A total of 30 patients were enrolled, with 15 patients evaluated in each group. Nineteen (63.4%) were male. Their age ranged from 6 to 144 months (median 15; IQR [10, 36]).
Twenty-three patients (76.7%) had ingested methamphetamine, either in the form of crystal powder (16 patients; 53.3%) or as water from a methamphetamine pipe (7 patients; 23.3%). Seven (23.3%) had been passively exposed to methamphetamine smoked by their parents (i.e. fathers, based on patient history).
Most exposures had happened at night (25 cases; 83.3%), including all passive smoking cases (7 cases; 23.3%), 14 cases (46.7%) of crystal powder ingestion, and 4 cases (13.3%) of pipe water ingestion.
The median elapsed time [IQR] between exposure and development of methamphetamine toxicity was one hour [1, 2] (30 minutes to 24 hours), and the median [IQR] time between exposure and hospital presentation was five hours [3, 6] (one hour to 72 hours; Table 1), according to parental report. Urine methamphetamine was positive in all cases.
Table 1: Demographics, on-arrival presentation, and treatment response by group
Variable
|
Total
(n=30)
|
Lorazepam
(n=15)
|
Clonazepam
(n=15)
|
P
(MWU test)
|
|
Median [IQR] (range)
|
|
Age (months)
|
15 [10, 36]
(6, 144)
|
15 [10, 37]
(6, 144)
|
17 [11, 33]
(6, 84)
|
0.637
|
Weight (kg)
|
11 [10, 14]
(6.5, 40)
|
11.5 [9.5, 15]
(8, 40)
|
10.7 [10, 13.7]
(6.5, 25)
|
0.697
|
Time elapsed between exposure and presentation (h)
|
3 [5, 6]
(1, 72)
|
5 [4, 9]
(2, 72)
|
3 [5, 6]
(1, 14)
|
0.377
|
Time elapsed between exposure and developments of symptoms (h)
|
1 [1, 2]
(0.5, 24)
|
1 [1, 2.2]
(0.5, 24)
|
1 [1, 2]
(0.5, 2)
|
0.275
|
Presentation on arrival
|
|
|
|
|
Temperature (C)
|
37 [36.5, 37]
(36, 37.7)
|
36.9 [36.5, 37]
(36, 37.3)
|
37 [36.7, 37.1]
(36.5, 37.5)
|
0.142
|
Systolic BP (mmHg)
|
90 [90, 100]
(80, 110)
|
92 [90, 100]
(80, 110)
|
90 [90, 100]
(80, 110)
|
0.400
|
Diastolic BP (mmHg)
|
50 [50, 60]
(40, 80)
|
60 [50, 70]
(50, 80)
|
50 [50, 60]
(40, 70)
|
0.160
|
Heart rate (per minute)
|
127 [110, 140]
(90, 160)
|
130 [110, 150]
(92, 160)
|
120 [102, 140]
(90, 150)
|
0.498
|
Respiratory rate (per minute)
|
30 [27, 35]
(16, 60)
|
31[26, 35]
(22, 60)
|
30 [28, 34]
(16, 60)
|
0.667
|
Creatine phosphokinase (U/L)
|
218 [148, 360]
(88, 1584)
|
225 [148, 461]
(117, 698)
|
211[126, 324]
(88, 1584)
|
0.697
|
Treatment response
|
|
|
|
|
Duration of symptoms (h)
|
4 [3, 5]
(2, 20)
|
3 [2, 4]
(2, 13)
|
5 [3, 7]
(2, 20)
|
0.166
|
Hospitalization period (h)
|
24 [24, 48]
(24, 72)
|
24 [24, 48]
(24, 48)
|
24 [24, 42]
(24, 72)
|
0.525
|
The most common signs and symptoms of toxicity were agitation (29 patients; 96.7%) followed by mydriatic pupils (26; 86.7%), tachycardia (20; 66.7%), insomnia (18; 60%), stereotypical movements (hand shaking, waving, or wringing, head banging, self-hitting, and self-biting;12; 40%), tachypnea (8; 26.7%), vomiting (7; 23.3%), and talkativeness (5; 16.6%). Other important signs and symptoms were delusion, tremor, and sweating (each in two patients; 6.7%), and hallucinations and seizure (each in one patient; 3.3%). One case (3.3%) had hyperthermia (axillary temperature >37.5 Ċ) on presentation. Hypotension was present in one patient (3.3%) and hypertension in another (3.3%). Three patients (9.9%) had low diastolic blood pressures (DBP). Rhabdomyolysis (CPK> 1000 U/L) was reported in one patient (3.3%).
Treatment response:
After initial administration of 0.2 mg/Kg IV diazepam in all patients, four patients (2 in each group) needed re-administration of IV diazepam (at 45 minutes, 50 minutes, 60 minutes, and 75 minutes after the first diazepam dose) due to persistent agitation after the first dose.
Oral BZOs were administered only once immediately after the patients became calm and could be switched to oral regimen (mean 1 hour; range, 0.5 to 3 h). 15 patients received oral clonazepam (0.05 mg/Kg) and another 15 received oral lorazepam (0.05 mg/Kg). The mean administered dose of oral BZO was 1.1 mg in both groups.
Statistical analysis showed that on-arrival vital signs were similar between the two groups after treatment (table 1; all Ps were higher than 0.05).
Almost 73% (22 cases) of patients responded to treatment within five hours of administration of the oral BZOs. All patients remain conscious during observation period and no adverse effects were seen following oral BZOs administration. In three cases (10%), symptoms persisted for 12 hours or more (i.e. up to 20 hours). Although the median duration of symptoms was less in those treated with lorazepam (3 versus 5 hours), the difference was not significant (p=0.166). Table 2 shows vital signs including respiratory rate during hospitalization period in a 6-hours basis after IV diazepam and initiation of oral BZOs.
The median [IQR] (range) hospitalization period was 24 hours [24, 48] (24, 72) hours, with 10 patients (33.3%) remaining hospitalized for 24-72 hrs. The duration of hospital stay (p=0.525) did not differ significantly between the groups.Figures 1-4 show pairwise multiple comparison of vital signs for each oral BZO in 6-hour time intervals.
Table 2: Vital sign time interval of patients after being calmed in ED and initiation of oral benzodiazepines (n=30)
Variable
|
BZOs
|
Time post initiation of oral benzodiazepine (hour)
|
Sig*
|
Pairs of difference
|
|
|
0
|
6
|
12
|
18
|
24
|
|
|
Heart rate†
|
Lorazepam
|
130 [110, 150]
(90, 160)
|
112 [110, 128]
(100, 140)
|
110 [102, 112]
(90, 120)
|
102 [100, 112]
(88, 130)
|
100 [99, 110]
(80, 126)
|
<0.001
|
T0 Vs.T24
T6Vs.T24
T0 Vs.T18
|
Clonazepam
|
120 [100, 140]
(92, 144)
|
115[106, 122]
(100, 148)
|
107 [100, 110]
(80, 127)
|
110 [97, 119]
(88, 123)
|
108 [98, 120]
(88, 120)
|
0.673
|
|
Temperature†
|
Lorazepam
|
37 [36.6, 37]
(36, 37.1)
|
37 [36.9, 37]
(36.7, 37.8)
|
36.8 [36.5, 37]
(36.2, 37.5)
|
36.8 [36.5, 37]
(36.2, 37.5)
|
36.5 [36.5, 36.8]
(36.2, 37)
|
0.002
|
T6 Vs.T24
|
Clonazepam
|
37 [36.6, 37]
(36, 37.2)
|
37 [36.9, 37]
(36.5, 37)
|
36.8 [36.5, 37]
(36, 37.2)
|
37 [36.5, 37]
(36.5, 37.2)
|
36.5 [36.5, 36.9]
(36.5, 37)
|
0.242
|
-
|
Respiratory rate†
|
Lorazepam
|
30 [26, 35]
(20, 60)
|
25 [22, 27]
(20 ,55)
|
25 [22, 25]
(18 ,50)
|
23 [22, 26]
(20 ,26)
|
22 [22, 24]
(21 ,25)
|
0.006
|
T0 Vs.T12
T6 Vs.T24
|
Clonazepam
|
30 [24, 33]
(16, 60)
|
29 [20, 32]
(20 ,40)
|
25 [21, 29]
(18 ,35)
|
25 [21, 29]
(18 ,30)
|
24 [19, 25]
(18 ,30)
|
0.003
|
T0 Vs.T24
T6 Vs.T24
|
Systolic blood pressure†
|
Lorazepam
|
92 [90, 100]
(80, 100)
|
92 [90, 90]
(80, 100)
|
90 [80, 97]
(80, 100)
|
90 [75, 100]
(70, 100)
|
90 [77, 92]
(70, 100)
|
0.647
|
-
|
Clonazepam
|
90 [90, 100]
(80, 110)
|
90 [90, 100]
(80, 110)
|
85 [80, 90]
(80, 100)
|
85 [80, 85]
(70, 90)
|
75 [70, 75]
(70, 100)
|
0.160
|
-
|
*Using Friedman's two-way ANOVA, †Median [IQR] (min, max)