Comparison of fentanyl and morphine in intravenous patient controlled analgesia after open gastrectomy surgery

Corresponding author: Nguyen Toan Thang, Departmentof Anesthesia and Critical Care, Hanoi Medical University E-mail: thanggmhs@gmail.com Received: 20 October 2016 Accepted: 10 December 2

Corresponding author: Nguyen Toan Thang, Department

of Anesthesia and Critical Care, Hanoi Medical University

E-mail: thanggmhs@gmail.com

Received: 20 October 2016

Accepted: 10 December 2016

COMPARISON OF FENTANYL AND MORPHINE IN

INTRAVENOUS PATIENT-CONTROLLED ANALGESIA AFTER

OPEN GASTRECTOMY SURGERY

Nguyen Toan Thang, Nguyen Huu Tu

Department of Anesthesia and Critical Care, Hanoi Medical University

A prospective and randomized study was conducted to assess the efficacy and adverse effects of a fentanyl intravenous patient - controlled analgesia (IV - PCA) compared with a morphine IV-PCA after open gastrectomy surgery Ninety patients were randomly allocated into two groups: Group F with a fentanyl concentration of 25 μg/mL, a bolus of 25 μg and a lockout time of 10 minutes and Group M with a morphine concentration of 1 mg/ml, a bolus of 1 mg and a lockout time of 10 minutes No background infusion was included in either group Pain severity was assessed by Visual Analogue Scale (VAS) at rest and on coughing, and the incidence of adverse effects was assessed postoperatively during the first 24 hours Group F showed significantly lower mean VAS scores at rest and on coughing compared to Group M The incidence of postoperative nausea and vomiting (PONV) in group M was 31.1% and in group F was 15.5%,

p < 0.05 The incidence of pruritus in group M was 17.8% and in group F was 8.9%, p < 0.05 The incidence

of patients reporting that they were very satisfied with their pain relief in Group F was higher than that in Group M (71.1% of patients in group F versus 51.1% of patients in group M, p < 0.05) No respiratory or cardiovascular complications were observed in either group The fentanyl IV - PCA is a more effective postoperative analgesia than the morphine IV - PCA, providing greater patient satisfaction and lower incidences of PONV and pruritus after open gastrectomy surgery.

Keywords: intravenous PCA, fentanyl, morphine, gastric surgery

I INTRODUCTION

Postoperative pain has substantial,

physi-cal and psychosocial effects on patients

Insuf-ficient analgesia can thereby delay patient

recovery Although there has been increased

understanding of the pathophysiology of pain

in recent years, as well as the recent

develop-ment of improved pharmacology and

analge-sic techniques, acute pain treatment after

surgery remains insufficient, even in

devel-oped countries [1; 2] Intravenous

Patient-Controlled Analgesia (IV - PCA) is a popular

and standard method of pain relief that allows patients to self - administer small preset boluses of opioids In comparison with conventional methods, IV - PCA provides slightly better pain control and higher patient satisfaction In the United States, there are approximately 13 millions patients per year using this method to control acute pain [3; 4]

In Vietnam, IV - PCA with opioids has also been widely adopted for postoperative pain management Traditionally, morphine is the most commonly utilized opioid in this setting, yet studies providing evidence that morphine

is the preferred opioid for IV - PCAs are lacking In spite of having strong analgesic effects and being low - cost, morphine can cause respiratory depression and other

adverse effects such as deep sedation,

nausea and vomiting, pruritus, and urinary

retention [1; 2]

Fentanyl is a 4 - amilidopiperidien

com-pound with high lipid solubility, which greatly

reduces the onset time of the analgesic effect

It takes 30 seconds for fentanyl to begin to

take effect, with its maximum effect reached

five minutes after administration Fentanyl is

also a potent and ideal drug for IV - PCA, as

its redistribution is rapid and wide with a short

duration, and it does not produce the active

metabolites that cause respiratory depression

[5, 6] Fentanyl is a µ opioid receptor agonist

with several advantageous pharmacological

characteristics, including strong analgesic

effects (approximately 80 - 100 times more

potent than morphine) and as mentioned

above, a more rapid onset of action compared

to morphine [7] Studies by Hutchison and

Stavropoulou suggested that fentanyl, with its

effective ability to relieve pain and its low

frequency of adverse effects such as

postop-erative nausea and vomiting (PONV), pruritus

or urinary retention, might be more preferable

than morphine for IV - PCA [8; 9] However,

little information in the literature has been

re-ported regarding the analgesic efficacy and

adverse effects of the fentanyl IV - PCA [10]

This study was carried out to prospectively

compare the postoperative analgesic efficacy

and adverse effects of IV - PCAs using

fentanyl and morphine in patients who just

recently underwent open gastrectomy

II SUBJECTS AND METHODS

1 Subjects

Ninety patients with American Society of

Anesthesiologists (ASA) physical status I - II

who were scheduled for open gastrectomy surgery under general anesthesia were en-rolled in this study Patients were excluded if they were younger than 18 years or older than

80 years old, had a history of allergy to opioids, had daily intake of opioids or other analgesics, had known or suspected drug addiction, or were unable to understand or use

a visual analogue scale (VAS) and a patient-controlled analgesia (PCA) device Patients with severe renal and hepatic diseases were also excluded

2 Study design

A prospective and randomized study was carried out in the Anesthesia and Critical Care Department of Bach Mai University Hospital in Hanoi, Vietnam from October 2014 to November 2015 In this study, patients were blinded to their group assignment, which was undertaken using a sealed envelope technique (Group F, n = 45; Group M, n = 45)

In the operating room, all patients were monitored using electrocardiography (ECG), noninvasive arterial blood pressure devices, and oxygen saturation and end-tidal carbon dioxide measuring equipment Patients were induced with 2 mg/kg of intravenous (IV) propofol After muscle relaxation had been achieved by IV administration of 0.6 mg/kg rocuronium bromide, the trachea was intubated and controlled ventilation was started Anesthesia was maintained by propofol infusion at a rate of 6 - 8 mg/kg/hour and intermittent IV injection of fentanyl and rocuronium At the end of surgery, all patients received one gram of paracetamol

Intensities of postoperative pain at rest and

on active coughing were evaluated using a

VAS, from 0 (“no pain”) to 10 (“the worst pain

imaginable”) Adequate analgesia was defined

as VAS < 3 at rest A Modified Ramsay

Sedation Scale (from 1 to 6), where 1 is

anxious or restless or both and 6 is no

response to stimulus, was used to determine

the appropriate level of sedation After

extubation, patients received 100 μg of

fen-tanyl or 1 mg of morphine every 10 min when

they experienced pain at rest until they

reached an adequate level of comfort before

starting the IV - PCA

The PCA device used a mechanical pump

(B Braun, Germany) In Group F, the PCA

pump was programmed with the following

set-tings: bolus, 1 mL; lockout time, 10 min; and

maximum dose per 4 hours, 15 mL/h The

in-fusion solution containing 1.25 mg of fentanyl

was adjusted to 50 mL by dilution with 0.9%

normal saline (the concentration of fentanyl

was 25 μg/mL) In Group M, the PCA device

was programmed with the following settings:

bolus, 1 mL; lockout time, 10 min; and

maxi-mum dose per 4 hours, 15 mL/h The infusion

solution containing 50 mg of morphine was

adjusted to 50 mL by dilution with 0.9% normal

saline (the concentration of morphine was 1

mg/mL) The background infusion dose was

not applied an both groups

During the first 24 hours postoperatively,

non-invasive artery blood pressure, heart rate,

oxygen saturation, respiratory rate and

occur-rence of untoward events were recorded at

two hour, three hour and six hour intervals

Hypotension (20% reduction in systolic blood

pressure compared with preoperative

base-line) was treated using a vasopressor and/or

IV fluid, at the anesthesiologist’s discretion If

a respiratory rate of less than 8 breaths per minute was observed, the PCA pump was stopped VAS at rest and on active coughing, any incidence of PONV, and the patient’s Ramsay scale were recorded at 2, 6, 12 and

24 hours after the end of surgery The degree

of patient satisfaction was evaluated and categorized into three levels at the 24th hour after surgery: very satisfied, satisfied, or dissatisfied For patients experiencing severe PONV, 10 mg of metoclopramide or 4 mg of ondansetron was given intravenously Oxygen (2 liters per minute) was administration for 24 hours postoperatively in all cases

Results were analysed using the Student's

t test, the Mann Whitney test and chi-square tests where appropriate and values of p < 0.05 were considered statistically significant

3.Research ethics

All study procedures complied with the ethical principles of biomedical research Written informed consent was obtained from patients All patient information was kept confi-dential and secure

III RESULTS

A total of 90 patients were involved in this study, with 45 patients receiving morphine (Group M) and 45 patients receiving fentanyl (Group F) The demographic, surgical, and anesthetic characteristics of all patients by group are shown in Table 1 There were no statistically significant differences between the two groups in terms of age, sex, weight, ASA physical classification, intraoperative an-esthetic sum, size of incision during surgery,

or surgical time (table 1)

Table 1 The demographic, surgical and anesthetic characteristics of

the participants in each group

Operating time (minutes)ª 103.8 ± 23.7 109.2 ± 24.5 Size of incision (cm)ª 21.3 ± 4.2 22.6 ± 3.8

Intraoperative fentanyl (mcg)ª 365.2 ± 65.4 373.1 ± 59.2 Intraoperative propofol (mg)ª 556.5 ± 98.6 563 ± 102.2

Groups

ª Mean value ± SD

0

2

4

6

8

Ext H0 H1 H2 H3 H6 H9 H12 H18 H24

Group F Group M

Time (hour)

VAS at rest

2 3 4 5 6 7

Ext H0 H1 H2 H3 H6 H9 H12 H18 H24

Group F Group M

Time (hour)

VAS at coughing

p* <0.05

Figure 1 VAS score during IV-PCA use

Participants’ postoperative pain scores at rest and on active coughing are presented in Figure

1 Mean VAS scores at rest were significantly lower in Group F than in Group M at the twelfth, eighteenth, and twenty-fourth hour after surgery Mean VAS scores on active coughing were significantly lower in Group F than in Group M at all time points from the third hour to the twenty-fourth hour during IV - PCA use (p < 0.05)

70

75

80

85

90

95

100

Ext Ho H1 H2 H3 H6 H9 H12 H18 H24

Group F Group M

Heart rate (bpm)

Time (hour) 70

74 78 82 86 90 94 98

Ext Ho H1 H2 H3 H6 H9 H12 H18 H24

Time (hour)

MAP (mmHg)

Figure 2 Changes in mean heart rate and mean arterial blood pressure (MAP)

The average values of heart rate and MAP at all time points evaluated in each group remained within normal limits There were no statistically significant differences between the two groups in terms of heart rate or MAP (Figure 2)

Table 2 Adverse events while using the IV-PCA and patient satisfaction with the IV - PCA

Adverse Events

Degree of satisfaction (%)

Very satisfied

Satisfied

51.1 44.4

71.1 26.7 < 0.05

Groups

PONV and pruritus were the two most

common adverse effects during IV - PCA use

Group M experienced higher rate of PONV

and pruritus than Group F (Table 2) The large

majority of patients (97.7%) from the two

groups were satisfied with the PCA - based

method of pain relief There was a statistically

significant higher incidence of patients in

Group F reporting feeling “very satisfied” with

their IV - PCA, as compared to the number of

patients reporting that they were "very

satis-fied" in Group M (p < 0.05) Three patients

were dissatisfied with analgesia In which, two

patients experienced vomiting (1 in group M, 1

in group F), and one patient in Group M had severe pain on nighttime awakening

Six patients from Group F and five patients from Group M showed scores of 4 on the Ramsay scale on the first day after surgery

No significant differences were found between groups, and no cases of Ramsay 5 (deep se-dation) or 6 (coma) were seen Respiratory depression, as indicated by a decrease in a patient's respiratory rate to less than 8 breaths per minute, was not observed among any pa-tients using the IV - PCA Oxygen saturation

was maintained at more than 92% among all

participants No hypotension was observed

among any participants in either group

IV DISCUSSION

Optimal pain management requires a

reasonable balance of adequate analgesia

and minimal adverse effects The selection of

the opioid to use for acute postoperative pain

management has not always been based on

the most up-to-date scientific evidence

Moreover, morphine has become the drug of

choice used for IV - PCAs because of its low

cost Recently, however, fentanyl has

emerged as a potentially more appropriate

opioid to use in IV - PCAs This study was

conducted to further clarify the role of fentanyl

in IV - PCA use [1; 4; 10]

Table 1 showed no statistically significant

differences in patients, anesthesia levels, or

surgery-related characteristics among

partici-pants in Group F and Group M These

charac-teristics may affect the severity and duration of

postoperative pain, analgesic consumption, as

well as the ability of tolerance to opioid-related

adverse effects The homogeneity of the two

groups in terms of these characteristics makes

the comparison between these groups more

accurate and objective

The present study indicates that an IV

-PCA for postoperative analgesia is more

effec-tive with fentanyl than with morphine Lower

pain scores both at rest (at the twelfth,

eight-eenth, and twenty-fourth hours after surgery)

and on active coughing (at time points from

the third hour on) were observed in patients

receiving the fentanyl IV - PCA when

compared to patients receiving the morphine IV

-PCA after open gastrectomy (Figure 1) These

results are consistent with what Hutchison et

al (2006) found in orthopedic patients In their study, they found that the median VAS on post -operative days one and two were significantly lower in fentanyl IV - PCA group compared to the morphine IV - PCA group [8] Stavropoulou

et al (2008) compared fentanyl and morphine

in patients who had just had major abdominal surgery and found that the patients in the fen-tanyl group had significantly improved pain relief [9] However, of note, Howell et al found

no differences in efficacy among the two anal-gesics [11]

In the present study, fentanyl may have provided the superior analgesic effects because of its pharmacological profile The onset of analgesic effects is more rapid with fentanyl than with morphine Since fentanyl shows 160 - fold greater liposolubility than morphine, penetration into tissues and elicitation of pain relief is much quicker Analgesic effects of bolus administration can thus be rapidly achieved for patients when they feel pain In addition, the analgesic potency of fentanyl is 50 - 100 times greater than that of morphine [7]

Group F using the fentanyl IV - PCA saw significantly lower rates of PONV and pruritus than Group M using the morphine IV - PCA Furthermore, the number of patients that were very satisfied with their pain relief was higher

in Group F than in Group M (Table 2) The incidence of patients with Ramsay 4 was comparable between Groups F and M (13.3% and 11.1 %, respectively, p > 0.05) at the time

of the twenty-fourth hour of measurement Hutchison et al (2006) found a higher rate of sedation, nausea/vomiting, and pruritus in the group of patients using morphine as the

IV-PCA in their study, as compared with the

group using fentanyl as the IV - PCA [8]

Stavropoulou et al found that the rates of

nausea and pruritus were also significantly

lower than among patients using fentanyl as

compared to those using morphine [9]

Patients on fentanyl and morphine

IV-PCAs saw similar heart rates, blood pressure

readings, and SpO2 measurements (figure 2)

No cases of respiratory arrest were observed

in either group These results are consistent

with the previous studies comparing fentanyl

to morphine [3; 9; 12]

V CONCLUSION

In summary, we found that an IV - PCA

using fentanyl had better analgesic efficacy,

led to higher patient satisfaction, and caused

fewer incidences of PONV and pruritus,

compared with using a morphine IV - PCA

Patients on both fentanyl and morphine

IV - PCAs had normal pulmonary and

cardiovascular vital signs throughout the twenty

-four hours that their use was monitored

Acknowledgement

We would like to express our sincere

thanks to the doctors and medical staff at the

Anesthesia and Critical Care Department in

the Bach Mai Hospital for their support during

this study

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