Embed Size (px)
Citation preview
ULTRASOUND GUIDED PARASTERNAL
MODIFIED INTERCOSTAL NERVE BLOCK:
ROLE AS A PREEMPTIVE ANALGESIC ADJUNT
IN FAST TRACKING FOR MITIGATING
POSTOPERATIVE STERNOTOMY PAIN
DISSERTATION
submitted for partial fulfilment of the requirement for the Degree of
DM in Cardiothoracic and Vascular Anaesthesia by
DR. V.SANTHOSH
DM CARDIOTHORACIC AND VASCULAR ANAESTHESIA RESIDENT
2017 – 2019
DIVISION OF CARDIOTHORACIC AND VASCULAR ANAESTHESIOLOGY
DEPARTMENT OF ANAESTHESIOLOGY
SREE CHITRA TIRUNAL INSTITUTE FOR MEDICAL SCIENCES AND
TECHNOLOGY, TRIVANDRUM, KERALA, INDIA – 695011
DECLARATION
I hereby declare that this thesis entitled, ULTRASOUND GUIDED PARASTERNAL
MODIFIED INTERCOSTAL NERVE BLOCK:ROLE AS A PREEMPTIVE
ANALGESIC ADJUNT IN FAST TRACKING FOR MITIGATING POSTOPERATIVE
STERNOTOMY PAIN has been prepared by me under the capable supervision and guidance
of Dr. Subin Sukesan, Associate Professor, Department of Cardiothoracic and Vascular
Anesthesiology, Dr. Rupa Sreedhar, Professor, Department of Cardiothoracic and Vascular
Anesthesiology, Dr. Shrinivas Gadhinglajkar, Professor, Department of Cardiothoracic and
Vascular Anesthesiology Dr.Prasanta Kumar Dash, Professor, Department of Cardiothoracic
and Vascular Anesthesiology , Dr.K.Jayakumar, Professor, Department of Cardiothoracic and
Vascular Surgery, Sree Chitra Tirunal Institute for Medical Sciences & Technology,
Thiruvananthapuram, Kerala.
Date: Dr. V.Santhosh
DM Cardiothoracic and Vascular
Place: Thiruvananthapuram Anesthesiology Resident,
Department of Anesthesiology,
SCTIMST, Thiruvananthapuram
CERTIFICATE
This is to certify that the thesis entitled ULTRASOUND GUIDED PARASTERNAL
MODIFIED INTERCOSTAL NERVE BLOCK: ROLE AS A PREEMPTIVE
ANALGESIC ADJUNT IN FAST TRACKING FOR MITIGATING POSTOPERATIVE
STERNOTOMY PAIN is the bonafide work of Dr. V. Santhosh, Senior Resident, conducted
in the Department of Cardiothoracic and Vascular Anesthesiology, at Sree Chitra Tirunal
Institute for Medical Sciences & Technology, Thiruvananthapuram under our supervision and
guidance. He has shown keen interest in preparing this project.
(GUIDE) (CO-GUIDE)
Dr. Subin Sukesan Dr. Rupa Sreedhar
Associate Professor, Professor,
Department of Cardiothoracic and Department of Cardiothoracic and
Vascular Anesthesiology, Vascular Anesthesiology,
SCTIMST, Thiruvananthapuram, SCTIMST, Thiruvananthapuram,
India. India.
(CO-GUIDE) (CO-GUIDE)
Dr. Shrinivas Gadhinglajkar Dr. Prasanta Kumar Dash
Professor, Professor,
Department of Cardiothoracic and Department of Cardiothoracic and
Vascular Anesthesiology, Vascular Anesthesiology,
SCTIMST, Thiruvananthapuram, SCTIMST, Thiruvananthapuram,
India. India.
(CO-GUIDE)
Dr. K.Jayakumar
Senior Professor,
Department of Cardiothoracic and
Vascular Surgery,
SCTIMST, Thiruvananthapuram,
India.
CERTIFICATE
This is to certify that the thesis entitled ULTRASOUND GUIDED
PARASTERNAL MODIFIED INTERCOSTAL NERVE BLOCK:ROLE AS
A PREEMPTIVE ANALGESIC ADJUNT IN FAST TRACKING FOR
MITIGATING POSTOPERATIVE STERNOTOMY PAIN has been prepared
by Dr. V.Santhosh, DM Cardiothoracic and Vascular Anesthesiology Resident,
Division of Cardiothoracic and Vascular Anesthesiology, at Sree Chitra Tirunal
Institute for Medical Sciences & Technology, Thiruvananthapuram.. He has shown
keen interest in preparing this project.
Dr. Thomas Koshy,
Senior Professor and Head,
Division of cardiothoracic and
vascular Anaesthesiology,
Date: Department of Anaesthesiology,
SCTIMST,
Place: Thiruvananthapuram.
ACKNOWLEDGEMENT
I take this opportunity to express my deep sense of gratitude and thanks to all those who have
been instrumental in the successful completion of this work. I am deeply indebted to my
esteemed teacher and guide, Dr. Subin Sukesan, Associate Professor, Department of
Cardiothoracic and Vascular Anesthesiology, Sree Chitra Tirunal Institute for Medical Sciences
and Technology for her unremitting encouragement, avid support and invaluable guidance
throughout the course of my study.
I would also like to express my deep gratitude and regards to my Co-guide,
Prof Dr. Rupa Sreedhar, Department of Cardiothoracic and Vascular Anesthesiology,
Sree Chitra Tirunal Institute for Medical Sciences and Technology. Without her guidance,
support and personal involvement, the work could never have been completed.
I express my sincere thanks to my Co-guides Prof. Dr. Shrinivas Gadhinglajkar,
Prof. Dr. Prashanta Kumar Dash for their constant support and guide throughout the conduct
of study.
I am indebted to my Co-guide, Dr K. Jayakumar, Senior Professor, Department of
Cardiothoracic and Vascular Surgery, Sree Chitra Tirunal Institute for Medical Sciences and
Technology for his insights and assistance in conduct of the study.
All my teachers, Prof. Dr. Thomas Koshy, Senior Professor & Head, Prof. Dr. Suneel P.R.,
Prof. Dr. Unnikrishnan K.P. and Dr. Saravana Babu, Assistant Professor, Department of
Cardiothoracic and Vascular Anesthesiology, Sree Chitra Tirunal Institute for Medical Sciences
and Technology have been extremely helpful during the conduct of the study and have given
their invaluable opinion and constructive criticism.
I am thankful to my fellow residents for their unconditional support throughout the study.
Dr. Don jose, Dr. Ankur, Dr. Kiran and Dr. Nayana deserve special mention. I am thankful to
all my seniors and juniors who gave valuable suggestion during course of the study.
I express my gratitude to nursing staff in adult post operative cardiothoracic and vascular
intensive care unit for their support to conduct the study in a successful manner.
I express my heartiest gratitude to my parents, my wife Dr. Sneha Chitra, son and my in-laws
who have been a constant source of motivation and encouragement.
I am grateful to god for his grace and wisdom .
Last, but not least, I would like to take this opportunity to thank and show my gratitude to all my
patients who volunteered to be part of this study and their cooperation
Date:
Place: Thiruvananthapuram Dr. V. Santhosh
TABLE OF CONTENTS
CHAPTER NO TITLE PAGE
NO 1 INTRODUCTION 1
2 AIMS AND OBJECTIVES 2
3 REVIEW OF LITERATURE 6 3.1 DEFINITIONS 6
3.2 PATHOPHYSIOLOGY OF POST OPERATIVE PAIN 7
3.3 PHYSIOLOGICAL EFFECTS OF ACUTE POST
OPERATIVE PAIN 13
3.4 PAIN MANAGEMENT AFTER CARDIAC SURGERY 16
3.5 SYSTEMIC ANALGESIA 19 3.6 REGIONAL ANALGESIA 26 3.7 PRE EMPTIVE ANALGESIA 38 3.8 FAST TRACKING IN CARDIAC SURGERY 41
4 MATERIALS AND METHODS 45
5 RESULTS 56
6 DISCUSSION 72
7 LIMITATIONS 82
8 CONCLUSION 83
9 BIBLIOGRAPHY 85 10 ANNEXURES i. NUMERICAL RATING SCALE
RAMSAY SEDATION SCALE
ii. PATIENT INFORMATION SHEET AND
INFORMED CONSENT
iii. OBSERVATION CHART
iv. INSTITUTIONAL ETHICS COMMITTEE
APPROVAL
v. DATA COLLECTION MASTER CHART
vi. PLAGIARISM CERTIFICATE
INTRODUCTION
1
INTRODUCTION Fear of uncontrolled pain is among the primary concerns of many patients who are about
to undergo surgery. Pain affects patients physiological and psychological recovery (1).
Adequate postoperative analgesia prevents unnecessary patient discomfort, may decrease
morbidity, may decrease postoperative hospital lengths of stay, and thus may decrease
costs. So aggressive implementation of well-planned pain management strategy is crucial
for decreasing post-sternotomy pain and resultant morbidity and mortality in
cardiothoracic surgeries (2)(3). Inadequate analgesia and/or an uninhibited stress
response during the postoperative period may increase morbidity by causing adverse
hemodynamic, metabolic, immunologic, and hemostatic alterations.
Analgesic medication modalities, providing optimal relief from pain-anxiety, can
facilitate early tracheal extubation, with minimal compromise on airway-reflexes during
post-tracheal extubation period after cardiac surgery. This would result in optimal patient
comfort-satisfaction without any post-operative pain (4).Also in the recent years, a
multimodal approach utilizing combined regional and systemic analgesics with different
mechanisms of action has been found to be promising and beneficial in terms of treating
acute pain and preventing chronic pain after cardiac surgery.
Pre-emptive analgesia execution assumes a critical role in blunting traumatic or surgical
damage induced stimulus modification in both peripheral and central nervous system, and
therefore this modality must be considered during the decision making of preoperative
analgesic techniques (5)(6).
AIMS AND OBJECTIVES
2
AIMS AND OBJECTIVES
AIM
The aim of this study is to analyze in post-operative cardiothoracic & vascular intensive
care setting:
Quality of pain relief with Pre-emptive analgesic technique
Role of fast tracking
when a single shot Parasternal modified-intercostal nerve block is administered before
sternotomy.
RATIONALE
1) There is an insufficient literature worldwide on ultrasound-guided parasternal
modified-intercostal nerve block for patients undergoing sternotomy for Cardiac
Surgeries, even though, it has been found to be useful in the cardiac surgical
patients for reducing analgesic requirement and improving postoperative
respiratory function.
2) Indian publications on this topic are lacking.
3) No study has been conducted on the utility of this technique in cardiac surgical
patients at our Institute.
3
OBJECTIVES
To assess the quality and effectiveness of postoperative pain relief after tracheal
extubation in intensive care, effected by a single shot Parasternal modified-
intercostal nerve block with routine in-hospital analgesic protocol, when
administered before sternotomy incision.
A) Quality and effectiveness of pain relief will be evaluated for 24 hours post extubation
using following parameter:
11-point 0-10 Verbal Numeric Rating Scale
B) Effects of the blockade on sedation, ventilation and requirement of concomitant
analgesics will be assessed using following methods:
a) Alertness of patients in peri-tracheal extubation period as assessed by Ramsay
Sedation scale in the initial 24 hrs after the block.
b) Any incidents such as;
1. Over-sedation leading to ETCO2 or PaCO2 build up during the ventilator
weaning phase or peri-tracheal extubation period
2. Any requirement for temporary discontinuation of opioid infusion.
3. Any postoperative requirement for other supplemental analgesics.
4
Secondary Objectives:
1) To assess the patient cooperation and patient comfort while performing the deep
inspiratory exercises, coughing, and incentive spirometry, in the immediate post
tracheal-extubation period and upto 24 Hours post-surgery.
Assessed by:
Documentation of any acute onset of pain or dull aching discomfort in the post-operative
sternal area on the chest while performing: -
a. Deep breathing exercises,
b. Coughing and expectoration
c. Incentive spirometry
2) To document the effects of procedural intervention on the:-
a. Presence or absence of any pain specific to sternotomy wound region site or drain
tube placement sites in the first 24hrs in the post-operative period.
b. Presence or absence of any other new onset chest wall pain in the first 24hrs in the
post postoperative period.
5
Hypothesis:
We have an existing intraoperative and postoperative Anaesthesia-Analgesia hospital
protocol.
We hypothesize that in addition to following this protocol, provision of ultrasound
guided parasternal intercostal block with an adequate time given for its onset of action
prior to the surgical incision, would result in better quality of post-operative pain control,
decreased risk of over-sedation and facilitation of fast tracking in adult cardiac surgery.
REVIEW OF LITERATURE
6
REVIEW OF LITERATURE
DEFINITIONS
PAIN
According to International Association for the Study of Pain, “Pain is an unpleasant
sensory and emotional experience associated with actual or potential tissue damage, or
described in terms of such damage”.
ACUTE PAIN IN THE PERIOPERATIVE SETTING
“ Pain that is present in a patient who underwent surgery is because of pre-existing
disease, the surgical procedure, or a combination of disease related or procedure related
sources” [ASA task force on pain management] (7). Pain is a normal functional and
physiologic reaction to tissue damage by surgery.
CHRONIC PAIN
Pain that recurs or persists (e.g. along a thoracotomy scar) for at least two months
following the surgical procedure.
Pain is always “subjective” varying among different individuals and “unpleasant”
and therefore also an “emotional discomfort” for the patients.
7
PATHOPHYSIOLOGY OF POSTOPERATIVE PAIN
It is well recognized that the etiology and treatment of pain produced by surgery is
different from other clinical pain conditions (8) (9). Pain is a direct response to
mechanical tissue damage caused during surgery. It is considered as a normal response to
tissue injury. Symptoms vary depending upon the type of tissue injured and the extent of
injury.
Acute postoperative pain is a type of Nociceptive Pain and usually it decreases as the
tissue injury heals.
Perception of nociceptive pain involves a complex relationship between three different
components:
Afferent nociceptive stimulation
Transmission, interpretation and modulation of these signals by central nervous
system
An efferent component (10)
A thorough knowledge regarding neurobiology of pain is essential for effective pain
management because there are enormous differences between the origin and mechanisms
of different types of pain.
8
NEUROBIOLOGY OF PAIN
1. PERIPHERAL STIMULUS .
NOCICEPTION –
“ The evoked response to a specific tissue stimulation from either mechanical, thermal or
chemical irritation applied to receptors on the nerve endings, that are potentially capable
of damaging nerve tissue” (11)(12).
NEUROGENIC INFLAMMATION
Surgery produces tissue injury with continuous release of histamine and inflammatory
mediators. The mediators released include Peptides(eg.bradykinins),lipids
(eg.prostaglandins), neurotransmitters (eg.serotonins) and neurotrophins (eg.nerve growth
factor) which in turn activate the nociceptors (13).
2. RECEPTORS FOR TRANSDUCTION
NOCICEPTOR
“ A sensory receptor that sends signals that cause the perception of pain in response to
potentially damaging stimulus”
Nociceptors are usually free nerve endings of two types of small nerve fibres.
a. THIN MYELINATED Aδ FIBRES
Diameter of 2-5mm and a conduction velocity of 6-30m/s
Conducts “FAST PAIN” – sharp, short lasting, pricking type of pain
b. UNMYELINATED C FIBRES
Diameter of <2 mm and conduction velocity of less than 2 m/ s.
Conducts “SLOW PAIN”- dull, poorly localized, burning type of pain
9
3. PERIPHERAL AFFERENT PATHWAYS
The nociceptors in the periphery when activated transmit action potential via afferent
nerves to the spinal cord. Primary afferent nociceptors belong to the type of
Pseudo- unipolar neurons. Their cell bodies are located in the Dorsal root ganglion.
Their central processes project into the Dorsal horn of the spinal cord.
NEUROBIOLOGY OF PAIN
4. SPINAL CORD PATHWAYS
The grey matter of the spinal cord is divided into Ten "laminae" by REXED in 1950.
The Laminae that are involved in pain transmission are
Lamina I - marginal nucleus of spinal cord
Lamina II - substantia gelatinosa
Lamina III- nucleus proprius.
Lamina V- neck of dorsal horn.
Laminae VII and VIII - intermedio nucleus of spinal cord.
A δ fibres terminate in laminae I to V
C fibres terminate in lamina II.
10
Important neurons in this region are :
Wide dynamic range neurons (WDR)
Found in Lamina V. These neurons receive impulses from both nociceptive nerve
terminals and myenilated A type nerve fibres. These neurons respond to gentle touch ,
play an important role in pain transmission. They also have the tendency to increase their
response if the stimulus increases in intensity.
Nociceptive specific neurons
Found in Lamina I. These neurons respond only to noxious stimuli. The dorsal horn of
the spinal cord also contains a wide range of Neurotransmitters like serotonin, Nor
epinephrine, substance P, glutamate, glycine and Neuromodulators like opioid peptides
like enkephalins, dysnorphins with their respective receptors. These interact in a
complex way and play an important role in modulation and transmission of pain.
Mechanism in which Neurotransmission occurs within the dorsal horn of the spinal cord
can be summarized as an interaction between:
• Excitatory transmitters released from primary afferent nociceptors
• Excitatory transmission between neurons of the spinal cord
• Inhibitory transmitters released by interneurons within the spinal cord
• Inhibitory transmitters from supra spinal sources
11
5. CENTRAL CONNECTIONS
Following modulation in the dorsal horn ,the pain impulses travel along a complex
array of spinal cord pathways. Some of the important pathways in which nociceptive
information is transmitted include
Spino-thalamic tract
Spino-reticular tract
Spino-mesencephalic tract
These tracts project to a number of nuclei in the thalamus.From the thalamus,the
terminal sites of pain appreciation are the Somato sensory cortex(sensoryaspect of
pain) and the limbic system(affective component of pain).
The cortex is considered to be the ultimate site of conscious awareness of sensory stimuli.
6. DESCENDING INHIBITORY PATHWAYS
Descending modulation of pain sensation originates from three main areas:
Cortex
Thalamus
Brainstem – Peri aqueductal grey matter (PAG).
Fibres pass from Peri aqueductal grey matter to the Reticular formation of the medulla.
Axons from there descend via the dorsolateral funiculus of the spinal cord. Finally the
neurons Synapse with the interneurones in the substantia gelatinosa of the spinal cord.
Pain impulses are inhibited by the stimulation of this pathway. Various neuro transmitters
like GABA, nor-epinephrine play an important role in the descending inhibition of pain.
12
PERIPHERAL AND CENTRAL SENSITIZATION
Continuous release of inflammatory mediators in the periphery sensitizes functional
nociceptors and activates dormant ones. Sensitization of peripheral nociceptors may
occur and results in a decreased threshold for activation, increased rate of discharge with
activation, and increased rate of basal (spontaneous) discharge (14)(15).
Central sensitization -“persistent postinjury changes in the CNS that result in pain
hypersensitivity”
Hyperexcitability - “exaggerated and prolonged responsiveness of neurons to normal
afferent input after tissue damage” This leads to permanent functional changes in the
dorsal horn of the spinal cord .As a result postoperative pain to be perceived as more
painful.
Pain Sensitization
Figure 2
Despite recent advances and ongoing research our knowledge about the roles of various
transmitters and receptors about the neurobiology of pain is still incomplete.
13
PHYSIOLOGICAL EFFECTS OF ACUTE POSTOPERATIVE PAIN
Perioperative stress peaks during the immediate postoperative period. Acute pain in the
postoperative period will cause detrimental effects on the patient recovery following
surgery and also lead to increased patients despair and suffering (16). Optimal
perioperative and postoperative analgesia will certainly decrease complications and
improve recovery following surgery (17). Some of the important major adverse effects of
acute pain on various organ systems are:
CENTRAL NERVOUS SYSTEM
Continous transmission of the nociceptive stimulus will lead to activation of the
neuroendocrine stress response. Local release of inflammatory mediators (eg-
prostaglandins, leukotrienes) unless controlled will sustain this response. Hypothalamic-
pituitary-adrenocortical axis and sympathetic system gets activated and will have adverse
effects on the patients outcome. Activation of this system will lead to increased
sympathetic tone, decreased secretion of anabolic hormones like insulin and increased
catabolic hormone secretion (cortisol ,antidiuretic hormone, glucagon). There will also be
an increase in metabolism and as a result oxygen consumption is greatly increased.
Therefore a hypermetabolic and a catabolic state ensues.
CARDIOVASCULAR SYSTEM
Activation of the sympathetic nervous system will lead to increased myocardial oxygen
consumption, coronary vasoconstriction making patients susceptible to myocardial
ischemia and infarction. Tachycardia and hypertension will increase cardiac workload
and increase myocardial oxygen demand, may lead to perioperative myocardial ischemia
(18).
14
RESPIRATORY SYSTEM
There will reflex spinal inhibition of phrenic nerve activity which will decrease
postoperative pulmonary function especially after cardiac and thoracic surgeries (19).
Decreased functional residual capacity, vital capacity, hypoxia, hypercarbia, ventilation
perfusion mismatch ensues which increases post operative morbidty and mortality.
GASTROINTESTINAL SYSTEM
Reflex inhibition of gastrointestinal motility, increased postoperative ileus, and
vomiting.
RENAL SYSTEM
Sodium and water retention, oliguria occurs which may have adverse metabolic
consequences
COAGULATION SYSTEM
There is increased levels of procogulants, increased platelet activity, decreased
fibrinolysis . The hypercoagulable state which happens may contribute to an increased
incidence of deep vein thrombosis , myocardial ischemia and vascular graft failure.
IMMUNOLOGICAL SYSTEM
There is increase cytokine production, acute phase reaction, lymphocyte proliferation,
neutrophil leucocytosis due to the stress response. It may also potentiate postoperative
immunosupression which lead to poor wound healing and recovery after surgery.
15
ACUTE PAIN AS PREDICTOR OF CHRONIC POSTOPERATIVE PAIN
Experimental and clinical studies suggest that acute pain after surgery can quickly
transient into chronic pain which persists several months after surgery(20). Continuous
noxious stimuli can lead to the expression of new genes in the dorsal horn of spinal cord
within 1 hour ,as a result there is alteration in the behavior of pain perception in these
areas for a long time (21).
CHRONIC POST STERNOTOMY PAIN
Cardiac surgery through median sternotomy is associated with the development of
chronic sternal pain with a reported incidence of 11% to 56% at 1 year after surgery(22).
Processes specific to cardiac surgery include neuropathy from anterior intercostal nerve
entrapment or injury during internal mammary harvest, arthritis or hypersensitivity
associated with sternal wire placement, musculoskeletal injury from surgical incision and
manipulation, sternal fracture or incomplete bone healing, and the development of sternal
wound infections. Despite best efforts, up to 80% of postoperative pain, including pain
following sternotomy, is not adequately managed (23). Without proper diagnosis and
treatment, chronic sternal pain can reduce quality of life affecting sleep, mood, activity
level, and overall satisfaction.
16
PAIN MANAGEMENT AFTER CARDIAC SURGERY
RATIONALE
In the immediate post operative period after cardiac surgery inadequate analgesia coupled
with uninhibited stress response may be lead to adverse hemodynamic, immunologic and
hemodynamic alterations. Release of stress hormones during cardiopulmonary bypass
and sympathetic nervous system activation may lead to myocardial ischemia. Evidences
suggest that aggressive control of pain and attenuation of stress responses after cardiac
surgery will beneficially improve the patients outcome (24).
POTENTIAL CLINICAL BENEFITS OF ADEQUATE POSTOPERATIVE
ANALGESIA
Hemodynamic stability
Metabolic stability
Immunologic stability
Hemostatic stability
Stress-response attenuation
Decreased morbidity
PATHOPHYSIOLOGY OF POST STERNOTOMY PAIN
The pathogenesis of post steronotomy pain impulse transmission and modulation is
complex. Nociceptive impulses after cardiac surgery is transmitted by multiple sensory
afferents.These nociceptive receptors are stimulated during surgery by skin incision,
spreading of the sternum and ribs, division of the intercostals muscles and injury to the
intercostals nerves. Sometimes there may fracture of the ribs, fracture of the costo
chondral joints and ligaments (25).
17
The parietal pericardium which is incised after surgery is continuously irritated by the
drains and blood from minimal oozing. These lead to prolonged stimulation of the
nociceptors which may proliferate at the site of injury and it amplifies the pain
transmission. Peripheral and central sensitization occurs, as a result the perceived pain is
much more severe.
SOURCES OF STERNOTOMY PAIN
There are various afferent somatic and visceral sensory nerves which transmit pain
impulses to the sensorium after cardiac surgery. Pain after cardiac surgery can be very
intense and it originates from many sources (26).
SOURCE AFFERENT SENSORY NERVES
Sternum , intraop tissue dissection and
handling
Intercostal nerves 2-7
Ribs ,pericardium Intercostal nerves 4-6
Chest tubes Intercostal nerves 5-8
Mediastinal pleura Vagus nerve
Diaphragmatic pleura Phrenic nerve
Ipsilateral shoulder pain Phrenic nerve (27)/brachial plexus
Patients in whom an internal mammary artery is surgically exposed and used as a bypass
graft may have substantially more postoperative pain(28). Another source of
postoperative pain in patients after cardiac surgery is thoracic cage rib fractures, which
may be common(29). Furthermore, sternal retraction, causing posterior rib fracture, may
lead to brachial plexus injury.
18
PAIN AFTER CARDIAC SURGERY – INFLUENCING FACTORS
1. AGE
Patients younger than 60 years of age often have greater pain intensity than patients older
than 60 years of age (30). Advancing age produces major changes in the perception of
pain. Changes in the structure and function of the central and peripheral nervous system
affects the signaling and processing of pain. There is also reduction in descending
inhibiting modulating systems. Elderly is also more sensitive to the side effects of the
various analgesic regimes especially systemic opoids. Therefore elderly with reduced
capacity pain modulating system in the body are more susceptible to the negative impacts
of pain (31).
2. SEX
Various studies have shown that there is difference among males and females in
perception of pain after surgery. Female patients are generally considered to be more
sensitive to nociceptive stimuli than males (32).Menstrual status plays a key role.
Reduction in the activation of the endogeneous opoid receptors is seen in low estradiol
states. But with advancing age pain perception seems to be similar in both the sexes
3. PSYCHOLOGICAL FACTORS
Perception of pain is found to be less among well informed, encouraged and reassured
patients. Preoperative anxiety and depressed mood is also found to be an important
predictor of more severe acute post operative pain (33).
19
POSTOPERATIVEANALGESIA AFTER CARDIAC SURGERY
There are various techniques that are currently available for providing analgesia after
sternotomy. Each method has its own merits and demerits. It is a matter of ongoing
debate and research about finding out the single ideal technique for managing pain after
sternotomy (34). Effective pain control cannot be achieved with a single method as many
factors has to be taken into considerations for each individual patient. Analgesic
technique should be determined by taking into account
Nature and severity of the disease
Patients - health ,preferences, co-morbid illness , contraindications
Type of surgery and incision
Post operative care and monitoring
Can be broadly divided into analgesia using systemic drugs and analgesia using
Regional techniques (35).
SYSTEMIC ANALGESIA
It is method of pain relief which is achieved by administering Analgesic drugs either
Intravenously (i.v) ,intramuscularly (i.m) or subcutaneously(s.c) route and drugs crosses
the blood brain barrier to produce central analgesic effects.
Drugs that are commonly used for systemic analgesia after thoracotomy are:
Opioids – long acting and short acting
Nonsteroidal Anti inflammatory drugs(NSAIDS)
Alpha2-Adrenergic Agonists
Paracetamol
Gabapentin.
20
These drugs with expection of paracetamol and gabapentins can be delivered by
intravenous, intramuscular or subcutaneous routes. With the routine use of PCA(patient
controlled analgesia) these drugs can be delivered safely and effectively. These drugs can
be used in combinations and is a simpler, economical and probably safer method which is
practiced in various institutions.
OPIOIDS
For many years systemic opioids form the mainstay of treatment of pain after cardiac
surgery. Opioids which include Morphine , Fentanyl ,Tramadol ,Pethidine ,buprenorphine
are widely used (36)(37). Opioids suppress pain by their action in the brain, spinal cord
and peripheral nervous system. Since 1990s with greater understanding of the molecular
pharmacology and isolation of DNA encoding opoid receptors, these drugs now widely
used for specific targets and with less side effect profile.
OPIOD RECEPTORS
In 1973, based on radioligand binding assays, three types of opoid receptors were
postulated, µ-, δ-, and κ-opioid receptors. The three opoid receptor genes DOR, MOR,
KOR which encode for µ-, δ-, and κ-opioid receptors were isolated in 1992. Since then
various subtypes of the opioid receptors such as µ1, µ2,µ3,δ1,δ2,κ1,κ2,κ3 have been
identified. These receptors are found in various regions of the central and peripheral
nervous system , spinal cord projections and interneurones , midbrain , cortex and
predominantly mediate pain inhibition (38). The receptors at peripheral, spinal and supra-
spinal sites mediate opioid induced analgesic effects. Systemically administered opioids
act on the peripheral opioid receptors (39).
21
MECHANISM OF ACTION OF OPIOIDS
The opioid receptors belong to G protein coupled receptor family. The primary
mechanism of action is inhibition of high voltage calcium channels through Gi activation
in the primary sensory Afferent neurons. Opioids also suppress the sodium currents in
the sensory nerve endings which result in inhibition of release of pro inflammatory
mediators like substance P,calcitonin (40). There is increase in the number of peripheral
opioid receptors in response to tissue injury, inflammation or damage. In the dorsal root
ganglion also there is upregulation of opioid receptors. As a result of breakade of
perineural barrier, opioid agonists diffuse to the receptor sites. Endogeneous opioid
peptides like endorphins,enkephalins and dynorphins are released which act
synergistically to improve analgesia (41).
CARDIOVASCULAR EFFECTS OF OPIOIDS
The predominant cardiovascular effect of exogenously administered opioids is
attenuation of central sympathetic outflow (42). Opioid receptors involved in regulating
the CVS have been localized centrally to the cardiovascular and respiratory centers of the
hypothalamus and brainstem and peripherally to cardiac myocytes, blood vessels, nerve
terminals, and the adrenal medulla. Opioid receptors are differentially distributed
between atria and ventricles. The highest specific receptor density for binding of κ-opioid
agonists is in the right atrium and least in the left ventricle. Actions may involve direct
opioid receptor–mediated actions, such as the involvement of the δ-opioid receptor in
ischemic preconditioning (PC), or indirect, dose-dependent, nonopioid-receptor–
mediated actions, such as ion channel blockade associated with the antiarrhythmic actions
22
of opioids. At clinically relevant doses, the cardiovascular actions of opioid analgesics
are limited.
PHARMACOKINETICS OF MORPHINE
Opioids in general are weak bases. With a pKa of 8.0 only a small fraction of the drug is
unionized at physiological pH. It also has low lipid solubility compared to other pioids.
Nearly 20-40% of drug is protein bound in plasma mostly albumin. Principal metabolism
is by conjugation in the liver and metabolites are excreted via the kidneys. The etabolites
are Morphine- 3-glucuronide (90%) and Morphine-6-glucuronide(10%). Since the
Hepatic extraction ratio of morphine is very high , bioavailability of morphine when
administered orally is very low when compared to intramuscular/subcutaneous routes
(43).
LIMITATIONS OF SYSTEMIC OPIOIDS
Nausea and vomiting
By acting on the δreceptors in the chemo receptor trigger zone in the medulla almost
all opiods induce nausea and vomiting (44). Anti emetic prophylaxis is essential
whenever opioids are employed for analgesia.
Sedation
Most common side effect of systemic opioids. Mechanisms not clearly elicited.
Opioid drugs interfere with sleep wake cycle,prolongs REM sleep . Monitoring
sedation is very important as it is a definite indicator of impending respiratory
depression (45).
23
Respiratory depression
Most Serious side effect of opioid use. These drugs directly act on the brainstem
respiratory centres and decrease the hypoxic ventilatory drive and reduce the
stimulatory effect of CO2 on ventilation. respiratory rate is affected more than tidal
volume, which may actually increase. With increasing doses of opioids, respiratory
rhythmicity is disturbed, resulting in the irregular gasping breathing characteristic of
opioid overdose (46)
Histamine release – can cause vasodilatation and hypotension
Bladder dysfunction – inhibit voiding reflex
Constipation
Opioid induced hyperalgesia
Tolerance and physical dependence
Opioid induced hormonal and immunologic effects.
Alteration in psychomotor performance
PATIENT CONTROLLED ANALGESIA(PCA) WITH OPIOIDS
PCA is now the most popular method for management of postoperative pain with opioids.
With this method treatment options are individualized and also patients play a active role
in pain management. It also have definite advantage of better side effects profile , reliable
analgesic effect,improved patient autonomy,decreased complications when compared to
other methods of administration (47).In cardiac surgery, it needs to be determined
whether PCA offers significant clinical advantages over traditional nurse controlled
24
analgesic techniques (48). Costs, patient education are the definite disadvantages.
Continuous intravenous infusion of opioids is still popular as it can be used in
sedated,mechanically ventilated patients .It is also effective in controlling breakthrough
pain.
USE OF OPIOIDS IN CARDIAC SURGERY
Systemic opioids can be used as a sole treatment option for pain management after
cardiac Surgery (49).Though they are effective in controlling background pain , doses
required to control acute pain during movement or exercises and is associated with
sedation and respiratory depression (36). Opioids play a major role in multimodal
analgesic regime after sternotomy.
NONSTEROIDAL ANTI INFLAMMATORY DRUGS
For more than 30 yrs NSAIDS have been used as an adjuvant in the management of post
sternotomy pain. Prostaglandins, prostacyclins, thromboxanes play an important role in
the perception of pain and mediate inflammatory process after tissue injury.NSAIDS by
inhibiting the enzyme cyclo-oxygenase block the synthesis of these inflammatory
mediators. Thus these drugs have both peripheral and central analgesic action. Unlike
opioids, which preferentially reduce spontaneous postoperative pain, NSAIDs have
comparable efficacy for both spontaneous and movement-evoked pain (50). NSAIDS
such as diclofenac, ibuprofen, ketorolac, lysine acetyl salicylate, naproxen, are mainly
used as adjuvants along with systemic opioids. They reduce opioid consumption by
>30% (51). Major adverse effects limiting the use in the postoperative period are,
gastrointestinal bleeding, increased risk of myocardial infarction and stroke, renal
impairment (salt and fluid retention) particularly in elderly and hypovolemic patients,
25
hyperkalemia and drug interactions. There can be Systemic bleeding associated with
platelet dysfunction irrespective of the route of administration (52).
ALPHA2-ADRENERGIC AGONISTS
The α2-adrenergic agonists like clonidine and dexmedetomidine provide analgesia,
sedation, and sympatholysis via stimulation of α2 receptors in the locus ceruleus and
spinal cord (53). Clinically important side effects are decrease in minute ventilation and
cardiovascular effects like decreased heart rate, decrease in systemic vascular resistance
and reduced myocardial contractility. Most research on α2-adrenergic agonists have been
focused on the intraoperative and postoperative period, for enhanced postoperative
hemodynamic stability and reduced postoperative myocardial ischemic events. There are
not much studies for its postoperative analgesia effects (54)(55).
PARACETAMOL
Forms a integral part of balanced multimodal analgesia after cardiac surgery (56) (57). It
is one of the safest analgesic agents. It produces its analgesic and anti inflammatory
effects by inhibiting prostaglandin synthesis and via the serotonergic system. Paracetamol
at analgesic doses have fewer side effects and contraindications. So it can be safely used
in patients with renal dysfunction and whom NSAIDS are contraindicated. Recent
metaanalysis have shown that addition of paracetamol to IV PCA morphine reduced
morphine consumption by 20% following major surgery (58). It is also very effective in
treating pain of non-cardiac origin like pain in the upper extremities, neck, head, and
midback area which can coexist in almost 65% of patients following sternotomy (59).
26
REGIONAL ANALGESIA
Sternotomy is a major surgical procedure and is associated with exaggerated adrenergic
stimulation resulting in various hormonal stress response and systemic inflammation. So
regional anaesthesia play an valuable role in preventing this stress response (60). This has
been extensively studied and proven that without regional technique, analgesia is never
complete and regional analgesia has definite advantage over systemic analgesia in
reducing morbidity and mortality after major surgery (61). Currently regional techniques
play a integral part in the multimodal analgesic regimens for opioid sparing in cardiac
surgeries(62). Common regional analgesic methods that are used for pain management
are used in post sternotomy pain management are
Parasternal Intercostal blocks
Paravertebral analgesia
Fascial blane blocks
Thoracic epidural analgesia Intra thecal analgesia
Continuous wound infiltration catheters
ANATOMY FOR REGIONAL ANALGESIA IN STERNOTOMY
As mentioned earlier afferent nociceptive pathway following cardiac surgery occur
predominantly through the anterior and posterior rami of the intercostals nerves. The
anterior divisions of the 2nd to 6th thoracic spinal nerves, also known as the thoracic
intercostal nerves, provide most of the sensory innervation to the thoracic chest wall.
Originally located within deeper structures, they eventually penetrate more superficially
and run below each rib within the neurovascular bundle between the internal and
27
innermost intercostal muscle layer. Before reaching the angle of the rib, the intercostal
nerve divides into the following three branches: the anterior and lateral cutaneous nerves
and the collateral branch, which ends as the accessory anterior cutaneous nerve near the
sternum. At various distances along their course, nerve branches pierce the muscle and
fascia layers to run more superficially, collateralize, and thus provide sensation to the
entire chest wall. The 7th intercostal nerve terminates at the xiphoid process (63).
Anterior primary rami — Incisional pain, chest wall and most of the parietal pleura
Sympathetic nerves — Visceral nocioception
So the technique of block determines which nerves are anaesthesized
ANATOMY OF INTERCOSTAL NERVE AND ITS BRANCHES
28
NERVE SUPPLY OF THE STERNAL REGION
above figure depicts the nerve innervation from the supra-clavicularis intermedium nerve
and anterior cutaneous branches of intercostal nerves supplying the skin and sternum.
EFFECT OF DIFFERENT REGIONAL TECHNIQUES ON AFFERENT
NOCICEPTIVE PATHWAYS
Technique Anterior rami Posterior rami Sympathetic N
Interfascial blocks Ipsilateral Not blocked Not blocked
Intercostal block Ipsilateral Not blocked Not blocked
Thoracic epidural analgesia Bilateral Bilateral Bilateral
Paravertebral block Ipsilateral Ipsilateral Ipsilateral
29
INTERFASCIAL PLANE BLOCKS
Thoracic interfascial plane blocks are a recent development in modern regional
anesthesia research and practice and which represents a new route of transmission for
local anesthetic. Under ultrasound guidance , performing these block have proven to be
technically simple, with a better safety profile and thus provides reliable analgesia (64).
Novel fascial plane blocks, namely the erector spinae plane(ESP), serratus anterior plane
block (SAPB) and the pectoral nerves (Pecs) II block, recently have been evaluated for
post sternotomy pain. There is encouraging literature demonstrating the superiority of
Intercostal nerve blocks and fascial plane blocks over systemic opioid based analgesic
regimens (65)(66).
INTERCOSTAL NERVE COURSE AND VARIOUS BLOCKS
30
ANTERIOR CHEST WALL BLOCKS
ERECTOR SPINAE PLANE BLOCK
The erector spinae plane block is a interfascial block in which local anesthetic is injected
either in the plane between the rhomboid major and erector spinae muscle or deep
between erector spinae muscle and the transverse process. It involves blockade of the
ventral and dorsal rami of the spinal nerve roots. Sensory block from T2 to T9
dermatomes over the posterolateral hemithorax is achieved (67). The erector spinae plane
block extends anteriorly with variable effect past the midclavicular line. Studies have
shown that bilateral erector spinae blocks provide reliable analgesia after cardiac surgery
(68).
31
SERATTUS ANTERIOR PLANE BLOCK (SAPB) AND PECTORAL NERVES II
(PECSII )BLOCK
SAPB involves the deposition of drug into a fascial plane deep to the serratus anterior
muscle.The block targets the lateral cutaneous branches of the intercostal nerves. It has
shown to provide adequate analgesia for anterior chest wall pain (69). The Pecs II block
in the setting of cardiac surgery, is aimed to provide chest wall analgesia, where in the
local anesthetic is deposited above the serratus anterior muscle. This fascial plane block
targets the III, IV, V, and VI intercostal nerves and long thoracic nerve (70).
PARASTERNAL INTERCOSTAL NERVE BLOCK
Blocking of the intercostal nerves at the end of surgery, under vision by the surgeon is
one of the safest ,reliable methods of analgesia and is practiced worldwide for many
years (71). The block is administered at the lower border of the rib in the region of
intercostal bundle along 4-5 spaces. Various methods for intercostal blockade are Single
shot of local anaesthetic before chest closure , as a single percutaneous injection , as
multiple percutaneous injections or via an indwelling intercostal catheter. The site of
injection is important for the spread of local anaesthetic solutions and it depends on the
angle of the ribs and attachment of the intercostals membranes. Single shot injection of a
long acting local anaesthetics like Bupivacaine can provide sufficient analgesia for more
than six hours (72).To achieve longer durations of analgesia a continuous intercostal
catheter is found to be more effective (73).One limitation of continuous infusion method
is that systemic uptake of local anaesthetic solution in the highly vascular intercostals
space is very high, so caution with dosage is needed. Some studies have shown that even
after continuous infusion for more than 5 days ,the plasma levels of local anaesthetic is
32
below the toxic levels (74). Parasternal nerve blocks, when administered at the
termination of surgery, have shown to be an effective anaesthetic technique in providing
analgesia for post-operative sternotomy pain and reduces the postoperative narcotic
analgesic requirement, and thereby producing a positive effect on postoperative recovery
parameters when studied (75). It is simple to administer and can easily be used even in
anti-coagulated patients (76).
ULTRASOUND GUIDED PARASTERNAL INTERCOSTAL NERVE BLOCK
TECHNIQUE
The intercostal nerves reside in the neurovascular space between the parietal pleura and
the internal intercostal membrane/muscle. This intercostal neurovascular space is
visualized as a thick space on the posterior chest wall and near the sternum. In the
intercostal neurovascular space near the sternum, the anterior cutaneous and the collateral
branch of the intercostal nerve from T1 to T6 are located and innervate the sternum and
the skin around the sternum. Using ultrasound , the fascial plane between the internal
intercostal muscle and innermost intercoastal muscle is identified. Local anaesthetic is
deposited in this plane to block the anterior cutaneous branches of the corresponding
intercostal muscles (77)(78).
33
34
INTRATHECAL AND THORACIC EPIDURAL TECHNIQUES
It is now well established that intrathecal and thoracic epidural techniques provide
adequate and reliable analgesia after cardiac surgery. Additional potential benefits
include stress response attenuation and thoracic cardiac sympathectomy (79).
The quality of analgesia obtained with thoracic epidural anesthetic techniques is
sufficient to allow cardiac surgery to be performed in awake patients without general
endotracheal anesthesia (80). However, applying regional anesthetic techniques to
patients undergoing cardiac surgery is not without risk. Side effects of local anesthetics
(hypotension) and opioids (pruritus, nausea/vomiting, urinary retention, and respiratory
depression), when used in this manner, may complicate perioperative management.
Increased risk of hematoma formation in this scenario has generated much of lively
debate regarding the acceptable risk-benefit ratio of applying regional anesthetic
techniques to patients undergoing cardiac surgery (62) Thoracic epidural analgesia(TEA)
is considered the gold standard method of analgesia after thoracic surgery (81) and still
the widely practiced method of providing analgesia after thoracic and major abdominal
surgery (82).
BENEFITS OF THORACIC EPIDUAL ANALGESIA IN CARDIAC SURGERY
IMPROVED PAIN RELIEF
Provides superior postoperative analgesia and is the gold Standard method of pain relief
after thoracic surgery (83).
35
IMPROVED POSTOPERATIVE PULMONARY FUNCTION
Prolonged diaphragmatic dysfunction is common after sternotomy. If not adequately
treated , will lead to atelectasis, intrapulmonary shuting, hypoxemia, retention of
secretions, pneumonia and increase pulmonary morbidity and mortality. Diaphragmatic
dysfunction occurs secondary to the reflex inhibition of phrenic nerve due to continuous
afferent visceral stimulation(84). Diaphragmatic contractility is not impaired. With TEA
it is proven that there is reversal of this diaphragmatic dysfunction (85). As a result of
this there is an increase in functional residual capacity improvement of ventilator
parameters (86)(87). With better analgesia, patients are able to cooperate better with
physiotherapy which helps in clearing out mucus , adequate expansion of the lung after
invasive ventilation.There is also Less nausea and vomiting. There is definite evidence
that incidence of pulmonary complications are less with TEA after major surgery (85) in
high risk patients with a FEV1<60%.
REDUCED CARDIOVASCULAR COMPLICATIONS
TEA is shown to improve perioperative cardiovascular morbidity and moratlity. The
effects are exerted through reduced pain, reduced stress response and reduction of
sympathetic activity. It also dilates the coronary arteries and improve the myocardial
demand supply ratio. So there is reduced incidence myocardial ischemia and infarction
(88) .
36
Arrythmias after Surgery
There is high incidence (20%-30%) of supraventricular arrhythmias atrial
fibrillation(65%-85%), atrial flutter , supraventricular tachycardias following cardiac
surgery. Arrhythmias appear within 3 days of surgery with a peak in the second post
operative day. Most of the arrhythmias spontaneously resolve. TEA is shown to be
beneficial in reducing the incidence of arrhythmias and improve cardiovascular outcome
(89).
Reduced thromboembolic events
By reducing the stress response associated with pain , TEA improves the fibrinolytic
function and also attenuates the hypercoagulable state post surgery. Early mobilization of
the patient with adequate pain relief also plays a role.
Others benefits include
Improvement in gastrointestinal function and reduction in post operative ileus.
Decreased post operative protein catabolism
Decreased duration of mechanical ventilation
LIMITATIONS AND ADVERSE EFFECTS OF THORACIC EPIDURAL
ANALGESIA IN CARDIAC SURGERY
EPIDURAL FAILURE
Insertion of a thoracic epidural catheter is a technically difficult procedure.
Depending on the expertise the failure rate can be as high as 15% (90).
37
Epidural hematoma
Most serious complication after epidurals with an incidence of 0.02%. Though the
overall incidence of central neuraxial block is low 0.007% (91)
Hypotension
Commonly occur after thoracic epidural because of the blockade of the cardiac
sympathetic fibres and also due to decrease in both preload and afterload. Should be
treated with vasopressors ,since there is limited response to increase in preload or
afterload (92).
Urinary retention
Occurs due to addition of epidural opioids.
Delayed gastric emptying
Respiratory depression
Nausea and pruritis.
38
PREMPTIVE ANALGESIA IN CARDIAC SURGERY
DEFINITION
“Anti- nociceptive treatment that prevents the establishment of altered central processing
of afferent input ,which amplifies acute post operative pain”. By decreasing the altered
central processing , pre emptive analgesia is thought to decrease the consequent
development of hyperalsegia and allodynia after surgery (93).
AIM
Though general anaesthesia and systemic opioids administered for analgesia during
surgery decreases the noxious impulse transmission from the site of injury to the brain
and spinal injury it does not completely block it. Various studies have shown that “
central and peripheral sensitization” occurs due to this continuous noxious noxious
stimulation . As a result of this post operative Hyper sensitivity occurs, “spinal wind
up” ,which is the reason for development of primary and secondary Hyperalgesia at the
site of injury (94). So Pre emptive analgesia aims at preventing the development of this
neuronal sensitization and decreases acute post operative pain and development of
chronic pain.
METHODS OF PRE EMPTIVE ANALGESIA
Pre emptive analgesia involves various stragies for blocking the transmission of pain
impulses at various sites along the pain pathways. It involves local infiltration with local
anaesthetics before skin incision , peripheral nerve blocks , epidural analgesia. Various
drugs like NMDAantagonists, gabapentin , systemic opioids , dexamethasone , tramadol
and celecoxib is also said to play a role.
39
EFFICACY OF PRE EMPTIVE ANALGESIA
The concept of pre emptive analgesia have evolved from favourable results from various
experiments in animal models. So the effect in clinical scenario is still controversial.
Conflictive results had been obtained from various clinical studies (95). It is generally
accepted that pre emptive analgesia is a valid phenomenon (93). This has led to the
development of concept of “PREVENTIVE ANALGESIA” which incorporates the
treatment of all the factors involved in the preoperative, intraoperative and the post
operative periods (96). So it aims to attenuate the occurrence of sensitization during the
entire perioperative period , not only preventing the noxious stimulus during skin
incision.
MULTIMODAL ANALGESIC APPROACH IN CARDIAC SURGERY
To maximize the beneficial effects of controlling post operative pain a multi modal
strategy should be implemented for patient care in the post operative period (97).
Principles of a multimodal strategy include control of postoperative pain to allow early
mobilization, early physiotherapy , education, and attenuation of the perioperative stress
response through the use of regional anesthetic techniques and a combination of analgesic
agents (i.e., multimodal analgesia). A multimodal approach involves the use of more than
one analgesic compound or modality of pain control to achieve an opioid-sparing effect
by obtaining additive or even synergistic analgesic effects while minimizing adverse
events and is currently the gold standard for postoperative pain management (57). The
use of regional analgesia (60) especially intercostal nerve blocks is an integral part of the
multimodal approach because of the superior analgesia and physiologic benefits
conferred by epidural analgesia.
This approach potentially decreases peri operative morbidity by decreasing the hormonal
and metabolic stress, reduced pain scores, earlier discharge from ICU, reduces length of
hospital stay and improved patient satisfaction.
40
PAIN MANAGEMENT ALONG THE PAIN PATHWAY
THE PAIN PATHWAY AND INTERVENTIONS THAT MODULATE PAIN AT
DIFFERENT POINTS
Pain can be attacked at different levels along its path of transmission from the nociceptors
to the Somatosensory cortex. Incorporating local anaesthetics in the management of pain
is very essential as its effective in blocking at different levels. So many options are
available for the treatment of post operative pain. By careful assessment of individual
patients incorporating the risks and benefits of each treatment modality and also
considering the patient preferences , post operative analgesic regimen should be
optimized for each patient.
41
FAST TRACKING IN CARDIAC ANAESTHESIA
DEFINITION
A perioperative anaesthetic management that aims to facilitate tracheal extubation of
patients within 1-6 hours of cardiac surgery. Many centers widely consider fast track
extubation upto 8-10 hrs after surgery (98). Over the years practice of cardiac
anaesthesia have shifted from based on high dose opioid technique to moderate dose of
opioids, short acting muscle relaxants and volatile anaesthetics, with the primary goal of
cost containment and effective resource use. This new development also led to renewed
interest in perioperative pain management involving multimodal analgesic techniques
that facilitate rapid tracheal exubation such as regional blocks, intrathecal, epidural
analgesic techniques and supplementary non steroidal anti inflammatory drugs (99).
BENEFITS
Decreased duration of intubation(100)
Decreased length of intensive care unit stay
Decreased cost
GOALS OF VENTILATORY MANAGEMENT IN FAST TRACKING
Initial Ventilation Parameters
Assist control ventilation at 10–12 beats/min
Tidal volume 8–10 mL/kg
PEEP 5 cm H2O
Maintenance of Arterial Blood Gases pH 7.35–7.45 PaCO2 35–45 mm Hg
PaO2 >90 mm Hg Saturations >95%
42
Extubation Criteria
normal Arterial blood gases
Awake and alert
Hemodynamically stable
No active bleeding (<400 mL/2 h)
Temperature >36°C
Return of muscle strength (>5 s, head lift/strong hand grip)
EVIDENCE
Several randomized trails and metaanalysis have addressed the efficacy and safety of fast
track cardiac surgery protocol and have found no evidence of increased risk of morbidity
and mortality (100). It is recommended to be a safer practice in low to moderate risk
cardiac surgical patients (98).
NUMERICAL RATING SCALE
Pain is a complex, subjective, perceptual phenomenon with a number of dimensions –
intensity, quality, time course , impact ,and personal meaning that are uniquely
expressed by each individual and can be measured indirectly only. Numerical rating
scale have been used in the social and behavioral sciences for measuring a number of
subjective phenomena. pain doesn’t take a discreet jump to be described as none,
mild,moderate,severe..etc. to bring out the idea that pain increases or decreases in
continuum, the numerical rating scale is an useful tool. Thus numerical rating scale is an
43
simple reporting instrument that can help to quantify a patients subjective pain. Various
studies have validated the accuracy of numerical rating scale for description of pain in
different study populations and proved to be efficient in acute postoperative pain(101)
Numerical rating scale (NRS)
The numerical rating scale is administered by asking the patient to verbally estimate her
pain from a scale of 1-10.can also be used as a written instrument by asking the patient to
point out the current perception of pain from the scale. Usually NRS 1-3 (mild pain) , 4-
6 (moderate pain) ,7-10(severe pain). As such is clearly highly subjective ,these scales
are of most value when looking at change within individuals, and are of less value for
comparing across a group of individuals at one time point. Many researchers prefer to use
a method of analysis that is based on the rank ordering of scores rather than their exact
values, to avoid reading too much into the precise NRS SCORE.
RAMSAY SEDATION SCALE
The Ramsay scale was described by Ramsay and colleagues in 1974 for the purpose of
monitoring sedation with alphaxalone-alphadolone (102). It continues to be the most
widely used scale for assessing and monitoring sedation in daily practice, as well as in
44
clinical research (103). It spans the continuum of sedation but does not clearly separate
purposeful from nonpurposeful responsesIt divides a patient's level of sedation into six
categories ranging from severe agitation to deep coma. Despite its frequent use, the
Ramsay Sedation Scale has shortcomings in patients with complex cases. When the scale
is applied at the bedside, many patients appear to conform to more than one level of
sedation.
Level Characteristics
1 Patient awake, anxious, agitated, or restless
2 Patient awake, cooperative, orientated, and tranquil
3 Patient drowsy, with response to commands
4 Patient asleep, brisk response to glabella tap or loud auditory stimulus
5 Patient asleep, sluggish response to stimulus
6 Patient has no response to firm nail-bed pressure or other noxious stimuli
MATERIALS AND METHODS
45
MATERIALS AND METHODS
STUDY SETTING
The study was conducted in Sree Chitra Institute for Medical Sciences and
Technology(SCTIMST), which is a University-level hospital, a Tertiary care Teaching
Hospital and Referral center, performing 1200-1400 Cardiac surgeries in a year.
APPROVAL FROM INSTITUTIONAL ETHICS COMMITTEE
Our study was approved by the Technical advisory committee (TAC) and Institutional
Ethics Committee(IEC) of our Institute, Sree Chitra Institute for Medical Sciences and
Technology(SCTIMST) ,Thiruvananthapuram, Kerala. (Annexure)
TAC APPROVAL NO: SCT-/S/2015/876 dated 25.01.2019
IEC APPROVAL NO: SCT/IEC/1267/AUGUST-2018
STUDY DESIGN
Study Type: Prospective, Double Blinded Intervention study.
Study Design: Allocation: - Randomised
Intervention Model: - Parallel Assignment
Masking: -Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
46
SUBJECTS
In this study we recruited all sequentially encountered patients older than 40 years of age
who underwent elective Coronary Artery Bypass surgery. Potential candidates for fast
tracking after cardiac surgery were recruited according to inclusion and exclusion
criteria.
We recruited a total of 90 patients over a period of 8 months.
INCLUSION CRITERIA
> 40 years old and < 75years old
Median sternotomy
Patient undergoing Coronary Artery bypass surgery.
EXCLUSION CRITERIA
Emergency Surgeries.
Redo-surgeries.
Open Sternum
Left Ventricular Ejection Fraction < 35%
Preoperative use of narcotics or illicit drug abuse.
History of chronic intractable non-cardiac pain.
Liver or Kidney disease
Allergy to Amide group of anaesthetics, Morphine or Fentanyl.
47
Arrhythmia history or rhythm disturbances documented in ECG.
Haemodynamically unstable patients already on preoperative inotropic support or
Intra-arterial balloon pumps (IABP).
Anticipated surgery or surgery lasting more than 6hrs.
Intubation time more than 12hrs or planned for overnight ventilation.
Patients refusing to participate.
Patients refusing the offered therapeutic options in either group.
Patients refusing for parting with medical data for analysis.
Patients refusing to participate after the start of study and desire to leave the study at
any point of time.
Patients currently enrolled in another study.
Patients with inability to provide informed written consent.
Inability to complete Pain assessments.
Post-operative complications with underlying cardio-respiratory cause requiring return
to operative room for re-explorations or reinstitution of mechanical ventilation.
48
INTERVENTION AND COMPARISON GROUPS
Patients who underwent elective sternotomies were randomly assigned to one of the two
groups.
Group A: – PARASTERNAL INTERCOSTAL BLOCK
Single shot Parasternal Nerve block using 0.5% preservative free Levo-bupivacaine
preparation under Ultrasound guidance 1-1.5ml on each side in the 2nd to 6th parasternal
intercostal space and Skin infiltration using 0.5% 5ml preservative free Levobupivacaine
prior to mediastinal-chest tube drain placement.
Group B: – CONTROL group- NO INTERCOSTAL BLOCK was administered.
Pain scores using NUMERICAL RATING SCALE(NRS) were compared between the
two groups in the first post-operative day. Ramsay Sedation Scale (RSS) during weaning
phase and post tracheal extubation period were compared between the two groups on the
first post operative day.
METHOD OF RANDOMIZATION AND BLINDING
This was a prospective randomized control trail. The patients were randomized onto one
of the two groups for analysing the quality of postoperative analgesia, using Computer
generated randomized numbers of block randomization technique in blocks of ten.
Allocation concealment was done using opaque envelopes containing the method of post
operative analgesia and the serial number was written on top of the envelope. The
envelopes were opened sequentially after finding a patient who met the inclusion criteria
and consented for taking part in this study.
49
The envelope was opened by the anaesthetist performing the case and the instructions to
be followed in each group were given to them. Intra-operative anaesthesia and
Parasternal modified intercostal block was administered by the anaesthesiologist not
involved in the study, keeping the standard in Hospital anesthesia protocols practiced in
our institute.
The data collection and assessment was made by separate Resident posted in Intensive
Care Unit(ICU) under the supervision of Principal-investigator. Here also both the
physicians in ICU were unaware of the study group the patients were randomised into.
The data analysis will be done by the statistician, who will also be unaware of the group
which could have the intervention arm or the control arm. The linking of the randomised
chart to patient identity was done by the Guide to segregate and correlate the patient data
into either of the study group, labelled A and B with the final statistical analysis.
All patients enrolled, were familiarized with the pain scoring documentation
methodology, incentive spirometry and deep breathing exercises a day prior to the
procedure, and also the baseline documentation of the pain-score were done by the
Principal Investigator.
Any patient who had prolonged surgery, lasting for 6 Hrs. or more, or tracheal intubation
time more than 12 Hrs., or are electively being planned for overnight ventilation post-
surgery, or any patient requiring re-exploration were excluded from the study and
subsequent analysis.
50
TARGET SAMPLE SIZE AND RATIONALE
The sample size was calculated based on a primary outcome variable – post operative
pain assessed by Numerical Rating Scale(NRS) from a previous study in JCTVA
2007(86). We found that the difference in pain scores between the two study groups was
1.1(SD1.5)
Mean NRS score in Ropivacaine group = 2.7 +/- 1.3
Mean NRS score in Saline group= 3.8+/- 2
Sample size was calculated using the formula n=2(Z1-α/2 +Z1-β)²σ²/δ²
Based on this sample size was calculated as 45 in each group assuming the population
mean NRS to be 4mm for the Levobupivacaine group and 5mm for the morphine
group; a common within-population standard deviation to be 3, and the dropout rate
as 5%. Sample size calculated is 45 for significance level (α) of 5 with power of 80.
METHODOLOGY
All the patients were seen by the investigator on the day prior to the surgery. The
procedure and study was explained to the patients. A written informed consent was taken
from patient prior to enrollment. The Numerical rating pain scale (NRS) was explained to
all the patients.
The Anaesthetist posted for the particular patient opened the envelope on the day of
surgery and will know which technique of Postoperative analgesia to follow. The
envelope and allocation sheet were destroyed after this.
51
ANAESTHESIOLOGY AND INTRA-OPERATIVE MANAGEMENT PROTOCOL
FOLLOWED :
All patients were premeditated with oral diazepam 0.2mg/Kg the night before surgery.
In the operating room, an 18-gauge IV cannula and a 20-gauge radial arterial cannula
inserted.
After monitoring electrocardiography and invasive arterial pressures, anaesthesia was
induced using 0.1 mg/Kg Midazolam, 5-10 μg/kg Fentanyl and 1 mg/kg Propofol, the
tracheal intubation to be facilitated using to 0.1 mg/kg Pancuronium. A triple-lumen
central venous catheter (14/16/16 Gauge) introduced into the right internal jugular vein,
for inotropes and dilators and Central venous Pressure monitoring. Mechanical
ventilation and tidal volume (8–10 ml/kg) regulated under a maintained respiratory rate
of 12-15 (Inspiratory to Expiratory ratio of 1:2) and end tidal CO2 (35±5 mmHg).
Standard of care Intraoperative monitoring included electrocardiography, invasive
arterial blood pressure, pulse oximetry, end-tidal carbon dioxide, and serial arterial blood
gas analysis. Central venous pressure, central nasopharyngeal temperature, and urine
output was continuously monitored as per our routine in hospital standard anesthesia
protocol.
In intercostal block group, Under Ultrasound guidance, parasternal modified nerve
blockade achieved using 0.5% Preservative free Levobupivacaine, 1-1.5ml on each side
in the 2nd to 6th parasternal intercostal space. Also 5ml of 0.5%levobupivacaine local
anaesthetic infiltration was give above the manubrium sterni to block the superficial
52
sensory nerves from T1 and supra clavicular nerve. Total drug dose dispensed is
maximum upto 3mg/Kg well below the toxic dose of levobupivacaine.
Anaesthesia maintained with 1% to 2% Sevoflurane/ Isoflurane in 50% oxygen and 50%
air and 10 to 20 μg/kg Fentanyl,according to hemodynamic response till sternotomy and
Cardiopulmonary Bypass maintaining a BIS (Bispectral Index) of less than 60. Following
heparin 400IU/Kg., activated clotting time (ACT) measured to reach > 480 seconds using
a coagulation analyzer.
Prior to the institution of cardiopulmonary Bypass(CPB), anaesthesia deepened by
administering pancuronium (0.05 mg/kg) and Fentanyl (2µg/kg). During
cardiopulmonary bypass(CPB), oxygenation achieved using a membrane oxygenator,
and sevoflurane/ Isoflurane will be administered using the oxygenator at 1.0%.
All of the patients included in the present study received IV morphine infusions at 10-
20mcgm/Kg/hr from institution of CPB till 48hrs post-surgery as a routine part of
standard in-hospital analgesia protocol. During rewarming phase Heparin administered
to keep ACT >480 seconds. Repeat dosing of Midazolam 0.05mg/Kg and Fentanyl upto
2µg/Kg was given to deepen the plane of anaesthesia.
At the conclusion of surgery, all anaesthetics discontinued and before the placement of
chest tube drains, skin entrance site for the chest tube placement was deeply infiltrated
with 5 mL of 0.5% preservative free Levobupivacaine in the intercostal block group.
Patients were transferred to the ICU as routinely practiced and connected to a mechanical
ventilator. Arterial oxygen saturation, invasive arterial pressures, and central venous
pressures monitored. The time from the tracheal intubation to tracheal extubation will be
defined as “extubation time.”
53
ICU tracheal-extubation criteria to be considered are as follows: Patient awake and
cooperative, steady rhythm, inspiratory sub-pressure >20 cmH2O, tidal volume >10
ml/Kg, airway opening pressure (PaO2) >80 mmHg, fraction of inspired oxygen (FIO2)
<50%, pH >7.30, temperature >36°C, drainage volume <100 mL/hrs for 2 hrs.
Pain intensity will be assessed at extubation and at 4hourly interval since tracheal-
extubation. Any pain complaints from the patient or supplemented Nurse monitored
analgesia were documented. All patients were given 1 g of acetaminophen 12 hourly from
the time of ICU admission as routinely practiced ICU analgesic protocol.
As per Nurse Controlled Analgesia(NCA) protocol ,rescue analgesia with IV Tramadol
50mg stat (slowly over 10-15minutes) and increase in morphine infusion at10µg/Kg/Hrs
with increment upto a maximum of 60µg/Kg/Hrs, alerting the ICU anesthesiologist on
duty. The IV morphine infusion will be tapered down, back to basal 10µg/Kg/hrs in
5µg/Kg/hrs tapering down dose at an half hourly interval when the patient is pain free
and Ramsay Sedation Score remains 1 or 2 without any PaCO2 buildup of >45mmHg as
shown in Arterial blood gas analysis.
Any patients not responding to the study protocol for pain management with further
scaling up of IV morphine infusion beyond 60µg/Kg/hrs. with complaints of pain were
labeled as “Failure of Study medications”,and will be managed as per other analgesic
supplemental modalities deemed clinically suitable for that patient.
Patients with RSS of 1 without any clinical or investigatory modality showing evidence
suggestive of any underlying cardio-respiratory cause for patient instability will be
labeled as “Delirious” and were managed accordingly.
54
Total opioid consumption intra-operatively, postoperatively and post tracheal-extubation
was documented along with requirement of Rescue analgesics intake, or top up physician
prescription of analgesics.
Any opioid-related side effects (nausea/ vomiting /shallow respiration) were recorded for
each patient. Postoperative nausea and vomiting was treated with 4 mg IV Ondansetron,
as required and documented. Physiotherapy and incentive spirometry were given to all
patients and pain scores were noted while performing breathing exercises.
55
STATISTICAL ANALYSIS
The data collected from the patients were entered in MICROSOFT EXCEL.
Numerical data were expressed as mean ± standard deviation or median with interquartile
range and categorical data as frequencies and percentage. Comparison of categorical
variables were tested using the chi-square and Fisher’s exact test Pain scores at different
time points 15MIN,4,8,12,16,20,24 hours during the first post operative day between the
two groups were compared using STUDENTS ‘t’ TEST or the MANN- WHITNEY U
TEST.
Results were considered statistically significant if p value is <0.05
The statistical software used was SPSS ver 16.0
RESULTS
56
RESULTS
Group A- PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP
Group B- CONTROL GROUP-NO BLOCK WAS ADMINISTERED
Ninety patients, 45 in each group were included in this study during the period of 8
months from AUGUST 2018 to APRIL 2019.
The baseline characteristics are shown in Table 1. The baseline data between the two
groups were compared. The data were comparable; there were no significant differences
as shown by p values in the table.
TABLE 1: BASELINE CHARACTERISTICS
PATIENT
CHARACTERISTICS
PARASTERNAL
INTERCOSTAL
NERVE BLOCK
GROUP
CONTROL
GROUP
T
VALUE
p
VALUE
MEAN SD MEAN SD
MEAN AGE (years) 59.9 9 59.6 7.5 0.91 0.849
MEAN WEIGHT(kg) 67.7 10.0 67.3 10.9 0.171 0.865
MEAN HEIGHT(cm) 166.7 7.4 165.6 7.5 0.723 0.472
BODY SURFACE
AREA
1.77 0.16 1.75 0.16 0.405 0.686
57
FIGURE 1 : SEX RATIO
Figure 1 shows the number of males and females separately in the parasternal intercostal
nerve block and control group. Overall the male patients who took part in the study were
more than the female patients (M:F=74:16)
Both the Groups had equal distribution of male and female patients(M:F=37:8)
Figure 1
37
8
37
8
M A L E
F E M A L E
SEX RATIO
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
58
TABLE 2 and FIGURE 2: AGE DISTRIBUTION
Figure 2shows the distribution of age between both the groups.
Intervention group had more number of patients <50 yrs of age(7 patients)
22 patients were more than 60 yrs of age in both groups.
However mean age for both intercostal and control groups were similar 59.9and
59.6)respectively.
TABLE 2 AGE DISTRIBUTION
AGE
PARASTERNAL
INTERCOSTAL NERVE
BLOCK GROUP(n=45)
CONTROL
GROUP(N=45) TOTAL
χ2 Df
p VALUE
N % n % n %
≤ 50 7 15.6 5 11.1 12 13.3
0.451
2
0.798
51 – 60 16 35.6 18 40 34 37.8
>60 22 48.9 22 48.9 44 48.9
Total 45 100 45 100 90 100
FIGURE 2
7
16
22
5
18
22
0
5
10
15
20
25
<50 51-60 >60
NO
OF
PA
TIEN
TS
AGE DISTRIBUTION
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP INTRAVENOUS MORPHINE GROUP
59
TABLE 3 PRE OP CARDIAC EVALUATION
CARDIAC EVALUATION
PARASTERNAL
INTERCOSTAL NERVE
BLOCK GROUP
CONTROL
GROUP
p VALUE
EJECTION FRACTION% 58.7% 60.1% 0.33
RECENT ACUTE
CORONARY
INSULT(<3MONTHS)
YES 13 28.9% 16 35.6%
0.499 NO 32 71.1% 29 64.4%
REGIONAL WALL
ABNORMALITY
YES
17 37.8% 19 42.2%
0.667
NO 28 62.2% 26 57.8%
The salient pre operative cardiac function parameters are summarized in table 3
FIGURE 3 EJECTION FRACTION
Figure 3 shows the mean of ejection fraction between the two groups. In the parasternal
intercostal block group the mean EF(%) was 58.7%(SD + 7.4%) and in the control group
the mean EF was 60.1%(SD + 5.9%). All patients in both the groups had pre operative
good left ventricular function and the difference was not statistically significant(p value
0.33)
58.7 60.1
40
45
50
55
60
65
70
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
EJE
CTI
ON
FR
AC
TIO
N(%
)
EJECTION FRACTION
60
FIGURE 4 RECENT CORONARY EVENTS
Figure 4 demonstrates the incidence of acute coronary events among the patients between
the two groups. In the parasternal intercostal group 28.9% of patients had history of
recent acute coronary event and 35.6% of patients in the intravenous morphine group.
FIGURE 5 REGIONAL WALL ABNORMALITY
Figure 5 shows the percentage of patients with regional wall abnormalities in pre
operative trans thoracic echocardiogram evaluation in both the groups.
28.9
71.1
35.6
64.4
0
10
20
30
40
50
60
70
80
YES NO
NO
OF
PA
TIEN
TS(%
)
RECENT CORONARY EVENTS
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
37.8 62.2
42.2
57.8
0
20
40
60
80
100
120
140
YES NO
NO
OF
PA
TIEN
TS(%
)
REGIONAL WALL MOTION ABNORMALITY
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
61
TABLE 4 INTRAOPERATIVE PARAMETERS
PARASTERNAL
INTERCOSTAL
NERVE BLOCK
GROUP(n=45)
CONTROL
GROUP(n=45)
t
VALUE
p
VALUE
MEAN SD MEAN SD
CPB TIME 104.9 13.1 101.9 12.3 1.166 0.12
AXC TIME 54.8 10.03 56.96 8.43 -0.88 0.19
TOTAL DOSE OF
FENTANYL (mcg) 675.6 188.8 976.7 169.1 -7.97 <0.001
FIGURE 6
The mean cardiopulmonary bypass time and aortic cross clamp time for both the groups
are demonstrated in figure 6. Duration of these parameters were not statistically
significant
104.9 101.9
90
95
100
105
110
PARASTERNALINTERCOSTALNERVE BLOCK
GROUP
CONTROL GROUP
CP
B T
IME
(min
)
CARDIOPULMONARY BYPASS TIME
54.8
56.96
50
52
54
56
58
60
PARASTERNALINTERCOSTAL NERVE
BLOCK GROUP
CONTROL GROUP
AX
C T
IME(
min
)
AORTIC CROSS CLAMP TIME
62
FIGURE 7 INTRAOPERATIVE FENTANYL DOSAGE
Total amount of fentanyl used in two groups is shown in figure 11.
The mean amount of fentanyl used in both groups(epidural 675.6g,morphine976.7)
vary significantly (<0.0001).
Patients in control group required higher dosage of fentanyl for adequate analgesia
intraoperatively.
675.6
976.7
500
600
700
800
900
1000
PARASTERNAL INTERCOSTAL NERVE BLOCKGROUP
CONTROL GROUP
FEN
TAN
YL(m
cg)
INTAOPERATIVE FENTANYL DOSAGE
63
TABLE 5 DURATION OF MECHANICAL VENTILATION
PARASTERNAL
INTERCOSTAL
NERVE BLOCK
GROUP(n=45)
CONTROL
GROUP(n=45) t VALUE
p VALUE
MEAN SD MEAN SD
DURATION OF
MECHANICAL
VENTILATION
5.38 0.43 5.54 0.40 -1.842 0.069
Figure 8
Fig 8 shows there was no statiscally significant difference in the duration of mechanical
ventilation in either of the groups
5.38 5.54
1
2
3
4
5
6
7
8
9
10
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
NO
OF
HO
UR
S
DURATION OF MECHANICAL VENTILATION
64
TABLE 6: NUMERICAL RATING SCALE(NRS)[PAIN SCORE]
AT REST POST EXTUBATION
TIME AFTER
EXTUBATION
NRS SCALE (POST EXTUBATION)
p
VALUE
PARASTERNAL
INTERCOSTAL NERVE
BLOCK GROUP
CONTROL GROUP
MEAN SD MEDIAN IQR MEAN SD MEDIAN IQR
15 minutes 3.29 0.79 3 3-4 4.82 0.68 5 4-5 <0.001
4 hrs 2.89 0.57 3 3-3 5.04 0.52 5 5-5 <0.001
8 hrs 3.58 0.5 4 3-4 5.09 0.51 5 5-5 <0.001
12 hrs 3.64 0.48 4 3-4 5.02 0.52 5 5-5 <0.001
16 hrs 3.42 0.62 3 3-4 5.07 0.53 5 5-5 <0.001
20 hrs 3.42 0.62 3 3-4 5.03 0.54 5 5-5 <0.001
24 hrs 3.49 0.76 3 3-4 5.09 0.54 5 5-5 <0.001
65
FIGURE 9 NUMERICAL RATING SCALE(NRS)[PAIN SCORE]
AT REST POST EXTUBATION
As seen from the figure 9 pain scores in the intercostal group were significantly less than
the control group. And the score were always less than 4 at different time points for 24
hrs showed patients in this group had better quality of analgesia compared to the other
group.
3.29 2.89
3.58 3.64 3.42 3.42 3.49
4.82 5.04 5.09 5.02 5.07 5.03 5.09
0
1
2
3
4
5
6
7
8
9
10
11
1 5 M I N U T E S 4 H R S 8 H R S 1 2 H R S 1 6 H R S 2 0 H R S 2 4 H R S
NR
S SC
OR
E
NUMERICAL RATING SCALE(NRS)[PAIN SCORE] AT REST POST EXTUBATION
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
66
TABLE 7 NUMERICAL RATING SCALE(NRS)[PAIN SCORE
DURING BREATHING EXERCISES POST EXTUBATION
TIME AFTER
EXTUBATION
NRS SCALE (POST EXTUBATION)
P
VALUE
PARASTERNAL
INTERCOSTAL NERVE
BLOCK GROUP
CONTROL GROUP
MEAN SD MEDIAN IQR MEAN SD MEDIAN IQR
4 hrs (Breathing
exercise) 2.96 0.3 3 3-3 5.07 0.54 5 5-5 <0.001
8 hrs (Breathing
exercise) 3.58 0.54 4 3-4 5.13 0.53 5 5-5 <0.001
12 hrs (Breathing
exercise) 3.6 0.5 4 3-4 5.05 0.53 5 5-5 <0.001
16 hrs (Breathing
exercise) 3.67 0.56 4 3-4 5.16 0.53 5 5-5 <0.001
20 hrs (Breathing
exercise) 3.62 0.56 4 3-4 5.11 0.53 5 5-5 <0.001
24 hrs (Breathing
exercise) 3.71 0.66 4 3-4 5.05 0.53 5 5-5 <0.001
67
FIGURE 10 NUMERICAL RATING SCALE(NRS)[PAIN SCORE]
DURING BREATHING EXERCISES POST EXTUBATION
Figure 10 shows the mean NRS pain scores at various time points, while was patient was
doing breathing exercises and respiratory physiotherapy. Pain scores were significantly
less in patients who received intercostal block
2.96 3.58 3.6 3.67 3.62 3.71
5.07 5.13 5.05 5.16 5.11 5.05
0
1
2
3
4
5
6
7
8
9
10
11
4 H R S ( B R E A T H I N G
E X E R C I S E )
8 H R S ( B R E A T H I N G
E X E R C I S E )
1 2 H R S ( B R E A T H I N G
E X E R C I S E )
1 6 H R S ( B R E A T H I N G
E X E R C I S E )
2 0 H R S ( B R E A T H I N G
E X E R C I S E )
2 4 H R S ( B R E A T H I N G
E X E R C I S E )
NR
S SC
OR
E
NUMERICAL RATING SCALE(NRS) DURING
BREATHING EX ERCISES POST EX TUBATION
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
68
TABLE 8 RAMSAY SEDATION SCALE AFTER EXTUBATION
TIME AFTER
EXTUBATION
PARASTERNAL
INTERCOSTAL COSTAL
NERVE BLOCK GROUP (n=45)
CONTROL GROUP (n=45)
p
VALUE
RAMSAY SEDATION SCALE
RAMSAY SEDATION SCALE
1
2
3
1
2
3
N % N % n % n % n % n %
15 minutes 11 24.4 31 68.9 3 6.7 5 11.1 33 73.3 7 15.6 0.141
4 hrs 0 0 45 100 0 0 1 2.2 34 75.6 10 22.2 0.002
8 hrs 0 0 28 62.2 17 37.8 5 11.1 37 82.2 3 6.7 <0.001
12 hrs 1 2.2 42 93.3 2 4.4 5 11.1 37 82.2 3 6.7 0.204
16 hrs 0 0 45 100 0 0 5 11.1 37 82.2 3 6.7 0.012
20 hrs 0 0 45 100 0 0 5 11.1 37 82.2 3 6.7 0.012
24 hrs 0 0 45 100 0 0 5 11.1 37 82.2 3 6.7 0.012
From Table 8 we could infer that, patients who received opioid based analgesia in the
post operative period were more sedated. There was significant difference in sedation
scale even 8 hrs after extubation. Patients in the control group were drowsy, arousable to
commands(NRS 3) where as almost all patients in the intercostal group were awake, alert
and comfortable(NRS 2)
69
TABLE 9 RESCUE ANALGESIA
Table 9 and Figure 11 depicits the no of patients requiring additional rescue analgesia.
Patients in intravenous morphine group required more rescue analgesics and it is
statiscally significant
RESCUE
ANALGESIA
PARASTERNAL
INTERCOSTAL COSTAL
NERVE BLOCK GROUP
(n=45)
CONTROL
GROUP (n=45)
P Value
n % n %
15min 0 0 3 6.6% 0.044
4 hrs 2 4.4 8 17.8 0.044
8 hrs 2 4.4 7 15.6 0.079
12 hrs 2 4.4 8 17.8 0.044
16 hrs 1 2.2 8 17.8 0.014
20 hrs 2 4.4 8 17.8 0.044
24 hrs 3 6.7 8 17.8 0.108
FIGURE 11 RESCUE ANALGESIA
0
2
4
6
8
10
15min 4 hrs 8 hrs 12 hrs 16 hrs 20 hrs 24 hrs
NO
OF
PA
TIE
NTS
RESCUE ANALGESIA
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
70
TABLE 10 SIDE EFFECTS
SIDE EFFECTS
(Post extubation)
PARASTERNAL
INTERCOSTAL
NERVE BLOCK
GROUP
CONTROL
GROUP Total
p VALUE
N % N % N %
15 minutes 0 0 1 2.2 1 1.1 0.315
4 hrs 1 2.2 6 13.3 7 7.8 0.049
8 hrs 1 2.2 7 15.5 8 8.8 0.026
12 hrs 1 2.2 7 15.5 8 8.8 0.026
16 hrs 1 2.2 7 15.5 8 8.8 0.026
20 hrs 1 2.2 7 15.5 8 8.8 0.026
24 hrs 1 2.2 7 15.5 8 8.8 0.026
FIGURE 12
The incidence of side effects like nausea, vomiting were higher in the control group and it
was statistically significant.
0
5
10
15
20
15 minutes 4 hrs 8 hrs 12 hrs 16 hrs 20 hrs 24 hrs
NO
OF
PA
TIEN
TS(%
)
INCIDENCE OF SIDE EFFECTS
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
71
TABLE 11 COOPERATION WITH SPIROMETRY
COOPERATION WITH SPIROMETRY
PARASTERNAL INTERCOSTAL NERVE
BLOCK GROUP CONTROL GROUP Total
p VALUE
n % N % N %
8 hrs 45 100 40 88.9 85 94.4 0.021
12 hrs 45 100 40 88.9 85 94.4 0.021
16 hrs 45 100 40 88.9 85 94.4 0.021
20 hrs 45 100 40 88.9 85 94.4 0.021
24 hrs 45 100 40 88.9 85 94.4 0.021
FIGURE 13
As seen in table 11 and figure 12,patients in intercostal block group were more
cooperative for spirometry and it was statistically significant.
80
82
84
86
88
90
92
94
96
98
100
8 hrs 12 hrs 16 hrs 20 hrs 24 hrs
NO
OF
PA
TIEN
TS(%
)
COOPERATION WITH SPIROMETRY
PARASTERNAL INTERCOSTAL NERVE BLOCK GROUP CONTROL GROUP
DISCUSSION
72
DISCUSSION
This study was done in the post operative adult cardiothoracic unit at Sree Chitra Tirunal
Institute for Medical Sciences and Technology(SCTIMST).
This study was designed as a randomized controlled trial and aimed for looking at the
Quality of pain relief with Pre-emptive analgesia technique effected from single shot
parasternal modified intercostal block and its role in Fast tracking after sternotomy in
post operative intensive care setting.
The purpose of this study is not to demonstrate the superiority of one analgesic regime
over other, but to find out whether ultrasound guided parasternal intercostal block as a
preemptive analgesic technique be effective in improving quality of post operative
analgesia .
This study is a Non- inferiority clinical trail.
Pain following sternotomy is described as very severe and the analgesia management of
such post operative situation is particularly challenging(104).
Adequate and effective pain management is pivotal in decreasing post operative
mortality and morbidity after cardiac surgery. Effective post operative analgesia relieves
suffering for the patient, promotes early recovery, leads to early mobilization, shortens
hospital stay and increase patient satisfaction apart from playing an important role in
reducing complications related to cardiac surgeries(105)
It is well known fact that pain control regimens should not be standardized; it should be
tailored to individual needs of the patient taking into account various factors . In general,
73
goal for all post operative patients is to minimize the side effects of various drugs , while
providing adequate analgesia.
This study was proposed after going through literature search using pubmed and
Cochrane database. Pain management after sternotomy have underwent extensive
modifications over several years. Various analgesic modalities had been proposed, and
extensively reviewed of their merits and demerits. Still no analgesic regime is found to be
the best with definite advantages over the others. Recently interfascial blocks are gaining
popularity as an ideal technique for post sternotomy analgesia (106).
Analgesia with opioids is one of the earliest and effective technique for post operative
analgesia for sternotomy, which is a still popular method practiced in various centres
including our institution. It is simple, safer, reliable and less time consuming. Opioids as
a sole post operative analgesia technique has its own drawbacks like nausea and
vomiting, sedation ,respiratory depression, poor control of breakthrough pain which are
detrimental especially when related to cardiac surgery (49).
Regional anaesthesia techniques like Intrathecal and epidural local anaesthetics with
opioids have been used in cardiac surgeries with some benefits. Stress response
attenuation, reliable analgesia, cardiac symphatectectomy are some of the definite
advantages. But it also carries huge risk of hematoma formation in anticoagulated
patients, dural puncture, hypotension, high failure rate which overweighs the benefits
(107). So Use of these neuraxial techniques in adult cardiac surgery patients still remains
controversial and debatable (108).
74
To overcome these dis advantages of neuraxial techniques, recently various interfascial
blocks have been described which are technically simple, long lasting without any
associated major complications (106). Some of the blocks described are pectoral nerve
block, serratus anterior plane block, pecto intercosto fascial (109) and transverse thoracic
plane block(110), intercostal nerve block ,erector spinae block (111). These regional
blocks form integral part of multimodal analgesic model in the era of fast tracking after
cardiac surgery (98). Though the safety and efficacy of these blocks are not firmly
established due to lack of large randomized control trails.
Intercostal nerve block with local anaesthetics have long been practiced in thoracic
surgeries where it is found to be a reliable and effective analgesic (112). In cardiac
surgeries, intercostal blocks have traditionally been practiced as single shot local
anaesthetic infiltration in each intercostal space under vision by the surgeon before
sternal closure (113). This technique have been studied widely and provide superior
analgesia than conventional opioid analgesic regimen (114)and can be administered even
in ani coagulated patients. The previous studies focusing on postoperative analgesic
effect exclusively with post-surgery parasternal block, just prior to sternal closure had
certain limitations .The limitations were about the concerns of confounding effect
produced by the general anaesthesia drugs, intraoperative opioids and activation of local
incisional inflammatory responses, which could have masked the benefits and results
under various clinical studies.
The concept of Pre emptive analgesia initiated before surgical incision have demonstrated
benefits in reducing acute post operative pain and prevents development of chronic
75
neuropathic pain (115) (116). It hasn’t been extensively studied in relation to cardiac
surgeries.
There are many studies which site the effects of preoperative or pre-procedural single
shot peripheral nerve blocks, showing to lower the pain scores postoperatively and
reduced supplemental analgesics consumption. These infiltrated local-anaesthetic nerve
block effect durations and the analgesic effects, were extending well beyond the intended
duration of pharmacodynamic profile of nerve blocks with the supplemental analgesic
and opioid usages (117).
The review of literature shows all studies, comparing and documenting the beneficial
effects of Parasternal intercoastal blocks in paediatric and adult patients, administered
just prior to sternal closure after surgery (113).
The Parasternal modified intercostal nerve block under Ultrasound guidance, is a simple
procedure (109), when compared with other interventions - epidural blocks or
paravertebral blocks, which are more invasive and skill intensive.
In this method, Blocks were performed from the lower border of the 2nd rib under
ultrasound guidance using a linear probe. The ultrasound scan was performed from lateral
to medial in the intercostal space. The intercostal muscles and pleura were identified
along the lower border of the rib. At the lateral border of the sternum, approximately 3-
4cm from midline, internal thoracic vessels lying anterior to transverse thoracic muscle
are identified using colour doppler. The needle is inserted carefully in-plane to follow its
tip perfectly to prevent pneumothorax or vascular injury. After negative aspiration,1-
1.5milliliters of 0.5%levo bupivacaine was injected beyond the internal intercostal
76
muscles, anterior to the transversus thoracic muscle to block the terminal anterior branch
of the intercostal nerve and spread to the perivascular sympathetic plexus. Spread of the
local anaesthetic identified by the separation of the fascial plane and depression of pleura.
Same technique was followed to block T3-T6 intercostal nerves at the level of lower
border of 3rd to 6th ribs. Contralateral side parasternal intercostal block was performed
along the corresponding ribs. Also 3ml of 0.5%levobupivacaine local anaesthetic
infiltration was give above the manubrium sterni to block the superficial sensory nerves
from T1 and supra clavicular nerve. At the end of surgery chest drain sites were
infiltrated with additional 3ml of 0.5% levobupivacaine. Levobupivacaine, pure S(-)
enantiomer of racemic bupivacaine is a long acting local anaesthetic, but with significant
lower cardiac and neuro toxicity profile than bupivacaine(118). Taking into consideration
of greater absorption area in the parasternal space, a total maximal dose of 3mg/kg was
used. No complications related were observed in our study.
COMPARISON OF BASELINE CHARACTERISTICS
Demographic characteristics were well matched in both the groups(Table 1). We
compared the following variables: age , sex , height , weight , BSA. Both groups were
comparable (p value.0.05).
Only CABG patient were included in this study taking into consideration of saphenous
vein harvesting.
4 patients recruited for the study were excluded in view of re exploration post
operatively.
77
PRE OPERATIVE PATIENT CARDIAC PROFILE COMPARISON
All the patients in both the groups had preoperative good left ventricular ejection fraction,
EF>55%. Pre operative cardiac illness like recent acute coronary events(<3months) were
comparable. Transthoracic echocardiographic evaluation of regional wall motion
abnormalities also showed no statistically significant difference between the two groups
INTRAOPERATIVE CHARACTERISTICS
This study was designed in such a way that, the intra operative management of
anaesthesia was standardized and similar in both the groups.
In the intercostal nerve block group, after induction of anaesthesia, under ultrasound
guidance, parasternal intercostal block was performed to block anterior cutaneous
branches of T2-T6 intercostal nerves. Adequacy of the block was determined with
hemodynamic response to skin incision, additional fentanyl boluses were given
accordingly.
There was highly signicant difference in the intraoperative fentanyl use p<0.0001,
suggesting higher opoioid requirements intraoperatively in patients without intercostal
nerve block. As per standard anaesthesia protocol intraoperative background morphine
infusion at 10-20mcg/kg/hr was started in both the groups at initiation of cardio
pulmonary bypass and continued postoperatively at 10-20mcg/kg/hr till decision of
weaning and dose adjusted according to clinical decision in ICU.
Duration of surgery, cardio pulmonary bypass time(104.9min vs101.9min) , aortic cross
clamp time(54.9min vs 56.96min) were comparable between the two groups and there
was no statiscally significant difference.
78
All patient were managed postoperatively as per fast tracking protocol practiced in our
institute. Duration of mechanical ventilation was similar in both groups(5.38hrs vs
5.54hrs). All patients were successfully weaned and tracheal-extubation achieved without
any adverse events in 6hrs after shifting to ICU(p<0.06).
In the control group, the opioid analgesic infusion is required to be stopped, because the
patients are reported to be over-sedated with an objective evidence of PaCO2 build up,
particularly during the ventilator weaning phase.
POST OPERATIVE ANALGESIA
COMPARISON OF PAIN SCORES BETWEEN PARASTERNAL
INTERCOSTAL BLOCK GROUP WITH CONTROL GROUP
We used NUMERICAL RATING SCALE (NRS) for assessing pain intensity, which is
rated by the patient themselves so that we can slightly reduce the observer bias, still the
patient bias existed. Lowest NRS score at various time points was taken for analysis.
We analysed pain scores at different time durations (15MIN,4,8,12,16,20,24 hours )
during 1st post operative day, since pain during the first postoperative day is considered
very severe and aggressive treatment of acute pain have long term benefits (119).
Quality and effectiveness of pain relief when evaluated for 24 hrs post extubation with
routine in-hospital analgesic protocol using 11-point 0-10 Verbal Numeric Rating
Scale(Figure 9), showed patients who received intercostal nerve block, had significantly
lower(p<0.001) median pain scores NRS<4 and better quality of analgesia during the
entire study period at rest and also during breathing exercises. The median pain scores
were in the range NRS5-5 in the other group (TABLE 4 AND 5).
79
The trend of NRS score for 24 hrs post extubation in both groups is depicted in figure 9
and the score were always less than 4 at different time points for 24 hrs demonstrates,
patients in the intercostal block group group had better quality of analgesia compared to
the other group supporting the beneficial effect of this preemptive analgesic strategy.
The results are consistent with similar studies by Mcdonald et al(120),Barr et al(75) that
have shown the analgesic efficacy of parasternal block. The analgesic efficacy extended
beyond the intended duration of pharmacological profile of local anaesthetic with in-
hospital based, basal-postoperative analgesic supplementation protocols (121).
MODIFIED PARASTERNAL INTERCOSTAL BLOCK TECHNIQUE
Thomas et al(109) in 2016 proposed a method of ultrasound guided parasternal
intercostal nerve for a isolated case of sternal fracture, which provided better analgesia
and improvement in ventilation. We modified this technique taking into consideration of
extent of sternotomy skin incision. And also the important aspect of left internal
mammary graft in CABG surgeries. Our needle entry point was 3-4cm away from
sternum, needle progression done under careful ultrasound guidance utilizing colour
doppler.
No adverse event of vascular injury/hematoma formation occurred in the course of our
study in all patients.
SEDATION SCALE
Post operative sedation is an important and common side effect of morphine infusion
with an incidence of 60%. Young McCaughan et al validated that sedation scale is also an
important important indicator of impending respiratory depression (43).
80
In our study , there was statistically significant difference in sedation score between the
two groups throughout the first post operative day(p<0.012).There was significant
difference in sedation scale even 8 hrs after extubation.
There is a common assumption that, adequate pain relief induces sleep. Paqueron et al
found that morphine induced sedation is not an appropriate indicator of adequate
analgesia(122). These findings , clinically induced sedation with opioids does not assure
adequate pain relief were also confirmed by a case controlled study done by lentschener
et al(123). Recent literature in 2012 by auburn et al also emphasized the titration of
intravenous morphine(124)
But in our study we demonstrated that though the sedation scores were significantly
different between the two groups, in the control group, mean scores were between 1-3
during first post operative day and only 82.2% of the patients had Ramsay score of 2 (ie)
patients were cooperative, calm, oriented .
Only during 15min after extubation, patients in both the groups had identical score. This
may be due to practice of withholding morphine infusion prior to extubation in the
control group. As a result pain scores were high in the control group at this time point
after extubation.
In our study there was one incidence of Over-sedation leading to PaCO2 build up during
the ventilator weaning phase and peri-tracheal extubation period in control group which
was not statistically significant.
81
RESCUE ANALGESIA
Apart from basal morphine infusion at 10mcg/kg/hr and 1 g of acetaminophen 12 hourly
from ICU admission, all patients whose pain score NRS>4 were given rescue analgesia as
routinely practiced ICU analgesic protocol.
As per Nurse Controlled Analgesia(NCA) IV Tramadol 50mg stat (slowly over 10-
15minutes) and increase in morphine infusion at10µg/Kg/Hrs increment upto a
maximum of 60µg/Kg/Hrs., alerting the ICU anesthesiologist on duty. The IV morphine
infusion will be tapered down, back to basal 20µg/Kg/hrs. in 5µg/Kg/hrs tapering down
dose at an half hourly interval when the patient is pain free and Ramsay Sedation Score
remains 2 any PaCO2 buildup of >45mmHg as shown in Arterial blood gas analysis.
In our study, Patients in the control group required rescue analgesia within 4 hrs of
extubation. There was a statically significant difference(7.5% vs 17.4%) in the number of
patients of requiring rescue analgesia between the two groups. Patients in intercostal
block group were more comfortable and demanded less additional analgesics from our
study. In this study there was no procedural intervention on the Presence of new onset
Chest wall pain in the first 24hrs in the post postoperative period.
SIDE EFFECTS
Main disadvantages of sole opioid based analgesic is the incidence of side effects like
nausea,vomiting, respiratory depression(125). The incidence of side effects were high in
the control group who received predominantly opioid based analgesics.
82
LIMITATIONS OF THE STUDY
It’s not a PLACEBO controlled study, as we considered giving intercostal block
with placebo in the control group as unethical.
All patients in this study are with good left ventricular function for CABG
surgeries, so the results may not be generalizable in other type of cardiac
surgeries.
We have not followed up patients until their discharge from hospital
No data was collected regarding the patient satisfication regarding the quality of
analgesia in both groups.
CONCLUSION
83
CONCLUSION
This randomized trial to assess the quality of analgesia with a single shot modified
parasternal intercostal nerve block highlights that
Patients who received intercostal block, had clinically and statistically significant
better pain scores at the end of first post operative day, both during rest and while
doing deep breathing exercises, physiotherapy sessions and coughing out
maneuvers(p<0.001).
There was less requirement of rescue analgesia and also less incidence of side
effects like nausea, vomiting, respiratory depression in patients who received
intercostal nerve block,which was statistically significant(p 0.002).
Clinically acceptable sedation scale was present throughout the study, in patient
groups who received intercostal nerve block when compared with control group
which was statistically significant (p <0.012).
The study results showed a better quality of analgesia with a intercostal nerve
block in postoperative period, which emphasized the importance of advocating
preemptive analgesia techniques in sternotomies.
All the patients included the study groups fulfilled the criteria of fast tracking and
could be weaned of ventilator as part of the study protocol.
The fact that this difference is clinically significant makes us to believe that ultrasound
guided modified parasternal intercostal blockade can be considered as an valid
alternative to traditional opioid based analgesics. This method of intercostals blockade
84
with morphine infusion ,which is practiced in our institution can be considered a easier,
safe, reliable ,less time consuming method for post sternotomy analgesia.
This study can be used as a pilot study for further extensive studies . A larger case series
and a longer follow up plan should be done which will probably give a much more
accurate estimation of pain relief. Future trails should take much more detailed
consideration of the pulmonary morbidity and sternal infections and outcome with
respect to better post operative analgesia.
BIBLIOGRAPHY
85
BIBLIOGRAPHY
1. Kianfar A, Shadvar K, Mahoori A, Azarfarin R. Pain after cardiac surgery. Crit
Care. 2007 Mar 22;11(2):P429.
2. Ferguson J, Gilroy D, Puntillo K. Dimensions of pain and analgesic
administration associated with coronary artery bypass grafting in an Australian
intensive care unit. J Adv Nurs. 1997 Dec;26(6):1065–72.
3. Ziyaeifard M, Azarfarin R, Golzari SE. A Review of Current Analgesic
Techniques in Cardiac Surgery. Is Epidural Worth it? J Cardiovasc Thorac Res.
2014;6(3):133–40.
4. Higgins TL. Pro: Early endotracheal extubation is preferable to late extubation in
patients following coronary artery surgery. J Cardiothorac Vasc Anesth. 1992
Aug 1;6(4):488–93.
5. Stein C, Schäfer M, Machelska H. Attacking pain at its source: new perspectives
on opioids. Nat Med. 2003 Aug;9(8):1003–8.
6. Ong CK-S, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive
analgesia for acute postoperative pain management: a meta-analysis. Anesth
Analg. 2005 Mar;100(3):757–73, table of contents.
7. Practice guidelines for acute pain management in the perioperative setting: an
updated report by the American Society of Anesthesiologists Task Force on Acute
Pain Management. Anesthesiology. 2012 Feb;116(2):248–73.
8. Brennan TJ. Pathophysiology of postoperative pain. Pain. 2011 Mar;152(3
Suppl):S33-40.
9. Brennan TJ, Zahn PK, Pogatzki-Zahn EM. Mechanisms of incisional pain.
Anesthesiol Clin N Am. 2005 Mar;23(1):1–20.
86
10. Wu CL, Raja SN. Treatment of acute postoperative pain. The Lancet. 2011
Jun;377(9784):2215–25.
11. Cross SA. Pathophysiology of pain. Mayo Clin Proc Mayo Clin. 1994
Apr;69(4):375–83.
12. Besson JM. The neurobiology of pain. Lancet. 1999 May 8;353(9164):1610–5.
13. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001 Sep
13;413(6852):203–10.
14. Carr DB, Goudas LC. Acute pain. Lancet. 1999 Jun 12;353(9169):2051–8.
15. Kissin I. Preemptive analgesia. Anesthesiology. 2000 Oct;93(4):1138–43.
16. Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000
Jul;85(1):109–17.
17. Kehlet H, Holte K. Effect of postoperative analgesia on surgical outcome. Br J
Anaesth. 2001 Jul;87(1):62–72.
18. Smith RC, Leung JM, Mangano DT. Postoperative myocardial ischemia in
patients undergoing coronary artery bypass graft surgery. S.P.I. Research Group.
Anesthesiology. 1991 Mar;74(3):464–73.
19. Wu CL, Fleisher LA. Outcomes research in regional anesthesia and analgesia.
Anesth Analg. 2000 Nov;91(5):1232–42.
20. Correll D. Chronic postoperative pain: recent findings in understanding and
management. F1000Research [Internet]. 2017 Jul 4 [cited 2019 Jul 18];6.
Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499782/
21. Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001 Sep
13;413(6852):203–10.
87
22. Chronic Poststernotomy Pain: Incidence, Risk Factors, Treatment, Prevention,
and the Anesthesiologist’s Role. - PubMed - NCBI [Internet]. [cited 2019 Jul 28].
Available from: https://www.ncbi.nlm.nih.gov/pubmed/28937533
23. The prevalence of chronic chest and leg pain following cardiac surgery: a
historical cohort study. - PubMed - NCBI [Internet]. [cited 2019 Jul 28].
Available from: https://www.ncbi.nlm.nih.gov/pubmed/12855337
24. Mazzeffi M, Khelemsky Y. Poststernotomy pain: a clinical review. J Cardiothorac
Vasc Anesth. 2011 Dec;25(6):1163–78.
25. Poststernotomy pain: a clinical review. - PubMed - NCBI [Internet]. [cited 2019
Jul 10]. Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=21955825
26. Mueller XM, Tinguely F, Tevaearai HT, Revelly JP, Chioléro R, von Segesser
LK. Pain location, distribution, and intensity after cardiac surgery. Chest. 2000
Aug;118(2):391–6.
27. Danelli G, Berti M, Casati A, Bobbio A, Ghisi D, Mele R, et al. Ipsilateral
shoulder pain after thoracotomy surgery: a prospective, randomized, double-blind,
placebo-controlled evaluation of the efficacy of infiltrating the phrenic nerve with
0.2%wt/vol ropivacaine. Eur J Anaesthesiol. 2007 Jul;24(7):596–601.
28. Meehan DA, McRae ME, Rourke DA, Eisenring C, Imperial FA. Analgesic
administration, pain intensity, and patient satisfaction in cardiac surgical patients.
Am J Crit Care Off Publ Am Assoc Crit-Care Nurses. 1995 Nov;4(6):435–42.
29. Moore R, Follette DM, Berkoff HA. Poststernotomy fractures and pain
management in open cardiac surgery. Chest. 1994 Nov;106(5):1339–42.
30. Greenwald LV, Baisden CE, Symbas PN. Rib fractures in coronary bypass
patients: radionuclide detection. Radiology. 1983 Aug;148(2):553–4.
88
31. Ip HYV, Abrishami A, Peng PWH, Wong J, Chung F. Predictors of postoperative
pain and analgesic consumption: a qualitative systematic review. Anesthesiology.
2009 Sep;111(3):657–77.
32. Hurley RW, Adams MCB. Sex, gender, and pain: an overview of a complex field.
Anesth Analg. 2008 Jul;107(1):309–17.
33. Egbert LD, Battit GE, Welch CE, Bartlett MK. REDUCTION OF
POSTOPERATIVE PAIN BY ENCOURAGEMENT AND INSTRUCTION OF
PATIENTS. A STUDY OF DOCTOR-PATIENT RAPPORT. N Engl J Med.
1964 Apr 16;270:825–7.
34. Cogan J. Pain management after cardiac surgery. Semin Cardiothorac Vasc
Anesth. 2010 Sep;14(3):201–4.
35. Nachiyunde B, Lam L. The efficacy of different modes of analgesia in
postoperative pain management and early mobilization in postoperative cardiac
surgical patients: A systematic review. Ann Card Anaesth. 2018 Oct 1;21(4):363.
36. Shulman M, Sandler AN, Bradley JW, Young PS, Brebner J. Postthoracotomy
pain and pulmonary function following epidural and systemic morphine.
Anesthesiology. 1984 Nov;61(5):569–75.
37. Slinger P, Shennib H, Wilson S. Postthoracotomy pulmonary function: a
comparison of epidural versus intravenous meperidine infusions. J Cardiothorac
Vasc Anesth. 1995 Apr;9(2):128–34.
38. Stein C, Schäfer M, Machelska H. Attacking pain at its source: new perspectives
on opioids. Nat Med. 2003 Aug;9(8):1003–8.
39. Lewanowitsch T, Irvine RJ. Naloxone methiodide reverses opioid-induced
respiratory depression and analgesia without withdrawal. Eur J Pharmacol. 2002
Jun 7;445(1–2):61–7.
89
40. Akins PT, McCleskey EW. Characterization of potassium currents in adult rat
sensory neurons and modulation by opioids and cyclic AMP. Neuroscience. 1993
Oct;56(3):759–69.
41. Kieffer BL, Gavériaux-Ruff C. Exploring the opioid system by gene knockout.
Prog Neurobiol. 2002 Apr;66(5):285–306.
42. Holaday JW. Cardiovascular effects of endogenous opiate systems. Annu Rev
Pharmacol Toxicol. 1983;23:541–94.
43. Stuart-Harris R, Joel SP, McDonald P, Currow D, Slevin ML. The
pharmacokinetics of morphine and morphine glucuronide metabolites after
subcutaneous bolus injection and subcutaneous infusion of morphine. Br J Clin
Pharmacol. 2000 Mar;49(3):207–14.
44. Watcha MF, White PF. Postoperative nausea and vomiting. Its etiology,
treatment, and prevention. Anesthesiology. 1992 Jul;77(1):162–84.
45. Young-McCaughan S, Miaskowski C. Definition of and mechanism for opioid-
induced sedation. Pain Manag Nurs Off J Am Soc Pain Manag Nurses. 2001
Sep;2(3):84–97.
46. Bray RJ, Woodhams AM, Vallis CJ, Kelly PJ. Morphine consumption and
respiratory depression in children receiving postoperative analgesia from
continuous morphine infusion or patient controlled analgesia. Paediatr Anaesth.
1996;6(2):129–34.
47. Walder B, Schafer M, Henzi I, Tramèr MR. Efficacy and safety of patient-
controlled opioid analgesia for acute postoperative pain. A quantitative systematic
review. Acta Anaesthesiol Scand. 2001 Aug;45(7):795–804.
48. Boldt J, Thaler E, Lehmann A, Papsdorf M, Isgro F. Pain management in cardiac
surgery patients: comparison between standard therapy and patient-controlled
analgesia regimen. J Cardiothorac Vasc Anesth. 1998 Dec;12(6):654–8.
90
49. Kwanten LE, O’Brien B, Anwar S. Opioid-Based Anesthesia and Analgesia for
Adult Cardiac Surgery: History and Narrative Review of the Literature. J
Cardiothorac Vasc Anesth. 2019 Mar 1;33(3):808–16.
50. Hynninen MS, Cheng DC, Hossain I, Carroll J, Aumbhagavan SS, Yue R, et al.
Non-steroidal anti-inflammatory drugs in treatment of postoperative pain after
cardiac surgery. Can J Anaesth J Can Anesth. 2000 Dec;47(12):1182–7.
51. Pavy T, Medley C, Murphy DF. Effect of indomethacin on pain relief after
thoracotomy. Br J Anaesth. 1990 Nov;65(5):624–7.
52. Gibson P, Weadington D, Winney RJ. NSAIDS in the postoperative period.
Clinical experience confirms risk. BMJ. 1993 Jul 24;307(6898):257–8.
53. Myles PS, Hunt JO, Holdgaard HO, McRae R, Buckland MR, Moloney J, et al.
Clonidine and cardiac surgery: haemodynamic and metabolic effects, myocardial
ischaemia and recovery. Anaesth Intensive Care. 1999 Apr;27(2):137–47.
54. Yin Y-C, Chow L-H, Tsao C-M, Chu C-C, Tsou M-Y, Chan K-H, et al. Oral
clonidine reduces myocardial ischemia in patients with coronary artery disease
undergoing noncardiac surgery. Acta Anaesthesiol Sin. 2002 Dec;40(4):197–203.
55. Howie MB, Hiestand DC, Jopling MW, Romanelli VA, Kelly WB, McSweeney
TD. Effect of oral clonidine premedication on anesthetic requirement, hormonal
response, hemodynamics, and recovery in coronary artery bypass graft surgery
patients. J Clin Anesth. 1996 Jun;8(4):263–72.
56. Rafiq S, Steinbrüchel DA, Wanscher MJ, Andersen LW, Navne A, Lilleoer NB,
et al. Multimodal analgesia versus traditional opiate based analgesia after cardiac
surgery, a randomized controlled trial. J Cardiothorac Surg. 2014 Mar 20;9:52.
57. Markham T, Wegner R, Hernandez N, Lee JW, Choi W, Eltzschig HK, et al.
Assessment of a multimodal analgesia protocol to allow the implementation of
enhanced recovery after cardiac surgery: Retrospective analysis of patient
outcomes. J Clin Anesth. 2019 May;54:76–80.
91
58. Remy C, Marret E, Bonnet F. Effects of acetaminophen on morphine side-effects
and consumption after major surgery: meta-analysis of randomized controlled
trials. Br J Anaesth. 2005 Apr;94(4):505–13.
59. Eisenberg E, Pultorak Y, Pud D, Bar-El Y. Prevalence and characteristics of post
coronary artery bypass graft surgery pain (PCP). Pain. 2001 May 1;92(1):11–7.
60. Chakravarthy M. Regional Analgesia in Cardiothoracic Surgery: A Changing
Paradigm Toward Opioid-Free Anesthesia? Ann Card Anaesth. 2018;21(3):225–
7.
61. Rodgers A, Walker N, Schug S, McKee A, Kehlet H, van Zundert A, et al.
Reduction of postoperative mortality and morbidity with epidural or spinal
anaesthesia: results from overview of randomised trials. BMJ. 2000 Dec
16;321(7275):1493.
62. Fascial Plane Blocks in Cardiac Surgery: Same but Different. - PubMed - NCBI
[Internet]. [cited 2019 Jul 23]. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/30340950
63. Davies F, Gladstone RJ, Stibbe EP. The Anatomy of the Intercostal Nerves. J
Anat. 1932 Apr;66(Pt 3):323–33.
64. Mittnacht AJC. Fascial Plane Blocks in Cardiac Surgery: Same but Different. J
Cardiothorac Vasc Anesth. 2019;33(2):426–7.
65. Ökmen K, Ökmen BM. The efficacy of serratus anterior plane block in analgesia
for thoracotomy: a retrospective study. J Anesth. 2017 Aug;31(4):579–85.
66. Versyck B, van Geffen GJ, van Houwe P. Prospective Double Blind Randomized
Placebo-Controlled Clinical Trial of the Pectoral Nerves (Pecs) Block Type II.
Surv Anesthesiol. 2017 Dec;61(5–6):140.
92
67. Kot P, Rodriguez P, Granell M, Cano B, Rovira L, Morales J, et al. The erector
spinae plane block: a narrative review. Korean J Anesthesiol. 2019
Jun;72(3):209–20.
68. Nagaraja PS, Ragavendran S, Singh NG, Asai O, Bhavya G, Manjunath N, et al.
Comparison of continuous thoracic epidural analgesia with bilateral erector spinae
plane block for perioperative pain management in cardiac surgery. Ann Card
Anaesth. 2018 Sep;21(3):323–7.
69. Blanco R, Parras T, McDonnell JG, Prats-Galino A. Serratus plane block: a novel
ultrasound-guided thoracic wall nerve block. Anaesthesia. 2013
Nov;68(11):1107–13.
70. Blanco R, Fajardo M, Parras Maldonado T. Ultrasound description of Pecs II
(modified Pecs I): a novel approach to breast surgery. Rev Esp Anestesiol
Reanim. 2012 Nov;59(9):470–5.
71. Faust RJ, Nauss LA. Post-thoracotomy intercostal block: comparison of its effects
on pulmonary function with those of intramuscular meperidine. Anesth Analg.
1976 Aug;55(4):542–6.
72. Toledo-Pereyra LH, DeMeester TR. Prospective randomized evaluation of
intrathoracic intercostal nerve block with bupivacaine on postoperative ventilatory
function. Ann Thorac Surg. 1979 Mar;27(3):203–5.
73. Sabanathan S, Smith PJ, Pradhan GN, Hashimi H, Eng JB, Mearns AJ.
Continuous intercostal nerve block for pain relief after thoracotomy. Ann Thorac
Surg. 1988 Oct;46(4):425–6.
74. Safran D, Kuhlman G, Orhant EE, Castelain MH, Journois D. Continuous
intercostal blockade with lidocaine after thoracic surgery. Clinical and
pharmacokinetic study. Anesth Analg. 1990 Apr;70(4):345–9.
93
75. Barr AM, Tutungi E, Almeida AA. Parasternal intercostal block with ropivacaine
for pain management after cardiac surgery: a double-blind, randomized,
controlled trial. J Cardiothorac Vasc Anesth. 2007 Aug;21(4):547–53.
76. Chaudhary V, Chauhan S, Choudhury M, Kiran U, Vasdev S, Talwar S.
Parasternal intercostal block with ropivacaine for postoperative analgesia in
pediatric patients undergoing cardiac surgery: a double-blind, randomized,
controlled study. J Cardiothorac Vasc Anesth. 2012 Jun;26(3):439–42.
77. Liu V, Mariano ER, Prabhakar C. Pecto-intercostal Fascial Block for Acute
Poststernotomy Pain: A Case Report. AA Pract. 2018 Jun 15;10(12):319.
78. de la Torre PA, García PD, Alvarez SL, Miguel FJG, Pérez MF. A novel
ultrasound-guided block: a promising alternative for breast analgesia. Aesthet
Surg J. 2014 Jan 1;34(1):198–200.
79. Chaney MA. Intrathecal and epidural anesthesia and analgesia for cardiac surgery.
Anesth Analg. 2006 Jan;102(1):45–64.
80. Chakravarthy M. Future of Awake Cardiac Surgery. J Cardiothorac Vasc Anesth.
2014 Jun 1;28(3):771–7.
81. Joshi GP, Bonnet F, Shah R, Wilkinson RC, Camu F, Fischer B, et al. A
systematic review of randomized trials evaluating regional techniques for
postthoracotomy analgesia. Anesth Analg. 2008 Sep;107(3):1026–40.
82. Wenk M, Schug SA. Perioperative pain management after thoracotomy. Curr
Opin Anaesthesiol. 2011 Feb;24(1):8–12.
83. Svircevic V, van Dijk D, Nierich AP, Passier MP, Kalkman CJ, van der Heijden
GJMG, et al. Meta-analysis of thoracic epidural anesthesia versus general
anesthesia for cardiac surgery. Anesthesiology. 2011 Feb;114(2):271–82.
94
84. Manikian B, Cantineau JP, Bertrand M, Kieffer E, Sartene R, Viars P.
Improvement of diaphragmatic function by a thoracic extradural block after upper
abdominal surgery. Anesthesiology. 1988 Mar;68(3):379–86.
85. Pöpping DM, Elia N, Marret E, Remy C, Tramèr MR. Protective effects of
epidural analgesia on pulmonary complications after abdominal and thoracic
surgery: a meta-analysis. Arch Surg Chic Ill 1960. 2008 Oct;143(10):990–9;
discussion 1000.
86. Fratacci MD, Kimball WR, Wain JC, Kacmarek RM, Polaner DM, Zapol WM.
Diaphragmatic shortening after thoracic surgery in humans. Effects of mechanical
ventilation and thoracic epidural anesthesia. Anesthesiology. 1993 Oct;79(4):654–
65.
87. Warner DO, Warner MA, Ritman EL. Human chest wall function during epidural
anesthesia. Anesthesiology. 1996 Oct;85(4):761–73.
88. Beattie WS, Badner NH, Choi P. Epidural analgesia reduces postoperative
myocardial infarction: a meta-analysis. Anesth Analg. 2001 Oct;93(4):853–8.
89. Oka T, Ozawa Y, Ohkubo Y. Thoracic epidural bupivacaine attenuates
supraventricular tachyarrhythmias after pulmonary resection. Anesth Analg. 2001
Aug;93(2):253–9, 1st contents page.
90. Davies RG, Myles PS, Graham JM. A comparison of the analgesic efficacy and
side-effects of paravertebral vs epidural blockade for thoracotomy--a systematic
review and meta-analysis of randomized trials. Br J Anaesth. 2006
Apr;96(4):418–26.
91. Cook TM, Counsell D, Wildsmith JAW. Major complications of central neuraxial
block: report on the Third National Audit Project of the Royal College of
Anaesthetists. Br J Anaesth. 2009 Feb;102(2):179–90.
92. Lundberg JF, Martner J, Raner C, Winsö O, Biber B. Dopamine or
norepinephrine infusion during thoracic epidural anesthesia? Differences in
95
hemodynamic effects and plasma catecholamine levels. Acta Anaesthesiol Scand.
2005 Aug;49(7):962–8.
93. Ong CK-S, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive
analgesia for acute postoperative pain management: a meta-analysis. Anesth
Analg. 2005 Mar;100(3):757–73, table of contents.
94. Woolf CJ, Salter MW. Neuronal plasticity: increasing the gain in pain. Science.
2000 Jun 9;288(5472):1765–9.
95. Gottschalk A, Smith DS. New concepts in acute pain therapy: preemptive
analgesia. Am Fam Physician. 2001 May 15;63(10):1979–84.
96. Salonen A, Kokki H, Tuovinen K. I.v. ketoprofen for analgesia after
tonsillectomy: comparison of pre- and post-operative administration. Br J
Anaesth. 2001 Mar;86(3):377–81.
97. Kehlet H. Multimodal approach to control postoperative pathophysiology and
rehabilitation. Br J Anaesth. 1997 May;78(5):606–17.
98. Wong W-T, Lai VK, Chee YE, Lee A. Fast‐track cardiac care for adult cardiac
surgical patients. Cochrane Database Syst Rev [Internet]. 2016 [cited 2019 Jul
17];(9). Available from:
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003587.pub3/fu
ll
99. Silbert BS, Myles PS. Is fast-track cardiac anesthesia now the global standard of
care? Anesth Analg. 2009 Mar;108(3):689–91.
100. Myles PS, Daly DJ, Djaiani G, Lee A, Cheng DCH. A systematic review of the
safety and effectiveness of fast-track cardiac anesthesia. Anesthesiology. 2003
Oct;99(4):982–7.
101. Pagé MG, Katz J, Stinson J, Isaac L, Martin-Pichora AL, Campbell F. Validation
of the numerical rating scale for pain intensity and unpleasantness in pediatric
96
acute postoperative pain: sensitivity to change over time. J Pain Off J Am Pain
Soc. 2012 Apr;13(4):359–69.
102. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with
alphaxalone-alphadolone. Br Med J. 1974 Jun 22;2(5920):656–9.
103. Sessler CN, Jo Grap M, Ramsay MA. Evaluating and monitoring analgesia and
sedation in the intensive care unit. Crit Care. 2008;12(Suppl 3):S2.
104. Kianfar A, Shadvar K, Mahoori A, Azarfarin R. Pain after cardiac surgery. Crit
Care. 2007;11(Suppl 2):P429.
105. Chaney MA. How Important Is Postoperative Pain After Cardiac Surgery? J
Cardiothorac Vasc Anesth. 2005 Dec 1;19(6):705–7.
106. Mittnacht AJC, Shariat A, Weiner MM, Malhotra A, Miller MA, Mahajan A, et
al. Regional Techniques for Cardiac and Cardiac-Related Procedures. J
Cardiothorac Vasc Anesth. 2019;33(2):532–46.
107. Barbosa FT, de Sousa Rodrigues CF, Castro AA, da Cunha RM, Barbosa TRBW.
Is there any benefit in associating neuraxial anesthesia to general anesthesia for
coronary artery bypass graft surgery? Braz J Anesthesiol Elsevier. 2016
Jun;66(3):304–9.
108. Ziyaeifard M, Azarfarin R, Golzari SE. A Review of Current Analgesic
Techniques in Cardiac Surgery. Is Epidural Worth it? J Cardiovasc Thorac Res.
2014;6(3):133–40.
109. Thomas KP, Sainudeen S, Jose S, Nadhari MY, Macaire PB. Ultrasound-Guided
Parasternal Block Allows Optimal Pain Relief and Ventilation Improvement After
a Sternal Fracture. Pain Ther. 2016 Jun;5(1):115–22.
110. Ueshima H, Hara E, Marui T, Otake H. The ultrasound-guided transversus
thoracic muscle plane block is effective for the median sternotomy. J Clin Anesth.
2016 Mar;29:83.
97
111. Forero M, Adhikary SD, Lopez H, Tsui C, Chin KJ. The Erector Spinae Plane
Block: A Novel Analgesic Technique in Thoracic Neuropathic Pain. Reg Anesth
Pain Med. 2016 Oct;41(5):621–7.
112. Perttunen K, Nilsson E, Heinonen J, Hirvisalo EL, Salo JA, Kalso E. Extradural,
paravertebral and intercostal nerve blocks for post-thoracotomy pain. Br J
Anaesth. 1995 Nov;75(5):541–7.
113. Barr AM, Tutungi E, Almeida AA. Parasternal intercostal block with ropivacaine
for pain management after cardiac surgery: a double-blind, randomized,
controlled trial. J Cardiothorac Vasc Anesth. 2007 Aug;21(4):547–53.
114. Chaudhary V, Chauhan S, Choudhury M, Kiran U, Vasdev S, Talwar S.
Parasternal intercostal block with ropivacaine for postoperative analgesia in
pediatric patients undergoing cardiac surgery: a double-blind, randomized,
controlled study. J Cardiothorac Vasc Anesth. 2012 Jun;26(3):439–42.
115. Ong CK-S, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive
analgesia for acute postoperative pain management: a meta-analysis. Anesth
Analg. 2005 Mar;100(3):757–73, table of contents.
116. Katz J, Clarke H, Seltzer Z. Review article: Preventive analgesia: quo vadimus?
Anesth Analg. 2011 Nov;113(5):1242–53.
117. Kocabas S, Yedicocuklu D, Yuksel E, Uysallar E, Askar F. Infiltration of the
sternotomy wound and the mediastinal tube sites with 0.25% levobupivacaine as
adjunctive treatment for postoperative pain after cardiac surgery. Eur J
Anaesthesiol. 2008 Oct;25(10):842–9.
118. Burlacu CL, Buggy DJ. Update on local anesthetics: focus on levobupivacaine.
Ther Clin Risk Manag. 2008 Apr;4(2):381–92.
119. Kehlet H, Dahl JB. Anaesthesia, surgery, and challenges in postoperative
recovery. Lancet Lond Engl. 2003 Dec 6;362(9399):1921–8.
98
120. Parasternal block and local anesthetic infiltration with levobupivacaine after
cardiac surgery with desflurane: the effect on postoperative pain, p... - PubMed -
NCBI [Internet]. [cited 2019 Jul 23]. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/15616047
121. Comparison of Parasternal Intercostal Block Using Ropivacaine or bupivacaine
for Postoperative Analgesia in Patients Undergoing Cardiac Surgery [Internet].
[cited 2019 Jul 23]. Available from:
https://www.scirp.org/journal/PaperInformation.aspx?PaperID=57528
122. Paqueron X, Lumbroso A, Mergoni P, Aubrun F, Langeron O, Coriat P, et al. Is
morphine-induced sedation synonymous with analgesia during intravenous
morphine titration? Br J Anaesth. 2002 Nov;89(5):697–701.
123. Lentschener C, Tostivint P, White PF, Gentili ME, Ozier Y. Opioid-induced
sedation in the postanesthesia care unit does not insure adequate pain relief: a
case-control study. Anesth Analg. 2007 Oct;105(4):1143–7, table of contents.
124. Aubrun F, Mazoit J-X, Riou B. Postoperative intravenous morphine titration. Br J
Anaesth. 2012 Feb;108(2):193–201.
125. Postoperative nausea and vomiting. Its etiology, treatment, and prevention. -
PubMed - NCBI [Internet]. [cited 2019 Jul 23]. Available from:
https://www.ncbi.nlm.nih.gov/pubmed/1609990
ANNEXURES
ANNEXURE – i
ANNEXURE – ii
PATIENT INFORMATION SHEET
SREE CHITRA TIRUNAL INSTITUTE OF MEDICAL SCIENCES AND TECHNOLOGY DEPARTMENT OF CARDIAC ANAESTHESIOLOGY
Ultrasound guided Parasternal Modified-Intercostal nerve block: Role as a preemptive analgesic adjunct in fast tracking for mitigating postoperative Sternotomy Pain Information sheet
You are being requested to participate in a study to see if a technique called INTERCOSTAL NERVE BLOCK can help give you better pain relief after cardiac surgery.
Routine pain management after cardiac surgery
Post operative pain after heart surgery is treated with intravenous/oral pain killers usually opoids(like
morphine) and NSAIDS(paracetamol). Some times these drugs can cause nausea, vomiting,
drowsiness. Occasionally pain relief may not be complete.
Hence we are doing this study to Identify the best possible method with minimal side effects for post
operative pain relief after heart surgery.
We hope to include about 90 patients in this study.
What is intercostal nerve block?
The major source of pain for the patients after any cardiac surgery, is from the Sternotomy-incision and pleuro-mediastinal drain tube placement sites
The intercostal space (ICS) is the space between 2 adjacent ribs of the thoracic cage There are 11 ICSs on each side There are 11 pairs of ICNs (T1-T11) which are anterior divisions of the thoracic spinal nerves. They course through the intercostal spaces accompanied by the intercostal vessels. They provide sensory and motor innervation to the thoracic and abdominal wall and sensory innervation to the parietal pleura and peritoneum.
An intercostal block is the injection of a local anesthetic in the area between two ribs where the intercostal nerve is located. We are planning to block the nerves carrying pain signals from the sternal wound site and pleuro mediastinal drain site ,that is, 6 (T3-T8)intercostal nerves on both sides will be blocked. It is done under ultrasound guidance to avoid any complications. It is a standard regional anaesthesia technique under ultrasound guidance. This procedure when undertaken with an anesthetic drug injected around the nerves that carry signal from that part of your body to spinal cord, could be instrumental in providing supplementary pain relief and preemptive analgesia at that operated site post surgically.
What are the potential problems with this technique?
Intercostal nerve block technique is being routinely practiced for various major thoracic surgeries and is proven to be very beneficial. There are no potential procedural complications reported under ultrasound guidance
You can be assured of the modified intercostal block, which is one of the standard regional anesthesia procedures, and will be done only by the qualified anaesthesia doctors under ultrasound guidance in cardiac Operation Theatre settings.
If you take part in this study what will you have to do?
If you agree to participate in this study, you will be allotted by computer to receive either an intercostal nerve block with anesthetic drug or Saline with usual intravenous morphine for pain relief after surgery.
In the preoperative and postoperative period, you will be asked to grade your pain on a scale scientifically devised and practiced all over the world. In case pain relief is inadequate, you will be given supplemental pain killers.
Can you withdraw from this study after it starts?
Your participation in this study is entirely voluntary and you are also free to decide, to withdraw permission to participate in this study. If you do so, this will not affect your usual treatment at this hospital in any way. In addition, If your recovery from surgery or postoperative course requires any additional surgical intervention for haemodynamic instability, bleeding or re-exploration, the study will be stopped and your routine treatment will continue as usual
What will happen if you develop any study related injury?
We do not expect any injury to happen to you but, if you do develop any side effects in form of pain due to the study, these will be treated promptly at no cost to you. We are unable to provide any monetary compensation, however for participation in this study.
Will you have to pay for drugs/participating in this study?
Drugs (local anaesthetic) for intercostal nerve block will be given free and are a part of the routine anaesthetic medications.
All other protocols for post-operative patients will be followed strictly as done in routine cases.
What happens after the study is over?
You may or may not benefit from the study drug that you are given. Once this study is over, and the technique scientifically do show any benefit for the relief of post operative pain , then this method will be used in future for all the patients undergoing cardiac surgery.
Will your personal details be kept confidential?
The results of this study will be published in a medical journal, but you will not be identified by name in any publication or presentation of results. However, your medical notes may be reviewed by people associated with the study, without your additional permission, should you decide to participate in this study.
If you have any further questions, please ask Dr v.santhosh (Senior resident, Department of Anaesthesiology), Telephone no. 9894462248, email id- [email protected] Dr. subin sukesan(Associate Professor, Department of Anaesthesiiology) Telephone no. 8289983726, email – [email protected]
For any clarifications regarding the study’s ethics clearance you may contact the Member Secretary of the SCTIMST-IEC – Dr Mala Ramanathan. The phone number is: 0471- 2524234 and the email id is [email protected]
CONSENT TO TAKE PART IN A CLINICAL TRIAL Study Title: Ultrasound guided Parasternal Modified-Intercostal nerve block: Role as a preemptive analgesic adjunct in fast tracking for mitigating postoperative Sternotomy Pain
Study Number: Participant’s name: Date of Birth / Age (in years): I_____________________________________________________________________________, son/daughter of___________________________________ (Please tick boxes) Declare that I have read the information sheet provide to me regarding this study and have clarified any doubts that I had. [ ] I also understand that my participation in this study is entirely voluntary and that I am free to withdraw permission to continue to participate at any time without affecting my usual treatment or my legal rights [ ] I also understand that neither I, nor my doctors, will have any choice or knowledge of whether I will get intercostal block for analgesia[ ] I understand that I will receive free treatment for any study related injury or adverse event but I will not receive and other financial compensation [ ] I understand that the study staff and institutional ethics committee members will not need my permission to look at my health records even if I withdraw from the trial. I agree to this access [ ] I understand that my identity will not be revealed in any information released to third parties or published [ ] I voluntarily agree to take part in this study [ ] Name: Name of witness: Signature: Relation to participant: Date: Date: (Person Obtaining Consent) I attest that the requirements for informed consent for the medical research project described in this form have been satisfied. I have discussed the research project with the participant and explained to him or her in nontechnical terms all of the information contained in this informed consent form, including any risks and adverse reactions that may reasonably be expected to occur. I further certify that I encouraged the participant to ask questions and that all questions asked were answered. ________________________________ ___________________ Name and Signature of Person Obtaining Consent (For Principal Investigator)
Witness:
If you have any further questions, please ask Dr V. Santhosh (Senior resident, Department of Anaesthesiology), Telephone no. 9894462248, email id- [email protected] Dr. subin sukesan (Associate Professor, Department of Anaesthesiiology) Telephone no. 8289983726, email – [email protected]
For any clarifications regarding the study’s ethics clearance you may contact the Member Secretary of the SCTIMST-IEC – Dr. Mala Ramanathan. The phone number is: 0471- 2524234 and the email id is [email protected]
ANNEXURE – iii
ANNEXURE – iv
CASE
NUM
BER
RAND
OMIZ
ATIO
N NO
DATE
AGE
yrs
SEX
M/F
HEIG
HT(cm
s)
WEI
GHT
kg
BSA
SURG
ERY
CAB
G/VA
LVE/
CABG
+VAL
VE
RECE
NT A
CUTE
COR
ONAR
Y IN
SULT
EJEC
TION
FRAC
TION
%
REGI
ONAL
WAL
L M
OTIO
N PR
EOPE
RATI
VE IN
CENT
IVE
SPIR
OMET
RY M
L AC
HIEV
ED
INTR
AOPE
RATI
VE M
ORPH
INE
INFU
SION
…...m
cg/kg
/hr
FENT
ANYL
…....
......m
cg
CPB
TIM
E
AXC
TIM
E
TIM
E OF
SHIF
TING
TO
ICU…
........
.hrs
TIM
E OF
EXT
UBAT
ION
DURA
TION
OF V
ENTI
LATI
ON
MOR
PHIN
E IN
FUSI
ON R
ATE
15M
IN PO
ST
EXTU
BATI
ONNR
S SCO
RE 15
MIN
POST
EXT
UBAT
ION
RAM
SAY
SEDA
TION
SCOR
E 15
MIN
POST
EXTU
BATI
ON
SIDE
EFF
ECTS
15M
IN PO
ST E
XTUB
ATIO
N
MOR
PHIN
E IN
FUSI
ON R
ATE
4HRS
POST
EXTU
BATI
ON
1 1 3/5/2018 68 M 170 64 1.74 CABGNO 55% YES 600 NO 1000 84MIN 37MIN 14:30 18:00 5HRS NIL 4 2 NIL 10MCG/KG/HR
2 1 3/7/2018 63 M 168 64 1.73 CABGNO 45% YES 900 NO 1000 110MIN70MIN 14:45 19:00 4HRS15MIN NIL 4 2 NIL 10MCG/KG/HR
3 1 3/8/2018 45 M 175 88 2.07 CABGNO 58% NO 900 YES@40MCG/KG/HR 1500 137MIN89MIN 14:00 19:00 5HRS NIL 5 1 NIL 10MCG/KG/HR
4 1 3/26/2018 76 M 165 53 1.56 CABGNO 50% NO 900 NO 750 125MIN80MIN 14:15 20:00 5HRS45MIN NIL 5 2 NIL 10MCG/KG/HR
5 1 19/3/2018 66 M 164 68 1.76 CABGNO 55% YES 900 YES@60MCG/KG/HR 1000 102MIN50MIN 15:00 20:00 5HRS NIL 4 1 NIL 10MCG/KG/HR
6 1 9/4/2018 63 M 167 59 1.65 CABGYES 48% YES 900 YES@40MCG/KG/HR 750 110MIN44MIN 14:30 20:05 5HRS35MIN NIL 4 1 NIL NIL
7 1 11/4/2018 66 M 170 61 1.7 CABGNO 65% NO 900 YES@60MCG/KG/HR 500 100MIN50MIN 14:20 19:30 5HRS50MIN NIL 3 1 NIL NIL
8 1 12/4/2018 59 F 172 70 1.83 CABGNO 55% NO 900 YES@40MCG/KG/HR 750 124MIN55MIN 14:35 20:30 6HRS NIL 3 1 NIL NIL
9 1 16/4/2018 59 M 170 73 1.86 CABGNO 60% NO 900 NO 1000 130MIN45MIN 14:30 20:15 5HRS15MIN NIL 3 2 NIL 10MCG/KG/HR
10 1 23/4/2018 45 M 165 58 1.63 CABGNO 60% NO 900 YES@60MCG/KG/HR 750 100MIN43MIN 14:35 20:00 5HRS25MIN NIL 3 2 NIL 10MCG/KG/HR
11 1 25/04/2018 61 M 165 68 1.77 CABGYES 55% YES 900 YES@40MCG/KG/HR 750 90MIN 40MIN 13:40 19:00 4HRS50MIN NIL 3 2 NIL NIL
12 1 30/04/2018 54 M 168 62 1.7 CABGNO 55% YES 600 YES@40MCG/KG/HR 700 110MIN45MIN 13:55 19:00 5HRS5MIN NIL 3 3 NIL NIL
13 1 9/5/2018 68 M 170 77 1.91 CABGYES 46% YES 900 YES@60MCG/KG/HR 600 95MIN 40MIN 14:15 20:30 6HRS NIL 4 2 NIL 10MCG/KG/HR
14 1 14/05/2018 69 F 165 57 1.62 CABGNO 62% NO 900 YES@40MCG/KG/HR 500 100MIN40MIN 14:05 20:00 6HRS NIL 3 3 NIL 10MCG/KG/HR
15 1 16/05/2018 69 M 168 75 1.87 CABGNO 65% YES 900 YES@40MCG/KG/HR 600 115MIN50MIN 14:00 19:30 5HRS30MIN NIL 3 2 NIL 10MCG/KG/HR
16 1 17/05/2018 63 M 180 94 2.17 CABGNO 45% YES 900 NO 750 110MIN45MIN 14:00 19:30 5HRS30MIN NIL 4 1 NIL 10MCG/KG/HR
17 1 28/05/2018 52 M 175 65 1.78 CABGYES 65% NO 900 NO 750 100MIN48MIN 14:00 19:30 5HRS30MIN NIL 3 2 NIL NIL
18 1 3/8/2018 53 M 178 85 2.05 CABGNO 55% YES 600 YES@40MCG/KG/HR 600 95MIN 40MIN 13:50 19:00 4HRS45MIN NIL 3 2 NIL NIL
19 1 6/8/2018 62 F 150 58 1.55 CABGNO 45% YES 900 YES@60MCG/KG/HR 500 100MIN50MIN 14:15 19:45 6HRS NIL 4 1 NIL NIL
20 1 7/8/2018 58 M 175 76 1.92 CABGNO 60% NO 600 NO 700 120MIN50MIN 14:15 20:30 5HRS45MIN NIL 3 2 NIL 10MCG/KG/HR
21 1 8/8/2018 76 M 165 77 1.88 CABGYES 65% NO 900 NO 700 100MIN45MIN 14:00 20:00 6HRS NIL 3 2 NIL 10MCG/KG/HR
22 1 13/08/2018 68 M 165 59 1.64 CABGNO 75% NO 900 YES@40MCG/KG/HR 600 110MIN50MIN 13:45 19:00 5HRS15MIN NIL 3 1 NIL 10MCG/KG/HR
ANNEXURE – v
23 1 16/08/2018 39 M 168 60 1.67 CABGYES 65% NO 600 YES@60MCG/KG/HR 650 92MIN 40MIN 13:45 19:00 5HRS15MIN NIL 3 1 NIL 10MCG/KG/HR
24 1 17/08/2018 45 M 180 95 2.18 CABGYES 60% NO 900 YES@40MCG/KG/HR 600 90MIN 40MIN 13:50 18:45 4HRS50MIN NIL 4 2 NIL 10MCG/KG/HR
25 1 20/08/2018 68 M 165 68 1.78 CABGYES 65% NO 600 YES@40MCG/KG/HR 750 100MIN45MIN 14:10 19:30 5HRS20MIN NIL 4 2 NIL 10MCG/KG/HR
26 1 28/08/2018 61 M 168 71 1.82 CABGNO 68% NO 900 YES@40MCG/KG/HR 600 125MIN62MIN 14:00 19:00 5HRS NIL 4 2 NIL 10MCG/KG/HR
27 1 30/08/2018 70 F 152 61 1.6 CABGNO 60% NO 900 YES@40FCG/KG/HR 500 97MIN 57MIN 13:50 20:00 6HRS10MIN NIL 4 3 NIL NIL
28 1 1/10/2018 54 M 162 57 1.6 CABGNO 72% NO 600 NO 600 90MIN 47MIN 14:10 19:30 5HRS20MIN NIL 4 2 NIL 10MCG/KG/HR
29 1 8/10/2018 63 M 160 61 1.65 CABGNO 65% NO 900 YES@40MCG/KG/HR 650 100MIN52MIN 14:15 19:45 5HRS30MIN NIL 4 2 NIL NIL
30 1 10/10/2018 67 M 168 75 1.87 CABGYES 52% YES 600 YES@40MNCG/KG/HR 750 125MIN55MIN 14:00 20:00 6HRS NIL 4 2 NIL 10MCG/KG/HR
31 1 10/10/2018 58 M 165 75 1.85 CABGYES 61% YES 900 NO 600 110MIN58MIN 14:15 20:00 5HRS45MIN NIL 4 1 NIL 10MCG/KG/HR
32 1 11/10/2018 49 F 145 64 1.61 CABGNO 52% YES 900 YES@20MNCG/KG/HR 500 95MIN 45MIN 13:45 19:00 5HRS15MIN NIL 2 2 NIL NIL
33 1 12/10/2018 57 M 168 65 1.74 CABGYES 58% NO 900 YES@30MCG/KG/HR 500 108MIN51MIN 14:10 19:30 5HRS20MIN NIL 3 2 NIL NIL
34 1 17/10/2018 58 M 162 53 1.54 CABGNO 58% NO 600 YES@20MCG/KG/HR 600 100MIN52MIN 13:45 19:25 5HRS40MIN NIL 2 2 NIL 10MCG/KG/HR
35 1 17/10/2018 60 F 152 67 1.68 CABGNO 60% NO 900 NO 750 95MIN 45MIN 13:50 19:00 5HRS10MIN NIL 3 2 NIL NIL
36 1 23/10/2018 54 M 165 60 1.66 CABGNO 67% NO 900 YES@20MCG/KG/HR 600 121MIN58MIN 14:00 19:45 5HRS45MIN NIL 2 2 NIL 10MCG/KG/HR
37 1 25/10/2018 50 F 155 65 1.67 CABGYES 70% NO 600 YES@20MCG/KG/HR 500 113MIN60MIN 13:45 19:30 5HRS45MIN NIL 3 1 NIL 10MCG/KG/HR
38 1 12/12/2018 45 M 175 71 1.86 CABGNO 58% NO 600 YES@20MCG/KG/HR 500 110MIN52MIN 14:00 19:00 5HRS NIL 2 2 NIL 10MCG/KG/HR
39 1 31/12/2018 68 M 165 61 1.67 CABGNO 65% NO 900 YES@20MCG/KG/HR 500 86MIN 53MIN 13:35 18:30 4HRS55MIN NIL 2 2 NIL NIL
40 1 3/1/2019 52 M 165 51 1.53 CABGNO 63% NO 900 NO 650 120MIN55MIN 13:45 18:30 4HRS45MIN NIL 2 2 NIL NIL
41 1 10/1/2019 58 M 170 65 1.75 CABGNO 50% YES 600 YES@30MCG/KG/HR 600 95MIN 48MIN 13:35 18:30 4HRS55MIN NIL 3 2 NIL 10MCG/KG/HR
42 1 14/01/2019 60 M 172 77 1.92 CABGNO 60% NO 900 NO 650 110MIN55MIN 14:10 19:30 5HRS20MIN NIL 3 2 NIL NIL
43 1 29/01/2019 78 M 175 75 1.91 CABGNO 62% NO 900 NO 600 90MIN 45MIN 13:45 19:00 5HRS15MIN NIL 4 2 NIL 10MCG/KG/HR
44 1 8/3/2019 67 F 165 69 1.78 CABGNO 48% YES 900 YES@20MCG/KG/HR 500 81MIN 48MIN 13:00 19:00 5HRS NIL 2 2 NIL 10MCG/KG/HR
45 1 19/03/2019 53 M 170 69 1.81 CABGYES 60% YES 900 YES@30MCG/KG/HR 500 100MIN52MIN 13:50 19:30 5HRS40MIN NIL 3 2 NIL NIL
NRS S
CORE
4HRS
POST
EXT
UBAT
ION
RAM
SAY
SEDA
TION
SCOR
E 4H
RS PO
ST
EXTU
BATI
ON
RESC
UE A
NALG
ESIA
4HRS
POST
EXTU
BATI
ON
SIDE
EFF
ECTS
4HRS
POST
EXT
UBAT
ION
COOP
ERAT
ION
WIT
H SP
IROM
ETRY
4HRS
POST
EXT
UBAT
ION
VOLU
ME
NRS S
CORE
4HRS
POST
EXT
UBAT
ION
WIT
H BR
EATH
ING
EXER
CISE
S
MOR
PHIN
E IN
FUSI
ON R
ATE
8HRS
POST
EXTU
BATI
ON
NRS S
CORE
8HRS
POST
EXT
UBAT
ION
RAM
SAY
SEDA
TION
SCOR
E 8H
RS PO
ST
EXTU
BATI
ON
RESC
UE A
NALG
ESIA
8HRS
POST
EXTU
BATI
ON
SIDE
EFF
ECTS
8HRS
POST
EXT
UBAT
ION
COPE
RATI
ON W
ITH
INCE
NTIV
E
SPIR
OMTR
Y Y/
N 8H
RS PO
ST
NRS S
CORE
8HRS
POST
EXT
UBAT
ION
WIT
H BR
EATH
ING
EXER
CISE
S
MOR
PHIN
E IN
FUSI
ON R
ATE
12HR
S POS
T
EXTU
BATI
ON
NRS S
CORE
12HR
S POS
T EX
TUBA
TION
RAM
SAY
SEDA
TION
SCOR
E 12
HRS P
OST
EXTU
BATI
ONRE
SCUE
ANA
LGES
IA 12
HRS P
OST
EXTU
BATI
ONSI
DE E
FFEC
TS 12
HRS P
OST
EXTU
BATI
ON
COPE
RATI
ON W
ITH
INCE
NTIV
E
SPIR
OMTR
Y Y/
N 12
HRS P
OST
EXTU
BATI
ONNR
S SCO
RE 12
HRS P
OST
EXTU
BATI
ON
WIT
H BR
EATH
ING
EXER
CISE
S
MOR
PHIN
E IN
FUSI
ON R
ATE
16HR
S POS
T
EXTU
BATI
ON
NRS S
CORE
16HR
S POS
T EX
TUBA
TION
2 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL NO 3 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL NO 3 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL NO 3 10MCG/KG/HR 4 2 NIL NIL YES 5 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4
3 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 3 NIL 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
4 2 NIL NIL YES 3 NIL 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 3 NIL 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 4 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4
3 2 NIL NIL YES 3 NIL 3 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
4 2 NIL NIL YES 3 NIL 3 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 3
3 2 NIL NIL NO 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3
3 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3
3 2 NIL NIL NO 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 3 10MCG/KG/HR 3
3 2 YES NIL YES 3 10MCG/KG/HR 3 2 YES NIL YES 3 10MCG/KG/HR 3 3 YES NIL YES 3 10MCG/KG/HR 4
3 2 NIL NIL YES 3 NIL 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3
2 2 NIL NIL NO 3 NIL 4 2 NIL NIL YES 4 10MCG/KG/HR 4 1 NIL NIL YES 4 10MCG/KG/HR 3
3 2 NIL NIL NO 3 NIL 3 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3
4 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3
2 2 NIL NIL NO 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3
ANNEXURE – v
3 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 2
3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3
4 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 2
2 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 2
3 2 NIL NIL YES 3 NIL 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 3
3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 3
4 2 NIL NIL YES 3 NIL 4 3 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3
3 2 NIL NIL NO 3 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL NO 2 NIL 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 3
3 2 NIL NIL YES 3 NIL 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 4
2 2 NIL NIL YES 2 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 3
2 2 NIL NIL YES 3 NIL 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3
2 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3
3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4
3 2 NIL NIL YES 3 NIL 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 3
2 2 NIL YES YES 2 NIL 3 3 NIL YES YES 3 10MCG/KG/HR 3 2 NIL YES YES 3 10MCG/KG/HR 4
2 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4
3 2 NIL NIL YES 3 NIL 4 3 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3
3 2 YES NIL YES 3 10MCG/KG/HR 3 2 YES NIL YES 4 10MCG/KG/HR 4 2 YES NIL YES 3 10MCG/KG/HR 4
3 2 NIL NIL YES 3 10MCG/KG/HR 4 3 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3
2 2 NIL NIL YES 3 NIL 3 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4
RAM
SAY
SEDA
TION
SCAL
E 16
HRS P
OST
EXTU
BATI
ON
RESC
UE A
NALG
ESIA
16HR
S POS
T
EXTU
BATI
ON
SIDE
EFFE
CS 16
HRS P
OST
EXTU
BATI
ON
COPE
RATI
ON W
ITH
INCE
NTIV
E
SPIR
OMTR
Y 16
HRS P
OST
EXTU
BATI
ON
NRS S
CORE
16HR
S POS
T EX
TUBA
TION
WIT
H BR
EATH
ING
EXER
CISE
S
MOR
PHIN
E IN
FUSI
ON R
ATE
20HR
S POS
T
EXTU
BATI
ON
NRS S
CORE
20HR
S POS
T EX
TUBA
TION
RAM
SAY
SEDA
TION
SCAL
E 20
HRS P
OST
EXTU
BATI
ON
RESC
UE A
NALG
ESIA
20HR
S POS
T
EXTU
BATI
ON
SIDE
EFFE
CS 20
HRS P
OST
EXTU
BATI
ON
COPE
RATI
ON W
ITH
INCE
NTIV
E
SPIR
OMTR
Y 20
HRS P
OST
EXTU
BATI
ONNR
S SCO
RE 20
HRS P
OST
EXTU
BATI
ON
WIT
H BR
EATH
ING
EXER
CISE
S
MOR
PHIN
E IN
FUSI
ON R
ATE
24HR
S POS
T
EXTU
BATI
ON
NRS S
CORE
24HR
S POS
T EX
TUBA
TION
RAM
SAY
SEDA
TION
SCAL
E 24
HRS P
OST
EXTU
BATI
ONRE
SCUE
ANA
LGES
IA 24
HRS P
OST
EXTU
BATI
ON
SIDE
EFFE
CS 24
HRS P
OST
EXTU
BATI
ON
COPE
RATI
ON W
ITH
INCE
NTIV
E
SPIR
OMTR
Y 24
HRS P
OST
EXTU
BATI
ONNR
S SCO
RE 24
HRS P
OST
EXTU
BATI
ON
WIT
H BR
EATH
ING
EXER
CISE
S
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 5 10MCG/KG/HR 4 2 NIL NIL YES 5 10MCG/KG/HR 4 2 NIL NIL YES 5
2 NIL NIL YES 5 10MCG/KG/HR 4 2 NIL NIL YES 5 10MCG/KG/HR 6 2 YES NIL YES 6
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 YES NIL YES 3 10MCG/KG/HR 4 2 YES NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
ANNEXURE – v
2 NIL NIL YES 4 10MCG/KG/HR 2 2 NIL NIL YES 4 10MCG/KG/HR 2 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 2 2 NIL NIL YES 4 10MCG/KG/HR 2 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 2 2 NIL NIL YES 4 10MCG/KG/HR 2 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3 10MCG/KG/HR 3 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL YES YES 3 10MCG/KG/HR 4 2 NIL YES YES 3 10MCG/KG/HR 4 2 NIL YES YES 3
2 NIL NIL YES 4 10MCG/KG/HR 4 2 NIL NIL YES 4 10MCG/KG/HR 5 2 YES NIL YES 5
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 4 2 YES NIL YES 3 10MCG/KG/HR 4 2 YES NIL YES 3
2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4 10MCG/KG/HR 3 2 NIL NIL YES 4
2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3 10MCG/KG/HR 4 2 NIL NIL YES 3
CA
SE
NU
MB
ER
RA
ND
OM
IZA
TIO
N N
O
DA
TE
AG
E y
rs
SE
X M
/F
HE
IGH
T(c
ms)
WE
IGH
T k
g
BS
A
SU
RG
ER
Y
CA
BG
/VA
LVE
/CA
BG
+V
ALV
E
RE
CE
NT
AC
UT
E
CO
RO
NA
RY
INS
ULT
<3M
ON
TH
S Y
ES
/NO
EJE
CT
ION
FR
AC
TIO
N %
RE
GIO
NA
L W
ALL
MO
TIO
N
AB
NO
RM
ALI
TIE
S Y
ES
/NO
PR
EO
PE
RA
TIV
E I
NC
EN
TIV
E
SP
IRO
ME
TR
Y M
L
AC
HIE
VE
D
INT
RA
OP
ER
AT
IVE
MO
RP
HIN
E IN
FU
SIO
N
…...
mcg
/kg/
hr
FE
NT
AN
YL
…...
....
...m
cg
CP
B T
IME
AX
C T
IME
TIM
E O
F S
HIF
TIN
G T
O
ICU
…...
....
..hr
s
TIM
E O
F E
XT
UB
AT
ION
DU
RA
TIO
N O
F
ME
CH
AN
ICA
L V
EN
TIL
AT
ION
MO
RP
HIN
E IN
FU
SIO
N
RA
TE
15M
IN P
OS
T
EX
TU
BA
TIO
N
NR
S S
CO
RE
15M
IN P
OS
T
EX
TU
BA
TIO
N
RA
MS
AY
SE
DA
TIO
N S
CO
RE
15M
IN P
OS
T E
XT
UB
AT
ION
SID
E E
FF
EC
TS
15M
IN P
OS
T
EX
TU
BA
TIO
N
MO
RP
HIN
E IN
FU
SIO
N R
AT
E
4HR
S P
OS
T E
XT
UB
AT
ION
NR
S S
CO
RE
4H
RS
PO
ST
EX
TU
BA
TIO
N
RA
MS
AY
SE
DA
TIO
N S
CO
RE
4HR
S P
OS
T E
XT
UB
AT
ION
RE
SC
UE
AN
ALG
ES
IA 4
HR
S
PO
ST
EX
TU
BA
TIO
N
SID
E E
FF
EC
TS
4H
RS
PO
ST
EX
TU
BA
TIO
N
CO
OP
ER
AT
ION
WIT
H
SP
IRO
ME
TR
Y 4
HR
S P
OS
T
EX
TU
BA
TIO
N V
OLU
ME
NR
S S
CO
RE
4H
RS
PO
ST
EX
TU
BA
TIO
N W
ITH
BR
EA
TH
ING
EX
ER
CIS
ES
1 2 25/04/2019 70 M 165 58 1.63 CABG NO 65% NO 900 60MCG/KG/HR 1000 90 60 13:45 19:00 5HRS15MIN NIL 4 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
2 2 24/04/2019 61 M 168 67 1.77 CABG NO 62% NO 900 40MCG/KG/HR 1200 110 65 12:50 18:30 5HRS40MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
3 2 11/4/2019 67 M 163 56 1.59 CABG YES 57% NO 900 60MCG/KG/HR 1000 95 55 13:45 20:00 6HRS15MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
4 2 11/4/2019 57 M 170 77 1.91 CABG NO 55% YES 600 60MCG/KG/HR 750 109 58 13:50 19:30 5HRS50MIN NIL 6 1 YES HIGH PCO2 10MCG/KG/HR 6 1 YES YES YES 5
5 2 5/4/2019 64 F 172 74 1.88 CABG NO 63% YES 900 60MCG/KG/HR 1000 100 60 14:00 20:00 6HRS NIL 4 2 NIL 10MCG/KG/HR 6 3 YES NIL YES 5
6 2 3/4/2019 46 M 170 76 1.89 CABG NO 70% NO 600 40MCG/KG/HR 1200 110 65 13:50 18:45 5HRS5MIN NIL 5 3 NIL 10MCG/KG/HR 5 3 NO NIL YES 5
7 2 1/4/2019 63 M 165 58 1.63 CABG YES 65% YES 600 40MCG/KG/HR 800 98 60 14:15 19:45 5HRS30MIN NIL 5 2 NIL 10MCG/KG/HR 6 2 NO NIL YES 5
8 2 29/03/2019 61 M 168 61 1.69 CABG YES 60% YES 900 60MCG/KG/HR 1000 110 66 14:30 20:00 5HRS30MIN NIL 3 3 NIL 10MCG/KG/HR 5 2 YES NIL YES 5
9 2 22/03/2019 75 M 166 65 1.73 CABG YES 58% YES 900 60MCG/KG/HR 1200 95 50 14:00 20:00 6HRS NIL 4 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 6
10 2 20/03/2019 50 F 150 80 1.83 CABG YES 65% NO 900 60MCG/KG/HR 1000 115 65 14:15 17:45 5HRS30MIN NIL 4 2 NIL 10MCG/KG/HR 5 3 NO NIL YES 5
11 2 19/03/2019 74 M 166 49 1.5 CABG YES 68% NO 600 60MCG/KG/HR 750 90 62 13:50 20:00 6HRS10MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 4
12 2 15/03/2019 52 M 165 67 1.75 CABG NO 52% YES 600 40MCG/KG/HR 800 95 55 13:30 19:30 6HRS NIL 5 3 NIL 10MCG/KG/HR 5 3 NO NIL YES 5
13 2 6/3/2019 77 M 172 67 1.79 CABG NO 55% NO 900 40MCG/KG/HR 800 98 58 13:45 19:45 6HRS NIL 6 1 NIL 10MCG/KG/HR 5 2 YES YES NO 5
14 2 6/3/2019 65 M 175 77 1.93 CABG YES 60% NO 600 60MCG/KG/HR 750 102 58 14:00 20:00 6HRS NIL 5 2 NIL 10MCG/KG/HR 5 2 YES NIL YES 5
15 2 5/3/2019 62 M 170 68 1.79 CABG NO 57% NO 600 60MCG/KG/HR 750 110 65 14:20 20:00 5HRS40MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 YES NIL YES 6
16 2 27/02/2019 61 M 176 92 2.12 CABG NO 64% NO 600 40MCG/KG/HR 800 98 55 13:30 19:30 6HRS NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL NO 5
17 2 25/02/2019 51 F 152 50 1.45 CABG YES 59% NO 900 60MCG/KG/HR 1200 130 70 14:00 19:15 5HRS15MIN NIL 4 3 NIL 10MCG/KG/HR 4 3 NO NIL YES 4
18 2 15/02/2019 59 M 172 82 1.98 CABG NO 62% NO 900 40MCG/KG/HR 1000 115 65 13:45 18:45 5HRS NIL 5 2 NIL 10MCG/KG/HR 5 3 NO NIL YES 5
19 2 11/2/2019 61 M 175 70 1.84 CABG NO 62% YES 900 40MCG/KG/HR 1000 90 54 14:00 19:30 5HRS30MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
20 2 26/11/2018 48 M 158 58 1.6 CABG NO 63% NO 600 60MCG/KG/HR 1200 125 62 14:30 19:45 5HRS45MIN NIL 6 1 NIL 10MCG/KG/HR 6 3 NO YES YES 6
21 2 26/11/2018 60 M 165 81 1.93 CABG NO 66% NO 900 60MCG/KG/HR 1000 110 65 13:50 18:45 5HRS5MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
22 2 19/11/2018 48 M 168 78 1.91 CABG NO 65% NO 600 40MCG/KG/HR 1000 102 55 13:35 19:00 5HRS25MIN NIL 4 2 NIL 10MCG/KG/HR 5 3 NO NIL YES 5
23 2 16/11/2018 53 F 155 87 1.94 CABG NO 58% YES 600 40FCG/KG/HR 1000 90 58 13:45 19:30 5HRS45MIN NIL 5 2 NIL 10FCG/KG/HR 5 2 NO NIL' YES 5
24 2 15/11/2018 62 M 162 50 1.5 CABG NO 65% YES 900 90MCG/KG/HR 1200 105 60 14:00 20:00 6HRS NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 6
25 2 14/11/2018 66 M 170 64 1.74 CABG NO 56% NO 900 90MCG/KG/HR 800 61 30 14:10 19:45 5HRS35MIN NIL 4 2 NIL 10MCG/KG/HR 5 3 NO NIL YES 5
26 2 14/11/2018 58 M 172 76 1.91 CABG NO 50% YES 900 90MCG/KG/HR 750 85 50 13:30 19:30 5HRS NIL 5 3 NIL 10MCG/KG/HR 4 2 NO NIL YES 4
27 2 13/11/2018 57 M 165 74 1.84 CABG YES 65% NO 600 60MCG/KG/HR 1000 95 52 13:25 18:45 5HRS20MIN NIL 6 1 NIL 10MCG/KG/HR 5 2 NO YES YES 5
28 2 12/11/2018 63 M 170 63 1.72 CABG NO 50% YES 600 40MCG/KG/HR 1200 105 62 14:00 19:30 5HRS30MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
29 2 30/10/2018 56 M 172 69 1.82 CABG YES 52% YES 900 40MCG/KG/HR 1000 102 65 14:45 19:45 5HRS NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
30 2 26/10/2018 57 M 170 75 1.88 CABG NO 65% NO 900 40MCG/KG/HR 1200 98 54 13:50 18:45 4HRS55MIN NIL 4 3 NIL 10MCG/KG/HR 4 2 NO NI YES 4
31 2 24/10/2018 57 M 165 71 1.8 CABG NO 70% NO 600 60MCG/KG/HR 800 70 37 13:20 19:00 5HRS40MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO YES YES 6
32 2 17/10/2018 61 F 145 62 1.58 CABG NO 65% NO 900 40FCG/KG/HR 750 100 56 14:00 20:00 6HRS NIL 4 2 NIL 10FCG/KG/HR 4 2 NO NIL NO 5
33 2 12/10/2018 54 F 148 57 1.53 CABG YES 48% YES 900 40MCG/KG/HR 1000 95 48 14:15 19:45 5HRS30MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 6
34 2 9/10/2018 68 M 165 76 1.87 CABG NO 72% NO 600 40MCG/KG/HR 1200 110 55 14:30 19:45 5HRS15MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL NO 5
35 2 4/10/2018 66 M 166 57 1.62 CABG NO 55% YES 900 40MCG/KG/HR 750 100 62 13:45 18:30 4HRS45MIN NIL 4 2 NIL 10MCG/KG/HR 4 2 NO NIL YES 4
36 2 27/09/2018 67 M 168 60 1.67 CABG NO 62% NO 900 60MCG/KG/HR 750 92 48 14:00 18:45 4HRS45MIN NIL 5 3 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
37 2 18/09/2018 53 M 165 58 1.63 CABG YES 65% YES 900 60MCG/KG/HR 1200 88 35 13:30 19:45 5HRS15MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
38 2 12/9/2018 43 M 170 69 1.81 CABG NO 48% YES 900 40MCG/KG/HR 1000 98 57 13:45 19:30 5HRS45MIN NIL 6 1 NIL 10MCG/KG/HR 6 2 NO NIL NO 5
39 2 10/9/2018 65 M 168 57 1.63 CABG NO 55% NO 600 60MCG/KG/HR 1000 82 49 13:15 18:45 5HRS30MIN NIL 4 2 NIL 10MCG/KG/HR 5 3 NO NIL YES 6
40 2 6/9/2018 55 M 175 80 1.97 CABG NO 60% NO 600 60MCG/KG/HR 1200 88 45 12:45 18:00 5HRS15MIN NIL 4 2 NIL 10MCG/KG/HR 5 2 NO YES YES 5
41 2 3/9/2018 54 M 162 42 1.37 CABG YES 54% YES 900 40MCG/KG/HR 1000 102 55 14:00 20:00 6HRS NIL 5 2 NIL 10MCG/KG/HR 6 2 YES NIL YES 5
42 2 31/08/2018 56 F 152 81 1.85 CABG YES 55% YES 900 60MCG/KG/HR 750 95 46 13:30 18:45 5HRS15MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
43 2 30/08/2018 60 F 155 58 1.58 CABG YES 60% YES 600 60FCG/KG/HR 1000 98 50 13:45 19:30 5HRS45MIN NIL 5 2 NIL 10FCG/KG/HR 5 2 NO NIL YES 5
44 2 21/08/2018 54 M 168 64 1.73 CABG YES 60% NO 900 40MCG/KG/HR 1000 105 55 14:00 20:00 6HRS NIL 6 2 NIL 10MCG/KG/HR 6 2 YES NIL YES 6
45 2 17/08/2018 65 M 172 68 1.8 CABG NO 62% NO 600 60MCG/KG/HR 1200 103 61 14:15 19:30 5HRS15MIN NIL 5 2 NIL 10MCG/KG/HR 5 2 NO NIL YES 5
MO
RP
HIN
E IN
FU
SIO
N R
AT
E
8HR
S P
OS
T E
XT
UB
AT
ION
NR
S S
CO
RE
8H
RS
PO
ST
EX
TU
BA
TIO
N
RA
MS
AY
SE
DA
TIO
N S
CO
RE
8HR
S P
OS
T E
XT
UB
AT
ION
RE
SC
UE
AN
ALG
ES
IA8H
RS
PO
ST
EX
TU
BA
TIO
N
SID
E E
FF
EC
TS
8H
RS
PO
ST
EX
TU
BA
TIO
N
CO
PE
RA
TIO
N W
ITH
INC
EN
TIV
E S
PIR
OM
TR
Y Y
/N
8HR
S P
OS
T E
XT
UB
AT
ION
NR
S S
CO
RE
8H
RS
PO
ST
EX
TU
BA
TIO
N W
ITH
BR
EA
TH
ING
EX
ER
CIS
ES
MO
RP
HIN
E IN
FU
SIO
N R
AT
E
12H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
12H
RS
PO
ST
EX
TU
BA
TIO
N
RA
MS
AY
SE
DA
TIO
N S
CO
RE
12H
RS
PO
ST
EX
TU
BA
TIO
N
RE
SC
UE
AN
ALG
ES
IA 1
2HR
S
PO
ST
EX
TU
BA
TIO
N
SID
E E
FF
EC
TS
12H
RS
PO
ST
EX
TU
BA
TIO
N
CO
PE
RA
TIO
N W
ITH
INC
EN
TIV
E S
PIR
OM
TR
Y Y
/N
12H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
12H
RS
PO
ST
EX
TU
BA
TIO
N W
ITH
BR
EA
TH
ING
EX
ER
CIS
ES
MO
RP
HIN
E IN
FU
SIO
N R
AT
E
16H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
16H
RS
PO
ST
EX
TU
BA
TIO
N
RA
MS
AY
SE
DA
TIO
N S
CO
RE
16H
RS
PO
ST
EX
TU
BA
TIO
N
RE
SC
UE
AN
ALG
ES
IA 1
6HR
S
PO
ST
EX
TU
BA
TIO
N
SID
E E
FF
EC
TS
16H
RS
PO
ST
EX
TU
BA
TIO
N
CO
PE
RA
TIO
N W
ITH
INC
EN
TIV
E S
PIR
OM
TR
Y Y
/N
16H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
16H
RS
PO
ST
EX
TU
BA
TIO
N W
ITH
BR
EA
TH
ING
EX
ER
CIS
ES
MO
RP
HIN
E IN
FU
SIO
N R
AT
E
20H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
20H
RS
PO
ST
EX
TU
BA
TIO
N
RA
MS
AY
SE
DA
TIO
N S
CO
RE
20H
RS
PO
ST
EX
TU
BA
TIO
N
RE
SC
UE
AN
ALG
ES
IA
20H
RS
PO
ST
EX
TU
BA
TIO
N
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 YES YES VOMITING YES 5 10MCG/KG/HR 5 2 YES YES VOMITINGYES 5 10MCG/KG/HR 5 2 YES YES VOMITINGYES 5 10MCG/KG/HR 5 2 YES
10MCG/KG/HR 6 1 YES NIL YES 5 10MCG/KG/HR 6 1 YES NIL YES 5 10MCG/KG/HR 6 1 YES NIL YES 5 10MCG/KG/HR 6 1 YES
10MCG/KG/HR 5 1 NO NIL YES 6 10MCG/KG/HR 5 1 NO NIL YES 6 10MCG/KG/HR 5 1 NO NIL YES 6 10MCG/KG/HR 5 1 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 YES NIL YES 5 10MCG/KG/HR 5 2 YES NIL YES 5 10MCG/KG/HR 5 2 YES NIL YES 5 10MCG/KG/HR 5 2 YES
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 4 3 NO NIL YES 4 10MCG/KG/HR 4 3 NO NIL YES 4 10MCG/KG/HR 4 3 NO NIL YES 4 10MCG/KG/HR 4 3 NO
10MCG/KG/HR 5 2 NO NL YES 5 10MCG/KG/HR 5 2 NO NL YES 5 10MCG/KG/HR 5 2 NO NL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 YES YES VOMITING NO 5 10MCG/KG/HR 5 2 YES YES VOMITINGNO 5 10MCG/KG/HR 5 2 YES YES VOMITINGNO 5 10MCG/KG/HR 5 2 YES
10MCG/KG/HR 5 2 YES NIL YES 5 10MCG/KG/HR 5 2 YES NIL YES 5 10MCG/KG/HR 5 2 YES NIL YES 5 10MCG/KG/HR 5 2 YES
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 6 2 NO NIL YES 6 10MCG/KG/HR 6 2 NO NIL YES 6 10MCG/KG/HR 6 2 NO NIL YES 6 10MCG/KG/HR 6 2 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 4 3 NO NIL YES 4 10MCG/KG/HR 4 3 NO NIL YES 4 10MCG/KG/HR 4 3 NO NIL YES 4 10MCG/KG/HR 4 3 NO
10MCG/KG/HR 5 2 NO YES NAUSEA NO 5 10MCG/KG/HR 5 2 NO YES NAUSEANO 5 10MCG/KG/HR 5 2 NO YES NAUSEANO 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 6 1 NO NIL YES 6 10MCG/KG/HR 6 1 NO NIL YES 6 10MCG/KG/HR 6 1 NO NIL YES 6 10MCG/KG/HR 6 1 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10FCG/KG/HR 6 1 NO NIL YES 6 10FCG/KG/HR 6 1 NO NIL YES 6 10FCG/KG/HR 6 1 NO NIL YES 6 10FCG/KG/HR 6 1 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO YES VOMITING YES 5 10MCG/KG/HR 5 2 NO YES VOMITINGYES 5 10MCG/KG/HR 5 2 NO YES VOMITINGYES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 4 2 NO NO YES 4 10MCG/KG/HR 4 2 NO NO YES 4 10MCG/KG/HR 4 2 NO NO YES 4 10MCG/KG/HR 4 2 NO
10MCG/KG/HR 5 2 NO NO NO 5 10MCG/KG/HR 5 2 NO NO NO 5 10MCG/KG/HR 5 2 NO NO NO 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NO YES 6 10MCG/KG/HR 5 2 YES NO YES 6 10MCG/KG/HR 5 2 YES NO YES 6 10MCG/KG/HR 5 2 YES
10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 4 3 NO NO YES 4 10MCG/KG/HR 4 3 NO NO YES 4 10MCG/KG/HR 4 3 NO NO YES 4 10MCG/KG/HR 4 3 NO
10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 6 1 NO YES VOMITING YES 6 10MCG/KG/HR 6 1 NO YES VOMITINGYES 6 10MCG/KG/HR 6 1 NO YES VOMITINGYES 6 10MCG/KG/HR 6 1 NO
10MCG/KG/HR 6 2 NO NO NO 5 10MCG/KG/HR 6 2 NO NO NO 5 10MCG/KG/HR 6 2 NO NO NO 5 10MCG/KG/HR 6 2 NO
10MCG/KG/HR 6 2 NO NO YES 6 10MCG/KG/HR 6 2 NO NO YES 6 10MCG/KG/HR 6 2 NO NO YES 6 10MCG/KG/HR 6 2 NO
10MCG/KG/HR 5 2 NO YES YES 5 10MCG/KG/HR 5 2 NO YES YES 5 10MCG/KG/HR 5 2 NO YES YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 YES YES YES 5 10MCG/KG/HR 5 2 YES YES YES 5 10MCG/KG/HR 5 2 YES YES YES 5 10MCG/KG/HR 5 2 YES
10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5 10MCG/KG/HR 5 2 NO
10MCG/KG/HR 6 2 YES NO YES 6 10MCG/KG/HR 6 2 YES NO YES 6 10MCG/KG/HR 6 2 YES NO YES 6 10MCG/KG/HR 6 2 YES
10MCG/KG/HR 5 2 NO NO NO 6 10MCG/KG/HR 5 2 NO NO NO 6 10MCG/KG/HR 5 2 NO NO NO 6 10MCG/KG/HR 5 2 NO
SID
E E
FF
EC
TS
20H
RS
PO
ST
EX
TU
BA
TIO
N
CO
PE
RA
TIO
N W
ITH
INC
EN
TIV
E S
PIR
OM
TR
Y Y
/N
20H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
20H
RS
PO
ST
EX
TU
BA
TIO
N W
ITH
BR
EA
TH
ING
EX
ER
CIS
ES
MO
RP
HIN
E IN
FU
SIO
N R
AT
E
24H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
24H
RS
PO
ST
EX
TU
BA
TIO
N
RA
MS
AY
SE
DA
TIO
N S
CO
RE
24H
RS
PO
ST
EX
TU
BA
TIO
N
RE
SC
UE
AN
ALG
ES
IA
24H
RS
PO
ST
EX
TU
BA
TIO
N
SID
E E
FF
EC
TS
24H
RS
PO
ST
EX
TU
BA
TIO
N
CO
PE
RA
TIO
N W
ITH
INC
EN
TIV
E S
PIR
OM
TR
Y Y
/N
24H
RS
PO
ST
EX
TU
BA
TIO
N
NR
S S
CO
RE
24H
RS
PO
ST
EX
TU
BA
TIO
N W
ITH
BR
EA
TH
ING
EX
ER
CIS
ES
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
YES VOMITINGYES 5 10MCG/KG/HR 5 2 YES YES VOMITINGYES 5
NIL YES 5 10MCG/KG/HR 6 1 YES NIL YES 5
NIL YES 6 10MCG/KG/HR 5 1 NO NIL YES 6
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 YES NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 4 10MCG/KG/HR 4 3 NO NIL YES 4
NL YES 5 10MCG/KG/HR 5 2 NO NL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
YES VOMITINGNO 5 10MCG/KG/HR 5 2 YES YES VOMITINGNO 5
NIL YES 5 10MCG/KG/HR 5 2 YES NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 6 10MCG/KG/HR 6 2 NO NIL YES 6
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 4 10MCG/KG/HR 4 3 NO NIL YES 4
YES NAUSEANO 5 10MCG/KG/HR 5 2 NO YES NAUSEANO 5
NIL YES 6 10MCG/KG/HR 6 1 NO NIL YES 6
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 6 10FCG/KG/HR 6 1 NO NIL YES 6
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NIL YES 5 10MCG/KG/HR 5 2 NO NIL YES 5
NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5
NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5
YES VOMITINGYES 5 10MCG/KG/HR 5 2 NO YES VOMITINGYES 5
NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5
NO YES 4 10MCG/KG/HR 4 2 NO NO YES 4
NO NO 5 10MCG/KG/HR 5 2 NO NO NO 5
NO YES 6 10MCG/KG/HR 5 2 YES NO YES 6
NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5
NO YES 4 10MCG/KG/HR 4 3 NO NO YES 4
NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5
YES VOMITINGYES 6 10MCG/KG/HR 6 1 NO YES VOMITINGYES 6
NO NO 5 10MCG/KG/HR 6 2 NO NO NO 5
NO YES 6 10MCG/KG/HR 6 2 NO NO YES 6
YES YES 5 10MCG/KG/HR 5 2 NO YES YES 5
YES YES 5 10MCG/KG/HR 5 2 YES YES YES 5
NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5
NO YES 5 10MCG/KG/HR 5 2 NO NO YES 5
NO YES 6 10MCG/KG/HR 6 2 YES NO YES 6
NO NO 6 10MCG/KG/HR 5 2 NO NO NO 6
ANNEXURE vi
