DOSAGE AND ADMINISTRATION
To avoid distress to the patient,
atracurium should not be administered before
unconsciousness has been induced. Atracurium
should not be mixed in the same syringe, or
administered simultaneously through the same
needle, with alkaline solutions (e.g., barbiturate
solutions).
Atracurium besylate should be
administered intravenously. DO NOT GIVE ATRACURIUM
BESYLATE BY INTRAMUSCULAR ADMINISTRATION.
Intramuscular administration of atracurium
besylate may result in tissue irritation and there
are no clinical data to support this route of
administration.
As with other neuromuscular blocking
agents, the use of a peripheral nerve stimulator
will permit the most advantageous use of
atracurium besylate, minimizing the possibility of
overdosage or underdosage, and assist in the
evaluation of recovery.
Bolus Doses for
Intubation and Maintenance of Neuromuscular
Block:
Adults:
An atracurium
besylate dose of 0.4 to 0.5 mg/kg (1.7 to 2.2
times the ED95), given as an
intravenous bolus injection, is the recommended
initial dose for most patients. With this dose,
good or excellent conditions for nonemergency
intubation can be expected in 2 to 2.5 minutes in
most patients, with maximum neuromuscular block
achieved approximately 3 to 5 minutes after
injection. Clinically required neuromuscular block
generally lasts 20 to 35 minutes under balanced
anesthesia. Under balanced anesthesia, recovery to
25% of control is achieved approximately 35 to
45 minutes after injection, and recovery is
usually 95% complete approximately 60 minutes
after injection.
Atracurium is potentiated by isoflurane
or enflurane anesthesia. The same initial
atracurium besylate dose of 0.4 to 0.5 mg/kg may
be used for intubation prior to administration of
these inhalation agents; however, if atracurium is
first administered under steady-state of
isoflurane or enflurane, the initial atracurium
besylate dose should be reduced by approximately
one-third, i.e., to 0.25 to 0.35 mg/kg, to adjust
for the potentiating effects of these anesthetic
agents. With halothane, which has only a marginal
(approximately 20%) potentiating effect on
atracurium, smaller dosage reductions may be
considered.
Atracurium besylate doses of 0.08 to
0.10 mg/kg are recommended for maintenance of
neuromuscular block during prolonged surgical
procedures. The first maintenance dose will
generally be required 20 to 45 minutes after the
initial atracurium besylate injection, but the
need for maintenance doses should be determined by
clinical criteria. Because atracurium lacks
cumulative effects, maintenance doses may be
administered at relatively regular intervals for
each patient, ranging approximately from 15 to 25
minutes under balanced anesthesia, slightly longer
under isoflurane or enflurane. Higher atracurium
doses (up to 0.2 mg/kg) permit maintenance dosing
at longer intervals.
Pediatric
Patients:
No atracurium
dosage adjustments are required for pediatric
patients two years of age or older. An atracurium
besylate dose of 0.3 to 0.4 mg/kg is recommended
as the initial dose for infants (1 month to 2
years of age) under halothane anesthesia.
Maintenance doses may be required with slightly
greater frequency in infants and children than in
adults.
Special
Considerations:
An
initial atracurium besylate dose of 0.3 to 0.4
mg/kg, given slowly or in divided doses over one
minute, is recommended for adults, children, or
infants with significant cardiovascular disease
and for adults, children, or infants with any
history (e.g., severe anaphylactoid reactions or
asthma) suggesting a greater risk of histamine
release.
Dosage reductions must be considered
also in patients with neuromuscular disease,
severe electrolyte disorders, or carcinomatosis in
which potentiation of neuromuscular block or
difficulties with reversal have been demonstrated.
There has been no clinical experience with
atracurium in these patients, and no specific
dosage adjustments can be recommended. No
atracurium dosage adjustments are required for
patients with renal disease.
An initial atracurium besylate dose of
0.3 to 0.4 mg/kg is recommended for adults
following the use of succinylcholine for
intubation under balanced anesthesia. Further
reductions may be desirable with the use of potent
inhalation anesthetics. The patient should be
permitted to recover from the effects of
succinylcholine prior to atracurium
administration. Insufficient data are available
for recommendation of a specific initial
atracurium dose for administration following the
use of succinylcholine in children and
infants.
Use by Continuous
Infusion:
Infusion in the
Operating Room
(OR):
After
administration of a recommended initial bolus dose
of atracurium besylate injection (0.3 to 0.5
mg/kg), a diluted solution of atracurium besylate
can be administered by continuous infusion to
adults and pediatric patients aged 2 or more years
for maintenance of neuromuscular block during
extended surgical procedures.
Infusion of atracurium should be
individualized for each patient. The rate of
administration should be adjusted according to the
patient’s response as determined by
peripheral nerve stimulation. Accurate dosing is
best achieved using a precision infusion
device.
Infusion of atracurium should be
initiated only after early evidence of spontaneous
recovery from the bolus dose. An initial infusion
rate of 9 to 10 mcg/kg/min may be required to
rapidly counteract the spontaneous recovery of
neuromuscular function. Thereafter, a rate of 5 to
9 mcg/kg/min should be adequate to maintain
continuous neuromuscular block in the range of
89% to 99% in most pediatric and adult
patients under balanced anesthesia. Occasional
patients may require infusion rates as low as 2
mcg/kg/min or as high as 15
mcg/kg/min.
The neuromuscular blocking effect of
atracurium administered by infusion is potentiated
by enflurane or isoflurane and, to a lesser
extent, by halothane. Reduction in the infusion
rate of atracurium should, therefore, be
considered for patients receiving inhalation
anesthesia. The rate of atracurium infusion should
be reduced by approximately one-third in the
presence of steady-state enflurane or isoflurane
anesthesia; smaller reductions should be
considered in the presence of
halothane.
In patients undergoing cardiopulmonary
bypass with induced hypothermia, the rate of
infusion of atracurium required to maintain
adequate surgical relaxation during hypothermia
(25° to 28°C) has been shown to be
approximately half the rate required during
normothermia.
Spontaneous recovery from neuromuscular
block following discontinuation of atracurium
infusion may be expected to proceed at a rate
comparable to that following administration of a
single bolus dose.
Infusion in the
Intensive Care Unit
(ICU):
The principles for
infusion of atracurium in the OR are also
applicable to use in the ICU.
An infusion rate of 11 to 13 mcg/kg/min
(range: 4.5 to 29.5) should provide adequate
neuromuscular block in adult patients in an ICU.
Limited information suggests that infusion rates
required for pediatric patients in the ICU may be
higher than in adult patients. There may be wide
interpatient variability in dosage requirements
and these requirements may increase or decrease
with time (see
PRECAUTIONS: Long-Term Use in Intensive Care Unit
[ICU]
). Following
recovery from neuromuscular block,
readministration of a bolus dose may be necessary
to quickly reestablish neuromuscular block prior
to reinstitution of the infusion.
Infusion Rate Tables:
The amount of infusion
solution required per minute will depend upon the
concentration of atracurium in the infusion
solution, the desired dose of atracurium, and the
patient’s weight. The following tables
provide guidelines for delivery, in mL/hr
(equivalent to microdrops/min when 60 microdrops =
1 mL), of atracurium solutions in concentrations
of 0.2 mg/mL (20 mg in 100 mL) or 0.5 mg/mL (50 mg
in 100 mL) with an infusion pump or a gravity flow
device.
Table 3: Atracurium Besylate Infusion
Rates for a Concentration of 0.2 mg/mL
Patient Weight
(kg)
|
Drug Delivery Rate
(mcg/kg/min)
|
5
|
6
|
7
|
8
|
9
|
10
|
11
|
12
|
13
|
Infusion Delivery
Rate (mL/hr)
|
30
|
45
|
54
|
63
|
72
|
81
|
90
|
99
|
108
|
117
|
35
|
53
|
63
|
74
|
84
|
95
|
105
|
116
|
126
|
137
|
40
|
60
|
72
|
84
|
96
|
108
|
120
|
132
|
144
|
156
|
45
|
68
|
81
|
95
|
108
|
122
|
135
|
149
|
162
|
176
|
50
|
75
|
90
|
105
|
120
|
135
|
150
|
165
|
180
|
195
|
55
|
83
|
99
|
116
|
132
|
149
|
165
|
182
|
198
|
215
|
60
|
90
|
108
|
126
|
144
|
162
|
180
|
198
|
216
|
234
|
65
|
98
|
117
|
137
|
156
|
176
|
195
|
215
|
234
|
254
|
70
|
105
|
126
|
147
|
168
|
189
|
210
|
231
|
252
|
273
|
75
|
113
|
135
|
158
|
180
|
203
|
225
|
248
|
270
|
293
|
80
|
120
|
144
|
168
|
192
|
216
|
240
|
264
|
288
|
312
|
90
|
135
|
162
|
189
|
216
|
243
|
270
|
297
|
324
|
351
|
100
|
150
|
180
|
210
|
240
|
270
|
300
|
330
|
360
|
390
|
Table 4: Atracurium Besylate Infusion
Rates for a Concentration of 0.5 mg/mL
Patient Weight (kg)
|
Drug Delivery Rate
(mcg/kg/min)
|
5
|
6
|
7
|
8
|
9
|
10
|
11
|
12
|
13
|
Infusion Delivery
Rate (mL/hr)
|
30
|
18
|
22
|
25
|
29
|
32
|
36
|
40
|
43
|
47
|
35
|
21
|
25
|
29
|
34
|
38
|
42
|
46
|
50
|
55
|
40
|
24
|
29
|
34
|
38
|
43
|
48
|
53
|
58
|
62
|
45
|
27
|
32
|
38
|
43
|
49
|
54
|
59
|
65
|
70
|
50
|
30
|
36
|
42
|
48
|
54
|
60
|
66
|
72
|
78
|
55
|
33
|
40
|
46
|
53
|
59
|
66
|
73
|
79
|
86
|
60
|
36
|
43
|
50
|
58
|
65
|
72
|
79
|
86
|
94
|
65
|
39
|
47
|
55
|
62
|
70
|
78
|
86
|
94
|
101
|
70
|
42
|
50
|
59
|
67
|
76
|
84
|
92
|
101
|
109
|
75
|
45
|
54
|
63
|
72
|
81
|
90
|
99
|
108
|
117
|
80
|
48
|
58
|
67
|
77
|
86
|
96
|
106
|
115
|
125
|
90
|
54
|
65
|
76
|
86
|
97
|
108
|
119
|
130
|
140
|
100
|
60
|
72
|
84
|
96
|
108
|
120
|
132
|
144
|
156
|
Compatibility and Admixtures:
Atracurium besylate infusion
solutions may be prepared by admixing atracurium
besylate injection with an appropriate diluent
such as 5% Dextrose Injection, 0.9% Sodium
Chloride Injection, or 5% Dextrose and
0.9% Sodium Chloride Injection. Infusion
solutions should be used within 24 hours of
preparation. Unused solutions should be discarded.
Solutions containing 0.2 mg/mL or 0.5 mg/mL
atracurium besylate in the above diluents may be
stored either under refrigeration or at room
temperature for 24 hours without significant loss
of potency. Care should be taken during admixture
to prevent inadvertent contamination. Visually
inspect prior to administration.
Spontaneous degradation of atracurium
besylate has been demonstrated to occur more
rapidly in Lactated Ringer’s solution than
in 0.9% sodium chloride solution. Therefore,
it is recommended that Lactated Ringer’s
Injection not be used as a diluent in preparing
solutions of atracurium besylate injection for
infusion.
Parenteral drug products should be
inspected visually for particulate matter and
discoloration prior to administration, whenever
solution and container permit.
|