Safety and Considerations of the Anaesthetic Management during Bronchoscopic Lung Volume Reduction Treatments.

BACKGROUND: Different bronchoscopic lung volume reduction approaches are available for a select group of patients with advanced COPD. General anaesthesia is the recommended method of sedation during these procedures. However, this patient population is at an increased risk of anaesthetic complications, and the best approach to general anaesthesia and mechanical ventilation is unknown. OBJECTIVES: The aims of this study were to describe the anaesthetic management techniques used during bronchoscopic lung volume reduction procedures and to investigate the number of anaesthesia-related events. METHODS: Data were retrospectively collected from all endobronchial valve and lung volume reduction coil procedures performed between January 2018 and March 2020 in our hospital. Primary outcomes measures were anaesthetic technique including airway management; ventilation mode and settings; and the incidence of anaesthesia-related events, classified as catastrophic, severe, significant, or moderate. RESULTS: 202 procedures were included. One procedure was performed under procedural sedation, 198 (98%) under general anaesthesia with endotracheal intubation, and 3 (1.5%) under general anaesthesia with laryngeal mask airway. Volume-controlled ventilation was used in 64% of the procedures and pressure-controlled in 36%. Patients were ventilated with a median respiration rate of 9.9 (IQR: 9.6-10.6) breaths per minute, mean tidal volume of 5.8 ± 1.4 mL/kg, and median inspiratory to expiratory (I:E) ratio of 1:2.8 (IQR: 1:2.1-1:3.2). No catastrophic anaesthesia-related events were observed. Hypotension was the most observed anaesthesia-related event. CONCLUSIONS: Despite the presence of advanced COPD, general anaesthesia and mechanical ventilation are well tolerated by patients undergoing endobronchial valve or lung volume reduction coil treatment. This is presumably strongly linked to the strict selection criteria. Other important considerations are using a low respiratory rate, low tidal volume, and high I:E ratio.

What's New in Intravenous Anaesthesia? New Hypnotics, New Models and New Applications.

New anaesthetic drugs and new methods to administer anaesthetic drugs are continually becoming available, and the development of new PK-PD models furthers the possibilities of using arget controlled infusion (TCI) for anaesthesia. Additionally, new applications of existing anaesthetic drugs are being investigated. This review describes the current situation of anaesthetic drug development and methods of administration, and what can be expected in the near future.

Intranasal midazolam for the sedation of geriatric patients with care-resistant behaviour during essential dental treatment: An observational study.

OBJECTIVES: To describe the efficacy and safety of intranasal midazolam for sedation during essential dental treatment of geriatric patients with major neurocognitive disorder (MND) and care-resistant behaviour (CRB). BACKGROUND: Dental treatment is often impossible in geriatric MND patients with CRB. Intranasal midazolam may provide a non-invasive sedation method, but there is currently no information on its use in geriatric patients. METHODS: In this observational study, we included geriatric patients with severe MND and CRB needing urgent dental treatment. Each patient received 5 mg midazolam intranasally. Agitation/sedation levels, heart rate, respiration rate and oxygen saturation were recorded at 5-minute intervals. RESULTS: Thirty two patients were included. Mean age was 84 (±7) years. Mean (SD) time to treatment start was 13 (±5) minutes, and mean time to maximum sedation 17 (±11) minutes. Sedation was sufficient to enable dental treatment to be completed in 31 (97%) patients. Anxiolysis/light sedation occurred in 16 (50%) patients, and moderate to deep sedation occurred in 16 (50%) patients. No patients suffered from apnoea, although 3 patients required a chin-lift manoeuvre. Hypoxaemia occurred in 1 of these patients and in 2 other patients without airway obstruction. All patients recovered uneventfully. In a regression model, age, weight and other sedative medication use were found not to be associated with maximum sedation depth. CONCLUSIONS: Of 5 mg intranasal midazolam facilitates treatment of geriatric patients with MND in the comfort of their own environment. More information is needed to guide titration to balance the desired sedation level and patient safety.

Hypotension during propofol sedation for colonoscopy: a retrospective exploratory analysis and meta-analysis.

BACKGROUND: Intraoperative and postoperative hypotension occur commonly and are associated with organ injury and poor outcomes. Changes in arterial blood pressure (BP) during procedural sedation are not well described. METHODS: Individual patient data from five trials of propofol sedation for colonoscopy and a clinical database were pooled and explored with logistic and linear regression. A literature search and focused meta-analysis compared the incidence of hypotension with propofol and alternative forms of procedural sedation. Hypotensive episodes were characterised by the original authors' definitions (typically systolic BP <90 mm Hg). RESULTS: In pooled individual patient data (n=939), 36% of procedures were associated with episodes of hypotension. Longer periods of propofol sedation and larger propofol doses were associated with longer-lasting and more-profound hypotension. Amongst 380 patients for whom individual BP measurements were available, 107 (28%) experienced systolic BP <90 mm Hg for >5 min, and in 89 (23%) the episodes exceeded 10 min. Meta-analysis of 18 RCTs identified an increased risk ratio for the development of hypotension in procedures where propofol was used compared with the use of etomidate (two studies; n=260; risk ratio [RR] 2.0 [95% confidence interval: 1.37-2.92]; P=0.0003), remimazolam (one study; n=384; RR 2.15 [1.61-2.87]; P=0.0001), midazolam (14 studies; n=2218; RR 1.46 [1.18-1.79]; P=0.0004), or all benzodiazepines (15 studies; n=2602; 1.67 [1.41-1.98]; P<0.00001). Hypotension was less likely with propofol than with dexmedetomidine (one study; n=60; RR 0.24 [0.09-0.62]; P=0.003). CONCLUSIONS: Hypotension is common during propofol sedation for colonoscopy and of a magnitude and duration associated with harm in surgical patients.

Moderate-to-Deep Sedation Using Target-Controlled Infusions of Propofol and Remifentanil: Adverse Events and Risk Factors: A Retrospective Cohort Study of 2937 Procedures.

BACKGROUND: In the University Medical Center Groningen in Groningen, the Netherlands, moderate-to-deep sedation is provided by nursing staff trained and supervised by the anesthesia department using protocol-based target-controlled infusions (TCIs) of propofol and remifentanil. The aim of this retrospective cohort study was to investigate the incidence of events with potential adverse health consequences within this service model and the risk factors for the occurrence of these events. METHODS: We retrospectively interrogated a database containing the computerized anesthetic records of 2937 procedures where moderate-to-deep sedation was provided using TCI administration of propofol and remifentanil between May 2014 and October 2017. The primary outcome measures were the incidence of sedation-related events with potential adverse health consequences and risk factors for the occurrence of such events. The events under investigation were unplanned intensive care unit (ICU) admission, need for cardiopulmonary resuscitation (CPR), death on the day of the procedure due to sedation-related events, cardiovascular events (arrhythmias, hypertension, and hypotension), pulmonary events (aspiration, desaturation, unplanned tracheal intubation), anaphylactic or allergic reactions, and the termination of the procedure due to sedation-related events. Cardiovascular and pulmonary events were classified as severe, significant, or moderate. Events were identified by using computer algorithms to search the computerized records from all included procedures. RESULTS: Data from 2937 procedures were analyzed. No patients suffered catastrophic events (death, need for CPR, or unplanned ICU admission). Thirty-two severe sedation-related events occurred in 32 procedures. Severe desaturation (0.6%; 95% confidence interval [CI], 0.4-0.9) and severe hypertension (0.2%; 95% CI, 0.04-0.37) were the most common severe events. Significant hypotension (8.8%; 95% CI, 7.73-9.77) and significant desaturation (1.6%; 95% CI, 1.12-2.02) were found to be the most common events with potential adverse health consequences. No patient suffered lasting health consequences. Average mean and maximum targeted effect-site concentrations (Cet) for propofol were 2.6 ± 0.83 and 3.3 ± 1.09 µg·mL, respectively, and for remifentanil 0.84 ± 0.18 and 0.99 ± 0.22 ng·mL, respectively. Maximum Cets of propofol were lower among patients with higher body mass index (BMI) and were higher among patients of younger age. Higher BMI was a risk factor for desaturation. Increased age and lower BMI were risk factors for hypotension. Longer procedure time was a risk factor for both desaturation and hypotension. CONCLUSIONS: Moderate-to-deep sedation by propofol and remifentanil TCI has a low incidence of catastrophic and severe events.

Intranasal dexmedetomidine in elderly subjects with or without beta blockade: a randomised double-blind single-ascending-dose cohort study.

BACKGROUND: The aim of this double-blind, placebo-controlled, single-ascending-dose study was to determine the safety and tolerability of intranasal dexmedetomidine in the elderly. METHODS: We randomly assigned 48 surgical patients ≥65 yr of age to receive single intranasal doses of dexmedetomidine or placebo (5:1 ratio) in four sequential dose cohorts: 0.5, 1.0, 1.5, and 2.0 µg kg-1. Each dose cohort comprised two groups of six subjects: a group of subjects using ß-blockers and a group not taking ß-blockers. Vital signs and sedation depth (Modified Observer's Assessment of Alertness and Sedation [MOAA/S] and bispectral index) were measured for 2 h after administration. Blood samples were taken to determine dexmedetomidine plasma concentrations. RESULTS: One subject (1.0 µg kg-1) had acute hypotension requiring ephedrine. Systolic arterial BP decreased >30% in 15 of 40 subjects (37.5%) receiving dexmedetomidine, lasting longer than 5 min in 11 subjects (27.5%). The MAP decreased >30% (>5 min) in 10%, 20%, 50%, and 30% of subjects receiving dexmedetomidine 0.5, 1.0, 1.5, and 2.0 µg kg-1, respectively, irrespective of ß-blocker use. HR decreased 10-26%. MOAA/S score ≤3 occurred in 18 (45%) subjects; eight (20%) subjects receiving dexmedetomidine showed no signs of sedation. Tmax was 70 min. Cmax was between 0.15 ng ml-1 (0.5 µg kg-1) and 0.46 ng ml-1 (2.0 µg kg-1). CONCLUSIONS: Intranasal dexmedetomidine in elderly subjects had a sedative effect, but caused a high incidence of profound and sustained hypotension irrespective of ß-blocker use. The technique is unsuitable for routine clinical use. CLINICAL TRIAL REGISTRATION: NTR5513 (The Netherlands Trial Registry 5513).

A New Oxygen Uptake Measurement Supporting Target Selection for Endobronchial Valve Treatment.

BACKGROUND: Adequate target lobe selection for endobronchial valve (EBV) treatment in patients with severe emphysema is essential for treatment success and can be based on emphysema destruction, lobar perfusion, lobar volume, and collateral ventilation. As some patients have >1 target lobe for EBV treatment, we were interested whether we could identify the least functional lobe. OBJECTIVES: The objective of this study was to investigate the relationship between endoscopic lobar measurement of oxygen uptake, lobar destruction, and vascular volume, and whether this could help in identifying the least functional lobe and thus optimal target for EBV treatment. METHOD: We prospectively included patients who were scheduled for EBV treatment in our hospital. A customized gas analysis setup was used to measure lobar O2 uptake after lobar balloon occlusion. Quantitative CT analysis was performed to assess the degree of emphysematous destruction and lobar arterial and venous volumes. RESULTS: Twenty-one (5 male/16 female) patients with emphysema (median age 63 years, FEV1 25% of predicted, residual volume 234% of predicted) were included, and 49 endoscopic lobar measurements were performed. A lower O2 uptake significantly correlated with a higher degree of emphysematous lobar destruction (Spearman's ρ: 0.39, p < 0.01), and lower arterial and venous vascular volumes of the lobes (-0.46 and -0.47, respectively; both p < 0.001). CONCLUSIONS: Endoscopic measurement of lobar O2 uptake is feasible in patients with emphysema. Measurement of lobar O2 uptake helped to identify the least functional lobe and can be used as additional tool for EBV target lobe selection.

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.

Performance of blow-by methods in delivering oxygen to pediatric patients during transport: A laboratory study.

BACKGROUND: Providing supplemental oxygen with a blow-by method is used to provide additional oxygen to patients who will not tolerate an oxygen delivery device in direct contact with their face. Blow-by methods are often improvised from parts of standard equipment. The performance is very dependent on the distance to the face and the direction of the gas flow. Blow-by methods are used by anesthetists during transport but their performance in delivering supplemental oxygen has only been tested in static situations. The aim of this nonclinical study was to determine the performance of different blow-by methods in the delivery of additional oxygen to pediatric patients during transport. METHODS: A manikin of a child with a facemask of appropriate size was transported along a 60 m corridor from the operating theater to the PACU. Oxygen delivery to the face of the manikin was measured during transport. Six blow-by methods were tested with oxygen flows of 3, 6, and 10 L/min and with the facemask at 0 cm from the face and at 5 cm from the face. The outcome parameter was: blow-by method reaching and maintaining an FiO2 >50% during transport from the pediatric operating theater to the PACU. RESULTS: At 0 cm from the face, five out of six blow-by methods maintained a FiO2 >50% with all three flow rates. At 5 cm only two of the blow-by methods were able to maintain an FiO2 >50% and this only at flow rates of 10 L/min. All other blow-by methods provided lower FiO2 s; in three, the FiO2 decreased to values only marginally above 21%. The decrease in FiO2 typically started within 6-12 m from the start of the transport. CONCLUSION: It is concluded that the ability of blow-by methods to deliver a FiO2 >50% depends on the method used and distance from the face.

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.

Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine.

Dexmedetomidine is an α2-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for α2-receptors with an α2:α1 ratio of 1620:1. Hemodynamic effects, which include transient hypertension, bradycardia, and hypotension, result from the drug's peripheral vasoconstrictive and sympatholytic properties. Dexmedetomidine exerts its hypnotic action through activation of central pre- and postsynaptic α2-receptors in the locus coeruleus, thereby inducting a state of unconsciousness similar to natural sleep, with the unique aspect that patients remain easily rousable and cooperative. Dexmedetomidine is rapidly distributed and is mainly hepatically metabolized into inactive metabolites by glucuronidation and hydroxylation. A high inter-individual variability in dexmedetomidine pharmacokinetics has been described, especially in the intensive care unit population. In recent years, multiple pharmacokinetic non-compartmental analyses as well as population pharmacokinetic studies have been performed. Body size, hepatic impairment, and presumably plasma albumin and cardiac output have a significant impact on dexmedetomidine pharmacokinetics. Results regarding other covariates remain inconclusive and warrant further research. Although initially approved for intravenous use for up to 24 h in the adult intensive care unit population only, applications of dexmedetomidine in clinical practice have been widened over the past few years. Procedural sedation with dexmedetomidine was additionally approved by the US Food and Drug Administration in 2003 and dexmedetomidine has appeared useful in multiple off-label applications such as pediatric sedation, intranasal or buccal administration, and use as an adjuvant to local analgesia techniques.

Dexmedetomidine versus Midazolam in Procedural Sedation. A Systematic Review of Efficacy and Safety.

OBJECTIVES: To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation. MATERIALS AND METHODS: We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (≥18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications. RESULTS: We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar. CONCLUSIONS: Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar.