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Table 2 Main outcomes, key findings, and risk of bias assessments for summarized studies

From: Prevention of alcohol withdrawal seizure recurrence and treatment of other alcohol withdrawal symptoms in the emergency department: a rapid review

Author

Participants

Intervention

Comparison

Main outcome(s)

Key results

Risk of bias

Benzodiazepines alone

    

Intervention group

Comparison group

 

Benzodiazepine vs. placebo

 D’Onofrio G, Rathlev NK, Ulrich AS, Fish SS, Freedland ES (1999) [31]

Adults with witnessed generalized seizure related to alcohol

Lorazepam 2 mg IV (n = 100)

Placebo (n = 86)

Seizure recurrence within 6 h of intervention

3/100 (3.0%) *

21/86 (24.4%)odds ratio 10.4

(95% CI: 3.6 to 30.2)

Low

 Naranjo CA, Sellers EM, Chater K, Iversen P, Roach C, Sykora K (1983) [39]

Adults with mild-to-moderate AWS (clinician assessment)

Scheduled lorazepam 2 mg PO q2h (max. 3 doses) (n = 21)

Placebo (n = 20)

Seizure recurrence within 6 h of intervention

1/21 (4.8%) *

3/20 (15.0%)

Low

Benzodiazepine selection

 Scheuermeyer FX, Miles I, Lane DJ, Grunau B, Grafstein E, Sljivic I, et al. (2020) [32]

Adults with AWS (ED discharge diagnosis) treated with lorazepam or diazepam

Lorazepam (dose and route at physician discretion)

(n = 394)

Diazepam (dose and route at physician discretion)

(n = 504)

1. Hospital admission (including ICU)

69/394 (17.5%) effect size: − 1.2

(95% CI: − 6.3 to 4.2)

94/504 (18.7%)

Serious

2. Seizures in ED before treatment

3/394 (0.8%) *effect size: −0.03

(95% CI: −1.7 to 1.5)

4/504 (0.8%)

3. ED length of stay (non-admitted patients)

Median 266 min

(IQR 163 to 387)effect size: −33

(95% CI: −75 to −6)

Median 299 min

(IQR 192 to 463)

Symptom-triggered therapy

 Ismail MF, Doherty K, Bradshaw P, O’Sullivan I, Cassidy EM (2019) [33]

Adults with AWS (clinician assessment) placed on treatment protocol in a short stay clinical decision unit

Symptom-triggered diazepam (route not specified) when CIWA ≥10 (n = 174)

N/A

1. Cumulative diazepam dose

Median 20 mg (IQR 80)

N/A

 

Serious

2. Duration of symptom-triggered protocol

Median 12 h (IQR 12)

3. Length of stay in clinical decision unit

Median 22 h (IQR 20)

  

4. ED discharge

169/174 (97.1%)

 Cassidy EM, O’Sullivan I, Bradshaw P, Islam T, Onovo C (2012) [40]

Adults with AWS (clinician assessment) treated in the ED clinical decision unit

Symptom-triggered benzodiazepine

(n = 49)

Fixed dose benzodiazepine

(n = 50)

1. Cumulative benzodiazepine dose (in diazepam equivalents)

Median 80 mg

(range 0 to 900) *

Median 170 mg

(range 15 to 720)

Serious

2. Hospital length of stay

Median 2 days

(range 1 to 9) *

Median 3 days

(range 1 to 12)

Combined phenobarbital and benzodiazepines

 Ibarra Jr. F (2020) [41]

Adults with moderate/severe AWS requiring treatment (clinician assessment)

Phenobarbital 130 to 260 mg IV + symptom-triggered lorazepam PO/IV (n = 40)

Symptom-triggered lorazepam PO/IV (n = 38)

1. Total lorazepam doses (Day 1)

Median 16 mg

(IQR 6 to 32)

Median 10 mg

(IQR 6 to 19)

Serious

2. Total lorazepam doses (Day 2)

Median 10 mg

(IQR 2 to 29)

Median 6 mg

(IQR 2 to 12)

3. Total lorazepam doses (Day 3)

Median 2 mg

(IQR 0 to 30)

Median 2 mg

(IQR 0 to 6)

4. ED discharge

4/40 (10.0%)

2/38 (5.3%)

5. Hospital admission (non-ICU)

34/40 (85.0%)

32/38 (84.2%)

6. ICU admission

2/40 (5.0%)

4/38 (10.5%)

7. Discharged within three days of admission

9/40 (22.5%)

2/38 (5.3%)

 Sullivan SM, Dewey BN, Jarrell DJ, Vadiei N, Patanwala AE (2019) [34]

Adults with primary ED diagnosis of AWS

Phenobarbital +/− symptom-triggered benzodiazepine

(n = 97)

Symptom-triggered benzodiazepine

(n = 112)

1. ICU admission

14/97 (14.4%)

12/112 (10.7%)

Serious

2. ED length of stay

Median 9 h

(IQR 6 to 14)

Median 9 h

(IQR 6 to 14)

3. Median hospital length of stay

3 days (IQR 2 to 5)

4 days (IQR 2 to 6)

4. Hospital admission (non-ICU)

41/97 (42.3%)

60/112 (53.6%)

5. ED discharge

42/97 (43.3%)

40/112 (35.7%)

6. CIWA scores at ED discharge

Median 7

(IQR 4 to 12)

Median 7

(IQR 4 to 14)

 Rosenson J, Clements C, Simon B, Vieaux J, Graffman S, Vahidnia F, et al. (2013) [35]

Adults with suspected AWS (clinician assessment)

Phenobarbital 10 mg/kg IV over 30 min + symptom-triggered lorazepam PO/IV (n = 100)

Symptom-triggered lorazepam PO/IV (n = 98)

1. ICU admission

4/51 (7.8%)effect size: 17

(95% CI 4 to 32)

13/51 (25.5%)

High

2. Telemetry unit admission

23/51 (45.1%)effect size: −6

(95% CI −25 to 13)

20/51 (39.2%)

3. General ward admission

24/51 (47.1%)effect size: −12

(95% CI −31 to 7)

18/51 (35.3%)

4. Hospital length of stay (non-ICU)

Median 76 h (IQR 54 to 114)effect size: 42

(95% CI −4 to 82)

Median 118 h (IQR 47 to 190)

5. ICU length of stay

Median 34 h (IQR 30 to 276) effect size: 60 (95% CI − 170 to 434)

Median 94 h (IQR 43 to 134)

Phenobarbital alone

 Nelson AC, Kehoe J, Sankoff J, Mintzer D, Taub J, Kaucher KA (2019) [36]

Adults requiring medical treatment for AWS (clinician assessment)

Phenobarbital IV (n = 100)

1. Diazepam IV (n = 100)2. Phenobarbital IV + lorazepam IV (n = 100)

1. ICU admission

13/100 (13.0%)

Diazepam: 8/100 (8.0%)Phenobarbital + lorazepam: 11/100 (11.0%)

Serious

2. Hospital admission (non-ICU)

41/100 (41.0%)

Diazepam: 27/100 (27.0%)Phenobarbital + lorazepam: 36/100 (36.0%)

3. Hospital length of stay (non-ICU)

96 h

Diazepam: 137 hPhenobarbital + lorazepam: 71 h

 Hendey GW, Dery RA, Barnes RL, Snowden B, Mentler P (2011) [42]

Adults with known or suspected AWS (clinician assessment)

Phenobarbital 260 mg IV (initial dose) + 130 mg IV (subsequent doses) repeated at physician discretion

(n = 25)

Lorazepam 2 mg IV (initial dose) + 2 mg IV (subsequent doses) repeated at physician discretion

(n = 19)

1. Change in CIWA score (from baseline to ED discharge)

−9.6

−12.6

Some concerns

2. ED length of stay

267 min

256 min

3. Hospital admission

12/25 (48.0%)

16/19 (84.2%)

Phenytoin alone

 Rathlev NK, D’Onofrio G, Fish SS, Harrison PM, Bernstein E, Hossack RW, et al. (1994) [37]

Adults with alcohol withdrawal seizure

Phenytoin 15 mg/kg IV over 20 min (n = 49)

Normal saline placebo (n = 51)

Post-infusion seizure recurrence within 6 h

10/49 (20.4%)effect size: 3

(95% CI: − 16 to 16)

12/51 (23.5%)

Low

 Chance JF (1991) [43]

Adults with alcohol withdrawal seizure

Phenytoin 15 mg/kg IV (maximum dose 1000 mg, maximum rate 37 mg/min) (n = 28)

Normal saline placebo (n = 27)

Post-infusion seizure recurrence within 6 h

6/28 (21.4%)effect size: 2

(95% CI: − 20 to 16)

5/27 (18.5%)

Low

 Alldredge BK, Lowenstein DH, Simon RP (1989) [38]

Adults with alcohol withdrawal seizure

Phenytoin 1000 mg IV over 20 min (n = 45)

Normal saline placebo (n = 45)

Post-infusion seizure recurrence within 12 h

6/45 (13.3%)effect size: 0

(95% CI: − 14 to 14)

6/45 (13.3%)

Some concerns

  1. * statistically significant difference between groups (p < 0.05)
  2. AWS = alcohol withdrawal syndrome
  3. CIWA = Clinical Institute Withdrawal Assessment for Alcohol
  4. ED = emergency department
  5. ICU = intensive care unit
  6. IV = intravenous