Federico Longhini

Effects of propofol on patient-ventilator synchrony and interaction during pressure support ventilation and neurally adjusted ventilatory assist.

Objectives:Evaluating the physiologic effects of varying depths of propofol sedation on patient-ventilator interaction and synchrony during pressure support ventilation and neurally adjusted ventilatory assist. Design:Prospective crossover randomized controlled trial. Setting:University hospital ICU. Patients:Fourteen intubated patients mechanically ventilated for acute respiratory failure. Interventions:Six 25-minute trials randomly performed applying both pressure support ventilation and neurally adjusted ventilatory assist during wakefulness and with two doses of propofol, administered by Target Control Infusion, determining light (1.26 ± 0.35 &mgr;g/mL) and deep (2.52 ± 0.71 &mgr;g/mL) sedation, as defined by the bispectral index and Ramsay Sedation Scale. Measurements and Main Results:We measured electrical activity of the diaphragm to assess neural drive and calculated its integral over time during 1 minute (∫electrical activity of the diaphragm/min) to estimate diaphragm energy expenditure (effort), arterial blood gases, airway pressure, tidal volume and its coefficient of variation, respiratory rate, neural timing components, and calculated the ineffective triggering index. Increasing the depth of sedation did not cause significant modifications of respiratory timing, while determined a progressive significant decrease in neural drive (with both modes) and effort (in pressure support ventilation only). In pressure support ventilation, the difference in ineffective triggering index between wakefulness and light sedation was negligible (from 5.9% to 7.6%, p = 0.97); with deep sedation, however, ineffective triggering index increased up to 21.8% (p < 0.0001, compared to both wakefulness and light sedation). With neurally adjusted ventilatory assist, ineffective triggering index fell to 0%, regardless of the depth of sedation. With both modes, deep sedation caused a significant increase in PaCO2, which resulted, however, from different breathing patterns and patient-ventilator interactions. Conclusions:In pressure support ventilation, deep propofol sedation increased asynchronies, while light sedation did not. Propofol reduced the respiratory drive, while breathing timing was not significantly affected. Gas exchange and breathing pattern were also influenced by propofol infusion to an extent that varied with the depth of sedation and the mode of ventilation.

Neurally Adjusted Ventilatory Assist in Preterm Neonates with Acute Respiratory Failure

Background: Neurally adjusted ventilatory assist (NAVA) is a novel mode of ventilation that has been demonstrated to improve infant-ventilator interaction, compared to the conventional modes in retrospective and short-term studies. Objectives: To prospectively evaluate the physiologic effects of NAVA in comparison with pressure-regulated volume control (PRVC) in two nonrandomized 12-hour periods. Methods: We studied 14 consecutive intubated preterm neonates receiving mechanical ventilation for acute respiratory failure. Peak airway pressure (Pawpeak), diaphragm electrical activity (EAdi), tidal volume (VT), mechanical (RRmec) and neural (RRneu) respiratory rates, neural apneas, and the capillary arterialized blood gases were measured. The RRmec-to-RRneu ratio (MNR) and the asynchrony index were also calculated. The amount of fentanyl administered was recorded. Results: Pawpeak and VT were greater in PRVC (p < 0.01). Blood gases and RRmec were not different between modes, while RRneu and the EAdi swings were greater in NAVA (p = 0.02 and p < 0.001, respectively). MNR and the asynchrony index were remarkably lower in NAVA than in PRVC (p = 0.03 and p < 0.001, respectively). 1,841 neural apneas were observed during PRVC, with none in NAVA. Less fentanyl was administered during NAVA, as opposed to PRVC (p < 0.01). Conclusions: In acutely ill preterm neonates, NAVA can be safely and efficiently applied for 12 consecutive hours. Compared to PRVC, NAVA is well tolerated with fewer sedatives.

New versus Conventional Helmet for Delivering Noninvasive Ventilation: A Physiologic, Crossover Randomized Study in Critically Ill Patients.

Background:The helmet is a well-tolerated interface for noninvasive ventilation, although it is associated with poor patient–ventilator interaction. A new helmet (NH) has proven to attenuate this limitation of the standard helmet (SH) in both bench study and healthy volunteers. The authors compared a NH and a SH in intensive care unit patients receiving noninvasive ventilation for prevention of postextubation respiratory failure; both helmets were also compared with the endotracheal tube in place before extubation. Methods:Fourteen patients underwent 30-min trials in pressure support during invasive ventilation and then with a SH and a NH in a random order. The authors measured comfort, triggering delays, rates of pressurization (airway pressure–time product [PTP] of the first 300 [PTP300-index] and 500 [PTP500-index] ms from the onset of effort, and the first 200 ms from the onset of insufflation [PTP200]), time of synchrony between effort and assistance (Timesynch/Tineu), respiratory drive and frequency, arterial blood gases (ABGs), and rate of asynchrony. Results:Compared with SH, NH improved comfort (5.5 [5.0 to 6.0] vs. 8.0 [7.8 to 8.0]), respectively, P < 0.001), inspiratory trigger delay (0.31 [0.22 to 0.43] vs. 0.25 [0.18 to 0.31] s, P = 0.007), and pressurization (PTP300-index: 0.8 [0.1 to 1.8] vs. 2.7 [7.1 to 10.0]%; PTP500-index: 4.8 [2.5 to 9.9] vs. 27.3 [16.2 to 34.8]%; PTP200: 13.6 [10.1 to 19.6] vs. 30.4 [24.9 to 38.4] cm H2O/s, P < 0.01 for all comparisons) and Timesynch/Tineu (0.64 [0.48 to 0.72] vs. 0.71 [0.61 to 0.81], P = 0.007). Respiratory drive and frequency, ABGs, and rate of asynchrony were not different between helmets. Endotracheal tube outperformed both helmets with respect to all variables, except for respiratory rate, ABGs, and asynchronies. Conclusions:Compared with a SH, a NH improved comfort and patient–ventilator interaction.

Neurally adjusted ventilatory assist.

Purpose of reviewCompared with the conventional forms of partial support, neurally adjusted ventilatory assist was repeatedly shown to improve patient–ventilator synchrony and reduce the risk of overassistance, while guaranteeing adequate inspiratory effort and gas exchange. A few animal studies also suggested the potential of neurally adjusted ventilatory assist in averting the risk of ventilator-induced lung injury. Recent work adds new information on the physiological effects of neurally adjusted ventilatory assist. Recent findingsCompared with pressure support, neurally adjusted ventilatory assist has been shown to improve patient–ventilator interaction and synchrony in patients with the most challenging respiratory system mechanics, such as very low compliance consequent to severe acute respiratory distress syndrome and high resistance and air trapping due to chronic airflow obstruction; enhance redistribution of the ventilation in the dependent lung regions; avert the risk of patient–ventilator asynchrony due to sedation; avoid central apneas; limit the risk of high (injurious) tidal volumes in patients with acute respiratory distress syndrome of varied severity; and improve patient–ventilator interaction and synchrony during noninvasive ventilation, irrespective of the interface utilized. SummarySeveral studies nowadays prove the physiological benefits of neurally adjusted ventilatory assist, as opposed to the conventional modes of partial support. Whether these advantages translate into improvement of clinical outcomes remains to be determined.

Outcomes of Preterm Neonates Transferred Between Tertiary Perinatal Centers.

Objective: To verify if preterm neonates transferred between tertiary referral centers have worse outcomes than matched untransferred infants. Design: Cohort study with a historically matched control group. Setting: Two tertiary-level neonatal ICUs. Patients: Seventy-five neonates per group. Interventions: Transfer between tertiary-level neonatal ICUs carried out by a fully equipped transportation team. Measurements and Main Results: We measured in-hospital mortality, frequency of intraventricular hemorrhage greater than 2nd grade, periventricular leukomalacia, necrotizing enterocolitis greater than or equal to grade 2, bronchopulmonary dysplasia, composite outcomes (in-hospital mortality/bronchopulmonary dysplasia, in-hospital mortality/intraventricular hemorrhage > 2nd grade, and bronchopulmonary dysplasia/periventricular leukomalacia/intraventricular hemorrhage > 2nd grade), length of neonatal ICU stay, weight at discharge, and time spent on ventilatory support. Seventy-five similar (except for antenatal steroids administration) neonates were enrolled in each cohort. Cohorts did not differ in mortality, bronchopulmonary dysplasia, intraventricular hemorrhage greater than 2nd grade, periventricular leukomalacia, necrotizing enterocolitis greater than or equal to grade 2, any composite outcomes, neonatal ICU stay, weight at discharge, and duration of respiratory support. Results were unchanged adjusting for antenatal steroids. Conclusions: Neonatal transfer between tertiary-level centers does not impact on clinical outcomes, if performed under optimal conditions.

Neural versus pneumatic control of pressure support in patients with chronic obstructive pulmonary diseases at different levels of positive end expiratory pressure: a physiological study

IntroductionIntrinsic positive end-expiratory pressure (PEEPi) is a “threshold” load that must be overcome to trigger conventional pneumatically-controlled pressure support (PSP) in chronic obstructive pulmonary disease (COPD). Application of extrinsic PEEP (PEEPe) reduces trigger delays and mechanical inspiratory efforts. Using the diaphragm electrical activity (EAdi), neurally controlled pressure support (PSN) could hypothetically eliminate asynchrony and reduce mechanical inspiratory effort, hence substituting the need for PEEPe. The primary objective of this study was to show that PSN can reduce the need for PEEPe to improve patient-ventilator interaction and to reduce both the “pre-trigger” and “total inspiratory” neural and mechanical efforts in COPD patients with PEEPi. A secondary objective was to evaluate the impact of applying PSN on breathing pattern.MethodsTwelve intubated and mechanically ventilated COPD patients with PEEPi ≥ 5 cm H2O underwent comparisons of PSP and PSN at different levels of PEEPe (at 0 %, 40 %, 80 %, and 120 % of static PEEPi, for 12 minutes at each level on average), at matching peak airway pressure. We measured flow, airway pressure, esophageal pressure, and EAdi, and analyzed neural and mechanical efforts for triggering and total inspiration. Patient-ventilator interaction was analyzed with the NeuroSync index.ResultsMean airway pressure and PEEPe were comparable for PSP and PSN at same target levels. During PSP, the NeuroSync index was 29 % at zero PEEPe and improved to 21 % at optimal PEEPe (P < 0.05). During PSN, the NeuroSync index was lower (<7 %, P < 0.05) regardless of PEEPe. Both pre-trigger (P < 0.05) and total inspiratory mechanical efforts (P < 0.05) were consistently higher during PSP compared to PSN at same PEEPe. The change in total mechanical efforts between PSP at PEEPe0% and PSN at PEEPe0% was not different from the change between PSP at PEEPe0% and PSP at PEEPe80%.ConclusionPSN abolishes the need for PEEPe in COPD patients, improves patient-ventilator interaction, and reduces the inspiratory mechanical effort to breathe.Trial registrationClinicaltrials.gov NCT02114567. Registered 04 November 2013.

New Setting of Neurally Adjusted Ventilatory Assist during Noninvasive Ventilation through a Helmet

Background:Compared to pneumatically controlled pressure support (PSP), neurally adjusted ventilatory assist (NAVA) was proved to improve patient–ventilator interactions, while not affecting comfort, diaphragm electrical activity (EAdi), and arterial blood gases (ABGs). This study compares neurally controlled pressure support (PSN) with PSP and NAVA, delivered through two different helmets, in hypoxemic patients receiving noninvasive ventilation for prevention of extubation failure. Methods:Fifteen patients underwent three (PSP, NAVA, and PSN) 30-min trials in random order with both helmets. Positive end-expiratory pressure was always set at 10 cm H2O. In PSP, the inspiratory support was set at 10 cm H2O above positive end-expiratory pressure. NAVA was adjusted to match peak EAdi (EAdipeak) during PSP. In PSN, the NAVA level was set at maximum matching the pressure delivered during PSP by limiting the upper pressure. The authors assessed patient comfort, EAdipeak, rates of pressurization (i.e., airway pressure-time product [PTP] of the first 300 and 500 ms after the initiation of patient effort, indexed to the ideal pressure–time products), and measured ABGs. Results:PSN significantly increased comfort to (median [25 to 75% interquartile range]) 8 [7 to 8] and 9 [8 to 9] with standard and new helmets, respectively, as opposed to both PSP (5 [5 to 6] and 7 [6 to 7]) and NAVA (6 [5 to 7] and 7 [6 to 8]; P < 0.01 for all comparisons). Regardless of the interface, PSN also decreased EAdipeak (P < 0.01), while increasing PTP of the first 300 ms from the onset of patient effort, indexed to the ideal PTP (P < 0.01) and PTP of the first 500 ms from the onset of patient effort, indexed to the ideal PTP (P < 0.001). ABGs were not different among trials. Conclusions:When delivering noninvasive ventilation by helmet, compared to PSP and NAVA, PSN improves comfort and patient–ventilator interactions, while not ABGs. (Anesthesiology 2016; 125:1181-9)

Bench Comparative Assessment of Mechanically Assisted Cough Devices

BACKGROUND: Mechanically assisted cough devices are used in patients with impaired cough to avoid secretion accumulation. We compared 5 mechanically assisted cough devices by bench testing using a breathing simulator and assessed their user-friendliness. METHODS: We measured inspiratory and expiratory airway pressures and peak expiratory flow, the strongest indicator of cough efficacy. We performed 2 bench tests: 1) to ascertain the differences between preset and actual settings in 3 different machines of each mechanically assisted cough device and 2) to assess the effects of varying respiratory impedance and air leaks on performance of the devices. We also evaluated the user-friendliness of the devices by measuring the time required and errors in accomplishing 4 tasks by 10 physicians unfamiliar with mechanically assisted cough devices compared with product specialists from the distributing companies. Physicians also scored the ease of use. RESULTS: Four mechanically assisted cough devices during insufflation and all 5 during exsufflation showed differences between preset and actual airway pressures. All but one device showed uneven actual pressure values between models of the same type. Peak expiratory flow was significantly influenced by the mechanical properties in 2 devices and by air leaks in 4 devices. The median time to accomplish all tasks by the product specialist (10 [interquartile range of 2–29] s) was overall significantly shorter compared with all physicians (from 19 [14–65] to 36 [19–116] s). The number of procedural errors, but not the perceived ease of use, differed significantly between the devices. CONCLUSIONS: The performance of different mechanically assisted cough devices was erratic and included variance between models from the same manufacturer; it was affected by respiratory system impedance and air leaks. Time and rate of errors for performing procedures were elevated. These findings indicate that the devices are not interchangeable and that the settings should be targeted for each patient with the specific machine being used. Improvements in reliability, performance, and user-friendliness are advisable.

Remifentanil effects on respiratory drive and timing during pressure support ventilation and neurally adjusted ventilatory assist

We assessed the effects of varying doses of remifentanil on respiratory drive and timing in patients receiving Pressure Support Ventilation (PSV) and Neurally Adjusted Ventilatory Assist (NAVA). Four incrementing remifentanil doses were randomly administered to thirteen intubated patients (0.03, 0.05, 0.08, and 0.1μg·Kg-1·min-1) during both PSV and NAVA. We measured the patients (Ti/Ttotneu) and ventilator (Ti/Ttotmec) duty cycle, the Electrical Activity of the Diaphragm (EAdi), the inspiratory (Delaytrinsp) and expiratory (Delaytrexp) trigger delays and the Asynchrony Index (AI). Increasing doses of remifentanil did not modify EAdi, regardless the ventilatory mode. In comparison to baseline, remifentanil infusion >0.05μg/Kg-1/min-1 produced a significant reduction of Ti/Ttotneu and Ti/Ttotmec, by prolonging the expiratory time. Delaytrinsp and Delaytrexp were significantly shorter in NAVA, respect to PSV. AI was not influenced by the different doses of remifentanil, but it was significantly lower during NAVA, compared to PSV. In conclusion remifentanil did not affect the respiratory drive, but only respiratory timing, without differences between modes.

Different effects of propofol and dexmedetomidine on preload dependency in endotoxemic shock with norepinephrine infusion

BACKGROUND To clarify whether propofol (PROP) and dexmedetomidine (DEX) differentially affect preload dependency in an endotoxemic model based on evaluations of the systemic vascular system and cardiac function. METHODS Animals were prepared under PiCCO monitoring (BL), and endotoxemic shock was induced using an intravenous bolus of lipopolysaccharide (055:B5) in 16 New Zealand ketamine-anesthetized rabbits. After fluid resuscitation and norepinephrine infusion (SD0), the animals were randomized to PROP (n = 8) or DEX (n = 8) sedation at two incremental doses (SD1 and SD2). The mean arterial pressure and the central venous pressure were monitored. Pulse pressure variation (PPV) was assessed to evaluate preload dependency. Global end-diastolic volume, vascular resistance, mean systemic filling pressure, and cardiac function index were assessed at each time point. RESULTS PPV progressively and significantly increased with increasing infusion rates of PROP (SD1 versus SD0, P < 0.01; SD2 versus SD0, P < 0.001; and SD2 versus SD1, P = 0.024) but not DEX. PPV was higher at SD1 and SD2 in the PROP group than in the DEX group (P < 0.001). PROP increased the heart rate without affecting cardiac contractility or vascular resistance. In contrast, DEX decreased heart contractility and increased vascular resistance at the highest dose. However, neither drug affected mean arterial pressure, central venous pressure, mean systemic filling pressure, global end-diastolic volume, or venous return. CONCLUSIONS PROP more effectively increased PPV than DEX in an endotoxemic shock model after fluid resuscitation during norepinephrine infusion. DEX, but not PROP, at the highest dose influenced vascular resistance and heart contractility.