Equivalent Dose Of Analgesic (Equianalgesic Dose) Oxycodone With

Continuous Intravenous Morphine in Post- Long Bone Surgery With

General Anesthesia In RSUP H. Adam Malik Medan
Tarigan Franz J, Hanafie Achsanuddin, Arifin Hasanul, Wijaya Dadik Wahyu.
Department of Anesthesiology and Intensive Therapy, Faculty of Medicine Universitas Sumatera Utara,
Medan, North Sumatera, Indonesia

ABSTRACT: Background: Oxycodone and morphine are powerful analgesic drugs used for post-operative
pain management. There is no studies have been conducted to assess the dose equivalency between the two
drugs.
Objective: To get an equianalgesic dose of Oxycodone and Morphine
Methods: This study was using a double-blind randomized clinical trials, 48 samples, ages 21-60 years, PS
ASA I-II, which will get an elective orthopedic surgery using general anesthesia
techniques. Oxycodone (group A) : Morphine (group B) (Initial 5mg than continuous 1 mg/hour : initial dose
4mg than continuous 0,5 mg/hour).
Results: Average drug dose for group that takes morphine and oxycodone (3.90 ± 0.46 mg : 1.46 ±
0.51 mg). No significant difference between the average dose (p <0.05).
Conclusion: Equianalgesic dose in group Oxycodone and Morphine is 1.4 mg : 3.9mg

Keywords: Oxycodone, Morphine, Opiates, Visual Analogue Score, Equianalgesic Dose

miosis, sweating, and drowsiness. will eventually in-

1 INTRODUCTION
Pain is a subjective feeling or experience that in-
volves sensory, emotional and unpleasant behavior
associated with tissue damage or potential damage to
tissue. If pain is not addressed, it can have a nega-
tive impact on post-surgical patients such as anxiety
(sleep disturbance) immunosuppression, hyperglyce-
mia, hemodynamic changes (hypertension, tachycar-
dia), decreased breathing movements, causing
coughing, fears to move will increase the risk of
thromboembolic complications and increase cate-
cholamine release leading to increased vascular re-
sistance, prolong catabolic phase, decrease blood
flow to the inferior extremity and decreases the
blood circulation to the splanchnicus The most
commonly used opioid drug today is morphine be-
cause of its rapid spontaneous analgesia and also its
duration of action. Opioid receptors are synthesized
and increase in the number of sensory nerves to both
central and peripheral, while endogenous opioids
binding to these receptors cause decreased neural fi-
bers' impaired stimulation.
Oxycodone is a receptor agonist of mu- and kap-
pa-opioid, structurally similar to codeine, but phar-
macodynamically similar to morphine. In addition to
having analgesia effects, oxycodone also causes an-
xiolysis, euphoria, calm feeling, and cough suppres-
sion, as well as respiratory depression, constipation,
crease the cost of treatment. (Morgan, 2013) (Rawal,
2008) (Stoelting, 2006)
Oxycodone in various preparations has a broad ef-
fect to be used as a therapeutic efficacy. Morphine is
an opioid used to treat severe pain and is used as a
reference to the work mekainsme of other opioid
drugs. Morphine should be used with caution against
people with renal failure because of its active me-
tabolites (morphine-6-glucoronide) that can cause
respiratory failure, (Misiolek, 2014)
2 METHODS
The design of this study used randomized controlled
and double-blinded clinical trials. To determine the
equivalence of analgesic dosage (equianalgesic
dose) oxycodone with continuous infusion morphine
in overcoming pain with VAS assessment after long
bone surgery under general anesthesia.
The study sample was a population that fulfilled
inclusion and exclusion criteria. This sample was di-
vided into 2 groups:
• Group A receives 5 cc intravenous continuous ox-
ycodone infusion with target VAS value ≤ 3.
• Group B receives intravenous continuous morphine
infusion with target values of VAS ≤3.
 Then the patient is separated by inclusion and ex-
clusion criteria
Inclusion Criteria:
1. Age 21-60 years old
2. Patients undergoing long bone surgery
3. Patients with ASA 1 and 2
4. Patients agree to participate in the study
Exclusion Criteria: Patients who have opioid an-
algesics prior to surgery
Drop Out Criteria: Cardiovascular and pulmonary
emergencies,There was an allergic reaction observed
after the use of the drugs.
After surgery, the patien’s extubated and the time
was recorded as T0, and VAS was assessed using
the VAS drawing table, then the patient assessed by
showing the scale corresponding to the perception of
pain felt by the patient. This assessment is done di-
rectly by researcher who are not involved in the ad-
ministration of drugs in these patients. Start time of
study where group A received continuous intrave-
nous oxycodone with initial bolus of 5 cc followed
by 1 cc / hour with target VAS value ≤ 3 for 24 h,
while group B received morphine intravenacontinu
with baseline 4 mg followed by 0.05 mg / kgbb / hr
then increased dose to 1 cc / hour with target VAS
value ≤ 3 for 24 hours.
This assessment is done directly by researcher
who are not involved in the administration of drugs
in these patients. The patients then be transferred to
the recovery room when the Aldrette Score value
was 10, then the assesment’s begun. Assessment of
the dose equivalency and the side effects of the
drug’s with the target vas ≤ 3 values, directly per-
formed by the researchers at 0 (T0), 1 (T1), 2 (T2) 3
(T3), 4 (T4), 6 (T5), 12 (T6) and 24 (T7) after sur-
gery ended.
The results of observational data in both groups
were statistically analyzed. After the data had been
collected, then the data was checked again on the
completeness before being tabulated and processed.
Then the data’ coded. Data is tabulated into master
tables using SPSS software. Numerical data is
shown in the mean + SD (standard deviation), while
the categorical data is displayed in the number (per-
centage).
Demographic data: Normal test of numerical data
used fisher exact test test, while for catagorical data
used chi-square test. The research hypothesis was
tested using Mann-Whitney test. The 95% confi-
dence interval with a value of p <0.05 was consid-
ered to be significantly significant.
Oxycodone’s taken 50 mg. then dissolved with 50
ml NaCl 0.9%, so every 1 ml of solution contains 1
mg oxycodone, connected to three way with exten-
tion tube, given by Syringe Pump, with initial ad-
ministration of 5 mg bolus and an increase of 1 mg /
hour (1ml) until the target VAS ≤ 3, then syringe’s
wrapped with paper.
Morphine was taken 25 mg then diluted with 50
ml 0.9% NaCl solution so that every 1 ml of the so-
lution contained 0.5 mg morphine, connected to a
three way extention tube, administered with Syringe
Pump, with initial administration of 4 mg and a dose
increase of 0.5 mg / hour (1ml) until the target value
VAS ≤ 3.These were wrapped with paper too.
Assessment of equivalent dosage and drug side ef-
fects with target vas ≤ 3 values were performed di-
rectly by the researchers at hour 0 (T0), 1 (T1), 2
(T2), 3 (T3), 4 (T4), 6 (T5), 12 (T6) and 24 (T7) af-
ter surgery ends.
After the necessary data had been collected, then
the data is checked again about the completeness be-
fore tabulated and processed. Then the data is coded.
Data is tabulated into master tables using SPSS
software.
3 RESULT
This study was followed by 48 patients with in-
clusion criteria, divided into two groups with the
same number, each consist of 24 people. Patients
aged 19-29 years in the morphine group were 12
people (50%), while in the oxycodone group were 7
people (29.2%). Patients aged 30-39 years in the
morphine group were 3 people (12.5%), while in the
oxycodone group were 2 people (8.3%). Patients
aged 40-49 years in the morphine group were 5 peo-
ple (20.8%), while in the oxycodone group were 6
people (25%) Patients aged 50-59 years in the mor-
phine group , 4 people (50%), while in the group
oxycodone as many as 9 people (37.5%). Based on
the age characteristics of the patients’d relative ho-
mogeneous data (p> 0.05).
From the statistical analysis results obtained
range of doses of oxycodone to achieve VAS ≤ 3 is
1 - 2 mg, with average time required 1.46 hours. The
morphine dose range achieving VAS ≤3 was 3-5 mg
with an average time of 2.13 hours. The average pa-
tient's body weight was 62.5 kg, then the average
dose of oxycodone was 0.02 s / d 0.04 mg / kgBB /
hr and Morphine’d between 0.02 s till 0.03 mg / kg.
It takes 1.4 mg of Oxycodone to obtain the same
analgesic effect in intravenous continuous infusion
3.9 mg morphine as the treatment of long bone sur-
gery pain at Haji Adam Malik General Hospital Me-
dan. The time required to achieve VAS ≤3 in the ox-
ycodone group is 87.6 minutes compared with the
morphine group 127.8 minutes.
4 DISCUSSON
This study assessed the dose of analgesic analge-
sic of oxycodone and intravenous continuous infu-
sion morphine in overcoming pain of post- long
bones surgery. This research is done because there
are differences of dose allocation from some existing
research / guidance. Research and guidelines for pre-
dose equation are limited to single dose and opioid
rotation, and no similar studies have been conducted
in Indonesia.
Inadequate pain management raises the Metabolic
Stress Response (MSR) which affects all body sys-
tems and aggravates the patient's condition. This will
hurt the patient as a result of physiological and psy-
chological changes such as cognitive (central)
changes, neurohumoral changes, neural plasticity
(kornu dorsalis) sympathadrenal activation, and neu-
roendocrine changes (Sommer, 2008), (Morgan,
2013).
Previous studies have suggested that although the
potential is ± 1.5 times greater than morphine, ox-
ycodone has the same onset, duration of action, and
effectiveness as analog analgesic dose (20mg ox-
ycodone = 30mg morphine). In addition, oxycodone
has a longer half-life and also has a high bioavaila-
bility. Oxycodone’s also has no "ceiling effect"
(when the dose’s increased but does not necessarily
increase the analgesic effect) (Benziger, 1997)
(Kalso, 2005).
The different results of this study is due to differ-
ences in the treatment of oxycodone and morphine.
This study used continuous infusion, whereas in oth-
er studies only use single bolus injection of oxyco-
done and morphine. In addition, in this study, the
purpose of the use of analgesic drugs is to achieve
VAS ≤3 while in other studies only assess the effec-
tiveness of oxycodone drug as substitution for opiate
analgesic. In the research Kalso (1991) did not do
VAS assessment, so the subjectivity of the study is
high.
time, any studies of opiate medications should as-
sess the side effects of certain opiate dose’s given.
5 REFERENCE
Choi Yoon-Ji, Park Sang-Wook, Kwon Hyun-Jung, dkk. Effi-
cacy of early intravenous bolus oxycodone or fentanyl in
emergence from general anaesthesia and postoperative an-
algesia following laparoscopic cholecystectomy: A random-
ized trial. Journal of International Medical Research. 2015:
43(6): 809-818.
Kim Nan-Seol, Kang Kyu Sik, Yoo Sin Hyeon, dkk. A Com-
parison Of Oxycodone And Fentanyl In Intravenous Pa-
tient-Controlled Analgesia After Laparoscopic Hysterecto-
my. Korean Journal Of Anesthesiology. 2014: 68(3): 261-
266.
Kokki H, Kokki M, Sjovall S. Oxycodone For The Treatment
Of Postoperative Pain. Expert Opin. Pharmacother. 2012:
13(7): 1045-1058.
Pain Assessment And Management Iniatitive (PAMI). Pain
Management And Dosing Guide. November 2016.
Park Joong-Ho, Lee Chiu, Shin Youngmin, dkk. Comparison
of oxycodone and fentanyl for postoperative patient-
controlled analgesia after laparoscopic gynecological
surgery. Korean Journal of Anesthesiology. 2015: 68(2):
153-158.

DIFFERENT DRUG DOSE RESPONSES

BASED ON DRUGS (mg)

4
3
2 3,90 mg

1 1,46 mg
0
Oxycodone Morphine

This study assessed the equivalence of analgesic

dose between continuous intravenous morphine and
oxycodone for treatment of pain in long bone sur-
gery with target VAS ≤ 3. The results of this study
were the equivalence of intravenous infusion dose
doses between the two drugs. This study did not as-
sess the incidence of adverse events occurring from
both drugs. Increased doses from the use of opiate
drugs increase the risk for adverse effects.. Next