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Suprane

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Suprane

CLINICAL PHARMACOLOGY

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 (desflurane, USP) are given in the following tables:

In 178 female outpatients undergoing laparoscopy, premedicated with fentanyl (1.52.0 μg/kg), anesthesia was initiated with propofol 2.5 mg/kg, desflurane/N2O 60% in O2 or desflurane/O2 alone. Anesthesia was maintained with either propofol 1.5-9.0 mg/kg/hr, desflurane 2.6-8.4% in N2O 60% in O2, or desflurane 3.1-8.9% in O2.

EMERGENCE AND RECOVERY AFTER OUTPATIENT LAPAROSCOPY 178 FEMALES, AGES 20-47 TIMES IN MINUTES: MEAN ± SD (RANGE)

Induction: Maintenance: Number of Pts: Propofol Propofol/N2O
N = 48
Propofol Desflurane /N2O
N = 44
Desflurane /N2O Desflurane /N2O
N = 43
Desflurane /O2 Desflurane /O2
N = 43
Median age 30
(20 - 43)
26
(21 - 47)
29
(21 - 42)
30
(20 - 40)
Anesthetic Time 49 ± 53
(8 - 336)
45 ± 35
(11 - 178)
44 ± 29
(14 - 149)
41 ± 26
(19 - 126)
Time to open eyes 7 ± 3
(2 - 19)
5 ± 2*
(2 - 10)
5 ± 2*
(2 - 12)
4 ± 2*
(1 - 11)
Time to state name 9 ± 4
(4 - 22)
8 ± 3
(3 - 18)
7 ± 3*
(3 - 16)
7 ± 3*
(2 - 15)
Time to stand 80 ± 34
(40 - 200)
86 ± 55
(30 - 320)
81 ± 38
(35 - 190)
77 ± 38
(35 - 200)
Time to walk 110 ± 6
(47 - 285)
122 ± 85
(37 - 375)
108 ± 59
(48 - 220)
108 ± 66
(49 - 250)
Time to fit fordischarge 152 ± 75
(66 - 375)
157 ± 80
(73 - 385)
150 ± 66
(68 - 310)
155 ± 73
(69 - 325)
*Differences were statistically significant (p < 0.05) by Dunnett's procedure comparing all treatments to the propofol-propofol/N2O (induction and maintenance) group. Results for comparisons greater than one hour after anesthesia show no differences between groups and considerable variability within groups

In 88 unpremedicated outpatients, anesthesia was initiated with thiopental 3-9 mg/kg or desflurane in O2. Anesthesia was maintained with isoflurane 0.7-1.4% in N2O 60%, desflurane 1.8-7.7% in N2O 60%, or desflurane 4.4-11.9% in O2.

EMERGENCE AND RECOVERY TIMES IN OUTPATIENT SURGERY 46 MALES, 42 FEMALES, AGES 19-70 TIMES IN MINUTES: MEAN ± SD (RANGE)

Induction: Maintenance: Number of Pts: Thiopental Isoflurane/N2O
N = 23
Thiopental Desflurane/N2O
N = 21
Thiopental Desflurane/O2
N = 23
Desflurane/O2Desflurane/O2
N = 21
Median age 43
(20 - 70)
40
(22 - 67)
43
(19 - 70)
41
(21-64)
Anesthetic Time 49 ± 23
(11 - 94)
50 ± 19
(16 - 80)
50 ± 27
(16 - 113)
51 ± 23
(19 - 117)
Time to openeyes 13 ± 7
(5 - 33)
9 ± 3*
(4 - 16)
12 ± 8
(4 - 39)
8 ± 2*
(4 - 13)
Time to statename 17 ± 10
(6 - 44)
11 ± 4*
(6 - 19)
15 ± 10
(6 - 46)
9 ± 3*
(5 - 14)
Time to walk 195 ± 67
(124 - 365)
176 ± 60
(101 - 315)
168 ± 34
(119 - 258)
181 ± 42
(92 - 252)
Time to fit fordischarge 205 ± 53
(153 - 365)
202 ± 41
(144 - 315)
197 ± 35
(155 - 280)
194 ± 37
(134 - 288)
*Differences were statistically significant
(p < 0.05) by Dunnett's procedure comparing all treatments to the thiopental-isoflurane/N2O (induction and maintenance) group. Results for comparisons greater than one hour after anesthesia show no differences between groups and considerable variability within groups.

Recovery from anesthesia was assessed at 30, 60, and 90 minutes following 0.5 MAC desflurane (3%) or isoflurane (0.6%) in N2O 60% using subjective and objective tests. At 30 minutes after anesthesia, only 43% of patients in the isoflurane group were able to perform the psychometric tests compared to 76% in the SUPRANE (desflurane, USP) group (p < 0.05).

RECOVERY TESTS: PERCENT OF PREOPERATIVE BASELINE VALUES 16 MALES, 22 FEMALES, AGES 20-65 PERCENT: MEAN ± SD

Maintenance: 60 minutes After Anesthesia 90 minutes After Anesthesia
Desflurane/N2O Isoflurane/N2O Desflurane/N2O Isoflurane/N2O
Confusion Δ 66 ± 6 47 ± 8 75 ± 7* 56 ± 8
Fatigue Δ 70 ± 9* 33 ± 6 89 ± 12* 47 ± 8
Drowsiness Δ 66 ± 5* 36 ± 8 76 ± 7* 49 ± 9
Clumsiness Δ 65 ± 5 49 ± 8 80 ± 7* 57 ± 9
Comfort Δ 59 ± 7* 30 ± 6 60 ± 8* 31 ± 7
DSST+ score 74 ± 4* 50 ± 9 75 ± 4* 55 ± 7
Trieger Tests++ 67 ± 5 74 ± 6 90 ± 6 83 ± 7
Δ Visual analog scale (values from 0-100; 100 = baseline)
+ DSST = Digit Symbol Substitution Test
++ Trieger Test = Dot Connecting Test
* Differences were statistically significant (p < 0.05) using a two-sample t-test

Desflurane was studied in twelve volunteers receiving no other drugs. Hemodynamic effects during controlled ventilation (PaCO2 38 mm Hg) were:

HEMODYNAMIC EFFECTS OF DESFLURANE DURING CONTROLLED VENTILATION 12 MALE VOLUNTEERS, AGES 16-26 MEAN ± SD (RANGE)

Total MAC Equivalent End-Tidal % Des/O2 End-Tidal % Des/N2O Heart Rate (beats/min) Mean Arterial Pressure (mm Hg) Cardiac Index (L/min/m²)
O2 N2O O2 N2O O2 N2O
0 0% / 21% 0% / 0% 69 ± 4 (63 - 76) 70 ± 6 (62 - 85) 85 ± 9 (74 - 102) 85 ± 9 (74 - 102) 3.7 ± 0.4 (3.0 - 4.2) 3.7 ± 0.4 (3.0 - 4.2)
0.8 6% / 94% 3% / 60% 73 ± 5 (67 - 80) 77 ± 8 (67 - 97) 61 ± 5* (55 - 70) 69 ± 5* (62 - 80) 3.2 ± 0.5 (2.6 - 4.0) 3.3 ± 0.5 (2.6 - 4.1)
1.2 9% / 91% 6% / 60% 80 ± 5* (72 - 84) 77 ± 7 (67 - 90) 59 ± 8* (44 - 71) 63 ± 8* (47 - 74) 3.4 ± 0.5 (2.6 - 4.1) 3.1 ± 0.4* (2.6 - 3.8)
1.7 12% / 88% 9% / 60% 94 ± 14* (78 - 109) 79 ± 9 (61 - 91) 51 ± 12* (31 - 66) 59 ± 6* (46 - 68) 3.5 ± 0.9 (1.7 - 4.7) 3.0 ± 0.4* (2.4 - 3.6)
*Differences were statistically significant (p < 0.05) compared to awake values, Newman-Keul's method of multiple comparison.

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 desflurane from 3% to 12% decreased tidal volume and increased arterial carbon dioxide tension and respiratory rate. The combination of N2O 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.

Figure 1: PaCO2 During Spontaneous Ventilation in Unstimulated Volunteers

PaCO2 During Spontaneous Ventilation in Unstimulated Volunteers - Illustration

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. SUPRANE (desflurane, USP) is a volatile liquid inhalation anesthetic minimally biotransformed in the liver in humans. Less than 0.02% of the desflurane absorbed can be recovered as urinary metabolites (compared to 0.2% for isoflurane). Eight healthy male volunteers first breathed 70% N2O/30% O2 for 30 minutes and then a mixture of desflurane 2.0%, isoflurane 0.4%, and halothane 0.2% for another 30 minutes. During this time, inspired and end-tidal concentrations (FI and FA) were measured. The FA/FI (washin) value at 30 minutes for desflurane was 0.91, compared to 1.00 for N2O, 0.74 for isoflurane, and 0.58 for halothane (see Figure 2). 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 FA/FAO (washout) value at 5 minutes was 0.12 for desflurane, 0.22 for isoflurane, and 0.25 for halothane (see Figure 3). The washout for desflurane was more rapid than that for isoflurane and halothane at all elimination time points. By 5 days, the FA/FAO for desflurane is 1/20th of that for halothane or isoflurane.

Figure 2: Desflurane Washin

Desflurane Washin - Illustration

Figure 3: Desflurane Washout

Desflurane Washout - Illustration

Clinical Studies

The efficacy of 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 SUPRANE (desflurane, USP) is described below. Although SUPRANE (desflurane, USP) 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). Oxyhemoglobin saturation below 90% occurred in 6% of patients (from pooled data, N = 370 adults).

Ambulatory Surgery

SUPRANE (desflurane, USP) plus N2O was compared to isoflurane plus N2O in multicenter studies (21 sites) of 792 ASA physical status I, II, or III patients aged 18-76 years (median 32).

Induction

Anesthetic induction begun with thiopental and continued with (desflurane, USP) was associated with a 7% incidence of oxyhemoglobin saturation of 90% or less (from pooled data, N = 307) compared with 5% in patients in whom anesthesia was induced with thiopental and isoflurane (from pooled data, N = 152).

Maintenance & Recovery

SUPRANE (desflurane, USP) with or without N2O or other anesthetics was generally well tolerated. There were no differences between SUPRANE (desflurane, USP) and the other anesthetics studied in the times that patients were judged fit for discharge.

In one outpatient study, patients received a standardized anesthetic consisting of thiopental 4.2-4.4 mg/kg, fentanyl 3.5-4.0 μg/kg, vecuronium 0.05-0.07 mg/kg, and N2O 60% in oxygen with either desflurane 3% or isoflurane 0.6%. Emergence times were significantly different; but times to sit up and discharge were not different (see Table 5).

TABLE 5 : RECOVERY PROFILES AFTER DESFLURANE 3% IN N2O 60% vs ISOFLURANE 0.6% IN N2O 60% IN OUTPATIENTS 16 MALES, 22 FEMALES, AGES 20-65 MEAN ± SD

  Isoflurane Desflurane
Number 21 17
Anesthetic time (min) 127 ± 80 98 ± 55
Recovery time to:
Follow commands (min) 11.1 ± 7.9 6.5 ± 2.3*
Sit up (min) 113 ± 27 95 ± 56
Fit for discharge (min) 231 ± 40 207 ± 54

*Difference was statistically significant from the isoflurane group (p < 0.05), unadjusted for multiple comparisons.

Cardiovascular Surgery

SUPRANE (desflurane, USP) 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 N2O/O2).

CARDIOVASCULAR PATIENTS BY AGENT AND TYPE OF SURGERY 418 MALES, 140 FEMALES, AGES 27-87 (MEDIAN 64)

Type of Surgery 13 Centers 1 Center 1 Center
Isoflurane Desflurane Sufentanil Desflurane Fentanyl Desflurane
CABG 58 57 100 100 25 25
Abd Aorta 29 25 - - - -
Periph Vasc 24 24 - - - -
Carotid Art 45 46 - - - -
Total 156 152 100 100 25 25

No differences were found in cardiovascular outcome (death, myocardial infarction, ventricular tachycardia or fibrillation, heart failure) among desflurane and the other anesthetics.

Induction

SUPRANE (desflurane, USP) should not be used as the sole agent for anesthetic induction in patients with coronary artery disease or any patients where increases in heart rate or blood pressure are undesirable. In the desflurane vs. sufentanil study, anesthetic induction with desflurane without opioids was associated with new transient ischemia in 14 patients vs. 0 in the sufentanil group. In the desflurane group, mean heart rate, arterial pressure, and pulmonary blood pressure increased and stroke volume decreased in contrast to no change in the sufentanil group. Cardiovascular drugs were used frequently in both groups: especially esmolol in the desflurane group (56% vs. 0%) and phenylephrine in the sufentanil group (43% vs. 27%). When 10 μg/kg of fentanyl was used to supplement induction of anesthesia at one other center, continuous 2-lead ECG analysis showed a low incidence of myocardial ischemia and no difference between desflurane and isoflurane. If desflurane is to be used in patients with coronary artery disease, it should be used in combination with other medications for induction of anesthesia, preferably intravenous opioids and hypnotics.

Maintenance & Recovery

In studies where SUPRANE (desflurane, USP) or isoflurane anesthesia was supplemented with fentanyl, there were no differences in hemodynamic variables or the incidence of myocardial ischemia in the patients anesthetized with desflurane compared to those anesthetized with isoflurane.

During the precardiopulmonary bypass period, in the desflurane vs. sufentanil study where the desflurane patients received no intravenous opioid, more desflurane patients required cardiovascular adjuvants to control hemodynamics than the sufentanil patients. During this period, the incidence of ischemia detected by ECG or echocardiography was not statistically different between desflurane (18 of 99) and sufentanil (9 of 98) groups. However, the duration and severity of ECG-detected myocardial ischemia was significantly less in the desflurane group. The incidence of myocardial ischemia after cardiopulmonary bypass and in the ICU did not differ between groups.

Geriatric Surgery

SUPRANE (desflurane, USP) plus N2O was compared to isoflurane plus N2O in a multicenter study (6 sites) of 203 ASA physical status II or III elderly patients, aged 5791 years (median 71).

Induction

Most patients were premedicated with fentanyl (mean 2 μg/kg), preoxygenated, and received thiopental (mean 4.3 mg/kg IV) or thiamylal (mean 4 mg/kg IV) followed by succinylcholine (mean 1.4 mg/kg IV) for intubation.

Maintenance & Recovery

Heart rate and arterial blood pressure remained within 20% of preinduction baseline values during administration of SUPRANE (desflurane, USP) 0.5-7.7% (average 3.6%) with 50-60% N2O. Induction, maintenance, and recovery cardiovascular measurements did not differ from those during isoflurane/N2O administration nor did the postoperative incidence of nausea and vomiting differ. The most common cardiovascular adverse event was hypotension occurring in 8% of the desflurane patients and 6% of the isoflurane patients.

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.

Induction

Induction consisted of standard neuroanesthetic techniques including hyperventilation and thiopental.

Maintenance

No change in cerebrospinal fluid pressure (CSFP) was observed in 8 patients who had intracranial tumors when the dose of SUPRANE (desflurane, USP) was 0.5 MAC in N2O 50%. In another study of 9 patients with intracranial tumors, 0.8 MAC desflurane /air/O2 did not increase CSFP above post induction baseline values. In a different study of 10 patients receiving 1.1 MACdesflurane /air/O2, CSFP increased 7 mm Hg (range 3-13 mm Hg increase, with final values of 11-26 mm Hg) above the pre-drug values.

All volatile anesthetics may increase intracranial pressure in patients with intracranial space occupying lesions. In such patients, SUPRANE (desflurane, USP) should be administered at 0.8 MAC or less, and in conjunction with a barbiturate induction and hyperventilation (hypocapnia) in the period before cranial decompression. Appropriate attention must be paid to maintain cerebral perfusion pressure. The use of a lower dose of SUPRANE (desflurane, USP) and the administration of a barbiturate and mannitol would be predicted to lessen the effect of desflurane on CSFP.

Under hypocapnic conditions (PaCO2 27 mm Hg) SUPRANE (desflurane, USP) 1 and 1.5 MAC did not increase cerebral blood flow (CBF) in 9 patients undergoing craniotomies. CBF reactivity to increasing PaCO2 from 27 to 35 mm Hg was also maintained at 1.25 MAC desflurane /air/O2.

Pediatric Surgery

In a clinical safety trial conducted in children aged 2 to 16 years (mean 7.4 years), following induction with another agent, SUPRANE (desflurane, USP) and isoflurane (in N2O/O2) 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.

MAINTENANCE IN NONINTUBATED PEDIATRIC PATIENTS (FACE MASK OR LMA USED; N=300) All Respiratory Events* ( > 1% of All Pediatric Patients)

  All Ages
(N=300)
2-6 yr
(N=150)
7-11 yr
(N=81)
12-16 yr
(N=69)
Any respiratory events 39% 42% 33% 39%
Airway obstruction 4% 5% 4% 3%
Breath-holding 3% 2% 3% 4%
Coughing 26% 33% 19% 22%
Laryngospasm 13% 16% 7% 13%
Secretion 12% 13% 10% 12%
Non-specific desaturation 2% 2% 1% 1%
*Minor, moderate and severe respiratory events

SUPRANE (desflurane, USP) 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. SpO2 of < 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.

Last reviewed on RxList: 10/3/2013
This monograph has been modified to include the generic and brand name in many instances.

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