Fomepizole dosing during continuous renal replacement therapy – an observational study

Figures & data

Table 1. Laboratory data on admission.

Patient	Age (years)	pH	pCO2 (kPa)	HCO3 (mmol/L)	Base deficit (mmol/L)	AG (mmol/L)	OG (mOsm /kgH2O)	S-ethanol (mmol/L)	S-methanol (mmol/L)	S-formate (mmol/L)	S-ethylene glycol (mmol/L)	S-glycolate (mmol/L)
1	31	7.07	1.1	2	30	43	242	ND	175	19.6	ND	ND
2	61	6.91	3.1	5	28	40	80	ND	62	19	ND	ND
3	45	6.98	1.8	3	29	46	40	ND	17	13.9	ND	ND
4	53	7.39	2.5	11	14	32	4	ND	NA	NA	2.6	17
5	50	6.72	2.9	3	33	44	34	ND	ND	NA	13	NA
6	63	6.82	1.6	2	31	NA	42	ND	ND	NA	20	NA
7	42	7.24	4.2	13	13	22	262	2.2	ND	NA	192	NA
8	54	6.81	1.3	2	33	39	36	ND	ND	ND	ND	ND
9	63	7.16	3.4	9	20	42	15	8.7	ND	ND	ND	ND
10	58	6.88	1.8	2	28	46	101	52.1	ND	NA	NA	NA

AG: anion gap; OG: osmolal gap; ND: not detected; NA: not analyzed.

Conversion factors: pCO₂ pKa to mmHg is 7.5, HCO₃, base deficit and anion gap mmol/L to mEq/L is 1, ethanol mmol/L to mg/dL is 4.6, methanol mmol/L to mg/dL is 3.2, formate mmol/L to mg/dL is 4.6, ethylene glycol mmol/L to mg/dL is 6.2, glycolate mmol/L to mg/dL is 7.6.

Patients 1–3 had confirmed methanol poisoning and patients 4–7 had confirmed ethylene glycol poisoning. Patients 8–10 had suspected toxic alcohol poisoning, but were later confirmed negative.

Figure 1. Fomepizole concentration in plasma, post-filter and dialysate in patient 2. CVVHD: Continuous veno-venous hemodialysis; IHD: Intermittent hemodialysis.

Figure 2. Fomepizole concentration in plasma in patient 1. CVVHD: continuous veno-venous hemodialysis; IHD: intermittent hemodialysis.

Table 2. Elimination kinetics of fomepizole during continuous renal replacement therapy (CRRT).

Patient	Dose	R^2 zero-order kinetics	R^2 first-order kinetics
1	2nd dose	0.90	0.92
	3rd dose	0.91	0.95
	4th dose	0.96	0.94
	5th dose	0.88	0.99
2	1st dose	N/A	N/A
	2nd dose	0.93	0.98
	3rd dose	0.95	0.99
3	2nd dose	0.98	0.99
	3rd dose	0.90	0.92
4	1st dose	0.98	0.99
	2nd dose	0.91	0.96
5	0.5 mg/kg/h	0.99	0.99
	1 mg/kg/h	N/A	N/A
6	1st dose	0.99	1.00
	2nd dose	0.98	1.00
	3rd dose	0.96	0.99
7	2nd dose	0.99	1.00
	3rd dose	N/A	N/A
	4th dose	N/A	N/A
8	1st dose	0.99	0.98
	2nd dose	0.98	0.99
9	1st dose	0.97	0.99
	2nd dose	0.76	0.84
10	1st dose	0.84	0.90
	2nd dose	0.91	0.98

N/A: not applicable.

Table 3. Dialysis modality, settings and clearance for fomepizole during continuous renal replacement therapy (CRRT).

Patient	Fomepizole maintenance dose	Dialysis modality	Weight (kg)	Blood flow rate (mL/min)	Dialysate flow rate (mL/h)	Replacement fluid post-dilution (mL/h)	Saturation coefficient (median)	Clearance CRRT (mL/min) (% of TBC)	Total body clearance (mL/min)	t1/2 for each dose (h)^c
1	Fixed doses	CVVHD	61	80	1500		0.87^b	22^b (15)	134	5.0, 4.7, 2.3, 1.3
2	Fixed doses	CVVHD	83	100	2000		0.96	32 (30)	106	5.6, 6.5
3	Fixed doses	CVVHD	90	120	2500		0.83	35 (22)	162	4.1, 4.5
4	Fixed doses	CVVHD	72	100	2000		0.87	29 (29)	99	6.2, 5.0
5	Continuous infusion	CVVHDF	70	140	1500	500	0.80	27 (N/A)	N/A	9.9
6	Fixed doses	CVVHDF	90	155^a	550^a	500	NC	NC	129	5.4, 5.7, 4.5
7	Fixed doses	CVVHDF	80	150	500	500	0.46	8 (9)	87	7.1
8	Fixed doses	CVVHD	84	100	2031^a		0.60	20 (16)	126	5.9, 4.4
9	Fixed doses	CVVHD	66	100	2000		0.89	30 (44)	68	7.9, 6.9
10	Fixed doses	CVVHD	116	120	2400		NC	NC	95	8.3, 10.5

CVVHD: continuous veno-venous hemodialysis; CVVHDF: continuous veno-venous hemodiafiltration; N/A: not analyzed; NC: not calculated because dialysate sample was not collected; TBC: total body clearance.

t_1/2: half-life.

^aAverage value because flow was not constant.

^bMissing dialysate samples, i.e., saturation coefficient and clearance are calculated only for the two last doses.

^cCalculated from first-order elimination.