The latest medical research on Anesthesiology

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Nurses' knowledge of the management of drug-induced peripherally inserted central catheter obstruction: A descriptive phenomenological study.

J Vasc Access

The purpose of this research is to describe and understand nurses' knowledge of drug-induced peripherally inserted central catheter obstruction management in developing countries. This research aims to identify the reasons why nurses lack knowledge of the management of drug-induced peripherally inserted central catheter obstruction and do not use the drug-induced peripherally inserted central catheter obstruction management techniques recommended by the Infusion Therapy Standards of Practice.

The descriptive phenomenological method was used to investigate nurses' knowledge of the management of drug-induced peripherally inserted central catheter obstruction. Semi-structured in-depth interviews with 17 nurses from three hospitals in northeast China were used in this qualitative study. Data collection and analysis were conducted simultaneously during the research. Nvivo software 12.0 was used to organize and code the data, and Colaizzi's seven phases of data analysis were used to form themes.

The findings showed that there is inconsistency in nurses' knowledge of drug-induced peripherally inserted central catheter obstruction and its management, and we suggest reasons for this phenomenon.

This research has shown that inconsistent practice in the management of drug-induced peripherally inserted central catheter obstruction is a more complex issue than originally thought. These inconsistencies are related to time pressure on nurses, nurses' knowledge of peripherally inserted central catheter obstruction, and limitations of the clinical work model.

Cost-utilization of peripheral intravenous cannulation in hospitalized adults: An observational study.

J Vasc Access

In modern healthcare there is increased focus on optimizing efficiency for every treatment or performed procedure, of which reduction of costs is an important part. With this study, authors aimed to calculate the cost of peripheral intravenous cannulation including all components that influence its price.

This observational cost-utilization study was conducted between May and October 2016. Hospitalized adults were included in this study, who received usual care. Peripheral intravenous cannulation was carried out according to current hospital protocols, based on international standards for peripheral intravenous catheter insertion. Device costs were assumed equal to the number of attempts multiplied by the fixed supply costs and applicable costs for additional attempts, whereas personnel costs for both nurses and physicians were based on their hourly salary.

A total of 1512 patients were included in this study, with a mean of 1.37 (±0.77) attempts and a mean time of 3.5 (±2.7) min were needed for a successful catheter insertion. Adjusted mean costs for peripheral intravenous cannulation were estimated to be €11.67 for each patient, but costs increase as the number of attempts for successful cannulation increases. The cost for patients with a successful first attempt was lower, at approximately €9.32 but increased markedly to €65.34 when five attempts were needed.

Prevention of multiple attempts may lower the costs, and furthermore, additional technologies applied by nurses to individual patients based on predicted difficult intravenous access will make the application of these additional technologies, in turn, more efficient.

Pharmacokinetics and Pharmacodynamics of Remimazolam (CNS 7056) after Continuous Infusion in Healthy Male Volunteers: Part I. Pharmacokinetics and Clinical Pharmacodynamics.

Anesthesiology

Remimazolam is rapidly metabolized to an inactive metabolite by tissue esterasesWhen administered as a 1-min infusion, it produced rapid onset and dose-dependent sedation at doses of 0.05 mg/kg and higherIts pharmacokinetics when administered as a 1-min infusion was characterized by relatively high elimination clearance, a small steady-state volume of distribution, and a short elimination half-life WHAT THIS ARTICLE TELLS US THAT IS NEW: Twenty adult male volunteers receiving remimazolam as continuous intravenous infusion at 5 mg/min for five min, then 3 mg/min for 15 min, and 1 mg/min for 15 min lost consciousness 5 ± 1 (mean ± SD) min after starting the infusion and were fully alert 19 ± 7 min after stopping itRemizolam produced moderate hemodynamic effects and no clinically significant effect on cardiac repolarizationThe disposition of remimazolam was characterized by a multicompartmental pharmacokinetic model with small distribution volumes and a high elimination clearance with small interindividual variability; its context-sensitive half time after a 4-h infusion was predicted to be 7 ± 2 min BACKGROUND:: Remimazolam (CNS 7056) is a new ultra-short-acting benzodiazepine for intravenous sedation and anesthesia. Its pharmacokinetics and pharmacodynamics have been reported for bolus administration. This study aimed to investigate the pharmacokinetics and pharmacodynamics of remimazolam after continuous infusion.

Twenty healthy male volunteers (20 to 38 yr, 64 to 99 kg) received remimazolam as continuous intravenous infusion of 5 mg/min for 5 min, 3 mg/min for the next 15 min, and 1 mg/min for further 15 min. Pharmacokinetics of remimazolam and its metabolite were determined from arterial plasma concentrations. Sedation was assessed using the Modified Observer's Assessment of Alertness and Sedation scale. Pharmacokinetic-pharmacodynamic modeling was performed by population analysis. Hemodynamics and the electrocardiogram were also investigated.

Pharmacokinetics was best described by a three-compartment model for remimazolam and a two-compartment model with transit compartment for the metabolite. Remimazolam showed a high clearance (1.15 ± 0.12 l/min, mean ± SD), a small steady-state volume of distribution (35.4 ± 4.2 l) and a short terminal half-life (70 ± 10 min). The simulated context-sensitive halftime after an infusion of 4 h was 6.8 ± 2.4 min. Loss of consciousness was observed 5 ± 1 min after start, and full alertness was regained 19 ± 7 min after stop of infusion. Pharmacodynamics of Modified Observer's Assessment of Alertness and Sedation score was best described by a sigmoid probability model with effect site compartment. The half-maximum effect site concentration for a Modified Observer's Assessment of Alertness and Sedation score less than or equal to 1 was 695 ± 239 ng/ml. The equilibration half-time between central and effect compartment was 2.7 ± 0.6 min. Mean arterial blood pressure decreased by 24 ± 6%, and heart rate increased by 28 ± 15%. Spontaneous breathing was maintained throughout the study. There was no significant prolongation of the QT interval of the electrocardiogram observed.

Remimazolam was characterized by a pharmacokinetic-pharmacodynamic profile with fast onset, fast recovery, and moderate hemodynamic side effects.

Socioeconomic Status and Days Alive and Out of Hospital after Major Elective Noncardiac Surgery: A Population-based Cohort Study.

Anesthesiology

Low socioeconomic status likely impairs many aspects of health and health careDays alive and out of hospital is a new outcome measure that assesses duration of hospitalization and readmission WHAT THIS ARTICLE TELLS US THAT IS NEW: The investigators evaluated more than 700,000 patients who had 13 types of surgeryDays alive and out of hospital in the initial postoperative months was about a quarter of a day longer in the lowest than the highest socioeconomic quintile, adjusted for potential confounding factorsConfounder-adjusted serious complications were also more common in the lowest quintile (5% vs. 3.9%), as was mortality (0.6% vs. 0.4%) BACKGROUND:: Socioeconomic status is an important but understudied determinant of preoperative health status and postoperative outcomes. Previous work has focused on the impact of socioeconomic status on mortality, hospital stay, or complications. However, individuals with low socioeconomic status are also likely to have fewer supports to facilitate them remaining at home after hospital discharge. Thus, such patients may be less likely to return home over the short and intermediate term after major surgery. The newly validated outcome, days alive and out of hospital, may be highly suited to evaluating the impact of socioeconomic status on this postdischarge period. The study aimed to determine the association of socioeconomic status with short and intermediate term postoperative recovery as measured by days alive and out of hospital.

The authors evaluated data from 724,459 adult patients who had one of 13 elective major noncardiac surgical procedures between 2006 and 2017. Socioeconomic status was measured by median neighborhood household income (categorized into quintiles). Primary outcome was days alive and out of hospital at 30 days, while secondary outcomes included days alive and out of hospital at 90 and 180 days, and 30-day mortality.

Compared to the highest income quintile, individuals in the lowest quintile had higher unadjusted risks of postoperative complications (6,049 of 121,099 [5%] vs. 6,216 of 160,495 [3.9%]) and 30-day mortality (731 of 121,099 [0.6%] vs. 701 of 160,495 [0.4%]) and longer mean postoperative length of stay (4.9 vs. 4.4 days). From lowest to highest income quintile, the mean adjusted days alive and out of hospital at 30 days after surgery varied between 24.5 to 24.9 days.

Low socioeconomic status is associated with fewer days alive and out of hospital after surgery. Further research is needed to examine the underlying mechanisms and develop posthospital interventions to improve postoperative recovery in patients with fewer socioeconomic resources.

Pharmacokinetics and Pharmacodynamics of Remimazolam (CNS 7056) after Continuous Infusion in Healthy Male Volunteers: Part II. Pharmacodynamics of Electroencephalogram Effects.

Anesthesiology

Intravenously administered remimazolam can produce deep sedation quickly from which the patient recovers rapidly due, in part, to its relatively high clearance by tissue esterasesElectroencephalogram measures with a significant correlation to sedation scales provide a continuous noninvasive method for quantifying central nervous system drug effects without the need to stimulate the patient WHAT THIS ARTICLE TELLS US THAT IS NEW: Electroencephalogram changes during remimazolam infusion in 20 adult male volunteers were characterized by an initial increase in the beta frequency band and a late increase in the delta frequency bandBeta ratio had a monotonic relationship to Modified Observer's Assessment of Alertness and Sedation scores and could be modeled using a standard sigmoid Emax pharmacodynamic modelThe standard sigmoid Emax model failed to describe the time course of the Narcotrend Index appropriately; it was necessary to extend the model by adding a second sigmoid term with a second effect site concentration BACKGROUND:: Remimazolam (CNS 7056) is a new ultra-short acting benzodiazepine for IV sedation. This study aimed to investigate the electroencephalogram (EEG) pharmacodynamics of remimazolam infusion.

Twenty healthy male volunteers received remimazolam as continuous IV infusion of 5 mg/min for 5 min, 3 mg/min for the next 15 min, and 1 mg/min for further 15 min. Continuous EEG monitoring was performed by a neurophysiologic system with electrodes placed at F3, F4, C3, C4, O1, O2, Cz, and Fp1 (10/20 system) and using the Narcotrend Index. Sedation was assessed clinically by using the Modified Observer's Assessment of Alertness and Sedation scale. Pharmacodynamic models were developed for selected EEG variables and Narcotrend Index.

EEG changes during remimazolam infusion were characterized by an initial increase in beta frequency band and a late increase in delta frequency band. The EEG beta ratio showed a prediction probability of Modified Observer's Assessment of Alertness and Sedation score of 0.79, and could be modeled successfully using a standard sigmoid Emax model. Narcotrend Index showed a prediction probability of Modified Observer's Assessment of Alertness and Sedation score of 0.74. The time course of Narcotrend Index was described by an extended sigmoid Emax model with two sigmoid terms and different plasma-effect equilibration times.

Beta ratio was identified as a suitable EEG variable for monitoring remimazolam sedation. Narcotrend Index appeared less suitable than the beta ratio for monitoring the sedative effect if remimazolam is administered alone.

Lung Ultrasound in Emergency and Critically Ill Patients: Number of Supervised Exams to Reach Basic Competence.

Anesthesiology

Transthoracic ultrasound may be clinically useful, but training is not standardized, and it remains unclear when naïve trainees have sufficient competency to perform exams unsupervised WHAT THIS ARTICLE TELLS US THAT IS NEW: A multicenter, international study was conducted in 10 intensive care units among residents and staff in anesthesiology, critical care, emergency medicine, and internal medicine who underwent supervised training, to determine the number of exams required to achieve basic competenceAfter 25 supervised examinations, 80% of lung regions were adequately classified by traineesUltrasound exam average duration was 8 to 10 min in experts and decreased from 19 (after 5 exams) to 12 min (after 25 exams) in trainees BACKGROUND:: Lung ultrasound is increasingly used in critically ill patients as an alternative to bedside chest radiography, but the best training method remains uncertain. This study describes a training curriculum allowing trainees to acquire basic competence.

This multicenter, prospective, and educational study was conducted in 10 Intensive Care Units in Brazil, China, France and Uruguay. One hundred residents, respiratory therapists, and critical care physicians without expertise in transthoracic ultrasound (trainees) were trained by 18 experts. The main study objective was to determine the number of supervised exams required to get the basic competence, defined as the trainees' ability to adequately classify lung regions with normal aeration, interstitial-alveolar syndrome, and lung consolidation. An initial 2-h video lecture provided the rationale for image formation and described the ultrasound patterns commonly observed in critically ill and emergency patients. Each trainee performed 25 bedside ultrasound examinations supervised by an expert. The progression in competence was assessed every five supervised examinations. In a new patient, 12 pulmonary regions were independently classified by the trainee and the expert.

Progression in competence was derived from the analysis of 7,330 lung regions in 2,562 critically ill and emergency patients. After 25 supervised examinations, 80% of lung regions were adequately classified by trainees. The ultrasound examination mean duration was 8 to 10 min in experts and decreased from 19 to 12 min in trainees (after 5 vs. 25 supervised examinations). The median training duration was 52 (42, 82) days.

A training curriculum including 25 transthoracic ultrasound examinations supervised by an expert provides the basic skills for diagnosing normal lung aeration, interstitial-alveolar syndrome, and consolidation in emergency and critically ill patients.

Mild Acute Kidney Injury after Noncardiac Surgery Is Associated with Long-term Renal Dysfunction: A Retrospective Cohort Study.

Anesthesiology

Perioperative acute kidney injury is commonIt is unclear whether this merely represents a transient increase in creatinine or has prognostic value WHAT THIS ARTICLE TELLS US THAT IS NEW: Patients with mild postoperative kidney injury (stage I) after noncardiac surgery had an estimated 2.4 times higher odds of having long-term renal dysfunction compared with patients without postoperative kidney injuryA quarter of patients who had stage I acute kidney injury postoperatively still had stage I kidney injury 1 to 2 yr later, and an additional 11% had even worse renal function BACKGROUND:: Perioperative acute kidney injury is common. However, it is unclear whether this merely represents a transient increase in creatinine or has prognostic value. Therefore, the long-term clinical importance of mild postoperative acute kidney injury remains unclear. This study assessed whether adults who do and do not experience mild kidney injury after noncardiac surgery are at similar risk for long-term renal injury.

This study is a retrospective cohort analysis of adults having noncardiac surgery at the Cleveland Clinic who had preoperative, postoperative, and long-term (1 to 2 yr after surgery) plasma creatinine measurements. The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) initiative criteria. The primary analysis was for lack of association between postoperative kidney injury (stage I vs. no injury) and long-term renal injury.

Among 15,621 patients analyzed, 3% had postoperative stage I kidney injury. Long-term renal outcomes were not similar in patients with and without postoperative stage I injury. Specifically, about 26% of patients with stage I postoperative kidney injury still had mild injury 1 to 2 yr later, and 11% had even more severe injury. A full third (37%) of patients with stage I kidney injury therefore had renal injury 1 to 2 yr after surgery. Patients with postoperative stage I injury had an estimated 2.4 times higher odds of having long-term renal dysfunction (KDIGO stage I, II, or III) compared with patients without postoperative kidney injury (odds ratio [95% CI] of 2.4 [2.0 to 3.0]) after adjustment for potential confounding factors.

In adults recovering from noncardiac surgery, even small postoperative increases in plasma creatinine, corresponding to stage I kidney injury, are associated with renal dysfunction 1 to 2 yr after surgery. Even mild postoperative renal injury should therefore be considered a clinically important perioperative outcome.

Anesthetic Management Using Multiple Closed-loop Systems and Delayed Neurocognitive Recovery: A Randomized Controlled Trial.

Anesthesiology

Cognitive changes after anesthesia and surgery represent a significant public health concern. We tested the hypothesis that, in patients 60 yr or older scheduled for noncardiac surgery, automated management of anesthetic depth, cardiac blood flow, and protective lung ventilation using three independent controllers would outperform manual control of these variables. Additionally, as a result of the improved management, patients in the automated group would experience less postoperative neurocognitive impairment compared to patients having standard, manually adjusted anesthesia.

In this single-center, patient-and-evaluator-blinded, two-arm, parallel, randomized controlled, superiority study, 90 patients having noncardiac surgery under general anesthesia were randomly assigned to one of two groups. In the control group, anesthesia management was performed manually while in the closed-loop group, the titration of anesthesia, analgesia, fluids, and ventilation was performed by three independent controllers. The primary outcome was a change in a cognition score (the 30-item Montreal Cognitive Assessment) from preoperative values to those measures 1 week postsurgery. Secondary outcomes included a battery of neurocognitive tests completed at both 1 week and 3 months postsurgery as well as 30-day postsurgical outcomes.

Forty-three controls and 44 closed-loop patients were assessed for the primary outcome. There was a difference in the cognition score compared to baseline in the control group versus the closed-loop group 1 week postsurgery (-1 [-2 to 0] vs. 0 [-1 to 1]; difference 1 [95% CI, 0 to 3], P = 0.033). Patients in the closed-loop group spent less time during surgery with a Bispectral Index less than 40, had less end-tidal hypocapnia, and had a lower fluid balance compared to the control group.

Automated anesthetic management using the combination of three controllers outperforms manual control and may have an impact on delayed neurocognitive recovery. However, given the study design, it is not possible to determine the relative contribution of each controller on the cognition score.

Timing of β-Blocker Reintroduction and the Occurrence of Postoperative Atrial Fibrillation after Cardiac Surgery: A Prospective Cohort Study.

Anesthesiology

For cardiac surgery patients under chronic β-blocker therapy, guidelines recommend their early postoperative reintroduction to decrease the incidence of postoperative atrial fibrillation. The authors hypothesized that the timing of β-blocker reintroduction affects their effectiveness on the incidence of postoperative atrial fibrillation.

This multicenter prospective French cohort study included patients on β-blockers (more than 30 days before surgery) in sinus rhythm without a pacemaker. The primary outcome, time sequence of β-blocker reintroduction, was analyzed for 192 h after surgery. The secondary outcome, relationship between the occurrence of postoperative atrial fibrillation and timing of β-blocker reintroduction, was analyzed based on pre- and intraoperative predictors (full and selected sets) according to landmark times (patients in whom atrial fibrillation occurred before a given landmark time were not analyzed).

Of 663 patients, β-blockers were reintroduced for 532 (80%) but for only 261 (39%) patients in the first 48 h after surgery. Median duration before reintroduction was 49.5 h (95% CI, 48 to 51.5 h). Postoperative atrial fibrillation or death (N = 4) occurred in 290 (44%) patients. After performing a landmark analysis to take into account the timing of β-blocker reintroduction, the adjusted odds ratios (95% CI) for predictor full and selected (increased age, history of paroxysmal atrial fibrillation, and duration of aortic cross clamping) sets for the occurrence of postoperative atrial fibrillation were: adjusted odds ratio (full) = 0.87 (0.58 to 1.32; P = 0.517) and adjusted odds ratio (selected) = 0.84 (0.58 to 1.21; P = 0.338) at 48 h; adjusted odds ratio (full) = 0.64 (0.39 to 1.05; P = 0.076) and adjusted odds ratio (selected) = 0.58 (0.38 to 0.89; P = 0.013) at 72 h; adjusted odds ratio (full) = 0.58 (0.31 to 1.07; P = 0.079) and adjusted odds ratio (selected) = 0.53 (0.31 to 0.91; P = 0.021) at 96 h.

β-Blockers were reintroduced early (after less than 48 h) in fewer than half of the cardiac surgery patients. Reintroduction decreased postoperative atrial fibrillation occurrence only at later time points and only in the predictor selected set model. These results are an incentive to optimize (timing, doses, or titration) β-blocker reintroduction after cardiac surgery.

Correlation of Thromboelastography with Apparent Rivaroxaban Concentration: Has Point-of-Care Testing Improved?

Anesthesiology

Concern remains over reliable point-of-care testing to guide reversal of rivaroxaban, a commonly used factor Xa inhibitor, in high-acuity settings. Thromboelastography (TEG), a point-of-care viscoelastic assay, may have the ability to detect the anticoagulant effect of rivaroxaban. The authors ascertained the association of apparent rivaroxaban concentration with thromboelastography reaction time, i.e., time elapsed from blood sample placement in analyzer until beginning of clot formation, as measured using TEG and TEG6S instruments (Haemonetics Corporation, USA), hypothesizing that reaction time would correlate to degree of functional factor Xa impairment.

The authors prospectively performed a diagnostic accuracy study comparing coagulation assays to apparent (i.e., indirectly assessed) rivaroxaban concentration in trauma patients with and without preinjury rivaroxaban presenting to a single center between April 2016 and July 2018. Blood samples at admission and after reversal or 24 h postadmission underwent TEG, TEG6S, thrombin generation assay, anti-factor Xa chromogenic assay, prothrombin time (PT), and ecarin chromogenic assay testing. The authors determined correlation of kaolin TEG, TEG6S, and prothrombin time to apparent rivaroxaban concentration. Receiver operating characteristic curve compared capacity to distinguish therapeutic rivaroxaban concentration (i.e., greater than or equal to 50 ng/ml) from nontherapeutic concentrations.

Eighty rivaroxaban patients were compared to 20 controls. Significant strong correlations existed between rivaroxaban concentration and TEG reaction time (ρ = 0.67; P < 0.001), TEG6S reaction time (ρ = 0.68; P < 0.001), and prothrombin time (ρ = 0.73; P < 0.001), however reaction time remained within the defined normal range for the assay. Rivaroxaban concentration demonstrated strong but not significant association with coagulation assays postreversal (n = 9; TEG reaction time ρ = 0.62; P = 0.101; TEG6S reaction time ρ = 0.57; P = 0.112) and small nonsignificant association for controls (TEG reaction time: ρ = -0.04; P = 0.845; TEG6S reaction time: ρ = -0.09; P = 0.667; PT-neoplastine: ρ = 0.19; P = 0.301). Rivaroxaban concentration (area under the curve, 0.91) and TEG6S reaction time (area under the curve, 0.84) best predicted therapeutic rivaroxaban concentration and exhibited similar receiver operating characteristic curves (P = 0.180).

Although TEG6S demonstrates significant strong correlation with rivaroxaban concentration, values within normal range limit clinical utility rendering rivaroxaban concentration the gold standard in measuring anticoagulant effect.

Associations of Intraoperative Radial Arterial Systolic, Diastolic, Mean, and Pulse Pressures with Myocardial and Acute Kidney Injury after Noncardiac Surgery: A Retrospective Cohort Analysis.

Anesthesiology

Arterial pressure is a complex signal that can be characterized by systolic, mean, and diastolic components, along with pulse pressure (difference between systolic and diastolic pressures). The authors separately evaluated the strength of associations among intraoperative pressure components with myocardial and kidney injury after noncardiac surgery.

The authors included 23,140 noncardiac surgery patients at Cleveland Clinic who had blood pressure recorded at 1-min intervals from radial arterial catheters. The authors used univariable smoothing and multivariable logistic regression to estimate probabilities of each outcome as function of patients' lowest pressure for a cumulative 5 min for each component, comparing discriminative ability using C-statistics. The authors further assessed the association between outcomes and both area and minutes under derived thresholds corresponding to the beginning of increased risk for the average patient.

Out of 23,140 patients analyzed, myocardial injury occurred in 6.1% and acute kidney injury in 8.2%. Based on the lowest patient blood pressure experienced for greater than or equal to 5 min, estimated thresholds below which the odds of myocardial or kidney injury progressively increased (slope P < 0.001) were 90 mmHg for systolic, 65 mmHg for mean, 50 mmHg for diastolic, and 35 mmHg for pulse pressure. Weak discriminative ability was noted between the pressure components, with univariable C-statistics ranging from 0.55 to 0.59. Area under the curve in the highest (deepest) quartile of exposure below the respective thresholds had significantly higher odds of myocardial injury after noncardiac surgery and acute kidney injury compared to no exposure for systolic, mean, and pulse pressure (all P < 0.001), but not diastolic, after adjusting for confounding.

Systolic, mean, and pulse pressure hypotension were comparable in their strength of association with myocardial and renal injury. In contrast, the relationship with diastolic pressure was poor. Baseline factors were much more strongly associated with myocardial and renal injury than intraoperative blood pressure, but pressure differs in being modifiable.

Static and Dynamic Transpulmonary Driving Pressures Affect Lung and Diaphragm Injury during Pressure-controlled versus Pressure-support Ventilation in Experimental Mild Lung Injury in Rats.

Anesthesiology

Pressure-support ventilation may worsen lung damage due to increased dynamic transpulmonary driving pressure. The authors hypothesized that, at the same tidal volume (VT) and dynamic transpulmonary driving pressure, pressure-support and pressure-controlled ventilation would yield comparable lung damage in mild lung injury.

Male Wistar rats received endotoxin intratracheally and, after 24 h, were ventilated in pressure-support mode. Rats were then randomized to 2 h of pressure-controlled ventilation with VT, dynamic transpulmonary driving pressure, dynamic transpulmonary driving pressure, and inspiratory time similar to those of pressure-support ventilation. The primary outcome was the difference in dynamic transpulmonary driving pressure between pressure-support and pressure-controlled ventilation at similar VT; secondary outcomes were lung and diaphragm damage.

At VT = 6 ml/kg, dynamic transpulmonary driving pressure was higher in pressure-support than pressure-controlled ventilation (12.0 ± 2.2 vs. 8.0 ± 1.8 cm H2O), whereas static transpulmonary driving pressure did not differ (6.7 ± 0.6 vs. 7.0 ± 0.3 cm H2O). Diffuse alveolar damage score and gene expression of markers associated with lung inflammation (interleukin-6), alveolar-stretch (amphiregulin), epithelial cell damage (club cell protein 16), and fibrogenesis (metalloproteinase-9 and type III procollagen), as well as diaphragm inflammation (tumor necrosis factor-α) and proteolysis (muscle RING-finger-1) were comparable between groups. At similar dynamic transpulmonary driving pressure, as well as dynamic transpulmonary driving pressure and inspiratory time, pressure-controlled ventilation increased VT, static transpulmonary driving pressure, diffuse alveolar damage score, and gene expression of markers of lung inflammation, alveolar stretch, fibrogenesis, diaphragm inflammation, and proteolysis compared to pressure-support ventilation.

In the mild lung injury model use herein, at the same VT, pressure-support compared to pressure-controlled ventilation did not affect biologic markers. However, pressure-support ventilation was associated with a major difference between static and dynamic transpulmonary driving pressure; when the same dynamic transpulmonary driving pressure and inspiratory time were used for pressure-controlled ventilation, greater lung and diaphragm injury occurred compared to pressure-support ventilation.