Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/976
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SUPRANE (Liquid)
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Deliver SUPRANE
(desflurane, USP) from a vaporizer specifically designed and designated
for use with desflurane. The administration
of general anesthesia must be individualized based on the patient's
response (seeINDIVIDUALIZATION
OF DOSE). The following two tables provide mean relative
potency based upon age and drug interaction studies in predominately ASA
physical status I or II patients. N = number of
crossover pairs (using up-and-down method of quantal response) Opioids or
benzodiazepines decrease the amounts of SUPRANE (desflurane, USP)
required to produce anesthesia. The following table is based on studies
of drug interaction (MAC reduction). SUPRANE
(desflurane, USP) decreases the doses of neuromuscular blocking agents
required (seePRECAUTIONS, Drug
Interactions). During the
maintenance of anesthesia with inflow rates of 2 L/min or more, the
alveolar concentration of desflurane will usually be within 10% of the
inspired concentration. (F/F, see Figure 1
inPharmacokinetics section.)
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SUPRANE
(desflurane, USP), a nonflammable liquid administered via vaporizer, is
a general inhalation anesthetic. It is (��)1,2,2,2-tetrafluoroethyl
difluoromethyl ether:<br/>Some physical
constants are::<br/>Partition
coefficients at 37��C::<br/>Mean Component/Gas
Partition Coefficients:: Desflurane
is nonflammable as defined by the requirements of International
Electrotechnical Commission 601-2-13. Desflurane
is a colorless, volatile liquid below 22.8��C. Data indicate that
desflurane is stable when stored under normal room lighting
conditions according to instructions. Desflurane
is chemically stable. The only known degradation reaction is
through prolonged direct contact with soda lime producing low
levels of fluoroform (CHF). The amount of
CHFobtained is similar to that produced with
MAC-equivalent doses of isoflurane. No discernible degradation
occurs in the presence of strong acids. Desflurane
does not corrode stainless steel, brass, aluminum, anodized aluminum, nickel plated brass, copper, or beryllium.
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SUPRANE
(desflurane, USP) is a volatile liquid inhalation anesthetic minimally
biotransformed in the liver in humans. Less than 0.02% of the SUPRANE
absorbed can be recovered as urinary metabolites (compared to 0.2% for
isoflurane). Minimum alveolar
concentration (MAC) of desflurane in oxygen for a 25 year-old adult is
7.3%. The MAC of SUPRANE (desflurane, USP) decreases with increasing age
and with addition of depressants such as opioids or benzodiazepines
(seeDOSAGE AND
ADMINISTRATION for details).<br/>Pharmacokinetics: Due to the
volatile nature of desflurane in plasma samples, the
washin-washout profile of desflurane was used as a surrogate of
plasma pharmacokinetics. Eight healthy male volunteers first
breathed 70% NO/30% Ofor 30 minutes and
then a mixture of SUPRANE (desflurane, USP) 2.0%, isoflurane
0.4%, and halothane 0.2% for another 30 minutes. During this
time, inspired and end-tidal concentrations (Fand
F) were measured. The
F/F(washin) value at 30 minutes for
desflurane was 0.91, compared to 1.00 for NO, 0.74
for isoflurane, and 0.58 for halothane (See Figure 1). The
washin rates for halothane and isoflurane were similar to
literature values. The washin was faster for desflurane than for
isoflurane and halothane at all time points. The
F/F(washout) value at 5 minutes was
0.12 for desflurane, 0.22 for isoflurane, and 0.25 for halothane
(See Figure 2). The washout for SUPRANE was more rapid than that
for isoflurane and halothane at all elimination time points. By
5 days, the F/Ffor desflurane is 1/20th of that for halothane or isoflurane.<br/>Pharmacodynamics: Changes in
the clinical effects of SUPRANE (desflurane, USP) rapidly follow
changes in the inspired concentration. The duration of
anesthesia and selected recovery measures for SUPRANE are given
in the following tables: In 178
female outpatients undergoing laparoscopy, premedicated with
fentanyl (1.5-2.0��g/kg), anesthesia was initiated with propofol
2.5 mg/kg, desflurane/NO 60% in Oor
desflurane/Oalone. Anesthesia was maintained
with either propofol 1.5-9.0 mg/kg/hr, desflurane 2.6-8.4% in
NO 60% in O, or desflurane 3.1-8.9%
in O. In 88
unpremedicated outpatients, anesthesia was initiated with
thiopental 3-9 mg/kg or desflurane in O. Anesthesia
was maintained with isoflurane 0.7-1.4% in NO 60%,
desflurane 1.8-7.7% in NO 60%, or desflurane
4.4-11.9% in O. Recovery
from anesthesia was assessed at 30, 60, and 90 minutes following
0.5 MAC desflurane (3%) or isoflurane (0.6%) in NO
60% using subjective and objective tests. At 30 minutes after
anesthesia, only 43% of the isoflurane group were able to
perform the psychometric tests compared to 76% in the desflurane
group (p<0.05). SUPRANE (desflurane, USP) was studied in twelve volunteers receiving no
other drugs. Hemodynamic effects during controlled ventilation
(PaCO38mm Hg) were: When the
same volunteers breathed spontaneously during desflurane
anesthesia, systemic vascular resistance and mean arterial blood
pressure decreased; cardiac index, heart rate, stroke volume,
and central venous pressure (CVP) increased compared to values
when the volunteers were conscious. Cardiac index, stroke
volume, and CVP were greater during spontaneous ventilation than
during controlled ventilation. During
spontaneous ventilation in the same volunteers, increasing the
concentration of SUPRANE (desflurane, USP) from 3% to 12%
decreased tidal volume and increased arterial carbon dioxide
tension and respiratory rate. The combination of NO
60% with a given concentration of desflurane gave results
similar to those with desflurane alone. Respiratory depression
produced by desflurane is similar to that produced by other
potent inhalation agents. The use of
desflurane concentrations higher than 1.5 MAC may produce apnea.<br/>CLINICAL TRIALS: SUPRANE
(desflurane, USP) was evaluated in 1,843 patients including
ambulatory (N=1,061), cardiovascular (N=277), geriatric (N=103),
neurosurgical (N=40), and pediatric (N=235) patients. Clinical
experience with these patients and with 1,087 control patients
in these studies not receiving desflurane are described below.
Although desflurane can be used in adults for the inhalation
induction of anesthesia via mask, it produces a high incidence
of respiratory irritation (coughing, breathholding, apnea,
increased secretions, laryngospasm). For incidence, seeADVERSE
REACTIONS. Oxyhemoglobin saturation below 90% occurred in 6% of patients (from pooled data, N = 370
adults).<br/>Ambulatory
Surgery: SUPRANE (desflurane, USP) plus NO was
compared to isoflurane plus NO in
multicenter studies (21 sites) of 792 ASA physical
status I, II, or III patients aged 18-76 years (median
32).<br/>Cardiovascular Surgery: Desflurane was compared to isoflurane, sufentanil or
fentanyl for the anesthetic management of coronary
artery bypass graft (CABG), abdominal aortic aneurysm,
peripheral vascular and carotid endarterectomy surgery in 7 studies at 15 centers involving a total of 558
patients. In all patients except the desflurane vs
sufentanil study, the volatile anesthetics were
supplemented with intravenous opioids, usually fentanyl.
Blood pressure and heart rate were controlled by changes
in concentration of the volatile anesthetics or opioids
and cardiovascular drugs if necessary. Oxygen (100%) was
the carrier gas in 253 of 277 desflurane cases (24 of
277 received NO/O). No
differences were found in cardiovascular outcome (death,
myocardial infarction, ventricular tachycardia or
fibrillation, heart failure) among desflurane and the
other anesthetics.<br/>Geriatric
Surgery: SUPRANE (desflurane, USP) plus NO was
compared to isoflurane plus NO in a
multicenter study (6 sites) of 203 ASA physical status
II or III elderly patients, aged 57-91 years (median
71).<br/>Neurosurgery: SUPRANE (desflurane, USP) was studied in 38 patients
aged 26-76 years (median 48 years), ASA physical status
II or III undergoing neurosurgical procedures for
intracranial lesions.<br/>Pediatric
Surgery: SUPRANE (desflurane, USP) is not recommended for
induction of anesthesia in pediatric patients because of
the high incidence of moderate to severe upper airway
adverse reactions, including laryngospasm, coughing,
breathholding, and secretions, seen in studies of
induction of anesthesia in pediatric patients.
. SUPRANE is not approved for maintenance of anesthesia
in non-intubated pediatric patients due to an increased
incidence of respiratory adverse reactions, including
coughing, laryngospasm and secretions, seen in one study of maintenance of anesthesia in non-intubated pediatric
patients. (seeWARNINGS andPRECAUTIONS���Pediatric
Use).<br/>INDIVIDUALIZATION
OF DOSE: (Also
seeDOSAGE AND
ADMINISTRATION)<br/>Preanesthetic Medication: Issues such as whether or not to premedicate and the
choice of premedicant(s) must be individualized. In
clinical trials, patients scheduled to be anesthetized
with desflurane frequently received IV pre-anesthetic
medication, such as opioid and/or
benzodiazepine.
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SUPRANE
(desflurane, USP) should not be used in patients with a known or
suspected genetic susceptibility to malignant hyperthermia. Known sensitivity
to SUPRANE (desflurane, USP) or to other halogenated agents.
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SUPRANE
(desflurane, USP), NDC 10019-641-24, is packaged in amber-colored
bottles containing 240 mL desflurane.<br/>Safety and Handling:<br/>Occupational Caution: There is no specific work exposure limit established
for SUPRANE (desflurane, USP). However, the National
Institute for Occupational Safety and Health
Administration (NIOSH) recommends that no worker should
be exposed at ceiling concentrations greater than 2 ppm of any halogenated anesthetic agent over a sampling
period not to exceed one hour. The
predicted effects of acute overexposure by inhalation of
SUPRANE (desflurane, USP) include headache, dizziness or
(in extreme cases) unconsciousness. There are no documented adverse effects of chronic
exposure to halogenated anesthetic vapors (Waste Anesthetic Gases or WAGs) in
the workplace. Although results of some epidemiological
studies suggest a link between exposure to halogenated
anesthetics and increased health problems (particularly
spontaneous abortion), the relationship is not
conclusive. Since exposure to WAGs is one possible
factor in the findings for these studies, operating room
personnel, and pregnant women in particular, should
minimize exposure. Precautions include adequate general
ventilation in the operating room, the use of a
well-designed and well-maintained scavenging system,
work practices to minimize leaks and spills while the
anesthetic agent is in use, and routine equipment
maintenance to minimize leaks.<br/>Storage: Store at room
temperature, 15��-30��C
(59��-86��F). SUPRANE
(desflurane, USP) has been demonstrated to be stable for
the period defined by the expiration dating on the
label. The bottle cap should be replaced after each use
of SUPRANE. Baxter and SUPRANE are trademarks of Baxter
International Inc. Manufactured for Baxter Healthcare
Corporation Deerfield, IL 60015 USA For
Product Inquiry 1 800 ANA DRUG
(1-800-262-3784) MLT-00070/8.0
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During the
maintenance of anesthesia, increasing concentrations of SUPRANE
(desflurane, USP) produce dose-dependent decreases in blood pressure.
Excessive decreases in blood pressure may be related to depth of
anesthesia and in such instances may be corrected by decreasing the
inspired concentration of SUPRANE. Concentrations of
desflurane exceeding 1 MAC may increase heart rate. Thus an increased
heart rate may not be a sign of inadequate anesthesia. In patients with
intracranial space occupying lesions, SUPRANE (desflurane, USP) should
be administered at 0.8 MAC or less, in conjunction with a barbiturate
induction and hyperventilation (hypocapnia). Appropriate measures should
be taken to maintain cerebral perfusion pressure (seeCLINICAL STUDIES,
Neurosurgery). In patients with
coronary artery disease, maintenance of normal hemodynamics is important
to the avoidance of myocardial ischemia. Desflurane should not be used
as the sole agent for anesthetic induction in patients with coronary
artery disease or patients where increases in heart rate or blood pressure are undesirable. It should be used with other medications,
preferably intravenous opioids and hypnotics (seeCLINICAL STUDIES,
Cardiovascular Surgery). Inspired
concentrations of SUPRANE (desflurane, USP) greater than 12% have been
safely administered to patients, particularly during induction of
anesthesia. Such concentrations will proportionately dilute the
concentration of oxygen; therefore, maintenance of an adequate
concentration of oxygen may require a reduction of nitrous oxide or air
if these gases are used concurrently. The recovery from
general anesthesia should be assessed carefully before patients are
discharged from the post anesthesia care unit (PACU). SUPRANE
(desflurane, USP), like some other inhalational anesthetics, can react
with desiccated carbon dioxide (CO) absorbents to produce
carbon monoxide which may result in elevated levels of carboxyhemoglobin
in some patients. Case reports suggest that barium hydroxide lime and
soda lime become desiccated when fresh gases are passed through the
COabsorber cannister at high flow rates over many hours
or days. When a clinician suspects that COabsorbent may be
desiccated, it should be replaced before the administration of SUPRANE
(desflurane, USP). As with other
halogenated anesthetic agents, SUPRANE (desflurane, USP) may cause
sensitivity hepatitis in patients who have been sensitized by previous
exposure to halogenated anesthetics .<br/>Drug Interactions: No
clinically significant adverse interactions with commonly used
preanesthetic drugs, or drugs used during anesthesia (muscle
relaxants, intravenous agents, and local anesthetic agents) were
reported in clinical trials. The effect of desflurane on the
disposition of other drugs has not been determined. Like
isoflurane, desflurane does not predispose to premature
ventricular arrhythmias in the presence of exogenously infused
epinephrine in swine.<br/>Benzodiazepines and Opioids (MAC Reduction): Benzodiazepines (midazolam 25-50��g/kg) decrease the
MAC of desflurane by 16% as do the opioids (fentanyl 3-6��g/kg) by 50% .<br/>Neuromuscular Blocking Agents: Anesthetic concentrations of desflurane at equilibrium
(administered for 15 or more minutes before testing)
reduced the EDof succinylcholine by
approximately 30% and that of atracurium and pancuronium
by approximately 50% compared to NO/opioid
anesthesia. The effect of desflurane on duration of
nondepolarizing neuromuscular blockade has not been
studied. Dosage reduction of neuromuscular blocking agents
during induction of anesthesia may result in delayed
onset of conditions suitable for endotracheal intubation
or inadequate muscle relaxation, because potentiation of
neuromuscular blocking agents requires equilibration of
muscle with the delivered partial pressure of
desflurane. Among nondepolarizing drugs, only pancuronium and
atracurium interactions have been studied. In the
absence of specific guidelines: 1.
For endotracheal intubation, do not reduce the dose of
nondepolarizing muscle relaxants or succinylcholine. 2.
During maintenance of anesthesia, the dose of
nondepolarizing muscle relaxants is likely to be reduced
compared to that during NO/opioid
anesthesia. Administration of supplemental doses of
muscle relaxants should be guided by the response to
nerve stimulation.<br/>Renal or Hepatic Insufficiency: Nine
patients receiving SUPRANE (desflurane, USP) (N=9) were compared
to 9 patients receiving isoflurane, all with chronic renal
insufficiency (serum creatinine 1.5-6.9 mg/dL). No differences
in hematological or biochemical tests, including renal function
evaluation, were seen between the two groups. Similarly, no
differences were found in a comparison of patients receiving
either SUPRANE (desflurane, USP) (N=28) or isoflurane (N=30)
undergoing renal transplant. Eight
patients receiving SUPRANE (desflurane, USP) were compared to
six patients receiving isoflurane, all with chronic hepatic
disease (viral hepatitis, alcoholic hepatitis, or cirrhosis). No
differences in hematological or biochemical tests, including
hepatic enzymes and hepatic function evaluation, were
seen.<br/>Carcinogenesis,
Mutagenesis, Impairment of Fertility: Animal
carcinogenicity studies have not been performed with SUPRANE
(desflurane, USP). In
vitro and in vivo genotoxicity studies did not demonstrate
mutagenicity or chromosomal damage by SUPRANE. Tests for
genotoxicity included the Ames mutation assay, the metaphase
analysis of human lymphocytes, and the mouse micronucleus assay. Fertility
was not affected after 1 MAC-Hour per day exposure (cumulative
63 and 14 MAC-Hours for males and females, respectively). At
higher doses, parental toxicity (mortalities and reduced weight
gain) was observed which could affect fertility.<br/>Pregnancy:<br/>Teratogenic
Effects: No
teratogenic effect was observed at approximately 10 and
13 cumulative MAC-Hour exposures at 1 MAC-Hour per day
during organogenesis in rats or rabbits. At higher doses
increased incidences of post-implantation loss and
maternal toxicity were observed. However, at 10
MAC-Hours cumulative exposure in rats, about 6% decrease
in the weight of male pups was observed at preterm
caesarean delivery.<br/>Labor and Delivery: The safety
of desflurane during labor or delivery has not been
demonstrated.<br/>Nursing Mothers: The
concentrations of desflurane in milk are probably of no clinical
importance 24 hours after anesthesia. Because of rapid washout,
desflurane concentrations in milk are predicted to be below
those found with other volatile potent anesthetics.<br/>Pediatric Use: SUPRANE (desflurane, USP) is approved for maintenance of anesthesia in
infants and children after induction of anesthesia with agents
other than SUPRANE, and tracheal intubation. SUPRANE is
not recommended for induction of general anesthesia via mask in
children because of the high incidence of moderate to severe
respiratory adverse reactions, including laryngospasm (50%),
coughing (72%), breathholding (68%), increase in secretions
(21%) and oxyhemoglobin desaturation
(SpO<90%) (26%) seen in clinical studies. SUPRANE is
not approved for maintenance of anesthesia in non-intubated
children due to an increased incidence of respiratory adverse
reactions (see below). In a
clinical safety trial conducted in children aged 2 to 16 years
(mean 7.4 years), following induction with another agent,
SUPRANE and isoflurane (in NO/O) were
compared when delivered via face mask or laryngeal mask airway
(LMA) for maintenance of anesthesia, after induction with
intravenous propofol or inhaled sevoflurane, in order to assess
the relative incidence of respiratory adverse events. SUPRANE was
associated with higher rates (compared with isoflurane) of
coughing, laryngospasm and secretions with an overall rate of
respiratory events of 39%. Of the pediatric patients exposed to
desflurane, 5% experienced severe laryngospasm (associated with
significant desaturation; i.e. SpOof<90% for>15
seconds, or requiring succinylcholine), across all ages, 2-16
years old. Individual age group incidences of severe
laryngospasm were 9% for 2-6 years old, 1% for 7-11 years old,
and 1% for 12-16 years old. Removal of LMA under deep anesthesia
(MAC range 0.6���2.3 with a mean of 1.12 MAC) was associated
with a further increase in frequency of respiratory adverse
events as compared to awake LMA removal or LMA removal under
deep anesthesia with the comparator. The frequency and severity
of non-respiratory adverse events were comparable between the
two groups. The
incidence of respiratory events under these conditions was
highest in children aged 2-6 years. Therefore, similar studies
in children under the age of 2 years were not
initiated.<br/>Geriatric Use: The average
MAC for SUPRANE (desflurane, USP) in a 70 year old patient is
two-thirds the MAC for a 20 year old patient (seeDOSAGE AND
ADMINISTRATION).<br/>Neurosurgical Use: SUPRANE
(desflurane, USP) may produce a dose-dependent increase in
cerebrospinal fluid pressure (CSFP) when administered to
patients with intracranial space occupying lesions. Desflurane
should be administered at 0.8 MAC or less, and in conjunction
with a barbiturate induction and hyperventilation (hypocapnia)
until cerebral decompression in patients with known or suspected
increases in CSFP. Appropriate attention must be paid to
maintain cerebral perfusion pressure (seeCLINICAL
STUDIES, Neurosurgery).
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In the event of
overdosage, or suspected overdosage, take the following actions:
discontinue administration of SUPRANE (desflurane, USP), maintain a
patent airway, initiate assisted or controlled ventilation with oxygen,
and maintain adequate cardiovascular function.
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desflurane
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SUPRANE (Liquid)
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Adverse event
information is derived from controlled clinical trials, the majority of
which were conducted in the United States. The studies were conducted
using a variety of premedications, other anesthetics, and surgical procedures of varying length. Most adverse events reported were mild and
transient, and may reflect the surgical procedures, patient
characteristics (including disease) and/or medications administered. Of the 2,143
patients exposed to SUPRANE (desflurane, USP) in clinical trials, 370
adults and 152 children were induced with desflurane alone and 987
patients were maintained principally with desflurane. The frequencies
given reflect the percent of patients with the event. Each patient was
counted once for each type of adverse event. They are presented in
alphabetical order according to body system.<br/>Frequency of Events
Occurring in Greater Than 1% of Clinical Trial Patients (in Reports
Deemed���Probably Causally Related���):<br/>Induction (use as a
mask inhalation agent):<br/>Maintenance
or Recovery:<br/>Frequency of Events
Occurring in Less Than 1% of Patients (in Reports Deemed���Probably
Causally Related���):<br/>Reported in 3 or
more patients, regardless of severity: Adverse
reactions reported only from postmarketing experience or in the
literature, not seen in clinical trials, are considered rare and are italicized.<br/>Frequency of Events
Occurring in Less Than 1% of Clinical Trial Patients (in Reports
Deemed���Causal Relationship Unknown���):<br/>Reported in 3 or
more patients, regardless of severity: SeeWARNINGS for information regarding pediatric use and
malignant hyperthermia. SUPRANE
(desflurane, USP) has been associated with perioperative
hyperkalemia . There have
been rare post-marketing reports of hepatic failure and hepatic
necrosis associated with the use of potent volatile anesthetic agents, including SUPRANE (desflurane USP). Due to the
spontaneous nature of these reports, the actual incidence and
relationship of SUPRANE (desflurane USP) to these events cannot
be established withcertainty.<br/>Laboratory Findings: Transient
elevations in glucose and white blood cell count may occur as
with use of other anesthetic agents.
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Perioperative
Hyperkalemia: Use of
inhaled anesthetic agents has been associated with rare
increases in serum potassium levels that have resulted in
cardiac arrhythmias and death in pediatric patients during the
postoperative period. Patients with latent as well as overt
neuromuscular disease, particularly Duchenne muscular dystrophy,
appear to be most vulnerable. Concomitant use of succinylcholine
has been associated with most, but not all, of these cases.
These patients also experienced significant elevations in serum
creatinine kinase levels and, in some cases, changes in urine
consistent with myoglobinuria. Despite the similarity in
presentation to malignant hyperthermia, none of these patients
exhibited signs or symptoms of muscle rigidity or hypermetabolic
state. Early and aggressive intervention to treat the
hyperkalemia and resistant arrhythmias is recommended, as is
subsequent evaluation for latent neuromuscular
disease.<br/>Malignant
Hyperthermia: In
susceptible individuals, potent inhalation anesthetic agents may
trigger a skeletal muscle hypermetabolic state leading to high
oxygen demand and the clinical syndrome known as malignant
hyperthermia. In genetically susceptible pigs, desflurane
induced malignant hyperthermia. The clinical syndrome is
signalled by hypercapnia, and may include muscle rigidity,
tachycardia, tachypnea, cyanosis, arrhythmias, and/or unstable
blood pressure. Some of these nonspecific signs may also appear
during light anesthesia: acute hypoxia, hypercapnia, and
hypovolemia. Treatment
of malignant hyperthermia includes discontinuation of triggering
agents, administration of intravenous dantrolene sodium, and
application of supportive therapy. (Consult prescribing
information for dantrolene sodium intravenous for additional
information on patient management.) Renal failure may appear
later, and urine flow should be monitored and sustained if
possible.<br/>Respiratory Adverse
Reactions in Pediatric Patients: SUPRANE
(desflurane, USP) is not recommended for induction of general
anesthesia via mask in children due to a high incidence of
moderate to severe respiratory adverse reactions seen in
clinical studies . SUPRANE is
not approved for maintenance of anesthesia in non-intubated
children due to an increased incidence of respiratory adverse
reactions, including coughing, laryngospasm and secretions .<br/>Administration of
Suprane: SUPRANE
(desflurane, USP) should be administered only by persons trained
in the administration of general anesthesia, using a vaporizer
specifically designed and designated for use with desflurane.
Facilities for maintenance of a patent airway, artificial
ventilation, oxygen enrichment, and circulatory resuscitation
must be immediately available. Hypotension and respiratory
depression increase as anesthesia is deepened.
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SUPRANE
(desflurane, USP) is indicated as an inhalation agent for induction
and/or maintenance of anesthesia for inpatient and outpatient surgery in
adults . SUPRANE
(desflurane, USP) is not recommended for induction of anesthesia in
pediatric patients because of a high incidence of moderate to severe
upper airway adverse events . After induction of anesthesia with agents other
than SUPRANE, and tracheal intubation, SUPRANE is indicated for
maintenance of anesthesia in infants and children.
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SUPRANE
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