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Postoperative Nausea and Vomiting in Adults: DOSAGE ADJUSTMENTS

No dosing adjustment is necessary for any of the three antiemetic agents in patients with renal impairment.

In patients with hepatic impairment, the clearance of ondan-setron is reduced and the half-life is increased significantly. In patients with mild, moderate, and severe hepatic impairment, the elimination half-life is 9.1 hours, 9.2 hours, and 20.6 hours, respectively. Therefore, the maximum daily dose of ondan-setron for a patient with hepatic dysfunction is 8 mg.

No dosing adjustment is necessary in patients with hepatic impairment who are using granisetron tablet or dolasetron.

STUDY POPULATION

Table 2 illustrates the basic characteristics of the three study groups. Most patients were female (65.3% vs. 34.7%). The majority of the procedures were abdominal (27%), orthopedic (23%), and gynecological (19%).

Table 2 Characteristics of 282 Patients Evaluated for Postoperative Nausea and Vomiting

Dolasetron Ondansetron

Granisetron

(Anzemet®)

(Zofran generic)

(Kytril drug)

(n = 89)

(n = 93)

(n = 100)

Demographics

Female (%)

49 (55%)

66 (7I%)

69 (69%)

Male (%)

40 (45%)

27 (29%)

3I (3I%)

Mean age ± SD

59 ± I8

47 ± 2I

52 ± I6

Type of Surgery

Cardiovascular

I3 (I5%)

4 (4%)

Neurological 3 (3%)

0 (0%)

0 (0%)

Genitourinary

I0 (II%)

II (I2%)

5 (5%)

Abdominal

I9 (2I%)

27 (29%)

30 (30%)

Orthopedic

20 (22%)

2I (23%)

23 (23%)

Gynecological

II (I2%)

I9 (20%)

24 (24%)

Other

I3 (I5%)

II (I2%)

I7 (I7%)

Length of Procedure

<I hour

I9 (2I%)

37 (40%)

33 (33%)

I-2 hours

3I (35%)

32 (34%)

36 (36%)

2-3 hours

I9 (2I%)

I2 (I3%)

I8 (I8%)

3-4 hours

II (I2%)

9 (I0%)

I2 (I2%)

4-5 hours 5 (6%)

0 (0%)

> 5 hours 4 (5%)

3 (3%)

0 (0%)

The mean age of the patients was approximately 52.3 ± 19 years. The median duration of the procedure was 1.5 hours, and the median number of anesthetic induction agents used for the procedures was four. The median length of recovery room stay was three hours.

RESULTS

Women were more likely to require a rescue drug than men (24.5% vs. 11.2%; P < .01). However, the need for a rescue agent did not depend on age. The mean age of patients receiving an antiemetic rescue drug was 50 ± 20 years vs. 53 ± 19 years for patients who did not receive a rescue drug (P = .28 by the Rank-Sum test).

As the duration of the procedure increased, the likelihood of requiring a rescue medication generally increased as follows (P = .11, Trend Test):

  • less than one hour, 12.4% of patients
  • one to two hours, 24.2% of patients
  • two to three hours, 24.5% of patients
  • three to four hours, 12.5% of patients
  • four to five hours, 33.3% of patients
  • more than five hours, 42.9% of patients

Similarly, as the number of anesthetic induction agents increased, the rescue rates increased accordingly, as follows: 9.1% with one agent, 19.4% with two agents, 10.5% with three agents, 23.1% with four agents, and 32.7% with five agents (P = .0114, Trend Test).

Certain combinations of the anesthetic induction agents were used more often than others (Table 3). However, the study sample size was not large enough to predict which agent was more emetogenic than the others.

Table 3 Number of Patients Receiving Induction Agents

Dolasetron

medication Ondansetron

Granisetron

(Anzemet®)

(Zofran®)

(Kytril tablet)
Induction Agent

(n = 89)

(n = 93)

(n = 100)
Propofol, sevoflurane, and fentanyl

7 (8%)

I9 (20%)

I5 (I5%)
Propofol, sevoflurane, fentanyl, and midazolam

7 (8%)

I3 (I4%)

I3 (I3%)
Propofol, midazolam, and fentanyl

5 (6%)

I2 (I3%)

I7 (I7%)
Propofol and fentanyl

5 (6%)

7 (8%)

4 (4%)
Propofol, midazolam, fentanyl, and desflurane

I9 (2I%)

I2 (I3%)

I9 (I9%)
Propofol, sevoflurane, and midazolam

2 (2%)

0 (0%)
Propofol, fentanyl, and desflurane

9 (I0%)

6 (6%)

I3 (I3%)
Midazolam and fentanyl

5 (6%)

3 (3%)

2 (2%)
Midazolam, fentanyl, and desflurane

3 (3%)

0 (0%)

0 (0%)
Sevoflurane and fentanyl

3 (3%)

0 (0%)

3 (3%)
Midazolam, fentanyl, and sevoflurane

2 (2%)

5 (5%)

0 (0%)
Propofol and midazolam

3 (3%)

2 (2%)
Propofol, isoflurane, midazolam, and fentanyl

4 (4%)

2 (2%)

Midazolam

3 (3%)

0 (0%)
Other combinations

I7%

II%

II%

Of the 282 patients, about 20% (56 patients) needed an antiemetic rescue drug. Of the 89 patients who received dolasetron 12.5 mg IV x 1 (for one dose) to prevent PONV, 23.6% (21 patients) needed a rescue medication. Of the 93 patients who received ondansetron 4 mg IV x 1 to prevent PONV, 11.8% (11 patients) needed a rescue medication. Of the 100 patients who received granisetron 0.1 mg IV x 1 to prevent PONV, 24% (24 patients) needed a rescue medication. Therefore, the need for a rescue agent was significantly reduced with ondansetron when compared with canadian granisetron (11.8% vs. 24%; P < .04), dolasetron (11.8°% vs. 23.6°%, P = .05), or a combination of the two (11.8% vs. 23.8%, P < .02) (Table 4).

Table 4 Number of Patients Receiving Antiemetic Agents

Dolasetron

Ondansetron

Granisetron
(Anzemet®)

(Zofran canadian)

(Kytril®)
12.5 mg IV x 1

4 mg IV x 1

0.1 mg IV x 1
(n = 89)

(n = 93)

(n = 100)
Perioperatively 81 (91%)

56 (60%)

97 (97%)
Postoperatively 8 (9%)

37 (40%)

3 (3%)
Required rescue medications 21 (23.6%) 11 (11.8%) 24 (24%)
Received ondansetron 4 mg IV x 1 15 (71%)

9 (82%)

22 (92%)
as the rescue drug
Received dolasetron 12.5 mg x 1 0 (0%)

1 (9%)

1 (4%)
as the rescue drug
Received ondansetron 4 mg IV x 1 5 (24%)

1 (9%)

1 (4%)
and dolasetron 12.5 mg x 1 as the
rescue drug
Received ondansetron 4 mg IV x 1 1 (5%)

0 (0%)

0 (0%)
and granisetron 0.1 mg IV x 1
as the rescue drug
IV = intravenous.

Ondansetron 4 mg IV was used more commonly as the rescue drug and adequately resolved the symptoms of breakthrough nausea and vomiting. However, it did not make a difference, with breakthrough nausea or vomiting, whether the antiemetic was administered perioperatively or postopera-tively. The rescue rate was 19.7% perioperatively and 20.8% postoperatively (P = .84).

The median LOS in the recovery room was four hours for patients who received a rescue medication and three hours for patients who did not (P = .0732). The median LOS in the recovery room was 2 hours with ondansetron canadian, 3.3 hours with dolasetron, and 3 hours with granisetron (P< .0001), according to the Kruskal-Wallis test. With the Tukey test (P < .05), the ondansetron patients had a statistically significant shorter LOS than the other two groups (Table 5).

Table 5 Patient Length of Stay in the Recovery Room

Antiemetic Agent

Median Length of Stay

Dolasetron I2.5 mg IV x I* Granisetron 0.I mg IV x I* Ondansetron 4 mg IV x I 3.3 hours 3.0 hours 2.0 hours

The LOS was also significantly positively correlated with the patient’s age (r = .30, P < .0001) and with the duration of the procedure (r = .31, P < .0001) but not with the number of anesthetic induction agents (r = .09, P = .11).

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