Pharmacist Educational Intervention in Intravenous Patient Controlled Analgesia is Associated with Decreased Postoperative PainPharmacist Educational Intervention in Intravenous Patient Controlled Analgesia is Associated with Decreased Postoperative Pain

1. Pharmacist Educational Intervention in
Intravenous Patient-controlled Analgesia is
Associated with Decreased Postoperative
Pain
Under the guidance of :
Miss. C. Anamika, M. Pharmacy
Department of : pharmacology
Presented by:
Sameena khatoon(13AD1R0052)

2. CONTENTS
Introduction
Aim and objective
Literature review
Materials and
methods
Drug profile
Plan of work
Result
Discussion
Conclusion
Reference

3. INTRODUCTION
 Pain is a distressing feeling often caused by intense or damaging
stimuli, such as stubbing a toe, burning a finger, putting alcohol on
a cut. Because it is a complex, subjective phenomenon, defining
pain has been a challenge. The “International Association for the
Study of Pain’s” widely used definition states: "Pain is an
unpleasant sensory and emotional experience associated with actual
or potential tissue damage, or described in terms of such damage."
 CLASSIFICATIONS:
 Responding to the need for a more useful system for
describing chronic pain, the International Association for the Study
of Pain classified pain according to specific characteristics:
• Region of the body involved (e.g. abdomen, lower limbs),
• System whose dysfunction may be causing the pain (e.g., nervous,
gastrointestinal),
• Duration and pattern of occurrence,
• Intensity and time since onset, and
• Cause.

4.  However, this system has been criticized by Clifford J Woolf and
others as inadequate for guiding research and treatment. Woolf
suggests three classes of pain:
• Nociceptive pain,
• Inflammatory pain which is associated with tissue damage and the
infiltration of immune cells, and
• Pathological pain which is a disease state caused by damage to the
nervous system or by its abnormal function (e.g. fibromyalgia,
peripheral neuropathy, tension type headache, etc.).
 Chronic pain:
• Pain is usually transitory, lasting only until the noxious stimulus is
removed or the underlying damage or pathology has healed, but
some painful conditions, such as rheumatoid arthritis, peripheral
neuropathy, cancer and idiopathic pain, may persist for years. Pain
that lasts a long time is called chronic or persistent, and pain that
resolves quickly is called acute.

5.  Nociceptive
• Nociceptive pain is caused by stimulation of sensory nerve
fibers that respond to stimuli approaching or exceeding harmful
intensity (nociceptors), and may be classified according to the mode
of noxious stimulation. The most common categories are "thermal"
(e.g. heat or cold), "mechanical" (e.g. crushing, tearing, shearing,
etc.) and "chemical" (e.g. iodine in a cut or chemicals released
during inflammation). Nociceptive pain may also be divided into
"visceral", "deep somatic" and "superficial somatic" pain.
 Neuropathic pain
• Neuropathic pain is caused by damage or disease affecting any part of
the nervous system involved in bodily feelings (the somatosensory
system). Peripheral neuropathic pain is often described as "burning",
"tingling", "electrical", "stabbing", or "pins and needles".
 Phantom pain
• Phantom pain is pain felt in a part of the body that has been lost or
from which the brain no longer receives signals. It is a type of
neuropathic pain.

6.  Psychogenic pain
• Psychogenic pain, also called psychalgia or somatoform pain, is
pain caused, increased, or prolonged by mental, emotional, or
behavioral factors. Headache, back pain, and stomach pain are
sometimes diagnosed as psychogenic.
 Breakthrough pain
• Breakthrough pain is transitory acute pain that comes on suddenly
and is not alleviated by the patient's regular pain management. It is
common in cancer patients who often have background pain that is
generally well-controlled by medications, but who also sometimes
experience bouts of severe pain that from time to time "breaks
through" the medication. The characteristics of breakthrough cancer
pain vary from person to person and according to the cause.
Management of breakthrough pain can entail intensive use
of opioids, including fentanyl.
 Incident pain
• Incident pain is pain that arises as a result of activity, such as
movement of an arthritic joint, stretching a wound, etc.

7. Treating post-operative pain
• When choosing options for pain management after surgery,
healthcare professionals aim to use the most effective treatments
while keeping side effects to a minimum.
• These are some of the medicines and methods used for post-operative
pain control:
Opioids,
Non-steroidal anti-inflammatory drugs (NSAIDs),
Cyclooxygenase (COX)-2 inhibitors,
 Patient-controlled analgesia (PCA),
 Music therapy,
 Other kinds of anesthesia.

8. AIM AND OBJECTIVE
 This study was conducted to compare the
clinical efficacy and adverse effects of
multimodal analgesic regimen of
morphine and nalbuphine combined with
ketorolac using IV PCA, and to study the
effect of structured preoperative
educational program on analgesic
efficacy, incidence of adverse effects,
and patients` satisfaction.

9. LITERATURE REVIEW
Yi MS1, Kang H2, et al Relationship between the
incidence and risk factors of postoperative nausea and
vomiting in patients with intravenous patient-controlled
analgesia. This study aims to evaluate retrospectively the
electronic medical records of surgical patients who received
intravenous patient-controlled analgesia, to identify
potential relationships between the incidence and risk
factors of postoperative nausea and vomiting (PONV).
Records of 6773 adult patients who received fentanyl-based
intravenous patient-controlled analgesia after surgery at
Chung-Ang University Hospital between January 1, 2010
and December 31, 2015 were reviewed. Multiple logistic
regressions were used to identify risk factors for PONV.

10. As the incidence of PONV was 2.8%, 6.0%, 11.7%, 15.2%,
21.1%, 50.0%, and 100% for patients who had 0, 1, 2, 3, 4, 5,
and all these risk factors, respectively, risk-adapted,
multimodal, or combination therapy should be applied for
patients receiving general anesthesia.
Despite the use of antiemetic prophylaxis, 18.0% of patients
with intravenous patient-controlled analgesia had PONV. Use
of desflurane and nitrous oxide, in addition to risk factors
included in the Apfel score (female gender, nonsmoking
status, history of PONV or motion sickness, and use
of postoperative opioids) were identified as independent risk
factors.

11.  Komasawa N1 et al Effects of stylet use during tracheal
intubation on postoperative pharyngeal pain in
anesthetized patients: A prospective randomized
controlled trial. This study aimed to compare the impact of
stylet application for tracheal intubation
for postoperative pharyngeal pain or hoarseness in patients
undergoing elective surgery. Randomized clinical trial.
Tracheal intubation was performed by anesthesiologists with
stylet group (Stylet group; 20 patients) or without stylet group
(Control group; 20 patients). Incidence
of postoperative pharyngeal pain or hoarseness was assessed.
The incidence of postoperative pharyngeal pain was
significantly higher in the Stylet group (10/20 patients) than
in the Control group (2/20 patients) (P=0.013). The incidence
of hoarseness did not significantly differ between the Stylet
group (6/20 patients) and the Control group (3/20 patients)
(P=0.45).

12. MATERIALS AND METHODS
 Patient Selection:
• The study was, after full history taking, physical examination and
complete investigations, from those patients who were admitted for
different types of surgical procedures. The local ethics committees
approved the protocol, and informed consent was obtained from all
patients before study entry. Recruitment included patients with
physical status of an American Society of Anesthesiologists (ASA) I
and II, aged between 33 - 68 years. Exclusion criteria included:
history of allergy to the study drugs, contraindication to the study
drugs, refuse of using PCA as a pain management method, history of
hepatic, cardiopulmonary or renal disease, hemodynamic instability,
history of any chronic pain or drug history of analgesics,
administration of opioid in the last 4 hours, history of substance abuse
and psychiatric disorder.

13. Study Design:
• The study was prospective randomized double blinded, in which
patients were randomized either to receive morphine for
postoperative analgesia using PCA disposable infusion device (group
M), or receive PCA nalbuphine for postoperative analgesia (group
N). The study was double blinded using opaque sealed envelope;
both patients and the anesthesiologists managing postoperative pain
were blinded to knowledge of the group to which they belonged.
Patients were selected randomly from either morphine or nalbuphine
group to attend additional structured preoperative educational
program provided by the pharmacist. Accordingly, patients in
morphine group were randomly sub classified into either morphine
control group (group M1) or morphine intervention group (group
M2); both groups received the usual hospital routine care for pain
management. Similarly patients in nalbuphine group were randomly
sub classified into either nalbuphine control group (group N1) or
nalbuphine intervention group (group N2); both groups received the
usual hospital routine care for pain management.

14.  Postoperative Assessment:
Primary Outcomes:
The primary outcomes measured postoperatively were pain intensity
using Blood Pressure (BP), respiratory rate(RR), heart rate(HR).
Assessment was carried out at zero time and every 1/2 hour for the first 4
hours then every 2 hours till the end of the second postoperative day.
Secondary Outcomes:
The secondary outcomes included level of sedation using the Ramsey
Sedation Scale and total cumulative opioid doses. Incidences and
severity of adverse effects and patient satisfaction were assessed. Arterial
blood sample was taken at 0, 12, 14, 36, 48 postoperative hours to assess
partial pressure of carbon dioxide (PaCO2), and oxygen saturation.
 Statistical Analysis:
The SPSS version 22 software and Microsoft office excel 2010 were
used for statistical analysis. Results are presented as means ± standard
deviations (SD) for continuous data, median and range for ordinal data,
and as frequencies and percentages for categorical data.

15. DRUG PROFILE
CONTENTS MORPHINE NALBUPHINE KETOROLAC
CHEMICAL
FORMULA
C17H19NO3 C21H27NO4 C15H13NO3
MOLECULAR
WEIGHT
285.34 g/mol 357.443g/mol 255.273g/mol
STRUCTURE

16. BIOAVAILABILIT
Y
PROTIEN
BINDING
METABOLITES
HALF LIFE
DURATION OF
ACTION
EXCRETION
20-30% by
mouth,36-71% by
rectally, 100% by
Intravenous and
intra muscular
30-40%
Hepatic
2-3 hours
3-7 hours
Renal 90%, biliary
10%
76%-81% by
intramuscular
>50%
Hepatic
3-5 hours
5-10 hours
93% by renal
30-40% by
intramuscular
>50%
Hepatic
4-5 hours
7-9 hours
92% by renal, 6%
by faeces
MECHANISM OF
ACTION
It binds to mu
receptor and shows
its pharmacological
effect
It binds kappa
receptor and shows
its action
Inhibits the
prostaglandin
synthesis by
blocking of enzyme
cox
USES Analgesic Analgesic Analgesic,
antipyretic

17. PLAN OF WORK
Sponsor
Protocol
Study design
Patient enrollment
Subject inclusive and exclusive criteria

18. ICF collection
Randomisation
Drug treatment
End of treatment

19. Collection of case report form
Statistical analysis
Thesis writing

20. RESULTS
Patient Enrollment and Baseline Characteristics a total of 60 patients
were enrolled and screened to be eligible for the study according to
the inclusion and exclusion criteria.
1. The two drug groups were comparable with respect to sex, age,
weight, ASA, drug history and type of surgery.
PARAMETERS Group M Group N P value
SEX 9/13 12/11 0.45
AGE 51.4±11.6 47.6±11.7 0.36
WEIGHT 61.2±7.4 63.7±10.0 0.35
ASA physical status classification 12/10 12/11 0.61

21. `Type of surgery: abdominal/thoracic
Abdominal(N): HIPEC/ Gastric pull p/
whipple/ Hysterectomy/ gastrectomy/
Radical cystectomy/ Abdominal
exploration
Thoracic(N): Lung lobectomy/ chest
wall mass
17/5
3/4/2/2/3/2/1
2/3
15/8
5/2/2/1/2/1/2
5/3
0.37
Co morbidities
Hypertension
Diabetes Mellitus
Ischemic heart disease
Bronchial Asthma
Smoking
5
6
1
1
2
7
5
1
0
3
0.50
0.73
1.00
0.30
0.80

22. Drug History:
Beta- blocker
Ca++ channel blocker
Diuretics
Oral hypoglycemic and insulin
Beta-2 agonist
2
1
5
6
1
3
2
3
5
0
0.80
1.00
0.40
0.73
0.30
Opioid Requirement:
Postoperative results revealed a statistically significant higher
cumulative opioid doses consumption for patients in group N
compared with those in group M (as morphine equivalents; on basis
of that 1mg nalbuphine=0.7 mg morphine). On the other hand,
numbers of patients that required additional analgesic doses
(additional dose of the study opioid drug) were not statistically
different in the two drug groups (P: 0.37)

23. Parameters Group M Group N P value
Cumulative opioid doses 68.6±6.2 92.2±6.8 <0.01
Number of patients received
additional analgesia
17 15 0.37
Incidence and
severity of adverse
effects
Group M Group N P value
Nausea 0(0-4) 0(0-2) 0.22
Drowsiness 0(0-2) 0(0-2) 0.68
Itching 0(0-2) 0(0-2) 0.03
Dizziness 0(0-2) 0(0-2) 0.27
Incidence and Severity of Adverse Effects
Regarding incidence and severity of adverse effect postoperatively,
ranged from 0 no itching to 10 severe itching, was lower in group N
than group M (P: 0.03*). Incidences of postoperative nausea,
drowsiness, dizziness were not statistically different in the two drug.

24. Patient satisfaction with pain management Median score of the least
pain in the first 24 postoperative hours was significantly lower in
group M than in group N (P<0.01*) as shown in Table 6. Also patients
in group N experienced a significantly higher percentage of time
experience of severe pain during the first 24 hours than those patients
in group M (P: 0.02*). While other scores of satisfaction were similar
between morphine and nalbuphine group.

25. DISCUSSION
 Postoperative pain is a major problem, for health care
professionals, which requires intense workup for
effective management. Postoperative pain control
decreases morbidity, facilitates rapid recovery and
reduces hospital length of stay. Opioids are commonly
used for postoperative pain control; however, nausea,
vomiting, pruritus, constipation, and respiratory
depression are major associated drawbacks. So pain
control should be balanced against these adverse
effects. PCA is commonly used postoperatively to
manage pain, however little is known about PCA
itself. Patient may neglect pain and avoid activation of
PCA due to fear of addiction from opioids or
occurrence of adverse effects when use it frequently.

26. Morphine is an opioid that produces analgesia through acting
on mu receptors. The many adverse effects of morphine are
related to mu receptor binding. Nalbuphine, on the other hand,
acts as an agonist on kappa receptors which provides analgesia
and as an antagonist on mu receptor. Nalbuphine has a ceiling
effect in its respiratory depression and is considered to be
safer than morphine with minimum incidence of postoperative
pruritus, nausea and vomiting. The analgesic effect of
nalbuphine through kappa receptors reaches a ceiling effect.
This can lead to unpredictable analgesic efficacy for surgical
procedures. So the analgesic efficacy depends on its complex
pharmacodynamics profile rather than pharmacokinetic. Results
of comparative studies between morphine and nalbuphine are
inconsistent. There is no evidence to indicate which is better for
pain control.

27. The present study was performed to compare the clinical
efficacy and adverse effects of PCA morphine and nalbuphine
combined with ketorolac in postoperative setting and evaluate
the effectiveness of a constructed educational program for pain
management on patients `outcomes. To accomplish the goal, a
combination of opioid analgesics, either morphine (morphine
group) or nalbuphine (nalbuphine group), and non-opioid
analgesic ketorolac was used for PCA administration. Groups
were subdivided into control and intervention groups. Patient
and nurse education on safe and effective use of PCA was
provided to the intervention groups.
Thus the structured preoperative educational program has a
positive impact attitude toward self-administration of analgesics,
better pain control and satisfaction with pain management using
PCA.

28. CONCLUSION
Morphine provides more effective postoperative analgesia than
nalbuphine when administered with ketorolac. The combination
of ketorolac allowed more pronounced synergistic effect with
morphine than that with nalbuphine. Preoperative patient and
nurse education improved analgesia and overall patient
satisfaction with their pain treatment protocol; the patient can
treat pain more in a more timely and individualized manner, thus,
increasing pain-management satisfaction. Preoperative PCA
education avoids patient’s confusion between PCA button and the
nurse call button, allows patients to be familiar with PCA
technique and reduces fear of addiction from frequent use of
PCA. Also education may allow patients to balance between
administration of analgesics and adverse events by self-adjusting
the dose of analgesic used. Limitation of the study: Pain intensity
is not estimated during rest and at movement/coughing which is
important to judge the analgesic efficacy.

29.  Dickerson DM. Acute pain management. Anesthesiol
Clin. 2014;32;495-504.
 Prabhakar A, et al. Preoperative analgesia outcomes
and strategies. Best Pract Res Clin Anesthesiol.
2014;28:105-115.
 Licht E, et al. Can the cognitively impaired safely use
patient-controlled analgesia?. J Opioid Manang.
2009;5:307-312
REFERENCE