Long-acting anticoagulant rodenticide poisoning: An evidence-based consensus guideline for out-of-hospital management

Figures & data

Table 1. Known outcome by reason for ingestion of LAAR for all ages reported to TESS 2000–2003

Reason	No effect or minor effect (%)	Moderate or major effect or death (%)	Total (%)
Unintentional	21,892 (93.7)	166 (0.7)	22,058 (94.4)
Intentional	1,012 (4.3)	301 (1.3)	1,313 (5.6)
Total	22,904 (98)	467 (2)	23,371

*Toxic Exposure Surveillance System of the American Association of Poison Control Centers (1).

Unintentional ingestions were 39 times more likely to have no effects or minor effects than intentional ingestions of LAAR. Odds ratio = 39.2 (95% CI, 31.9–48.1).

Table 2. Long-acting anticoagulant rodenticides

Substance (common name)	CAS Registry number	Available forms, % by weight, (selected trade names)
Brodifacoum	56073-10-0	0.005% pellets or loose bait
		0.25% solid, concentrate
		(D-Con, Havoc, Klerat, PP 581, Ratak Plus, Talon)
Bromadilone	28772-56-7	96.5%, 93.5%, 1.0% and 0.005% solids: blue pellets (Tomcat Ultra; Maki; Bromone; Super-Caid; Super-Rozol)
Chlorophacinone	3691-35-8	96.03% technical grade
		5.34% spray
		0.28% mineral oil concentrate
		Available in tracking powder, dust, and ready-to-use formulations (Enforcer Rat and Mouse Killer, Drat)
Difenacoum	56073-07-5	0.005% grain-based bait (Neosorexa PP580; Ratak)
Diphacinone	82-66-6	99%, 0.2%, 0.1%, 0.01%, and 0.005% solids: yellow crystals, pale green pellets, and solid bloc (Tomcat, Tomcat all Weather Bait Chunx, Tomcat Ground Squirrel Bait)
	23710-76-1	0.106% liquid concentrate (Tomcat Liquid Concentrate)
		It is available in meal, pellet, wax block, liquid bait, tracking powder, and concentrate formulations.

*Registered with the EPA as of July 1998 (71).

Table 3. Summary of individual US poison control center guidelines, 2004

Poison center	Give ipecac?	Perform gastric lavage?	Give activated charcoal?	Criteria for homeobservation	Indications for referral to healthcare facility	Time after exposure for obtaining prothrombin time	Time to home follow-up call
1	No		Large, intentionalingestion only		Unknown dosage amount	48–96 hr, all exposures	4–6 hr
					Greater than one pellet ingested.
					Chronic ingestion
2	No	No	Yes	Unintentional ingestion of <0.5 mg active ingredient	0.5 mg or more of active ingredient	Intentional ingestion: 24 and 72 hr	5 days
					Ingestion of any product >0.025%	Unintentional ingestion: 72 hr if 0.05mg or more
					Chronic ingestion	Chronic: immediately
3				All unintentional exposures	Bruising, bleeding, epistaxis	None if asymptomatic	None
4				Less than 1 mg brodifacoum	Unknown product	Home observation: none	48 hr
				Less than 1.5 mg all other compounds	1 mg or more of brodifacoum	HCF: 48 hr
					1.5 mg or more of other compounds
5				Less than one mouthful	Greater than one mouthful, refer for PTonly	72 hr if greater than one mouthful
6		Consider if <1 hr after ingestion	Consider if <1 hr after ingestion	Unknown or small amount	Ingestion of >one packet	48 hr for large or chronic ingestion	72 hr
					Chronic ingestion
					Intentional ingestion
					Bleeding or bruising
7			Yes	<0.25 mg (<1 tsp. of 0.005% rat bait)	Acute ingestion of 0.25 mg or more	Acute: 48 hr
					All chronic ingestions	Chronic: 0, 24, 48 hr
8	No	Consider if <1 hr after ingestion	Consider if <1 hr after ingestion	Hydroxy-coumarins: <1.25 mg	>1.25 mg of hydroxy-coumarins or 0.25 mg of indandiones	24 and 48 hr
				Indandiones: <0.25 mg	Chronic ingestion
					Presence of malnutrition, bleeding disorder, hepatic dysfunction, or anticoagulant therapy
9			Yes, if <4 hr after ingestion	All acute, single exposures in children <5 yrs old	All patients older than 5 year of age.	48 hr	3 days and 5–7days
					Chronic exposure
					History of pre-existing bleeding disorders
					Bleeding or bruising
					Children with abnormal behavioral development
10	No		Yes, for intentional ingestions <1 hr	All acute ingestions in children <6 years old	All chronic ingestions		48–72 hr
11	No			All acute ingestions in children < 6 years old
12	Yes, if <1 hr after unintentional ingestion of > 1m mg brodifacoum		Yes, if <1 hr after ingestion of >1 mg brodifacoum	Unintentional ingestion of <1.0 mg of brodifacoum	Chronic ingestion	48 hr if ingested >1 mg brodifacoum	48–72 hr
					Unknown amount
					Intentional ingestion
					Suspected child abuse
					Underlying bleeding or clotting disorder
					Concurrent warfarin therapy
13	No		If <1 hr of ingestion	<5 mg/kg warfarin equivalents	≥5 mg/kg warfarin equivalents	48 hr	48 hr and 7 days
					Bleeding disorder
					Concurrent anticoagulant therapy
					Neurologic or psychiatric disorder
14				Single, acute, unintentional ingestions	Massive or intentional acute ingestion	48 hr
					Repeated ingestion
					Bleeding or brushing

Table 4. Cases with dose information on acute toxicity in patients 6 years of age and older

Agent	Dose	Age (yr)	Mitigating factors	Effect	Symptom onset^†	Confirm conc.?^‡	Ref. (LOE)
Brodifacoum	One “mouthful” (est. 20 mL) of a 0.005% solution (∼1 mg brodifacoum)	20	NR	Moderate	NR	C	48 (6)
	One “handful” of Talon (0.005%)	44	Munchausen syndrome; noncompliant with treatment	Moderate	NR	B	3 (4)
	“One container (43 g)” of 0.005% bait (2.15 mg brodifacoum)	62	Also ingested alcohol and methanol-containing antifreeze	Moderate	<4 wk	C	51 (4)
	“One box of brodifacoum containing rat poison”	19	22 wk pregnant	Maternal: moderate Fetal: NR	8 d	C	52 (4)
	52.5 g of 0.005% bait (2.6 mg brodifacoum)	25	Ingestion of brodifacoum 2 mo prior	Death	<2 wk	NR	27 (4)
	7.5 mg (0.12 mg/kg)	17	NR	Moderate	NR	C	4 (4)
	8.5–10.6 mg (0.12–0.15 mg/kg)	39	NR	Moderate	<6 d	C	52 (4)
	172 g of 0.005% bait (8.6 mg brodifacoum)	22	NR	Severe	NR	B	50 (4)
	10 mg	20	NR	Moderate	4 d	C	2 (4)
	200 g of 0.005% bait (10 mg)	32	NR	Moderate	4 d	C	30 (4)
	17.5 mg	20	Depression	Moderate	NR	B	16 (4)
	344 g of 0.005% bait (17.2 mg brodifacoum)	52	HIV, depression on chronic fluoxetine,methylphenidate, testosterone, and clonazepam	Moderate	<6 d	B	17 (4)
	“15 boxes” of 0.005% bait	41	NR	Moderate	<2 wk	B	49 (6)
	“1.5 lbs. of brodifacoum”	35	Alcoholism	Moderate	Over 2 wk	C	47 (6)
Bromadiolone	12.5 mg	42	NT	NT	NT	NT	54 (4)
Chlorphacinone	∼100 mg [∼1.6 mg/kg]	18	NT	Moderate	<3 d	B	57 (4)
	250 mg	20	NR	Moderate	<7 d	B	19 (4)
	Case series of 11 adults with acute anticoagulant ingestions, 9 of whom ingested chlorphacinone. Doses ranging from 375 to 750–1000 mg resulted in moderate to severe toxicity.						55 (4)
	∼625 mg in liquid paraffin	37	NR	Mod	Over several d	C	56 (4)
	1825 mg	33	NR	Mod	2–3 d	B	20 (4)
Difenacoum	500 g of rat bait containing difenacoum	17	Also ingested razor blades and pins	Mod	NR	C	58 (4)
Unknown or Unspecified	One full container	24	Also ingested antifreeze	Mod	NR	C	23 (4)

*Mild = local effects only, Moderate = systemic effects (coagulopathy and/or non-life-threatening bleeding), Severe = life-threatening systemic effects (e.g., life-threatening hemorrhage).

^†Maximal time of onset; (i.e., symptoms were present on admission but may have begun earlier).

^‡B = blood, U = urine, C = confirmed only by presence of coagulopathy.

NR = not reported or none reported; NT = not fully translated.

LOE = level of evidence.

Table 5. Cases with dose information on chronic toxicity

Agent	Dose	Age (yr)	Mitigating factors	Effect	Symptom onset	Confirm conc.	Ref. (LOE)
Brodifacoum	168 g of 0.005% over about 12 hr (8.4 mg brodifacoum)	25	NR	Severe	Over the next 9 d	C	27 (4)
	4 boxes over 4 d	23	Also ingested broken glass	Moderate	NR	B	63 (6)
	1500 g of Talon-G over 2 d (75mg brodifacoum)	31	Also slashed wrists	Moderate	<5 d	C	18 (4)
	2 packages on two occasions (13 mg brodifacoum, total)	26	none	Severe	<several d	C	62 (4)
	“Sprinkled on cereal” for 4 d	2	None	Moderate	4 d	B	7 (4)
Difenacoum	4 mg daily for 1 mo	34	On dothiepin chronically; drinking alcohol heavily; self-inflicted wrist lacerations	Moderate	NR	B	64 (4)
	850 g of Dephenex over 2 wk	36	NR	Severe	<2 wk	C	65 (4)
	∼1800 g of rat bait containing difenacoum over 2 wk	17	Also ingested pins	Moderate	NR	C	4 (4)
Diphacinone	Dermal exposure to 0.106% liquid in boot for several d	18	NR	Moderate	<7 d	B	8 (4)

*Mild = local effects only, Moderate = systemic effects (coagulopathy and/or non-life-threatening bleeding), Severe = life-threatening systemic effects (e.g., life-threatening hemorrhage).

^†Maximal time of onset; (i.e., symptoms were present on admission but may have begun earlier).

^‡B = blood, U = urine, C = confirmed only by presence of coagulopathy.

NR = not reported or none reported; NT = not fully translated.

LOE = level of evidence.

Table 6. Cases with dose information of unknown acuity

Agent	Dose	Age (yr)	Mitigating factors	Effect	Symptom onset^†	Confirm conc.?^‡	Ref. (LOE)
Brodifacoum	Smoked about 3/4 of a box of D-Con Mouse Pruf III (0.005%)	17	Smoked LAAR mixed possible co-administration of heparin or other drugs	Moderate	NR	C	9 (4)
	Ingested 2 boxes of D-Con	61	Depression, hypothyroidism, on chronic zolpidem, clorazepate, levothyroxine, and carbamazepine	Moderate	∼9 d	C	29 (4)
	17.5 mg	20	NR	Severe	NR	B	16 (4)

*Moderate = systemic effects (coagulopathy and/or non-life-threatening bleeding), Severe = life-threatening systemic effects (e.g., life-threatening hemorrhage).

^†Maximal time of onset; (i.e., symptoms were present on admission but may have begun earlier).

^‡B = blood, C = confirmed only by presence of coagulopathy.

LOE = level of evidence.

Table 7. Toxic dose conversion: LAAR concentration to dry weight

Concentration (%) of LAAR active ingredient	Grams (dry wt.) equal to 1 mg active ingredient	Ounces (dry wt.) equal to 1 mg active ingredient
0.005	20	0.7
0.01	10	0.36
0.1	1	0.04
0.2	0.5	0.02
0.25	0.4	0.014
1	0.1	0.004
99	0.001	0.00004

Conversion factor: one ounce = 28 g dry weight.

Table

Grade of Recommendation	Level of Evidence	Description of Study Design
A	1a	Systematic review (with homogeneity) of randomized clinical trials
	1b	Individual randomized clinical trials (with narrow confidence interval)
	1c	All or none (all patients died before the drug became available, but some now survive on it; or when some patients died before the drug became available, but none now die on it.)
B	2a	Systematic review (with homogeneity) of cohort studies
	2b	Individual cohort study (including low quality randomized clinical trial)
	2c	“Outcomes” research
	3a	Systemic review (with homogeneity) of case-control studies
	3b	Individual case-control study
C	4	Case series, single case reports (and poor quality cohort and case control studies)
D	5	Expert opinion without explicit critical appraisal or based on physiology or bench research
Z	6	Abstracts

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