# Abstract

 

## Background Low-dose haloperidol is known to be effective for the prevention of postoperative nausea and vomiting (PONV). However, precise dose-response studies have not been completed, especially in patients at high risk for PONV who require combination therapy. This study sought to identify which dose of haloperidol 1mg or 2mg could be combined with dexamethasone without adverse effects in high-risk patients undergoing gynecological laparoscopic surgery. 

## Methods Female adults (*n* = 150) with three established PONV risk factors based on Apfel's score were randomized into one of three study groups. At the end of anesthesia, groups H0, H1, and H2 were given intravenous (IV) saline, haloperidol 1 mg, and haloperidol 2 mg, respectively. All patients were given dexamethasone 5 mg during the induction of anesthesia. The overall early (0--2 h) and late (2--24 h) incidences of nausea, vomiting, rescue anti-emetic administration, pain, and adverse effects (cardiac arrhythmias and extrapyramidal effects) were assessed postoperatively. The sedation score was recorded in the postanesthesia care unit (PACU). 

## Results The total incidence of PONV over 24 h was significantly lower in groups H1 (29 %) and H2 (24 %) than in group H0 (54 %; *P* = 0.003), but there was no significant difference between groups H1 and H2. In the PACU, group H2 had a higher sedation score than groups H1 and H0 (*P* \< 0.001). 

## Conclusions For high-risk PONV patients undergoing gynecological laparoscopic surgery, when used with dexamethasone, 1-mg haloperidol was equally effective as 2 mg in terms of preventing PONV with the less sedative effect. 

## Trial Registration ClinicalTrials.gov ([NCT01639599](#)). # Results Of the 150 patients registered for the study, one was excluded due to an intra-operative conversion to laparotomy (Fig. [1](#)). The remaining 149 patients, consisting of 50, 49, and 50 patients in groups H0, H1, and H2, respectively, completed the study. The patient characteristics, PONV risk factors, type of surgery, duration of anesthesia, intra-operative remifentanil use, 24-h postoperative PCA fentanyl use, postoperative pain severity, and rescue analgesic requirements were similar among the three groups (Table [1](#)). <figure> <p><img src="" /></p> <figcaption>CONSORT diagram showing the flow of participants</figcaption> </figure> ::::table-wrap

::: caption
Patient characteristics and variables associated with PONV
:::

```
                                       Group H0 (*n* = 50)   Group H1 (*n* = 49)   Group H2 (*n* = 50)
```

______________________________________________________________________

Age (year) 40 (20--60) 39 (20--60) 41 (21--58)
Weight (kg) 56.9 (5.7) 55.0 (7.9) 54.4 (5.3)
Height (cm) 158.7 (4.9) 159.1 (5.5) 157.3 (5.5)
ASA I/II 40/10 41/8 39/11
PONV or motion sickness history 26 (52 %) 28 (57 %) 28 (56 %)
Anesthesia duration (min) 150.3 (43.1) 157.9 (39.4) 156.4 (31.4)
Remifentanil consumption (μg) 104.7 (36.2) 97.2 (31.3) 92.5 (29.2)
Surgical type\
Lap. ovarian cystectomy 17 (34 %) 12 (24 %) 13 (26 %)
Lap. hysterectomy 23 (46 %) 22 (45 %) 26 (52 %)
Diagnostic laparoscopy 5 (10 %) 11 (22 %) 6 (12 %)
Lap. myomectomy 4 (8 %) 3 (6 %) 4 (8 %)
Lap. adhesiolysis 1 (2 %) 1 (2 %) 1 (2 %)
PCA fentanyl consumption for 24 h (μg) 470.1 (105.5) 465.6 (102.6) 467.8 (99.5)
Postoperative pain\
0-2 h 4.9 (1.7) 4.8 (1.8) 4.6 (2.1)
2-24 h 2.2 (2.1) 2.8 (1.6) 2.2 (1.9)
Rescue analgesic requirements 15 (30 %) 11 (22 %) 10 (20 %)

Values are means (SD) or number (proportion). No statistically
significant difference was observed among the groups

Group H0 = saline, H1 = haloperidol 1 mg, and H2 = haloperidol 2 mg

*PONV* postoperative nausea and vomiting; *Lap* laparoscopic; *PCA*
patient-controlled analgesia:::: Overall, the frequency of PONV within 24 h postoperatively was lower in groups H1 and H2 than in group H0, while there was no statistical difference between groups H1 and H2 (29, 24, and 54 % in groups H1, H2, and H0, respectively; *P* = 0.003). Table [2](#) summarizes the results at each postoperative time point. ::::table-wrap
::: caption
PONV outcomes
:::

```
                     Group H0     Group H1     Group H2     
```

______________________________________________________________________

```
                     (*n* = 50)   (*n* = 49)   (*n* = 50)   *P**
```

Early time (0--2 h)\
Nausea 15 (30 %) 5 (10 %)† 9 (18 %) 0.04
Vomiting 7 (14 %) 3 (6 %) 4 (8 %) 0.37
Total PONV 17 (34 %) 5 (10 %)† 10 (20 %) 0.02
Rescue anti-emetics 12 (24 %) 3 (6 %)† 6 (12 %) 0.03
Late time (2--24 h)\
Nausea 17 (34 %) 10 (20 %) 9 (18 %) 0.13
Vomiting 6 (12 %) 5 (10 %) 3 (6 %) 0.57
Total PONV 21 (42 %) 11 (22 %) 10 (20 %) 0.03
Rescue anti-emetics 11 (22 %) 7 (14 %) 7 (14 %) 0.48

Values are numbers (proportion). Groups H0 = saline, H1 = haloperidol 1
mg, and H2 = haloperidol 2 mg

*PONV* postoperative nausea and vomiting

\*Unadjusted *P* value

†*P* \< 0.017, compared with group H0:::: In the PACU (0--2 h), group H1 had a lower incidence of PONV and reduced requirements for rescue anti-emetics than group H0, while group H2 did not differ significantly from group H0. In the ward (2--24 h), the incidence of PONV was lower in groups H1 and H2 than in group H0, but there was no statistically significant difference between groups H1 and H2 (22 % in group H1 and 20 % in group H2 *vs*. 42 % in group H0). The change in the sedation score in the PACU clearly differed among the groups according to the dose of haloperidol. Group H2 had an overall higher sedation score than groups H1 and H0 over the 2-h observation period (*P* \< 0.001, Fig. [2](#)), while there was no significant difference between groups H1 and H0. In addition, three patients in group H2 required treatment with ephedrine in the PACU, due to hypotension (systolic 75--80/diastolic 50--55 mmHg). <figure> <p><img src="" /></p> <figcaption>Postanesthesia care unit-sedation scores recorded using a 10 cm visual analogue scale (VAS; 0 = wide awake and 10 = maximally asleep) in patients receiving saline (▲), haloperidol 1 mg (●) or haloperidol 2mg (■). \*<em>P</em> \< 0.05 compared with saline. †<em>P</em> \< 0.05 compared with haloperidol 1 mg</figcaption> </figure> The QTc intervals before administering the study drug were similar among the groups (group H0, 423.85 ± 21.94 ms; group H1, 425.23 ± 0.21 ms; and group H2, 426.35 ± 15.13 ms). The QTc interval measured in the PACU also did not differ among the groups (group H0, 426.75 ± 19.64 ms; group H1, 430.67 ± 21.92 ms; and group H2, 431.95 ± 23.14 ms). No cardiac arrhythmias were observed in the PACU. No patient showed evidence of twitching, dystonia, akathisia, or other extrapyramidal reactions during the 24-h postoperative observation period.


Extracted trial result:
Outcome: The sedation score recorded in the postanesthesia care unit (PACU) over the 2-h observation period (continuous)
Intervention: and H2 (haloperidol 2 mg)
Comparator: H1(haloperidol 1 mg)
Intervention group size: 50
Comparator group size: 49
Notes: Data is in figure.