Efficiency of CONTRAfluran™ in reducing sevoflurane pollution from maintenance anaesthesia in minimal flow end-tidal control mode for laparoscopic surgery: Efficiency of CONTRAfluran™.

BACKGROUND: Recommendations exist that aim to mitigate the substantial ecological impact of anaesthesia. One option is to use anaesthetic gas capturing technology at anaesthesia workstation exhausts to harvest and recycle volatile agents. However, the efficiency of such technology is mainly unverified in vivo. METHODS: The efficiency of CONTRAfluran™ in capturing sevoflurane from an anaesthesia workstation exhaust (when set to minimal flow and end-tidal control mode) was evaluated in 70 adult patients scheduled for general or bariatric laparoscopic surgery. The weight of the sevoflurane vaporiser and CONTRAfluran canister was measured before and after each case, to calculate total sevoflurane consumption and retention. Retention was measured after the minimal flow maintenance phase and after the high flow washout phase. The total retention efficiency was the fraction of all consumed sevoflurane captured by the CONTRAfluran canister. The primary objective was to examine the retention efficiency of CONTRAfluran in a clinical surgical setting, where all feasible strategies to minimise sevoflurane consumption and optimise the efficacy of CONTRAfluran were utilised. The secondary objective was to analyse the correlation between mass transfer and the duration of the case. RESULTS: Mean (SD) volume of sevoflurane captured using CONTRAfluran was 4.82 (1.41) ml, representing 45% (95%CI 42-48%) of all sevoflurane administered. The highest amount of retention was found during the washout phase. Retention efficiency did not correlate with the duration of the case. CONCLUSIONS: Over half of the sevoflurane administered was not captured by the CONTRAfluran canister when minimal flow techniques were used, likely due to residual accumulation of sevoflurane in the patient after tracheal extubation or, to a lesser extent, due to ventilation system leakage. However, as every prevented emission is commendable, CONTRAfluran may be a potentially valuable tool for reducing the environmental footprint of sevoflurane-based anaesthesia.

Implementation of a Bayesian based advisory tool for target-controlled infusion of propofol using qCON as control variable.

This single blinded randomized controlled trial aims to assess whether the application of a Bayesian-adjusted CePROP (effect-site of propofol) advisory tool leads towards a more stringent control of the cerebral drug effect during anaesthesia, using qCON as control variable. 100 patients scheduled for elective surgery were included and randomized into a control or intervention group (1:1 ratio). In the intervention group the advisory screen was made available to the clinician, whereas it was blinded in the control group. The settings of the target-controlled infusion pumps could be adjusted at any time by the clinician. Cerebral drug effect was quantified using processed EEG (CONOX monitor, Fresenius Kabi, Bad Homburg, Germany). The time of qCON between the desired range (35-55) during anaesthesia maintenance was defined as our primary end point. Induction parameters and recovery times were considered secondary end points and coefficient of variance of qCON and CePROP was calculated in order to survey the extent of control towards the mean of the population. The desired range of qCON between 35 and 55 was maintained in 84% vs. 90% (p = 0.15) of the case time in the control versus intervention group, respectively. Secondary endpoints showed similar results in both groups. The coefficient of variation for CePROP was higher in the intervention group. The application of the Bayesian-based CePROP advisory system in this trial did not result in a different time of qCON between 35 and 55 (84 [21] vs. 90 [18] percent of the case time). Significant differences between groups were hard to establish, most likely due to a very high performance level in the control group. More extensive control efforts were found in the intervention group. We believe that this advisory tool could be a useful educational tool for novices to titrate propofol effect-site concentrations.

Neuromuscular end-point predictive capability of published rocuronium pharmacokinetic/pharmacodynamic models: An observational trial.

BACKGROUND: Objective neuromuscular monitoring remains the single most reliable method to ensure optimal perioperative neuromuscular management. Nevertheless, the prediction of clinical neuromuscular endpoints by means of Pharmacokinetic (PK) and Pharmacodynamic (PD) modelling has the potential to complement monitoring and improve perioperative neuromuscular management.s STUDY OBJECTIVE: The present study aims to assess the performance of published Rocuronium PK/PD models in predicting intraoperative Train-of-four (TOF) ratios when benchmarked against electromyographic TOF measurements. DESIGN: Observational trial. SETTING: Tertiary Belgian hospital, from August 2020 up to September 2021. PATIENTS AND INTERVENTIONS: Seventy-four patients undergoing general anaesthesia for elective surgery requiring the administration of rocuronium and subject to continuous EMG neuromuscular monitoring were included. PK/PD-simulated TOF ratios were plotted and synchronised with their measured electromyographic counterparts and their differences analysed by means of Predictive Error derivatives (Varvel criteria). MAIN RESULTS: Published rocuronium PK/PD models overestimated clinically registered TOF ratios. The models of Wierda, Szenohradszky, Cooper, Alvarez-Gomez and McCoy showed significant predictive consistency between themselves, displaying Median Absolute Performance Errors between 38% and 41%, and intra-individual differences (Wobble) between 14 and 15%. The Kleijn model outperformed the former with a lower Median Absolute Performance Error (16%, 95%CI [0.01; 57]) and Wobble (11%, 95%CI [0.01; 34]). All models displayed considerably wide 95% confidence intervals for all performance metrics, suggesting a significantly variable performance. CONCLUSIONS: Simulated TOF ratios based on published PK/PD models do not accurately predict real intraoperative TOF ratio dynamics. TRIAL REGISTRATION: NCT04518761 (clinicaltrials.gov), registered on 19 August 2020.

Urinary Biomarkers in a Living Donor Kidney Transplantation Cohort-Predictive Value on Graft Function.

Early non-invasive detection and prediction of graft function after kidney transplantation is essential since interventions might prevent further deterioration. The aim of this study was to analyze the dynamics and predictive value of four urinary biomarkers: kidney injury molecule-1 (KIM-1), heart-type fatty acid binding protein (H-FABP), N-acetyl-ß-D-glucosaminidase (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in a living donor kidney transplantation (LDKT) cohort. Biomarkers were measured up to 9 days after the transplantation of 57 recipients participating in the VAPOR-1 trial. Dynamics of KIM-1, NAG, NGAL, and H-FABP significantly changed over the course of 9 days after transplantation. KIM-1 at day 1 and NAG at day 2 after transplantation were significant predictors for the estimated glomerular filtration rate (eGFR) at various timepoints after transplantation with a positive estimate (p < 0.05), whereas NGAL and NAG at day 1 after transplantation were negative significant predictors (p < 0.05). Multivariable analysis models for eGFR outcome improved after the addition of these biomarker levels. Several donor, recipient and transplantation factors significantly affected the baseline of urinary biomarkers. In conclusion, urinary biomarkers are of added value for the prediction of graft outcome, but influencing factors such as the timing of measurement and transplantation factors need to be considered.

Utility of the SmartPilot® View advisory screen to improve anaesthetic drug titration and postoperative outcomes in clinical practice: a two-centre prospective observational trial.

BACKGROUND: The advisory system SmartPilot® View (Drägerwerk AG, Lübeck, Germany) provides real-time, demographically adjusted pharmacodynamic information throughout anaesthesia, including time course of effect-site concentrations of administered drugs and a measure of potency of the combined drug effect termed the "'Noxious Stimulation Response Index' (NSRI). This dual-centre, prospective, observational study assesses whether the availability of SmartPilot® View alters the behaviour of anaesthetic drug titration of anaesthetists and improves the Anaesthesia Quality Score (AQS; percentage of time spent with MAP 60-80 mm Hg and Bispectral Index [BIS] 40-60 [blinded]). METHODS: We recruited 493 patients scheduled for elective surgery in two university centres. A control group (CONTROL; n=170) was enrolled to observe drug titration in current practice. Thereafter, an intervention group was enrolled, for which SmartPilot® View was made available to optimise drug titration (SPV; n=188). The AQS, haemodynamic and hypnotic effects, recovery times, pain scores, and other parameters were compared between groups. RESULTS: There were 358 patients eligible for analysis. Anaesthesia quality score was similar between CONTROL and SPV (median AQS [Q1-Q3]) 25.3% [7.4-41.5%] and 22.2% [8.0-44.4%], respectively; P=0.898). Compared with CONTROL, SPV patients had less severe hypotension and hypertension, less BIS <40, faster tracheal extubation, and lower early postoperative pain scores. CONCLUSIONS: Adding SmartPilot® View information did not affect average drug titration behaviour. However, small improvements in control of MAP and BIS and early recovery suggest improved titration for some patients without increasing the risk of overdosing or underdosing. CLINICAL TRIAL REGISTRATION: NCT01467167.

Immune Modulatory Effects of Nonsteroidal Anti-inflammatory Drugs in the Perioperative Period and Their Consequence on Postoperative Outcome.

Nonsteroidal anti-inflammatory drugs are among the most commonly administered drugs in the perioperative period due to their prominent role in pain management. However, they potentially have perioperative consequences due to immune-modulating effects through the inhibition of prostanoid synthesis, thereby affecting the levels of various cytokines. These effects may have a direct impact on the postoperative outcome of patients since the immune system aims to restore homeostasis and plays an indispensable role in regeneration and repair. By affecting the immune response, consequences can be expected on various organ systems. This narrative review aims to highlight these potential immune system-related consequences, which include systemic inflammatory response syndrome, acute respiratory distress syndrome, immediate and persistent postoperative pain, effects on oncological and neurologic outcome, and wound, anastomotic, and bone healing.

Perioperative SARS-CoV-2 infections increase mortality, pulmonary complications, and thromboembolic events: A Dutch, multicenter, matched-cohort clinical study.

BACKGROUND: A direct comparison of severe acute respiratory syndrome coronavirus 2 positive patients with a severe acute respiratory syndrome coronavirus 2 negative control group undergoing an operative intervention during the current pandemic is lacking, and a reliable estimate of the assumed difference in morbidity and mortality between both patient categories remains unknown. METHODS: We included all consecutive patients with a confirmed pre- or postoperative severe acute respiratory syndrome coronavirus 2 positive status (operated in 27 hospitals) and negative control patients (operated in 4 hospitals) undergoing emergency or elective operations. A propensity score-matched comparison of clinical outcomes was performed between severe acute respiratory syndrome coronavirus 2 positive and negative tested patients (control group). Primary outcome was overall 30-day mortality rate between both groups. Main secondary outcomes were overall, pulmonary, and thromboembolic complications. RESULTS: In total, 161 severe acute respiratory syndrome coronavirus 2 positive and 342 control severe acute respiratory syndrome coronavirus 2 negative patients were included in this study. The 30-day overall postoperative mortality rate was greater in the severe acute respiratory syndrome coronavirus 2 positive cohort compared with the negative control group (16% vs 4% respectively; P = .007). After propensity score matching, the severe acute respiratory syndrome coronavirus 2 positive group consisted of 123 patients (median 70 years of age [interquartile range 59-77] and 55% male) were compared with 196 patients in the matched control group (median 69 years (interquartile range 58-75] and 53% male). The 30-day mortality rate and risk were greater in the severe acute respiratory syndrome coronavirus 2 positive group compared with the matched control group (12% vs 4%; P = .009 and odds ratio 3.4 [95% confidence interval 1.5-8.5]; P = .005, respectively). Overall, pulmonary and thromboembolic complications occurred more often in severe acute respiratory syndrome coronavirus 2 positive patients (P < .01). CONCLUSION: Patients diagnosed with perioperative severe acute respiratory syndrome coronavirus 2 have an increased risk of 30-day mortality, pulmonary complications, and thromboembolic events. These findings serve as an evidence-based argument to postpone elective surgery and selected emergency cases.

Improved haemodynamic stability and cerebral tissue oxygenation after induction of anaesthesia with sufentanil compared to remifentanil: a randomised controlled trial.

BACKGROUND: Balanced anaesthesia with propofol and remifentanil, compared to sufentanil, often decreases mean arterial pressure (MAP), heart rate (HR) and cardiac index (CI), raising concerns on tissue-oxygenation. This distinct haemodynamic suppression might be attenuated by atropine. This double blinded RCT, investigates if induction with propofol-sufentanil results in higher CI and tissue-oxygenation than with propofol-remifentanil and if atropine has more pronounced beneficial effects on CI and tissue-oxygenation in a remifentanil-based anaesthesia. METHODS: In seventy patients scheduled for coronary bypass grafting (CABG), anaesthesia was induced and maintained with propofol target controlled infusion (TCI) with a target effect-site concentration (Cet) of 2.0 µg ml- 1 and either sufentanil (TCI Cet 0.48 ng ml- 1) or remifentanil (TCI Cet 8 ng ml- 1). If HR dropped below 60 bpm, methylatropine (1 mg) was administered intravenously. Relative changes (∆) in MAP, HR, stroke volume (SV), CI and cerebral (SctO2) and peripheral (SptO2) tissue-oxygenation during induction of anaesthesia and after atropine administration were analysed. RESULTS: The sufentanil group compared to the remifentanil group showed significantly less decrease in MAP (∆ = - 23 ± 13 vs. -36 ± 13 mmHg), HR (∆ = - 5 ± 7 vs. -10 ± 10 bpm), SV (∆ = - 23 ± 18 vs. -35 ± 19 ml) and CI (∆ = - 0.8 (- 1.5 to - 0.5) vs. -1.5 (- 2.0 to - 1.1) l min- 1 m- 2), while SctO2 (∆ = 9 ± 5 vs. 6 ± 4%) showed more increase with no difference in ∆SptO2 (∆ = 8 ± 7 vs. 8 ± 8%). Atropine caused higher ∆HR (13 (9 to 19) vs. 10 ± 6 bpm) and ∆CI (0.4 ± 0.4 vs. 0.2 ± 0.3 l min- 1 m- 2) in sufentanil vs. remifentanil-based anaesthesia, with no difference in ∆MAP, ∆SV and ∆SctO2 and ∆SptO2. CONCLUSION: Induction of anaesthesia with propofol and sufentanil results in improved haemodynamic stability and higher SctO2 compared to propofol and remifentanil in patients having CABG. Administration of atropine might be useful to counteract or prevent the haemodynamic suppression associated with these opioids. TRIAL REGISTRATION: Clinicaltrials.gov on June 7, 2013 (trial ID: NCT01871935 ).

Influence of an "Electroencephalogram-Based" Monitor Choice on the Delay Between the Predicted Propofol Effect-Site Concentration and the Measured Drug Effect.

BACKGROUND: Clinicians can optimize propofol titration by using 2 sources of pharmacodynamic (PD) information: the predicted effect-site concentration for propofol (Ceprop) and the electroencephalographically (EEG) measured drug effect. Relation between these sources should be time independent, that is, perfectly synchronized. In reality, various issues corrupt time independency, leading to asynchrony or, in other words, hysteresis. This asynchrony can lead to conflicting information, making effective drug dosing challenging. In this study, we tried to quantify and minimize the hysteresis between the Ceprop (calculated using the Schnider model for propofol) and EEG measured drug effect, using nonlinear mixed-effects modeling (NONMEM). Further, we measured the influence of EEG-based monitor choice, namely Bispectral index (BIS) versus qCON index (qCON) monitor, on propofol PD hysteresis. METHODS: We analyzed the PD data from 165 patients undergoing propofol-remifentanil anesthesia for outpatient surgery. Drugs were administered using target-controlled infusion (TCI) pumps. Pumps were programmed with Schnider model for propofol and Minto model for remifentanil. We constructed 2 PD models (direct models) relating the Schnider Ceprop to the measured BIS and qCON monitor values. We quantified the models' misspecification due to hysteresis, on an individual level, using the root mean squared errors (RMSEs). Subsequently, we optimized the PD models' predictions by adding a lag term to both models (lag-time PD models) and quantified the optimization using the RMSE. RESULTS: There is a counterclockwise hysteresis between Ceprop and BIS/qCON values. Not accounting for this hysteresis results in a direct PD model with an effect-site concentration which produces 50% of the maximal drug effect (Ce50) of 6.24 and 8.62 µg/mL and RMSE (median and interquartile range [IQR]) of 9.38 (7.92-11.23) and 8.41(7.04-10.2) for BIS and qCON, respectively. Adding a modeled lag factor of 49 seconds to the BIS model and 53 seconds to the qCON model improved both models' prediction, resulting in similar Ce50 (3.66 and 3.62 µg/mL for BIS and qCON) and lower RMSE (median (IQR) of 7.87 (6.49-9.90) and 6.56 (5.28-8.57) for BIS and qCON. CONCLUSIONS: There is a significant "Ceprop versus EEG measured drug effect" hysteresis. Not accounting for it leads to conflicting PD information and false high Ce50 for propofol in both monitors. Adding a lag term improved the PD model performance, improved the "pump-monitor" synchrony, and made the estimates of Ce50 for propofol more realistic and less monitor dependent.

Effects of propofol and dexmedetomidine with and without remifentanil on serum cytokine concentrations in healthy volunteers: a post hoc analysis.

BACKGROUND: Anaesthetic agents are likely to alter circulating cytokine concentrations. Because preceding studies have not been able to exclude the contribution of surgical trauma, perioperative stress, or both to circulating cytokine concentrations, the effects of anaesthesia remain unclear. The aim of this study was to quantify serum cytokines in healthy volunteers administered i.v. anaesthetic agents in the absence of surgical trauma and perioperative stress. METHODS: Serum samples obtained during previous standardised studies from healthy volunteers were compared before and 6-8 h after induction of anaesthesia with propofol (n=31), propofol/remifentanil (n=30), dexmedetomidine (n=17) or dexmedetomidine/remifentanil (n=15). Anaesthetic regimens were standardised and volunteers did not undergo any surgical intervention. Serum concentrations of interleukin (IL)2, IL4, IL6, IL10, IL17, IL18, IL21, IL22, IL23, C-X-C motif ligand 8, interferon gamma, E-selectin, L-selectin, major histocompatibility complex class I chain-polypeptide-related sequence (MIC)A, MICB, Granzyme A, and Granzyme B were quantified using a multiplexed antibody-based assay (Luminex). RESULTS: Samples were obtained from volunteers of either sex aged 18-70 yr. After anaesthesia with propofol alone, concentrations of IL4 (P=0.012), IL6 (P=0.027), IL21 (P=0.035), IL22 (P=0.002), C-X-C motif ligand 8 (P=0.004), MICB (P=0.046), and Granzyme A (P=0.045) increased. After anaesthesia with propofol and remifentanil, IL17 (P=0.013), interferon gamma (P=0.003), and MICA (P=0.001) decreased, but IL6 (P=0.006) and L-selectin (P=0.001) increased. After dexmedetomidine alone, IL18 (P=0.002), L-selectin (P=0.017), E-selectin (P=0.002), and Granzyme B (P=0.023) decreased. After dexmedetomidine with remifentanil no changes were observed. CONCLUSIONS: In healthy volunteers not undergoing surgery, different i.v. anaesthesia regimens were associated with differential effects on circulating cytokines.

Ten years of the Helsinki Declaration on patient safety in anaesthesiology: An expert opinion on peri-operative safety aspects.

: Patient safety is an activity to mitigate preventable patient harm that may occur during the delivery of medical care. The European Board of Anaesthesiology (EBA)/European Union of Medical Specialists had previously published safety recommendations on minimal monitoring and postanaesthesia care, but with the growing public and professional interest it was decided to produce a much more encompassing document. The EBA and the European Society of Anaesthesiology (ESA) published a consensus on what needs to be done/achieved for improvement of peri-operative patient safety. During the Euroanaesthesia meeting in Helsinki/Finland in 2010, this vision was presented to anaesthesiologists, patients, industry and others involved in health care as the 'Helsinki Declaration on Patient Safety in Anaesthesiology'. In May/June 2020, ESA and EBA are celebrating the 10th anniversary of the Helsinki Declaration on Patient Safety in Anaesthesiology; a good opportunity to look back and forward evaluating what was achieved in the recent 10 years, and what needs to be done in the upcoming years. The Patient Safety and Quality Committee (PSQC) of ESA invited experts in their fields to contribute, and these experts addressed their topic in different ways; there are classical, narrative reviews, more systematic reviews, political statements, personal opinions and also original data presentation. With this publication we hope to further stimulate implementation of the Helsinki Declaration on Patient Safety in Anaesthesiology, as well as initiating relevant research in the future.

Pharmacodynamic Interaction of Remifentanil and Dexmedetomidine on Depth of Sedation and Tolerance of Laryngoscopy.

BACKGROUND: Dexmedetomidine is a sedative with modest analgesic efficacy, whereas remifentanil is an opioid analgesic with modest sedative potency. Synergy is often observed when sedative-hypnotics are combined with opioid analgesics in anesthetic practice. A three-phase crossover trial was conducted to study the pharmacodynamic interaction between remifentanil and dexmedetomidine. METHODS: After institutional review board approval, 30 age- and sex- stratified healthy volunteers were studied. The subjects received consecutive stepwise increasing target-controlled infusions of dexmedetomidine, remifentanil, and remifentanil with a fixed dexmedetomidine background concentration. Drug effects were measured using binary (yes or no) endpoints: no response to calling the subject by name, tolerance of shaking the patient while shouting the name ("shake and shout"), tolerance of deep trapezius squeeze, and tolerance of laryngoscopy. The drug effect was measured using the electroencephalogram-derived "Patient State Index." Pharmacokinetic-pharmacodynamic modeling related the administered dexmedetomidine and remifentanil concentration to these observed effects. RESULTS: The binary endpoints were correlated with dexmedetomidine concentrations, with increasing concentrations required for increasing stimulus intensity. Estimated model parameters for the dexmedetomidine EC50 were 2.1 [90% CI, 1.6 to 2.8], 9.2 [6.8 to 13], 24 [16 to 35], and 35 [23 to 56] ng/ml, respectively. Age was inversely correlated with dexmedetomidine EC50 for all four stimuli. Adding remifentanil did not increase the probability of tolerance of any of the stimuli. The cerebral drug effect as measured by the Patient State Index was best described by the Hierarchical interaction model with an estimated dexmedetomidine EC50 of 0.49 [0.20 to 0.99] ng/ml and remifentanil EC50 of 1.6 [0.87 to 2.7] ng/ml. CONCLUSIONS: Low dexmedetomidine concentrations (EC50 of 0.49 ng/ml) are required to induce sedation as measured by the Patient State Index. Sensitivity to dexmedetomidine increases with age. Despite falling asleep, the majority of subjects remained arousable by calling the subject's name, "shake and shout," or a trapezius squeeze, even when reaching supraclinical concentrations. Adding remifentanil does not alter the likelihood of response to graded stimuli.

Collateral Ventilation Measurement Using Chartis: Procedural Sedation vs General Anesthesia.

BACKGROUND: Absence of interlobar collateral ventilation is key to successful endobronchial valve treatment in patients with severe emphysema and can be functionally assessed by using the Chartis measurement. This system has been validated during spontaneous breathing, undergoing procedural sedation (PS), but can also be performed under general anesthesia. Performing the Chartis measurement under PS is often challenging because of coughing, mucus secretion, and difficulties in maintaining an adequate level of sedation. The objective of this study was to investigate whether there is a difference in Chartis measurement outcomes between PS and general anesthesia. METHODS: In this prospective study, patients underwent Chartis measurements under both PS and general anesthesia. Study outcomes were Chartis measurement duration, number of measurements, feasibility, and success rate. RESULTS: The study included 30 patients with severe emphysema (mean age, 62 years; median FEV1, 29% of predicted). Chartis measurement duration was significantly longer under PS than under general anesthesia (mean, 20.3 ± 4.2 min vs 15.1 ± 4.4 min; P < .001). There was no difference in the number (median [range]) of measurements performed (2 [1-3] for PS vs 1 [1-3] for general anesthesia; P = 1.00). Chartis measurement was more feasible during general anesthesia (median sum of all feasibility scores, 12 [range, 6-26] for PS vs 7 [5-13] for general anesthesia; P < .001). There was no statistical difference in success rate: 77% of PS cases vs 97% of general anesthesia cases (P = .07). CONCLUSIONS: This study found that Chartis measurement under general anesthesia is faster and more feasible to perform compared with performance with PS, without affecting measurement outcomes. TRIAL REGISTRATION: Clinicaltrials.gov; No. NCT03205826; URL: www.clinicaltrials.gov.

Drug selection for ambulatory procedural sedation.

PURPOSE OF REVIEW: Ambulatory procedural sedation is used to relieve anxiety, pain and discomfort in a broad spectrum of patients during many types of diagnostic or therapeutic procedures. This review focuses on recent comparative studies of commonly used and new drugs for adult ambulatory sedation. RECENT FINDINGS: Midazolam and propofol are commonly used for ambulatory sedation. Their pharmacological properties offer many advantages and there is much experience with their use. Ketamine can be a useful addition to hypnotic drugs but the advantage of the use of ketofol (a mixture of propofol and ketamine) is, although often practiced, difficult to assess. Dexmedetomidine is a relatively new sedative drug and many studies suggest advantages. New findings about its effects, however, show that the hemodynamic consequences of the use of dexmedetomidine may last for several hours. New sedative drugs for procedural sedation are still being developed: remimazolam has many properties that would make it an ideal sedative and has been studied in a phase 3 study. SUMMARY: The properties that would constitute the ideal sedative have yet to be combined in one drug. The selection of the drugs used for ambulatory sedation depends on many factors such as procedure type, patient characteristics and the expectations of patients and the healthcare provider. Because of this, the literature cannot yet provide a definitive answer to the question which drug is best selected in a specific situation.

Comparing peri-operative complications of paediatric and adult anaesthesia: A retrospective cohort study of 81 267 cases.

BACKGROUND: Comparisons of peri-operative complications associated with paediatric (≤16 years) and adult anaesthesia are poorly available, especially in which cardiac surgery, organ transplantation and neurosurgery are involved. OBJECTIVE: The aim of this study was to evaluate the nature and incidence of peri-operative complications that might be due to anaesthesia and to identify independent risk factors for complications in children and adults, including those undergoing cardiac surgery, organ transplantation and neurosurgery. DESIGN: Retrospective cohort study. SETTING: The study was performed at the University Medical Centre Groningen in the 4 years between 1 January 2010 and the 31 December 2013. MAIN OUTCOME MEASURES: Complications and their severity were graded according to the standard complication score (20 items) of the Dutch Society of Anaesthesia. Univariate and multivariate regression analysis was used to identify independent risk factors for the reported complications. RESULTS: A total of 81 267 anaesthetic cases were included. In the paediatric cohort, there were 410 (2.9%) complications and 1675 (2.5%) in the adults. In both cohorts age, American Society of Anaesthesiologists classification and emergency treatment were independent risk factors for complications. With respect to age, infants less than 1 year were at the highest risk, whereas in the adult cohort, increased age was related to a greater number of complications. The incidences of the specific complications were different between both cohorts. Upper airway obstruction was more frequently observed in paediatric patients (26%), whereas in the adults, complications with the highest incidence concerned conversion of regional-to-general anaesthesia (25%) and hypotension (17%). CONCLUSION: Risk factors for all peri-operative complications were similar for paediatric and adult anaesthesia. However, the incidence of specific complications differed between both age categories.

European Society of Anaesthesiology and European Board of Anaesthesiology guidelines for procedural sedation and analgesia in adults.

: Procedural sedation and analgesia (PSA) has become a widespread practice given the increasing demand to relieve anxiety, discomfort and pain during invasive diagnostic and therapeutic procedures. The role of, and credentialing required by, anaesthesiologists and practitioners performing PSA has been debated for years in different guidelines. For this reason, the European Society of Anaesthesiology (ESA) and the European Board of Anaesthesiology have created a taskforce of experts that has been assigned to create an evidence-based guideline and, whenever the evidence was weak, a consensus amongst experts on: the evaluation of adult patients undergoing PSA, the role and competences required for the clinicians to safely perform PSA, the commonly used drugs for PSA, the adverse events that PSA can lead to, the minimum monitoring requirements and post-procedure discharge criteria. A search of the literature from 2003 to 2016 was performed by a professional librarian and the retrieved articles were analysed to allow a critical appraisal according to the Grading of Recommendations Assessment, Development and Evaluation method. The Taskforce selected 2248 articles. Where there was insufficiently clear and concordant evidence on a topic, the Rand Appropriateness Method with three rounds of Delphi voting was used to obtain the highest level of consensus among the taskforce experts.These guidelines contain recommendations on PSA in the adult population. It does not address sedation performed in the ICU or in children and it does not aim to provide a legal statement on how PSA should be performed and by whom. The National Societies of Anaesthesiology and Ministries of Health should use this evidence-based document to help decision-making on how PSA should be performed in their countries. The final draft of the document was available to ESA members via the website for 4 weeks with the facility for them to upload their comments. Comments and suggestions of individual members and national Societies were considered and the guidelines were amended accordingly. The ESA guidelines Committee and ESA board finally approved and ratified it before publication.

Patient safety during procedural sedation using capnography monitoring: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of capnography monitoring on sedation-related adverse events during procedural sedation and analgesia (PSA) administered for ambulatory surgery relative to visual assessment and pulse oximetry alone. DESIGN AND SETTING: Systematic literature review and random effects meta-analysis of randomised controlled trials (RCTs) reporting sedation-related adverse event incidence when adding capnography to visual assessment and pulse oximetry in patients undergoing PSA during ambulatory surgery in the hospital setting. Searches for eligible studies published between 1 January 1995 and 31 December 2016 (inclusive) were conducted in PubMed, the Cochrane Library and EMBASE without any language constraints. Searches were conducted in January 2017, screening and data extraction were conducted by two independent reviewers, and study quality was assessed using a modified Jadad scale. INTERVENTIONS: Capnography monitoring relative to visual assessment and pulse oximetry alone. PRIMARY AND SECONDARY OUTCOME MEASURES: Predefined endpoints of interest were desaturation/hypoxaemia (the primary endpoint), apnoea, aspiration, bradycardia, hypotension, premature procedure termination, respiratory failure, use of assisted/bag-mask ventilation and death during PSA. RESULTS: The literature search identified 1006 unique articles, of which 13 were ultimately included in the meta-analysis. Addition of capnography to visual assessment and pulse oximetry was associated with a significant reduction in mild (risk ratio (RR) 0.77, 95% CI 0.67 to 0.89) and severe (RR 0.59, 95% CI 0.43 to 0.81) desaturation, as well as in the use of assisted ventilation (OR 0.47, 95% CI 0.23 to 0.95). No significant differences in other endpoints were identified. CONCLUSIONS: Meta-analysis of 13 RCTs published between 2006 and 2016 showed a reduction in respiratory compromise (from respiratory insufficiency to failure) during PSA with the inclusion of capnography monitoring. In particular, use of capnography was associated with less mild and severe oxygen desaturation, which may have helped to avoid the need for assisted ventilation.

Prophylactic atropine administration attenuates the negative haemodynamic effects of induction of anaesthesia with propofol and high-dose remifentanil: A randomised controlled trial.

BACKGROUND: Induction of anaesthesia with propofol and remifentanil often induces unwanted bradycardia and hypotension, raising concerns regarding tissue oxygenation. The electrophysiological cardiac effects of remifentanil can be reversed by atropine. OBJECTIVE: To investigate if prophylactic administration of atropine can attenuate the negative haemodynamic effects of propofol and a high dose of remifentanil during induction of anaesthesia. DESIGN: A double-blind, randomised controlled trial. SETTING: Single-centre, University Medical Center Groningen, The Netherlands. PATIENTS: Sixty euvolaemic patients scheduled for surgery under general anaesthesia. INTERVENTIONS: Anaesthesia was induced and maintained with a target-controlled infusion of propofol with a target effect-site concentration (Ce) of 2.5 µg ml, remifentanil (target-controlled infusion), (Ce 8 ng ml) and cis-atracurium. Methylatropine (500 µg) or 0.9% saline was administered at immediately before induction of anaesthesia. MAIN OUTCOME MEASURES: The changes (Δ) in mean arterial pressure (MAP), heart rate (HR), cardiac index (CI), rate pressure product, cerebral tissue oxygenation and peripheral tissue oxygenation between induction of anaesthesia (T0) and 10 min later (T10). RESULTS: Atropine significantly attenuated the changes in the outcome measures between T0 and T10. Median (inter-quartile range) changes were MAP, Δ = -24 (-40 to -21) vs. Δ = -37 mmHg (-41 to -31) (P = 0.02); HR, Δ = 0 ±â€Š13 vs. -19 ±â€Š11 bpm (P < 0.01); CI, Δ = -0.4 ±â€Š0.7 vs. -0.9 ±â€Š0.6l min m (P < 0.01) and rate pressure product, Δ = -3241 (-5015 to -613) vs. Δ = -5712 mmHg min (-6715 to -3917) (P < 0.01). Cerebral tissue oxygenation and peripheral tissue oxygenation did not change in either group. Maximum HR after atropine was 102 (86 to 116) vs. 85 bpm (76 to 95). CONCLUSION: Administration of atropine, before induction of anaesthesia with propofol and high-dose remifentanil, can significantly reduce the decreases in HR, MAP and CI. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01871922.

Longitudinal analysis of cytokine expression during neoadjuvant chemoradiotherapy and subsequent surgery in esophageal cancer patients.

BACKGROUND: The purpose of this study was to provide more insight in the course of cytokine concentrations related to pathologic response (pR) and complications after neoadjuvant chemoradiotherapy (NCRT) and esophagectomy in esophageal cancer patients. METHODS: Patients treated with NCRT followed by transthoracic esophagectomy (n = 35) or transthoracic esophagectomy alone (n = 8) were included. Eight different cytokine concentrations were determined during NCRT, esophagectomy, and the first postoperative week. RESULTS: Platelet-activating factor before NCRT was associated with pR (P = .011) and remained elevated in patients with a better response. Concentrations of intestinal fatty acid-binding protein and angiopoietin 1 (Ang-1) were different between patients with and without NCRT. Decreased concentrations of Ang-1 on the third postoperative day were associated with postoperative complications (P = .046). CONCLUSIONS: In this observational study, elevated platelet-activating factor concentrations before NCRT were associated with pR. NCRT is associated with decreased Ang-1 concentrations, whereas reduced Ang-1 concentrations were associated with postoperative complications.

Computer-guided normal-low versus normal-high potassium control after cardiac surgery: No impact on atrial fibrillation or atrial flutter.

INTRODUCTION: This study was designed to determine the effect of 2 different potassium regulation strategies with different targets (within the reference range) on atrial fibrillation (AF) or atrial flutter (AFL) in a cohort of intensive care unit patients after cardiac surgery. METHODS: The GRIP-COMPASS study was a prospective double-blinded interventional study in 910 patients after cardiac surgery (coronary artery bypass grafting and/or valvular surgery). Patients were assigned to either the normal-low potassium target (nLP group, 4.0 mmol/L) or the normal-high potassium target (nHP group, 4.5 mmol/L) in alternating blocks of 50 patients. Potassium levels were regulated using a validated computer-assisted potassium replacement protocol (GRIP-II). The primary end point was the incidence of AF/AFL on a 12-lead electrocardiogram during the first postoperative week. RESULTS: Of the 910 patients, 447 were assigned to the nLP group; and 463, to the nHP group, with no baseline differences between the 2 groups. The mean daily administered dose of potassium was 30 ± 23 mmol (nLP) versus 52 ± 27 mmol (nHP) (P < .001), which resulted in mean intensive care unit potassium concentration of 4.22 ± 0.36 mmol/L and 4.33 ± 0.34 mmol/L, respectively (P < .001). The incidence of AF/AFL after cardiac surgery did not differ: 38% in the nLP group and 41% in the nHP group. Also in several subgroups (eg, patients not known with prior AF/AFL or with valve surgery), there were no differences. CONCLUSIONS: There were no differences in incidence of AF/AFL with 2 potassium regulation strategies with different potassium targets and different amounts of potassium administered in patients after cardiac surgery.