Gianmaria Cammarota

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.

Thoracic epidural analgesia in post-thoracotomy patients: comparison of three different concentrations of levobupivacaine and sufentanil

BACKGROUND Relative effects of dosage, volume and concentration of local anaesthetics used for postoperative thoracic epidural analgesia are still under debate. In this randomized, prospective, double-blinded study, we evaluated the incidence of side-effects such as changes in arterial pressure, postoperative nausea, vomiting, and pruritus in patients admitted for thoracic surgery during continuous thoracic epidural infusion using levobupivacaine and sufentanil mixture in three different volumes. METHODS We studied 150 patients who underwent thoracotomy with a thoracic epidural catheter placed between T4 and T7. The patients were randomized into three groups which received 10 mg h(-1) of levobupivacaine at three different concentrations (0.5%, 0.25%, and 0.15%), in combination with sufentanil at 2.6 microg h(-1). Haemodynamic effects, pruritus, nausea, vomiting, sensory and motor block, pain score, additional analgesic requirement, sedation, and patient satisfaction were registered immediately after the surgical operation and on the first, second, and third postoperative days. RESULTS We did not detect any differences in the incidence of side-effects such as changes in arterial pressure, and also postoperative nausea, vomiting, and pruritus. The three groups were also similar with regard to patient characteristics, sensory and motor block, pain score, analgesic rescue dose, sedation, and patient satisfaction. CONCLUSIONS The same dose of a mixture of levobupivacaine and sufentanil administered in three different volumes and concentrations during continuous thoracic epidural infusion for thoracotomy provided an equal incidence of adverse haemodynamic effects, nausea, vomiting, or pruritus.

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.

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)

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.

Patient-ventilator asynchrony affects pulse pressure variation prediction of fluid responsiveness.

PURPOSE During partial ventilatory support, pulse pressure variation (PPV) fails to adequately predict fluid responsiveness. This prospective study aims to investigate whether patient-ventilator asynchrony affects PPV prediction of fluid responsiveness during pressure support ventilation (PSV). MATERIALS AND METHODS This is an observational physiological study evaluating the response to a 500-mL fluid challenge in 54 patients receiving PSV, 27 without (Synch) and 27 with asynchronies (Asynch), as assessed by visual inspection of ventilator waveforms by 2 skilled blinded physicians. RESULTS The area under the curve was 0.71 (confidence interval, 0.57-0.83) for the overall population, 0.86 (confidence interval, 0.68-0.96) in the Synch group, and 0.53 (confidence interval, 0.33-0.73) in the Asynch group (P = .018). Sensitivity and specificity of PPV were 78% and 89% in the Synch group and 36% and 46% in the Asynch group. Logistic regression showed that the PPV prediction was influenced by patient-ventilator asynchrony (odds ratio, 8.8 [2.0-38.0]; P < .003). Of the 27 patients without asynchronies, 12 had a tidal volume greater than or equal to 8 mL/kg; in this subgroup, the rate of correct classification was 100%. CONCLUSIONS Patient-ventilator asynchrony affects PPV performance during partial ventilatory support influencing its efficacy in predicting fluid responsiveness.

High-dose rocuronium for rapid-sequence induction and reversal with sugammadex in two myasthenic patients.

The anesthetic management of patients affected by myasthenia gravis is usually challenging in elective surgery and even more so in emergency procedures. The difficulties involved are several‐fold, ranging from the choice of an appropriate muscle relaxant (i.e. one that enables safe and rapid airway management) to neuromuscular monitoring and normal muscular recovery. Additionally, optimizing patient conditions – either pharmacologically or with plasmapheresis – before intervention is well beyond the realm of possibility. We discuss the anesthetic management of two myasthenic patients undergoing emergency surgery (for sigmoid perforation and upper gastrointestinal bleeding respectively). In both cases, we opted for rapid‐sequence induction with high‐dose rocuronium to prevent inhalation of gastric contents. We also report on the implication of neuromuscular monitoring. We found that the rocuronium–sugammadex combination was a useful and effective option in the emergency setting.

Looking for the Grail, Finding Traces on the Way.

Critical Care Medicine www.ccmjournal.org 1237 The ventilator yellow alarm rings (Peak airways pressure limit? Low tidal volume? High minute volume? High/ low respiratory rate?). This event may occur several times per patient each ICU shift. What is creating the antagonism between patient and ventilator? From the patient side, troubles might develop from lung (i.e., dynamic hypeinflation/ intrinsic positive end-expiratory pressure [PEEP], resistance, and elastance), from muscles function (respiratory muscle deficit or weakness) or from central nervous system (respiratory drive), the latter being influenced by mechanical and chemical feedbacks, as well as over-/undertitration of sedatives and opiates (1, 2). From the ventilator side, it is even more problematic, i.e., trigger (both inspiratory and expiratory), cycling criteria, modality of ventilation, support, and PEEP all intertwined over a respiratory cycle (3). Sometimes it seems that “this marriage cannot take place.” Due to the increasing interest in patient-ventilator interaction (PVi) (4), several studies in the past decade reported strategies to improve (5), or better recognize PVi (6, 7), including the study of techniques able to provide assistance proportionally to patient’s effort (i.e., proportionally assisted ventilation plus [PAV+] [8, 9] and neurally adjusted ventilator assist [9, 10]). These articles often show superiority of the new technique in terms of patient-machine coordination, but without clear-cut benefit on patient’s outcome. However, most of these studies are small clinical trials with a limited number of patients enrolled and are not specifically designed to assess outcome endpoints. In this issue of Critical Care Medicine, Bosma et al (11) aim to assess PSV and PAV+ in terms of patient outcome. The study is well conducted, and the number of patients enrolled is appropriate. In this protocol, only patients with more than 36 hours of mechanical ventilation before the screening were enrolled; it is likely the first randomized clinical trial (RCT) with PAV+ with a study period longer than 48 hours, as opposed to previous shorter term physiologic studies. The authors not only demonstrated the feasibility and safety of the protocol (primary endpoint) but also found a reduction of the ICU length of stay (LOS) in PAV+ group when compared with the PSV one. This encouraging result (as secondary endpoint) rises a question: Is it really possible to modify ICU mortality or LOS adjusting only a single variable? This is a fascinating hypothesis, the Grail for a researcher. Technical progress in the last 30–40 years has made a difference in ICU setting, increasing (12), or maintaining (13) the rate of survival despite the admission of more severe and older patients (13). The complexity of an ICU patient with multidisciplinary treatments and numbers of specialists coordinated by the intensivist make it harder and harder to identify the direct cause-effect relationship of a new technique or drug application on patient outcome. In this complex environment, other nonmedical factors might influence patient outcome, including organizational issues (14). It is important to take all variables into account when the targets of the research are LOS, ICU mortality, or an analogous surrogate. Not surprisingly, in recent years, RCTs targeting clinical outcome, based on the promising results of physiological studies, failed to demonstrate clinical benefit (15–17). When comparing a novel but infrequently used technique with a traditional one, it is well known that the expertise of the treatment team is crucial and may heavily influence the results in both directions. On the one hand, if the team is uncomfortable with the new technique, the results might underestimate the benefit. On the other hand, if the team is well trained, results might be influenced by the great ability of the personnel to handle the new technique. Bosma et al (11) worked in a single-center environment, and the good result might rely, once again, on their experience with PAV+. Reproducibility is a cornerstone of the scientific method and, from this perspective, if a broad application of a technique is unable to replicate the positive results, we have “a real-world” problem. Whether subsequent multicenter RCTs that will follow will be positive or negative is yet to be seen, but looking for the Grail, we should remember that the journey is more important than the destination and that even small traces, such the ones left by Bosma et al (11), might indicate the right direction on the way.