Intravitreal Injections: Improving Sustainability by Reducing Clinical Waste. / Intravitreale Injektionen: Nachhaltigkeit durch Reduktion von Klinikabfall.

BACKGROUND: Intravitreal injections are one of the most commonly performed ophthalmic procedures. It is estimated that over 1 million intravitreal injections are performed in Germany annually. The aim of this study was to quantify the waste and carbon footprint associated with single-use injection sets, and to establish a waste reduction strategy. MATERIAL AND METHODS: The clinical waste and associated carbon footprint from standard disposable injection sets used by tertiary referral centres in Germany (n = 6) and the United Kingdom (n = 2) were assessed. The safety of performing intravitreal injections with a minimalistic material-sparing approach was evaluated. RESULTS: The average weight of an injection set (and hence the waste generated from each injection) was 165 g. On average, each injection set comprised 145 g (88%) of plastic, 2.1 g (1.3%) of metal, 4.3 g (2.6%) of paper, and 12.9 g (7.8%) of gauze/swabs. The production of such injection sets was extrapolated to a CO2 equivalent of 752.6 tonnes (t), and the incineration of the resulting waste to a CO2 equivalent of 301.7 t. For 1 million injections, this equates to 145.2 t of plastic, 2.1 t of metal, 4.3 t of paper, and 12.9 t of gauze/swabs. A material-sparing approach can reduce injection set-associated waste by 99% without necessarily compromising patient safety. CONCLUSION: A resource-saving approach to intravitreal injections can minimise the generation of clinical waste and its associated carbon footprint, thereby supporting sustainability.

Respiration and rapid eye movement (REM) sleep substructure: short versus long episodes.

Rapid eye movement (REM) sleep in rodents is defined by the presence of theta rhythm in the absence of movement. The amplitude and frequency of theta oscillations have been used to distinguish between tonic and phasic REM sleep. However, tonic REM sleep has not been further subdivided, although characteristics of network oscillations such as cross-frequency coupling between theta and gamma vary within this sub-state. Recently, it has been shown that theta-gamma coupling depends on an optimal breathing rate of ~5 Hz. The frequency of breathing varies strongly throughout REM sleep, and the duration of single REM sleep episodes ranges from several seconds to minutes, whereby short episodes predominate. Here we studied the relation between breathing frequency, accelerometer activity, and the length of REM sleep periods. We found that small movements detected with three-dimensional accelerometry positively correlate with breathing rate. Interestingly, breathing is slow in short REM sleep episodes, while faster respiration regimes exclusively occur after a certain delay in longer REM sleep episodes. Thus, merging REM sleep episodes of different lengths will result in a predominance of slow respiration due to the higher occurrence of short REM sleep periods. Moreover, our results reveal that not only do phasic REM sleep epochs predominantly occur during long REM sleep episodes, but that the long episodes also have faster theta and higher gamma activity. These observations suggest that REM sleep can be further divided from a physiological point of view depending on its duration. Higher levels of arousal during REM sleep, indicated by higher breathing rates, can only be captured in long REM sleep episodes.

Effects of Ketamine Infusion on Breathing and Encephalography in Spontaneously Breathing ICU Patients.

BACKGROUND: Preclinical studies suggest that ketamine stimulates breathing. We investigated whether adding a ketamine infusion at low and high doses to propofol sedation improves inspiratory flow and enhances sedation in spontaneously breathing critically ill patients. METHODS: In this prospective interventional study, twelve intubated, spontaneously breathing patients received ketamine infusions at 5 mcg/kg/min, followed by 10 mcg/kg/min for 1 h each. Airway flow, pressure, and esophageal pressure were recorded during a spontaneous breathing trial (SBT) at baseline, and during the SBT conducted at the end of each ketamine infusion regimen. SBT consisted of one-minute breathing with zero end-expiratory pressure and no pressure support. Changes in inspiratory flow at the pre-specified time points were assessed as the primary outcome. Ketamine-induced change in beta-gamma electroencephalogram power was the key secondary endpoint. We also analyzed changes in other ventilatory parameters respiratory timing, and resistive and elastic inspiratory work of breathing. RESULTS: Ketamine infusion of 5 and 10 mcg/kg/min increased inspiratory flow (median, IQR) from 0.36 (0.29-0.46) L/s at baseline to 0.47 (0.32-0.57) L/s and 0.44 (0.33-0.58) L/s, respectively (p = .013). Resistive work of breathing decreased from 0.4 (0.1-0.6) J/l at baseline to 0.2 (0.1-0.3) J/l after ketamine 10 mcg/kg/min (p = .042), while elastic work of breathing remained unchanged. Electroencephalogram beta-gamma power (19-44 Hz) increased compared to baseline (p < .01). CONCLUSIONS: In intubated, spontaneously breathing patients receiving a constant rate of propofol, ketamine increased inspiratory flow, reduced inspiratory work of breathing, and was associated with an "activated" electroencephalographic pattern. These characteristics might facilitate weaning from mechanical ventilation.

Capsule Dynamics, Implantation, and Explantation of the Smaller Incision, New-Generation Implantable Miniature Telescope: a Miyake-Apple Study.

PURPOSE: The smaller incision, new-generation implantable miniature telescope is a novel implant to optimize vision in retinal patients with central vision loss. Using Miyake-Apple techniques we visualized the device implantation, repositioning, and explantation, while noting capsular bag dynamics. METHODS: Using the Miyake-Apple technique, we assessed capsular bag deformation after successful implantation of the device in human autopsy eyes. We assessed rescue strategies for converting a sulcus implantation to a capsular implantation and explantation strategies. We noted the occurrence of posterior capsule striae, zonular stress, and the haptics' arc of contact with the capsular bag after implantation. RESULTS: Acceptable zonular stress was observed during the successful implantation of the SING IMT. When it was implanted in the sulcus, one could reposition the haptics into the bag with two spatulas using counter-pressure in an effective strategy despite inducing tolerable, medium zonular stress. A similar technique, in reverse, allows safe explantation without damaging the rhexis or the bag, while inducing similar medium, tolerable zonular stress. In all eyes we examined, the implant considerably stretches the bag, inducing a capsular bag deformation and posterior capsule striae. CONCLUSION: The SING IMT can be safely implanted without significant zonular stress. In sulcus implantation and explantation, repositioning of the haptic is achievable without perturbing zonular stress using the presented approaches. It stretches average-sized capsular bags to support its weight. This is achieved by an increased arc of contact of the haptics with the capsular equator.

Temporal Relations between Cortical Network Oscillations and Breathing Frequency during REM Sleep.

Nasal breathing generates a rhythmic signal which entrains cortical network oscillations in widespread brain regions on a cycle-to-cycle time scale. It is unknown, however, how respiration and neuronal network activity interact on a larger time scale: are breathing frequency and typical neuronal oscillation patterns correlated? Is there any directionality or temporal relationship? To address these questions, we recorded field potentials from the posterior parietal cortex of mice together with respiration during REM sleep. In this state, the parietal cortex exhibits prominent θ and γ oscillations while behavioral activity is minimal, reducing confounding signals. We found that the instantaneous breathing frequency strongly correlates with the instantaneous frequency and amplitude of both θ and γ oscillations. Cross-correlograms and Granger causality revealed specific directionalities for different rhythms: changes in θ activity precede and Granger-cause changes in breathing frequency, suggesting control by the functional state of the brain. On the other hand, the instantaneous breathing frequency Granger causes changes in γ frequency, suggesting that γ is influenced by a peripheral reafference signal. These findings show that changes in breathing frequency temporally relate to changes in different patterns of rhythmic brain activity. We hypothesize that such temporal relations are mediated by a common central drive likely to be located in the brainstem.

THE NOVEL USE OF HIGH-FLOW POLYIMIDE CANNULAS TO IMPROVE SILICONE OIL INJECTABILITY IN VITREORETINAL SURGERY.

PURPOSE: The injection of high-viscosity silicone oil lengthens injection time. New polyimide cannulas offer a greater inner diameter than conventional metal cannulas at the same gauge. We compared the injection time for polyimide and metal cannulas at 23 G for a variety of silicone oils including a 12,500-mPas prototype oil. METHODS: In this laboratory study, injection time was measured three times per cannula and per oil. Warming the oil before injection to up to 42°C was also evaluated. Finally, the feasibility of polyimide cannulas was tested in vitrectomized porcine eyes. RESULTS: The 23-G polyimide cannula mostly decreased injection times. The time to inject 5 mL of Siluron Xtra and Siluron 5000 decreased by 6:02 (76.9%) minutes (483 vs. 121 seconds) and 12:01 (74.7%) minutes (973 vs. 252 seconds), respectively. Although the 23-G metal cannula failed to inject 12,500 mPas oil, 5 mL was injected in 10:21 minutes using the polyimide cannula. Prewarming Siluron 5000 to 42°C lowered the injection time by 9.0% and by 12.1% when using the metal or polyimide cannula, respectively. CONCLUSION: Polyimide cannulas allow a clinically relevant decrease in injection time. They may not only shorten surgery time but could also ease the use of next-generation ultra-high-viscosity silicone oils. Prewarming silicone oil leads to decreased injection times.

Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network.

OBJECTIVES: Two previously published trials (ARDS et Curarisation Systematique [ACURASYS] and Reevaluation of Systemic Early Neuromuscular Blockade [ROSE]) presented equivocal evidence on the effect of neuromuscular blocking agent infusions in patients with acute respiratory distress syndrome (acute respiratory distress syndrome). The sedation regimen differed between these trials and also within the ROSE trial between treatment and control groups. We hypothesized that the proportion of deeper sedation is a mediator of the effect of neuromuscular blocking agent infusions on mortality. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Intubated and mechanically ventilated ICU patients with acute respiratory distress syndrome (Berlin definition) admitted between January 2008 until June 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The proportion of deeper sedation was defined as days with nonlight sedation as a fraction of mechanical ventilation days in the ICU after acute respiratory distress syndrome diagnosis. Using clinical data obtained from a hospital network registry, 3,419 patients with acute respiratory distress syndrome were included, of whom 577 (16.9%) were treated with neuromuscular blocking agent infusions, for a mean (sd) duration of 1.8 (±1.9) days. The duration of deeper sedation was prolonged in patients receiving neuromuscular blocking agent infusions (4.6 ± 2.2 d) compared with patients without neuromuscular blocking agent infusions (2.4 ± 2.2 d; p < 0.001). The proportion of deeper sedation completely mediated the negative effect of neuromuscular blocking agent infusions on in-hospital mortality (p < 0.001). Exploratory analysis in patients who received deeper sedation revealed a beneficial effect of neuromuscular blocking agent infusions on mortality (49% vs 51%; adjusted odds ratio, 0.80; 95% CI, 0.63-0.99, adjusted absolute risk difference, -0.05; p = 0.048). CONCLUSIONS: In acute respiratory distress syndrome patients who receive neuromuscular blocking agent infusions, a prolonged, high proportion of deeper sedation is associated with increased mortality. Our data support the view that clinicians should minimize the duration of deeper sedation after recovery from neuromuscular blocking agent infusion.

Supraglottic airway device versus tracheal intubation and the risk of emergent postoperative intubation after general anaesthesia in adults: a retrospective cohort study.

BACKGROUND: We examined the association between emergent postoperative tracheal intubation and the use of supraglottic airway devices (SGAs) vs tracheal tubes. METHODS: We included data from adult noncardiac surgical cases under general anaesthesia between 2008 and 2018. We only included cases (n=59 991) in which both airways were deemed to be feasible options. Multivariable logistic regression, instrumental variable analysis, propensity matching, and mediation analysis were used. RESULTS: Use of a tracheal tube was associated with a higher risk of emergent postoperative intubation (adjusted absolute risk difference [ARD]=0.80%; 95% confidence interval (CI), 0.64-0.97; P<0.001), and a higher risk of post-extubation hypoxaemia (ARD=3.9%; 95% CI, 3.4-4.4; P<0.001). The effect was modified by the use of non-depolarising neuromuscular blocking agents (NMBAs); mediation analyses revealed that 28.9% (95% CI, 14.4-43.4%; P<0.001) of the main effect was attributable to NMBA. Airway management modified the association of NMBA and risk of emergent postoperative intubation (Pinteraction=0.02). Patients managed with an SGA had higher odds of NMBA-associated reintubation compared to patients managed with a tracheal tube (adjusted odds ratio [aOR]=3.65, 95% CI, 1.99-6.67 vs aOR=1.68, 95% CI, 1.29-2.18 [P<0.001], respectively). CONCLUSIONS: In patients undergoing procedures under general anaesthesia that could be managed with either SGA or tracheal tube, use of an SGA was associated with lower risk of emergent postoperative intubation. The effect can partly be explained by use of NMBAs. Use of NMBAs in patients with an SGA appears to increase the risk of emergent postoperative intubation.

A Tool to Predict Readmission to the Intensive Care Unit in Surgical Critical Care Patients-The RISC Score.

BACKGROUND: Readmission to the Intensive Care Unit (ICU) is associated with a high risk of in-hospital mortality and higher health care costs. Previously published tools to predict ICU readmission in surgical ICU patients have important limitations that restrict their clinical implementation. We sought to develop a clinically intuitive score that can be implemented to predict readmission to the ICU after surgery or trauma. We designed the score to emphasize modifiable predictors. METHODS: In this retrospective cohort study, we included surgical patients requiring critical care between June 2015 and January 2019 at Beth Israel Deaconess Medical Center, Harvard Medical School, MA, USA. We used logistic regression to fit a prognostic model for ICU readmission from a priori defined, widely available candidate predictors. The score performance was compared with existing prediction instruments. RESULTS: Of 7,126 patients, 168 (2.4%) were readmitted to the ICU during the same hospitalization. The final score included 8 variables addressing demographical factors, surgical factors, physiological parameters, ICU treatment and the acuity of illness. The maximum score achievable was 13 points. Potentially modifiable predictors included the inability to ambulate at ICU discharge, substantial positive fluid balance (>5 liters), severe anemia (hemoglobin <7 mg/dl), hyperglycemia (>180 mg/dl), and long ICU length of stay (>5 days). The score yielded an area under the receiver operating characteristic curve of 0.78 (95% CI 0.74-0.82) and significantly outperformed previously published scores. The performance of the underlying model was confirmed by leave-one-out cross-validation. CONCLUSION: The RISC-score is a clinically intuitive prediction instrument that helps identify surgical ICU patients at high risk for ICU readmission. The simplicity of the score facilitates its clinical implementation across surgical divisions.

Discharge Prediction for Patients Undergoing Inpatient Surgery: Development and validation of the DEPENDENSE score.

BACKGROUND: A substantial proportion of patients undergoing inpatient surgery each year is at risk for postoperative institutionalization and loss of independence. Reliable individualized preoperative prediction of adverse discharge can facilitate advanced care planning and shared decision making. METHODS: Using hospital registry data from previously home-dwelling adults undergoing inpatient surgery, we retrospectively developed and externally validated a score predicting adverse discharge. Multivariable logistic regression analysis and bootstrapping were used to develop the score. Adverse discharge was defined as in-hospital mortality or discharge to a skilled nursing facility. The model was subsequently externally validated in a cohort of patients from an independent hospital. RESULTS: In total, 106 164 patients in the development cohort and 92 962 patients in the validation cohort were included, of which 16 624 (15.7%) and 7717 (8.3%) patients experienced adverse discharge, respectively. The model was predictive of adverse discharge with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI 0.87-0.88) in the development cohort and an AUC of 0.86 (95% CI 0.86-0.87) in the validation cohort. CONCLUSION: Using preoperatively available data, we developed and validated a prediction instrument for adverse discharge following inpatient surgery. Reliable prediction of this patient centered outcome can facilitate individualized operative planning to maximize value of care.

The association of nitrous oxide on length of stay in the postanesthesia care unit: a retrospective observational study.

PURPOSE: To assess whether intraoperative use of nitrous oxide (N2O) as an adjunct to general anesthesia is associated with a shorter length of stay in the postanesthesia care unit (PACU). METHODS: We analyzed data from adult patients who underwent non-cardiothoracic surgery under general anesthesia between May 2008 and December 2018. We assessed the association between intraoperative low- and high-dose N2O and PACU length of stay. RESULTS: A total of 148,284 patients were included in the primary analysis. After adjusting for a priori defined confounders, a high dose of N2O significantly decreased PACU length of stay, with a calculated difference of -9.1 min (95% confidence interval [CI], -10.5 to -7.7; P < 0.001). Patients who received high-dose N2O had a lower incidence of both short- and prolonged-duration of intraoperative hypotension (adjusted odds ratio [aOR], 0.85; 95% CI, 0.83 to 0.88; P < 0.001 and aOR, 0.76; 95% CI, 0.73 to 0.80; P < 0.001, respectively) and received a lower total intraoperative vasopressor dose (-0.04 mg of norepinephrine equivalents; 95% CI, -0.06 to -0.01; P = 0.01). The effect of high-dose N2O on PACU length of stay was modified by surgical complexity (adjusted absolute difference: -26.1 min; 95% CI, -29.2 to -23.1; P < 0.001; P for interaction < 0.001), and most pronounced in patients who underwent complex surgery and received intraoperative antiemetic therapy (adjusted absolute difference: -38.9 min; 95% CI, -43.1 to -34.6; P < 0.001; P for interaction < 0.001). CONCLUSIONS: Nitrous oxide was dose-dependently associated with a decreased PACU length of stay. The effect was clinically relevant (> 30 min difference) in patients who underwent complex surgical procedures and received intraoperative antiemetic therapy.

RéSUMé: OBJECTIF: L'objectif de cette étude était de déterminer si l'utilisation peropératoire de protoxyde d'azote (N2O) en complément à l'anesthésie générale était associée à une durée de séjour écourtée en salle de réveil (SDR). MéTHODE: Nous avons analysé les données de patients adultes qui ont subi une chirurgie non cardiothoracique sous anesthésie générale entre mai 2008 et décembre 2018. Nous avons évalué l'association entre une faible dose et une dose élevée de N2O peropératoire et la durée du séjour en SDR. RéSULTATS: Au total, 148 284 patients ont été inclus dans notre analyse primaire. Après ajustement tenant compte des facteurs de confusion définis a priori, une dose élevée de N2O a considérablement écourté la durée du séjour en salle de réveil, avec une différence calculée de −9,1 min (intervalle de confiance [IC] à 95 %, −10,5 à −7,7 ; P < 0,001). Chez les patients ayant reçu une dose élevée de N2O, l'incidence d'hypotension peropératoire de courte ou plus longue durée était plus faible (rapport de cotes ajusté [RCA], 0,85; IC 95 %, 0,83 à 0,88; P < 0,001 et RCA, 0,76; IC 95 %, 0,73 à 0,80; P < 0,001, respectivement); en outre, ces patients ont reçu une dose totale de vasopresseurs peropératoires inférieure (−0,04 mg d'équivalents de norépinéphrine; IC 95 %, −0,06 à −0,01; P = 0,01). L'effet d'une dose élevée de N2O sur la durée du séjour en SDR a été modifié par la complexité de la chirurgie (différence absolue ajustée : −26,1 min; IC 95 %, −29,2 à −23,1; P < 0,001; P pour l'interaction < 0,001), et était le plus prononcé chez les patients ayant subi une chirurgie complexe et reçu un traitement antiémétique peropératoire (différence absolue ajustée : −38,9 min; IC 95 %, −43,1 à −34,6; P < 0,001; P pour l'interaction < 0,001). CONCLUSION: Le protoxyde d'azote a été associé de façon dose-dépendante à une réduction de la durée du séjour en SDR. L'effet était cliniquement pertinent (différence > 30 minutes) chez les patients qui subissaient des interventions chirurgicales complexes et recevaient un traitement antiémétique peropératoire.

Development of an Instrument for Preoperative Prediction of Adverse Discharge in Patients Scheduled for Cardiac Surgery.

OBJECTIVE: Inability of home discharge occurs in nearly a third of patients undergoing cardiac surgery and is associated with increased mortality. The authors aimed to evaluate the incidence and risk factors for adverse discharge disposition (ADD) after cardiac surgery and develop a prediction tool for preoperative risk assessment. DESIGN: This retrospective cohort study included adult patients undergoing cardiac surgery between 2010 and 2018. The primary outcome was ADD, defined as in-hospital mortality, discharge to a skilled nursing facility, or transfer to a long-term care hospital. The authors created a prediction tool using stepwise backward logistic regression and used 5-fold and leave-one-out cross-validation. SETTING: University hospital network. PARTICIPANTS: Adult patients living at home prior to surgery, who underwent coronary artery bypass grafting and/or valve procedures at the authors' institution. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 3,760 patients were included in the final study cohort. The observed rate of ADD was 33.3%. The prediction model showed good discrimination and accuracy, with C-statistic of 0.78 (95% confidence interval [CI] 0.76-0.79) and unmodified Brier score of 0.177 (reliability 0.001). The final model comprised 14 predictors. Patients who experienced ADD were more likely to be older, of female sex, to have had higher length of hospital stay prior to surgery, and to have undergone emergency surgery. CONCLUSIONS: The authors present an instrument for prediction of loss of the ability to live independently in patients undergoing cardiac surgery. The authors' score may be useful in identifying high-risk patients such that earlier coordination of care can be initiated in this vulnerable patient population.

What Factors Predict Adverse Discharge Disposition in Patients Older Than 60 Years Undergoing Lower-extremity Surgery? The Adverse Discharge in Older Patients after Lower-extremity Surgery (ADELES) Risk Score.

BACKGROUND: Adverse discharge disposition, which is discharge to a long-term nursing home or skilled nursing facility is frequent and devastating in older patients after lower-extremity orthopaedic surgery. Predicting individual patient risk allows for preventive interventions to address modifiable risk factors and helps managing expectations. Despite a variety of risk prediction tools for perioperative morbidity in older patients, there is no tool available to predict successful recovery of a patient's ability to live independently in this highly vulnerable population. QUESTIONS/PURPOSES: In this study, we asked: (1) What factors predict adverse discharge disposition in patients older than 60 years after lower-extremity surgery? (2) Can a prediction instrument incorporating these factors be applied to another patient population with reasonable accuracy? (3) How does the instrument compare with other predictions scores that account for frailty, comorbidities, or procedural risk alone? METHODS: In this retrospective study at two competing New England university hospitals and Level 1 trauma centers with 673 and 1017 beds, respectively; 83% (19,961 of 24,095) of patients 60 years or older undergoing lower-extremity orthopaedic surgery were included. In all, 5% (1316 of 24,095) patients not living at home and 12% (2797 of 24,095) patients with missing data were excluded. All patients were living at home before surgery. The mean age was 72 ± 9 years, 60% (11,981 of 19,961) patients were female, 21% (4155 of 19,961) underwent fracture care, and 34% (6882 of 19,961) underwent elective joint replacements. Candidate predictors were tested in a multivariable logistic regression model for adverse discharge disposition in a development cohort of all 14,123 patients from the first hospital, and then included in a prediction instrument that was validated in all 5838 patients from the second hospital by calculating the area under the receiver operating characteristics curve (ROC-AUC).Thirty-eight percent (5360 of 14,262) of patients in the development cohort and 37% (2184 of 5910) of patients in the validation cohort had adverse discharge disposition. Score performance in predicting adverse discharge disposition was then compared with prediction scores considering frailty (modified Frailty Index-5 or mFI-5), comorbidities (Charlson Comorbidity Index or CCI), and procedural risks (Procedural Severity Scores for Morbidity and Mortality or PSS). RESULTS: After controlling for potential confounders like BMI, cardiac, renal and pulmonary disease, we found that the most prominent factors were age older than 90 years (10 points), hip or knee surgery (7 or 8 points), fracture management (6 points), dementia (5 points), unmarried status (3 points), federally provided insurance (2 points), and low estimated household income based on ZIP code (1 point). Higher score values indicate a higher risk of adverse discharge disposition. The score comprised 19 variables, including socioeconomic characteristics, surgical management, and comorbidities with a cutoff value of ≥ 23 points. Score performance yielded an ROC-AUC of 0.85 (95% confidence interval 0.84 to 0.85) in the development and 0.72 (95% CI 0.71 to 0.73) in the independent validation cohort, indicating excellent and good discriminative ability. Performance of the instrument in predicting adverse discharge in the validation cohort was superior to the mFI-5, CCI, and PSS (ROC-AUC 0.72 versus 0.58, 0.57, and 0.57, respectively). CONCLUSION: The Adverse Discharge in Older Patients after Lower Extremity Surgery (ADELES) score predicts adverse discharge disposition after lower-extremity surgery, reflecting loss of the ability to live independently. Its discriminative ability is better than instruments that consider frailty, comorbidities, or procedural risk alone. The ADELES score identifies modifiable risk factors, including general anesthesia and prolonged preoperative hospitalization, and should be used to streamline patient and family expectation management and improve shared decision making. Future studies need to evaluate the score in community hospitals and in institutions with different rates of adverse discharge disposition and lower income. A non-commercial calculator can be accessed at www.adeles-score.org. LEVEL OF EVIDENCE: Level III, diagnostic study.

Ventilatory frequency during intraoperative mechanical ventilation and postoperative pulmonary complications: a hospital registry study.

BACKGROUND: High ventilatory frequencies increase static lung strain and possibly lung stress by shortening expiratory time, increasing intrathoracic pressure, and causing dynamic hyperinflation. We hypothesised that high intraoperative ventilatory frequencies were associated with postoperative respiratory complications. METHODS: In this retrospective hospital registry study, we analysed data from adult non-cardiothoracic surgical cases performed under general anaesthesia with mechanical ventilation at a single centre between 2005 and 2017. We assessed the association between intraoperative ventilatory frequency (categorised into four groups) and postoperative respiratory complications, defined as composite of invasive mechanical ventilation within 7 days after surgery or peripheral oxygen desaturation after extubation, using multivariable logistic regression. In a subgroup, we adjusted analyses for arterial blood gas parameters. RESULTS: A total of 102 632 cases were analysed. Intraoperative ventilatory frequencies ranged from a median (inter-quartile range [IQR]) of 8 (8-9) breaths min-1 (Group 1) to 15 (14-18) breaths min-1 (Group 4). High ventilatory frequencies were associated with higher odds of postoperative respiratory complications (adjusted odds ratio=1.26; 95% confidence interval, 1.14-1.38; P<0.001), which was confirmed in a subgroup after adjusting for arterial partial pressure of carbon dioxide and the ratio of arterial oxygen partial pressure to fractional inspired oxygen. We identified considerable variability in the use of high ventilatory frequencies attributable to individual provider preference (ranging from 22% to 88%) and temporal change; however, the association with postoperative respiratory complications remained unaffected. CONCLUSIONS: High intraoperative ventilatory frequency was associated with increased risk of postoperative respiratory complications, and increased postoperative healthcare utilisation.

Succinylcholine and postoperative pulmonary complications: a retrospective cohort study using registry data from two hospital networks.

BACKGROUND: Neuromuscular blocking agents (NMBAs) with a non-depolarising mechanism of action carry the risk of postoperative residual paralysis and are associated with postoperative pulmonary complications (POPC). Owing to the shorter duration of action, the depolarising NMBA succinylcholine may be associated with less postoperative residual paralysis, and hence fewer POPC. We tested the association of succinylcholine administration during anaesthesia and POPC. METHODS: In a retrospective cohort study of registry data from two large US academic medical centres, 244 850 adult noncardiac surgical patients undergoing general anaesthesia were included. The primary outcome was POPC, defined as post-extubation haemoglobin oxygen de-saturation to <90%, or re-intubation requiring intensive care unit admission within 7 days after surgery. The association between succinylcholine and POPC and its dose-dependency were tested in a hierarchical fashion using a multivariable logistic regression model. RESULTS: A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [ORAdj]=1.11; 95% confidence interval [CI], 1.06-1.16; P<0.001; adjusted risk=5.18%; 95% CI, 5.06-5.30 without and 5.69%; 95% CI, 5.53-5.85 with succinylcholine), with a dose-dependent relationship (ORAdj=1.08; 95% CI, 1.05-1.11 per mg kg-1; P<0.001). In patients receiving non-depolarising NMBAs, succinylcholine further increased the risk of POPC (ORAdj=1.08; 95% CI, 1.03-1.14; P=0.001). The association between succinylcholine and POPC was modified (P=0.03 for interaction) by the duration of surgery with higher odds of POPC in patients undergoing surgeries of <2 vs ≥2 h (ORAdj=1.24; 95% CI, 1.15-1.33 and 1.05; 95% CI, 1.00-1.10, respectively). CONCLUSIONS: In contrast to our prediction, succinylcholine administration was associated with an increased risk of POPC. This association was dose-dependent and magnified in surgeries of shorter duration.

Forward Light Scattering of the Vitreous Gel After Enzymatic Aging: An In Vitro Model to Study Vitreous Opacification.

Purpose: Symptomatic vitreous opacifications, so-called floaters, are difficult to objectively assess majorly limiting the possibility of in vitro studies. Forward light scattering was found previously to be increased in eyes with symptomatic floaters. Using an objective setup to measure forward light scattering, we studied the effects of enzymatically digesting the components of the vitreous body on straylight to develop an in vitro model of vitreous opacifications. Methods: Fifty-seven porcine vitreous bodies were digested using hyaluronidase, collagenase, trypsin, and bromelain, as well as using a combination of hyaluronidase + collagenase and hyaluronidase + bromelain. A modified C-Quant setup was used to objectively assess forward light scattering. Results: Depletion of hyaluronic acid majorly increased vitreous straylight (mean increase 34.4 deg2/sr; P = 0.01), whereas primarily digesting the vitreous gel with collagenase or trypsin did not significantly affect straylight. When collagenase or bromelain is applied in hyaluronic acid depleted vitreous gels, the increase in forward light scattering is reversed partially. Conclusions: The age-related loss of hyaluronic acid primarily drives the increase in vitreous gel straylight induced by conglomerates of collagen. This process can be reversed partially by digesting collagen. This in vitro model allows the objective quantification and statistical comparison of straylight burden caused by vitreous opacities and, thus, can serve as a first testing ground for pharmacological therapies, as demonstrated with bromelain.

In Vitro Physicochemical and Pharmacokinetic Properties of Bevacizumab Dissolved in Silicone Oils Compared to Hydrogel-Substitutes and Porcine Vitreous Bodies.

Anti-VEGF agents, e.g., bevacizumab, are used in retinal surgery, while their interaction with silicone oils and novel hydrogels remains unclear. This study examines the in vitro pharmacokinetics of bevacizumab in silicone oil-filled eyes compared to various hydrogel replacements and the porcine vitreous body as well as its impact on the interface tension of silicone oils. An in vitro model filled with light or heavy silicone oil, porcine vitreous bodies, or hydrogels (alginate and polyethylene glycol (PEG)-based) was equilibrated with a balanced salt solution. Monitoring of bevacizumab in the aqueous phase was conducted for up to 24 h, and its effect on interfacial tension was studied. Significant differences in bevacizumab partitioning were observed across endotamponades after 24 h. In silicone oils, bevacizumab was found exclusively in the aqueous phase, while in the other endotamponades, it accumulated in the gel phase (96.1% in porcine vitreous body, 83.5% in alginate, and 27.6% in PEG-based hydrogel). Bevacizumab significantly reduced interfacial tension (40 to 8 mN/m), possibly enhancing silicone oil emulsification. The type of endotamponade heavily influenced the bevacizumab concentration in the aqueous. The vitreous body and replacement hydrogels likely serve as a drug reservoir, highlighting the need for in vivo studies to explore these interactions prior to clinical application.

Viscoelastic, Optical, and Surgical Properties of Vitreous Body Replacement Hydrogels After Aging Compared to Porcine Vitreous Bodies And Silicone Oils.

Purpose: First- (monomers), second- (pre-gelated), and third- (in situ gelating after injection) generation hydrogels were previously introduced to replace the vitreous body after vitrectomy surgery. In this study, we evaluated the surgical, optical, and viscoelastic properties of vitreous body replacement hydrogels before and after an accelerated aging protocol previously applied to intraocular implants. Methods: Measurements of injection force, removal speed using a clinically established vitrectomy setup, as well as evaluation of forward light scattering and viscoelastic properties before and after an accelerated aging protocol were conducted. Results were compared to porcine and human vitreous bodies, as well as currently clinically applied lighter- and heavier-than-water silicone oils. Results: Removal speed of all tested hydrogels is substantially lower than the removal speed of porcine vitreous body (0.2 g/min vs. 2.7 g/min for the best performing hydrogel and porcine vitreous body, respectively). Forward light scattering in second-generation vitreous body replacement hydrogels was higher after the aging process than the straylight of the average 70-year-old vitreous body (9.4 vs. 5.5 deg2/sr, respectively). The viscoelastic properties of all hydrogels did not change in a clinically meaningful manner; however, trends toward greater stiffness and greater elasticity after aging were apparent. Conclusions: This study demonstrates surgical weaknesses of the hydrogels that need to be addressed before clinical use, especially low removal speed. Pre-linked hydrogels (second-generation) showed inferior performance regarding surgical properties compared to in situ gelating hydrogels (third-generation). Translational Relevance: This study highlights possible pitfalls regarding surgical and optical properties when applying vitreous replacement hydrogels clinically.

Introducing Dynamic Stimulation Aberrometry: Binocular Objective Accommodation versus Subjective Measures.

Purpose: The objective measurement of binocular accommodation remains a challenge. The dynamic stimulation aberrometry (DSA) system uses wavefront measurements to dynamically assess accommodation. In this study, we sought to introduce this method in a large number of patients of varying age and compared it with the subjective push-up method as well as the historical results of Duane. Design: This study is an evaluation of diagnostic technology. Subjects: Ninety-one patients aged 20 to 67 years (70 healthy, phakic eyes and 21 myopic eyes after phakic intraocular lens implantation) were enrolled at a tertiary eye hospital. Methods: All patients underwent DSA measurements; the accommodative amplitude of 13 patients chosen at random was additionally examined using the subjective push-up method introduced by Duane. DSA measurements were also compared with Duane's historical results. Main Outcome Measures: Accommodative amplitude, dynamic parameters of accommodation, and near pupil motility. Results: Dynamic stimulation aberrometry allowed objective measurement of binocular accommodation, which decreased with age (e.g., 30-39 years vs. > 50 years; 3.8 ± 0.9 diopters [D] and 0.1 ± 0.4 D, respectively). Dynamic parameters, such as time delay of the commencement of accommodation after near target presentation, increased with age (0.26 ± 0.14 seconds for 20-30 years vs. 0.43 ± 0.15 seconds for 40-50 years, P = 0.0002). The objective accommodative amplitude was significantly smaller than Duane's historic results (P = 0.001) as well as the subjective push-up method. Dynamic stimulation aberrometry records pupil motility dynamically in parallel to wavefront measurements. Maximum pupil motility during accommodation significantly decreased with age (P = 0.0002). Maximum pupillary speed did not correlate significantly with age. Conclusions: Dynamic stimulation aberrometry allows objective, dynamic, binocular measurement of accommodation and pupil motility with high time resolution in subjects with accommodative amplitudes up to 7 D. This article introduces the method in a large study population and may serve as a control for further studies. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.