Chapter 18

Safe sedation: where are we today? (Fuchs-Buder, Struys)

Introduction

Over the last decades there has been a remarkable increase in demand for procedural sedation and analgesia (PSA), driven by an increasing number of minimally invasive diagnostic and therapeutic procedures. All this has been facilitated by the availability of potent short-acting analgesic and sedative drugs, leading to the perception that PSA can also be managed easily by nonanaesthesiologists. In addition, improved medical devices and instruments combined with new imaging and ultrasound equipment now allow major surgical procedures to be performed by minimally invasive techniques, for example, endovascular or perendoscopic procedures. This has resulted in an ever-increasing number of patients presenting for PSA with more and more of them being managed by nonanaesthesiologists. The ESA and the EBA have published guidelines for PSA in adult patients.

Sedation is also a topic of the Helsinki Declaration on Patient Safety in Anaesthesiology, signed in 2010 by the ESA, EBA and NASC (National Anaesthesia Societies Committee) and by numerous countries and anaesthesia societies all over the world thereafter. This chapter will briefly highlight the key messages of the 2017 ESA/EBA guidelines on PSA and it will make a few recommendations about how patient safety during PSA could be further improved.⁶⁰⁰

Key messages of the European Society of Anaesthesiology/European Board of Anaesthesiology guidelines for procedural sedation and analgesia in adults

The main objectives of these guidelines are to provide evidence-based recommendations on the preprocedure evaluation of patients undergoing PSA; the role and competence required from clinicians to safely administer PSA; the minimum monitoring requirements; prevention and management of adverse events; the commonly used drugs for PSA; and postprocedure discharge criteria.

During their initial development, the joint ESA/EBA guidelines successfully followed the ESA rules for guideline development. If there was insufficient evidence about a specific safety recommendation, the Rand Appropriateness Method with three rounds of Delphi voting was used. These guidelines were then reviewed externally and posted on the ESA website for 30 days to allow ESA members to comment. NASC members of the EBA and of the ESA NASC were also consulted; all resulting in detailed and valuable suggestions to improve the original document, and the guidelines were amended accordingly.

Strong recommendations could be made for all of the following items [the respective level of evidence (LoE) is also indicated – more detailed information is available in the original document⁶⁰⁰].

What type of comorbidities and patients require preprocedural evaluation and procedural sedation and analgesia by an anaesthesiologist?

• (1) Patients with cardiovascular diseases should be carefully evaluated and optimised, which involves full evaluation of the physical status and cardiac reserve prior to PSA. However, for emergency procedures (e.g. gastroscopy for bleeding) this evaluation may have to be limited (LoE: A).
• (2) Patients with a documented or suspected risk of obstructive sleep apnoea syndrome (OSAS) are more vulnerable to drug-induced cardiopulmonary depression during deep sedation. There are different validated questionnaires to identify patients at risk for OSAS like the Berlin or STOP BANG score. Patients with OSAS therefore should also be assessed and managed by an anaesthesiologist (LoE: B).
• (3) Morbidly obese patients are at higher risk of respiratory complications during PSA. It is proposed that the severity of OSAS (Berlin or STOP BANG questionnaire) be assessed in these patients. Endotracheal intubation is proposed as the default choice of airway management (LoE: A).
• (4) Patients with chronic hepatic disease often need PSA for diagnostic purposes (e.g. oesophageal varices; portal hypertensive gastropathy). Hepatic dysfunction, however, can significantly change the metabolism and pharmacokinetic properties of hypnotic drugs. Preprocedural assessment and PSA should therefore be performed by an anaesthesiologist (LoE: A).
• (5) There are many age-related physiological changes in the cardiac, pulmonary, renal, hepatic, endocrine and nervous systems of the elderly that need to be assessed to judge PSA-related risk such as hypotension, hypoxaemia, cardiac arrhythmias and aspiration (LoE: A).
• (6) ASA physical status III and IV should also be assessed and managed by an anaesthesiologist (LoE: A) prior to PSA.

What are the requirements to provide well tolerated procedural sedation and analgesia?

• (1) Because the majority of severe complications of PSA are upper airway obstruction and/or respiratory depression, examination of the upper airway before PSA is essential (LoE: B).
• (2) All personnel in charge of PSA should be certified for CPR (LoE: B). Staff directly involved in PSA need specific certified training (LoE: B).
• (3) PSA should be carried out only in locations where an anaesthesiologist is immediately available (LoE: C).
• (4) The risks, benefits and techniques to deliver PSA have to be explained to the patient by the clinician prior to the procedure (LoE: B).
• (5) There should be a dedicated room for PSA (LoE: B) and an algorithm for difficult airway management. A difficult airway cart or specific prepacked material should be immediately available (LoE: B).
• (6) Continuous visual bedside observation represents the basic level of clinical monitoring during and after any PSA (LoE: B). Intermittent noninvasive measurement of BP, continuous ECG monitoring and pulse oximetry are considered mandatory in all patients undergoing PSA (LoE: B). Capnography should be used for continuous evaluation of ventilation in all patients receiving deep sedation for PSA (LoE: A).
• (7) PSA can be the cause of a wide range of complications that can happen during and after the procedure, for example, respiratory depression, airway obstruction, hypertension, hypotension, chest pain, cardiac arrest or an allergic reaction. The clinician involved in the administration of PSA should be able to recognise these complications early and manage them appropriately (LoE: B). Supplemental oxygen should be available whenever PSA is started, and it can be administered to prevent hypoxia (LoE: B).
• (8) Patients must be monitored in a recovery room for at least 30 min after PSA (LoE: B).

How to further improve patient safety

To further improve the safety of patients undergoing PSA, the authors of this chapter suggest the following be considered.

Improve guideline implementation: The ESA/EBA guidelines for PSA in adults, embedded in the Helsinki Declaration on Patient Safety in Anaesthesiology, are conceived as an evidence/consensus-based document on which different National Societies of Anaesthesiology may build their own recommendations about to how professionals should deliver PSA and how PSA can be provided in the safest possible way. By limiting the heterogeneity in the manner in which PSA is administered across Europe, patient safety should improve, but this can only happen if the guidelines are implemented in routine clinical practice. Surveys, continuing medical education, training courses and quality insurance programmes may serve that goal, and thus contribute to increasing the acceptance and implementation of the guidelines.

Better training: All national and international guidelines advocate healthcare professionals be trained in providing sedation with the help of theoretical courses, workshops, bed side teaching and continuing medical education. This would include topics such as patient selection, improved understanding of pharmacokinetics and pharmacodynamics of drugs, airway management, infrastructural requirements to provide safe sedation including monitoring and treatment of complications. These workshops, supervised bed-side training and certification should be mandatory: examples of these can be found in the United Kingdom, the Netherlands and various other countries.⁴⁵³ On the contrary, a diverse offer of training programmes that all lead to a ‘sedationist’ certificate exists. Because the quality of these programmes is inconsistent, uniform and well described course requirements should be developed that are audited by an authorised accrediting body.

Better define what constitutes ‘sedation’: Guidelines differ in their definition of the various levels of sedation. The ESA and EBA guidelines on PSA in adults use the five-level Ramsay scale to define the various levels of sedation, with level five defining general anaesthesia (unconsciousness and no response to a strong physical stimulus).⁶⁰⁰ In contrast, the 2018 ASA Practice Guidelines for Moderate Procedural Sedation and Analgesia and the 2018 American Society of Gastrointestinal Endoscopy (ASGE) Guidelines for sedation and anaesthesia in gastro-intestinal endoscopy uses a four-level scale to define the various levels of sedation.^601,602 The American guidelines apply to moderate sedation only. On top of this, various national societies have defined their own standards. As a result, ‘sedation’ might be interpreted differently among healthcare professionals involved in clinical care across the globe, which complicates the interpretation of study results on quality, safety, adverse events and outcome, and making bench-marking difficult.^603,604 Certainly, for deep sedation levels, uniform guidelines and interpretation of what is considered to be ‘sedation’ should be promoted: small margins exist between deep sedation and general anaesthesia with a (hopefully) still spontaneously breathing patient but with an unprotected airway and requiring support for the cardiovascular system.

Better drugs/improved drug delivery: For mild sedation, various hypnotic drugs are still considered state-of-the art, ranging from a low dose of midazolam, propofol and ketamine to dexmedetomidine.^605,606 For moderate-to-deep sedation, continuous administration of propofol is still considered the most appropriate drug due to its favourable pharmacokinetic and dynamic properties.⁶⁰⁷ However, propofol has well known side effects such as pain on injection, dose-dependent cardiovascular and respiratory depression, and hyperlipidaemia secondary to the infusion of the required lipid formulation.⁶⁰⁷ Because propofol has no clinically relevant antinociceptive effect, remifentanil administration in particular may be considered because of its potency combined with short-acting onset and offset. It can be used in combination with propofol or as a standalone sedative.⁶⁰⁵ Target-controlled infusion (TCI) based on pharmacokinetic-dynamic models can be used to fine-tune the administration of both, propofol and remifentanil.⁶⁰⁸ TCI is considered a mature technology and being as safe as manual administration of intravenous drugs.⁶⁰⁸ Recently, new general purpose pharmacokinetic-dynamic models for both propofol and remifentanil have been developed allowing general application of this technology for sedation in a broad patient group.^609–611

Targeting a lower concentration of remifentanil in combination with higher targets for propofol results in the highest probability of tolerating oesophageal instrumentation without unacceptable ventilatory problems. Nevertheless, caution is always warranted because no guaranteed ‘safe zone’ without respiratory depression exists.⁶¹² In an attempt to lower respiratory and cardiovascular side effects, the combination of propofol and ketamine or lidocaine has been studied in an attempt to lower respiratory and cardiovascular side effects.^613,614 Another useful drug may be dexmedetomidine, an alpha-2 agonist known for its combined sedative, anxiolytic and analgesic properties. It has been recently approved for procedural sedation by the European Medicines Agency.^605,615 The ASA presents dexmedetomidine as an alternative to propofol in their 2018 Practice Guidelines for Moderate Procedural Sedation and Analgesia. It has a slower onset and offset than propofol, with sustained arousability during sedation, even when combined with remifentanil.^616–619 It causes less respiratory depression than propofol,⁶²⁰ but has a profound and complex effect on haemodynamic stability (certainly during rapid infusion): initial hypertension is followed by hypotension and HR changes.^616–618

Because the existing drugs are still less than perfect, various new compounds have been developed, none of which is clinically available yet. These drugs are soft-analogues from existing drugs and alternative formulations.⁶²¹ Remimazolam is a short-acting benzodiazepine currently undergoing phase III trials in ASA III and IV patients undergoing general anaesthesia (ClinicalTrials.gov, NCT02296892) and in phases IIa and IIb trials in patients undergoing sedation. During upper gastrointestinal endoscopy, a single administration of remimazolam (0.10 to 0.20 mg kg⁻¹) rapidly induced sedation, followed by a quick recovery. The safety profile was favourable and appeared to be similar to that of midazolam.⁶²² A single dose of remimazolam or midazolam, followed by top-up doses to maintain suitable sedation, provided adequate sedation during colonoscopy in a phase III study, with 92 and 75% success rate in the remimazolam and midazolam group, respectively. There was no requirement for mechanical ventilation in any group; procedure failures in both groups were all related to administration of rescue sedatives.⁶²³ Remimazolam is likely to be introduced into the market for sedation in the near future.

Better monitoring: It should be stressed that sedation should be provided and patients should be monitored by a trained and certified healthcare professional other than the person involved in the procedure. Continuous observation of the level of sedation according to well defined clinical endpoints is mandatory. Vital signs that have to be monitored include NIBP, electrocardiography and pulse oximetry. The use of capnography remains controversial. ESA–EBA and ASA support the use of capnography.^600,601 A meta-analysis concluded that capnography reduced the incidence of respiratory compromise (ranging from respiratory insufficiency to failure). There is less mild and severe oxygen desaturation, which may reduce the need for assisted ventilation. In contrast, the ASGE guidelines only recommend capnography during procedures under deep but not moderate sedation.⁶⁰² These guideline discrepancies should be avoided for medico-legal reasons and because they cause confusion when translating these guidelines into institutional standard operating procedures.⁶²⁴

Conclusion

The common set of guidelines for PSA published by ESA and EBA is a first important step towards more homogeneity in the way PSA is provided across Europe. These guidelines must be implemented in routine clinical practice and certified training programmes must be proposed to further improve patient safety. The ESA should be a strong stakeholder in this process.

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