Sedation for flexible bronchoscopy: current and emerging evidence

Ricardo J. José; Shahzad Shaefi; Neal Navani

doi:10.1183/09059180.00006412

Tables

Table 1. Ramsay sedation scale

1	Patient is anxious and agitated or restless, or both
2	Patient is cooperative, oriented and tranquil
3	Patient responds to commands only
4	Patient exhibits brisk response to light glabellar tap or loud auditory stimulus
5	Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus
6	Patient exhibits no response

Table 2. Pre-sedation flexible bronchoscopy checklist

Patient identifier (name, date of birth)

Consent form signed

Responsible adult available to escort the patient post-procedure

Adequate fasting period

Allergies

Hepatic and renal function (if the clinical history suggests these could be abnormal)

Observations (vital signs)

Continuous pulse oximetry available

Intravenous access functioning

Medications checked

Resuscitation trolley available with emergency drugs

Reversal drugs available (flumazenil and naloxone)

Oxygen available (including variety of oxygen delivery devices)

All staff ready for the procedure to commence

Data from [22].

Table 3. Pharmacological properties of common sedatives used in bronchoscopy

Drug	Fentanyl	Alfentanil	Morphine	Midazolam	Lorazepam	Diazepam	Propofol 1%	Fospropofol
Dose i.v.	Initial: 25–50 μg	Initial: 250 μg	Initial: 2.5 mg	Initial: 2–2.5 mg (0.5–1 mg in the elderly)	Initial dose: 1.5–2 mg	Initial dose: 5–10 mg	Initial: 10–50 mg titrated to effect	Initial: 6.5 mg·kg⁻¹
	Supplemental: 25 μg	Supplemental: 250 μg	Supplemental: 2.5 mg	Supplemental: 1 mg (0.5–1 mg in the elderly) at 2–5 min intervals	Supplemental: usually not required Wait at least 10 min	Supplemental: usually not required Wait at least 10 min	Supplemental: 25% of initial dose	Supplemental: 1.6 mg·kg⁻¹
							Infusion: 25–100 μg·kg⁻¹·min⁻¹
Onset of action	3–5 min	Immediate	5–10 min	30–60 s	8–15 min	1 min	30–60 s	6.5 min
Peak effect	5 min	Immediate	15–30 min	5–10 min	15–30 min	2–3 min	2 min	12 min
Duration of action	1–2 h	1–2 h	1–6 h	30–120 min	8 h	1–3 h	4–8 min	17 min
Metabolism	Hepatic	Hepatic	Hepatic	Hepatic	Hepatic	Hepatic	Hepatic	Hepatic
Renal excretion	<5%	<1%	90%	<1%	<1%	<1%	70%	70%
Elimination half-life	3–4 h	1–2 h	2 h	1.5–2.5 h	11–22 h	20–50 h	3–12 h	45 min
Major/common adverse evens	Respiratory depression, nausea and vomiting	See fentanyl	See fentanyl	Respiratory depression, hypotension	See midazolam	See midazolam	Respiratory depression, bradycardia, hypotension, pain at the injection site	Respiratory depression, hypotension, paraesthesiae, pruritus
Antagonists	Naloxone 100–200 μg (1.5-3 μg·kg⁻¹) with supplemental doses of 100 μg every 2 min until reversal occurs			Flumazenil 0.2 mg, repeated every 60 s up to 1 mg; if a continuous infusion is required the dose is 0.1–0.4 mg·h⁻¹			No antagonist available
Comments	Combination with benzodiazepines may enhance respiratory depression Administer prior to the benzodiazepines, as a lower dose of benzodiazepine will be required to achieve the desired degree of sedation	See fentanyl	See fentanyl	Combination with opiates may enhance respiratory depression	See midazolam	See midazolam	Combination with opiates may enhance respiratory depression Dose and rate of administration should be adjusted according to desired level of sedation and response For patients >65 years or with severe systemic disease reduce the dose by 25%	See propofol

Adapted from [10, 18, 36].

Table 4. Summary of clinical studies of propofol in flexible bronchoscopy

Article	Study type	Drug	Main results
Clarkson [54]	Randomised, double-blind, prospective-controlled study	Propofol (n=21) versus midazolam (n=20)	More rapid onset and recovery from sedation seen in the propofol group No significant difference in the amount of topical anaesthetic required or in oxygen desaturation
Crawford [55]	Randomised, double-blind, prospective-controlled study	Propofol (n=21) versus midazolam–alfentanil (n=21)	In three patients in the midazolam–alfentanil and five in the propofol group the depth of sedation exceeded the moderate level Recovery to an appropriate level was more rapid in the latter group Oxygen saturations decreased in both groups and there were no significant differences in blood pressure Those in the midazolam group had more amnesia and longer recovery time
Gonzalez [5]	Randomised, single-blind, prospective-controlled study	Propofol (n=9) versus no sedation (n=9)	Less cough, pain, sensation of asphyxiation, total amnesia and improved tolerance of the procedure in the propofol group No differences in oxygen saturations between the groups
Hwang [47]	Randomised, double-blind, prospective-controlled study	Propofol–alfentanil (n=138) versus propofol–ketamine (n=138) for patient-controlled sedation	Patients in the propofol–ketamine group reported greater amnesia and satisfaction Haemodynamic stability and adequate oxygenation during the procedure in both groups; however, a significant drop in oxygen saturations below 90% was seen in both groups immediately before the procedure This was transient and with no sequelae
Clark [20]	Randomised, double-blind, prospective-controlled study	Propofol (n=43) versus midazolam (n=39)	Propofol resulted in faster recovery from sedation and patient tolerance and satisfaction were improved There were no differences in operator satisfaction Safely administered by non-anaesthetis
Stoltz [56]	Randomised, non-blinded, prospective-controlled study	Propofol (n=100) versus midazolam–hydrocodone (n=100)	Mean oxygen saturation and desaturation below 90% were similar in both groups Patients receiving propofol had less tachycardia during the procedure and faster recovery from sedation
Grendelmeier [12]	Prospective case series	Propofol (n=440)	Systolic blood pressure dropped below 90 mmHg in 15.4% and oxygen saturation dropped below 90% in 16.4% of patients but some of these had higher American Society of Anesthesiology scores and were already hypotensive or hypoxaemic prior to the sedation None of the patients required intubation
Lo [21]	Randomised, non-blinded, prospective-controlled study	Propofol (n=243) versus midazolam (n=249)	Bispectral index-guided propofol infusion is as safe as clinically judged midazolam sedation The proportion of patients with hypoxemia or hypotensive events were not different in the two groups but those in propofol group had the lowest mean arterial blood pressure and oxygen saturation readings Those in the propofol group had less cough, improved procedure tolerance and faster recovery from sedation
Yoon [57]	Randomised, double-blind, prospective-controlled study	Propofol (n=32) versus propofol–alfentanil (n=32)	They did not find differences in patient or bronchoscopist satisfaction or in degree of coughing but those in the alfentanil group had significantly lower oxygen saturation levels. However, the lower levels of oxygen saturation reported in the alfentanil are most likely not clinically significant
Schlatter [58]	Randomised, double-blind, prospective-controlled study	Propofol (n=154) versus propofol–hydrocodone (n=146)	This combination suppressed coughing and reduced patient discomfort during flexible bronchoscopy compared to placebo alone with no differences in complication rates
Carmi [59]	Randomised, non-blinded, prospective-controlled study	Propofol (n=56) versus midazolam–alfentanil (n=59)	Those in the midazolam–alfentanil group rather than the propofol group had higher carbon dioxide tension values and required more oxygen supplementation or airway support; however, both were considered equally safe and effective