heart rate, parameters of pressure and SvO2. In both groups, during portal clamp, SVR increased while Cl and DO2 decreased with respect to basal and the other intra- and postoperative values. Gastric pHi decreased in both groups after portal clamp. These alterations were significantly lower in the group treated with dobutamine when compared with the control group. Serum lactate level increased in both groups. This increase was lower in Group I. Differences between groups were not statistically significant. In conclusion, during hepatectomy important haemodynamic and metabolic impairments occur. Dobutamine, by reducing such impairments, can be usefully employed in this kind of surgery.

[Management of postoperative pain in stomatology with ibuprofen L-arginine and naproxen]. / Trattamento del dolore postoperatorio in odontostomatologia con ibuprofene L-arginina e naprossene.

BACKGROUND: The aim of this prospective, randomized study is to compare the efficacy and safety of ibuprofen L-arginine and naproxen in the treatment of postoperative dental pain. METHODS: Seventy patients undergoing removal of impacted third molars were randomly allocated to receive 4 hours after surgery a single oral dose of either ibuprofen L-arginine 400 mg or naproxen 550 mg. Ten patients dropped out from the study because they took the study drug before the allowed time. Using a self-rating record, patients rated their pain and its relief for 1 hour after the drug administration. Remedication, if needed, and mean time of remedication were also recorded. RESULTS: A statistically significant reduction in pain scores with respect to the baseline values was recorded 5 minutes and 15 minutes after the drug administration in the ibuprofen L-arginine and in the naproxen-treated group, respectively. The summed pain intensity difference (SPID) over 60 minutes resulted significantly higher in the ibuprofen L-arginine than in the naproxen-treated group. A complete abolition of pain 60 minutes after medication was obtained in 12/28 patients (42.9%) in the ibuprofen L-arginine and in 5/32 patients (15.6%) in the naproxen-treated group, respectively (p = 0.04). Number of patients requiring remedication, mean time of remedication and drug related adverse effects did not significantly differ in the two treatment group. CONCLUSIONS: Global evaluation of the drugs by the patients showed ibuprofen more effective drug than naproxen.

[Is pain therapy just an ethical-behavioral problem?]. / La terapia del dolore è solo un problema etico-compartamentale?

Pain is a subjective sensation caused not only by pathological events which trigger signals perceived as algogenic (sensory component), but also by emotional mechanisms and critical assessments which modify its perception, both quantitatively and qualitatively. Therefore pain is an unique and unrepeatable experience resulting from the interaction of these three components. When faced with a patient suffering pain, it is fundamental to establish the respective quantitative incidences of these three components, in order to define the correct therapy of the pain in its totality. Whereas there are numerous therapies for dealing with the sensory component, the same cannot be said of the emotional and critical elements. We therefore suggest a number of guidelines for tackling the problem and for developing therapeutic strategies. In the literature there are few perspective and randomized studies that may evaluate the real effectiveness of the different treatments; it follows that the tested and accepted by scientific community therapeutical protocols are very few. Only recently some studies that intend to evaluate the different therapeutical strategies in connection with the different algesic syndromes are being published in the most important scientific journals.