Effectiveness of pharmacist dosing adjustment for critically ill patients receiving continuous renal replacement therapy: a comparative study

Figures & data

Table 1 Recommended drug dosing in critically ill patients receiving continuous renal replacement therapy

Drugs	Dosing recommendations based on ultrafiltration ratea
	1,500 mL/h	2,000–2,500 mL/h	3,000 mL/h
Drugs eliminated primarily via renal clearance
Ceftazidime^Citation2,Citation7	1 g every 6 h	2 g every 8 h	2 g every 8 h
Ceftriaxone^Citation2	2 g every 12–24 h	2 g every 12–24 h	2 g every 12–24 h
Cefoperazone-sulbactamb	1–2 g every 6 h	1–2 g every 6 h	2 g every 6 h
Cefepime^Citation8	1 g every 8 h	1 g every 6 h	1 g every 6 h
Piperacillin-tazobactam^Citation2,Citation7,c	3.375 g every 6 h	4.5 g every 6 h	4.5 g every 6 h
Imipenem-cilastatin^Citation2,d	0.5 g every 8 h	0.5 g every 6 h	0.5 g every 6 h
Meropenem^Citation2,Citation7	0.5 g every 6 h	1 g every 8 h	1 g every 8 h
Vancomycine	15 mg/kg LD+	15 mg/kg LD+	15 mg/kg LD+
Teicoplanin^Citation4	LD+ 1,200 mg	LD+ 1,200 mg	LD 1,200 mg
	600–1,800 mg once daily	600–1,800 mg once daily	600–1,800 mg once daily
Levofloxacin^Citation2	500 mg LD^+	500 mg LD^+	500 mg every 24 h
	250 mg every 24 h	250 mg every 24 h
Amikacin^Citation2,e	10 mg/kg LD+	10 mg/kg LD^+	10 mg/kg LD^+
Linezolid^Citation2	600 mg every 12 h	600 mg every 12 h	600 mg every 12 h
Fosfomycin^Citation6	4 g every 6 h	4 g every 6 h	4 g every 6 h
Fluconazole^Citation2	200–400 mg every 24 h	400–800 mg every 24 h	400–800 mg every 24 h
Sodium chloride	Dosing adjustment according to the lab test or serum drug concentration
Potassium chloride Digoxine
Drugs eliminated primarily via nonrenal clearancef,g
Voriconazole, caspofungin, amphotericin B, moxifloxacin, metronidazole, heparin,h omeprazole, midazolam,i propofol,i amiodarone, warfarin,j aminophylline, etc

Notes: Special consideration: If CRRT system is discontinued or switched to another mode of renal replacement therapy, dosages should be adjusted to the patient’s intrinsic renal function or to the new mode of renal replacement therapy.

a It is assumed that patients have normal hepatic function and are anuric

b available commercially in a fixed ratio of 500 mg to 500 mg

c available commercially in a fixed ratio of 4 g to 0.5 g

d available commercially in a fixed ratio of 250 mg to 250 mg

e serum drug concentrations should be monitored (trough level: vancomycin 10–15 mg/mL; amikacin 5–10 mg/mL; digoxin 0.8–2.0 ng/mL; aminophylline)

f the renal clearance of a drug is less than 25%–30% of total body clearance

g drug dosing similar with normal renal function patients, dosing adjustments do not have to be considered

h dosing adjustment according to activated partial thromboplastin time

i dosing adjustment according to Ramsay sedation scale

j dosing adjustment according to international normalized ratio.

Abbreviations: CRRT, continuous renal replacement therapy; h, hours; LD+, loading dose.

Table 2 Patient characteristics

Parameter	No-intervention	Intervention	P value
Patients, n	103	106	0.61
Male	57	61
Female	46	45
Age, years	61.3±16.9	58.9±17.3	0.28
Weight, kg	63.4±19.7	59.6±21.3	0.42
APACHE II score^Citation15	22.8±8.9	21.4±10.2	0.73
Admission creatinine concentration, mmol/L	260.44±119.78	267.11±109.99	0.44
Admission urea concentration, mmol/L	22.53±12.19	21.78±8.57	0.30
Admission diagnosis, n (%)
Pneumonia and/or ARDS	23 (22.81)	25 (23.58)	0.39
Septic shock	20 (19.30)	17 (16.04)	0.41
CHF/pulmonary edema	18 (17.54)	21 (19,81)	0.38
Cardiac/aortic surgery	9 (8.77)	7 (6.60)	0.48
Gastrointestinal surgery	9 (8.77)	15 (14.15)	0.17
MODS	14 (14.04)	9 (8.49)	0.21
Othersa	23 (22.81)	27 (25.47)	0.31
Length of CRRT treatment, h	91.13±89.52	85.92±96.96	0.28
Drugs used in ICU, n	9.18±3.7	9.92±4.18	0.41

Notes: Data are expressed as n (%) or mean ± standard deviation.

a Including cerebrovascular accident, trauma, severe pancreatitis, hyperkalemia, and hypercalcemia.

Abbreviations: ARDS, adult respiratory distress syndrome; CHF, congestive heart failure; CRRT, continuous renal replacement therapy; h, hours; ICU, intensive care unit; MODS, multiple organ dysfunction syndrome; n, number; APACHE II: Acute Physiology and Chronic Health Evaluation II.

Table 3 Type of drugs with most dosing errors

Drugs	Primary route of elimination	n (%)
Antibiotics		168 (72.10)
Ceftriaxone	Hepatic	4 (1.72)
Ceftazidime	Renal	6 (2.56)
Cefepime	Renal	10 (4.29)
Cefoperazone-sulbactam	Hepatic/renal	25 (10.73)
Piperacillin-tazobactam	Renal/renal	30 (12.88)
Imipenem-cilastatin	Renal/renal	14 (6.01)
Meropenem	Renal	16 (6.87)
Vancomycin	Renal	24 (10.30)
Teicoplanin	Renal	15 (6.44)
Levofloxacin	Renal	9 (3.86)
Amikacin	Renal	1 (0.43)
Linezolid	Hepatic	8 (3.43)
Fosfomycin	Renal	6 (2.58)
Electrolytes		23 (9.87)
Sodium chloride	Renal	7 (3.00)
Potassium chloride	Renal	11 (4.72)
Calcium chloride	Renal	5 (2.15)
Sedatives		13 (5.58)
Midazolam	Hepatic	7 (3.00)
Propofol	Hepatic	6 (2.58)
Antifungals		11 (4.72)
Fluconazole	Renal	6 (2.58)
Voriconazole	Hepatic	2 (0.86)
Caspofungin	Hepatic	2 (0.86)
Amphotericin B (liposomal)	Unknown	1 (0.43)
Cardiovascular medications		9 (3.86)
Digoxin	Renal	4 (1.72)
Heparin	Hepatic	2 (0.86)
Low molecular heparin	Renal	3 (1.29)
Other medications		9 (3.86)
Omeprazole	Hepatic	4 (1.72)
Aminophylline	Hepatic	4 (1.72)
Aciclovir	Renal	1 (0.43)
Total		233 (100)

Abbreviation: n, number.

Table 4 Clinical and economic outcomes after pharmacist dosing adjustment for critically ill patients receiving CRRT

Parameter	No-intervention	Intervention	P value
Mortality, n (%)	31 (30.10)	29 (27.36)	0.39
Length of ICU stay, days
Mean (SD)	8.93±8.96	7.68±7.63	0.26
Median	8.1	7.3
Antibiotics cost, $US/case
Mean (SD)	2,321.09±1,453.52	1,531.30±1,092.36	0.013
Median	1,934.58	1,354.37
Drug cost,* $US/case
Mean (SD)	3,935.94±3,790.63	2,710.47±2,773.81	0.026
Median	3,062.70	1,871.82
ICU hospitalization cost
Mean (SD)	10,462.53±9,004.41	8,116.55±8,959.2	0.031
Median	8,419.68	6,932.85

Note:

* Including antibiotics and other drug costs.

Abbreviations: $US, US dollars; CRRT, continuous renal replacement therapy; ICU, intensive care unit; n, number; SD, standard deviation.

Table 5 Comparison of adverse drug events between the no-intervention group and the intervention group

Parameter	No-intervention n (%)	Intervention n (%)	P value
Preventability
Preventable	19 (54.28)	5 (27.77)	0.03
Unpreventable	16 (45.71)	13 (72.22)	0.18
Causality
Highly	15 (42.86)	5 (27.78)	0.02
Probable	11 (31.43)	7 (38.89)	0.26
Possible	9 (25.71)	6 (33.33)	0.21
Seriousness
Serious	7 (20.00)	3 (16.67)	0.11
Significant	17 (48.57)	8 (44.44)	0.02
Insignificant	11 (31.43)	7 (38.89)	0.19
Main drug class related ADEs
Antibiotics	12 (34.29)	6 (33.33)	0.03
Electrolytes	9 (25.71)	4 (22.22)	0.28
Cardiovascular drugs	6 (17.14)	3 (16.67)	0.19
Sedatives	3 (8.57)	3 (16.67)	0.68
Others	5 (14.29)	2 (11.11)	0.16
Total	35 (100)	18 (100)	<0.001

Abbreviations: ADE, adverse drug event; n, number.

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