9 – Personalized Sedation and Analgesia




Abstract




The practice of medicine often requires procedures that cause pain and anxiety. With the advent of modern anaesthesia these procedures have become commonplace and tolerable. Procedures with the greatest degree of pain are frequently accomplished during a state of general anaesthesia. Many procedures, however, are performed under sedation and analgesia. In contrast to general anaesthesia, sedation and analgesia use short acting medications to alleviate pain and anxiety while leaving patients capable of maintaining their airway and basic physiological functions.





9 Personalized Sedation and Analgesia


Michael M. Beck , Jeffrey B. Horn and Ken B. Johnson



Introduction


The practice of medicine often requires procedures that cause pain and anxiety. With the advent of modern anaesthesia these procedures have become commonplace and tolerable. Procedures with the greatest degree of pain are frequently accomplished during a state of general anaesthesia. Many procedures, however, are performed under sedation and analgesia. In contrast to general anaesthesia, sedation and analgesia use short acting medications to alleviate pain and anxiety while leaving patients capable of maintaining their airway and basic physiological functions.


This chapter discusses goals, terminology, key elements and challenges of procedural sedation and analgesia (PSA). It also reviews application of existing drug delivery technology to enhance sedation practice and selected innovations that have the potential to better personalize sedation and analgesia. Existing drug delivery technologies in sedation practice include manually controlled and target-controlled infusions (TCI) and patient controlled sedation and analgesia. Selected innovations include the introduction of drug display technologies that provide real-time visualization of sedative–analgesic interactions and the development of a computer assisted personalized sedation (CAPS) device for moderate sedation.



Goals of Sedation and Analgesia


There are several objectives when providing sedation and analgesia, some of which may be in opposition to one another. The primary objective, keeping a patient safe (e.g. oxygenated and ventilated), can conflict with the goals of providing amnesia, relaxation (immobility) and analgesia to optimize surgical conditions for a successful procedure. Thus, providing sedation and analgesia is a delicate and occasionally dangerous endeavour that mandates the need for practitioners with specialized training in the realm of anaesthesiology.



Patient Safety


As healthcare costs continue to rise, proceduralists seek opportunities to perform increasingly complex surgical procedures out-of-the-operating-room (OOR) with the use of PSA. With an ageing population and the potential serious concomitant comorbidities, sedation practitioners must be adept at patient selection, drug choice and recognizing the dangers associated with deeper than intended sedation.


Patient safety can be defined as the avoidance of adverse events during PSA. Adverse events that may occur during PSA include apnoea, airway obstruction, haemodynamic instability, cardiac arrhythmia or arrest, permanent neurological deficits and death. OOR procedures continue to be performed with minimal uniformity in guidelines by healthcare providers often with no accredited training in anaesthesiology and a wide range of sedation training and experience. Because of this, it is difficult to collect data on the frequency of adverse events during PSA. Although recommended by many authors, no standard in reporting adverse events during PSA exists.



Patient Comfort


While secondary to patient safety, patient comfort is an important goal of PSA. Patient comfort begins with communication prior to beginning sedation or the procedure. The sedation practitioner and proceduralist should explain to the patient what to expect and the sedation practitioner should elicit the patient’s expectations as well. The goal is to provide an agreed upon level of anxiolysis, amnesia and analgesia while maintaining patient safety.


Generally, these goals are largely achieved through medications; however, it is important to consider non-pharmacological adjuncts as well. Ensuring that the patient is in a comfortable position that is also acceptable to the proceduralist before initiating sedation can avoid difficulties later during the procedure. With paediatric patients, it can be beneficial to consider the benefit of the presence or absence of a parent or caregiver.



Procedure Optimization


A final goal of PSA is to optimize conditions for safe completion of the procedure. Key elements include (1) minimizing patient movement and providing patient relaxation and (2) communication between the proceduralist and sedation practitioner and between the sedation practitioner and the patient to adjust dosing of sedatives and analgesics as needed.



Terminology



The Sedation Continuum


Although the accepted definition of sedation is easily interpreted as a decreased level of consciousness or awareness, a clinically relevant definition has yet to be elucidated or accepted. The historically popular term ‘Conscious Sedation’ has fallen out of favour while many other terms continue to be used interchangeably in the literature, including: monitored anaesthesia care (MAC), monitored sedation, procedural sedation, deep sedation, moderate sedation, light sedation, sedation and analgesia, and anxiolysis.


Standardized terminology provides a basis for improving sedation quality and patient safety, and reporting adverse outcomes. Due to incongruent regulations and guidelines, patients, proceduralists and sedation practitioners adhere to a wide range of sedation expectations. Patients may expect no pain or awareness during a procedure. Proceduralists may expect patients to lie still during critical segments of a procedure. Sedation practitioners may expect their patient to respond to verbal prompts and breathe spontaneously. A succinct description of sedation levels in characterizing the goals of these competing expectations is therefore needed.


In 1999, the American Society of Anesthesiologists (ASA) published a sedation continuum as part of their practice guidelines for sedation and analgesia by non-anaesthesiologists [1] (Table 9.1). The continuum separates sedation and analgesia into four distinct yet subtle phases: (1) minimal sedation, (2) moderate sedation and analgesia, (3) deep sedation and analgesia and (4) general anaesthesia. Each phase is characterized by the impact on patient responsiveness, airway patency, ventilatory drive and cardiovascular function, which is followed by a brief summary of the rescue skills a non-anaesthesiologist should have when targeting a desired phase of PSA.




Table 9.1. The sedation continuum.








































Minimal Sedation (Anxiolysis) Moderate Sedation/Analgesia (Conscious Sedation) Deep Sedation/Analgesia General Anaesthesia
Responsiveness Normal response to verbal stimulation Purposeful* response to verbal or tactile stimulation Purposeful* response after repeated or painful stimulation Unarousable, even with painful stimulus
Airway Unaffected No intervention required Intervention may be required Intervention often required
Spontaneous ventilation Unaffected Adequate May be inadequate Frequently inadequate
Cardiovascular function Unaffected Usually maintained Usually maintained May be impaired


* Reflex withdrawal from a painful stimulus is not considered a purposeful response.


Developed by the American Society of Anesthesiologists; approved by the ASA House of Delegates 13 October, 1999.


A couple of important points of this sedation continuum merit additional explanation. First, labels of moderate and deep sedation include both ‘sedation and analgesia’. This is a more accurate representation that reflects the common practice of combining sedatives and analgesics for procedures associated with brief intermittent painful stimuli. Second, while under moderate sedation and analgesia, patients should maintain capability of responding to verbal and tactile stimuli, breathe spontaneously and maintain cardiovascular function. This feature makes moderate sedation attractive to sedation practitioners with limited airway skills and experience in managing cardiac or ventilatory depression. Given that patients remain responsive to verbal and tactile stimuli, one disadvantage of moderate sedation is the possibility of experiencing awareness and/or pain during portions of a procedure.


Deep sedation and analgesia is defined as a patient responsive to verbal and painful stimuli. It may be associated with impaired ventilatory function that may require airway manipulation and manual ventilatory support. Patients are less likely to be aware and/or perceive portions during their procedure. This is an attractive feature to patients that wish to be unaware of the procedure; however, deep sedation necessitates practitioners to possess advanced airway management skills, provide life-saving temporary ventilatory support, and have the capability of recognizing and treating subtle changes in cardiovascular function (e.g. high or low blood pressure, fast or slow heart rate).


Sedation practitioners with limited experience in airway management and cardiopulmonary support may intend to deliver moderate sedation, but for various reasons, administer a deeper plane of sedation that may require rescue manoeuvres beyond their skill or experience level. Reasons for unintended deeper plane of sedation may include excessive drug administration, perceived patient awareness or pain, or requests from proceduralists to provide additional sedation and analgesia. A crucial element of sedation practice is the ability to recognize deeper than intended sedation while undertaking life-saving measures to lighten the depth of sedation.


Finally, the transition from one phase of sedation to another can be subtle. Detection of a transition to deeper than intended level of sedation requires heightened vigilance with repeated assessments of responsiveness, airway patency and ventilatory function in order to provide timely rescue manoeuvres.



Self-Rescue and Loss of Responsiveness


Loss of responsiveness to verbal and tactile stimulation marks an important transition from moderate to deep sedation. This crucial transition is associated with an increased likelihood of adverse cardiopulmonary events. Responsive patients can ‘self-rescue’ from a partial or complete airway obstruction as well as hypoventilation when prompted to breathe. Once a patient is rendered unresponsive, the burden of rescue has transitioned to the sedation practitioner. Rescue manoeuvres may require advanced airway skills and prompt pharmacological intervention. Provider rescue may involve calling for help, stopping delivery of sedatives and analgesics, administration of reversal agents if appropriate, positioning the patient to optimize airway management, returning the patient to the intended sedation state and communication with the proceduralist regarding the most prudent course of action (e.g. cancelling the procedure if unsafe or difficult to complete at the intended sedation state, or proceeding to a general anaesthetic).


Sedation practitioners may tolerate brief periods of loss of responsiveness as long as pulmonary function is not compromised. A major concern with sedatives, especially propofol, is the relaxation of oropharyngeal structures that increases the likelihood of partial or complete airway obstruction. Dosing to achieve moderate but not deep sedation is advised when non-anaesthesia trained practitioners administer PSA. If patients cannot tolerate a procedure with moderate sedation, then a physician anaesthesiologist may be required to provide deep sedation and/or general anaesthesia. As always, sedation practitioners should practise within their scope of credentialing, experience and clinical skills.



Key Elements of Sedation


Key elements of a safe sedation practice include a dedicated sedation practitioner who is a distinctive person from the proceduralist, appropriate sedation practitioner training and qualifications, careful patient selection, use of appropriate patient monitors, and a working knowledge of the clinical pharmacology of sedatives and analgesics. Additional detail regarding patient monitoring and the clinical pharmacology of sedatives and analgesics is presented below.



Patient Monitoring


Patient monitoring during sedation and analgesia is primarily directed at detecting adverse cardiopulmonary events [2, 3]. Monitoring standards [1] for sedation recommend frequent assessment of responsiveness, blood pressure, respiratory rate, temperature and oxygen-haemoglobin saturation. In addition, continuous monitoring of the electrocardiogram is recommended along with the ability to detect common arrhythmias. Emergency airway equipment, supplemental oxygen and reversal agents should be immediately available in the procedural suite and post-procedural care area [1]. This section will briefly review monitoring of oxygenation, ventilation, capnography and circulation.



Oxygenation

Assessments of oxygenation include skin colour and pulse oximetry. Pulse oximetry is a standard of care throughout the world and mandated by numerous agencies [4]. Randomized controlled trials [5, 6], however, have reported earlier identification and response to hypoxia, but have failed to demonstrate a reduction in adverse events or an improvement in patient outcomes. Although there are conflicting findings in the literature, pulse oximetry is an innocuous monitor that allows earlier detection of hypoxia compared to no pulse oximetry monitoring.


One limitation of pulse oximetry is the delay between the onset of apnoea, hypopnoea or airway obstruction and a decrease in oxygen-haemoglobin saturation. While breathing room air, healthy individuals can take several minutes before their oxygen saturation drops. Supplemental oxygen only prolongs that delay. For this reason, some sedation practitioners elect not to provide supplemental oxygen. Capnography, by contrast, can detect a decrease or absence of exhaled carbon dioxide much sooner than a decrease in oxygen saturation.



Ventilation

Assessments of ventilatory function include visual observation of chest rise, facemask fogging, impedance measurements of respiratory rate via the electrocardiogram leads, and presence of exhaled carbon dioxide. Detection of inadequate ventilation can be difficult in a sedation setting. Patients may exhibit chest wall movement yet have inadequate ventilation due to partial or complete airway obstruction.



Capnography

In 2011, the ASA added capnography to the recommended list of required monitors for moderate and deep sedation. The aim was to improve monitoring of ventilatory function through continuous detection of exhaled carbon dioxide. Capnography can be more effective at detecting apnoea and/or hypopnoea than pulse oximetry or even direct patient observation.


Capnography may also help sedation practitioners detect partial obstruction even in the presence of chest wall movement. Sedatives can produce airway obstruction before they substantially impair ventilatory drive. In this condition, patients exhibit chest wall movement, but do not ventilate the lungs. This can lead to a paradoxical chest wall movement (a dyssynchronous movement of the chest and abdomen) that, with the abdominal wall and chest covered by the procedure drapes, may appear as normal ventilatory effort.


Proper interpretation of the capnogram may warrant some additional considerations. First, some upper endoscopy procedures may use carbon dioxide to distend the gastrointestinal tract to better visualize tissues. Capnography signals in this case do not represent lung exhalation and do not confirm adequate ventilation. Second, if using high oxygen flows near the carbon dioxide sampling line, exhaled carbon dioxide may be washed away and go undetected or be detected intermittently. Third, most capnography monitors are designed to report a value for the end-tidal carbon dioxide level. The monitor assumes that the signal source is an endotracheal tube or supraglottic airway. When used in sedation practice, there is no endotracheal tube or supraglottic airway present, and the capnography sensor is placed within a face mask or nasal cannula. The gas analyser thus will not be exclusively sampling end-expired gas, but a mixture of end-expired gas and gas from the immediate environment. Consequently, when used in this configuration, the sampled gas does not represent end-tidal gas, and may provide spurious respiratory rates because sampling of these mixed gases may cause CO2 oscillations that are interpreted as consecutive respiratory efforts. To sedation practitioners unfamiliar with this nuance, the capnograph can be difficult to interpret. Capnography monitors should be configured to present the presence or absence of carbon dioxide, not quantify it, and may not accurately present the respiratory rate.


Selected professional societies (The American Society for Gastrointestinal Endoscopy, ASGE, the American Gastroenterological Association, AGA, and the American College of Gastroenterology, ACG) and various studies [7, 8] have pointed out insufficient or conflicting data demonstrating improved clinical outcomes with the use of capnography. The ASGE, AGA and ACG suggest that the use of capnography will lead to excess cost without a proven benefit. Additionally, without standardized definitions and appropriate clinical responses to capnography findings, the use of this technology for PSA is claimed to be questionable. These professional groups do, however, endorse further collaboration with the ASA to develop and validate definitions and appropriate interventions based on capnography. Although the literature presents conflicting outcomes, the authors recommend the use of capnography in all patients undergoing PSA and affirm that it will provide indispensable and timely information to avert preventable sources of morbidity and mortality including hypoxic neurological damage and death. Clinical assessments [2, 9] or a single monitor of ventilation may be misleading and unreliable [10, 11]. To fully monitor ventilatory function (O2 delivery and CO2 removal), complementary measures (pulse oximetry and capnography) should be used.


Chapter 10 discusses the pathophysiology of respiratory depression in anaesthesia and a full discussion of monitoring systems to quantify it.



Circulation

Haemodynamic monitoring during sedation and analgesia includes continuous electrocardiography, non-invasive blood pressure and heart rate. Monitoring standards recommend that the blood pressure be measured at 5-minute intervals while the heart rate and electrocardiogram be continuously monitored [1]. It is important to keep in mind that these parameters are a surrogate of end-organ perfusion and should be used with procedures that require sedation.



Clinical Pharmacology of Sedatives and Analgesics


The pharmacological profiles of selected common sedative and analgesic drugs are presented in Table 9.2 [12, 13]. Approaches to drug delivery for sedation and analgesia include intermittent boluses and continuous infusions. Infusions can be manually controlled, target controlled or patient controlled. Several core principles of clinical pharmacology are important to consider when formulating a safe and effective dosing regimen. These include time to peak effect, titration and opioid–sedative interactions. The reader is also referred to Chapters 1 and 3 for further discussion of pharmacological concepts.




Table 9.2. Pharmacological profile of selected sedatives and analgesics [12, 13].
























































































































Drug Name Mechanism of Action Onset of Action (min) Time to Peak Effect (min) Duration of Action (min) Sedative/Analgesic Dosing Titrate to Effect Antagonist/ Reversal Agent Side Effect Profile
Benzodiazepines
Midazolam GABA agonist 1–2 3–4 30–80 0.02–0.03 mg/kg Flumazenil


  • Dose-dependent respiratory depression

Diazepam 2–3 3–5 360 5–15 mg

Hypotension

Opiods
Remifentanil μ-receptor agonist 1–3 3–5 3–10 0.5–3 μg/kg Naloxone


  • Dose-dependent respirator depression



  • Nausea/Vomiting

Fentanyl 1–2 3–5 30–60 0.5–2 μg/kg


  • Dose-dependent respiratory depression



  • Nausea/Vomiting



  • Bradycardia



  • Muscle rigidity

Meperidine 3–6 5–7 60–180 5–10 mg


  • Dose-dependent respiratory depression



  • Nausea/Vomiting



  • Active metabolite [Twitching]



  • Interaction with MAOI

Other
Dexmeditomidine α2-Agonist 3–5 15 Unknown 0.5–1 μg/kg over 10 minutes None


  • Hypotension



  • Bradycardia

Ketamine NMDA antagonist <1 1 10–15 1–2 mg/kg


  • Hallucination



  • Laryngospasm

Propofol GABA agonist <1 1–2 4–8 0.25–1 mg/kg


  • Dose-dependent respiratory depression



  • Cardiovascular instability



  • Pain on injection

Antagonists/Reversal Agents
Naloxone μ-receptor antagonist 1–2 5 30–45


  • Overdose: 0.4–2 mg



  • Respiratory depression: 0.04–0.4 mg

None


  • Hypertension



  • Tachycardia

Flumazenil GABA antagonist 1–2 3 60


  • 0.2 mg every 1 minute



  • Not to exceed 1 mg




  • Agitation



  • Flushing



  • Headache



  • Muscle tension



Time to Peak Effect

Perhaps the safest approach to sedation is the titration of small boluses over time to achieve a desired effect using the least amount of drug possible. This approach requires an understanding of the time to peak effect, which can be longer than expected for selected drugs used in sedation practice. Initial bolus doses are based on observations in patient populations. Subsequent bolus doses are titrated based on individual patient responses. Large bolus doses used to achieve a desired effect quickly have the disadvantage of excessive effect leading to deeper than intended sedation. The times to peak effect for selected sedatives and analgesics are presented in Table 9.3. A few clinical nuances of these times to peak effect include the following:




  • Remifentanil has a substantially faster time to peak effect than fentanyl or morphine. Central ventilatory depression can be more pronounced with remifentanil. Its rapid onset limits the amount of time for blood carbon dioxide levels to rise and offset opioid ventilatory depression.



  • The long time to peak effect for morphine is important to consider for procedures of brief duration and a planned same day discharge. It will reach peak effect long after the procedure has been completed and will likely still have an effect even after discharge to home.



  • The time to onset of anxiolysis for midazolam is rapid (seconds) and may be misconstrued as the peak effect. Sedation practitioners should keep in mind the time to peak effect may be up to 5 minutes after the first manifestation of anxiolysis.



  • When titrating midazolam and propofol, patients may exhibit a biphasic response. This manifests as an excitatory disinhibition at lower effect-site concentrations followed by decreased responsiveness or unresponsiveness at higher effect-site concentrations. The time to peak effect is important to consider when administering additional bolus doses to achieve the desired level of sedation. This can be challenging when providing sedation for brief but stimulating procedures.



  • Patients that chronically consume opioids and/or benzodiazepines may require larger doses to achieve desired effects. The concentration–effect relationship in this patient group is difficult to ascertain. Suggested initial bolus doses based on prior observations in otherwise healthy patient populations can be ineffective. Accounting for the time to peak effect can be useful when carefully titrating to effect in this patient group.




Table 9.3. Simulations of time to peak effect for bolus doses of select sedatives and analgesics.





































Drug Time to Peak Effect (minutes)
Sedatives
Propofol 1–1.5
Midazolam 6–9
Ketamine 2–10
Opioids
Remifentanil 1–1.5
Sufentanil 1–3
Fentanyl 3–5
Morphine 75–90


Titration

Careful titration is used to achieve desired effects (sedation and analgesia) while minimizing adverse effects (unresponsiveness, ventilatory depression). Titration consists of many small doses rather than one large one. As an example, consider Fig. 9.1. It presents two dosing schemes for the same amount of propofol, 75 mg, based on published propofol dosing regimens for endoscopy procedures [12]. Administering the 75 mg in four divided doses separated by three minutes produces a much different profile in the probability of unresponsiveness than administering all 75 mg at once.


Aug 31, 2020 | Posted by in ANESTHESIA | Comments Off on 9 – Personalized Sedation and Analgesia
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