Optimal sedation and management of anxiety in patients undergoing endobronchial ultrasound (EBUS) Georgios Dadoudis Anesthesiologist ICU DIRECTOR INTERBALKAN MEDICAL CENTER
Optimal performance requires: patient s comfort physician s ease of execution minimal risk No standardized practice for the use of sedation with a good deal of variation among physicians regarding the use of pre-procedure medication and pharmacological sedatives Ongoing debate about: proceduralist-administered versus anaesthetist-administered sedation Growing body of evidence that non-anaesthetist administered sedation is safe and cost-effective
Sedation Sedation is defined as a continuum of altered consciousness levels, including minimal sedation (anxiolysis), moderate sedation (conscious sedation), deep sedation, and general anesthesia The extent of sedation can vary based on the patient, the procedural settings and complexity and duration of the procedure. The depth of sedation should always be monitored throughout the procedure and documented using the Ramsay scale
Sedation Sedation is defined as a continuum of altered consciousness levels, including minimal sedation (anxiolysis), moderate sedation (conscious sedation), deep sedation, and general anesthesia The extent of sedation can vary based on the patient, the procedural settings and complexity and duration of the procedure. The depth of sedation should always be monitored throughout the procedure and documented using the Ramsay scale Moderate sedation is commonly used and is defined as a drug-induced depression in consciousness where in patients can respond purposefully to verbal commands while maintaining a functional airway, spontaneous ventilation, and cardiovascular function (< Level 3) Deep sedation is less commonly used and causes a deeper state of depressed consciousness in which patients cannot be easily aroused but respond purposefully to repeated or painful stimulation and may have compromised airway function and spontaneous ventilation; cardiovascular function is usually maintained
Optimal sedation Intravenous sedation should be offered to patients undergoing procedure, provided there are no contraindications (Grade B) Some patients will tolerate un-sedated procedure well, and patient preference should be sought (Grade B) Sedative drugs should be titrated to provide the desired depth of sedation, given significant inter-patient variability in required doses (Grade B) The desired depth of sedation is one in which verbal contact is possible at all times (Grade D)
Monitoring ECG monitoring BP Respiratory Rate Before, during and after the procedure Oxygen Saturation by Pulse Oximetry
Use of pre-medication With the present methods of sedation, pre-medication: does not appear to be necessary to improve procedure tolerance and patient satisfaction leads to the potential of over-sedation and adverse effects Anticholinergics should not routinely be used prior to procedure due to a lack of clinical benefit and a possible increased risk of haemodynamic changes (Grade A)
Use of Topical Anesthesia Topical anesthesia before and during procedure decreases cough and reduces the dose of sedation needed Lidocaine is the suggested preferred topical anesthetic The minimum effective dose should be used and caution should be exercised in patients with advanced age, impaired liver function or congestive heart failure Cardiac and neurologic toxicity (circumoral paraesthesia, seizures, and cardiac arrhythmias) are dose-related and can occur if the total topical dose exceeds 7 mg/kg
Use of Sedative and Analgesic Agents Benzodiazepines Benzodiazepines are the suggested preferred sedation agents for use because of their favorable effects, including: sedation anterograde amnesia decreased patient discomfort improved tolerance of procedure willingness of patients to undergo a repeat procedure improved working conditions for physicians They have hypnotic, anxiolytic, anti-convulsant and muscle relaxing properties
Use of Sedative and Analgesic Agents Benzodiazepines Benzodiazepines and fentanyl are metabolised by CYP 3A4!!! risk of prolonged sedation in those receiving concomitant medications that inhibit these enzymes such as antifungals, antiretrovirals, calcium channel blockers and macrolide antibiotics Natural variability in the action of cytochrome P450 (CYP) 3A4 and 3A5, responsible for benzodiazepine metabolism, may prolong elimination half life by up to six-fold in 5 8% of the population Adjustment in dosages is recommended in patients with advanced age and liver cirrhosis because these patients may metabolize benzodiazepines more slowly and are more prone to adverse effects, including drowsiness, ataxia, hangover effects, confusion, and falls
Use of Sedative and Analgesic Agents Benzodiazepines Benzodiazepines have relatively small cardiovascular depressant effects and only result in slight decreases in arterial blood pressure and increases in heart rate The ventilatory drive is depressed and although apnea is not usually seen with low doses used for moderate sedation this may occur with higher doses, in those with comorbidities and when used in combination with other respiratory depressants They may lengthen recovery time, but is not associated with an increase in complication rate
Use of Sedative and Analgesic Agents Benzodiazepines The availability of an effective reversal agent for benzodiazepines further solidifies their suitability as a sedation agent Flumazenil must be immediately available, although its administration should not be part of routine sedation practice It has a shorter half-life than the benzodiazepines used so its effect may cease before that of the benzodiazepine and lead to re-depression of the respiratory drive unless supplemental doses are given For reversal of benzodiazepine sedation, the dose of flumazenil is 0.2 mg, repeated every 60 s up to 1 mg
Use of Sedative and Analgesic Agents Midazolam The suggested preferred benzodiazepine agent quick onset of action rapid peak effect relatively short duration of effect (Grade B) The dose is 0.06 to 0.07 mg/kg No more than 5 mg should be initially drawn up into any syringe prior to procedure for patients under the age of 70 (2 mg for patients over 70) to prevent over-sedation (Grade D) Only low-strength (1 mg/ml) should be available within bronchoscopy suites (Grade D)
Use of Sedative and Analgesic Agents Opioids Opioids are ideal agents because of their primary action in the brain (sedation), their exert physiologic effects, such as analgesia and cough suppression and the availability of an effective reversal agent The use of combination of benzodiazepines and opioids is suggested because of synergistic effects on patient tolerance during the procedure and the added antitussive properties of opioids (Grade B) When combination sedatives are used, opioids should be administered first and allowed time to become maximally effective before administration of any other agent (Grade D) For over-sedated patients who have received benzodiazepine and opioid, initial reversal with flumazenil (rather than naloxone) is recommended, unless the patient has received a particularly high dose of opioid
Use of Sedative and Analgesic Agents Opioids They are mainly metabolised by the liver and excreted in by the kidneys Due to renal elimination, opioids (especially morphine) can accumulate (metabolites) in patients with renal failure leading to prolonged sedation and ventilatory depression In high doses opioids lead to bradycardia and associated hypotension but do not depress cardiac contractility The effects on the respiratory system are more noteworthy, particularly reduction of the respiratory rate resulting in ventilatory depression
Use of Sedative and Analgesic Agents Opioids Fentanyl is the suggested preferred opioid agent in bronchoscopy because of its quick onset of action, rapid peak effect, and relatively short duration of effect (Grade D) The recommended dose in moderate sedation is 50 200 μg followed by supplemental doses of 50 μg Caution!!! at the upper limit of this range, ventilatory depression is more likely, especially when co-administered with other sedatives Therefore, an initial dose of 25 50 μg is recommended with supplemental doses of 25 μg as required until the desired effect is achieved or a total dose of 200 μg has been reached.
Use of Sedative and Analgesic Agents Opioids Naloxone is the competitive opioid antagonist The intravenous dose for reversal of opioid respiratory depression and over sedation is usually 100-200 μg (1.5 3 μg/kg) with supplemental doses of 100 μg every 2 min until reversal occurs to the desired level of respiration and consciousness With a short mean half-life of 64 min, oversedation may recure and an infusion or repeated dosing every 1 2 h may be required
Use of Sedative and Analgesic Agents Propofol An i.v anesthetic that produces sedation, anxiolysis and amnesia but has no direct analgesic properties Can achieve similar sedation, amnesia, and patient tolerance compared with the combined administration of benzodiazepines and opioids No difference in adverse events, particularly hypoxia, between propofol and the combined administration of benzodiazepines and opiates, with the added advantage of shorter recovery time for patients sedated with propofol When administered as a sole agent, a single intravenous bolus dose of 0.5 1.0 mg/kg given at a rate of 40 mg over 10 s until the desired level of sedation is achieved (1 2.5 mg/kg for induction of anaesthesia) with top up doses of 25 50 mg every few minutes as required
Use of Sedative and Analgesic Agents Propofol It causes a decrease in systemic vascular resistance and cardiac contractility resulting in a drop in the arterial blood pressure It can attenuate upper airway reflexes and can cause profound respiratory depression leading to apnoea at induction doses and in doses used for conscious sedation it can inhibit the hypoxic ventilatory drive It may cause pain on injection Allergy??
Use of Sedative and Analgesic Agents Propofol There is no antagonist The administration of propofol in the endoscopy suite by non-anesthesiologists has been an area of debate and is currently subject to local regulation It is impossible to predict how individual patients may respond to agents such as propofol Non-anesthesia personnel administering propofol should be qualified to adequately treat patients whose level of sedation becomes deeper than initially intended (Grade B)
Use of Sedative and Analgesic Agents Ketamine Especially for the paediatric population Dissociative anaesthesia with the patient appearing conscious but unable to respond to sensory input It is bio-transformed in the liver and excreted in the urine It has a short-elimination half-life of 2 h Ketamine results in an increased heart rate, cardiac output and arterial blood pressure due to stimulation of the sympathetic nervous system When used alone it has minimal effect on ventilatory drive, generally preserving airway patency and respiratory function, but may cause apnoea when used in combination with other pharmacological sedatives and opioids. An advantage of ketamine is that it is a potent bronchodilator and analgesic, but it has the disadvantage of causing increased salivation and secretions, not attenuating upper airway reflexes and resulting in emergence delirium (e.g. confusion and hallucinations) in 10 20% of adults
Use of Sedative and Analgesic Agents Dexmedetomidine A selective a2-agonist with sedative and analgesic properties It has the advantage of only causing mild respiratory depression at higher doses Sympathomimetic and vagolytic actions that may lead to bradycardia and hypotension continuous cardiovascular monitoring to avoid unwanted complications Dexmedetomidine does not have anti-tussive properties like the opioids so increased cough is expected
EBUS and Sedation EBUS is usually performed under procedural sedation and local anesthesia If needed EBUS can be done in general anesthesia The use of a laryngeal mask airway allows access to upper paratracheal nodes, which may not be accessible with endotracheal tube in place The size of endotracheal tube should be at least No. 8 or larger, to accommodate the CP-EBUS bronchoscope Patient should be NPO for at least 6 hours
Compare deep sedation (DS) versus moderate sedation (MS) in patients undergoing EBUS-TBNA procedure PubMed, EMBASE, MEDLINE, and Cochrane Library for English studies of clinical trials comparing the two different methods of sedations in EBUS-TBNA until December 2015 The overall diagnostic yield, LN size sampling, procedural time, complication, and safety were evaluated Six studies with 3000 patients
The overall diagnostic yield of DS method was 52.3% 100% and MS method was 46.1% 85.7% The overall sensitivity of EBUS-TBNA of DS method was 98.15% 100% as compared with 80% 98.08% in MS method The overall procedural times were 27.2 50.9 min and 20.6-44.1 min in DS and MS groups, respectively The numbers of LN sampled were between 1.33 3.20 nodes and 1.36 2.80 nodes in DS and MS groups, respectively The numbers of passes per LN were 3.21 3.70 passes in DS group as compared to 2.73 3.00 passes in MS group The mean of LN size was indifferent between two groups None of the studies included reported serious adverse events
Conclusions In the absence of contraindications, topical anesthesia, analgesia, and sedation are suggested in all patients because of enhanced patient tolerance and satisfaction(grade B) Anticholinergics should not routinely be used prior to procedure due to a lack of clinical benefit and a possible increased risk of haemodynamic changes(grade A) Lidocaine is the preferred topical anesthetic The use of a combination of benzodiazepines and opiates is suggested Propofol is an effective agent for sedation and can achieve similar sedation, amnesia, and patient tolerance when compared with the combined administration of benzodiazepines and opiates
Conclusions Bronchoscopist-delivered sedation should be carefully titrated using small incremental doses to avoid oversedation, particularly given significant variability of patient response to sedatives The practice of non-titrated single large bolus dose sedation regimes infusion strongly discouraged (arm brain circulation time high) or continuous The desired depth of sedation is usually conscious sedation, although interventional bronchoscopy may occasionally require deeper sedation provided by formal anaesthetic support Patients who are more deeply sedated should have the same level of care and monitoring as those undergoing a formal general anaesthetic
Conclusions Experience in procedure Drug experience Place of procedure Duration/complex of procedure Monitoring Anaesthesiologist?
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