EVALUATION OF ANALGESIC EFFECT OF THE KETAMINE
ON PAIN INJECTION OF PROPOFOL IN PATIENTS
UNDERGOING GENERAL ANESTHESIA
Reza Akhondzadeh1* ,NooshinRunassi2
1
Assistant Professor, Department of Anesthesiology, Ahvaz Jundishapur University of
Medical Science, Ahvaz, Iran
2
Anaesthesiology , Department of Anesthesiology, Ahvaz Jundishapur University of
Medical Science, Ahvaz, Iran
Corresponding Author
*Reza Akhondzadeh,
Assistant Professor of Anesthesiology, Pain Research CenterEmamkhomaini
Hospital, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Post Code:
6193673166, BOX: 1519 ,E-mail: rezaakh@hotmail.com,tel:0098916113520100986113738045
ABSTRACT
Introduction: The most commonly used Intravenousanesthetic is propofol, an
alkylphenol which provides rapid onset and offset, but its intravenous injection pain
is one of the most important complications. Many methods used to reduce this pain,
have been examined up to now. In this study, effect of Ketamine on reducing the pain
during Propofolinjection,onset, duration and prevalence of this effect was surveyed.
Methods:This study is a randomized double- blinded clinical trial on 44 patients
undergoing elective surgery.The patients were randomly divided into two groups of
22 persons. Pain severity of Propofolinjection, during injection and recovery ٬sixand 12
hours after injection were measured by Verbal Rating Scale system (VRS)
.onset,duration and prevalence of this effect were measured ٫then the data were
analyzed by SPSS software (version.16) and chi square test and Tukey’s test.
Results: .Reducing pain injection of propofol by ketamine is more effective than
normal saline in all times, but the difference is significant statistically only in times of
injection and recovery.Ketamin̓s analgesic effect was initiated at recovery time and
had been increasd over time.Up to 12 hour after injection,the analgesic effect of
ketamine had been continued.
Conclusion: Ketamine is more effective than normal saline in reducing the pain due to
Propofol injectionin all times and Ketamin̓ s analgesic effect first appeared at recovery
time.
Keywords: Analgesia, General Anesthesia, Ketamine, Pain, Propofol
INTRODUCTION
Propofol is the most frequently use Intravenous( IV) anesthetic today.Among its
benefits is rapid and complete awake after anaesthesia and the least nausea and
vomiting in recovery.Induction of anesthesia with propofol is associated with several
side effects, including pain on injection,hypotension, and, rarely, thrombophlebitis 1.
Pain during injection is one of the most unwilling characteristic of using this drug 2.
Pain prevalence during Propofol injection in adults was mentioned from 28 to 91% 3.
And the severity of this pain according to VAS pain (Visual Analog Scale for pain)was
5/6±2/3, which shows severe pain 4.
Pain during injection causes stress for the patient and interferes with good and proper
anesthesia. It is assumed that a direct stimulus may cause rapid pain feeling or an
indirect effect depending on mediator release,causes pain generation with a delay start5.
a
Delayed pain (after 10 to 20 seconds) , is caused by an indirect effect on endothelium
(due to Kinogenes release ) 6 . Lipid solvent causes increase an activity in Kallikrein –
Kinin System in plasma, which then leads to bradykin production. This interplay causes
peripheral vein dilation and permeability increases , and this is the reason to increase
Propofol aqua phase contact with vascular endothelium and free efferent nerve endings
between media and intima of the vascular wall ; and finally , causing pain7.
Overall,Propofol is one of the drugs which causes stimulation of the skin, mucosa and
the internal wall of the veins8. Until now, many methods to reduce the incidence and
pain severity during Propofol injection were suggested and surveyed. Among these
methods,using different emulsion usage of Propofol 9,10and different drugs like
lidocaine 11 Thiopental 12, narcotic and Granisetron 13can be named. Also methods like
slow injection 14, warming up andcooling down 15, and diluting of the drug 16 are used
to reduce the injection pain.
Ketamine is one of the non-barbiturate anaesthesic drugs and belongs to the
Phencyclidine group. Good Analgesiceffect, low respiratory depression, maintenance
of airway reflexes and bronchial dilation and low price are the Ketamine’s advantages
compared to other anesthesia drugs.But one of the limitations of the Ketamine is the
hemodynamic changes1.
using available and efficient drug methods that can be beneficial effects on anaesthesia
induction, led to pose the issue of surveying Ketamineeffect on the pain of thePropofol
injection site and to find onset,duration and prevalence of this effect.
METHODS
This study is a randomized double- blinded clinical trial conducted on 44 patients
undergoing elective surgerywith ASA class I and II in Ahvaz Imam Khomeini Hospital
in the year 2012. The study was approved by Ahvaz Jundishapur University of Medical
sciences Ethical Committee,A consent form was received from the patients prior to the
study. , and all participants were signed the informed consent prior to enrollment. The
patients were randomly divided into two groups of 22 persons. After the patient
preparation and his transmission into the operative room, first Intravenous (IV)
20Gcannula was fix on the cubital forearmand before starting the anesthesia, the
patients were being monitored:Electrokardiogram(EKG),pulse oximetry and
Noninvasive boodpersure( NIBP) .
Inclusion Criteria: patients candidate Electivesurgery , general anesthesia, age 1850,ASA classI,II,Body Mass Index(BMI) of 18-50 were include.
Exclusion Criteria: patients under age 18 or over age 50, ASA, III, to V class, Obese
Class II (BMI>35), history of Liver dysfunction, , hypersensitivity or allergy to
Poropofol,AnyContandication to KetaminAdmition,Adiction to Opioide were
Excluded.
Groups one, two, Injected 2 cc Normal saline 0.9%, 0.1 mg/kg intravenous
Ketaminerespectively.The surveyed drugs included Ketamine manufactured by
RotexmedicaCompany, Germany, and Propofolmanufactured by Claris Company,
India.
After about 45 seconds injection of these drugs , one – fourth of the Propofol induction
dose (1.5 mg/kg) was injected to each patient with the speed of 1 ml per second, and
everyfive seconds, besides considering the patient’s face, the patient were asked about
the pain during injection , using VRS method(Verbal Rating Scale).
In VRS system, each number shows a clinical condition. Zero, one, two, and three
show the no-pain condition , feeling pain or low discomfort, moderate pain, and severe
b
pain with change in facial expression, pulling back the hand,forearm or both,
respectively.
Sedation and the disability of the verbal communication was the factor to exclude the
patient from the study. After asking the patient , the rest dose of Propofol was injected
and immediately after loss of consciousness , 0.5 mg/kg of the Atracurium drug was
injected slowly and the patient was intubated . Maintenance of anesthesia with
Isoflurane 1-2% and N2O 50% -O2 50%. Finally, after endigthe surgery , the patients
were reversed ( neostigmine 0.05 mg /kg , atropine 0.02 mg/kg) and they were
extubated and transmitted to the recovery . Also , the patient’s pain score was asked
and registered according to VRS in the recovery , 6 and 12 hours after injection
time.
RESULTS AND DISCUSSION
In this survey, there were 20 women and 24 men . Sexual ratio of men to women in
ketamin group was higher (1.4), and in the Normal saline group was the lower(0.83).
In this study, the lower average age, was in the group taking Ketamine (36.86 ± 15/75
years), and the higher average age was in the group Normal salin or the control group
(42/32 ± 13.67). Considering the present age differences among different therapeutic
groups, statistically, there was not a significant difference about the age of the groups.
According to VRS system, no patient of the Ketamine and Normal-Saline groups had
score 0 (no pain) during Propofol injection.Also 19 patients out of 22 patients (86%) in
the group taking Normal saline, during Propofol injection, described the pain severity
high (rankthree) according to VRS system.(table 1)
All patients taking Ketamine, had experienced pain with different severities during
injection.Onset of analgesic effect of ketamine was initiated at recovery time in 54 %
patients in ketamine group.
Six hours after injection , no patient participating in the study , felt pain with moderate
and high severity (ranks two and three) . Meanwhile, 18 patients of ketamine
group(81%) had no pain,and the others(4 patints) experienced low pain.On the other
hand,in the saline group, 12 patients(54%),had no pain,and the rest of patiens had low
pain.
12 hours after injection, only one patient from the Saline group , makes acomplaint
about a low pain (rank one) at the site of the Propofol injection, and another 65
patients, felt no pain at the injection site. After 12 hours,there was no significant
difference among the twosurveyed drugs according to their ability to generate
analgesia.(Fig 1)
Ketamin̓s analgesic effect was initiated at recovery time and had been increasd over
time.Up to 12 hour after injection,the analgesic effect of ketamine had been continued.
The results showed that Ketamine, similar to normal saline,had no analgesic effect on
pain during injection of propofol,but at the recoverytime and 6 hours after
injection,ketamine is more effective to reduce painexperience than Normal Saline.
The time needed for Ketamine effect, according to its easy transmission through the
blood - brain barrier, is about 30 seconds to one minute which is so rapid. But, even
during the injectionof the drug with the interval of 45 seconds,there was no analgesic
effect of Ketamine, which this issue is considerable.
In a survey conducted by anaesthesia and pain control department in South Korea in
Seoul in the year 2006 by Koo et al., researchers stated that if before prescription of
Propofol,100 µg/kg Ketamine is injected, the incidence and pain severity of
Propofol injection will be reduced without huge hemodynamic complication 17.
c
Results from Safavie et al.’s research 18was similar to our study from the viewpoint of
Ketamine prominence compared to Normal Saline in reducing pain during Propofol
injection, and the present difference is statistically significant.
In a study, SedighiNezhad , stated that in spite of the pain reduction due to Propofol
intravenous injection by threestudied Pre-medication (Alfentanil, Ketamine and
Magnesium sulfate), no priority can be considered for any of them ,while pain severity
during injection for all these three drugs is less than Normal Saline 19.
Also in another study registered in the Internet Journal of Anesthesiology in the year
2009, results showed that Pre-treatment with 0.2 mg/kg intravenous Ketamine is useful
in reducing the pain of Propofol injection 20.
Overall,to relieve pain caused by Propofol injection, using Pre-medication, one should
pay attention to the time needed to start and for the maximum effect of the Premedication and also its dose in order to reduce the possible errors in deduction. Also
the patient’s conditions and situations are among important factors in choosing a proper
Pre-medication.
CONCLUSION
This study showed that Ketamine is more effective in reducing the pain of the
Propofol injection site than normal saline.It̓s analgesic effect(score 0),first appeared at
recovery time,and had been increasd over time.
ACKNOWLEDGMENTS
This paper is issued from thesis of NooshinRunassi,. At last, we appreciate all the
persons
helping
us
in
performingparticularlyPainResearchCenterofAhvazJundishapurUniversityMedicalScie
ncesforfinancialsupport.
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Table1: Prevalence of patients in both groups via VRS
Summary
0
7
12
25
44
N/S
gr.
0
0
3
19
22
e
Ketamine gr
VRS rank
0
7
9
6
22
0
1
2
3
Summary
f