High-flow nasal oxygen therapy in intensive care and anaesthesia.

Oxygen therapy is first-line treatment for hypoxaemic acute respiratory failure (ARF). High-flow nasal oxygen therapy (HFNO) represents an alternative to conventional oxygen therapy. HFNO provides humidified, titrated oxygen therapy matching or even exceeding the patients' inspiratory demand. The application of HFNO is becoming widespread in Intensive Care Units (ICUs), favoured by increasing evidence based on numerous studies supporting its efficacy. The mechanisms of action and physiological effects of HFNO are not yet fully understood. Pharyngeal dead space washout, decrease in airway resistance, generation of a positive end-expiratory pressure, and enhanced delivery of oxygen are all alleged to be potential mechanisms. The emerging evidence suggests that HFNO is effective in improving oxygenation in most patients with hypoxaemic ARF of different aetiologies. Notwithstanding the potential benefit of HFNO in the management of hypoxaemia, further large cohort studies are necessary to clarify the indications, contraindications and factors associated with HFNO failure. HFNO may also be valuable in reducing the need for tracheal intubation in the management of post-extubation ARF. In addition, HFNO has been proposed to limit oxygen desaturation by prolonging apnoeic oxygenation during intubation both in ICUs and operating theatres.

Ten important articles on noninvasive ventilation in critically ill patients and insights for the future: A report of expert opinions.

BACKGROUND: Noninvasive ventilation is used worldwide in many settings. Its effectiveness has been proven for common clinical conditions in critical care such as cardiogenic pulmonary edema and chronic obstructive pulmonary disease exacerbations. Since the first pioneering studies of noninvasive ventilation in critical care in the late 1980s, thousands of studies and articles have been published on this topic. Interestingly, some aspects remain controversial (e.g. its use in de-novo hypoxemic respiratory failure, role of sedation, self-induced lung injury). Moreover, the role of NIV has recently been questioned and reconsidered in light of the recent reports of new techniques such as high-flow oxygen nasal therapy. METHODS: We conducted a survey among leading experts on NIV aiming to 1) identify a selection of 10 important articles on NIV in the critical care setting 2) summarize the reasons for the selection of each study 3) offer insights on the future for both clinical application and research on NIV. RESULTS: The experts selected articles over a span of 26 years, more clustered in the last 15 years. The most voted article studied the role of NIV in acute exacerbation chronic pulmonary disease. Concerning the future of clinical applications for and research on NIV, most of the experts forecast the development of innovative new interfaces more adaptable to patients characteristics, the need for good well-designed large randomized controlled trials of NIV in acute "de novo" hypoxemic respiratory failure (including its comparison with high-flow oxygen nasal therapy) and the development of software-based NIV settings to enhance patient-ventilator synchrony. CONCLUSIONS: The selection made by the experts suggests that some applications of NIV in critical care are supported by solid data (e.g. COPD exacerbation) while others are still waiting for confirmation. Moreover, the identified insights for the future would lead to improved clinical effectiveness, new comparisons and evaluation of its role in still "lack of full evidence" clinical settings.

Nasal/orotracheal tube switch to reduce length of mechanical ventilation in neurocritical patients: A propensity score matched analysis.

INTRODUCTION AND OBJECTIVES: Nasotracheal intubation was advocated to increase patients comfort and tube tolerance, but no study showed a clear benefit of nasotracheal intubation over orotracheal intubation. Neurocritically ill patients are a fragile group with specific requirements regarding ventilation and sedation. The aim of this study was to evaluate whether nasotracheal intubation might reduce length of mechanical ventilation in neurocritically ill patients. MATERIALS AND METHODS: We conducted a retrospective cohort study with propensity matched analysis including all patients who underwent prolonged mechanical ventilation in the neurocritical Intensive Care Unit. RESULTS: A total of 4030 patients were admitted during the period of interest and 312 entered the final analysis. Propensity score analysis identified 74 matched couples. Length of mechanical ventilation in patients who underwent early nasotracheal intubation resulted to be statistically significantly shorter than patients who underwent orotracheal intubation. Accordingly, length of sedation was significantly lower in patients with nasotracheal intubation, while no difference in complications occurred with similar length of stay. CONCLUSIONS: In critical care units using nasotracheal intubation in the standard management of patients, the nasotracheal route was associated with lesser need for sedatives leading to shorter mechanical ventilation in neurocritical patients. However, causality has to be proven by future randomized controlled trials.

Predictors of intubation in COVID-19 patients treated with out-of-ICU continuous positive airway pressure.

BACKGROUND: As delayed intubation may worsen the outcome of coronavirus disease 2019 (COVID-19) patients treated with continuous positive airway pressure (CPAP), we sought to determine COVID-specific early predictors of CPAP failure. METHODS: In this observational retrospective multicentre study, we included all COVID-19 patients treated with out-of-ICU CPAP, candidates for intubation in case of CPAP failure. From these patients, we collected demographic and clinical data. RESULTS: A total of 397 COVID-19 patients were treated with CPAP for respiratory failure, with the therapeutic goal of providing intubation in case of CPAP failure. Univariable analysis showed that, age, lactate dehydrogenase (LDH) and white cell counts were all significantly lower in patients with successful CPAP treatment compared to those failing it and undergoing subsequent intubation. The percentage changes between baseline and CPAP application in the ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2), PaO2, respiratory rate and ROX index were higher in patients experiencing successful CPAP compared to those failing it. FiO2 and male gender were also significantly associated with intubation. Multivariable analysis adjusting for age, gender, Charlson comorbidity index, percentage change in PaO2/FiO2 or PaO2 and FiO2 separately, lactate, white blood cell count, LDH and C-reactive protein levels led to an area under the curve of 0.818 and confirmed that age, LDH and percentage increase in PaO2/FiO2 are predictors of intubation. CONCLUSIONS: In COVID-19 patients requiring CPAP, age, LDH and percentage change in PaO2/FiO2 after starting CPAP are predictors of intubation.

Impact on grafted kidney function of rocuronium-sugammadex vs cisatracurium-neostigmine strategy for neuromuscular block management. An Italian single-center, 2014-2017 retrospective cohort case-control study.

BACKGROUND: The impact of sugammadex in patients with end-stage renal disease undergoing kidney transplantation is still far from being defined. The aim of the study is to compare sugammadex to neostigmine for reversal of rocuronium- and cisatracurium-induced neuromuscular block (NMB), respectively, in patients undergoing kidney transplantation. METHODS: A single-center, 2014-2017 retrospective cohort case-control study was performed. A total of 350 patients undergoing kidney transplantation, equally divided between a sugammadex group (175 patients) and a neostigmine group (175 patients), were considered. Postoperative kidney function, evaluated by monitoring of serum creatinine and urea and estimated glomerular filtration rate (eGFR), was the endpoint. Other endpoints were anesthetic and surgical times, post-anesthesia care unit length of stay, postoperative intensive care unit admission, and recurrent NMB or complications. RESULTS: No significant differences in patient or, with the exception of drugs involved in NMB management, anesthetic, and surgical characteristics, were observed between the two groups. Serum creatinine (median [interquartile range]: 596.0 [478.0-749.0] vs 639.0 [527.7-870.0] µmol/L, p = 0.0128) and serum urea (14.9 [10.8-21.6] vs 17.1 [13.1-22.0] mmol/L, p = 0.0486) were lower, while eGFR (8.0 [6.0-11.0] vs 8.0 [6.0-10.0], p = 0.0473) was higher in the sugammadex group than in the neostigmine group after surgery. The sugammadex group showed significantly lower incidence of postoperative severe hypoxemia (0.6% vs 6.3%, p = 0.006), shorter PACU stay (70 [60-90] min vs 90 [60-105] min, p < 0.001), and reduced ICU admissions (0.6% vs 8.0%, p = 0.001). CONCLUSIONS: Compared to cisatracurium-neostigmine, the rocuronium-sugammadex strategy for reversal of NMB showed a better recovery profile in patients undergoing kidney transplantation.

What the pulmonary specialist should know about the new inhalation therapies.

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.

Intravenous infusion of magnesium sulfate and postoperative analgesia in total knee arthroplasty.

BACKGROUND: The effectiveness of combining magnesium (Mg) administration with both general and spinal anesthesia to reduce postoperative pain and analgesic consumption is still debated. We evaluated the effects of an intravenous (IV) infusion of Mg sulphate on analgesic consumption and postoperative pain score after total knee arthroplasty performed under spinal anesthesia. METHODS: We studied 40 patients who underwent spinal anesthesia with bupivacaine plus morphine. Patients were randomly assigned to two groups, each of 20 patients, who received either treatment (i.e., intravenous Mg sulphate 40 mg kg(-1) followed by an infusion of 10 mg kg(-1) h(-1)), or the same amounts of isotonic saline (controls). Irrespective of the group of randomization, all patients received postoperative paracetamol, ketorolac, and patient-controlled analgesia with morphine. RESULTS: The Mg postoperative blood level was 0.85 ± 0.02 mmol/L and 1.25 ± 0.11 mmol/L for C and Mg groups, respectively (P<0.001). Sensory level of the spinal block, height of spinal block, mean time to first pain and incidence of PONV were similar in the two groups. Morphine consumption did not show any statistically significant difference between the two groups. The pain score was not significantly different between the two groups. No severe adverse effects were recorded after Mg infusion. CONCLUSION: IV perioperative administration of Mg did not influence postoperative pain control and analgesic consumption after total knee arthroplasty. More studies should be performed with different intra and postoperative pain protocols to enhance the potential anti-nociceptive effect of Mg.

Osteopontin induces soluble urokinase-type plasminogen activator receptor production and release.

BACKGROUND: Osteopontin (OPN) and soluble urokinase plasminogen activator receptor (suPAR) have been proposed as markers of disease severity and risk-stratification in infection and inflammation. In breast cancer, OPN and the membrane bound form of urokinase plasminogen activator receptor (uPAR) are functionally related, as OPN-induced cell migration depends on uPAR triggering by urokinase plasminogen activator (uPA). The aim of this study was to prospectively evaluate the kinetic of OPN and suPAR blood levels in patients developing septic shock (SS) compared to those not developing SS, and to investigate the relationships between these two biomarkers in immune cells in vitro. METHODS: We measured the levels of OPN and suPAR for 15 days in forty-three patients, defined a priory as at risk to develop septic shock. Moreover, we investigated in vitro the effect of recombinant OPN on uPAR and suPAR expression in monocytes. RESULTS: We found that OPN and suPAR levels were directly correlated to each other both at intensive care unit admission and on the day patients met SIRS/sepsis or septic shock criteria. In patients developing septic shock, OPN increased prior to suPAR and was already detectable up to 4 days before the shock development. In vitro, OPN induced suPAR production in monocytes by increasing both uPAR gene expression, and suPAR release from the cell surface. CONCLUSION: These data suggest that OPN is partly responsible for the increased plasma levels of suPAR and might be a valuable tool to predict the occurrence of septic shock.

Noninvasive vs. conventional mechanical ventilation in patients with chronic obstructive pulmonary disease after failure of medical treatment in the ward: a randomized trial.

OBJECTIVE: We conducted a randomized prospective study comparing noninvasive positive pressure ventilation (NPPV) with conventional mechanical ventilation via endotracheal intubation (ETI) in a group of patients with chronic obstructive pulmonary disease who failed standard medical treatment in the emergency ward after initial improvement and met predetermined criteria for ventilatory support. DESIGN AND SETTING: Prospective randomized study in a university hospital 13-bed general ICU. PATIENTS: Forty-nine patients were randomly assigned to receive NPPV (n=23) or conventional ventilation (n=26). RESULTS: both NPPV and conventional ventilation significantly improved gas exchanges. The two groups had similar length of ICU stay, number of days on mechanical ventilation, overall complications, ICU mortality, and hospital mortality. In the NPPV group 11 (48%) patients avoided intubation, survived, and had a shorter duration of ICU stay than intubated patients. One year following hospital discharge the NPPV group had fewer patients readmitted to the hospital (65% vs. 100%) or requiring de novo permanent oxygen supplementation (0% vs. 36%). CONCLUSIONS: The use of NPPV in patients with chronic obstructive pulmonary disease and acute respiratory failure requiring ventilatory support after failure of medical treatment avoided ETI in 48% of the patients, had the same ICU mortality as conventional treatment and, at 1-year follow-up was associated with fewer patients readmitted to the hospital or requiring for long-term oxygen supplementation. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1503-3).

Comparison of static and dynamic measurements of intrinsic PEEP in anesthetized cats.

Dynamic measurements of intrinsic positive end-expiratory pressure (PEEPi,dyn) considerably underestimate values obtained under static conditions (PEEPi,stat) in patients with severe airway obstruction. This may be related to regional differences in respiratory system mechanical properties and/or viscoelastic behavior. To evaluate this concept, PEEPi,stat and PEEPi,dyn were compared in six anesthetized paralyzed cats during dynamic hyperinflation produced by inverse ratio ventilation (IRV) and aerosolized methacholine (MCh). PEEPi,stat did not differ between IRV and MCh, averaging 2.70 +/- 0.33 (SE) and 2.70 +/- 0.25 cmH2O, respectively. PEEPi,dyn was significantly less with MCh (0.25 +/- 0.05 cmH2O) than IRV (2.05 +/- 0.28 cmH2O) (P < 0.0001), resulting in a lower PEEPi,dyn/PEEPi,stat ratio for MCh (0.10 +/- 0.02) than for IRV (0.76 +/- 0.03) (P < 0.0001). Compared with control values (33.5 +/- 3.7 cmH2O.l-1.s), maximum resistance (Rmax) was unchanged during IRV (29.1 +/- 2.1 cmH2O.l-1.s) but increased considerably with MCh (288.8 +/- 18.4 cmH2O.l-1.s) (P < 0.0001). Similar changes in minimum resistance (Rmin) and delta R (Rmax-Rmin) were noted. There was a strong inverse relationship between delta P, an index of time constant inequalities and viscoelastic pressure losses and PEEPi,dyn/PEEPi,stat ratio. No correlation was found between this ratio and Rmax, Rmin, delta R, or compliance. In conclusion, PEEPi,dyn considerably underestimates PEEPi,stat in acute nonhomogeneous airway obstruction with MCh in contrast to IRV, where the magnitude and distribution of mechanical properties remain unaltered. These findings support the concept that the difference between PEEPi,dyn and PEEPi,stat is related to regional time constant inequalities and/or increased viscoelastic pressure losses.

Influence of site of tracheal pressure measurement on in situ estimation of endotracheal tube resistance.

In situ measurement of distal tracheal pressure (Ptr) via an intraluminal side-hole catheter (IC) has been used to determine endotracheal tube (Rett) and intrinsic patient (Rpt) resistances in intubated subjects. Because of differences in cross-sectional area between the endotracheal tube (ETT) and trachea, fluid dynamic principles predict that IC position should critically influence these results. Accordingly, the aim of this study was to determine the effect of IC position on Rett. Ptr was recorded in vitro through an IC from 2 cm inside, at the tip of, or 2 cm outside an ETT (7, 8, and 9 mm ID) situated within an artificial trachea (13, 18, and 22 mm ID). A reference value of Rett was also obtained. Results were unaffected by IC position during inspiration, overestimating Rett by 7.9 +/- 0.7% (SE). In contrast, during expiration, Rett fell as IC position changed from outside to inside the ETT and was underestimated by 41.3 +/- 3.6% with Ptr recorded inside the ETT. Varying ETT or tracheal size had little effect on the relative error in Rett. The IC itself did increase Rett due to a reduction in effective cross-sectional area, the change varying directly with IC size and inversely with ETT caliber. In vivo values in 11 intubated patients were comparable to in vitro results. In summary, IC position and size can have important consequences on in situ measurements of Ptr and should be considered when clinically monitoring Rett or Rpt.

Orthopnea and inspiratory effort in chronic heart failure patients.

STUDY OBJECTIVE: Orthopnea is a typical feature of patients with chronic heart failure (CHF), the factors contributing to it are not completely understood. We investigated changes in dyspnea and other respiratory variables, induced by altering posture (from sitting to supine) in 11 CHF patients (NYHA classes II-IV) and 10 control subjects. METHODS AND RESULTS: We measured dyspnea (Borg scale) the diaphragm pressure time product per minute (PTPdi/m, index of metabolic consumption), and mechanical properties of the lung (lung compliance (C,L) and resistances (R,L). CHF patients also underwent a trial of non-invasive mechanical ventilation (NIMV) in the supine position in order to ascertain whether unloading the inspiratory muscles could somehow relieve dyspnea. While sitting the PTPdi/min was significantly higher in CHF patients than in controls (181 +/- 54 cm H2O x s/min vs. 96 +/- 32; P<0.05). Assuming a supine position caused no major changes in controls, whereas CHF patients showed a significant worsening in dyspnea, a rise in PTPdi/min (243 +/- 97 p<0.01) and R,L (4.7 +/- 1.2 cm H2O/L x s sitting vs. 7.9 +/- 2.5 supine; P<0.01) and a decrease in C,L (0.08 +/- 0.02 L/cm H2O sitting vs. 0.07 +/- 0.01 supine; P<0.05). Applying NIMV to supine CHF patients significantly reduced the PTPdi/min to 81 +/- 42 (P<0.001). Changes in dyspnea, produced by varying position or applying NIMV, were significantly correlated with PTPdi/min (r=0.80, P<0.005 and r=0.58, P<0.01, respectively). CONCLUSIONS: CHF patients had a higher PTPdi/min than controls when sitting, and assuming a supine position induced severe dyspnea, a large rise in R,L, and a reduction in C,L so that PTPdi/min increased further. Orthopnea was strongly correlated with the increased diaphragmatic effort.

Use of bronchodilators during non-invasive mechanical ventilation.

Bronchodilators represent one of the most important therapeutic weapons for the treatment of airway obstructive diseases and the inhaled route of administration is very often employed due to the greater drug availability and reduced magnitude of side effects. During acute exhacerbations, it is not unfrequent that the elastic and resistive loads imposed on the ventilatory pump overcome the force sustainable by the respiratory muscles and the patient requires ventilatory assistance, in order to relieve fatigue and to optimize alveolar gas exchange. During these episodes, inhaled bronchodilators, far from being discontinued, sometime must be administered during mechanical ventilation, that, in hypercapnic ventilatory failure can be frequently applied noninvasively with a good rate of success. While in the current literature there are a lot of data about inhaled drug administration during invasive mechanical ventilation, very few data are available on the topic of aerosol therapy during noninvasive mechanical ventilation. With the present paper we want to analyze the rationale, the feasibility and the current data dealing with the administration of inhaled drugs during noninvasive mechanical ventilation.

Prolonged weaning: from the intensive care unit to home.

Weaning is the process of withdrawing mechanical ventilation which starts with the first spontaneous breathing trial (SBT). Based on the degree of difficulty and duration, weaning is classified as simple, difficult and prolonged. Prolonged weaning, which includes patients who fail 3 SBTs or are still on mechanical ventilation 7 days after the first SBT, affects a relatively small fraction of mechanically ventilated ICU patients but these, however, requires disproportionate resources. There are several potential causes which can lead to prolonged weaning. It is nonetheless important to understand the problem from the point of view of each individual patient in order to adopt appropriate treatment and define precise prognosis. An otherwise stable patient who remains on mechanical ventilation will be considered for transfer to a specialized weaning unit (SWU). Though there is not a precise definition, SWU can be considered as highly specialized and protected environments for patients requiring mechanical ventilation despite resolution of the acute disorder. Proper staffing, well defined short-term and long-term goals, attention to psychological and social problems represent key determinants of SWU success. Some patients cannot be weaned, either partly or entirely, and may require long-term home mechanical ventilation. In these cases the logistics relating to caregivers and the equipment must be carefully considered and addressed.

Bench comparative evaluation of a new generation and standard helmet for delivering non-invasive ventilation.

OBJECTIVE: To evaluate the performance of a new helmet (NH) recently introduced into clinical use relative to that of the standard helmet (SH) in terms of delivering non-invasive continuous positive airway pressure (nCPAP) and pressure support ventilation (nPSV). DESIGN: This was a bench study using a mannequin connected to an active lung simulator. The SH was fastened to the mannequin by armpit braces, which are not needed to secure the NH. MEASUREMENTS: The inspiratory and expiratory variations in nCPAP delivered with two different simulated efforts (Pmus), were determined relative to the preset CPAP level. nPSV was applied at two simulated respiratory rates (RR) and two cycling-off flow thresholds. We measured inspiratory trigger delay (Delay trinsp), expiratory trigger delay (Delay trexp), time of synchrony (Time sync), trigger pressure drop (ΔP trigger), airway pressure-time product during the triggering phase (PTPt), the initial 200 ms from the onset of the ventilator pressurization (PTP 200), and the initial 300 and 500 ms from the onset of the simulated effort; this two latter parameters were expressed as the percentage of the area of ideal pressurization (PTP 300-index and PTP 500-index, respectively). RESULTS: In nCPAP, at both Pmus, the differences between the two interfaces at both Pmus were small and clinically irrelevant. In nPSV, regardless of the setting, NH resulted in significantly smaller trigger delays, ΔP trigger, and PTPt. Time sync, PTP 200, PTP 300-index, and PTP 500-index were also significantly higher with the NH compared to the SH, irrespective of the setting. CONCLUSIONS: Compared to the SH, the NH is equally effective in delivering nCPAP and more effective in delivering nPSV, and it is used to avoid the need for armpit braces.