Managing acute acetaminophen poisoning with oral versus intravenous N-acetylcysteine: a provider-perspective cost analysis

Figures & data

Figure 1. PO or IV N-acetylcysteine regimen. Patients with documented acetaminophen poisoning enter the model and are treated with PO or IV N-acetylcysteine according to their approved uses. Patients are managed for the acute poisoning as well as subsequent potential clinical consequences including possible but unlikely liver failure.

Table 1. Model assumptions.

• Modeled patients have signs, symptom, and/or history of acute APAP poisoning• Modeled patients have similar toxic APAP plasma levels at treatment initiation• Modeled patients have possible/probable hepatotoxicity per Rumack-Mathew nomogram• Modeled patients are treated for acute non-sequential APAP poisoning, not concomitant physical or mental illnesses• Modeled patients receive FDA-licensed PO or IV NAC per approved treatment protocols• Modeled patients are treated with either PO or IV NAC within 10 hours or 10–24 hours of acetaminophen ingestion• PO and IV NAC treatment protocols provide similar clinical outcomes• The limiting adverse reaction to PO NAC is vomiting, which must be controlled with common antiemetics (e.g., promethazine, metoclopramide, or ondansatron)• Uncontrolled vomiting is managed with switch to the alternate IV formulation• The limiting adverse reaction to IV NAC is anaphylactoid reaction, which must be controlled with slower intravenous administration and/or antihistamines• Treatment for extensive vomiting is incorporated into the PO model; anaphylactoid reactions are incorporated into the IV model• Patients are admitted through the emergency department and managed either on medical wards or in ICUs, different scenarios are tested• ICU admission is necessitated in response to signs of serious liver injury• All IV-treated patients incur an additional half hospital day to account for usual first-day overnight stay• All treated patients survive to hospital discharge• Liver transplantation is necessitated for acute hepatic failure• Point estimates that are representative of different categories of patients are used as data inputs for the model. In reality, an infinite number of distinct scenarios exists but are impossible to model in totality because complete datasets are unavailable

Table 2. Model inputs. Base-case scenario, patient treated <10 hours post-ingestion.

Variable	Source	Input	Range
Probability
Vomiting c/ PO	Flanagan^18, Culley^10	50%	(50–70%)
Vomiting resolved	Culley	95.5%	(95.5%)
Vomiting persists c/ switch to IV	Culley	4.5%	(4.5%)
Anaphylactoid reaction c/ IV NAC	Sunman^19, Yip^20	3%	(0.3–20.8%)
Anaphylactoid reaction resolved	Bailey^21	100%	(100%)
Anaphylactoid reaction persists	Bailey^21	0%	(0%)
Hepatotoxicity c/ PO	Smilkstein^6,9, Rumack^7,8	6%	(6–16%)
Hepatotoxicity c/ PO switch to IV	Buckley^3, Prescott^4	30%	(8–53%)
Hepatotoxicity c/ IV	Prescott^4, Buckley^3	3%	(2–4%)
Hepatotoxicity c/ acute liver failure	Nourjah, Bower, Larson^22, Med-ERA	3%	(3%)
Acute liver failure c/ transplant	Fontana^23	10%	(10%)
Unit costs
ED visit (level 3,4 or 5 + MD fees)	UMDNJ, Ferris^13, Med-ERA	$1,064	($846–1,306)
ED labs	Ferris	$381	($381–559)
ED supplies/charcoal	Ferris	$86	($86)
ED observation for vomiting	Ferris	$89	($89)
ED meds (antiemetic/antihistamine)	Ferris	$5	($5)
Cost ED injection	Ferris	$39	($39)
ICU day 1 + consults, testing	Ferris, UMDNJ, Dasta^24	$1,637	($1,637)
ICU day 2 + consults, testing	Ferris, UMDNJ, Dasta	$1,461	($1,461)
ICU day 3 + consults, testing	Ferris, UMDNJ, Dasta	$788	($788)
General ward	UMDNJ	$640	($640)
PO NAC	Culley	$208	($208)
IV NAC (drug Acetadote)	Culley	$537	($537)
Acute liver failure (ALF)	Bond^17 inflated to 2007	$3,935	($3,935)
Transplant	Ferris, Evans^25 inflated to 2007	$118,861	($118,861)
Hepatotoxicity (arm)	Bond inflated to 2007	$1,544	($1,544)
Other
Cost to charge ratio	UMDNJ, Friedman^15	33%	(33%)
Healthcare inflation rate 1995–2007	Compounded annually @ 7.2%	230%	(230%)

NAC, N-acetylcysteine; UMDNJ, University of Medicine and Dentistry of New Jersey.

Table 3. Model calculated costs. Base-case scenario, patient treated <10 hours post-ingestion.

Tree node	Cost
No vomiting (arm)	$5,743
Vomiting (arm)	$5,892
Resolution of vomiting (arm)	$117
Persistent vomiting c/ switch (arm)	$587
Anaphylactoid reaction (arm)	$3,803
No anaphylactoid reaction (arm)	$3,764
Resolution of anaphylactoid (arm)	$59
Persistence of anaphylactoid (arm)	$98
No hepatotoxicity (arm)	$0
Oral NAC (tree)	$5,817
IV NAC (tree)	$3,765
Cost differential (tree)	$2,052 (–35%)

NAC, N-acetylcysteine.

Table 4. Model inputs. Base-case scenario, patient treated 10–24 hours post-ingestion.

Variables	Source	Input	Range
Probability
Vomiting c/ PO NAC	Flanagan, Culley	50%	(50–70%)
Vomiting resolved	Culley	95.5%	(95.5%)
Vomiting persists c/ switch to IV	Culley	4.5%	(4.5%)
Anaphylactoid reaction c/ IV NAC	Sunman, Yip	3%	(0.3–20.8%)
Anaphylactoid reaction resolved	Bailey	100%	(100%)
Anaphylactoid reaction persists	Bailey	0%	(0%)
Hepatotoxicity c/ PO	Smilkstein, Rumack	26%	(26–45%)
Hepatotoxicity c/ PO switch to IV	Buckley, Prescott	30%	(8–53%)
Hepatotoxicity c/ IV	Prescott, Buckley	30%	(8–53%)
Hepatotoxicity c/ acute liver failure	Nourjah, Bower, Larson, Med-ERA	3%	(3%)
Acute liver failure c/ transplant	Fontana	10%	(10%)
Unit costs
ED visit (level 3,4 or 5 + MD fees)	UMDNJ, Ferris, Med-ERA	$1,064	($846–1,306)
ED labs	Ferris	$381	($381–559)
ED supplies/charcoal	Ferris	$86	($86)
ED observation for vomiting	Ferris	$89	($89)
ED meds (antiemetic/antihistamine)	Ferris	$5	($5)
Cost ED injection	Ferris	$39	($39)
ICU day 1 + consults, testing	Ferris, UMDNJ, Dasta	$1,637	($1,637)
ICU day 2 + consults, testing	Ferris, UMDNJ, Dasta	$1,461	($1,461)
ICU day 3 + consults, testing	Ferris, UMDNJ, Dasta	$788	($788)
General ward	UMDNJ	$640	($640)
PO NAC	Culley	$208	($208)
IV NAC (drug Acetadote)	Culley	$537	($537)
Acute liver failure (ALF)	Bond inflated to 2007	$3,935	($3,935)
Transplant	Ferris, Evans inflated to 2007	$118,861	($118,861)
Hepatotoxicity (arm)	Bond inflated to 2007	$1,544	($1,544)
Other
Cost-to-charge ratio	UMDNJ, Friedman	33%	(33%)
Healthcare inflation rate 1995–2007	Compounded annually @ 7.2%	230%	(230%)

NAC, N-acetylcysteine; UMDNJ, University of Medicine and Dentistry of New Jersey.

Table 5. Model calculated costs. Base-case scenario, patient treated 10–24 hours post-ingestion.

Tree node	Cost ($)
No vomiting (arm)	6,134
Vomiting (arm)	6,265
Resolution of vomiting (arm)	509
Persistent vomiting c/ switch (arm)	587
Anaphylactoid reaction (arm)	4,331
No anaphylactoid reaction (arm)	4,292
Resolution of anaphylactoid (arm)	587
Persistence of anaphylactoid (arm)	626
No hepatotoxicity (arm)	0
Oral NAC (tree)	6,200
IV NAC (tree)	4,293
Cost differential (tree)	1,906 (–31%)

NAC, N-acetylcysteine.

Table 6. Analytic results all scenarios.

Scenario	PO NAC ($)		IV NAC ($)		Differential ($)
	ICU	Ward	ICU	Ward	ICU	Ward
<10 hours
Base case	5,817	3,850	3,765	2,768	2,052 (35%)	1,083 (28%)
Best case	5,590	3,624	3,527	2,530	2,063 (37%)	1,094 (30%)
Worse case	6,470	4,503	4,211	3,214	2,259 (35%)	1,290 (29%)
10–24 hours
Base case	6,200	4,233	4,293	3,296	1,906 (31%)	937 (22%)
Best case	5,579	4,006	3,645	2,647	1,934 (35%)	1,359 (34%)
Worse case	6,783	5,053	5,169	4,172	1,614 (24%)	881 (17%)

All values rounded off to nearest dollar amount.

ICU and Ward designations reflect location of care depicted in various modeling scenarios.

NAC, N-acetylcysteine; ICU, intensive care unit.

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