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Three Part Question

In [patients with atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia requiring electrical cardioversion] are [there medications superior in safety and efficacy] in [achieving procedural sedation]?

Clinical Scenario

An 38 year old male arrives in your emergency department complaining of palpitations and feels slightly light headed. He has never had these symptoms before and is certain that they started 1 hour prior to arrival. He is awake and alert with a blood pressure of 134/82 and a pulse of 128. His physical exam is unremarkable with the exception of tachycardia and an irregularly irregular rhythm.

Search Strategy

Medline 1966-08/06 using the OVID interface, Cochrane Library (2006)
[exp Tachycardia, Ectopic Atrial/ OR exp Atrial Fibrillation/ or atrial.mp. OR exp Atrial Flutter/ OR fibrillation.mp. OR flutter.mp.
OR exp Tachycardia, Supraventricular/ OR exp Tachycardia, Atrioventricular Nodal Reentry/ OR supraventricular.mp. or exp Tachycardia, Paroxysmal/] AND [exp "Hypnotics and Sedatives"/ OR sedation.mp. OR sedat$.mp. OR hypnotic$.mp.] LIMIT to humans and English language

Search Outcome

373 papers found, of which 7 had randomised trials comparing agents for sedation for cardioversion and were felt to be of sufficient quality to include.

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Gale et al, 1993, USA	Thirty adult patients with atrial fibrillation, atrial flutter, or paroxysmal supraventricular tachycardia requiring electrical cardioversion. Patients were randomized to receive one of three study drugs: propofol, midazolam, or methohexital.	Randomized Trial	digital-brachial pressure index (ratio of digital to brachial artery systolic blood pressures), digital temperature and in 10 patients digital artery blood flow was measured using duplex scanner.	Marginal decrease in digital-brachia pressure index after the block (19%, SD 14.6%), finger tip temperature showed mean increase of 0.8 degree celcius (SD 2.3), digital artery blood flow in 10 patients showed initial decrease in 5 to 10 minutes, but in all returned to normal by 1 hour. No one had ischemic damage to the finger	Groups slightly dissimilar at baseline. Small study, power study not done.
			Hemodynamics	No significant difference
			Dose requirements	Propofol: 1.69 +/- 0.46 mg/kg. Methohexital: 1.07+/- 0.34 mg/kg. Midazolam: 0.16 +/- 0.06 mg/kg.
			Time to awakening	Propofol: 11.2+/- 4.4 min. Methohexital: 9.4 +/- 2.8 min. Midazolam: 33.1+/- 15.1 min.
			Adverse effects	Propofol: 2/10 patients recalled shock one hour after event. Pain on injection noted. Methohexital: One patient recalled shock. Midazolam: 5/10 patients with post-recovery confusion lasting > 10 mins.
Coll-Vincent et al, 2003, USA	Thirty two hemodynamically stable adult patients undergoing cardioversion in the ED. These patients were randomized receive etomidate, propofol, midazolam, or midazolam followed by flumazenil.	Randomized control trial	Induction time	Propofol: 50 (30-100) seconds. Etomidate: 90 (25-120) sec. Midazolam: 120 (30-180) sec. Midazolam + Flumazenil: 112 (30-350) sec.	Small study, no power study done
			need for further injection of local anaesthetic, need for tourniquet and ischemic complications.	Need for tourniquet (20/29 of plain lignocaine group vs 9/31 of adrenaline group, p<0.002), need for further anaesthetic (5/29 of plain lignocaine vs 1/31 of adrenaline group, p=0.098), no ischemic complications in the adrenaline group
			Hemodynamics	No significant differences
			Time to awakening	Propofol: 8 (3-15) min. Etomidate: 9.5 (5-11). Midazolam: 21 (1-42). Midazolam + Flumazenil: 3 (2-5).
			Adverse effects	Propofol: 1/9 broncho-spasm. Etomidate: 4/9 myoclonus, 1 bronchospasm, 4 pain at injection site, 2 cough Midazolam: 3 dizziness Midazolam + Flumazenil: 5 resedation
Valtonen et al, 1988, Finland	35 patients undergoing elective cardioversion due to atrial fibrillation. 30 patients received one cardioversion. 5 patients were cardioverted twice in the study period and received the other form of sedation the on the second occasion.	Patients were randomised to receive either 2.5mg/kf propofol or 5mg/kg thipentone and then observed until unresponsive to speech. The patient was then given up to 3 DC shocks.	Need for tourniquet, degree of analgesia, duration of analgesia and ischemic damage to the digit	Need for tourniquet (Gp A= 20%, Gp B= none), pain score at 1 hour (Gp A=4.1 and Gp B=1.4), duration of analgesia ( Gp A=2.4 hrs, Gp B=4.6 hrs), No case of ischemic damage to finger	Small group. Much of the data provided in form of graphs so unable to extract it to put in table form.
			Induction time	72.0+/-20.0s for propofol vs. 60.3+/-13.0s for thiopentone
			Anatomical, radiographic and fucntional results	158 patients successfully treated
			Time to orientation - from end of procedure	7.7+/-2.9 min for propofol vs. 6.5+/-4.4 min for thiopentone.
			Successful cardioversion	11/15 for propofol, 13/15 for thiopentone.
Ford, S; Maze, M; Gaba, D 1991 USA	16 male patients undergoing elective cardioversion for atrial fibrillation or flutter.	Patients were randomised to receive 0.2% etomidate or 2.5% thiopental. The drugs were administered at 2ml every 15 sec until the patient no longer responded to verbal commands. Observer blinded to drug received.	Change in mean heart rate.	Etomidate decreased the mean heart rate by 5%, thiopental increased it by 7%.	Small study.
			Digital ischemic complications	None
			Change in mean arterial pressure	Etomidate decreased MAP by 4%, Thiopental decreased it by 3%.
			Failure of cardioversion	1 in each group.
			Pt recall of cardioversion	1 in each group.
			Time of onset of adequate sedation (min)	Etomidate 1.8±0.2; Thiopental 2.3±0.2
			Orientation time (min)	Etomidate 7.4±1.2; Thiopental 10.1±3.5
			Myoclonus	Etomidated 3/8 pts; Thiopental 0/8 pts.
Canessa, R; Lema, G; Urzua, J; Dagnino, J; Concha M 1991 Chile	44 patients with atrial flutter or fibrillation attending for elective cardioversion. All patients received 1.5µg/kg fentanyl in addition to the sedative.	Patients randomised by last digit of case-note number to one of 4 agents for sedation. 12 pts received 3mg/kg thiopental (T), 10 patients received 0.15mg/kg etomidate (E), 12 patients received 1.5mg/kg propofol (P) and 10 patients received 0.15mg/kg midazolam (M).	Change in mean systolic blood pressure.	T decreased by 19%, E no significant difference, P decreased by 29%, M decreased by 19%.	Small groups. Poor method of randomisation (treating physician knows which drug patient will receive before decides whether or not to recruit them). Not clear how randomised between four outcomes using ten digits.
			digital gangrene from use of adrenaline in finger	Total 21 cases of digital gangrene reported involved use of adrenaline, all from early 20th century. Analysis of individual cases did not support adrenaline itself as the cause. Inappropriate mixing of adrenaline, inappropriate use of tourniquet, use of hot soaks, infection, and use of large volume of anaesthetic were associated the cases.
			Successful cardioversion	T 12/12; E 7/10; P ?11/12 (given as 90%); M 9/10
			Mean induction time in seconds (range)	T 31(10-50); E 34 (12-49); P 17 (10-40); M 68 (30-220)
			Myoclonus	T 0; E 3; P 0; M 0
			Apnoea (loss of ventilatory effort >30sec)	T 2/12; E 1/10; P 7/12; M 1/10
Mitchell, A; Chalil, S; Boodhoo, L; Bordoli, G; Patel, N; Sulke, N 2003 UK	141 patients attending one unit for elective cardioversion of an atrial tachyarrhythmia who had not been cardioverted under sedation previously.	Patients were randomised to receive diazepam (5-10mg bolus followed additional 5-10mg doses every minute up to a maximum of 70mg) or midazolam (5mg bolus plus 1-2mg every minute up to a maximum of 30mg).	Successful cardioversion	87% of pts receiving diazepam vs. 89% of patients receiving midazolam.	Only patients blinded to drug received.
			Digital artery blood flow.	Statistically significant drop in blood flow at 10 minutes after the block in all subjects. In all cases blood flow returned to normal by 60 to 90 minutes.Vasoconstrictive effect of adrenaline is not persistent.
			Episode of hypotension (decrease in systolic BP >20mmHg or systolic BP <100mmHg.	7% of pts receiving diazepam vs. 20% of patients receiving midazolam.
			Episode of oxygen desaturation (<99% despite supplementary oxygen)	No patients receiving diazepam vs. 3% of patients receiving midazolam.
			Time for adequate sedation (min)	Diazepam 6.5±3.4 vs. midazolam 5.0±3.4.
			Time till awake and orientated (min)	Diazepam 39±24 vs. midazolam 77±46.
			Pt able to recall events	1 in diazepam group, none in midazolam group.
Herregods, L; Bossuyt, G; Baerdemaeker, L; et al 2003 Belgium	34 patients with atrial arrhthmias who were scheduled to receive repetitive electrical cardioversion. 9 patients were not successfully cardioverted at the first or second session and so only 25 patients were analysed.	Patients randomised in prospective double-blinded study to receive either 0.2mg/kg etomidate or 1mg/kg propofol. The patients were then cardioverted again at least one week later using the alternative agent. Patients who were not successfully cardioverted by four attempts at either session were excluded.	Digital gangrene	48 cases of digital gangrene, only 21 involved use of adrenaline. None of the cases indicate adrenaline solely as the cause of gangrene. Other factors like high concentration of adrenaline, use of older agents, excessive volume of injection, prolonged use of tourniquet, infection and use of hot soaks	No information about induction times. Small group.
			Required manually assisted ventilation.	7/25 etomidate vs. 5/25 propofol.
			Time to opening eyes (sec)	6.1±2.0 etomidate vs 4.7±1.2 propofol.
			Myoclonus	6/25 etomidate vs 0/25 propofol.
			Signficant decrease in BP	No patients in either group.

Comment(s)

All of the agents used in these studies had relatively short time of onset and short duration of action with the exception of the benzodiazepines which were considerably longer for both. All anaesthetic agents have the potential to cause hypotension though this did not cause any serious adverse events in any of the patients who participated in these studies. Etomidate may cause less hypotension than other agents but does cause myoclonus in some patients.

Clinical Bottom Line

Propofol, methohexital, thiopentone and etomidate all appear to be good choices for procedural sedation for patients requiring electrical cardioversion for atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia. Midazolam and diazepam have a significantly longer recovery time, and can produce confusion in the recovery period as well. They should be considered a second line agents for sedation for cardioversion.

Level of Evidence

Level 3 - Small numbers of small studies or great heterogeneity or very different population.

References

1. Gale DW, Grissom TE, Mirenda JV. Titration of intravenous anesthetics for cardioversion: A comparison of propofol, methohexital, and midazolam. Critical Care Medicine 21(10):1509-13, 1993 Oct.
2. Coll-Vincent B, Xavier S, Fernandez C et al. Sedation for cardioversion in the Emergency Department: Analysis of Effectiveness in Four Protocols. Annals of Emergency Medicine 42(6):767-72, 2003 Dec.
3. Valtonen, M; Kanto, J; Klossner, J Anaesthesia for cardioversion: A comparison of propofol and thiopentone Canadian Journal of Anaesthesia 35(5):479-83, 1988 Sep.
4. Ford, S; Maze, M; Gaba, D A Comparison of Etomidate and Thiopental Anesthesia for Cardioversion Journal of Cardiothoracic and Vascular Anesthesia 1991; 5 (6) p563-565
5. Canessa, R; Lema, G; Urzua, J; Dagnino, J; Concha M Anesthesia for Elective Cardioversion: A Comparison of Four Anesthetic Agents Journal of Cardiothoracic and Vascular Anesthesia 1991; 5 (6) p566-568
6. Mitchell, A; Chalil, S; Boodhoo, L; Bordoli, G; Patel, N; Sulke, N Diazepam or midazolam for external DC cardioversion (The DORM Study) Europace 2003; 5 p391-395
7. Herregods, L; Bossuyt, G; Baerdemaeker, L; et al Ambulatory Electrical External Cardioversion with Propofol or Etomidate Journal of Clinical Anesthesia 2003; 15 p91-96