Complication Rates of Central Venous Catheters: A Systematic Review and Meta-Analysis.

Importance: Central venous catheters (CVCs) are commonly used but are associated with complications. Quantifying complication rates is essential for guiding CVC utilization decisions. Objective: To summarize current rates of CVC-associated complications. Data Sources: MEDLINE, Embase, CINAHL, and CENTRAL databases were searched for observational studies and randomized clinical trials published between 2015 to 2023. Study Selection: This study included English-language observational studies and randomized clinical trials of adult patients that reported complication rates of short-term centrally inserted CVCs and data for 1 or more outcomes of interest. Studies that evaluated long-term intravascular devices, focused on dialysis catheters not typically used for medication administration, or studied catheters placed by radiologists were excluded. Data Extraction and Synthesis: Two reviewers independently extracted data and assessed risk of bias. Bayesian random-effects meta-analysis was applied to summarize event rates. Rates of placement complications (events/1000 catheters with 95% credible interval [CrI]) and use complications (events/1000 catheter-days with 95% CrI) were estimated. Main Outcomes and Measures: Ten prespecified complications associated with CVC placement (placement failure, arterial puncture, arterial cannulation, pneumothorax, bleeding events requiring action, nerve injury, arteriovenous fistula, cardiac tamponade, arrhythmia, and delay of ≥1 hour in vasopressor administration) and 5 prespecified complications associated with CVC use (malfunction, infection, deep vein thrombosis [DVT], thrombophlebitis, and venous stenosis) were assessed. The composite of 4 serious complications (arterial cannulation, pneumothorax, infection, or DVT) after CVC exposure for 3 days was also assessed. Results: Of 11 722 screened studies, 130 were included in the analyses. Seven of 15 prespecified complications were meta-analyzed. Placement failure occurred at 20.4 (95% CrI, 10.9-34.4) events per 1000 catheters placed. Other rates of CVC placement complications (per 1000 catheters) were arterial canulation (2.8; 95% CrI, 0.1-10), arterial puncture (16.2; 95% CrI, 11.5-22), and pneumothorax (4.4; 95% CrI, 2.7-6.5). Rates of CVC use complications (per 1000 catheter-days) were malfunction (5.5; 95% CrI, 0.6-38), infection (4.8; 95% CrI, 3.4-6.6), and DVT (2.7; 95% CrI, 1.0-6.2). It was estimated that 30.2 (95% CrI, 21.8-43.0) in 1000 patients with a CVC for 3 days would develop 1 or more serious complication (arterial cannulation, pneumothorax, infection, or DVT). Use of ultrasonography was associated with lower rates of arterial puncture (risk ratio [RR], 0.20; 95% CrI, 0.09-0.44; 13.5 events vs 68.8 events/1000 catheters) and pneumothorax (RR, 0.25; 95% CrI, 0.08-0.80; 2.4 events vs 9.9 events/1000 catheters). Conclusions and Relevance: Approximately 3% of CVC placements were associated with major complications. Use of ultrasonography guidance may reduce specific risks including arterial puncture and pneumothorax.

Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.

Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Effects of mobility dose on discharge disposition in critically ill stroke patients.

BACKGROUND: Mobilization in the intensive care unit (ICU) has the potential to improve patient outcomes following acute stroke. The optimal duration and intensity of mobilization for patients with hemorrhagic or ischemic stroke in the ICU remain unclear. OBJECTIVE: To assess the effect of mobilization dose in the ICU on adverse discharge disposition in patients after stroke. DESIGN: This is an international, prospective, observational cohort study of critically ill stroke patients (November 2017-September 2019). Duration and intensity of mobilization was quantified daily by the mobilization quantification score (MQS). SETTING: Patients requiring ICU-level care were enrolled within 48 hours of admission at four separate academic medical centers (two in Europe, two in the United States). PARTICIPANTS: Participants included individuals (>18 years old) admitted to an ICU within 48 hours of ischemic or hemorrhagic stroke onset who were functionally independent at baseline. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome was adverse discharge disposition. RESULTS: Of the patients screened, 163 were eligible for inclusion in the study. One patient was subsequently excluded due to insufficient data collection (n = 162). The dose of mobilization varied greatly between centers and patients, which could not be explained by patients' comorbidities or disease severity. High dose of mobilization (mean MQS > 7.3) was associated with a lower likelihood of adverse discharge (adjusted odds ratio, [aOR]: 0.14; 95% confidence interval [CI]: 0.06-0.31; p < .01). CONCLUSION: The increased use of mobilization acutely in the ICU setting may improve patient outcomes.

Cost-Utility of Rhegmatogenous Retinal Detachment Repair With Pars Plana Vitrectomy, Scleral Buckle, and Pneumatic Retinopexy: A Microsimulation Model.

PURPOSE: To assess the cost-effectiveness of primary noncomplex rhegmatogenous retinal detachment (RRD) repair, comparing 3 different strategies, pars plana vitrectomy (PPV), scleral buckle (SB), and pneumatic retinopexy (PnR) from the health care payer perspective over a lifetime. DESIGN: Model-based cost-utility analysis. METHODS: A simulated cohort of 100,000 adult patients (≥18 years old) requiring primary noncomplex RRD repair in theoretical surgical centers in the United States. Quality-adjusted life years (QALYs), lifetime costs (2022 United States dollars), and the incremental cost-effectiveness ratio (ICER) of the 3 interventions were projected over a lifetime horizon, with a cost-effectiveness threshold of ≤$50,000 per gained QALY. RESULTS: Based on inputted parameters, the primary anatomical success was highest for PPV (95.00%) compared to SB (91.76%) and PnR (63.41%). The QALYs associated with PPV, SB, and PnR were (11.87, SD 1.62), (11.84, SD 1.63), and (11.59, SD 1.72), respectively. The incurred lifetime costs of RRD repair and associated postoperative surgeries for PPV, SB, and PnR were $4445.72 (SD 655.75), $4518.04 (662.92), and $3978.45 (728.50), respectively. Parameter-level simulations suggested that PPV was most likely to be the most cost-effective therapy compared to SB and PnR beyond a threshold of $3000/QALY. The incremental cost-effectiveness ratio for PPV compared to PnR was $1693.54. SB was dominant in all scenarios. Threshold analyses indicated that the success rate of PnR would have to be 100% and/or the cost would have to be $2000 or less over lifetime for it to be more cost-effective than PPV. CONCLUSIONS: This study found PPV to be the most cost-effective primary procedure for RRD repair at a threshold of $50,000/QALY gained over a lifetime horizon from the health care payer perspective.

Comparative Effectiveness of Fludrocortisone and Hydrocortisone vs Hydrocortisone Alone Among Patients With Septic Shock.

Importance: Patients with septic shock may benefit from the initiation of corticosteroids. However, the comparative effectiveness of the 2 most studied corticosteroid regimens (hydrocortisone with fludrocortisone vs hydrocortisone alone) is unclear. Objective: To compare the effectiveness of adding fludrocortisone to hydrocortisone vs hydrocortisone alone among patients with septic shock using target trial emulation. Design, Setting, and Participants: This retrospective cohort study from 2016 to 2020 used the enhanced claims-based Premier Healthcare Database, which included approximately 25% of US hospitalizations. Participants were adult patients hospitalized with septic shock and receiving norepinephrine who began hydrocortisone treatment. Data analysis was performed from May 2022 to December 2022. Exposure: Addition of fludrocortisone on the same calendar day that hydrocortisone treatment was initiated vs use of hydrocortisone alone. Main Outcome and Measures: Composite of hospital death or discharge to hospice. Adjusted risk differences were calculated using doubly robust targeted maximum likelihood estimation. Results: Analyses included 88 275 patients, 2280 who began treatment with hydrocortisone-fludrocortisone (median [IQR] age, 64 [54-73] years; 1041 female; 1239 male) and 85 995 (median [IQR] age, 67 [57-76] years; 42 136 female; 43 859 male) who began treatment with hydrocortisone alone. The primary composite outcome of death in hospital or discharge to hospice occurred among 1076 (47.2%) patients treated with hydrocortisone-fludrocortisone vs 43 669 (50.8%) treated with hydrocortisone alone (adjusted absolute risk difference, -3.7%; 95% CI, -4.2% to -3.1%; P < .001). Conclusions and Relevance: In this comparative effectiveness cohort study among adult patients with septic shock who began hydrocortisone treatment, the addition of fludrocortisone was superior to hydrocortisone alone.

Prevalence and association of non-medical cannabis use with post-procedural healthcare utilisation in patients undergoing surgery or interventional procedures: a retrospective cohort study.

Background: There is paucity of data regarding prevalence and key harms of non-medical cannabis use in surgical patients. We investigated whether cannabis use in patients undergoing surgery or interventional procedures patients was associated with a higher degree of post-procedural healthcare utilisation. Methods: 210,639 adults undergoing non-cardiac surgery between January 2008 and June 2020 at an academic healthcare network in Massachusetts, USA, were included. The primary exposure was use of cannabis, differentiated by reported ongoing non-medical use, self-identified during structured, preoperative nursing/physician interviews, or diagnosis of cannabis use disorder based on International Classification of Diseases, 9th/10th Revision, diagnostic codes. The main outcome measure was the requirement of advanced post-procedural healthcare utilisation (unplanned intensive care unit admission, hospital re-admission or non-home discharge). Findings: 16,211 patients (7.7%) were identified as cannabis users. The prevalence of cannabis use increased from 4.9% in 2008 to 14.3% by 2020 (p < 0.001). Patients who consumed cannabis had higher rates of psychiatric comorbidities (25.3 versus 16.8%; p < 0.001) and concomitant non-tobacco substance abuse (30.2 versus 7.0%; p < 0.001). Compared to non-users, patients with a diagnosis of cannabis use disorder had higher odds of requiring advanced post-procedural healthcare utilisation after adjusting for patient characteristics, concomitant substance use and socioeconomic factors (aOR [adjusted odds ratio] 1.16; 95% CI 1.02-1.32). By contrast, patients with ongoing non-medical cannabis use had lower odds of advanced post-procedural healthcare utilisation (aOR 0.87; 95% CI 0.81-0.92, compared to non-users). Interpretation: One in seven patients undergoing surgery or interventional procedures in 2020 reported cannabis consumption. Differential effects on post-procedural healthcare utilisation were observed between patients with non-medical cannabis use and cannabis use disorder. Funding: This work was supported by an unrestricted philantropic grant from Jeff and Judy Buzen to Maximilian S. Schaefer.

Subjective Assessment of Motor Function by the Bedside Nurses in Mechanically Ventilated Surgical Intensive Care Unit Patients Predicts Tracheostomy.

OBJECTIVE: In many institutions, intensive care unit (ICU) nurses assess their patients' muscle function as part of their routine bedside examination. We tested the research hypothesis that this subjective examination of muscle function prior to extubation predicts tracheostomy requirement. METHODS: Adult, mechanically ventilated patients admitted to 7 ICUs at Beth Israel Deaconess Medical Center (BIDMC) between 2008 and 2019 were included in this observational study. Assessment of motor function was performed every four hours by ICU nurses. Multivariable logistic regression analysis controlled for acute disease severity, delirium risk assessment through the confusion assessment method for the ICU (CAM-ICU), and pre-defined predictors of extubation failure was applied to examine the association of motor function and tracheostomy within 30 days after extubation. RESULTS: Within 30 days after extubation, 891 of 9609 (9.3%) included patients required a tracheostomy. The inability to spontaneously move and hold extremities against gravity within 24 h prior to extubation was associated with significantly higher odds of 30-day tracheostomy (adjusted OR 1.56, 95% CI 1.27-1.91, p < 0.001, adjusted absolute risk difference (aARD) 2.8% (p < 0.001)). The effect was magnified among patients who were mechanically ventilated for >7 days (aARD 21.8%, 95% CI 12.4-31.2%, p-for-interaction = 0.015). CONCLUSIONS: ICU nurses' subjective assessment of motor function is associated with 30-day tracheostomy risk, independent of known risk factors. Muscle function measurements by nursing staff in the ICU should be discussed during interprofessional rounds.

How We Escalate Vasopressor and Corticosteroid Therapy in Patients With Septic Shock.

Septic shock is defined by the need for vasopressor agents to correct hypotension and lactic acidosis resulting from infection, with 30%-40% case fatality rates. The care of patients with worsening septic shock involves multiple treatment decisions involving vasopressor choices and adjunctive treatments. In this edition of "How I Do It", we provide a case-based discussion of common clinical decisions regarding choice of first-line vasopressor, BP targets, route of vasopressor delivery, use of secondary vasopressors, and adjunctive medications. We also consider diagnostic approaches, treatment, and monitoring strategies for the patient with worsening shock, as well as approaches to difficult weaning of vasopressors.

Prolonged mechanical ventilation after cardiac surgery: substudy of the Transfusion Requirements in Cardiac Surgery III trial.

PURPOSE: Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications. METHODS: Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored. RESULTS: Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications. CONCLUSION: In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial.

RéSUMé: OBJET: La ventilation mécanique (VM) prolongée est une complication majeure après chirurgie cardiaque. Nous avons effectué une analyze secondaire de l'étude TRICS III sur les besoins de transfusion au cours de la chirurgie cardiaque pour décrire la durée de la VM, identifier les facteurs associés à une VM prolongée et examiner les associations de la VM prolongée avec la mortalité et les complications. MéTHODES: Quatre mille huit cent neuf participants subissant une chirurgie cardiaque dans 71 hôpitaux à travers le monde ont été inclus. La VM prolongée a été définie à partir de la définition de la Society of Thoracic Surgeons comme un événement durant 24 heures ou plus. Des associations ajustées de facteurs liés aux patients et à la chirurgie avec la VM prolongée ont été examinées en utilisant une régression logistique multifactorielle. Des associations de la VM prolongée avec des complications ont été évaluées en utilisant des rapports de cotes; les associations ajustées entre VM prolongée et mortalité ont été évaluées au moyen d'une régression multinominale. Les associations d'une VM de plus courte durée avec la survie et des complications ont été explorées. RéSULTATS: La VM prolongée est survenue chez 15 % (725/4 809) des participants. Une VM prolongée a été associée à des facteurs chirurgicaux indicateurs de complexité (comme une chirurgie cardiaque antérieure, la durée de la circulation extracorporelle et les tentatives de débranchement) et à des facteurs liés au patient (comme un état préopératoire critique, une défaillance ventriculaire gauche, une insuffisance rénale et une hypertension pulmonaire). La VM prolongée a été associée à des complications périopératoires, mais pas à des complications à long terme. Après ajustement pour le risque, la VM prolongée a été associée à la mortalité périopératoire; son association avec la mortalité à long terme des survivants a été plus faible. Les durées plus courtes de VM n'ont pas été associées à une augmentation du risque de mortalité ou à des complications. CONCLUSION: Dans cette étude auxiliaire de l'essai TRICS III, la VM prolongée a été fréquente après chirurgie cardiaque et a été associée à des facteurs de risque liés au patient et à la chirurgie. Bien que la VM prolongée ait présenté de fortes associations avec les complications périopératoires et la mortalité, elle n'a pas été associée avec des complications à long terme et était plus faiblement associée à la mortalité à long terme parmi les survivants. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT02042898); enregistrée le 23 janvier 2014. Il s'agit d'une étude auxiliaire de l'étude TRICS III sur les besoins de transfusion en chirurgie cardiaque.

First-Line Vasopressor Use in Septic Shock and Route of Administration: An Epidemiologic Study.

Rationale: Norepinephrine is a first-line agent for the treatment of hypotension in septic shock. However, its frequency of use and potential barriers to its use are unclear. Objectives: To evaluate the frequency of use of norepinephrine in septic shock, to identify potential barriers to its use, and to evaluate trends in use of vasopressors over time. Methods: We conducted a retrospective population-based cohort study of patients with septic shock in Alberta, Canada, between July 1, 2012, and December 31, 2018. The primary outcome was receipt of a first-line vasopressor other than norepinephrine ("nonnorepinephrine vasopressor"). Predictors of receiving a nonnorepinephrine vasopressor were assessed using a multivariable-adjusted, multilevel logistic regression model with intensive care unit as a random effect. Results: Among 6,343 patients with septic shock, the proportion of patients receiving nonnorepinephrine vasopressors as first-line treatment decreased steadily from 11.5% in 2012 to 3.0% in 2018. Two factors most strongly associated with their receipt were having peripheral intravenous access only (adjusted odds ratio [aOR], 6.15; 95% confidence interval [CI], 4.58-8.26; P < 0.001) and year of admission (aOR, 0.74 per year after 2012; 95% CI, 0.69-0.80; P < 0.001). Other factors that had associations after adjustment included admission to a nonteaching hospital (aOR, 2.19; 95% CI, 1.23-3.89; P = 0.007), admission to a coronary care unit (aOR, 2.56; 95% CI, 1.001-6.54; P = 0.05), Sequential Organ Failure Assessment score (aOR, 0.92 per unit increase; 95% CI, 0.88-0.96; P < 0.001), and heart rate (aOR, 0.92 per 10-beat per minute increase; 95% CI, 0.87-0.97; P = 0.002). Conclusions: In a large cohort of patients in Alberta, Canada, we found a steady decrease in use of first-line vasopressors other than norepinephrine in septic shock. The strongest factor associated with their use was the presence of only peripheral venous access, suggesting that this may still be considered a barrier to administration of norepinephrine.

Association between intraoperative tidal volume and postoperative respiratory complications is dependent on respiratory elastance: a retrospective, multicentre cohort study.

BACKGROUND: The impact of high vs low intraoperative tidal volumes on postoperative respiratory complications remains unclear. We hypothesised that the effect of intraoperative tidal volume on postoperative respiratory complications is dependent on respiratory system elastance. METHODS: We retrospectively recorded tidal volume (Vt; ml kg-1 ideal body weight [IBW]) in patients undergoing elective, non-cardiothoracic surgery from hospital registry data. The primary outcome was respiratory failure (requiring reintubation within 7 days of surgery, desaturation after extubation, or both). The primary exposure was defined as the interaction between Vt and standardised respiratory system elastance (driving pressure divided by Vt; cm H2O/[ml kg-1]). Multivariable logistic regression models, with and without interaction terms (which categorised Vt as low [Vt ≤8 ml kg-1] or high [Vt >8 ml kg-1]), were adjusted for potential confounders. Additional analyses included path mediation analysis and fractional polynomial modelling. RESULTS: Overall, 10 821/197 474 (5.5%) patients sustained postoperative respiratory complications. Higher Vt was associated with greater risk of postoperative respiratory complications (adjusted odds ratio=1.42 per ml kg-1; 95% confidence interval [CI], 1.35-1.50]; P<0.001). This association was modified by respiratory system elastance (P<0.001); in patients with low compliance (<42.4 ml cm H2O-1), higher Vt was associated with greater risk of postoperative respiratory complications (adjusted risk difference=0.3% [95% CI, 0.0-0.5] at 41.2 ml cm H2O-1 compliance, compared with 5.8% [95% CI, 3.8-7.8] at 14 ml cm H2O-1 compliance). This association was absent when compliance exceeded 41.2 ml cm H2O-1. Adverse effects associated with high Vt were entirely mediated by driving pressures (P<0.001). CONCLUSIONS: The association of harm with higher tidal volumes during intraoperative mechanical ventilation is modified by respiratory system elastance. These data suggest that respiratory elastance should inform the design of perioperative trials testing intraoperative ventilatory strategies.

Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study From a New England Health Care Network.

OBJECTIVES: To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to -3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients who received a high proportion of deep sedation using benzodiazepine compared with propofol-based sedation (adjusted absolute difference, -1.17 d; 95% CI, -0.64 to -1.69; p < 0.001). This differential effect was magnified in elderly patients (age > 65) and in patients with liver or kidney failure (p-for-interaction < 0.001) but not observed in patients who received a low proportion of deep sedation (p = 0.95). GABAergic-induced deep sedation days during mechanical ventilation was a better predictor of post-extubation delirium than the GABAergic daily average effective dose (area under the curve 0.76 vs 0.69; p < 0.001). CONCLUSIONS: Deep sedation during mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.