Role of penehyclidine in acute organophosphorus pesticide poisoning

doi:10.5847/wjem.j.1920-8642.2020.01.006

Abstract

Abstract:

BACKGROUND: Penehyclidine is a newly developed anticholinergic agent. We aimed to investigate the role of penehyclidine in acute organophosphorus pesticide poisoning (OP) patients.

METHODS: We searched the Pubmed, Cochrane library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical literature (CBM) and Wanfang databases. Randomized controlled trials (RCTs) recruiting acute OP patients were identified for meta-analysis. Main outcomes included cure rate, mortality rate, time to atropinization, time to 60% normal acetylcholinesterase (AchE) level, rate of intermediate syndrome (IMS) and rate of adverse drug reactions (ADR).

RESULTS: Sixteen RCTs involving 1,334 patients were identified. Compared with the atropine- or penehyclidine-alone groups, atropine combined with penehyclidine significantly increased the cure rate (penehyclidine+atropine vs. atropine, 0.97 vs. 0.86, RR 1.13, 95% CI [1.07-1.19]; penehyclidine+atropine vs. penehyclidine, 0.93 vs. 0.80, RR 1.08, 95% CI [1.01-1.15]) and reduced the mortality rate (penehyclidine+atropine vs. atropine, 0.015 vs. 0.11, RR 0.17, 95% CI [0.06-0.49]; penehyclidine+atropine vs. penehyclidine, 0.13 vs. 0.08, RR 0.23, 95% CI [0.04-1.28]). Atropine combined with penehyclidine in OP patients also helped reduce the time to atropinization and AchE recovery, the rate of IMS and the rate of ADR. Compared with a single dose of atropine, a single dose of penehyclidine also significantly elevated the cure rate, reduced times to atropinization, AchE recovery, and rate of IMS.

CONCLUSION: Atropine combined with penehyclidine benefits OP patients by enhancing the cure rate, mortality rate, time to atropinization, AchE recovery, IMS rate, total ADR and duration of hospitalization. Penehyclidine combined with atropine is likely a better initial therapy for OP patients than atropine alone.

Key words: Penehyclidine, Organophosphorus pesticide poisoning, Meta-analysis

Shi-yuan Yu, Yan-xia Gao, Joseph Walline, Xin Lu, Li-na Zhao, Yuan-xu Huang, Jiang Tao, An-yong Yu, Na Ta, Ren-ju Xiao, Yi Li. Role of penehyclidine in acute organophosphorus pesticide poisoning[J]. World Journal of Emergency Medicine, 2020, 11(1): 37-47.

Figures/Tables 6

Figure 1.

Table 1

Included articles

First author	Journal	Organophosphate component	N	Drug administration
Lin et al^[2] 2016	Chinese Journal of Modern Drug Application	Not reported	150	Penehyclidine+atropine group, atropine 10-20 mg IV and penehyclidine 1 mg IM three times a day, then atropine 5-10 mg every 5-10 minutes until atropinization; penehyclidine group, penehyclidine 4-6 mg IM then penehyclidine 2-3 mg every 1-2 hours until atropinization; atropine group, atropine 10-20 mg IV then 5-10 mg IV every 5-10 minutes until atropinization
Wu et al^[4] 2016	Heilongjiang Medical Journal	Not reported	83	Penehyclidine group, penehyclidine 4-6 mg IV initially; atropine group, atropine 10-20 mg IV initially
Fu et al^[10] 2015	11th National Conference on Disaster Medicine with Integrated Traditional Chinese Medicine and Western Medicine	Not reported	62	Penehyclidine group, penehyclidine 4-6 mg IM initially then 1-2 mg until atropinization; atropine group, atropine 20-40 mg IV initially
Zhao et al^[11] 2015	World Notes	Not reported	48	Penehyclidine+atropine group, penehyclidine 4-6 mg IM initially, atropine 1-2 mg every 8-12 hours; atropine group, atropine 10-20 mg IM every 1 hour until atropinization
Liang et al^[13] 2014	Contemporary Medicine	Not reported	120	Penehyclidine+atropine group, atropine 10-20 mg IV initially then 5-10 mg every 5-10 minutes until atropinization, then Penehyclidine 1-2 mg IM every 8-12 hours; atropine group, atropine 10-20 mg IV initially then 5-10 mg every 5-10 minutes until atropinization
Sun et al^[14] 2012	China Modern Medicine	Not reported	58	Penehyclidine+atropine group, penehyclidine 4-5 mg IM+atropine 10-20 mg IV initially; atropine group, atropine 10-20 mg IV then additional atropine every 10-30 minutes until atropinization
Zeng et al^[18] 2011	Fujian Medicine Journal	Not reported	62	Penehyclidine group, penehyclidine 4-6 mg IM initially; atropine group, atropine 3-5 mg IV then 5-15 mg every 5-10 minutes until atropinization
Liu et al^[19] 2012	Medical Innovation of China	Dichlorvos, omethoate, rogor, methamidophos, dipterex	64	Penehyclidine group, penehyclidine 5 mg IV, then 3 mg every 30-60 minutes until atropinization; atropine group, atropine 10 mg IV initially
Chen et al^[20]2011	Guide of China Medicine	Cynamid, alkron, demeton, methamidophos, rogor	80	Penehyclidine+atropine group, penehyclidine 1 mg IM+atropine 10-20 mg IV, then atropine 10 mg every 10-15 minutes until atropinization
Guan et al^[21] 2015	World Latest Medicine Information	Not reported	60	Penehyclidine+atropine group, penehyclidine 4-6 mg IM initially, then atropine IV until atropinization; atropine group, atropine 10-15 mg IV every 10-30 minutes until atropinization
Wang et al^[22] 2010	Chinese Journal of Modern Drug Application	Cynamid, alkron, methamidophos, dichlorvos, rogor, azodrin, phoxime	76	Penehyclidine+atropin group, penehyclidine 2-3 mg IM +atropine 5-10 mg IV, then 5-10 mg atropine every 5-10 minutes until atropinization; penehyclidine group, 4 mg IM, additional drug due to patients condition until atropinization; atropine group, 5-10 mg atropine IV, then 5-10 mg atropine every 5-10 minutes until atropinization
Yi et al^[23] 2010	Journal of Lingnan Emergency Medicine	Dichlorvos, methamidophos, acephate, alkron, malathion	102	Penehyclidine+atropin group, atropine 10 mg intravenously (IV) + penehyclidine 5 mg intramuscularly (IM), then 5 mg atropine every 5-10 minutes until atropinization; penehyclidine group, 6 mg penehyclidine IM then 3 mg penehyclidine IM every 30 minutes until atropinization; atropine group, 10 mg atropine IV then 5 mg atropine IV until atropinization
Luo et al^[24] 2014	Medicine	Methamidophos, dichlorvos, rogor, dipterex	98	Penehyclidine+atropine group, atropine 10-15 mg IV and penehyclidine 4-6 mg IM, then atropine IV until atropinization; penehyclidine group, penehyclidine 4-6 mg IM initially; atropine group, atropine 10-15 mg IV every 10-30 minutes until atropinization
Shi et al^[25] 2012	Journal of Clinical Emergency	Omethoate, dichlorvos, methamidophos	56	Penehyclidine group, penehyclidine 6 mg IV, then 3 mg every 30-60 minutes until atropinization; atropine group, atropine 20 mg IV initially
Zhou et al^[26] 2012	Occupation and Health	Dichlorvos, alkron, rogor, methamidophos, cynamid, demeton	180	Penehyclidine+atropine group, penehyclidine 4-6 mg IM+atropine 3-5 mg IV, then atropine 3-5 mg atropine every 3-5 minutes until atropinization; penehyclidine group, penehyclidine 4-6 mg IM, then 2-3 mg after 30-60 minutes, then 1-2 mg until atropinization; atropine group, atropine 5-10 mg IV, then 5-10 mg every 5-10 minutes until atropinization
Liu et al^[27] 2011	Modern Journal of Integrated Traditional Chinese and Western Medicine	Not reported	35	Penehyclidine group, penehyclidine 4-6 mg IM initially; atropine group, atropine 10-20 mg IV then 5-15 mg every 15-30 minutes until atropinization

Table 1

Figure 2.

Figure 3.

Figure 4.

Table 2

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Variables	Penehyclidine and atropine vs. Atropine			Penehyclidine vs. Atropine			Penehyclidine and atropine vs. Penehyclidine
	RR or SMD	95% CI	P	RR or SMD	95% CI	P	RR or SMD	95% CI	P
Cured rate	1.13	1.07-1.19	<0.00001	1.16	1.08-1.24	<0.00001	1.08	1.01-1.15	0.02
Mortality rate	0.17	0.06-0.49	0.0009	0.35	0.19-0.65	0.001	0.23	0.04-1.28	0.09
Time to atropinization	-1.44	-2.37- -0.51	0.002	1.00	0.75-1.26	<0.00001	-1.53	-1.53- -1.24	<0.00001
Time of AchE back to 60%	-1.69	-1.89- -1.48	<0.00001	-1.27	-1.53- -1.01	<0.00001	-0.77	-1.83-0.30	0.16
Rate of IMS	0.31	0.15-0.64	0.002	0.39	0.21-0.70	0.002	0.70	0.28-1.78	0.45
Rate of total ADR	0.19	0.09-0.41	<0.00001	-	-	-	-	-	-
Time of hospitalization	-1.35	-1.74- -0.95	<0.00001	-0.42	-0.85-0.01	0.06	-1.40	-3.64-0.84	0.22

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