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., the 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.
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. On arrival, 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%).
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 vital signs were similar between the two groups on arrival and after BZO treatment (see 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 the hospitalization period in 6-hour intervals, following IV diazepam treatment as well as initiation of oral BZO treatment.
Further pairwise analyses showed that neither oral BZOs had a significant impact on systolic blood pressure over the time. Both clonazepam and lorazepam were effective at decreasing the respiratory rate. The median [IQR] (range) hospitalization period was 24 [24, 48] (24, 72) hours, with 10 patients (33.3%) remaining hospitalized for 24-72 hours. The duration of the hospital stay did not differ significantly between the groups (median: 24 hours, p=0.525; see Table 1). Figures 1-4 show pairwise multiple comparison of the vital signs for both groups in 6-hour time intervals.