CHAPTER I

INTRODUCTION

1.1 BACKGROUND

Pain is a subjective feeling or experience that involves sensory, emotional

and bad behavior are associated with tissue damage or potential damage to the

tissue. If it is not treated, it would have a negative impact on postoperative

sufferers such as anxiety (sleeping disturbances), immunosuppression,

hyperglycemia, hemodynamic changes (hypertension, tachycardia), decreased

breath movements that causes inability to cough, be able to facilitate the

occurrence of atelectase, a mobilization fear will increase the risk of

thromboembolic complications, and increase catecholamine discharge which

causes increased vascular resistance, extension catabolic phase, decreasing

blood flow to the inferior extremity and decreasing blood circulation to

splanchnicus. The above conditions will result a slow healing, impaired

mobilization, risk factors for chronic pain, increased length of hospitalization

and it will increase the cost of treatment. (Morgan, 2013) (Rawal, 2008)

(Stoelting, 2006)

Spinal anesthesia is the local injection of anesthetic drugs into the

intrathecal space which results analgesia. Giving a local anesthetic anesthesia

into the intrathecal space or subarachnoid space in the lumbar region between

the vertebra L2-3, L3-4, L4-5, to produce rapid onset of anesthesia with a high

degree of success. Although this technique is simple, with anatomical knowledge,

the physiological effects of spinal anesthesia and the factors which influence

the distribution of local anesthetics in intrathecal space and complications of

spinal anesthesia will optimize the success of spinal anesthesia blocks.

Spinal anesthesia is produced by the injection of a local anesthetic

solution into the lumbar subarachnoid space. Local anesthetic solution is

inserted into the lumbar cerebrospinal fluid, working on the superficial layer of

the spinal cord, but the main workplace is preganglionic fibers, because it leaves

the spinal cord in the anterior rami. Because preganglionic sympathetic nervous

of system fibers are blocked by inadequate concentrations of local anesthetics

to affect sensory and motor fibers, the level of sympathetic nervous system

denervation during spinal anesthesia extends about two cephalad spinal

segments from the level of sensory anesthesia. For the same statement, the

level of motor anesthesia averages two segments under sensory anesthesia.

Every patient who has a high trauma (pressure, temperature, chemistry)

or post-surgery must be treated with perfect pain, because the impact of the

pain itself will lead to a metabolic stress response (MSR) which will affect all

body systems and aggravate the patient's condition. It will harm the patient due

to change in the patient's own physiology and psychology. Surgical pain

undergoes at least two changes, first due to the surgery itself which causes

nociceptive stimulation and the second after the surgical process occurs the

inflammatory response in the area around the operation, in which release of

chemicals (prostaglandins, histamine, serotonin, bradykinin, substance P and

lecotreine ) by damaged tissue and inflammatory cells. These chemicals are

released which contribute to the process of transduction of pain.

The American Society of Anesthesiologists (ASA) states that multimodal

analgesia is the key to treating postoperative pain. Good pain management will

increase the end result of surgery by reducing morbidity and speeding up

recovery time. Multimodal analgesia has been shown to reduce postoperative

stress, reduce pain in patients with comorbidities related to breathing, heart

disease, thrombotic complications, nausea, vomiting, ileus, increased catabolism,

cognitive dysfunction, facilitate recovery by accelerating nutrition, mobilization,

and also reduce hospitalization.

In Tanra's research, 2014, it was concluded that magnesium sulfate or

MgSO4 is an antagonist of N-methyl-D-aspartate (NMDA) receptors and

calcium channel blockers (Cachannel blockers). As an NMDA receptor

antagonist, magnesium sulfate works to inhibit central nerve sensitization due to

peripheral stimulation and eliminates hypersensitivity reactions, magnesium

sulfate has been shown to have antinociceptive effects through calcium channel

inhibition (Tanra AH, 2005).

In a research which conducted by Dhani et al in 2013 randomized,

controlled, double-blind aims to assess the effect of intravenous magnesium

sulfate bolus on visual analog scale (VAS) values and the number of pethidine

analgesic requirements in 30 female patients with ASA I-II physical status, age

18-60 years old, who will undergo gynecological abdominal elective surgery under

general anesthesia in the central operating room of the Dr. Hasan Sadikin

Bandung in June-September 2013. The research subjects were divided into two

groups which will get bolus and maintenance of intravenous MgSO4 (group M) or

0.9% NaCl (group S). The results showed that the VAS value and the amount of

petidine analgesic given to M group were statistically lower compared to group S

(p <0.05). The conclusions of the study were perioperative intravenous bolus

magnesium sulphate able to show VAS values when lower postoperative

mobilization and reduce the need for pethidine analgesics in patients after

gynecological abdominal surgery (Dhani B, et al, 2013).

In a research which conducted by Hengki et al, 2014, the double blind

block clinical trial method. Thirty-six subjects aged 21–55 years were allocated

to group A who were given intravenous 15 minutes of MgSO4 30 mg / kg,

continued 15 mg / kg / hr until the end of surgery and B group was given 0.9%

NaCl with the same volume undergoing surgery. major in Sanglah Hospital

Denpasar in June-August 2014. The results of the research were analyzed by

Mann-Whitney Test. Visual analog scale (VAS) being silent and moving in 4th and

8th hours of the Mg group were significantly different (p <0.05). The

difference in postoperative morphine consumption at the 4th, 8th, and 24th

hours was significantly different (p <0.05). The conclusion of this research is

that intravenous MgSO4 administration during surgery improves the effect of

analgesia and decreases postoperative morphine requirements (Hengki I, et al,

2014).

In the Atiyat B research, Cloub, 2009 Patients post abdominal surgery

and thoracotomy who received multimodal pain therapy were shown to

experience smaller metabolic and hormonal stress, shorter extubation time,

lower pain score, and faster recovery time. Multimodal pain therapy is done by

giving opioids as the main analgesic added with other analgesic drugs (eg

paracetamol, cyclooxygenase inhibitors, or nonsteroidal anti-inflammatory

drugs) and classes of coanalgesia drugs (clonidine and N-methyl-D-aspartate

(NMDA) receptor antagonists, eg ketamine or MgSO4 (magnesium sulfate) The

use of combination therapy can strengthen the opioid class analgesic potential,

reduce dosage requirements, tolerance and opioid side effects, and accelerate

patient recovery (Atiyat B, Cloub et al, 2009).

Lysakowsky's reserach in 2017 showed that there was a decrease in

postoperative magnesium but postoperative hypomagnesaemia mechanism was

not known with certainty, it was thought to be related to a decrease in albumin

levels in the blood so that the protein and magnesium bonds also decreased. The

decreased protein levels and albumin are closely related to the amount of fluid

given. The incidence of hypomagnesaemia increased from 19.2% at preoperative

to 71% immediately after surgery, and it will decrease to 65.6% after 24 hours
later. Decreased magnesium levels in the blood below the physiological threshold

can increase the responsiveness of N-methyl-D-aspartate (NMDA) receptors

(Lysakowsky c, 2007).

In the 2013 research, it was found that morphine consumption in 24

hours postoperatively in the lower MgSO4 group was 5.28 mg compared to the

NaCl group. The results of this study are in line with the research conducted by

Hwang et al. 10 and Pastore et al. 12 research using 50 mg / kgBg of intravenous

bolus followed by 15 mg / kg / hour of total hip replacement surgery by using

spinal anesthesia can reduce morphine requirements. postoperatively with a

lower pain score. The study conducted by Dabbagh et al. 5 in lower extremity

orthopedic surgery showed that the administration of 8 mg / kg of MgSO4 until

the end of the surgery showed a pain scale and lower morphine requirements

compared to the control group (Bernards, 2013).

From the background above, the researchers wanted to know whether the

administration of Magnesium Sulfate 30 mg / kgBB mg intravenously as

preemptive analgesia could further reduce the value of postoperative VAS

compared with ketorolac 30 mg intravenously.

1.2 Problem Formulation

Are differences in VAS and duration of analgesia on magnesium sulfate

with intravenous ketorolac in postoperative patients with spinal anesthesia.

1.3 Hypothesis

There were differences in VAS and duration of analgesics on the

administration of magnesium sulfate with intravenous ketorolac in postoperative

patients with spinal anesthesia.

1.4 Research Objectives

1.4.1 General Purpose

To determine the comparison of VAS and anlagetic duration on

intravenous use of magnesium sulfate with intravenous ketorolac in treating

postoperative pain in spinal anesthesia patients

1.4.2 Special Purpose

1. To get the benefits of giving magnesium sulfate to overcome pain in

postoperative spinal anesthesia patients

2. To get the benefits of giving Ketorolac to treat pain in postoperative

spinal patients with anesthesia

3. To get a comparison of the value of VAS on the administration of

Magnesium Sulfate with ketorolac

1.5 Benefits of Research

1.5.1 Academic Benefits

The results of this research are expected to be used as additional

reference sources in further research on efforts to treat pain in surgery

1.5.2 Practical Benefits

The results of this study are expected to be used as a basis for

perioperative pain management in the following circumstances:

a) As data for further research regarding the use of 20% magnesium

sulfate to treat pain compared to other perioperative intravenous

ketorolac.

b) As data for 20% magnesium sulfate dose compared with ketorolac in

treating postoperative pain.

1.5.3 Benefits of Community Services

a) Obtain the condition of patients with mild pain at postoperative time

with administration of 20% magnesium sulfate and Bupivacain compared with

intravenous ketorolac

CHAPTER 3

RESEARCH METHODS

3.1. Design

This research used a double blind randomized clinical trial method to

determine the comparison of Visual Analogue Scale from administration of 20%

Magnesium sulfate 30 mg / kgBW with intravenous Ketorolac as a postoperative

multimodal analgesia with spinal anesthesia.

3.2. Place and Time

A. Place

General Central Hospital of H. Adam Malik Medan.

B. Time

The research was conducted in May to June 2018.

3.3. Population and Samples

a Population

The population was all patients who underwent elective surgery with spinal

anesthesia in addition to Cesarean Sectio patients at General Central Hospital

of H. Adam Malik Medan,

b. Sample

Taken from the population that fulfills the inclusion and exclusion criteria who

will undergo elective surgery with spinal anesthesia by using hyperbaric

bupivacaine 0.5% 15 mg.

After being calculated statistically, the entire sample are divided

randomly into 2 groups. Group A received 20% Magnesium sulfate 30 mg / kg

intravenously and group B received Ketorolac 30 mg / kg intravenously.

3.4. Criteria for inclusion and exclusion

a Inclusion Criteria

1. Willing to participate in research

2. Age 18-60 years.

3. PS ASA 1-2.

4. Pre operating VAS 0-1

5. Ideal body weight according to BMI (18,5-24,9)

b. Exclusion Criteria

1. Patients with contraindications to spinal anesthesia.

2. Patients who have a history of hypersensitivity to 20% Magnesium sulfate and

Ketorolac drugs.

3. Patients with impaired kidney function.

4. Patients with a history of taking pain relievers 24 hours earlier.

c. Test Break Criteria

1. An allergic reaction occurs after administration of the drug under study.

2. The spinal is failed.

3. Emergency operations occur, such as shock, anaphylactic reactions, and

respiratory disorders.
3.5. Sample Estimation

The sample is the research population fulfilling the inclusion and exclusion

criteria. After being calculated statistically, all samples are divided into 2

groups, namely:

a. A Group: receiving 20% Magnesium sulfate Intravenously 30 mg / kg

intravenously after spinal administration followed by 20% magnesium sulfate

drip with sisinge pump at a dose of 15 mg / kgBB.

b. B Group: receiving Ketorolac 30 mg intravenously after spinal anesthesia

followed by drip ketorolac with siringe pump at a dose of 30 mg.

The estimated number of samples is obtained by using the test formula:

n1  n2 
Z (1 / 2 ) 2 P (1  P )  Z (1  ) P1 (1  P1 )  P2 (1  P2 ) 
2

P1  P2 2
Information:

n = minimum sample size

Z (1-α / 2) = standard deviation alpha for α = 0.05 then the normal default

value is 1.96

Z (1-β) = alpha standard deviation for β = 0.10 then the default value is

normally 1.2282

P1 = Estimated proportion of ketorolac effectiveness to relieve pain

by = 0.50 (50%) (formula)

P2 = The average estimated proportion of the effectiveness of MgSo4

eliminates pain by = 0.85 (85%)

P1 - P2 = different proportions meaningful set at = 0.35

Then the minimum sample for each treatment group is 36 people

From the calculation of the number of samples for the research taken

the calculation of the total sample size n1 = n2 = 36; plus 5-10% for the dropout
rate of 2 people. So the total number of samples needed in this research is at

least 80 people.

3.6.Informed Consent

After obtaining approval from the USU Medical Faculty Ethics Committee

and the Haji Adam Malik General Hospital ethics committee, the patient

received an explanation of the procedure to be followed and stated in writing

his readiness on the informed consent sheet.

3. 7 TOOLS, MATERIALS AND HOW TO WORK

3.7.1 Tools

1. 18G size intravenous catheter. (Terumo)

2. Infusion set (Terumo)

3. Quincke size 25G spinal needle (spinocan®, B-Braun).

4. Needle for pinprick test, the mandrain of the spinal needle.

5. Syringe / syringe 3 ml, 5 ml, 10 ml, 20 ml, and 50 ml.

6. GE Dash 2000TMPatient Monitor is an automatic non-invasive monitor

(blood pressure, pulse frequency, ECG, and oxygen saturation).

7. Sterile tools for spinal anesthesia

8. Foley (Rusch) urine catheter

9. Laryngoscope set (macinthos) and face mask / adult size mask with

Endotracheal tube (ETT) tools no: 6, 5, 7, and 7.5.

10. Adult size nasal cannula oxygen

11. Sterile gauze, sterile gloves.

12. Pillow
3.7.2. material

1. Liquid: 500 ml lactate ringer, 0.9% NaCl 500 ml.

2. Local Anesthetic Drugs: Hyperbaric 0.5% Bupivacain (Marcain® 0.5%

Hyperbaric, Astra Zeneca).

3. 20% Magnesium Sulphate (Otsu-MgSO4 20)

4. Ketorolac 30 mg

5. Materials for aseptic and antiseptic action: betadine, 70% alcohol

6. Ondansetron (Vometraz®)

7. Emergency medications: 5 mg / ml of ephedrine prepared, sulfas

atropine 0.5 mg prepared, epinephrine, aminophylline and dexamethasone

3.7.3 How it works

a. This research first received approval from the research ethics

committee in the field of health, Faculty of Medicine, University of North

Sumatra and Haji Adam Malik General Hospital Medan.

b. The researcher then conducted informed consent to the patient during

the pre-trial visit.

c. All samples will undergo surgery and comply with the inclusion criteria

and are asked to sign an agreement for participation in the study.

d. The patient is explained about the plan to give the drug for surgery

and spinal anesthesia and research procedures that use drugs that are

commonly used.

e. Randomization by trained volunteers, randomization was done using

block method, each block consists of 6 sequences. Then with the eyes closed

the pen is dropped over a random number. The number designated by the pen is

the initial number to determine the appropriate sequence. Then choose 6

numbers with 2 digits to the side of the first number until you get the number
of sequences that correspond to the size of the sample. Then the sequences

obtained are arranged sequentially according to the envelope number.

f. The drug was prepared with the help of volunteer I who had

randomized it (the researcher did not know the medication given). After

randomizing and preparing the medicine, (20% Magnesium sulfate and ketorolac

drugs are put into a syringe and one in siringe pump, then volunteer I gives

treatment to volunteer II to be given on the day of the research.

On the day of the research:

a This research was conducted under the supervision of an anesthetist

consultant on duty on that day.

b. Both groups underwent elective surgery preparation procedures.

c. After the patient arrives at the operating room waiting room, the

patient is re-examined by the researcher for identity, diagnosis, plan for

anesthesia, access to infusion.

d. Both groups are given an infusion of preload of lactate ringer fluid as

much as 10 ml / kg of fluid before spinal anesthesia was performed.

e. The patient is informed of the sense of pain described to the patient

before carrying out the operation with the prepared VAS numerical scale. Then

the VAS value, and the initial measurement of blood pressure, pulse frequency,

breathing frequency.

f. Before the patient enters the operating room, an anesthetic machine is

connected to an oxygen source. Also prepared is an endo tracheal intubation set

(ETT), injection emergency medication such as epinephrine, sulfas atropine,

ephedrine and dexamethasone.

g. After the patient enters the operating room, lying on his back, a

monitoring device is installed in the form of an ECG monitor, tensimeter, oxygen

saturation on the patient's body.

 h. After that, the patient is tilted to the lateral decubitus position for

spinal anesthesia with a 0.5 mg hyperbaric bupivacaine 15 mg after being

positioned supine or sloping position depending on the operating action, and given

2 L / minute oxygen nasal prong. Spinal anesthesia is performed by PPDS

anesthesia.

i. The block height is set as high as Thorakal 6 by performing a head up

position which is confirmed by the prick test pin.

j. Recording and observation of patients on vital signs (blood pressure,

heart rate, respiratory frequency) at T0 (2 hours after anesthesia), T1 (3

hours), T-2 (4 hours), T-3 (5 hours), T- 4 (6 hours), T-5 (7 hours), T-6 (8 hours),

T-7 (9 hours), and T-8 (10 Hours) after anesthesia is carried out. VAS score is

assessed when the room is post-surgery using a table VAS images are asked to

the patient by showing images that correspond to the pain perception felt by

the patient. This assessment was carried out directly by researchers and

volunteers III who were not involved in giving drugs to these patients at T0 (2

hours after anesthesia), T1 (3 hours), T-2 (4 hours), T-3 (5 hours), T-4 (6

hours), T-5 (7 hours), T-6 (8 hours), T-7 (9 hours), and T-8 (10 hours)

j. Side effects that occur after surgery are noted T0 (2 hours after

anesthesia), T1 (3 hours), T-2 (4 hours), T-3 (5 hours), T-4 (6 hours), T-5 (7

hours), T-6 (8 hours), T-7 (9 hours), and T-8 (10 hours) decreased physiological

reflexes, anuria, decreased frequency of breathing, allergic reactions, nausea

and vomiting other complaints that may occur, or even shortness of breath .

k. The research will be stopped when there is a total spinal block, a

warning of airway, heart, lung and brain emergency.

l. If the patient has an elevated spinal block exceeding th4 then the

patient will be given oxygen therapy by using a hood. Treatment of hypotension

due to spinal action, where systolic blood pressure <90 mmHg and MAP <60

mmHg, will be treated with administration of 10 mg of ephedrine and infusion of

RL 20 cc / kgBB resuscitation fluid for 30 minutes.

m. If the patient feels a total spinal or respiratory depression, the

patient will be given a breath assistance.

n. The length of surgery in minute will be calculated starting from the

operator to cut the skin until accomplish sewing / closing the skin.

o. Bromage Score is a criterion for assessing the patient's general

condition during treatment in the observation room.

Table 3.1. Bromage Score (Miller et al, 2015)

3.8. Identification of variable

3.8.1. Independent variable:

a Intravenous magnesium sulfate

b. Ketorolac intravenously

3.8.2. Dependent variable:

a VAS value

3.9. Management plan and analysis data

a The required data is collected, then the data is checked again about its

completeness before being tabulated and processed. Then the data is given a

coding to facilitate tabulation. The data is tabulated into the master table by
using Microsoft Office Excel Software. Data analysis includes descriptive

analysis and hypothesis testing by using the SPSS for Windows program.

b. Numerical data is displayed in mean values ± SD (standard deviation)

while categorical data are displayed in amounts (percentage).

c. Demographic data: Normality tests for numerical data were used by

the Fisher Exact Test, normality of categorical data using the chi-square test.

d. To analyze differences in changes in pain scores between the two

intervention groups, the Mann Whitney test was used.

e. To analyze the presence or absence of additional analgesic use and the

occurrence of side effects, chi square test was used.

f. A 95% confidence interval with p value <0.05 was considered

statistically significant.

3.10. Operational definition

In this research the variables studied were VAS and side effects after

administration of 20% magnesium sulfate and intravenous ketorolac.

• Magnesium (Mg) is the fourth most important cation in the body

(after phosphorus, calcium and potassium), and is the second most

important cation in the cell (after potassium). The release of

acetylcholine at the presynaptic depends on the action of magnesium.

Magnesium can provide analgesic effects through its work as an

antagonist of NMDA receptors. Magnesium can also cause systemic and

coronary vasodilation and can reduce reperfusion injury.

• Ketorolac or ketorolac trometamine is a non-steroidal anti-

inflammatory drug, which belongs to the heterocyclic acetic acid

derivative group in which the chemical structure is related to

indomethacin. Ketorolac shows a potent analgesic effect but only has

moderate anti-inflammatory activity if given intramuscularly or

 intravenously.

• Spinal anesthesia is an anesthetic procedure by giving local

anesthetic drugs to the subarachnoid space. This technique is quite effective

and easy to do. The most widely used local anesthetic drug is hyperbaric 0.5%

bupivacaine, because bupivacaine has a long period of sensory and motoric

blockade.

• Pain assessment is determined using Visual Analog Scale (VAS),

VAS is one assessment with a straight line of 10 cm, where the beginning of the

line (0) marks no pain and the end of the line (10) indicates severe pain. The

patient is asked to make the line mark to express the pain that is felt. This

assessment was carried out directly by researchers who were not involved in

drug administration in these patients.

• Additional analgesics (rescue analgetic) is an analgesic drug given

when VAS> 3, the drug given is injection of tramadol50 mg intravenously.

• Pain in post-bedahlower abdomen is divided into somatic pain and

visceral pain. The nature of this pain can be known by asking questions:

• Somatic pain: "Is the pain felt to come from the site of surgery, and is

the pain sharp?"

• Visceral pain: "Does the pain that is felt come from inside the

stomach, and is pain blunt and spread?"

• The side effects are an adverse or undesirable impact or effect

that arises as a result of a treatment or other intervention.

• Body mass index (BMI) is an estimate of human body shape based

on height and mass. BMI formula :

 BMI = Weight

Height

Underweight /

< 18,5 : malnutrisi

18,5 – 24,9 : Normal

25,0 – 29,9 : Overweight

> 30 : Obesity

3.11. Ethical issues

a. This research was carried out after obtaining permission from the

health research ethics commission of the Faculty of Medicine, University of

North Sumatra and Haji Adam Malik Central General Hospital Medan.

b. Patients were previously given an explanation of the purpose, benefits,

and risks and matters related to the study. Then asked to fill in the willingness

form to be an informed consent subject.

c. The taken action in this research was a common practice for patients

before anesthesia and the research process began, emergency devices were

prepared (oro / nasopharyngeal airway, ambu bag, oxygen source, laryngoscope,

endotracheal tube adult patient size, suction set) , monitor (pulse oxymetry,

blood pressure, ECG, heart rate), emergency medication (ephedrine, adrenaline,

sulfas atropine, lidocaine, aminophylline, dexamethasone).

d. If there was an emergency in the airway, heart, lung and brain during

anesthesia and the research process takes place, anticipation and treatment

were carried out according to the standard techniques, tools and medicines as

prepared in advance.
 Population

Inklusion Eksklusion

Sample

Randomisasion
A Group B Group

Before the patient enters the operating room the patient is given ringer lactate fluid 10cc /
kgBB to fulfill requirement volume in 30 in patient's reception room.
Spinal anesthesia with needles, Quincke 25 G, Position of LLD, Puncture, Lumbal 3-4,
hyperbaric Bupivacain medicine 0.5% 15 mg as much as 3 cc. The height of the block must
be parallel to Th 6.

20% MgSO4 at a dose of 30 mg / KgBB which has been
diluted with 0.9% NaCl to 20 cc with a 20 ml syringe is
given in 15 minutes after spinal anesthesia at rate 80 cc
per hour and continue with MgSO4 20% 15 mg / KgBB
which has been diluted with NaCL 0.9% to 50 cc in a 50
ml syringe with a rate 50 cc in a Syringe pump.
Ketorolac at a dose of 30 mg which has been diluted
with 0.9% NaCl to 20 cc with a 20 ml syringe is inserted
in 15 minutes after spinal anesthesia at rate of 80 cc per
hour and continue with ketorolac 30 mg diluted with
0.9% NaCL to 50 cc in 50 ml syringe with rate 50 cc in
the syringe pump.

Pain Scale Assessment using the VAS method

T0 (2 hours after anesthesia), T1 (1 hour after T0), T2 (2 hours after T0), T3 (3
hours after T0), T4 (4 hours after T0), T5 (5 hours after T0), T6 ( 6 hours after T0),
T7 (7 hours after T0), and T8 (8 hours after T0)

Data Tabulation

Image 3.1. Research Order